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8220896

Effect of endopeptidase-24.11 inhibition and of atrial natriuretic peptide clearance receptor ligand on the response to rat brain natriuretic peptide in the conscious rat.

1. The present studies examined the effect of (a) a specific endopeptidase-24.11 (E-24.11) inhibitor (candoxatrilat) and (b) a ligand for the atrial natriuretic peptide (ANP) clearance receptor (SC 46542) on the renal and blood pressure response to brain natriuretic peptide (BNP) in conscious rats. 2. Infusion of BNP 200 ng kg-1 min-1 for 60 min produced a small rise in urinary sodium and guanosine 3':5'-cyclic monophosphate (cyclic GMP) excretion with a non-significant fall in mean arterial blood pressure. 3. Candoxatrilat (3 mg kg-1) alone had no significant effect on sodium excretion or blood pressure but markedly potentiated the natriuretic response to BNP. 4. Similarly SC 46542 (68 micrograms kg-1; 6.8 micrograms kg-1 min-1) which produced no significant effect on its own, potentiated the natriuresis-induced by BNP, although the effect was of shorter duration compared to that of candoxatrilat. 5. The data indicate two approaches to the potentiation of the renal activity of BNP and suggest that BNP may mediate some of the activity of E-24.11 inhibitors reported in cardiac failure.

Animals,Atrial Natriuretic Factor,Blood Pressure,Cyclic GMP,Cyclohexanecarboxylic Acids,Diuretics,Glomerular Filtration Rate,Infusions, Intravenous,Kidney,Ligands,Male,Natriuretic Peptide, Brain,Neprilysin,Nerve Tissue Proteins,Peptide Fragments,Rats,Rats, Wistar,Receptors, Atrial Natriuretic Factor,Sodium

1309330,1320540,1330165,1385630,1387023,1480667,1532887,1650147,1664804,1723349,1849149,1850687,1914098,1992461,1998506,2043123,2136732,2142023,2156886,2156897,2166956,2260971,2351430,2521788,2521834,2522777,2528349,2529858,2565386,2570286,2673236,2742583,2964562,3038078

8220897

Lack of effect of L-687,414 ((+)-cis-4-methyl-HA-966), an NMDA receptor antagonist acting at the glycine site, on cerebral glucose metabolism and cortical neuronal morphology.

1. N-methyl-D-aspartate (NMDA) receptor ion channel antagonists have been reported to cause pronounced increases in cerebral glucose metabolism (CMRglc) and transient reversible vacuolation within pyramidal cortical neurones. The present studies examined in rats the effects of the NMDA receptor antagonist, L-687,414 (R-(+)-cis-4-methyl-3-amino-l-hydroxypyrolid-2-one (+)-cis-4-methyl-HA-966) on regional CMRglc and cortical neuronal morphology. 2. L-687,414 was given as a steady state intravenous infusion for 4 h in a neuroprotective dose regime of 17.5 mg free base kg-1 bolus followed by 225 micrograms kg-1 min-1 (n = 8) or at the higher dose rate of 35 mg kg-1 bolus followed by 440 micrograms kg-1 min-1 (n = 10). Data were compared to a parallel series of experiments in rats given the NMDA receptor ion channel antagonist, dizocilpine for 4 h in the optimum intravenous neuroprotective dose-regime of 0.12 mg kg-1 bolus followed by 1.8 micrograms kg-1 min-1 (n = 8) or at the higher dose rate of 0.4 mg kg-1 bolus followed by 6 micrograms kg-1 min-1 (n = 4; morphology only studied). A saline-infused group of rats (n = 8) were used as controls. 3. CMRglc was studied by use of [14C]-2-deoxyglucose and autoradiography (n = 4 each group) whilst plasma drug levels were in a steady state during the final 45 min of the 4 h drug infusion. Effects on cortical neuronal morphology were assessed at the end of the 4 h infusion period using light microscopic techniques (n = 4-6 each group).4. The results showed a selective activation of limbic CMRglc by dizocilpine at optimal neuroprotective dose levels and showed that this dose was at the threshold for the neuronal vacuolation response as I of 4 rats showed morphological changes in the pyramidal neurones in the posterior cingulate and retrosplenial cortices. At the higher dose rate of dizocilpine, all 4 animals showed extensive morphological changes in these cortical neurones. In contrast, L-687,414 did not increase limbic CMRglc, nor evoke vacuolation when given in the neuroprotective dose-regime or at the higher dosage rate.5. The findings of the present study suggest that neuroprotection mediated through the NMDA receptor complex can be achieved without changes in CMRglc or cortical neuronal morphology by antagonism at the glycine modulatory site.

Animals,Blood Glucose,Blood Pressure,Brain Chemistry,Cerebral Cortex,Deoxyglucose,Dizocilpine Maleate,Glucose,Glycine,Heart Rate,Hemodynamics,Male,Neurons,Pyrrolidinones,Rats,Rats, Sprague-Dawley,Receptors, N-Methyl-D-Aspartate

864466,1533903,1535595,1686067,1829603,1830483,1835799,1838680,1912992,1931486,2043932,2150161,2159360,2201346,2283390,2403696,2544522,2553203,2660263,2684992,2847086,2904493,3121648,4398849,6416613,6824954,6892475,7903796

8220898

Comparison of contractile responses to 5-hydroxytryptamine and sumatriptan in human isolated coronary artery: synergy with the thromboxane A2-receptor agonist, U46619.

1. The interaction between the thromboxane A2 receptor agonist, U46619 and two 5-hydroxytryptamine (5-HT) receptor agonists, the non-selective, naturally occurring agonist, 5-HT and the selective 5-HT1-like agonist, sumatriptan were studied in human epicardial coronary arteries in vitro. 2. Coronary artery rings (2-4 mm in diameter) were prepared from epicardial arteries from explant hearts of patients undergoing heart transplant (cardiomyopathy, n = 13; ischaemic heart disease, n = 10) and unused donor hearts (n = 5). Each ring of artery was set at optimal resting conditions to record changes in isometric force. 3. The majority of artery rings developed phasic, rhythmic contractions either spontaneously or in response to all vasoconstrictor agonists tested. Both the spontaneous and agonist-induced phasic contractions were abolished by nifedipine (0.1 microM). 4. Concentration-contraction curves to 5-HT-receptor agonists and noradrenaline (NA), were first constructed in artery rings that did not develop phasic activity. 5-HT and ergometrine were the most potent agonists with EC50 values of 6.8 +/- 0.2 and 7.7 +/- 0.2 (-log M) respectively. Potencies (EC50's) to sumatriptan, methysergide and noradrenaline could not be determined due to their poor ability to contract the coronary artery. Maximum contractions (Emax; normalized as a percentage of the contraction to a maximum-depolarizing concentration of K+ in physiological salt solution (KPSS)) for 5-HT, ergometrine, sumatriptan, methysergide and noradrenaline were 40 +/- 10, 9 +/- 3, < 5, < 5 and < 5% respectively. 5. In arteries without phasic activity, U46619 (1 nM) caused an increase in force of 3.8 +/- 1% KPSS. With U46619 present, the Emax values for 5-HT, ergometrine, sumatriptan and methysergide were all markedly increased. For 5-HT and sumatriptan, E., values were 92+/- 4% and 49 +/- 14% KPSSrespectively. The presence of U46619 did not significantly change the sensitivity (EC50) to 5-HT.6. In a separate series of arteries, nifedipine (0.1 microM) was used to block phasic, contractile activity. The synergy observed between U46619 and 5-HT or sumatriptan still occurred although the Emax values for each agonist were depressed but the EC50 values were again unaffected.7. In conclusion, these in vitro studies indicate that the normally poor contractions to sumatriptan, inhuman coronary arteries are significantly enhanced when active force is induced with a thromboxane A2-receptor agonist, U46619. The enhanced response is not specific for either sumatriptan or 5-HT,-like receptors since contractions to 5-HT, ergometrine and methysergide were also potentiated by U46619.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid,Coronary Vessels,Drug Synergism,Ergonovine,Humans,In Vitro Techniques,Isometric Contraction,Methysergide,Muscle Contraction,Muscle, Smooth, Vascular,Nifedipine,Norepinephrine,Prostaglandin Endoperoxides, Synthetic,Receptors, Thromboxane,Serotonin,Serotonin Receptor Agonists,Sumatriptan,Thromboxane A2,Vasoconstrictor Agents

862138,1320974,1320980,1322216,1327368,1329294,1337261,1422590,1617772,1628398,1647495,1665260,1725306,1849768,1852778,1991363,1994246,1994247,2022013,2029502,2105666,2194695,2234096,2272071,2338652,2427147,2451132,2496936,2538184,2538191,2538194,2542039,2544281,2544282,2544286,2544291,2688219,2850055,2875415,2910540,3009791,3078080,3652429,3708917,3967774,4854225,6114172,6126180,6157956,6188910,6621711,6660308,6690109,6705164,6733873,6783306,7379260,7398759

8220899

Involvement of cholecystokinin receptor types in pathways controlling oxytocin secretion.

1. Intravenous administration of cholecystokinin (CCK) results in a transient activation of oxytocin neurones in the rat, and hence to oxytocin secretion: this activation is followed by expression of c-fos mRNA and of Fos-like immunoreactivity (Fos-LI) in magnocellular oxytocin neurones. Fos-like immunoreactivity is also induced in the regions of the brainstem that are thought to relay information from the periphery to the hypothalamus. 2. Administration of the selective CCKA receptor antagonist MK-329, but not the CCKB receptor antagonist L-365,260, prior to CCK injection, prevented oxytocin release as measured by radioimmunoassay and oxytocin neuronal activation as measured by electrophysiology and by the lack of induction of c-fos mRNA. 3. MK-329 abolished the release of adrenocorticotrophic hormone (ACTH) following injection of CCK. 4. MK-329 prevented the expression of Fos-LI in the hypothalamic magnocellular nuclei and in the area postrema and dorsal vagal complex of the brainstem. 5. L-365,260 had no effect on the expression of Fos-LI in the brainstem, but attenuated that seen in the hypothalamic magnocellular nuclei. 6. We conclude that CCK acts on CCKA receptors, either in the area postrema or on peripheral endings of the vagus nerve, to cause the release of hypothalamic oxytocin and ACTH. Information may be carried to the hypothalamus in part by CCK acting at CCKB receptors.

Adrenocorticotropic Hormone,Animals,Basal Ganglia,Benzodiazepinones,Brain Chemistry,Cholecystokinin,Devazepide,Electrophysiology,Female,Gene Expression,Genes, fos,Hypothalamus,In Situ Hybridization,Neurons,Oxytocin,Phenylurea Compounds,Proto-Oncogene Proteins c-fos,RNA, Messenger,Rats,Rats, Wistar,Receptors, Cholecystokinin

1312423,1312449,1611536,1822561,1847854,2108708,2168320,2337783,2457171,2621594,2721567,2725863,2740351,2827855,3014519,3017374,3018820,3128125,3325886,3409022,3625281,3625542,3661761,3715453,3998651,6713189,6713193,6987667,8426907,19215354,19215514,19215523,21554590

8220900

Effect of trimebutine on voltage-activated calcium current in rabbit ileal smooth muscle cells.

1. The effect of trimebutine on the voltage-dependent inward Ca2+ current was investigated by the whole-cell voltage-clamp technique in single smooth muscle cells from rabbit ileum. 2. Trimebutine (3-100 microM) reduced the Ca2+ current in a concentration-dependent manner. The inhibitory effect on the Ca2+ current was also dependent on the holding potential. The Ca2+ current after a low holding potential was inhibited to a greater extent than that after a high membrane potential: the IC50 values were 7 microM and 36 microM at holding potentials of -40 mV and -60 mV, respectively. The Ca2+ current elicited from a holding potential of -80 mV could not be reduced by as much as 50% of the control by trimebutine at concentrations as high as 100 microM. 3. Trimebutine (30 microM) shifted the voltage-dependent inactivation curve for the Ca2+ current by 18 mV in the negative direction. The affinity of the drug for Ca2+ channels was calculated to be 36 times higher in the inactivated state than in the closed-available state. 4. Blockade of the Ca2+ current by trimebutine, unlike verapamil, was not use-dependent. 5. The results suggest that trimebutine inhibits the voltage-dependent inward Ca2+ current through a preferential binding to Ca2+ channels in the inactivated state in the smooth muscle cell from rabbit ileum. The inhibitory effect of trimebutine on gastrointestinal motility is discussed in the light of the present findings.

Action Potentials,Animals,Calcium Channel Blockers,Calcium Channels,Electrophysiology,Ileum,In Vitro Techniques,Male,Muscle, Smooth,Rabbits,Trimebutine,Verapamil

456734,1665731,1868878,2161373,2171963,2432624,2439984,3601643,3959348,6088117,6270629,6306139,6748369,6988171,7173739,7214854,8389715

8220901

Nitric oxide-dependent and -independent hyperaemia due to calcitonin gene-related peptide in the rat stomach.

1. Calcitonin gene-related peptide (CGRP) potently enhances mucosal blood flow in the rat stomach. The aim of this study was to examine whether CGRP also dilates extramural arteries supplying the stomach and whether the vasodilator action of CGRP involves nitric oxide (NO). 2. Rat CGRP-alpha (0.03-1 nmol kg-1, i.v.) produced a dose-dependent increase in blood flow through the left gastric artery (LGA) as determined by an ultrasonic transit time technique in urethane-anaesthetized rats. Blockade of NO synthesis by NG-nitro-L-arginine methyl ester (L-NAME, 20 and 60 mumol kg-1, i.v.) significantly reduced basal blood flow (BF) in the LGA and attenuated the hyperaemic activity of CGRP by a factor of 2.8-4. D-NAME tended to enhance basal BF in the LGA but had no influence on the dilator activity of CGRP. The ability of vasoactive intestinal polypeptide to increase left gastric arterial blood flow remained unaltered by L-NAME. 3. L-NAME (20 and 60 mumol kg-1, i.v.) evoked a prompt and sustained rise of mean arterial blood pressure (MAP) and caused a slight decrease in the hypotensive activity of CGRP. In contrast, D-NAME induced a delayed and moderate increase in MAP and did not influence the hypotensive activity of CGRP. 4. Rat CGRP-alpha dilated the isolated perfused bed of the rat LGA precontracted with methoxamine and was 3 times more potent in this respect than rat CGRP-beta. The dilator action of rat CGRP-alpha in this preparation was not affected by L-NAME or D-NAME (40 microM). 5. L-NAME (60 micromol kg-1, i.v.) reduced gastric mucosal blood flow as assessed by laser Doppler flowmetry and diminished the hyperaemic activity of rat CGRP-alpha in the gastric mucosa by a factor of 4.5, whereas D-NAME was without effect.6. These data show that CGRP is a potent dilator of mucosal and extramural resistance vessels in the rat stomach. Its dilator action involves both NO-dependent and NO-independent mechanisms.

Anesthesia,Animals,Arginine,Blood Pressure,Calcitonin Gene-Related Peptide,Dose-Response Relationship, Drug,Female,Gastric Mucosa,Heart Rate,Hyperemia,In Vitro Techniques,Muscle, Smooth, Vascular,NG-Nitroarginine Methyl Ester,Nitric Oxide,Perfusion,Rats,Rats, Sprague-Dawley,Regional Blood Flow,Stomach,Vasoactive Intestinal Peptide,Vasodilation

1361870,1385168,1504730,1590437,1595321,1596678,1628157,1656776,1688944,1702035,1706208,1727750,1828305,1852778,1878760,1915576,1979444,1982771,2003604,2076481,2304629,2328404,2455875,2457081,2783534,2801993,2813856,2839796,2841625,6353273

8220902

Bradykinin-induced release of PGI2 from aortic endothelial cell lines: responses mediated selectively by Ca2+ ions or a staurosporine-sensitive kinase.

1. Bradykinin (100 nM) triggers release of nitric oxide and prostacyclin from both AG07680A and AG04762 bovine cultured aortic endothelial cells. The exposure of these cells to bradykinin is in each case associated with a striking rise in intracellular calcium ion concentration. 2. Exposure of AG07680A cells to 250 nM ionomycin was followed also by a significant release of prostacyclin, whereas 250 nM ionomycin had no capacity to stimulate release of prostacyclin from AG04762 cells. 3. There was a similar concentration-dependent increase in intracellular calcium ion concentration on exposure of AG07680A and AG04762 cells to ionomycin. 4. Exposure of AG04762 cells for 10 min to staurosporine produced a concentration-dependent inhibition (IC50 = 107 +/- 14 nM) in bradykinin-stimulated prostacyclin release. There was no similar inhibitory effect of staurosporine in AG07680A cells. 5. Bradykinin (10 nM) triggered release of nitric oxide from both AG07680A and AG04762 cells, and the effect was not inhibited by 500 nM staurosporine. There was a similar ionomycin-dependent release of nitric oxide from both cell types. 6. These results identify a common pathway for bradykinin-dependent nitric oxide release from both AG07680A and AG04762 cells, involving increases in intracellular calcium ion concentration. In contrast, the bradykinin-dependent release of prostacyclin may involve one of two pathways (involving an increase in intracellular calcium or activation of a staurosporine-sensitive kinase), and the two pathways are selectively exploited in AG07680A and AG04762 cells, respectively.

6-Ketoprostaglandin F1 alpha,Alkaloids,Animals,Aorta, Thoracic,Arginine,Bradykinin,Calcium,Cattle,Cell Line,Endothelium, Vascular,Epoprostenol,Ionomycin,Nitric Oxide,Phosphotransferases,Signal Transduction,Staurosporine,omega-N-Methylarginine

802670,1361398,1847633,1852778,1909974,2451132,2508628,3064854,3291862,3304132,3495737,3838314,6253831

8220903

Specific inhibition of leukotriene B4 (LTB4)-induced neutrophil emigration by 20-hydroxy LTB4: implications for the regulation of inflammatory responses.

1. The interaction between leukotriene B4 (LTB4) and its metabolite, 20-hydroxy LTB4 in the control of neutrophil emigration was examined in guinea-pig skin. 2. Leukotriene B4 (10-300 ng) elicited a dose-dependent increase in neutrophil infiltration (as measured by myeloperoxidase activity) 4 h after injection into guinea-pig skin. In contrast, 20-hydroxy LTB4 (30-1000 ng) displayed only weak inflammatory activity in this assay. 3. Although 20-hydroxy LTB4 had low agonist activity, this metabolite caused a potent dose-dependent inhibition of responses to LTB4 (100 ng), when administered systemically (ED50 = 1.3 micrograms kg-1, s.c.) without significantly affecting neutrophil infiltration in response to C5a (2 micrograms). Systemic administration of 20-carboxy LTB4 (10 micrograms) did not affect neutrophil accumulation in response to LTB4 or C5a. In addition, neither 15(S)-hydroxy 5(S)-HPETE(10 micrograms) nor lipoxin A4 (10 micrograms) inhibited responses to LTB4. 4. Addition of 20-hydroxy LTB4 (10(-11)-10(-8) M) to human blood prior to isolation of the neutrophils led to concentration-dependent decrease in the number of LTB4 receptors and decreased chemotactic responsiveness to LTB4 without affecting responses to C5a. Incubation of blood with 20-carboxy LTB4 (10(-8) M) did not reduce LTB4 receptor number of chemotactic responsiveness to LTB4. 5. These data indicate that although 20-hydroxy LTB4 is a weak agonist at LTB4 receptors, it can desensitize neutrophils to the effects of LTB4 via down-regulation of the high affinity receptor and thus provides evidence for a mechanism whereby inflammatory responses may be regulated.

