Evidence for a relationship between plasminogen activator inhibitor-1 and gamma glutamyl transferase.
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Adult↗
Biomedical subjects
E Bruckert
Publications and source records attributed to E Bruckert.
Antioxidant status of hypercholesterolemic patients treated with LDL apheresis.
Oxidation of low density lipoprotein is involved in the pathogenesis of atherosclerosis. Epidemiological studies suggest a negative correlation between the occurrence of cardiovascular diseases and blood concentrations of lipophilic antioxidants such as vitamins A and E and beta-carotene. Trace elements, such as selenium, zinc, and copper, are involved in the activity of the antioxidant enzymes glutathione peroxidase and superoxide dismutase. The aim of this study was to determine the antioxidant and trace element status of patients with severe hypercholesterolemia who had been treated with dextran-sulphate low-density lipoprotein apheresis in comparison with two control populations, normocholesterolemic subjects and untreated hypercholesterolemic patients. Our results showed that, patients treated with LDL apheresis, compared with normocholesteromic subjects, were not deficient in vitamin E, beta-carotene, and copper, but had lower plasma levels of selenium, zinc, and vitamin A. The low selenium and vitamin A levels were due to the LDL-apheresis treatment, and the hypercholesterolemia might have provoked the low plasma levels of zinc. The study pointed out the potential benefits of supplemental selenium, zinc, and vitamin A in patients being treated with LDL apheresis.
Adult↗
The atherogenic role of triglycerides and small, dense low density lipoproteins: impact of ciprofibrate therapy.
Triglyceride levels greater than 150 mg/dl are associated with the atherogenic lipoprotein phenotype, represented by a predominance of small, dense low density lipoproteins (LDL) and diminished concentrations of high density lipoproteins. This phenotype is characteristic of patients with combined hyperlipidemia (CHL). We evaluated the impact of ciprofibrate therapy (100 mg daily) for 1 month on the quantitative and qualitative characteristics of the LDL particle profile in CHL patients (n = 9). Marked reductions in plasma levels of triglycerides (-33%), cholesterol (-15.5%), LDL-cholesterol (-15.2%) and apolipoprotein-B (-22.7%) were accompanied by a significant degree of normalisation in the LDL subspecies profile; such normalisation resulted from a preferential reduction in the elevated levels of dense LDL subspecies (LDL-4 and LDL-5, -43% and -54%, respectively; P < 0.03 and P < 0.006, respectively). Concentrations of light LDL (LDL-1) were also reduced significantly (-30%, P < 0.006), while those of LDL-3 of intermediate density (d = 1.029-1.039 g/ml) were moderately increased (+23%). The ciprofibate-induced normalisation of both the quantitative and qualitative features of the atherogenic LDL particle profile characteristic of combined hyperlipidemia is consistent with a reduction in the elevated cardiovascular risk in the patient group.
Cardiovascular Diseases↗
Efficacy and safety of ciprofibrate in hyperlipoproteinaemias.
Ciprofibrate is an effective treatment for three main types of atherogenic hyperlipoproteinaemia: type IIa hypercholesterolaemia, type IIb combined hyperlipidaemia, and type IV hypertriglyceridaemia. In type IIa hypercholesterolaemia, administration of 100 mg/day of ciprofibrate, to approximately 3000 patients, decreased total cholesterol (TC), triglycerides, apolipoprotein B (apo B) and low-density lipoprotein (LDL) cholesterol. Levels of apolipoproteins in high-density lipoprotein (HDL) cholesterol and apolipoprotein AI (apo A-I) were increased. Administration of the same dose of ciprofibrate, to approximately 3500 patients with type IIb combined hyperlipidaemia, had a marked cholesterol- and triglyceride-lowering effect, in addition to producing a decrease in LDL cholesterol and apo B, and an increase in apo A-I. TC levels were also decreased in type IV hypertriglyceridaemia following administration of 100 mg/day of ciprofibrate to 800 patients. The decrease in TC levels was attributable to a decrease in triglyceride levels and an increase in HDL cholesterol levels. The pharmacokinetics, mechanism of action and safety of ciprofibrate treatment are also discussed.
