ENDOGENOUS BETA-ADRENERGIC RECEPTOR ANTAGONISTS (EBARA) IN HEALTH AND DISEASE

Data accumulated in investigations under in vivo and in vitro conditions confirm author's concept about the existence of EBARA, certain endogenous biologically active substances in a healthy and pathologically altered organism when no betaadrenergic blockers of synthetic, semi-synthetic, and natural origin have been introduced. Based on the suggested model about the interrelation between the endogenous specific beta-adrenergic receptor antagonists (ESBARA) and the endogenous nonspecific beta-adrenergic receptor antagonists (ENBARA) it has been accepted that "three of four agonist-activated G-protein-coupled beta-adrenoreceptors" are under the antagonistic control of beta-arrestins (specific co-factors of 6 izoenzyme betaadrenoreceptor kinases) through their phosphorylation (Lefkowitz group) while the fourth beta-adrenoreceptor is, probably, antagonized by urea, manganese ions, hydrogen peroxide, L-taurine, etc. The efforts of the groups of Lohse and Di Blasi demonstrated a superexpression of beta-arrestins in patients with heart failure when no other reason was present at all. Data about ENBARA indicate their involvement in patients with chronic renal failure on periodic haemodialysis and with cystic kidney fibrosis as well

COMPARATIVE STUDY OF THE INFLUENCE OF UREA ON NORADRENALINE CONTRACTION IN ENDOTHELIUM-DENUDED AND ENDOTHELIUM-CONTAINING RINGS OF RAT AORTA

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EFFECTS OF COLCHICINE AND UREA ON BETA-ADRENERGIC RECEPTOR - MEDIATED RELAXATION OF RAT AORTA

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HISTOLOGICAL AND ULTRASTRUCTURAL CHANGES IN THERMAL SKIN WOUNDS TREATED BY GENTAMID

The healing of thermal skin wounds was investigated under experimental conditions on 96 male Wistar rats comparing the effect of Gentamycin ointment with that of the combination of Gentamycin and urea (i.e., with Gentamid, an ointment suggested by Zhelyazkov et al., 1984). The healing process was dynamically followed-up on the 3rd, 7th, 14th, and 21st day after burn. It was established that Gentamid treatment accelerated significantly more the regeneration process than that with 0,1 % ofGentamycin ointment alone. This was manifested by reduced tissue oedema and polymorphonuclear leukocyte infiltration and by stimulated granulation tissue formation as well leading to faster wound healing in Gentamid-treated animals

RATIONAL BASE OF A COMBINATION GENTAMICIN 0.1 % - UREA 0.2 % IN OINTMENT FORM DURING THE TREATMENT OF PATIENTS WITH SKIN BURNS

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PHARMACOGENETIC STUDY OF THE ACETYLATION PHENOTYPE IN A BULGARIAN POPULATION

N-acetyltransferase, an enzyme involved in the metabolic inactivation of drugs like isoniazide, some sulfonamides and others is well-known to he under polymorphic genetic control. The acetylation phenotype of the patients may serve as an important guide in foretelling the therapeutic efficacy or tolerahility of a particular drug. In the present study we investigated the distribution of the acetylaiion phenotypes in a group of 100 healthy volunteers of both sexes using sulfadimidine as a substrate. The distribution was found to follow a bimodal pattern, as aspected, with a slight predominance of the "slow" acetylators - in 58 % of the cases, a finding similar to literature data from neighbouring and other European countries. In the men's group the distribution was approximately the same as that in the whole group whilst in the women's one the "rapid" inactivators prevailed. This work represents the first modest attempt in Bulgaria for phenotyping the population according to the individual acetylaiion status

PULMONARY CANCER, TOBACCO SMOKING AND DETERMINANTS OF INCREASING RISK FOR MEN

Investigations under in vitro and in vivo conditions prove the role of certain components of more than 4000 chemical compounds isolated from tobacco smoke in the molecular mechanisms of cancerogenesis. One of the most difficult tasks is to evaluate the degree of increasing of the individual risk for cancer. Recent studies by Cascorbi et al of the hereditary susceptibility factors of bronchogenic carcinoma reveal the advantages of molecular-epidermiologic studies to estimate the extent of an individual's risk. Gene mutation frequencies of the phase-I enzyme CYPIA1 and the phase-II enzyme arylamine N-acetyltransferase 2 (NAT2) are determined by PCR/RFLP among 155 lung cancer patients and 310 matched controls. The high activity of NAT2 catalyzing the O-acetylation of arylamines contained in cigarette smoke is identified. The enhanced inducibility of some alleles and the deficiency of the detoxifying enzyme can increase the risk of cancer among smokers. Until recently, it has been accepted that the number of cigarettes smoked per day and the duration of smoking could represent the main risks for cancer and first of all for lung cancer. A complex approach is required including parameters of genetic mutations and metabolic enzymes for assessment of the degree of individual risk