Biomedical subjects
Publications and source records attributed to V Varró.
The author critically analyses the involvement of prostaglandins in peptic ulceration. Clinical evidence suggests that for the treatment of peptic ulcer other available drugs (e.g. H2-blockers) are as effective and have fewer side-effects. A potential role in prevention of drug induced gastric mucosal damage (NSAID, ASA) may be verified in further studies.
In 1984, a hypertension screening programme was carried out on 13,772 adult subjects in conjunction with a radiological tuberculosis project in the Hungarian town of Csongrád. Among other factors, the effects of a long-lasting and heavy alcohol intake on blood pressure levels were investigated. 21.4% of the men and 2.3% of women admitted to being regular alcohol consumers. Direct and significant relationships were found between the quantity of alcohol consumed and both the systolic (p less than 0.001) and diastolic (p less than 0.05) blood pressures. The prevalence of hypertension (WHO criteria) was higher in heavy drinkers (29.9%) than in abstinent subjects (20.5%, p less than 0.001). When participants were subgrouped according to age groups only the men provided sufficient data. The systolic blood pressure of heavy drinkers was elevated as compared with that of non-drinkers.
Histological examination of the gastric mucosa was performed in 44 patients with primary Sjögren's syndrome with extraglandular symptoms (mean age 51.9, range 22-76). Biopsy specimens were taken from each of three separate regions: the antrum, the corpus, and the transitional zone between the antrum and the corpus. The incidence of chronic atrophic gastritis was considerably higher in patients with Sjögren's syndrome than in the controls. In the young patients with Sjögren's syndrome atrophic lesions were more common both in the antrum and in the corpus than in the control group. In middle aged patients, however, only the antrum, and in the elderly only the corpus, was much more commonly affected than in the controls. All three types of chronic atrophic gastritis occurred in patients with Sjögren's syndrome. Decreased gastric acid secretion was associated mainly with atrophic gastritis of types A and AB, whereas hypergastrinaemia occurred almost exclusively in gastritis of type A.
This study was undertaken to evaluate the number of the immunoglobulin producing cells in the lamina propria of the small intestine by immunocytochemical techniques, using peroxidase-antiperoxidase (PAP) complex in normacid patients with CSBS. 25 patients were studied including 13 patients with bacterial overgrowth, where the bacterial concentration was higher than 10(4) colony forming units/ml, and 12 subjects with normal bacterial concentration, served as control. The patients with CSBS were treated with antibiotics according to the antibiotic resistance. After treatment the luminal bacterial concentrations was lower than 10(4) cfu/ml in 7 of 13 patients (CSBS I. group). In 6 patients the bacterial concentration remained high (CSBS II. group). The immunoglobulin producing cells were determined in biopsy specimens taken from the lower part of duodenum. The number of the IgA and IgM producing immunocytes was significantly decreased only in the CSBS II. group. Our results show that temporary immunological alterations may play an important role in the mechanism of the recurrent CSBS.
Factors influencing the effectivity of replacement therapy with Panpur and Creon were controlled by in vivo and in vitro investigations. Both enteric coated preparations were equally acid protected, they even seemed to be more effective in hyperacid than in anacid chronic pancreatitis patients. Thus the uneven results of Panpur treatment in pancreatic steatorrhea cannot be explained by acid inactivation of the enzymes. Creon dose-dependently ameliorated the steatorrhea as well as vitamin B12 absorption while crushed but not the intact Panpur has only some insignificant effect. Good mixing of pancreatin with the B12-intrinsic factor - R protein complex and with the protein containing meal seems to be important for digestion of protein as well as fat. Unbound, overflowing trypsin activity of Panpur resulted in fast proteolytic inactivation of lipase. This could be diminished by soybean trypsin inhibitor which increased the in vivo effectiveness of the preparate. In summary Creon fulfilled two important factors of replacement therapy more successfully than Panpur: good mixing with meals and stability of lipase against proteolytic splitting, that is why it proved to be more effective for replacement therapy of pancreatic insufficiency.
