Structure and Function of Cyanobacterial DHDPS and DHDPR.

Lysine biosynthesis in bacteria and plants commences with a condensation reaction catalysed by dihydrodipicolinate synthase (DHDPS) followed by a reduction reaction catalysed by dihydrodipicolinate reductase (DHDPR). Interestingly, both DHDPS and DHDPR exist as different oligomeric forms in bacteria and plants. DHDPS is primarily a homotetramer in all species, but the architecture of the tetramer differs across kingdoms. DHDPR also exists as a tetramer in bacteria, but has recently been reported to be dimeric in plants. This study aimed to characterise for the first time the structure and function of DHDPS and DHDPR from cyanobacteria, which is an evolutionary important phylum that evolved at the divergence point between bacteria and plants. We cloned, expressed and purified DHDPS and DHDPR from the cyanobacterium Anabaena variabilis. The recombinant enzymes were shown to be folded by circular dichroism spectroscopy, enzymatically active employing the quantitative DHDPS-DHDPR coupled assay, and form tetramers in solution using analytical ultracentrifugation. Crystal structures of DHDPS and DHDPR from A. variabilis were determined at 1.92 Å and 2.83 Å, respectively, and show that both enzymes adopt the canonical bacterial tetrameric architecture. These studies indicate that the quaternary structure of bacterial and plant DHDPS and DHDPR diverged after cyanobacteria evolved.

The effect of simvastatin on systemic inflammation and endothelial dysfunction induced by periodontitis.

BACKGROUND AND OBJECTIVE: It has been demonstrated that periodontitis induces systemic inflammation, which may impair endothelial function leading to increased cardiovascular risk. The aim of this study was to evaluate the effect of simvastatin on systemic inflammatory markers and endothelial dysfunction induced by periodontitis. MATERIAL AND METHODS: Wistar rats were subjected to ligature-induced experimental periodontitis. Eight days after the procedure, the ligature and sham groups were randomly assigned to receive simvastatin or vehicle once a day until the 14th day, when the effects of acetylcholine and sodium nitroprusside on blood pressure were evaluated. Blood samples were collected and evaluated for plasma interleukin-6C, -reactive protein and lipids. The maxilla and mandible were removed for bone loss analysis. RESULTS: Simvastatin treatment reduced systemic inflammation and endothelial dysfunction induced by periodontitis. Furthermore, simvastatin improved the blood lipid profile and reduced alveolar bone loss. CONCLUSION: Simvastatin treatment, in addition to the improvement on serum lipid profile, may reduce other predictors of cardiovascular events associated with periodontitis.

Comparison of pregnancy characteristics and outcomes between HIV-infected and HIV-non-infected women in Brazil.

The aim of this study is to evaluate the characteristics of pregnant women whether they are HIV infected or not and their prenatal care. It is a cross-sectional study. HIV-infected women were derived from a cohort study of all HIV-infected pregnant women followed from 1995 to 2005, at the Instituto de Puericultura e Pediatria Martagão Gesteira - Rio de Janeiro. HIV-non-infected women were derived from a random sample of all pregnant women who gave birth at Rio de Janeiro municipality between 1999 and 2001. All relevant sociodemographic, clinical, and pregnancy outcomes data were retrieved from both studies. To evaluate the prenatal care, we calculated the Kotelchuck Modified Index (KMI). The index is based on the months of initiation of prenatal care and the proportion of visits observed in each trimester, according to gestational age at birth. Comparisons were performed using Student t- and chi-square tests. Variables with p-value < 0.25 were included in an unconditional logistic regression model. There were 713 HIV-infected women and 2145 HIV-non-infected women. Variables independently associated with HIV status were: inadequate KMI (OR=4.08, 95% CI=3.17-5.24); lower educational level (OR=1.32, 95% CI=1.04-1.68); does not live with a partner (OR=3.54, 95% CI=2.66-4.64); lower family income (OR=4.71, 95% CI=3.62-6.14); tobacco use (OR=2.17, 95% CI=1.63-2.88); and hypertension (OR=1.47, 95% CI=1.01-2.17). Prematurity was not independently associated with HIV status. Although in Brazil, the HIV care is free of charge, pregnant women are still having difficulty to reach the specialized care. Better access to care must be offered to this population and studies of prematurity in the HIV-infected women must evaluate their prenatal care.

The effect of age on avian influenza viral shedding in mallards (Anas platyrhynchos).

Avian influenza virus (AIV) prevalence in wild aquatic bird populations varies with season, geographic location, host species, and age. It is not clear how age at infection affects the extent of viral shedding. To better understand the influence of age at infection on viral shedding of wild bird-origin low pathogenicity avian influenza (LPAI) viruses, mallards (Anas platyrhynchos) of increasing age (2 wk, 1 mo, 2 mo, 3 mo, and 4 mo) were experimentally inoculated via choanal cleft with a 10(6) median embryo infectious dose (EID50) of either A/Mallard/MN/355779/00 (H5N2) or A/Mallard/MN/199106/99 (H3N8). Exposed birds in all five age groups were infected by both AIV isolates and excreted virus via the oropharynx and cloaca. The 1-month and older groups consistently shed virus from 1 to 4 d post inoculation (dpi), whereas, viral shedding was delayed by 1 d in the 2-wk-old group. Past 4 dpi, viral shedding in all groups varied between individual birds, but virus was isolated from some birds in each group up to 21 dpi when the trial was terminated. The 1-mo-old group had the most productive shedding with a higher number of cloacal swabs that tested positive for virus over the study period and lower cycle threshold values on real-time reverse-transcription PCR. The viral shedding pattern observed in this study suggests that, although mallards from different age groups can become infected and shed LPAI viruses, age at time of infection might have an effect on the extent of viral shedding and thereby impact transmission of LPAI viruses within the wild bird reservoir system. This information may help us better understand the natural history of these viruses, interpret field and experimental data, and plan future experimental trials.

