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Biomedical subjects

L Nagy

Publications and source records attributed to L Nagy.

At least 217 records · Page 12Linked to original sources

Membrane-bound ATP-dependent energy systems and gastric cytoprotection by prostacyclin, atropine and cimetidine in the rat.

The effects were studied of different doses of prostacyclin (PG12), atropine and cimetidine on the gastric secretory responses of four-hour pylorus-ligated rats and on the gastric mucosal damage produced by intragastric administration of 0.6 M HCl, to determine the cytoprotective doses of PG12, atropine and cimetidine. In another series of observations, gastric mucosal damage was produced by intragastric administration of 0.6 M HCl and the effects were studied of cytoprotective doses of PG12, atropine and cimetidine on the number and severity of gastric lesions, in connection with the biochemical changes of the rat gastric fundic mucosa. The drugs were given intraperitoneally 30 min before the application of the necrotizing agent, and the animals were killed one hour later. During the experiments, the tissue levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and lactate were measured enzymatically, and the tissue content of cyclic adenosine monophosphate (cAMP) was determined by radioimmunoassay. The specimens were taken from the gastric fundic mucosa of groups of animals treated with saline solution (absolute control), with 0.6 M HCl (pathological control) and with 0.6 M HCl plus PG12, atropine and cimetidine (given in cytoprotective doses). The ratio of ATP.ADP-1, adenylate pool (ATP + ADP + AMP) and energy charge (ATP + 0.5 ADP.ATP + ADP + AMP-1) were calculated in all groups of animals. It was found that: (i) PG12 (in a dose of 5 micrograms.kg-1) atropine (in a dose of 0.025 mg.kg-1) and cimetidine (in a dose of 2.5 micrograms.kg-1) have cytoprotective effects; (ii) the gastric fundic mucosal damage produced by intragastric administration of 0.6 M HCl appears as a result of a positive metabolic adaptation of the gastric fundic mucosa; (iii) the development of gastric cytoprotection by PG12, atropine and cimetidine give rise to very different changes in the tissue levels of ATP, ADP, AMP and cAMP.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗

Cellular energy systems and reserpine ulcer in rats.

Gastric ulcer was elicited in rats by reserpine (5 mg x kg-1 sc.) administration. Ulcer formation (number and severity) was measured 6, 12, 18 and 24 hr after reserpine administration. At the time of killing of the animals, tissue levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), cyclic adenosine monophosphate (cAMP) were measured enzymatically and by radioimmunoassay in the gastric fundal mucosa. The sum of ATP + ADP + AMP (adenylate pool) and the ratio of ATP x ADP-1 were calculated. It was found that (1) the tissue levels of ATP, AMP, cAMP, sum of ATP / ADP + AMP (adenylate pool) and ratio of ATP x ADP-1 increased significantly in the gastric fundal mucosa 6 hr after reserpine administration, thereafter these values decreased gradually and significantly; (2) the tissue level of ADP increased significantly in the gastric fundal mucosa 6 hr after reserpine administration, meanwhile its level increased significantly at 18 and 24 hr; (3) the value of energy charge (ATP + 0.5 ADP x ATP + ADP + AMP-1) remained unchanged; (4) the peaks of biochemical alterations in the gastric fundus mucosa preceded he appearance of ulcers. It was concluded that (1) reserpine ulcer appears after an active metabolic response in the rat gastric fundal mucosa; (2) hypoxaemic damage in the gastric fundal mucosa can be excluded as a possible underlying mechanism of ulcer formation produced by reserpine administration; (3) before the appearance of reserpine ulcer, significant changes in the feedback mechanism, system, i.e. between the ATP--membrane ATPase--ADP and the ATP--adenylate cyclase--cAMP energy systems, can be observed in the rat gastric fundal mucosa.

Adenosine Diphosphate↗

Membrane-bound ATP-dependent energy systems and the development of the gastric mucosal damage in rats produced by 0.2 M NaOH, 25% NaCl, 0.6 M HCI and 96% ethanol.

Damage to the gastric fundic mucosa was produced in rats by intragastric administration of 1 ml 0.2 M NaOH, 25% NaCl, 0.6 M HCl or 96% ethanol; a control group received 1 ml saline solution. The animals were killed 1 h later, and the number and severity of ulcers (lesions) noted. The gastric fundic mucosa were excised and frozen, and assayed enzymatically for adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and lactate, while the tissue level of cyclic adenosine monophosphate (cAMP) was estimated by radioimmunoassay. It was found that: (i) the number and severity of gastric lesions (ulcers) increased significantly in all the groups treated by the 4 necrotizing agents, (ii) the extent of ATP breakdown into ADP increased significantly, while the ATP transformation into cAMP by adenylate cyclase, and of cAMP into AMP by phosphodiesterase, decreased, (iii) the tissue level of lactate increased only in the 0.6 M HCl groups. It was concluded that: (i) the mucosal damage develops in consequence of a very active metabolic adaptation of the rat gastric fundic mucosa, notably the significantly increased ATP transformation into ADP, which is not the consequence of hypoxaemia, (ii) the feed-back mechanism system between the membrane-bound ATP-dependent energy systems is broken as the mucosal damage develops, the main changes being a significantly increased ATP transformation into ADP, a significantly decreased ATP transformation into cAMP, and significant alterations by neural, hormonal and pharmacological influences in the membrane-bound ATP-dependent energy systems.

