Combining enteral with parenteral nutrition to improve postoperative glucose control.

The provision of parenteral nutrition (PN) to 'stressed' patients often results in hyperglycaemia, which may be detrimental. In animal models limited amounts of enteral nutrition (EN) improve intestinal integrity and stimulate intestinal incretin production, which may lead to improved glucose control. We set out to assess if combining EN with PN results in improved glucose homeostasis rather than PN given alone.

Unsaturated fatty acids as cytoprotective agents in the pancreatic beta-cell.

It is widely accepted that, in type 2 diabetes, elevated levels of free fatty acids and glucose contribute to a state of glucolipotoxicity in which beta-cell function declines and, ultimately, cell viability is compromised. This suggests that beta-cells do not readily tolerate chronic elevations in fatty acid levels. In vitro studies suggest, however, that beta-cells respond differentially to long chain fatty acids, such that saturated species are lipotoxic whereas long chain mono-unsaturated fatty acids can provide cytoprotection.

Mutations in FLVCR2 are associated with proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (Fowler syndrome).

Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (PVHH), also known as Fowler syndrome, is an autosomal-recessively inherited prenatal lethal disorder characterized by hydranencephaly; brain stem, basal ganglia, and spinal cord diffuse clastic ischemic lesions with calcifications; glomeruloid vasculopathy of the central nervous system and retinal vessels; and a fetal akinesia deformation sequence (FADS) with muscular neurogenic atrophy. To identify the molecular basis for Fowler syndrome, we performed autozygosity mapping studies in three consanguineous families. The results of SNP microarrays and microsatellite marker genotyping demonstrated linkage to chromosome 14q24.

"I got your back": friends' understandings regarding college student spring break behavior.

Behaviors that pose threats to safety and health, including binge drinking and unprotected sex, increase during a week-long break from university. Understandings with peers regarding these behaviors may be important for predicting behavior and related harms. College students (N = 651; 48% men) reported having understandings with their friends regarding alcohol use (59%) and sexual behavior (45%) during Spring Break.

Mutations in TTC37 cause trichohepatoenteric syndrome (phenotypic diarrhea of infancy).

Background & Aims: Trichohepatoenteric syndrome (THES) is an autosomal-recessive disorder characterized by life-threatening diarrhea in infancy, immunodeficiency, liver disease, trichorrhexis nodosa, facial dysmorphism, hypopigmentation, and cardiac defects. We attempted to characterize the phenotype and elucidate the molecular basis of THES.

Methods: Twelve patients with classic THES from 11 families had detailed phenotyping.

Mutations in SLC29A3, encoding an equilibrative nucleoside transporter ENT3, cause a familial histiocytosis syndrome (Faisalabad histiocytosis) and familial Rosai-Dorfman disease.

The histiocytoses are a heterogeneous group of disorders characterised by an excessive number of histiocytes. In most cases the pathophysiology is unclear and treatment is nonspecific. Faisalabad histiocytosis (FHC) (MIM 602782) has been classed as an autosomal recessively inherited form of histiocytosis with similarities to Rosai-Dorfman disease (RDD) (also known as sinus histiocytosis with massive lymphadenopathy (SHML)).

Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis.

Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes. These dominantly acting mutations prevent normal folding of proinsulin, which leads to beta-cell death through endoplasmic reticulum stress and apoptosis. We now report 10 different recessive INS mutations in 15 probands with neonatal diabetes.

G-protein coupled receptors mediating long chain fatty acid signalling in the pancreatic beta-cell.

It is increasingly clear that some of the effects of both free and derivatised long chain fatty acids in pancreatic beta-cells are mediated by a group of G-protein coupled receptors. Some of these display close structural homology while others are more divergent. This Commentary reviews the expression and functional roles of three such molecules, GPR40, GPR119 and GPR120.

Functional CB2 type cannabinoid receptors at CNS synapses.

