bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced effect of caffeine on twitch contraction of oesophageal striated muscle from stroke‐prone spontaneously hypertensive rats
Authors: Sekiguchi Fumiko , Kawata Kyoko , Shimamura Keiichi , Sunano Satoru
Published: December 2004

1. There are known differences in the sensitivity to caffeine between skeletal muscle (soleus) of normotensive Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The present study was performed in order to examine differences in the effects of caffeine on twitch contraction between visceral striated muscle using the outer layer of the oesophagus from WKY rats and stroke‐prone SHR (SHRSP).

2. Caffeine, at concentrations ranging from 0.3 to 10 mmol/L, exhibited potentiating effects on twitch contraction in preparations from both WKY rats and SHRSP. The potentiating effect of caffeine was markedly less prominent in preparations from SHRSP compared with preparations from WKY rats.

3. The rate of contraction and relaxation, the time to peak tension and 80% relaxation time were not significantly altered by caffeine at concentrations lower than 3 mmol/L in preparations from either strain.

4. With 10 mmol/L caffeine, the rate of relaxation was markedly reduced and the 80% relaxation time was prolonged, with no significant changes in the rate of contraction, in preparations from WKY rats. These changes were significantly smaller in preparations from SHRSP.

5. The duration of the action potential was greater in preparations from SHRSP than in preparations from WKY rats, although the membrane potential and the amplitude of the action potential were not significantly different between preparations from WKY rats and SHRSP.

6. Caffeine, at 10 mmol/L, prolonged the duration of the action potential in preparations from both strains. The effect of caffeine was not different between preparations from WKY rats and SHRSP.

7. The results of the present study suggest that caffeine augments release of Ca2+ from the sarcoplasmic reticulum (SR) at low concentrations and attenuates Ca2+ re‐uptake at 10 mmol/L. Decreased reactivity of SR to caffeine may be a cause of the lesser potentiation of twitch contraction by caffeine in preparations from SHRSP.
Effects of hypochlorite and hydrogen peroxide on cardiac autonomic receptors and vascular endothelial function
Authors: Sand Carsten , Peters Stephan LM , Pfaffendorf Martin , Van Zwieten Pieter A
Published: December 2004

1. Reactive oxygen species (ROS) are known to be involved in the progression of various cardiovascular diseases. One source of ROS is activated neutrophils, which can release superoxide anion radicals and hydrogen peroxide by membrane‐bound NAD(P)H oxidases. These ROS not only destroy bacteria, but may also affect mammalian tissue. In addition, hydrogen peroxide serves as a substrate for myeloperoxidase, an enzyme that is released by activated neutrophils during inflammatory processes, as seen, for instance, in reperfusion injury and atherosclerosis. Myeloperoxidase catalyses the oxidation of chloride by hydrogen peroxide, yielding hypochlorite, an extremely potent oxidant.

2. The purpose of the present study was to evaluate the effects of hypochlorite on a variety of receptor‐dependent processes in rat isolated left atria and rat thoracic aorta and to compare these results with the phenomena observed after incubation with hydrogen peroxide.

3. In the presence of hypochlorite (300 µmol/L), the positive inotropic response of α1‐adrenoceptor stimulation by methoxamine (300 µmol/L) was converted into a negative inotropic response. In contrast, the positive inotropic effects of the β1/β2‐adrenoceptor agonist isoprenaline (3 µmol/L) and endothelin (ET)‐1 (100 nmol/L) remained largely unaffected.

4. The inversion of α1‐adrenoceptor‐mediated inotropy was not obtained in the presence of hydrogen peroxide (500 µmol/L). Hydrogen peroxide did not affect the positive inotropic response of isoprenaline, but it completely abolished the inotropic effect of ET‐1.

5. The effect of cardiac M2‐receptor stimulation was studied in the presence of hypochlorite and hydrogen peroxide. The negative inotropic response to acetylcholine (ACh) was significantly enhanced after hypochlorite incubation compared with control.

6. In the rat thoracic aorta, endothelial function, evaluated by means of ACh‐induced vasodilation, was completely abolished in the presence of hypochlorite (100 µmol/L), but remained unaffected by treatment with the same concentration of hydrogen peroxide.

7. From these data, we conclude that hypochlorite exerts more toxic properties than its precursor hydrogen peroxide, leading to substantial physiological alterations in cardiac and vascular tissue.
Deficient prepulse inhibition of acoustic startle in Hooded‐Wistar rats compared with Sprague‐Dawley rats
Authors: Van Den Buuse Maarten
Published: December 2004

1. Prepulse inhibition of acoustic startle has been suggested as a model of sensorimotor gating and central sensory information processing. Prepulse inhibition is impaired in patients with schizophrenia and responses can be restored by antipsychotic drug treatment. In the present study, startle and prepulse inhibition of startle were compared in different rat strains.

2. Sprague‐Dawley rats showed robust inhibition of startle responses by increasing intensities of prepulse delivered just before the startle stimulus. In contrast, at both 4 and 10 weeks of age, rats of the Hooded‐Wistar line had markedly reduced prepulse inhibition, although startle responses were not different.

3. Treatment with the dopamine receptor agonist apomorphine (0.1 mg/kg) or the N‐methyl‐d‐aspartate (NMDA) receptor antagonist MK‐801 (0.1 mg/kg) caused disruption of prepulse inhibition in Sprague‐Dawley rats. In Hooded‐Wistar rats, apomorphine further reduced the already low level of prepulse inhibition, but MK‐801 treatment had no significant effect. This suggests that the impaired prepulse inhibition in Hooded‐Wistar rats could be caused by changes in glutamatergic activity and/or NMDA receptors in these rats.

