Aquaporins: important but elusive drug targets.

The aquaporins (AQPs) are a family of small, integral membrane proteins that facilitate water transport across the plasma membranes of cells in response to osmotic gradients. Data from knockout mice support the involvement of AQPs in epithelial fluid secretion, cell migration, brain oedema and adipocyte metabolism, which suggests that modulation of AQP function or expression could have therapeutic potential in oedema, cancer, obesity, brain injury, glaucoma and several other conditions. Moreover, loss-of-function mutations in human AQPs cause congenital cataracts (AQP0) and nephrogenic diabetes insipidus (AQP2), and autoantibodies against AQP4 cause the autoimmune demyelinating disease neuromyelitis optica. Although some potential AQP modulators have been identified, challenges associated with the development of better modulators include the druggability of the target and the suitability of the assay methods used to identify modulators

The wrist hyperflexion and abduction of the thumb (WHAT) test : a more specific and sensitive test to diagnose de Quervain tenosynovitis than the Eichhoff's test

De Quervain's disease has different clinical features. Different tests have been described in the past, the most popular test being the Eichhoff's test, often wrongly named as the Finkelstein's test. Over the years, a misinterpretation has occurred between these two tests, the latter being confused with the first. To compare the Eichhoff's test with a new test, the wrist hyperflexion and abduction of the thumb test, we set up a prospective study over a period of three years for a cohort of 100 patients (88 women, 12 men) presenting spontaneous pain over the radial side of the styloid of the radius (de Quervain tendinopathy). The purpose of the study was to compare the accuracy of the Eichhoff's test and wrist hyperflexion and abduction of the thumb test to diagnose correctly de Quervain's disease by comparing clinical findings using those tests with the results on ultrasound. The wrist hyperflexion and abduction of the thumb test revealed greater sensitivity (0.99) and an improved specificity (0.29) together with a slightly better positive predictive value (0.95) and an improved negative predictive value (0.67). Moreover, the study showed us that the wrist hyperflexion and abduction of the thumb test is very valuable in diagnosing dynamic instability after successful decompression of the first extensor compartment. Our results support that the wrist hyperflexion and abduction of the thumb test is a more precise tool for the diagnosis of de Quervain's disease than the Eichhoff's test and thus could be adopted to guide clinical diagnosis in the early stages of de Quervain's tendinopathy

Prevalence and genotypes of GB Virus C/Hepatitis G virus among blood donors in Central Brazil

A survey was conducted in a blood donor population of Central Brazil aiming to investigate the prevalence of GB virus C (GBV-C)/hepatitis G virus (HGV) infection and also to analyze the virus genotypes distribution. A total of 241 voluntary blood donors were interviewed at the State Blood Bank in Goiânia, State of Goiás, Brazil. Blood samples were collected and serum samples tested for GBV-C/HGV RNA by polymerase chain reaction. Genotypes were determined by restriction fragment length polymorphism (RFLP) analysis. Seventeen samples were GBV-C/HGV RNA-positive, resulting in a prevalence of 7.1% (95% CI: 4.2-11.1). A significant trend of GBV-C/HGV RNA positivity in relation to age was observed, with the highest prevalence in donors between 29-39 years old. Ten infected individuals were characterized by reporting parenteral (30%), sexual (18%), both (6%) and intrafamiliar (6%) transmission. However, 7 (40%) GBV-C/HGV RNA-positive donors did not mention any potential transmission route. RFLP analysis revealed the presence of genotypes 1 and 2 of GBV-C/HGV; more precisely, 10 (58.9%) samples were found belonging to the 2b subtype, 4 (23.5%) to the 2a subtype, and 3 (17.6%) to genotype 1. The present data indicate an intermediate endemicity of GBV-C/HGV infection among this blood donor population, and a predominant circulation of genotype 2 (subtype 2b) in Central Brazil

Study of the HIV-2 Env cytoplasmic tail variability and its impact on Tat, Rev and Nef

Background: The HIV-2 env's 3′ end encodes the cytoplasmic tail (CT) of the Env protein. This genomic region also encodes the rev, Tat and Nef protein in overlapping reading frames. We studied the variability in the CT coding region in 46 clinical specimens and in 2 reference strains by sequencing and by culturing. The aims were to analyse the variability of Env CT and the evolution of proteins expressed from overlapping coding sequences. Results: A 70% reduction of the length of the CT region affected the HIV-2 ROD and EHO strains in vitro due to a premature stop codon in the env gene. In clinical samples this wasn't observed, but the CT length varied due to insertions and deletions. We noted 3 conserved and 3 variable regions in the CT. The conserved regions were those containing residues involved in Env endocytosis, the potential HIV-2 CT region implicated in the NF-kB activation and the potential end of the lentiviral lytic peptide one. The variable regions were the potential HIV-2 Kennedy region, the potential lentiviral lytic peptide two and the beginning of the potential lentiviral lytic peptide one. A very hydrophobic region was coded downstream of the premature stop codon observed in vitro, suggesting a membrane spanning region. Interestingly, the nucleotides that are responsible for the variability of the CT don't impact rev and Nef. However, in the Kennedy-like coding region variability resulted only from nucleotide changes that impacted Env and Tat together. Conclusion: The HIV-2 Env, Tat and Rev C-terminal part are subject to major length variations in both clinical samples and cultured strains. The HIV-2 Env CT contains variable and conserved regions. These regions don't affect the rev and Nef amino acids composition which evolves independently. In contrast, Tat co-evolves with the Env CT. © 2013 Bakouche et al