Clinico-pathological evaluation of patients with homozygous familial hypercholesterolemia]

The authors have studied 8 patients with Homozygous Familial Hypercholesterolemia (FHO) an autosomal genetic dominant disease due to mutation of the gene encoding a cell surface receptor for LDL. Anatomic and pathologic abnormalities caused by LDL-cholesterol and B-Apolipoprotein high plasma levels were found. We also measured malondialdehyde levels in plasma and atherosclerotic plaques of the only autoptic case observed. MDA-levels are an index of lipid peroxidation. Cutaneous xanthomatosis lesions and severe cardiovascular disease were also present

Relations between vasoactive hormones and diastolic function in hypertensive uraemic patients.

BACKGROUND: Arterial hypertension is a significant risk factor for the high rate of cardiovascular disease in chronic uraemic (CU) patients. Any role that hypertension may play in CU patient outcomes assumes added significance. The elevation of some hormonal factors in early clinical stage could represent a valuable marker of cardiac disease in CU. AIM: This study first investigated the role of several hormones on cardiac diastolic properties in CU patients. Moreover, the study investigated the association of hypertension with both diastolic function and release of vasoactive hormones in CU patients. RESULTS: We have reported that the early impairment of diastolic function is correlated with the elevation of both circulating plasma atrial natriuretic factor and endothelin-1 (ET-1) in hypertensive CU patients. Since the effect of ET-1 on diastolic function is still poorly understood, we have investigated also this issue. In eight additional patients with reduced E/A ratio, but without uraemia, hypertension or chronic heart failure, we have showed a high inverse correlation between the values of E/A ratio and ET-1 plasma concentrations. CONCLUSIONS: These results strongly suggest that the elevation in ET-1 levels was correlated with diastolic dysfunction in man. This phenomenon may have important pathophysiological implications suggesting the possibility of an early therapeutic approach in these patients

Relations between vasoactive hormones and diastolic function in hypertensive uraemic patients

Arterial hypertension is a significant risk factor for the high rate of cardiovascular disease in chronic uraemic (CU) patients. Any role that hypertension may play in CU patient outcomes assumes added significance. The elevation of some hormonal factors in early clinical stage could represent a valuable marker of cardiac disease in CU

Metformin induces apoptosis and downregulates pyruvate kinase M2 in breast cancer cells only when grown in nutrient-poor conditions

Metformin is proposed as adjuvant therapy in cancer treatment because of its ability to limit cancer incidence by negatively modulating the PI3K/AKT/mTOR pathway. In vitro, in addition to inhibiting cancer cell proliferation, metformin can also induce apoptosis. The molecular mechanism underlying this second effect is still poorly characterized and published data are often contrasting. We investigated how nutrient availability can modulate metformin-induced apoptosis in three breast cancer cell lines

Histological findings and evidence of lipid conjugated dienes and malonyldialdehyde in human fetal aortas.

Recent evidence strongly suggests that peroxidative modification of lipids may play a significant role in atherogenesis. In our present research, we investigated if the oxidative stress mediated by oxygen free radicals was a pathophysiologic condition that occurred in the early stages of human development. Thus the aim of this research was to examine lipid peroxidation in human fetal aortas. Human fetal aortas and proximal iliac arteries (n = 8) were obtained from fetuses aged 7 +/- 2 months, immediately after autopsy. Lipids from the initial fatty streak lesions (LFS) and the vessels uninvolved (LUV) were extracted by the chloroform/methanol method. Lipid peroxidation levels were measured by two different methods: determination of lipid conjugate dienes (the spectrum trend was recorded from 320 to 200 nm with a spectrophotometer) and malonyldialdehyde (MDA) content (TBA method). We observed that lipid conjugated dienes were present in LFS, but not in LUV, with a characteristic absorption peak at 233 nm. In addition, MDA levels were significantly higher when the LFS = 3.85 +/- 0.91 nmol than when the LUV = 0.41 +/- 0.12 nmol (p < 0.001 versus LUV). The presence of lipid peroxidation in our samples could be mediated by free radical production in the first stages of human development. Thus these data suggest that LFS peroxidation mediated by free radicals occurs in the vascular circulation in the early stages of human development. This could influence the progression of vascular damage and atherosclerotic disease

[Morphological and biochemical study of the lipid components of the fetal aorta].

We made a biochemical and histochemical study of the lipidic component of intima of fetal aortas on 8 autopsy cases (7 +/- 2 months aged) arrived at our observation in the Pathology's Institute of II Faculty of Naples. We made a study with freeze-sections stained with Oil-Red 0 and after dissociation of the intima by the adventitia, it is valued biochemically the lipidic peroxidation studying the levels of malonyldialdehyde (MDA) like indirect marker of peroxidation. It is known that is present a lipidic component in the intima of fetal aorta whether intracellular or extracellular (Fig. 1, 2). Sometimes this component can accumulate until to determinate true lipidic striae. The aim of this study is a detection of MDA in lipids extracted from human fetal aortas. MDA levels was measured by Thiobarbituric method (TBA): lipids were extracted both intima and adventitia by Chloroform/methanol method, after surgery immediately. The results are expressed in nMoles/mg of lipids +/- Standard Deviation. Controls of spontaneous lipid peroxidation was take at a different times. It is known that in vitro incubation of LDL with cultured endothelial cells, smooth muscle cells or macrophages leads to peroxidation of LDL phospholipids and oxidatively modified LDL become atherogenic via foam cells production. In addition lipid peroxidation was formed by the direct peroxidation of unsaturated fatty acids and their esters are capable of further lipoperoxide production by oxygen free radical; chain reactions. In this context lipid peroxidation could be an important factor in the first stage of human pathophysiological development and this phenomenon may be related by an early free radical production