Antimicrobial Resistance in Streptococcus pneumoniae before and after the Introduction of Pneumococcal Conjugate Vaccines in Brazil: A Systematic Review.

Streptococcus pneumoniae causes serious illnesses, such as pneumonia, bacteremia, and meningitis, mainly in immunocompromised individuals and those of extreme ages. Currently, pneumococcal conjugate vaccines (PCVs) are the best allies against pneumococcal diseases. In Brazil, the 10-valent and 13-valent PCVs have been available since 2010, but the threat of antimicrobial resistance persists and has been changing over time. We conducted a systematic review of the literature with works published since 2000, generating a parallel between susceptibility data on isolates recovered from colonization and invasive diseases before and after the implementation of PCVs for routine childhood use in Brazil. This systematic review was based on the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Literature Reviews and Meta-Analyses (PRISMA) guidelines. Despite the inclusion of PCVs at a large scale in the national territory, high frequencies of non-susceptibility to important drugs used in pneumococcal diseases are still observed, especially penicillin, as well as increasing resistance to macrolides. However, there are still drugs for which pneumococci have a comprehensive sensitivity profile.

Development and validation of a rabbit model of Pseudomonas aeruginosa non-ventilated pneumonia for preclinical drug development.

Background: New drugs targeting antimicrobial resistant pathogens, including Pseudomonas aeruginosa, have been challenging to evaluate in clinical trials, particularly for the non-ventilated hospital-acquired pneumonia and ventilator-associated pneumonia indications. Development of new antibacterial drugs is facilitated by preclinical animal models that could predict clinical efficacy in patients with these infections. Methods: We report here an FDA-funded study to develop a rabbit model of non-ventilated pneumonia with Pseudomonas aeruginosa by determining the extent to which the natural history of animal disease reproduced human pathophysiology and conducting validation studies to evaluate whether humanized dosing regimens of two antibiotics, meropenem and tobramycin, can halt or reverse disease progression. Results: In a rabbit model of non-ventilated pneumonia, endobronchial challenge with live P. aeruginosa strain 6206, but not with UV-killed Pa6206, caused acute respiratory distress syndrome, as evidenced by acute lung inflammation, pulmonary edema, hemorrhage, severe hypoxemia, hyperlactatemia, neutropenia, thrombocytopenia, and hypoglycemia, which preceded respiratory failure and death. Pa6206 increased >100-fold in the lungs and then disseminated from there to infect distal organs, including spleen and kidneys. At 5 h post-infection, 67% of Pa6206-challenged rabbits had PaO2 <60 mmHg, corresponding to a clinical cut-off when oxygen therapy would be required. When administered at 5 h post-infection, humanized dosing regimens of tobramycin and meropenem reduced mortality to 17-33%, compared to 100% for saline-treated rabbits (P<0.001 by log-rank tests). For meropenem which exhibits time-dependent bactericidal activity, rabbits treated with a humanized meropenem dosing regimen of 80 mg/kg q2h for 24 h achieved 100% T>MIC, resulting in 75% microbiological clearance rate of Pa6206 from the lungs. For tobramycin which exhibits concentration-dependent killing, rabbits treated with a humanized tobramycin dosing regimen of 8 mg/kg q8h for 24 h achieved Cmax/MIC of 9.8 ± 1.4 at 60 min post-dose, resulting in 50% lung microbiological clearance rate. In contrast, rabbits treated with a single tobramycin dose of 2.5 mg/kg had Cmax/MIC of 7.8 ± 0.8 and 8% (1/12) microbiological clearance rate, indicating that this rabbit model can detect dose-response effects. Conclusion: The rabbit model may be used to help predict clinical efficacy of new antibacterial drugs for the treatment of non-ventilated P. aeruginosa pneumonia.

Two years of COVID-19 pandemic: Framework of health interventions in a Brazilian city.