4. In photocell cages, spontaneous exploratory activity and inner zone activity were significantly lower in Hooded‐Wistar rats than in Sprague‐Dawley rats. Similarly, on the elevated plus‐maze, Hooded‐Wistar rats showed a lower propensity to visit the open arms. In contrast, amphetamine (0.5 mg/kg)‐induced locomotor hyperactivity, an animal model of psychosis, was enhanced in Hooded‐Wistar rats.

5. These data suggest that the Hooded‐Wistar line could be a useful genetic animal model to study the interaction of glutamatergic and dopaminergic mechanisms in anxiety and schizophrenia.
Depressor effect induced by dipeptide, Val‐Tyr, in hypertensive transgenic mice is due, in part, to the suppression of human circulating renin–angiotensin system
Authors: Matsui Toshiro , Hayashi Atsumi , Tamaya Kei , Matsumoto Kiyoshi , Kawasaki Terukazu , Murakami Kazuo , Kimoto Ko‐ichi
Published: December 2004

1. In the present study, the depressor action of the dipeptide Val‐Tyr, with an in vivo antihypertensive effect, was investigated in transgenic mice carrying the human renin gene cross‐mated with mice bearing the human angiotensinogen gene (Tsukuba Hypertensive Mouse; THM).

2. Single oral administration of Val‐Tyr (0.1 mg/g) to 11‐week‐old THM resulted in a prolonged reduction of blood pressure for up to 9 h. The effect clearly demonstrated that the Val‐Tyr absorbed acted on the enhanced human renin–angiotensin system (RAS).

3. After Val‐Tyr administration, an approximate eightfold higher increment of plasma Val‐Tyr was observed at 1 h (3406 ± 211 fmol/mL plasma) compared with the level observed at 0 h; plasma concentrations of Val‐Tyr returned to baseline levels at 6 h.

4. Transient changes in plasma concentrations of angiotensin (Ang) I and AngII only at 1 h were consistent with plasma Val‐Tyr concentrations, suggesting that that the long‐lasting reduction in blood pressure was achieved by the latent hypotensive mechanism of Val‐Tyr and not by transient suppression of the circulatory RAS.

5. Ageing of the THM greatly affected the depressor action of Val‐Tyr, with no significant reduction in blood pressure observed in 18‐ and 24‐week‐old THM.
The p42/44mitogen‐activated protein kinase inhibitor PD 98059, but not U 0126, increases a K+ current in cardiomyocytes
Authors: Aimond F , Fauconnier J , Donadille D , Vassort G
Published: December 2004

1. The effects of the mitogen‐activated protein kinase (MAPK) inhibitors PD 98059 and U 0126, useful tools to investigate MAPK involvement in intracellular signal transduction pathways, were assessed on cardiomyocytes.

2. In rat freshly isolated ventricular myocytes, under current‐clamp conditions, PD 98059 (40 µmol/L) shortened the action potential. Under whole‐cell patch‐clamp, this compound slowly induced a fast activating sustained outward K+ current that was sensitive to 1 mmol/L Ba2+, 100 µmol/L Gd3+, 3 mmol/L 4‐aminopyridine and 100 µmol/L tetracain. The PD 98059‐induced current was prevented by 40 µmol/L AACOCF3, a cytosolic phospholipase A2 inhibitor.

3. U 0126 (1 µmol/L), a recently developed highly potent p42/44 MAPK inhibitor, did not alter K+ currents.

4. PD 98059, but not U 0126, increased arachidonic acid content, probably as a consequence of its reported cyclo‐oxygenase inhibitory effect.

5. These observations indicate that PD 98059 activates a TREK‐1 like current. Thus, this MAPK inhibitor has to be used with caution because alterations in cell metabolism can be secondary to changes in electrophysiological behaviour.
Oxidized LOw‐density lipoprotein sensitizes human vascular smooth muscle cells to FAS (CD95)‐mediated apoptosis
Authors: Takarada Shigeho , Imanishi Toshio , Hano Takuzo , Nishio Ichiro
Published: December 2004

1. It was investigated in the present study whether oxidized low‐density lipoprotein (oxLDL) was implicated in the susceptibility of human vascular smooth muscle cells (VSMC) to Fas‐mediated death. Human fetal aorta smooth muscle cells were treated with agonistic anti‐Fas antibody (CH11) and oxLDL and cell death was then determined by viability and DNA fragmentation.

2. The results of the present study show that cross‐linking of Fas receptor with anti‐Fas antibody in the presence of oxLDL induced death and DNA fragmentation in human VSMC, which were blocked by the caspase inhibitor z‐VAD.fmk, followed by the upregulation of cell surface Fas.

3. The data indicate that oxLDL is implicated in death in VSMC and provide evidence that oxLDL is involved in Fas signal transduction. The present study proposes a novel mechanism(s) by which VSMC become susceptible to Fas ligand.

4. One of the mechanisms proposed by which oxLDL upregulates cell surface Fas is by inhibiting the degradation of Fas through the ubiquitin–proteasome pathway.
Role of angiotensin II, sympathetic stimulation and salt in the development of structural vascular changes in rat kidney
Authors: Simon Geza , Jäckel Marta , Illyes Gyorgy
Published: December 2004

1. Functional and structural vasoconstriction of renal cortical arteries is the earliest change leading to hypertension. In the present study, the interaction of a subpressor dose of angiotensin (Ang) II, a 2% NaCl diet and sympathetic stimulation in the form of overnight cold exposure was investigated in the development of renal structural vascular changes in male Sprague‐Dawley rats.

2. Morphometric measurements of renal cortical resistance arteries and volume density measurements of renal cortical components were performed in eight groups of rats after 12 weeks of treatment: AngII; 2% NaCl diet; cold exposure (5°C); AngII plus 2% NaCl diet; AngII plus cold exposure; cold exposure plus 2% NaCl diet; ANG II plus 2% NaCl diet plus cold exposure; and sham operation and treatment (control).