The effect of a specific cholecystokinin (CCK) receptor blocker from Rotta Research Laboratorium (Monza/Milano, Italy), CR 1409 (Lorglumide), on pancreatic secretion was investigated. CR 1409 caused a rightward and parallel shift in the dose-response curve of CCK-8-stimulated pancreatic protein secretion in anesthetized rats, demonstrating a competitive mechanism of inhibition. The mean pA2 value, showing the 50% inhibitory dose of CR 1409, was 6.4. CR 1409 proved to be about 1,000 times more potent as a CCK receptor blocker than proglumide, the first glutaramic acid analogue with anti-CCK potential. In conscious rats, pancreatic protein and water secretion were significantly diminished for about 2 h in response to 300 micrograms/kg of CR 1409 given subcutaneously during diversion of pancreatic juice, demonstrating inhibition of endogenous CCK by this new glutaramic acid derivative. By contrast, during reintroduction of precollected pancreatic juice into the duodenum, when the release of CCK is almost totally eliminated, pancreatic secretion was not modified by the same dose.
The effects of lorglumide (CR 1409), a potent cholecystokinin (CCK) receptor blocker developed recently by the Rotta Research Laboratories, were studied on pancreatic growth and enzyme composition. In secretory studies, the inhibitory effect of 4 mg/kg of lorglumide administered subcutaneously proved to last more than 3 h. The trophic effect of exogenous CCK (600 ng/kg given three times daily for 2 weeks) was significantly decreased by the simultaneous administration of 4 mg/kg of lorglumide. To study the role of endogenous CCK released by feeding while maintaining pancreatic trophism, 4 mg/kg of lorglumide was administered subcutaneously four times daily during the feeding period for 2 weeks. Lorglumide significantly decreased pancreatic weight, pancreatic content of soluble protein, trypsinogen, and chymotrypsinogen, while decreases in DNA, lipase, and amylase failed to reach statistical significance. According to our experiments, high-doses of lorglumide could inhibit not only the trophic effect of exogenous CCK but also the effect of endogenous CCK released by food and lorglumide itself.
The authors present three patients having primary microbacterial infections which involved the gastrointestinal tract. A short survey of the clinical features and the difficulties arriving at definitive diagnosis is given. They discuss the differential diagnostic problems in each case--without an unequivocal bacterial findings--on the basis of histologyc data and of therapeutic response which ultimately proved the mycobacterial nature of the infection.
The authors interpret a case report on a secondary amyloidosis involving the whole gastrointestinal tract, and manifested in a rare clinical phenomenon, the malabsorption syndrome. Their histological observations advance the understanding of the pathomechanism of malabsorption.
The aim of this study was to examine histologic and biochemical alterations in experimental acute interstitial pancreatitis (AIP) induced by serial repeated supramaximal cholecystokinin-octapeptide (CCK-OP) stimulation in rats. High doses of CCK-OP (60 micrograms/kg body wt) were administered subcutaneously (sc) six times at hourly intervals for 1 d (Group I) or for 3, 5, or 7 d (Group II). Rats were killed after 1, 3, 5, 7, and 10 d in both groups and also after 13, 20, and 27 d in Group II. During the course of the AIP, the morphological alterations were more pronounced in the repeatedly treated rats, but their appearance and disappearance essentially occurred in parallel in the two groups. Increased mitotic activity of the centroacinar and acinar cells were observed in d 5 and rose further even in Group II. The pancreatic weight and the protein and DNA contents reached a minimum on d 5 in both groups. The lowest enzyme activities did not occur in parallel. Thereafter, functional regeneration occurred despite continuing CCK-OP overstimulation in Group II. The toxicity of repeated CCK-OP hyperstimulation, thus, was limited: after its fifth administration, it failed to further aggravate the acute pancreatic damage or prevent the regeneration. This might be explained by a decreased CCK-OP sensitivity of the preexisting acinar cells, and/or increased CCK-OP tolerance of newly-formed ones.
Influence of alcohol administration on the trophic effect of cholecystokinin-octapeptide and soybean trypsin inhibitor administration was examined in male Wistar rats. Two x 4 mL of 20% alcohol given intragastrically during 2 wk did not significantly influence pancreatic weight, DNA, protein, trypsin, chymotrypsin, amylase, lipase, or trypsin inhibitor contents of the pancreas. It diminished the hypertrophy but not the hyperplasia seen after CCK-8 treatment, and eliminated the hyperplasia, as well as the hypertrophy provoked by SBTI administration. Secretory studies and CCK measurements demonstrated decreased CCK release in response to SBTI stimulation after 3-d alcohol administration. The results indicate that alcohol inhibits the enzyme synthesis of the CCK stimulated dividing and/or newly formed acinar cells and the endogenous CCK release.
