bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects on infarct size and on arrhythmias by controlling reflow after myocardial ischaemia in pigs
Authors: Sjaastad  , Grund  , Ilebekk
Published: March 2003

Part of the myocardial damage after an ischaemic period might be related to the reperfusion conditions. Many abrupt changes occurring in the heart during reperfusion may add to the damage during the preceding ischaemic period, and increase in infarct size. In this study we tested the hypothesis that infarct size and occurrence of ventricular arrhythmias might be reduced by restricting reflow after an ischaemic period. Seventeen pigs underwent 45 min of total occlusion of the left anterior descending coronary artery with an hydraulic occluder. In the intervention group reperfusion was restricted to 50% of baseline during the first minute, to 100% during the next minute, kept constant for 1 min, and thereafter allowed to increase by 50% of baseline flow every minute until free reflow. In the control group reflow was not restricted. Arrhythmias were recorded. After 2.5 h of reperfusion the heart was excised. Infarct size was measured by using triphenyltetrazolium chloride (delineation of necrosis), fluorescent microspheres (delineation of area at risk) and planimetry. No reduction in infarct size (% of area at risk) was found between the intervention group and the control group (75.9 ± 5.3% vs. 72.4 ± 4.3%). The incidence of ventricular arrhythmias and ventricular fibrillation were not found to be different between the groups during reperfusion. Hemodynamic parameters were not significantly different between the two groups. Our data indicate that no substantial protection against myocardial infarct or ventricular arrhythmias could be achieved by controlling reflow using the present protocol after a period of myocardial ischaemia in pigs. Accordingly, our data do not support the notion that control of reflow may be beneficial when treating coronary artery occlusion with percutaneous coronary angioplasty (PCA).
Free radical generation and oxidative stress with ageing and exercise: Differential effects in the myocardium and liver
Authors: Bejma  , Ramires  , Ji
Published: March 2003

Reactive oxygen species and other oxidants are implicated in the mechanisms of biological ageing and exercise‐induced tissue damage. The present study examined the effects of ageing and an acute bout of exercise on intracellular oxidant generation, lipid peroxidation, protein oxidation and glutathione (GSH) status in the heart and liver of young adult (8 month, N=24) and old (24 month, N=24) male Fischer 344 rats. Young rats ran on treadmill at 25 m min–1, 5% grade until exhaustion (55.4 ± 2.7 min), whereas old rats ran at 15 m min–1, 5% until exhaustion (58.0 ± 2.7 min). Rate of dichlorofluorescin (DCFH) oxidation, an indication of intracellular oxidant production, was significantly higher in the homogenates of aged heart and liver compared with their young counterparts. In the isolated heart and liver mitochondria, ageing increased oxidant production by 29 and 32% (P < 0.05), respectively. Acute exercise increased oxidant production in the aged heart but not in the liver. When nicodinamide dinucleotide phosphate (reduced), adenosine diphosphate and Fe3+ were included in the assay, DCFH oxidation rate was 47 and 34% higher (P < 0.05) in the aged heart and liver homogenates, respectively, than the young ones. The age differences in the induced state reached 83 and 140% (P < 0.01) in isolated heart and liver mitochondria, respectively. Lipid peroxidation was increased in the aged liver and exercised aged heart, whereas protein carbonyl content was elevated only in the aged heart (P < 0.05). Although our data using DCFH method probably underestimated cellular oxidant production because of time delay and antioxidant competition, it is clear that oxidative stress was enhanced in both heart and liver with old age. Furthermore, aged myocardium showed greater susceptibility to oxidative stress after heavy exercise.
Nitric oxide modulates acetylcholine‐induced vasodilatation in the hepatic arterial vasculature of the dual‐perfused rat liver
Authors: Yang W. , Benjamin I. S. , Alexander B.
Published: March 2003

The role of nitric oxide in the modulation of hepatic arterial vascular reactivity was investigated in an isolated dual‐perfused rat liver preparation. Twelve male Wistar rats (200–250 g) were anaesthetized with sodium pentobarbitone (60 mg kg–1 i.p.). The livers were then excised and perfused in vitro through hepatic arterial and portal venous cannulae at constant flow rates. Concentration‐dependent dose–response curves to acetylcholine (10–8–10–5 M), sodium nitroprusside (10–6–5 × 10–4 M), and adenosine triphosphate (ATP) (10–8–10–5 M) in the hepatic artery were constructed after the tone was raised by addition of methoxamine (3 μM L–1). Acetylcholine‐induced vasodilatation in the hepatic artery was significantly attenuated with inhibition of nitric oxide synthase by using NG‐nitro‐L‐arginine methyl ester (30 μM), Emax=51.7 ± 2.8 vs. 32.5 ± 3.1 mmHg, before vs. after NG‐nitro‐L‐arginine methyl ester, respectively. ATP‐induced hepatic arterial vasoconstriction which was significantly enhanced with L‐NAME, Emax=94.0 ± 9.3 vs. 127.0 ± 8.0 mmHg, before vs. after NG‐nitro‐L‐arginine methyl ester, respectively. Sodium nitroprusside‐induced hepatic arterial vasodilatation remained unchanged with NG‐nitro‐L‐arginine methyl ester, Emax=57.0 ± 3.4 vs. 57.0 ± 4.1, before vs. after NG‐nitro‐L‐arginine methyl ester, respectively. The data from the present study suggest that acetylcholine‐induced vasodilatation in the intrahepatic arterial vasculature of the rat liver is at least, in part, mediated by the release of nitric oxide. In addition, ATP‐induced hepatic arterial vasoconstriction is also modulated by the release of nitric oxide (*P < 0.05, Student’s paired t‐test).
Effects of lactoferrin on rat dermal interstitial fluid pressure (Pif) and in vitro endothelial barrier function
Authors: Erga K. S. , Peen E. , Enestrøm S. , Reed R. K.
Published: March 2003