3. The average weekly systolic blood pressure of AngII‐treated plus salt‐fed rats was increased, whereas that of cold‐stressed plus salt‐fed rats at room temperature decreased compared with controls. The blood pressure rise of the former group was accompanied by an increased wall‐to‐lumen ratio (WLR) of cortical resistance arteries and decreased glomerular volume, whereas the reduction in blood pressure in the latter group was accompanied by a decreased WLR of cortical resistance arteries and increased volume density of cortical renal tubules. There were no changes in either the blood pressure or renal structure of the other groups.

4. There is a parallel relationship between changes in preglomerular structural vascular resistance and changes in blood pressure in rats. It remains to be determined whether renal cortical structural changes are the cause of, or are compensatory for, chronic changes in blood pressure.
Dietary mushroom (Pleurotus ostreatus) ameliorates atherogenic lipid in hypercholesterolaemic rats
Authors: Hossain Shahdat , Hashimoto Michio , Choudhury Emran Kabir , Alam Nuhu , Hussain Shahjalal , Hasan Moynul , Choudhury Shahabuddin Kabir , Mahmud Ishtiaq
Published: December 2004

1. The effects of edible oyster mushroom Pleurotus ostreatus on plasma and liver lipid profiles and on the plasma total anti‐oxidant status were estimated in hyper‐ and normocholesterolaemic Long Evans rats.

2. The feeding of 5% powder of the fruiting bodies of P. ostreatus mushrooms to hypercholesterolaemic rats reduced their plasma total cholesterol by approximately 28%, low‐density lipoprotein–cholesterol by approximately 55%, triglyceride by approximately 34%, non‐esterified fatty acid by approximately 30% and total liver cholesterol levels by > 34%, with a concurrent increase in plasma high‐density lipoprotein–cholesterol concentration of > 21%. However, these effects were not observed in mushroom‐fed normocholesterolaemic rats.

3. Mushroom feeding significantly increased plasma fatty acid unsaturation in both normo‐ and hypercholesterolaemic rats.

4. Plasma total anti‐oxidant status, as estimated by the oxidation of 2,2′‐azino‐bis‐[3‐ethylbenz‐thiazoline‐6‐sulphonic‐acid], was significantly decreased in mushroom‐fed hypercholesterolaemic rats, concomitant with a decrease in plasma total cholesterol.

5. The present study suggests that 5% P. ostreatus supplementation provides health benefits, at least partially, by acting on the atherogenic lipid profile in the hypercholesterolaemic condition.
Insulin resistance modifies plasma fatty acid distribution and decreases cardiac tolerance to in vivo ischaemia/reperfusion in rats
Authors: Morel S , Berthonneche C , Tanguy S , Toufektsian M‐C , Foulon T , De Lorgeril M , De Leiris J , Boucher F
Published: December 2004

1. The early stage of insulin resistance, also termed the ‘prediabetic state’, is characterized by the development of hyperinsulinaemia, which maintains normoglycaemia under fasting conditions. The metabolic disorders induced in myocardial cells during this stage of the disease may constitute a basis for an alteration of the tolerance of the heart to ischaemia and reperfusion.

2. To test this hypothesis, male Wistar rats were fed a 66% fructose diet for 4 weeks, inducing a prediabetic state. Rats were then subjected to in vivo left coronary artery ligation followed by reperfusion. Blood samples were collected for plasma lipid profile determination.

3. The prediabetic state significantly increased the severity of ischaemia‐induced arrhythmias (arrhythmia score 1.4 ± 0.2 vs 2.0 ± 0.0 in control and fructose‐fed rats, respectively; P < 0.05) and the size of infarction (infarct size 41.2 ± 3.0 vs 56.0 ± 2.0% in control and fructose‐fed rats, respectively; P < 0.01). This alteration of the tolerance to in vivo ischaemia/reperfusion may be the consequence of an increase in mono‐unsaturated fatty acids and a decrease in ω3 polyunsaturated fatty acids in fructose‐fed‐rats.

4. In conclusion, because it is known that the prediabetic state increases the incidence of cardiovascular diseases by promoting coronaropathy, our study suggests that this metabolic disorder may also affect the prognosis of heart disease by decreasing the tolerance of cardiomyocytes to ischaemic insults.
Exaggerated response to restraint stress in rats congenic for the chromosome 1 blood pressure quantitative trait locus
Authors: Cui Zong Hu , Ikeda Katsumi , Kawakami Kohei , Gonda Tatsuo , Nabika Toru , Masuda Junichi
Published: December 2004

1. To understand the roles of a putative hypertension gene in the chromosome 1 quantitative trait locus (QTL) region, the response to restraint stress was studied in strains congenic for this QTL.

2. To establish congenic strains, the QTL region was introgressed from stroke‐prone spontaneously hypertensive rats (SHRSP)/Izm to Wistar‐Kyoto/Izm (WKY/Izm) rats by repeated backcrossing. Two congenic strains (WKYpch1.0 and WKYpch1.1) were established to cover the whole QTL region between D1Wox29 and D1Arb21 (approximately 40 cM) and a smaller region between D1Smu11 and D1Arb21 (approximately 10 cM), respectively. After telemetry probes were implanted, rats were exposed to restraint stress to investigate the blood pressure response.

3. Basal blood pressure measured by radiotelemetry differed significantly between WKY rats and WKYpch1.0 (103 ± 10 and 116 ± 4 mmHg, respectively; P = 0.002 by anova). When exposed to restraint stress, WKYpch1.0 showed a greater increase in blood pressre than did WKY rats. The exaggerated response in the WKYpch1.0 strain was abolished by chemical sympathectomy using guanethidine. The WKYpch1.1 rats did not differ significantly from WKY rats either in basal blood pressure or in the response to restraint stress.

