Interleukin-6 as an early marker for fat embolism

Background  

Fat Embolism is a complication of long bone fractures, intramedullary fixation and joint arthroplasty. It may progress to fat embolism syndrome, which is rare but involves significant morbidity and can occasionally be fatal. Fat Embolism can be detected at the time of embolization by transoesophageal echocardiography or atrial blood sampling. Later, a combination of clinical signs and symptoms will point towards fat embolism but there is no specific test to confirm the diagnosis. We investigated serum Interleukin-6 (IL-6) as a possible early marker for fat embolism.     

美国糖尿病协会关于糖尿病神经病变的诊断和治疗指南

本文系统地介绍了美国糖尿病协会关于糖尿病神经病变的诊断和治疗指南,包括糖尿病周围神经病变的定义和分类、诊断标准和临床表现、流行病学,如何早期筛查、预防及治疗原则.     

Squalene synthase: a critical enzyme in the cholesterol biosynthesis pathway

High levels of plasma low-density lipoprotein cholesterol (LDL-C) are a significant risk factor for heart disease. Statins (3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors) have been extensively used to treat high-plasma LDL-C levels and are effective in preventing heart disease. However, statins can be associated with adverse side effects in some patients and do not work effectively in others. As an alternative to statins, the development of cholesterol-lowering agents that directly inhibit squalene synthase have shown promise. Clinical studies have shown that squalene synthase inhibitors are effective in lowering plasma levels of total cholesterol and LDL-C. Squalene synthase plays an important role in the cholesterol biosynthesis pathway as it is responsible for the flow of metabolites into either the sterol or the non-sterol branches of the pathway. In addition, variants of the squalene synthase gene appear to modulate plasma cholesterol levels in human populations and therefore may be linked to cardiovascular disease. In this review, we examine squalene synthase and the gene that codes for it (farnesyldiphosphate farnesyltransferase 1). In particular, we investigate their role in the regulation of cellular and plasma cholesterol levels, including data that suggest that squalene synthase may be involved in the etiology of hypercholesterolemia.     

Incorporating natural variation into IVF clinic league tables: The Expected Rank

Background  

Rankings based on outcome are often used to present health care provider performance. These rankings do however not reflect that part of the variation in outcome between providers is caused by natural variation, and not by any differences in quality of care. The aim of this study is to compare standard methods for ranking with a novel method that takes into account natural variation.     

The role of glutathione reductase in maintaining human granulocyte function and sensitivity to exogenous H2O2

Human granulocytes (polymorphonuclear leukocytes, PMN) produce H2O2 and other reactive oxygen species while undergoing phagocytosis. To examine the role of the glutathione cycle in metabolizing H2O2, we incubated PMN with 1,3-bis (2-chloroethyl) nitrosourea (BCNU). Incubation of PMN with BCNU results in a dose-dependent inhibition of PMN glutathione reductase (GRED), with 50% inhibition occurring at approximately 2 micrograms/mL BCNU. PMN hexose monophosphate shunt activity stimulated with an exogenous H2O2-generating system was inhibited only when the GRED activity was reduced to less than 30% of control. BCNU-treated cells contained lower levels of reduced sulfhydryls and reduced glutathione, which decreased even more in the presence of an exogenous H2O2-generating system. The effect of BCNU and exogenous H2O2 on various aspects of phagocytosis were examined. Exposure of BCNU-treated PMN to an H2O2-generating system resulted in an inhibition of chemotactic peptide-induced shape changes and degranulation. The ability of BCNU-treated cells to produce O2- was diminished only when the PMN were incubated with an H2O2-generating system in the presence of cyanide. Ingestion of opsonized bacteria by BCNU-treated PMN was unaffected by incubation in an H2O2-generating system even in the presence of cyanide. We conclude that PMN GRED is inhibited by BCNU, the ability of PMN to metabolize H2O2 is affected only when GRED is reduced more than 70%, this inhibition affects the glutathione content of these cells, and some, but not all of the phagocytic functions of GRED-inhibited PMN are inhibited after exposure to an H2O2-generating system.     

Lack of plasminogen activator inhibitor-1 effect in a transgenic mouse model of metastatic melanoma

Tumor cell invasion and metastasis is a complex, multistep process that is postulated to require degradation of extracellular matrix at several steps. Urokinase-type plasminogen activator (uPA) is expressed on the cell surface of B16 murine melanoma cells and is thought to contribute to the pericellular proteolysis necessary for tumor cell migration. In vitro modification of B16 melanoma cell surface uPA activity has been shown to alter the invasive and metastatic potential of these murine melanoma cells in vivo. Plasminogen activator inhibitor-1 (PAI-1), a rapid inhibitor of both uPA and tissue-type plasminogen activator (tPA) is the major physiologic regulator of plasminogen activator activity. To test the role of host PAI-1 in the invasive and metastatic capacity of B16 melanoma cells we analyzed local tumor growth and pulmonary metastasis in transgenic mice engineered to overexpress murine PAI-1 in multiple tissues including lung, and in mice completely deficient in PAI-1. No significant difference in the number of pulmonary metastases was observed after intravenous inoculation of tumor cells into PAI-1- overexpressing and PAI-1-deficient mice when compared with wild-type controls. Similarly, in a spontaneous metastasis model, PAI-1- overexpressing and PAI-1-deficient mice demonstrated no difference in primary tumor size or overall survival. These data demonstrate that wide variations of host PAI-1 expression, from complete absence to marked overexpression, does not significantly influence the metastatic potential of B16 melanoma cells in a murine model.