We recently demonstrated that intravenous (i.v.) injection of the iron‐binding protein lactoferrin (Lf) followed by antilactoferrin (aLf) antibodies or iron‐saturated Lf alone increased albumin extravasation in vivo in several tissues including skin. Increased driving pressure for blood‐tissue exchange or direct effects of Lf on the endothelial barrier are possible mechanisms. We therefore, firstly, measured interstitial fluid pressure (Pif) in dermis of rats given 1 mg Lf i.v. followed 30 min later by aLf or saline and circulatory arrest 1 or 5 min thereafter and compared with controls. Secondly, transmonolayer passage of Evans blue labelled albumin (EB‐albumin) was evaluated in porcine pulmonary artery endothelial cells exposed to iron‐free or iron‐saturated Lf (both 100 μg mL–1) in the absence and presence of 0.5 mM hydrogen peroxide. Pif increased significantly at 11–30 min following Lf to +2.1 ± 0.3 and +1.7 ± 0.2 mmHg at 11–20 and 21–30 min, respectively, compared with +0.1 ± 0.2 mmHg before Lf (P < 0.05, n=25). Endothelial transmonolayer passage of EB‐albumin during 3 h was not affected by iron‐free or iron‐saturated Lf neither in the absence nor presence of hydrogen peroxide that increased passage 3.5 times compared with controls. In conclusion, Lf‐induced increase in albumin extravasation in rat skin is not explained by changes in Pif (because Lf raised Pif significantly) or direct effects of Lf on the endothelial barrier.
The pathophysiology of type 2 diabetes mellitus: an overview
Authors: Östenson C.‐G.
Published: March 2003

Type 2 diabetes mellitus is a heterogeneous disorder characterized by chronic hyperglycaemia. The aetiological heterogeneity is suggested by genetic inheritance and its interplay with environmental factors. Impaired insulin secretion and decreased insulin sensitivity are the main pathophysiological features, responsible for development of hyperglycaemia in type 2 diabetes. However, the genetic basis of these defects has been demonstrated only in small subgroups of patients. Whether impaired secretion or action of insulin is the primary defect in the majority of patients is not known, although it is generally agreed that defective insulin release is a requirement for the disease to develop.
Effects of heterotopic‐ and segmental counter‐stimulation on the nociceptive withdrawal reflex in humans
Authors: Terkelsen A. J. , Andersen O. K. , Hansen P. O. , Jensen T. S.
Published: March 2003

A nociceptive withdrawal reflex in 12 human volunteers was elicited by painful electrical stimulation applied to the cutaneous innervation area of the sural nerve. The evoked electromyographic reflex activities were recorded with surface electrodes placed on the short head of the biceps femoris muscle ipsi‐lateral to sural nerve stimulation, before, during and after conditioning stimuli. The nociceptive withdrawal reflex was conditioned by nociceptive and non‐nociceptive, heterotopic and segmental counter‐stimulation. Heterotopic nociceptive counter‐stimulation and segmental nociceptive counter‐stimulation were induced by ice water applied to the contra‐lateral hand and foot, respectively. Heterotopic nociceptive counter‐stimulation produced a significant inhibition of the nociceptive withdrawal reflex and the associated pains rating to sural nerve stimulation. Segmental nociceptive counter‐stimulation inhibited the pain rating and tended to inhibit the nociceptive withdrawal reflex. There was no obvious correlation between visual analogue scale (VAS) and the nociceptive withdrawal reflex elicited by sural nerve stimulation neither in the group nor in the individual subject. This suggests that the nociceptive withdrawal reflex cannot always be used as a quantitative measure of pain.
Comparison of fatigue produced by various electrical stimulation trains
Authors: Binder‐Macleod S. A. , Scott W. B.
Published: March 2003

Previous work has shown that variable‐frequency trains (VFTs) that use an initial doublet to take advantage of the catch‐like property of muscle produce more force in fatigued muscle than constant‐frequency trains (CFTs); however, it is unclear whether repetitive activation with VFTs is more or less fatiguing than repetitive activation with CFTs. The purpose of this research was to investigate the forces and fatigue produced by various stimulation trains during repetitive isometric muscle contractions. Two force measurements, peak force and force–time integral, were used to measure the performance of the human quadriceps muscle. Three fatiguing protocols, each consisting exclusively of either CFTs, trains with an initial doublet (VFTs), or trains with doublets separated by longer intervals [doublet‐frequency trains (DFTs)], were tested. In addition, force responses to each of the three train types were tested before and immediately following each fatiguing protocol. Regardless of the fatiguing protocol, the doublet‐frequency testing trains produced the greatest peak forces and force–time integrals before and immediately following the fatiguing protocols. Repetitive activation with exclusively DFTs produced greater attenuation of the testing trains than repetitive activation with CFTs or VFTs. These results suggest that clinical applications of electrical stimulation to activate skeletal muscle may need to contain a combination of train types to optimize performance.
Cardiac hypertrophy and failure: lessons learned from genetically engineered mice
Authors: Takeishi Y. , Walsh R. A.
Published: March 2003

