bluuebunny/crossref_metadata_2025 huggingface dataset:
Erythropoietin concentrations during 10 days of normobaric hypoxia under controlled environmental circumstances
Authors: BERGLUND B. , GENNSER M. , ÖRNHAGEN H. , ÖSTBERG C. , WIDE L.
Published: March 2003

Serum erythropoietin levels (s‐[epo]), haemoglobin concentration ([Hb]), haematocrit (hct), and ferritin concentration ([fer]) were measured in seven healthy male volunteers (20–23 years) exposed continuously to hypoxia (PO2 14 kPa) for 10 days. Serum erythropoietin concentration increased significantly from 9.5 ± 3.51 to 33.6 ± 11.64 U L–1 (P < 0.05) after 2 days of hypoxia. Thereafter, s‐[epo] decreased. However, after 10 days s‐[epo] was 18.7 ± 5.83 U L–1 which was still increased above the pre‐hypoxia level (P < 0.05). Serum haemoglobin concentration and hct increased over the 10 days of hypoxia, [Hb] from 152 ± 8.9 to 168 ± 9.2 gL–1 (P < 0.001), and hct from 43 ± 2.4 to 49 ± 2.6% (P < 0.001). Ferritin concentration decreased significantly during the hypoxic exposure from 82 ± 46.9 to 44 ± 31.7 mmol L–1 after 10 days (P < 0.01). In conclusion, the initial increase of s‐[epo] under controlled normobaric hypoxia was marked, 353%, and levelled off after 5–10 days at 62–97% above normoxia level. There was also a significant increase in [Hb] and hct and a decrease in [fer] after 10 days of exposure to normobaric hypoxia.
Effects of moderate and intensive training on the hypothalamo–pituitary–adrenal axis in rats
Authors: CHENNAOUI M. , GOMEZ MERINO D. , LESAGE J. , DROGOU C. , GUEZENNEC C. Y.
Published: March 2003

The influence of the two distinct training programmes, moderate (M) and intensive (I), on hypothalamo–pituitary–adrenal (HPA) axis was investigated, in rats. Changes in plasma concentrations of adrenocorticotropin hormone (ACTH) and corticosterone were followed in response to (i) a 60‐min acute running session performed on 2nd, 4th and 6th of the seven training weeks (ii) an acute restraint stress of 40 min applied after the final training programme. After 2nd, 4th and 6th week of the two training programmes, a 60‐min running resulted in an enhanced secretion of ACTH and corticosterone, compared with both the baseline values (i.e. before running) and to the sedentary (S) group. However, on 4th and 6th weeks compared with 2nd week, ACTH and corticosterone remained elevated in intensive group when they are significantly reduced in moderate group. We could suggest that a moderate training resulted in an adapted hormonal response whereas a deadapted process occurred for the intensive programme. The day after the last training session, basal ACTH, corticosterone and corticosteroid‐binding globulin (CBG) capacity were not affected by training. Hypothalamic corticotropin‐releasing factor tissue‐content (CRF) was increased significantly in the two trained groups. When compared with the sedentary group, the body weight of the rats in the two trained groups was significantly decreased with a total adrenal mass increasing but only in intensive group. The surimposed restraint stress resulted in significant increases in plasma ACTH and corticosterone both in trained and in sedentary animals. This result suggests that the adapted HPA axis response induced by both a moderate and intensive training do not prevent against the effects of a novel stress such as restraint stress.
Evidence that brain glucose availability influences exercise‐enhanced extracellular 5‐HT level in hippocampus: a microdialysis study in exercising rats
Authors: Béquet F. , Gomez‐Merino D. , Berthelot M. , Guezennec C. Y.
Published: March 2003

The relationship between brain glucose and serotonin is still unclear and no direct evidence of an action of brain glucose on serotonergic metabolism in central fatigue phenomena has been shown yet. In order to determine whether or not brain glucose could influence the brain 5‐hydroxytryptamine (5‐HT) system, we have monitored in microdialysis the effects of a direct injection of glucose in rat brain hippocampus on serotonergic metabolism [i.e. 5‐HT, 5‐hydroxyindoleacetic acid (5‐HIAA) and tryptophan (TRP)], during high intensive treadmill running. The injection was performed just before and after exercise. We have shown that glucose induced a decrease of brain 5‐HT levels to a minimum of 73.0 ± 3.5% of baseline after the first injection (P < 0.01) and to 68.5 ± 5.5% of baseline after the second injection (P < 0.01) and consequently prevented the exercise‐induced 5‐HT enhanced levels. We have observed the same phenomenon concerning the 5‐HIAA, but brain TRP levels were not decreased by the injections. In conclusion, this study demonstrates that brain glucose can act on serotonergic metabolism and thus can prevent exercise‐induced increase of 5‐HT levels. The results also suggest that extracellular brain glucose does not act on the synthesis way of 5‐HT, but probably on the release/reuptake system.
Altered sarcoplasmic reticulum function in rat diaphragm after high‐intensity exercise
Authors: Matsunaga S. , Inashima S. , Tsuchimochi H. , Yamada T. , Hazama T. , Wada M.
Published: March 2003

