Hypoglycemia Following Pancreas Transplant: A Diagnostic Challenge in the Immediate Posttransplant Setting.

Few studies have described glucose metabolism in the immediate posttransplant period. Here, we report a 37-year-old female patient who had transient hypoglycemia after combined pancreas and kidney transplant for poorly controlled type 1 diabetes and renal failure. Although the patient's blood sugar decreased from 420 to less than 120 mg/dL and the kidney demonstrated graft function immediately posttransplant, at 19 hours after transplant, the patient's blood glucose decreased to below the normal range at a nadir of 59 mg/dL. When treated with intravenous dextrose, her blood glucose levels increased over 7 hours to 119 mg/dL but then again declined, appearing to follow a circadian rhythm, with hypoglycemia shown during early morning hours and then improving during the afternoon. This prompted treatment with a continuous infusion of 5% dextrose on day 2, resulting in blood sugar levels returning to normal by day 4 and discharge on day 6. She has since remained euglycemic. The differential diagnosis of hypoglycemia immediately after kidney-pancreas transplant is wide. Indeed, after we excluded ischemia-reperfusion injury, impaired renal clearance, insulin-associated antibodies, and lack of pancreatic innervation, we believe that cause was most likely due to impairment of early glucose counterregulatory responses or delayed alpha cell function.

HCV Genotype 6 Increased the Risk for Hepatocellular Carcinoma Among Asian Patients With Liver Cirrhosis.

OBJECTIVES: Hepatitis C virus (HCV) infection is a well-documented risk factor for hepatocellular carcinoma (HCC). Seven HCV genotypes have been classified, and the genotypes show a great variety of geographic distribution. HCV genotype 6 is prevalent in Southeast Asia and has been less studied than the other genotypes. METHODS: This follow-up study was designed to evaluate the natural history of HCV genotype 6. The cohort enrolled 851 Asian patients consisting of 222 with HCV genotype 6 and 629 with other genotypes. The incidence of HCC per 1,000 person-years of various HCV genotypes was estimated by dividing the new HCC cases to the person-years of follow-up. The adjusted hazards ratios (HRs) with 95% confidence intervals (CIs) were estimated by Cox's proportional hazards models. RESULTS: After 4072 person-years of follow-up, there were 96 newly-developed HCC cases, confirming an incidence of 23.6 per 1000 person-years. By stratifying cirrhosis at study entry, the cumulative risk of HCC among HCV genotype 6 vs. non-6 was 2.9 vs. 2.2% for those without cirrhosis (P=0.45) and 76.2% (95% CI: 55.6-96.8%) vs. 36.2% (95% CI: 28.7-39.1%) for those with cirrhosis (P<0.05), respectively. Among patients with cirrhosis, HCV genotype 6 was significantly associated with HCC compared to patients with non-6 genotypes, with the adjusted HR=2.12 (1.33-3.39), P<0.05. In a model treating patients with genotypes other than 1 or 6 as the reference, the adjusted HR for HCC for HCV genotypes 1 and 6 were 1.13 (0.56-2.27) and 2.34 (1.12-4.86), respectively. CONCLUSIONS: Among patients with cirrhosis, those with HCV genotype 6 infection should be given high priority for antiviral therapy to decrease HCC risk and for vigilant adherence to HCC surveillance.

DAPK interacts with Patronin and the microtubule cytoskeleton in epidermal development and wound repair.

Epidermal barrier epithelia form a first line of defense against the environment, protecting animals against infection and repairing physical damage. In C. elegans, death-associated protein kinase (DAPK-1) regulates epidermal morphogenesis, innate immunity and wound repair. Combining genetic suppressor screens and pharmacological tests, we find that DAPK-1 maintains epidermal tissue integrity through regulation of the microtubule (MT) cytoskeleton. dapk-1 epidermal phenotypes are suppressed by treatment with microtubule-destabilizing drugs and mimicked or enhanced by microtubule-stabilizing drugs. Loss of function in ptrn-1, the C. elegans member of the Patronin/Nezha/CAMSAP family of MT minus-end binding proteins, suppresses dapk-1 epidermal and innate immunity phenotypes. Over-expression of the MT-binding CKK domain of PTRN-1 triggers epidermal and immunity defects resembling those of dapk-1 mutants, and PTRN-1 localization is regulated by DAPK-1. DAPK-1 and PTRN-1 physically interact in co-immunoprecipitation experiments, and DAPK-1 itself undergoes MT-dependent transport. Our results uncover an unexpected interdependence of DAPK-1 and the microtubule cytoskeleton in maintenance of epidermal integrity.

The wounded worm: Using C. elegans to understand the molecular basis of skin wound healing.

The ability to heal wounds is an ancient and conserved function of epidermal epithelial layers. The importance of skin wound healing to human life and biology has long been evident, however many of the molecular mechanisms underlying wound repair remain little understood. In the past several years, analysis of the C. elegans innate immune response to fungal infection of the epidermis has led to investigations of the ability of the C. elegans skin to respond to damage. In a recent paper we used live imaging to investigate the cell biological basis of wound repair in the adult C. elegans epidermis. We found that needle or laser injury of the skin triggers a large and sustained increase in epidermal calcium. Epidermal calcium signals appear to specifically promote actin-dependent processes of wound closure. The innate immune and wound closure responses act in parallel to promote survival after injury. Our findings indicate that wounding triggers multiple signals in the C. elegans skin. C. elegans offers a tractable model to dissect how epidermal epithelia activate coordinated responses to repair damage.

The Caenorhabditis elegans epidermis as a model skin. I: development, patterning, and growth.

The skin of the nematode Caenorhabditis elegans is composed of a simple epidermal epithelium and overlying cuticle. The skin encloses the animal and plays central roles in body morphology and physiology; its simplicity and accessibility make it a tractable genetic model for several aspects of skin biology. Epidermal precursors are specified by a hierarchy of transcriptional regulators. Epidermal cells form on the dorsal surface of the embryo and differentiate to form the epidermal primordium, which then spreads out in a process of epiboly to enclose internal tissues. Subsequent elongation of the embryo into a vermiform larva is driven by cell shape changes and cell fusions in the epidermis. Most epidermal cells fuse in mid-embryogenesis to form a small number of multinucleate syncytia. During mid-embryogenesis the epidermis also becomes intimately associated with underlying muscles, performing a tendon-like role in transmitting muscle force. Post-embryonic development of the epidermis involves growth by addition of new cells to the syncytia from stem cell-like epidermal seam cells and by an increase in cell size driven by endoreplication of the chromosomes in epidermal nuclei.