Congestive heart failure is a major and growing public health problem. Because of improved survival of myocardial infarction patients produced by thrombolytic therapy or per‐cutaneous revascularization it represents the only form of cardiovascular disease with significantly increased incidence and prevalence. Clinicians view this clinical syndrome as the final common pathway of diverse pathologies such as myocardial infarction and haemodynamic overload. Insights into mechanisms for heart failure historically derived from physiological and biochemical studies which identified compensatory adaptations for the haemodynamic burden associated with the pathological condition including utilization of the Frank Starling mechanism, augmentation of muscle mass, and neurohormonal activation to increase contractility. Therapy has largely been phenomenological and designed to prevent or limit the deleterious effects of these compensatory processes. More recently insights from molecular and cell biology have contributed to a more mechanistic understanding of potential causes of cardiac hypertrophy and failure. Many different analytical approaches have been employed for this purpose. These include the use of conventional animal models which permit serial observation of the onset and progression of heart failure and a sequential analysis of underlying biochemical and molecular events. Neonatal murine cardiomyocytes have been a powerful tool to examine in vitro subcellular mechanisms devoid of the confounding functional effects of multicellular preparations and heterogeneity of cell type. Finally, significant progress has been made by utilizing tissue from human cardiomyopathic hearts explanted at the time of orthotopic transplantation. Each of these methods has significant advantages and disadvantages. Arguably the greatest advance in our understanding of cardiac hypertrophy and failure over the past decade has been the exploitation of genetically engineered mice as biological reagents to study in vivo the effects of alterations in the murine genome. The power of this approach, in principle, derives from the ability to precisely overexpress or ablate a gene of interest and examine the phenotypic consequences in a cardiac specific post‐natal manner. In contrast to conventional animal models of human disease which employ some form of environmental stress, genetic engineering involves a signal known molecular perturbation which produces the phenotype.
Role of nitric oxide in inflammation
Authors: Laroux F. S. , Pavlick K. P. , Hines I. N. , Kawachi S. , Harada H. , Bharwani S. , Hoffman J. M. , Grisham M. B.
Published: March 2003

A number of laboratories have sought to elucidate the role of nitric oxide (NO) in both acute and chronic inflammatory diseases. It is now well appreciated that NO can influence many aspects of the inflammatory cascade ranging from its own expression to recruitment of leucocytes to the effected tissue. With the advent of mice selectively deficient in the various isoforms of nitric oxide synthase (NOS), the role that NO may play in various disease states can now be examined in vivo. One such syndrome that has gained much attention in recent years is ischaemia and reperfusion‐induced tissue injury. Ischaemia–reperfusion (I/R) injury is an important clinical consideration in situations such as transplantation, trauma, liver or bowel resection and haemorrhagic shock. A hallmark of I/R is the production of reactive oxygen species (ROS) during the reperfusion phase and it is thought that the production of ROS mediate much of the post‐ischaemic tissue injury. This review will examine the current state of knowledge regarding the regulatory mechanisms by which NO can influence various aspects of the inflammatory cascade as well as its role in a model of I/R injury in vivo.
Circulatory responses to a meal in patients with a newly transplanted heart
Authors: WAALER B. A. , HISDAL J. , ERIKSEN M.
Published: March 2003

It is well established that consumption of a meal releases a gradually developing and quite marked increase in blood flow to the gastrointestinal organs and a similar and simultaneous increase in cardiac output (CO). It is not known through which mechanism the pumping of the heart adjusts so accurately to the gastrointestinal flow increase. We have approached this problem by serving a standardized, mixed meal to five patients with recently transplanted and thus denervated hearts and to five sex‐ and age‐matched controls. Pre‐ and postprandial levels of CO and blood flow in the superior mesenteric artery (SMA) were recorded with Doppler ultrasound technique. The patients with transplanted hearts had significantly higher preprandial levels of heart rate (HR) and CO than the controls. With a timing similar to that seen in the controls did all five patients develop considerable and synchronous postprandial increases in superior mesenteric arterial flow and in CO. Increases in superior mesenteric arterial flow were significantly greater than the controls. Also, COs, high even before meals were given, increased further and to the same relative extent as in the control persons. The marked postprandial increase in CO, probably secondary to the increase in intestinal blood flow, could hardly come about through any sort of nervous reflex to the recently transplanted and denervated hearts. It appears more likely that a humoral connection of some sort exists between the two circulatory events.
A tyrosine kinase regulates propofol‐induced modulation of the β‐subunit of the GABAA receptor and release of intracellular calcium in cortical rat neurones
Authors: BjÖrnstrÖm K. , SjÖlander A. , Schippert Å. , Eintrei C.
Published: March 2003

Propofol, an intravenous anaesthetic, has been shown to interact with the β‐subunit of the γ‐amino butyric acidA (GABAA) receptor and also to cause changes in [Ca2+]i. The GABAA receptor, a suggested target for anaesthetics, is known to be regulated by kinases. We have investigated if tyrosine kinase is involved in the intracellular signal system used by propofol to cause anaesthesia. We used primary cell cultured neurones from newborn rats, pre‐incubated with or without a tyrosine kinase inhibitor before propofol stimulation. The effect of propofol on tyrosine phosphorylation and changes in [Ca2+]i were investigated. Propofol (3 μg mL−1, 16.8 μM) increased intracellular calcium levels by 122 ± 34% (mean ± SEM) when applied to neurones in calcium free medium. This rise in [Ca2+]i was lowered by 68% when the cells were pre‐incubated with the tyrosine kinase inhibitor herbimycin A before exposure to propofol (P < 0.05). Propofol caused an increase (33 ± 10%) in tyrosine phosphorylation, with maximum at 120 s, of the β‐subunit of the GABAA‐receptor. This tyrosine phosphorylation was decreased after pre‐treatment with herbimycin A (44 ± 7%, P < 0.05), and was not affected by the absence of exogenous calcium in the medium. Tyrosine kinase participates in the propofol signalling system by inducing the release of calcium from intracellular stores and by modulating the β‐subunit of the GABAA‐receptor.
Associations of HDL phospholipids and paraoxonase activity with coronary heart disease in postmenopausal women
Authors: Horter M. J. , Sondermann S. , Reinecke H. , Bogdanski J. , Woltering A. , Kerber S. , Breithardt G. , Assmann G. , Von Eckardstein A.
Published: March 2003