A pilot study to evaluate the safety and feasibility of the administration of AZT/3TC fixed dose combination to HIV infected pregnant women and their infants in Rio de Janeiro, Brazil.

OBJECTIVES: To evaluate the safety and feasibility of zidovudine and lamivudine (AZT/3TC) given to HIV infected pregnant women and their infants in Rio de Janeiro, Brazil. METHODS: This open label phase II study enrolled 40 HIV infected antiretroviral naive women >or=20 weeks gestation, CD4 <500 cells x10(6)/l, from two public hospitals. TREATMENT: fixed dose AZT 300 mg/3TC 150 mg by mouth every 12 hours until labour; AZT 300 mg by mouth every 3 hours until delivery; infants: AZT 4 mg/kg every 12 hours plus 3TC 2 mg/kg every 12 hours for 6 weeks. Blood haematology and chemistry were monitored; adherence evaluated by pills count; efficacy measured by changes in lymphocyte (CD4) and viral load, and by HIV RNA-PCR tests performed at birth, 6 and 12 weeks, to diagnose infant infection. No women breast fed. PATIENT CHARACTERISTICS: mean age 24.48 (SD 3.5) years; gestational age 24.5 (4.5) weeks; AZT/3TC duration 14.4 (4.4) weeks; vaginal delivery: 11/39; caesarean section: 28/39. Entry and pre-labour CD4: 310/486 cells x10(6)/l (p<0.001); entry and pre-labour viral load: 53 818/2616 copies/ml (p<0.001). Thirty nine women tolerated treatment with >80% adherence; one was lost to follow up. Five newborns were excluded from 3TC receipt. All 39 babies were uninfected. Haematological toxicity in newborns was common: anaemia in 27; neutropenia in five (two severe); platelets counts <100000 in two. All values recovered on study completion. CONCLUSIONS: Fixed dose AZT/3TC is well accepted, gives improvements in CD4 and viral load; no infants were HIV infected. Haematological toxicity in infants needs careful monitoring.

[Analysis of adequacy and effectiveness in the use of tocolytics in preterm labor]. / Anlise da adequação e da efetividade do uso de tocolíticos no trabalho de parto prematuro.

The objective of this study was to assess quality of care for premature labor at public maternity facilities in Rio de Janeiro, Brazil, using referents, indicators, and standards of care derived from scientific evidence. The standard utilized in the process analysis for use of betamimetic tocolytics was 100%, considering the related referents. For outcome analysis, the standard applied was the occurrence of premature delivery in 11% of patients within 24 h and in 24% of patients (referent) within 48 h of hospital admission. Use of tocolytics was observed in 18.7% of patients admitted in premature labor. At gestational age from 28 weeks to 33 weeks and 6 days, especially critical for neonatal survival, tocolytics were used in 32.6% of patients. Premature birth occurred in 59% of patients within 24 h and in 64% within 48 h. These outcomes were consistent with the low rate of utilization of tocolytics. Effectiveness of care for preterm labor measured by rate of premature birth was low. Results of the corresponding process and outcomes analysis were consistent.

[Assessment of quality of obstetric hospital care: use of corticoid in preterm labor]. / Avaliação da qualidade da assistência hospitalar obstétrica: uso de corticóides no trabalho de parto prematuro.

This study aimed to assess quality of obstetric care for preterm labor patients, using referents, indicators, and standards derived from scientific evidence, focusing on antenatal corticotherapy. Available meta-analyses and randomized controlled trials were examined to establish referents, defining indicators and estimating process and outcome standards for the present study. Data from hospital discharge summaries of seven public maternity hospitals in Rio de Janeiro were analyzed. The standard of process used was 100%. It was not possible to estimate outcome standards, since the necessary adjustment for gestational age was not feasible. Utilization of antenatal corticotherapy in the present study was very low, about 4% and 2%, considering patients up to 33 weeks and 6 days and 36 weeks and 6 days, respectively. Failure to use antenatal corticotherapy when formally indicated deserves attention by health planners and managers, considering: a) the ease in incorporating such a technology, in contrast to the adequate incorporation of special/intensive neonatal care; b) benefits and costs associated with this technology compared to those of delivering neonatal care to premature babies.

Estimating the effectiveness of perinatal care technologies by expert opinion.

The majority of technologies in use in perinatal care were organized into 45 technological functions. Forty-six experts from 19 different regions of Brazil and other Latin American countries then selected a "basic package" (BP) of 15 technological functions. Considering the 12 main causes of perinatal mortality in Brazil, the experts estimated the number of preventable deaths, assuming universal coverage by the BP and the additional reductions that could be obtained by gradually adding other technological functions to the BP. A simulation was performed for the 26 states of Brazil to identify regional priorities for the diffusion of technological functions. For most regions, the BP appears to be the most effective intervention, with the potential of reducing perinatal mortality by 33%, followed by "coordination of services and referral of pregnant women" (14%), and "treatment of respiratory conditions" (11.8%).