To date, it has been thought that cannabinoid receptors in CNS are primarily of the CB1R subtype, with CB2R expressed only in glia and peripheral tissues. However, evidence for the expression of CB2 type cannabinoid receptors at neuronal sites in the CNS is building through anatomical localization of receptors and mRNA in neurons and behavioural studies of central effects of CB2R agonists. In the medial entorhinal area of the rat, we found that blockade of CB1R did not occlude suppression of GABAergic inhibition by the non-specific endogenous cannabinoid 2-AG, suggesting that CB1R could not account fully for the effects of 2-AG.

Human and rodent pancreatic beta-cells express IL-4 receptors and IL-4 protects against beta-cell apoptosis by activation of the PI3K and JAK/STAT pathways.

Secretion of pro-inflammatory cytokines is associated with loss of pancreatic beta-cell viability and cell death. IL-4 (interleukin-4) has been reported to mediate a protective effect against the loss of pancreatic beta-cells, and IL-4 receptors have been found in rat pancreatic beta-cells at both the RNA and the protein level. The aim of the present study was to investigate IL-4 receptor expression in human islet cells and to examine the signalling pathways by which IL-4 exerts its effects using the rat beta-cell lines, BRIN-BD11 and INS-1E.

The incubation and monitoring of cell viability in primary rat islets of Langerhans and pancreatic beta-cell lines.

This chapter describes a method to measure the viability of isolated intact islets of Langerhans from rat pancreas and considers the use of isolated islets and of pancreatic beta-cell lines to study cell viability following culture. The islet isolation method is based on the use of preparations of collagenase to selectively digest the bulk of the exocrine tissue while leaving the endocrine islets intact and separated from their surrounding acini. The islets can be obtained in relatively pure form and are suitable for use in hormone secretion assays as well as for measurement of cell viability.

An assessment of the long-term health outcome of renal transplant recipients in Ireland.

Background: Renal transplantation remains the preferred method of renal replacement therapy in terms of patient survival, quality of life and cost. However, patients have a high risk of complications ranging from rejection episodes, infection and cancer, amongst others.

Aims And Methods: In this study, we sought to determine the long-term health outcomes and preventive health measures undertaken for the 1,536 living renal transplant patients in Ireland using a self-reported questionnaire.

Pantothenate kinase-associated neurodegeneration (PKAN): molecular confirmation of a Turkish patient with a rare frameshift mutation in the coding region of the PANK2 gene.

Here we report the clinical, neuroimaging, and molecular findings of a classic pantothenate kinase-associated neurodegeneration (PKAN) patient of Turkish origin. Our patient is the first reported case of PKAN in Turkey with molecular genetic confirmation of the diagnosis. The frameshift mutation c.

Homozygous loss-of-function mutations in the gene encoding the dopamine transporter are associated with infantile parkinsonism-dystonia.

Genetic variants of the SLC6A3 gene that encodes the human dopamine transporter (DAT) have been linked to a variety of neuropsychiatric disorders, particularly attention deficit hyperactivity disorder. In addition, the homozygous Slc6a3 knockout mouse displays a hyperactivity phenotype. Here, we analyzed 2 unrelated consanguineous families with infantile parkinsonism-dystonia (IPD) syndrome and identified homozygous missense SLC6A3 mutations (p.

Initiation codon mutation in betaB1-crystallin (CRYBB1) associated with autosomal recessive nuclear pulverulent cataract.

Purpose: To identify the molecular basis for autosomal recessively inherited congenital non-syndromic pulverulent cataracts in a consanguineous family with four affected children.

Methods: An autozygosity mapping strategy using high density SNP microarrays and microsatellite markers was employed to detect regions of homozygosity. Subsequently good candidate genes were screened for mutations by direct sequencing.

Nanoscintillator conjugates as photodynamic therapy-based radiosensitizers: calculation of required physical parameters.

The recent demonstration of nanoscale scintillators has led to interest in the combination of radiation and photodynamic therapy. In this model, scintillating nanoparticles conjugated to photosensitizers and molecular targeting agents would enhance the targeting and improve the efficacy of radiotherapy and extend the application of photodynamic therapy to deeply seated tumors. In this study, we calculated the physical parameters required for these nanoparticle conjugates to deliver cytotoxic levels of singlet oxygen at therapeutic radiation doses, drawing on the published literature from several disparate fields.

