bluuebunny/crossref_metadata_2025 huggingface dataset:
Caffeine stimulates the reverse mode of Na+/Ca2+ exchanger in ferret ventricular muscle
Authors: Léoty C. , Huchet‐Cadiou C. , Talon S. , Choisy S. , Hleihel W.
Published: March 2003

This study investigated the effect of caffeine on the sarcolemmal mechanisms involved in intracellular calcium control. Ferret cardiac preparations were treated with ryanodine and thapsigargin in order to eliminate the sarcoplasmic reticulum (SR) function. This treatment abolished caffeine contracture irreversibly in normal solution. The perfusion with K‐free medium that blocked the Na+–K+ pump resulted in a recovery of slow relaxing caffeine contractures similar to Na‐free contractures. The amplitude of caffeine contractures was dependent on the bathing [caffeine]o and [Ca2+]o. Divalent cations Ni2+ and Cd2+, which have an inhibitory effect on the Na+/Ca2+ exchanger, produced dose‐dependent inhibition of caffeine responses with apparent Ki of 780 ± 19  and 132 ± 5 μM, respectively. Caffeine also caused dose‐dependent inhibition of Na‐free contractures (Ki=4.62 ± 1.5 mM), and the reduction or removal of [Na+]o exerted an inhibitory effect on caffeine contractures (Ki=73.5 ± 17.12 mM). These experiments indicate that the increase in resting tension following exposure to caffeine was mediated by Na+/Ca2+ exchanger, which represents an additional element of complexity in caffeine action on cardiac muscle.
Acute effects of pulmonary artery banding in sheep on right ventricle pressure–volume relations: relevance to the arterial switch operation
Authors: Hon J. K. F. , Steendijk P. , Khan H. , Wong K. , Yacoub M.
Published: March 2003

The first stage of the two‐stage arterial switch operation (ASO) for transposition of the great arteries (TGA) is associated with depressed ventricular function and an unstable immediate post‐operative course. It is unclear if this is because of the acute increase in afterload of the thin‐walled, low‐pressure ventricle by pulmonary artery banding (PAB). To determine the acute effects of afterload increase on the contractile function of thin‐walled ventricles, we studied the right ventricular pressure–volume relations of seven sheep before and 30 min after PAB using combined pressure–conductance catheters during inflow reduction. Load independent indices of systolic and diastolic performance were derived from these relations. Pulmonary artery banding increased the mean ratio between right and left ventricular systolic pressure from 0.34 ± 0.05 to 0.64 ± 0.10, P < 0.05 (mean ± SD). There were no significant changes in heart rate and end‐systolic volume after banding although there was an incremental trend in the end‐diastolic volume and stroke volume. Right ventricular output (530 ± 163–713 ± 295 mL min–1, P < 0.05), slope of the end‐systolic pressure–volume relation (ESPVR) (3.7 ± 2.8–10.0 ± 4.8 mmHg mL–1, P < 0.05) and slope of the pre‐load recruitable stroke work (PRSW) relation (9.6 ± 1.8–15.0 ± 3.1 mmHg, P < 0.05) were significantly increased indicating improved contractile state after banding. The diastolic function curve was unchanged after banding although the right ventricle (RV) was operating at a larger end‐diastolic volume. Hence, the RV of sheep responded to acute pressure overload by demonstrating enhanced contractility and evidence of the Frank–Starling mechanism without associated change in right ventricular diastolic performance.
An ordinary mixed meal transiently impairs endothelium‐dependent vasodilation in healthy subjects
Authors: Sarabi M. , Fugmann A. , Karlström B. , Berne C. , Lithell H. , Lind L.
Published: March 2003

This study was designed to evaluate the effects of an ordinary mixed meal on endothelium‐dependent vasodilation. Ten young healthy volunteers were given a mixed meal (minced meat sauce with rice, 900 kcal, 34% of the energy content was fat). In the fasting state, at 60 and 120 min after the start of the meal, endothelium‐dependent vasodilation and endothelium‐independent vasodilation were evaluated by local infusion of metacholine (4 μg min–1) and sodium nitroprusside (10 μg min–1) in the brachial artery. Blood flow in the forearm was measured using venous occlusion plethysmography. Endothelium‐dependent vasodilation decreased from 15.4 ± 3.3 (mean ± SD) at fasting to 13.7 ± 3.5 mL min–1 (100 mL tissue)–1 (P < 0.01) 60 min after feeding, but had returned to the fasting level at 120 min. At 60 min, but not in the fasting state, the serum level of free fatty acids was inversely related to endothelium‐dependent vasodilation (r=–0.74, P < 0.05), although no significant net changes in FFA levels were seen. Endothelium‐independent vasodilation was not affected by the mixed meal. No similar attenuations in endothelium‐dependent vasodilation were seen during control meals. In conclusion, an ordinary mixed meal transiently attenuated endothelium‐dependent vasodilation. Free fatty acids may be involved in this effect on endothelial function.
Additive hypothermic effects of the 5‐HT1A receptor agonist 8‐OH‐DPAT and the dopamine D2/3 receptor agonist 7‐OH‐DPAT in the rat
Authors: Eltayb A. , Lindblom S. , Oerther S. , Ahlenius S.
Published: March 2003