The effect of starvation for 3, 5, or 7 d on body weight, fat stores, pancreatic weight, and enzyme composition was studied in 300 g rats and was compared with a 3-d fast in 200 g rats. In the 300 g animals, fasting led to a gradual hypotrophy of the pancreas with a marked, continuous decrease in amylase content. Pancreatic lipase, trypsinogen, chymotrypsinogen, proelastase, and secretory trypsin inhibitor contents increased temporarily, but by d 7, they declined to about the initial values. This decline in enzyme levels coincided with the exhaustion of fat stores. The decrease in amylase content could be related to decreases in circulating insulin levels, whereas the temporary increase in lipase content may be owing to changes in plasma free fatty acid concentrations. In 200 g rats, starvation for 3 d led to exhaustion of fat stores that was accompanied by greater losses of pancreatic weight, protein, and amylase contents. In addition, the levels of trypsinogen and chymotrypsinogen decreased and lipase was unchanged. These findings indicate that during starvation, changes in pancreatic secretory enzymes are time-dependent and vary with the age, body weight, and/or adipose tissue mass of the rats.
Local variations of prostaglandin (PG) I2 and F2 alpha were studied in the pancreatic tissue during the first hour of an acute experimental necrohemorrhagic pancreatitis. The local pancreatitis was induced by trypsin injection into the interstitium of the splenic part of rat pancreas, and a saline injection was given into the interstitium in the duodenal part of the same pancreas as control. PGF2 alpha level was measured by specific radioimmunoassay (RIA), and the stable degradation product of PGI2, the 6-keto-PGF1 alpha, was determined also by RIA as an index of PGI2 level. The results were compared between the two regions and with control intact pancreata. The PGI2 level transiently decreased, whereas the PGF2 alpha increased in the region of localized hemorrhagic pancreatitis when compared with the intact pancreata. By contrast, the quickly disappearing edematous reaction induced by saline injection was accompanied by opposite changes in the two PGs studied: PGI2 was transiently elevated and PGF2 alpha diminished. In consequence, the ratio of the two PGs was shifted in favor of PGI2 in a transient edematous reaction and in favor of PGF2 alpha in hemorrhagic pancreatitis. It was concluded that PGI2 plays some protective role while PGF2 alpha might be one of the aggressive mediators in the inflammatory process. Their biological importance must be limited since PGF2 alpha alone did not induce pancreatitis nor did PGI2 protect against the trypsin-induced local pancreatitis.
The effect of prostacyclin and its analogues, -6-keto-prostaglandin-F1 alpha and 6-beta-prostaglandin-I1, on cysteamine induced duodenal ulceration of rats has been investigated. It seems that neither prostacyclin nor its analogues have antiulcerogenic effect in this model.
The intracellular effect of exogenously administered prostacyclin in the gastric mucosa seems to be a polyphasic effect, namely: 1. Effect on the cyclic nucleotide (cAMP, cGMP), turnover; 2. Effect on the calmodulin-content; 3. DNA and RNA changes; 4. Influence on protein synthesis; 5. New cell formation. While the endogenous prostacyclin exerts a natural protection against damaging noxae.
The authors examined the quantitative changes in the glycogen content in rat's small intestinal mucosa under the effect of insulin. They found that glycogen content increases significantly during the first 60 minutes, then it decreases gradually, and regains the control value only after 6 hours. It appears that as regards its metabolic activity, the small intestinal mucosa is not an insulin resistant organ.
In conjunction with a radiological tuberculosis project, a hypertension screening programme was carried out in 1984 on 13,772 people (74% of the eligible adult population) in the Hungarian town of Csongrád. In the younger age groups the blood pressure was found to be higher amongst men, whilst in older groups the women had higher blood pressures. By the WHO criteria, systolic hypertension was detected in one-third of the population and diastolic hypertension in one-sixth. Of the hypertensive patients detected, 34% were previously unaware of their diagnosis. The prevalence of hypertension was elevated particularly amongst obese persons and in the sub-group of physical (blue collar) workers aged over 60 years. There was a significant correlation between alcohol consumption and both systolic and diastolic blood pressures. Hypertension was found in 29.9% of heavy drinkers but in only 20.5% of moderate drinkers or total abstainers.
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