Homocysteinylation of low-density lipoproteins (LDL) from subjects with Type 1 diabetes: effect on oxidative damage of human endothelial cells.

BACKGROUND: Homocysteine (Hcy) is an independent risk factor for cardiovascular disease (CVD). Individuals with Type 1 and Type 2 diabetes are more susceptible to the effects of homocysteine than non-diabetic subjects. The interaction between homocysteine-thiolactone (Hcy-thiolactone), a reactive product of Hcy, and low-density lipoproteins (LDL) induces the formation of homocystamide-LDL adducts (Hcy-LDL) and it has been suggested that homocysteinylation could increase atherogenicity of lipoproteins. AIM: The aim of the study was to compare the effect of in vitro homocysteinylation of LDL isolated from healthy control subjects (C-LDL) and from Type 1 diabetic patients (DM-LDL) and to investigate the effect of homocysteinylated LDL (Hcy-C-LDL and Hcy-DM-LDL) on peroxynitrite production of endothelial cells. METHODS: The in vitro homocysteinylation of LDL isolated from control (n = 12) and DM subjects (n = 12) was carried out by incubating lipoproteins with Hcy-thiolactone. The reaction was verified by quantifying the increase in sulphydryl groups (-SH groups) in Hcy-LDL with respect to control LDL. Control and homocysteinylated LDL were incubated with human aortic endothelial cells (HAEC) in culture. Peroxynitrite production in cells treated in different experimental conditions was assayed by a fluorimetric method. RESULTS: The increase in -SH groups after incubation with homocysteine was greater in LDL from diabetic subjects compared with LDL from control subjects (P < 0.001). In addition, peroxynitrite production from HAEC incubated with Hcy-LDL from diabetic patients was greater than after incubation with Hcy-LDL from control subjects and untreated LDL from diabetic patients (P < 0.001). CONCLUSIONS: These results show that LDL from diabetic patients is more susceptible to in vitro homocysteinylation than LDL from non-diabetic individuals and demonstrate that the compositional changes in Hcy-LDL from diabetic subjects have cytotoxic effects on human endothelial cells.     

肿瘤微血管密度与肝癌病理及预后关系

目的 探讨肿瘤微血管密度（MVD）与肝细胞性肝癌临床病理及预后的关系。方法对30例肝细胞性肝癌根治性切除病理组织切片进行苏木精伊红染色．并用CD34单克隆抗体进行免疫组化染色，计数被CD34抗体染色的肿瘤血管内皮细胞数，以测定MVD。对MVD与临床病理因素及术后生存率关系进行分析。结果 单因素分析结果表明．MVD水平与肿瘤大小、TNM分期都是影响肝细胞性肝癌预后的因素；多因素分析结果表明．肝癌大小及肿瘤分期是肝细胞性肝癌独立预后因素。结论 MVD是肝细胞性肝癌一种预后因素。     

Cyclic tensile stretch load and oxidized low density lipoprotein synergistically induce lectin-like oxidized ldl receptor-1 in cultured bovine chondrocytes, resulting in decreased cell viability and proteoglycan synthesis.

Mechanical stimulation is known to be an essential factor in the regulation of cartilage metabolism. We tested the hypothesis that expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) can be modulated by cyclic tensile stretch load in chondrocytes. Cyclic loading of repeated stretch stress at 10 cycles per minute with 10 kPa of stress for 6 h induced expression of LOX-1 to 2.6 times control in cultured bovine articular chondrocytes, equivalent to the addition of 10 microg/mL oxidized low density lipoprotein (ox-LDL) (2.4 times control). Application of the cyclic load to the chondrocytes along with 10 microg/mL ox-LDL resulted in synergistically increased LOX-1 expression to 6.3 times control. Individual application of cyclic loading and 10 microg/mL ox-LDL significantly suppressed chondrocytes viability (84.6% +/- 3.4% and 80.9% +/- 3.2% of control at 24 h, respectively; n = 3; p < 0.05) and proteoglycan synthesis [81.0% +/- 7.1% and 85.7% +/- 5.2% of control at 24 h, respectively; p < 0.05 when compared with 94.6% +/- 4.6% for native-LDL (n = 3)]. Cyclic loading and 10 microg/mL ox-LDL synergistically affected cell viability and proteoglycan synthesis, which were significantly suppressed to 45.6% +/- 4.9% and 48.7% +/- 6.7% of control at 24 h, respectively (n = 3; p < 0.01 when compared with individual application of cyclic loading or 10 microg/mL ox-LDL). In this study, we demonstrated synergistic effects of cyclic tensile stretch load and ox-LDL on cell viability and proteoglycan synthesis in chondrocytes, which may be mediated through enhanced expression of LOX-1 and which has important implications in the progression of cartilage degeneration in osteoarthritis.     

High-density lipoprotein subfractions,apolipoproteins and antipyrine clearance in normal subjects

Summary Serum high density lipoprotein (HDL) subfractions HDL₂ and HDL₃, apolipoproteins, and plasma antipyrine clearance (AP-CL) rate, an index of liver microsomal enzyme activity, were determined in 21 healthy subjects. High HDL cholesterol and HDL₂ cholesterol concentrations and HDL cholesterol/cholesterol and HDL₂/HDL₃ cholesterol ratios were associated with high AP-CL. Phenobarbital enhanced antipyrine elimination and increased the apolipoprotein A-I/A-II ratio. Subjects who had high AP-CL had a more antiatherogenic HDL subfraction and apolipoprotein profile than those with low AP-CL.     

