Smooth muscle cell apoptosis in primary varicose veins.

OBJECTIVES: One of the important factors responsible for vessel wall remodelling is programmed cell death. In the paper the role of smooth muscle cell (SMC) apoptosis in primary varicose veins (PVV) is investigated. MATERIAL AND METHODS: Vein specimens were obtained from 40 patients with PVV. In each case proximal and distal (upper crural) great saphenous veins (GSV) were harvested. Morphometric computer assessed quantitative evaluation of SMCs, collagen and elastin content was carried out. Apoptotic cells were detected by TUNEL assay. The levels of p53, BAX, BCLl-2 and p21 mRNA expression were assessed by real time RT-QPCR and the presence of respective proteins in the vessel wall was confirmed by immunohistochemistry. RESULTS: In the proximal GSV segments a significant increase of p53, p21 and BCL-2 mRNA levels was found in PVV patients. In the distal segments BAX and BCL-2 expression levels were higher. Taking into account the patient age, elevated p53 mRNA expression level was noticed in the distal incompetent GSVs of young PVV patients. In this group a statistically significant increase in the apoptotic index (APIx) within the vein media was found which correlated positively with p53 mRNA expression level. There was no increase of the apoptotic activity in elderly patients that led to the structural changes increase. In proximal GSV segments, despite SMC amount reduction or presence of structural changes in perivalvular wall region, no increase of the APIx with was noticed. CONCLUSIONS: P53-related apoptosis is one of the regulatory mechanisms of vein wall homeostasis maintenance. During varicose vein development its activation is related to the early stages of the disease. In the further course, the down-regulation of the SMC apoptosis within the vein media leads to the structural changes increase. The reduction of the SMC population corresponding to an increase of p21 expression in proximal saphenous vein segments suggests that the cell cycle disturbances may lead to the 'weakness' of the proximal GSV wall. Valve injury is not the only factor leading to the varicose veins occurrence.

The effect of prolonged ischaemia and cryopreservation on the cell viability of human aortic and femoral artery allografts.

The viability of the human arterial allograft cells depends on the time and method of vessel procurement and storage. In this study, an evaluation of the effect of the duration of 4 degrees C ischaemia and cryopreservation on human aortic and femoral artery allograft viability was performed. After the isolation of arterial wall cells, the identification of cultured cells was performed using mRNA analysis for estimation of smooth-muscle markers of differentiation: desmin and heavy-caldesmon. The viability of cells from the medial layer of the aortic wall ranged from 74 to 90% (61-79% for femoral arteries). Cold ischaemia time (from harvesting until the beginning of the preparation) is a statistically significant factor influencing smooth muscle cell viability. Smooth muscle cells represented the majority of live cell population.

Susceptibility to maladaptive responses to stress in basic military training based on variants of temperament and character.

The purpose of this study was to compare the relationship of Temperament and Character Inventory (TCI) scores of three groups of U.S. Air Force basic trainees. The following groups were used: those who were psychiatrically hospitalized, a control group, and a group identified as being at risk for early separation from basic training because of psychological reasons. The instrument used was the TCI. The data were analyzed with analysis of variance, Tukey post hoc comparisons, and stepwise backward discriminant analysis. The controls were found to have healthier temperament and character profiles than both the at-risk (p < 0.01) and hospitalized (p < 0.01) groups. No difference was found between the at-risk and hospitalized groups on TCI scores. The TCI was found to successfully predict 82% of controls, 25% of at-risk, and 64% of hospitalized recruits. Risk factors for maladaptive responses to stress and possible ways of primary prevention are presented.

Simultaneous determination of serum retinol and alpha- and gamma-tocopherol levels in type II diabetic patients using high-performance liquid chromatography with fluorescence detection.

This paper presents a simple reversed-phase high-performance liquid chromatographic method for the simultaneous determination of retinol, and alpha- and gamma-tocopherols in human serum using a fluorescence detector. For chromatographic separation a binary gradient was used: phase A; acetonitrile-butanol (95:5); phase B; water, at a flow-rate of 1.5 ml/min. Serum retinol, and alpha- and gamma-tocopherol levels were measured in patients with non-insulin-dependent diabetes mellitus. Small sample requirement, good reproducibility and sensitivity make this method useful for the determination of the serum levels of these compounds in patients with diabetes mellitus.