The present study examined the effects of acute high‐intensity exercise on Ca2+ uptake and release rates and Ca2+‐adenosine triphosphatase (ATPase) activity of the sarcoplasmic reticulum (SR) from the costal diaphragm. The rats were run on a treadmill at an estimated requirement of 100% of maximal O2 consumption until fatigued (average time to exhaustion: 4.79 min). Muscle lactate and inorganic phosphate after exercise were increased by 65% (P < 0.05) and 35% (P < 0.05), respectively. With exercise, Ca2+ uptake and release, which were detected in homogenates using the Ca2+ fluorescent dye indo‐1, were decreased by 24% (P < 0.05) and 22% (P < 0.05), respectively. The reduction in Ca2+ uptake was paralleled by decreased activity of SR Ca2+‐ATPase in both the absence and presence of Ca2+ ionophore. These findings demonstrate that, in the diaphragm as well as in the locomotor muscles that have been explored in previous studies, the attenuations of the SR function is brought about by acute high‐intensity exercise. These changes in the SR of the diaphragm may contribute, at least in part, to deteriorations in exercise tolerance and work productivity resulting from repetitive physical activities.
Proposed role of the paraventricular nucleus in cardiovascular deconditioning
Authors: Mueller P. J. , Cunningham J. T. , Patel K. P. , Hasser E. M.
Published: March 2003

AbstractAim: Cardiovascular deconditioning occurs in individuals exposed to prolonged spaceflight or bedrest and is associated with the development of orthostatic intolerance. Although the precise mechanisms remain to be fully elucidated, astronauts returning from space or bedrest patients returning to normal upright posture present with decreases in plasma volume and alterations in autonomic function. The hindlimb unloaded (HU) rat has been a useful model to study the effects of cardiovascular deconditioning as it mimics many of the changes that occur after spaceflight and bedrest.

Results: Experiments performed in HU rats suggest that cardiovascular deconditioning attenuates baroreflex mediated sympathoexcitation and enhances cardiopulmonary receptor mediated sympathoinhibition. These alterations appear to be due to changes in the central nervous system and may contribute to the pre disposition towards orthostatic intolerance associated with cardiovascular deconditioning. The paraventricular nucleus (PVN) of the hypothalamus is important in basal and reflex control of sympathetic outflow. Recent evidence suggests that nitric oxide (NO) is an important inhibitory neurotransmitter in the PVN and that alterations in nitroxidergic transmission in the PVN may be involved in elevated sympathetic tone in certain disease states.

Conclusion: Based on evidence from other laboratories and published and preliminary data from our own laboratories, this review proposes a role for the PVN in cardiovascular deconditioning. In particular, we discuss the hypothesis that increased NO in the PVN contributes to the altered cardiovascular reflexes observed following deconditioning and how these reflexes may be related to the orthostatic intolerance observed after prolonged spaceflight or bedrest.
Medullary and supramedullary mechanisms regulating sympathetic vasomotor tone
Authors: Dampney R. A. L. , Horiuchi J. , Tagawa T. , Fontes M. A. P. , Potts P. D. , Polson J. W.
Published: March 2003

Aim:Neurons in the rostral ventrolateral medulla (RVLM) that project directly to sympathetic preganglionic neurons in the spinal cord play a critical role in maintaining tonic activity in sympathetic vasomotor nerves. Intracellular recordingsin vivofrom putative RVLM presympathetic neurons have demonstrated that under resting conditions these neurons display an irregular tonic firing rate, and also receive both excitatory and inhibitory synaptic inputs. This paper will briefly review some recent findings on the role of glutamate, GABA and angiotensin II (Ang II) receptors in maintaining the tonic activity of RVLM presympathetic neurons.

Results:Based on these findings, the following hypotheses will be discussed: (1) RVLM neurons receive tonic glutamatergic excitatory inputs, which originate from both medullary and supramedullary sources; (2) at least some neurons that project to and tonically inhibit RVLM presympathetic neurons are themselves tonically inhibited by GABAergic inputs originating from neurons in the caudalmost part of the ventrolateral medulla (caudal pressor area); (3) under normal conditions, Ang II receptors in the RVLM do not contribute significantly to the tonic activity of RVLM presympathetic neurons, but may do so in abnormal conditions such as heart failure or neurogenic hypertension; (4) RVLM presympathetic neurons maintain a significant level of tonic resting activity even when glutamate, GABA and Ang II receptors on the neurons are completely blocked. Under these conditions, the tonic activity is a consequence either of the intrinsic membrane properties of the neurons (autoactivity) or of synaptic inputs mediated by receptors other than glutamate, GABA or Ang II receptors.

Conclusion:The current evidence indicates that the resting activity of RVLM presympathetic neurons is determined by the balance of powerful tonic excitatory and inhibitory synaptic inputs. Ang II receptors also contribute to the raised resting activity of these neurons in some pathological conditions.
Arousal increases baroreflex inhibition of muscle sympathetic activity
Authors: Gunnar Wallin B. , Donadio V. , Karlsson T. , Kallio M. , Nordin M. , Elam M.
Published: March 2003

Aim: Surprising sensory stimuli causing arousal are known to evoke short‐lasting activation of human sympathetic activity in skin but not in muscle nerves. In fact, anecdotal observations suggest that muscle sympathetic activity may be inhibited. To test this hypothesis, the effects of surprising somatosensory (electrical skin pulses) or visual (flash) stimuli on multiunit muscle sympathetic activity were studied in 36 healthy subjects, aged 19–71 years.

