bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycine‐extended gastrin‐17 stimulates acid secretion only via CCK‐2 receptor‐induced histamine release in the totally isolated vascularly perfused rat stomach
Authors: CUI G.‐L. , SANDVIK A. K. , MUNKVOLD B. , WALDUM H. L.
Published: March 2003

The effects of gastrin precursors have been discussed during recent years. However, the mechanism for their action, whether through a novel receptor on the parietal cell or a cholecystokinin‐2 (CCK‐2) receptor on the enterochromaffin like (ECL) cells, is still not settled. This study examines the effect of glycine‐extended gastrin‐17 (Gly‐G‐17), the main non‐amidated gastrin precursor, on gastric acid secretion and histamine release in the totally isolated vascularly perfused rat stomach. Glycine‐extended gastrin‐17 at the concentrations from 0.52 to 520 nmol L–1 was administered to the totally isolated vascularly perfused rat stomach. Glycine‐extended gastrin‐17 at 52 or 520 nmol L–1, and gastrin‐17 at 0.52 nmol L–1 were co‐administered to examine whether glycine‐extended gastrin augmented maximal gastrin stimulated acid secretion and histamine release. Both Gly‐G‐17 at 52 nmol L–1 and gastrin‐17 (G‐17) at 0.52 nmol L–1 were administered together with the histamine‐2 receptor antagonist ranitidine at 10 μmol L–1. Gastric acid and venous histamine output were measured. Glycine‐extended gastrin‐17 at lower concentrations from 0.52 to 5.2 nmol L–1 did not stimulate gastric acid output or histamine release, whereas higher concentrations from 52 to 520 nmol L–1 elicited a concentration‐dependent increase in acid secretion and histamine release. The outputs of acid and histamine at 520 nmol L–1 Gly‐G‐17 were at the same level as those found for G‐17 at its maximally effective concentration of 0.52 nmol L–1. Glycine‐extended gastrin‐17 at maximally effective concentration of 520 nmol L–1 did not augment maximal gastrin stimulated acid secretion or histamine release. Ranitidine inhibited G‐17 and Gly‐G‐17 stimulated acid secretion to a similar degree. This study confirms that the stimulatory effect of Gly‐G‐17 on gastric acid secretion is via a CCK‐2 receptor on the ECL cell.
Expression of cyclooxygenase‐2 in intestinal goblet cells of pre‐diabetic NOD mice
Authors: LUO C. , LAINE V. J. O. , YLINEN L. , TEROS T. , MÄKINEN M. , RISTIMÄKI A. , SIMELL O.
Published: March 2003

Cyclooxygenase, the rate‐limiting enzyme in prostaglandin synthesis, is expressed in constitutive (COX‐1) and inducible (COX‐2) isoforms. The COX‐2 has been proposed to be involved in development of autoimmune type 1 diabetes (T1D). We examined COX‐2 expression in the gut‐associated lymphoid tissue (GALT), and found COX‐2 was strongly expressed in goblet cells of non‐obese diabetic (NOD) mice at the apical villi at the age of 2.5 weeks, clearly before the onset of insulitis, while the expression in the control BALB/c mice was weak or absent at all ages (P < 0.001). Lipopolysaccharide (LPS) given intraperitoneally slightly increased COX‐2 expression in the goblet cells and epithelium of both NOD and BALB/c mice. High‐resolution confocal microscopy showed that the surroundings of the goblet cells contained no COX‐2, implying that the enzyme is synthesized by the goblet cells. The COX‐2 is secreted from goblet cells into the intestinal lumen along with mucins. The COX‐2 concentration in the goblet cell of BALB/c and especially of NOD mice was markedly higher than that in the intraepithelial lymphocytes or lamina propria macrophages. High mucin COX‐2 from goblet cells may increase luminal prostaglandin synthesis, alter epithelial permeability, modulate intestinal immune responses and modify functional properties of the lymphocytes in the GALT, which all may be important for the initiation of the autoimmune phenomenon in the NOD mice.
Resistance training increases glucose uptake and transport in rat skeletal muscle
Authors: Yaspelkis B. B. , Singh M. K. , Trevino B. , Krisan A. D. , Collins D. E.
Published: March 2003

The aim of this investigation was to determine if resistance training exercise improved glucose uptake and transport in rodent skeletal muscle. Sprague–Dawley rats were assigned to one of the three groups: control (CON), resistance trained (RT) and aerobic exercise trained (AT). Resistance trained rats were placed in a rodent squat apparatus and performed three sets of 10 repetitions at 75% of their one repetition maximum 3 days week−1 for 12 weeks. Aerobic exercise training consisted of running the rats 3 days week−1 for 45 min over a 12‐week period on a motor‐driven treadmill (32 m min−1, 15% grade). Following the training period, all animals were subjected to hind limb perfusion in the presence of 500 μU mL−1 insulin. Hind limb glucose uptake was similar in the RT (9.91 ± 0.7 μmol g−1 h−1) and AT (10.23 ± 1.0 μmol g−1 h−1) animals and significantly greater than control (CON) (6.40 ± 0.6 μmol g−1 h−1). Rates of 3‐O‐methyl‐d‐glucose transport in the RT animals were elevated in the muscles utilized for RT while in the AT animals rates of 3‐O‐methyl‐d‐glucose transport were increased in those muscles recruited for running. The increased rates of 3‐O‐methyl‐d‐glucose transport in the skeletal muscles of the resistance trained and aerobic exercise trained animals appeared to be, in part, because of an increased GLUT4 protein concentration. These findings suggest that both resistance or aerobic training exercise can improve insulin‐stimulated skeletal muscle glucose uptake and transport, but the training adaptations are restricted to the muscles recruited for the exercise performance.
Lithium and KB‐R7943 effects on mechanics and energetics of rat heart muscle
Authors: Bonazzola P. , Egido P. , Marengo F. D. , Savio‐Galimberti E. , Ponce‐Hornos J. E.
Published: March 2003

