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Biomedical subjects

J Lonovics

Publications and source records attributed to J Lonovics.

At least 91 records · Page 5Linked to original sources
PubMed1993

Cicletanine attenuates overdrive pacing-induced global myocardial ischemia in rabbits: possible role of cardiac cyclic nucleotides.

BACKGROUND: This study examined whether cicletanine, an antihypertensive drug with cGMP phosphodiesterase inhibitory effect, could alleviate ventricular overdrive pacing-induced myocardial ischemia in chronically instrumented rabbits. METHODS: An electrode-catheter implanted into the right ventricle was used for pacing (500 bpm over 5 min) and for measuring intracavital ST-segment elevation and ventricular effective refractory period (VERP). PQ and QT intervals were measured in the chest-lead ECG, and dP/dtmax as well as left ventricular end-diastolic pressure (LVEDP) were recorded through a left intraventricular catheter. In separate groups, mean arterial blood pressure (MABP) was monitored from the right carotid artery. Experiments were performed on conscious rabbits after a week of convalescence. In anesthetized, open-chest rabbits, samples were taken from the left ventricle before and after drug treatment and/or overdrive pacing for determination of cGMP and cAMP contents by radioimmunoassay. RESULTS: Intravenous cicletanine, 30 mg/kg body weight, did not change resting MABP, dP/dtmax, and LVEDP, but it did reduce heart rate and prolonged PQ and QT intervals and VERP. Overdrive pacing produced intracavital ST-segment elevation, increased LVEDP, and decreased dP/dtmax and MABP. Cicletanine administered 15 minutes before pacing significantly attenuated ST-segment elevation, increased LVEDP, and decreased dP/dtmax and MABP. In anesthetized animals, cicletanine itself slightly increased cardiac cGMP and cAMP contents. Overdrive pacing moderately increased cGMP and profoundly elevated cAMP, and in overpaced rabbits, cicletanine further increased cGMO and markedly attenuated cAMP content increased by overdrive pacing. CONCLUSIONS: These results suggest that in correlation with alterations of cardiac cycle nucleotide contents, cicletanine protects the heart against pacing-induced myocardial ischemia.

Animals↗
PubMed1991

[A case of inflammatory fibroid polyp of unusual localization].

The case of an inflammatory fibroid polyp of infrequent localization is presented. Altogether 100 cases are reported by summarizing publications in the literature and only a small part of them showed duodenal localization. The patient whose case is presented was subjected to internal examination and later to operation because of acute spastic abdominal pain and loss of weight. Following the description of the case the authors analyse the etiology of this rare disease and the problems of terminology. Radical, curative operation is considered expedient in these cases. The presented case can be regarded as a special one both from the viewpoint of diagnostics and of its duodenal localization.

Duodenal Neoplasms↗
PubMed1991

Types of atrophic gastritis in patients with primary Sjögren's syndrome.

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.

Adult↗
PubMed1990

Modulation of posttranslational processing of gastrin precursor in dogs.

The precursor of the acid-stimulating hormone gastrin is processed in pyloric antral gastrin cells by steps involving sulfation, phosphorylation, cleavage, and amidation. We describe here changes in posttranslational processing in dogs with a surgically excluded antrum; in the preparation we used there was an intact pylorus but antral mucosa was excluded from the normal influence of the luminal contents. Three to five months after the operation, basal plasma gastrin increased from 30.1 +/- 4.0 to 66.1 +/- 16.1 pmol/l, and concentrations of gastrin in the excluded mucosa were 9.23 +/- 1.75 compared with 3.2 +/- 0.56 nmol/g in control antral mucosa. Calculations based on the metabolic clearance rate and plasma and tissue gastrin concentrations suggest two-fold lower fractional release rates from the excluded G-cells compared with normal G-cells. Radioimmunoassay of tissue extracts using antisera specific for the extreme COOH-terminus of progastrin, for glycine-extended G-17, and for the COOH-terminus of G-17, combined with gel filtration and ion exchange chromatography, indicated normal endopeptidase cleavage of progastrin. However there was significantly reduced phosphorylation of the COOH-terminal tryptic fragment of progastrin, and there was also decreased conversion of Gly-extended intermediates to the biologically active COOH-terminally amidated forms of gastrin. Thus, in spite of hypergastrinaemia, the excluded antral mucosa showed evidence of decreased secretory rates associated with decreased progastrin phosphorylation and amidating enzyme activity. The results suggest that contact of antral mucosa with the luminal contents is able to modulate the posttranslational processing of progastrin and so determine the production of biologically active hormone.

