Plants and Fungal Products with Activity Against Tuberculosis

Tuberculosis (TB) is becoming an ever more serious worldwide problem. This contagious disease kills four people every minute somewhere in the world and accounts for more than 2 million deaths per year. Due to the rapid spread of TB strains resistant to all the major anti-TB drugs on the market, and the association of TB with human immunodeficiency virus (HIV) infection in AIDS, we urgently need to develop new drugs to fight against TB. In this context, due to the importance of nature in the development of new drugs, the aim of the present review is to highlight a series of new and promising anti-TB agents derived from plants and fungi discovered between 2001 and 2005

Ação da l-arginina na evolução de retalhos cutâneos de ratos sob exposição à nicotina L-arginine action in cutaneous flap evolution under nicotine exposure in rats

OBJETIVO: Avaliar se o tratamento com L-arginina influencia a cicatrização de retalhos cutâneos em ratos expostos à nicotina. MÉTODOS: Foram utilizados 40 ratos Wistar pesando 142,4±10,1g separados em quatro grupos: GC- tratamento com solução tampão fosfatos pH 7,4, confecção de retalho cutâneo, observação por 10 dias; GN- exposição à nicotina por quatro semanas, confecção de retalho cutâneo, observação por dez dias; GA- tratamento com solução tampão fosfatos pH 7,4 por quatro semanas, confecção de retalho cutâneo, tratamento com arginina por dez dias; GAN- exposição à nicotina por quatro semanas, confecção de retalho cutâneo, tratamento com arginina por dez dias. Foram avaliadas as áreas de necrose, re-epitelização, reação inflamatória e formação de tecido de granulação, pela coloração HE, a área de deposição total e a diferenciação de colágenos I e III por histometria com a coloração de picrosirius, e, através da marcação imunoistoquímica com anticorpo monoclonal anti-CD34, a densidade vascular cicatricial. RESULTADOS: As porcentagens de áreas de necrose de GN e GNA foram maiores (p<0,001) do que GC e GA. Nos escores histológicos, a deposição de colágeno e a porcentagem de colágeno tipo I, no GC e GA foram similares (p>0,05) e maiores (p<0,001) do que em GA e em GNA e, nas densidades vasculares, GN e GAN foram menores (p<0,001) do que em GC e em GA. CONCLUSÃO: A exposição à nicotina inibiu os efeitos da arginina, e nos ratos não expostos, induziu melhora na angiogênese e na deposição de colágeno total nos retalhos cutâneos.<br>OBJECTIVE: To evaluate whether treatment with L-arginine influences the healing of skin flaps in rats exposed to nicotine. METHODS: 40 male Wistar rats weighing 142.4 ± 10.1 g were separated into four groups: GC: treatment with 7.4 pH phosphate buffer, submitted to skin flap and observation for ten days; GN: exposure to nicotine for four weeks, submitted to skin flap and observation for ten days; GA: treatment with 7.4 pH phosphate buffer for four weeks, submitted to skin flap and arginine treatment for ten days; GAN: exposure to nicotine for four weeks, submitted to skin flap and treatment with arginine for ten days. We evaluated: areas of necrosis, re-epithelialization, inflammatory reaction and formation of granulation tissue by HE stain; the total area of deposition and differentiation of collagens I and III by histometry with picrosirius staining; and the scar vascular density by immunohistochemical staining with monoclonal anti-CD34 antibodies. RESULTS: The percentages of necrotic areas in GN and GNA were higher (p <0.001) than in GC and GA. In histological scores, collagen deposition, and the percentage of type I collagen, GA and GC were similar to each other (p> 0.05), but higher (p <0.001) than GA and GNA; as for vascular densities, they were lower in GN and GAN (p <0.001) than in GC and GA. CONCLUSION: Exposure to nicotine inhibited the effects of arginine and in unexposed mice there was induction of angiogenesis and improvement in the total collagen deposition in the skin flaps

Investigation of the mechanism of action of mefloquine and derivatives against the parasite Echinococcus multilocularis

Alveolar echinococcosis (AE) is caused by infection with the fox tapeworm E. multilocularis. The disease affects humans, dogs, captive monkeys, and other mammals, and it is caused by the metacestode stage of the parasite growing invasively in the liver. The current drug treatment is based on non-parasiticidal benzimidazoles. Thus, they are only limitedly curative and can cause severe side effects. Therefore, novel and improved treatment options for AE are needed.Mefloquine (MEF), an antimalarial agent, was previously shown to be effective against E. multilocularis in vitro and in experimentally infected mice. However, MEF is not parasiticidal and needs improvement for successful treatment of patients, and it can induce strong neuropsychiatric side-effects. In this study, the structure-activity relationship and mode of action of MEF was investigated by comparative analysis of 14 MEF derivatives. None of them showed higher activity against E. multilocularis metacestodes compared to MEF, but four compounds caused limited damage. In order to identify molecular targets of MEF and effective derivatives, differential affinity chromatography combined with mass spectrometry was performed with two effective compounds (MEF, MEF-3) and two ineffective compounds (MEF-13, MEF-22). 1′681 proteins were identified that bound specifically to MEF or derivatives. 216 proteins were identified as binding only to MEF and MEF-3. GO term enrichment analysis of these proteins and functional grouping of the 25 most abundant MEF and MEF-3 specific binding proteins revealed the key processes energy metabolism and cellular transport and structure, as well as stress responses and nucleic acid binding to be involved. The previously described ferritin was confirmed as an exclusively MEF-binding protein that could be relevant for its efficacy against E. multilocularis. The here identified potential targets of MEF will be further investigated in the future for a clear understanding of the pleiotropic effects of MEF, and improved therapeutic options against AE