The role of calcium influx on energy expenditure during cardiac contraction was studied. For this purpose, the described ability of lithium and KB‐R 7943 (KBR) to diminish Ca entry through Na–Ca exchanger (Ponce‐Hornos & Langer, J Mol Cell Cardiol 1980, 12, 1367, Satoh et al., Circulation 2000, 101, 1441) were used. In isolated contractions (contractions elicited after at least 5 min of rest) LiCl 45 mmol L−1 decreased pressure developed and pressure–time integral from 42.3 ± 2.7 and 14.5 ± 1.2 to 32.1 ± 3.4 mN mm−2 and 8.3 ± 0.9 mN mm−2 s, respectively. A similar effect was observed in regular contractions (at 0.16 Hz stimulation). The presence of KBR (5 μmol L−1) in the perfusate induced a slight but not significant decrease in pressure developed and pressure–time integral in steady‐state contractions. As it was previously described, the heat involved in a heart muscle contraction can be decomposed into several components (H1, H2, H3 and H4), but only one (H3) was associated with force generation. While H3 decreased with lithium in both types of contractions, H3/PtI ratio remained unaltered, indicating that the economy for pressure maintenance was unaffected. To further investigate the role of Ca entry on force development, a condition in which the contraction is mainly dependent on extracellular calcium was studied. An ‘extra’ stimulus applied 200 ms after the regular one in a muscle stimulated at 0.16 Hz induces a contraction with this characteristic (Marengo et al., Am J Physiol 1999, 276, H309). Lithium induced a strong decrease in pressure–time integral and H3 associated with this contraction (43 and 45%, respectively) with no change in H3/PtI ratio. Lithium also reduced (53%) an energy component (H2) associated with Ca cycling. The use of KBR showed qualitatively similar results [i.e. a 33% reduction in pressure–time integral associated with the extrasystole (ES) with no changes in H3/PtI ratio and a 30% reduction in the H2 component]. Li and KBR effects appear to be additive and in the presence of 45 mmol L−1 Li and 5 μmol L−1 KBR the extrasystole was abolished in 77%. Lithium and KBR effects particularly for the extrasystole can be explained through the inhibition of Ca entry via Na–Ca exchange giving support to the participation of the Na–Ca exchanger in the Ca influx from the extracellular space. In addition, the results also suggest the possibility of an effect of Li on an additional Ca sensitive locus (different than the Na–Ca exchanger). In this connection, in isolated contractions lithium decreased the energy release fraction related to mitochondrial processes (H4) increasing the economy of the overall cardiac contraction.
Cardiovascular responses to angiotensin II in atherosclerosis
Authors: Wilfert K. , Guski H. , Persson P. B. , Stauss H. M.
Published: March 2003

Atherosclerosis is associated with increased angiotensin II AT1‐receptor expression and vascular hyperresponsiveness to angiotensin II. Nevertheless, atherosclerosis is often not accompanied by hypertension. We studied if the hypertensive effect of angiotensin II is more pronounced in atherosclerosis. Rabbits were fed a high‐cholesterol diet (n = 10) for 12 weeks, followed by a standard diet for another 6 weeks. Control animals received the standard diet (n = 8) for 18 weeks. After 18 weeks, haemodynamic measurements were performed during a baseline recording and during an intravenous infusion of angiotensin II (0.4 μg kg−1 min−1). Atherosclerosis in the high‐cholesterol group was verified by histological and lipidchemical tissue examinations. During angiotensin II infusion, total peripheral resistance (TPR) increased more in the high‐cholesterol group than in controls (+81.6 ± 12.4 vs. +40.6 ± 9.7 mmHg min L−1, P < 0.05). While cardiac output and stroke volume (SV) decreased more in the high‐cholesterol group (P < 0.05), reflex bradycardia was stronger in the control group (P < 0.05), indicating a reduced baroreceptor reflex sensitivity in atherosclerosis. Despite the larger increase in TPR and the reduced baroreceptor reflex sensitivity in the high‐cholesterol group, maximum blood pressure response to angiotensin II was similar in both groups. The lack of a greater blood pressure response to angiotensin II in the high‐cholesterol group could be the result of the early stages of heart failure. Under resting conditions, heart failure seems to be fully compensated, as baseline haemodynamic parameters were similar in the high‐cholesterol group and in controls. However, during angiotensin II infusion, the compensatory mechanisms do not prevent a stronger fall in cardiac output and SV. Therefore, the blood pressure response to angiotensin II is not exaggerated in atherosclerotic animals, as vascular hyperresponsiveness to angiotensin II is opposed by the stronger fall in cardiac output and SV.
Muscle fibre type, efficiency, and mechanical optima affect freely chosen pedal rate during cycling
Authors: Hansen E. A. , Andersen J. L. , Nielsen J. S. , Sjøgaard G.
Published: March 2003