4. In conclusion, a QTL for high blood pressure was successfully introgressed in the established congenic strain, WKYpch1.0. A gene (or genes) in the chromosome 1 QTL region modulates the cardiovascular responses to restraint stress in these congenic rats, probably through the sympathetic nervous system.
Effect of denuded endothelial cells on arginine amidase activity released from rabbit arteries
Authors: Naito Tatsuya , Ishii‐Nozawa Reiko , Miyazaki Kyosuke , Shimokawa Ken‐ichi , Matsuda Yoshifumi , Takeuchi Koichi
Published: December 2004

1. We examined the secretion of arginine amidase activity from rabbit aorta and ear arteries.

2. The amount of arginine amidase activity spontaneously secretion from the aorta was significantly less than that secreted from the ear artery. Dermatan sulphate significantly facilitated the secretion of arginine amidase activity from both the aorta and ear artery.

3. The dermatan sulphate‐enhanced secretion of arginine amidase activity from the aorta and ear artery was reduced by denudation of the endothelium.

4. These findings may indicate that spontaneous release of arginine amidase activity from vascular smooth muscle and the enhancement of secretion of arginine amidase activity produced by dermatan sulphate depends on the endothelium.
Effects of reserpine on nerve stimulation‐induced constrictions in canine isolated splenic artery
Authors: Yang Xiao‐Ping , Chiba Shigetoshi
Published: December 2004

1. Our previous studies have demonstrated that peri‐arterial electrical nerve stimulation (PNS) of the canine splenic artery induces a double‐peaked vasoconstriction consisting of an initial transient, dominantly P2X purinoceptor‐mediated constriction, followed by a prolonged, mainly α1‐adrenoceptor‐induced response. In the present study, we examined the effects of reserpine on PNS‐induced double‐peaked responses.

2. The vasoconstrictor response to tyramine was abolished after reserpine treatment, but the responses to noradrenaline (NA) and ATP were not significantly modified.

3. The PNS‐induced second peak vasoconstrictor responses were markedly reduced in reserpinized vessels, whereas the first peak vasoconstrictor responses were not so strongly influenced (i.e. they were not significantly affected at 1 Hz, but were significantly affected at 4 and 10 Hz).

4. All reserpine‐resistant responses were unaffected by treatment with prazosin, but were abolished by subsequent application of α,β‐methylene ATP. The exposure of reserpine‐treated tissues to NA almost completely restored tyramine‐induced vasoconstriction and the second neurogenic peak vasoconstrictor response, but failed to affect the first neurogenic response.

5. The present results indicate that ATP and NA are cotransmitters responsible for the double‐peaked vasoconstrictor responses of canine splenic artery. In addition, it is suggested that PNS causes NA release not only from intragranular NA storage sites, but also from tyramine‐sensitive cytoplasmic sites.
Effects of ovariectomy and 17β‐oestradiol replacement on [Ca2+]i in female rat cardiac myocytes
Authors: Curl Claire L , Wendt Igor R , Canny Benedict J , Kotsanas George
Published: December 2004

1. The present study investigated the effects of ovariectomy (OVX) and 17β‐oestradiol replacement on [Ca2+]i in rat freshly isolated cardiac myocytes.

2. Myocytes were isolated from the hearts of sham, OVX and OVX + 17β‐oestradiol‐replaced female rats by enzymatic digestion with collagenase. Changes in [Ca2+]i in response to varied extracellular [Ca2+] were measured using the Ca2+‐sensitive dye fura‐2, with the contractile responses of each cell measured as cell shortening.

3. Increasing extracellular [Ca2+] resulted in increased [Ca2+]i in all three groups. Peak [Ca2+]i and the amplitude of the Ca2+ transient were significantly greater (P < 0.01) in cells from OVX animals compared with cells from both sham and 17β‐oestradiol‐replaced OVX animals.

4. The time‐course of decay of the Ca2+ transient was significantly faster (P < 0.02) in OVX cells compared with both sham and 17β‐oestradiol‐replaced cells. In addition, time to 50% relaxation was significantly faster (P < 0.04) and extent of shortening significantly greater (P < 0.01) in OVX cells than in either sham or 17β‐oestradiol cells.

5. These data demonstrate clear differences in peak [Ca2+]i and the amplitude of the Ca2+ transient between OVX female rat cardiac myocytes compared with intact and 17β‐oestradiol‐replaced OVX female rat cardiac myocytes. This suggests that oestrogen may play a long‐term role in limiting Ca2+ entry into the cardiac myocyte.
Beneficial effect of hyperbaric oxygen pretreatment on lipopolysaccharide‐induced shock in rats
Authors: Pedoto Alessia , Nandi Jyotirmoy , Yang Zhong‐jin , Wang Jingping , Bosco Gerardo , Oler Albert , Hakim Tawfic S , Camporesi Enrico M
Published: December 2004

1. We investigated the effect of hyperbaric oxygenation (HBO2) pretreatment on the production of exhaled nitric oxide (ENO) and the expression of lung inducible nitric oxide synthase (iNOS) by Escherichia coli lipopolysaccharide (LPS)‐induced shock in an experimental rat model.

2. Rats were randomized into four groups, anaesthetized, mechanically ventilated with room air and infused with normal saline (2 mL/h) through the jugular vein for 5 h. Group 1 (NS) received only normal saline. Group 2 (HBO2‐NS) was pretreated with HBO2 at 2.8 absolute atmospheres for 2 h and then received normal saline. Group 3 (LPS) received LPS, 20 mg/kg, i.v., bolus. Group 4 (HBO2‐LPS) was pretreated with HBO2 for 2 h, followed by LPS.

