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Biomedical subjects

A Vincze

Publications and source records attributed to A Vincze.

At least 19 recordsLinked to original sources
PubMed2001

Mechanisms of action of retinoids in gastrointestinal mucosal protection in animals, human healthy subjects and patients.

UNLABELLED: Retinoids prevent chemically induced gastric mucosal damage without inhibiting gastric acid secretion ("nutritional gastric cytoprotection"). The gastroprotective effects of retinoids do not depend on 1) vitamin A activity; 2) number of unsaturated double bonds; 3) the presence of a characteristic chemical structure of their terminal components; however, they depend on 1) intact vagal nerve and 2) adrenals in experimental animals. The gastric cytoprotective effect of retinoids produces a dose-dependent inhibition of ATP-transformation into ADP. It also increases the transformation of ATP into cAMP. Other features of these gastric cytoprotective effects of retinoids include: 1) The retinoid-induced gastric mucosal protection differs from that of PGs; 2) The cAMP is an intracellular signal in the development of gastric mucosal damage produced by chemicals (e.g., ethanol, HCl, indomethacin) and in the protection of gastric mucosa induced by retinoids (but not by PGs); 3) The gastric mucosal protection induced by retinoids and gastric mucosal permeability can be separated in time. The existence of gastric mucosal protection can be demonstrated in healthy persons (against indomethacin treatment), in patients with gastric ulcer (GU) and duodenal ulcer (DU) without any inhibition of gastric acid secretion. The serum levels of vitamin A and zeaxanthin were significantly decreased in patients with chronic gastrointestinal (GI) inflammatory diseases (e.g., terminal ileitis, ulcerative colitis), colorectal polyposis, and different (e.g., esophageal, gastric, pancreatic, hepatocellular and colorectal) malignant diseases. The serum levels of vitamin A provitamins were unchanged and their GI mucosal protective effects do not depend on vitamin A activity. CONCLUSIONS: 1) Abundant experimental and human observations clearly proved the defensive role of retinoids in the GI tract; 2) There is a correlation between the a) scavenger properties of retinoids vs. intact vagal nerve; b) scavenging properties vs. intact adrenals. 3) The GI mucosal protective effect of retinoids is correlated with biochemical changes in the GI mucosa.

Adenosine Diphosphate↗
PubMed2001

Four response stages of capsaicin-sensitive primary afferent neurons to capsaicin and its analog: gastric acid secretion, gastric mucosal damage and protection.

Capsaicin is the active component of red hot peppers, which modifies specifically the capsaicin-sensitive sensory afferent nerves. The action of capsaicin is an initial short-lasting stimulation, which is followed by desensitization to capsaicin itself, and to other stimuli of afferent sensory nerves. Four response stages of capsaicin-sensitive primary afferents exist to capsaicin, depending on the dose and duration of exposure to the drug. These are excitation, a sensory blocking effect, long-term selective neurotoxic impairment, and irreversible cell destruction. The possible roles of four stages of capsaicin-sensitive primary afferents can be evaluated in relation to gastric acid secretion, and to the details of the defensive side of gastric mucosa against different chemicals, physical agents, drugs and other pathological stress. Capsaicin inhibited the gastric acid secretion in pylorus-ligated rats when it was given intragastrically at a dose of 0.4-1.8 microg/kg. Small doses of capsaicin (up to 800 microg, i.g.) produced a dose-dependent inhibition (ID50 = 400 microg), and its inhibitory effect was exerted for 1 h in healthy human subjects. While a small dose (5 microg/kg) of capsaicin caused inhibition, a high dose (50-100 mg/kg) enhanced the gastric mucosal lesions productivity by causing hyperacidity in pylorus-ligated animals. Capsaicin and its analog inhibited the development of different chemically induced gastric mucosal damage in various experimental models if they were given intragastric doses (microg/kg). The final effects of capsaicin depend on the dosage and timing. The different effects are excitation, a sensory-blocking effect, long-term selective neurotoxic impairment and irreversible cell destruction.

Afferent Pathways↗
PubMed1999

Characterization of O,O-diethylphosphoryl oximes as inhibitors of cholinesterases and substrates of phosphotriesterases.

