Synthesis and acid ionization constants of cyclic cystine peptides

Cyclic peptide disulfides of the general formula were synthesized from the corresponding peptide derivatives [Boc-Cys(Trt)(Gly)-_n-Cys(Trt)-OBu^t] by oxidation with iodine in methanol and by subsequent removal of the terminal groups with trifluoroacetic acid. Acid ionization constants of the obtained peptides were determined by potentiometric titration in aqueous KCl (0.1 mol/L) medium. All compounds have two dissociable hydrogens, corresponding to carboxyl (pK¹= 2.35–2.84) and to terminal amino group (pK₂= 5.61–6.93); pK₁, values show first an upward and then a downward trend with the increase in ring size; the opposite is true for pK₂, values. These trends could be tentatively attributed to the intramolecular salt bridge (-COO——-NH⁺₃-) formation.     

Diagnosis,treatment and prevention of type 2 diabetes mellitus in children and adolescents

During the last two decades, there have been several reports of an increasing incidence of type 2 diabetes mellitus (T2DM) in children and adolescents, especially among those belonging to minority ethnic groups. This trend, which parallels the increases in prevalence and degree of pediatric obesity, has caused great concern, even though T2DM remains a relatively rare disease in children. Youth T2DM differs not only from type 1 diabetes in children, from which it is sometimes difficult to differentiate, but also from T2DM in adults, since it appears to be an aggressive disease with rapidly progressive β-cell decline, high treatment failure rate, and accelerated development of complications. Despite the recent research, many aspects of youth T2DM still remain unknown, regarding both its pathophysiology and risk factor contribution, and its optimal management and prevention. Current management approaches include lifestyle changes, such as improved diet and increased physical activity, together with pharmacological interventions, including metformin, insulin, and the recently approved glucagon-like peptide-1 analog liraglutide. What is more important for everyone to realize though, from patients, families and physicians to schools, health services and policy-makers alike, is that T2DM is a largely preventable disease that will be addressed effectively only if its major contributor (i.e., pediatric obesity) is confronted and prevented at every possible stage of life, from conception until adulthood. Therefore, relevant comprehensive, coordinated, and innovative strategies are urgently needed.     

Counseling Fathers (2010) by C.Z. Oren and D.C. Oren

No abstract available for this article.     

A GCH1 haplotype confers sex‐specific susceptibility to pain crises and altered endothelial function in adults with sickle cell anemia

GTP cyclohydrolase (GCH1) is rate limiting for tetrahydrobiopterin (BH4) synthesis, where BH4 is a cofactor for nitric oxide (NO) synthases and aromatic hydroxylases. GCH1 polymorphisms are implicated in the pathophysiology of pain, but have not been investigated in African populations. We examined GCH1 and pain in sickle cell anemia where GCH1 rs8007267 was a risk factor for pain crises in discovery (n = 228; odds ratio [OR] 2.26; P = 0.009) and replication (n = 513; OR 2.23; P = 0.004) cohorts. In vitro, cells from sickle cell anemia subjects homozygous for the risk allele produced higher BH4. In vivo physiological studies of traits likely to be modulated by GCH1 showed rs8007267 is associated with altered endothelial dependent blood flow in females with SCA (8.42% of variation; P = 0.002). The GCH1 pain association is attributable to an African haplotype with where its sickle cell anemia pain association is limited to females (OR 2.69; 95% CI 1.21–5.94; P = 0.01) and has the opposite directional association described in Europeans independent of global admixture. The presence of a GCH1 haplotype with high BH4 in populations of African ancestry could explain the association of rs8007267 with sickle cell anemia pain crises. The vascular effects of GCH1 and BH4 may also have broader implications for cardiovascular disease in populations of African ancestry. Am. J. Hematol. 89:187–193, 2014. © 2013 Wiley Periodicals, Inc.     

Growth and function in childhood of a normal solitary kidney from birth or from early infancy

Background

Children with a solitary kidney (SK) have an increased long-term risk of hypertension, albuminuria and glomerulosclerosis. In this study, we assessed the early signs of impaired glomerular filtration in children with a SK from birth or from early infancy.

Methods

Renal growth and function at ages 4–15.5 years were studied in 38 children with SK and 40 matched control subjects in terms of accelerated growth.

Results

The systolic/diastolic blood pressure Z-scores (p?=?0.01/<0.05) and the resistance index (RI) of the arcuate arteries (p?=?0.05) were higher in the children with SK. Creatinine clearance and 24-h protein and albumin urinary excretion showed no difference. All but seven children with SK had 99mTc diethylene-triamine pentaacetic acid glomerular filtration rate values of >80 ml/min/1.73 m². An independent positive correlation was found between length of the follow-up time and 24-h albumin urinary excretion (β?=?0.54, p?<?0.01). Accelerated postnatal growth was positively related with kidney volume (β?=?0.35, p?<?0.05).

Conclusions

Among our patient cohort, renal function was well preserved at ages 4–15.5 years in children who were born with a SK. However, both their higher blood pressure and RI and the correlation of 24-h albumin urinary excretion with length of follow-up time underline the need for monitoring to detect early signs of glomerular hyperfiltration and, if necessary, implement timely intervention. SK hypertrophy was found to be correlated with postnatal growth.     

提高孕产期保健质量是降低贫困地区壮族妇女孕产妇死亡的有力措施

目的 :提高贫困地区壮族农村住院分娩率 ,加强产时保健 ,提高贫困地区壮族农村产科质量 ,降低产后出血死亡率。在广西 30个老少边山穷地区 ,以项目和“母亲安全工程”为载体 ,在经济条件困难 ,基础设施落后 ,围产保健服务管理滞后的情况下 ,积极贯彻落实《母婴保健法》,依法规范围产保健服务管理 ,多方筹措资金 ,加强产科软、硬件建设 ,以项目工作为龙头 ,以科研为先导 ,积极推广适宜技术。以健康促进为目的 ,大力开展健康教育和生殖保健活动 ,使围产保健工作取得了较好成绩。30个贫困地区壮族农村近半数以上乡卫生院产科建设已达自治区标准 ,基本能满足贫困地区农民住院分娩的需求 ,并带动广西妇幼卫生工作的发展