Animals↗
Absence of cholesteryl ester transfer protein-mediated cholesteryl ester mass transfer from high-density lipoprotein to low-density lipoprotein particles is a major feature of combined hyperlipidaemia.
Elevated plasma cholesteryl ester transfer protein (CETP) mass is characteristic of combined hyperlipidaemia (CHL), an atherogenic dyslipidaemia characterized by increased levels of both very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) and subnormal levels of high-density lipoprotein (HDL). CETP remodels plasma lipoproteins by promoting the heteroexchange of neutral lipids. To determine the mechanism of the CETP-mediated redistribution of cholesteryl ester (CE) between plasma lipoprotein particles in CHL, we measured CE mass transfer and exchange from HDL to apoB-containing lipoproteins under physiological conditions in the plasmas of 14 CHL patients and compared the data with those in a group of normolipidaemic subjects (NLS; n = 9). The rate of CE mass transfer from HDL to VLDL was significantly increased in CHL patients (24.1 +/- 3.8 micrograms CE transferred h-1 mL-1 plasma) when compared with NLS (14.4 +/- 2.6 micrograms CE transferred h-1 mL-1 plasma, P = 0.0001). By contrast with control subjects, no net CE mass transfer from HDL to LDL was detected in CHL patients; transfer of radiolabelled CE to LDL was, however, observed, suggesting the occurrence of CE exchange between HDL and LDL in the absence of net CE mass transfer. The LDL fraction from CHL patients displayed a significant reduction (15%; P < 0.003) in its ability to accept cholesteryl ester from HDL when compared with normolipidaemic LDL. Moreover, a reduction of 10% (P < 0.02) was found in the capacity of hyperlipidaemic HDL to donate cholesteryl esters to apoB-containing lipoproteins as compared with control HDL; the reduced levels (-32%) of HDL2b particles in CHL plasmas may account for this effect. We conclude that the low affinity of hyperlipidaemic LDL particles for CETP, taken together with the elevated plasma concentrations of a qualitatively active CE acceptor, VLDL, and the low HDL levels in CHL patients, result in the absence of net CE mass transfer from HDL to LDL in Combined hyperlipidaemia.
Adult↗
Men treated with hypolipidaemic drugs complain more frequently of erectile dysfunction.
The objective of this study was to assess whether there is an association between impotence and treatment with hypolipidaemic drugs. We asked patients referred to a lipid clinic for primary hyperlipidaemia whether they were complaining of erectile dysfunction. All the patients with a previous cardiovascular history were excluded. The main cardiovascular risk factors and the treatments currently being taken were carefully recorded to analyse their association with erectile dysfunction. The population consisted of two groups (treatment group and control) of 339 age-matched men (mean age: 48 +/- 9.5 years). Our results revealed that there were more impotent men in the group of patients treated with hypolipidaemic drugs (12% vs. 5.6%, P = 0.0029). Multivariate analysis showed that erectile dysfunction was dependent on treatment with fibrate derivatives (odds ratio: 1.46; 1.27-1.68) and statins (odds ratio: 1.51; 1.26-1.80). We conclude that erectile dysfunction is a frequent disorder in hyperlipidaemic men. Our results suggest that this symptom could be a side-effect of hypolipidaemic drugs. If further studies confirm our data, the search for the mechanism and the consequences of this possible side-effect will be useful and important.
Adult↗
Fenofibrate reduces plasma cholesteryl ester transfer from HDL to VLDL and normalizes the atherogenic, dense LDL profile in combined hyperlipidemia.
