Delineation of glutamate pathways and secretory responses in pancreatic islets with β-cell-specific abrogation of the glutamate dehydrogenase.

In pancreatic β-cells, glutamate dehydrogenase (GDH) modulates insulin secretion, although its function regarding specific secretagogues is unclear. This study investigated the role of GDH using a β-cell-specific GDH knockout mouse model, called βGlud1(-/-). The absence of GDH in islets isolated from βGlud1(-/-) mice resulted in abrogation of insulin release evoked by glutamine combined with 2-aminobicyclo[2.

The [corrected] SEC23-SEC31 [corrected] interface plays critical role for export of procollagen from the endoplasmic reticulum.

COPII proteins are essential for exporting most cargo molecules from the endoplasmic reticulum. The membrane-facing surface of the COPII proteins (especially SEC23-SEC24) interacts directly or indirectly with the cargo molecules destined for exit. As we characterized the SEC23A mutations at the SEC31 binding site identified from patients with cranio-lenticulo-sutural dysplasia, we discovered that the SEC23-SEC31 interface can also influence cargo selection.

Transient receptor potential canonical channels are required for in vitro endothelial tube formation.

In endothelial cells Ca(2+) entry is an essential component of the Ca(2+) signal that takes place during processes such as cell proliferation or angiogenesis. Ca(2+) influx occurs via the store-operated Ca(2+) entry pathway, involving stromal interaction molecule-1 (STIM1) and Orai1, but also through channels gated by second messengers like the transient receptor potential canonical (TRPC) channels. The human umbilical vein-derived endothelial cell line EA.

Resveratrol-activated SIRT1 in liver and pancreatic β-cells: a Janus head looking to the same direction of metabolic homeostasis.

Sirtuins are energy sensors which mediate effects of calorie restriction-induced lifespan extension. The mammalian sirtuin homolog SIRT1 is a protein deacetylase playing a central role in metabolic homeostasis. SIRT1 is one of the targets of resveratrol, a polyphenol that has been shown to increase lifespan and to protect animal models against high-calorie diet induced obesity and insulin resistance.

Mechanisms of hepatitis C virus-related insulin resistance.

The hepatitis C virus (HCV) infection has been shown to have direct and/or indirect effects on glucose metabolism, leading to insulin resistance and, in predisposed individuals, type 2 diabetes. This is supported by several experimental, clinical and epidemiological data. The detailed molecular events leading to insulin resistance in HCV-infected patients are unclear.

Resveratrol potentiates glucose-stimulated insulin secretion in INS-1E beta-cells and human islets through a SIRT1-dependent mechanism.

Resveratrol, a polyphenol compound, is known for its effects on energy homeostasis. With properties of energy sensors mediating effects of calorie restriction, sirtuins are targets of resveratrol. The mammalian sirtuin homolog SIRT1 is a protein deacetylase playing a role in glucose metabolism and islet function.

From intraoperative angiography to advanced intraoperative imaging: the geneva experience.

Objective: We aimed at the integration of recent flat panel technology in a joint interventional suite for neurosurgeons and neuroradiologists.

Methods: A Flat Panel system, allowing for intraoperative performance of 2D and 3D DSA, for automated segmentation of vascular structures, and for performance of computed tomography, was connected with a surgical microscope and neuronavigation. All surgical and neurointerventional cases were monitored and stored in a prospective data base.

Hepatitis C virus-induced steatosis: an overview.

The pathogenesis of liver damage associated with the chronic hepatitis C virus (HCV) infection is largely immunomediated. However, some frequent histopathological features, such as fatty liver, suggest a direct cytopathic effect of HCV. The direct responsibility of HCV in the pathogenesis of steatosis is shown by: (1) the association with HCV genotype 3 infection, suggesting that some viral sequences are involved in the intracellular accumulation of triglycerides; (2) the correlation between the severity of steatosis and HCV replication levels; and (3) the association between the response to antivirals and the disappearance of steatosis.

Electrophysiological characterization of store-operated and agonist-induced Ca2+ entry pathways in endothelial cells.

In endothelial cells, agonist-induced Ca(2+) entry takes place via the store-operated Ca(2+) entry pathway and/or via channel(s) gated by second messengers. As cell stimulation leads to both a partial Ca(2+) store depletion as well as the production of second messengers, these two pathways are problematic to distinguish. We showed that passive endoplasmic reticulum (ER) depletion by thapsigargin or cell stimulation by histamine activated a similar Ca(2+)-release-activated Ca(2+) current (CRAC)-like current when 10 mM Ba(2+)/2 mM Ca(2+) was present in the extracellular solution.

Simultaneous bedside assessment of global cerebral blood flow and effective cerebral perfusion pressure in patients with intracranial hypertension.

Background: We examined a bedside technique transcerebral double-indicator dilution (TCID) for global cerebral blood flow (CBF) as well as the concept of effective cerebral perfusion pressure (CPP(eff)) during different treatment options for intracranial hypertension, and compared global CBF and CPP(eff) with simultaneously obtained conventional parameters.

Methods: Twenty-six patients developing intracranial hypertension in the course of traumatic brain injury or subarachnoid hemorrhage were prospectively analyzed using a combined assessment during elevated ventilation (n = 15) or osmotherapy (hypertonic saline or mannitol). For calculation of global CBF, injections of ice-cold indocyanine green boluses were performed and temperature and dye concentration changes were monitored in the thoracic aorta and the jugular bulb.