Animals,Chemotaxis, Leukocyte,Guinea Pigs,In Vitro Techniques,Inflammation,Injections, Intradermal,Leukotriene B4,Male,Neutrophils,Peroxidase,Receptors, Leukotriene,Skin

429307,722104,1320692,1322257,1645377,1665290,1848634,1963796,1965311,2110012,2822802,2826589,3005343,3016754,3067055,3138250,6090507,6091105,6091186,6097945,6100110,6128450,6141244,6179872,6250050,6267608,6270742,6274465,6302739,6305369,6316858,6319219,6323613,6326110,6326579,6330213,6793392,7464931,8380189

8220904

Cerebral blood flow and cerebrovascular reactivity after inhibition of nitric oxide synthesis in conscious goats.

1. The role of nitric oxide in the cerebral circulation under basal conditions and after vasodilator stimulation was studied in instrumented, conscious goats, by examining the action of inhibiting endogenous nitric oxide production with NG-nitro-L-arginine methyl ester (L-NAME). 2. In 6 unanaesthetized goats, blood flow to one brain hemisphere (electromagnetically measured), systemic arterial blood pressure and heart rate were continuously recorded. L-NAME (35 mg kg-1 by i.v. bolus) decreased resting cerebral blood flow by 43 +/- 3%, increased mean arterial pressure by 21 +/- 2%, and decreased heart rate by 41 +/- 2%; cerebrovascular resistance increased by 114 +/- 13% (P < 0.01); the immediate addition of i.v. infusion of L-NAME (0.15-0.20 mg kg-1 during 60-80 min) did not significantly modify these effects. Cerebral blood flow recovered at 72 h, arterial pressure and cerebrovascular resistance at 48 h, and heart rate at 6 days after L-NAME treatment. 3. A second treatment with L-NAME scheduled as above reproduced the immediate haemodynamic effects of the first treatment, which (except bradycardia) reversed with L-arginine (200-300 mg kg-1 by i.v. bolus). 4. Acetylcholine (0.01-0.3 micrograms), sodium nitroprusside (3-100 micrograms) and diazoxide (0.3-9 mg), injected into the cerebral circulation of 5 conscious goats, produced dose-dependent increases in cerebral blood flow, and decreases in cerebrovascular resistance; sodium nitroprusside (30 and 100 micrograms) also caused hypotension and tachycardia. 5. The reduction in cerebrovascular resistance from resting levels (in absolute values) to lower doses,but not to the highest dose, of acetylcholine was diminished, to sodium nitroprusside was increased, and to diazoxide was unaffected after L-NAME, compared to control conditions. The effects on cerebrovascular resistance to acetycholine normalized within 24 h and to sodium nitroprusside within 48 h after L-NAME treatment.6. This study provides information about the evolution of the changes in cerebral blood flow and cerebrovascular reactivity after inhibition of endogenous nitric oxide in conscious animals. The results suggest: (a) endogenous nitric oxide is involved in regulation of the cerebral circulation by producing a resting vasodilator tone, (b) the cerebral vasodilatation to acetylcholine is mediated, at least in part, by nitric oxide release, and (c) inhibition of nitric oxide production induces supersensitivity of cerebral vasculature to nitrovasodilators.

Acetylcholine,Animals,Arginine,Blood Gas Analysis,Blood Pressure,Cerebrovascular Circulation,Diazoxide,Dose-Response Relationship, Drug,Female,Goats,Heart Rate,NG-Nitroarginine Methyl Ester,Nitric Oxide,Nitroprusside,Vascular Resistance,Vasodilation,Vasodilator Agents

1126910,1130531,1374717,1504740,1522509,1539692,1548305,1566832,1570313,1628153,1700301,1706208,1848694,1852778,1887947,1912988,1928387,1933136,2043923,2043932,2121050,2124388,2188578,2240240,2328404,2332239,2484705,2497467,2501869,2719705,2924084,3009791,3142279,3715949,3950722,4043223,5034978

8220905

Endothelin-1 (ET-1)-induced contraction in rat isolated trachea: involvement of ETA and ETB receptors and multiple signal transduction systems.

1. Quantitative autoradiographic, biochemical and functional studies were performed to investigate the endothelin receptor subtypes and signal transduction systems that mediate endothelin-1 (ET-1)-induced contraction in rat isolated tracheal smooth muscle. 2. Specific binding of 0.5 nM [125I]-ET-1 to tracheal smooth muscle was inhibited by at least 40% in the presence of either the ETA receptor selective ligand BQ-123 (1 microM) or the ETB receptor-selective ligand sarafotoxin S6c (30 nM), indicating the presence of both ETA and ETB receptors in this tissue. 3. ET-1 and sarafotoxin S6c were both potent spasmogens of rat isolated tracheal smooth muscle preparations. Sarafotoxin S6c-induced contractions were unaffected in the presence of the ETA receptor antagonist BQ-123 (10 microM), but were markedly attenuated in tissue previously exposed to 100 nM sarafotoxin S6c to induce ETB receptor desensitization. ET-1-induced contractions were, at most, only partially attenuated either by blocking the ETA receptor-effector system (with 10 microM BQ-123) or by desensitizing the ETB receptor-effector system with sarafotoxin S6c. However, ET-1-induced contractions were markedly attenuated by blocking both receptor-effector systems simultaneously. These findings suggest that ET-1 could induce contraction by stimulating either ETA or ETB receptors. 4. ET-1 (10 microM) induced a 7 fold increase in intracellular [3H]-inositol phosphate accumulation over basal levels in rat isolated tracheal smooth muscle. In contrast, sarafotoxin S6c (2.5 microM) increased intracellular [3H]-inositol phosphate accumulation by only 2 fold. ET-1-induced accumulation of [3H]-inositol phosphates was abolished by 10 microM BQ-123. 5. In Ca2+-free Krebs bicarbonate solution, 100 nM ET-1 induced a significantly larger contraction than that induced by 100 nM sarafotoxin S6c (46.6 +/- 5.6% C,., versus 8.8 +/- 2.8% Cmax, n = 5-7). This presumed intracellular Ca2+-dependent phase of contraction induced by ET-1 was significantly inhibited by 10 microM BQ-123 (7.5 +/- 1.0% C.). Subsequent addition of 2.5 mM Ca2+ induced a second phase of contraction. The extracellular Ca2+-dependent phase of contraction induced by ET-1 was similar inmagnitude to that induced by sarafotoxin S6c (63.6 +/- 4.5% C.. versus 58.0 +/- 3.7% C.) and was not inhibited by BQ-123. Sarafotoxin S6c-induced contractions were not inhibited by the L-type Ca2+-channel antagonists, nicardipine or verapamil.6. In summary, ETA and ETB receptors coexist in rat isolated tracheal smooth muscle and stimulation of both receptor subtypes contributes to ET-l-induced contraction in this tissue. However, stimulation of these receptor subtypes appears to induce contraction by activating different second messenger pathways; ETA receptor stimulation induces phosphoinositide turnover and subsequent release of intracellular Ca2+ whereas stimulation of ETB receptors facilitates the influx of extracellular Ca2+.

Animals,Autoradiography,Carbachol,Endothelin Receptor Antagonists,Endothelins,In Vitro Techniques,Inositol Phosphates,Iodine Radioisotopes,Male,Muscle Contraction,Muscle, Smooth,Peptides, Cyclic,Potassium Chloride,Rats,Rats, Wistar,Receptors, Endothelin,Signal Transduction,Trachea,Vasoconstrictor Agents,Viper Venoms

1310132,1321937,1323655,1380080,1393278,1397009,1472961,1596675,1652952,1657061,1696155,1850245,2015424,2072309,2169940,2198895,2479437,3006855,3068063,7379260,7679333

8220906

Suppression of inflammatory responses to 12-O-tetradecanoyl-phorbol-13-acetate and carrageenin by YM-26734, a selective inhibitor of extracellular group II phospholipase A2.

1. YM-26734 [4-(3,5-didodecanoyl-2,4,6-trihydroxyphenyl)-7-hydroxy-2-(4-hydroxyph eny l) chroman] dose-dependently inhibited the activities of extracellular phospholipase A2 (PLA2): rabbit platelet-derived group II and porcine pancreas-derived group I PLA2, with IC50 values of 0.085 (0.056-0.129, n = 5) and 6.8 (5.0-9.6, n = 5) microM, respectively. 2. In contrast, YM-26734 did not reduce the activity of intracellular PLA2 prepared from mouse macrophages, which preferentially hydrolyzed arachidonoyl phospholipids at concentrations up to 50 microM. YM-26734 also showed no effect against either sheep seminal vesicle cyclo-oxygenase or rat leukocyte 5-lipoxygenase. 3. Linewater-Burk analysis showed that YM-26567-1 behaved as a competitive inhibitor of group II PLA2 derived from rabbit platelets, with a Ki value of 48 nM. 4. In mice, YM-26734 inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA, 1 microgram/ear)-induced ear oedema in a dose-dependent manner, with ED50 values of 45 (30-67) micrograms/ear (n = 5) and 11 (4-32) mg kg-1, i.v. (n = 5), but did not decrease arachidonic acid (4 mg/ear)-induced ear oedema at 1 mg/ear and 30 mg kg-1, i.v. 5. In rats, the accumulation of exudate fluids and leukocytes in the pleural cavity in response to carrageenin injection (2 mg) was significantly less in a group treated with YM-26734 (20 mg kg-1, i.v.) than in the control group (0.43 +/- 0.02 vs 0.59 +/- 0.03 g per cavity and 3.8 +/- 0.2 vs 4.9 +/- 0.3 x 10(7) cells per cavity, respectively; n = 5). 6. These results suggest that YM-26734 is a potent and competitive inhibitor of extracellular PLA2 with selectivity for group II PLA2, and that the inhibition of group II enzymes activity may cause the suppression of inflammatory responses to TPA and carrageenin.

Animals,Anti-Inflammatory Agents, Non-Steroidal,Arachidonic Acid,Carrageenan,Chromans,Cyclooxygenase Inhibitors,Ear, External,Edema,Extracellular Space,Female,In Vitro Techniques,Inflammation,Lipoxygenase Inhibitors,Male,Mice,Mice, Inbred ICR,Phenols,Phospholipases A,Phospholipases A2,Pleurisy,Rabbits,Rats,Rats, Wistar,Sheep,Tetradecanoylphorbol Acetate

636934,1469636,1793011,1903717,1904318,2023201,2033260,2051918,2121134,2182625,2217203,2320562,2337412,2384146,2494067,2526543,2825898,2833314,2840081,2924072,2925633,2974738,2995499,3006856,3012653,3081518,3303066,3597343,3920331,3936896,6084855,6401312,6658003,6799509,6800832,13641241

8220907

Vascular actions of purines in the foetal circulation of the human placenta.

1. The vasoactive effects of adenosine triphosphate (ATP), adenosine and other purines in the foetal circulation of the human placenta were examined. Single lobules of the placenta were bilaterally perfused in vitro with Krebs buffer (maternal and foetal sides 5 ml min-1 each, 95% O2:5% CO2, 37 degrees C). Changes in foetal vascular tone were assessed by recording perfusion pressure during constant infusion of each purine. To allow recording of the vasodilator effects, submaximal vasoconstriction was induced by concomitant infusion of prostaglandin F2 alpha (0.7-2.0 mumol l-1). 2. ATP (1.0-100 mumol l-1) usually caused concentration-dependent reductions in perfusion pressure. However, biphasic with initial transient increases, or only increases in pressure were sometimes observed. Falls in pressure caused by ATP were significantly reduced by addition to the perfusate of NG-nitro-L-arginine (L-NOARG) (100 mumol l-1) but not NG-nitro-D-arginine (D-NOARG) (100 mumol l-1). They were not influenced by addition of indomethacin (10 mumol l-1) or L-arginine (100 mumol l-1). 3. Adenosine (0.01-1.0 mmol l-1) consistently caused concentration-dependent reductions in perfusion pressure, this effect not being influenced by indomethacin. L-NOARG, but not D-NOARG, reduced the potency of adenosine approximately three fold. L-Arginine, but not D-arginine enhanced its potency by a similar amount. 4. 2-Methylthio-ATP, a selective P2 gamma agonist was approximately 50 times more potent than ATP as a vasodilator agent, always causing decreases in perfusion pressure. 5. Beta-gamma-Methylene ATP, a selective P20 agonist, was approximately 100 times more potent than ATP as a vasoconstrictor, but only caused transient increases in perfusion pressure.6. The rank order of vasodilator potencies of a selection of adenosine receptor agonists was, 2-chloroadenosine>>5-(N-cyclopropyl)-carboxamidoadenosine, >5-N-ethylcarboxamidoadenosine, >2-chloro-N6-cyclopentyladenosine, >CGS-21680 > N6-cyclohexyladenosine = adenosine. Vasodilatation due to adenosine was inhibited by the PI-A2 receptor antagonist 3,7-dimethyl-l-propargylxanthine(DMPX).7. These results suggest that ATP may cause an endothelium-dependent vasodilatation in the foetal vessels of the human placenta via activation of a P2y receptor linked to the formation of nitric oxide(NO). Vasodilatation caused by ATP may mask an accompanying vasoconstrictor effect mediated, via a P2X receptor, in the villous vascular smooth muscle. Adenosine acting on P1-A2 receptors, which are also present in the foetal vasculature, may require synergistic interaction with NO to achieve a maximal vasodilator response.

Adenosine,Adenosine Triphosphate,Adolescent,Adult,Arginine,Blood Pressure,Female,Fetus,Humans,In Vitro Techniques,Nitric Oxide,Nitroarginine,Oxygen,Perfusion,Placenta,Pregnancy,Prostaglandins,Purinergic P1 Receptor Antagonists,Purinergic P2 Receptor Antagonists,Purines,Receptors, Purinergic P1,Receptors, Purinergic P2,Regional Blood Flow,Vasodilation

1296206,1364833,1426003,1685566,1878749,1884115,1979408,2194223,2314480,2439921,2600819,2771515,2795469,2981319,2984001,2990944,2996968,3002694,3064854,3193854,3216901,3390182,3407908,3552706,3559983,3572809,3688085,3828655,4085554,4263799,6100842,6141801,6279840,6304067,6313897,7225296,7232336,16994064

8220908

The effect of ions and second messengers on long-term potentiation of chemical transmission in avian ciliary ganglia.

1. The effects of tetanic stimulation of the oculomotor nerve on transmission through the avian ciliary ganglion have been determined by use of the amplitude of the compound action potential recorded in the ciliary nerve, in the presence of hexamethonium (300 microM), as a measure of synaptic efficacy. 2. Tetanic stimulation for 20 s at 30 Hz potentiated the chemical phase of the compound action potential by at least 100% of its control level. This potentiation, reflecting an increase in synaptic efficacy, decayed over two distinct time courses: firstly, a rapid decay with a time constant in the order of minutes, and secondly, a slower decay, representing a smaller potentiation, with a time constant in the order of an hour. The large increase in synaptic efficacy is attributed to post-tetanic potentiation (PTP) whereas the smaller but longer lasting increase is attributed to long-term potentiation (LTP). 3. Higher frequencies of tetanic stimulation gave increased PTP and LTP. 4. In order to test whether the influx of calcium ions into the nerve terminal during the tetanus is likely to be involved in potentiation, facilitation was measured during PTP and LTP. Facilitation was reduced to approximately zero during PTP but recovered to normal values about 15 min into LTP. A requirement for the induction of LTP was shown to be the presence of calcium in the bathing solution. However, blocking synaptic transmission with a high concentration of hexamethonium (3 mM) during the tetanic stimulation did not block the induction of LTP. 5. Application of the muscarinic inhibitor, atropine (2 microM), did not affect the magnitude of PTP or LTP. 5. Application of the muscarinic inhibitor, atropine (2 tM), did not affect the magnitude of PTP or LTP.6. The activator of protein kinase C, phorbol 12,13-dibutyrate (2 microM) potentiated synaptic transmission and reduced the potentiation due to PTP although it did not affect that due to LTP, but the inhibitor of this kinase, staurosporine (0.5 microM), partially blocked the appearance of LTP without affecting PTP after the tetanus.7. An inhibitor of calmodulin, W-7 (5 microM), reversibly blocked the appearance of LTP significantly after a tetanus although the size of PTP was not affected.8. The results presented here suggest that the initiation of LTP in the ciliary ganglion is due to an influx of calcium ions into the calyciform nerve terminal during the tetanus and that the mechanism for LTP involves a calcium-calmodulin-dependent process.

Action Potentials,Animals,Atropine,Calcium,Calmodulin,Chickens,Electric Stimulation,Ganglia, Parasympathetic,In Vitro Techniques,Ions,Long-Term Potentiation,Oculomotor Nerve,Presynaptic Terminals,Protein Kinase C,Second Messenger Systems,Synaptic Transmission

165286,209171,234601,1484356,1577987,1657055,1662519,1685189,2114039,2157237,2648947,2795140,2855347,2860240,2860242,3457562,4306543,4308865,4322855,5683552,5840798,6093940,6110695,6128372,6251156,6278593,6299453,6316332,14062687,14193934,14241155,14241156

8220909

Mediation of the neuroprotective action of R-phenylisopropyl-adenosine through a centrally located adenosine A1 receptor.

1. Systemic injections of kainic acid, 10 mg kg-1, into adult rats resulted in lesions in the hippocampus, as assessed by peripheral benzodiazepine ligand binding. Co-administration of clonazepam at 1 mg kg-1 or 0.2 mg kg-1 prevented major seizures associated with kainate injections, but did not alter significantly the production of hippocampal damage. 2. The co-administration of the adenosine A1 agonist R-phenylisopropyladenosine (R-PIA, 25 micrograms kg-1, i.p.) abolished the lesions induced by kainic acid. 3. The presence of the selective A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (250 or 50 micrograms kg-1, i.p.) abolished the R-PIA neuroprotective action. 4. The A1/A2 antagonist, 8-(p-sulphophenyl)theophylline (20 mg kg-1, i.p.) which cannot cross the blood brain barrier, did not alter significantly the neuroprotective action of R-PIA, indicating that the neuroprotective action of the purine may be predominantly central. 5. The time course of the neuroprotection was also examined. R-PIA was effective when administered 2 h before or after kainate administration. 6. The results emphasise the potential utility of systemically active adenosine A1 receptor ligands in reducing CNS gliosis induced by the activation of excitatory amino acid receptors.

Animals,Clonazepam,Hippocampus,Isoquinolines,Kainic Acid,Male,Neurons,Phenylisopropyladenosine,Purinergic P1 Receptor Antagonists,Rats,Rats, Wistar,Receptors, GABA-A,Receptors, Purinergic P1,Theophylline

421146,729642,1282227,1293870,1334240,1347249,1348522,1353335,1354544,1357102,1403815,1432095,1461571,1491809,1540242,1613806,1613814,1640796,1676492,1690430,1829014,1830897,1833668,1855150,1884753,1893916,1922933,1969938,1970230,1985301,2006013,2027518,2028499,2072098,2085727,2106010,2146779,2146780,2170163,2209775,2255391,2264080,2264081,2274264,2469166,2543557,2746235,2747922,2771165,2804547,2864783,2902196,2907698,3034525,3234492,3370479,3574492,3693425,3805165,3808315,6119136,6122480,6125916,6131686,6149259,6234446,6287270,6288896,6498619,6793881,6822273,6842403,7272738,7402461,8358536,14907713

8220910

Differential effects of B2 receptor antagonists upon bradykinin-stimulated phospholipase C and D in guinea-pig cultured tracheal smooth muscle.

