Delta cell secretory responses to insulin secretagogues are not mediated indirectly by insulin.

Aims/hypothesis: Somatostatin from islet delta cells inhibits insulin and glucagon secretion, but knowledge of the regulation of pancreatic somatostatin release is limited. Some insulin secretagogues stimulate somatostatin secretion, and here we investigated whether delta cell secretory responses are indirectly regulated in a paracrine manner by insulin released from beta cells.

Methods: Hormone release from static incubations of primary mouse islets or somatostatin-secreting TGP52 cells was measured by RIA.

Role of the D-loops in allosteric control of ATP hydrolysis in an ABC transporter.

ABC transporters couple ATP hydrolysis to movement of substrates across cell membranes. They comprise two transmembrane domains and two cytosolic nucleotide-binding domains forming two active sites that hydrolyze ATP cooperatively. The mechanism of ATP hydrolysis is controversial and the structural dynamic basis of its allosteric control unknown.

Excitotoxic perirhinal cortex lesions leave stimulus-specific habituation of suppression to lights intact.

Previous experiments demonstrate a normal decline in unconditioned responding in rats with perirhinal cortex lesions but attenuated performance on spontaneous object recognition (SOR), a finding supporting the assertion that distinct systems support these phenomena. This finding informs on the nature of these two fundamental forms of learning and may be taken as support for certain contemporary theories of memory. However, we cannot quantify the relative contributions of genuine habituation and alternative, trivial sources in response decline from effector fatigue and sensory adaptation in these demonstrations.

Nano-scale encapsulation enhances allograft survival and function of islets transplanted in a mouse model of diabetes.

Aims/hypothesis: The success of islet transplantation as a treatment for type 1 diabetes is currently hampered by post-transplantation loss of functional islets through adverse immune and non-immune reactions. We aimed to test whether early islet loss can be limited and transplant survival improved by the application of conformal nano-coating layers to islets.

Methods: Our novel coating protocol used alternate layers of phosphorylcholine-derived polysaccharides (chitosan or chondroitin-4-sulphate) and alginate as coating materials, with the binding based on electrostatic complexation.

The Plasmodium falciparum malaria M1 alanyl aminopeptidase (PfA-M1): insights of catalytic mechanism and function from MD simulations.

Malaria caused by several species of Plasmodium is major parasitic disease of humans, causing 1-3 million deaths worldwide annually. The widespread resistance of the human parasite to current drug therapies is of major concern making the identification of new drug targets urgent. While the parasite grows and multiplies inside the host erythrocyte it degrades the host cell hemoglobin and utilizes the released amino acids to synthesize its own proteins.

GPR54 peptide agonists stimulate insulin secretion from murine, porcine and human islets.

This study was designed to determine the effects of 10 and 13 amino acid forms of kisspeptin on dynamic insulin secretion from mammalian islets since it is not clear from published data whether the shorter peptide is stimulatory while the longer peptide inhibits insulin release. Insulin secretion was measured by radioimmunoassay following perifusion of human, pig, rat and mouse isolated islets with kisspeptin-10 or kisspeptin-13 in the presence of 20 mM glucose. Both peptides stimulated rapid, reversible potentiation of glucose-stimulated insulin secretion from islets of all species tested.

Automated coring and apical connector insertion device for aortic valve bypass surgery.

Purpose: The technical difficulty of performing the left ventricular apical anastomosis has limited the adoption of aortic valve bypass surgery for the treatment of aortic stenosis. We report the successful use of an automated coring and apical connector device to perform aortic valve bypass surgery.

Description: A 74-year-old man, with a history of prior coronary bypass surgery with patent grafts and a porcelain ascending aorta, presented with symptomatic critical aortic stenosis.

Type II ABC permeases: are they really so different?

Structural and biochemical data reported by Tirado-Lee et al. (2011) in this issue of Structure reveal the existence of high and low affinity ABC transporters for the same substrate in a single organism, thus raising questions about structural and mechanistic differences within the ABC superfamily.

The Flex-Tip™ tracheal tube does not reduce the incidence of postoperative sore throat: a randomized controlled trial.

Purpose: Sore throat after tracheal intubation is common with an incidence of 30-70%. The Parker Flex-Tip™ endotracheal tube (ETT) is designed to reduce trauma during ETT placement. This randomized single-blinded trial was designed to assess whether using the Flex-Tip ETT would reduce the incidence of postoperative sore throat and/or vocal change.