Methods: The stimuli were given either 200 or 400 ms after the R‐wave of the electrocardiogram. Dummy stimuli, consisting of trigger pulses without sensory stimuli, served as controls.

Results: On a group basis, a single sensory stimulus of either type attenuated the amplitude of one or two sympathetic bursts, while no such effects occurred after dummy stimuli. Individually, the inhibition was evoked by at least one stimulus modality or delay in 16 subjects, whereas in three subjects no significant inhibition occurred. Electrodermal signs of skin sympathetic activation were present in all subjects. Compared with one, five repeated electrical skin pulses induced only minor additional inhibition of muscle sympathetic activity, indicating marked habituation of the neural response. In nine subjects, the experiments were repeated once and in three subjects twice (with intervals of 2–3 months); in 11 of the12 subjects, the sympathetic effects were reproducible. In the group of subjects without significant sympathetic inhibition the stimuli induced a small, transient increase of mean blood pressure, which was not present in the group with sympathetic inhibition.

Conclusion: The finding that different sensory stimuli induce similar effects that habituate markedly on repetition suggests that the inhibition of muscle sympathetic activity is because of arousal. The interindividual differences in sympathetic and blood pressure effects may be part of interindividual differences in behavioural responses to stress.
Abundance and distribution of mammals in Katavi National Park, Tanzania
Authors: Caro T. M.
Published: March 2003

Ground transects were used to determine densities of 24 larger mammals in Katavi National Park. The Park consists of miombo woodland habitat and two seasonal lakes. Mammalian biomass was extremely high due primarily to large numbers of buffalo. The highest mammal densities were found around Lake Chada to the south‐east of the Park. Contrary to earlier reports, species’ densities did not differ significantly between dry, wet and intermediate seasons, suggesting that, aside from elephant and warthog, mammals did not enter or leave the Park in large numbers. Similarly, aside from zebra and waterbuck, sightings of species in different vegetation types did not change markedly between seasons. Thus, seasonal lakes in Katavi National Park support very high local concentrations rather than acting as dry season refuges for mammals outside the Park.
Structure and composition of benthic macroinvertebrates of a tropical forest stream, River Nyamweru, western Uganda
Authors: Tumwesigye Charles , Yusuf S. Kizito , Makanga Boniface
Published: March 2003

Benthic invertebrates from River Nyamweru, a tropical forest stream in western Uganda were sampled bimonthly between April and December 1997 using a modified Hess Sampler. A total of 3708 benthic fauna from thirteen taxonomic orders were collected. Benthic samples were dominated by Diptera (mainly Chironomidae) representing over 60% of all the organisms, followed by Ephemeroptera. Benthic invertebrate densities ranged from 63 ± 9.03 organisms/m2 to 300 ± 33.36 organisms/m2, with higher densities occurring during the dry season and lower densities during the wet season. The benthic community structure in River Nyamweru reflected mainly collectors and scrapers as the most important groups (83%), while predators were very rare (3.1%). River discharge influenced benthic abundance, with more invertebrates at lower discharge and fewer invertebrates at higher discharge. The applicability of the River Continuum Concept to tropical forest stream situation is discussed.
Diet composition and habitat selection of eland in semi‐arid shrubland
Authors: Watson Laurence H. , Owen‐Smith Norman
Published: March 2003

This study investigated the diet composition and habitat selection of eland in semi‐arid shrubland, dominated by microphyllous and leptophyllous browse species offering low leaf: stem ratios. Browse (succulent, forb and woody species) contributed 94% to the annual diet of eland. The annual proportion of grass in eland diet was low (6%), even though palatable grass species were abundant in habitats favoured by eland. Most grass was eaten in the early wet season when grasses offered young green foliage. Woody species comprising dwarf shrubs and shrubs made up the bulk of the food eaten by eland. In each season, favoured woody species contributed substantial proportions to the diet of eland. Eland used the plateau habitats in the early wet season, but valleys and slopes in the late wet and dry seasons. Habitats favoured by eland contained high abundances of plants of woody species favoured by eland. Chemical analysis indicated that woody species favoured by eland offered lower total fibre contents than other woody species available to eland. The results of the study indicated that eland are browsers that select browse of low fibre content.
The influence of food supplementation on a coastal dune rodent community
Authors: Koekemoer A. C. , Van Aarde R. J.
Published: March 2003

Studies of the rodent community in regenerating coastal dune forest areas north of Richards Bay, South Africa, have indicated that a number of species occupy newly rehabilitating areas. Unstable environmental conditions result in habitat changes, rather than competitive interactions, being the major determinant of rodent community development. This led to the present study, which investigated the effects of supplementary food on rodent assemblages. We attempted to stabilize food availability in order to elucidate some of the mechanisms responsible for the development of the rodent community. By only increasing an existing portion of the resource spectrum, we reduced species diversity, probably through dominance by competitive superior exploiters of the augmented resource. Thus, species diversity decreased with food supplementation, as a result of an increase in the abundance of Mastomys natalensis rather than because of a change in the number of species or the abundance of other species.
Effects of large herbivores and fire on the regeneration of Acacia erioloba woodlands in Chobe National Park, Botswana
Authors: Barnes Myra E.
Published: March 2003

