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Abstract: The C825T polymorphism of the beta-3 subunit of the protein G (GNB3) has been related to an increased activity of the Na+/H+ exchanger (NHE-1) through the synthesis of an anomalous hyperactive protein. Because of the important role of this system in essential hypertension (EH), we analysed the distribution of the different genotypes of this polymorphism in normotensive subjects (NS) and essential hypertensive patients (EHP), their relationship with the condition of salt sensitivity, plasma sodium and potassium concentrations and plasma renin activity (PRA) in EHP. 144 subjects (78 EHP and 76 NS) were studied. Salt sensitivity was assessed by the rapid protocol of Weinberger and genotype determination for GNB3 C825T polymorphism was performed by PCR. The distribution of the different genotypes was similar among EHP (CC 37.2%; CT 41.1%; TT 16.7%) and NS (CC 32.9%; CT 55.3%; TT 11.8%). In regard to general characteristics of EHP (including blood pressure levels) and the condition of salt sensitivity, there were no differences among the different genotypes. Plasma sodium concentration was higher and plasma potassium was lower in TT patients (141.0±1.7 and 3.7±0.1) than in CC patients (139.1±1.9 and 4.0±0.3) p <0.05. CT patients had intermediate values (139.9±1.9 and 3.9±0.2). PRA values were similar in the three genotypes as were the rest of analytical parameters studied. Our data demonstrate an association between the C825T polymorphism of the GNB3 and plasma sodium and potassium concentrations in EHP, as expression of an increase in NHE-1 activity, without modifications in PRA nor relationship with salt sensitivity. [Copyright &y& Elsevier]

This letter comments on the article by Joseph Ouslander. [ABSTRACT FROM AUTHOR]

Zona occludens-2 (ZO-2) is a protein present at the tight junction and nucleus of epithelial cells. ZO-2 represses the transcription of genes regulated by the Wnt/β-catenin pathway. This pathway plays a critical role in podocyte injury and proteinuria. Here, we analyze whether the overexpression of ZO-2 in the glomerulus, by hydrodynamics transfection, prevents podocyte injury mediated by the Wnt/β-catenin pathway in the mouse model of adriamycin (ADR) nephrosis. By immunofluorescence and immunogold electron microscopy, we show that ZO-2 is present in mice glomerulus, not at the slit diaphragms where nephrin concentrates, but in the cytoplasm and at processes of podocytes. Our results indicate that in the glomeruli of mice treated with ADR, ZO-2 overexpression increases the amount of phosphorylated β-catenin, inhibits the expression of the transcription factor snail, prevents nephrin and podocalyxin loss, reduces podocyte effacement and massive fusions, restrains proteinuria, and supports urea and creatinine clearance. These results suggest that ZO-2 could be a new target for the regulation of hyperactive Wnt/β-catenin signaling in proteinuric kidney diseases. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Patient-Centered Care for Older Adults With Multiple Chronic Conditions: A Stepwise Approach From the American Geriatrics Society" by the American Geriatrics Society Expert Panel on the Care of Older Adults with Multimorbidity.