3. Arterial blood gases, blood pressure, blood pH and ENO production were measured every 30 min. Plasma nitrite/nitrate (NOx) concentrations were assessed at the beginning (baseline) and at the end of the study. Lung myeloperoxidase (MPO) activity, iNOS expression and histological scores were measured for the evaluation of lung injury.

4. Administration of LPS was associated with decreased blood pressure and pH, increased ENO production, plasma NOx concentrations, lung iNOS expression and MPO activity.

5. Pretreatment with HBO2 significantly alleviated the LPS‐induced hypotension, acidosis and decreased ENO production, plasma NOx concentrations, lung MPO activity and expression of iNOS. Hyperbaric O2 had no effect on control rats.

6. Our data show that HBO2 pretreatment has beneficial haemodynamic effects in rats with endotoxin shock. The beneficial effects of HBO2 may be partially mediated by decreased ENO production via reduced LPS‐induced lung iNOS expression.
Drugs acting at the GABAA receptor attenuate ethanol‐induced gastric mucosal damage in vitro*
Authors: Najim Rafid A , Saaed Hiwa K
Published: December 2004

1. Benzodiazepines (BZ) have been reported to protect against ethanol‐induced gastric damage in rats in both in vivo and in vitro models. However, the effects of some drugs in the new in vitro model do not agree with results reported previously in in vivo studies.

2. Therefore, the aim of the present study was to modify the new in vitro model to a model that more closely resembles the in vivo model and, using the new in vitro model, to reassess the gastroprotective effects of some BZ and to assess the effects of some new compounds.

3. The rat stomach was isolated from the whole animal and kept in aerated Krebs' solution at 37°C in an organ bath. Gastric mucosal damage was induced by instillation of 1 mL of 100% ethanol into the stomach. Drugs or their vehicle were administered inside the bath 15 min before ethanol instillation into the stomach. One hour after the instillation of ethanol, the stomach was removed from the organ bath, opened along the greater curvature and then examined for gastric mucosal damage.

4. The results indicate that, compared with vehicle pretreatment, ethanol‐induced gastric mucosal damage was significantly reduced in a dose‐dependent manner by pretreatment with clonazepam, a drug that acts as an agonist at central BZ sites of the GABAA receptor, and Ro 15‐4513, a partial inverse agonist at BZ sites of the GABAA receptor. Flumazenil (an antagonist of central BZ sites of the GABAA receptor) did not affect gastric mucosal lesions provoked by ethanol. However, flumazenil significantly reversed the mucosal protective effects of clonazepam and Ro 15‐4513.

5. CGS 9896 (a partial agonist at BZ sites of the GABAA receptor, with anxiolytic and anticonvulsant but no sedative effects) did not offer any protection against ethanol‐induced gastric mucosal damage. Ro 5‐3663, an atypical BZ that binds to the picrotoxin site of the GABAA receptor and reported to be a potent convulsant and only a weak antagonist of GABA, did not show any protection against the development of lesions.

6. The results suggest local gastric mediation of the effects of ethanol, as well as the gastric protective effects of BZ, through an action at local central‐type BZ sites of the GABAA receptor located in the rat stomach.
Retinal detachment in cytomegalovirus retinitis: intravenous versus intravitreal therapy
Authors: Young Stephanie , McCluskey Peter , Minassian Darwin C , Joblin Paul , Jones Colin , Coroneo Minas T , Lightman Susan
Published: December 2004

Purpose:  To compare the rate of retinal detachment in a group of patients treated with intravitreal ganciclovir to the rate of retinal detachment in a group of patients treated with systemic ganciclovir.

Methods:  A retrospective non‐randomized comparative case series was conducted. The participants were 186 consecutive patients with cytomegalovirus (CMV) retinitis treated at two centres over the period from June 1990 to May 1997. Of the 186, 133 patients had systemic therapy of whom 113 had intravenous ganciclovir or foscarnet and 20 had oral ganciclovir, and 53 patients had intravitreal induction and maintenance therapy. The main outcome measure was the rate of retinal detachment, which was calculated using person‐months‐at‐risk denominators. The effect measure used in the main comparative analysis was the hazard ratio obtained from multiple regression using the Cox proportional hazards model.

Results:
 Retinal detachment occurred in three of 53 patients in the intravitreal therapy group, one of 20 patients receiving oral maintenance therapy and 21 of 113 patients receiving intravenous maintenance therapy. The risk of retinal detachment with systemic therapy was 14‐fold higher than with intravitreal therapy (P < 0.001) and up to fourfold higher with oral maintenance therapy.

Conclusions:  Intravitreal therapy offers a significant advantage over systemic therapy in the treatment of CMV retinitis by substantially reducing the risk of CMV‐related retinal detachment.
Limited macular translocation for subfoveal choroidal neovascularization in age‐related macular degeneration
Authors: Chang Andrew A , Tan Weichuan , Beaumont Paul E , Zeldovich Alina
Published: December 2004

Purpose: To examine the safety and efficacy of limited macular translocation followed by laser photocoagulation in the management of subfoveal choroidal neovascularization (CNV) in age‐related macular degeneration (AMD).

Methods: A prospective study was conducted on eight consecutive patients undergoing limited macular translocation followed by laser photocoagulation for the treatment of subfoveal classic CNV form of AMD. Patients were followed up for a minimum of 12 months. The magnitude of foveal translocation, visual outcomes and complications were assessed.

Results: In all cases the fovea was successfully translocated inferiorly, with a median displacement of 1.1 mm. Thermal laser photocoagulation was subsequently performed in all cases. Visual acuity improved in five eyes, remained unchanged in two eyes and worsened in one eye. The mean improvement in visual acuity was by 0.19 logMAR. At 12 months, six of the eight patients (75%) achieved Snellen visual acuity of at least 6/15, with four patients (50%) achieving Snellen visual acuity of 6/9.