The objective of this study was to examine possible interactions between serotonergic and dopaminergic agents lowering core temperature via stimulation of 5‐HT1A and dopamine (DA) D2 receptors, respectively. The effects of the 5‐HT1A receptor agonist (±)‐8‐hydroxy‐2‐(di‐n‐propylamino)tetralin HBr (8‐OH‐DPAT) and the DA D2/3 receptor agonist 7‐OH‐DPAT on core temperature was monitored in adult male Wistar rats, approximately 300 g body weight. The temperature probe was connected to a PC‐assisted temperature instrument, and an automated printer device was activated when the temperature reading had stabilized (±0.1 °C) for 10 s. As expected, 7‐OH‐DPAT [0.5 and 2.0 μmol kg–1 subcutaneous (s.c.)] as well as 8‐OH‐DPAT (0.15–2.4 μmol kg–1 s.c.), produced a dose‐dependent hypothermia. When combined, there were additive effects of the two compounds, although the effects of 7‐OH‐DPAT were attenuated by 8‐OH‐DPAT at the higher doses (0.6–2.4 μmol kg–1), in all probability because of emerging DA D2 receptor blocking properties of the latter compound.
Splanchnic ischaemia–reperfusion injury: mechanistic insights provided by mutant mice
Authors: Granger D. N. , Stokes K. Y. , Shigematsu T. , Cerwinka W. H. , Tailor A. , Krieglstein C. F.
Published: March 2003

Reperfusion of ischaemic tissues often leads to microvascular dysfunction that is manifested as impaired endothelium‐dependent dilation of arterioles, enhanced fluid filtration and leucocyte plugging in capillaries, and the trafficking of leucocytes and plasma protein extravasation in postcapillary venules. Efforts to define the mechanisms that underlie these microvascular responses to ischaemia and reperfusion have largely relied on pharmacological agents and monoclonal antibodies. Gene‐targeting technology has been applied to the production of transgenic and knockout mice that are rapidly gaining acceptance as tools for mechanistic studies of ischaemia–reperfusion (I/R) injury that obviate some of the concerns (e.g. specificity) raised about previously employed experimental strategies. This review summarizes some of our efforts to apply gene‐targeted mice to the study of I/R injury in the splanchnic vascular bed. A role for endothelial cell adhesion molecules (CAMs) and reactive oxygen metabolites is supported by results from mutant mice. Low density lipoprotein receptor mice also reveal that the microvascular and inflammatory responses to I/R are greatly exaggerated during chronic hypercholesterolaemia. The wide variety of mutant mice that have been produced for inflammation‐related research makes this experimental strategy particularly promising for mechanistic investigations of the tissue responses to I/R.
The relationship of natural killer cell counts, perforin mRNA and CD2 expression to post‐exercise natural killer cell activity in humans
Authors: MILES M. P. , MACKINNON L. T. , GROVE D. S. , WILLIAMS N. I. , BUSH J. A. , MARX J. O. , KRAEMER W. J. , MASTRO A. M.
Published: March 2003

The aim of this study was to further investigate the mechanism of suppression of natural killer (NK) cell cytotoxic activity in peripheral blood following strenuous exercise. Blood was collected for analysis of NK cell concentration, cytotoxic activity, CD2 surface expression and perforin gene expression from runners (RUN, n=6) and resting controls (CONTROL, n=4) pre‐exercise, 0, 1.5, 5, and 24 h following a 60‐min treadmill run at 80% of VO2 peak. Natural killer cytotoxic activity, measured using a whole blood chromium release assay, fluctuated minimally in the CONTROL group and increased by 63% and decreased by 43% 0 and 1.5 h post‐exercise, respectively, in the RUN group (group × time, P < 0.001). Lytic index (cytotoxic activity per cell) did not change. Perforin mRNA, measured using quantitative real‐time polymerase chain reaction (QRT–PCR) decreased from pre‐ to post‐exercise and remained decreased through 24 h. The decrease from pre‐ to 0 h post‐exercise was seen predominately in the RUN group and was inversely correlated (r=– 0.95) to pre‐exercise perforin mRNA. The NK cell surface expression of CD2 (lymphocyte function‐associated antigen‐2) was determined using fluorescent antibodies and flow cytometry. There was no change in the proportion of NK cells expressing CD2 or CD2 density. We conclude that (1) numerical redistribution accounted for most of the change in NK cytotoxic activity following a strenuous run, (2) decrease in perforin gene expression during the run was inversely related to pre‐exercise levels but did not parallel changes in cytotoxic activity, and (3) CD2 surface expression was not affected by exercise.
Analysis of the tubuloglomerular feedback mechanism in renal autoregulation
Authors: KIIL F.
Published: March 2003

Along the juxtaglomerular segment of the afferent arteriole the luminal pressure p approaches the glomerular capillary pressure of 55–60 mmHg. At such low luminal pressures the myogenic mechanism contracts only if extravascular pressure pex is subatmospheric. According to Poiseuille's formula complete autoregulation requires that blood flow is F=5Kr04/Δx at arterial pressures exceeding 65 mmHg; r0 is the radius of the relaxed segment at transmural pressure p – pex ≤ 60 mmHg, where pex is the extravascular pressure; Δx is the length of the main preglomerular segment, 10 times longer than the juxtaglomerular segment. Consistent with in vitro studies a myogenic mechanism may reduce the relaxed juxtaglomerular radius rjx=0.7r0 by 40% at a transmural pressure of 140 mmHg. Fifty and 60% reductions are also considered. Integration of Poiseuille's formula shows that complete autoregulation of preglomerular blood flow requires negative extravascular pressures pex=–90 to –55 mmHg dependent on contractile force. Negative pressure of this magnitude is generated by effective hyperosmolality <5 mOsm across the membrane separating cleft from pole cushion. Negative pressure stays constant at arterial pressures exceeding 90–110 mmHg, implying constant tubuloglomerular feedback, but approaches atmospheric pressure at lower arterial pressure, suggesting maintenance of blood flow by reduction in the glomerular filtration rate; a rise in macula densa concentrations [NaCl]md by 0.15 mM or [NaHCO3]md by 2 mM raises extravascular pressure towards atmospheric levels by ≈40 mmHg. A 40‐mmHg rise in interstitial pressure exerts the same effect. Loop diuretics nullify osmotic force and dilate juxtaglomerular and main segments by raising juxtaglomerular extravascular pressure towards atmospheric levels.
Mechanisms of intercellular hypertonicity and isotonic fluid absorption in proximal tubules of mammalian kidneys
Authors: KIIL F.
Published: March 2003

