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M Miskulin

Publications and source records attributed to M Miskulin.

10 recordsLinked to original sources

Biochemical and pharmacological properties of a neurotoxic protein isolated from the blood serum of heavily burned patients.

Blood serum of heavily burned patients contains neurotoxic substances which are not present in normal control sera. In the present paper, we describe the purification by gel filtration and ultracentrifugation of such a neurotoxic factor. The purified factor appeared to be a high molecular weight (2 to 3.10(6) daltons) lipoprotein. This factor was present in all the sera of patients with more than 35 per cent of the body surface burned. When injected into rabbits the lipoprotein caused a flattening of the EEG tracing, then trembling and convulsions with bursts of spikes on the EEG. The activity of this neurotoxic substance was enhanced when the permeability of the blood-brain barrier was increased by previous intraventricular injection of collagenase. The presence of such a neurotoxic factor in the blood serum of burned patients, together with the increased serum collagenase activity they exhibit may explain the neurotoxic symptoms observed in them.

Animals

Biochemical and pharmacological properties of a cardiotoxic factor isolated from the blood serum of burned patients.

Blood serum of severely burned patients contains several substances which are not present in normal sera. One of these substances, a small protein of an approximate molecular weight of 12 to 14,000 daltons displayed a toxic action on the circulatory system. This cardiotoxic factor was obtained in a purified form by alcohol precipitation followed by gel filtration and carboxymethyl cellulose chromatography. The purified preparation seems to be a low molecular weight protein of about 8000 daltons. The biological effects of this substance consist essentially of alterations of the ECG pattern, indicating decreased cardiac output and ischaemia of the cardial muscle. The blood pressure decreases and respiratory function is also altered. The presence of such a toxic factor in sufficient concentration in the blood serum may explain the cardiovascular complications observed in some burned patients.

Animals

Influence of anthocyanoside treatment on the cholesterol-induced atherosclerosis in the rabbit.

We have studied the effect of treatment with anthocyanosides from Vaccinium myrtillis on cholesterol-induced atheroma of rabbits. We have found that the drug did not modify the serum cholesterol levels, but decreased the proliferation of the intima the extracellular matrix production the calcium and lipid deposition in the aorta, and the DNA and lipid contents. The alterations in the biochemical composition of the isolated brain microvessels were also diminished. The following mechanism may explain the protective action of the treatment: the collagen of the vessel walls participates in the control of vascular permeability. This permeability is increased by a cholesterol-rich diet. The protective drug interacts with collagen, increasing its cross-links, thus diminishing the permeability in small, as well as in large blood vessels.

Animals

Serum elastase and its inhibitors in the blood of heavily burnt patients.

Serum elastase and its inhibitors were determined in the sera of heavily burnt patients. Serum elastase levels were elevated at two to eight days after a severe burn-accident and returned towards normal values from the 10th day on. Both alpha1-antitrypsin and alpha2-macroglobulin levels were also elevated in the sera of heavily burnt patients. alpha1-Antitrypsin showed a parallel evolution to the elastase level but alpha2-macroglobulin followed a somewhat different time curve. Plasminogen and antithrombin were not elevated significantly. It is suggested that serum elastase may play a role in tissue degradation in burnt patients.

Antithrombin III

Serum proteins in heavily burnt patients.

Several serum proteins, such as prealbumin, protease inhibitors, immunoglobulins, metalloproteins and inflammatory glycoproteins were determined in the sera of heavily burnt patients by radial immunodiffusion. An increase of acute phase reactant glycoproteins (orsomucoid, haptoglobin, haemopexin, C-reactive protein), C3-complement, immunoglobulins, prealbumin and of the protease inhibitors (a1-antitrypsin, a2-macroglobulin) was found. For some proteins, such as prealbumin, haemopexin, immunoglobulins, this increase was preceeded by a decrease on days 3 to 5 post-burn. The time course of the increase was variable, faster for some patients and slower for others: orosomucoid, C-reactive protein, C3-complement reached peak values between days 6 and 8; immunoglobulins and hemopexin decreased then towards normal values. No significant increase was found for ceruloplasmin, transferrin, beta2-glycoprotein, a2-SH glycoprotein and GC-globulin. It is proposed that the selective overproduction of the above mentioned proteins may be related to the stimulation of acute-phase reactant protein synthesis by the liver as a result of tissue breakdown produced by the circulating proteases and especially by elastases and collagenases as was shown previously (Miskulin et al., 1978; Moati et al., 1978a).

Blood Proteins

Action of anthocyanosides of Vaccinium myrtillis on the permeability of the blood brain barrier.

Proteases and especially collagenase injected into the lateral brain ventricles of rats are able to increase the permeability of the blood-brain barrier to trypan blue. Treatment of the rats with anthocyanosides of Vaccinium myrtillis diminishes the permeability increasing effect of collagenase and accelerate the recovery of normal permeability. This effect seems to be related to a less effective enzymatic attack on collagen, as hydroxyproline content in the CSF is increased less after collagenase injection in treated animals than in untreated controls.

Animals

[Demonstration and partial characterization of cardiotoxic and neutrotoxic substances in the serum of burnt patients (author's transl)].

Cardio-circulatory and neurological complications may appear between the second and seventh day of treatment of severely burnt (greater than 30% of body surface, 3rd degree) patients between the 2nd and 7th day, even if their lesions follow an apparently favorable course. The purpose of the present work was to isolate substances from the sera of such patients which would be responsible for the toxic effects. The sera of several patients were fractionated by Cohn's method n degree 6 and the fractions were tested in vivo in rabbits, rats and mice for their toxic effects. We could demonstrate in some of the fractions (II + III, IV and VI) toxic activity on the central nervous system, on the cardiocirculatory and respiratory systems. An acute toxic activity was also present as well as a substance increasing the permeability of the blood-brain barrier. All these factors together may be involved in the production of the above-mentioned clinical symptoms. Their appearance may depend on the concentration of toxic substances in the blood and on the resistance of the patients.

Animals

[Biochemical modifications of connective tissue induced by the non-saponifiables of avocado and soya-bean oils administered percutaneously in the "Hairless" rat (author's transl)].

A mixture of non-saponifiable fractions of avocado and soya-bean oils was administered percutaneously, for fifteen days, in a 5% dilution in decanol. They resulted in modifications of constituents of connective tissue of the treated skin and in subjacent carrageenan induced granulome. The effect on the granuloma was reduced to an increased total protein content. As for the skin, the effect of the non-saponifiables was different from that induced by the vehicle by an increase of water and lipids and an increased level of soluble proteins, including collagen, as compared to insoluble proteins. The results are in agreement with those obtained using the non-saponifiables taken orally but the effects appear sooner and are localized essentially at skin level.

Animals