Peroxisome proliferator-activated receptor alpha (PPARalpha) protects against oleate-induced INS-1E beta cell dysfunction by preserving carbohydrate metabolism.

Aims/hypothesis: Pancreatic beta cells chronically exposed to fatty acids may lose specific functions and even undergo apoptosis. Generally, lipotoxicity is triggered by saturated fatty acids, whereas unsaturated fatty acids induce lipodysfunction, the latter being characterised by elevated basal insulin release and impaired glucose responses. The peroxisome proliferator-activated receptor alpha (PPARalpha) has been proposed to play a protective role in this process, although the cellular mechanisms involved are unclear.

Peroxisome proliferator-activated receptors and hepatitis C virus-induced insulin resistance.

Insulin resistance and type 2 diabetes are associated with hepatitis C virus infection. A wealth of clinical and experimental data suggests that the virus is directly interfering with the insulin signalling in hepatocytes. In the case of at least one viral genotype (the type 3a), insulin resistance seems to be directly mediated by the downregulation of the peroxisome proliferator-activated receptor gamma.

Hepatitis C viral kinetics in plasma and peripheral blood mononuclear cells during pegylated interferon-alpha2a/ribavirin therapy.

Background/aims: Analysis of hepatitis C virus (HCV) RNA kinetics in compartments other than plasma may help in understanding HCV replication and identifying clinically significant patterns of treatment response.

Methods: After 6 weeks of pegylated interferon-alpha2a/ribavirin therapy, 74 chronic hepatitis C patients were randomized to individualized or standard treatments for another 42 weeks. HCV RNA was quantified in peripheral blood mononuclear cells (PBMCs) by TaqMan-based real-time PCR and compared to plasma HCV RNA.

WITHDRAWN: Role of NCAM in Spine Dynamics and Synaptogenesis.

Increasing evidence indicates that adhesion molecules are critically involved in the regulation of mechanisms of synaptic plasticity including synapse formation, but also synaptic remodeling associated to changes in synaptic strength. Among these, the Neural Cell Adhesion Molecule (NCAM) and its polysialylated form PSA-NCAM are important candidates. Here we review recent results that point to a possible role of these two molecules in regulating the structural properties of excitatory synapses and namely the composition and stability of the postsynaptic density, thereby accounting for their contribution to mechanisms of synaptogenesis and activity-dependent synaptic plasticity.

Dual effect of cell-cell contact disruption on cytosolic calcium and insulin secretion.

Cell-to-cell interactions play an important role in insulin secretion. Compared with intact islets, dispersed pancreatic beta-cells show increased basal and decreased glucose-stimulated insulin secretion. In this study, we used mouse MIN6B1 cells to investigate the mechanisms that control insulin secretion when cells are in contact with each other or not.

The genetic basis of a craniofacial disease provides insight into COPII coat assembly.

Proteins trafficking through the secretory pathway must first exit the endoplasmic reticulum (ER) through membrane vesicles created and regulated by the COPII coat protein complex. Cranio-lenticulo-sutural dysplasia (CLSD) was recently shown to be caused by a missense mutation in SEC23A, a gene encoding one of two paralogous COPII coat proteins. We now elucidate the molecular mechanism underlying this disease.

Evidence for a receptor-activated Ca2+ entry pathway independent from Ca2) store depletion in endothelial cells.

Ca(2+) entry in endothelial cells is a key signaling event as it prolongs the Ca(2+) signal activated by a receptor agonist, and thus allows an adequate production of a variety of compounds. The possible routes that lead to Ca(2+) entry in non-excitable cells include the receptor-activated Ca(2+) entry (RACE), which requires the presence of an agonist to be activated, and the store-operated Ca(2+) entry (SOCE) pathway, whose activation requires the depletion of the ER Ca(2+) store. However, the relative importance of these two influx pathways during physiological stimulation is not known.

Ex vivo lentivirus transduction and immediate transplantation of uncultured hepatocytes for treating hyperbilirubinemic Gunn rat.

Background: Ex vivo liver gene therapy provides an attractive alternative to orthotopic liver transplantation for the treatment of liver diseases. We previously reported a protocol in which human primary hepatocytes are highly transduced in Suspension with Lentiviral vectors and Immediately Transplanted (SLIT). Here, we evaluated the SLIT approach in Gunn rats, the animal model for Crigler-Najjar syndrome type 1, a defect in bilirubin UDP-glucuronosyltransferase (BUGT).

The free serratus anterior flap and its cutaneous component for reconstruction of the face: a series of 27 cases.

Background: The serratus anterior flap is commonly used without its cutaneous component and is covered with a skin graft. The authors have successfully used the free serratus anterior flap along with its skin paddle and have found it to be valuable for reconstruction of the face.

Methods: Fresh cadaveric dissections and arteriography were performed to identify perforator vessels to the skin overlying the muscle.

Inducible expression of Snail selectively increases paracellular ion permeability and differentially modulates tight junction proteins.

Constitutive expression of the transcription factor Snail was previously shown to trigger complete epithelial-mesenchymal transition (EMT). The aim of this study was to determine whether inducible expression of Snail could modify epithelial properties without eliciting full mesenchymal conversion. For this purpose, we expressed mouse Snail (mSnail) cDNA in Madin-Darby canine kidney (MDCK) cells under the control of a doxycycline-repressible transactivator.