The main purpose of this theoretical analysis (second of two articles) is to examine whether transjunctional diffusion of NaCl causes intercellular hypertonicity, which permits transcellular water transport across solute‐impermeable lateral cell membranes until osmotic equilibration. In the S2 segment with tubular NaCl concentration 140 mM, the calculated apical intercellular NaCl concentration is c0 ≈ 132 mM, which exceeds peritubular NaCl concentration by 12 mM or 22 mOsm kg–1. Variations in volume flow, junctional reflection coefficient (σNaCl=0.25–0.50), gap distance (g=6–8 Å), junctional depth (d=18–100 Å), intercellular diffusion coefficient (DLIS=500–1500 μm2 s–1) and hypothetical active NaCl transport alter c0 only by a fraction of 1 mM. However, dilution and back‐leakage of NaHCO3 lower apical intercellular hyperosmolality to ≈18 mOsm kg–1. Water transport through solute‐impermeable lateral cell membranes continues until intercellular and cellular osmolalities are equal. Transcellular and transjunctional volume flow are of similar magnitude (2 nL min–1 mm–1 tubule length) in the S2 segment. Thus, diffusion ensures isotonic absorption of NaCl. Two‐thirds of NaHCO3 and other actively transported sodium salts are extruded into the last third of the exponentially widening intercellular space where the exposure time is only 0.9 s. Osmotic equilibration is dependent on aquaporins in the cell membranes. If permeability to water is low, transcellular water transport stops; tubular fluid becomes hypotonic; NaCl diffusion diminishes, but transjunctional water transport remains unaltered as long as transcellular transport of NaHCO3 and other solutes provides the osmotic force.
Regulation of apical transporter of L‐DOPA in human intestinal Caco‐2 cells
Authors: FRAGA S. , SAMPAIO‐MAIA B. , SERRÃO M. P. , SOARES‐DA‐SILVA P.
Published: March 2003

The present study examined the nature of the apical inward L‐3,4‐dihydroxyphenylalanine (L‐DOPA) transporter in human intestinal epithelial Caco‐2 cells, and whether protein kinases modulate the activity of this transporter. The apical inward transfer of L‐DOPA was promoted through an energy‐dependent and sodium‐insensitive transporter (Km=33 μM; Vmax=2932 pmol/mg protein/6 min). This transporter was insensitive to N‐(methylamino)‐isobutyric acid, but competitively inhibited by 2‐aminobicyclo(2,2,1)‐heptane‐2‐carboxylic acid (BCH; IC50=83 μM). The organic cation inhibitor decynium 24 failed to affect the accumulation of L‐DOPA, whereas the organic anion inhibitor 4,4′‐diisothiocynatostilbene‐2,2′‐disulphonic acid (DIDS) competitively inhibited L‐DOPA uptake (IC50=83 μM). However, the apical‐to‐basal and basal‐to‐apical transepithelial transport and the cell accumulation of [3H]‐PAH was close to that of [14C]‐sorbitol and insensitive to DIDS (300 μM). Modulators of protein kinase A (PKA) [cyclic adenosine monophosphate (cAMP), forskolin, H‐89 and cholera toxin], protein kinase G (PKG) [cyclic guanosine monophosphate (GMP), zaprinast, LY 83583 and sodium nitroprusside] and protein kinase C (PKC) (phorbol 12,13‐dibutirate and chelerythrine) failed to affect the accumulation of L‐DOPA. The Ca2+/calmodulin inhibitors calmidazolium and trifluoperazine inhibited L‐DOPA uptake (IC50s of 53 and 252 μM, respectively), but the rise of intracellular Ca2+ by A23187 (1 μM) and thapsigargin (1 μM) played no role on L‐DOPA uptake. It is concluded that Caco‐2 cells take up L‐DOPA over the apical cell border through the sodium‐independent and pH‐sensitive L‐type amino acid transporter.
Intracellular sodium modulates the state of protein kinase C phosphorylation of rat proximal tubule Na+,K+‐ATPase
Authors: IBARRA F. R. , CHENG S. X. JUN , AGRÉN M. , SVENSSON L.‐B. , AIZMAN O. , APERIA A.
Published: March 2003

The natriuretic hormone dopamine and the antinatriuretic hormone noradrenaline, acting on α‐adrenergic receptors, have been shown to bidirectionally modulate the activity of renal tubular Na+,K+‐adenosine triphosphate (ATPase). Here we have examined whether intracellular sodium concentration influences the effects of these bidirectional forces on the state of phosphorylation of Na+,K+‐ATPase. Proximal tubules dissected from rat kidney were incubated with dopamine or the α‐adrenergic agonist, oxymetazoline, and transiently permeabilized in a medium where sodium concentration ranged between 5 and 70 mM. The variations of sodium concentration in the medium had a proportional effect on intracellular sodium. Dopamine and protein kinase C (PKC) phosphorylate the catalytic subunit of rat Na+,K+‐ATPase on the Ser23 residue. The level of PKC induced Na+,K+‐ATPase phosphorylation was determined using an antibody that only recognizes Na+,K+‐ATPase, which is not phosphorylated on its PKC site. Under basal conditions Na+,K+‐ATPase was predominantly in its phosphorylated state. When intracellular sodium was increased, Na+,K+‐ATPase was predominantly in its dephosphorylated state. Phosphorylation of Na+,K+‐ATPase by dopamine was most pronounced when intracellular sodium was high, and dephosphorylation by oxymetazoline was most pronounced when intracellular sodium was low. The oxymetazoline effect was mimicked by the calcium ionophore A23187. An inhibitor of the calcium‐dependent protein phosphatase, calcineurin, increased the state of Na+,K+‐ATPase phosphorylation. The results imply that phosphorylation of renal Na+,K+‐ATPase activity is modulated by the level of intracellular sodium and that this effect involves PKC and calcium signalling pathways. The findings may have implication for the regulation of salt excretion and sodium homeostasis.
Attenuation of the exercise‐induced increase in skeletal muscle Flt‐1 mRNA by nitric oxide synthase inhibition
Authors: GAVIN T. P. , WAGNER P. D.
Published: March 2003

