The Asp298 allele of endothelial nitric oxide synthase is a risk factor for myocardial infarction among patients with type 2 diabetes mellitus

Background: Endothelial dysfunction plays a central role in atherosclerotic progression and cardiovascular complications of type 2 diabetes mellitus (T2DM). Given the role of nitric oxide in the vascular system, we aimed to test hypotheses of synergy between the common endothelial nitric oxide synthase (eNOS) Asp(298) allele and T2DM in predisposing to acute myocardial infarction (AMI). Methods: In a population-based patient survey with 403 persons with T2DM and 799 healthy subjects from the population without diabetes or hypertension, we analysed the relation between T2DM, sex and the eNOS Asp(298) allele versus the risk for AMI. Results: In an overall analysis, T2DM was a significant independent risk factor for AMI. In patients with T2DM, homozygosity for the eNOS Asp(298) allele was a significant risk factor (HR 3.12 [1.49-6.56], p = 0.003), but not in subjects without diabetes or hypertension. Compared to wild-type non-diabetic subjects, all patients with T2DM had a significantly increased risk of AMI regardless of genotype. This risk was however markedly higher in patients with T2DM homozygous for the Asp(298) allele (HR 7.20 [3.01-17.20], p < 0.001), independent of sex, BMI, systolic blood pressure, serum triglycerides, HDL -cholesterol, current smoking, and leisure time physical activity. The pattern seemed stronger in women than in men. Conclusion: We show here a strong independent association between eNOS genotype and AMI in patients with T2DM. This suggests a synergistic effect of the eNOS Asp(298) allele and diabetes, and confirms the role of eNOS as an important pathological bottleneck for cardiovascular disease in patients with T2DM

Monitoring the referral system through benchmarking in rural Niger: an evaluation of the functional relation between health centres and the district hospital

BACKGROUND: The main objective of this study is to establish a benchmark for referral rates in rural Niger so as to allow interpretation of routine referral data to assess the performance of the referral system in Niger. METHODS: Strict and controlled application of existing clinical decision trees in a sample of rural health centres allowed the estimation of the corresponding need for and characteristics of curative referrals in rural Niger. Compliance of referral was monitored as well. Need was matched against actual referral in 11 rural districts. The referral patterns were registered so as to get an idea on the types of pathology referred. RESULTS: The referral rate benchmark was set at 2.5 % of patients consulting at the health centre for curative reasons. Niger's rural districts have a referral rate of less than half this benchmark. Acceptability of referrals is low for the population and is adding to the deficient referral system in Niger. Mortality because of under-referral is highest among young children. CONCLUSION: Referral patterns show that the present programme approach to deliver health care leaves a large amount of unmet need for which only comprehensive first and second line health services can provide a proper answer. On the other hand, the benchmark suggests that well functioning health centres can take care of the vast majority of problems patients present with

マンソン住血吸虫感染の血清診断に応用可能なタンデムリピート抗原に関する研究

The diagnosis of schistosome infection, followed by effective treatment and/or mass drug administration, is crucial to reduce the disease burden. Suitable diagnostic tests and field-applicable tools are required to sustain schistosomiasis control programs. We therefore assessed the potential of tandem repeat (TR) proteins for sero-diagnosis of Schistosoma mansoni infection using an experimental mouse model.TR genes in the genome of S. mansoni were searched in silico and 7 candidates, named SmTR1, 3, 8, 9, 10, 11 and 15, were selected. Total RNA was extracted from S. mansoni adult worms and eggs. Target TR genes were amplified, cloned, and the proteins were expressed in Escherichia coli competent cells. Female BALB/c mice were infected with 100 S. mansoni cercariae and sera were collected each week post-infection for 18. weeks. The levels of IgG antibodies to SmTR antigens were compared to those to soluble egg antigen (SEA) and to soluble worm antigen preparation (SWAP). Sera of infected mice reacted to all the antigens whereas those of naive mice did not. IgG responses to SmTR1, 3, 9 and 10 were detected at the early stage of infection. Interestingly, antibodies reacting to SmTR3, 9, 10 and 15 dramatically decreased 4. weeks after treatment with praziquantel, while those against SEA and SWAP remained elevated.Our study suggests that TR proteins, especially SmTR10, may be suitable antigens for sero-diagnosis of infection by S. mansoni and are potential markers for monitoring and surveillance of schistosomiasis, including re-infection after treatment with praziquantel.長崎大学学位論文 学位記番号:博(医歯薬)甲第803号 学位授与年月日:平成27年9月18日Author: Yombo Dan Justin Kalenda, Kentaro Kato, Yasuyuki Goto, Yoshito Fujii, Shinjiro HamanoCitation: Parasitology International, 64(6), pp.503-512; 2015Nagasaki University (長崎大学)課程博