Previous adaptation triggers distinct molecular pathways and modulates early and long-term neuroprotective effects of pregnancy swimming preventing neonatal hypoxia-ischemia damage in rats.

Neonatal hypoxia-ischemia (HI) is one of the main causes of neurological damage in newborns. Pregnancy swimming (PS) alters brain maturation and has neuroprotective effects following HI; however, variables such as timing play a decisive role in its effects. Prior to mating, we tested if adaptation of female rats to a tank filled with water at 32 °C for 7 days before mating, modulates PS benefits. After mating, rats swam 20 min/day or remained in standard cages. Seven-day-old pups were subjected to HI (right common carotid artery occlusion followed by FiO2 8% for 60 min). Animals were divided into 8 experimental groups, adaptation, swimming and injury. Astrocytic reactivity, apoptosis-related proteins, neurotrophins and cell survival markers expression were assessed in the hippocampus 24 h after HI. From PND45, animals performed behavioral tests followed by histological assessment. Three-way ANOVA showed a significant increase in astrogliosis only in non-adapted HI animals. Swimming decreased apoptotic cell death despite adaptation period in both exercised groups. Cylinder evidenced HI impairments; no effect of swimming or adaptation period were observed. In the open field, only HI animals whose mothers had been adapted had increased locomotion; moreover, swimming reversed HI damage. Hemisphere and hippocampus were preserved only in the HI group whose mothers swam before mating, suggesting a preconditioning effect mediated by the adaptation. In summary, adaptation period plays a major role in the mechanisms involving neuroprotection afforded by PS and needs to be further explored in future studies involving damage to the neonatal brain.

Outcomes from patients with presumed drug resistant tuberculosis in five reference centers in Brazil.

BACKGROUND: The implementation of rapid drug susceptibility testing (DST) is a current global priority for TB control. However, data are scarce on patient-relevant outcomes for presumptive diagnosis of drug-resistant tuberculosis (pDR-TB) evaluated under field conditions in high burden countries. METHODS: Observational study of pDR-TB patients referred by primary and secondary health units. TB reference centers addressing DR-TB in five cities in Brazil. Patients age 18 years and older were eligible if pDR-TB, culture positive results for Mycobacterium tuberculosis and, if no prior DST results from another laboratory were used by a physician to start anti-TB treatment. The outcome measures were median time from triage to initiating appropriate anti-TB treatment, empirical treatment and, the treatment outcomes. RESULTS: Between February,16th, 2011 and February, 15th, 2012, among 175 pDR TB cases, 110 (63.0%) confirmed TB cases with DST results were enrolled. Among study participants, 72 (65.5%) were male and 62 (56.4%) aged 26 to 45 years. At triage, empirical treatment was given to 106 (96.0%) subjects. Among those, 85 were treated with first line drugs and 21 with second line. Median time for DST results was 69.5 [interquartile - IQR: 35.7-111.0] days and, for initiating appropriate anti-TB treatment, the median time was 1.0 (IQR: 0-41.2) days. Among 95 patients that were followed-up during the first 6 month period, 24 (25.3%; IC: 17.5%-34.9%) changed or initiated the treatment after DST results: 16/29 MDRTB, 5/21 DR-TB and 3/45 DS-TB cases. Comparing the treatment outcome to DS-TB cases, MDRTB had higher proportions changing or initiating treatment after DST results (p = 0.01) and favorable outcomes (p = 0.07). CONCLUSIONS: This study shows a high rate of empirical treatment and long delay for DST results. Strategies to speed up the detection and early treatment of drug resistant TB should be prioritized.

Drug-resistant tuberculosis in six hospitals in Rio de Janeiro, Brazil.

SETTING: Tuberculosis (TB) drug resistance survey in six hospitals in Rio de Janeiro, Brazil. OBJECTIVE: To estimate resistance to at least one drug (DR) and multidrug resistance (MDR) and identify associated factors. DESIGN: One-year cross-sectional survey. Hospitals were included as a convenience sample. RESULTS: Of 595 patients investigated, 156 (26.2%) had previously undergone anti-tuberculosis treatment, 433 (72.8%) were not previously treated and information on the remaining 6 was not available. Overall, DR and MDR rates were high, at respectively 102 (17.1%, 95%CI 14.3-20.5) and 44 (7.4%, 95%CI 5.5-9.9) cases. Among individuals not previously treated, 17 had MDR (3.9%, 95%CI 2.4-6.3) and diagnosis in a TB reference hospital was independently associated with MDR (prevalence ratio [PR] 3.3, 95%CI 1.2-8.7) after multivariate analysis. Among previously treated individuals, 27 had MDR (17.3%, 95%CI 11.7-24.2). MDR-TB was independently associated with diagnosis in a TB reference hospital (PR 3.6, 95%CI 1.5-8.7), male sex (PR 2.3, 95%CI 1.2-4.4) and dyspnoea (PR 0.3, 95%CI 0.1-0.7). CONCLUSION: We found high levels of DR- and MDR-TB. Our study design did not permit us to determine the contribution of community versus nosocomial transmission. Further studies are needed to establish this. Nevertheless, hospitals should be recognised as a potential source of transmission of resistant TB strains and urgent measures to avoid nosocomial TB transmission should be taken.