1. Guinea-pig tracheal smooth muscle cells were isolated and maintained in culture for 14-21 days prior to the study of the effect of a selective bradykinin B1 agonist and B2 antagonists upon bradykinin-stimulated phospholipase C and D activities. 2. Bradykinin-stimulated phospholipase C activity was determined by mass measurement of inositol (1,4,5)trisphosphate (Ins(1,4,5)P3) in unlabelled cells, whereas phospholipase D activity was assayed by the accumulation of [3H]-phosphatidylbutanol ([3H]-PtdBut) in [3H]-palmitate-labelled cells, which were stimulated in the presence of butan-1-o1 (0.3%, v/v). 3. Bradykinin elicited the rapid and transient formation of Ins(1,4,5)P3, in a concentration-dependent manner (log EC50 = -7.55 +/- 0.1 M, N = 3). Bradykinin also rapidly activated the concentration-dependent (log EC50 = -8.3 +/- 0.4 M, n = 3) phospholipase D-catalysed accumulation of [3H]-PtdBut; the accumulation of [3H]-PtdBut was sustained. These effects were not inhibited by pretreatment of the cells with indomethacin (1 microM). 4. The bradykinin B1 agonist, desArg9-bradykinin (1 microM) was without effect upon phospholipase C or phospholipase D activity. Bradykinin-stimulated (10 nM, EC40) Ins(1,4,5)P3 formation was inhibited by B2 receptor antagonists, D-Arg-[Hyp3,D-Phe7]-bradykinin (NPC 567) and D-Arg-[Hyp3,Thi5,8,D-Phe7]-bradykinin (NPC 349), with log IC50 values of -6.3 +/- 0.5 M and -6.3 +/- 0.4 M, respectively. However, bradykinin-stimulated (10 nM, EC100) [3H]-PtdBut accumulation was poorly inhibited and with low potency by each B2 receptor antagonist and bradykinin-stimulated phospholipase D activity persisted at concentrations of antagonist that completely blocked bradykinin-stimulated Ins(1,4,5)P3 formation (30 microM). 5. These observations suggest that the activation of phospholipase C by bradykinin may be mediated through a bradykinin B2 receptor population, whereas bradykinin-stimulated phospholipase D may be activated via a distinct population of bradykinin receptors that do not appear to be either B1 or B2 receptor types, based upon pharmacological specificity. The mechanism of the activation of phospholipase D by bradykinin and the role of the putative B3 bradykinin receptor are discussed.

Animals,Bradykinin,Bradykinin Receptor Antagonists,Culture Techniques,Glycerophospholipids,Guinea Pigs,Indomethacin,Inosine Triphosphate,Male,Muscle, Smooth,Palmitic Acid,Palmitic Acids,Phosphatidic Acids,Phospholipase D,Receptors, Bradykinin,Trachea,Type C Phospholipases

1318673,1330177,1335332,1649478,1663158,1848087,1889516,2201284,2338649,2417230,2508487,2546044,2547478,2548874,2645779,2906146,3165977,3289575,3540008,3661694,8442759

8220911

Human liver microsomal metabolism of the enantiomers of warfarin and acenocoumarol: P450 isozyme diversity determines the differences in their pharmacokinetics.

1. To explain the large differences in (the stereoselectivity of) the clearances of the enantiomers of warfarin and acenocoumarol (4'-nitrowarfarin) their human liver microsomal metabolism has been studied and enzyme kinetic parameters determined. The effects of cimetidine, propafenone, sulphaphenazole, and omeprazole on their metabolism has been investigated. 2. The 4-hydroxycoumarins follow similar metabolic routes and are mainly hydroxylated at the 6- and 7-position (accounting for 63 to 99% of the metabolic clearances). 3. Due to the lower Km values of R- and S-acenocoumarol and higher Vmax values of S-acenocoumarol, the overall metabolic clearances of R/S acenocoumarol exceed those of R/S warfarin 6 and 66 times respectively. 4. The metabolism of both compounds is stereoselective for the S-enantiomers, which is 10 times more pronounced in the case of acenocoumarol. 5. Except for the 7-hydroxylation of the R-enantiomers (r = 0.90; P < 0.025), the 6- and 7-hydroxylation rates of R/S warfarin do not correlate with those of R/S acenocoumarol. 6. Sulphaphenazole competitively inhibits the 7- and in some samples partly (up to 50%) the 6-hydroxylation of S-warfarin as well as the 7-hydroxylation of R- and S-acenocoumarol and the 6-hydroxylation of S-acenocoumarol (Kis ranging from 0.5-1.3 microM). 7. Omeprazole partly (40-80%) inhibits the 6- and 7-hydroxylation of R-warfarin (Ki = 99 and 117 microM) and of R- (Ki = 219 and 7.2 microM) and S-acenocoumarol (Ki = 6.1 and 7.7 microM) but not S-warfarin in a competitive manner. 8. Differences in the partial (up to 40%) inhibition of the metabolism of the enantiomers of the 4-hydroxycoumarins were also observed for the relatively weak inhibitors, propafenone and cimetidine.9. The results suggest that the coumarin ring hydroxylations of both compounds are catalysed by different combinations of P450 isozymes. The 7-hydroxylation of R/S acenocoumarol and the 6-hydroxylation of S-acenocoumarol are at least partly conducted by (a) P450 isozyme(s) of the 2C subfamily different from P450 2C9 (the main S-warfarin 7- and 6-hydroxylase).

Acenocoumarol,Adolescent,Adult,Biotransformation,Chromatography, High Pressure Liquid,Cytochrome P-450 Enzyme Inhibitors,Cytochrome P-450 Enzyme System,Female,Humans,Hydroxylation,In Vitro Techniques,Isoenzymes,Male,Microsomes, Liver,Middle Aged,Stereoisomerism,Warfarin

369763,660532,1493083,1527724,1537465,1581537,1764870,1857342,1862655,1958448,1983149,1991046,2299601,2509183,2568906,2718223,2719902,2818630,2865109,2873991,2910635,3187945,3439870,3474093,3485990,3542339,3567019,3621782,3621785,3758150,4352876,4830225,6418201,6762773,7350395,8423765,8493912,14907713

8220912

Antitussive effects of GABAB agonists in the cat and guinea-pig.

1. GABAB agonists inhibit neuronal processes which are important in the pathogenesis of airway disease, such as bronchospasm. Cough is a prominent symptom of pulmonary disease, but the effects of GABAB agonists on this airway reflex are unknown. Experiments were conducted to determine the antitussive effect of GABAB receptor agonists in comparison to the known antitussive agents, codeine and dextromethorphan. 2. Unanaesthetized guinea-pigs were exposed to aerosols of 0.3 mM capsaicin to elicit coughing, which was detected with a microphone and counted. Cough also was produced in anaesthetized cats by mechanical stimulation of the intrathoracic trachea and was recorded from electromyograms of respiratory muscle activity. 3. In guinea-pigs, the GABAB agonists baclofen and 3-aminopropyl-phosphinic acid (3-APPi) produced dose-dependent inhibition of capsaicin-induced cough when administered by subcutaneous or inhaled routes. The potencies of baclofen and 3-APPi compared favourably with codeine and dextromethorphan. 4. The GABAB antagonist, CGP 35348 (0.3- 30 mg kg-1, s.c.) inhibited the antitussive effect of baclofen (3.0 mg kg-1, s.c.). However, CGP 35348 (10 mg kg-1, s.c.) had no effect on the antitussive activity of codeine (30 mg kg-1, s.c.). The antitussive effect of baclofen was not influenced by the GABAA antagonist, bicuculline (3 mg kg-1, s.c.) or naloxone (0.3 mg kg-1, s.c.). 5. In the cat, baclofen (0.3-3.0 mg kg-1, i.v.) decreased mechanically-induced cough in a dose-dependent manner. In this model, baclofen (ED50 = 0.63 mg kg-1) was less potent than either codeine or dextromethorphan. The antitussive effect of baclofen in the cat was antagonized by the GABAB antagonists, CGP 35348 (10 mg kg-1, i.v.) and 3-aminopropylphosphonic acid (3 mg kg-1, i.v.).6. We show that baclofen and 3-APPi have antitussive effects in the guinea-pig and cat and these effects are mediated by GABAB receptors.

Animals,Antitussive Agents,Baclofen,Capsaicin,Cats,Codeine,Cough,Dextromethorphan,Electromyography,GABA Antagonists,GABA-A Receptor Antagonists,Guinea Pigs,Irritants,Male,Organophosphorus Compounds,Respiratory Muscles,gamma-Aminobutyric Acid

582141,1159627,1358650,1555640,1666856,1717893,1778930,1901691,2034840,2156065,2456810,2477104,2559518,2691260,2829504,2917915,2965557,3304810,3349236,3474865,3666045,3776651,3820862,3981459,5761951,6255135,6354197,13199253

8220913

The paradoxical vascular interactions between endothelin-1 and calcitonin gene-related peptide in the rat gastric mucosal microcirculation.

1. The interactions between local intra-arterial infusion of endothelin-1 (ET-1) and rat alpha-calcitonin gene-related peptide (alpha-CGRP) on gastric mucosal damage and blood flow have been investigated in the pentobarbitone-anaesthetized rat. 2. Close-arterial infusion of ET-1 (2-200 pmol kg-1 min-1) induced a significant and dose-dependent increase in gastric mucosal haemorrhagic injury. 3. Close-arterial infusion of the higher doses of ET-1 (100 and 200 pmol kg-1 min-1) resulted in a biphasic effect on mucosal blood flow, as determined by laser Doppler flowmetry (LDF). This consisted of an initial transient increase followed by a pronounced and sustained fall in LDF. 4. Local microvascular constriction may thus contribute to the mechanisms underlying the gastric injury induced by these higher doses of ET-1. 5. However, close-arterial infusion of lower doses of ET-1 (2-50 pmol kg-1 min-1), that also provoked substantial mucosal damage, induced only a sustained and significant mucosal hyperaemia, which may be secondary to microvascular injury. 6. Concurrent dose-arterial administration of rat alpha-CGRP (50 pmol kg-1 min-1) significantly inhibited the extent of gastric mucosal injury induced by ET-1 (5 pmol kg-1 min-1). 7. Furthermore, concurrent close-arterial infusion of this dose of alpha-CGRP, which itself increased mucosal LDF, significantly inhibited the hyperaemic response induced by close-arterial infusion of ET-1 (5 pmol kg-1 min-1). 8. These results indicate a damaging action on the gastric mucosa by low doses of ET-1 which is independent of local vasoconstriction, that may involve a direct injury of the microvascular endothelium. The protective action of alpha-CGRP thus seems unlikely to be due to a local vasodilator effect but may reflect protective actions on the microvascular endothelium

Animals,Calcitonin Gene-Related Peptide,Endothelins,Gastric Mucosa,Gastrointestinal Hemorrhage,Laser-Doppler Flowmetry,Male,Microcirculation,Rats,Rats, Wistar,Regional Blood Flow

1385168,1596678,1655302,1656776,1702035,1855123,2003604,2175396,2175397,2193690,2293601,2311873,2408198,2451132,2455875,2473281,2473311,2479442,2551438,2649896,2650567,2758231,2783534,2813856,2907490,3045827,3059352,3064852,3064853,3527854,3871087,3917554,6207071,6273253,8220913,8467364

8220914

Glycine stimulates striatal dopamine release in conscious rats.

1. Glycine is an inhibitory neurotransmitter in the spinal cord and brainstem. The mechanism of this inhibition is via binding of glycine to specific receptors, increasing transmembrane Cl- conductance and hyperpolarizing neurones. Strychnine selectively antagonizes these effects. The role of glycinergic neurones in supraspinal regions is poorly understood. 2. Effects of glycine on release of catecholamines in the striatum were examined by microdialysis in freely-moving rats. Transcription of the genes encoding strychnine-sensitive glycine receptors was assessed in the striatum and substantia nigra, by use of reverse transcription followed by the polymerase chain reaction. 3. Glycine administered via the microdialysis probe dose-dependently increased concentrations of dopamine and its metabolites, dihydroxyphenylacetic acid and homovanillic acid, in the perfusate, indicating increased local release and metabolism of dopamine. Strychnine markedly attenuated these responses. Whereas striatal tissue did not contain mRNA for either the adult or neonatal form of strychnine-sensitive glycine receptor, nigral tissue contained a message for the adult form. 4. The results suggest that dopaminergic cells in the substantia nigra synthesize strychnine-sensitive glycine receptors and transport the receptors to terminals in the striatum. Occupation of the glycine receptors then exerts a net stimulatory effect on striatal dopamine release in vivo.

Animals,Base Sequence,Chromatography, High Pressure Liquid,Corpus Striatum,DNA Primers,Dialysis,Dopamine,Glycine,Homovanillic Acid,Male,Molecular Sequence Data,Polymerase Chain Reaction,RNA, Messenger,Rats,Rats, Sprague-Dawley,Receptors, Glycine,Strychnine,Substantia Nigra,Transcription, Genetic

438822,497000,620345,1422825,1426016,1651228,1797336,2150375,2157604,2160740,2176511,2338557,2440339,2842697,3037383,4200724,5721755,6418249,6697228,7108557

8220915

Desensitization of the P2-purinoceptors on the rat colon muscularis mucosae.

1. Adenosine 5'-triphosphate (ATP) and adenosine have been shown to contract the rat colon muscularis mucosae, and the receptors at which they act have been classified as P2Y and A1 respectively. Uridine 5'-triphosphate (UTP) also contracts this tissue, and desensitization was used to investigate the receptors by which it acts, in the light of recent suggestions that specific pyrimidinoceptors may exist for UTP, or that nucleotide receptors may exist which are responsive to both ATP and UTP but not to some ATP analogues such as 2-methylthioadenosine 5'-triphosphate (2-MeSATP). 2. ATP, UTP and adenosine each contracted the rat colon muscularis mucosae in a concentration-dependent manner over the concentration range 0.3-300 microM, although maximal responses to ATP and UTP were not obtained. ATP was approximately 4 times as potent as UTP and approximately equipotent with adenosine although the maximal response to adenosine appeared to be less than that to ATP or UTP. 3. Desensitization of the tissue with ATP (200 microM) given immediately before each concentration of the agonists reduced subsequent contractions induced by ATP itself and also by UTP, but did not reduce contractions induced by adenosine. Desensitization of the tissues with UTP (200 microM) also reduced contractions induced by ATP and UTP but not by adenosine, whereas desensitization with adenosine (200 microM) reduced contractions induced by adenosine itself but not by ATP or UTP. 4. Desensitization of the tissue with 2-MeSATP (200 microM), which is a more potent agonist than ATP at P2Y-purinoceptors, greatly reduced the responses to ATP and to UTP, but had no effect on responses induced by adenosine. Attempts to desensitize the tissue with adenosine 5'-(alpha,beta-methylene)triphosphonate(AMPCPP), which is a more potent agonist than ATP at P2X-purinoceptors but is less potent atP2y-purinoceptors, were unsuccessful.5. These results show that cross desensitization to ATP and UTP occurred and was specific for these agonists rather than being due to a general decrease in the ability of the muscle to contract. This implies that ATP and UTP act at the same receptor, which does not support the existence of specificpyrimidinoceptors but which could be taken as evidence for the existence of a nucleotide receptor on this tissue. However, the ability of 2-MeSATP, which is inactive at the proposed nucleotide receptors,also selectively to desensitize this receptor indicates instead that ATP and UTP are both acting at a purinoceptor of the P2Y type in this tissue.

Adenosine,Adenosine Triphosphate,Animals,Colon,In Vitro Techniques,Intestinal Mucosa,Muscle Contraction,Muscle, Smooth,Purinergic P2 Receptor Antagonists,Rats,Rats, Wistar,Thionucleotides,Uridine Triphosphate

1195136,1448182,1504717,1559130,1698498,1707633,1797327,2063479,2118236,2178007,2196860,2234104,2291527,2331585,2690427,2822441,2996968,3437923,7202513

8220916

Mediation by B1 and B2 receptors of vasodepressor responses to intravenously administered kinins in anaesthetized dogs.

1. Vasodepressor responses to intravenous (i.v.) injection of bradykinin (BK) and des-Arg9-BK, a selective B1 kinin receptor agonist, were characterized following i.v. pretreatment with selective B1 ([Leu8]-des-Arg9-BK) and B2 (Hoe 140) kinin receptor antagonists in anaesthetized dogs. 2. Des-Arg9-BK (0.05-3.3 nmol kg-1) produced dose-dependent decreases in mean arterial blood pressure with a ED50 0.4 nmol kg-1. The vasodepressor effects evoked by des-Arg9-BK (0.6 nmol kg-1) and BK (0.2 nmol kg-1) were greater after i.v. and i.a. injections, respectively. 3. The vasodepressor response to BK (0.6 nmol kg-1) but not to des-Arg9-BK (0.6 nmol kg-1) was significantly (P < 0.001) blocked by pretreatment with the B2 receptor antagonist, Hoe 140. 4. The vasodepressor response to des-Arg9-BK (0.6 nmol kg-1) but not to BK (0.6 nmol kg-1) was significantly (P < 0.001) reduced by pretreatment with the selective B1 receptor antagonist, [Leu8]-des-Arg9-BK. Although both B1 and B2 receptor antagonists caused a transient fall in blood pressure, their inhibitory action was unlikely to be related to a desensitization mechanism. 5. Inhibition of prostaglandin synthesis with indomethacin prevented the vasodepressor response induced by arachidonic acid (1 mg kg-1, i.v.) but not that to BK or des-Arg9-BK (0.6 nmol kg-1). 6. These results suggest, firstly, that the vasodepressor responses to i.v. BK and des-Arg9-BK are mediated by the activation of B2 and B1 receptors, respectively; secondly, that prostaglandins are not involved in the vasodepressor responses to kinins.These findings provide pharmacological evidence for the existence of functionally active B1 receptors in canine cardiovascular homeostasis.

Anesthesia,Animals,Blood Cell Count,Blood Chemical Analysis,Blood Pressure,Bradykinin,Bradykinin Receptor Antagonists,Depression, Chemical,Dogs,Dose-Response Relationship, Drug,Female,Indomethacin,Injections, Intravenous,Kinins,Male,Receptors, Bradykinin

427648,1310238,1313585,1364851,1364852,1601053,1656406,1662280,1769370,1936912,2015416,2545457,3676593,6113153,6132853,6170411,7015371

8220917

Membrane current responses to externally-applied ATP in the longitudinal muscle of the chicken rectum.