A low high‐density lipoprotein‐cholesterol (HDL‐C) is an established indicator for increased risk of coronary heart disease (CHD). Multiple functional relationships between HDL and CHD have been discussed. We tested the clinical relevance of some of these relationships in a cross‐sectional coronary angiography (CA) study of 87 post‐menopausal women between 48 and 73 years. In addition to established cardiovascular risk factors we measured concentrations of phosphatidylcholine (PC) and sphingomyelin (SPM) in HDL as indirect markers of cholesterol efflux capacity, the serum activity of the paraoxonase (PON) as a measure of the antioxidative capacity and serum concentrations of insulin/C‐peptide and C‐reactive protein (CRP) as indirect markers of insulin sensitivity and inflammation, respectively. Upon multivariate analysis of data from 55 women with angiographically assessed CHD differed from 32 women with angiographically excluded CHD, HDL‐SPM had the strongest association with the presence of CHD among all HDL‐related parameters. It was also the only HDL‐related parameter which had a significant and independent correlation with the number of coronary stenoses. As HDL‐SPM was previously shown to correlate with cholesterol efflux capacity of plasma, we conclude that reduced cholesterol efflux capacity is an important factor accounting for the inverse association between HDL‐cholesterol and CHD.
Photosynthesis and related physiological processes in two mangrove species, Rhizophora mucronata and Ceriops tagal, at Gazi Bay, Kenya
Authors: Mwangi Theuri M. , Kinyamario J. I. , Van Speybroeck D.
Published: March 2003

Measurements were carried out of the gas exchange properties (namely, photosynthesis, stomatal conductance and transpiration rates), water use efficiency and water relations of two mangrove species, Rhizophora mucronata and Ceriops tagal at Gazi Bay, Kenya. Rhizophora mucronata had significantly higher photosynthetic rates than C. tagal. Internal CO2 concentrations were higher during the wet season than the dry season in both species. Gas exchange properties were correlated positively with photon flux density in both species. Leaf water potentials were highest during the morning and lowest at midday and were also highest in the lower canopy leaves in both species. The two mangrove species had conservative water use. Management potential for the East African mangroves based on the results of this study is suggested.
Disturbances and species distribution of the riparian vegetation of a Rift Valley stream
Authors: Mathooko Jude M. , Kariuki Samuel T.
Published: March 2003

The Njoro River riparian vegetation species composition, distribution, disturbances and uses are presented and discussed. Montane Juniperus procera‐Olea europaea spp. africana and submontane Acacia abyssinica forests were identified as the main riparian vegetation groups. Approximately 55% of the riparian vegetation species are used for herbal medicine, treating more than 330 health problems, and only 11% of the plants are edible. Albizzia gummifera in the Syzygium cordatum‐Pittosporum abyssinicum‐Hibiscus diversifolius forest is cut selectively for herbal medicine preparations. Disturbances on the riparian vegetation zone are broadly classified as those induced by man, livestock and wildlife. Comprehensive effects of disturbance included loss of vegetation vertical strata, increase/decrease of species diversity, introduction of alien plant species, and reduction of plant sizes and vegetation hectarage. The effects of grazing on the vegetation were severe around livestock watering points. Grazing and browsing by wildlife were the main disturbances of the vegetation near the Njoro River estuary at the Lake Nakuru National Park. Periodic flooding, as a natural disturbance, regulates growth and survival of vegetation at the Lake Nakuru drawdown. Quantification of species diversity and the extent of disturbance by humans and livestock is important for future management of the vegetation and, consequently, the river.
Effects of grazing and cultivation on forest plant communities in Mount Elgon National Park, Uganda
Authors: Reed Mark S. , Clokie Martha R. J.
Published: March 2003

Plant communities in the montane forest of Mount Elgon National Park were studied in order to assess the impact of grazing and cultivation on species composition. Present and former land uses, tree, shrub and herb species, soil properties and the percentage cover and height of trees, shrubs and herbs were determined in 40 plots. An indirect ordination of these plots showed that species composition was primarily determined by successional stage and agricultural disturbance. In forest plots (ordinated separately) where the widest range of former and current grazing intensities had occurred, evidence of grazing history, soil phosphorus and vegetation height correlated negatively with the strongest ordination axis. Least grazed forest plots had fewer tree seedlings and saplings than more intensively grazed plots. This may be due to the increase in Mimulopsis alpina (Acanthaceae) in less grazed forest where tree regeneration might otherwise be more advanced. Tree seedlings and saplings were uncommon in the forest, rarely exceeding 30cm in height and there was no tree understorey. Although grazing is important for preserving species diversity in Mount Elgon National Park through the maintenance of species‐rich grasslands, long‐term effects on montane forest communities must be considered in future park management.
Distribution and habitat of grivet monkeys (Cercopithecus aethiops aethiops) in eastern and central Eritrea
Authors: Zinner Dietmar , Peláez Fernando , Torkler Frank
Published: March 2003