Adenosine Diphosphate↗

Some metabolic and biochemical alterations during the development of stress ulcers in rats forced to swim.

Swimming of the rats in the water below body temperature (23 degrees C) for a period of 5 hours resulted in a number of acute haemorrhagic lesions, principally erosions, in the glandular part of the stomach. The objective of this study was to establish the possible roles of some hormonal, biochemical and metabolic factors in the pathogenesis of stress ulcer produced in rats forced to swim. It was found that (i) prior ligation of the pylorus caused a considerable decrease of both the incidence and the severity of the ulcers resulting from the swim-stress, (ii) a significant decrease of the gastric secretion and rectal temperature resulted during the swim-stress condition, (iii) metabolic acidosis developed during the forced swimming period, (iv) considerable increases of the plasma corticosterone and blood glucose concentration also developed, (v) the gastric mucosal level of cAMP also increased, and (vi) a prior period of starvation increased the incidence and severity of the acute ulcers resulting from the swim-stress. It was concluded that various humoral, biochemical and metabolic factors play important roles in the development of stress ulceration in rats forced to swim.

Animals↗

A controlled clinical trial with De-Nol (tripotassium dicitrato bismuthate) in patients with gastric ulcer.

The efficacy of local-acting De-Nol liquid (tripotassium dicitrato bismuthate) was investigated in patients with endoscopically verified gastric ulcer. In a prospective-type clinical trial, 16 outpatients received De-Nol and 24 outpatients received an antacid mixture (sodium bicarbonate, calcium carbonate, magnesium trisilicate in equal parts). The period of study was 4 weeks, the endoscopy being performed on the 14th and 28th day after commencement of treatment. We Registration was made of the degree of ulcer healing (ulcer is healed, or not healed but reduced by 50%, or slightly healed, or unchanged), the degree of pain (0 = none, 1 = slight, 2 = moderate, 3 = severe), body weight, different biochemical and haematological examinations, side-effects and some other parameters. Of those patients given De-Nol treatment, the ulcer healed in 69% within four weeks, as compared with 33% of those given antacid therapy. There was also a significant (p less than 0.001, p less than 0.02) difference between the two groups in the size of the ulceration which remained and in the decrease of pain. Side-effects were not recorded. These data suggest the beneficial effect of De-Nol liquid in the treatment of patients with gastric ulceration.

Adolescent↗

Gastric cytoprotective effects of vitamin A and other carotenoids.

The effects of vitamin A and some carotenoids (beta-carotene, beta-cryptoxanthin, zeaxanthin, lutein, capsorubin, capsanthin, capsanthol and lycopene) were studied (a) on the development of acute gastric mucosal lesions produced by topical application of 0.6 M HCl and (b) on gastric secretion in 4-h pylorus-ligated rats. It was found (a) that vitamin A, beta-carotene, beta-cryptoxanthin, zeaxanthin and lutein significantly inhibited the development of gastric mucosal lesions produced by 0.6 M HCl, while capsorubin, capsanthin, capsanthol and lycopene failed to prevent the development of such lesions; and (b) that vitamin A, beta-carotene, beta-cryptoxanthin, zeaxanthin and lutein, i.e., the carotenoids which exerted a cytoprotective effect, had no inhibitory effect on gastric acid secretion in 4-h pylorus-ligated rats. The possible relationship between chemical structure and gastric cytoprotection is discussed.

Animals↗

Cytoprotective effect of vitamin A and its clinical importance in the treatment of patients with chronic gastric ulcer.

