bluuebunny/crossref_metadata_2025 huggingface dataset:
β ‐Adrenoceptor agonist sensitizes the dopamine‐1 receptor in renal tubular cells
Authors: Brismar H. , Agrèn M. , Holtbäck U.
Published: March 2003

The renal effects of dopamine are mainly mediated via the dopamine‐1 receptor (D1 receptor). This receptor is recruited from intracellular compartments to the plasma membrane by dopamine and atrial natriuretic peptide (ANP), via adenylyl cyclase activation. We have studied whether isoproterenol, a β‐adrenoceptor (β‐AR) agonist that may interact with dopamine in the regulation of rat renal Na+, K+‐adenosine triphosphatase (ATPase) activity, can recruit D1 receptors to the plasma membrane. The spatial regulation of D1 receptors was examined using confocal microscopy techniques in LLCPK cells and the functional interaction between dopamine and isoproterenol was examined by studying their effects on Na+, K+‐ATPase activity in microdissected single proximal tubular segments from rat. Isoproterenol was found to translocate the D1 receptors from the interior of the cell towards the plasma membrane. The recruitment of dopamine 1 receptors was found to be cyclic adenosine phosphate (cAMP) dependent, while protein kinase C (PKC) activation was not involved. The functional studies on Na+, K+‐ATPase activity showed that the effect of isoproterenol was abolished by a D1‐like receptor antagonist (SCH 23390), and mediated via protein kinase A (PKA) and PKC dependent pathways. The results provide an explanation for the interaction between G protein‐coupled receptors. The effects of isoproterenol on Na+, K+‐ATPase activity can be explained by a heterologous recruitment of D1 receptors to the plasma membrane.
Reduced calcium tolerance in rat cardiomyocytes after myocardial infarction
Authors: Sjaastad I. , Bentzen J. G. , Semb S. O. , Ilebekk A. , Sejersted O. M.
Published: March 2003

During ischaemia and reperfusion the intracellular Na+ concentration is elevated in the cardiomyocytes and the cells are depolarized, both favouring reverse mode Na,Ca‐exchange loading of the cell with Ca2+. We examined whether cardiomyocytes from rats with congestive heart failure (CHF) and younger rats (HINCX) which both have a high expression of the Na,Ca‐exchanger protein (NCX) showed reduced tolerance to extracellular Ca2+. The CHF was induced in Isofluran anaesthetized rats by left coronary artery ligation. Isolated cardiomyocytes were loaded with Fura‐2AM and 140 mm Na+ and exposed to 0.05 mm Ca2+. Expression of the Na,Ca‐exchanger protein was analysed. Fura‐2 340/380 ratio rose more rapidly in HINCX and CHF than in SHAM, and the rise was abolished by Ni2+. Hypercontracture developed more frequently in HINCX and CHF than in SHAM cells. The amount of NCX was 54% higher in HINCX and 76% higher in CHF compared with SHAM. Na+‐loaded cardiomyocytes from CHF and HINCX rats are more susceptible to Ca2+ overload than SHAM cells because of the increased capacity for Na,Ca‐exchange.
Muscle morphology, self‐reported physical activity and insulin resistance syndrome
Authors: Hedman A. , Byberg L. , Reneland R. , Lithell H. O.
Published: March 2003

In a population‐based sample of 475 men the associations between muscle morphology, self‐reported physical activity (PA) and insulin resistance (IR) syndrome were investigated. Also, we studied to what degree muscle morphology contributes to the association between PA and IR syndrome. Muscle morphology and the components of IR syndrome were compared in four groups categorized according to self‐reported habitual PA data. We found a significantly higher percentage of type I fibres, fibre area and number of capillaries around the fibres and a lower proportion of type IIB fibres with higher level of PA. The relative distribution of type I fibres and capillarization were positively related to high density lipoprotein (HDL) cholesterol and negatively to serum triglycerides (TG) and plasminogen activator inhibitor‐1 (PAI‐1) activity. The percentage of type IIB fibres was were inversely related to HDL cholesterol and positively to serum TG, PAI‐1 activity and resting heart rate. Insulin sensitivity was positively and independently related to PA level (P < 0.001). Regression analysis including all relevant variables regarding insulin sensitivity indicated that the significant explanatory variables left in the equation were body mass index (BMI), glucose intolerance, PAI‐1 activity, serum free fatty acid concentration, proportion of type IIB fibres, HDL cholesterol level, drug treatment, PA level, and waist‐to‐hip ratio, which together explained 55% of the variation in the insulin sensitivity index. In conclusion, both fibre type distribution and muscle capillary density might contribute to the beneficial effect of PA on IR syndrome.
Responses of the bronchial and pulmonary circulations to short‐term nitric oxide inhalation before and after endotoxaemia in the pig
Authors: Middelveld R. J. M. , Alving K.
Published: March 2003