The COVID-19 pandemic and its effects on public health have urgently demanded effective health policies to avoid the spread of COVID-19. Thus, public administrators have implemented non-pharmacological and pharmacological interventions to mitigate the pandemic's impacts and strengthen health services. The aim of this ecological study is to describe the scenario of COVID-19 pandemic in a Brazilian city, during 2 years. This ecological study was carried out in Nova Friburgo, a Brazilian city, for 105 weeks (two years), from March 29, 2020 (week 1) to April 02, 2022 (week 105). Data on COVID-19 cases and COVID-19 deaths, occupation of COVID-19 exclusive beds in hospitals, community mobility, vaccination, government regulation on the opening of city establishments and city risk assessment were collected from public datasets. Four waves of COVID-19 cases and deaths were observed during this period. The first case occurred in week 1 and first death in week 3 of this study. The highest peaks of cases and deaths were observed during the third wave with 1,131 cases (week 54) and 47 deaths (week 55) and where the highest occupation of COVID-19 exclusive beds in local hospitals occurred. Interventions from more restrictive to more flexible, were implemented throughout this study, including lockdown and gradual return in economic and social strata levels. Vaccination began on week 43 and at the end of this study 89.91% of the total population was vaccinated with at least one dose, being 83.22% fully vaccinated. A deep description of several interventions used to avoid COVID-19 spread in a Brazilian city during 2 years of this pandemic can help promote better decision-making in the future while it exposes the challenges of conducting public health policies in a pandemic scenario.

Cytocompatibility and antimicrobial activity of a novel endodontic irrigant combining citric acid and chlorhexidine.

OBJECTIVES: This study aimed to evaluate the antibacterial ability and cytocompatibility of a new irrigant solution for endodontic treatment composed of 10% citric acid (CA) and 1% chlorhexidine (CHX). METHODS: Thirty-five extracted single-canal human teeth were selected and de-crowned. Canal systems (n = 7/group) were infected with Enterococcus faecalis for 4 weeks and subject to irrigation with 1% CHX; 10% CA; irrigating solution 10% CA associated with 1% CHX (CACHX); 2.5% NaOCl or sterile water (control). Microbiological samples were collected immediately and 18 h after irrigation (enriched samples). The canals were filled with culture medium post irrigation to verify the bacterial presence/absence qualitatively and quantitatively through colony counting (log10 CFU/mL). A multiparametric assay was performed after exposure of human periodontal ligament fibroblasts (HPdLF) to the test solutions. The Kruskal-Wallis test with Dunn´s post-test and Fisher's exact test were employed at the 95% confidence level to compare differences among groups. RESULTS: All tested solutions were cytocompatible with human periodontal ligament fibroblasts. No difference was observed on antibacterial activity between 1% CHX, 10% CA, CACHX and 2.5% NaOCl (p > 0.05). Eighteen hours after irrigation, CACHX samples were the only that did not present E. faecalis in the root canal system. CONCLUSIONS: The demonstrated good in vitro biocompatibility and elimination of E. faecalis suggest a potential use of 10% CA associated with 1% CHX as a solution for microbiological control during endodontic treatment. CLINICAL RELEVANCE: Irrigants play an essential role during endodontic therapy. This irrigating solution, based on the association of 10% citric acid with 1% chlorhexidine, seems viable for clinical procedures.

Virulence of Lactobacillus spp. misidentified as Enterococcus faecalis from children's carious dentine.

Objective: This study aimed to search for Enterococcus faecalis in children's deep carious dentine and characterize their virulence traits.Material and Methods: Eight isolates from 15 carious molars identified by 16S rDNA species-specific PCR as E. faecalis were included. These eight isolates were subject to identification by MALDI-TOF and characterized regarding: (i) bacterial aggregation and biofilm formation on polystyrene and glass, with/without saliva, as single or dual-species (associated to Streptococcus mutans); (ii) environmental pH measurement before and after 24 h incubation; (iii) acidogenicity; (iv) gelatinase production; (v) macrophage adherence; and (vi) toxicity towards Caenorhabditis elegans. Statistical analyses were performed using two-way ANOVA/Tukey or Fisher's exact tests.Results: All isolates initially identified as E. faecalis by PCR were correctly identified as Lactobacillus by MALDI-TOF, being designated as Lactobacillus misidentified as Enterococcus (LME). These isolates produced biofilm in the presence of saliva and in the dual-species assays. Bacterial aggregation was only observed in the dual-species model. After 24 h, environmental pH dropped from 7.5 to 4.5 for seven of eight isolates, and to 4.0 in all dual-species models. LME isolates were acidogenic, none of them produced gelatinase or adhered to macrophages, but all presented toxicity towards C. elegans.Conclusions: No E. faecalis were identified in the children's caries lesions. All LME isolates presented important virulence traits, including biofilm formation and high acidogenicity, which cause enamel demineralization, that might increase the risk of dental caries in children carrying LME. Thus, the correct identification and in-depth virulence characterization of microorganisms isolated from dental caries are important to understand the dynamics of this disease.