1. Membrane current responses to ATP in enzymically-dispersed single smooth muscle cells from the chicken rectum were investigated by the whole-cell voltage clamp technique. 2. In cells dialysed with a KCl-rich solution under voltage clamp at a holding potential of -40 mV, ATP (10 microM) produced an inward current followed by an outward current. When the holding potential was changed to 0 mV and -80 mV, the biphasic current response to ATP was converted to an outward current alone and an inward current alone, respectively. 3. External application of tetraethylammonium (TEA, 5 mM), intracellular dialysis with a CsCl-rich solution, or inclusion of EGTA (10 mM) in the pipette abolished the outward current response to ATP. 4. Neither depletion of Ca2+ store with caffeine (10 mM) nor block of voltage-gated Ca2+ channels with nifedipine (10 microM) affected the biphasic current response to ATP. After removal of the extracellular Ca2+ the outward current response to ATP was abolished. 5. alpha,beta-methylene ATP (100 microM) elicited a current similar to the ATP-induced current. In the presence of alpha,beta-methylene ATP (100 microM), application of ATP (100 microM) was without effect. 6. In CsCl-filled cells, ATP analogues elicited an inward current and the order of potency was ATP not equal to alpha, beta-methylene ATP > ADP >> AMP. 7. Inclusion of GTP gamma S (0.2 mM) or GDP beta S (2 mM) in the pipette did not affect the ATP-induced inward current in CsCl-filled cells. The reversal potential of the ATP-induced inward current was about 0 mV and was completely inhibited after replacement of the cations in the bath solution by Tris. The reversal potential remained almost unchanged after replacement of Na+ in the bath solution with 1 10 mM Ca2+, but shifted in the negative direction after replacement of Na+ or both Na+ and Ca2+ with glucosamine.8. The results suggest that ATP acts on P2 purinoceptors to cause activation of cation channels with selectivity for Ca2+ over Na+. Moreover, it appears that no G-protein-mediated mechanism is involved and increased Ca2+ entry through the cation channels causes activation of Ca2+-activated K+ channels.

Adenosine Triphosphate,Animals,Calcium,Calcium Channels,Cesium,Chickens,Chlorides,Female,GTP-Binding Proteins,Guanosine 5'-O-(3-Thiotriphosphate),Guanosine Diphosphate,In Vitro Techniques,Male,Membrane Potentials,Muscles,Potassium Channels,Potassium Chloride,Rectum,Signal Transduction,Tetraethylammonium Compounds,Thionucleotides

197428,916385,1432705,1472975,1694399,1697199,1725183,2115389,2120427,2410183,2439921,2442353,2442722,2459375,2559977,2585296,2611483,2840995,2908125,2910869,3032169,3116214,3171994,3219484,3502344,3735806,3999045,4043228,6142947,6152212,6199538,6270629,6291151,6294167,13576452

8220918

The positive inotropic effect of compound II, a novel analogue of sotalol, on guinea-pig papillary muscles and single ventricular myocytes.

1. Compound II is a novel analogue of sotalol which has been reported to be free of beta-adrenoceptor and L-type calcium channel blocking actions. The effects of compound II on the contraction of guinea-pig papillary muscles (at 2 microM) and single ventricular myocytes (at 100 nM) were investigated. 2. Exposure to compound II caused a significant increase in the contraction of both preparations. 3. Compound II prolonged the action potential of the single myocytes and increased the magnitude of the Ca-activated current which was used as a qualitative indicator of the intracellular calcium transient. 4. The ratio of first/steady state Ca-activated currents evoked by short action potentials was not modified. This may indicate that compound II does not influence the normal functioning of the sarcoplasmic reticulum stores. 5. The observations are consistent with the hypothesis that action potential prolongation by compound II reduces Ca2+ extrusion via the Na-Ca exchange. This in turn allows increased uptake of calcium into the sarcoplasmic reticulum stores so that more calcium is available for release by subsequent action potentials, leading to an increase in intracellular calcium transients and contractions.

Action Potentials,Animals,Calcium,Calcium Channels,Cardiotonic Agents,Cytosol,Guinea Pigs,Heart Ventricles,In Vitro Techniques,Membrane Potentials,Myocardial Contraction,Myocardium,Papillary Muscles,Sarcoplasmic Reticulum,Sotalol

1393293,1685242,1700210,1711611,1742012,2033581,2223056,2257440,2482358,2575750,6251204,6320942,6770893

8220919

Local action transcutaneous flurbiprofen in the treatment of soft tissue rheumatism.

The objective of the present study was to establish the efficacy and tolerability of local action transcutaneous flurbiprofen (flurbiprofen LAT) in the treatment of soft tissue lesions. A randomized, double-blind, parallel-group placebo-controlled study was carried out in two hospital outpatient rheumatology clinics. One hundred and four patients aged 18-75 yr were randomized to receive a non-woven polyester-backed patch supporting a formulation containing 40 mg flurbiprofen 12-hourly over 14 days; or a non-medicated (but otherwise identical) control. Statistically significant differences in favour of the active preparation were seen at both days 7 (P = 0.02) and 14 (P = 0.009) for the investigator's overall opinion of severity of the condition, and at day 7 for the investigator's assessment of pain severity (P = 0.04 intention-to-treat; P = 0.052 N.S. eligible data). The need for further treatment in the form of steroid injections after the trial was greater in the controls (29/44, 66%) than in the flurbiprofen LAT group (17/46, 37%) (chi 2 = 7.54 on 1 d.o.f., P = 0.006). Plasma flurbiprofen levels in 11 patients ranged from 13.4 to 338.7 ng/ml (mean 116; median 57.9). Eight out of 53 (15%) patients receiving flurbiprofen LAT reported a total of 10 adverse events, compared with three out of 51 (6%) reporting seven events among controls. Patients found the patch convenient and soothing. We conclude that flurbiprofen LAT is an effective and acceptable treatment for soft tissue lesions, and should be considered as an alternative therapy to local steroid injection.

Administration, Cutaneous,Adult,Double-Blind Method,Female,Flurbiprofen,Humans,Male,Middle Aged,Pain Measurement,Rheumatic Diseases,Self-Assessment

1864449,1888621,2040104,2206836

8220920

Amyloid arthritis associated with IgM kappa lymphoplasmacytoid lymphoma.

Amyloid arthritis is an uncommon cause of locomotor disease and may closely resemble RA. Macroglobulinaemia is rarely associated with amyloidosis and there has been only one report of amyloid arthritis in this setting, the patient having had Waldenstrom's macroglobulinaemia. We report the occurrence of amyloid joint disease in the course of an IgM kappa B-cell dyscrasia which evolved over 16 years to an overt lymphoplasmacytoid lymphoma.

Amyloidosis,Arthritis, Rheumatoid,Female,Femoral Fractures,Humans,Immunoglobulin M,Immunoglobulin kappa-Chains,Leukemia, Lymphocytic, Chronic, B-Cell,Middle Aged,Monoclonal Gammopathy of Undetermined Significance,Radiography

357639,415063,718283,4565934,4958952,4978194,7097685,7353815

8220921

Glomerulonephritis in rheumatoid arthritis.

We present data on 10 patients with RA who developed glomerulonephritis which was not related to gold or penicillamine therapy. Although two of these patients had received gold this had been discontinued 13 and 18 yr before the diagnosis of glomerulonephritis. Seven patients presented with nephrotic syndrome and three with proteinuria and microscopic haematuria. Renal histology showed a membranous nephropathy (five patients), mesangial IgA nephropathy (two patients), focal segmental necrotizing glomerulonephritis (two patients) and focal segmental glomerulosclerosis (one patient).

Adult,Aged,Antibodies, Antinuclear,Arthritis, Rheumatoid,Female,Glomerulonephritis,Humans,Kidney,Male,Middle Aged,Nephrotic Syndrome,Rheumatoid Factor

392746,661557,1005658,1178811,1247260,2867313,2889238,3119021,3132218,3607380,3675007,3740996,3783320,3802589,3829481,3945363,5827631,6509803,6627762,6742907,7387747,13196950,14487628

8220922

Re-evaluating the need for hospitalization following synovectomy using Yttrium-90 silicate.

In 51 patients treated with Yttrium-90 (Y-90) synovectomy for rheumatoid (inflammatory) arthritis (IA) and OA of the knee we found that decreased retained knee activity (RKA) and increased extra-articular activity in lymph nodes and liver are more likely to be found in IA than OA and following bilateral knee injections. Joint inflammation, as assessed by radionuclide blood pool scan but not by SF white cell count, correlates with decreased RKA and increased activity in lymph nodes. Intra-articular steroid had no significant effect on retention or extra-articular uptake. Strict hospital immobilization improves RKA of Y-90 in IA but not in OA. Y-90 synovectomy in OA shows good RKA and low extra-articular uptake. We recommend strict immobilization following Y-90 synovectomy, particularly in IA patients and/or those with high joint blood flow.

Adult,Aged,Aged, 80 and over,Arthritis, Rheumatoid,Bed Rest,Evaluation Studies as Topic,Female,Hospitalization,Humans,Knee,Liver,Lymph Nodes,Male,Middle Aged,Osteoarthritis,Patient Discharge,Postoperative Period,Radionuclide Imaging,Silicates,Synovial Membrane,Yttrium,Yttrium Radioisotopes

46959,337466,970995,1139094,1257709,1550415,2031157,2840863,4634769,4712010,4821385,6778548,14087255

8220924

Chronic polyarthritis due to Pseudomonas aeruginosa.

We present a 45-year-old male patient with chronic obstructive lung disease treated with low-dose corticosteroids, who developed a chronic septic polyarthritis due to Pseudomonas aeruginosa following a surgical wound infection. Due to the mild synovitis and the absence of systemic signs of infection the diagnosis was delayed for nearly 2 years and resulted in severe joint destruction.

Arthritis,Chronic Disease,Humans,Lung Diseases, Obstructive,Male,Middle Aged,Prednisone,Pseudomonas Infections,Pseudomonas aeruginosa,Surgical Wound Infection

337494,2335053,2496048,3883171,4207743,5008465,5096640,6121485,6773530,6987870,6993944

8220933

A new biochemical marker for joint injury. Analysis of YKL-40 in serum and synovial fluid.

We report the development of the first radioimmunoassay for YKL-40, a M(r) = 40 kDa protein which is secreted at high levels by human synovial cells and articular cartilage chondrocytes, and by the human osteosarcoma cell line MG63. This assay uses YKL-40 purified from the conditioned medium of MG63 cells as standard and tracer, and as antigen for immunizing rabbits. With this assay we have discovered high levels of YKL-40 antigen in serum and SF. The molecular weight of serum and SF YKL-40 is identical to purified YKL-40. To evaluate the possible utility of YKL-40 in the assessment of joint disease, we measured YKL-40 in serum and SF of 49 patients with various forms of inflammatory and degenerative joint disease and in the serum of 50 normal adults. The YKL-40 level in serum was significantly higher (P < 0.001) in the patients compared to the normal adults, but there was no difference in serum YKL-40 between the patients with inflammatory joint diseases and OA. The SF levels of YKL-40 were 15-fold higher than serum levels and there was a significant correlation (r = 0.55, P < 0.001) between YKL-40 concentration in SF and serum. Although the tissue distribution of YKL-40 secretion is presently unknown, these observations suggest that a major portion of serum YKL-40 in fact arises from the joint.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipokines,Adult,Aged,Aged, 80 and over,Amino Acid Sequence,Biomarkers,Chitinase-3-Like Protein 1,Female,Glycoproteins,Humans,Joints,Lectins,Male,Middle Aged,Molecular Sequence Data,Proteins,Radioimmunoassay,Rheumatic Diseases,Synovial Fluid,Wounds and Injuries

218153,1615759,1705186,1859483,1903212,1934688,2104896,2464001,2846219,3069706,3264282,3354390,3358796,3359606,3500054,3503559,3718552,6254989,7316186

8220934

Mechanical conditioning of articular cartilage to prevalent stresses.

The possible correlation between joint stresses and cartilage compressive modulus is examined. The stresses acting upon different areas of the joints and cartilage compressive modulus in these areas were obtained for 15 pairs of ipsilateral human ankle and knee autopsy joint specimens. It was found that the cartilage compressive modulus was significantly correlated with the mechanical stress (r = 0.889 at P < 0.02 level of significance) in such a manner that cartilage subjected to higher predominant stresses was significantly stiffer than that subjected to lower predominant stresses. This was true when comparing ankle with knee joints, and also when comparing different regions within one single joint. Such a correlation is significant in that it indicates that cartilage may well be conditioned mechanically by the prevalent stress it is subject to. However, this correlation of data obtained from autopsy specimens is a necessary, but not sufficient condition, for the above hypothesis to be true. It is, therefore, concluded that further work on animals is necessary.

Adaptation, Physiological,Ankle Joint,Biomechanical Phenomena,Cadaver,Cartilage, Articular,Humans,Knee Joint,Middle Aged,Stress, Mechanical,Weight-Bearing

444315,496444,858731,1150683,2120402,2312519,2324854,2455486,2703928,3701728,4117785,4708019,5122817,5521530,6844402,7054208,7382457

8220935

Immunoassay of platelet-derived growth factor in the plasma of patients with scleroderma.

It has been postulated that platelet-derived growth factor (PDGF) is responsible for the abnormal fibroblast proliferation observed in scleroderma. In one previous study, plasma samples from patients with scleroderma caused increased mitogenesis in cultured fibroblasts, suggesting that the pathogenesis of scleroderma is related to increased plasma PDGF concentrations. To test this hypothesis, we used a sensitive, monoclonal antibody-based ELISA to measure PDGF in the plasma of 12 scleroderma patients. A rigorous sampling protocol prevented false elevations in plasma PDGF levels from ex vivo platelet degranulation: beta-thromboglobulin concentrations were measured in each plasma sample to monitor platelet lysis. Plasma PDGF concentrations in the scleroderma patients were not statistically different from those observed in age- and sex-matched normal controls, and patients with RA. While it is possible that changes in PDGF activity at a local level alter fibroblast function, we cannot conclude that elevated plasma concentrations of PDGF play a role in the pathogenesis of scleroderma.

Adolescent,Adult,Aged,Arthritis, Rheumatoid,Enzyme-Linked Immunosorbent Assay,Female,Humans,Male,Middle Aged,Osmolar Concentration,Platelet-Derived Growth Factor,Reference Values,Scleroderma, Systemic,beta-Thromboglobulin

90059,1750797,1868437,2142571,2460450,2502943,2536714,2598468,2665755,2679266,2717622,2918236,3358796,3670088,4260235,6266431,6885904,7142300

8220936

Avascular necrosis of the hip in systemic lupus erythematosus: the role of magnetic resonance imaging.

The value of magnetic resonance imaging (MRI) in the early diagnosis of avascular necrosis (AVN) of the hip in SLE was investigated. Twenty females with severe SLE were studied prospectively. Each underwent 6-monthly X-rays, technetium -99m (Tc-99m) pyrophosphate bone scans and MRI of the hips over a 3-yr period. AVN was diagnosed in five hips of three patients (15%) during the study period. It was confirmed histologically in three hips of two patients who underwent core decompression. Radiological evidence of AVN was present in two patients at diagnosis. One patient developed progressive radiological changes despite core decompression. Bone scintigraphy was abnormal at some stage in all three patients with AVN however failed to detect the early ischaemic stage of AVN. MRI was the most reliable investigation and was able to detect asymptomatic AVN prior to the appearance of radiological or scintigraphic abnormalities.

Adolescent,Adult,Female,Femur Head,Hip Joint,Humans,Lupus Erythematosus, Systemic,Magnetic Resonance Imaging,Osteonecrosis,Prospective Studies,Technetium Tc 99m Pyrophosphate,Tomography, Emission-Computed, Single-Photon

3261787,3393676,3487233,3597492,3740994,3768054,3772929,3782202,3809484,3875700,4061472,6238510,7360042

8220937

A study of the early and late 99technetium scintigraphic images and their relationship to symptoms in osteoarthritis of the hands.

Thirty-five patients with OA of the hands had an early and late phase isotope bone scan performed at entry and 1 yr later. Simultaneous assessment of symptoms was made by a visual analogue pain score (VAS) and a tender joint articular index (AI) and comparisons were made between the clinical and scintigraphic findings. Sixty-five percent of joints were classed as positive in the late phase compared to 17% in the early phase scan. Thirteen per cent of joints were positive only in the early phase and 49% only in the late phase. There was no significant overall change in either phase of the scan in 1 yr. The pattern of positive joints showed considerable symmetry and wrist involvement. There was a high degree of correlation between AI and the late phase scan but none with the early phase scan. VAS showed no correlation with the late phase scan but did correlate significantly with the early phase scan at 1 yr.

Aged,Female,Hand,Humans,Male,Middle Aged,Osteoarthritis,Pain Measurement,Radionuclide Imaging,Technetium Tc 99m Medronate,Time Factors

1929584,2027126,2302268,3740990,3740991,6238825,6658397

8220938

Effects of fish oil supplementation on non-steroidal anti-inflammatory drug requirement in patients with mild rheumatoid arthritis--a double-blind placebo controlled study.

Maxepa contains eicosapentaenoic acid (EPA) (171 mg/capsule) and docosahexaenoic acid (DHA) (114 mg/capsule). EPA acts as an alternative substrate to arachidonate, leading to the formation of the less proinflammatory prostaglandins ('3' series) and leukotrienes ('5' series). If Maxepa has anti-inflammatory properties it could be expected to reduce the requirement for NSAIDs in patients with RA. This has not been investigated nor has Maxepa therapy been studied over a full 1-yr period. Sixty-four patients with stable RA requiring NSAID therapy only were studied. Patients received either 10 Maxepa or air-filled placebo capsules per day for 12 months. All then received placebo capsules for a further 3 months. Patients were reviewed at 3-monthly intervals. NSAID requirement at entry visit for each patient was assigned as 100%. Patients were instructed to slowly reduce their NSAID dosage providing there was no worsening of their symptoms. Clinical and laboratory parameters of RA activity were also measured. There was a significant reduction in NSAID usage in patients on Maxepa when compared with placebo from month 3 [mean (95% C.I. for mean) requirement--71.1 (55.9-86.2)% and 89.7 (73.7-105.7)%, respectively]. This effect reached its maximum at month 12 [40.6 (24.5-56.6)% and 84.1 (62.7-105.5)%, respectively] and persisted to month 15 [44.7 (27.6-61.8)% and 85.8 (60.5-111.1)%, respectively] (P < 0.001, ANOVA). These patients were able to reduce their NSAID requirement without experiencing any deterioration in the clinical and laboratory parameters of RA activity.

Anti-Inflammatory Agents, Non-Steroidal,Arthritis, Rheumatoid,Docosahexaenoic Acids,Double-Blind Method,Drug Combinations,Eicosapentaenoic Acid,Erythrocyte Membrane,Fatty Acids,Fatty Acids, Omega-3,Female,Fish Oils,Humans,Male,Middle Aged,Patient Satisfaction

826136,2138449,2180386,2363736,2552571,2666994,2833184,2849682,2857265,2996057,3030173,3324106,3358796,3930652,4082084,4877784,6096400,6253525,6304720,6316858,6330066

8220939

The prevention and healing of acute non-steroidal anti-inflammatory drug-associated gastroduodenal mucosal damage by misoprostol.