Acacia erioloba woodlands provide important forage and shade for wildlife in northern Botswana. Mortality of mature trees caused by browsing elephants has been well documented but the lack of regeneration of new trees has received little attention. Annual growth of new shoots and changes in height were measured to determine the influence of elephants and small ungulate browsers, rainfall and fire on the growth and survival of established A. erioloba seedlings from 1995 to 1997 in the Savuti area of Chobe National Park. All above‐ground vegetation was removed from 40% of established seedlings in 1995 and 28% in 1997 by browsing elephants, and the mean height of remaining seedlings decreased from >550 mm to <300 mm. When seedlings browsed by kudu, impala and steenbok but not elephants are considered, mean seedling height increased <50 mm per year, even though mean new shoot growth remaining at the end of the dry season was 100–200 mm. Fires burned portions of the study area in 1993 and 1997, killing above‐ground vegetation, but most established A. erioloba seedlings survived, producing coppice growth from roots. While elephants and fire caused the greatest reduction in established seedling height and number, small browsers suppressed growth, keeping seedlings vulnerable to fire and delaying growth to reproductive maturity.
Feeding ecology and foraging behaviour of impala Aepyceros melampus in Lake Mburo National Park, Uganda
Authors: Wronski Torsten
Published: March 2003

Intersexual and seasonal variation in foraging behaviour of impala (Aepyceros melampus), was studied in the Lake Mburo National Park, Uganda. There was a moderate seasonal difference in foraging efficiency (as measured by ‘acceptable food abundance’), with a minimum in dry season and a maximum in Rainy season. The variation between sexes was more distinct with a pronounced minimum in time spent browsing of males in early wet season. By distinguishing between feeding time spent grazing and feeding time spent browsing the seasonal variation was confirmed. The proportion of foraging time spent feeding (expressed as ‘food ingestion rate’) showed an inverse pattern with a maximum in the late dry season (75.5%), decreasing values throughout the Rainy season and a minimum in early dry season (57.8%). Differences between sexes were explained in terms of reproductive demands and seasonal balance in terms of moderate climate throughout the year. Impala foraging patterns in the bimodal tropics (two Rainy seasons) is discussed and compared with unimodal tropics. The findings are matched against current ideas on optimal foraging.
Addressing management questions for Ngorongoro Conservation Area, Tanzania, using the Savanna modelling system
Authors: Boone Randall B. , Coughenour Michael B. , Galvin Kathleen A. , Ellis James E.
Published: March 2003

Ngorongoro Conservation Area (NCA), in northern Tanzania, is a multiple‐use area of importance to Maasai pastoralists and wildlife conservation. We adapted the Savanna modelling system to the NCA, creating an Integrated Management and Assessment System that allows users to assess responses to alternative management actions. We used the system to conduct fifteen experiments reflecting potential management questions. Results suggest that: the distribution of rainfall throughout the year may have a greater impact on the ecosystem than its quantity; cattle may be near a carrying capacity determined not by forage limitations but because of disease risks; increasing survival and reducing disease in livestock yields greater returns than increasing birth rates; allowing livestock to graze in areas where they are currently excluded may lead to a slight increase in livestock populations, but sometimes leads to large declines in wildlife populations; few ecosystem effects were noted when households and cultivation were allowed to grow at 3% per year for 15 years; and when up to 5% of the study area was in cultivation, there were declines ≤16% in livestock and wildlife populations, except for elephants, which declined by 48%. Users may modify our experiments using tools we have developed, or address other NCA management questions.
Body size and measurement of species diversity in large grazing mammals
Authors: Oindo Boniface O.
Published: March 2003

Species are by definition different from each other. This fact favours ranking rather than additive indices. However, ecologists have measured species diversity in terms of species richness, or by combining species richness with the relative abundance of species within an area. Both methods raise problems: species richness treats all species equally, while relative abundance is not a fixed property of species but varies widely temporally and spatially, and requires a massive sampling effort. The functional aspect of species diversity measurement may be strengthened by incorporating differences between species such as body size as a component of diversity. An index of diversity derived from a measure of variation in body size among species is proposed for large grazing mammals. The proposed diversity index related positively to species abundance, indicating that the use of body size as a surrogate for diversity is adequate. Because the proposed index is based on presence or absence data, the expensive and time consuming counting of individuals per species in each sampling unit is not necessary.
Species composition of termites of the Nyika plateau forests, northern Malawi, over an altitudinal gradient
Authors: Donovan Sarah E. , Eggleton Paul , Martin Andy
Published: March 2003