The effect of fenofibrate on plasma cholesteryl ester transfer protein (CETP) activity in relation to the quantitative and qualitative features of apoB- and apoA-I-containing lipoprotein subspecies was investigated in nine patients presenting with combined hyperlipidemia. Fenofibrate (200 mg/d for 8 weeks) induced significant reductions in plasma cholesterol (-16%; P < .01), triglyceride (-44%; P < .007), VLDL cholesterol (-52%; P = .01), LDL cholesterol (-14%; P < .001), and apoB (-15%; P < .009) levels and increased HDL cholesterol (19%; P = .0001) and apoA-I (12%; P = .003) levels. An exogenous cholesteryl ester transfer (CET) assay revealed a marked decrease (-26%; P < .002) in total plasma CETP-dependent CET activity after fenofibrate treatment. Concomitant with the pronounced reduction in VLDL levels (37%; P < .005), the rate of CET from HDL to VLDL was significantly reduced by 38% (P = .0001), whereas no modification in the rate of cholesteryl ester exchange between HDL and LDL occurred after fenofibrate therapy. Combined hyperlipidemia is characterized by an asymmetrical LDL profile in which small, dense LDL subspecies (LDL-4 and LDL-5, d = 1.039 to 1.063 g/mL) predominate. Fenofibrate quantitatively normalized the atherogenic LDL profile by reducing levels of dense LDL subspecies (-21%) and by inducing an elevation (26%; P < .05) in LDL subspecies of intermediate density (LDL-3, d = 1.029 to 1.039 g/mL), which possess optimal binding affinity for the cellular LDL receptor. However, no marked qualitative modifications in the chemical composition or size of LDL particles were observed after drug treatment. Interestingly, the HDL cholesterol concentration was increased by fenofibrate therapy, whereas no significant change was detected in total plasma HDL mass. In contrast, the HDL subspecies pattern was modified as the result of an increase in the total mass (11.7%) of HDL2a, HDL3a, and HDL3b (d = 1.091 to 1.156 g/mL) at the expense of reductions in the total mass (-23%) of HDL2b (d = 1.063 to 1.091 g/mL) and HDL3c (d = 1.156 to 1.179 g/mL). Such changes are consistent with a drug-induced reduction in CETP activity. In conclusion, the overall mechanism involved in the fenofibrate-induced modulation of the atherogenic dense LDL profile in combined hyperlipidemia primarily involves reduction in CET from HDL to VLDL together with normalization of the intravascular transformation of VLDL precursors to receptor-active LDLs of intermediate density.
Adult↗
[Granular cell tumors. Rare tumors of the neurohypophysis].
Granular cell tumours of neurohypophysis are rare. These tumours are more often encountered as incidental autopsy findings seen in up to 17% of unselected adult autopsy cases. There are few reports of parasellar granular cell tumours large enough to cause symptoms. We present three cases of neurohypophysis granular cell tumour and a review of the literature. In one patient, the asymptomatic granular cell tumour was incidentally discovered at surgical removal of a corticotroph microadenoma. The remaining 2 patients had a symptomatic tumour which caused neurological symptoms such as visual disturbance and headaches and endocrine disorders such as hypopituitarism or hyperprolactinaemia. In these 2 cases, computerized tomography showed a well-circumscribed, contrast-enhanced, intrasellar and suprasellar mass. Magnetic resonance imaging demonstrated an isointense gadolinium-enhanced mass in T1-weighted images. Transsphenoidal partial resection was performed and histology was interpreted as a granular cell tumour. The immunohistochemical study was positive for glial fibrillary acidic protein (GFAP) and neuron specific enolase (NSE) in 1 of the 2 tumours and positive for S100 protein and vimentin in both tumours but negative for CD68. The histogenesis of neurohypophysis granular cell tumours is still controversial but ultrastructural and immunohistochemical studies support the theory that they may arise from pituicytes, the glial cells of neurohypophysis. Management of these benign, slow-growing, tumours is based mainly on neurosurgical resection. Data from the literature do not support a beneficial effect of postoperative radiation therapy on postoperative recurrences.