This double-blind study assessed the acute development of NSAID-associated gastroduodenal (GD) damage and its prevention by misoprostol. Patients requiring chronic NSAID therapy were stratified into two groups depending on initial endoscopic appearance, Group I: normal (n = 223); Group II: non-ulcer lesions (n = 78). After 2 weeks of therapy with NSAID and either misoprostol 400-800 micrograms daily or placebo the incidence of severe mucosal damage (including ulcers) was significantly reduced by misoprostol (odds ratio; 95% CI). Group I: 4.52; 1.94, 10.51 (P = 0.018); Group II: 10.93; 1.09, 109.60 (P = 0.014); Groups I and II combined: 5.95; 3.23, 10.94 (P = 0.0003). Misoprostol exerted a significant protective effect against progression of minor to severe damage in Group II (P < 0.001). Endoscopic findings did not correlate significantly with gastrointestinal symptoms and misoprostol did not interfere with the NSAID efficacy. Significant GD damage occurs early in the course of NSAID treatment and misoprostol significantly reduces the incidence of such damage.

Adult,Aged,Aged, 80 and over,Anti-Inflammatory Agents, Non-Steroidal,Double-Blind Method,Duodenal Ulcer,Endoscopy,Female,Gastroscopy,Humans,Intestinal Mucosa,Male,Middle Aged,Misoprostol,Risk Factors,Stomach Ulcer

314764,1671893,1681960,1905501,1987872,1987878,2015469,2106956,2253535,2493366,2602546,2646087,2869207,2888943,2904006,2909442,3134266,3140938,3144369,3310942,3382267,3492182,3499815,3596332,3596334,3609658,3612597,3917814

8220940

Effect of a non-steroidal anti-inflammatory drug, naproxen, on faecal microbial flora.

Faecal Clostridium perfringens counts have been observed to be elevated in RA patients. The use of NSAIDs has been suggested as being responsible for this increase. To clarify the potential of NSAIDs to change faecal flora, 10 male volunteers were given naproxen 500 mg twice daily for 2 weeks in a randomized, placebo-controlled and double-blind study, and 10 other volunteers were given a placebo in tablets of identical appearance. Stool samples were collected and subjected to direct stool sample gas-liquid chromatography of bacterial fatty acids. The method has proved to be practical and sensitive in detecting overall changes in faecal flora. The samples were also cultured for Cl. perfringens. No significant change of faecal flora was observed by either method. The results show that naproxen given in doses and over a period in excess of the levels reported to increase intestinal permeability, does not change intestinal flora.

Anti-Inflammatory Agents, Non-Steroidal,Chromatography, Gas,Clostridium perfringens,Colony Count, Microbial,Double-Blind Method,Feces,Humans,Male,Naproxen,Placebos

1093952,1482187,1501650,1628165,1747146,2007639,2257450,2877709,2888943,2889500,3183021,3466837,3609658,4308036,4335983,4355210,5765565,6357937,7068826

8220941

The theory of reasoned action and cooperative behaviour: it takes two to use a condom.

The applicability of the Theories of Reasoned Action and Planned Behaviour to the cooperative behaviour of condom use were examined. Seventy-one male and 78 female students, all sexually active unmarried heterosexuals aged 17 to 21 years, gave information about their intentions for the next sexual encounter, as well as their attitude, subjective norm, expectancy-value attitude and subjective norm (including normative beliefs for their sexual partner), and their past behaviour with respect to condom use. After their next sexual encounter, they completed a questionnaire on their actual condom use. Results indicated that when behavioural conditions including the availability of a condom and an agreement with the partner to use it were satisfied, intention interacted with past behaviour to predict actual behaviour. These results imply that intentions which are consistent with past behaviour are stable enough to be carried out in the face of the interpersonal dynamics of a sexual encounter. Further, normative belief for the sexual partner had a direct influence on attitudes, subjective norm and intention. Neither the Theory of Reasoned Action nor the Theory of Planned Behaviour can fully explain these results, which point to the need for further theoretical inquiry into the dynamics of cooperative behaviour.

Adolescent,Adult,Condoms,Female,HIV Infections,Health Knowledge, Attitudes, Practice,Humans,Male,Risk Factors,Sexual Behavior,Sexual Partners

1594721,2716660,4045706,4078673,6491868,6644542,6842361

8220942

The patello-femoral joint--a critical appraisal of its geometric assessment utilizing conventional axial radiography and computed arthro-tomography.

In the quest for treatable causes of anterior knee pain, plain film skyline views of the patello-femoral joint are requested, often in 30 degrees, 60 degrees and 90 degrees of flexion, to assess the functional relationships of the joint. Patello-femoral malalignment predisposes to recurrent subluxation and dislocation, articular cartilage damage and premature degenerative change. The aim of this study is to evaluate critically, by comparative assessment, the information provided by skyline views and axial computed arthro-tomography (CTA). Measurements of the patello-femoral angle (assesses patellar tilt), the congruence angle (assesses patellar lateralization) and the trochlear depth were made on Merchant's skyline views and on axial CTA on each of 50 symptomatic knees. Results are presented in graphic form with visual examples indicating a poor correlation between the two imaging methods. We conclude that skyline views are inaccurate and unsuitable primarily because they cannot be obtained in less than 30 degrees of flexion. We suggest that skyline views have no role to play in screening for maltracking as even florid examples must be missed, and would strongly urge that no surgery be performed on their basis alone as this would result in inappropriate operations. Although computed tomography is the preferred mode of assessing patello-femoral geometry, difficulties are still encountered and the ways of circumventing them are discussed.

Femur,Humans,Knee Joint,Patella,Tomography, X-Ray Computed

500754,535219,582201,624759,2278014,3714207,3956015,4433362,5676827,6851329,7112142,27743060

8220943

Computed tomographic cholangiography using spiral scanning and 3D image processing.

Volumetric computed tomography (CT) scans ("spiral CT") were performed after intravenous (i.v.) cholangiography followed by additional 3D surface reconstructions of gallbladder and biliary ducts. 34 patients were investigated prior to cholecystectomy. No allergic adverse reactions were observed. The scan time was 24 s. Contrast enhancement in the extrahepatic bile duct and gallbladder were measured. All CT image series were reviewed independently by four experienced physicians (two radiologists, two surgeons) and compared for quality with conventional cholangiography on a three-point scale. The average rating for the demonstration of the biliary tract was significantly better for spiral CT than for conventional cholangiography (p < 0.01). In all cases sufficient contrast was found in the common bile duct (mean 315 HU). 3D imaging was considered to be helpful for intraoperative orientation during laparoscopic surgery.

Adult,Aged,Cholangiography,Cholelithiasis,Humans,Image Processing, Computer-Assisted,Middle Aged,Tomography, X-Ray Computed

1459013,1555363,1561373,1932729,1961153,2353088,2389050,6689758

8220944

Elevation of the larynx on normal and abnormal cineradiogram.

The relationship between bolus volume (2.5, 5, 10 and 20 ml) and larynx elevation during swallowing was assessed in 10 non-dysphagic and 10 dysphagic individuals without pharyngeal dysfunction. Laryngeal elevation in different types of pharyngeal dysfunction was assessed in 60 non-dysphagic and 75 dysphagic patients. All subjects were examined with liquid barium and cineradiography at 50 frames/s. The laryngeal elevation was measured at the moment when the bolus reached the level of the valleculae and at maximum elevation. Elevation of the larynx, both the initial and maximal, was not influenced by sex, age or presence of dysphagia. Elevation of the larynx at the moment when the bolus reached the valleculae, when expressed in per cent of maximum elevation, was lower with 10 and 20 ml bolus volumes compared with 2.5 ml bolus volume (p < 0.05) in the 10 dysphagic individuals. Pharyngeal dysfunction was associated with significantly lower initial elevation of the larynx, at the moment when the bolus reached the level of the valleculae, although the maximal laryngeal elevation was normal. Initial elevation was 30% lower (p = 0.03) in patients with aspiration of bolus material into the trachea, 22% lower (p = 0.007) in those with defective closure of the laryngeal vestibule without aspiration and 16% lower (p = 0.06) in those with incoordination of the cricopharyngeal muscle compared with patients without dysfunction.

Adolescent,Adult,Aged,Aged, 80 and over,Cineradiography,Deglutition,Deglutition Disorders,Female,Humans,Larynx,Male,Middle Aged,Prospective Studies

3371625,3561135,3751676,3877418,3931423,4029539,6718012,6751694,7034008,7066633,13460261,13465315,14372088,14903812,14935150

8220945

The histological response of the lungs of rats to potentially suitable water soluble bronchographic contrast agents iotrolan (a non-ionic dimer) and iopamidol (a non-ionic monomer).

The recent need for selective bronchography during bronchoscopy in certain patients, together with paediatric indications for tracheo-bronchography, raises the question as to which contrast medium is both safe and efficient. The purpose of the present experimental study was to define the tissue reaction caused by iotrolan and iopamidol in the bronchi and lungs of rats. 60 animals used in this study were divided into five groups receiving iotrolan 300, iopamidol 370, iopamidol 150, physiological saline and anaesthetic only, the last two acting as control groups. Statistically there was no significant difference in the histological reaction between iotrolan 300, iopamidol 370 and iopamidol 150 compared with the control groups, although iotrolan 300 appeared to result in the least tissue reaction. With its adequately high iodine concentration, low osmolality and relatively high viscosity, iotrolan 300 would appear to be a suitable contrast medium for bronchography.

Animals,Bronchi,Contrast Media,Inflammation,Iopamidol,Lung,Male,Radiography,Rats,Rats, Wistar,Triiodobenzoic Acids

1853212,2253632,2402728,2713601,3069297,3123418,3686461,4942355,5648074,6333166,6462811,6487960,6600337,6719372,7177732

8220946

The effects of radiographic contrast media on leucocyte orientation.

The effects of radiographic contrast media (RCM) on leucocyte orientation in vitro were studied using a Zigmond chamber. Leucocyte orientation was assessed following exposure of the leucocytes to iotrolan, iohexol, ioxaglate and diatrizoate. The RCM used were diluted to a concentration similar to that obtained in vivo during routine angiography. At this concentration there was a significant reduction in leucocyte orientation for all RCM investigated but the effect was more pronounced in the monomeric than the dimeric RCM. The results may have significance when deciding which radiographic contrast medium to use in selected patients, particularly those who are immunosuppressed or septicaemic.

Chemotaxis, Leukocyte,Contrast Media,Diatrizoate,Humans,Ioglycamic Acid,Iohexol,Leukocytes,Triiodobenzoic Acids

85650,264125,415989,429705,2261305,6567445,6616134,6618818,7164034

8220947

The management of stroke during intraarterial thrombolysis.

Intraarterial thrombolytic therapy is being increasingly used in the treatment of acute limb ischaemia. When strokes occur during thrombolytic therapy treatment is usually stopped because of the suspicion of cerebral haemorrhage. If the stroke is not haemorrhagic then stopping the treatment jeopardizes the ischaemic limb. If the stroke is proven to be non-haemorrhagic on computed tomography (CT) then the thrombolytic therapy should be recommenced. We present three case histories of patients who suffered a stroke during thrombolytic therapy over a 30-month period, in whom CT confirmed non-haemorrhagic stroke and we suggest that managing the ischaemic limb with anticoagulant and thrombolytic therapy can be safe in the early period following the stroke. We also discuss the probable aetiology of the strokes and whether cardiac echocardiography should be performed in these patients.

Adult,Aged,Aged, 80 and over,Arm,Brachial Artery,Cerebrovascular Disorders,Female,Femoral Artery,Humans,Infusions, Intra-Arterial,Ischemia,Leg,Male,Popliteal Artery,Streptokinase,Thrombolytic Therapy,Thrombosis

1573601,2021837,2021840,2070163,2514002

8220948

T1 rho dispersion imaging of diseased muscle tissue.

T1 rho dispersion, or the frequency dependence of T1 relaxation in the rotating frame, was used for in vivo muscle tissue characterization in 13 patients with primary skeletal muscle disease and in eight normal subjects for comparison. T1 rho dispersion measurements represent a new approach to magnetic resonance tissue characterization, possibly reflecting the macromolecular constituents of tissue. A definite, statistically significant, difference was found between the relative T1 rho dispersion values of normal and diseased muscle tissue. T1 rho dispersion measurements and images may increase the accuracy of identification of diseased muscles. Early identification of affected muscles is important for accurate diagnosis by muscle biopsy.

Adolescent,Adult,Child,Child, Preschool,Female,Humans,Magnetic Resonance Imaging,Male,Muscles,Muscular Diseases,Muscular Dystrophies

1182262,1556921,2268764,2400872,2447503,2532710,2550719,2607895,2607958,2615628,2628687,2811618,3031439,3170136,3343998,3684364,3940397,4056129,5792660,6482839,6522611,6522615,6533107,6927208

8220949

Gastrointestinal manifestations in the Hallopeau-Siemens variant of recessive dystrophic epidermolysis bullosa.

Epidermolysis bullosa encompasses a group of rare disorders typified by blister formation following minor trauma to the skin. Gastrointestinal tract involvement may occur in the extremely rare recessive dystrophic variants. The gastrointestinal manifestations present in 25 patients with the Hallopeau-Siemens variant of recessive dystrophic epidermolysis bullosa are reviewed. In the oesophagus both anatomical and motility abnormalities were observed. Features seen included a generally shortened oesophagus, strictures including those resembling webs, hiatus herniae, decreased peristalsis, oesophageal atony and pseudodiverticulum formation. These patients also had faecal impaction.

Adolescent,Adult,Child,Child, Preschool,Epidermolysis Bullosa Dystrophica,Esophageal Stenosis,Esophagus,Female,Humans,Male,Radiography

406782,1628178,2060880,3284470,3499795,4843578,4851891,5021034,5073676,5635122,5765157,5777236,6020390,6606328,7254996,13710345,14068136

8220950

Stab wounds of the heart: two new signs of pneumopericardium.

The diagnosis of a small traumatic pneumopericardium may be difficult and differentiation from a left medial pneumothorax or pneumomediastinum is important. Two new signs which only occur in pneumopericardium are described: the "transverse band of air" sign on the frontal radiograph representing air in the transverse sinus of the pericardium, and the "triangle of air" sign as noted on the lateral radiograph. If there is still doubt, a left-side-down decubitus radiograph will establish the diagnosis.

Adolescent,Adult,Heart Injuries,Humans,Male,Pneumopericardium,Radiography, Thoracic,Wounds, Stab

3257136,3498317,3872026

8220951

Changes in the radiation treatment of cancer of the anus in Glasgow.

The survival and complication rate of two groups of patients with carcinoma of anus were compared. The first group of 20 patients were treated between 1974 and 1983 by double plane implantation using radium or equivalent caesium needles and supplementary external beam radiotherapy to groin nodes if present. The second group of 26 patients were treated between 1984 and 1990 by external beam radiotherapy followed by a jig implant using afterloading iridium needles. 5-year survival was superior in the second group (73% vs. 40%) with a lower incidence of radiation-induced complications.

Adenocarcinoma,Aged,Aged, 80 and over,Anus Neoplasms,Brachytherapy,Carcinoma, Squamous Cell,Cesium Radioisotopes,Female,Humans,Iridium Radioisotopes,Male,Middle Aged,Radium,Scotland

696400,1938508,3934775,4041732,4173821,5416607,6499614,6831349,7225745,13719398

8220952

Digital storage phosphor radiography for treatment verification in radiotherapy.

The potential of digital storage phosphor radiography (SR) to improve image quality of portal radiographs is evaluated. Conventional film radiographs (FR) and corresponding SR verification images of an anthropomorphic phantom and various irradiation ports of patients were obtained with high-energy photon beams. For both techniques conventional films and storage phosphor screens were placed into a cassette with steel screens. Images were evaluated according to contrast and spatial resolution, delineation of anatomical structures, position of shielding blocks and accuracy of field alignments. Evaluation of 33 pairs of SR and FR portal images yielded a superior contrast resolution of SR in 47% (contrast air-soft tissue) and 37% (bone-soft tissue). Thus SR allows quick and easy detectability of anatomical structures as well as a better definition of block positions and field alignments. Shorter exposure times for computed images may result in a reduction of motion artefacts. SR images are indispensable in modern radiation therapy units, as they are instantly available in a computerized network for further image processing and analysis.

Humans,Models, Structural,Radiographic Image Enhancement,Radiometry,Radiotherapy, High-Energy,Treatment Outcome

117869,683155,1696399,2347724,2382211,2492269,2674080,3097464,3125620,3187009,3570904,3600529,3768624,6286086,6691118,6878707

8220953

Is there a danger in delaying radiotherapy in childhood medulloblastoma?

Approximately 45-50% of children with medulloblastoma are cured by conventional surgery and radiotherapy, but survivors may face severe late neuropsychological toxicity. Studies showing good partial responses to platinum-based chemotherapy in relapsed patients and the theoretical possibility of a therapeutic window immediately after surgery have prompted neoadjuvant treatment studies which are ongoing. However, the absolute benefit of chemotherapy for the treatment of medulloblastoma in childhood is, as yet, not proven. There is a danger that chemotherapy may simply delay radiotherapy, and in so doing reduce the radiological impact of this known effective treatment. We report four children with medulloblastoma presenting consecutively to this unit over a 6-month period, whose management was problematic because of either failure to respond to neoadjuvant chemotherapy or their very young age. These cases are discussed in the light of the current literature and future treatment strategies that must seek to improve the therapeutic ratio of multimodality therapy.

Cerebellar Neoplasms,Child,Child, Preschool,Female,Humans,Infant,Male,Medulloblastoma,Neoplasm Recurrence, Local,Postoperative Complications,Time Factors

456106,597384,1599290,1611434,1739930,1908345,1913045,1940946,2141512,2180567,2319316,2340529,2540867,2736225,2915244,3040919,3391815,3546620,3889800,3944633,5111749,5774280,6478430,6737054,6818190,7108593,7241214,7393422,8428261

8220954

Reduced bone mineral density in long-term survivors of medulloblastoma.

Bone mineral density (BMD) reaches a peak at approximately 30 years of age, and may be influenced by radiotherapy before completion of skeletal maturation. Regional BMD has been measured using dual energy X-Ray absorptiometry (DEXA) in adults following craniospinal irradiation for medulloblastoma between ages 4 and 19 years, receiving doses of 3500-4000 cGy to the brain and spinal cord. Lumbar spine (LS) and was failure to achieve normal adult BMD at both LS and FN, with a mean reduction at LS of 12.1% +/- 2.4% (p < 0.01) and a mean reduction at FN of 14.3% +/- 3.4% (p < 0.01). The mean body mass index (BMI) was also less than that of a standard population (21.8 +/- 1.5), as were mean standing and sitting heights. No relationship was found between reduction in BMD at either site and age at irradiation, time elapsed since irradiation or BMI at time of scanning. Biochemical and endocrine markers including corrected calcium, alkaline phosphatase, sex hormones and IGF-1 were normal in all seven patients. The reduction in BMD outside the irradiated area suggests that indirect factors may be important in this effect.

Adolescent,Adult,Body Height,Bone Density,Cerebellar Neoplasms,Child,Female,Femur Neck,Humans,Lumbar Vertebrae,Male,Medulloblastoma

1656486,1914437,1931763,2008183,2109197,2116509,2349926,3262626,3281002,3606177,4199354,12994000

8220955

Clinical high resolution skeletal single photon emission tomography using a triple-headed gamma camera.