The physiological responses of the bronchial circulation to acute lung injury and endotoxin shock are largely unexplored territory. This study was carried out to study the responsiveness of the bronchial circulation to nitric oxide (NO) inhalation before and after endotoxaemia, in comparison with the pulmonary circulation, as well as to study changes in bronchial blood flow during endotoxaemia. Six anaesthetized pigs (pre‐treated with the cortisol‐synthesis inhibitor metyrapone) received an infusion of 10 µg/kg endotoxin during 2 h. Absolute bronchial blood flow was measured via an ultrasonic flow probe around the bronchial artery. The pigs received increasing doses of inhaled NO over 5 min each (0, 0.2, 2 and 20 ppm) before and after 4 h of endotoxaemia. The increase in bronchial vascular conductance during 5 min of inhalation of 20 ppm NO before endotoxin shock was significantly higher (area under curve (AUC) 474.2 ± 84.5% change) than after endotoxin shock (AUC 118.2 ± 40.4%, P < 0.05 Mann–Whitney U‐test). The reduction of the pulmonary arterial pressure by 20 ppm NO was not different. A short rebound effect of the pulmonary arterial pressure occurred after discontinuation of inhaled NO before endotoxaemia (AUC values above baseline 54.4 ± 19.7% change), and was virtually abolished after endotoxaemia (AUC 6.1 ± 4.0%, P = 0.052, Mann–Whitney U‐test). Our results indicate that the responsiveness of the bronchial circulation to inhalation of increasing doses of inhaled NO during endotoxin shock clearly differ from the responsiveness of the pulmonary circulation. The reduced responsiveness of the bronchial circulation is probably related to decreased driving pressure for the bronchial blood flow. The absence of the short rebound effect on pulmonary arterial pressure (PAP) after induction of shock could be related to maximum constriction of the pulmonary vessels at 4 h.
Fatty acids are important for the Frank–Starling mechanism and Gregg effect but not for catecholamine response in isolated rat hearts
Authors: Pagliaro P. , Chiribiri A. , Gattullo D. , Penna C. , Rastaldo R. , Recchia F. A.
Published: March 2003

In some pathophysiological conditions myocardial metabolism can switch from mainly long chain fatty acid (LCFA) oxidation to mainly glucose oxidation. Whether the predominant fatty acid or glucose oxidation affects cardiac performance has not been defined. In a buffer perfused isovolumetrically contracting rat heart, oxidation of endogenous pool LCFA was avoided by inhibiting carnitine‐palmitoyl‐transferase I (CPT‐I) with oxfenicine (2 mm). In order to restore fatty acid oxidation, hexanoate (1 mm), which bypasses CPT‐I inhibition, was added to the perfusate. Three groups of hearts were subjected to either an increase in left ventricular volume (VV, +25%) or an increase in coronary flow (CF, +50%), or inotropic stimulation with isoproterenol (10−8 and 10−6 m). The increase in VV (the Frank–Starling mechanism) increased rate–pressure product (RPP) by 21 ± 2% under control conditions, but only by 6 ± 2% during oxfenicine‐induced CPT‐I inhibition. The contractile response to changes in VV recovered after the addition of hexanoate. Similar results were obtained in hearts, in which an increase in CF was elicited (the Gregg phenomenon). Isoproterenol caused a similar increase in contractility regardless of the presence of oxfenicine or hexanoate. In all groups, a commensurate increase in oxygen consumption accompanied the increase in contractility. The fatty acid oxidation is necessary for an adequate contractile response of the isolated heart to increased pre‐load or flow, whereas the inotropic response to adrenergic β‐receptor stimulation is insensitive to changes in substrate availability.
Nitric oxide: a local signalling molecule controlling the activity of pre‐autonomic neurones in the paraventricular nucleus of the hypothalamus
Authors: Stern J. E. , Li Y. , Zhang W.
Published: March 2003

Abstract Aim:  The gas molecule nitric oxide (NO) has been shown to modulate autonomic function by acting both peripherally and centrally. Accumulating evidence indicates that the paraventricular nucleus (PVN) of the hypothalamus is an important locus mediating central NO actions on autonomic function, under both physiological and pathological conditions. However, the cellular targets and mechanisms mediating NO actions within the PVN are still poorly understood.

Results:  By combining in vitro patch‐clamp recordings with neuronal tract tracing techniques, we show that neuronal excitability of autonomic‐related neurones in the PVN is tonically inhibited by an endogenous NO input. Furthermore, immunohistochemical studies show that ∼25% of autonomic‐related PVN neurones express neuronal nitric oxide synthase, suggesting that at least a proportion of them contribute to the cellular sources of NO within the PVN.

Conclusion:  In summary, this work suggests that NO modulation of the firing activity of autonomic‐related PVN neurones constitutes an efficient mechanism mediated central NO regulation of autonomic function.
The diet of chimpanzees in the Budongo Forest Reserve, Uganda
Authors: Newton‐Fisher Nicholas E.
Published: March 2003

Chimpanzee diets are highly variable, but in all cases dominated by ripe fruit. Previous work has suggested that in the Budongo Forest Reserve, Uganda, ripe fruit remains available throughout the year, but dietary data for chimpanzees at this site remain sparse. This paper details the diet of a recently habituated community of Budongo chimpanzees living in the Sonso region. Chimpanzees of this community spent 64.5% of their feeding time eating fruit, and 19.7% eating arboreal leaves. Terrestrial herbaceous vegetation formed only a minor component of the diet. In these general dietary characteristics, Budongo chimpanzees show greater similarity to those of the Gombe National Park than they do to those in the geographically closer and floristically more similar Kibale Forest National Park. The diet was dominated by the fruit of four species and leaves of two species, although the composition of the diet varied from month to month, remaining diverse. Figs were consumed throughout much of the year, and in consequence, should perhaps be regarded as a staple, rather than fallback, food. A period of food scarcity was not apparent in this study and future comparative nutritional investigation will be required to determine whether these chimpanzees face a time of dietary hardship.
Surface and leaf‐litter arthropods in the coastal forests of Tanzania
Authors: Burgess N. D. , Ponder K. L. , Goddard J.
Published: March 2003