A 5‐month survey was conducted in Eritrea with the aim of collecting information on the distribution and habitats of primate species, including grivet monkeys (Cercopithecus aethiops aethiops). The survey area covered more than 22 000 km2 (N 14°17′−16°19′, E 37°13′−39°53′). Grivet monkey habitats were described by altitude, precipitation, normalized difference vegetation index (NDVI), vegetation classes and distances to nearest settlements and rivers. We detected grivet monkeys at 44 sites, making Eritrea probably the northern most range of the current grivet monkey distribution. Average group size was 9.1. Grivet monkeys were, at different sites, sympatric with either hamadryas (Papio hamadryas hamadryas) or olive (P. h. anubis) baboons. Grivet ‘home‐ranges’ had a NDVI significantly higher than the average of the area of survey (AoS), and the proportion of wooded and forested areas within the ‘home‐ranges’ was also greater than the average of the AoS. Of all grivet monkey records in Eritrea, 63.7% were closer than 1500 m to the nearest river or riverbed, indicating the importance of riverine forest and woodland for grivet monkeys in the otherwise arid habitats. Conflicts between humans and grivet monkeys were reported from almost every site because both use the riverine habitats extensively. In 37.2% of the cases, the distance between a grivet monkey record and the nearest agricultural area (>5 ha) was less than 500 m and 31.8% of the monkey sites were found within 1000 m of the nearest village. An increasing human population (especially due to resettlement projects for refugees) and an intensification of agricultural activities, particularly in the riverine habitats through modern irrigation techniques, is likely to increase the conflict and will probably have a negative impact on the grivet monkey population in Eritrea.
A note on group sizes of oribi (Ourebia ourebi, Zimmermann, 1783) from two contrasting sites in Zambia, with and without predation
Authors: Goldspink C. R. , Holland R. K. , Sweet G. , Stewart L.
Published: March 2003

The oribi (Ourebia ourebi, Zimmermann, 1783) is a small species of antelope widely represented across open grasslands of sub‐Saharan Africa. Although largely territorial, differences in group size and mating systems (monogamy/polygamy), have been linked to habitat conditions and population density. At high population densities, additional males are recruited to assist in territorial defence. Other factors which might impact on group size, include predation threat, especially at low population densities. In this study (1995–98), we recorded group sizes of oribi across two contrasting areas (c. 300 km2 each) of Zambia with (Kafue), and without (Bangweulu), large vertebrate predators. A total of 412 groups was recorded across the two sites, with mean sizes of 2.31 (n = 217) at Bangweulu and 2.33 (n = 195) at Kafue. The modal group size was two throughout (range 1–6). Groups were more variable in size and sex composition at Kafue than at Bangweulu, but there was no significant difference in estimates of population density between sites. Mean estimates were 2.02 and 1.90 km−2 for Bangweulu and Kafue, respectively. Sex ratios (males : females) were biased towards females (1 : 1.72 and 1 : 3.55, respectively) at both sites. Adult males were particularly scarce at Kafue. However, values of density and group size, were both unexceptional for the species. Whilst a modal group size of two is consistent with a monogamous mating system, variations in group composition and size were more difficult to explain. Adult females appeared to retain or recruit additional animals to groups, irrespective of the needs of territorial defence. This suggests that vigilance is an important function of groups on large open plains, especially in the presence of predators. By extension, reversed sexual dimorphism in oribi could reflect increased selection for vigilance duties in females. Predators had no apparent effect on population density, but oribi groups were more variable in size and sex composition in their presence. Adult males may be particularly vulnerable to predation when defending territorial borders at low population densities. However, further work is needed to define group dynamics in this species and to identify causes of mortality amongst adult males.
Time‐course changes of ECL cell markers in acetic acid‐induced gastric ulcers in rats
Authors: Kazumori H. , Ishihara S. , Fukuda R. , Kinoshita Y.
Published: March 2003

Background and aim:

Enterochromaffin‐like (ECL) cells are the major source of histamine for the regulation of gastric acid secretion, and also contain histidine decarboxylase (HDC), vesicular monoamine transporter 2 (VMAT2), and chromogranin A (CgA). Although gastric acid secretion is suppressed during ulcer healing, the role of ECL cells in that process is not yet fully understood. In the present study, we investigated the changes in ECL cell number during healing of experimental ulcers in rats.

Materials and methods:

Seven‐week‐old male Wistar rats were used. Acetic acid‐induced ulcers were caused by an application of 100% acetic acid to the serosal surface of the rat stomachs. At different time points following the induction (12 h‐15 days), time‐course changes of HDC, VMAT2, and CgA mRNA expression were investigated by Northern blot analysis. The expressions of HDC, VMAT2, and CgA were immunostained on gastric mucosal sections with ulcers.

Results:

HDC, VMAT2, and CgA mRNA in gastric mucosa each showed an initial marked transient decrease, followed by an increase on day 10 back to the initial value. HDC, VMAT2, and CgA‐immunoreactive cells at the ulcer margin were reduced in number on day 3, compared with those in distant areas. On day 10, however, they returned to levels similar to those in distant areas.

