Insulin Receptors

Much of the emphasis in the pathogenesis of diabetes mellitus has justifiably been placed on the endocrine gland, the pancreas. Extensive studies on the biosynthesis and release of insulin from the beta cell, bihormonal control of metabolism by insulin and glucagon, and more recently the role of somatostatin have attracted the attention of students of the subject; but considerable evidence exists to suggest at least some role of tissue resistance to insulin in the pathogenesis of this disorder. There have been many advocates for extra pancreatic factors causing diabetes. One of the first was Mirsky, who proposed that diabetes might be due to excessive amounts of hepatic insulinase, an enzyme which degrades insulin. Vallance-Owen suggested that a circulating insulin antagonist labeled synalbumin might be the cause of insulin resistance in diabetes. This factor was later shown to be an artifact. Others, such as Antoniades, proposed that insulin might circulate predominantly in a bound form in diabetic subjects and thus not exert full biologic activity

A Cyproheptadine-Reversible Defect in ACTH Control Persisting after Removal of the Pituitary Tumor in Cushing\u27s Disease

Abstract We studied two phases of cortisol feedback suppression of ACTH in nine patients who had had adrenalectomy for Cushing\u27s disease. Four had been treated by adrenalectomy alone and presumably had ACTH-secreting pituitary tumors. Five others were studied two or more years after transsphenoidal removal of an ACTH-secreting microadenoma. In both groups, cortisol-ACTH feedback during the first 30 minutes of cortisol infusion was abnormal; plasma ACTH fell only 2.7±2.6 per cent (mean ±S.E.), as compared with 28.0±10.1 per cent in five hypoadrenal controls (P\u3c0.01). The fall in ACTH during the second phase of cortisol infusion was similar in the patients and the controls. Cyproheptadine corrected the feedback abnormality occurring during the first phase in both groups of patients with Cushing\u27s disease; ACTH fell by 24.4±4.8 per cent (P\u3c0.005). Persistence of a cortisol-ACTH feedback abnormality after removal of the pituitary tumor in Cushing\u27s disease, as well as the correction by cyproheptadine, suggests that higher centers have a role in the pathophysiology of Cushing\u27s disease. (N Engl J Med. 1981; 305:1244–8.

Dopamine agonists and ischemic complications in Parkinson’s disease: a nested case–control study

Personalised Therapeutic

Hepatitis B virus infection in post-vaccination South Africa : occult HBV infection and circulating surface gene variants

No abstract availableNational Health Laboratory Services (NHLS)Research Trust [grant number: GRANT004_94329] and the Poliomyelitis Research Foundation (PRF) [grant number: 11/74 (MSc)].http://www.elsevier.com/locate/jcvhb201

A Novel Inhibitor of Human La Protein with Anti-HBV Activity Discovered by Structure-Based Virtual Screening and In Vitro Evaluation

Background: Over 350 million people worldwide are infected with hepatitis B virus (HBV), a major cause of liver failure and hepatocellular carcinoma. Current therapeutic agents are highly effective, but are also associated with development of viral resistance. Therefore, strategies for identifying other anti-HBV agents with specific, but distinctive mechanisms of action are needed. The human La (hLa) protein, which forms a stabilizing complex with HBV RNA ribonucleoprotein to promote HBV replication, is a promising target of molecular therapy. Aims: This study aimed to discover novel inhibitors of hLa that could inhibit HBV replication and expression. Methods: A multistage molecular docking approach was used to screen a Specs database and an in-house library against hLa binding sites. Sequential in vitro evaluations were performed to detect potential compounds with high scores in HepG2.2.15 cells. Results: Of the 26 potential compounds with high scores chosen for experimental verification, 12 had HBV DNA inhibition ratios of less than 50 % with P,0.05. Six had significant inhibition of HBV e antigen (HBeAg) levels, and 13 had significant inhibition of HBV surface antigen (HBsAg) levels by in vitro assays. Compounds HBSC-11, HBSC-15 and HBSC-34 (HBSC is system prefix for active compounds screened by the library) were selected for evaluation. HBSC-11 was found to have an obvious inhibitory effect on hLa transcription and expression

Mapping and monitoring carbon stocks with satellite observations: a comparison of methods

Mapping and monitoring carbon stocks in forested regions of the world, particularly the tropics, has attracted a great deal of attention in recent years as deforestation and forest degradation account for up to 30% of anthropogenic carbon emissions, and are now included in climate change negotiations. We review the potential for satellites to measure carbon stocks, specifically aboveground biomass (AGB), and provide an overview of a range of approaches that have been developed and used to map AGB across a diverse set of conditions and geographic areas. We provide a summary of types of remote sensing measurements relevant to mapping AGB, and assess the relative merits and limitations of each. We then provide an overview of traditional techniques of mapping AGB based on ascribing field measurements to vegetation or land cover type classes, and describe the merits and limitations of those relative to recent data mining algorithms used in the context of an approach based on direct utilization of remote sensing measurements, whether optical or lidar reflectance, or radar backscatter. We conclude that while satellite remote sensing has often been discounted as inadequate for the task, attempts to map AGB without satellite imagery are insufficient. Moreover, the direct remote sensing approach provided more coherent maps of AGB relative to traditional approaches. We demonstrate this with a case study focused on continental Africa and discuss the work in the context of reducing uncertainty for carbon monitoring and markets

Acute Hepatitis C Virus in an HIV Clinic: A Screening Strategy, Risk Factors, and Perception of Risk

Abstract Acute hepatitis C virus (HCV) infection is being acquired undetected among HIV-infected individuals. A practical way to regularly screen HIV-infected patients for acute HCV irrespective of perceived risk or symptoms is needed. We piloted implementation of an acute HCV screening strategy using routine HIV clinical care schedules and the least costly blood tests, in a Rhode Island HIV care center. Study participants had ongoing HCV risk, completed questionnaires encompassing risk behaviors and perception of risk, and were screened with quarterly alanine aminotransferase (ALT). ALT rise triggered HCV RNA testing, with pooled rather than individual specimen HCV RNA testing for underinsured participants. Participants were primarily older, collegeeducated men who have sex with men (MSM) with history of sexually transmitted infection other than HIV. One of 58 participants developed acute HCV in 50 person-years of observation for an annual incidence of 2.0% per year (95% confidence interval [CI] 0.05-11.1%). The majority (54%) of MSM did not perceive that traumatic sexual and drug practices they were engaging in put them at risk for HCV. Unprotected sex often occurred under the influence of drugs or alcohol. Self-reported HCV risk and participation in several risk behaviors declined during the study. It was possible to collect frequent ALTs in a busy HIV clinic with 71% of total projected ALTs obtained and 88% of participants having at least one ALT during the 9-month follow-up period. All instances of ALT rise led to reflexive HCV RNA testing. Tracking quarterly ALT for elevation to systematically prompt HCV RNA testing before seroconversion is a promising approach to screen for acute HCV in a real-world HIV clinical setting