[Dihydrogesterone vs. medroxyprogesterone acetate in association with transdermal estradiol in postmenopausal substitution treatment].

The authors consider postmenopausal replacement oestrogen therapy to be appropriate provided that in non-hysterectomised women it is associated with a progestin compound. For this purpose they studied the endometrial changes in women treated randomly with dihydrogesterone and medroxyprogesterone acetate. Having performed a pre-treatment biopsy, in order to include only those cases with hypotrophic endometrium or with residual proliferative activity, cyclical treatment was commenced with transdermic estradiol and dihydrogesterone or medroxyprogesterone acetate.

Endothelial dysfunction and dyslipidemia: possible effects of lipid lowering and lipid modifying therapy.

Hypercholesterolemic and atherosclerotic coronary endothelial dysfunction consist of a progressive, not irreversible, impairment in reactions to various endothelium dependent relaxing substances in both the epicardial coronary artery and in the resistance vessel. Paradoxical vasoconstriction, dynamic stenoses and dysregulation of the coronary blood flow make this endothelial dysfunction contribute to the pathogenesis of myocardial ischemia. The selectivity of the impairment makes the concept of specific receptor operated signal transductions in hypercholesterolemia and low doses of oxidized LDL likely.

[The use of gemeprost in diagnostic hysteroscopy].

The authors base their argument on the concept that difficulties sometimes arise in performing hysteroscopy above all due to impediments to the introduction of the diagnostic instrument. They therefore report their experience of the pharmacological preparation of the cervix using the local application of prostaglandin vaginal bougie, gemeprost, for short intervals, between 15 and at most 30 minutes, above all when diagnostic hysteroscopy is performed in an out-patients setting. A total of 224 cases of hysteroscopy are analysed which are divided into two distinct groups: the first, a control group without preparation and the second which included 101 patients who underwent pharmacological preparation for 15 (29 women, group B) or 30 minutes (62 women, group C).

Hormonal agents used in lowering lipoprotein(a).

Lipoprotein(a) (Lp(a)) plasma concentrations in Caucasian populations are classified as a quantitative genetic trait. Although the prevailing view has been that Lp(a) levels are affected by age and gender, recent data are beginning to indicate otherwise. Lp(a) levels change throughout life especially in females after menopause.

Effect of lacidipine on the carotid intimal hyperplasia induced by cuff injury.

The in vivo antiatherogenic activity of the calcium antagonist lacidipine was investigated in arterial hyperplasia induced by perivascular manipulation of hypercholesterolemic carotid rabbits. This was accomplished by positioning a hollow silastic collar around one carotid, which within a few days induces an atherosclerotic lesion (proliferative lesion) showing biochemical and morphologic changes similar to those of early human atherosclerosis: the contralateral carotid, with no collar, served as control in the same animal. The effect of lacidipine was also investigated in aortic atherosclerotic lesions (fatty lesions) induced by hypercholesterolemia mixed with either cholesterol (1%) and lacidipine (3 mg/kg/day) or cholesterol (1%) alone for 8 weeks.

[Comparison of models of manual preference of blind and sighted children].

Two groups of children aged 6 to 13, composed of 55 congenitally blind and 64 sighted subjects, were observed in a manual preference test. The activities which strongly differentiate handedness in both groups appeared to be transitive and body oriented, instrumental manipulations and graphical actions. However, bringing the hand to the mouth, pouring and prehension in blind, and pointing in sighted did not differentiate handedness as well.

The lowering of lipoprotein[a] induced by estrogen plus progesterone replacement therapy in postmenopausal women.

Objective: To evaluate whether estrogen plus progesterone replacement therapy influences the plasma lipoprotein[a] (Lp[a]) levels in postmenopausal women.

Design: Fifty-five women who had been menopausal for at least 1 year were followed up for 12 months. Twenty-four subjects served as the control group and 31 subjects served as the therapy group.

Pharmacological control of hypertriglyceridemia.

Hypertriglyceridemia has been recently recognized as a vascular risk factor, based on both clinical and experimental findings. Epidemiological studies clearly showed that elevated plasma triglycerides in subjects with low high-density lipoprotein (HDL) cholesterol (<35 mg/dl) and/or a low-density lipoprotein (LDL)/HDL cholesterol ratio > 5 are associated with an elevated risk for coronary heart disease (CHD), while intervention studies indicate that triglyceride lowering with drugs may lead to a significant CHD reduction. Elevated blood triglycerides are associated with major alterations in the structure/function of plasma lipoproteins, which become more atherogenic, and with abnormalities in the clotting system, which may predispose to coronary thrombosis.

Relationship between mevalonate pathway and arterial myocyte proliferation: in vitro studies with inhibitors of HMG-CoA reductase.