Termites were surveyed at three altitudes (Brachystegia woodland at 1676 m and 1905 m, and Juniper woodland at 2210 m) in forests within the Nyika Plateau, northern Malawi. Sampling was by a standardized 100 m transect protocol. Termite diversity was highest in the mid‐altitude site and lowest in the Juniper forest. The assemblages were dominated by soil‐feeding termites in the Termitidae subfamilies Apicotermitinae and Termitinae, and included one new soldierless Apicotermitinae genus. The structure of the assemblages was clearly due to a mixture of altitudinal and site history factors. This was especially true of the lowest altitude forest where burning and other anthropogenic disturbance factors appear to have reduced termite diversity relative to the mid‐altitude site. The Nyika plateau shows a much higher diversity at mid‐altitudes than similar SE Asian sites, probably due to the larger area of highland in Africa than in SE Asia. In addition, the clade composition of the Nyika assemblages differs completely from that found at similar altitudes in SE Asia. This preliminary study supports the hypothesis that mid‐ to high‐ altitude assemblages in both SE Asia and Africa appear to be derived from depauperated random subsets of the lowland fauna rather than from clades specifically adapted to higher altitudes.
Persistent increase in myofibroblasts in Helicobacter heilmannii‐infected mice but not in Helicobacter pylori‐infected Mongolian gerbils: colocalization of COX‐2 and bFGF immunoreactivity
Authors: Nakamura M. , Takahashi S. , Matsui H. , Nishikawa K. , Akiba Y. , Ishii H.
Published: March 2003

Background:

The clinical significance of Helicobacter heilmannii infection remains uncertain, owing to the lack of a specific detection method. Recently, we reported a marked increase in myofibroblasts in the early stage of Helicobacter pylori infection in Monglian gerbils.

Aim:

The present study was designed to clarify changes in myofibroblasts, and in the immunoeactivities of basic fibroblast growth factor, cyclooxygenase‐2 and inducible nitric oxide synthase after H. pylori infection in Monglian gerbils and H. heilmannii infection in mice.

Methods:

After oral inoculation, changes in the location of bacteria and the immunoreactivity of myofibroblasts, basic fibroblast growth factor, cyclooxygenase‐2 and inducible nitric oxide synthase were stained with the indirect immunofluorescent method and observed by confocal laser microscopy.

Results:

In H. heilmannii‐infected mice, the increases in myofibroblasts and in immunoreactivities of these three markers were sustained 12 months after infection. In H. pylori‐infected Monglian gerbils, however, these increases were significant at 3 months but had returned to control levels at 12 months.

Conclusions:

Two types of Helicobacter infection showed different patterns of myofibroblast proliferation, coinciding with the extent of inflammation. These findings suggest that this difference may be related to the consequences of the infection.
The effect of heparin on trinitrobenzene sulphonic acid‐induced colitis in the rat
Authors: Fries  , Pagiaro  , Canova  , Carraro  , Gasparini  , Pomerri  , Martin  , Carlotto  , Mazzon  , Sturniolo  , Longo
Published: March 2003

Background:

Reduced blood coagulability seems to protect against inflammatory bowel disease; pilot studies using heparin in patients with inflammatory bowel disease have reported positive results.

Aim:

To evaluate the effects of heparin treatment on microangiographic and on inflammatory parameters in experimental colitis, induced by trinitrobenzene sulphonic acid (TNBS)‐ethanol.

Methods:

Four groups of rats: (i) controls (saline enema), TNBS‐induced colitis with (ii) sham treatment (saline, s.c.), (iii) dexamethasone (0.25 mg/kg/day s.c.) and (iv) heparin (500 U/kg t.d.s., s.c.). Microangiography was performed 2 and 4 days after colitis induction. Partial thromboplastin time, colonic wet weight, macroscopic damage score and mucosal myeloperoxidase (MPO) activity were determined at day 4.

Results:

TNBS‐induced colitis caused a reduction in visible bowel wall vessels, which was prevented by heparin (P < 0.05) but not by steroids. The macroscopic damage scores and colon wet weights were similar in all colitis groups. Compared to untreated colitis the MPO activity in heparin‐treated animals was of borderline significance.

Conclusions:

Heparin treatment improved microangiographic features and reduced inflammation to a certain degree. Steroids delayed development of colon hypoperfusion, but were ineffective on MPO activity. It remains to be determined if the observed effects are due to the antithrombotic activity of heparin or to an anti‐inflammatory action.
Which form of erythromycin should be used to treat gastroparesis? A pharmacokinetic analysis
Authors: Ehrenpreis  , Zaitman  , Nellans
Published: March 2003

Background:

Erythromycin is a macrolide antibiotic that exhibits prokinetic effects. It has been shown to enhance antral contractility and accelerates gastric emptying rates, primarily by stimulating motilin receptors.

Aim:

To determine the optimal dosage form of erythromycin for use as a prokinetic agent.

Methods:

Eight normal volunteers and three patients with documented gastroparesis ingested 250 mg erythromycin in tablet, suspension and intravenous forms. Serum erythromycin levels were determined at frequent intervals. These data were plotted vs. time and analysed for lag time, time to maximum concentration (tmax), maximum concentration (Cmax) and bioavailability (F).

Results:

The absorption kinetics of the erythromycin suspension was notable for short lag times and early tmax, while lag times and tmax were delayed with the tablet form. Median lag time was 15 min for the suspension vs. 90 min for the tablet (P < 0.005). Median tmax for the suspension was 45 min vs. 180 min for the tablet (P < 0.005). A non‐significant decrease in F was seen with the suspension compared to the tablet (P = 0.12).