This study investigated the variation in freely chosen pedal rate between subjects and its possible dependence on percentage myosin heavy chain I (%MHC I) in m. vastus lateralis, maximum leg strength and power, as well as efficiency. Additionally, the hypothesis was tested that a positive correlation exists between percentage MHC I and efficiency at pre‐set pedal rates but not at freely chosen pedal rate. Twenty males performed cycling at low and high submaximal power output (∼40 and 70% of the power output at which maximum oxygen uptake (VO2max) was attained at 80 r.p.m.) with freely chosen and pre‐set pedal rates (61, 88, and 115 r.p.m.). Percentage MHC I as well as leg strength and power were determined. Freely chosen pedal rate varied considerably between subjects: 56–88 r.p.m. at low and 61–102 r.p.m. at high submaximal power output. This variation was only partly explained by percentage MHC I (21–97%) as well as by leg strength and power. Interestingly, %MHC I correlated significantly with the pedal rate at which maximum peak crank power occurred (r = −0.81). As hypothesized, %MHC I and efficiency were unrelated at freely chosen pedal rate, which was in contrast to a significant correlation found at pre‐set pedal rates (r = 0.61 and r = 0.57 at low and high power output, respectively). Conclusions: Subjects with high percentage MHC I chose high pedal rates close to the pedal rates at which maximum peak crank power occurred, while subjects with low percentage MHC I tended to choose lower pedal rates, favouring high efficiency. Nevertheless, the considerable variation in freely chosen pedal rate between subjects was neither fully accounted for by percentage MHC I nor by leg strength and power. Previously recognized relationships between percentage Type I (∼%MHC I) and efficiency as well as between pedal rate and efficiency were confirmed for pre‐set pedal rates, but for freely chosen pedal rate, these variables were unrelated.
Modifications to central neural circuitry during heart failure
Authors: Weiss M. L. , Kenney M. J. , Musch T. I. , Patel K. P.
Published: March 2003

Abstract Aim:  During heart failure (HF), excess sodium retention is triggered by increased plasma renin–angiotensin–aldosterone activity and increased basal sympathetic nerve discharge (SND). Enhanced basal SND in the renal nerves plays a role in sodium retention. Therefore, as a hypothetical model for the central sympathetic control pathways that are dysregulated as a consequence of HF, the cental neural pathways regulating the sympathetic motor output to the kidney are reviewed in the context of their role during HF.

Conclusion:  From these findings, a model of the neuroanatomical circuitry that may be affected during HF is constructed.
Bursting into space: alterations of sympathetic control by space travel
Authors: Eckberg D. L. ,   the Neurolab Autonomic Nervous System Team
Published: March 2003

Aim:Astronauts return to Earth with reduced red cell masses and hypovolaemia. Not surprisingly, when they stand, their heart rates may speed inordinately, their blood pressures may fall, and some may experience frank syncope. We studied autonomic function in six male astronauts (average ± SEM age: 40 ± 2 years) before, during, and after the 16‐day Neurolab space shuttle mission.

Method:We recorded electrocardiograms, finger photoplethysmographic arterial pressures, respiration, peroneal nerve muscle sympathetic activity, plasma noradrenaline and noradrenaline kinetics, and cardiac output, and we calculated stroke volume and total peripheral resistance. We perturbed autonomic function before and during spaceflight with graded Valsalva manoeuvres and lower body suction, and before and after the mission with passive upright tilt.

Results:In‐flight baseline sympathetic nerve activity was increased above pre‐flight levels (by 10–33%) in three subjects, in whom noradrenaline spillover and clearance also were increased. Valsalva straining provoked greater reductions of arterial pressure, and proportionally greater sympathetic responses in space than on Earth. Lower body suction elicited greater increases of sympathetic nerve activity, plasma noradrenaline, and noradrenaline spillover in space than on Earth. After the Neurolab mission, left ventricular stroke volume was lower and heart rate was higher during tilt, than before spaceflight. No astronaut experienced orthostatic hypotension or pre‐syncope during 10 min of post‐flight tilting.

Conclusion:We conclude that baseline sympathetic outflow, however measured, is higher in space than on earth, and that augmented sympathetic nerve responses to Valsalva straining, lower body suction, and post‐flight upright tilt represent normal adjustments to greater haemodynamic stresses associated with hypovolaemia.
Pathological sympathoexcitation: how is it achieved?
Authors: Elam M. , Sverrisdottir Y. B. , Rundqvist B. , Mckenzie D. , Gunnar Wallin B. , Macefield V. G.
Published: March 2003

Aim:  Congestive heart failure (CHF) and obstructive sleep apnoea syndrome (OSAS) are both associated with an intense sympathoexcitation, including an increased muscle sympathetic nerve activity (MSNA). We have studied the firing characteristics of single vasoconstrictor fibres to the muscle vascular bed in CHF and OSAS patients, at rest and during transient sympathoexcitatory stimuli, to elucidate the mechanisms by which vasoconstrictor output is augmented in these conditions.

Results:  The main alternatives for augmenting sympathetic output are an increased firing frequency of individual nerve fibres and an increased recruitment of nerve fibres. Starting with the frequency alternative, the inherent bursting character of MSNA provides two possibilities to increase the firing of individual fibres: (1) by increasing the proportion of neural bursts in which the fibre is active (increased firing probability) and (2) by increasing the number of spikes a fibre generates per burst (increased multiple within‐burst firing). At rest and in cardiac sinus rhythm, an increased firing probability is seen in both CHF and OSAS patients, whereas increased multiple within‐burst firing is found in OSAS but not in CHF. In response to transient sympathoexcitatory stimuli (such as pre‐mature heart beats), both patient groups show marked shifts towards multiple within‐burst firing. Thus, both mechanisms for augmenting discharge frequency are operating in these two pathological conditions, but the firing characteristics at rest differ significantly. During recording sessions in sympathoexcited patients, we have encountered vasoconstrictor fibres that are active almost exclusively during periods of transient sympathoexcitation, while being virtually silent at rest. This suggests that recruitment of previously inactive vasoconstrictor fibres, the second main alternative for increasing vasoconstrictor output, contributes to transient sympathoexcitatory responses in these patients. Although it seems reasonable to assume that recruitment may also contribute to the resting level of MSNA in CHF and OSAS, this issue is difficult to resolve in microneurographic studies.