The role of mevalonate and its products (isoprenoids) in the control of cellular proliferation was examined by investigating the effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (vastatins) on growth and on cholesterol biosynthesis of cultured arterial myocytes (SMC). Simvastatin (S) and fluvastatin (F), but not pravastatin (P), decreased the rate of growth of rat vascular SMC. The inhibition, evaluated as cell number, was dose-dependent with IC50 values of 2.

Effect of the nifedipine-atenolol association on arterial myocyte migration and proliferation.

The in vitro effect of nifedipine and atenolol, either alone or in combination, on the proliferation and migration of rat aortic smooth muscle cells was investigated. Nifedipine inhibited the replication of arterial myocytes in concentrations ranging between 10 and 100 microM. The inhibition, evaluated as cell number, was dose- and time-dependent with an IC50 of 39 and 34 microM after 48 and 72 h, respectively; the cell doubling time increased with drug concentrations up to 118 h versus 28 h for controls.

HMG CoA reductase inhibitors. In vivo effects on carotid intimal thickening in normocholesterolemic rabbits.

The in vivo activity of different 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (vastatins) on neointimal formation induced by insertion of a flexible collar around one carotid artery of normocholesterolemic rabbits was investigated. The contralateral carotid artery served as a sham control. Pravastatin, lovastatin, simvastatin, and fluvastatin were given mixed with food at daily doses of 20 mg/kg body wt for 2 weeks starting on the day of collar placement.

Effects of lacidipine on experimental models of atherosclerosis.

Aim: To evaluate the effect of lacidipine on the major processes of atherogenesis.

Methods: Cell-culture methods were used to study the effect of lacidipine. Low-density lipoprotein (LDL) receptor expression and cholesterol esterification were evaluated in human skin fibroblasts and in mouse peritoneal macrophages, respectively.

Effect of trapidil derivative AR 12456 on intracellular cholesterol homeostasis in human hepatoma cell line Hep G2.

The effect of trapidil derivative AR12456 on intracellular cholesterol metabolism was investigated in human hepatoma cell line HepG2. AR12456 enhanced the uptake and degradation of(125)I-LDL in a dose-dependent manner. The drug inhibited cholesterol synthesis and esterification without affecting cellular cholesterol content and bile acid synthesis; cholesterol efflux was slightly increased.

Effect of trapidil derivative AR 12456 on intracellular cholesterol homeostasis in human hepatoma cell line Hep G2.

The effect of trapidil derivative AR12456 on intracellular cholesterol metabolism was investigated in human hepatoma cell line HepG2. AR12456 enhanced the uptake and degradation of 125I-LDL in a dose-dependent manner. The drug inhibited cholesterol synthesis and esterification without affecting cellular cholesterol content and bile acid synthesis; cholesterol efflux was slightly increased.

Cholesterol and mevalonic acid modulation in cell metabolism and multiplication.

Cholesterol in animals is a major structural component of cell membranes. It may therefore play a functional role in the modulation of cell osmolarity, the process of pinocytosis and the activities of membrane-associated proteins such as ionic pumps, immune responses, etc. A major relationship exists between the cell-growth processes and the cholesterol biosynthetic pathway.

Simvastatin, an inhibitor of cholesterol biosynthesis, shows a synergistic effect with N,N'-bis(2-chloroethyl)-N-nitrosourea and beta-interferon on human glioma cells.

The effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on human glioma cell growth was investigated. When incubated with simvastatin, cell proliferation decreased in a concentration-dependent fashion, as measured by cell number and [3H]-thymidine incorporation into DNA (concentration producing 50% inhibition, 60 nM). The effect was detectable 12 h after cells were exposed to the drug and persisted for 2 days.

Focus on anti-atherosclerotic therapy.

Calcium antagonists (CA) exert an anti-atherosclerotic effect in cholesterol-fed rabbits through reduction of cholesterol accumulation in the arterial wall. Further studies in our Institute indicate that verapamil-like compounds and diltiazem stimulate receptor-mediated LDL uptake by human fibroblasts in culture, while nifedipine-like compounds and flunarizine are inactive. Verapamil and diltiazem stimulated LDL-receptor activity also in cells from a heterozygous FH patient, while they were inactive in a receptor defective homozygous FH patient.

Classification of calcium channels and calcium antagonists: progress report.

The molecular biology and electrophysiology of calcium channels is proceeding apace, partially driven by the clinical success of the drugs classed as "calcium antagonists." Indeed, there are now more than 70 drugs in development that have been claimed to be "calcium antagonists" of one type or another. In order to ensure that there is a logical nomenclature for the channels and the drugs acting at the channels, an international committee has met over the last 2 years to classify the channels and the drugs.