Adult↗
Preferential depletion of selenoprotein P in hypercholesterolaemic patients treated by LDL-apheresis.
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Adolescent↗
[Substitutive hormonal treatment of menopause. Effects on lipoprotein metabolism].
A number of epidemiological studies have clearly shown that post-menopausal women on hormone therapy (which tends to simulate normal ovarian production) have a reduced risk of cardiovascular disease (coronary heart disease, stroke and thrombotic events). In fact most of the studies have involved equine oestrogen (Premarin) taken orally. The effects of oestrogens and the progestins depend on the type of administration (oral or percutaneous administration) and the variety of the drug chosen and finally is also dose dependent. The most favourable effect is obtained in normolipidaemic women with the combination of conjugated oestrogens given orally and a non-androgenic progestins. Such therapy is associated with an increase in HDL-cholesterol and a decrease in LDL-cholesterol. HDL subfraction analysis shows that HDL2 are the main species involved in this increase. The mechanism of action of oestrogens and progestins can be summarized as follows: oestrogens stimulate hepatic triglyceride secretion, inhibit the action of hepatic lipase, augment LDL breakdown via the cellular receptor apo B-E and may decrease LDL oxidability and Lp(a) levels. Although several points remain obscure, we may notice that most of studies show that the atherogenic profile of the women who are currently being treated tends to improve.
Cardiovascular Diseases↗
Blood antioxidants (vitamin E and beta-carotene) in long-term low density lipoprotein apheresis.
We measured vitamin E and beta-carotene in the serum and in circulating lipoproteins in a large population of 15 patients with familial hypercholesterolaemia who were undergoing long-term treatment by low density lipoprotein (LDL) apheresis. The technique used for apheresis was dextran sulphate cellulose adsorption. The results showed that before LDL apheresis, patients had high vitamin E and normal beta-carotene levels in the serum and in the VLDL+LDL fraction. There were no relationships between serum levels of vitamin E and beta-carotene and the duration of LDL-apheresis. Low vitamin E and beta-carotene levels in the HDL fraction could be related to the low HDL concentrations in these patients. Vitamin E/cholesterol ratios were similar to those of the normolipaemic controls whereas beta-carotene/cholesterol ratios were lower. After LDL-apheresis treatment, the ratios in the HDL fraction fell whereas the ratios in the serum and in the VLDL and LDL fraction did not change. This study shows that these patients exhibited no deficiency in either serum of VLDL-LDL of vitamin E or beta-carotene after long-term treatment by LDL-apheresis and that the status of these antioxidants in serum was independent of the duration of treatment.
Adolescent↗
Comparison of the efficacy of simvastatin and standard fibrate therapy in the treatment of primary hypercholesterolemia and combined hyperlipidemia.
Five multicenter, randomized, double-blind, placebo-controlled studies were conducted in France to compare the efficacy and safety of once-daily simvastatin treatment (10-40 mg/day) with conventional therapy with gemfibrozil 900 mg/day, ciprofibrate 100 mg/day, bezafibrate 400 mg/day, and fenofibrate 300 or 400 mg/day in a total of 800 patients with hypercholesterolemia. Simvastatin was associated with statistically significantly greater (p < or = 0.01) mean percent reductions in plasma low-density lipoprotein (LDL) cholesterol compared with each of the five fibrate regimens, even when administered at its recommended starting dose of 10 mg/day. Furthermore, approximately 90% of patients treated once daily with simvastatin experienced an at least 20% decrease in plasma LDL cholesterol compared with only 36 to 68% of patients treated with the individual fibrate agents (p < or = 0.05). The effectiveness of simvastatin in reducing LDL cholesterol did not differ as a function of the baseline plasma concentrations of total cholesterol or triglycerides. In contrast, the effectiveness of fibrate therapy in lowering plasma LDL cholesterol levels was significantly diminished (p < or = 0.05) among patients with triglyceride concentrations > 1.7 mmol/l. Plasma high-density lipoprotein (HDL) cholesterol levels were increased by approximately 10% after treatment with simvastatin or the fibrates. Although fibrate therapy was more effective overall in lowering plasma triglyceride levels, the effectiveness of simvastatin in reducing plasma triglyceride levels was generally 2- to 4-fold greater in patients with hypercholesterolemia associated with triglyceride levels > or = 2.3 mmol/l than in those with hypercholesterolemia associated with triglyceride levels < 2.3 mmol/l. The results of these studies confirm the superiority of simvastatin to standard fibrate therapy in reducing plasma levels of total and LDL cholesterol. They further indicate that once-daily treatment with simvastatin is effective in patients with isolated hypercholesterolemia or hypercholesterolemia associated with elevated triglyceride levels.
