Reactive Oxygen Species Precede the ε Isoform of Protein Kinase C in the Anesthetic Preconditioning Signaling Cascade

Background: Protein kinase C (PKC) and reactive oxygen species (ROS) are known to have a role in anesthetic preconditioning (APC). Cardiac preconditioning by triggers other than volatile anesthetics, such as opioids or brief ischemia, is known to be isoform selective, but the isoform required for APC is not known. The authors aimed to identify the PKC isoform that is involved in APC and to elucidate the relative positions of PKC activation and ROS formation in the APC signaling cascade.

Methods: Isolated guinea pig hearts were subjected to 30 min of ischemia and 120 min of reperfusion. Before ischemia, hearts were either untreated or treated with sevoflurane (APC) in the absence or presence of the nonspecific PKC inhibitor chelerythrine, the PKC-[delta] inhibitor PP101, or the PKC-[epsilon] inhibitor PP149. Spectrofluorometry and the fluorescent probes dihydroethidium were used to measure intracellular ROS, and effluent dityrosine as used to measure extracellular ROS release.

Results: Previous sevoflurane exposure protected the heart against ischemia-reperfusion injury, as previously described. Chelerythrine or PP149 abolished protection, but PP101 did not. ROS formation was observed during sevoflurane exposure and was not altered by any of the PKC inhibitors.     

Carriage of Neisseria meningitidis serogroup W135 ST-2881

Serogroup W135 ST-2881 meningococci caused a cluster of meningitis cases in Niger in 2003. Of 80 healthy persons in the patients' villages, 28 (35%) carried meningococci; 20 of 21 W135 carrier strains were ST-2881. Ten months later, 5 former carriers were still carriers of W135 ST-2881 strains. The serum bactericidal antibody activity changed according to carrier status.     

Intestinal parasitosis during AIDS diarrhoea

The main goal of this work was to study the parasitic infections during AIDS diarrhoea. A longitudinal study was carried out from October 2000 to November 2001 in the Hepato-Gastro-Enterology department of Gabriel Toure Hospital and in the Department of Epidemiology and Parasitic infections of Faculty of Medicine, Pharmacy and Odonto-stomatology of Bamako (Mali), concerning HIV positive patients suffering from diarrhoea. Detecting microbes in stools has been done through direct microscopic examination and according to procedures of Henricksen Poblenz Baerman, Kato Katz and the PCR. Among the 70 patients involved, the sex-ratio was 53%, the average age was 35 +/- 8.4 years. Fever weight loss, skin affections and digestive mycosis were often associated. Opportunistic infections have been relatively frequent with Cryptosporidium parvum with 20%, Isospora belli with 8.5% and Microsporidium with 11.5% of cases. Other non-opportunistic microbes were found. Death within the first two weeks seems more important in case of infection by Cryptosporidium parvum. The frequency and the danger of those opportunistic infections require their efficient diagnosis and care management.     

Rift Valley fever in small ruminants, Senegal, 2003

During the 2003 rainy season, the clinical and serologic incidence of Rift Valley fever was assessed in small ruminant herds living around temporary ponds located in the semi-arid region of the Ferlo, Senegal. No outbreak was detected by the surveillance system. Serologic incidence was estimated at 2.9% (95% confidence interval 1.0-8.7) and occurred in 5 of 7 ponds with large variations in the observed incidence rate (0%-20.3%). The location of ponds in the Ferlo Valley and small ponds were correlated with higher serologic incidence (p = 0.0005 and p = 0.005, respectively). Rift Valley fever surveillance should be improved to allow early detection of virus activity. Ruminant vaccination programs should be prepared to confront the foreseeable higher risks for future epidemics of this disease.     

Species-specific class I gene expansions formed the telomeric 1 mb of the mouse major histocompatibility complex

We have determined the complete sequence of 951,695 bp from the class I region of H2, the mouse major histocompatibility complex (Mhc) from strain 129/Sv (haplotype bc). The sequence contains 26 genes. The sequence spans from the last 50 kb of the H2-T region, including 2 class I genes and 3 class I pseudogenes, and includes the H2-M region up to Gabbr1. A 500-kb stretch of the H2-M region contains 9 class I genes and 4 pseudogenes, which fall into two subfamilies, M1 and M10, distinct from other mouse class I genes. This M1/M10 class I gene-cluster is separated from the centromeric H2-T and the telomeric H2-M4, -5 and -6 class I genes by "nonclass I genes". Comparison with the corresponding 853-kb region of the human Mhc, which includes the HLA-A region, shows a mosaic of conserved regions of orthologous nonclass I genes separated by regions of species-specific expansion of paralogous Mhc class I genes. The analysis of this mosaic structure illuminates the dynamic evolution of the Mhc class I region among mammals and provides evidence for the framework hypothesis.     