The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes.

Aims/hypothesis: Evidence that the beta cells of human patients with type 1 diabetes can be infected with enterovirus is accumulating, but it remains unclear whether such infections occur at high frequency and are important in the disease process. We have now assessed the prevalence of enteroviral capsid protein vp1 (vp1) staining in a large cohort of autopsy pancreases of recent-onset type 1 diabetic patients and a range of controls.

Methods: Serial sections of paraffin-embedded pancreatic autopsy samples from 72 recent-onset type 1 diabetes patients and up to 161 controls were immunostained for insulin, glucagon, vp1, double-stranded RNA activated protein kinase R (PKR) and MHC class I.

Germline mutation in DOK7 associated with fetal akinesia deformation sequence.

Background: Fetal akinesia deformation sequence syndrome (FADS) is a heterogeneous disorder characterised by fetal akinesia and developmental defects including, in some case, pterygia. Multiple pterygium syndromes (MPS) are traditionally divided into prenatally lethal and non-lethal (such as Escobar) types. Previously, we and others reported that homozygous mutations in the fetal acetylcholine receptor gamma subunit (CHRNG) can cause both lethal and non-lethal MPS, demonstrating that pterygia resulted from fetal akinesia, and that mutations in the acetylcholine receptor subunits CHRNA1, CHRND, and Rapsyn (RAPSN) can also result in a MPS/FADS phenotype.

Fatty acids and beta-cell toxicity.

Purpose Of Review: The rising incidence of type 2 diabetes is due, in part, to the detrimental effects of certain fatty acids on pancreatic beta-cell function and viability. The present review examines recent advances in the understanding of the molecular mechanisms by which fatty acids influence the life and death of beta cells.

Recent Findings: There are important differences in the cytotoxic potential of fatty acids, with long-chain saturated molecules being the most potent.

Design, synthesis and structure-activity relationships of azole acids as novel, potent dual PPAR alpha/gamma agonists.

The design, synthesis and structure-activity relationships of a novel series of N-phenyl-substituted pyrrole, 1,2-pyrazole and 1,2,3-triazole acid analogs as PPAR ligands are outlined. The triazole acid analogs 3f and 4f were identified as potent dual PPARalpha/gamma agonists both in binding and functional assays in vitro. The 3-oxybenzyl triazole acetic acid analog 3f showed excellent glucose and triglyceride lowering in diabetic db/db mice.

Predicting mortality and uptake of renal replacement therapy in patients with stage 4 chronic kidney disease.

Background: Novel strategies are required to efficiently manage the increasing number of patients diagnosed with chronic kidney disease (CKD). We sought to identify factors predicting outcome in patients with stage 4 CKD and to determine whether low-risk patients could be managed in primary care.

Methods: We performed a two-centre, retrospective cohort study including 396 patients with stage 4 CKD referred to nephrology clinics from 1998 to 2002.

Analysis of islet inflammation in human type 1 diabetes.

The immunopathology of type 1 diabetes (T1D) has proved difficult to study in man because of the limited availability of appropriate samples, but we now report a detailed study charting the evolution of insulitis in human T1D. Pancreas samples removed post-mortem from 29 patients (mean age 11.7 years) with recent-onset T1D were analysed by immunohistochemistry.

Modulation of network oscillatory activity and GABAergic synaptic transmission by CB1 cannabinoid receptors in the rat medial entorhinal cortex.

Cannabinoids modulate inhibitory GABAergic neurotransmission in many brain regions. Within the temporal lobe, cannabinoid receptors are highly expressed, and are located presynaptically at inhibitory terminals. Here, we have explored the role of type-1 cannabinoid receptors (CB1Rs) at the level of inhibitory synaptic currents and field-recorded network oscillations.

Radiographic appearance of cardiogenic pulmonary oedema in 23 cats.

Objective: To describe the radiographic appearance of pulmonary oedema in cats with cardiac failure.

Methods: Thoracic radiographs of 23 cats presented to a first opinion practice with signs of cardiac failure were reviewed. All cats had tachypnoea and/or dyspnoea and enlarged left atrium on echocardiography.