We investigated the vascular endothelial growth factor (VEGF) receptor [fms‐like‐tyrosine kinase (Flt‐1 and fetal liver kinase‐1 (Flk‐1)] response to acute exercise. In female Wistar rats, the VEGF receptor messenger RNA (mRNA) response to a single acute exercise bout was examined using semi‐quantitative Northern blot from the left gastrocnemius muscles at rest and post‐exercise at 0, 1, 2, 4, 8, 16, 24 and 48 h. Exercise altered both Flt‐1 and Flk‐1 mRNA, with significant increases in Flt‐1 mRNA at 1 and 24 h. However, post‐hoc analysis was unable to discern the time point where a significant increase in Flk‐1 mRNA occurred. To investigate the regulation of Flt‐1 mRNA by exercise we examined if nitric oxide synthase (NOS) inhibition alters the Flt‐1 mRNA response. Eight groups [Condition: Rest or Exercise; Drug: Saline, 30 mg kg–1Nω‐nitro‐L‐arginine methyl ester (L‐NAME), 300 mg kg–1L‐NAME or 300 mg kg–1D‐NAME] were used to determine the effect of NOS inhibition on the Flt‐1 mRNA response to exercise. L‐NAME, a known NOS inhibitor, attenuated the exercise‐induced increase in Flt‐1 mRNA by ∼50%. These findings suggest that: (1) exercise alters Flt‐1 and Flk‐1 gene expression; and (2) NO is important in the regulation of the Flt‐1 gene response to exercise.
Evidence that action potential generation is not the exclusive determinant to trigger spontaneous myogenic contraction of guinea‐pig urinary bladder smooth muscle
Authors: Imai T. , Tanaka Y. , Okamoto T. , Yamamoto Y. , Horinouchi T. , Tanaka H. , Koike K. , Shigenobu K.
Published: March 2003

Urinary bladder smooth muscle (UBSM) exhibits spontaneous contraction. This spontaneous mechanical activity is myogenic and can be closely related to the UBSM cell action potential to facilitate Ca2+ influx through voltage‐gated Ca2+ channels. In the present study, to know whether this membrane electrical event is the exclusive mechanism to trigger spontaneous smooth muscle contraction, we compared the inhibitory effects of Ca2+ channel blockers on the spontaneous action potential and mechanical activity in the isolated guinea‐pig UBSM. Both action potential and rhythmic contraction were generated spontaneously in the presence of atropine (1 µM), phentolamine (1 µM), propranolol (1 µM), suramin (10 µM) and tetrodotoxin (1 µM), which suggest that both phenomena were myogenic in origin. Nisoldipine (100 nM) and diltiazem (10 µM) completely eliminated the generation of action potential whereas its frequency was dramatically increased by a dihydropyridine Ca2+ agonist, BayK 8644 (1 µM). In contrast to disappearance of action potential in the presence of Ca2+ channel blockers, spontaneous contraction of UBSM was inhibited only partly by nisoldipine or diltiazem and most of the mechanical components persisted in these channel blockers. These results indicate that spontaneous action potential in UBSM cell is generated through the activation of L‐type voltage‐gated Ca2+ channels. The subsequent elevation of intracellular Ca2+ concentrations during a burst of action potentials can be partly responsible for the induction of UBSM mechanical activity. In addition, the present study provides evidence that UBSM spontaneous mechanical activity is also attributable to the mechanism(s) other than the generation of Ca2+ spike.
Nitric oxide modulates and adenosine mediates the tubuloglomerular feedback mechanism
Authors: Persson A. E. G. , Brown R. , Liu R. , Ollerstam A.
Published: March 2003

The tubuloglomerular feedback (TGF) mechanism is an important regulator of the glomerular filtration rate (GFR) and urine excretion rate. It operates by sensing the distal delivery of fluid at the macula densa site and adjusting the tone of the glomerular arterioles to control GFR. We found evidence that nitric oxide is an important modulator of the setting of the sensitivity of the TGF mechanism. Studies on adenosine A1 receptor deficient mice have shown that these animals lack the TGF response and have an increased renin release. These findings show the important role of adenosine as a mediator of the signal for the TGF mechanism and as an inhibitor of renin release.
PGE1 induced transcapillary transport of 51Cr‐EDTA in rat skin measured by microdialysis
Authors: Iversen V. V. , Reed R. K.
Published: March 2003

Interstitial fluid pressure (Pif) is a key determinant in increasing the transcapillary driving pressure, pulling fluid from the microcirculation into the interstitial space at the onset of acute inflammatory reactions and the oedema formation associated with these. Prostaglandin E1 (PGE1) induces lowering of Pif in rat skin which increases transcapillary transport of 51Cr‐EDTA into the center of a tumor as measured by microdialysis. The aim of this study was twofold: First, to evaluate and develop the microdialysis technique thoroughly with regard to its suitability for investigating transcapillary water transport in rat skin using 51Cr‐EDTA as a tracer. Secondly, to evaluate the effect of PGE1 on transcapillary transport of 51Cr‐EDTA. This study demonstrates that PGE1 increases transcapillary transport of 51Cr‐EDTA into skin interstitium. There were no significant differences between the experimental probe and the control probe when calculations from the entire experiment (90 min) were compared. On the other hand, significant differences were observed by examining the experiment in smaller time intervals. PGE1 increased transcapillary transport of 51Cr‐EDTA during the first 15 min when administered through the microdialysis probe. This observation suggests that increased blood flow and/or permeability‐surface area product are responsible for raising the transcapillary transport of 51Cr‐EDTA, i.e. the transport is diffusion limited. Administration of PGE1 through the probe rather than around the probe resulted in less scatter between experiments than when PGE1 was injected subcutaneously around the probe.
Myosin remodelling in the contracting A7r5 smooth muscle cell
Authors: Fultz M. E. , Wright G. L.
Published: March 2003

