In vivo and in vitro characterization of [18F]-FE-(+)-DTBZ as a tracer for beta-cell mass

IntroductionThe positron emission tomography (PET) tracer 9-[¹⁸F]fluoroethyl-(+)-dihydrotetrabenazine ([¹⁸F]-FE-(+)-DTBZ) is a potential candidate for quantifying beta-cell mass in vivo. The purpose was to investigate in vitro and in vivo utility of this tracer for the assessment of beta-cell mass.MethodsThree pigs were intravenously administered [¹⁸F]-FE-(+)-DTBZ and examined by PET/computed tomography. Binding parameters were estimated by kinetic modeling. In vitro k_D and B_max were determined by saturation binding studies of endocrine and exocrine human tissue homogenates. In vitro pancreatic uptake was determined by tissue autoradiography with pancreases from patients with types 1 (T1DM) and 2 diabetes mellitus (T2DM) and healthy controls.Results[¹⁸F]-FE-(+)-DTBZ had a k_D of 3.5±1.0 nM, a B_max of 382±108 fmol/mg protein and a specificity of 89±1.8% in islet homogenates. The total exocrine uptake was lower and 65% was nondisplaceable. No uptake difference was observed in pancreatic tissue slices from patients with T1DM, T2DM or healthy controls. The in vivo porcine pancreatic uptake reached a peak of standardized uptake value (SUV) of 2.8 with a low distribution volume ratio in all animals. Moderate to high tracer uptake was identified in the bile system and in bone.Conclusions[¹⁸F]-FE-(+)-DTBZ binds to vesicular monoamine transporter 2 (VMAT2) with high specificity in pure islet tissue in vitro. However, there is high nondisplaceable binding to exocrine tissue. In addition, in vivo tracer metabolism and dehalogenation result in severe underestimation of porcine pancreatic VMAT2 expression and BCM. The results do not support [¹⁸F]-FE-(+)-DTBZ as a suitable tracer for in vivo beta-cell imaging.     

Interaction of the hepatitis C virus (HCV) core with cellular genes in the development of HCV-induced steatosis

Hepatitis C virus (HCV) has chronically infected a large number of patients, leading to the development of steatosis, cirrhosis and, ultimately, hepatocellular carcinoma. The pathogenesis of HCV has not been fully explained, although steatosis is considered to contribute greatly to liver fibrosis progression, modulating host-cell lipid metabolism. Suspected underlying molecular mechanisms include interactions between HCV proteins and intracellular lipid metabolic pathways. Recent studies have suggested that the nucleocapsid of HCV (core) acts as a pathogenic factor involved in lipid droplet accumulation, changes in lipogenic gene expression and/or the activity of lipogenic proteins in a genotype-specific manner. In this review, we have tried to summarize the current knowledge regarding HCV-induced steatosis and the regulation of expression of host genes and receptors that aid in the viral life cycle and promote liver diseases.     

Fabrication of functionalized carbon nanotube modified glassy carbon electrode and its application for selective oxidation and voltammetric determination of cysteamine

The functionalized carbon nanotube electrode was fabricated by electrodeposition of 1,2-naphthoquinone-4-sulfonic acid sodium (Nq) on single-wall carbon nanotube (SWNT) modified glassy carbon electrode (GCE). This electrode was characterized by scanning electron microscopy (SEM) and the results showed that Nq can rapidly and effectively be deposited on the surface of SWNT film with high stability. The electrochemical properties of functionalized SWNT/GCE with Nq (SWNT–Nq/GCE) were studied using cyclic voltammetry, double step potential chronoamperometry and differential pulse voltammetry methods. The results indicated that SWNT could improve the electrochemical behavior of Nq and greatly enhances its redox peak currents. The SWNT–Nq/GCE exhibited a pair of well-defined redox peaks. The experimental results also demonstrated that the Nq deposited species on SWNT could catalyze cysteamine oxidation and SWNT–Nq exhibited a high performance with lowering the overpotential by more than 710 mV. The effect of pH value, number of scans and Nq concentration were investigated on the electrochemical behavior of cysteamine. The selectivity of the reaction has been assessed with no interference from tyrosine, lysine, methionine, tryptophan, alanine and glutathione. The presented method has highly selectivity for voltammetric detection of cysteamine in the dynamic range from 5.0 × 10⁻⁶ M to 2.7 × 10⁻⁴ M and with a detection of limit (3σ) 3.0 × 10⁻⁶ M.     

Role of protease activated receptor-2 in lymph node metastasis of uterine cervical cancers

Background  

Protease activated receptor-2 (PAR-2) has been implicated in cellular proliferation, invasion and metastasis in various tumors. Lymph node metastasis is an important patient prognostic factor for uterine cervical cancers. This prompted us to study the role of PAR-2 in lymph node metastasis of uterine cervical cancers.     

Persistent protein losing enteropathy in post measles diarrhoea.

Faecal alpha 1 antitrypsin was measured in two groups of children with diarrhoea aged 6 months to 6 years during the acute and recovery stages of the illness. Group 1 comprised 19 children with a history of measles in the two weeks preceding admission to hospital. In this group there were six cases of Shigella species, six enterotoxigenic Escherichia coli, and five rotavirus, and two did not yield an aetiologic agent. Group 2 comprised 15 children with diarrhoea only. In this group there were five cases of Shigella species, five enterotoxigenic Escherichia coli, and five rotavirus. Children with rotavirus diarrhoea belonging to both groups showed a transient high faecal clearance of alpha 1 antitrypsin during the acute stage. Post measles cases of diarrhoea showed significantly higher faecal clearance of alpha 1 antitrypsin than group 2 subjects in both the acute and recovery stages. The faecal clearance of alpha 1 antitrypsin in both groups was significantly higher during the acute stage compared with the recovery stage. Highest faecal clearances of alpha 1 antitrypsin were observed in children with post measles shigellosis in the acute stage and they also had persistently raised concentrations, thus suggesting prolonged protein losing enteropathy.     