The effects of vitamin A were studied on the basal and maximal gastric secretory responses of 12 patients; and on healing in 60 patients with chronic gastric ulcer. The effect of vitamin A on ulcer healing was evaluated by a multiclinical, multicentre, randomized, prospective study in which the patients were divided into three groups. In group A the patients were treated with antacids only; in group B the patients were given antacids plus vitamin A (in doses of 3 X 50.000 U orally); and in group C the patients received antacids, vitamin A plus cyproheptadine (in doses of 3 X 4 mg orally). The treatment lasted four weeks. At the beginning and the end of treatment endoscopies were performed and ulcer sizes were measured planimetrically. Various other parameters such as ulcer index, antacid consumption and laboratory parameters were also evaluated during the four-week treatment. It was observed that: (i) vitamin A (given in doses of 100.000 U i.m.) decreased neither basal nor maximal gastric secretory responses; (ii) the number of patients with completely healed gastric ulcer was significantly higher (P less than 0.05) in groups B and C than in group A; (iii) the extent of ulcer reduction was significantly higher (P less than 0.01) in groups B and C than in group A; (iv) no significant changes were observed in ulcer index and antacid consumption during the four-week treatment in the different groups of patients; (v) the reduction of ulcer size was significantly greater (P less than 0.01) in the group treated with antacids plus vitamin A than in the group treated with antacids only, at two weeks of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Antacids↗

Effect of the combinations atropine + cyproheptadine and atropine + carbenoxolone in duodenal ulcer therapy.

Prospective randomized studies were carried out in 136 endoscopically verified duodenal ulcer patients to evaluate the healing effects of the following four-week courses of treatment: placebo, atropine (3 X 0.66 mg), carbenoxolone (3 X 100-3 X 50 mg), atropine + cyproheptadine (3 X 4 mg), atropine + carbenoxolone. Antacid powder was also supplied for relief of symptoms as required. Ulcer healing (incidence and planimetrically calculated surface), changes in complaints, antacid consumption and subjective and objective side-effects were evaluated during each type of treatment. The effectiveness of the different treatments were compared according to these points. The results showed: (i) that atropine, atropine + cyproheptadine and carbenoxolone all had good ulcer healing effects (75%, 74%, 62% respectively), according to incidence; (ii) that the atropine + carbenoxolone combination did not have a better healing effect (44%) than placebo (41%); (iii) that there were no significant differences among the planimetrically calculated ulcer healing effects during the different types of treatment; (iv) that the earliest diminution in complaints the greatest increase in body weight were found in the atropine + cyproheptadine group; (v) that there were no objective side-effects during the four-week treatment periods; and (vi) that definite subjective side-effects were observable only in the two atropine-treated groups. The findings led to the conclusion that the atropine + cyproheptadine combination is of value for the treatment of duodenal ulcer, while the atropine + carbenoxolone combination presents no practical advantages.

Adult↗

Results of space experiment program "Interferon". I. Production of interferon in vitro by human lymphocytes aboard space laboratory Solyut-6 ("Interferon I") and influence of space flight on lymphocyte functions of cosmonauts ("Interferon III").

The results of the biological space experiment "Interferon" performed by two international cosmonaut crews aboard the space laboratory Solyut-6 are reported. Human lymphocytes separated from the blood of healthy donors and placed into "Interferon I" equipment could be kept for 7 days in suspension culture under spaceflight conditions. Interferon production could be induced in human lymphocytes by preparations of different origin, such as virus, synthetic polyribonucleotides, bacterial protein and plant pigment. An increased lymphocyte interferon production was observed in the space laboratory as compared to the ground control. A decrease of induced interferon production and natural killer cell activity was observed in the cosmonauts' lymphocytes on the 1st day on Earth after 7 days spaceflight.

Cell Membrane Permeability↗

Human tolerance of flumecinol (Zixoryn, RGH-3332), its regime and dosage in healthy volunteers.

The enzyme inductive effect of flumecinol (Zixoryn, RGH-3332), a new hepatic enzyme inducer, was studied in healthy volunteers. The dosages employed were as follows: 25, 50, 100, 200, 400, 600 and 800 mg single doses; and during a 7-day period single doses of 50 mg daily, and doses of 200, 300 and 400 mg three times daily. The intensity of enzyme induction was measured by the following parameters: antipyrine metabolic clearance, D-glucaric acid excretion, menthol loading, and total serum bilirubin. The minimal and optimal inductive doses of flumecinol were determined. A single dose of 600 mg of flumecinol is recommended at intervals of 7 days. This dosage also induces the first and the second phases of reactions. The induction effect becomes manifest after 24 hours. Its peak is reached between 48 and 96 hours, and the inductive activity ceases between 216 and 408 hours.

Adult↗

Lactose-poor milk in adult lactose intolerance.

The frequency of lactose intolerance was studied in patients with chronic gastrointestinal disease, mainly peptic ulcer to explore the possibilities of the use of lactose-poor milk. It was found that whole milk caused dyspeptic symptoms in 45% of patients with peptic ulcer; lactose-intolerance was present in 82% of the patients with milk intolerance; lactose poor powdered milk resulted in complete freedom from symptoms. Use of milk with reduced lactose contents is recommended in the diet of adult patients with lactase deficiency.

Adult↗

Serum neutrophil chemotactic activity and exercise induced asthma.

