Phenotypic and molecular analyses of yellow fever 17DD vaccine viruses associated with serious adverse events in Brazil

The yellow fever (YF) 17D virus is one of the most successful vaccines developed to data. Its use has been estimated to be over 400 million doses with an excellent record of safety. In the past 3 years, yellow fever vaccination was intensified in Brazil in response to higher risk of urban outbreaks of the disease. Two fatal adverse events temporally associated with YF vaccination were reported. Both cases had features similar to yellow fever disease, including hepatitis and multiorgan failure. Two different lots of YF 17DD virus vaccine were administered to the affected patients and also to hundreds of thousands of other individuals without any other reported serious adverse events. The lots were prepared from the secondary seed, which has been in continuous use since 1984. Nucleotide sequencing revealed minor variations at some nucleotide positions between the secondary seed lot virus and the virus isolates from patients; these differences were not consistent across the isolates, represented differences in the relative amount of each nucleotide in a heterogeneous position, and did not result in amino acid substitutions. Inoculation of rhesus monkeys with the viruses isolated from the two patients by the intracerebral (ic) or intrahepatic (ih) route caused minimal viremia and no clinical signs of infection or alterations in laboratory markers. Central nervous system histological scores of rhesus monkeys inoculated ic were within the expected range, and there were no histopathological lesions in animals inoculated ih. Altogether, these results demonstrated the genetic stability and attenuated phenotype of the viruses that caused fatal illness in the two patients. Therefore, the fatal adverse events experienced by the vaccinees are related to individual, genetically determined host factors that regulate cellular susceptibility to yellow fever virus. Such increased susceptibility, resulting in clinically overt disease expression, appears to be extremely rare.     

Search of antimeasles antibodies in HIV-infected children after basic immunization

OBJECTIVE: To determine the presence of antimeasles antibodies in children perinatally infected with HIV and properly immunized. METHODS: A retrospective cohort study conducted in Belo Horizonte by the Universidade Federal de Minas Gerais, between 1995 and 1996. Twenty one children perinatally infected with HIV and 29 immunocompetent noninfected children were included in the study. Information about measles vaccination was obtained from patient? immunization charts. The presence of neutralizing antibodies against the measles was determined by the plaque reduction neutralization test and IgM was measured by ELISA. The level of significance was set at 5% in all the performed statistical analyses. RESULTS: Median age was 44.5 months for HIV-infected patients and 62.0 months for noninfected children (P=0.64). Both groups received on average two doses of antimeasles vaccine. All HIV-seronegative patients presented antimeasles antibody titers greater than 50 mIU/ml, whereas 57.1% of infected children presented titers above this value (P=0.0001). The geometric mean titer of neutralizing antibodies was significantly lower in the group of HIV-infected children (433.5 mIU/ml) than in noninfected children (1,668.1 mIU/ml), P=0.001. All patients in both groups were negative for antimeasles IgM. CONCLUSION: In the present study, HIV-infected children showed a lower seroprevalence of antimeasles antibody after immunization than noninfected children. These results emphasize the risk of acquisition of measles virus and the need to evaluate alternatives to the vaccination of HIV-infected children in an attempt to maximize the protection against the measles in this group of patients.     

Risk factors for abdominal scar endometriosis after obstetric hysterotomies: a case-control study

OBJECTIVE: To identify risk factors that are associated with the development of scar endometriosis after obstetric hysterotomies. The hypothesis is that early hysterotomy in pregnancy (before 22nd week) is the main risk factor for the development of scar endometriosis. METHODS: The authors conducted a case-control study between April 2000 and June 2003. A total of 117 women were selected, including 39 cases and 78 controls. Exposure and confounding variables were measured by a standardized questionnaire, which included sociodemographic characteristics, reproductive/physiologic history, past pathological history, history of obstetric surgeries, family history, and social history. The odds ratio (OR) and its 95% confidence interval (CI) were calculated using bivariate analysis for each possible risk factor. These estimates were obtained by multivariate analysis using unconditional logistic regression. Tests were made to assess the fit of the final model. RESULTS: In the multivariate analysis, positive associations were observed between scar endometriosis and hysterotomy type (early versus late: OR = 42.99; CI 8.77-210.81), amount of the menstrual blood flow (heavy versus light/normal: OR = 11.97; CI 2.35-60.82), and alcoholic consumption (yes versus no: OR = 5.31; CI 1.22-23.11). Negative association was observed between scar endometriosis and parity (OR = 0.61; CI 0.31-1.23), however it was not statistically significant (p>0.05). CONCLUSIONS: Early hysterotomy in pregnancy is the main risk factor for scar endometriosis. Increased menstrual flow and alcohol consumption are also risk factors, while high parity may be a protecting factor.     

Impact of untreated dental caries severity on the quality of life of preschool children and their families: a cross-sectional study

Purpose

Untreated dental caries is a persistent oral problem among preschool children. Although there is vast evidence regarding the impact of dental caries on oral health-related quality of life (OHRQoL) in this age group, evidence on the impact of untreated caries severity is scarce. The purpose of this study was to investigate the impact of untreated caries severity on the OHRQoL of preschool children and their families.

Methods

A cross-sectional study was conducted with 563 individuals in the city of Goiania, Brazil. Data were collected through interviews with parents/caregivers and clinical examinations of their children. The OHRQoL was measured by the Brazilian version of the Early Childhood Oral Health Impact Scale. Untreated dental caries severity was assessed using validated indices. Other independent variables were socioeconomic, toothache prevalence, and the questionnaire respondent. Statistical analysis involved bivariate comparisons and Poisson regression analyses.