Reactivators of organophosphate (OP)-inhibited cholinesterases (ChEs) are believed to give rise to phosphorylated oximes (POX) that reinhibit the enzyme. Diethylphosphoryl oximes (DEP-OX) that were generated in situ were demonstrated in the past to be unstable, yet were more potent inhibitors of acetylcholinesterase (AChE) than the parent OPs. In view of the inconsistencies among reported results, and the potential toxicity of POXs, it seemed important to characterize authentic DEP-OXs, and to evaluate their interference with reactivation of diethylphosphoryl-ChE (DEP-ChE) conjugates. To this end, the diethylphosphoric acid esters of 1-methyl-2-pyridinium carboxaldehyde oxime (DEP-2PAM) and 1-methyl-4 pyridinium carboxaldehyde oxime (DEP-4PAM) were synthesized and chemically defined. The half-lives of DEP-2PAM and DEP-4PAM in 10 mM Tris buffer, pH 7.8, at 29 degrees were found to be 10 and 980 sec, respectively. The two DEP-OXs inhibited ChEs with the following ranking order: for DEP-2PAM, human butyrylcholinesterase (HuBChE, k(i) = 2.03 x 10(9) M(-1) min(-1)) > mouse AChE (MoAChE) approximately equal to fetal bovine serum AChE (FBS-AChE) approximately equal to equine BChE (EqBChE); for DEP-4PAM, HuBChE (k(i) = 0.71 x 10(9) M(-1) min(-1)) > EqBChE > MoAChE > FBS-AChE. A dialkylarylphosphate hydrolase (phosphotriesterase; PTE) from Pseudomonas sp. catalyzed the hydrolysis of DEP-4PAM with k(cat)/Km = 3.56 x 10(7) M(-1) min(-1) and Km = 0.78 mM. Reactivation of DEP-ChEs was enhanced by PTE when 4-PAM-based oximes were used as reactivators, whereas reactivation with 2-PAM-based oximes was not affected by PTE. This observation is attributed primarily to the short half-life of DEP-OXs derived from the latter oximes. Relatively low doses of PTE can detoxify large quantities of DEP-OXs rapidly, and thereby augment the efficacy of antidotes that contain the oxime function in position 4 of the pyridine ring.

Animals↗
PubMed1999

Decrease in serum levels of vitamin A and zeaxanthin in patients with colorectal polyp.

OBJECTIVE: Several retrospective and prospective epidemiological investigations have demonstrated that a diet rich in carotenoids could prevent the development of pre-cancerous and neoplastic lesions of the digestive tract. The aim of this examination was to analyse the correlation between colorectal polyps with different histological classifications and serum carotenoid levels. DESIGN AND METHODS: A 10 ml blood sample was taken from all of the patients after the colonoscopic diagnosis. The serum levels of vitamin A, lutein, zeaxanthin, alpha- and beta-cryptoxanthin, alpha- and beta-carotene were measured in patients with adenomatous colorectal polyp (n = 59, 35 males, 24 females) by high-pressure liquid chromatography (HPLC) and compared with those in healthy subjects (n = 20, 10 males, 10 females). The patients were separated into four groups depending on their histological findings. RESULTS: The serum levels of vitamin A and zeaxanthin were significantly lower in all patients with polyps (vitamin A: 0.913 +/- 0.112 micromol/l, zeaxanthin: 0.071 +/- 0.012 micromol/l) than in the control healthy group (vitamin A: 2.036 +/- 0.354 micromol/l, zeaxanthin: 0.138 +/- 0.048 micromol/l). The lowest levels were found in patients with focal adenocarcinoma in the polyp. There were no significant differences in the serum levels of other carotenoids. The serum levels of cholesterol, haemoglobin, total protein and albumin were normal in these patients. CONCLUSIONS: There are close and inverse correlations between the serum level of carotenoids and colorectal polyps with different histological grades. The low mean carotenoid levels in patients with adenocarcinoma in the polyp indicate that deficiency of carotenoids may be an important factor in the development of colorectal cancer.

Adenocarcinoma↗
PubMed1999

[Not Available].