Planar skeletal scintigraphy has become established as a standard diagnostic test performed within the nuclear medicine department. Since the 1970s good quality images have been produced using an Anger gamma camera and 99Tcm-labelled diphosphonates. Single photon emission tomography (SPET) has improved the sensitivity of detection and the ability to localize bony pathology, particularly benign bone disease in the spine. Recently multi-detector gamma cameras dedicated to SPET have become available. One such system, the Toshiba GCA-9300A, has been used to perform routine clinical skeletal SPET in 81 patients. Good quality images have been obtained using an 8 min acquisition in the axial skeleton and a 16 min acquisition protocol in the peripheral skeleton. Multiple sites can be tomographed in the same patient during the same examination using two or more 8 min acquisitions. Such a multi-detector gamma camera offers advantages over the standard single-headed rotating camera for skeletal SPET in terms of both imaging time and image quality. A cost analysis was performed which demonstrated that the additional cost of purchasing such a multidector gamma camera was less than 30.00 pounds per SPET study.

Bone Neoplasms,Bone and Bones,Cost-Benefit Analysis,Femur,Foot,Gamma Cameras,Humans,Knee Joint,Lumbar Vertebrae,Thorax,Tomography, Emission-Computed, Single-Photon

1563442,1613590,2292159,2341895,3136236,3155479,3261787,3303342,3875700,6229308

8220956

Radiation doses to paediatric patients undergoing less common radiological procedures involving fluoroscopy.

A semi-automated dosimetry survey has been undertaken to monitor the radiation doses to patients in a paediatric fluoroscopy room. The doses were assessed using large area Diamentor ionization chambers to measure dose x area product, and by means of thermoluminescent dosemeters attached to the patient's skin in various places. Details of patients and examinations were entered into a computer, all information being stored on a data base. Many radiological examinations have been monitored, including renal and jejunal biopsies, nephrostograms, loopograms, tracheograms and fistulograms. Patients included in the study have been divided into three age bands for dose assessment. Radiation doses for different types of examination have been compared, including more common examinations for which data have been previously presented.

Adolescent,Age Factors,Child,Child, Preschool,Fluoroscopy,Humans,Infant,Radiation Dosage,Radiation Tolerance,Risk Factors

1547450

8220957

Technical note: physical evaluation of recent Kodak films for mammography.

Four Kodak films for mammography were evaluated for image quality and dose. Processing times and storage effects have also been evaluated.

Mammography,X-Ray Film

1509043,2268767,2310905,2781032,2924096,3191319,3814998

8220958

Technical note: the implementation of patient position correction using a megavoltage imaging device on a linear accelerator.

The problem of using information from the analysis of megavoltage images to adjust patient set-up has been addressed. In the case of rotational corrections it has been assumed that the treatment head is to be adjusted, although for gantry angles of 0 degree and 180 degrees couch rotation may be used. In the case of translational shifts adjustment of the collimator jaws or of the couch have both been considered for arbitrary combinations of couch and gantry angle. For couch movement the case has been considered where it is desirable to minimize both the number of parameters to be adjusted and also the magnitude of the change in the patient's position. Values obtained for frequently used set-up parameters have been presented. Adjustment of the treatment couch positioning is the most desirable option, as this should bring the patient closer to the correct position for subsequent treatment fields. However, rotational errors are not correctable for all gantry angles and furthermore the collimator settings may be set more accurately than those of the treatment couch. Hence, in some cases, adjustment of the collimation system may be desirable or necessary. The formulae given in Equations (13) to (18) are currently being used in an intervention study to correct patient set-up during the course of a treatment fraction.

Humans,Mathematics,Posture,Radiation Dosage,Radiation Protection,Radiotherapy, High-Energy

1393398,1727113,1771184,1995549,2320664,3182312,3580742

8220959

Case report: accessory lobe of the liver mimicking lesser omental lymphadenopathy.

An accessory lobe of the liver is an uncommon occurrence and often an incidental finding. We present the case of a middle-aged man whose upper abdominal pain was relieved following removal of an accessory lobe. His preoperative imaging had led us to believe that he had lesser omental lymphadenopathy. We draw attention to the fact that this congenital abnormality can cause diagnostic confusion.

Diagnosis, Differential,Humans,Liver,Lymphatic Diseases,Male,Middle Aged,Omentum,Peritoneal Diseases,Tomography, X-Ray Computed

1273019,2407309,2917536,3236169,3244089,3819124,3833290,6607640,6691106,14895157

8220965

Complications of intraarterial digital subtraction angiography in patients investigated for cerebral vascular disease.

395 patients (236 males, mean age 55.6 years: 159 females, mean age 52.2 years) with suspected transient ischaemic attacks or previous strokes underwent intraarterial digital subtraction angiography (IADSA) over a 3-year period ending in March 1991. All procedures were performed via the femoral approach and the majority consisted of arch studies followed by selective catheterization. 253 (64.1%) of the patients had extracranial vascular disease confirmed at angiography. A retrospective analysis of the patients' records was made to extract all possible complications. Complications were defined as any untoward symptoms or signs occurring within 48 h and which could have been related to the angiogram. Neurological complications occurred in 15 (3.89%) patients. 10 (2.5%) patients had transient complications which resolved completely within 24 h. In three (0.8%) patients the neurological deficit was reversible, recovering fully within 6 days. Two (0.52%) patients were left with residual disability from stroke at 10 days. The permanent neurological complication rate is in the lower range of the rates recorded in previous conventional angiographic studies. We conclude that IADSA is a relatively safe and reliable form of investigation in patients with suspected cerebral vascular disease.

Adult,Aged,Angiography, Digital Subtraction,Cerebrovascular Disorders,Female,Humans,Ischemic Attack, Transient,Male,Middle Aged,Nervous System Diseases,Recurrence,Retrospective Studies,Time Factors,Vascular Diseases

101045,2234388,2406993,2790421,3686597,5936091,6387992

8220966

Ultrasound diagnosis of splenic lymphoma: ROC analysis of multidimensional splenic indices.

To assess the efficacy of splenic size in the sonographic diagnosis of lymphomatous involvement of the spleen, the authors studied 31 patients with splenic lymphoma (Hodgkin's disease, 17 and non-Hodgkin's lymphoma, 14) and 218 individuals without evidence of splenic disease. All subjects were studied with both a linear and a sector transducer. The longitudinal, transverse and diagonal diameters of the spleen were measured, and two- and three-dimensional splenic indices were calculated. The analysis of the diagnostic performance of these criteria, compared by means of receiver-operating characteristic (ROC) curves, revealed that diagnosis of splenic involvement by malignant lymphoma was considerably more reliable with a sector than with a linear scanner. If the longitudinal diameter was measured with a sector scanner, sensitivities were 66% and 74%, at specificities of 95% and 90% respectively (cut-off points: 12.5 cm and 11.3 cm, respectively). For the sector scanner, there was no advantage in using other diameters or multidimensional indices. Additional ROC analysis of recently published data indicating excellent discrimination capacity of a computed tomography index revealed that these results were largely owing to patient selection. In contrast, our data suggest that the potential of current non-invasive assessment of splenic lymphoma is limited. However, ultrasound may eventually help to eliminate staging laparotomy in selected cases, e.g. in patients with low risk of abdominal disease and with increased surgical risk.

Adult,Female,Hodgkin Disease,Humans,Lymphoma, Non-Hodgkin,Male,Middle Aged,ROC Curve,Spleen,Splenic Neoplasms,Ultrasonography

1846375,2027974,2048509,2649915,2655388,2702587,2736109,2783273,2953366,2997873,3095258,3279735,3292476,3292604,3304508,3420274,3515414,3873789,3961163,3969481,6271856,6473784,6622701

8220967

Quality assurance in obstetric ultrasound.

Ultrasound examination is a routine element of antenatal care, and an accurate and reliable ultrasound service is essential for confident patient management. Qualitative findings, e.g. fetal normality and placental site, may be confirmed at delivery, but this form of audit is not suitable for fetal measurements owing to the variation in gestation at delivery and the complexity of neonatal assessment. Our aim was to develop a simple audit method applied a short time after the ultrasound scan. The method was based on assessment of measured images against measurement criteria which are clearly defined in the literature, results for each criterion being recorded in a spreadsheet. Two main forms of report were generated, the first showing overall achievement of satisfactory measurements for each sonographer, the second providing graphical information to show which criteria required greater attention by individual sonographers. Over several phases of audit problems of quality recognition and technical skill were isolated, graphical reports were used to guide tuition and the levels of performance were improved. The method itself and the results satisfy managers at all levels that standards are in place and are being maintained.

Embryonic and Fetal Development,Female,Fetal Growth Retardation,Fetus,Gestational Age,Humans,Medical Audit,Obstetrics,Pregnancy,Quality Assurance, Health Care,Ultrasonography, Prenatal

1515891,1611369,1747613,2161010,2425202

8220968

A double blind study to evaluate the tolerability of gadodiamide injection and its effect on renal function in patients undergoing cerebral magnetic resonance imaging.

Gadodiamide injection was administered intravenously to 28 patients with cancer undergoing cerebral magnetic resonance imaging (MRI). Two parallel groups were used to evaluate the safety of single doses of 0.1 and 0.3 mmol per kilogram body weight (kgbw). Adverse events, vital signs, blood chemistry, haematology and urinalysis were the principal measures of safety. Four patients, all in the 0.1 mmol kgbw-1 group, experienced a total of six adverse events. No adverse events were reported in the 0.3 mmol kgbw-1 group. No clinically significant changes in blood chemistry, haematology or urinalysis occurred. No significant changes in renal tubular function or glomerular filtration rate were observed after injection at either dose. Overall, this study suggests that gadodiamide injection is a safe and effective contrast medium for use in patients undergoing cerebral MRI at both the 0.1 and 0.3 mmol kgbw-1 doses.

Adult,Aged,Brain Neoplasms,Contrast Media,Double-Blind Method,Female,Gadolinium DTPA,Humans,Kidney,Kidney Function Tests,Lung Neoplasms,Magnetic Resonance Imaging,Male,Melanoma,Middle Aged,Organometallic Compounds,Pentetic Acid

1732960,1947084,2187515,2195593,2283251,2681935

8220969

Does the Whitaker test add to antegrade pyelography in the investigation of collecting system dilatation in renal allografts?

Significant pelvicalyceal dilatation in renal allografts is currently investigated by antegrade pyelography. However, the clinical significance of a radiologically demonstrated narrowing of the ureter is unclear. Over a 21-month period 26 of 155 renal allografts with pelvicalyceal dilatation were investigated by antegrade pyelography. In eight allografts no ureteric stenosis could be identified. Two grafts were shown to have ureteric necrosis and required surgical intervention and 16 of the other grafts appeared to have a ureteric stenosis. 15 of the 16 allografts with radiological ureteric stenosis underwent a concurrent pressure flow study to assess the functional relevance of the ureteric narrowing. As shown by a pressure rise of > 7 mmHg at a perfusion rate of 10 ml min-1, 11 of the 15 grafts were functionally obstructed and were treated by a nephrostomy catheter followed by antegrade insertion of a ureteric stent. The four grafts with a negative pressure flow study were subsequently shown on biopsy to have rejection. The diagnosis of allograft rejection was also confirmed by biopsy in seven of the eight allografts without a radiological ureteric stenosis. The last of the eight allografts was found to be cyclosporin toxic. Pelvicalyceal dilatation of renal allografts is appropriately investigated by antegrade pyelography in combination with a pressure flow study which identifies those grafts with mechanical obstruction.

Adult,Constriction, Pathologic,Dilatation, Pathologic,Female,Graft Rejection,Humans,Kidney Calices,Kidney Pelvis,Kidney Transplantation,Male,Postoperative Complications,Pressure,Prospective Studies,Radiography,Rheology,Ureteral Obstruction

695143,1870753,3544032,3804751,4566354,4690146,4783984,4903519,5331812,6385628,7109106,7317729,7410018,14282523,21322980

8220970

Quantification of image persistence in a digital angiography system.

Image persistence, as a characteristic of video imaging systems affecting the quality of fast moving fluoroscopic images, is shown to vary considerably. A simple quantitative method for measuring image persistence in a digital angiography system is presented, together with a series of image intensifier exposure-response curves. For the Saticon tube, used with the Siemens 3VA Digitron, it was found that persistence increased for low exposure rates and may increase to 31% at a 120 ms interval. In addition, a sharp increase in image persistence, from 8.3% to 33%, was observed within 18 months from installation of the system.

Angiography, Digital Subtraction,Fluoroscopy,Humans,Technology, Radiologic,Time Factors

3952315,4716619,5906194,6691117

8220971

Fat suppressed magnetic resonance imaging at 0.5 T using binomial radiofrequency pulses.

Fat suppressed MR imaging can be achieved by selectively saturating lipid protons, just before applying a conventional spin-echo rf pulse sequence. The difference in the Larmor frequency between fat and water protons is only 3.5 ppm, so that the frequency response of the suppressing pulse, or pulses, has to be carefully designed. The choice of suitable binomial and modified trains of hard rf pulses was investigated by computer simulation, phantom testing and T1 weighted spin-echo imaging of a normal volunteer's optic nerve at 0.5 T.

Computer Simulation,Fats,Humans,Image Enhancement,Lipids,Magnetic Resonance Imaging,Models, Structural,Optic Nerve,Protons,Radio Waves

1540803,2014300,2811618,4001160,6144846,6470246,6482839

8220972

Evolution of diagnostic radiology in a big hospital during a 5 year period, and the derived collective dose.

An analysis is presented of the trends in the annual number of radiological examinations and in the average effective dose equivalent for each type of examination in a big Spanish hospital. Annual frequencies for each type of examination, annual average effective dose equivalent values for each study group, and the contribution of each examination group to the collective dose are presented. Also, sex and age distributions for several important examinations are given, and their impact on the collective dose is reviewed.

Adolescent,Adult,Aged,Child,Child, Preschool,Female,Hospitals, University,Humans,Infant,Male,Middle Aged,Radiation Dosage,Radiography,Radiology Department, Hospital,Spain

1954535,2070186,2236205,2400894,2704768,2914187,3280075,3350660,20863787

8220973

Radiation exposure to the hands of orthopaedic surgeons during procedures under fluoroscopic X-ray control.

The hands of the surgeon are most likely to be directly exposed to ionizing radiation during fluoroscopic screening in the orthopaedic theatre. There is however little information available on the level of exposure to radiation during the normal working pattern of individual surgeons. The purpose of this study was to directly measure the radiation exposure to the hands during fluoroscopic screening in a series of consecutive cases over a month in order to establish whether these staff need to be designated classified persons, and if not, whether they need to be routinely monitored. Extremity monitoring was carried out using thermoluminescent dosimeters. The dosimeter was secured to the operating surgeon's dominant index finger. 44 procedures were carried out by nine different surgeons. The total radiation dose received per surgeon ranged from 48-2329 microSv. In 80% of procedures the dose of radiation to the surgeon's hand was less than 100 microSv. The extrapolated annual dose, even for the surgeon with the highest radiation exposure, was well below the annual dose limit for extremities of 500 mSv per year recommended by the International Commission on Radiological Protection, and embodied in the Ionizing Radiations Regulations 1985. Despite the relatively low doses of radiation received by surgeons in this study, occupational exposure to all personnel should be kept to the lowest practicable levels, and a review of procedures, including dose measurements, from time to time is advised.

Fingers,Fluoroscopy,Hand,Humans,Occupational Exposure,Operating Rooms,Orthopedics,Physicians,Radiation Dosage,Radiation Monitoring

1587871,3597477,7364839

8220974

Dual X-ray absorptiometry: a comparison between fan beam and pencil beam scans.

The recent introduction of dual X-ray absorptiometry (DXA) systems with fan beam instead of conventional pencil beam scanning geometry represents a significant technical advance in bone densitometry. This report describes phantom and in-vivo studies of the effect of the change in beam configuration on DXA measurements. Fan beam and pencil beam measurements acquired on one of the new generation scanners, the Hologic QDR-2000, were compared with scans performed on an earlier pencil beam model, the Hologic QDR-1000. The variation with height above the scanning table of fan beam measurements of an anthropomorphic spine phantom were: bone mineral content (BMC): -3.1% cm-1; projected area (AREA): -2.8% cm-1; bone mineral density (BMD): -0.2% cm-1. For pencil beam scans the magnitude of height variation was less than 0.1% cm-1. QDR-2000 fan and pencil beam scan results for 20 volunteers correlated closely with QDR-1000 pencil beam data (r = 0.966-0.998). For BMD measurements on the spine and hip, differences between fan and pencil beam data were consistent with the errors expected from measurement precision. For AREA and BMC data, however, larger differences were observed with individual deviations which correlated with body habitus of the subjects. Although the change from pencil to fan beam geometry significantly affected AREA and BMC data, the effect on the clinically more important BMD measurements was negligibly small.

Absorptiometry, Photon,Adult,Bone Density,Female,Femur,Humans,Lumbar Vertebrae,Male,Models, Structural

2036569,2493329,2666997,2758245,2921984,3193817,3417851,8453507,8472126

8220975

The 62 MeV proton beam for the treatment of ocular melanoma at Clatterbridge.

A second treatment room and beam line has been constructed at the Cyclotron Unit at Clatterbridge for the purpose of using 62 MeV protons for the treatment of ocular melanoma. A uniform beam is produced by a double foil scattering system. The initial Bragg peak is spread across the target volume by the use of beam modulators. These are rotating four-vaned stepped absorbers made from Perspex. Two beam lines can be configured with different positions of modulators and range limiters. The first has a maximum penetration of 31.9 +/- 0.2 mm in water and the second a penetration of 31.2 +/- 0.2 mm. The second configuration has the advantage of less variation in beam penumbra, with a typical value of 1.7 +/- 0.1 mm for the 90% to 10% decrement lines. The patients are treated with individually shaped collimators. Beam output varies by less than 2% over the range of collimator areas used. The resulting whole-body dose equivalent to patient has also been assessed. In the first three years of operation over 250 patients have been treated.

Eye Neoplasms,Humans,Melanoma,Protons,Radiation Dosage,Radiotherapy Dosage,Radiotherapy, High-Energy,Scattering, Radiation

99132,407436,2020756,4624458,6251410,6300000,6308407,6327577

8220976

Radiation risks to personnel and public during the treatment of malignant glioma using interstitial brachytherapy.

125I seeds are used in brachytherapy for the treatment of malignant gliomas. The use of such radioactive sources is associated with a certain radiological hazard to both personnel and members of the public. This hazard should be quantified so that the ALARA principle of radiological protection may be implemented satisfactorily. A study was undertaken to derive isodose rate contours in the vicinity of an anthropomorphic phantom with 125I seeds positioned at typical tumour sites within the cranial cavity. These contours are illustrated for seed positions appropriate to deep and superficial temporal tumours. Results indicate that the annual doses to personnel and public should not exceed those recommended by the International Commission on Radiological Protection.

Air Pollutants, Radioactive,Brachytherapy,Glioma,Head and Neck Neoplasms,Humans,Iodine Radioisotopes,Models, Structural,Occupational Exposure,Radiation Dosage,Risk Factors

1472320

8220977

The detection and modification of the hypoxic fraction in quiescent cell populations in murine solid tumours.

