Discovery and characterization of novel TRPML1 agonists.

Screening a library of >100,000 compounds identified the substituted tetrazole compound 1 as a selective TRPML1 agonist. Both enantiomers of compound 1 were separated and profiled in vitro and in vivo. Their selectivity, ready availability and CNS penetration should enable them to serve as the tool compounds of choice in future TRPML1 channel activation studies. SAR studies on conformationally locked macrocyclic analogs further improved the TRPML1 agonist potency while retaining the selectivity.

Innate host defense requires TFEB-mediated transcription of cytoprotective and antimicrobial genes.

Animal host defense against infection requires the expression of defense genes at the right place and the right time. Understanding such tight control of host defense requires the elucidation of the transcription factors involved. By using an unbiased approach in the model Caenorhabditis elegans, we discovered that HLH-30 (known as TFEB in mammals) is a key transcription factor for host defense. HLH-30 was activated shortly after Staphylococcus aureus infection, and drove the expression of close to 80% of the host response, including antimicrobial and autophagy genes that were essential for host tolerance of infection. TFEB was also rapidly activated in murine macrophages upon S. aureus infection and was required for proper transcriptional induction of several proinflammatory cytokines and chemokines. Thus, our data suggest that TFEB is a previously unappreciated, evolutionarily ancient transcription factor in the host response to infection.

Ovicidal response of NYDA formulations on the human head louse (Anoplura: Pediculidae) using a hair tuft bioassay.

Using the in vitro rearing system in conjunction with the hair tuft bioassay, NYDA and NYDA without fragrances formulations (92% wt:wt dimeticones) were 100% ovicidal (0% of treated eggs hatched) after an 8-h exposure of the eggs of the human head louse (Pediculus humanus capitis De Geer) following the manufacturer's instructions. Comparatively, 78 and 66% of eggs similarly exposed hatched after distilled deionized water or Nix (1% permethrin) treatments, respectively. NYDA and NYDA without fragrances formulations were also statistically and substantially more ovicidal than either distilled deionized water or Nix treatments after 10, 30 min, and 1 h exposures. Only the 10 min exposure of eggs to NYDA and NYDA without fragrances formulations resulted in hatched lice that survived to adulthood (5-8% survival). Of the lice that hatched from eggs exposed to NYDA formulations for 10 min, there were no significant differences in the time it took them to become adults, female fecundity or the viability of eggs laid by surviving females. The longevity of adults, however, was reduced after the 10 min treatments of eggs with NYDA and NYDA without fragrances formulations compared with either the distilled deionized water or Nix treatments.

Ivermectin acts as a posteclosion nymphicide by reducing blood feeding of human head lice (Anoplura: Pediculidae) that hatched from treated eggs.

The 0.5% ivermectin topical cream formulation was not directly ovicidal to treated eggs of head lice, as hatchability was not decreased. Nevertheless, the percent of hatched lice from treated eggs that took a blood meal significantly decreased (80-95%) compared with lice that hatched from untreated eggs and all treated lice died within 48 h of hatching, including those that fed. Dilutions of ivermectin formulation of 0.15 and 0.2 microg/ml, which were topically applied to 0-8 d old eggs, were not lethal to lice at 24 h posteclosion. However, 9 and 16% less lice fed when hatched from these treated eggs, respectively. Total [3H] inulin ingested by untreated first instars significantly increased over a 48 h feeding interval but was significantly less in instars that hatched from eggs receiving the 0.15 (36% less) and 0.2 (55% less) microg/ml ivermectin treatments compared with placebo. The reduced feeding that occurred after the 0.15 and 0.2 microg/ml ivermectin treatments occurred in the absence of mortality and suggests a unique mode of action of ivermectin on feeding that is separate from the mode of action of ivermectin leading to mortality. Failure of hatched instars to take a blood meal after egg treatments with formulated ivermectin is likely responsible for its action as a posteclosion nymphicide.

