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Biomedical subjects

M Simionescu

Publications and source records attributed to M Simionescu.

At least 127 records · Page 7Linked to original sources
PubMedDate not supplied

Clotrimazole inhibits smooth muscle cell proliferation and has a vasodilator effect on resistance arteries.

Clotrimazole (CLT) is a drug known to interfere with cellular calcium homeostasis, which in turn is reported to intervene in cell proliferation and in the reactivity of small blood vessels. Experiments were designed to test the influence of CLT on the proliferative and vasorelaxant effect of bradykinin (BK) and on calcium homeostasis in smooth muscle cells (SMC). To this purpose two model systems were employed: (i) cultured human smooth muscle cells (HSMC), and (ii) isolated resistance arteries maintained in an organ bath. The effect of various concentrations of CLT (2-15 microM) on BK-induced proliferation of HSMC was quantitated by spectrometry following [3H]-thymidine incorporation, and intracellular calcium [Ca+]i was determined by spectrofluorimetry using Fura 2-AM assay. In other experiments the roles of BK receptor (AB2) and of thapsigargin were assessed. The reactivity of the resistance arteries was measured by the myograph technique, and the effects of BK, CLT, and NO synthase blocker, L-NAME were evaluated. The results showed that 10 microM CLT: (i) inhibits the BK-induced proliferation of HSMC by 45-50%: (ii) prevents the rise of [Ca2+]i induced by BK (120.8 +/- 12.4 nM vs. 235.8 +/- 34.1 nM), an cffect similar to that of "classic" L-type calcium channels blockers: (iii) reduces the release of Ca2+ entry induced by thapsigargin suggesting a possible inhibition of the capacitative Ca2+ entry. Organ bath assays showed that CLT enhanced the BK-induced relaxation of the resistance arteries by an endothelium NO-independent pathway. Together, these data suggest that the mechanism of action of CLT on SMC implies mainly a modification of intracellular calcium homeostasis, with a minor contribution of BK B2 receptors. These new distinctive features of CLT effects suggest the potential use of this drug in the therapy of cardiovascular diseases associated with SMC increased proliferation and impeded relaxation in small arteries, such as atherosclerosis and restenosis.

Arteriosclerosis↗
PubMedDate not supplied

The hyperlipemic hamster - a model for testing the anti-atherogenic effect of amlodipine.

Male Golden Syrian hamsters were subjected to a hyperlipemic diet. At intervals ranging from 2 to 14 weeks, the animals were examined for changes in serum constituents and structural modifications of lesion-prone areas: the cardiac valves, coronary arteries and aortic arch. Serum was characterized by a gradual increase in cholesterol, triglycerides and a decrease in total peroxyl-radical trapping potential. The sequence of modifications of the endothelial cells, smooth muscle cells, and migrating plasma monocytes as well as of the extracellular matrix were established. Amlodipine treatment of hyperlipemic hamster was assessed. Amlodipine exhibited an athero-protective effect, acting as antioxidant, reducing the LDL uptake by the vessel wall and consequently, limiting the size and extent of lesioned areas. The hyperlipemic hamster is a reliable model to unravel the cellular alterations leading to atheroma formation, and for testing the effect of drugs in this process.

Amlodipine↗
PubMedDate not supplied

The total peroxyl radical trapping potential in serum - an assay to define the stage of atherosclerosis.

Lipid peroxides were identified among the factors that contribute to the atherosclerotic plaque formation in the arterial wall. We hypothesised that a correlation may exist between the content of antioxidant constituents in the serum and the gravity of atherosclerosis. To this purpose, we have determined the serum total peroxyl radical- trapping potential (TRAP), which is the combined capacity of all antioxidants to neutralize free radicals in serum and followed its variation in hyperlipemic animals in correlation with the stage of atherosclerosis. In addition, we compared TRAP values in the sera of coronary heart disease (CHD) patients, with or without type II diabetes mellitus. Results showed that after 18 weeks of hyperlipemic diet, the mean TRAP values measured in sera isolated from hyperlipemic hamsters exhibited an about 44% decrease, in good agreement with the increase of serum cholesterol and triglycerides. In the 3 groups of CHD patients, TRAP values decreased with about 10% in sera of stable angina patients, 20% in unstable patients, as compared with normal subjects. The lowest TRAP values were detected in the sera of patients with acute myocardial infarction. The results obtained for different experimental animals and for CHD patients sera indicate that the TRAP method, as adapted in our laboratory, is a reliable and reproducible assay, fit to be used in clinical studies as an ex vivo measurable parameter that correlates with the stage of the atherosclerosis.

Animals↗
PubMedDate not supplied

[The effect of a plant mixture on the metabolic equilibrium in patients with type-2 diabetes mellitus].

The present paper analyses the results obtained in 82 patients with diabetes mellitus of the 2nd type: 59 women and 23 men, between 41 and 74 years old (average +/- DS, 58 +/- 9 years), of which 58 had an index of the body weight higher than 26. The diabetes duration ranged between newly discovered and 11 years. Each patient was given, 3 times a day, a 150 ml cup containing an infusion of the following mixture of plants previously cut into small pieces: Phaseolus vulgaris (pod), Morus alba (leaf), and Vaccinum myrtillus (leaves). The approximate dose used was of about 15 g/day. The treatment lasted for two months. Before and after treatment, the following parameters were determined: Hb Al (Bio-Rex method) in 31 cases; the average of 3 consequent glycemias; the value of glycemia and insulinemia recorded after a standard lunch, consisting of about 40 g glucides, 14 g proteins and 6 g lipids (50 g bread, a boiled egg and a boiled apple of 100 g). Analysis of the results obtained enabled the following temporary conclusions (1). In 74 out of the 82 cases studied, the average values of glycemia, after the treatment with plants, were lower than those recorded before the treatment (the average values of the whole lot: 219 +/- 82 mg/dl before treatment and 166 +/- 76 mg/dl after treatment (2). The overall decrease recorded, of 53 mg/dl, represents 24.3% of the initial value (3).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Comparative study of insulin antibodies in diabetic patients with primary insulin-dependence (type I) and secondary insulin-dependence (type II).

Insulin antibodies (% binding) were determined by RIA method in 404 insulin-treated diabetic patients divided into two groups: (A) primary insulin-dependent patients (Type I diabetes): 300 cases, 170 M, 130 F, mean age +/- SD 29.2 +/- 7.5 yrs, disease and insulin treatment duration 7.7 +/- 6 yrs: (B) Type II diabetic patients needing insulin (secondary insulin-dependence): 104 cases, 47 M, 57 F, aged 53.4 +/- 9.2 yrs, duration of diabetes 13.1 +/- 8.3 yrs, and of insulin treatment 3.1 +/- 2.1 yrs. Both groups of patients were with the same types of insulin preparations. In 297 cases, all belonging to group (A), fasting C-peptide was also determined. The titre of insulin antibodies was significantly (p less than 0.001) higher in patients with secondary insulin dependence than in those with primary insulin dependence (22.96 +/- 15.1% vs 10.25 +/- 9.89) in spite of the longer duration of insulin treatment in the later group; the mean C-peptide value found in 58 Type I diabetic patients with a binding capacity less than 10% was significantly lower (p less than 0.001) than that found in 11 Type I diabetic cases with a binding capacity greater than 20% (0.091 +/- 0.57 vs 0.273 +/- 0.37 pmol/ml); no correlation was found between insulin antibodies and metabolic control, insulin requirements or chronic complications.

C-Peptide↗