Compound profiling and 3D-QSAR studies of hydrazone derivatives with activity against intracellular Trypanosoma cruzi.

Chagas disease is a tropical disease caused by the parasite Trypanosoma cruzi, which is endemic in Central and South America. Few treatments are available with effectiveness limited to the early (acute) stage of disease, significant toxicity and widespread drug resistance. In this work we report the outcome of a HTS-ready assay chemical library screen to identify novel, nontoxic, small-molecule inhibitors of T. cruzi. We have selected 50 compounds that possess hydrazone as a common group. The compounds were screened using recombinant T. cruzi (Tulahuen strain) expressing beta-galactosidase. A 3D quantitative structure-activity relationship (QSAR) analysis was performed using descriptors calculated from comparative molecular field analysis (CoMFA). Our findings show that of the fifty selected hydrazones, compounds LpQM-19, 28 and 31 displayed the highest activity against T. cruzi, leading to a selectivity index (SI) of 20-fold. The 3D-QSAR analysis indicates that a particular electrostatic arrangement, where electron-deficient atoms are aligned along the molecule main axis positively correlates with compound biological activity. These results provide new candidate molecules for the development of treatments against Chagas disease.

2-Pyridyl thiazoles as novel anti-Trypanosoma cruzi agents: structural design, synthesis and pharmacological evaluation.

The present work reports on the synthesis, anti-Trypanosoma cruzi activities and docking studies of a novel series of 2-(pyridin-2-yl)-1,3-thiazoles derived from 2-pyridine thiosemicarbazone. The majority of these compounds are potent cruzain inhibitors and showed excellent inhibition on the trypomastigote form of the parasite, and the resulting structure-activity relationships are discussed. Together, these data present a novel series of thiazolyl hydrazones with potential effects against Chagas disease and they could be important leads in continuing development against Chagas disease.

Effects of controlled and pressure support mechanical ventilation on rat diaphragm muscle.

PURPOSE: The objective of this study was to analyze the effects of Pressure Controlled Ventilation mode (PCV-C) and PSV mode in diaphragm muscle of rats. METHODS: Wistar rats (n=18) were randomly assigned to the control group or to receive 6 hours of PCV and PSV. After this period, animals were euthanized and their diaphragms were excised, frozen in liquid nitrogen and stored in at -80º C for further histomorphometric analysis. RESULTS: Results showed a 15% decrease in cross-sectional area of muscle fibers on the PCV-C group when compared to the control group (p<0.001) and by 10% when compared to the PSV group (p<0.05). Minor diameter was decreased in PCV-C group by 9% when compared with the control group (p<0.001) and by 6% when compared to the PSV group (p<0.05). When myonuclear area was analyzed, a 16% decrease was observed in the PCV-C group when compared to the PSV group (p<0.05). No significant difference between the groups was observed in myonuclear perimeter (p>0.05). CONCLUSION: Short-term controlled mechanical ventilation seems to lead to muscular atrophy in diaphragm fibers. The PSV mode may attenuate the effects of VIDD.

Effects of controlled and pressure support mechanical ventilation on rat diaphragm muscle / Efeitos da ventilação mecânica controlada e por pressão de suporte no músculo diafragma de ratos

PURPOSE: The objective of this study was to analyze the effects of Pressure Controlled Ventilation mode (PCV-C) and PSV mode in diaphragm muscle of rats. METHODS: Wistar rats (n=18) were randomly assigned to the control group or to receive 6 hours of PCV and PSV. After this period, animals were euthanized and their diaphragms were excised, frozen in liquid nitrogen and stored in at -80º C for further histomorphometric analysis. RESULTS: Results showed a 15 percent decrease in cross-sectional area of muscle fibers on the PCV-C group when compared to the control group (p<0.001) and by 10 percent when compared to the PSV group (p<0.05). Minor diameter was decreased in PCV-C group by 9 percent when compared with the control group (p<0.001) and by 6 percent when compared to the PSV group (p<0.05). When myonuclear area was analyzed, a 16 percent decrease was observed in the PCV-C group when compared to the PSV group (p<0.05). No significant difference between the groups was observed in myonuclear perimeter (p>0.05). CONCLUSION: Short-term controlled mechanical ventilation seems to lead to muscular atrophy in diaphragm fibers. The PSV mode may attenuate the effects of VIDD.

