Gene transfer of endothelial NO synthase and manganese superoxide dismutase on arterial vascular cell adhesion molecule-1 expression and superoxide production in deoxycorticosterone acetate-salt hypertension

Enhanced vascular cell adhesion molecule-1 (VCAM-1) expression directly contributes to vascular dysfunction in hypertension. Decreased NO and/or increased superoxide are causative factors for such an event in the vessel wall. The present study was undertaken to determine whether gene transfer of endothelial NO synthase (eNOS) or manganese superoxide dismutase (MnSOD) affects VCAM-1 levels in arteries from hypertensive rats. Isolated carotid and femoral arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive rats were transduced for 4 hours with adenoviral vectors encoding eNOS, MnSOD, or beta-galactosidase reporter genes. Recombinant eNOS or MnSOD expression was evident morphologically and quantitatively 24 hours after gene transfer. Immunohistochemistry, ELISA, and Western blot techniques were used to determine VCAM-1 expression and levels. In addition, endogenous eNOS and MnSOD and in situ superoxide levels were analyzed by immunoblotting and fluorescence confocal microscopy, respectively. Arterial VCAM-1 expression was significantly higher in DOCA-salt hypertensive rats than in sham-operated rats; this expression was accompanied by decreased MnSOD but unaltered endogenous eNOS levels. VCAM-1 expression was significantly lower in MnSOD- and eNOS-transduced hypertensive arteries, with a concomitant reduction of superoxide level. These results suggest that gene transfer of MnSOD or eNOS suppresses arterial VCAM-1 expression in DOCA-salt hypertension by reducing the superoxide level.     

Electron injection into organic semiconductor devices from high work function cathodes

We show that polymer light-emitting diodes with high work-function cathodes and conjugated polyelectrolyte injection/transport layers exhibit excellent efficiencies despite large electron-injection barriers. Correlation of device response times with structure provides evidence that the electron-injection mechanism involves redistribution of the ions within the polyelectrolyte electron-transport layer and hole accumulation at the interface between the emissive and electron-transport layers. Both processes lead to screening of the internal electric field and a lowering of the electron-injection barrier. The hole and electron currents are therefore diffusion currents rather than drift currents. The response time and the device performance are influenced by the type of counterion used.     

Vaginal colonization with mycoplasma hominis and ureaplasma urealyticum

Vaginal cultures obtained from unselected young women who consulted the gynecologist in a student health service were examined for Ureaplasma urealyticum and Mycoplasma hominis. Each participant completed a confidential questionnaire. Multiple logistic regression analysis was used to determine which variables, of a large number ascertained, were associated with mycoplasmal colonization. U. urealyticum was isolated from 273 (56.8%) of 481 participants. The following variables were significantly predictive of colonization with U. urealyticum: black race, absence of antibiotic use, cigarette smoking, and number of sexual partners during the last year. Lifetime number of sexual partners was significantly predictive only in women who used nonbarrier methods of contraception. M. hominis was isolated from 85 (17.7%) of the 481 participants. Independent variables that were significantly predictive of colonization with M. hominis included black race, young age, and, for users of nonbarrier methods of contraception, lifetime number of sexual partners.     

H1N1 (2009) influenza A infection in transplant recipient patients: a comparative study versus non-transplanted patients

Objective

To compare H1N1 (2009) influenza A infection characteristics between transplant recipient patients and non-transplanted patients. To assess the evolution of transplanted patients up to 6 months following infection.

Methods

Patients diagnosed with confirmed influenza A infection from three Parisian transplant centers between September 1st, 2009 and February 15th, 2010. Clinical symptoms, biological, and radiological findings, and management were analysed and retrospectively compared between transplanted (T) and non-transplanted patients (NT). The evolution was assessed by a follow-up questionnaire, CT results 1 to 3 months after influenza infection and FEV1 variation.

Results

Seventy patients were included. Thirteen patients had an allograft (lung: eight, kidney: four, stem cells: one): (1) hospitalization: 100% (13 out of 13) in group T, 54% (31 out of 57) in group NT (P = 0.0013); (2) pneumonia: 62% (eight out of 13) in group T, 26% (eight out of 57) in group NT (P = 0.004); (3) mortality rate among hospitalized patients: 7.7% (one out of 13) in the group T, 9.7% (three out of 57) in group NT (P = NS); (4) chest CT scan abnormalities remained in four lung transplanted patients; (5) a minimum 10% decrease in FEV1 was detected in four lung transplant recipients.

Conclusion

Our results suggest that H1N1(2009) influenza A infection in transplant recipient patients compared to non-transplanted patients: (1) more often leads to hospitalization; (2) is more frequently associated with pneumonia; (3) is responsible for a persistent graft functional impairment in lung transplant recipients; (4) has a low mortality rate similar to admitted non-transplanted patients.     

Biochemical and molecular mechanisms of action of bisphosphonates

This review describes the key discoveries over the last 15 years that have led to a clearer understanding of the molecular mechanisms by which bisphosphonate drugs inhibit bone resorption. Once released from bone mineral surfaces during bone resorption, these agents accumulate intracellularly in osteoclasts. Simple bisphosphonates such as clodronate are incorporated into non-hydrolysable analogues of adenosine triphosphate, which induce osteoclast apoptosis. The considerably more potent nitrogen-containing bisphosphonates are not metabolised but potently inhibit farnesyl pyrophosphate (FPP) synthase, a key enzyme of the mevalonate pathway. This prevents the synthesis of isoprenoid lipids necessary for the post-translational prenylation of small GTPases, thereby disrupting the subcellular localisation and normal function of these essential signalling proteins. Inhibition of FPP synthase also results in the accumulation of the upstream metabolite isopentenyl diphosphate, which is incorporated into the toxic nucleotide metabolite ApppI. Together, these properties explain the ability of bisphosphonate drugs to inhibit bone resorption by disrupting osteoclast function and survival. These discoveries are also giving insights into some of the adverse effects of bisphosphonates, such as the acute phase reaction that is triggered by inhibition of FPP synthase in peripheral blood monocytes.     

Psychological profiles and adolescent adjustment: a person-centered approach

The association between young adolescents' psychological profiles and their subsequent adjustment was examined in a sample of 606 adolescents (ages 12-13) drawn from the mother-child data set of the National Longitudinal Survey of Youth. Cluster analysis was used to identify distinct groups of youth based on self-regulation, proneness to risk, self-worth, and perceived academic competence. Five replicable clusters were identified corresponding to optimal, average, behavioral risk, low self-regulation, and emotional risk groups. These clusters were associated with distinct patterns of adjustment 4 years later. At ages 16-17, youth in the optimal group tended to report better academic performance, less problem behavior, and less depression than youth in the three risk groups; however, their functioning did not differ significantly from youth in the average group. The three risk groups differed in self-reported depression symptoms and academic performance but not in levels of problem behavior. Differences among the five groups persisted when demographic and contextual variables were controlled. These results support the existence of different groups of youth who follow distinct developmental trajectories and may experience different patterns of adjustment.