Surface and leaf litter arthropod assemblages of the seasonal lowland coastal forests of eastern Tanzania were investigated from eleven sites over a 3‐year period (1991–93). Pit‐fall trap data show that four groups comprise more than 10% of the total sample: ants (Hymenoptera: Formicidae, 31%), grasshoppers and crickets (Orthoptera, 22%), beetles (Coleoptera: 17.39%) and spiders (Araneae: 13.48%). Arthropod abundance varies considerably with season, with greater total numbers of arthropods in all groups found in wetter periods. Arthropod abundance also varies considerably according to habitat, with greatest numbers found in forests with the most intact canopy cover, and in valley‐bottom forest as compared to ridge‐top forest; the valleys are normally both wetter and with a more complete and taller canopy. Tullgren Funnel data show that over 50% of the leaf litter fauna comprises tiny arthropods of the groups Collembola and Acarina. Abundance of arthropods in the leaf litter of these forests varies from a maximum of ≈ 16,000 m–2, to a minimum of 780 m–2. Abundance is highest in wetter periods, in the forest areas with the most intact canopy cover, and in valley‐bottom as opposed to ridge‐top habitats.
Biogeography and species richness of endophagous insects associated with Proteaceae in South Africa
Authors: Wright Mark G. , Samways Michael J.
Published: March 2003

The endophagous insects associated with Proteaceae of the Cape fynbos were compared to endophage assemblages from more northern non‐Capensis Proteaceae. Insects were collected from Proteaceae in the Cape on a regular basis and additional records obtained from insect collections. Northern samples were collected more opportunistically or records were obtained from collections or through personal communication. The Cape fynbos genus Protea is utilized by many more insect taxa than the non‐fynbos Protea species. The fynbos Proteaceae has very few species in common with the northern Proteaceae, yet each has many of their own distinct species. This suggests that the fynbos endophage insect fauna is distinct from that of the other regions. It appears that the high diversity of host plants in the fynbos has contributed to generating high, local endophagous insect diversity.
Short‐term responses of rehabilitating coastal dune forest ground vegetation to livestock grazing
Authors: Wassenaar Theo D. , Van Aarde Rudi J.
Published: March 2003

We investigated the responses of the ground vegetation in a 17‐year‐old coastal dune forest plant community to four levels of experimentally applied livestock grazing (three grazing levels and one ungrazed control) from May 1994 to March 1996. The effects of grazing were apparently subordinate to site‐specific intrinsic vegetation change and there were some indications that rainfall interacted with grazing level. Grazing had some apparent but no significant effects on plant species composition, significantly affected plant species richness over time, and significantly increased the range of species richness and vegetation cover values as well as the relative abundance and numbers of plant species with erect growth forms. Vegetation cover changed significantly over time, independently of grazing. Our results point to two important, easily measured mechanisms for the conservation management of coastal dune forests – the interaction of disturbance type with plant growth form and the increase of variation in community structural variables under disturbance. These mechanisms, although they potentially have wide application and predictive power, have not been studied adequately.
Aspects of the feeding ecology of Sargochromis codringtonii in Lake Kariba, Zimbabwe
Authors: Moyo Ngonidzashe A. G.
Published: March 2003

Sargochromis codringtonii
has always been considered a good candidate for the biological control of snails. However, there is lack of data on the feeding ecology of this species. The diet of
S. codringtonii
was examined by an analysis of stomach contents. The food of adult
S. codringtonii
in Lake Kariba is dominated by prosobranch snails. Pulmonate snails form a small insignificant component of the diet of
S. codringtonii
, and the reasons for this are discussed. Electivity indices were used to investigate prey selection.
S. codringtonii
does not show a particular preference for any snail species. It feeds on any snail species that is readily available. A morphometrical analysis of the feeding structures of
S. codringtonii
showed that the fish is well adapted to handling a molluscivorous diet. The daily food consumption of
S. codringtonii
was estimated over different seasons using the
Elliot & Persson (1978
) model [
J. Anim. Ecol.47.977–991]. Estimates of food consumption indicate that the fish consumed 14.0% of their dry body weight per day in summer and this falls to 4.5% in winter. The low consumption of pulmonates means that S. codringtonii cannot be a successful biological control agent against the vectors of schistosomiasis.
Vegetation structure and ecology of the Cufada Lagoon (Guinea‐Bissau)
Authors: Catarino Luís , Martins Eurico S. , Diniz Maria Adélia
Published: March 2003

The Cufada Lagoon, in the southern part of Guinea‐Bissau, West Africa, is a shallow lagoon with a surface area of 190 ha in the rainy season. The vascular flora and physico‐chemical characteristics of the lagoon were studied in December 1997 (end of the wet season) and May 1998 (dry season). The lagoon water is soft, with acid pH, low conductivity and low transparency. The maximum depth is 2.25 m in the rainy season and 1.20 m in the dry season.

A total of 46 vascular plant species were recorded, 32 being emergent macrophytes, mostly Gramineae and Cyperaceae, five floating‐leaved, three submerged, one surface‐floating and also five shrubs.

Cluster analysis of the floristic data shows two main groups of inventories in both seasons, grouping almost nine‐tenths of the vegetation samples. The inventories in these groups correspond to two main vegetation types and can be spatially arranged. In the deepest inner part of the lagoon, Nymphaea lotus is the most important species, while Oryza longistaminata dominates in the shallower part. In spite of the shallow depth, the middle of the lagoon remains uncolonized by macrophytes. The main factors limiting the colonization by plants of the lagoon seem to be the low mineral and nutrient content of the water and its low transparency.
The occurrence and ecology of a marine hydrobiid mudsnail in the southern hemisphere: the Knysna Estuary, South Africa
Authors: Barnes R. S. K.
Published: March 2003