OBJETIVO: Avaliar os efeitos do modo ventilatório controlado por pressão controlada (PCV-C) e do modo PSV sobre o músculo diafragma de ratos. MÉTODOS: Ratos (n = 18) da linhagem Wistar foram distribuídos no grupo controle (RE) ou para receber AVM por 6 horas no modo PCV-C e no modo PSV. Após esse período, os animais foram eutanasiados, o diafragma retirado e encaminhado para a análise histológica e morfométrica. RESULTADOS: Os resultados revelaram uma redução da área das fibras musculares de 15 por cento no grupo PCV-C em comparação ao controle (p<0,001) e de 10 por cento quando comparado ao grupo PSV (p<0,05). Já com relação ao diâmetro menor observou-se uma redução de 9 por cento do grupo PCV-C em comparação ao controle (p<0,001) e de 6 por cento em relação ao grupo PSV (p<0,05). Quando avaliada a área dos mionúcleos, notou-se uma redução de 16 por cento desse parâmetro no grupo PCV-C, comparado ao PSV (p<0,05). Não houve diferença significativa no perímetro dos mionúcleos entre os grupos estudados (p>0,05). CONCLUSÃO: O grupo PCV-C apresentou atrofia muscular em um período curto de ventilação mecânica. O modo PSV parece atenuar os efeitos da DDIV.

Interventions for wound healing among diabetic patients infected with Staphylococcus aureus: a systematic review.

CONTEXT AND OBJECTIVE: Staphylococcus aureus is the most frequent agent isolated in diabetic foot infections and may be associated with changes to wound healing times. The aim of this study was to perform a systematic review of the literature, including studies that assessed the efficacy of any clinical or surgical intervention, as well as oral or topical therapy for diabetic ulcers infected with S. aureus. DESIGN AND SETTING: Systematic review with a search conducted in databases. METHODS: We conducted a systematic review with a comprehensive search in the Lilacs, SciELO, PubMed/Medline, Old Medline, Embase and Cochrane Library databases, for articles published from 1966 to 2010. The articles selected were limited to studies on diabetic patients with wounds infected with S. aureus for whom their healing was followed up, with the use of either antibiotics or experimental treatments. Animal studies and those that did not report the wound healing, as well as review articles, were excluded. RESULTS: Five studies that met the inclusion and exclusion criteria were analyzed. CONCLUSIONS: There are few studies reporting the healing of wounds infected with S. aureus in diabetic patients, although this is the most commonly found pathogen in this type of wound and it frequently consists of methicillin-resistant S. aureus (MRSA). There is insufficient evidence to support early use of broad-spectrum antibiotics against MRSA to promote healing of diabetic ulcers, since antibiotic resistance may develop from such treatment. This highlights the need for further studies on the subject.

Atypical glandular cells and cervical cancer: systematic review.

Atypical glandular cells are a common finding in cervical cytology in cervical cancer screening and its occurrence has increased in the last decades. The identification of these cells is clinically very important due to its association with cervical and endometrial dysplasic lesions and cancer. Using a systematic approach, this article reviewed studies investigating cervical lesions that are characteristic in patients previously diagnosed as having atypical glandular cells. Studies in which diagnostic investigation did not include histopathological diagnosis were excluded. A comprehensive search for available material in LILACS, SciELO, PubMed/ Medline and Old Medline databases, dated between 1966 and 2009 was performed. Articles omitted by the electronic database search were also included. Nineteen articles met the inclusion criteria and were selected. This report aims at evaluating whether atypical glandular cells, initially found in cervical cytology and subsequently identified at the histological analysis, are related to the presence of benign, pre-malignant and malignant lesions. Eleven out of 19 selected articles showed the highest correlation between atypical glandular cells with benign diseases and six with squamous pre-malignant lesions.

Interventions for wound healing among diabetic patients infected with Staphylococcus aureus: a systematic review / Intervenções para a cicatrização de feridas de pacientes diabéticos infectados com Staphylococcus aureus: uma revisão sistemática

CONTEXT AND OBJECTIVE: Staphylococcus aureus is the most frequent agent isolated in diabetic foot infections and may be associated with changes to wound healing times. The aim of this study was to perform a systematic review of the literature, including studies that assessed the efficacy of any clinical or surgical intervention, as well as oral or topical therapy for diabetic ulcers infected with S. aureus. DESIGN AND SETTING: Systematic review with a search conducted in databases. METHODS: We conducted a systematic review with a comprehensive search in the Lilacs, SciELO, PubMed/Medline, Old Medline, Embase and Cochrane Library databases, for articles published from 1966 to 2010. The articles selected were limited to studies on diabetic patients with wounds infected with S. aureus for whom their healing was followed up, with the use of either antibiotics or experimental treatments. Animal studies and those that did not report the wound healing, as well as review articles, were excluded. RESULTS: Five studies that met the inclusion and exclusion criteria were analyzed. CONCLUSIONS: There are few studies reporting the healing of wounds infected with S. aureus in diabetic patients, although this is the most commonly found pathogen in this type of wound and it frequently consists of methicillin-resistant S. aureus (MRSA). There is insufficient evidence to support early use of broad-spectrum antibiotics against MRSA to promote healing of diabetic ulcers, since antibiotic resistance may develop from such treatment. This highlights the need for further studies on the subject.