Prevalence of oxacillin-susceptible methicillin-resistant Staphylococcus aureus nasal carriage and their clonal diversity among patients attending public health-care facilities.

Context: Nosocomial infections arise from many microorganisms, including Staphylococcus aureus. Aims: The aim of this study is to determine the molecular epidemiology of circulating methicillin-resistant S. aureus (MRSA) clones among patients attending community and health-care facilities in Nova Friburgo, RJ, Brazil. Methods: A total of 1002 nasal swab samples were collected from May 2010 to September 2015. S. aureus isolates were identified through phenotypic tests, submitted to antimicrobial susceptibility tests and genotypic analysis to detect mecA, panton-valentine leucocidin (PVL) genes, SCCmec, SPA and multilocus sequencing typing (MLST) typing. Results: We identified 294 (29.3%) isolates as S. aureus and 91 (9.1%) as MRSA. A total of 17 isolates did not present a correlation between phenotypic and genotypic resistance profiles. Among MRSA isolates, 17 (18.7%) carried PVL genes. A total of 20 different SPA types were determined, being grouped by MLST into eight different sequence types. ST5/t002 was the most prevalent genotype found among these isolates. Conclusions: There is a gradual colonisation shift happening in the infection pattern by S. aureus in Brazil. The Brazilian Epidemic Clone (ST239-SCCmec IIIa-PVL-) seems to be substituted by isolates from different clonal complexes, such as ST5, ST8 and ST30. The non-correlation between phenotypic/genotypic resistance profile observed in some isolates suggests the presence of other methicillin resistance mechanisms different from mecA presence or a difference in the nucleotide sequence, which prevents the primers to identify the specific region during polymerase chain reaction reactions. MRSA identification should be based on phenotypic and genotypic testing to ensure the various types of resistance mechanisms.

COVID-19: An Alert to Ventilator-Associated Bacterial Pneumonia.

This manuscript aims to highlight the risk of Ventilator-Associated Bacterial Pneumonia (VAP) in COVID-19 inpatients. The co-infection has the potential to worsen clinical condition and increase mortality in these patients, as well as to prolong and increase the costs of hospitalization. Preventing, identifying and treating early VAP can increase the chances of successful treatment in patients with COVID-19.

Prevalence of PspA families and pilus islets among Streptococcus pneumoniae colonizing children before and after universal use of pneumococcal conjugate vaccines in Brazil.

In 2010, the 10-valent (PCV10) and 13-valent (PCV13) pneumococcal conjugate vaccines were introduced in Brazil to immunize children, resulting in serotype replacement. We analyzed 253 carriage isolates recovered from children aged <6 years in Brazil, including 124 and 129 isolates from the pre-PCV10/13 (December 2009-July 2010) and post-PCV10/13 (September-December 2014) periods, respectively, to investigate the prevalence of PspA families and pilus islets, potential vaccine candidates. Serotypes and resistance profiles were previously characterized. We used PCR to type PspA families (Fam1-3) and pilus islets (PI-1 and PI-2). We identified the PspA family of 130 (51.4%) isolates. PspA families 1, 2, and 3 were identified in 12.2%, 38.7%, and 0.4% of the isolates, respectively. Eighteen (58.1%) Fam1 isolates were serogroup 6. Nine (81.8%) of 11 serotype 14 isolates were Fam2. Fam1 isolates resistant to penicillin (50%), erythromycin (43.7%), clindamycin (31.2%), and chloramphenicol (6.2%) were only found after PCV10/13 introduction. Resistance among Fam2 isolates was higher in the post-PCV10/13 period to erythromycin (1.8% vs. 18.6%), clindamycin (0 vs. 13.9%), and tetracycline (10.9% vs. 16.3%). PI-I was detected in 42 (16.6%) isolates. Fourteen (56%) of 25 serotype 15B/C and nine (81.8%) of 11 serotype 14 isolates had PI-1 (p < 0.01). Eight (3.2%) isolates had PI-2, and six (75%) were serogroup 19. Five (2%) serogroup 19 isolates had both PI-1 and PI-2. We found associations between serogroups/serotypes, PspA families, and pilus islets, but distribution of PspA families and pilus islets was similar in both periods. After universal vaccination, we observed higher antimicrobial resistance frequencies, regardless PspA or pilus types.

