Physiological role of the putative ammonium transporter RhCG in the mouse.

Ammonium excretion into urine is a major process essential to the regulation of acid-base homeostasis. We have shown that Rh-type proteins, including renal RhCG, belong to the Mep/Amt family of ammonium transporters and promote bi-directional ammonium transport upon heterologous expression in yeast. To study the physiological role of RhCG and to test a potential function in ammonium excretion, we have generated mice bearing an invalidation of the corresponding gene.     

A systematic review of outcomes assessed in randomized controlled trials of surgical interventions for carpal tunnel syndrome using the International Classification of Functioning, Disability and Health (ICF) as a reference tool

Background  

A wide range of outcomes have been assessed in trials of interventions for carpal tunnel syndrome (CTS), however there appears to be little consensus on what constitutes the most relevant outcomes. The purpose of this systematic review was to identify the outcomes assessed in randomized clinical trials of surgical interventions for CTS and to compare these to the concepts contained in the International Classification of Functioning, Disability and Health (ICF).     

Antiparasitic properties of homoallylamines and related compounds

A study of some antiparasitic properties of several homoallylamines and related tetrahydroquinolines and quinolines, previously described, was carried out using in vitro activity assays against the epimastigote form of Trypanosoma cruzi and against Trichomonas vaginalis. Unspecific cytotoxicity against murine macrophages was also studied. Although the antichagasic and trichomonacidal activities are not comparable to those of the standard drugs, nifurtimox and metronidazole, some of the compounds exhibit an interesting specific antiparasitic activity.     

Implications of postvaccination hepatitis B surface antigenemia in the management of exposures to body fluids.

A neonate vaccinated against HBV was the source of an occupational exposure to blood. She was tested for hepatitis B surface antigen and found to be positive, leading to unnecessary treatment, retesting, and concern. Evaluation of the infectious status of HBV should rely on other means if vaccination has recently occurred.     

Assessment of disease activity in rheumatoid arthritis with (18)F-FDG PET.

The aim of this study was to assess synovitis by (18)F-FDG PET in an individual joint analysis and in a global analysis of rheumatoid arthritis (RA) disease activity and to compare (18)F-FDG PET parameters with clinical, biologic, and sonographic (US) rheumatoid parameters. METHODS: Three hundred fifty-six joints were assessed in 21 patients with active RA: the knees in all subjects and either wrists as well as metacarpophalangeal and proximal interphalangeal joints in 13 patients, or ankles and the first metatarsophalangeal joints in the remaining 8 patients. PET analysis consisted of a visual identification of (18)F-FDG uptake in the synovium and measurements of standardized uptake values (SUVs). Independent assessors performed the clinical and US examinations. RESULTS: PET positivity was found in 63% of joints, whereas 75%, 79%, and 56% were positive for swelling, tenderness, and US analysis, respectively. Both the rate of PET-positive joints and the SUV increased with the number of positive parameters present (swelling, tenderness, US positivity) and with the synovial thickness. The mean SUV was significantly higher in joints where a power Doppler signal was found. In a global PET analysis, the number of PET-positive joints and the cumulative SUV were significantly correlated with the swollen and tender joint counts, the patient and physician global assessments, the erythrocyte sedimentation rate and C-reactive protein serum levels, the disease activity score and the simplified disease activity index, the number of US-positive joints, and the cumulative synovial thickness. CONCLUSION: (18)F-FDG PET is a unique imaging technique that can assess the metabolic activity of synovitis and measure the disease activity in RA.     

Molecular biology in prostate cancer

Summary Genes involved in cancer generation are usually tumor suppressors and oncogenes. Progressive genetic alterations in these genes are involved in the mechanisms of tumorigenesis. In prostate cancer, additionally several chromosomal loci that should harbor mutated genes have been proposed. Some genes have been found altered in prostate cancer, such as PTEN, TP53, AR, RNASEL (HPC1), ELAC2 (HPC2), CDKN2A and MSR1 and those can be natural targets for new strategies of treatment. Besides, gene therapy has been suggested to be suitable for prostate cancer treatment. This approach includesex vivo corrective therapy, suicide, and antisense therapy.     

The Intestinal Absorption of a Prodrug of the mGlu2/3 Receptor Agonist LY354740 is Mediated by PEPT1: In Situ Rat Intestinal Perfusion Studies

LY354740 is a potent mGlu2/3 agonist with a limited oral bioavailability. Its alanyl prodrug, LY544344, showed high affinity to the intestinal peptide transporter PEPT1, and improved the oral bioavailability of LY354740 in various animal models. The aim of the present study was to investigate the mechanism of in vivo absorption of the dipeptidic prodrug LY544344. The permeabilities of LY544344 and LY354740 were examined in the rat in situ single‐pass intestinal perfusion model. The intestinal absorptive flux of LY354740 was shown to be very low in comparison with LY544344. The absorptive flux of LY544344 could best be described by a Michaelis–Menten process in parallel with a linear process. The estimated parameters were: J_max = 26.7 × 10^?5 µmol/(cm²‐s), K_m = 2.6 mM. The absorptive permeability of LY544344 was reduced to approximately 5% of control in the presence of excess Gly‐Sar, a known PEPT1 substrate. Intracellular accumulation of LY354740 and LY544344, estimated postperfusion, showed high levels of LY354740 over LY544344 at all perfusate concentrations studied. However, there was a decline in the intracellular ratio of LY354740 to LY544344 at higher concentrations, suggesting that the metabolic activation to release LY354740 is saturable. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1574–1581, 2010     

A tumor-targeted and conditionally replicating oncolytic adenovirus vector expressing TRAIL for treatment of liver metastases.

We have constructed a new capsid-modified adenovirus (Ad) vector that specifically replicates in tumor cells and expresses TNF-related apoptosis-inducing ligand (TRAIL). The Ad capsid contains short-shafted fibers derived from Ad serotype 35, which allow for efficient infection of malignant tumor cells, and largely avoids innate toxicity after intravenous application. Replication-dependent homologous recombination in Ad genomes was used to achieve tumor-specific expression of Ad E1a (to mediate viral replication) and TRAIL (to mediate apoptosis and enhance release of progeny virus from infected cells). We demonstrated that our oncolytic vector (Ad5/35.IR-E1A/TRAIL) induced apoptosis in human tumor cell lines derived from colorectal, lung, prostate, and liver cancer. Both in vitro and in vivo tumor models showed efficient intratumoral spread of this vector. In a model for metastatic colon cancer, tail vein infusion of Ad5/35.IR-E1A/TRAIL resulted in elimination of preestablished liver metastases. Intravenous injection of this vector caused a transient elevation of serum glutamic pyruvic transaminase in tumor-bearing mice, which we attributed to factors released from apoptotic tumor cells. Liver histology analyzed at day 14 after virus injection did not show signs of hepatocellular damage. This new oncolytic vector represents a potentially efficient means for gene therapy of metastatic cancer.