Estimated Glomerular Filtration Rate —A More Stable Indicator than Creatinine Clearance in Peritoneal Dialysis Practice

Objective: The usefulness of estimated glomerular filtration rate may not be restricted to pre-dialysis patients, since we reported that estimated glomerular filtration rate was well correlated with measured total creatinine clearance in peritoneal dialysis patients. To clarify the clinical usefulness of estimated glomerular filtration rate as a parameter for peritoneal dialysis adequacy, we retrospectively surveyed estimated glomerular filtration rate and total creatinine clearance in peritoneal dialysis patients treated at JA Toride Medical Center.Patients and Methods: A total of 114 data sets of estimated glomerular filtration rate and total creatinine clearance from 21 PD patients treated at JA Toride Medical Center were collected from November 2010 to October 2011. The patients consisted of 15 men and six women with an average age of 66.6 ± 12.6 years (46–95 years old). The average number of samples was 5.4 ± 1.5 (2 to 7) per patient.Results: The collected data showed less correlation of estimated glomerular filtration rate and total creatinine clearance (r. = 0.435) than that of a previous cross-sectional study (r. = 0.836). As reported in pre-dialysis patients, the differences between estimated glomerular filtration rate and total creatinine clearance were correlated with total creatinine excretion in urine and PD effluent (r. = 0.821). The differences were also correlated with normalized protein catabolic rate, which was one of the main determinant factors for total creatinine excretion (r. = 0.636). A similar tendency was apparently observed in one patient with poor compliance to diet therapy and fluctuating dietary intake. From the analysis of these data, serum creatinine seemed to fluctuate less possibly due to compensatory capacity of the residual renal function in small solute clearance.Conclusions: Consequently, estimated glomerular filtration rate was turned out to be a more stable parameter than total creatinine clearance, which might be a desirable feature in long-term follow-up of peritoneal dialysis patients.     

A chronic toxicity study of diphenylarsinic acid in F344 rats in drinking water for 52 weeks

Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. The purpose of the present study was to evaluate the potential toxicity of DPAA when administered to rats in their drinking water for 52 weeks. DPAA was administered to groups 1–4 at concentrations of 0, 5, 10, and 20 ppm in their drinking water for 52 weeks. There were no significant differences in the final body weights between the control groups and the treatment groups in male or female rats. In serum biochemistry, in females 20 ppm DPAA significantly increased alkaline phosphatase and γ-glitamyl transferase compared to controls, and 10 and 20 ppm DPAA significantly increased total cholesterol compared to controls. Absolute and relative liver weights were significantly increased in females treated with 20 ppm DPAA compared to the control group. Dilation of the common bile duct outside the papilla of Vater and stenosis of the papilla of Vater was observed in all male and female rats administered 20 ppm DPAA. The incidence of intrahepatic bile duct hyperplasia was significantly increased in male and female rats treated with 20 ppm DPAA compared to the control groups. These results suggest that DPAA is toxic to the bile duct epithelium in rats. The no-observed adverse effect levels of DPAA were estimated to be 10 ppm (0.48 mg/kg b.w./day) for males and 5 ppm (0.35 mg/kg b.w./day) for females under the conditions of this study.     

Gene delivery from supercharged coiled-coil protein and cationic lipid hybrid complex

A lipoproteoplex comprised of an engineered supercharged coiled-coil protein (CSP) bearing multiple arginines and the cationic lipid formulation FuGENE HD (FG) was developed for effective condensation and delivery of nucleic acids. The CSP was able to maintain helical structure and self-assembly properties while exhibiting binding to plasmid DNA. The ternary CSP·DNA(8:1)·FG lipoproteoplex complex demonstrated enhanced transfection of β-galactosidase DNA into MC3T3-E1 mouse preosteoblasts. The lipoproteoplexes showed significant increases in transfection efficiency when compared to conventional FG and an mTat·FG lipopolyplex with a 6- and 2.5-fold increase in transfection, respectively. The CSP·DNA(8:1)·FG lipoproteoplex assembled into spherical particles with a net positive surface charge, enabling efficient gene delivery. These results support the application of lipoproteoplexes with protein engineered CSP for non-viral gene delivery.     

Regional prevalence of health worker absenteeism in Tanzania

Absenteeism of health workers in developing countries is common and can severely undermine the reliability of the health system. Therefore, it is important to understand where the prevalence of absenteeism is high. We develop a simple imputation method that combines a Service Delivery Indicators survey and a Service Provision Assessment survey to estimate the prevalence of absenteeism of health workers at the level of regions in Tanzania. The resulting estimates allow one to identify the regions in which the prevalence of absenteeism is significantly higher or lower than the national average and help policymakers determine priority areas for intervention.     

Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers

The family Arenaviridae, genus Arenavirus, consists of two phylogenetically independent groups: Old World (OW) and New World (NW) complexes. The Lassa and Lujo viruses in the OW complex and the Guanarito, Junin, Machupo, Sabia, and Chapare viruses in the NW complex cause viral hemorrhagic fever (VHF) in humans, leading to serious public health concerns. These viruses are also considered potential bioterrorism agents. Therefore, it is of great importance to detect these pathogens rapidly and specifically in order to minimize the risk and scale of arenavirus outbreaks. However, these arenaviruses are classified as BSL-4 pathogens, thus making it difficult to develop diagnostic techniques for these virus infections in institutes without BSL-4 facilities. To overcome these difficulties, antibody detection systems in the form of an enzyme-linked immunosorbent assay (ELISA) and an indirect immunofluorescence assay were developed using recombinant nucleoproteins (rNPs) derived from these viruses. Furthermore, several antigen-detection assays were developed. For example, novel monoclonal antibodies (mAbs) to the rNPs of Lassa and Junin viruses were generated. Sandwich antigen-capture (Ag-capture) ELISAs using these mAbs as capture antibodies were developed and confirmed to be sensitive and specific for detecting the respective arenavirus NPs. These rNP-based assays were proposed to be useful not only for an etiological diagnosis of VHFs, but also for seroepidemiological studies on VHFs. We recently developed arenavirus neutralization assays using vesicular stomatitis virus (VSV)-based pseudotypes bearing arenavirus recombinant glycoproteins. The goal of this article is to review the recent advances in developing laboratory diagnostic assays based on recombinant viral proteins for the diagnosis of VHFs and epidemiological studies on the VHFs caused by arenaviruses.