Postprandial factor VII metabolism: the effect of the R353Q and 10 bp polymorphisms

Elevated levels of coagulation factor VII activity (FVIIc) are associated with increased risk of CHD. FVIIc is strongly determined by two polymorphisms (R353Q and 0/10 base pairs (bp)) and plasma triacylglycerol (TAG) concentrations. The Q and 10 bp polymorphisms show strong linkage disequilibrium and have been associated with lower levels of fasting FVII, but there has been little investigation of the effect of these genotypes on the postprandial FVII metabolism. The present study demonstrated that fasting activated factor VII (FVIIa) and factor VII antigen (FVIIag) levels were significantly lower in the heterozygotes carrying the Q and 10 bp alleles (n 12), than in the R/0 bp homozygotes (n 12) (43.0 (SE 4.8) v. 23.9 (SE 6.5) mU/ml and 85.7 (SE 5.4) v. 71.6 (SE 7.5)% respectively). During postprandial lipaemia there was a significant increase in FVIIa in R/0 bp homozygotes but not in the heterozygotes carrying the Q and 10 bp alleles. The proportion of FVIIa (FVIIa:FVIIag) increased in the homozygotes but not in the heterozygotes (2.04 (SE 0.35) v. 1.20 (SE 0.26) respectively). Therefore possession of the relatively common Q and 10 bp alleles is not associated with postprandial activation of FVII, which may in turn have a protective effect against CHD.     

Naturally occurring amino acid substitutions at Arg1174 in the human insulin receptor result in differential effects on receptor biosynthesis and hybrid formation, leading to discordant clinical phenotypes

Missense mutations in the tyrosine kinase domain of the human insulin receptor frequently result in a dominantly inherited form of insulin resistance. We noted a marked disparity in the clinical phenotypes of our study subjects with different missense mutations at the same residue (Arg1174) of the insulin receptor. Subjects with a tryptophan substitution (W) were only moderately hyperinsulinemic, whereas those with a glutamine substitution (Q) had severe clinical and biochemical insulin resistance. Studies were undertaken to explore the molecular mechanisms underlying these differences. Both W and Q mutant receptors bound insulin normally but were kinase inactive. The W mutation resulted in more rapid degradation of newly synthesized mutant receptor, which contrasted with the near-normal biosynthesis of the Q receptor. The propensity of the W receptor to form hybrids with the cotransfected wild-type (WT) receptor was also markedly impaired compared with the Q receptor, to an extent greater than could be explained by lower steady-state expression. Thus, the more clinically benign consequences of the heterozygous W mutant receptor are likely to relate to its impaired biosynthesis and/or reduced capacity to form hybrids with WT receptors. In addition to providing an explanation for the milder phenotype of 1174W versus 1174Q carriers, these studies provide further support for the notion that the dominant-negative effect of insulin receptor tyrosine kinase mutations involves the competition between inactive mutant homodimers and WT/mutant hybrids with active WT homodimers for both ligands and intracellular substrates.     

Factors causing malnutrition in patients with chronic uremia

There is abundant evidence that patients with chronic renal failure (CRF), including those treated by hemodialysis or peritoneal dialysis, have evidence of malnutrition with decreased body weight and subnormal values of serum proteins (suggesting a loss of visceral protein stores). Potential causes of an abnormal nutritional status that have been identified include an inadequate intake of protein or calories, an inability to activate the metabolic responses that are needed to achieve nitrogen and protein balance, or the presence of a disease that prevents activation of these metabolic responses or acts to stimulate the breakdown of body protein stores. Three critical metabolic responses to a limited protein intake have been identified: a reduction in the irreversible degradation of amino acids and the degradation of protein breakdown and an increase in protein synthesis in response to a meal. Metabolic acidosis blocks the first two responses and hence contributes to malnutrition in patients with chronic uremia. Other factors that could contribute to malnutrition include an inadequate intake because of anorexia or hormonal imbalances that impair protein turnover. In evaluating CRF patients with malnutrition, the first task is to ensure an adequate intake and to eliminate factors that impair the ability to achieve nitrogen balance.     

完全腹腔镜Roux—en—Y吻合术式应用于远端胃癌根治术20例

目的探讨完全腹腔镜Roux．en—Y吻合术式应用于远端胃癌根治术的安全性和可行性。方法回顾性分析福建省肿瘤医院腹部外科2012年8月至2013年3月对腹腔镜胃大部切除术后实施完全腹腔镜Roux．en—Y吻合术的20例胃癌患者的术中和术后临床资料。结果20例患者均成功实施完全腹腔镜远端胃癌根治术,无一例中转开腹或中转腹腔镜辅助手术。手术时间（190．8±53．6）min,术中出血量（122．4±57．7）ml,淋巴结清扫数（31．2±5．7）枚,术后病理切缘均为阴性。术后排气时间为（2．6±1．6）d,住院时间为（8．1±2．0）d。有1例术后出现肺部感染,但无吻合术相关并发症发生。结论完全腹腔镜Roux—en—Y吻合术式应用于远端胃癌根治术安全且可行。