Amino Acid Sequence↗
PubMed1988

Peptide YY and gallbladder contraction. Studies in vivo and in vitro.

The purpose of this study was to examine the effect of peptide YY on contraction of the gallbladder in vivo and in vitro and on contraction of the sphincter of Oddi in vitro. In conscious dogs that were prepared with strain-gauge force transducers implanted in the gallbladder wall, peptide YY (400 ng/kg, bolus; 800 pmol/kg.h, infusion) did not affect the resting contractile pattern of the gallbladder, nor did it inhibit cholecystokinin-octapeptide (CCK-8)-stimulated gallbladder contraction. In contrast, the cholecystokinin antagonist proglumide (5, 10, 20, 40, or 80 mg/kg), given in vivo, inhibited CCK-8-stimulated gallbladder contraction in a dose-related manner. The highest dose of proglumide (80 mg/kg) completely abolished contraction of the gallbladder stimulated by CCK-8. In vitro studies showed that peptide YY (0.25, 0.5, or 1 microgram/ml) did not affect the resting tension of rabbit gallbladder strips, and it did not inhibit CCK-8-stimulated contraction of gallbladder strips. Proglumide (0.4, 0.8, 1.6, or 3.2 mg/ml) inhibited CCK-8-stimulated tension of gallbladder strips in a dose-related manner. Peptide YY and CCK-8 had no effect on the motility of the canine sphincter of Oddi in vitro, whereas acetylcholine caused contraction and adrenergic agonists caused relaxation. These results suggest that peptide YY and pancreatone (a peptidelike substance, extracted from ileal and colonic mucosa, that inhibits CCK-8-stimulated gallbladder contraction in vivo) do not appear to be identical.

Ampulla of Vater↗
PubMed1986

Cholecystokinin-destroying activities of canine tissue homogenates.

We have studied the capacity of different canine tissue homogenates to destroy cholecystokinin in vitro. Tissues from the kidney cortex, lung, pancreas, and small bowel contained significant cholecystokinin-destroying activity. Only small amounts of activity were found in the liver, and no activity was detected in the kidney medulla, the gastric antrum, gallbladder, spleen, or in serum or plasma. The kidney cortex was the richest source of activity. The cholecystokinin-destroying enzyme isolated from the kidney cortex was heat-labile, non-dialyzable, and trypsin-resistant, with an optimum pH between 7 and 7.4. The enzyme was inhibited by chelating agents and by phenylalanine amide, although it was little affected by phenylalanine itself or proteinase inhibitors. The enzyme required divalent cation cofactors for its activity. After inhibition by EDTA, the enzyme could be reactivated completely with Mn2+, but not with Ca2+ or Mg2+ alone. The cholecystokinin-destroying enzyme was bound strongly to membranes, and during differental centrifugation, was sedimented with mitochondrial fractions of kidney cortex. The supernatant fraction of the solubilized enzyme obtained at 105,000 X g had a molecular weight of about 480,000 dalton. Since the enzyme could be inhibited by phenylalanine-amide, it would appear to act at the C-terminal end of the cholecystokinin molecule.

Animals↗
PubMed1984

Synthesis of potent heptapeptide analogues of cholecystokinin.

Nine new analogues of acetyl-CCK-heptapeptide (Ac-Tyr(SO3H)2-Met3-Gly4-Trp5-Met6-Asp7-Phe8-NH2 ) were synthesized by solid-phase methodology. In a first series, the Asp7 residue was replaced by hydroxy amino acid sulfate esters. In another series, Gly4 was substituted by D-Ala, while Trp5 and Met6 were replaced by their D enantiomer. The introduction of the sulfate ester was performed with a new, mild, crystalline, and stable reagent, pyridinium acetyl sulfate. Each analogue that contained Tyr(SO3H)2 and a hydroxy amino acid sulfate ester [Ser(SO3H), Thr(SO3H), or Hyp(SO3H)] in position 7 proved to be more potent (1.9, 1.7, and 3.0 times, respectively) than CCK-8 in vitro (isolated gallbladder strips). While devoid of gastrin-like activity in vivo, these analogues had potent anticonvulsive activity. The analogues containing a D-amino acid residue were less potent than the parent compound in vitro. The D-Ala4 replacement, however, yielded a compound that was 40% as potent as CCK-8 in the in vitro test but showed prolonged duration of action on sphincter Oddi. While the 7-substituted Ac-CCK heptapeptides are among the most potent CCK analogues reported so far, the D-Ala4 replacement resulted, for the first time, in prolonged activity in vivo.

