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Predisposed Subjects (predisposed + subject)
Selected AbstractsInsulin resistance , a common link between type 2 diabetes and cardiovascular diseaseDIABETES OBESITY & METABOLISM, Issue 3 2006Harold E. Lebovitz Evidence suggests that diabetes and cardiovascular disease (CVD) may share an underlying cause(s), a theory known as the ,common soil' hypothesis. Insulin resistance is central both to the progression from normal glucose tolerance to type 2 diabetes and to a constellation of cardiovascular risk factors known as the metabolic syndrome. These risk factors include visceral obesity and dyslipidaemia characterized by low levels of high-density lipoprotein cholesterol, hypertriglyceridaemia and raised small dense low-density lipoprotein particle levels. Changes in adipose tissue mass and metabolism may link insulin resistance and visceral obesity, a condition that is common in type 2 diabetes. Furthermore, weight reduction, increased physical activity, metformin and acarbose have been shown to reduce the development of type 2 diabetes in genetically predisposed subjects and may decrease the high cardiovascular risk of patients with diabetes. Some fatty acid derivatives can affect energy metabolism by activating peroxisome proliferator-activated receptors (PPARs), nuclear receptors that play a key role in energy homeostasis. These receptors represent an ideal therapeutic target for reducing cardiovascular risk, because they are involved in the regulation of both insulin action and lipid metabolism. In addition to lifestyle changes, PPAR, agonists such as thiazolidinediones are frequently beneficial and have been shown to ameliorate insulin resistance, while activation of PPAR, (e.g. by fibrates) can lead to improvements in free fatty acid oxidation and lipid profile, and a reduction in cardiovascular events. The development of agents with both PPAR, and PPAR, activity promises added benefits with amelioration of insulin resistance, delayed progression to and of type 2 diabetes and a reduction of CVD. [source] CD31+/Annexin V+ microparticles in healthy offsprings of patients with coronary artery diseaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2009D. Bulut ABSTRACT Background, First-degree relatives of patients with premature coronary artery disease (CAD) develop endothelial dysfunction even in the case they are apparently healthy. In this study we wanted to clarify whether reduced blood levels of circulating endothelial progenitor cells (EPCs), an endogenous repair mechanism to replace dysfunctional endothelium, or elevated endothelial-derived microparticles (EMPs), an indicator and a mediator of increased endothelial cell damage/apoptosis, are an initial step in the pathogenesis of endothelial dysfunction in genetically predisposed subjects. Materials and methods, Fifty-six healthy young men (aged 23 to 31 years) from a fire brigade were enrolled, of which 20 subjects had a positive family history (FH) for premature CAD. Subjects with or without a positive FH did not differ with respect to age, body mass index, risk factors and C-reactive protein. Endothelial function was assessed by hyperaemia-mediated relaxation of the brachial artery, blood levels of EPCs (VEGFR2+CD34+ cells) and number of EMPs (CD31+(bright)/Annexin V+ particles) were analysed by flow cytometry. Results, Hyperaemia-mediated relaxation of the brachial artery was similar in both groups, and the blood levels of EPCs were comparable. However, the number of EMPs were significantly increased in subjects with a positive FH compared to those with a negative FH (neg. FH: 55·31 ± 4·88 vs. pos. FH: 70·37 ± 6·32 particles µL,1 platelet poor plasma; P < 0·05). Number of EMPs correlate inversely with the FMD response. Conclusions, These results suggest that increased plasma levels of EMPs may be an initial step in the development of endothelial dysfunction in genetically predisposed subjects. [source] HLA DPB1*0201 allele is negatively associated with immunoglobulin E responsiveness specific for house dust mite allergens in TaiwanCLINICAL & EXPERIMENTAL ALLERGY, Issue 4 2000Background House dust mite (HDM) Dermatophagoides pteronyssinus is the most important source of indoor allergens that cause allergic diseases in Taiwan. We prepared purified HDM allergens (Der p 1, Der p 2 and Der p 5) to detect allergen-specific immunoglobulin (Ig) E responsiveness among a large number of test subjects. The robust genetic typing system for HLA class II genes also facilitated the study on association of HLA and allergic response toward HDM. Objective This study intended to investigate the association between HLA class II alleles and the IgE responsiveness to the major allergens from HDM, D. pteronyssinus. Methods Two hundred and forty-eight subjects were selected for HLA association study. Plasma HDM allergen (Der p 1, Der p 2, Der p 5) -specific IgE and Der p 2-specific IgG antibodies were detected by ELISA, while HLA class II -DRB1, -DQA1, -DQB1, -DPB1 genetic polymorphism was determined by polymerase chain reaction/sequence-specific oligonucleotide probe hybridization (PCR/SSOPH). Statistical comparison of the allelic distribution of each HLA class II genes among the individuals with/without HDM allergen-specific IgE and IgG antibodies were performed. Results There was no significant association between HLA DRB1, DQB1, DQA1 alleles and HDM-specific IgE responsiveness noted. Only DRB1*0803 and the linked DQA1*0103 alleles showed positive association with Der p 5-specific IgE responsiveness. However, we found that HLA-DPB1*1301 predisposed subjects to IgE responsiveness to HDM Der p 5. HLA DPB1*0501 was weakly associated with the IgE responsiveness to HDM Der p 1 and Der p 5. There was a strong negative association between the HLA-DPB1*0201 allele with IgE responsiveness to Der p 1 (OR: 0.30, P , 0.0001, P , 0.0007, Pc , 0.010). Conclusion We clearly observed the association between HLA DPB1 alleles and specific IgE responsiveness to HDM major allergens. The molecular mechanism of HLA-DPB1*0201 involvement in protecting subjects from HDM-specific IgE responsiveness awaits further investigation. [source] Allergic rhinitis in children: environmental factorsCLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 1 2004Y. Okamoto Summary Increasing numbers of patients with allergic rhinitis are being noted on a global scale. Over 90% of Japanese patients with perennial allergic rhinitis show allergic reaction to the mite antigen and major pollen allergens such as Japanese cedar and Japanese cypress, which are carried long distances (> 100 km) by wind and hence can produce substantial harmful effects even in metropolitan areas. This situation is distinct from that in the West, where the most common anemophilous allergen, ragweed, travels much shorter distances of up to only several hundred metres. Environmental factors such as increased antigen, air pollution, diet, intestinal microflora, decreased incidence of infections, smoking, breastfeeding and vaccination may play important roles in the development and manifestation of allergic rhinitis in genetically predisposed subjects. In particular, in newborn infants, who carry the Th2 predominant state, environmental factors may greatly affect the development of balanced production of Th1 and Th2 cytokines. However, the contribution of any environmental factor to the postnatal development of allergic rhinitis has not been sufficiently determined. A better understanding of the processes involved may lead directly to better treatment or cure of allergic rhinitis. [source] | ||||||||||