Conclusion:

Based on the kinetic data from this study, erythromycin suspension is the ideal dosage form for administration of this drug as a prokinetic agent.
glycyrrhizin as a potential treatment for chronic hepatitis C
Authors: Rossum T. G. J. Van , Vulto  , Man R. A. De , Brouwer  , Schalm
Published: March 2003

Chronic hepatitis C is a slowly progressive liver disease that may evolve into cirrhosis with its potential complications of liver failure or hepatocellular carcinoma. Current therapy with α‐interferon is directed at viral clearance, but sustained response is only achieved in 20–40% of patients without cirrhosis, and less than 20% in patients with cirrhosis who have the greatest need for therapy. Treatment for those who do not respond to anti‐viral therapy is highly desirable.

In Japan glycyrrhizin has been used for more than 20 years as treatment for chronic hepatitis. In randomized controlled trials, glycyrrhizin induced a significant reduction of serum aminotransferases and an improvement in liver histology compared to placebo. Recently, these short‐term effects have been amplified by a well‐conducted retrospective study suggesting that long‐term usage of glycyrrhizin prevents development of hepatocellular carcinoma in chronic hepatitis C.

The mechanism by which glycyrrhizin improves liver biochemistry and histology are undefined. Metabolism, pharmacokinetics, side‐effects, and anti‐viral and hepatoprotective effects of glycyrrhizin are discussed.
The management of acute liver failure
Authors: Plevris  , Schina  , Hayes
Published: March 2003

Acute liver failure (ALF) is a relatively uncommon but dramatic clinical syndrome with high mortality rates, in which a previously normal liver fails within days or weeks. Paracetamol overdose remains the major cause of ALF in the UK, while viral hepatitis is the commonest cause world‐wide. Cerebral oedema is the leading cause of death in patients with ALF. Despite advances in intensive care and the development of new treatment modalities, ALF remains a condition of high mortality best managed in specialist centres. Orthotopic liver transplantation is the only new treatment modality that has made a significant impact in improving outcome. Bioartificial liver support systems and hepatocyte transplantation are new promising treatment options that may change the management of ALF in the future.
Review article: short chain fatty acids in health and disease
Authors: Cook  , Sellin
Published: March 2003

Short chain fatty acids (SCFAs) have been the subject of much research over the past few decades. They play a vital role in maintenance of colonic integrity and metabolism. They are produced when dietary fibre is fermented by colonic bacteria. SCFAs are avidly absorbed in the colon, at the same time as sodium and water absorption and bicarbonate secretion. Once absorbed, SCFAs are used preferentially as fuel for colonic epithelial cells and have trophic effects on the epithelium. Clinically, SCFAs have been studied as possible therapeutic agents in diversion colitis, ulcerative colitis, radiation proctitis, pouchitis and antibiotic‐associated diarrhoea. Although some promising effects have been observed in uncontrolled studies, a specific therapeutic role for SCFAs remains to be defined. SCFAs may be the effector of the beneficial role of fibre in prevention of colon cancer.
Mebeverine decreases mass movements and stool frequency in lactulose‐induced diarrhoea
Authors: Washington  , Ridley  , Thomas  , Spiller  , Watts  , Wilson
Published: March 2003

Background:

In spite of its frequent use in the treatment of irritable bowel disease little is known about mebeverine’s mode of action in man.

Aim:

To examine mebeverine’s effect on transit though the gut during lactulose‐induced diarrhoea.

Methods:

Nine healthy volunteers undertook a two‐way randomized crossover study. Diarrhoea was induced using lactulose pre‐treatment (20 m t.d.s., 4 days) and subjects received either mebeverine (135 mg t.d.s.) or no treatment. Transit of two enteric‐coated capsules containing radiolabelled 8.4 mm tablets and 180–250 μM ion exchange resin were followed using gamma scintigraphy. Stool frequency and symptoms were assessed by diary cards.

Results:

Mebeverine reduced mean daily stool frequency associated with lactulose ingestion from a median of 2.25 (interquartile range (IQR) 1.75–2.75) to 1.5 (IQR 1.25–2.25) movements. Mebeverine significantly reduced the number of mass movements observed in the colon during the 11 h of the study from 2 (2–2) to 1 (1–2), and the number of retrograde movements from 1 (0–2) to 0 (0–0) (P < 0.05). Mebeverine did not significantly alter the gastric emptying rate of the intact capsule (2.9 (1.9–3.2) to 2.8 (2.6–4.0) h) however it induced a small but significant acceleration in small intestinal transit of the capsule (1.6 (0.8–2.0) h to 1.0 (0.52–1.32) h, P = 0.02).

Conclusion:

Mebeverine reduces the diarrhoeal effect of lactulose by decreasing the mass movements induced in the ascending colon. This effect may contribute to its clinical effect in irritable bowel syndrome.
Development of a digestive health status instrument: tests of scaling assumptions, structure and reliability in a primary care population
Authors: Shaw  , Talley  , Adlis  , Beebe  , Tomshine  , Healey
Published: March 2003

Background:

The absence of valid and reliable health status measures for functional gastrointestinal illness has limited research and patient care for this common group of disorders. A self‐report survey has been developed.

Methods:

Initial development focused on extensive pre‐testing of patients, primary care physicians and gastroenterologists. The disease‐specific portion included the Rome criteria for dyspepsia subgroups and the Manning and Rome criteria for irritable bowel syndrome. The Short Form‐36 was added. Psychometric analyses included techniques of multitrait scaling, scale internal consistency and criterion validation.

