The Biocompatibility Analysis of Artificial Mucin-Like Glycopolymers.

The ocular surface is covered by a tear film consisting of an aqueous/mucin phase and a superficial lipid layer. Mucins, highly O-glycosylated proteins, are responsible for lubrication and ocular surface protection. Due to contact lens wear or eye disorders, lubrication of the ocular surface can be affected. Artificial glycopolymers which mimic natural mucins could be efficient in ophthalmic therapy. Various neutral, positively, and negatively charged mucin-mimicking glycopolymers were synthesized (n = 11), cultured in different concentrations (1%, 0.1%, and 0.01% w/v) with human corneal epithelial cells (HCE), and analyzed by various cytotoxicity/viability, morphology, and immunohistochemistry (IHC) assays. Six of the eleven glycopolymers were selected for further analysis after cytotoxicity/viability assays. We showed that the six selected glycopolymers had no cytotoxic effect on HCE cells in the 0.01% w/v concentration. They did not negatively affect cell viability and displayed both morphology and characteristic markers as untreated control cells. These polymers could be used in the future as mucin-mimicking semi-synthetic materials for lubrication and protection of the ocular surface.

Pediatric liver transplantation for inherited metabolic liver disease: a single-center experience.

OBJECTIVE: We performed single-center outcome comparison of pediatric recipients who underwent liver transplantation for either genetic or metabolic disease including the clinical impact of using heterozygote parents as living donors. MATERIALS AND METHODS: Pediatric liver transplant recipients from September 2007 to December 2010 were included. Patients were separated into 2 categories by etiology of liver disease: (1) genetic or metabolic liver disease (G/M) and (2) nongenetic or metabolic liver disease (non-G/M), which included all other remaining etiologies combined. Patient demographics, recipient and donor characteristics, graft type, operative data, recipient complications, allograft and patient survival were analyzed. RESULTS: Forty liver transplants were performed on 40 patients; 18 were transplanted for G/M; mean waiting time was 101 days for G/M group and 57 days for non-G/M group; 9 patients were listed as status 1, 5 were granted PELD/MELD exceptions; the overall mean PELD/MELD score was 21. Four G/M patients had hepatocellular carcinoma in the explant without microvascular invasion. Overall complications requiring either surgery or interventional radiology occurred in 14 patients-G/M (n = 5); CMV viremia was seen in 11 patients (G/M, n = 1); detectable EBV DNA was detectable in 8 patients (G/M, n = 4), acute cellular rejection was seen in 10 (G/M, n = 5), postransplant lymphoproliferative disease occurred in 2 G/M patients; and 1 G/M patient showed significantly improved posttransplant neurologic motor function. Children with G/M who received a living donor liver transplant from heterozygote parents did well without any signs of expressing underlying metabolic disease. Posttransplant graft and patient overall survival at 12 months for G/M and non-G/M was 100%, and at 36 months, 83% and 100%, respectively. CONCLUSION: The majority of children transplanted for either genetic or metabolic disease were status 1 or awarded UNOS exception points. Cadaveric split livers and live donors including obligate heterozygotes resulted in excellent allograft and patient survival outcomes. In metabolic and genetic liver diseases, close follow-up and timely transplantation can preclude malignant spread and prevent disease progression and consequences, as well as reverse neurologic sequelae.

Cyclosporine-Induced neurotoxicity during treatment of Crohn's disease: lack of correlation with previously reported risk factors.

A 13-yr-old boy with severe Crohn's disease was admitted with persistent hematochezia requiring transfusion. Cyclosporine A was begun on hospital day 22 because of continued diarrhea and rectal bleeding despite high doses of i.v. corticosteroids. Six days into cyclosporine therapy, the patient developed multiple episodes of generalized tonic-clonic seizures accompanied with magnetic resonance imaging findings typical, although not pathognomonic, of cyclosporine A central nervous system neurotoxicity. Further investigations demonstrated that severe cyclosporine neurotoxicity may occur in the absence of previously reported clinical risk factors. Experience from the pediatric and adult GI transplant and neurological literature is discussed.

Role of thyroid hormone in stimulating liver repopulation in the rat by transplanted hepatocytes.

Recently, we reported near-complete repopulation of the rat liver by transplanted hepatocytes using retrorsine (RS), a pyrrolizidine alkaloid that alkylates cellular DNA and blocks proliferation of resident hepatocytes, followed by transplantation of normal hepatocytes in conjunction with two-thirds partial hepatectomy (PH). Because two-thirds PH is not feasible for use in humans, in the present study, we evaluated the ability of thyroid hormone (triiodothyronine [T(3)]), a known hepatic mitogen, to stimulate liver repopulation in the retrorsine model. Because T(3) initiates morphogenesis in amphibians through a process involving both cell proliferation and apoptosis, we also determined whether apoptosis might play a role in the mechanism of hepatocyte proliferation induced by T(3). Following hepatocyte transplantation and repeated injections of T(3), the number of transplanted hepatocytes in the liver of RS-pretreated animals increased progressively to repopulate 60% to 80% of parenchymal cell mass in 60 days. We show further that T(3) treatment augments proliferation of normal hepatocytes, as evidenced by increased histone 3 mRNA and cyclin-dependent kinase 2 (cdk2) expression, and this is followed by apoptosis. These combined effects of T(3) lead to selective proliferation of transplanted hepatocytes in RS-pretreated rats, while endogenous hepatocytes, which are blocked in their proliferative capacity by RS, mainly undergo apoptosis. Thus, T(3) can replace PH in the RS-based rat liver repopulation model and therefore represents a significant advance in developing methods for hepatocyte transplantation.