Amino Acid Sequence↗
PubMed1983

Subcellular localization of bioactive cholecystokinin-like peptides in the rat cerebral cortex.

The subcellular distribution of cholecystokinin (CCK), especially its exact localization within the synaptosome, was studied in the rat cerebral cortex. Highest CCK-like bioactivity was measured in the synaptic membrane fractions, paralleling the distribution of (Na+ + K+)-dependent ATPase. In the synaptic vesicles, which were characterized by high acetylcholine content and by the absence of (Na+ + K+)-ATPase, only minimal quantities of CCK were detected.

Animals↗
PubMed1981

Pancreatic polypeptide. A review.

Pancreatic polypeptide (PP), 36-amino acid peptide, may function as an important feedback inhibitor of pancreatic secretion after a meal. It arises from both islet and acinar cells of the pancreas. Release of PP by a meal, primarily protein, occurs in a biphasic manner. The first rapid release occurs as a result of vagal stimulation; the second, more prolonged rise (the so-called intestinal phase) occurs in response to hormonal stimulation, predominantly cholecystokinin. Plasma PP levels increase with age; PP levels are elevated above those of age-controlled normal subjects in diabetic patients and in some patients with pancreatic amine precursor uptake decarboxylase tumors. The value of plasma PP as a possible marker for pancreatic tumors is as yet unsettled but may be a valuable tool.

Animals↗
PubMed1981

Hormone-stimulated release of pancreatic polypeptide before and after vagotomy in dogs.

Concentrations of pancreatic polypeptide (PP) in peripheral blood were measured before, during, and after infusions of graded doses of synthetic human gastrin I (SHG-I), cholecystokinin 99% pure (CCK-99%), CCK octapeptide (CCK-OP), and pure natural porcine secretin in six dogs with gastric and duodenal fistulas. Studies were repeated after truncal vagotomy. Significant increases in concentrations of PP were found with 1 microgram . kg-1 . h-1 of SHG-I, 0.25 and 1.0 microgram . kg-1 . h-1 of CCK-99%, and 0.06 and 0.25 micrograms . kg-1 . h-1 of CCK-OP. Significant increases persisted after vagotomy, except at the lower dose of CCK-OP. Postvagotomy responses were significantly less than prevagotomy, except at the higher doses of CCK-99% and CCK-OP. Pure secretin did not change concentrations of PP in blood before or after vagotomy. The most potent stimulant for PP release on a molar basis was CCI-99%, followed by CCK-OP and SHG-I. The results suggest that cholinergic and humoral agents of the gastrin-cholecystokinin family interact in the normal physiological response of PP to food and that, in dogs, CCK-like peptides are more potent than gastrin.

Animals↗
PubMed1981

Action of pancreatic polypeptide on exocrine pancreas and on release of cholecystokinin and secretin.

We have studied the effect of exogenous porcine pancreatic polypeptide (PP; 0.8 and 2.1 microgram/kg . h, iv) on endogenously stimulated pancreatic exocrine secretion in five pancreatic-fistula dogs. Plasma levels of cholecystokinin (CCK), secretin, and PP were measured in addition to pancreatic secretion of water, bicarbonate, and protein. Intraduodenal infusions of acid and a mixture of phenylalanine and tryptophan were used to stimulate hormone release. PP caused a dose-dependent inhibition of endogenously stimulated pancreatic secretion, whereas the release of CCK and secretin was not affected. Duodenal acidification and intraduodenal infusion of phenylalanine and tryptophan caused a significant release of PP. This study shows that: 1) PP suppresses pancreatic secretion by means of a mechanism that is probably direct; this effect is not mediated through inhibition of release of CCK or secretin, and 2) phenylalanine and tryptophan, both strong stimulants of CCK release, cause a substantial rise in PP in peripheral blood. The mechanism of PP release may involve CCK (in previous studies, we have shown a rise in circulating PP levels after iv CCK infusion).

Animals↗
PubMed1981

Cholecystokinin-like bioactivity in rat cerebral cortex.

Cholecystokinin (CCK)-like bioactivity was studied in extracts of rat cerebral cortex by three different bioassays. Positive results were obtained by all procedures used. A fairly good quantitative correlation was found when testing the same extracts by two of the methods. A considerable amount of CCK-like activity was demonstrated in the various subcellular fractions (synaptic membranes, synaptic vesicles, and synaptic fragments) corresponding to synaptic structures. The results are in accordance with the findings of several authors who demonstrated CCK-like immunoreactivity in the brain, especially in the cortex. The use of three different bioassays in three species (rabbit, rat, dog) seems to prove that some bioactive molecular form of CCK exists in the brain, mainly in the cortical area. The findings that subcellular elements of the synaptic structures contain relatively high concentrations of CCK raises the question of the possible role of CCK in the neuronal transmission.