Cholesterol atheromatous embolism: an increasingly recognized cause of acute renal failure

BACKGROUND.: Cholesterol atheromatous embolism is a systemic disease resultingfrom cholesterol crystal embolization to many organs, includingthe kidney. Vascular surgery, vascular radiology investigationsand anticoagulation have been identified as inciting factors. METHODS.: Fifteen patients with extensive atherosclerosis, presentingwith simultaneous occurrence of acute renal failure and peripheralischaemic changes were diagnosed as having acute renal failuredue to cholesterol atheromatous embolism. RESULTS.: The patients, 12 men and three women, had an average age of65 years. In one patient, spontaneous occurrence of the diseasewas observed. An inciting factor was identified in 14 patients:aortography in 10, aortic surgery in two, and thrombolysis intwo. Clinical course of acute renal failure was quite variable.Four patients required dialysis; 11 were conservatively managed.All patients had concomitant skin lesions, including digitalmottling, cyanosis and gangrene of the toes, and livedo reticularisof the lower limb and abdomen. Eosinophilia was the most commonlaboratory abnormality. The diagnosis of cholesterol atheromatousembolism was confirmed by tissue examination in eight; in threeit was based on the finding of retinal cholesterol emboli; infourpatients it was made on clinical grounds. Seven patientsdied within 36 months. Death was most commonly from cardiaccauses. CONCLUSIONS.: Since the population at risk for cholesterol embolism is growingand the disease is iatrogenic in origin, we should expect todetect cholesterol embolism with greater frequency as causeof acute renal failure in the future.     

紫外分光光度法测定SOD活性的应用及其意义

本文对SOD的紫外分光光度法测定进行了实用性研究。结果表明,本文方法具有用血量少,重现性好,快速、灵敏,试剂廉价等优点。西宁地区与平原地区人群的比较测定显示,前者SOD活性明显高于后者(P<0.01)。     

Ultrastructural alterations in caudate nucleus in aged cats

These studies provide information on the changes in the ultrastructure in the caudate nucleus of aged cats. The major findings was that there was a decrease in the density of synapses in caudate neuropil. This decrease occurred in animals after 3 years of age and remained relatively constant in older animals. In conjunction with this change a population of unusually long synapses also occurred. These larger synaptic appositions were associated with enlarged spine heads. The caudate also showed a number of qualitative ultrastructural alterations. Many neurons contained accumulations of lipofuscin or lipopigment granules in aged animals. These inclusions occurred in both soma and dendrites of neurons and all types of glial cells. A unique configuration of collapsed agranular cisterns also was observed in aged animals. The present results indicate that decreases in synaptic density may by one morphological event underlying functional alterations observed in caudate neurons in aged cats.     

Modern day film-screen combinations do not obey conventional exposure rules

Purpose: Following the widespread adoption of energy-dependent rare earth intensifying screens this study investigates the relevance of two conventions (the 10 kVp and kVp-to-the-4th-power rules) commonly used to calculate the kVp/mAs relationship.Methods: A stepwedge was exposed at standard kVp and mAs setting. The kVp was then increased in increments of 5 kVp, and appropriate mAs values were determined using a densitometer. These values were then compared with approximations from the rules previously mentioned.Results: Wide discrepancies are reported between appropriate and approximated values with the latter overestimating exposure by a factor of two.Discussion: Traditional theorems used to estimate the kVp/mAs relationship should no longer be used in modern imaging departments. Each film screen combination should be evaluated individually to ensure appropriate exposure settings.     

Cultured human granulosa cells as a model for corpus luteum function: relative roles of gonadotrophin and low density lipoprotein studied under defined culture conditions.

In primates, corpus luteum development involves both gonadotrophin stimulation and exposure to low density lipoprotein (LDL) delivered through vascularization of the granulosa cell-derived layer. These regulatory influences were modelled in vitro using granulosa cells obtained during in-vitro fertilization (IVF) cycles controlled with gonadotrophin releasing hormone (GnRH) analogue, human menopausal gonadotrophin (HMG) and human chorionic gonadotrophin (HCG). Granulosa cells were cultured in defined medium on extracellular matrix. Without gonadotrophin or LDL in the medium, progesterone production declined progressively. With LDL alone, there was a short-lived elevation of progesterone output which subsequently declined. Culture with HCG alone resulted in a relatively unchanged rate of steroid production over 5 days despite morphological development. This contrasted with a marked and sustained increase in progesterone output over the same time when granulosa cells were cultured with combined HCG/LDL. Cultures were challenged with combined HCG/LDL on day 5. Where initial incubation included HCG, the challenge resulted in a recovery of progesterone output to values comparable to those of granulosa cells exposed to continuous HCG/LDL. Initial incubation without gonadotrophin led to a reduced response. Results suggest that LDL delivery to granulosa cells of the early corpus luteum causes a short-lived period of progesterone production. Sustained luteinization of granulosa cells and maintenance of gonadotrophin responsiveness requires continued exposure to gonadotrophin in the luteal phase.