Conclusion: In this small case series, limited macular translocation was found to be an effective and reproducible means of treating small well‐defined subfoveal CNV.
Golf‐related ocular injuries
Authors: Jayasundera Thiran , Vote Brendan , Joondeph Brian
Published: December 2004

Purpose: To examine patient outcomes from golf‐related ocular injuries.

Methods: A retrospective case review was undertaken of subjects with golf‐related ocular injuries treated at the Auckland and Waikato Hospitals during the 5‐year period from 1997 to 2002.

Results: Of 11 injuries treated in the 5‐year period, five of the subjects incurred globe rupture with two subjects requiring enucleation. Seven of the injuries were from golf balls and four injuries were from golf clubs. Six of the subjects had a final visual acuity of 6/48 or worse.

Conclusion: Golfing injuries, though uncommon, are frequently associated with severe ocular trauma and poor visual outcome. Although unpredictable and difficult to avoid, proper golf etiquette and safety may diminish the incidence of golf‐related ocular injures. Injuries caused by golf clubs occurred only in children.
Fornix‐based trabeculectomy using the ‘anchoring’ corneal suture technique
Authors: Ng Philip WC , Yeung Barry YM , Yick Doris WF , Tsang Chi‐wai , Lam Dennis SC
Published: December 2004

Aim: To assess the safety and efficacy of fornix‐based tra­beculectomy with the ‘anchoring’ corneal suture technique in Chinese patients.

Methods: A retrospective non‐comparative case series of 66 eyes of 63 Chinese patients who underwent fornix‐based trabeculectomy combined with intraoperative mitomycin C (MMC) 0.4 mg/mL for 2−5 min were studied. Conjunctival wound closure of all eyes was with the anchoring corneal suture technique using a 9−0 nylon suture to prevent leakage at the corneolimbal interface. The success rate, with or without anti‐glaucoma medication, the complication rate and the longevity of the drainage blebs were analyzed.

Results: At a mean follow‐up period of 447.36 ± 337.98 days, the mean intraocular pressure decreased from 26.83 ± 7.90 mmHg to 17.74 ± 8.74 mmHg (P < 0.001). The mean glaucoma medication decreased from 2.95 ± 0.98 preoperatively to 1.23 ± 1.41 postoperatively (P < 0.001). Thirty‐one eyes (47.0%) required no anti‐glaucoma medication postoperatively. Twenty eyes (30.3%) had qualified success postoperatively. Eight eyes (12.1%) had early wound leakage that resolved with conservative treatment. Three eyes (4.5%) required surgical repair. One eye (1.5%) had hypotonous maculopathy. No other major complications were encountered.

Conclusion: Fornix‐based trabeculectomy with adjunctive mitomycin C employing the anchoring corneal suture technique appears to be both safe and effective in Chinese patients.
Effect of millimeter wave radiation on the expression of proliferating cell nuclear antigen, CDK4 and P16 in rat hepatocellular carcinoma
Authors: RONG Lan , SUN Da Yu , MEI Lin , ZHOU Bing Da , LU Wei
Published: December 2004

OBJECTIVE:  To study the effects of millimeter wave (MMW) radiation on rat hepatocellular carcinoma.

METHODS:  Forty male Wistar rats were randomly divided into four groups, and the liver region of the rats was directly radiated by MMW (35.8 GHz, 100 mW/cm2) for 20 min twice per week. Rats in groups 1 to 3 were fed with diethlnitrosamine (DEN). Group 1 was a tumor control group with sham radiation. Group 2 was given radiation for 10 weeks starting from week 5 and group 3 was radiated for 5 weeks starting from week 10. Group 4 was a normal control group radiated for 5 weeks and given distilled water. At week 14, all rats were sacrificed. A serological test for γ‐glutamyltransferase (γ‐GT) and immunohistochemical staining of proliferating cell nuclear antigen (PCNA), CDK4 and P16 in liver tissue were performed.

RESULTS:  The serum level of γ‐GT in group 1 (18.44 ± 4.88 U/L) was higher than that in group 2 (13.75 ± 2.41 U/L, P < 0.05), and the level of γ‐GT in group 3 (16.43 ± 2.12 U/L) was lower than that in group 1, but the difference was not significant. Based on histological examination of the livers, adenocarcinoma only developed in group 1. In the other DEN‐induced tumor groups, only eosinophilic and basophilic nodules were formed in the liver; no carcinoma cells were found. Expression of proliferating cell nuclear antigen (PCNA) and CDK4 staining in liver tissue in groups 2 and 3 were significantly lower than those in group 1, but the expression of P16 in the former was higher than that in the latter.

CONCLUSIONS:  Millimeter wave radiation partially inhibits cell proliferation and suppresses DEN‐induced hepatocellular carcinoma in rats.
Short‐ and long‐term effects of balloon dilatation on esophageal motility in achalasia
Authors: WANG Zhi Feng , KE Mei Yun , QIN Ming Wei
Published: December 2004

OBJECTIVE:  To explore the effect of balloon dilatation on esophageal motility in patients with achalasia.

METHODS:  In 48 patients diagnosed with achalasia based on clinical observations, barium radio­graphy, endoscopy and esophageal manometry, the following parameters were evaluated before dilatation, and 4 and 12−24 weeks after dilatation: symptom score, maximal width of esophagus (MWE), lower esophageal sphincter pressure (LESP), lower esophageal sphincter relaxation rate (LESRR), and contraction amplitude of esophageal body.

