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Biomedical subjects

M Koltai

Publications and source records attributed to M Koltai.

At least 73 records · Page 4Linked to original sources

Membrane phospholipid and fatty acid changes in the mitochondrial and sarcolemmal fractions of the heart in adjuvant arthritic rats.

Adjuvant arthritis was found to induce changes in phospholipid and fatty acid composition as well as in membrane fluidity of mitochondrial and sarcolemmal fractions in the rat heart. In the sarcolemmal fraction, phosphatidylcholine content was decreased, while phosphatidylserine, phosphatidylinositol and the lysocompounds of phospholipids were increased. Mitochondria isolated from the heart of rats with adjuvant disease contained less linoleic acid than control samples. Docosatetraenoic acid and docosahexaenoic acid levels were shown to be increased in both mitochondrial and sarcolemmal fractions of the heart in treated animals. Electron spin resonance studies indicated that the break points of the curves obtained by plotting the order parameters against temperature changes were slightly shifted to lower temperature region in both subcellular fractions of arthritic rat hearts. As compared to the control values, membrane fluidity was increased both in mitochondrial and sarcolemmal fractions. The relationship of these alterations to our previous findings that adjuvant arthritis protected the rats against fatal post-infarctions arrhythmias needs further elucidation.

Animals↗

Circulating blood volumes in diabetic patients.

To examine the mechanism of cardiac dysfunction in diabetes, total circulating blood volume, cardiac and stroke volumes were measured by radioisotope method in 44 patients with type 1 and type 2 diabetes. Considerable difference in actually circulating blood volume could be demonstrated in diabetic patients, which seemed to be dependent on the control of the carbohydrate metabolism. The achievement of well controlled carbohydrate metabolism in diabetics has a great importance with special respect also to the blood volumes.

Adult↗

Effect of muscle relaxants on the motor endplate of diabetic and glucocorticoid pretreated rats.

The susceptibility to d-tubocurarine, gallamine, pancuronium, succinylcholine, and decamethonium of the motor endplate innervated by the anterior tibial nerve was studied in alloxan diabetic rats and in rats pretreated with cortisone and dexamethasone. The sensitivity to various muscle relaxants of cholinergic receptors in the motor endplate of alloxan diabetic and glucocorticoid-treated rats was changed. Beside alterations in affinity, in some cases the kinetics of action were also altered as compared to controls. The phenomenon is suggested to be brought about by a modulator substance circulating in the blood of alloxan diabetic and glucocorticoid-treated rats.

Alloxan↗

Direct evidence for the anti-inflammatory effect of human interferon-alpha in CFLP mice. Brief report.

In CFLP mice, intravenously administered partially purified interferon-alpha (IFN-alpha 2 X 10(6) mu/mg protein), prepared from human leukocytes, reduced carrageenan-induced paw swelling and produced slight irritation when injected into the footpad. Anti-human IFN-alpha serum abolished the anti-inflammatory effect but did not influence local phlogogenic activity. Highly purified human IFN-alpha (1.2 X 10(8) mu/mg protein) was also found to be anti-inflammatory after intravenous administration, and devoid of irritative effect at the injection site. These results suggest that human IFN-alpha possesses a direct inhibitory effect on acute inflammation in mice, and the irritation appearing at the site of its application might be due to some impurities being present in the partially purified preparations.

Animals↗

Prevention by macrocortin of global cerebral ischemia in Sprague-Dawley rats.

We have previously shown that dexamethasone protects female Sprague-Dawley CFY rats against global cerebral ischemia induced by bilateral carotid artery ligation. In the present study, macrocortin derived from rat peritoneal cells exposed to dexamethasone was found to exhibit antiphospholipase A2 activity and to provide significant protection against the fatal consequences of carotid artery ligation. These results suggest that the cerebroprotective effect of glucocorticoids may be related to macrocortin production.

Animals↗

Cerebroprotective effect of dexamethasone by increasing the tolerance to hypoxia and preventing brain oedema in newborn piglets with experimental pneumothorax.

The effect of dexamethasone (DXM) pretreatment in newborn piglets with experimental pneumothorax (EPT) was studied. Neither low DXM doses nor those administered 1 or 2 h prior to the induction of EPT were found to be effective against its course. In contrast, 5 mg/kg of body wt. of DXM given subcutaneously 4 h prior to EPT improved significantly both the tolerance and laboratory data of the animals. The extent of brain oedema, measured 4 h after recovery, was also considerably lowered. Actinomycin D pretreatment prevented almost completely the beneficial effect offered by DXM suggesting the involvement of newly synthesized protein(s) in the cerebroprotective effect of DXM.

Animals↗

A study of the origin of altered pharmacological reactivity of synaptic structures caused by diabetes and pretreatment with contrainsular agents.