Aim:  Using confocal microscopy and standard immunohistochemical techniques, changes in the structure of α‐actin and β‐actin as well as the distribution of myosin II were studied in the contracting A7r5 smooth muscle cell.

Results:  Prior to stimulation, each of the three proteins were incorporated into filamentous structures extending the length of the cell body. At 30 min after stimulation by phorbol 12, 13 dibutyrate (PDBu), the system of densely packed β‐actin fibres was retained. By comparison, α‐actin and myosin were observed to undergo significant remodelling, characterized by loss in fibre structure and the formation of brightly fluorescing peripheral bodies. Co‐immunoprecipitation of α‐actin and myosin II suggested an association between the proteins. Consistent with this observation, dual immunostaining for α‐actin and myosin revealed strong co‐localization of the two proteins prior to stimulation. Following PDBu stimulation myosin II was observed to partially disassociate from α‐actin structure but showed significant co‐localization with α‐actin filaments and peripheral bodies throughout the interval of contraction. The use of cytochalasin B to block actin polymerization or the selective dissolution of α‐actin cable structure by thapsigargin produced similar patterns of change in α‐actin structure and the localization of myosin II.

Conclusion:  The results support the concept of myosin liability and potential for remodelling. The results suggest that myosin undergoes extensive relocalization in association with α‐actin remodelling which may be an important determinant of contractile function in the A7r5 smooth muscle cell.
Blood flow distribution during elevated intraperitoneal pressure in the rat
Authors: Lindström P. , Källskog Ö. , Wadström J. , Persson A. E. G.
Published: March 2003

Aim:  Oliguria is seen during elevated intraperitoneal pressure, but the physiological mechanisms are not yet clarified. The purpose of the present study was to investigate the changes in renal function, cardiac output and distribution of systemic blood flow (BF) that occur in connection with an elevation of intra‐abdominal pressure (IAP) in a rat model by isotope‐labelled microsphere technique.

Methods:  A 5 or 10 mmHg IAP was created by CO2 insufflation and maintained for 90 min in anaesthetized and mechanically ventilated rats. Rats with normal IAP served as controls. Blood flow and cardiac output measurements by injection of isotope‐labelled microspheres were conducted at three time points. Acid–base balance, urine output, glomerular filtration rate (GFR) and urinary excretion products were also followed.

Results:  Glomerular filtration rate decreased [0.7–0.1 mL min−1 g−1 kidney weight (KW)] with elevated IAP, as did urine output (8.5–0.6 μL min−1 g−1 KW). Dramatic decreases were seen in renal excretion of sodium (by 97%), potassium (by 94%) and osmotic active substances (by 93%). Cardiac output was diminished by 54% at 5 mmHg and by 65% at 10 mmHg intraperitoneal pressure and systemic vascular resistance (SVR) was elevated threefold.

Conclusion:  Cardiac output, measured by microsphere technique, decreased during elevated intraperitoneal pressure by CO2 in anaesthetized rats, while SVR was elevated and renal excretory functions were decreased to a large extent.
Sympathetic nerve activity in metabolic control – some basic concepts
Authors: Fagius J.
Published: March 2003

A role for the sympathetic nervous system in hypertension has been looked for in relation to the ‘metabolic syndrome’ with associations between body weight, insulin sensitivity and hypertension. By use of microneurography human sympathetic responses to hypoglycaemia, normoglycaemic hyperinsulinaemia and food intake have been studied. A strong but differentiated influence of insulin‐induced hypoglycaemia comprises increase in muscle sympathetic nerve activity (MSNA) and the sudomotor part of skin sympathetic nerve activity (SSNA), whereas vasoconstrictor SSNA is inhibited. Responses to infusion of 2‐deoxy‐d‐glucose are identical, suggesting central nervous system glucopenia and not insulin to be the causative factor. Insulin infusion during normoglycaemia evokes a moderate increase in MSNA; SSNA and blood pressure does not change.

After glucose ingestion MSNA displays a sustained increase, which is only partly elicited by insulin. A significant albeit weaker increase occurs after pure protein or fat meals, and after glucose ingestion in C‐peptide‐negative diabetic patients, with no insulin secretion. In healthy elderly people the MSNA response to food intake is weak, because of a high outflow already at rest; this is suggested to explain postprandial hypotension in the elderly, a paradoxical mechanism behind clinical autonomic failure.