Results:

Six hundred and ninety patients presenting to their primary care physician for treatment of heartburn, abdominal pain or discomfort completed the 98 question survey. The disease‐specific portion revealed five components including reflux, dysmotility, a two‐domain bowel dysfunction complex, and a pain index. Internal consistency measures demonstrated good to excellent reliability. Scaling successes were observed on multitrait scaling. The disease‐specific portion was reduced to 34 questions. Criterion validity was demonstrated with the correlation of the disease‐specific questions to the SF‐36.

Conclusions:

The psychometric analyses lend credence to the concept of stomach and bowel symptom subgrouping as proposed by expert consensus. The psychometric properties of the five summated disease‐specific scales compare favourably with standardized health status measures.
Effects of tablet and effervescent formulations of ranitidine 75 mg and cimetidine 200 mg on gastric acidity and oesophageal acid exposure in healthy humans
Authors: Varannes S. Bruley Des , Duquesnoy  , Mamet  , Slama  , Galmiche  , Scarpignato
Published: March 2003

Background:

Because of their tolerance and safety, low doses of H2‐receptor antagonists are now increasingly used in some countries for self‐care medication of gastro‐oesophageal reflux symptoms.

Aim:

The purpose of this randomized, double‐blind, placebo‐controlled, five‐way crossover study was to determine and to compare the effects of low doses of ranitidine and cimetidine both on gastric pH and on oesophageal acid exposure.

Methods:

Gastric and oesophageal pH were simultaneously monitored in 20 healthy subjects using two glass pH electrodes, after placebo and single doses of ranitidine 75 mg and cimetidine 200 mg (effervescent and tablet forms), for 4 h before and after a meal.

Results:

During the fasting period, median gastric pH rose significantly with both drugs, but more rapidly with the effervescent forms; the oesophageal acid exposure was significantly decreased by all drug regimens. After the meal, although there was no significant difference in gastric pH values, oesophageal acid exposure was significantly decreased in comparison with placebo with both forms of ranitidine (P < 0.05), and also for ranitidine tablets in comparison with cimetidine tablets (P < 0.05).

Conclusions:

Low doses of ranitidine and cimetidine increase gastric pH, with a more pronounced effect for ranitidine. Effervescent formulations of both drugs induce a slightly more rapid initial increase in pH than tablets. Ranitidine demonstrates a more prolonged effect than cimetidine and decreases oesophageal acid exposure monitored after a meal ingested 4 h after the drug intake.
Comparison of rabeprazole 20 mg versus omeprazole 20 mg in the treatment of active duodenal ulcer: a European multicentre study
Authors: Dekkers  , Beker  , Thjodleifsson  , Gabryelewicz  , Bell  , Humphries  ,   THE EUROPEAN RABEPRAZOLE STUDY GROUP
Published: March 2003

Background:

Rabeprazole sodium is the newest member of a class of substituted benzimidazole molecules known as proton pump inhibitors. Other proton pump inhibitors have been shown to be effective in healing active duodenal ulcer.

Method:

This randomized, double‐blind, multicentre study, conducted at 25 European sites, compared the efficacy and tolerability of rabeprazole and omeprazole in patients with active duodenal ulcers. One hundred and two patients with active duodenal ulcer received rabeprazole 20 mg and 103 patients omeprazole 20 mg once daily for 2 or 4 weeks, with ulcer healing monitored by endoscopy.

Results:

After 2 weeks, complete ulcer healing was documented in 69% of patients given rabeprazole 20 mg and in 62% of patients given omeprazole 20 mg (N.S.). After 4 weeks, healing rates were 98% in the rabeprazole group and 93% in the omeprazole group (P = 0.083). Rabeprazole‐treated patients had significantly greater improvement in daytime pain symptom relief than those treated with omeprazole at the conclusion of the study (P = 0.038). Both drugs were well tolerated over the 4‐week treatment period. Mean changes from baseline to end‐point in fasting serum gastrin were significantly greater in the rabeprazole group, but at end‐point mean values were well within normal limits for both groups. No clinically meaningful changes or other between‐group differences were observed in laboratory parameters.

Conclusion:

In this study, rabeprazole produced healing rates equivalent to omeprazole at weeks 2 and 4, and provided significantly greater improvement in daytime pain. Both treatments were well tolerated.
Review article: mechanisms and management of hepatotoxicity in ecstasy (MDMA) and amphetamine intoxications
Authors: Jones  , Simpson
Published: March 2003

The social use of ecstasy (methylenedioxymethampheta‐mine, MDMA) and amphetamines is widespread in the UK and Europe, and they are popularly considered as ‘safe’. However, deaths have occurred and hepatotox‐icity has featured in many cases of intoxication with amphetamine or its methylenedioxy analogues such as ecstasy. Recreational use of these drugs presents an important but often concealed cause of hepatitis or acute liver failure, particularly in young people. The patterns of liver damage and multiple putative mechanisms of injury are discussed. Recognition of the aetiological agent requires a high index of suspicion. Optimum management of the resultant liver damage, including the controversial role of liver transplantation for fulminant hepatic failure, is also discussed.
The DU‐MACH study: eradication of Helicobacter pylori and ulcer healing in patients with acute duodenal ulcer using omeprazole based triple therapy
Authors: ZANTEN S. J. O.VELDHUYZEN VAN , BRADETTE  , FARLEY  , LEDDIN  , LIND  , UNGE  , BAYERDÖRFFER  , SPILLER  , O'MORAIN  , SIPPONEN  , WRANGSTADH  , ZEIJLON  , SINCLAIR
Published: March 2003

Aim

: To investigate the efficacy of two omeprazole triple therapies for the eradication of Helicobacter pylori, ulcer healing and ulcer relapse during a 6‐month treatment‐free period in patients with active duodenal ulcer.