Antimicrobial Photodynamic Therapy as an Adjunct for Clinical Partial Removal of Deciduous Carious Tissue: A Minimally Invasive Approach.

This study aimed to evaluate the use of antimicrobial photodynamic therapy (aPDT) as an adjunct for minimally invasive treatment (partial removal of carious tissue-PRCT) of deciduous carious tissue evaluating its efficacy in reducing microorganisms. For that, a clinical study was design including children with deciduous molars with active deep caries lesions (DCL). PRCT was performed and remaining dentin was treated with 100 µg mL-1 methylene blue solution (5 min) and than irradiated with a low power laser emitting red light (InGaAIP-indium gallium aluminum phosphide; λ = 660 nm; 100 mW; 300 J cm-2 ; 90 s; 9 J). The colony forming units (CFU) count after PRCT and after PRCT + aPDT/mg of dentin were compared for total microorganisms, including Candida spp., the mutans streptococci group, Streptococcus spp. and Lactobacillus spp. The dentin was classified (color, consistency and humidity). The microbial reduction varied from 69.88% to 86.29% and was significantly observed for total microorganisms, mutans streptococci, Streptococcus spp. and Lactobacillus spp (P < 0.001). The dentin type did not influence reduction of microorganisms (P > 0.05). The aPDT presents a promising future for clinical use as an adjunct for the reduction of microorganisms in PRCT of DCL in all kinds of dentin.

Influence of thickness, color, and polishing process of ethylene-vinyl-acetate sheets on surface roughness and microorganism adhesion.

BACKGROUND/AIM: The surface roughness of dental materials can make cleaning difficult, thus facilitating retention of food debris and accumulation of microorganisms. The aim of this study was to assess whether thickness, color, and the polishing process influence the surface roughness of ethylene-vinyl-acetate (EVA) sheets and the amount of microorganisms that adhere to them. MATERIALS AND METHODS: A total of 180 samples of EVA (5 × 5 mm) were divided into 9 groups according to thickness (G1 = 2 mm; G2 = 3 mm; and G3 = 4 mm), color (G4 = black and G5 = white), and type of polishing (G6 = Scheu™; G7 = Scheu™ associated with hot-air burner; G8 = Erkodent™ and G9 = Erkodent™ associated with hot-air burner). Mean value of 3 roughness parameters was assessed: Ra, Rq, and Rz (one-way ANOVA test and Tukey's test, P < .05). Seven samples of each group (n = 63) were inoculated with saliva for 2 hours to promote microbial adhesion and count the number of colony-forming units (CFUs) (one-way ANOVA test, P < .05). Scanning electron microscopy (SEM) of microbial adhesion and the effects of the polishing process on the surface was assessed. RESULTS: Only the polishing parameter presented less roughness (G2, G7 and G9; P < .05) as also observed on SEM. SEM characterized microbial adhesion but the CFU count was not statistically significant, independent of the assessed parameters. CONCLUSION: The polishing systems, Scheu™ and Erkodent™ in association with a hot-air burner, were effective in decreasing the surface roughness without influencing the amount of adhered microorganisms.

Increased Root Canal Endotoxin Levels are Associated with Chronic Apical Periodontitis, Increased Oxidative and Nitrosative Stress, Major Depression, Severity of Depression, and a Lowered Quality of Life.