A pathophysiological role of MSNA in the metabolic syndrome with hypertension has been speculated. An association between obesity and elevated level of MSNA at rest is established; observed relationships to chronic insulin levels and hypertension are less unanimous. The adipous tissue regulating hormone leptin has become one focus of interest in ongoing attempts to elucidate a possible role of the human sympathetic nervous system in the ‘metabolic syndrome’ and hypertension.
Population dynamics of Mus minutoides and Steatomys pratensis (Muridae: Rodentia) in a subtropical grasslandin Swaziland
Authors: Monadjem A.
Published: March 2003

The population dynamics of Mus minutoides and Steatomys pratensis are virtually unknown. These two species were live‐trapped over a 12‐month period in a subtropical grassland in Swaziland. Numbers of M. minutoides were relatively high in winter, declined in spring and the population disappeared in summer and autumn. By contrast, numbers of S. pratensis increased gradually from winter to summer and reached a peak in autumn. There were no differences between the mean weights of male and female M. minutoides and S. pratensis. There were, however, seasonal differences in the mean weight of male S. pratensis, with highest weights recorded in summer. Individuals of both species came into breeding condition in spring (October–November). Reproduction had ceased by the end of autumn (April–May). Monthly survival rates of M. minutoides were highest in winter, but did not vary seasonally in S. pratensis. Burning had a pronounced effect on the distribution of S. pratensis. Steatomys pratensis individuals selected recently burnt but revegetated areas over unburnt areas. The effect of burning on the M. minutoides population is difficult to assess, as this species disappeared shortly after the fire.
A comparison of methods used to count the elephant population of the Addo Elephant National Park, South Africa
Authors: Whitehouse A. M. , Hall‐Martin A. J. , Knight M. H.
Published: March 2003

Evaluation of alternative techniques used to estimate elephant population sizes is important in order to assess the accuracy of the results obtained, upon which management decisions may be based. Data from annual helicopter surveys carried out in the Addo Elephant National Park (1978–97) are compared with registration counts obtained from intensive ground surveys in which all elephants within the park are individually known. On average, total population size estimated in aerial surveys is 8.0% lower than registration counts (n1997 = 251), aerial calf (< 1 year) counts are 48.8% lower than registration counts, and aerial carcass counts are 50% below the total number of deaths documented in ground surveys. Registration counts provide more accurate demographic data than aerial surveys, the results of which are shown to vary widely and unpredictably, thus compromising their value. Where population estimates rely exclusively on aerial surveys, replicate counts are recommended in order to generate confidence intervals.
The elephant population of Samburu and Buffalo Springs National Reserves, Kenya
Authors: Wittemyer George
Published: March 2003

A 21‐month individual identification project on the Samburu and Buffalo Springs National Reserves' elephant population was conducted between November 1997 and July 1999. The free ranging population, of at least 767 elephants, which relied heavily on areas outside the reserves, was individually identified. The numbers of elephants observed per day fluctuated but were greater during dry periods then wet. However, the sizes of aggregations were greater during wet periods. Preliminary investigation suggested that the population could be divided into two groups, which were designated resident and non‐resident family units. The groups comprised approximately equal numbers of cows and calves, but temporally had different reserve use patterns and calving peaks. The daily numbers of males and musth males were correlated with numbers of females. The reserves appeared to be a focal area for calving, indicating that the study area was of reproductive importance to the population. Demographic data indicated a female biased population sex ratio, with over twice the number of mature females to males. The observed sex skew was greatest for older age classes, and the density of musth bulls in the study area was low. The population was affected by poaching. Continued monitoring will assist conservation efforts by alerting authorities of major demographic or range use changes.
Effect of PPARγ ligands on the viability of gastric epithelial cells
Authors: Kojima K. , Shimada T. , Mitobe Y. , Yoshiura K. , Hiraishi H. , Terano A.
Published: March 2003

Backgournd:

Peroxisome proliferator‐activated receptors (PPAR) are a family of three nuclear receptors (PPARα, PPARδ, and PPARγ). Although recent evidence suggests a role for PPARγ in the regulation of colonic epithelial cell growth, the role for PPARγ in the stomach has not been established.

Aim:

To examine the expression of PPARγ and the effects of PPARγ ligands on the viability of gastric epithelial cells.

Methods:

MKN45 cells and primary cultured rat gastric epithelial cells were used. Troglitazone (TGZ) and 15‐deoxy‐Δ12, 14‐prostaglandin J2 (15d‐PGJ2) were used as PPARγ ligands. Expression of PPARγ was examined by RT–PCR and Western blot analysis. Cell viability was measured by WST‐1 assay and TUNEL assay was performed to detect apoptosis.

Results:

MKN45 cells expressed all subtypes of PPAR. PPARγ ligands decreased cell viability and induced cell death in a dose‐dependent manner, whereas ligands for PPARα and PPARδ had no significant effect. TUNEL assay showed that this cell death is apoptosis. Primary cultured rat gastric epithelial cells also expressed PPARγ and activation of PPARγ decreased cell viability.

Conclusion:

These results suggest that PPARγ plays an important role in the regulation of cell growth and cell death in gastric epithelial cells.
Treatment of mild to moderate ulcerative colitis and pouchitis
Authors: Gionchetti P. , Amadini C. , Rizzello F. , Venturi A. , Campieri M.
Published: March 2003

The meta‐analyses of published trials have shown topical therapy with 5‐aminosalicylic acid (5‐ASA) to be the treatment of choice in active distal ulcerative colitis. Oral aminosalicylates are effective for both distal and extensive ulcerative colitis, but in distal colitis the rates of improvement and remission are usually lower than those reported for rectal 5‐ASA therapy. An alternative to 5‐ASA therapy is represented by the new steroids; budesonide and beclometasone dipropionate (BDP) enemas, the most extensively studied, have been shown to be as effective as conventional steroids but with a significantly lower inhibition of plasma cortisol. Patients who do not respond to 5‐ASA or new steroids should be treated with oral steroids. Azathioprine or 6‐mercaptopurine may be effective in patients who do not respond or cannot be weaned off steroids. Treatment of pouchitis is largely empirical and few controlled studies have been carried‐out. Antibiotics are the treatment of choice and most patients make a good response to metronidazole or ciprofloxacin. Chronic refractory pouchitis may benefit from a prolonged course of a combination of antibiotics. Highly concentrated probiotics (VSL#3) are effective both for the prevention of pouchitis onset and the prevention of relapses.
Review article: esomeprazole − the first proton pump inhibitor to be developed as an isomer
Authors: Kendall M. J.
Published: March 2003