Conclusion:  In conclusion, pathological sympathoexcitation appears to depend on both recruitment and increased firing frequency. A shift towards multiple within‐burst firing, at rest or in response to transient stimuli, may constitute a risk factor per se as it entails neural volleys with high instantaneous firing frequencies and consequently higher release of neurotransmitters.
The activity of single vasoconstrictor nerve units in hypertension
Authors: Mary D. A. S. G. , Stoker J. B.
Published: March 2003

Aim:  It has long been established from controlled experiments in anaesthetized animals that it is more accurate to quantify the mean frequency of efferent sympathetic nerve activity from single unit than from multi‐unit bursts recordings. More recently, sympathetic nerve hyperactivity has been reported in patients with essential hypertension (EHT) when using microneurographic recordings from peripheral efferent nerves. This review will focus on the mean frequency of single unit of muscle sympathetic nerve activity (s‐MSNA) in relation to that of multi‐unit bursts (MSNA) as obtained by microneurography in EHT.

Results:  We have shown that the resting levels of s‐MSNA and MSNA were increased in uncomplicated EHT, white coat hypertension and in EHT complicated by left ventricular hypertrophy. There was a relatively greater increase in s‐MSNA than in MSNA in mild hypertension and in complicated EHT. We also found that both s‐MSNA and MSNA were increased to a similar extent in conditions known to affect reflexes emanating from the heart and influencing sympathetic output, such as acute myocardial infarction. In other preliminary studies, the increase of s‐MSNA in response to the discomfort of cold pressor test was greater than that of MSNA and this difference was abolished by the centrally sympatholytic agent moxonidine.

Conclusion:  These results are consistent with the hypothesis that an increase in the mean frequency of central sympathetic discharge to the periphery (greater s‐MSNA than MSNA) is involved in the pathogenesis and complications of EHT. Target organ damage may in turn lead to an increase in overall sympathetic output (excessive MSNA increase) through the operation of peripheral reflex mechanisms.
Chemical quality of the burnt and non‐burnt grass layer in the Nylsvlei Nature Reserve, South Africa
Authors: DÖrgeloh Werner G.
Published: March 2003

The forage quality of the herbaceous layer in burnt and non‐burnt plant communities was determined seasonally to serve as a baseline for managing the food supply. The near‐infrared reflectance spectroscopy method and wet chemical analyses were applied to analyse the grass samples. Differences in forage quality were found between plant communities. The Sporobolus ioclados–Acacia tortilis Savanna had the highest forage quality throughout the year. Plant communities on the lithosols had a low forage quality. The highest total calcium and total phosphorus concentrations were found in the Eragrostis pallens–Burkea africana Savanna, total potassium in the plant communities on the lithosols, and total sodium in the Sporobolus ioclados–Acacia tortilis Savanna and floodplain. The most optimum Ca:P ratio was found in the Eragrostis pallens–Burkea africana Savanna when burnt and non‐burnt. In non‐burnt areas the highest K:Na ratio was found in the Sporobolus ioclados–Acacia tortilis Savanna.

Burning increased the forage quality in some plant communities. In general, only percentage in vitro organic matter digestibility differed significantly between burnt and non‐burnt plant communities. The forage quality did not increase significantly in plant communities on lithosols and on vertisols. Mineral ratios did not differ between newly burnt plant communities. A low protein and mineral content in the winter forage should be countered with supplementary feeding or burning of grass to improve the condition of animals.
Habitat use and ranging behaviour of tree hyrax, Dendrohyrax arboreus, in the Virunga Volcanoes, Rwanda
Authors: Milner Jos M. , Harris Stephen
Published: March 2003

Habitat use and ranging behaviour of tree hyrax were investigated by radio‐tracking in the Parc National des Volcans, Rwanda. Individuals were predominantly arboreal and showed a daily pattern of vertical movement, being found highest in the canopy at night. Hyrax often spent the night in tree cavities and spent the day resting on branches. Habitat use is discussed in terms of thermoregulation and predator avoidance. Tree selection, modelled by logistic regression analysis, was most influenced by shelter properties. These criteria were best satisfied by large, cavity‐forming Hagenia abyssinica, which were preferentially used. Tree hyrax population density was potentially limited by the availability of shelter. Home ranges were identified by minimum convex polygons for ten individuals. Total area and number of trees used were positively correlated with body mass, whilst the core area was negatively correlated with tree density. Ranges were not stable over the 4‐month tracking period. There was considerable overlap of core areas between individuals. Core areas of mature males encompassed those of several females but no evidence of adult male range overlap was found. Female core areas tended to overlap with individuals of different ages. Male–female pair bonds were observed but the commonest association was parent–offspring.
The territorial system of the kob antelope (Kobus kob kob) in the Comoé National Park, Côte d’Ivoire
Authors: Fischer Frauke , Linsenmair K. Eduard
Published: March 2003

