Sulfotransferase 1C2 Increases Mitochondrial Respiration by Converting Mitochondrial Membrane Cholesterol to Cholesterol Sulfate.

Hypothesis: In this communication, we test the hypothesis that sulfotransferase 1C2 (SULT1C2, UniProt accession no. Q9WUW8) can modulate mitochondrial respiration by increasing state-III respiration.

Methods And Results: Using freshly isolated mitochondria, the addition of SULT1C2 and 3-phosphoadenosine 5 phosphosulfate (PAPS) results in an increased maximal respiratory capacity in response to the addition of succinate, ADP, and rotenone.

Margin ACcentuation for resectable Pancreatic cancer using Irreversible Electroporation - Results from the MACPIE-I study.

Introduction: Margin accentuation (MA) using Irreversible electroporation (IRE) offers an unique opportunity to reduce the R1 resections in resectable pancreatic cancer (RPC). This study aims to assess the rate of margin positivity using IRE for MA during pancreaticoduodenectomy (PD) for resectable pancreatic head tumours.

Materials And Methods: Following ethical approval, MA using IRE was carried out in 20 consecutive patients to posterior and superior mesenteric vein (SMV) margin, and the pancreatic neck, prior to the PD resection.

Selective Phosphodiesterase 1 Inhibitor BTTQ Reduces Blood Pressure in Spontaneously Hypertensive and Dahl Salt Sensitive Rats: Role of Peripheral Vasodilation.

Regulation of the peripheral vascular resistance via modulating the vessel diameter has been considered as a main determinant of the arterial blood pressure. Phosphodiesterase enzymes (PDE1-11) hydrolyse cyclic nucleotides, which are key players controlling the vessel diameter and, thus, peripheral resistance. Here, we have tested and reported the effects of a novel selective PDE1 inhibitor (BTTQ) on the cardiovascular system.

Kidney surveillance in the spotlight: contrast-induced acute kidney injury illuminated.

Acute kidney injury comprises a heterogeneous group of conditions characterized by a sudden decrease in renal function over hours to days. Contrast-induced acute kidney injury (CI-AKI) is caused by radiographic contrast agents used in diagnostic imaging. In the current issue of the JCI, Lau et al.

Exogenous Gene Transmission of Isocitrate Dehydrogenase 2 Mimics Ischemic Preconditioning Protection.

Ischemic preconditioning confers organ-wide protection against subsequent ischemic stress. A substantial body of evidence underscores the importance of mitochondria adaptation as a critical component of cell protection from ischemia. To identify changes in mitochondria protein expression in response to ischemic preconditioning, we isolated mitochondria from ischemic preconditioned kidneys and sham-treated kidneys as a basis for comparison.

Hydrodynamic Isotonic Fluid Delivery Ameliorates Moderate-to-Severe Ischemia-Reperfusion Injury in Rat Kidneys.

Highly aerobic organs like the kidney are innately susceptible to ischemia-reperfusion (I/R) injury, which can originate from sources including myocardial infarction, renal trauma, and transplant. Therapy is mainly supportive and depends on the cause(s) of damage. In the absence of hypervolemia, intravenous fluid delivery is frequently the first course of treatment but does not reverse established AKI.

A wandering path toward prevention for acute kidney injury.

Acute kidney injury (AKI) is a common cause of hospital-related mortality; therefore, strategies to either prevent or treat this complication are of great interest. In this issue of the JCI, Inoue, Abe, and colleagues have uncovered a targetable neuroimmunomodulatory mechanism that protects mice from ischemia-reperfusion injury (IRI) and subsequent AKI. Specifically, the authors demonstrate that vagus nerve stimulation (VNS) activates the cholinergic antiinflammatory pathway (CAP), resulting in activation of antiinflammatory effects via α7 nicotinic acetylcholine receptor-expressing splenic macrophages.

Severn School of Psychiatry education fellowships: a new way to promote educational practice and research.