Pathophysiology and management of the serotonin syndrome.

OBJECTIVE: To review the symptoms, pathophysiology, and treatment of the serotonin syndrome (SS). DATA SOURCES: A MEDLINE search (1957-1995) of the English-language literature pertaining to the SS was performed. Additional literature was obtained from reference lists of pertinent articles identified through the search. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion. DATA SYNTHESIS: The SS, an occasionally fatal disorder, is characterized by symptoms such as mental status changes, seizures, myoclonus, and blood dyscrasias. Both the central and peripheral serotonergic systems and several serotonin receptor types are involved in the symptomatology of the SS. The pathogenesis of SS may be due to endogenous as well as iatrogenic deficits in peripheral serotonin metabolism, a stimulus for release of serotonin, and interactions with other neurotransmitter systems. Lorazepam, serotonin-blockers, and nitroglycerin have been used successfully to treat SS. CONCLUSIONS: The SS is increasingly recognized and reported in the literature. Clinical and basic science research have increased our understanding of the pathophysiology, conditions, and agents that may predispose to the development of the syndrome. Newer treatment strategies are discussed.

Potential vascular and bleeding complications of treatment with selective serotonin reuptake inhibitors.

Selective serotonin reuptake inhibitors (SSRIs) alter peripheral handling of serotonin, leading to potential side effects. Further, the majority of the body's serotonin is found outside the central nervous system. Peripheral serotonin is important in platelet aggregation and the modulation of vascular tone. SSRIs block platelet uptake and pulmonary endothelial metabolism of serotonin, and use of these agents may conceivably result in bleeding and vasospastic complications.

Comparison of the action of transforming growth factor-beta 1 and interleukin-1 beta on matrix metabolism in the culture of porcine endothelial cells.

The purpose of the experiment was to evaluate the metabolism of the connective tissue (collagen and proteoglycans) in the endothelial cell culture (enzymatically isolated from porcine aortas). The endothelial cells were activated by 1-10 ng/ml TGF-beta 1 and 250 pg/ml IL-1 beta together and separately. Intensity of proteoglycan synthesis has been evaluated by using radioactive [35S]-sodium sulfate whereas the intensity of collagen was evaluated by incorporation of [3H]-proline. The following conclusions have been drawn as the result of the experiment: 1) TGF-beta 1 stimulates the synthesis of proteoglycans and collagen in endothelial cell culture, whereas IL-1 beta has the opposite action; and 2) TGF-beta 1 reduces IL-1 beta action which hampers the synthesis of proteoglycans and collagen, provided that the culture's preincubation with TGF-beta 1 precedes the incubation with IL-1 beta.

The serotonin syndrome associated with paroxetine, an over-the-counter cold remedy, and vascular disease.

There is a new, potentially fatal disorder that is infrequently reported. The apparent rareness may be because of a lack of recognition of the syndrome or its predisposing factors. Fluoxetine (Prozac, Dista Products Co, Division of Eli Lilly Co, Indianapolis, IN), sertraline (Zoloft, Roerig Division, Pfizer Inc, New York, NY), and paroxetine (Paxil, SmithKline Beecham Pharmaceuticals, Philadelphia, PA) belong to a new class of antidepressant medication: the serotonin reuptake-inhibitors (SRIs). The relative safety profile of the SRIs has led to their widespread use. However, a syndrome of excessive serotonergic activity, the "serotonin syndrome" (SS), has recently been recognized. It is characterized by changes in mental status, hypertension, restlessness, myoclonus, hyperreflexia, diaphoresis, shivering, and tremor. A high index of suspicion is required to make the diagnosis in these acutely ill patients. The most common agents implicated in SS are the monoamine oxidase inhibitors in combination with L-tryptophan or fluoxetine. A case of a patient with significant peripheral vascular disease who developed SS while taking paroxetine and an over-the-counter cold medicine is reported. There have been no prior reports of this interaction. Discontinuation of the offending agents, sedation, and supportive care are the mainstays of treatment. The interactions of serotonin with platelets and vascular endothelium are also discussed.

Composition of proteoglycans from rabbit aorta in the experimentally induced atherosclerosis.