Methods

: This was a double‐blind, randomized study in 15 centres across Canada. Patients (n = 149) were randomized to omeprazole 20 mg once daily (O) or one of two 1‐week b.d. eradication regimens: omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg (OMC) or omeprazole 20 mg, amoxycillin 1000 mg and clarithromycin 500 mg (OAC). All patients were treated for three additional weeks with omeprazole 20 mg once daily. Ulcer healing was assessed by endoscopy after 4 weeks of study therapy. H. pylori eradication was determined by a 13C‐urea breath test and histology, performed at pre‐entry, at 4 weeks after the end of all therapy and at 6 months.

Results

: The intention‐to‐treat (intention‐to‐treat) analysis contained 146 patients and the per protocol (per protocol) analysis, 114 patients. The eradication rates were (intention‐to‐treat/per protocol): OMC—85% and 92%, OAC—78% and 87% and O—0% (O). Ulcer healing (intention‐to‐treat) was greater than 90% in all groups. The differences in the eradication and relapse rates between O vs. OMC and O vs. OAC were statistically significant (all, P < 0.001). Treatment was well tolerated and compliance was high.

Conclusion

: The OMC and OAC 1‐week treatment regimens are safe and effective for eradication, healing and the prevention of relapse in duodenal ulcer patients.
Review article: current status of gastrointestinal carcinoids
Authors: LÄUFFER  , ZHANG  , MODLIN
Published: March 2003

Carcinoid tumours are enigmatic, slow growing malignancies which occur most frequently (74%) in the gastrointestinal tract. In recent years, it has become apparent that the term `carcinoid' represents a wide spectrum of different neoplasms originating from a variety of different neuroendocrine cell types. Carcinoid lesions are usually identified histologically by their affinity for silver salts, by general neuroendocrine markers, or more specifically by immunocytochemistry using antibodies against their specific cellular products. Within the gut, the most frequent sites are the small bowel (29%), the appendix (19%) and rectum (13%). Clinical manifestations are often vague or absent. Nevertheless, in approximately 10% of patients the tumours secrete bioactive mediators which may engender various elements of characteristic carcinoid syndrome. In many instances the neoplasms are detected incidentally at the time of surgery for other gastrointestinal disorders. The tendency for metastatic spread correlates with tumour size, and is substantially higher in lesions larger than 2.0 cm. An association with noncarcinoid neoplasms is ascribed in 8–17% of lesions. Treatment consists of radical surgical excision of the tumour, although gastric (type I and II) and rectal carcinoids may be managed with local excision. Overall 5‐year survival is excellent for carcinoids of the appendix (86%) and rectum (72%), whereas small intestinal (55%), gastric (49%) and colonic carcinoids (42%) exhibit a far worse prognosis.
Antioxidant effects of aminosalicylates and potential new drugs for inflammatory bowel disease: assessment in cell‐free systems and inflamed human colorectal biopsies
Authors: SIMMONDS  , MILLAR  , BLAKE  , RAMPTON
Published: March 2003

Background

: The therapeutic efficacy of 5‐aminosalicylic acid in inflammatory bowel disease may be related to its antioxidant properties.

Aim

: To compare in vitro the antioxidant effects of conventional drugs (5‐aminosalicylic acid, corticosteroids, metronidazole), with new aminosalicylates (4‐aminosalicylic acid, balsalazide) and other potential therapies (ascorbate, N‐acetylcysteine, glutathione, verapamil).

Methods

: Compounds were assessed for efficacy in reducing the in vitro production of reactive oxygen species by cell‐free systems (using xanthine/xanthine oxidase, with or without myeloperoxidase) and by colorectal biopsies from patients with ulcerative colitis using luminol‐amplified chemiluminescence.

Results

: 5‐aminosalicylic acid and balsalazide were more potent antioxidants than 4‐aminosalicylic acid or N‐acetyl‐5‐aminosalicylic acid in cell‐free systems. 5‐aminosalicylic acid (20 m M) and balsalazide (20 m
M) inhibited rectal biopsy chemiluminescence by 93% and 100%, respectively, compared with only 59% inhibition by 4‐aminosalicylic acid (20 m
M). Hydrocortisone, metronidazole and verapamil had no significant effect on chemiluminescence in any system. Ascorbate (20 m
M) inhibited chemiluminescence by 100% in cell‐free systems and by 60% in rectal biopsies. N‐acetyl cysteine (10 m
M), and both oxidized and reduced glutathione (10 m
M), completely inhibited chemiluminescence in cell‐free systems, but not with rectal biopsies.

Conclusions

: The antioxidant effects of compounds varies between cell‐free systems and inflamed colorectal biopsies. The effect of drugs on the chemiluminescence produced by these two assay systems is useful for screening potentially new antioxidant treatments for inflammatory bowel disease. Ascorbate seems worth further study as a novel therapy.