Mice bearing SCC VII or EMT6/KU tumours were irradiated after receiving 10 injections of 5-bromo-2'-deoxyuridine (BUdR) to label all proliferating tumour cells, and the tumours were then excised and trypsinized. The tumour cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BUdR labelling was determined using immunofluorescence staining to BUdR. This MN frequency was then used to calculate the surviving fraction of unlabelled cells from the regression line for the relation between MN frequency and the surviving fraction of all tumour cells. Thus a cell survival curve could be determined for cells not labelled by BUdR, which can be regarded as quiescent tumour cells for all practical purposes. Assays performed immediately after irradiation of both normally aerated and hypoxic tumours showed that quiescent cells contained higher hypoxic fractions than the tumour cells as a whole. Furthermore, administration of nicotinamide before irradiation or the placement of mice in a circulating carbogen (95% O2, 5% CO2) chamber for 30 min before and during irradiation altered the acutely and chronically hypoxic fractions of the proliferating and quiescent tumour cell populations in a way which depended on the tumour system. Combined nicotinamide and carbogen therapy was shown to have a large potential to sensitize cells to low-dose radiation in vivo. In addition, this assay method appears to be useful for determining the size of the hypoxic fraction of quiescent tumour cells in murine solid tumours.

Animals,Carbon Dioxide,Carcinoma, Squamous Cell,Cell Survival,Female,Mice,Mice, Inbred BALB C,Mice, Inbred C3H,Niacinamide,Oxygen,Radiation Tolerance,Radiation-Sensitizing Agents,Sarcoma,Tumor Cells, Cultured

69192,277250,486895,624118,850735,1410588,1705716,1835542,1902320,1974577,2138679,2141694,2147577,2523079,2564035,2573679,2595530,3095287,3179180,3282077,3884559,4005844,4075848,4684814,4797025,5067983,6735758,14472535

8220981

Case report: primary intrathoracic rhabdomyosarcoma: a rare childhood malignancy.

Primary intrathoracic rhabdomyosarcoma is a rare tumour in childhood. Three cases are presented and the radiological findings and clinical course are reviewed. The radiological manifestations are varied but a rapidly growing soft tissue mass with compression of adjacent structures is the most common. A rare association with an underlying congenital pulmonary cyst is described. The prognosis is worse than for rhabdomyosarcoma at other sites, with a predisposition for cerebral metastases.

Brain Neoplasms,Child,Child, Preschool,Female,Humans,Lung Neoplasms,Male,Mediastinal Neoplasms,Rhabdomyosarcoma,Tomography, X-Ray Computed,Ultrasonography

336175,880565,2235763,2407808,2781034,3045426,3275486,3276383,7046905,7277149,7393674

8220982

Case report: an unusual cause of epistaxis: non-traumatic intracavernous carotid aneurysm. A case report with 12 year follow-up and review of the literature.

Intracavernous carotid aneurysms are uncommon. We report the natural history and radiological appearances of a giant, non-traumatic, intracavernous carotid aneurysm which extended through the skull base to the anterior nares and caused epistaxis. The magnetic resonance imaging appearances of such an aneurysm have not been previously described. The importance of correct diagnosis is discussed.

Aged,Aneurysm,Carotid Artery Diseases,Carotid Artery, Internal,Epistaxis,Follow-Up Studies,Humans,Male,Tomography, X-Ray Computed

224124,424978,872841,1265635,1561338,1636524,1724297,1776523,1791940,2112306,2345510,2362671,2980423,3745564,3755981,3786749,3966131,4058691,5032739,5108508,5488803,5973594,6940554,13487017,13784831,14471553

8220983

Case report: infected false aneurysm at the site of an iliac stent.

False aneurysm formation at the site of iliac artery stent placement is an uncommon but serious complication of the procedure. We report a case of infected false aneurysm at the site of an iliac stent, complicated by renal failure.

Acute Kidney Injury,Aneurysm, False,Aneurysm, Infected,Arterial Occlusive Diseases,Humans,Iliac Artery,Male,Middle Aged,Staphylococcal Infections,Stents,Tomography, X-Ray Computed

1423389,1832069,2137638,2528172,2957018,2961399,6230061,7241894

8220985

Incidentally discovered solid renal masses: what are they?

In 36 of 99 consecutive patients operated on for the presumptive diagnosis of renal carcinoma the tumour was discovered accidentally during investigations for a variety of complaints. CT and ultrasound scans were responsible for discovery of the tumour in 24 of the 36 patients. Renal carcinoma accounted for 92% of incidentally discovered solid renal masses. Of 33 incidentally diagnosed renal carcinomas 27 were stage 1. An incidentally discovered solid renal mass should be regarded as a low stage renal carcinoma until proven otherwise.

Aged,Carcinoma, Renal Cell,Female,Follow-Up Studies,Humans,Kidney Neoplasms,Male,Middle Aged,Prognosis

2644658,2660538,3066275,3277239,3319006,3411657,3897735,3940366,4057398,5765875,7180965

8220986

Severe sepsis following percutaneous or endoscopic procedures for urinary tract stones.

Nine cases of severe sepsis following percutaneous or endoscopic procedures for upper urinary tract stones are reported. The mortality rate was 66%. Despite the fact that approximately 700 procedures were carried out in males and females in roughly equal proportions, a striking but inexplicable feature was that all 9 patients in the study group were female. Severe systemic sepsis has a high mortality rate and any procedure that may put patients at risk of this complication should not be undertaken lightly (and certainly not as an out-patient procedure). Recovery is possible with a high index of suspicion, early intervention and intensive treatment.

Adolescent,Adult,Aged,Aged, 80 and over,Endoscopy,Female,Fever,Hemodynamics,Humans,Hypotension,Hypothermia,Lithotripsy,Middle Aged,Nephrostomy, Percutaneous,Postoperative Complications,Sepsis,Sex Factors,Urinary Calculi

1559102,1824030,1895450,1993270,2055068,2295231,2651003,2679705,2733105,2835680,3119090,6384378,7042206,7388346

8220987

The ureter in vitro: normal motility and response to urinary pathogens.

The effects of bacteria on in vitro ureteric contractility were studied, using a model which allowed selective exposure of organisms to the ureteric mucosa and smooth muscle, respectively. A cannula attached to a pressure transducer was ligated into the proximal lumen of 2.5-cm segments of canine ureter. The distal ureter was ligated to form a closed pressure monitored system, and the segment suspended in a 20-ml organ bath containing Krebs Henseleit buffer at physiological pH and temperature. Following onset of spontaneous activity, broths of Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa and Staphylococcus aureus were added to either the buffer solution or ureteric lumen in doses of > 10(6) organisms/ml. Experiments were repeated using heat-killed organisms, bacterial filtrates and E. coli endotoxin. Ureteric contractility was stimulated by organisms added to the buffer medium, but reversibly inhibited by bacteria placed in the ureteric lumen. Heat-killed organisms, endotoxin and live filtrates had no effect on normal motility when exposed to either the ureteric mucosa or muscularis respectively. These findings reflect the conflicting changes in ureteric motility seen in vivo when bacteria are administered systemically or directly into the ureteric lumen.

Animals,Bacterial Infections,Dinoprost,Dogs,Endotoxins,Escherichia coli Infections,Gentamicins,Histamine,Muscle Contraction,Organ Culture Techniques,Staphylococcal Infections,Ureter,Urinary Tract Infections

99855,4597432,4628237,4871354,5050427,14065706

8220988

Ureteric peristalsis studies in loin pain and haematuria syndrome: another diagnostic disappointment.

Although not a cause of progressive renal damage, loin pain and haematuria syndrome is nevertheless associated with significant morbidity. The management of pain often presents a formidable problem to urologists, physicians and general practitioners. An earlier study noted hold-up of urine in the renal pelvis and implicated this in the pathogenesis of pain. In this study we have failed to demonstrate an excess incidence of disordered urinary peristalsis in loin pain and haematuria syndrome.

Back Pain,Hematuria,Humans,Muscle Contraction,Radionuclide Imaging,Syndrome,Ureter

2236480,2702399,4180519,4227314

8220989

Metabolic appraisal of the effects of dietary modification on hypersensitive bladder symptoms.

The concentration of certain metabolites and amino acids appears to be changed in patients with the painful bladder syndrome interstitial cystitis. A study of the metabolism of the arylalkylamines (tryptophan, tyrosine, tyramine, phenylalanine) was carried out in 250 patients (237 females, 13 males), revealing an inability to synthesise normal amounts of serotonin and MHPG, a noradrenaline metabolite. Furthermore, the absence of ammonia and tryptophan in urine confirmed the presence of a membrane leak. Dietary restriction lessened the symptoms but did not alter specific abnormalities in dopamine metabolism. Dietary management offers a cost-effective therapeutic approach.

Amino Acids,Ammonia,Cystitis,Female,Hair Color,Humans,Male,Methoxyhydroxyphenylglycol,Serotonin,Tyramine

1933154,2207540,2685811,2896464,4353428,4397955,6435545,14803464

8220990

Response of the human neurogenic bladder to KCl, carbachol, ATP and CaCl2.

The in vitro pharmacological responses of the human neurogenic bladder to KCl, carbachol, ATP and CaCl2 have been analysed. The contractility (contractile strength and ED50) of neurogenic bladders was significantly increased when treated with carbachol, ATP and CaCl2. In contrast, there was no apparent difference in the responsiveness of neurogenic bladders when treated with KCl. There was no apparent correlation between pharmacological responsiveness and clinical parameters, such as gender, age or cystometric data, in the neurogenic bladders.

Adenosine Triphosphate,Adolescent,Adult,Calcium Chloride,Carbachol,Child,Child, Preschool,Culture Techniques,Dose-Response Relationship, Drug,Female,Humans,Male,Muscle Contraction,Potassium Chloride,Urinary Bladder,Urinary Bladder, Neurogenic

25686,37533,1683039,1875516,2070213,2545931,2874237,4027512,5866712,6209921,6296468,6308285,7426994

8220991

Search for mycobacteria in interstitial cystitis using mycobacteria-specific DNA probes with signal amplification by polymerase chain reaction.

The aetiology of interstitial cystitis is not known. Various infective agents have been postulated and although recognised as perpetrators of chronic inflammatory conditions, mycobacteria have never been satisfactorily excluded from interstitial cystitis. If present in interstitial cystitis tissue, mycobacteria exist either in very small numbers or in forms which contemporary staining techniques fail to recognise. We used a polymerase chain reaction with mycobacteria-specific DNA probes and found no evidence of mycobacterial involvement in 8 cases of proven interstitial cystitis.

Cystitis,DNA Probes,DNA, Bacterial,Electrophoresis, Agar Gel,Female,Humans,Mycobacterium,Mycobacterium avium,Polymerase Chain Reaction,Urinary Bladder

1195397,1349051,1851124,2471938,2999980,3044930,3197996,3260837,3379688,3451923,3625848,6626895

8220992

Urinary fibronectin in diagnosis and follow-up of patients with urinary bladder cancer.

The levels of fibronectin in urine from 106 patients with urinary bladder cancer, from 13 patients with benign urological disease and from 24 healthy control individuals were determined by an enzyme-linked immunosorbent assay (ELISA). The fibronectin levels in urine from patients with bladder cancer were higher than in patients with benign urothelial disease and in healthy controls. In 9 patients with bladder cancer, sampling was done both pre- and post-operatively. In these cases the fibronectin levels after operation were significantly lower than they had been before. Among 14 patients treated with BCG intravesically for superficial bladder tumours, those with complete remission of disease had less urinary fibronectin than those who did not respond to treatment. The data suggest that urinary fibronectin may be a useful marker for detecting urinary bladder cancer and for selecting patients for BCG treatment.

Albuminuria,BCG Vaccine,Biomarkers, Tumor,Fibronectins,Follow-Up Studies,Humans,Urinary Bladder Neoplasms,Urologic Diseases

534500,820877,1672916,1706234,3525861,7358503

8220993

Post-operative retention associated with acute prostatic infarction.

Twenty-one patients with post-operative retention following unassociated surgery and requiring transurethral resection of the prostate were compared with patients with acute retention (control group). Histological evidence of acute prostatic infarction was significantly increased in the post-operative retention group. Prolonged operative hypotension was associated with acute prostatic infarction, as were smoking and pre-existing cardiovascular disease.

Acute Disease,Age Factors,Aged,Aged, 80 and over,Humans,Infarction,Male,Postoperative Complications,Prostate,Prostatectomy,Urinary Retention

1709058,2059695,2478248,3208051,3793939,3949343,15405276,18144087

8220994

Evolving experience with radical prostatectomy.

Thirty-six radical prostatectomies were performed over an 8-year period; 25 suitable patients (70%) presented with symptoms of bladder outflow obstruction. In 15 cases (44%), initial digital rectal examination was not indicative of malignancy. The primary tumour was understaged pre-operatively in 17 patients (48%). In 14 cases (41%) the pre-operative biopsy grade was different from the grade assigned to the tumour following radical prostatectomy. Radical prostatectomy is being performed with increasing frequency: trends in morbidity have been identified.

Adult,Aged,Erectile Dysfunction,Humans,Male,Middle Aged,Neoplasm Staging,Prostatectomy,Prostatic Neoplasms,Urinary Incontinence

74424,1171723,2017806,2231891,2329614,2451037,2468796,2473221,2577187,3050542,3336108,3761443,4813554,5010714,5443849,6065517,6534493,6690752,6694916,6811766,6823718,6854789,7206085,7218450,7370941,18148289,20994811,29603168

8220995

Epinephrine reduces the severity of catheter-induced urethral inflammation by action at the alpha 2-adrenoceptors.

We have studied the contribution of epinephrine to experimentally induced urethral inflammation in the rat. Inflammation was induced by inserting latex strips into the urethra. The effects of various experimental procedures were assessed according to a 4-point scale based on histological findings. The results showed that 0.5 mg/kg epinephrine decreased the severity of catheter-induced urethral inflammation. This effect was blocked by the alpha 2-adrenergic agonist, yohimbine, but not by alpha 1 (prazosin), beta 1 (M32 MTC), or beta 2 (butoxamine) antagonists. The results suggest that the suppressive effect of epinephrine is mediated by action at the alpha 2 adrenergic receptor.

Animals,Epinephrine,Female,Rats,Rats, Sprague-Dawley,Receptors, Adrenergic, alpha,Urethra,Urethritis,Urinary Catheterization,Yohimbine

567626,1606988,1608545,2234496,2837769,2862149,6824864,6843427

8220996

Electromyography of cavernous smooth muscle during flaccidity: evaluation of technique and normal values.

Objective evaluation of the penile innervation in impotent patients is mostly restricted to examination of the somatic pudendal pathways. These tests provide little information on the pelvic-cavernous autonomic innervation of the corporeal bodies. Electromyography of the flaccid penile smooth muscle is a reproducible and non-invasive method of evaluating these autonomic pathways and the status of intrinsic smooth muscle. Examination techniques and normal values have been studied in 15 young and potent volunteers. Recordings in 13 patients with neuropathology and 57 impotent patients are discussed.

Adult,Alprostadil,Autonomic Nervous System,Electrodes,Electromyography,Erectile Dysfunction,Humans,Male,Muscle, Smooth,Penile Erection,Penis,Peripheral Nervous System Diseases

205522,1875491,2161208,2401304,2769848,2863393,3344558,6357906,6626852,7251326,7356219

8220997

Renal transplantation in young boys with posterior urethral valves: preliminary report.

Seven boys (mean age 38 months) with posterior urethral valves underwent renal transplantation between June 1988 and August 1991. Urodynamic studies were performed before transplantation in 6/7 patients. In 4 the investigation indicated bladders of capacity and compliance which were deemed suitable for transplantation. Two patients had poorly compliant bladders; one of these underwent bladder augmentation before engraftment and the other proceeded to transplantation without bladder surgery. Six patients have functioning renal allografts with a mean follow-up of 1.3 years and a mean plasma creatinine of 51.6 mumol/l. Mean glomerular filtration rate (ml/min/1.73 m2 SA) 6 months after transplantation was 76.8 and at 1 year it was 84.5. In one patient early rejection was followed by transplant nephrectomy. Careful pre-operative evaluation is mandatory for a successful outcome of renal transplantation in young boys with posterior urethral valves.

Body Height,Child, Preschool,Follow-Up Studies,Glomerular Filtration Rate,Humans,Infant,Kidney Transplantation,Male,Postoperative Period,Preoperative Care,Retrospective Studies,Urethra,Urinary Bladder,Urodynamics

458949,952550,1571214,1682747,1942347,2336745,2359158,2652648,3054157,3057230,3408870,4032575,6834505,6999174,7112792,7288943,8220998,14257744

8220998

Antenatal diagnosis of posterior urethral valves.

The antenatal histories of 42 patients with posterior urethral valves diagnosed between June 1987 and September 1990 were reviewed. The mothers of all patients had at least one ultrasound scan during pregnancy. Despite this, fetal uropathy was diagnosed in only 19 cases. The remaining 23 undiagnosed children presented acutely, all within the first 6 months of life. In 33 of 36 pregnancies scanned before 24 weeks' gestation, fetal urological pathology was undetected. Mean plasma creatinine (pCr) at presentation in the group antenatally diagnosed was 139 mumol/l and in those presenting acutely was 238 mumol/l. All pCr analysed were taken after at least 48 h of life. Renal function as measured by follow-up pCr was better in the antenatally diagnosed group during the first year of life. It would appear that a routine second ultrasound scan at 26 weeks' gestation or later would reveal more cases of posterior urethral valves and this information may improve the outcome in terms of renal function.

Acute Disease,Creatinine,Female,Follow-Up Studies,Humans,Kidney,Male,Pregnancy,Ultrasonography, Prenatal,Urethra

2106931,2186540,2186541,2207535,2404297,2647045,3046507,3408870,3724830,3944901,4625784,6875771,7189794

8221000

Intravesical ureteric plication and reimplantation for megaureters in children.

Historically, megaureters have always been a surgical dilemma for paediatric urologists. However, the evolution of modern diagnostic and surgical methods such as tailoring, folding and plication have made it possible to ensure successful correction in most patients. We report 17 megaureters (11 refluxing and 6 obstructing) in 11 children who were treated with intravesical plication and the trans-trigonal advancement technique between January 1986 and April 1991. Results were excellent in 11 ureters and satisfactory in 4. In one ureter additional surgery was needed because of obstruction at the implantation site and in another ureter reflux persisted. Intravesical plication and reimplantation is a good alternative procedure for grossly dilated ureters owing to its low morbidity and high success rate.

Child,Child, Preschool,Follow-Up Studies,Humans,Infant,Replantation,Ureter,Ureteral Obstruction,Urology,Vesico-Ureteral Reflux

380724,468516,845762,904053,1148615,4020983,5776032,7080323,7354523

8220999

Internal ureteric stenting following pyeloplasty reduces length of hospital stay in children.

The advent of totally internal ureteric stents has the potential to reduce hospital stay in paediatric pyeloplasty. Traditionally, discharge from hospital has followed removal of an external trans-anastomotic drain, usually 5 days to a week post-operatively. The use of totally internal catheters negates the need for nursing supervision by removing external attachments that a paediatric patient might inadvertently dislodge. The length of hospital stay for pyeloplasty using a Double-J ureteric stent was compared with our previous method of trans-anastomotic feeding tube nephrostomy drainage. The results show the use of Double-J stenting to be advantageous in paediatric pyeloplasty by decreasing considerably the length of hospital stay. This is clearly of benefit to the patient, who returns to the family setting much earlier. Despite the need for an outpatient endoscopic procedure to remove the stent, savings in treatment costs and improved efficiency of bed use are also achieved.