Earlier published records of the gastropod Hydrobia from the warm temperate Knysna Lagoon on the Indian Ocean coast of South Africa are in error. Nevertheless, an animal hitherto identified as an Assiminea (Assimineidae) or as a Tomichia (Pomatiopsidae) is in fact a Hydrobia s.l., and it does occur intertidally within the Knysna system. The same species also occurs in salt pans in the cool temperate Great Berg Estuary on the Atlantic coast of South Africa. This extends the distribution of confirmed species of the dominant coastal hydrobiid mudsnails of the northern hemisphere into the southern hemisphere. H. knysnaensis (Krauss) occurs patchily at low density near the head of the Knysna Estuary in waters of low salinity. This appears to be a suboptimal habitat, and it is suggested that Hydrobia is restricted to this zone as a result of interference competition from potamidid mudwhelks and ocypodid crabs. The prevalence of potamidids and ocypodids in the tropics and in the temperate southern hemisphere may account for the rareness or absence of hydrobiids in these areas. Unlike its equally intertidal relative, the widespread North Atlantic/Arctic H. ulvae, H. knysnaensis develops directly like other Hydrobia.
Effects of annual rainfall and habitat types on the body mass of impala (Aepyceros melampus) in the Zambezi Valley, Zimbabwe
Authors: Bourgarel M. , Fritz H. , Gaillard J‐M. , De Garine‐Wichatitsky M. , Maudet F.
Published: March 2003

Body mass is often considered as a good indicator of body condition of individuals in ungulates, hence of their fitness, and thus, may be used as an index to monitor the status of populations subject to harvesting schemes. Here, we report the influence of annual rainfall (a proxy for primary production) and habitat on the body mass of impala in a population cropped for meat in a communal area of Zimbabwe. We analyzed the data from 2 contrasted years for rainfall, in two different habitats. In the good year (i.e. high annual rainfall) impala were heavier than in the poor year, and adult females seemed to be less affected than males by variation in primary production. We show that adult males were suffering from a seasonal decrease in body mass, supposedly linked to the rut, particularly in good habitat. Overall, the habitat effect appeared to be dominated by the rainfall effect, and this may be due to the very high animal densities in the good habitat, i.e. fast resource depletion. Our results also suggest that males (juvenile and adult) are more susceptible to changes in food resource abundance and quality than females, which supports previous studies on sexually dimorphic and polygynous species.
Circadian rhythm of melatonin and prostaglandin in modulation of stress‐induced gastric mucosal lesions in rats
Authors: Kato K. , Murai I. , Asai S. , Takahashi Y. , Nagata T. , Komuro S. , Mizuno S. , Iwasaki A. , Ishikawa K. , Arakawa Y.
Published: March 2003

Background:

We previously demonstrated the circadian variation of water‐immersion restraint stress (WRS)‐induced gastric mucosal lesions in rats.

Aim:

To investigate the roles of melatonin and prostaglandin in the gastric mucosa in circadian modulation of WRS.

Methods:

Fasted rats were subjected to 4‐h WRS during both the diurnal and nocturnal phases of a light/dark cycle. Mucosal lesions, serum melatonin concentrations, mucosal generation of prostaglandin E2 (PGE2) and mucosal gene expressions of cyclooxygenase (COX)‐1 and ‐2 were evaluated.

Results:

Lesion area after 4‐h stress during the dark phase was significantly smaller than that in light‐phase controls. Serum melatonin concentration in control rats during the light phase was significantly increased 4 h after WRS, but PGE2 generation was decreased by 48% as compared to that in intact mucosa before stress. In the dark phase, melatonin concentration after 4‐h WRS was significantly depressed as compared with the control level at the corresponding time. PGE2 concentrations after 4‐h WRS in the dark phase were not decreased compared with the control level at the corresponding time, although PGE2 level was significantly lower than that in light‐phase controls. Expression of COX‐1 and COX‐2 mRNA was detected after exposure to stress in both the light and dark phases.

Conclusion:

These results suggest that circadian rhythm has an important role in the formation of stress‐induced gastric mucosal lesions in rats. The circadian rhythm of melatonin responses and PGE2 generation may contribute to nocturnal/diurnal rhythmicity of gastric mucosal defences between day and night.
Effect of taurine on ulcerogenic response and impaired ulcer healing induced by monochloramine in rat stomachs
Authors: Kato S. , Umeda M. , Takeeda M. , Kanatsu K. , Takeuchi K.
Published: March 2003

Background:

It is well known that neutrophil‐derived hypochlorous acid interacts with ammonia (NH4OH) to generate monochloramine (NH2Cl) and that NH2Cl irritates the gastric mucosa and impairs ulcer healing.

Aim:

To examine the effect of taurine, a hypochlorous acid scavenger, on the mucosal ulcerogenic and the impaired healing response induced by NH2Cl in rat stomachs, in comparison with those of methionine and glycine.

Methods and results:

Under anaesthesia, oral administration of NH2Cl (120 mmol/L) produced severe lesions in male Sprague–Dawley rat stomachs. Taurine (10–100 mg/kg) given p.o. 30 min prior to NH2Cl dose‐dependently prevented these lesions in response to NH2Cl. This action was mimicked by methionine (3–30 mg/kg) but not by glycine (10–100 mg/kg). Under urethane anaesthesia, mucosal exposure to NH4OH (120 mmol/L) caused a marked reduction of potential difference (PD) in the ex vivo chambered stomachs after induction of ischaemia, resulting in severe lesions. These ulcerogenic and PD responses by NH4OH plus ischaemia were also mitigated by taurine and methionine, but not glycine, applied to the chamber 20 min before the onset of NH4OH plus ischaemia. Moreover, oral administration of 100% ethanol produced severe haemorrhagic lesions in rat stomachs, all of which rapidly healed within 7 days after lesion induction. Daily administration of NH2Cl (20 mmol/L) significantly delayed the healing of these lesions, but recovery of this impaired healing response was obtained by concurrent administration of taurine. Both taurine and methionine showed a potent scavenging effect against NH2Cl in vitro.