Functional analysis of human islets of Langerhans maintained in culture.

Islets of Langerhans isolated from experimental animals, such as mice and rats, have contributed much to our understanding of the mechanisms by which pancreatic β-cells secrete insulin in a regulated manner, and this knowledge is important in identifying potential novel therapies for Type 2 diabetes. However, although many of the signal transduction pathways identified in rodent islets are common to humans, some critical differences have been demonstrated experimentally. It is, therefore, essential that experiments are performed using islets isolated from human pancreas to provide robust data defining whether the key observations made in rodents are also applicable to the human situation.

Insulin-producing surrogate β-cells from embryonic stem cells: are we there yet?

Embryonic stem cells (ESCs) harbor the potential to generate every cell type of the body by differentiation. The use of hESCs holds great promise for potential cell replacement therapies for degenerative diseases including diabetes mellitus. The recently discovered induced pluripotent stem cells (iPSCs) exhibit immense potential for regenerative medicine as they allow the generation of autologous cells tailored to the patients' immune system.

Clinical applications of 3-hydroxy fatty acid analysis by gas chromatography-mass spectrometry.

Background: L-3-Hydroxy fatty acids are unusual metabolites and rarely occur in significant quantities in normal human physiology. Genetic defects of both long-chain and medium-/short-chain mitochondrial L-3 hydroxyacyl coenzyme A dehydrogenases (LCHAD, M/SCHAD) have been identified as significant metabolic diseases in humans often with severe clinical phenotypes and pathophysiology that appears to differ from other defects of straight chain fatty acid oxidation. It is felt that accumulation of these atypical fatty acid species may play a role in this pathology.

Differences in disease presentation, treatment outcomes, and toxicities in African American patients treated with radiation therapy for prostate cancer.

Objectives: We analyzed differences in disease presentation, outcomes, and toxicities between African American (AA) and White (W) men treated with definitive radiation therapy for their prostate cancer.

Methods: Three thousand one hundred eighty cases of prostate cancer treated with various radiation modalities at a single institution were reviewed. The cohort consisted of 92% W patients and 8% AA patients.

Molecular-dynamics simulations of the ATP/apo state of a multidrug ATP-binding cassette transporter provide a structural and mechanistic basis for the asymmetric occluded state.

ATP-binding cassette transporters use the energy of ATP hydrolysis to transport substrates across cellular membranes. They have two transmembrane domains and two cytosolic nucleotide-binding domains. Biochemical studies have characterized an occluded state of the transporter in which nucleotide is tenaciously bound in one active site, whereas the opposite active site is empty or binds nucleotide loosely.

Stem cells and the endocrine pancreas.

Background: Diabetes can be treated by β-cell replacement therapy but the supply of graft material from human donors is too limited to make a significant clinical impact. Substitute β-cells generated from stem cell populations offer a potential source for the large numbers of cells required.

Sources Of Data: Primary peer-reviewed reports of experimental studies.

Cannabinoid receptor agonists and antagonists stimulate insulin secretion from isolated human islets of Langerhans.

Aims: The role of cannabinoid receptors in human islets of Langerhans has not been investigated in any detail, so the current study examined CB1 and CB2 receptor expression by human islets and the effects of pharmacological cannabinoid receptor agonists and antagonists on insulin secretion.

Methods: Human islets were isolated from pancreases retrieved from heart-beating organ donors. Messenger RNAs encoding human CB1 and CB2 receptors were amplified from human islet RNA by RT-PCR and receptor localization within islets was identified by immunohistochemistry.

Down-regulation of proliferation does not affect the secretory function of transformed β-cell lines regardless of their anatomical configuration.

Aims And Objectives: Proliferation in transformed β-cell lines is high compared to primary islet cells and is accompanied by reduced insulin content and release. Our aim was to determine whether experimental reduction of proliferation restores the cells to a more authentic β-cell phenotype in terms of secretory function and to investigate the potential beneficial effect of their configuration as islet-like structures.

Results: Mitosis inhibitor mitomycin c treatment neither altered the rate of proliferation nor improved the secretory responses of MIN6 monolayer cells.

Overshadowing and associability change.