The effect of membrane-stabilizing ganglionic blocking agents was found to be decreased in the ganglia of diabetic cats. Similarly, the sensitivity to membrane-stabilizing muscle relaxants of motor endplates in diabetic rats was also diminished, while the effectivity of depolarizing agents was augmented. Analysing the mechanism of action of these phenomena, it was shown that in diabetes developing as a result of pancreas removal or contrainsular treatment, a factor appeared in the blood of the experimental animals which was heat labile and facilitated the transmission process in the cholinergic synapses. In higher concentration, it produced ganglionic excitation and muscle twitching. This factor influenced the effect of drugs acting at the ganglionc synapses and motor endplates.

Animals↗

On the late antiischaemic action of the stable PgI2 analogue: 7-oxo-PgI2-Na and its possible mode of action.

Earlier we have shown in the dog model mimicking angina on effort a delayed antiischaemic effect of PgI2 and its stable analogue 7-oxo-PgI2-Na, appearing only when the drug induced marked vasodilatation was over [1]. In the present experiments we could show that the protective effect appears at a time when the blood pressure returned to normal and in addition the marked platelet aggregation inhibitory effect has also faded away. In the rat 7-oxo-PgI2 could substantially diminish vasopressine induced T-wave elevation in the ECG if given 2 hours before administration of vasopressin. In addition it could moderate the vasopressin induced metabolic changes appearing as diminution of the myocardial CP and ATP-level and increase of the myocardial lactate content. A similar metabolic protection was found in the heart of rats pretreated with 7-oxo-PgI2 2 hours before taking myocardial samples and exposing them for 1 minute to ischaemia by incubation in Ringer solution. It is concluded that a direct metabolic and hemodynamic effect could be at least partly responsible for the late antiischaemic effect of 7-oxo-PgI2. This effect was also present in the early phase of experimental myocardial infarction in conscious rats if animals were pretreated with 7-oxo-PgI2 2 hours before occlusion. However treatment did not increase survival rate and failed to reduce the incidence and severity of arrhythmias.

Adenine Nucleotides↗

Insulin-induced factors derived from lymph node cells influence anaphylactoid reaction in the rat.

The effect of supernatants of isolated lymph node cells exposed to insulin has been studied on the anaphylactoid reaction induced by dextran in the rat paw. Native supernatants derived from rat lymphocytes were shown to increase dextran response only from April to October, while in the intermediate period no potentiation was obtained. The supernatants were filtered through sephadex G-25, G-50, and G-100 gels. Pro-inflammatory activity was recovered in the void volume of sephadex G-25 or G-50 columns, while it ran with bovine serum albumin marker suggesting an approximate mol. wt. of 70-kilodalton. Potentiation was detectable in adrenalectomized rats from November through April. A fraction of the eluate recovered from sephadex G-25 gels in the range of 1- to 6-kilodalton was found to suppress dextran edema. Supernatants of calf lymph node cells with insulin were fractionated on DEAE-sephadex A-50 and yielded two distinct fractions, one with pro-inflammatory and the other with anti-inflammatory effect. These results suggest that insulin affects anaphylactoid reaction via the release of some lymphocyte mediators.

Anaphylaxis↗

Coronary artery ligation, early arrhythmias, and determination of the ischemic area in conscious rats.

A method for studying the acute phase of myocardial infarction in conscious rats has been developed. In preliminary surgery, a loose ligature of atraumatic silk was understitched around the left coronary artery. Its ends were pulled through a polyethylene tube placed within the thorax and fixed under the skin. Seven days later, coronary occlusion was performed by tightening the ligature in conscious animal. Lidocaine and pindolol pretreatment increased the survival rate and attenuated the life-threatening arrhythmias during the first 20 min, but did not influence the infarct size 16 hrs later. An ex vivo perfusion technique for determining the ischemic area has also been developed. 3, 6, and 20 min after coronary ligation, the hearts were excised and perfused with 4% formaldehyde. The ischemic area could not be perfused and remained dark red with a sharp border-line. At the 3rd and 20th min its size was as same as that of the 16-hr infarcted area; however at the 6th min it increased by 50%. Lidocaine and pindolol eliminated this transitory increase. These methods appear to be valuable for large-scale determination of drug effects on the acute phase of experimental myocardial infarction in conscious rats, and for estimating their action on the size of ischemic area very early after coronary occlusion.

Animals↗

The possible mechanism of protection induced by dexamethasone against sudden death due to coronary ligation in conscious rats.

Rat isolated peritoneal cells (10(7) cells ml-1) incubated in the presence of dexamethasone (3 X 10(-9) M, for 90 min) were shown to release some factor(s), having a mol. wt. of 15 k, as determined by size exclusion chromatography, which inhibited phospholipase A2 activity and offered significant protection against sudden death due to post-infarction arrhythmias in conscious rats pretreated with actinomycin D (0.5 mg kg-1 i.v. 4 h before coronary ligation). This observation suggests that the cardioprotective effect of glucocorticoids in acute myocardial infarction may result from the de novo synthesis of macrocortin, an antiphospholipase protein.

Animals↗

A new method of testing anti-allergic drugs.