This paper describes a model of training in leadership and project management skills for advanced trainees, using educational projects within the Severn School of Psychiatry. Fellowships lasting 1 year have been developed to enable trainees, working with a senior consultant trainer associated with the School of Psychiatry, to support important new educational initiatives. Linkage with the local university training and learning for health professionals research module has provided academic support for the trainees and the projects.

Benign histology after pancreaticoduodenectomy for suspected malignancy. Lessons to be learned--a single centre experience.

Unlabelled: The aim of the study was to perform a comprehensive analysis of patients with a benign final histology after pancreaticoduodenectomies (PD) for suspected pancreatic and periampullary cancer.

Material And Methods: We searched the pathology database at the King's College Hospital for negative PD specimens submitted between January 2004-December 2010. Clinical, diagnostic, surgical,histopathological and outcome data were collected retrospectively.

A systems life cycle approach to managing the radiology profession: an Australian perspective.

Objective: Although the medical system has expanded considerably over the past two decades in almost all countries, so too has the demand for health care. The radiology specialisation may be an early system indicator, being especially sensitive to changes in supply and demand in both rural and urban environments. The question is whether the new policies of increasing the number of radiologists can be a proper long-term solution for the imbalance of workforce supply and demand or not.

A regional teaching fellow community of practice.

Background: Increasing numbers of clinical teaching fellows are responsible for a significant proportion of undergraduate teaching nationally. Developing a regional community of practice can help overcome the isolation of these posts, with potential benefits for all involved.

Context: A community of practice relies on the mutual engagement of people in a similar situation working towards a common goal.

Improved outcome of severe acute pancreatitis in the intensive care unit.

Background. Severe acute pancreatitis (SAP) is associated with serious morbidity and mortality. Our objective was to describe the case mix, management, and outcome of patients with SAP receiving modern critical care in the Intensive Care Unit (ICU).

A method to facilitate and monitor expression of exogenous genes in the rat kidney using plasmid and viral vectors.

Gene therapy has been proposed as a novel alternative to treat kidney disease. This goal has been hindered by the inability to reliably deliver transgenes to target cells throughout the kidney, while minimizing injury. Since hydrodynamic forces have previously shown promising results, we optimized this approach and designed a method that utilizes retrograde renal vein injections to facilitate transgene expression in rat kidneys.

Utility of drain fluid amylase measurement on the first postoperative day after pancreaticoduodenectomy.

Background: Early detection of pancreatic fistula (PF) may improve the outcome after pancreaticoduodenectomy, and exclusion of PF may allow earlier drain removal and accelerate recovery. The aim of the present study was to evaluate the relationship between drain fluid amylase on the first postoperative day (DFA(1)) and PF.

Patients And Methods: This work was designed as a prospective study and included patients undergoing pancreaticoduodenectomy in a single center.

Dishevelled-associated activator of morphogenesis 1 (Daam1) is required for heart morphogenesis.

Dishevelled-associated activator of morphogenesis 1 (Daam1), a member of the formin protein family, plays an important role in regulating the actin cytoskeleton via mediation of linear actin assembly. Previous functional studies of Daam1 in lower species suggest its essential role in Drosophila trachea formation and Xenopus gastrulation. However, its in vivo physiological function in mammalian systems is largely unknown.

RhoA/Rho kinase (ROCK) alters fetuin-A uptake and regulates calcification in bovine vascular smooth muscle cells (BVSMC).

RhoA/Rho kinases (ROCK) play a critical role in vascular smooth muscle cell (VSMC) actin cytoskeleton organization, differentiation, and function and are implicated in the pathogenesis of cardiovascular disease. We have previously determined that an important step in the regulation of calcification is fetuin-A endocytosis, a process that is dependent on changes in the cytoskeleton, which, in turn, is known to be affected by the RhoA/ROCK signaling pathway. In the present study, bovine VSMC (BVSMC) were treated with the ROCK inhibitor Y-27632 or transfected with ROCK small interfering (si) RNA to knock down ROCK expression.