Three appetitive Pavlovian conditioning experiments with rats examined the associability of stimuli A and B that had a history of compound conditioning (AB+), relative to stimuli X and Y that had a history of conditioning in isolation (X+, Y+). Following this training, Experiment 1 revealed that conditioned responding was higher to X and Y than to A and B (overshadowing). In a subsequent AY+, AX-, BY- test discrimination, the AY/BY discrimination was solved more readily than the AY/AX discrimination.

Collagenolytic activities of the major secreted cathepsin L peptidases involved in the virulence of the helminth pathogen, Fasciola hepatica.

Background: The temporal expression and secretion of distinct members of a family of virulence-associated cathepsin L cysteine peptidases (FhCL) correlates with the entry and migration of the helminth pathogen Fasciola hepatica in the host. Thus, infective larvae traversing the gut wall secrete cathepsin L3 (FhCL3), liver migrating juvenile parasites secrete both FhCL1 and FhCL2 while the mature bile duct parasites, which are obligate blood feeders, secrete predominantly FhCL1 but also FhCL2.

Methodology/principal Findings: Here we show that FhCL1, FhCL2 and FhCL3 exhibit differences in their kinetic parameters towards a range of peptide substrates.

Calcium/calmodulin-dependent kinase IV controls glucose-induced Irs2 expression in mouse beta cells via activation of cAMP response element-binding protein.

Aims/hypothesis: Irs2, which is upregulated by glucose, is important for beta cell plasticity. Cyclic AMP response element-binding protein (CREB) stimulates beta cell Irs2 expression and is a major calcium/calmodulin-dependent kinase (CaMK)(IV) target in neurons. We therefore hypothesised that CaMK(IV) mediates glucose-induced Irs2 expression in beta cells via CREB activation.

Comparison of MAX-ACT and K-ACT values when using bivalirudin anticoagulation during minimally invasive hybrid off-pump coronary artery bypass graft surgery.

Objective: To compare the kaolin-activated coagulation time (K-ACT) to the MAX-ACT for monitoring anticoagulation with bivalirudin in patients undergoing hybrid off-pump coronary artery revascularization procedures.

Design: A prospective, observational study.

Setting: A cardiac surgical operating room of a university-affiliated hospital.

Co-transplantation of mesenchymal stem cells maintains islet organisation and morphology in mice.

Aims/hypothesis: Recent studies have shown that mesenchymal stem cells (MSCs) secrete several factors that improve survival and function of transplanted islets. Implantation of islets beneath the kidney capsule results in morphological changes, due to interactions of the graft with the host, thus impairing islet function. We co-transplanted MSCs with islets to determine their effects on the remodelling process and studied graft function in a mouse model of minimal islet mass.

Cue interactions in flavor preference learning: a configural analysis.

Four experiments showed that the preference normally established to a neutral flavor cue that was paired with maltodextrin was attenuated when that cue was conditioned in compound with another flavor--overshadowing. Furthermore, two experiments showed that the preference for a neutral flavor conditioned as part of a compound was further attenuated if the other element in that compound was separately paired with the reinforcer--blocking. These results stand in contrast to a number of previous compound flavor preference conditioning experiments, which have not revealed reliable cue competition effects.

Costus pictus extracts stimulate insulin secretion from mouse and human islets of Langerhans in vitro.

Plant-derived extracts have been used as folk remedies for Type 2 diabetes mellitus (T2DM) for many centuries, and offer the potential of cheap and readily available alternatives to conventional pharmaceuticals in developing countries. Extracts of Costus pictus (CP), a plant belonging to the Costaceae family, are reported to have antidiabetic activity in vivo. The exact molecular mode of action(s) of CP is unclear but the antihyperglycemic effect seen in animal studies was associated with dramatic increases in insulin secretion so in our study we have measured the effect of aqueous CP extract on insulin secretion in vitro from the MIN6 β-cell line and isolated mouse and human islets.

A randomized comparison of the GlideRite(®) Rigid Stylet to a malleable stylet for orotracheal intubation by novices using the GlideScope(®).

Purpose: A stylet is usually necessary when using the GlideScope(®) videolaryngoscope for orotracheal intubation. A special stylet, the GlideRite(®) Rigid Stylet (GRS), was designed for this purpose. A previous trial involving experienced operators showed that the GRS offered no performance improvement vs a standard malleable stylet (SMS).