Evidence indicates that major depression is accompanied by increased translocation of gut commensal Gram-negative bacteria (leaky gut) and consequent activation of oxidative and nitrosative (O&NS) pathways. This present study examined the associations among chronic apical periodontitis (CAP), root canal endotoxin levels (lipopolysaccharides, LPS), O&NS pathways, depressive symptoms, and quality of life. Measurements included advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), lipid peroxides (LOOH), -sulfhydryl (SH) groups, total radical trapping antioxidant parameter (TRAP), and paraoxonase (PON)1 activity in participants with CAP, with and without depression, as well as healthy controls (no depression, no CAP). Root canal LPS levels were positively associated with CAP, clinical depression, severity of depression (as measured with the Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory) and O&NS biomarkers, especially NOx and TRAP. CAP-related depression was accompanied by increased levels of NOx, LOOH, AOPP, and TRAP. In CAP participants, there was a strong correlation (r = 0.734, p < 0.001) between root canal LPS and the HDRS score. There were significant and positive associations between CAP or root canal endotoxin with the vegetative and physio-somatic symptoms of the HDRS as well as a significant inverse association between root canal endotoxin and quality of life with strong effects on psychological, environmental, and social domains. It is concluded that increased root canal LPS accompanying CAP may cause depression and a lowered quality of life, which may be partly explained by activated O&NS pathways, especially NOx thereby enhancing hypernitrosylation and thus neuroprogressive processes. Dental health and "leaky teeth" may be intimately linked to the etiology and course of depression, while significantly impacting quality of life.

Antimicrobial Photodynamic Therapy Associated with Conventional Endodontic Treatment: A Clinical and Molecular Microbiological Study.

This study evaluated antimicrobial photodynamic therapy (aPDT) as an adjunct to endodontic treatment. Ten uniradicular teeth (control group (CG) = 4 (2 and test group (TG) = 6) with primary endodontic infections, from both genders, between 17 and 65 years old, were analyzed. Microbiological samples were collected before and after chemical-mechanical instrumentation (CMI), after aPDT (for the TG), and after the removal of the temporary restorations (second session). In TG, the aPDT was performed with 100 µg mL-1 methylene blue and irradiated with low power laser (InGaAIP, 660 nm; 100 mW; 40 s) with a fiber-coupled optical laser. Another irradiation (3 J; 30 s; spot size of 3 mm2 ) was performed in the gingiva close to the apical foramen. The PCR was performed, after previous whole-genome amplification, for Enterococcus faecalis, Candida genus and Bacteria domain. For TG, a positive tooth for Candida spp. before of the CMI presented negative results in subsequent samples. Additionally, E. faecalis species was present in four samples before CMI, two after CMI, in one after the aPDT and was not detected at the second session. aPDT may be an effective adjunct therapy, resulting in a reduction (P = 0.0286) of the incidence of E. faecalis before root canal obturation.

Effect of the antimicrobial photodynamic therapy on microorganism reduction in deep caries lesions: a systematic review and meta-analysis.

This study aimed to perform a systematic review to assess the effectiveness of antimicrobial photodynamic therapy (aPDT) in the reduction of microorganisms in deep carious lesions. An electronic search was conducted in Pubmed, Web of Science, Scopus, Lilacs, and Cochrane Library, followed by a manual search. The MeSH terms, MeSH synonyms, related terms, and free terms were used in the search. As eligibility criteria, only clinical studies were included. Initially, 227 articles were identified in the electronic search, and 152 studies remained after analysis and exclusion of the duplicated studies; 6 remained after application of the eligibility criteria; and 3 additional studies were found in the manual search. After access to the full articles, three were excluded, leaving six for evaluation by the criteria of the Cochrane Collaboration's tool for assessing risk of bias. Of these, five had some risk of punctuated bias. All results from the selected studies showed a significant reduction of microorganisms in deep carious lesions for both primary and permanent teeth. The meta-analysis demonstrated a significant reduction in microorganism counts in all analyses (p<0.00001). Based on these findings, there is scientific evidence emphasizing the effectiveness of aPDT in reducing microorganisms in deep carious lesions.

Complicações diagnósticas na fibrose cística: métodos de rotina e novas alternativas / Complications in cystic fibrosis diagnostic: routine methods and new alternatives

A Fibrose Cística (FC) é uma doença grave presente em nosso meio. Apesar dos avanços nos métodos diagnósticos e no tratamento do paciente, existem inúmeros casos que ainda apresentam dificuldades para a definição desta doença. Os métodos mais comuns de diagnóstico são o teste de suor e análise de mutação para confirmação. Porém uma grande parcela dos pacientes com FC é portador de uma mutação não identificada e devem ser diagnosticados por várias outras medidas de disfunções orgânicas relatadas nesse artigo. O presente trabalho teve por objetivo descrever os principais meios de diagnosticar fibrose cística e a importância de uma definição precoce para que melhores resultados terapêuticos sejam atingidos.