Animals↗
PubMed1980

Role of gastrin in vagally-stimulated pancreatic secretion.

In an attempt to clarify the contribution of antral gastrin to the vaginal stimulation of pancreatic secretion, we have measured the effect of total excision of the antral mucosa on pancreatic secretion induced by electrical vagal stimulation in eight anesthetized dogs. Stimulation was done before excision of the mucosa, and after excision, with and without a gastrin background. Mucosal excision reduced pancreatic volume response to 25% and pancreatic protein response to 32% of the respective responses obtained before excision; gastrin release in response to vagal stimulation was completely abolished. With a gastrin background (0.5 microgram/kg-hr of synthetic human gastrin-17-I), which resulted in serum gastrin concentrations higher than those obtained by vagal stimulation before excision of antral mucosa, the pancreatic volume and protein response showed only partial restoration. These studies provide evidence that vagal pancreatic secretion is only partially gastrin-dependent, and that other antral factors, probably vagally modulated intramural cholinergic pathways, are involved.

Animals↗
PubMed1980

Effects of gastrin on circulating levels of somatostatin, pancreatic polypeptide, and vasoactive intestinal peptide in dogs.

The effect of synthetic human gastrin I, infused at two doses, on the concentrations of somatostatin, pancreatic polypeptide, and vasoactive intestinal peptide in portal and systemic blood was studied in six anesthetized dogs. Intragastric pH was maintained at 5.5, and acid output was measured by intragastric titration. Significant increases in somatostatin and pancreatic polypeptide concentrations in portal blood were found with the lower dose of gastrin (0.5 microgram/kg . h) infused for 40 min. When gastrin was infused at 1.5 microgram/kg . h for 100 min, both portal and systemic blood concentrations of somatostatin and pancreatic polypeptide rose significantly. Cimetidine (300 mg, as an iv bolus), given 40 min after the beginning of the second infusion, did not affect gastrin-stimulated release of somatostatin and pancreatic polypeptide, whereas acid output was completely abolished. Vasoactive intestinal peptide concentrations did not change with the infusion of either dose of gastrin. This daily shows that gastrin releases somatostatin and pancreatic polypeptide in a dose-dependent fashion, and since this release was not acid mediated, it appears likely to be a direct action of gastrin.

Animals↗
PubMed1980

Release of pancreatic polypeptide in humans by infusion of cholecystokinin.

Plasma levels of pancreatic polypeptide were measured after a test meal and after infusion of graded doses of 99% pure cholecystokinin in 6 healthy volunteers. Initial attempts at sterilization of 99% pure cholecystokinin resulted in complete inactivation. Successful sterilization was accomplished by filtration by using specially treated silver-coated filters. Biologic activity of sterilized material was confirmed with cholecystokinin bioassay, and plasma levels of sterilized cholecystokinin achieved by exogenous infusions were measured with a specific cholecystokinin radioimmunoassay. Significant increases in plasma levels of pancreatic polypeptide were found with a test meal and with infusions of 0.25 and 0.5 micrograms/kg-hr of 99% pure cholecystokinin. Integrated values of pancreatic polypeptide released by the low-dose and the high-dose infusions of 99% pure cholecystokinin were 59% and 50% of that obtained by food, respectively. Integrated levels of cholecystokinin after 45 min of infusion of 0.25 micrograms/kg-hr were equal to those after a standard meal. Cholecystokinin, therefore, is an effective humoral releaser of pancreatic polypeptide in humans and may play an important role in the intestinal phase of release of pancreatic polypeptide.

Adult↗
PubMed1980

BOC-14C-glycine pentapeptide metabolism in vitro in rat organ homogenates.

BOC-14C-glycine pentapeptide undergoes hydrolysis on incubation with tissue homogenates. The enzyme activities responsible for hydrolysis have the pancreas, lung and small intestine as their sites. No enzyme activity is demonstrable in liver, kidney and muscle. While intrapulmonary enzyme activity is marked by thermolability, the activities of the pancreatic and intestinal tissues are scarcely affected by heat. The optimum pH is 7.1 for the pulmonary, 7.1 and 10 for the pancreatic and small intestinal enzyme activity. EDTA has proved inhibitory to the enzyme activities of all three organs, in contrast to Gordox and to soybean trypsin inhibitor which leave these activities unaltered.

Animals↗