Conclusions:

(1) NH2Cl generated either exogenously or endogenously damages the gastric mucosa and impairs the healing response; (2) taurine exerts a prophylactic effect against the deleterious effects of NH2Cl, mainly due to its scavenging action against NH2Cl; and (3) this effect of taurine may be useful for treatment of gastritis associated with Helicobacter pylori infection.
Ten‐year prospective follow‐up study on the relationship between Helicobacter pylori infection and progression of atrophic gastritis, particularly assessed by endoscopic findings
Authors: Sakaki N. , Kozawa H. , Egawa N. , Tu Y. , Sanaka M.
Published: March 2003

Aim:

To ascertain the progression of atrophic gastritis due to Helicobacter pylori infection, we conducted a 10‐year prospective follow‐up study with annual endoscopy of the stomach.

Methods:

Prospective endoscopic observation was started in 53 subjects in 1989 and 1990 after informed consent was obtained. The progression of atrophic gastritis was evaluated mainly by the endoscopic pattern of atrophy. Histological assessment was performed on biopsy specimens taken from the lesser curvature of the lower corpus. By 2000, 43 patients (20 males, 23 females, mean age 56.7 years at entry) had completed at least 10 years of endoscopic follow‐up.

Results:

Eight H. pylori‐negative patients with normal fundic mucosa showed no change endoscopically or histologically. In 35 H. pylori‐positive patients, the progression of histological atrophy was observed in 46% and intestinal metaplasia was observed in 49%. Fifteen of 35 H. pylori‐positive cases exhibited a cephaloid shift of the endoscopic atrophic border. The cephaloid shift of the atrophic area occured suddenly. The cumulative progression rate of atrophic patterns was 6% after 2 years, 22% after 4 years, 34% after 6 years and 43% after 10 years. These atrophic changes were related to neutrophil infiltration.

Conclusion:

The progression of atrophic gastritis is a result of chronic active gastritis caused by H. pylori infection.
Effect of acid suppression therapy on development of gastric erosions after cure of Helicobacter pylori infection
Authors: Miyake K. , Tsukui T. , Futagami S. , Tatsuguchi A. , Shinoki K. , Hiratsuka T. , Iizumi T. , Nagata K. , Shinji Y. , Wada K. , Yamada N. , Kobayashi M. , Sakamoto C.
Published: March 2003

Background:

Helicobacter pylori eradication markedly improves histological inflammation and decreases peptic ulcer recurrence, but little is known about the subsequent development of gastric mucosal injury.

Aim:

To investigate whether acid suppression treatment after eradication influences the development of gastric erosions.

Methods:

Eighty‐one patients (gastritis or peptic ulcer) after successful H. pylori eradication were divided into two groups: 40 received an H2‐blocker for 6 months (H2‐blocker‐positive) and 41 received no treatment (H2‐blocker‐negative). Endoscopy was performed before, and at 3 and 6 months after completion of eradication.

Results:

Cumulative prevalence of gastric erosions in the H2‐blocker‐positive group was significantly lower than in the H2‐blocker‐negative group, 25% vs. 42%, respectively. In the H2‐blocker‐negative group but not the H2‐blocker‐positive group, the cumulative prevalence of gastric erosions after eradication was higher in patients with less severe corpus atrophy or more severe corpus gastritis.

Conclusions:

Development of gastric erosions after H. pylori eradication may be controlled by acid suppression treatment. Less severe atrophy or more severe gastritis in oxyntic glands before eradication may be involved in the development of gastric erosions. These results support the idea that recovery of acid secretion may be one of factors for development of gastric mucosal erosions after successful eradication.
No difference in the level of gastric mucosal cell apoptosis and proliferation in Helicobacter pylori‐colonized p53 heterozygous knockout mice
Authors: Suzuki H. , Miyazawa M. , Kai A. , Suzuki M. , Suematsu M. , Miura S. , Ishii H.
Published: March 2003

Background:

We previously reported that attenuated epithelial apoptosis and enhanced proliferation in comparison with mice might link to the specific carcinogenesis in Mongolian gerbils and suggested that the difference in both strains might be due to a difference in genetic background. p53 is a well‐known tumour suppressor gene, mutation of which is also known to be involved in gastric cancer formation.

Aim:

The present study was designed to examine the level of gastric epithelial apoptosis and proliferation in p53 heterozygous knockout mice (p53+/−) colonized with Helicobacter pylori(Sydney strain: SS1).

Methods:

Female p53+/− mice and wild‐type controls were orally inoculated with SS1 and the stomachs were examined 24 weeks later. DNA fragmentation was measured by levels of cytoplasmic mono‐ & oligo‐nucleosomes as well as by the TUNEL method. Gastric mucosal proliferative activity was morphometrically evaluated from the PCNA‐stained tissue specimens. Gastric mucosal myeloperoxidase (MPO) activity was measured to evaluate mucosal inflammation.

Results:

DNA fragmentation and the number of TUNEL‐positive cells, as well as PCNA‐positive cell number increased significantly in both groups of H. pylori‐infected mice, suggesting that levels of apoptosis and proliferation may be independent of a deficiency of one p53 allele. MPO activity in p53+/− mice and wild‐type controls increased to the same level.