Induction of neuropilins-1 and -2 and their ligands, Sema3A, Sema3F, and VEGF, during Wallerian degeneration in the peripheral nervous system

The neuropilins, NP-1 and NP-2, are coreceptors for Sema3A and Sema3F, respectively, both of which are repulsive axonal guidance molecules. NP-1 and NP-2 are also coreceptors for vascular endothelial growth factor (VEGF). The neuropilins and their ligands are known to play prominent roles in axonal pathfinding, fasciculation, and blood vessel formation during peripheral nervous system (PNS) development. We confirmed a prior report (Exp. Neurol. 172 (2001) 398) that VEGF mRNA levels rise during Wallerian degeneration in the PNS and herein demonstrate that NP-1, NP-2, Sema3A, and Sema3F mRNA levels increase in peripheral nerves distal to a transection or crush injury. In a sciatic nerve crush model, in which axonal regeneration is robust, the highest levels of Sema3F mRNA below the injury site are in the epi- and perineurium. Our results suggest the possibility that the neuropilins and their semaphorin ligands serve to guide, rather than to impede, regenerating axons in the adult PNS.     

A comparative study of body iron status and lipid profile in acute myocardial infarction patients

This study was carried out to evaluate the relationship between body iron status and lipid profile in hospital admitted clinically diagnosed AMI patients considering the concept that there is a potential association between body iron status and coronary heart disease (CHD). Total 80 subjects were selected, of which 40 were healthy adults and 40 were AMI patients. Fasting blood samples were collected from healthy adults. Blood samples of AMI patients were collected within 24 hours of the attack of myocardial infarction. Body iron status was measured in term of 3 variables serum total iron concentration, TIBC and transferrin saturation. Lipid profile variables measure were total cholesterol, triglyceride, LDL-cholesterol and HDL-cholesterol. No correlation was found between serum iron and the variables of lipid profile. TIBC was found to maintain negative correlation with total cholesterol, triglyceride and LDL-cholesterol but positive correlation with HDL-cholesterol. Transferrin saturation was found to maintain strongly positive correlation with total cholesterol, triglyceride and LDL-cholesterol but strongly negative correlation with HDL-cholesterol. This correlation of TIBC and transferrin saturation with lipid profile supports the hypothesis that there is a potential association between body iron status and coronary heart disease.     

Role of work permits in teen workers' experiences

BACKGROUND: Work permits are required for working teenagers under 18 in 41 US states, but little is known about the work experience of those with work permits compared with those without such permits. This study examines job hazards, training, and knowledge of child labor laws reported by students in a predominantly Latino high school in Los Angeles and compares the responses of those who obtained work permits with those who did not. METHODS: Student responses to a 60 item questionnaire were supplemented with information from focus groups and a survey of work permits issued by the school. RESULTS: Students without work permits were more likely to perform hazardous tasks and to use certain types of dangerous equipment and less likely to receive health and safety training than those with permits. CONCLUSION: Possible explanations for the findings and suggested areas in need of policy change or research are considered.     

A randomized, single blind comparative trial of norethindrone enanthate and depo-medroxyprogesterone acetate in Bangladesh

A randomized, single blind comparative trial of norethindrone enanthate (NET-ENT) and depo-medroxyprogesterone acetate (DMPA) was conducted in the Model Clinic, Decca, Bangladesh, to determine if there were differences in reported side effects, reasons for discontinuation and discontinuation rates of these two injectables. On all follow-up visits the proportion of women reporting no bleeding (amenorrhea) was higher for the DMPA clients compared to the NET-ENT clients. Concurrent with these findings, the proportion of women reporting irregular bleeding was consistently higher for the NET-ENT clients. Concurrent with these findings, the proportion of women reporting irregular bleeding was consistently higher for the NET-ENT clients compared to those receiving DMPA. By the fourth injection, less than 15% of the clients in both drug groups still reported having regular cyclic bleeding (4 of the 26 DMPA clients and 4 of the 28 NET-ENT clients). Five of the 133 women on DMPA and 6 of the 106 women on NET-ENT became pregnant while using the injectables. At the end of one year of follow-up, 14 of the 133 DMPA and 14 of the 106 NET-ENT clients were still continuing (came back for a fifth injection).     

Hyperacute therapy of ischemic stroke: intravenous thrombolysis

Stroke is the third most common cause of death in the United States following heart disease and cancer. Following the success of thrombolysis for myocardial infarction in the early 1990s, major trials for evaluation of this new therapeutic approach for ischemic stroke were initiated. The majority of ischemic strokes are due to occlusion of a cerebral vessel by a blood clot. Occlusion of a cerebral blood vessel leads to a core of infracted tissue surrounded by a relatively hypoperfused but viable brain tissue (the ischemic penumbra), which can be potentially salvaged by rapid recanalization of the target vessel. The underlying rationale for introduction of thrombolytic drugs is the lysis of an obliterating thrombus and reestablishment of blood flow. In this article we review the major intravenous thrombolysis trials leading to approval of intravenous recombinant tissue plasminogen activator, the only FDA approved treatment available today for acute ischemic stroke.