Blood glucose control in patients with severe sepsis and septic shock

The main pathophysiological feature of sepsis is the uncontrollable activation of both pro-and anti-inflammatory responses arising from the overwhelming pro-duction of mediators such as pro-and anti-inflammatory cytokines. Such an uncontrollable inflammatory response would cause many kinds of metabolic derangements. One such metabolic derangement is hyperglycemia. Accordingly, control of hyperglycemia in sepsis is considered to be a very effective therapeutic approach. However, despite the initial enthusiasm, recent studies reported that tight glycemic control with intensive insulin therapy failed to show a beneficial effect on mortality of patients with severe sepsis and septic shock. One of the main reasons for this disappointing result is the incidence of harmful hypoglycemia during intensive insulin therapy. Therefore, avoidance of hypoglycemia during intensive insulin therapy may be a key issue in effective tight glycemic control. It is generally accepted that glycemic control aimed at a blood glucose level of 80-100 mg/dL, as initially proposed by van den Berghe, seems to be too tight and that such a level of tight glycemic control puts septic patients at increased risk of hypoglycemia. Therefore, now many researchers suggest less strict glycemic control with a target blood glucose level of 140-180 mg/dL. Also specific targeting of glycemic control in diabetic patients should be considered. Since there is a significantcorrelation between success rate of glycemic control and the degree of hypercytokinemia in septic patients, some countermeasures to hypercytokinemia may be an important aspect of successful glycemic control. Thus, in future, use of an artificial pancreas to avoid hypoglycemia during insulin therapy, special consideration of septic diabetic patients, and control of hypercytokinemia should be considered for more effective glycemic control in patients with severe sepsis and septic shock.

Molecular basis of cleft palates in mice

Cleft palate, including complete or incomplete cleft palates, soft palate clefts, and submucosal cleft palates, is the most frequent congenital craniofacial anomaly in humans. Multifactorial conditions, including genetic and environmental factors, induce the formation of cleft palates. The process of palatogenesis is temporospatially regulated by transcription factors, growth factors, extracellular matrix proteins, and membranous molecules; a single ablation of these molecules can result in a cleft palate in vivo. Studies on knockout mice were reviewed in order to identify genetic errors that lead to cleft palates. In this review, we systematically describe these mutant mice and discuss the molecular mechanisms of palatogenesis.

Identification of shared and unique gene families associated with oral clefts

Oral clefts, the most frequent congenital birth defects in humans, are multifactorial disorders caused by genetic and environmental factors. Epidemiological studies point to different etiologies underlying the oral cleft phenotypes, cleft lip(CL),CL and/or palate(CL/P) and cleft palate(CP). More than 350 genes have syndromic and/or nonsyndromic oral cleft associations in humans. Although genes related to genetic disorders associated with oral cleft phenotypes are known, a gap between detecting these associations and interpretation of their biological importance has remained. Here, using a gene ontology analysis approach, we grouped these candidate genes on the basis of different functional categories to gain insight into the genetic etiology of oral clefts. We identified different genetic profiles and found correlations between the functions of gene products and oral cleft phenotypes. Our results indicate inherent differences in the genetic etiologies that underlie oral cleft phenotypes and support epidemiological evidence that genes associated with CL/P are both developmentally and genetically different from CP only, incomplete CP, and submucous CP. The epidemiological differences among cleft phenotypes may reflect differences in the underlying genetic causes. Understanding the different causative etiologies of oral clefts is important as it may lead to improvements in diagnosis, counseling, and prevention.