The territorial system of kob antelopes in the Comoé National Park, Côte d’Ivoire, was studied from March 1993 until April 1997. Whereas size and shape of territories remained constant between 1993 and 1994, the number of territories decreased from 1994 onwards. A decline of the population density probably led to the decline in territory numbers and also to variations in size and shape of the remaining territories. The decline of kob numbers is the result of heavy poaching in the study area. Whereas a lekking system was present in the study area prior to 1975 when the population density was approximately 14.4 kobs/km2, males switched to the resource defence territorial system present today after the population density decreased to 12.5/km2 in 1993 and finally to 2.3/km2 in 1997. Compared to other research areas with higher population densities, territories in the Comoé National Park are larger, almost all adult males are capable to defend a territory, fights over territories are rare and loss of territory tenureship is almost exclusively due to the death of the territorial male. We suggest that those differences can all be related to the low population density in the study area.
Structural analysis of the Chambura Gorge forest (Queen Elizabeth National Park, Uganda)
Authors: Grillini Carlo R. Lenzi , Orioli Lorenzo , Piussi Pietro , Kakuru Willy
Published: March 2003

The Chambura Gorge, part of the Queen Elizabeth National Park (QENP), is completely covered by a forest which so far has not been exploited and whose species, composition and structure are barely known. It was therefore of interest to analyse this area as a typical example of a primary natural forest and as a peculiar habitat inside the QENP ecosystem. The forest cover has a typical structure, distributed into layers, but the lower layer is locally poor of saplings belonging to a possible cohort of regeneration. This process is likely to be observable on a wider scale of analysis. None of the species reach their potential maximum height, as measured in other areas and in a typical rain forest. However, the vegetation of Chambura Gorge is very representative of the local edaphic conditions and microclimate. In the structural analysis no relationships were found between the diameters and heights of the observed trees, if considered all together. If considered individually, only the most abundant species, Cleistopholis patens, showed any relationship between diameter and height.
The impact of giraffe, rhino and elephant on the habitat of a black rhino sanctuary in Kenya
Authors: Birkett Alan
Published: March 2003

The habitat in an enclosed black rhino sanctuary, the Sweetwaters Game Reserve in Kenya, is being altered as populations of elephant, giraffe and black rhino increase. Height‐specific browse impact data were recorded for 1075 trees of the dominant species, the whistling thorn, Acacia drepanolobium. Rhinos and elephants browsed 18% of these trees in 1 year, including 5% that were killed or removed. The remaining trees were subjected to high levels of giraffe browse and low rainfall and grew by only 7.5 cm in a year. A mathematical model has been constructed that predicts how the number of trees ha−1 will change with time under different browsing impacts. The model compares recruitment rate with removal rate and estimates that the number of trees ha−1 will fall by 2% per year under the current browsing impact of black rhino (0.27 per km2), elephant (1.1 per km2) and giraffe (1.9 per km2). In 7 years, if the rhino and elephant populations continue to increase at the current rates, tree density will be falling by 5% per year and nearly one‐third of the trees will have been removed. These conditions are unsustainable and will result in habitat change and may affect rhino breeding. Several ways of alleviating the problem are discussed.
Clarithromycin increases the release of heat shock protein B from Helicobacter pylori
Authors: Tsuzuki T. , Ina K. , Ohta M. , Hasegawa T. , Nagasaka T. , Saburi N. , Ueda M. , Konagaya T. , Kaneko H. , Imada A. , Nishiwaki T. , Nobata K. , Ando T. , Kusugami K.
Published: March 2003

Background:

Clarithromycin (CAM) may have certain indirect effects on Helicobacter pylori (H. pylori) other than its inhibitory activity on bacterial growth, as indicated in other infections with Gram‐negative micro‐organisms. In the present study, we examined the effects of lower concentrations of CAM on the release of heat shock protein B (HspB), one of the major antigenic proteins from H. pylori cells, as well as the changes in humoral immune response and histological degree of antral gastritis in patients who received eradication therapy with CAM.

Methods:

The H. pylori strain 26695 and three CAM‐resistant clinical isolates were cultured in broth with and without CAM (2–500 ng/mL). Expression of H. pylori proteins was examined by two‐dimensional (2D)‐electrophoresis followed by N‐terminal amino acid sequencing. Changes in host immune response and histological degree of antral gastritis were monitored in patients with peptic ulcer disease who received H. pylori eradication therapy.

Results:

2D electrophoresis showed 26 spots in extracellularly released proteins with different profiles from those in cytoplasmic proteins. The release of HspB increased after incubation with CAM (30–500 ng/mL) in all three H. pylori clinical isolates tested. Patients with failed H. pylori eradication after triple therapy with CAM, but not those with failed eradication after dual therapy without CAM, showed an increase in serum IgG1 and IgG2 antibodies against HspB along with a decrease in the degree of neutrophil and H. pylori colonization density in tissue sections.

