Relation of C-reactive protein to body fat distribution and features of the metabolic syndrome in Europeans and South Asians.

OBJECTIVE: To investigate the association between circulating C-reactive protein (CRP) concentrations and indices of body fat distribution and the insulin resistance syndrome in South Asians and Europeans. DESIGN: : Cross-sectional study. SUBJECTS: A total of 113 healthy South Asian and European men and women in West London (age 40-55 y, body mass index (BMI) 17-34 kg/m(2)). MEASUREMENTS: Fatness and fat distribution parameters (by anthropometry, dual-energy X-ray absorptiometry and abdominal CT scan); oral glucose tolerance test with insulin response; modified fat tolerance test; and CRP concentration by sensitive ELISA. RESULTS: Median CRP level in South Asian women was nearly double that in European women (1.35 vs 0.70 mg/1, P=0.05). Measures of obesity and CRP concentration were significantly associated in both ethnic groups. The correlation to CRP was especially strong among South Asians (P0.15). CONCLUSION: We suggest that adiposity and in particular visceral adipose tissue is a key promoter of low-grade chronic inflammation. This observation may in part account for the association of CRP with markers of the metabolic syndrome. Future studies should confirm whether CRP concentrations are elevated in South Asians and whether losing weight by exercise or diet, or reduction in visceral fat mass, is associated with reduction in plasma CRP concentrations

Reduction of circulating cholesterol and apolipoprotein levels during sepsis

Sepsis with multiple organ failure is frequently associated with a substantial decrease of cholesterol levels. This decrease of cholesterol is strongly associated with mortality suggesting a direct relation between inflammatory conditions and altered cholesterol homeostasis. The host response during sepsis is mediated by cytokines and growth factors, which are capable of influencing lipid metabolism. Conversely lipoproteins are also capable of modulating cytokine production during the inflammatory response. Therefore the decrease in circulating cholesterol levels seems to play a crucial role in the pathophysiology of sepsis. In this review the interaction between cytokines and lipid metabolism and its clinical consequences will be discussed

Role of Heparanase on Hepatic Uptake of Intestinal Derived Lipoprotein and Fatty Streak Formation in Mice

BACKGROUND: Heparanase modulates the level of heparan sulfate proteoglycans (HSPGs) which have an important role in multiple cellular processes. Recent studies indicate that HSPGs have an important function in hepatic lipoprotein handling and processes involving removal of lipoprotein particles. PRINCIPAL FINDINGS: To determine the effects of decreased HSPGs chain length on lipoprotein metabolism and atherosclerosis, transgenic mice over-expressing the human heparanase gene were studied. Hepatic lipid uptake in hpa-Tg mice were evaluated by giving transgenic mice oral fat loads and labeled retinol. Sections of aorta from mice over-expressing heparanase (hpa-Tg) and controls (C57/BL6) fed an atherogenic diet were examined for evidence of atherosclerosis. Heparanase over-expression results in reduced hepatic clearance of postprandial lipoproteins and higher levels of fasting and postprandial serum triglycerides. Heparanase over-expression also induces formation of fatty streaks in the aorta. The mean lesion cross-sectional area in heparanase over-expressing mice was almost 6 times higher when compared to control mice (23,984 µm(2)±5,922 vs. 4,189 µm(2)±1,130, p<0.001). CONCLUSIONS: Over-expression of heparanase demonstrates the importance of HSPGs for the uptake of intestinal derived lipoproteins and its role in the formation of fatty streaks

Low dose warfarin treatment for calcinosis in patients with systemic sclerosis

Methods: Three patients with disseminated subcutaneous calcinosis were treated with low doses of warfarin for 1 year. Subcutaneous calcinotic lesions, coagulation blood parameters, and the tendency for bleeding were followed up during the year. Results: Two of the patients, who had newly diagnosed, diffuse, and relatively small calcinotic lesions, responded to warfarin treatment, with complete resolution of the calcinosis. The other patient, with larger and longer standing calcinotic lesions, did not respond to warfarin treatment. None of the three patients showed a prolongation of prothrombin time or partial thromboplastin time, nor did any have an increased tendency for bleeding. Conclusions: Low dose warfarin may serve as an effective treatment for calcinosis in a selected group of patients who have small and relatively new onset calcinosis. This treatment does not prolong the coagulation of blood and there is no increased tendency for bleeding

Reduction of jaw opening (trismus) in giant cell arteritis

Methods: the prevalence of such symptoms in patients with GCA was evaluated by performing a retrospective analysis of all patients with GCA and polymyalgia rheumatica who were diagnosed during admission to Hadassah University Hospital. Ten patients reported previously in the literature were also evaluated. Results: Six patients out of 88 (6.8%) had complaints of reduction in jaw opening. These six patients seemed to have a much more abrupt onset of disease with shorter duration until diagnosis, higher prevalence of eye involvement (50% v 27%), and a higher rate of positive pathology (100%). Conclusions: Reduction in jaw opening in the appropriate setting may indicate the presence of GCA. This sign should not be overlooked in the presence of the claudication sign as it seems to reflect more severe GCA disease

Association of the MIC-A gene and HLA-B51 with Behçet's disease in Arabs and non-Ashkenazi Jews in Israel

Background: Behçet's disease is known to be strongly associated with HLA-B51 in many different ethnic groups. Recently, it was suggested that MIC-A (major histocompatibility complex class I related gene A) is the pathogenic gene after strong association was found between the MIC-A A6 allele of the transmembrane region and the disease in Japanese and Greek patients, although in Greek patients this association was found to be due to linkage disequilibrium with HLA-B51. Objectives: To investigate microsatellite polymorphism in Arab and non-Ashkenazi Jewish (NAJ) patients in Israel, to determine whether this association occurs in these groups with Behçet's disease, and elucidate the associated HLA allele of the disease. Methods: Forty four Israeli patients with Behçet's disease, including 20 Arabs and 24 NAJ, and 130 ethnically matched healthy controls were examined for MIC-A microsatellite polymorphism of the transmembrane region using polymerase chain reaction, autoradiography, and sequence analysis. Results: The MIC-A A6 allele was significantly more frequent in the Arab patient group (19/20 (95%)) than in healthy Arab controls (25/42 (60%)) (p(corr)=0.015, OR=12.92), but not in the NAJ patients (16/24 (67%)) compared with NAJ healthy controls (48 /88 (55%)) (p(corr)=1.02, OR=1.667). In stratification analysis of the Arab subgroup, on the confounding effect of MIC-A A6 on HLA-B51 association and vice versa, Behçet's disease was distinctly associated only with HLA-B51. Conclusions: These results imply strong association between the MIC-A A6 allele and the disease in Israeli Arabs, but not in Israeli NAJ patients. The stratification analysis indicates that this association results secondarily from a strong linkage disequilibrium with HLA-B51, and the real disease susceptibility gene which plays a part in the development of Behçet's disease is most probably the HLA-B51 allele itself