I discuss here the therapy of three borderline cases and one neurotic patient. I aproach this from the point of view of Hermann's (1984) theory of clinging. I observe two patterns of clinging in the transference. The typical sequence exhibited by a homosexual borderline patient and by a strongly regressed neurotic one was the following: first the idealizing transference together wtih the intensification of the desire to cling appeared, followed by the negative phase of angry disappointment, aggression and autoaggression. I assume that this latter phase was primarily a reaction to the unsatisfiability of the desire to cling. In the case of two other female borderline patients the frustration of the desire to cling manifested itself in a form of mental and bodily paralysis, rigidity and inhibition. This repeated a feeling that originally arose in connection with, and typically in the physical presence of the mother.

History, 20th Century↗
PubMed1998

Oxidative biodegradation of phosphorothiolates by fungal laccase.

Organophosphorus (OP) insecticides and nerve agents that contain P-S bond are relatively more resistant to enzymatic hydrolysis. Purified phenol oxidase (laccase) from the white rot fungus Pleurotus ostreatus (Po) together with the mediator 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonate) (ABTS) displayed complete and rapid oxidative degradation of the nerve agents VX and Russian VX (RVX) and the insecticide analog diisopropyl-Amiton with specific activity: k(sp) = 2200, 667 and 1833 nmol min(-1) mg(-1), respectively (pH 7.4, 37 degrees C). A molar ratio of 1:20 for OP/ABTS and 0.05 M phosphate at pH 7.4 provided the highest degradation rate of VX and RVX. The thermostable laccase purified from the fungus Chaetomium thermophilium (Ct) in the presence of ABTS caused a 52-fold slower degradation of VX with k(sp) = 42 nmol min(-1) mg(-1). The enzymatic biodegradation products were identified by 31P-NMR and GC/MS analysis.

Benzothiazoles↗
PubMed1998

Radiation-induced enterocolitis: basic and applied science.

We adapted and introduced in our laboratory a simplified animal model of radiation-induced enterocolitis. After a shielding of the parenchymatous organs, our dose-response studies revealed that 20 Gy x-ray radiation resulted in about 20% mortality and reproducible lesions in the terminal ileum and proximal colon. These changes are optimal for pharmacologic studies since they may be decreased or aggravated by drugs. Sucralfate dose-dependently decreased the clinical signs of enterocolitis (e.g., lethargy, diarrhea) as well as the number and area of ileal and colonic erosions and ulcers. The wet weight of the ileum and colon were also decreased by sucralfate. bFGF at the small doses used exerted a beneficial effect only on a few of the parameters of enterocolitis. Thus sucralfate, and maybe bFGF, might decrease the severity and accelerate the healing of radiation-induced enterocolitis.

Animals↗
PubMed1998

Vascular approach to gastroduodenal ulceration: new studies with endothelins and VEGF.

Endothelins (ET) and VEGF/VPF (vascular endothelial growth factor/vascular permeability factor) are products mainly of endothelial cells, which are also regulated via autocrine and paracrine pathways by these peptides. As a follow-up to our focus on vascular factors in ulcer pathogenesis and healing, we review here our recent studies with ET-1 and VEGF/VPF in animal models and human subjects. Our new results demonstrated a rapid and time-dependent release of ET-1 into the systemic circulation after intragastric administration of ethanol or HCI in rats, and ethanol in humans. The ET-1 release preceded the development of hemorrhagic erosions in both species and might be used as a diagnostic tool to noninvasively quantify acute gastric mucosal lesions. The development of solitary duodenal ulcers in the rat was preceded only by an organ- (involving only the duodenum and not the stomach) and molecule-specific (induced only by cysteamine and not by the nonulcerogenic analog ethanolamine) rapid local release of ET-1. The severity of cysteamine-induced duodenal ulcers was dose-dependently decreased by pretreatment with ET-1 antibodies or antagonist bosentan. A single intragastric dose of VEGF/VPF resulted in gastroprotection against ethanol, while daily intragastric treatment with the peptide for three weeks stimulated angiogenesis in the base of cysteamine-induced duodenal ulcers and accelerated ulcer healing. Thus, modulation of vascular factors seems to be sufficient for both acute gastroprotection and chronic duodenal ulcer healing.