Conclusions:

CAM may induce a humoral immune response against H. pylori and a decrease in gastric mucosal inflammation through up‐regulation of the release of HspB from the bacteria in infected patients.
Monitoring activity in ulcerative colitis
Authors: Rizzello F. , Gionchetti P. , Venturi A. , Amadini C. , Romagnoli R. , Campieri M.
Published: March 2003

The monitoring of patients with ulcerative colitis is easier than in patients with Crohn's disease for several reasons: the severity of symptoms and activity of inflammation tend to run parallel in ulcerative colitis when involvement of the large bowel is more extensive. The easy accessibility of the colonic mucosa by endoscopic and histologic examination provides further information concerning the degree of inflammation. In severe attacks, the patient must be admitted to hospital and monitored carefully. Clinical and laboratory parameters (such as daily stools, CRP, fever, haemoglobin, albumin, etc.) and plain abdominal X‐ray are useful in monitoring the activity of the disease and to predict the outcome. In mild to moderate attacks, endoscopic and histologic evaluation are the best methods for choosing the appropriate treatment and for assessing response.
Monitoring the activity of Crohn's disease
Authors: Biancone L. , De Nigris F. , Del Vecchio Blanco G. , Monteleone I. , Vavassori P. , Geremia A. , Pallone* F.
Published: March 2003

Crohn's disease is characterized by a chronic inflammation of the intestine of unknown aetiology. One of the main problems when treating patients with Crohn's disease, is the identification of patients undergoing early clinical relapse, for timely treatment and the possible prevention of complications. No sub‐clinical markers are currently available that predict relapse during remission. Several parameters have been proposed for this purpose. Although none have proven useful, growing evidence suggests a possible benefit in the clinical management of Crohn's disease. Among these, we may identify: clinical behaviour, the characteristics of the host, clinical activity, markers of intestinal inflammation and markers of immune activation. In particular, the possible relationship between cytokine pattern and the clinical behaviour of Crohn's disease has been addressed. Overall, these observations suggest that mucosal immune activation is a feature of Crohn's disease, and may persist in the form of activated immunocompetent cells during remission. On the basis of this evidence, studies are currently investigating whether the down‐regulation of immune activation markers is associated with clinical remission in Crohn's disease. It has been shown that higher mucosal levels of TNF‐α and an increased state of activation of lamina propria mononuclear cells in patients with inactive Crohn's disease, are significantly associated with an earlier clinical relapse of the disease. These observations suggest that a persistent local immune activation during remission may represent a marker of early clinical relapse of Crohn's disease.
Indication and type of surgery in Crohn's disease
Authors: Poggioli G. , Pierangeli F. , Laureti S. , Ugolini F.
Published: March 2003

The large majority of patients affected by Crohn's disease require surgery during their clinical history. Radical resection originally advocated for Crohn's disease does not decrease the recurrence rate, and repeated resections predispose patients to the development of short‐bowel syndrome. Over the last few years, conservative surgery has become accepted by many authors as a safe means of treating obstructive Crohn's disease. In this review article we analyse the efficacy and safety of conservative techniques, in comparison with resective surgery. Indications, advantages and technical aspects of resective and conservative surgery are reported.

The experience with 489 patients treated for complicated or treatment refractory Crohn's disease in our Institution suggests that strictureplasty is a safe and effective procedure in many cases, as reported by other authors. The risk of cancer in areas of active disease as in stenosis treated with strictureplasty seems to be negligible. Resective surgery still represents the `gold standard' in patients with perforating Crohn's disease; however, conservative surgery, usually contraindicated in perforating Crohn's disease, can be advocated in patients with localized perforating disease presenting an actual risk of short bowel syndrome.
Drug‐induced hypochlorhydria causes high duodenal bacterial counts in the elderly
Authors: Pereira  , Gainsborough  , Dowling
Published: March 2003

Background:

Small bowel bacterial overgrowth secondary to drug‐induced hypochlorhydria may be of particular importance in the elderly, in whom anti‐ulcer drugs are commonly prescribed and the consequences of malabsorption may be severe.

Methods:

Duodenal aspirates were obtained from elderly individuals before (n=24) and during a 2‐month treatment course with either omeprazole (20 mg daily; n=8) or ranitidine (300 mg b.d.; n=6), and from six patients with small bowel bacterial overgrowth who had diarrhoea and malabsorption.

Results:

Before treatment, duodenal bacterial counts were normal (< 104 colony forming units/mL) in 23 elderly subjects (96%). However, six of 14 patients (43%) treated with omeprazole (5 of 8) or ranitidine (1 of 6) developed bacterial counts>  105 cfu/mL. All remained asymptomatic and had normal lactulose breath H2 profiles during treatment.

Conclusion:

Drug‐induced hypochlorhydria causes high duodenal bacterial counts in the elderly but, in the short term, this bacterial overgrowth is not associated with malabsorption.
Primary gastroduodenal prophylaxis with omeprazole for non‐steroidal anti‐inflammatory drug users
Authors: Cullen  , Bardhan  , Eisner  , Kogut  , Peacock  , Thomson  , Hawkey
Published: March 2003

Aim:

To investigate the efficacy of omeprazole 20 mg o.m. as primary prophylaxis against non‐steroidal anti‐inflammatory drug (NSAID)‐associated ulcer disease or dyspeptic symptoms.

Methods:

A parallel group study compared patients randomized to receive omeprazole 20 mg o.m. or placebo as co‐therapy with on‐going NSAID treatment, over 6 months, in 19 specialist centres in Ireland, Hungary, France, the UK and the USA. One hundred and sixty‐nine patients taking NSAIDs regularly, chronically and above defined minimum doses entered the trial. The main outcome measure was the development of gastric or duodenal ulcers detected endoscopically, the development of multiple erosions in the stomach or duodenum, or the onset of moderate or severe dyspeptic symptoms.

Results:

The estimated probability of remaining free of these end‐points for 6 months for patients taking omeprazole was 0.78 compared to 0.53 for placebo (P = 0.004). Fourteen patients receiving placebo (16.5%) developed 15 ulcers, comprising nine gastric and six duodenal ulcers, compared to three patients (3.6%) receiving omeprazole (all gastric ulcers). Logistic regression analysis showed that older patients were less likely, whilst those with rheumatoid arthritis were more likely, to remain free of NSAID‐associated problems.