RESULTS:  The symptom score and MWE decreased significantly after dilatation (P < 0.05). The LESP decreased (P < 0.05) and LESRR increased (P < 0.05) significantly 4 weeks and 12−24 weeks after dilatation. The percentages of patients with LESP <2.67 kPa were 45.41% before dilatation, and 82.48% and 85.87% 4 weeks and 12−24 weeks after dilatation, respectively (P < 0.05). The percentages of patients with LESRR ≥80% were 6.74% before dilatation, and 55.97% and 43.78% 4 weeks and 12−24 weeks after dilatation, respectively (P < 0.05). Peristaltic waves were not observed after dilatation in any patient.

CONCLUSIONS:  Balloon dilatation may significantly improve the symptoms of achalasia and reduce esophageal distention by decreasing LESP and increasing LESRR. The mechanism by which balloon dilatation increases LESRR needs to be further studied.
Expression and distribution of protein translation initiation factor C2 gene in hepatocellular carcinoma and gastric cancer tissue
Authors: ZHANG Qing , LIU Jie , ZHANG Li , LI Qing , ZHANG Xue Mei , WANG Xin , QIAO Tai Dong , FAN Dai Ming , FEITELSON Mark
Published: December 2004

OBJECTIVE:  To study the expression, distribution and significance of the C2 gene in hepatocellular carcinoma (HCC) and gastric cancer tissue.

METHODS:  The avidin‐biotin‐peroxidase complex (ABC) immunohistochemical method was used to detect the expression of C2 protein in 60 specimens of HCC and 58 specimens of gastric cancer tissue, and the western blot technique was used to detect the expression of C2 protein in 10 specimens of HCC and associated pericancerous tissue.

RESULTS:  In 60 specimens of HCC and 42 specimens of associated pericancerous tissue, the rates of C2 protein detection were 27.3 and 83.3%, respectively; the latter being significantly greater than the former (P < 0.001). The expression of C2 protein was significantly correlated with the patient's age, HBsAg and α−fetoprotein (AFP; P < 0.05). The findings from western blotting were consistent with those from immunohistochemical methods. The rate of C2 protein detection was 20.4% in 49 specimens of HCC that were hepatitis‐B virus encoded X antigen (HBxAg)‐positive, but 63.6% in 11 HCC specimens that were HbxAg‐negative. The rate of C2 protein detection was significantly lower in HbxAg‐positive tissue than in HbxAg‐negative tissue (P < 0.05). In 58 specimens of gastric cancer tissue and 44 specimens of associated pericancerous tissue, the rates of C2 protein detection were 41.4 and 77.3%, respectively. The rate was significantly higher in gastric cancer tissue than in associated pericancerous tissue (P < 0.05), and C2 protein detection was significantly correlated with pathological grading, tumor size and the depth of invasion (P < 0.05).

CONCLUSIONS:  Low expression of the C2 gene might be involved in the development of HCC and gastric cancer. The suppression of C2 by HBxAg may play an important role in the development of HCC. C2 may be a potential tumor suppression gene.
Seroepidemiological comparison of Helicobacter pylori infection rates in Shanghai urban districts in 1990 and 2001
Authors: CHEN Sheng Liang , XIAO Shu Dong
Published: December 2004

BACKGROUND:  The incidence of diseases related to Helicobacter pylori infection, such as gastric cancer, has been decreasing in developed countries and areas where the economy is rapidly developing. This is also the situation in Shanghai, the largest city in China. However, the prevalent trend of Helicobacter pylori infection in Shanghai is unknown.

OBJECTIVE:  To investigate changes in the sero‐prevalence rate of Helicobacter pylori infection in Shanghai residents between 1990 and 2001.

METHODS:  We tested serum H. pylori immuno­globulin G antibodies in 1557 blood samples from healthy residents of the Shanghai urban area in 2001 using the ELISA method. The sero‐prevalence rate of H. pylori infection in 2001 was compared with that in 1990.

RESULTS:  In the Shanghai urban area the overall sero‐prevalence rate of H. pylori infection in 2001 was 58.3%, higher than that in 1990 (40.5%, P = 0.001). No significant differences in sero‐prevalence rates were found in subjects aged 1−9, 10−19 and 20−29 years between 1990 and 2001 (19.8, 42.7, 52.4 vs 27.4, 39.6, and 41.4; P = 0.683, 0.707 and 0.068, respectively). In subjects older than 30 years, a significantly higher prevalence rate of H. pylori infection was observed in 2001 than in 1990 (P < 0.05).

CONCLUSION:  The prevalence of H. pylori infection in urban Shanghai residents in 2001 was greater than that found in 1990.
Management of soft tissue sarcomas of the abdomen and pelvis
Authors: Mackenzie S. , Reid R. , Barrett A. , O'Dwyer P. J.
Published: December 2004

Objective Soft tissue sarcomas of the abdomen or pelvis are rare tumours that usually arise in the retroperitoneum but may also arise from the gastrointestinal tract or other abdominal organs. The aim of this study was to assess patient outcome following treatment of these tumours at a tertiary referral centre.

Patients and methods Data on all patients with soft tissue tumours treated under the care of one surgeon between January 1990 and December 2000 was reviewed.

Results Over the 11‐year period 61 patients underwent 79 operations for a soft tissue sarcoma of the abdomen or pelvis. Macroscopic clearance of tumour at operation was achieved in 45 (74%) of the 61 patients, for primary tumours this was 97%, recurrent tumours 50% and metastases 33%. The median survival for those undergoing complete resection was 50 months (range 3–238 months, median follow‐up 33 months). This compared with a median survival of only 6 months range (1–127 months) for those that had incomplete resection (P = 0.001). The 5‐year survival for patients that had complete resection was 61.5%, however, over one‐third of the 5‐year survivors have since recurred.