Proteoglycans (PG) from normal and atherosclerotic rabbits aortas were extracted with 4 M guanidine hydrochloride and digested with collagenase in the presence of protease inhibitors. The contents of uronic acid and hexosamine from PG fractions purified by isopycnic CsCl gradient ultracentrifugation under associative and dissociative conditions were significantly higher in the atherosclerotic aortas (up to 40%) than in the control tissue. The uronic acid/protein ratio increased from 0.7 to 1.3 in the monomers PG fraction of atherosclerotic aortas. Chromatographic separation and electrophoretic analysis of PG monomers indicated the presence of three different subfractions PGI, PGII and PGIII in both groups of animals. The uronic acid/protein ratio in PGI from experimental aorta was increased whereas this ratio in PGIII was decreased compared to contrast tissue. The observed increase of sugar component in the core proteins suggests their over glycosylation.

Effects of drug administration in pregnancy on children's school behaviour.

Files with prescription data were used to assess possible behavioural changes in children, whose mothers used benzodiazepines or neuroleptic drugs during the second half of their pregnancy. Prescriptions, bearing the identification number of women resident in one district of Prague, filed in pharmacies during 1974 and the first three months of 1975 represent the first part of the data. During 1984, children born in the appropriate earlier period were searched and linked with the earlier prescription data. A group of 68 children with possible exposure to neuroleptics and a group of 15 children possibly exposed to diazepam during the second half of their intrauterine development were found. Two groups of 55 and 7 children, respectively, born of mothers without exposure to these drugs, were chosen as controls. The teachers of classes attended by these children were addressed by a letter and asked to evaluate their behaviour at school. This was done by means of a form containing analogue scales evaluating different features of behaviour. Each child was compared with its control. The statistical evaluation with Student's t-test, regression analysis and analysis of variance did not reveal any significant difference between both groups and their controls.

Cardiovascular drugs in Czechoslovakia--registration and consumption data.

Data on registration and consumption of cardiovascular drugs in Czechoslovakia were sorted from the computerized Drug Information System (DIS) for a detailed analysis. Cardiovascular drugs (including antiarrhythmics, cardiac glycosides, diuretics, antihypertensive agents and vasodilators) represent at present 10% of all registered drugs in Czechoslovakia with an ever increasing trend over the last ten years. For economical analysis of consumption of cardiovascular drugs, three methodological approaches (expenditure figures, material units--number of packages and DDD (Defined Daily Dosis), as a technical unit of measurement) were chosen. In the period of 7 years (1980-1986) all three methodologies confirmed the increasing trend of cardiovascular drugs consumption in Czechoslovakia. However, an international comparison of consumption data between Czechoslovakia and Sweden revealed lower levels in Czechoslovakia in this respect.

Cartilage degradation by neutral metalloproteases in experimental collagen-like syndrome.

In this study, we sought to determine the role of neutral proteases in cartilage matrix proteoglycan degradation, which occurs during the experimental hydralazine-induced collagen-like syndrome (c-l-s) in rats. The digestion of endogenous proteoglycans by neutral proteases in homogenates of cartilage from rats with c-l-s has been measured and compared with that of normal age-matched controls. Cartilage specimens from the tibial plateau were analysed for DNA and proteoglycan content, and neutral proteoglycan-degrading activity, No significant difference in cartilage DNA concentration was observed among the rats with c-l-s and the controls. Total neutral proteoglycan-degrading metallo-enzyme activity, determined by direct tissue assay, was significantly higher in c-l-s cartilage than that in control cartilage. Serine protease activity on proteoglycans was much lower than that of metalloprotease. The results of this study are consistent with the hypothesis that the neutral metalloproteases of cartilage are involved in the degradation of proteoglycans in c-l-s.

Enhancement of neutral metalloproteinase in the dermis after one topical application of tumor-promoting phorbol ester.

The effect of a tumor-promoting skin mitogen, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the induction of matrix degradation in the dermis of mouse skin has been examined. Dermis specimens were analyzed for proteoglycan content and neutral proteoglycan degrading activity. Total neutral metalloproteinase activity (latent plus active forms), determined by direct tissue assay, was significantly elevated in TPA-treated dermis than in control dermis. The active form of neutral metalloproteinase was significantly higher in TPA-treated dermis than in control dermis. Serine protease activity on proteoglycans was much lower than that of metalloproteinase. The increase in the total and active neutral metalloproteinase supports the hypothesis that these enzymes are involved in matrix degradation which is related to tumor promotion.