Conclusion:

The present study revealed a local down‐regulation of HDC, VMAT2, and CgA in ECL cells at the ulcer margin. As a result, we concluded that a suppression of ECL cell activity during ulcer healing may be involved in suppressed gastric acid secretion.
Detection of cancer cells in peripheral blood of stomach cancer patients using RT–PCR amplification of tumour‐specific mRNAs
Authors: Shin J‐H. , Chung J. , Kim H‐O. , Kim Y‐H. , Hur Y‐M. , Rhim J‐H. , Chung H‐K. , Park S‐C. , Park J‐G. , Yang H‐K.
Published: March 2003

Background:

RT–PCR amplification of tumour‐specific mRNA has been used for the detection of cancer cells in peripheral blood.

Aim:

To evaluate the characteristics of the tumour specific mRNA species in peripheral blood of stomach cancer patients.

Methods:

We analysed CEA, GalNAc‐T, MUC‐1, c‐MET and hTERT mRNA expression in the stomach cancer cell lines and tissues, lymph nodes and peripheral blood of stomach cancer patients using RT–PCR.

Results:

In RT–PCR analysis of the peripheral blood, 4%, 8%, 21%, 46%, and 100% of stomach cancer patients were positive for CEA, GalNAc‐T, c‐MET, hTERT and MUC‐1 mRNA, respectively, but MUC‐1 mRNA was also positive in all normal blood samples. The detection of hTERT mRNA was correlated with poor differentiation (P=0.01) and lymph node metastasis (P=0.009). The presence of c‐MET mRNA was correlated with T stage (P=0.025), lymph node metastasis (P=0.036), distant metastasis (P=0.031), and stage of the stomach cancer (P=0.023).

Conclusions:

Our study suggest that hTERT mRNA in peripheral blood can be a molecular marker for gastric cancer. We also showed that each molecular marker can be correlated with the clinicopathological features of the patients.
Treatment of mild and severe cases of GERD
Authors: Tytgat G. N. J.
Published: March 2003

GERD prevalence continues to rise in contrast to peptic ulcer disease. The spectrum contains reflux esophagitis and so‐called `endoscopy‐negative GERD' or `non‐erosive GERD' (NERD) or S‐GERD and patients with `normal' overall 24‐h esophageal acidification but with a high `symptom‐index'.

The majority of reflux patients will not need endoscopy initially. Prompt referral for endoscopy is indicated only if the patient has atypical symptoms or alarm symptoms such as dysphagia, anemia, weight loss, severe abdominal pain, or pain that does not respond to acid neutralization or suppression, or develops symptoms after the age of 50 years. Antireflux therapy consist of raising the head of the bed, maintaining normal weight, and avoidance of foods and drugs that precipitate symptoms, together with antacids or over‐the‐counter H2receptor antagonists (H2RAs). If symptoms persist after these simple measures or if antacids or H2RAs are needed quite often, then a more formal first‐line treatment should be started. Many experts feel that a stepdown approach instead of a stepup approach is clinically and economically a more appropriate way of installing such first‐line therapy. Physicians increasingly consider prescribing a (low‐ or standard dose) once‐a‐day proton pump inhibitor (PPI) as firstline therapy. If symptoms recur after 4‐week trial or are in sufficiently relieved, then the patient should be referred for endoscopy. Endoscopy may reveal no abnormalities (NERD) or evidence of reflux‐induced damage.

Treatment of endoscopy‐negative reflux disease should be directed towards rapid relief of symptoms and then maintenance of relief using minimum effective therapy. Responses to PPIs are somewhat lower in endoscopy‐negative patients compared to esophagitis. Some form of long‐term therapy is needed in the majority of patients. `On demand' PPI therapy to control reflux symptoms is a new and attractive option.

The goal of treatment of GERD should be to relieve symptoms and to heal lesions. Symptom severity and much less endoscopic abnormalities, drives the therapy. When symptoms are mild or intermittent and when esophagitis is absent or minimal, standard dose PPI is usually reinstituted. If there is moderate or severe esophagitis or if symptoms are particularly troublesome, then the patient should start again with standard‐dose PPI therapy once a day, but not uncommonly a b.i.d. dosage maybe necessary. Once a dose of the acid suppressant that relieves symptoms is found, this dose should be maintained for a period of 3 months. After this time, an attempt should be made to reduce the dose. A plan should be formulated for long‐term treatment.
Effect of octreotide on gastric and small bowel motility in patients with gastroparesis
Authors: Edmunds  , Chen  , Soykan  , Lin  , McCallum
Published: March 2003

Background:

Octreotide has been shown to have effects on gastric and small bowel motility with implications for its role in treating patients with upper gastrointestinal dysmotility syndromes. Our aim was to investigate the effect of octreotide on antral and small bowel motility in patients with gastroparesis.

Methods:

Upper gastrointestinal manometry was carried out continuously for a period of 30 h in 11 patients with gastroparesis. The spontaneous migrating motor complex (MMC) in the fasting state and octreotide‐induced MMCs were characterized and compared with regard to site of origin, duration of phase III, amplitude of phase III and propagation velocity of the MMC along the gut. The 2‐h postprandial motility index was compared after a control meal as well as after a 100 μg octreotide administration.

Results:

In all 11 gastroparetic patients, octreotide induced a phase III‐like activity front within minutes after administration and this primarily originated in the small bowel (86% of activity fronts compared with 32% of fronts originating in the small bowel prior to octreotide administration (P < 0.004)). Gastric initiation of these activity fronts dramatically decreased after octreotide administration, occurring in 68% of activity fronts prior to octreotide administration and 14% of occasions after octreotide injection (P < 0.05). The postprandial antral motility index was markedly reduced after octreotide administration (11.33 ± 0.39 vs. 7.96 ± 0.76, P < 0.0003) and octreotide re‐established a motility pattern during the postprandial period that was similar to that normally seen in the interdigestive state. The octreotide‐induced phase III activity fronts appeared at a higher frequency and had a higher propagative velocity compared to the spontaneous phase III fronts in the fasting state (9.27 ± 0.82 vs. 5.56 ± 0.81 cm/min, P < 0.05).