Conclusion This study confirms that most primary soft tissue sarcomas of the abdomen or pelvis are resectable and the majority of patients will experience a long disease free interval following resection.
Colorectal cancer in the south of Israel; comparison of the clinical characteristics and survival between two periods, 1981–2 and 1986–7
Authors: Lebel E. , Fraser D. , Fraser G. M. , Niv Y.
Published: December 2004

Background  Colorectal cancer has the highest incidence of all malignant tumours in men and women in Israel. The public was introduced to the concept of screening in the early 1980s, and full programs began in 1983.

Objectives  The study compares patients with colorectal cancer (CRC) who were diagnosed before screening and five years later, for stage differences and survival.

Methods  All patients with CRC who were diagnosed from 1981 to 1982 (period I) and 1986–87 (period II) at Soroka Medical Centre and who were residents of the Negev area were eligible for the study. Data were collected retrospectively from the Israel Cancer Registry and patient files and endoscopic, histological and surgical reports from the Departments of Pathology, Gastroenterology, Oncology and Surgery at Soroka Medical Centre.

Results  The study groups included 207 patients with CRC, 85‐from period I and 122‐from period II. The mean annual incidence of CRC for these 2 periods was 18 and 24.8 cases per 100, 000, respectively, for an increase of 37% (P < 0.001). Five‐year‐survival in period I was 53.3% and in period II, 39.6% (P = 0.025). Survival did not differ by origin or gender. Dukes' stage, well and moderately differentiated tumours, and left‐sided tumours were associated with better prognosis (P = 0.03). Forty‐two percent of the cases were less than 64‐year‐old‐at diagnosis, compared with 27% of 2069 Israeli patients in whom CRC was diagnosed in 1991 (P < 0.001).

Conclusions  Before a nation wide decision is made with regard to public screening for CRC with fecal occult blood tests or sigmoidoscopy, the available data should be thoroughly evaluated, and further in‐depth investigations performed to determine trends in diagnosis and prognosis.
Micrometastasis in regional lymph nodes of extirpated colorectal carcinoma: immunohistochemical study using anti‐cytokeratin antibodies AE1/AE3
Authors: Palma R. T. , Waisberg J. , Bromberg S. H. , Simão A. B. , Godoy A. C.
Published: December 2004

Objective The main objectives of this study were to identify, by immunohistochemistry, possible micrometastasis in the regional lymph nodes previously considered free by conventional histopathological examination, and to assess their influence on the survival of patients with colorectal cancer that had been extirpated in a radical manner.

Patients and methods From 38 patients with Dukes B staging (Colorectal Carcinoma Stage II (T3 N0 M0 or T4 N0 M0)) colorectal carcinoma, 383 lymph nodes were studied in paraffin blocks that had previously been considered free by conventional histopathological examination. These were submitted to immunohistochemical study using AE1/AE3 anti‐cytokeratin monoclonal antibodies to identify neoplastic epithelial cells.

Results Seven lymph nodes (1.82%) in six patients (15.78%) contained micrometastasis. The survival of the patients with extirpated colorectal carcinoma staged as Dukes B who had lymph node metastasis was less than in the group of patients without micrometastasis, although these values were not statistically significant.

Conclusion This immunohistochemical method can be employed successfully in the detection of neoplastic cells in lymph nodes previously considered free. In this study, there was a trend towards lower survival in node‐positive patients but this did not reach statistical significance.
Does the need to self‐digitate or the presence of a large or nonemptying rectocoele on proctography influence the outcome of transanal rectocoele repair?
Authors: Stojkovic S. G. , Balfour L. , Burke D. , Finan P. J. , Sagar P. M.
Published: December 2004

Introduction Transanal repair of anterior rectocoele is a well described technique with variable success rate. In our department we offer repair to patients who fit the following criteria; the need to self digitate (transvaginal or perineal); a large rectocoele; a nonemptying rectocoele. Using these selection criteria previous authors have shown excellent results. The aim of our study was to review our results using this selective approach and also to determine whether the need to self digitate, the presence of a large rectocoele and the degree of emptying could predict which patients would achieve a successful result.

Methods Fifty‐five patients underwent repair over a three‐year period. The main presenting symptom was noted for each patient and also whether self‐digitation was required in order to achieve successful evacuation. Dynamic evacuation proctography was performed on all patients. Size of rectocoele, percentage of paste expelled and other proctographic abnormalities were noted for each patient. Follow up was at 6 weeks and 6 months at which point patients were asked whether their symptoms had resolved, improved, remained the same or had worsened.

Results Complete data were available for 48 of the patients (median age 52 years, IQR 43–63). The presenting complaint was constipation in 22 patients, obstructive defeacation in 15, incomplete evacuation in 5, postdefaecation soiling in 4 and dyspareunia in 2. Thirty‐eight patients noted the need to self‐digitate, 10 did not. Proctography revealed a large rectocoele (> 4 cm) in 22 patients and a medium or small rectocoele (< 4 cm) in 26 patients. There was a rectocoele alone in 34 patients, in combination with perineal descent in 11 and with intussusception in 3. Median percentage of paste expelled was 70% (range 20–95).

At 6 weeks postoperatively, 43 patients had complete resolution of their symptoms whilst 5 reported only some or no improvement. At 6 months, 37 patients sustained complete resolution of their symptoms and 11 did not. Pre‐operative factors were compared for these two groups of patients. There was no difference in age (P > 0.05, Mann–Whitney U‐test) between the two groups There was also no difference in size of rectocoele, degree of emptying, the presence of another proctographic abnormality and the need to self‐digitate between the two groups (P > 0.05, Fisher's exact test).

Discussion No factors were seen to distinguish between the successful and unsuccessful groups of patients following rectocoele repair, however, an overall success rate of 75% was achieved using our selection criteria. This figure is in keeping with reported success rates in the literature.