Comparisons of human-landing catches and odor-baited entry traps for sampling malaria vectors in Senegal

A comparative study of human-landing catches (HLCs) and odor-baited entry traps (OBETs) for sampling malaria vectors was conducted in two different bioclimatic areas of Senegal, the Sahelian and Sudano-Guinean phytogeographic zones, from September to December 2002. Mosquitoes were collected by the two methods both indoors and outdoors. The reliability of OBET samples was tested by comparing the two methods. Overall, HLC was more effective indoors and for surveying the anopheline fauna. Both methods were effective in sampling the four known malaria vectors in Senegal [Anopheles gambiae s.s., An. arabiensis Patton, An. funestus Giles, and An. nili (Theobald) ], and mosquito age structures and infectivity rates did not differ between methods.     

Rapid detection of important human pathogenic Phleboviruses.

BACKGROUND: Rapid diagnostics are not available for several human pathogens in the genus Phlebovirus of the Bunyaviridae. OBJECTIVES: To develop RT-PCR assays for Sandfly Fever Sicilian virus (SFSV), Sandfly Fever Naples virus (SFNV), Toscana virus (TOSV) and Rift Valley Fever virus (RVFV). STUDY DESIGN: RNA standards were generated and used to test the performance of the assays. RESULTS: A detection limit of 10-100 RNA molecules was determined for the SFSV, TOSV and RVFV assays. The sensitivity of the SFNV assay was not determined. The TOSV and the RVFV assays detected recent isolates from Spain and Africa, respectively. CONCLUSION: The assays should help to improve surveillance of pathogenic Phleboviruses.     

Race-specific associations between health-related quality of life and cellular aging among adults in the United States: evidence from the National Health and Nutrition Examination Survey

Purpose

Poor health-related quality of life (HRQOL) could lead to higher morbidity and mortality through telomere attrition or accelerated cellular aging. We conducted a cross-sectional analysis to examine the relationship between four dimensions of HRQOL and leukocyte telomere length (LTL) among a nationally representative sample of 3547 US adults (≥20 years) using the data from the 2001–2002 National Health and Nutrition Examination Survey.

Method

We used HRQOL survey information collected on individuals’ self-rated general health, recent physical health, recent mental health, and recent activity limitation. Telomere length was assessed using quantitative polymerase chain reaction. Multiple linear regressions were used to estimate the relationship between each dimension of HRQOL and log-transformed values of LTL with adjustment for sample weights and design effects.

Results

HRQOL-race interactions were significant, and the results were stratified by race. After controlling for demographic factors, disease conditions, and lifestyle variables, worse general health was significantly associated with shorter LTL for Blacks (coefficient, β: ?0.022, 95% Confidence Interval, 95% CI: ?0.03 to ?0.01), but not for Whites or Mexican Americans. Unwell physical health was associated with shorter telomere length for Whites (β: ?0.005, 95% CI: ?0.01 to ?0.001) only. Unwell mental health showed no significant association with LTL in any race.

Conclusions

Although longitudinal studies are needed to prove causality, our findings suggest that HRQOL could be associated with LTL shortening. We also found a possible racial difference in this association and recommend additional multiethnic studies to confirm this and to understand the reasons and consequences of this difference.

     

A New Potent Secondary Amphipathic Cell�Cpenetrating Peptide for siRNA Delivery Into Mammalian Cells

RNA interference constitutes a powerful tool for biological studies, but has also become one of the most challenging therapeutic strategies. However, small interfering RNA (siRNA)-based strategies suffer from their poor delivery and biodistribution. Cell-penetrating peptides (CPPs) have been shown to improve the intracellular delivery of various biologically active molecules into living cells and have more recently been applied to siRNA delivery. To improve cellular uptake of siRNA into challenging cell lines, we have designed a secondary amphipathic peptide (CADY) of 20 residues combining aromatic tryptophan and cationic arginine residues. CADY adopts a helical conformation within cell membranes, thereby exposing charged residues on one side, and Trp groups that favor cellular uptake on the other. We show that CADY forms stable complexes with siRNA, thereby increasing their stability and improving their delivery into a wide variety of cell lines, including suspension and primary cell lines. CADY-mediated delivery of subnanomolar concentrations of siRNA leads to significant knockdown of the target gene at both the mRNA and protein levels. Moreover, we demonstrate that CADY is not toxic and enters cells through a mechanism which is independent of the major endosomal pathway. Given its biological properties, we propose that CADY-based technology will have a significant effect on the development of fundamental and therapeutic siRNA-based applications.