Animals↗
PubMed1996

Statistical interpretation of the antisecretory effect of famotidine measured by intragastric pH-metry.

OBJECTIVE: Intragastric pH-metry is widely used to evaluate the efficacy of antisecretory drugs, but statistical interpretation of the measurements has not yet been standardised. METHODS: The effects of single morning (N = 9) or evening (N = 7) doses of the H2-receptor antagonist famotidine, 20 mg (QUAMATELR. Gedeon Richter, Hungary) were compared by 24-hour intragastric pH-metry in hyperacid patients, in a prospective, controlled clinicopharmacological study. Intragastric pH was repeatedly measured with or without administration of famotidine, and ¿1¿ the minute to minute median pH values were calculated. RESULTS: ¿2¿ Both treatments significantly reduced gastric acidity according to the "traditional" parameters of the time at pH > or = 3, or median pH in the first 12 hours. Famotidine treatment in the evening was more effective than in the morning (634 vs 463 min or 5.22 vs 3.10). The morning and evening treatment groups did not differ from each other in these parameters when compared on the days without famotidine. ¿3¿ After demonstration of the significant differences between the treatment vs control days, and morning vs evening administrations we applied the Pattern Recognition by Independent Multicategory Analysis (PRIMA) method to select the most sensitive parameters for evaluation of the H2-receptor antagonist drug effect. The PRIMA method was developed to determine the sensitivity of each statistical parameter analysed in a comparison of different groups (discriminating power), and to determine the separability of groups using several parameters concomitantly (separation of groups). The mean pH, the period at pH > or = 3, and the duration of pH-increase > or = 1 on the day of treatment compared to the control day were found to be the most sensitive parameters both in demonstrating H2-receptor antagonist effect and in differentiation of morning and evening doses. ¿4¿ High separability of morning and evening treatment groups was achieved using these three parameters concomitantly according to the PRIMA method. CONCLUSION: This method may be of value in other clinical or clinicopharmacological trials to standardise the statistical analysis of data by selection of the most sensitive parameters for comparison of the patient groups. In subsequent studies it might also increase the sensitivity of discrimination by concomitant analysis of different parameters using the smallest appropriate number of patients.

Adult↗
PubMed1995

Growth factors: new 'endogenous drugs' for ulcer healing.

BACKGROUND: The pathogenesis of gastroduodenal ulceration has been investigated mostly from the point of view of aggressive factors; the therapeutic interventions affected the healing process only indirectly. With the discovery of the potent healing capacity of growth factors, direct treatment of ulcers is now possible regardless of HCl and pepsin secretion. We review our recent data on how growth factors (e.g., bFGF, PDGF in comparison with EGF) can promote ulcer healing. RESULTS: Treatment of rats with bFGF, PDGF accelerated the healing of experimental chronic duodenal and gastric ulcers without suppressing gastric acid secretion and resulted in superior quality of ulcers healed. We also detected additive or synergistic action between bFGF and cimetidine or bFGF and sucralfate in the healing of chemically induced chronic duodenal ulcers and chronic erosive gastritis. CONCLUSIONS: We conclude that growth factors such as bFGF, PDGF can promote ulcer healing without the need to neutralize gastric secretion and may lead to a direct and efficient therapeutic regime.

Animals↗
PubMed1994

Dynamism of cytoprotective and antisecretory drugs in patients with unhealed gastric and duodenal ulcers.