CONTEXTO: Staphylococcus aureus é o agente mais frequentemente isolado nas infecções de pé em pacientes diabéticos e pode estar associado a mudança no tempo de cicatrização de feridas. O objetivo deste estudo foi realizar uma revisão sistemática da literatura, incluindo estudos que avaliaram a eficácia de qualquer intervenção clínica, cirúrgica, bem como terapia oral ou tópica para o tratamento de úlceras diabéticas infectadas com o S. aureus. TIPO DE ESTUDO E LOCAL: Revisão sistemática com busca realizada em bancos de dados. MÉTODOS: Realizamos uma revisão sistemática com uma busca abrangente nos bancos de dados Lilacs, SciELO, PubMed/Medline, Old Medline, Embase e no banco de dados da biblioteca Cochrane, publicados entre 1966 e 2010. Os artigos selecionados foram limitados aos estudos com feridas infectadas por S. aureus de pacientes diabéticos, que tiveram cicatrização relatada, quer pela utilização de antibióticos ou por substâncias experimentais. Foram excluídos os estudos com animais e os que não relataram a cicatrização das feridas, bem como artigos de revisão. RESULTADOS: Foram analisados cinco estudos que obedeceram aos critérios de inclusão e exclusão. CONCLUSÕES: Raros estudos relataram cicatrização de feridas infectadas com S. aureus em pacientes diabéticos, embora este seja o patógeno mais comumente encontrado neste tipo de ferida, sendo frequentemente resistente à meticilina MRSA (methicillin-resistant S. aureus). Não há evidências suficientes que suportem a utilização precoce de antibióticos de amplo espectro contra MRSA para promoção da cicatrização de úlceras diabéticas, uma vez que o desenvolvimento de resistência a antibióticos pode decorrer desse tipo de tratamento. Isso evidencia a necessidade de novos estudos sobre o assunto.

Células glandulares atípicas e câncer de colo uterino: revisão sistemática / Atypical glandular cells and cervical cancer: systematic review

Atipias de células glandulares em esfregaços cervicovaginais é um achado citológico na rotina de rastreamento do câncer cervical, que aumentou nas últimas décadas. Sua constatação é importante clinicamente, pois é alta a percentagem de casos associados com doença cervical e endometrial de alto grau e câncer. Este trabalho avaliou, por meio de uma revisão sistemática, estudos que investigaram o perfil das lesões de colo uterino em avaliações histológicas de seguimento de pacientes já diagnosticadas com células glandulares atípicas. Foram excluídos os estudos cuja investigação diagnóstica não incluísse o diagnóstico histopatológico. Realizou-se uma busca abrangente de publicações no período de 1966 a 2009, nas bases do LILACS, SciELO, PubMed/Medline e Old Medline. Os artigos omitidos na busca eletrônica também foram incluídos. Estavam de acordo com os critérios de inclusão 19 artigos, que foram selecionados. Este estudo tem como objetivo avaliar se a atipia celular glandular observada inicialmente na citologia relacionava-se histologicamente com a presença de lesões benignas, pré-neoplásicas ou neoplásicas. Dos 19 estudos selecionados, 11 mostraram maior correlação entre atipia glandular com patologias benignas e seis com lesões escamosas pré-malignas.

Atypical glandular cells are a common finding in cervical cytology in cervical cancer screening and its occurrence has increased in the last decades. The identification of these cells is clinically very important due to its association with cervical and endometrial dysplasic lesions and cancer. Using a systematic approach, this article reviewed studies investigating cervical lesions that are characteristic in patients previously diagnosed as having atypical glandular cells. Studies in which diagnostic investigation did not include histopathological diagnosis were excluded. A comprehensive search for available material in LILACS, SciELO, PubMed/ Medline and Old Medline databases, dated between 1966 and 2009 was performed. Articles omitted by the electronic database search were also included. Nineteen articles met the inclusion criteria and were selected. This report aims at evaluating whether atypical glandular cells, initially found in cervical cytology and subsequently identified at the histological analysis, are related to the presence of benign, pre-malignant and malignant lesions. Eleven out of 19 selected articles showed the highest correlation between atypical glandular cells with benign diseases and six with squamous pre-malignant lesions.