Anticholesteremic Agents↗
Estrogens and progestins in postmenopausal women: influence on lipid parameters and cardiovascular risk.
Postmenopausal women are 2-3 times more likely to have a heart attack than premenopausal women. According to the results of the Framingham study, angina is one of the main manifestations of coronary heart disease in women, whereas myocardial infarction and sudden death are more frequent in men. Cigarette smoking, high blood pressure and hypercholesterolemia are major risk factors for coronary heart disease in both men and women, while diabetes mellitus and hypo-high-density lipoproteinemia are more clearly associated with cardiovascular disease in women than in men. Endogenous and exogenous hormones may be a major determinant of the cardiovascular risk in women. Premenopausal women have a considerably lower incidence of coronary heart disease than postmenopausal women, and estrogen therapy is associated with a reduced risk in the latter. Part of this protective effect seems to be due to the influence of estrogen therapy on lipoprotein metabolism, i.e. a decrease in LDL cholesterol and an increase in HDL cholesterol. Progestins, to an extent which depends on their androgenic potency, have the opposite effects. A large study (the Postmenpausal Estrogen Progestin Intervention Trial) has been launched to test the effect of the estrogen-progestin combination on various cardiovascular risk factors.
Cardiovascular Diseases↗
Are free fatty acids related to plasma plasminogen activator inhibitor 1 in android obesity?
Plasminogen activator inhibitor 1 (PAI-1) levels are elevated in obese insulin-resistant subjects. However the mechanism underlying increased PAI-1 levels is unknown. To determine the impact of diabetes on PAI-1 levels and its possible relationship to insulin resistance, hyperinsulinemic euglycemic clamp studies were performed in nine lean control subjects, nine non-diabetic obese subjects and eight obese patients with NIDDM. Fasting plasma PAI-1 levels were 4.0 to 4.7 fold higher in the two obese groups than in the control group. During the 40 mU/m2 x min insulin infusion, suppression of FFA concentration was correlated with fasting plasma PAI-1 levels in both obese non-diabetic and obese NIDDM subjects. It is concluded that (1) obesity rather than diabetes itself plays a major role for the increased PAI-1 levels in NIDDM; (2) resistance to the antilipolytic effect of insulin, resulting in increased FFA concentrations, may participate in producing elevated PAI-1 levels in android obese subjects.
Adult↗
[Genetic aspects of primary atherogenic dyslipoproteinemia].
Large progress have been made in the last 15 years about knowledge of genetic of atherogenic dyslipoproteinemias. The genes of apolipoproteins, lipoprotein receptors and enzymes of lipoprotein metabolism are now located and their structures are known. Many gene defects are described and are responsible of definite diseases such as familial hypercholesterolemia, familial dysbetalipoproteinemia, familial hypoalphalipoproteinemia. Beside this pure genetic disorders, other atherogenic dyslipoproteinemias are result of interactions of genetic and environmental factors. This new physio-pathological approach gives a better comprehension of the clinical features than phenotype classification based on plasma cholesterol and triglycerides levels and lipoprotein electrophoretic pattern.