Omeprazole is a racemate, from which the R‐ and S‐isomers can be isolated. At the cellular level, both of these isomers convert to the same inhibitor of the H+,K+‐ATPase and produce the same reduction in gastric acid secretion. However, the S‐isomer, esomeprazole, is metabolized more slowly and reproducibly than the R‐isomer and omeprazole, and therefore produces higher plasma concentrations for longer and, as a result, inhibits gastric acid production more effectively and for longer. Thus, esomeprazole has the pharmacological properties of a more effective form of treatment for disorders related to gastric acid secretion. Clinical studies have confirmed the anticipated increased efficacy, but have shown no evidence of impaired tolerability or increased toxicity when compared with omeprazole.
The management of acid‐related dyspepsia in general practice: a comparison of an omeprazole versus an antacid‐alginate/ranitidine management strategy
Authors: Mason  , Millar  , Sheikh  , Evans  , Todd  , Turbitt  , Taylor
Published: March 2003

Background:

There is need for an evidence‐based comparison of clinical management strategies to provide the rationale for selection of a particular therapeutic approach to treatment. Ideal dyspepsia treatment should quickly and conveniently alleviate patient symptoms whilst also minimizing the use of healthcare resources.

Aim:

To examine dyspepsia symptom relief over 16 weeks and compare an omeprazole clinical management strategy with a commonly used combination of antacid–alginate followed by H2‐antagonist.

Methods:

Seven hundred and twenty‐five patients participated in this randomized, open, parallel group comparison over 16 weeks. Patients were randomized to receive either an omeprazole treatment strategy (363) consisting of omeprazole 10 mg stepping up to 20 mg and 40 mg as required, or an antacid–alginate/ranitidine treatment strategy (362) consisting of antacid–alginate 10 mL q.d.s. stepping up to ranitidine 150 mg b.d. and 150 mg q.d.s. as required.

Results:

A greater proportion of patients receiving the omeprazole clinical management strategy had achieved the stringent health target of complete symptom relief (61 vs. 40%, P < 0.0001) at 16 weeks. Forty‐six per cent of omeprazole‐treated patients were symptom free after the first 10 mg step compared to only 17% in the antacid–alginate treated group (P = 0.0001). Total relief of heartburn, the most common symptom at entry, was achieved by more patients in the omeprazole treatment group than the antacid–alginate/ranitidine treatment group, 62 vs. 36%, respectively, at 4 weeks, and 81 vs. 60% at 16 weeks (P = 0.0001).

Conclusion:

Treatment with the omeprazole clinical management strategy was superior to the antacid–alginate/ranitidine management strategy in providing relief of acid‐related dyspepsia symptoms after 16 weeks. In addition, the omeprazole treatment strategy involved fewer GP consultations and thus minimized the use of other healthcare resources.
Nitric oxide and gall‐bladder motor function
Authors: Luman  , Ardill  , Armstrong  , Smith  , Brett  , Lessells  , Haynes  , Gray  , Mickley  , Webb  , Palmer
Published: March 2003

Background:

The L‐arginine: nitric oxide (NO) pathway has been shown to be important in the regulation of intestinal motility and NO may be the mediator for nonadrenergic noncholinergic (NANC) neurotransmission.

Aim:

To determine the role of the L‐arginine: NO pathway in gall‐bladder motor function.

Methods:

Strips of fresh bovine and human gall‐bladders were stimulated with cholecystokinin (CCK). The effects of glyceryl trinitrate (GTN), sodium nitroprusside and Kreb’s solution upon CCK‐stimulated muscle contraction were examined. The effect of the NO synthase inhibitor, L‐NG‐monomethyl‐arginine (L‐NMMA) upon basal muscle tone was also examined. Ten human gall‐bladders were immunohistochemically stained for nitric oxide synthase (NOS) and product 9.5 to identify neurones. Postprandial gall‐bladder emptying was measured on separate occasions in six healthy volunteers during systemic intravenous infusion of normal saline; glyceryl trinitrate; sodium nitroprusside (SNP), hydralazine and L‐NMMA.

Results:

In the in vitro study, GTN and SNP significantly reduced the tension of CCK‐stimulated muscle contraction whilst Kreb’s solution had no effect. L‐NMMA increased tonic and phasic muscle contractions. Immunohistochemical staining for NOS was consistently absent in human gall‐bladders. In the in vivo study, both GTN and SNP caused significant impairment of gall‐bladder emptying; the ejection fraction was only 50% at the end of the study period involving these infusates, this contrasted with ejection fractions in excess of 80% during infusions with hydralazine, saline and L‐NMMA.

Conclusion:

Pharmacological doses of NO donors impair postprandial gall‐bladder emptying in vivo and relax gall‐bladder smooth muscle in vitro. However, negative immunohistochemical staining suggest NOS is unlikely to be the neurotransmitter for NANC innervation regulating gall‐bladder motility.
Treatment of Helicobacter pylori infection in infants in rural Bangladesh with oral immunoglobulins from hyperimmune bovine colostrum
Authors: Casswall  , Sarker  , Albert  , Fuchs  , Bergström  , Björck  , Hammarström
Published: March 2003

Background:

Antibodies from hyperimmune bovine colostrum have been shown to be effective in treatment against a variety of microorganisms, including Helicobacter pylori in adults.

Aim:

To test this form of treatment in a small group of H. pylori infected children in a periurban community in Bangladesh.

Methods:

Twenty‐four infants, 4–29 months old (mean age 16.5 ± 7.7 months) and infected with H. pylori, were treated with purified immunoglobulins from hyperimmune bovine colostrum for 1 month, in a placebo‐controlled, double‐blind pilot study. Diagnosis was established with 13C‐urea breath test (UBT) before and after the treatment period and at a 1‐month follow‐up.