Conclusions:

Omeprazole is an effective agent for gastroduodenal prophylaxis in patients taking NSAIDs. Its main effect is to reduce the rate of development of gastric and duodenal ulcers.
Acid suppression by omeprazole does not affect orally administered metronidazole bioavailability and metabolism in healthy male volunteers
Authors: David  , Silva C. M. F. Da , Mendes  , Ferraz  , Muscara  , Moreno  , Nucci G. De , Pedrazzoli
Published: March 2003

Background:

The addition of omeprazole to classical triple therapy for eradication of H. pylori may enhance compliance through reducing ulcer symptoms and side‐effects. The aim of this study was to investigate the effects of a 5‐day administration of omeprazole on metronidazole pharmacokinetics.

Methods:

Fourteen healthy male volunteers were selected. The study had an open, randomized, two‐period crossover design with a 21‐day washout period between the phases. Plasma concentrations of metron‐idazole and its hydroxy‐metabolite were measured by reversed‐phase HPLC with ultraviolet detection.

Results:

Administration of omeprazole did not affect the pharmacokinetic parameters of orally administered metronidazole.

Conclusion:

Our results indicate that short‐term treatment with omeprazole in healthy volunteers does not alter the extent or the rate of metronidazole absorption, and does not affect metronidazole clearance.
Review article: non‐steroidal anti‐inflammatory drug‐induced gastrointestinal permeability
Authors: Davies
Published: March 2003

Non‐steroidal anti‐inflammatory drugs induce damage throughout the entire gastrointestinal tract. Administration of site‐specific permeability probes is a non‐invasive technique for assessing the functional integrity of the gastrointestinal mucosa. A systematic search for NSAID‐induced permeability studies using MEDLINE and EMBASE, and an analysis of the literature on NSAID‐induced gastrointestinal permeability, were carried out. The advantages and disadvantages of the various probes and study protocols are discussed.

Identification of the underlying mechanisms of regulatory control of the epithelial tight junction is still needed. A greater appreciation of the pharmacokinetics and distribution of NSAIDs, coupled with gastrointestinal permeability studies, may help delineate the pathogenesis of NSAID‐induced gastrointestinal toxicity. Non‐invasive tests of gastric, intestinal and colonic permeability have shown promise in both basic research and in clinical practice. While such tests could not replace endoscopy, they may represent clinically useful techniques for identifying patients who would benefit from endoscopy, to assess the response to treatment, and perhaps to predict the clinical course of disease.
Effect of intracolonic benzalkonium chloride on trinitrobenzene sulphonic acid‐induced colitis in the rat
Authors: Miampamba  , Parr  , McCafferty  , Wallace  , Sharkey
Published: March 2003

Background:

We investigated the effects of benzalkonium chloride (BAC) on trinitrobenzene sulphonic acid (TNBS)‐induced colitis in rats.

Methods:

TNBS was administered intrarectally before and/or after BAC treatment. In the first study, the effects of treatment with BAC 6, 12 or 24 h after TNBS were examined. In the second study, animals were treated with BAC before, after or before and after TNBS, and were examined 7 days later. The severity of colitis was assessed by macroscopic and histological scoring of the colonic damage and by determination of colonic myeloperoxidase (MPO) activity. Macrophages and CD4+ and CD8+ T cells were examined by immuno‐histochemistry.

Results:

When BAC was instilled into the colon 6, 12 or 24 h after TNBS, weight loss and macroscopic and histological features of the colon were similar to that of controls (TNBS alone). In contrast, MPO activity was significantly reduced in all three groups post‐treated with BAC. In the groups examined 7 days after TNBS treatment, rats post‐treated with BAC exhibited increased weight gain and significantly reduced macroscopic damage and MPO activity compared to the TNBS control group. Rats pre‐treated with BAC exhibited less macroscopic damage of the colon than rats receiving only TNBS, but histological damage, MPO and weight gain were unchanged from TNBS controls. Immunohistochemistry revealed that BAC pre‐treatment increased the numbers of macrophages and T cells in the colon. After TNBS treatment, macrophage accumulation was evident in the colon, but T cells were scarce. However, these cells were preserved or enhanced in the colonic mucosa in TNBS‐treated rats that had been pre‐treated with BAC.

Conclusions:

Treatment with BAC, particularly after induction of colitis, produces a significant reduction in the severity of tissue injury and inflammation through mechanisms that are not fully understood.
Comparison between theophylline and spironolactone in the management of cirrhotic ascites: a randomized controlled study
Authors: Stanley  , Forrest  , Dabos  , Gilchrist  , Hayes
Published: March 2003

Background:

It has been suggested that adenosine is involved in the renal haemodynamic and tubular abnormalities observed in cirrhosis. Low‐dose theophylline is an adenosine antagonist and recent studies have shown that this drug can improve renal blood flow and sodium excretion in cirrhotic patients.

Methods:

Fifteen patients with newly diagnosed cirrhotic ascites were randomized to receive either 100 mg spironolactone daily for 7 days or 250 mg theophylline on days 1, 2, 4 and 6. Baseline clinical and urinary and serum biochemical data were collected and compared following therapy.

Results:

After 7 days of spironolactone there were increases in urinary sodium excretion (43.5 ± 15.6 vs. 106.8 ± 34.7 mmol/day; P < 0.05) and urine volume (769.1 ± 206.5 vs. 1541.6 ± 342.6 mL/day; P < 0.05). No changes in the patients’ weight, creatinine clearance or serum electrolytes were observed. No change was detected in any of these parameters following theophylline therapy.