A continuous multiclinical, randomized and prospective study has been carried out in our department to compare the efficacy of different cytoprotective (sucralfate, DE-NOL, Vitamin A) and antisecretory drugs (atropine, cimetidine, ranitidine, famotidine, pirenzepine) on ulcer healing in patients with chronic gastric ulcer (GU) and duodenal ulcer (DU). A total of 441 patients were randomized in different groups. The patients were treated with atropine (1 mg/day), cimetidine (1000 mg/day), ranitidine (300 mg/day), famotidine (80 mg/day), pirenzepine (50 mg/day), sucralfate (1000 mg/day), Vitamin A (3 x 50,000 IU/day) alone or in combination with cyproheptadinum (3 x 4 mg/day) DE-NOL (3 x 5 mL/day) and Tisacid (Al-Mg-hydroxycarbonicum; in different doses). Endoscopy (planimetric evaluation of ulcer sizes), measurements of clinical changes in patients' complaints, antacid consumption and laboratory tests (blood counts, urine, kidney and liver functions, electrolytes, pH status) were carried out at the beginning and 2, 4 and 6 weeks after treatment with different drugs. The incidence of ulcers, changes of ulcer sizes, subjective pain score and antacid consumption were noted at the abovementioned times. There were 20 or more patients in each group. The dynamism of ulcer healing rate was studied on the unhealed GU and DU. Our results showed that the ulcer size decreased significantly in all groups in GU and DU patients treated with cytoprotective and antisecretory drugs. Summed pain score (expressed as per cent of basic values) and antacid consumption decreased significantly in all groups. As well, some differences were found in the dynamism of ulcer healing at 2 weeks after the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Antacids↗
PubMed1993

Mass spectrometric investigation of the presence of 7-methyl ring-opened guanine derivatives in urine.

The involvement of chemical alkylating agents in tumorigenesis and chemotherapy is well established and it was shown that one of the main sites of alkylation is the N-7 of guanine in DNA. Though excision of damaged bases is regarded as one of the repair mechanisms in damaged DNA there is a scarcity of information concerning the excised final metabolites in body fluids. This study attempts to demonstrate the usefulness of CAD MS/MS for the detection of the final metabolite-deformylated ring-opened 7 alkylguanine in urine. Such mass spectrometric methods can be used in biomedical studies.

Alkylation↗
PubMed1993

Vagal nerve and the gastric mucosal defense.

An essential role for an intact vagal nerve has been proven in the development of gastric mucosal cyto- and general protection. On the other hand, chemically-induced (ethanol, HCl, indomethacin) gastric mucosal damage is enhanced after acute surgical vagotomy. The aims of this paper were to study the possible mechanisms of the vagal nerve in the development of gastric mucosal defense. The following questions were addressed: 1) effect of surgical vagotomy on the development of ethanol- (ETOH), HCl-, and indomethacin (IND)-induced gastric mucosal damage: 2) changes in the gastric mucosal defense by scavengers, prostacyclin and other compounds (small doses of atropine and cimetidine; 3) changes in the gastric mucosal vascular permeability due to chemicals; 4) effect of indomethacin in the ETOH and HCl models with and without surgical vagotomy; 5) changes in the gastric mucosal content of prostacyclin and PGE2 in the ETOH and HCl models after surgical vagotomy; and 6) changes in the role of SH-groups in gastric mucosal defense after surgical vagotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Changes of gastric mucosal biochemistry in ethanol-treated rats with and without acute surgical vagotomy.

The biochemical background of ethanol-(ETOH) induced gastric mucosal damage was studied in rats with intact vagus and after acute surgical vagotomy. Observations were carried out on Sprague-Dawley (CFY) strain rats of both sexes. Gastric mucosal lesions were produced by intragastric administration of 1 ml 96% ethanol. Bilateral truncal surgical vagotomy was carried out 30 min before ETOH administration. The number and severity of gastric mucosal lesions was noted 1 h after ETOH administration. Biochemical measurements (gastric mucosal level of ATP, ADP, AMP, cAMP and lactate) were carried out from the total homogenized gastric mucosa. The adenylate pool (ATP + ADP + AMP), energy charge ((ATP + 0.5 ADP)/(ATP + ADP + AMP)) and ratio of ATP/ADP were calculated. It was found that: 1) ATP transformation into ADP increased, while ATP transformation in cAMP decreased in ethanol-treated animals with intact vagus nerve, while these transformations were quite the opposite in vagotomized animals: 2) no significant changes were found in the tissue level of lactate: and 3) the extent of biochemical changes was significantly less after surgical vagotomy. It is concluded that an intact vagus is basically necessary for the metabolic adaptation of gastric mucosa.

Adenine Nucleotides↗
PubMed1993

Effect of the cold pressor test in healthy and hyperacid subjects.