Results:

None of the hyperimmune bovine colostrum‐treated children became UBT negative. Five children initially positive in the UBT screening spontaneously became negative by the start of the study with hyperimmune bovine colostrum/placebo. At the end of the 1‐month study period, three had became positive again.

Conclusion:

Hyperimmune bovine colostrum does not eradicate H. pylori infection in infants. Transient H. pylori infection is common among infants in high endemic areas, as is reinfection after clearance. This presents obstacles to evaluation of therapeutic investigations in young children in areas where H. pylori is prevalent.
The organ extraction and splanchnic haemodynamic effects of octreotide in cirrhotic patients
Authors: Ottesen  , Flyvbjerg  , Møller  , Bendtsen
Published: March 2003

Background:

Intravenous octreotide is an established treatment of oesophageal variceal haemorrhage in the cirrhotic patient.

Aim:

To examine the organ extraction and splanchnic haemodynamic effects of octreotide in cirrhotic patients with portal hypertension.

Methods:

Thirteen patients with cirrhosis had hepatic venous catheterization performed. Hepatic venous pressure gradient (HVPG), indocyanine green (ICG) clearance and hepatic blood flow (HBF) were determined in the basal state and during 60 min of octreotide infusion by bolus injection (0.75 μg/kg) followed by continuous infusion of 0.75 μg/kg.h. Blood samples were simultaneously drawn from the femoral artery and the hepatic and renal veins.

Results:

The extraction fraction of octreotide in the liver was 0.05 (− 0.01–0.14) (median (interquartile range)) and in the kidneys 0.16 (− 0.06–0.35). The extraction fraction ratio (Eliver/Ekidney) was 0.69 (− 0.20–1.06). Hepatic clearance was 47 mL/min (3–88) (n = 11). No correlations were found between liver biochemistry or galactose elimination capacity (GEC; a metabolic measure of liver function) and renal extraction fraction or liver clearance. Octreotide had no effect on HVPG or wedged hepatic venous pressure although free hepatic venous pressure increased during octreotide infusion: 6 mmHg (5–9) vs. 7 mmHg (6–10) (P = 0.02). No effect on HBF was observed while ICG clearance decreased significantly.

Conclusions:

Octreotide is extracted in cirrhotic patients by both the liver and the kidney, the latter being the most important organ of elimination. Octreotide decreases liver metabolic activity determined by the ICG clearance technique, but no significant effects of octreotide on HVPG or HBF could be demonstrated.
Variation in taste of topical lignocaine anaesthesia for gastroscopy
Authors: Asante  , Northfield
Published: March 2003

Aim:

To study the distribution and determinants of taste variation for lignocaine spray (Xylocaine; Astra Pharmaceuticals, King’s Langley, UK).

Methods:

Sixty‐nine patients (male:female 49:20, mean age 48.5 years) attending for open access upper gastrointestinal endoscopy were studied. Taste perceived after applying 4 doses (40 mg) of lignocaine spray to the oro‐pharynx was recorded prior to endoscopy.

Results:

37/69 (54%, 95% CI: 41–66%) perceived the taste of the lignocaine spray as bitter, whilst 24/69 (35%, 95% CI: 24–47%) and 6/69 (9%, 95% CI: 3–18%) perceived the taste as either fruity/sweet or tasteless. The variation in taste did not correlate with either demographic features or H. pylori infection, but duodenal ulceration was slightly more common amongst bitter tasters.

Conclusion:

The taste of lignocaine is not uniform, but the basis of this variability is uncertain.
Relationship between fundic endocrine cells and gastric acid secretion in hypersecretory duodenal ulcer diseases
Authors: Annibale  , Aprile  , Ferraro  , Marignani  , Angeletti  , D′ambra  , Caruana  , Bordi  , Fave G. Delle
Published: March 2003

Background:

Acid hypersecretion is associated with duodenal ulcer disease in the following conditions: Zollinger–Ellison syndrome (ZES) and antral gastrin cell hyperfunction (AGCH) due to hypergastrinaemia, or hypersecretory duodenal ulcer (HDU) without hypergastrinaemia.

Aim:

To evaluate whether quantitative changes in fundic ECL and D cells may be involved in acid hypersecretion.

Patients and Methods:

Seven ZES, six AGCH and six HDU Helicobacter pylori‐positive patients were compared. Basal (BAO) and pentagastrin‐stimulated gastric acid secretions (PAO), and morphometry of fundic ECL and D cells were performed. The six AGCH and six HDU patients were investigated again using the same tests 1 year after H. pylori eradication.

Results:

Median PAO values were no different in all the hypersecretory conditions studied. The median volume density of ECL cells in ZES was significantly higher than in controls (2.75, range 1.74–5.8 vs. 0.73, 0.52–1.11; P < 0.05), whereas it was in the control range in AGCH and HDU patients (0.77, range 0.20–1.39 and 0.99, range 0.42–1.51; respectively). The count of fundic D cells was significantly lower in AGCH patients than in all other investigated groups (median 0.16, range 0.1–0.52; P < 0.05). Cure of infection in AGCH and HDU patients did not modify the ECL cell volume density, whereas a significant increase in the count of fundic D cells was observed in AGCH patients. Thus, the ECL/D cell index was significantly affected in AGCH patients (P < 0.05), being higher during H. pylori infection (median 6, range 0.7–9.25) than after the cure (median 2.12, range 1.10–3.5). BAO and PAO were not affected by H. pylori eradication in either group.

Conclusions:

The study provides evidence, for the first time, that quantitative alterations in the fundic endocrine cells are not involved in acid hypersecretion of patients with hypersecretory states, and that eradication of H. pylori does not restore normal acid secretion values.