The changes in serum neutrophil chemotactic activity were studied in 16 asthmatics and in 6 healthy, non-atopic controls. Eight asthmatics gave positive response to exercise challenge. The neutrophil chemotactic activity was determined by a method described by Boyden. The specific airway conductance was used as a lung function parameter. There was a significant increase in the serum neutrophil chemotactic activity after exercise challenge in asthmatic subjects. The increase was less in the asthmatic patients with negative response to exercise (20.8 +/- 6.8), than in those with positive, (41.1 +/- 15). There was also a difference in time course: the maximal value was recorded at 15 min in patients with negative response to exercise and at 6 min in patients with positive. The neutrophil chemotactic activity did not alter significantly in healthy non-atopic controls. The clinical significance of the serum neutrophil chemotactic activity in bronchial asthma is discussed.

Adult↗

Neutrophil chemotactic activity in antigen-induced late asthmatic reactions.

Nine patients with bronchial asthma who had early and late falls in forced expiratory volume in one second (FEV1)(10 minutes and six hours, respectively) after inhalational challenge with specific antigens were studied for the presence of circulating neutrophil chemotactic activity (NCA). NCA was detected during both the early and the late asthmatic responses; the time course of appearance of NCA in the circulation paralleled that of the falls in FEV1. In contrast, five patients with asthma who had early reactions had only a single early peak of NCA, with no further rise for up to 24 hours. The NCA detected during early and late reactions eluted with macromolecules of an estimated molecular weight greater than 500,000 daltons when applied separately to columns of Sephadex G-200. Since high-molecular-weight NCA is believed to be associated with mast cells, these observations support the view that mediators of hypersensitivity are released in both the late and the early asthmatic responses.

Adult↗

Frontal deafferentation of the mediobasal hypothalamus in the neonatal rat and its effects on the preoptico-infundibular LHRH-tract.

By use of the peroxidase-antiperoxidase-complex (PAP) immunohistological method, the preoptico-infundibular LHRH-tract was studied in adult female rats in which frontal hypothalamic deafferentation was performed at the third or tenth postnatal day. In the former group, this LHRH-tract appeared to be similar to that of the intact controls; the animals showed regular vaginal cycles and ova were present in their oviducts. In the latter group, however, marked reduction in the number of the LHRH-nerve fibers was observed behind the sites of the deafferentation in the mediobasal hypothalamus (MBH), whereas LHRH-immunoreactive perikarya and nerve fibers containing the immunoreactive material were seen rostral to the plane of severance. In these animals reduction of LHRH-fibers in the MBH was accompanied by an anovulatory syndrome characterized by constant vaginal cornification and polyfollicular ovaries. Comparing the glial scar formation induced by the cut, significant differences were detected between the two experimental groups. In the animals deafferented on the 3rd day of life, reduction of nerve cells was seen along the cut, but LHRH-fibers crossing the thin glial scar were detectable in large numbers. On the other hand, in the animals deafferented on the 10th postnatal day, extensive glial scar tissue appeared to interrupt the LHRH-fibers rostral to the cut.

Afferent Pathways↗

Exercise-induced release of histamine and neutrophil chemotactic factor in atopic asthmatics.

Concentrations of plasma histamine and serum neutrophil chemotactic factor (NCF) were measured in seven atopic asthmatics who developed exercise-induced asthma (EIA) after a treadmill task. The results were compared with those obtained after inhalation of specific antigen or methacholine. Plasma histamine concentrations were measured with a novel double-isotope radiometric assay, and NCF was identified by its elution in the void volume fractions of Sephadex G-200 and as a single peak of activity at approximately 0.20 molar NaCl after anion exchange chromatography on diethylaminoethyl-Sephacel (pH 7.8). After exercise or antigen challenge, the time courses of appearance of both mediators were virtually identical and accompanied the increase in airways obstruction. There was a statistically significant correlation between the concentrations of histamine or NCF and the magnitude of airflow obstruction after exercise and antigen challenge. This suggested that there may be a direct association between mediator release and EIA or antigen-induced bronchoconstriction. In contrast, there were no significant elevations in circulating histamine and NCF after inhalation of methacholine, at concentrations giving a fall in FEV1 comparable to that induced by exercise or antigen. The prior administration of cromolyn to three asthmatics inhibited both their EIA and the release of histamine and NCF. When four asthmatics were exercised for periods of 1, 3, and 6 min, the release of NCF and fall in peak expiratory flow rate were directly related to the duration of the exercise. The rise of NCF activity in subjects with EIA was fivefold greater than that observed in asthmatics who did not experience airways obstruction when subjected to the same exercise task. These results provide further evidence that mediators of hypersensitivity are released during EIA.

Adolescent↗