Results

A higher prevalence of impact on OHRQoL was found among preschool children with untreated dental caries with clinical consequences (PR 1.31; 95% CI 1.01–1.70) compared to those without caries; those aged 5 years (PR 1.47; 95% CI 1.18–1.82), compared to those aged two; and those with a toothache (PR 1.54; 95% CI 1.34–1.76), compared to those without toothache. Moreover, fathers (PR 0.71; 95% CI 0.55–0.92) and other respondents (PR 0.70; 95% CI 0.52–0.96) perceived less impact on the OHRQoL in comparison to mothers.

Conclusions

Severe untreated dental caries with clinical consequences had a negative impact on the children’s OHRQoL, regardless of toothache and socioeconomic factors.

     

Placental metal concentrations and birth outcomes: The Environment and Childhood (INMA) project

Objective

To examine the association of placental levels of arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), manganese (Mn), and chromium (Cr) with birth outcomes (birth weight, length, and head circumference, low birth weight [LBW], gestational age, preterm delivery, and small for gestational age [SGA]) in mother-child pairs from the Environment and Childhood (INMA) Project in Spain.

Evaluation of antiulcer activity of the main phenolic acids found in Brazilian Green Propolis

Aim of the study

In a previous study, our group described the gastric protective effect of the hydroalcoholic extract of Brazilian green propolis. The main compounds found in Brazilian green propolis include phenolic acids, such as: caffeic, ferulic, p-coumaric and cinnamic acids. This study was therefore carried out to evaluate the antiulcerogenic property of the main phenolic acids found in Brazilian Green Propolis.

Material and methods

The anti-ulcer assays were performed using the following protocols: nonsteroidal-antiinflammatory drug (NSAID)-induced ulcer, ethanol-induced ulcer, and stress-induced ulcer. The effects of the phenolic acids on gastric content volume, pH and total acidity, using the pylorus ligated model, were also evaluated.

Results

It was observed that treatment using doses of 50 and 250 mg/kg of caffeic, ferulic, p-coumaric and cinnamic acids and positive controls (omeprazol or cimetidine) significantly diminished the lesion index, the total area of the lesion and the percentage of lesion in comparison with the negative control groups. In addition, the percentage of ulcer inhibition was significantly higher in the groups treated with the different phenolic acids, cimetidine or omeprazol, in all the protocols used, compared with the negative control groups. In the model to determine gastric secretion, using ligated pylorus, treatment with phenolic acids and cimetidine reduced the volume of gastric juice and total acidity and significantly increased the gastric pH (p < 0.05), compared with the control group, with the exception of the group treated with 50 mg/kg of p-coumaric acid, in which no significant difference was observed, compared with the control. In relation to the acute toxicity, none sign of toxicity was observed when phenolic acids, used in this study, were administered for rats in dose of 2000 mg/kg.

Conclusions

In conclusion, the results of this study show that caffeic, ferulic, p-coumaric and cinnamic acids display antiulcer activity.     

A randomized, naturalistic, parallel-group study for the long-term treatment of panic disorder with clonazepam or paroxetine

This long-term extension of an 8-week randomized, naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam (n = 47) and paroxetine (n = 37) over a 3-year total treatment duration. Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine (both taken at bedtime). This study reports data from the long-term period (34 months), following the initial 8-week treatment phase. Thus, total treatment duration was 36 months. Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine, but patients with partial primary treatment success were switched to the combination therapy. At initiation of the long-term study, the mean doses of clonazepam and paroxetine were 1.9 (SD, 0.30) and 38.4 (SD, 3.74) mg/d, respectively. These doses were maintained until month 36 (clonazepam 1.9 [SD, 0.29] mg/d and paroxetine 38.2 [SD, 3.87] mg/d). Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)-Improvement rating than treatment with paroxetine (mean difference: CGI-Severity scale -3.48 vs -3.24, respectively, P = 0.02; CGI-Improvement scale 1.06 vs 1.11, respectively, P = 0.04). Both treatments similarly reduced the number of panic attacks and severity of anxiety. Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine (28.9% vs 70.6%, P < 0.001). The efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course. There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events.     

In vitro antioxidant activity and in vivo antidepressant-like effect of α-(phenylselanyl) acetophenone in mice

In this study, the antioxidant and antidepressant-like effects of α-(phenylselanyl) acetophenone (PSAP), an organoselenium compound, were investigated. To assess the in vitro antioxidant properties, PSAP was evaluated in four test systems (DPPH, ABTS, FRAP and inhibition of lipid peroxidation). PSAP (100-500 μM) showed potent antioxidant activity and protected against lipid peroxidation. Additionally, we investigated whether PSAP, when administered in mice (100, 200 and 400 mg/kg, per oral, p.o.), could cause acute toxicity. Our results demonstrated that PSAP did not cause the death of any animal, significantly reduce body weight or cause any oxidative tissue stress following treatment. This study also evaluated the effect of PSAP (0.1-10 mg/kg, p.o) on mice in a forced swim test (FST) and tail suspension test (TST), assays that are predictive of depressant activity and motor activity in the open-field. PSAP (5-10 mg/kg) significantly reduced immobility time in the FST and TST without affecting motor activity. In addition, the antidepressant-like effect caused by PSAP (5 m/kg, p.o) in mice during the TST was dependent on an interaction with the serotonergic system (5-HT_1A receptors), but not with the noradrenergic, dopaminergic or adenosinergic system. Together, these results suggest that PSAP possesses antioxidant and antidepressant-like properties and may be of interest as a therapeutic agent for the treatment of depressive disorders.