Conclusions:

We conclude that octreotide’s marked inhibitory effect on antral contractility may serve to worsen clinical symptoms in patients with gastroparesis and therefore this agent should not be given in the peri‐prandial period. Those gastroparetic patients with associated small bowel dysmotility and diarrhoea from bacterial overgrowth may benefit from the nocturnal administration of octreotide because of its stimulatory effect of phase III MMC activity as well as its known inhibitory effect on small bowel secretions.
US double‐blind, controlled trials of omeprazole and amoxycillin for treatment of Helicobacter pylori
Authors: Laine  , Johnson  , Suchower  , Ronca  , Hwang  , Neil
Published: March 2003

Background:

Widely variable Helicobacter pylori eradication rates have been reported with omeprazole/amoxycillin dual therapy. We present the first US double‐blind, controlled trials of this dual therapy.

Methods:

Three separate studies were performed: Studies 1 and 2 included patients with an active duodenal ulcer and Study 3 included patients with a documented history of duodenal ulcer. H. pylori eradication regimens in all studies were omeprazole plus amoxycillin vs. omeprazole vs. amoxycillin for 2 weeks. Doses in Study 1 were omeprazole 40 mg b.d. and amoxycillin 500 mg t.d.s., and in Studies 2 and 3 they were omeprazole 20 mg b.d. and amoxycillin 1 g t.d.s. Endoscopic biopsy tests were used for H. pylori diagnosis, and testing for H. pylori eradication was done at least 4 weeks after the completion of therapy. Amoxycillin sensitivities were performed in Study 2.

Results:

Intention‐to‐treat (ITT) and per protocol (PP) analyses showed that eradication rates with omeprazole/amoxycillin [ITT: 39%, 40%, 46% (n = 72, 62, 48); PP: 50%, 46%, 54% (n = 54, 52, 37)] were significantly greater than monotherapy with either omeprazole (ITT: 0–4%; PP: 0–5%) or amoxycillin (ITT: 2–5%; PP: 0–11%). No patients taking the dual therapy discontinued therapy due to adverse events. Amoxycillin resistance was not seen at baseline (n = 76) or after amoxycillin therapy (n = 56).

Conclusions:

Omeprazole/amoxycillin dual therapy is well tolerated but the eradication rate which can be expected in the USA is at best about 50%.
Effect of pepper and bismuth subsalicylate on gastric pain and surface hydrophobicity in the rat
Authors: Lichtenberger  , Romero  , Carryl  , Illich  , Walters
Published: March 2003

Background

The mechanism by which dietary pepper causes dyspepsia and epigastric pain is poorly understood, as is the ability of bismuth subsalicylate (BSS) to relieve these symptoms.

Aim

To investigate the ability of black pepper, red pepper and BSS to affect gastric surface hydrophobicity and induce/relieve visceral pain in rat model systems.

Methods

Fasted rats were administered intragastrically Vivonex containing varying concentrations of either black or red pepper (0–200 mg/mL) and gastric contact angles were read after 1–24 h. Some rats were post‐treated with BSS (2.0–17.5 mg/mL) and contact angles were read after 2–18 h. To study pain sensitivity in rats treated with pepper/BSS, we compared tail‐flick latencies after the application of radiant heat.

Results

Both black and red pepper rapidly (< 1 h) induced a decrease in gastric surface hydrophobicity in a dose‐dependent fashion. This spice‐induced increase in surface wettability was long‐lasting, could be enhanced in the presence of ethanol and reversed by post‐treating the rats with BSS. Both black and red pepper induced an increase in pain sensitivity, consistent with the presence of gastric pain, which could also be reversed by post‐treating the rats with BSS.

Conclusion

Both black and red pepper may induce epigastric pain by removing the stomach’s hydrophobic lining and activating intramucosal pain receptors. BSS may provide relief from postprandial dyspepsia by restoring the stomach’s non‐wettable properties.
Omeprazole 20 or 40 mg daily for healing gastroduodenal ulcers in patients receiving non‐steroidal anti‐inflammatory drugs
Authors: Claar G. Massimo , Monaco  , Blanco C. Del Veccho , Capurso  , Fusillo  , Annibale
Published: March 2003

Background

Non‐steroidal anti‐inflammatory drugs (NSAIDs) are strongly associated with gastroduodenal ulcers, and the management of patients with NSAID‐associated ulcers represents a common clinical dilemma.

Aim

To assess NSAID‐associated ulcer healing during treatment with either standard (20 mg) or high dosage (40 mg) omeprazole.

Methods

One hundred and sixty‐nine patients chronically ingesting diclofenac, ketoprofen, indome‐thacin or naproxen for osteoarthritis or rheumatoid arthritis, who had abdominal pain and an endoscopically proven gastroduodenal ulcer, were evaluated in a randomized, double‐blind, dose regimen trial with omeprazole 20 mg o.m. (n = 81) or omeprazole 40 mg o.m. (n = 88). Ulcer healing was assessed endoscopically at 4 and 8 weeks in the case of unhealed ulcers. Patients continued their usual daily dose of anti‐inflammatory medication throughout the study period.