Conclusion:

Although H. pylori inoculation per se induces an increase in cell turnover in mice, heterozygous mutation of p53 did not significantly modify the balance in cell apoptosis and proliferation.
Review article: colonic sensorimotor physiology in health, and its alteration in constipation and diarrhoeal disorders
Authors: Camilleri  , Ford
Published: March 2003

Aim:

To review the physiology of colonic motility and sensation in healthy humans and the pathophysiological changes associated with constipation and diarrhoea.

Source:

Medline Search from 1965 using the index terms: human, colonic motility, sensation, pharmacology, neurohormonal control, gastrointestinal transit, constipation, diarrhoea and combinations of these.

Results:

In health, the ascending and transverse regions of colon function as reservoirs to accommodate ileal chyme and the descending colon acts as a conduit; the neuromuscular functions and transmitters control colonic motility and sensation and play pivotal roles in disorders associated with constipation and/or diarrhoea. Disorders of proximal colonic transit contribute to symptoms in idiopathic constipation, diarrhoea‐predominant irritable bowel syndrome and carcinoid diarrhoea. Colonic function in patients presenting with constipation is best assessed clinically by colonic transit time using radiopaque markers ingested orally. Measurements of colonic contractility are less useful clinically but they can help identify motor abnormalities including colonic inertia; in some patients with irritable bowel syndrome, abdominal pain, urgency and diarrhoea are temporally associated with high amplitude contractions, which originate in the proximal colon and traverse the distal conduit at very high propagation velocities. Visceral hypersensitivity contributes to the urgency and tenesmus in irritable bowel syndrome and inflammatory bowel disease. Colonic motility and sensation can be reduced by anticholinergic agents, somatostatin analogues and 5HT3 antagonists.

Conclusion:

Physiological and pharmacological studies of the human colon have provided new insights into the pathophysiology of colonic disorders, and offer possibilities of novel therapeutic approaches for constipation or diarrhoea associated with colonic motor or sensory dysfunction.
oesophageal mucosal resistance
Authors: Orlando
Published: March 2003

The human oesophagus is lined by a moist, partially keratinized, stratified squamous epithelium, one important property of which is to serve as a barrier between the outside (luminal) world and the internal world of the organism. This phenomenon in clinical parlance is known as ‘oesophageal mucosal resistance’. This article details the structure and functions of the oesophageal mucosa that contribute to its defence against injury upon exposure to refluxed gastric acid.
Comparison of the effect of the antacid Rennie versus low‐dose H2‐receptor antagonists (ranitidine, famotidine) on intragastric acidity
Authors: Netzer  , Brabetz‐Höfliger  , BrÜndler  , Flogerzi  , Hüsler  , Halter
Published: March 2003

Background:

Symptoms of functional dyspepsia are common and patients often self‐medicate with antacids, or with low‐dose H2‐antagonists which are available as over‐the‐counter medications. To date, there has been limited information available comparing the effects on intragastric acidity of these two types of over‐the‐counter medication. Therefore we studied the effect of the antacid Rennie and two H2‐antagonists on the intragastric pH of fasting volunteers.

Methods:

Sixteen healthy, fasting volunteers were randomized into a double‐blind, placebo‐controlled, four‐way crossover study comparing Rennie (calcium‐magnesium carbonate) 1360 mg, ranitidine 75 mg, famotidine 10 mg and placebo. Their effect on gastric pH was monitored by a 4‐h gastric pH‐metry. The primary efficacy parameter was the time lag before an intragastric pH > 3.0 was reached after drug administration.

Results:

The median time lag before pH > 3.0 was reached after drug administration was 5.8 min for Rennie, 64.9 min for ranitidine, 70.1 min for famotidine and 240.0 min for placebo. The percentage of time with values of pH > 3.0 was 10.4% for Rennie, 61.4% for ranitidine, 56.6% for famotidine and 1.4% for placebo.

Conclusion:

The onset of action in fasting volunteers was significantly faster with the antacid than with the two H2‐antagonists. The duration of action was significantly longer with an H2‐antagonist than with the antacid. This suggests that the two products should be used for different indications: antacids are superior for rapid pain relief, whereas H2‐antagonists might be better for symptom prophylaxis—for example for nocturnal dyspepsia.
Low rate of emergence of clarithromycin‐resistant Helicobacter pylori with amoxycillin co‐therapy
Authors: Laine L. , Suchower L. , Frantz J. , Connors A. , Neil G.
Published: March 2003

Background:

Patients with persistent Helicobacter pylori infection following treatment with clarithromycin or omeprazole plus clarithromycin often develop clarithromycin resistance.

Aim:

To assess pre‐ and post‐treatment antibiotic resistance in three double‐blind trials of triple therapy with omeprazole, amoxycillin and clarithromycin.

Methods:

Patients with H. pylori and duodenal ulcer (studies 1 and 2) or history of duodenal ulcer (study 3) were randomly assigned to 10 day courses of omeprazole 20 mg b.d., amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (OAC) or placebo, amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (AC). Endoscopy was performed at baseline and 4 weeks after completion of therapy in studies 1 and 2, and at 4–6 weeks after therapy in study 3. At baseline, H. pylori was diagnosed by CLO test with confirmation by histology, or by culture. Eradication was defined as no positive biopsy test and ≥ 2 negative tests. Susceptibility testing was performed using the Etest.

Results:

In the 91 patients with pre‐treatment susceptible isolates who had persistent infection after AC, 10 developed resistance, eight had intermediate susceptibility and 73 continued to have clarithromycin‐susceptible H. pylori isolates. In the 10 patients with pre‐treatment susceptible isolates who had persistent infection after OAC, three developed clarithromycin resistance and seven still had susceptible isolates.