Anastomosis, Surgical,Child,Child, Preschool,Female,Humans,Infant,Kidney Pelvis,Length of Stay,Male,Postoperative Complications,Reoperation,Stents,Ureter,Ureteral Obstruction

753465,942750,2671411,2746781,3427329

8221017

An introduction to free radical biochemistry.

Free radicals are chemical species possessing an unpaired electron that can be considered as fragments of molecules and which are generally very reactive. They are produced continuously in cells either as accidental by-products of metabolism or deliberately during, for example, phagocytosis. The most important reactants in free radical biochemistry in aerobic cells are oxygen and its radical derivatives (superoxide and hydroxyl radical), hydrogen peroxide and transition metals. Cells have developed a comprehensive array of antioxidant defences to prevent free radical formation or limit their damaging effects. These include enzymes to decompose peroxides, proteins to sequester transition metals and a range of compounds to 'scavenge' free radicals. Reactive free radicals formed within cells can oxidise biomolecules and lead to cell death and tissue injury. Establishing the involvement of free radicals in the pathogenesis of a disease is extremely difficult due to the short lifetimes of these species.

Animals,Cells,Disease,Free Radicals,Humans,Hydrogen Peroxide,Reactive Oxygen Species,Superoxides

24176,431730,1554345,1593209,1672815,1937131,1989966,2000375,2159941,2172697,2180924,2283087,2345493,2352934,3007102,3289484,3290908,3319224,3753454,3944273,5925327,6306767,6326753,6557906,6830261

8221018

Measuring free radical reactions in vivo.

The increasing interest in the role of free radicals in the pathogenesis of human disease has led to an increased need for techniques to measure free radicals and their reactions in vivo and, most importantly, in the clinical situation. Free radicals are extremely reactive and thus short lived. Consequently, free radicals are not amenable to direct assay and free radical activity is usually assessed by indirect methods such as measurement of the various end products of reactions with lipids, proteins and DNA. A vast array of analytical techniques has been developed to measure these end products though not all of them are applicable to the clinical situation where the only samples normally available are blood, urine and expired breath. Lipid peroxidation is the most intensively studied process and provides a number of possibilities for assays. Protein and nucleic acid oxidation are attracting increasing attention at the present time. The techniques currently available, however, are limited to semi-quantitative assays of damage to broad classes of biomolecules and there is an urgent need for more specific and informative methods.

Animals,Antioxidants,DNA Damage,Electron Spin Resonance Spectroscopy,Free Radicals,Humans,Lipid Peroxidation,Proteins,Spin Labels

1376430,1591898,1606707,1650736,1663908,1785679,1958055,1978225,2122182,2130945,2233304,2233308,2806945,3026319,3311420,3319233,3593759,3719870,3769049,3954031,6265070,6427549,6592579,6727672,6727673

8221019

Free radicals in inflammation: second messengers and mediators of tissue destruction.

In recent years it has become increasingly apparent that, in man, free radicals play a role in a variety of normal regulatory systems, the deregulation of which may play an important role in inflammation. As examples, we discuss the second messenger roles of: NO in the regulation of vascular tone, O2.- in fibroblast proliferation and H2O2 in the activation of transcription factors such as NF kappa B. Other control mechanisms, the physiological function of which may be perturbed in inflammation, include: the oxidative modification of low density lipoprotein, the oxidative inactivation of alpha-1-protease inhibitor, DNA damage/repair and heat shock protein synthesis. At sites of inflammation, increased free radical activity is associated with the activation of the neutrophil NADPH oxidase and/or the uncoupling of a variety of redox systems, including endothelial cell xanthine dehydrogenase. Although free radicals, thus produced, have the capacity to mediate tissue destruction, either alone or in concert with proteases, we argue that disturbances in the second messenger and regulatory activities of free radicals may also contribute significantly to the inflammatory process.

Antioxidants,Free Radicals,Gene Expression Regulation,Humans,Inflammation,Joint Diseases,Lipid Peroxidation,Oxidation-Reduction,Reactive Oxygen Species,Respiratory Burst,Second Messenger Systems

24176,203852,1336435,1379434,1414678,1509265,1540043,1567393,1617671,1622409,1705416,1731812,1747135,1768159,1852778,1988141,1991041,1995350,2060830,2065663,2083718,2139072,2154966,2175606,2180385,2312718,2365992,2424462,2466695,2538368,2563454,2565501,2569096,2692124,2699880,2777815,2861323,2892049,2911585,3001140,3029864,3190747,3259248,3678827,3729941,3927174,4026409,4193527,4708010,6229408,6245661,6254535,6589630,6979049

8221020

Oxidative mechanisms in carcinogenesis.

Cancer in humans and animals is a multistep disease process. In this process, a single cell can develop from an otherwise normal tissue into a malignancy that can eventually destroy the organism. The complex series of cellular and molecular changes that occur through the development of cancers can be mediated by a diversity of endogenous and environmental stimuli. Active oxygen species and other free radicals have long been known to be mutagenic; further, these agents have more recently emerged as mediators of the other phenotypic and genotypic changes that lead from mutation to neoplasia. Free radical production is ubiquitous in all respiring organisms, and is enhanced in many disease states, by carcinogen exposure, and under conditions of stress. Free radicals may therefore contribute widely to cancer development in humans. This review explores the molecular mechanisms through which free radicals can participate in the carcinogenic process.

Animals,Copper,DNA Damage,Free Radicals,Gene Expression Regulation,Humans,Mutation,Neoplasms,Oxidation-Reduction,Oxygen,Reactive Oxygen Species

531105,1309939,1323299,1423838,1489934,1542496,1543538,1557408,1559619,1565630,1617671,1620118,1638701,1641400,1649454,1740012,1782351,1826106,1846971,1849843,1883198,1899997,1907361,1944333,1949015,1974571,1988141,1991121,1992344,2052015,2052552,2103319,2118682,2133096,2153054,2154966,2183352,2193855,2200535,2205403,2206282,2223758,2302755,2351135,2352934,2398062,2445498,2473778,2505261,2507133,2531845,2546943,2584227,2585501,2594029,2670300,2671703,2682525,2691340,2711187,2720899,2789690,2797048,2824034,2981433,2988786,3084079,3141421,3281769,3283542,3338107,3574469,3657837,3769133,3975611,5123332,5725551,6249344,6261698,6292719,6351251,6363924,6760198,6857269,6866091,11272116,16590131,18906315,19871084

8221021

Free radicals and myocardial reperfusion injury.

Ischaemic myocardial tissue will, inevitably, necrose if blood flow is not restored. Whilst reperfusion is always beneficial in terms of potential recovery of heart muscle, reperfusion in itself is believed to bring about cellular injury. While the causes of this 'reperfusion injury' are apparently multifactorial, there is now an increasing body of evidence to suggest that oxygen free radicals play a major role in the pathogenesis of reperfusion injury. The initial evidence for this hypothesis was indirect, based on the ability of free radical scavengers to limit myocardial injury in animal models. More recent work has utilised the highly specific technique of electron spin resonance (ESR) spectroscopy and ESR spin trapping to detect the free radical species. The evidence for free radical production on myocardial reperfusion will be presented along with details of human studies. The potential for a therapeutic intervention will also be briefly discussed.

Animals,Dogs,Free Radicals,Guinea Pigs,Humans,Mice,Myocardial Infarction,Myocardial Reperfusion Injury,Myocardium,Oxidation-Reduction,Oxygen,Rabbits,Reactive Oxygen Species,Thiobarbituric Acid Reactive Substances,Xanthine Dehydrogenase,Xanthine Oxidase

156,1175182,1309623,1525250,1663908,1670647,1845919,1973474,1985364,2088852,2167254,2223301,2297827,2397579,2496008,2822281,2822709,2833754,2981404,2985221,3018363,3029779,3283000,4726499,4749271,6263247,6282134,6323522,6420544,6638163,6837725,6869078,7060232,8385646

8221022

Involvement of oxygen radicals in shock related cell injury.

Shock-related organ failure evolves from a variety of starting points--ischemia, reperfusion, non-bacterial or bacterial inflammation--several mechanisms are involved. In addition to the effects of xanthine oxidase after ischemia/reperfusion, toxic oxygen species from phagocytes that accumulate in both intra- and extravascular tissue spaces are of central importance. A critical event is the contact (adhesion) of leukocytes to endothelial cells, which consequently are the targets for leukocyte products. Damage of membranes by lipid peroxidation and by exposure to mediators such as platelet activating factor (PAF), leukotrienes and proteases, leads to increased permeability, tissue oedema and organ dysfunction. Thus antioxidants and other agents that control phagocyte function are likely to contribute to the protection of the permeability barrier in shock states.

Burns,Free Radicals,Humans,Ischemia,Phagocytes,Reactive Oxygen Species,Reperfusion Injury,Shock, Hemorrhagic

1538604,1672794,1691539,1777958,2178795,2178796,2244491,2293967,2296063,2310102,2316621,2341349,2555632,2570531,2684447,2722020,2756341,2766820,2782442,2791564,2867261,2981404,2983902,3020994,3027453,3028669,3087941,3168171,3182491,3198764,3278007,3286599,3378479,3400111,3516882,3546193,3589678,3594734,3606663,3733595,3742740,3807357,3924109,4031060,6327114,6499481,6600748,6689876,6720220,6842628,6843043,7436121,7458923

8221023

Lipid peroxidation and its role in atherosclerosis.

A crucial step in the pathogenesis of atherosclerosis is believed to be the oxidative modification of low density lipoprotein (LDL). The oxidation of LDL is a free radical driven lipid peroxidation process and the aldehyde products of lipid hydroperoxide breakdown are responsible for the modification of the LDL apoprotein. Aldehyde-modified apoB protein has altered receptor affinity, causing it to be scavenged by macrophages in an uncontrolled manner with the development of foam cells and the initiation of the atherosclerotic lesion. The aldehydic products of lipid peroxidation may also be involved in other aspects of the development of the lesion. The oxidation of LDL may be prevented by its endogenous antioxidant compounds, most prominent of which is alpha-tocopherol. Consequently, an improved antioxidant status may offer possibilities for the prevention of this major disease.

Arteriosclerosis,Foam Cells,Free Radicals,Humans,Lipid Peroxidation,Lipoproteins, LDL,Oxidation-Reduction

1329721,1348295,1349935,1398217,1495978,1510670,1558837,1576117,1590824,1591855,1637852,1690354,1693069,1756027,1770314,1798277,1819474,1861629,1884464,1937142,1978674,1985404,1991843,2072039,2130945,2302177,2322097,2455346,2648148,2722022,3102491,3472245,6587396,7073805

8221024

Free radicals in brain metabolism and pathology.

Reactive oxygen metabolites (ROM), namely superoxide and hydroxyl free radicals and hydrogen peroxide, are produced as a consequence of the physiological metabolic reactions and functioning of the central nervous system. ROM have also been implicated in the aetiopathogenic processes of a number of pathological conditions of the brain. While primarily indirect, evidence for this view is accumulating, and credence for the participation of free radical oxidative interactions in promoting tissue injury in such conditions as brain trauma, ischaemia, and toxicity, and in neurodegenerative diseases such as Parkinson's disease, Alzheimer's dementia, multiple sclerosis, and lipofuscinosis, is growing. Concomitant with this new understanding of the injurious role of free radical oxidants in neural pathology, is the increasing appreciation for the need for both fundamental and clinical research into the development of the potential preventative and therapeutic benefits that are now being foreseen for a variety of antioxidant nutritional and pharmacological interventions.

Alzheimer Disease,Antioxidants,Brain,Brain Diseases,Brain Ischemia,Free Radicals,Humans,Parkinson Disease,Reactive Oxygen Species,Superoxide Dismutase

1353273,1372157,1497677,1538834,1575097,1673789,1674295,1683703,1757340,1886545,1892331,1907518,1970085,2016074,2036620,2058418,2082650,2146522,2325161,2359533,2484393,2576375,2657463,2663662,2677252,2746294,2747857,2765907,2771164,2824645,2861853,2866501,2890848,2903225,2966094,3057813,3343616,3676717,4031880,6217779,6704790,7074296,15374445

8221025

Free radicals and lung disease.

The involvement of reactive oxygen species (ROS) in the pathogenesis of several lung diseases/injuries has been suggested. ROS are believed primarily to be generated by leukocytes (e.g. infiltrating neutrophils) although other ROS generating systems such as the xanthine/xanthine oxidase system may also be of importance. ROS may through oxidative changes exert a number of toxic effects which have been demonstrated in many different biological systems. At limited oxidative stress events such as modification of receptor activity and signalling, as well as release of endogenous mediators of inflammation may occur. One such ROS induced event, probably of importance for several lung diseases, is arachidonic acid (AA) release and metabolism to active product(s). In the lung, the release of AA results in both vaso- and bronchoconstriction, primarily caused by thromboxane A2. The molecular events leading to oxidant induced AA release and thromboxane formation are only partially elucidated.

Free Radicals,Humans,Ischemia,Lung,Lung Diseases,Reactive Oxygen Species,Reperfusion Injury

1346826,1355574,1728243,1757354,1860458,1898844,1905406,1928210,2018144,2026843,2116734,2120740,2123406,2172722,2253331,2260676,2272532,2405761,2412265,2452740,2459100,2467923,2499570,2514605,2536967,2543821,2606858,2732159,2734729,2905259,3007208,3019528,3039883,3122612,3143279,3144200,3188006,3289484,3491382,3740648,3767130,3917993,6100034,6167268,6209387,7305901

8221026

Liver damage due to free radicals.

The involvement of free radical reactions in the pathogenesis of liver injury has been investigated for many years in a few defined experimental systems using carbon tetrachloride, excess iron or ethanol as prooxidant agents. More recently, the hepatotoxicity of several other free radical-generating compounds has been characterised mainly in the rat hepatocyte model. In particular, the mechanisms by which drugs like paracetamol, halothane, paraquat or conditions such as ischemia-reperfusion exert their damaging activity to the liver have mostly been clarified. Since we are not trying to cure diseases occurring only in rats, the likely relevance of free radical reactions also in the genesis and progression of human liver injury has been carefully considered. Increasing evidence of free radical involvement is reported for chronic ethanol intoxication and iron overload, but the most striking proof of a causative role of ree radical chain reactions, namely lipid peroxidation, in the acute lethal damage of the hepatocyte has been obtained so far in ischemic hepatitis.

Alcoholism,Animals,Carbon Tetrachloride,Chemical and Drug Induced Liver Injury,Disease Models, Animal,Ethanol,Free Radicals,Humans,Iron,Lipid Peroxidation,Liver,Liver Diseases,Mice,Oxidation-Reduction,Rats

36387,444227,475847,629802,739842,1252619,1323148,1398481,1505665,1599497,1701572,1740015,1884917,1891769,1934311,1937131,1973179,2039543,2040703,2111233,2153094,2187293,2327791,2337417,2344369,2370854,2604730,2628233,2684438,2777815,2827172,2837334,2917023,3032192,3055109,3059192,3280885,3282347,3307585,3319224,3378038,3682765,3718853,3755798,3803133,3943787,3968976,4004782,4039940,4378683,4821036,5541769,6181068,6254573,6288023,6290784,6348456,6383353,6860357,6985597,7159389

8221027

Involvement of reactive oxygen species in kidney damage.

There is considerable evidence suggesting that reactive oxygen species (ROS) are implicated in the pathogenesis of ischemic, toxic, and immunologically-mediated renal injury. In experimental renal ischemia, ROS sources include the electron transport chain, oxidant enzymes (xanthine oxidase), phagocytes, and auto-oxidation of epinephrine. ROS cause lipid peroxidation of cell and organelle membranes and, hence, disruption of the structural integrity and capacity for cell transport and energy production, especially in the proximal tubule segment. In experimental immune glomerulonephritis, ROS are generated by both infiltrating blood-borne cells (polymorphonuclear leukocytes and monocytes) and resident glomerular cells, mainly mesangial cells. Their formation results in morphologic lesions and in modifications of glomerular permeability to proteins through activation of proteases and reduction of proteoglycan synthesis. Additionally, they promote a reduction in glomerular blood flow and glomerular filtration rate through liberation of vasoconstrictory bioactive lipids (prostaglandins, thromboxane, and platelet activating factor) and, possibly, inactivation of relaxing nitric oxide. Further studies are needed to address the role of ROS in human glomerular diseases.

Humans,Kidney,Kidney Diseases,Kidney Glomerulus,Reactive Oxygen Species,Reperfusion Injury

1319220,1386085,1405339,1600128,1631123,1635356,1657945,1662318,1721553,1753921,1910124,2074654,2176255,2298907,2540375,2671460,2926243,3022602,3025261,3414803,6086713,6090809,6315851,7300122

8221028

Free radicals and muscle damage.

Muscle tissue is unique in its requirement and ability to undertake very rapid and co-ordinated changes in energy supply and oxygen flux during contraction. Several studies have suggested that this renders the tissue particularly prone to oxygen radical-mediated damage. Free radicals have been postulated to play a role in muscle damage induced by different forms of exercise and in various pathological disorders, such as the muscular dystrophies, malignant hyperthermia and alcoholic myopathy. However, conclusive evidence for a fundamental role for free radicals and protective effect of antioxidants remains elusive in all these situations and much further work on the relevant pathogenetic mechanisms is still required.

Animals,Antioxidants,Exercise,Free Radicals,Humans,Lipid Peroxidation,Muscles,Muscular Diseases,Rats

108286,448449,466816,579051,730598,1315657,1629069,1647917,1647925,1767636,1845917,1889565,1932145,1967823,2054745,2119221,2221920,2316631,2323584,2360189,2361912,2540451,2829976,2919833,2932118,2981404,2995229,2998478,3066491,3166626,3173492,3298399,3319190,3356628,3378967,3698311,3716883,3821787,3826874,3847097,3893544,3935926,3989240,4042285,4404507,6145845,6291524,6420110,6437835,6471926,6471931,6557905,6557908,6726273,6822050,6826426,6846068,6861450,7113765,7246094,7253831,7261410,7398093,7410473

8221029

Diabetes mellitus and free radicals. Free radicals, transition metals and oxidative stress in the aetiology of diabetes mellitus and complications.

Diabetes mellitus is a syndrome initially characterized by a loss of glucose homeostasis. The disease is progressive and is associated with high risk of atherosclerosis, kidney and nerve damage as well as blindness. Abnormalities in the regulation of peroxide and transition metal metabolism are postulated to result in establishment of the disease as well as its longer term complications. Diabetes mellitus is associated with oxidative reactions, particularly those which are catalyzed by decompartmentalized transition metals, but their causative significance in diabetic tissue damage remains to be established.

Alloxan,Animals,Arginine,Diabetes Complications,Diabetes Mellitus,Free Radicals,Glucose,Humans,Lipid Peroxidation,Lysine,Metals,Oxidation-Reduction,Oxygen Consumption,Rats,Reactive Oxygen Species,Streptozocin

233637,454385,496003,669100,1117971,1247213,1378415,1554398,1628764,1733803,1797628,1904866,1904867,1909528,1946446,2043128,2120080,2125497,2227114,2298912,2384174,2492477,2513322,2521836,2792574,2836250,2851978,3075947,3082871,3117042,3135299,3328701,3408736,3409983,3557287,3918302,3924690,3930319,3945267,3956733,3995058,4010088,4046501,4828815,6097689,6357907,6373141,6422213,6439587,6495252,6582514,6698315,6758791,6818073,6852773,6858545,7113741,7297791