Results

One hundred and fifty‐six patients completed the study (77 patients taking 20 mg omeprazole and 79 patients taking 40 mg omeprazole); 12 patients were lost during follow‐up and one patient reported an adverse event. Cumulative ulcer intention‐to‐treat healing rates at 8 weeks were 88% (95% confidence interval (CI) = 79–95%) for the 20 mg omeprazole group and 96.2% (95% CI = 89–99%) for the 40 mg group, and 97.1% (95% CI = 90–100%) for the 20 mg omeprazole group and 98.6% (95% CI = 93–100%) for the 40 mg group by per protocol analysis. There were no statistically significant differences between the two groups. Symptom relief did not differ significantly between the two treatment groups.

Conclusion

Both standard and high doses of omeprazole are equally safe and effective regimens for the treatment of NSAID‐induced gastroduodenal ulcers when anti‐inflammatory treatment is not discontinued.
Effects of cholinergic agents on anorectal physiology
Authors: Siproudhis  , Bellissant  , Juguet  , Allain  , Bretagne  , Gosselin
Published: March 2003

Background:

Despite their potential therapeutic benefit, the effects of cholinergic agents on anal function have been poorly investigated.

Aim:

To analyse the effects of neostigmine and atropine on anorectal responses to rectal isobaric distension.

Methods:

This was a placebo‐controlled, randomized, double‐blind crossover study, performed in 12 healthy volunteers who received intravenously, on 3 separate days, neostigmine, atropine or the placebo. During each day of the experiment, seven pressure steps (ranging from 1 to 31 mmHg) in three different protocols of rectal isobaric distension (phasic, stepwise and tonic) were applied using an electronic barostat. Manometric responses of the anal canal, adaptative volumes and perception scores of the rectum were recorded.

Results:

During stepwise distension, a significant drug effect was encountered at the anal level. No drug effect was observed on the other investigated parameters (rectal volumes and rectal perception scores) or for the other modes of distension. Compared to placebo, neostigmine significantly decreased pressures at the upper level of the anal canal for both recto anal inhibitory reflex and mean resting pressures. In contrast, atropine significantly increased pressures at the lower part of the anal canal but did not modify upper anal pressures.

Conclusion:

The present study suggests that cholinergic effects result more from an indirect action on intermediate neurotransmitters and rectal myenteric neurons, than from a direct action on anal targets.
An evaluation of whole blood testing for Helicobacter pylori in general practice
Authors: Talley  , Lambert  , Howell  , Xia  , Lin  , Agreus
Published: March 2003

Background:

Rapid whole blood tests for Helicobacter pylori infection were developed to assist in the management of patients with dyspepsia in general practice. However, they have not been extensively tested in this setting.

Aim:

To investigate the test characteristics of the BM‐Test (Helisal Quick Test) when used in general practice.

Method:

One hundred and ten dyspeptic patients attending local general practitioners were recruited into the study. The BM‐Test was administered by the general practitioner at the screening visit according to standard instructions supplied with the test kit. The patient was then referred to Nepean or Mornington Peninsula Hospitals for further assessment, including a 14C‐urea breath test. The test kit was forwarded to the appropriate hospital centre for an independent, blinded reading. The sensitivity and specificity of the BM‐Test were evaluated against the results of the 14C‐UBT.

Results:

Based on general practitioner readings, the BM‐Test had a sensitivity of 59.3% and a specificity of 90.2%. The positive and negative predictive values were 87.5% and 65.7%, respectively. When based on independent readings, sensitivity rose to 71.2% and specificity fell to 88.2%. The BM‐Test was more sensitive for older patients than for younger patients when based on both the general practitioner and independent readings.

Conclusion:

The BM‐Test performs below the generally recommended sensitivity and specificity of 90% required for clinical practice.
Helicobacter pylori eradication and ulcer healing with daily lansoprazole, plus 1 or 2 weeks co‐therapy with amoxycillin and clarithromycin
Authors: Louw J. A. , Rensburg C. J. Van , Moola S. , Kotze D. , Marks I. N.
Published: March 2003

Background:

Proton pump inhibitor based combination therapy is one standard strategy for Helicobacter pylori eradication.

Aim:

To compare the eradication and duodenal ulcer healing efficacy of two 2‐week, single dose, lansoprazole based combination therapies.

Methods:

Healthy adult patients with endoscopically confirmed, H. pylori associated duodenal ulcer disease (3 mm > ulcer < 20 mm) were eligible for the study. All patients received a 14 day course of lansoprazole 30 mg o.m., and were randomized to receive either 7 or 14 days of amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. Patients were endoscoped at entry and 14–17 days later. Symptomatic, unhealed patients received a further 14 days of therapy with lansoprazole 30 mg o.m. Eradication was confirmed a minimum of 28 days after cessation of all therapy by urease reaction and histological assessment of gastric body and antral biopsies (three biopsies each site).

Results:

Sixty‐two patients were randomized to a treatment arm, of which 58 could be included in an intention‐to‐treat and key‐point‐available analysis. H. pylori eradication rates were identical, at 93% (95% CI: 73–98% (1 week), 78–99% (2 week)). In the combined group, all but 13 ulcers were healed at 2 weeks; six required further therapy because of symptoms, while six of the seven asymptomatic patients went on to heal.

Conclusion:

An eradication regimen, based on a 2‐week course of single dose lansoprazole with 1 week of antibiotic co‐therapy, is effective in eradicating H. pylori, while the 2 weeks of acid suppression is usually effective in duodenal ulcer healing.