Background: High-risk human Papillomavirus infection is a necessary factor for cervical squamous intraepithelial lesions and invasive cervical cancer. In HIV-1-infected women, HPV infection is more prevalent and a higher risk of cervical cancer has been identified. We aimed to calculate the prevalence of infection by HR-HPV, determine the factors associated with this infection and abnormal cytology findings and to describe the history of cervical cancer screening in HIV-1-infected women. Methods: We enrolled 479 HIV-1-infected women from the PISCIS cohort. Each patient underwent a gynecological check- up, PAP smear, HPV AND Hybrid capture, HPV genotyping, and colposcopy and biopsy, if necessary. We applied questionnaires to obtain information on sociodemographic, behavioral, clinical, and cervical screening variables. We present a cross-sectional analysis. Results: Median age was 42 years. The prevalence of HR-HPV infection was 33.2% and that of high-grade squamous intraepithelial lesions (HSIL) was 3.8%. The most common genotypes were 16(23%), 53(20.3%), and 52(16.2%). The factor associated with HR-HPV infection was age ,30 years (odds ratio[OR],2.5; 95%confidence interval[CI],1.1-5.6). The factors associated with the presence of HSIL or low-grade squamous intraepithelial lesions (LSIL) were CD4T-lymphocyte count <200cells/mm³ versus .500cells/mm³ (OR,8.4; 95%CI,3.7-19.2), HIV-1 viral load .10,000copies/mL versus ,400copies/mL (OR,2.1; 95%CI,1.0-4.4), and use of oral contraceptives (OR,2.0; 95%CI,1.0-3.9). Sixty percent of HIV-1-infected women had had one Pap smear within the last 2 years. Conclusions: The high prevalence of HPV infection and cervical lesions in the HIV-1-infected population in Catalonia, as well as the low coverage and frequency of screening in this group, means that better preventive efforts are necessary and should include vaccination against HPV, better accessibility to screening programs, training of health care professionals, and specific health education for HIV-1-infected women. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) circulates in human and sylvatic cycles. Sylvatic strains are both ecologically and evolutionarily distinct from endemic viruses. Although sylvatic dengue cycles occur in West African countries and Malaysia, only a few cases of mild human disease caused by sylvatic strains and one single case of dengue hemorrhagic fever in Malaysia have been reported. Here we report a case of dengue hemorrhagic fever (DHF) with thrombocytopenia (13000/µl), a raised hematocrit (32% above baseline) and mucosal bleeding in a 27-year-old male returning to Spain in November 2009 after visiting his home country Guinea Bissau. Sylvatic DENV-2 West African lineage was isolated from blood and sera. This is the first case of DHF associated with sylvatic DENV-2 in Africa and the second case worldwide of DHF caused by a sylvatic strain. Author Summary: Dengue viruses are mosquito borne pathogens that cause up to 100 million infections annually. Dengue viruses circulate in either humans or non-human primates in two separate cycles: human and sylvatic. All four different serotypes infect humans causing frequent epidemics and severe disease, including hemorrhagic fever. Until a few years ago, viruses circulating in the sylvatic cycle had been associated with asymptomatic to mild disease only in humans. For example, retrospective analysis of human serum samples collected in Nigeria from the 1960s proved that sylvatic dengue was able to cause an outbreak of dengue fever in human population. Recently a case of DHF in Asia was linked to sylvatic DENV-2 (strain DKD811) infection. Here, we report the first case of DHF associated with sylvatic DENV-2 infection in Africa caused by a complete different lineage of the virus. All these events underscore the need to be vigilant about the re-emergence of DHF from sylvatic cycles. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) circulates in human and sylvatic cycles. Sylvatic strains are both ecologically and evolutionarily distinct from endemic viruses. Although sylvatic dengue cycles occur in West African countries and Malaysia, only a few cases of mild human disease caused by sylvatic strains and one single case of dengue hemorrhagic fever in Malaysia have been reported. Here we report a case of dengue hemorrhagic fever (DHF) with thrombocytopenia (13000/μl), a raised hematocrit (32% above baseline) and mucosal bleeding in a 27-year-old male returning to Spain in November 2009 after visiting his home country Guinea Bissau. Sylvatic DENV-2 West African lineage was isolated from blood and sera. This is the first case of DHF associated with sylvatic DENV-2 in Africa and the second case worldwide of DHF caused by a sylvatic strain. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To report on a case with a mitochondrial DNA (mtDNA) depletion syndrome. Design and methods: Laboratory studies were done in muscle biopsy and fibroblasts to evaluate coenzyme Q10 (CoQ10) status and quantify mitochondrial DNA. Results: Decreased CoQ10 values and a 78% of mtDNA depletion were detected in muscle. Mutational studies failed to reveal any pathogenic mutation in nuclear genes related with mtDNA maintenance. Conclusions: mtDNA depletion syndrome was associated with CoQ10 deficiency in our patient. [Copyright &y& Elsevier]

Abstract: Exposure to hexavalent chromium (Cr6+) causes mutagenic, carcinogenic, and toxic effects, some of which have been associated with its oxidative capacity. In the kidney, Cr6+ has been claimed to provoke necrosis of the proximal tubular cells. Our aim was to assess the functional involvement of the different segments that form the nephron in a model of acute renal failure caused by potassium dichromate and the participation of oxidative damage in this process. We also studied the possible protective effect of α-tocopherol (α-TOC) against renal damage. Wistar female rats 200g body weight (bw) received potassium dichromate (15mg/kg, sc, single dose). Lipid peroxidation and renal function were evaluated on days 0, 1, 2, 3, 7, 10, and 14. A second group received α-TOC (125mg/kg, by gavage) 5 days before and during dichromate exposure (same dose as for the first group), and was monitored at 0, 2, and 7 days of exposure. Creatinine clearance, glucose and sodium fractional excretions, p-aminohippurate uptake, free-water and osmolal clearances were also measured. Thiobarbituric acid-reactive substances were quantified in renal cortex. The results revealed altered proximal tubule function, decreased glomerular filtration, and distal segment dysfunction, accompanied by oxidative damage 48h after exposure to dichromate. In the α-TOC-treated group proximal reabsorptive and secretory functions were preserved, suggesting that oxidative damage is a participating mechanism in dichromate toxicity on these functions. In contrast α-TOC did not prevent glomerular or distal dysfunction, indicating selectivity of the protection afforded by this compound on the toxicity of dichromate, at the several components of the nephron. [Copyright &y& Elsevier]