Phenotypic and genotypic variant of MDR-Mycobacterium tuberculosis multiple isolates in the same tuberculosis episode, Rio de Janeiro, Brazil

Assuming that the IS6110-restriction fragment length polymorphism (RFLP) changes at a constant rate of 3.2 years, this methodology was applied to demonstrate, for the first time, variant patterns of Mycobacterium tuberculosis (MTB) in multiple isolates obtained at short time intervals from sputum and blood of an HIV+ patient with multiple admissions to the Emergency Room and to the multidrug-resistant tuberculosis (MDR-TB) Reference Center of a secondary-care hospital in Rio de Janeiro, Brazil. In sputum, the IS6110-RFLP appeared in isolates with two variant patterns with 10 and 13 IS6110 copies. However, blood presented only the pattern corresponding to 10 copies, suggesting compartmentalization. With regard to the exact match of 10 of 13 bands, this may be a subpopulation with the same clonal origin and this may be related to the IS6110 transposition. A susceptibility test demonstrated an MDR profile (INH R, RIF R, SM R, and EMB R), with the sputum isolate also exhibiting EMB S (R = resistant; S = sensitive). A gene mutation confirmed resistance only to streptomycin. There was agreement between the results of the phenotypic test and the clinical response to MDR-TB treatment, suggesting serious implications with regard to treatment administration based exclusively on molecular methods, and calling attention to the fact that more effective control strategies against the emergence of MDR strains must be implemented by the TB control program to prevent transmission of MDR-MTB strains at health facilities in areas highly endemic for TB.

Phenotypic and genotypic variant of MDR-Mycobacterium tuberculosis multiple isolates in the same tuberculosis episode, Rio de Janeiro, Brazil.

Assuming that the IS6110-restriction fragment length polymorphism (RFLP) changes at a constant rate of 3.2 years, this methodology was applied to demonstrate, for the first time, variant patterns of Mycobacterium tuberculosis (MTB) in multiple isolates obtained at short time intervals from sputum and blood of an HIV+ patient with multiple admissions to the Emergency Room and to the multidrug-resistant tuberculosis (MDR-TB) Reference Center of a secondary-care hospital in Rio de Janeiro, Brazil. In sputum, the IS6110-RFLP appeared in isolates with two variant patterns with 10 and 13 IS6110 copies. However, blood presented only the pattern corresponding to 10 copies, suggesting compartmentalization. With regard to the exact match of 10 of 13 bands, this may be a subpopulation with the same clonal origin and this may be related to the IS6110 transposition. A susceptibility test demonstrated an MDR profile (INH(R), RIF(R), SM(R), and EMB(R), with the sputum isolate also exhibiting EMB(S) (R = resistant; S = sensitive). A gene mutation confirmed resistance only to streptomycin. There was agreement between the results of the phenotypic test and the clinical response to MDR-TB treatment, suggesting serious implications with regard to treatment administration based exclusively on molecular methods, and calling attention to the fact that more effective control strategies against the emergence of MDR strains must be implemented by the TB control program to prevent transmission of MDR-MTB strains at health facilities in areas highly endemic for TB.

Retreatment tuberculosis cases. Factors associated with drug resistance and adverse outcomes.

STUDY OBJECTIVE: Risk factors associated with treatment failure and multidrug-resistant tuberculosis (MDR-TB) were examined among HIV-seronegative patients who were previously treated for tuberculosis (TB). DESIGN: Prospective, cohort study of patients referred to the study hospital for retreatment of TB between March 1986 and March 1990. PATIENTS: The patients belonged to three groups, according to outcomes following their previous treatment: 37 patients who abandoned treatment or suffered relapse after completion of therapy (group A), 91 patients who failed to respond to the first-line drug regimen (group B), and 78 patients who failed to respond to the second-line drug regimen (group C). RESULTS: Patients with Mycobacterium tuberculosis strains resistant to rifampin and isoniazid were found in 2 (6%) in group A, 29 (33%) in group B, and 49 (65%) in group C. Cure was achieved in 77% in group A, 54% in group B, and 36% in group C. Death occurred in none of the patients in group A, 8% in group B, and 24% in group C. In a multivariate logistic regression analysis, unfavorable response (failure to sterilize sputum culture, death, and abandonment) was significantly associated with infection with a multidrug-resistant M tuberculosis strain (p = 0.0002), cavitary disease (p = 0.0029), or irregular use of medications (p < 0.0001). CONCLUSIONS: These observations show that a previous treatment outcome and current clinical and epidemiologic histories can be used to predict the development of MDR-TB and adverse outcomes in patients undergoing retreatment for TB. Such information may be useful for identifying appropriate patient candidates for programs such as directly observed therapy.