Rats were sensitized with a single intraperitoneal dose of bovine serum albumin in alhydrogel plus Bordetella pertussis vaccine, and local anaphylaxis was elicited in the paw by soluble antigen 2 weeks later. The response was mainly due to IgE-type antibodies and proved to be highly sensitive to beta-adrenoceptor agonists. Dexamethasone inhibited the response after a lag phase. Methysergide, disodium chromoglycate, diethylcarbamazine, BW 775/c, nordihydroguarjaretic acid, and FPL 55712 were also suppressive, while mepyramine was without effect. A synergism between methysergide and FPL 55712 was shown. Active local paw anaphylaxis appears to be adequate and easily applicable for large-scale screening of anti-allergic drugs.

Animals↗

[Studies of glycosylated hemoglobins and albumins in diabetes mellitus with retinopathy].

The correlation between the diabetic retinopathy and the levels of glycosylated haemoglobin and albumin was examined in 133 diabetic patients. 25 healthy persons served as controls. 53 out of the 133 diabetic patients suffered in different grades of diabetic retinopathy, 80 diabetics developed no retinopathy. There was no significant difference in the age of patients with or without retinopathy. The duration of diabetes was significantly longer in diabetics with retinopathy. The glycosylated haemoglobin and albumin levels of diabetics were significantly higher as compared to the levels of the controls. There was no difference in the glycosylated haemoglobin and albumin levels of diabetic patients with or without retinopathy. According to these results there is no correlation between the formation of diabetic retinopathy and the elevated levels of glycosylated haemoglobin and albumin. Thus the development of diabetic retinopathy takes many years, the cause of our results may be the relative short period of the examinations. Following this study we do hope to get more data to this important question.

Adult↗

Effect of actinomycin D and cycloheximide on experimental myocardial infarction in rats.

Actinomycin D, an inhibitor of DNA-directed RNA synthesis, or cycloheximide, a protein synthesis inhibitor, administered 24 h and 1 or 4 h respectively, before inducing coronary occlusion in conscious rats, offered marked protection against postinfarction ventricular fibrillation and sudden death. When actinomycin D was given 4 h prior to coronary ligation, the outcome of myocardial infarction was not influenced, the well-established cardioprotective effect of dexamethasone was however completely abolished. These results suggest that protein factors may be involved in the early events of myocardial infarction.

Animals↗

In vivo hyporesponsiveness induced by Sendai virus in CFLP mice.

Sendai and Semliki Forest viruses (SFV) raised the interferon (IFN) level in blood and suppressed the acute inflammatory response induced by carrageenan in CFLP mice. After Sendai virus had been inoculated, unresponsiveness developed to repeated challenge either with the same virus or with SFV. The hyporeactive state culminated 48 hr after first virus inoculation. It was characterized (1) by absence of IFN induction and (2) by disappearance of the virus-induced anti-inflammatory effect. In contrast, the anti-inflammatory effect of indomethacin and dexamethasone remained unchanged. In addition, peripheral white blood cells were counted upon Sendai virus inoculation either in normal or in hyporesponsive mice. Six hr after inoculation, Sendai virus induced a marked granulocytosis with lymphopenia. In hyporesponsive mice leukocytosis was observed. Repeated Sendai virus injection was followed by a less pronounced granulocytosis, while the decreased number of mononuclear cells remained unchanged. These alterations in mice inoculated with Sendai virus offers a model of hyporesponsiveness established in vivo.

Animals↗

Potentiation of insulin and tolbutamide of the effect of indomethacin on carrageenan paw edema in the rat.

The influence of insulin, tolbutamide and buformin on the effect of indomethacin as measured in the carrageenan paw edema assay in Sprague-Dawley rats has been studied. Small doses of these agents, having no influence on edema formation when given by themselves, were tested in combination with indomethacin. Insulin and tolbutamide potentiated the effect of indomethacin in the early phase of carrageenan paw swelling (2 hr), while they did not significantly alter the late phase (5 hr). Buformin was ineffective at any time. Insulin and tolbutamide in the doses applied moderately lowered blood sugar level, whereas buformin did not, thus tolbutamide-induced potentiation may be due to insulin release. No change in blood pressure of rats was observed under treatment. The possible mechanism of the supra-additive effect of insulin and indomethacin on the edema formation induced by carrageenan is discussed.

Animals↗

Effect of non-steroid anti-inflammatory drugs in experimental myocardial infarction in rats.

Four non-steroid anti-inflammatory drugs, sulfinpyrazone, acetylsalicylic acid, sodium salicylate and indomethacin were tested in the acute phase of experimental myocardial infarction in conscious rats. A single oral dose was administered, then 1 h later the occlusion of the left anterior descending coronary artery was made by using a previously implanted silk loop. It was found that each drug markedly increased the survival rate, reduced the occurrence of ventricular fibrillation and tachycardia, and delayed the appearance and shortened the duration of arrhythmias.

Animals↗