Conclusion:

Adenosine antagonism in the form of low‐dose theophylline is less efficacious than spironolactone in the management of cirrhotic ascites.
Bone turnover during short‐term therapy with methylprednisolone or budesonide in Crohn’s disease
Authors: D’haens  , Verstraete  , Cheyns  , Aerden  , Bouillon  , Rutgeerts
Published: March 2003

Background:

Glucocorticosteroids are used frequently for the treatment of relapses of Crohn’s disease.

Aim:

To investigate the influence of the new topically active glucocorticosteroid budesonide in comparison with methylprednisolone on bone turnover in a randomized open trial.

Methods:

Twenty‐nine patients received either budesonide (controlled ileal release formulation) 9 mg for 10 weeks, or methylprednisolone 32 mg (equivalent to 40 mg prednisone) orally for 3 weeks with subsequent tapering.

Results:

Patients who completed the trial with methylprednisolone (n = 8) had suppression of serum osteocalcin (30.2 ± 2.6 to 20.4 ± 2.0 ng/mL, P < 0.01), whereas no changes in this parameter of bone synthesis were observed during budesonide treatment (n = 11) (34.8 ± 3.1 to 33.0 ± 3.5 ng/mL). Urinary pyridinolines and deoxypyridinolines, highly sensitive markers of bone degradation, did not change in either group.

Conclusion:

Short‐term methylprednisolone therapy impairs osteoblast activity in patients with Crohn’s disease whereas budesonide does not.
Prospective evaluation of a new anti‐ulcer agent, ecabet sodium, for the treatment of Helicobacter pylori infection
Authors: Ohkusa  , Takashimizu  , Fujiki  , Araki  , Ariake  , Shimoi  , Honda  , Enomoto  , Sakurazawa  , Horiuchi  , Suzuki  , Ishii  , Ishikura
Published: March 2003

Background

A new anti‐ulcer agent, ecabet sodium, is active against Helicobacter pylori.

Aim

To assess the efficacy of ecabet sodium for the eradication of H. pylori in patients with gastroduodenal diseases.

Methods

In a prospective, randomized and controlled study, patients infected with H. pylori were assigned to one of the following two groups: group LA, who received lansoprazole 30 mg o.d. + amoxycillin 500 mg q.d.s. after meals for 2 weeks, and group LAE, who received lansoprazole 30 mg o.d. + amoxycillin 500 mg q.d.s. + ecabet sodium 1000 mg b.d. after meals for 2 weeks. H. pylori status was determined before and at least 4 weeks after the therapy by rapid urease test, histology and a urea breath test.

Results

Of 101 patients (mean age 53 years, range 17–77 years, M/F: 68/33) enrolled in the study, 97 patients completed the protocol. Four patients were withdrawn because of diarrhoea (three from group LA) and skin rash (one from group LAE). The eradication of H. pylori was achieved in 28/48 (58%) patients in group LA and 38/49 (78%) patients in group LAE. The rate of eradication of H. pylori produced by the LAE treatment was significantly higher than that produced by the LA treatment. Side‐effects appeared in two patients (malaise 1, skin rash 1) in group LAE and in seven patients (diarrhoea 6, dizziness 1) in group LA. These side effects disappeared spontaneously with cessation of the treatment.

Conclusions

Ecabet sodium in combination with lansoprazole and amoxycillin increased the rate of eradication of H. pylori. Ecabet sodium appeared to reduce the incidence of diarrhoea as a side‐effect of the dual LA therapy.
Factors affecting solubility and penetration of clarithromycin through gastric mucus
Authors: Grübel  , Cave
Published: March 2003

Background:

Factors influencing the pharmacokinetics of clarithromycin in gastric mucus are poorly defined.

Aim:

To determine: (i) whether the clinical formulation of clarithromycin (Biaxin granules and powdered Biaxin tablets) affects the water solvency of the antibiotic or changes the barrier properties of pig gastric mucus (PGM), thereby influencing the penetration of clarithromycin through the gastric mucus layer; and (ii) whether topically active anti‐ulcer agents affect clarithromycin penetration through gastric mucus.

Methods:

Solubility of clarithromycin in aqueous solution was studied at pH 7. PGM viscosities were determined using a falling ball microviscometer. Permeability of clarithromycin through PGM with and without added anti‐ulcer drugs at pH 7 was monitored using a microfiltration device and an agar diffusion bioassay.

Results:

Clarithromycin showed the poorest solubility at pH 7, whereas both Biaxin formulations demonstrated identical solubility of their antibiotic ingredient. Clarithromycin and both Biaxin formulations markedly increased mucin viscosity over the pH range 2–7. PGM markedly retarded the penetration of clarithromycin: unformulated clarithromycin and Biaxin tablets penetrated more rapidly through mucus than Biaxin granules. Pre‐treatment of PGM with aluminium‐magnesium‐containing antacids (Riopan and Talcid preparations) decreased the rate of clarithromycin penetration, whereas Carafate and Peptobismol had no significant effect on mucus penetration of clarithromycin.

Conclusions:

The availability of clarithromycin in gastric mucus is significantly influenced by its clinical formulation, which affects its solubility as well as the viscous properties of mucus. Pulverized Biaxin tablets provide better local distribution of clarithromycin in mucus than Biaxin granules. Pre‐treatment of mucus with anti‐ulcer medications does not increase the penetration of clarithromycin through mucus.