Cystic Fibrosis (CF) is a several disease present in our midst despite the advances in diagnostic methods and patient's treatment. Despite the improvement there are still many cases that have complicated and unclear diagnosis. There are several ways to diagnosis cystic fibrosis, being more common the sweat test and mutation analysis to confirm. However, a large proportion of CF patients has a mutation that cannot be identified. These patients should be investigated by several other measures of organ dysfunction that this article reports. This study aimed to describe the principal means of diagnosing cystic fibrosis and the importance of an appropriate definition as soon as possible for better therapeutic results.

Thalidomide administration inhibits the clinical evolution of the experimental autoimmune encephalomyelitis (eae) in lewis rats: preliminar results

Multiple sclerosis (MS) is a chronic neurodegenerative inflammatory disease of the central nervous system. Several immunomodulatory agents have been used to prevent MS acute exacerbations. Tumor Necrosis factor alpha (TNFα) and interferon gamma (IFN-γ) are two major inflammatory mediators. Recently, we investigated in our laboratory the therapeutic value of thalidomide, a recognized TNF-α inhibitor, for the treatment of MS using the classical Lewis rat model of experimental autoimmune encephalomyelitis ( EAE). The experimental study revealed that thalidomide reduces the incidence of EAE development in 90% of the cases. Hence we hypothesized that thalidomide may be an important therapeutical tool for prevention of acute exacerbations of the MS.

Avaliação da eficiência de programas de treinamento de resistência na indução de hipertrofia cardíaca em ratos Wistar / Evaluation of the effectiveness of resistance training programs in the induction of cardiac hypertrophy in Wistar rats

Propôs-se avaliar e comparar o efeito do treinamento físico em modelo experimental na indução de hipertrofia cardíaca em ratos Wistar, utilizando-se a natação. A amostra de 24 ratos Wistar, machos, foi dividida em 3 grupos: grupo 1 (n = 8) treinado com carga progressiva (5, 6 e 7% do peso corporal (PC); grupo 2 (n = 8) com carga contínua (5% do PC) e grupo 3 (n = 8) controle. O treinamento compreendeu oito semanas, entre as 13 e 17 horas, durante 5 dias da semana, em piscina artesanal com temperatura de 32 ± 2°C. Ao final de 8 semanas, os animais foram sacrificados e seus corações retirados para avaliação do peso do coração isolado e relação peso do coração/peso corporal. Procedeu-se análise estatística, utilizando-se de testes paramétricos (teste T-student) e, quando recomendado, testes não paramétricos (Kruskal-Wallis e Mann-Whitney). Quanto ao peso do coração isolado, obteve-se um resultado significativo (p < 0,05) somente quando comparado o grupo sedentário com os ratos treinados com carga contínua. Diferença significativa foi obtida também ao comparar-se o peso do coração/peso corporal de ratos do grupo 2, em relação ao grupo 1 e 3. Estes dados sugerem hipertrofia cardíaca somente entre os animais treinados com carga contínua. A ineficiência do protocolo de carga progressiva pode ter sido resultante do pouco tempo para a resposta adaptativa que envolve mudanças moleculares e estruturais no miocárdio dos animais treinados.

This study aims at evaluating and comparing the effect of physical training in an experimental model in the induction of cardiac hypertrophy in Wistar rats, using swimming exercises. 24 male rats were divided into 3 groups: group 1 (n = 8) trained with progressive loading (5, 6 and 7% of body weight (BW), group 2 (n = 8) with continuous loading (5% of the PC), and group 3 (n = 8) control. The training program included eight weeks, between 13 and 17:00 PM, for 5 days a week, in a craft pool with temperature of 32 ± 2°C. At the end of 8 weeks, the animals were sacrificed and their hearts removed for evaluation of the isolated heart weight and the relation heart weight / body weight. In order to perform the statistical analysis it was used parametric tests (test T-student), and when recommended, non parametric tests (Kruskal-Wallis and Mann-Whitney). Regarding the isolated heart weight, the result was significant (p < 0.05) when compared the sedentary group with the trained rats with continuous loading. There was significant difference when compared the heart weight/body weight of rats in Group 2, compared to group 1 and 3. These data suggests cardiac hypertrophy only among animals trained with continuous load. Inefficiency of the protocol of progressive loading may have occurred due to little time for the adaptive response that involves molecular and structural changes in the myocardium of animals in a training program.