Conclusions:

Use of amoxycillin co‐therapy results in a low rate of clarithromycin resistance developing in patients with persistent H. pylori infection following therapy with a clarithromycin‐containing regimen.
Review article: economic issues in Crohn’s disease — assessing the effects of new treatments on health‐related quality of life
Authors: Feagan B.G.
Published: March 2003

The advent of highly effective yet costly new treatments for Crohn’s disease will force clinicians, patients, and society to make important choices regarding the allocation of resources. Pharmacoeconomic analyses can be useful in deciding whether new technologies are of good value in comparison to established treatment regimens. In Crohn’s disease conventional cost‐effectiveness analyses are of limited use because surgery, death, and disease‐related complications occur relatively infrequently. Alternatively, cost‐utility models relate the incremental cost of new treatments to improvements in health‐related quality of life. These analyses require the collection of valid cost and utility inputs that have only recently become available. Ultimately, cost‐utility models should allow decision makers to make sensible choices for patients and society. This article describes the techniques of pharmacoeconomic analysis and reviews existing data on the measurement of costs and quality‐of‐life outcomes in Crohn’s disease.
Polaprezinc protects gastric mucosal cells from noxious agents through antioxidant properties in vitro
Authors: Hiraishi  , Sasai  , Oinuma  , Shimada  , Sugaya  , Terano
Published: March 2003

Background:

Polaprezinc has been shown to exert an anti‐oxidant property in a tube experiment, protect gastric mucosa from experimental ulcerations in vivo, and accelerate the healing of gastric ulcer in humans.

Aim:

To examine a possible protective effect of polaprezinc on oxidant‐mediated injury in primary monolayer cultures of rat gastric fundic mucosa.

Methods:

Cytotoxicity was quantified by measuring 51Cr release. Whether or not polaprezinc exerts an antioxidant property was investigated by determining the effect of this agent on hydrogen peroxide (H2O2)‐induced injury. The effects of polaprezinc on superoxide (O2–·) generation as well as on ethanol (EtOH)‐induced injury were also examined. Generation of O2–· was assessed by the reduction in cytochrome c.

Results:

H2O2 caused a time‐ and dose‐dependent increase in 51Cr release. The dose‐response curve of 51Cr release by H2O2 shifted to the right in the presence of polaprezinc. Polaprezinc, at submillimolar concentrations, prevented H2O2‐induced 51Cr release. EtOH also caused a dose‐dependent increase in 51Cr release, which was prevented by the addition of polaprezinc. The incubation of cells with EtOH caused an increase in cytochrome c reduction, as the concentrations of EtOH increased. Polaprezinc inhibited EtOH‐induced cytochrome c reduction. Protection by polaprezinc was microscopically associated with the prevention of monolayer disruption.

Conclusions:

Polaprezinc is antioxidative and directly protects gastric mucosal cells from noxious agents through its antioxidant properties in vitro. This finding may provide the theoretical basis for the usage of an antiulcer drug with antioxidant properties for the treatment of gastric inflammation, such as that induced by ethanol.
Effect of CYP2C19 polymorphism on serum levels of vitamin B12 in patients on long‐term omeprazole treatment
Authors: SAGAR  , JANCZEWSKA  , LJUNGDAHL  , BERTILSSON  , SEENSALU
Published: March 2003

Background:

The S‐mephenytoin hydroxylase is a polymorphic cytochrome P450 (CYP) enzyme, identified as CYP2C19, which catalyses the metabolism of omeprazole and some other drugs.

Aim:

To determine whether long‐term treatment with omeprazole affects serum vitamin B12 levels, and if so to what extent it depends on CYP2C19 activity.

Methods:

Serum vitamin B12 levels (pmol/L) were assessed in 179 patients. Genotyping for wild‐type (wt) and mutated (mut) CYP2C19 alleles was performed by allele‐specific PCR amplification.

Results:

One‐hundred and eleven of the patients received one dose of 20 mg omeprazole. No difference in B12 levels were found between heterozygous (wt/mut) (n = 23) and homozygous (wt/wt) (n = 85) patients (mean ± s.d., 350 ± 82 vs. 315 ± 87 pmol/L, respectively). Three patients were mut/mut, with serum vitamin B12 levels of 303 ± 50 pmol/L. In the 68 patients on long‐term (>1 year) therapy with 20 mg omeprazole daily, serum vitamin B12 levels were lower in the heterozygous (wt/mut) (n = 19) compared to homozygous wt/wt (n = 49) (246 ± 71 vs. 305 ± 98 pmol/L, P = 0.01, respectively). In one patient (mut/mut) who was studied both after a single dose and after long‐term (15 months) treatment with omeprazole, serum vitamin B12 decreased from 360 to 178 pmol/L. In the wt/mut, but not in the wt/wt group, serum vitamin B12 levels were significantly lower in patients on long‐term therapy compared with those receiving one dose (246 ± 71 vs. 350 ± 82 pmol/L, P < 0.0001, respectively).

Conclusions:

CYP2C19 polymorphism significantly affected serum vitamin B12 levels in patients on long‐term therapy with omeprazole. In the future, genotyping of CYP2C19 may be useful for patients in need of long‐term treatment with omeprazole or other proton pump inhibitors.
Citric acid or orange juice for the 13C‐urea breath test: the impact of pH and gastric emptying
Authors: Leodolter  , Domínguez‐Muñoz J. Enrique , Von Arnim  , Malfertheiner
Published: March 2003

Background

: There is an ongoing debate about the optimal test drink to be used in the 13C‐urea breath test (13C‐UBT). We recently reported that a citric acid solution is the optimal test drink in the 13C‐UBT, because it provides a high 13CO2 recovery and the excellent accuracy of the test appears optimal compared to other test meals. Orange juice, because of a better taste, is also propagated as a test drink in the 13C‐UBT.