A possible variant of Bouveret's syndrome presenting as a duodenal stump obstruction by a gallstone after Roux-en-Y gastrectomy: a case report.

Introduction: Bouveret's syndrome is characterized by gastric outlet obstruction due to a gallstone in the duodenum, usually in association with a cholecystoduodenal fistula.

Case Presentation: We report the case of a 69-year-old Caucasian man who developed duodenal stump obstruction due to an impacted gallstone after having previously undergone Roux-en-Y gastrectomy.

Conclusions: Duodenal stump obstruction after Roux-en-Y gastrectomy is rare, and may be difficult to manage.

siRNA targeted to p53 attenuates ischemic and cisplatin-induced acute kidney injury.

Proximal tubule cells (PTCs), which are the primary site of kidney injury associated with ischemia or nephrotoxicity, are the site of oligonucleotide reabsorption within the kidney. We exploited this property to test the efficacy of siRNA targeted to p53, a pivotal protein in the apoptotic pathway, to prevent kidney injury. Naked synthetic siRNA to p53 injected intravenously 4 h after ischemic injury maximally protected both PTCs and kidney function.

Cytokine-induced F-actin reorganization in endothelial cells involves RhoA activation.

Acute ischemic kidney injury results in marked increases in local and systemic cytokine levels. IL-1alpha, IL-6, and TNF-alpha orchestrate various inflammatory reactions influencing endothelial permeability by altering cell-to-cell and cell-to-extracellular matrix attachments. To explore the role of actin and the regulatory proteins RhoA and cofilin in this process, microvascular endothelial cells (MS1) were exposed to individual cytokines or a cytokine cocktail.

A fluorescently tagged C-terminal fragment of p47phox detects NADPH oxidase dynamics during phagocytosis.

The assembly of cytosolic p47(phox) and p67(phox) with flavocytochrome b(558) at the membrane is crucial for activating the leukocyte NADPH oxidase that generates superoxide for microbial killing. p47(phox) and p67(phox) are linked via a high-affinity, tail-to-tail interaction involving a proline-rich region (PRR) and a C-terminal SH3 domain (SH3b), respectively, in their C-termini. This interaction mediates p67(phox) translocation in neutrophils, but is not required for oxidase activity in model systems.

p21-activated kinase regulates mast cell degranulation via effects on calcium mobilization and cytoskeletal dynamics.

Mast cells are key participants in allergic diseases via activation of high-affinity IgE receptors (FcepsilonRI) resulting in release of proinflammatory mediators. The biochemical pathways linking IgE activation to calcium influx and cytoskeletal changes required for intracellular granule release are incompletely understood. We demonstrate, genetically, that Pak1 is required for this process.

Fc gamma R-stimulated activation of the NADPH oxidase: phosphoinositide-binding protein p40phox regulates NADPH oxidase activity after enzyme assembly on the phagosome.

The phagocyte NADPH oxidase generates superoxide for microbial killing, and includes a membrane-bound flavocytochrome b(558) and cytosolic p67(phox), p47(phox), and p40(phox) subunits that undergo membrane translocation upon cellular activation. The function of p40(phox), which binds p67(phox) in resting cells, is incompletely understood. Recent studies showed that phagocytosis-induced superoxide production is stimulated by p40(phox) and its binding to phosphatidylinositol-3-phosphate (PI3P), a phosphoinositide enriched in membranes of internalized phagosomes.

Bilateral retrovascular femoral hernia.

A 34-year-old woman with cystic fibrosis presented with bilateral femoral hernias, which were found to be retrovascular at operation. The hernias were not amenable to conventional open or laparoscopic repair, and were repaired using pre-peritoneal mesh inserted deep to transversalis fascia. The anatomical basis and management of uncommon variants of femoral hernia are discussed.