Desmame precoce em prematuros participantes do Método Mãe Canguru / Early weaning in premature babies participants of the Kangaroo Mother Care

OBJETIVO: Identificar a prevalência e as causas de desmame precoce nos recém-nascidos pré-termo, participantes do Método Mãe Canguru em uma maternidade-escola em Alagoas. MÉTODOS: Foi aplicado um questionário contendo questões objetivas com 33 genitoras dos recém-nascidos pré-termo/ lactentes, que estavam internos na enfermaria canguru e que compareceram aos retornos ambulatoriais, no período de fevereiro a junho de 2006. Periodicamente, foi realizada a análise dos prontuários dos bebês após a alta hospitalar, observando a manutenção do aleitamento materno, a ocorrência de desmame precoce e suas respectivas causas. Após os dados obtidos serem caracterizados com a utilização de técnicas de estatística descritiva, foram aplicados os testes de aderência de Kolmogorov-Smirnov e Shapiro-Wilk e os testes de Mann-Withney e de correlação bivariada. As diferenças foram consideradas significativas para valores de p menores que 0,05 e o erro beta admitido foi de 0,1. RESULTADOS: Todos os bebês se encontravam em aleitamento materno exclusivo na alta hospitalar. O percentual de desmame foi de 27,3 por cento, com maior ocorrência no terceiro mês de vida, constatado no período dos retornos. A causa de desmame precoce de maior prevalência está relacionada aos fatores sócio-culturais. CONCLUSÃO: O estudo revelou baixos índices de desmame precoce quando comparados aos percentuais observados em pesquisas realizadas no âmbito nacional. A maior causa de desmame precoce na população estudada está relacionada aos fatores sócio-culturais. Desta forma, o programa de atenção humanizada Método Mãe Canguru mostrou-se eficaz no que diz respeito ao incentivo ao aleitamento materno exclusivo.

PURPOSE: To identify the early weaning prevalence and risk factors in preterm newborns participants of the Kangaroo Mother Care in a school-maternity in Alagoas, Brazil. METHODS: Thirty-three mothers of preterm newborns that were at the Kangaroo Mother infirmary and showed up for the ambulatory returns in the period from February to June 2006 answered a questionnaire that included objective questions. After the infants were discharged, their files were periodically analyzed, observing the maintenance of the breastfeeding, the occurrence of early weaning and its causes. The data were analyzed with descriptive statistic techniques, Kolmogorov-Smirnov and Shapiro-Wilk tests and the Mann-Withney and bivaried correlation tests. Differences were considered significant for p-values below 0,05 and the beta error was of 0,1. RESULTS: When discharged, all infants were exclusively breastfed. The percentage of early weaning was 27,3 percent, mostly occurring at the third month, as detected at the returns. The most prevalent early weaning cause regarded socio-cultural factors. CONCLUSION: Low indices of early weaning were observed in this study, when compared to the percentages described in previous national researches. The major cause of early weaning regarded socio-cultural factors. Therefore, the Mother Kangaroo Care program of humanized attention proved to be efficient for the promotion of exclusive breastfeeding.

Uma estratégia para a prevençäo da endocardite infecciosa / A strategy fot the prevention of infectious endocarditis

Säo apresentadas as indicaçöes médicas e os regimes terapêuticos para a prevençäo da endocardite infecciosa, baseados no último encontro do Comitê da American Heart Association adaptados à realidade do nosso país. Apresenta-se a estratégia utilizada no Instituto de Cardiologia do Rio Grande do Sul, enfatizando a importância de uma conduta uniformizada, assim também como a utilizaçäo de material impresso para ser fornecido aos pacientes

Endocardite em prótese biológica por Candida parapsilosis / Endocarditis in biological prosthesis by Candida parapsilosis

Relata-se um caso de endocardite causada pela Candida parapsilosis numa prótese valvular biológica em posiçäo mitral. Revisa-se brevemente a literatura brasileira sobre o assunto