Humans↗
[Elevation of lipoprotein(a) levels in patients following transplantation for ischemic cardiopathy].
OBJECTIVES: Increased levels of serum lipoprotein (a) in heart transplant patients has been recently shown to be related to early recurrence of coronary artery disease. In order to evaluate the effect of the ischaemic origin of the heart disease we compared lipoprotein (a) levels observed in heart transplant patients who underwent transplantation due to ischaemic heart disease and non-obstructive cardiomyopathy with those in healthy control subjects. METHODS: Serum levels lipoprotein (a) were measured in 62 cardiac transplantation recipients who had a hyperlipidemia. The results were compared with those of 212 control subjects matched for age and who were referred for hyperlipidemia. RESULTS: In the whole population 40 patients had been operated on for coronary heart disease and 22 for idiopathic cardiomyopathy. The two populations did not differ with regard to their cardiovascular risk factors except for the smoking status. The mean Lp(a) values were significantly higher in the subjects with coronary heart disease as compared with those with idiopathic cardiomyopathy (0.33 +/- 0.24 and 0.21 +/- 0.17 mg/dl respectively; p < 0.05). The latter were not different from the control group (0.22 +/- 0.19 mg/ml). We did not find any difference between the two populations concerning the drugs taken by the patients (especially cyclosporine), LDL-cholesterol, creatinine, fasting blood glucose and TSH. CONCLUSION: Our data confirm the relation between coronary atherosclerosis and high lipoprotein (a) levels.
Adult↗
[Endocrine diseases in POEMS syndrome. Apropos of 4 cases].
POEMS syndrome is a rare systemic multi-organ disease usually reported in Japanese patients. The clinical course is slow with a 5-year survival of 60%. Death is caused by polyneuropathy and or anasarka. We observed four cases in our ward (all males, aged 39, 57, 54 and 54 years) who all presented at least four characteristic clinical signs. Gynecomasty together with impotency was seen in all patients. All had hypogonadism and borderline hyperprolactinaemia. Hyperoestrogenism was seen in two. In three patients, rare endocrinopathies were part of the POEMS syndrome. One patient had diabetes mellitus. The clinical course was variable and a function of the effectiveness of plasmocyte dyscrasia therapy. Little work has been done on endocrinopathies in POEMS syndrome. In most cases, gonadotrope function is impaired with gynecomasty and impotency in men, amenorrhoea in women. Generally the hypogonadism is hypogonadotropic. Hyperoestrogenism is frequent and prolactin levels are normal or high with an exaggerated response to thyroid releasing hormone stimulation. The aetiology of POEMS syndrome is unknown. Current research is based on an immunologic theory based on the discovery of high levels of interleukin 6 in POEMS patients with or without Castleman's disease. The cytokine would affect the different organs and lead to clinical expression. Corticosteroids are usually effective in most patients, particularly in reducing the oedema and controlling the polyneuropathy.
Adult↗
[Iatrogenic hypertriglyceridemia].
Several recent studies have confirmed the pathogenic effect of endogenous hypertriglyceridaemia (type IV) on atherosclerosis and thrombosis. Our understanding of the pathophysiological mechanism involved in these hypertriglyceridaemias is constantly improving. Iatrogenic hypertriglyceridaemia can be caused by several classes of drugs including synthetic oestrogens, especially the oestrogen-progesterone contraceptives, and to a lesser extent natural oestrogens taken orally as replacement treatment during menopause, certain hypotensive drugs (non-cardioselective beta-blockers and thiazidic diuretics), corticosteroids, retinoids, cyclosporine, enzyme inductors and iodine produces (by iodine-induced hypothyroidism). All these situations should be recognized and when high lipid levels are observed treatment protocols should be modified or interrupted. Whether associated with a rise or a fall in cholesterol-LDL, such conditions should always taken into consideration due to the increased risk of atherosclerosis, thrombosis or even acute or subacute pancreatitis.
Adrenal Cortex Hormones↗