Aim

: To compare the diagnostic accuracy of the 13C‐UBT with either orange juice or citric acid solution as a test drink. Furthermore, the effect of these test drinks on the gastric emptying rate was determined.

Methods

: H. pylori status was assessed by histology, rapid urease test and culture in 50 consecutive dyspeptic patients. A 13C‐UBT was performed on two consecutive days by giving 75 mg of 13C‐urea randomly dissolved in 200 mL 0.1 M citric acid solution or 200 mL orange juice. The 13CO2/12CO2 ratio was measured in breath samples taken before and 15, 30, 45 and 60 min after administration of the test drink. The gastric emptying rate of orange juice and citric acid solution was compared to that of water in 10 healthy subjects on three consecutive days by means of a 13C‐sodium acetate breath test; 50 mg of 13C‐sodium acetate was dissolved in 200 mL of each solution and breath samples were collected before and every 10 min for 90 min after administration of the test drink.

Results

: Twenty‐six out of 50 patients (52%) were infected with H. pylori. Significantly higher values over baseline (35.7 ± 5.2‰ vs. 23.2 ± 3.4‰, P < 0.001) and higher area under the curve (1507 ± 198 vs. 927 ± 128, P < 0.001) were observed in H. pylori‐positive patients when citric acid solution was administered compared with orange juice. Sensitivity of the 13C‐UBT was 100% when citric acid was used as a test drink and 88% with orange juice. Specificity was 100% with both test drinks. Gastric emptying of citric acid solution (t1/2= 60.9 ± 3.5 min) was significantly slower than that of orange juice (t1/2 = 49.7 ± 3.1 min, P < 0.001).

Conclusion

: 13C‐UBT loses diagnostic accuracy when orange juice instead of citric acid is used as a test drink. The faster gastric emptying of orange juice might be responsible for the lower diagnostic accuracy of the 13C‐UBT.
On demand therapy of reflux oesophagitis — a prospective study of symptoms, patient satisfaction and quality of life
Authors: Wilhelmsen  , Hatlebakk  , Olafsson  , Berstad
Published: March 2003

Background

: In patients with low‐grade reflux oesophagitis adequate symptom control is the aim of treatment. Effervescent tablets alleviate heartburn more rapidly than ordinary tablets.

Aim

: To investigate symptom control, patient satisfaction, health‐related quality of life and disease progress when ranitidine 150 mg effervescent tablets were offered as on demand treatment. We also wanted to investigate whether any biological or psycho‐social factor could predict patient satisfaction.

Method

: Consecutive patients with endoscopically verified reflux oesophagitis grade I–II were followed up for 12 months. 24 h pH‐metry, disease history, symptoms and several psycho‐social factors were registered at baseline and 12 months follow‐up.

Results

: Eighty‐one patients were included. Mean age was 50.7 years (range 21–82), 63% were men. Mean tablet consumption was 1.21 per day (range 7–1016 tablets/year). At the 1‐year follow‐up discomfort resulting from reflux symptoms was significantly reduced (P < 0.001), and the patients’ social and vocational life improved. Eighty‐four percentage of the patients were satisfied with the treatment. 24 h pH‐metry or number of reflux episodes did not change. We did not find any factors able to predict patient satisfaction.

Conclusions

: On demand therapy with ranitidine effervescent tablets was well accepted by the majority of patients with reflux oesophagitis grade I. Even though the number of reflux episodes did not change, the patients experienced less discomfort due to reflux symptoms, and their social and vocational life was better. There was no significant progression of the disorder during the 1‐year follow‐up. No predictive factor for patient satisfaction was found.
Enteric coating of aspirin significantly decreases gastroduodenal mucosal lesions
Authors: Dammann  , Burkhardt  , Wolf
Published: March 2003

Background

: Low‐dose aspirin (acetylsalicylic acid, ASA) increases the risk of developing peptic ulceration.

Aim

: To investigate the gastroduodenal mucosal tolerability of enteric‐coated ASA (EC‐ASA) 100 mg/day compared to either placebo (study 1) or plain ASA 100 mg/day (study 2) in healthy volunteers.

Methods

: Study 1: In this double‐blind study 18 volunteers received randomized dosing with either EC‐ASA 100 mg or placebo for 15 days. Study 2: 41 volunteers underwent randomized 7‐day dosing of either EC‐ASA 100 mg or plain ASA 100 mg in this double‐blind, parallel‐group, comparison study. In both studies acute gastroduodenal mucosal lesions were assessed endoscopically before treatment, on the morning of day 1 after the first dose (only in study 2), and on the morning after the last dose of the test medication.

Results

: Study 1 did not reveal any significant differences between the lesion scores of EC‐ASA and placebo. In contrast, in study 2 significantly higher total gastroduodenal mucosal lesion scores were observed on day 1 after the first dose and after 7 days of dosing with plain ASA (mean sum of the lesion scores in the gastric fundus, body, antrum and in the duodenal bulb: day 1: plain ASA 3.95 ± 3.38 vs. EC‐ASA 1.43 ± 1.91, P=0.03; day 7: plain ASA 6.35 ± 4.10 vs. EC‐ASA 2.00 ± 2.02, P=0.0004). Tolerance of the test drugs was good, and no other adverse events were observed.

Conclusions

: Enteric‐coated aspirin 100 mg/day causes significantly less gastroduodenal damage over 7 days than the same dose of plain aspirin, when given to healthy subjects. There was little gastric injury and no significant differences between EC‐ASA and placebo in this respect.