Early mitochondrial dysfunction, superoxide anion production, and DNA degradation are associated with non-apoptotic death of human airway epithelial cells induced by Pseudomonas aeruginosa exotoxin A.

It has been shown that bacterial exoproducts may induce airway epithelium injury. During the epithelial repair process, the respiratory epithelial cells no more establish tight junctional intercellular complexes and may be particularly susceptible to bacterial virulence factors. In this study, we analyzed the effect of Pseudomonas aeruginosa exotoxin A (ETA) at different periods of time and concentrations on 16 HBE 14o(-) human bronchial epithelial cells in culture conditions inducing a phenotype of repairing cells. ETA treatment for 24 and 48 h led to the killing of 40.0 +/- 5.7% and 79.0 +/- 1.4% of the cells, respectively, as determined by the dimethylthiazole 2,5 diphenyl tetrazolium bromide assay. At 1,000 ng/ml, ETA led to the killing of 25.2 +/- 6.6, 59.4 +/- 5.9, and 82.3 +/- 3.7% of the cells, after treatment periods of 7, 24, and 48 h, respectively. Cell death could not be inhibited by z-VAD-fmk, a broad spectrum caspase inhibitor. By transmission electron microscopy, ultrastructural characteristics described in apoptosis were not detected in ETA-treated cells. Instead, the mitochondria of cells treated for 24 and 48 h with ETA at 100 and 1,000 ng/ml were highly condensed. Human nasal polyp epithelial cells in primary culture exposed to ETA at 1,000 ng/ml did not exhibit characteristic features of apoptotic cells either. Cytofluorometric analysis of ETA-treated 16 HBE 14o(-) cells labeled with DiOC(6)(3) and hydroethidine showed a time- and dose-dependent reduction of the mitochondrial transmembrane potential, detected 7 h after ETA treatment, and an increase in superoxide production, detected at 24 h, respectively. By a photometric assay, DNA degradation was also detected 7 h after cell treatment with ETA at 100 and 1,000 ng/ml. Taken together, our results show that ETA-induced death of epithelial respiratory cells was preceded by early mitochondrial dysfunction and superoxide anion production, but was not followed by the classically described apoptotic pathways.

Incidência de microbactérias näo-tuberculosas e perfil de sensibilidade a drogas antimicrobianas de mycobacterium tuberculosis isoladas de pacientes atendidos no Hospital Universitário Pedro Ernesto, da Universidade do Estado do Rio de Janeiro / Non tuberculous mycobateria incidence and antimicrobial susceptibility of mycobacterium tuberculosis isolated from patients treated at the Hospital Pedro Ernesto from the State University of Rio de Janeiro

De março de 1994 a junho de 1995 foram isoladas 56 cepas de micobactérias de pacientes atendidos no Hospital Universitário Pedro Ernesto, da UERJ, sendo 45 (80,3 por cento) identificadas como Mycobacterium tuberculosis (MTB) e 11 (19,6 por cento), como micobactérias näo-tuberculosas (MNTs), por meio dos testes de reduçäo do nitrato, produçäo de niacina e catalase após aquecimento a 68ºC. Das 56 cepas, 11 (19,6 por cento) foram procedentes de pacientes portadores do vírus HIV. De oito desses pacientes (72,7 por cento), foram isoladas cepas classificadas como MNT. Dos 45 pacientes näo-portadores do vírus, 93,3 por cento apresentaram infecçäo por MTB. O percentual de cepas de MTB susceptíveis às drogas antimicrobianas estadas (isoniazida, rifampicina, estreptomicina, pirazinamida, etambutol e etionamida) foi baixo: 40 por cento e 28,6 por cento das amostras isoladas de pacientes virgens de tratamento e daqueles previamente tratados com drogas antimicobacterianas, respectivamente. Os percentuais de resistência a uma das seis drogas e os percentuais de resistência a duas ou mais drogas foram de 37,8 por cento e 28,9 por cento, respectivamente. Das 45 cepas de MTB, 31,1 por cento apresentaram resistência à isoniaida; 20 por cento, à estreptomicina; 13,3 por cento, à rifampicina; e 7 por cento, à associaçäo isoniazida-rifampicina