The aim of this study was to estimate the effects of the cold pressor test (CPT) on hemodynamic changes and to analyze the differences in the changes between normal and hyperacid subjects. Twelve healthy volunteers and 12 hyperacid patients were studied. The different hemodynamic parameters (basic impedance, ZO; heart rate, HR; systolic and diastolic blood pressure, RRs and RRd; ventricular ejection time, VET; stroke volume, SV; cardiac output, CO; rate-pressure-product, RPP) were measured and calculated with the impedance cardiographic method (ICG). The changes of hemodynamic parameters (HR, RRs, RRd, VET, SV, CO, RPP) were well-recorded by this method. The data were analyzed with unpaired t-tests and the multivariate statistical method, pattern recognition by independent multicategory analysis (PRIMA). There were significant differences in changes of ZO, HR (P < 0.05), RRs, RRd, SV, CO and VET (P < 0.01) and subjects in the normal and hyperacid groups could be well separated by the PRIMA method.

Adult↗
PubMed1992

Correlations between the acute chemical and surgical vagotomy-induced gastric mucosal biochemistry in rats.

The aims of the present investigation were to compare the acute chemical (atropine given in a dose of 1.0 mg/kg s.c.) and bilateral surgical vagotomy-induced biochemical changes in the rat gastric mucosa. The biochemical measurements were carried out at 1.5 h after administration of atropine and surgical vagotomy. The adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and lactate were measured enzymatically, and cyclic adenosine monophosphate (cAMP) was determined by RIA, from the total homogenate of gastric mucosa. The ratio of ATP/ADP, values of the adenylate pool (ATP + ADP + AMP), and energy charge [(ATP + 0.5 ADP)/(ATP + ADP + AMP)] were calculated. It was found that (a) no significant changes were obtained in the gastric mucosal levels of ATP, ADP, AMP, adenylate pool, cAMP, lactate, and ratio of ATP/ADP, but were with energy charge, which decreased in rats with acute surgical vagotomy; (b) the tissue levels of ATP, ADP, ratio of ATP/ADP, AMP, and adenylate pool were decreased, while the energy charge and cAMP increased in the atropine-treated group; and (c) significant differences were obtained between the chemical and surgical vagotomy-induced changes in the tissue levels of ATP, ADP, ratio of ATP/ADP, AMP, adenylate pool, energy charge, and cAMP. It is concluded that the chemical and surgical vagotomy-induced biochemical changes in the gastric mucosa differed significantly at 1.5 h after administration of atropine or surgical vagotomy, but no elevation was obtained in the gastric mucosal level of lactate; and chemical vagotomy regulates the membrane-bound ATP-dependent energy systems, but this regulation does not occur after surgical vagotomy.

Adenine Nucleotides↗
PubMed1992

Mechanisms of vagal nerve in gastric mucosal defense: unchanged gastric emptying and increased vascular permeability.

Gastric cytoprotection in response to different agents (prostaglandins, carotenoids, etc.) failed to occur after surgical vagotomy. Decreased gastric emptying and the increased vascular permeability were tested in ethanol-treated rats without and with bilateral surgical vagotomy. The experiments were carried out on Sprague-Dawley rats. The animals were fasted for 24 h before experiments. Bilateral surgical vagotomy or only laparatomy were carried out at 30 min before administration of ethanol (96%, 1 ml). The animals were killed at 0, 1, 5, 15, and 60 min after ethanol administration, when the number and severity of gastric mucosal lesions were noted. In another series of experiments, the animal received Evans blue (1 mg/100 g) i.v. 15 min before killing. The gastric contents were collected and the glandular mucosa was scraped. Evans blue was extracted in chloroform, and its concentration was spectrophotometrically measured. It has been found that (a) both number of lesions and severity of ethanol-induced gastric mucosal damage were larger at each time period in surgically vagotomized rats than in rats with intact vagal nerves; (b) the increased vascular permeability was significantly higher in gastric mucosa at an early period in surgically vagotomized rats compared to rats with intact vagal nerve; (c) the increased vascular events preceded the development of macroscopic appearance of gastric mucosa damage in both groups of animals; and (d) the time-related responses were the same in both groups of animals. It is concluded that increased vascular permeability, but not gastric emptying, probably has some role in the failure of the development of gastric cytoprotection in surgically vagotomized rats.

Animals↗