The use of biodiversity as source of new chemical entities against defined molecular targets for treatment of malaria, tuberculosis, and T-cell mediated diseases: a review

The modern approach to the development of new chemical entities against complex diseases, especially the neglected endemic diseases such as tuberculosis and malaria, is based on the use of defined molecular targets. Among the advantages, this approach allows (i) the search and identification of lead compounds with defined molecular mechanisms against a defined target (e.g. enzymes from defined pathways), (ii) the analysis of a great number of compounds with a favorable cost/benefit ratio, (iii) the development even in the initial stages of compounds with selective toxicity (the fundamental principle of chemotherapy), (iv) the evaluation of plant extracts as well as of pure substances. The current use of such technology, unfortunately, is concentrated in developed countries, especially in the big pharma. This fact contributes in a significant way to hamper the development of innovative new compounds to treat neglected diseases. The large biodiversity within the territory of Brazil puts the country in a strategic position to develop the rational and sustained exploration of new metabolites of therapeutic value. The extension of the country covers a wide range of climates, soil types, and altitudes, providing a unique set of selective pressures for the adaptation of plant life in these scenarios. Chemical diversity is also driven by these forces, in an attempt to best fit the plant communities to the particular abiotic stresses, fauna, and microbes that co-exist with them. Certain areas of vegetation (Amazonian Forest, Atlantic Forest, Araucaria Forest, Cerrado-Brazilian Savanna, and Caatinga) are rich in species and types of environments to be used to search for natural compounds active against tuberculosis, malaria, and chronic-degenerative diseases. The present review describes some strategies to search for natural compounds, whose choice can be based on ethnobotanical and chemotaxonomical studies, and screen for their ability to bind to immobilized drug targets and to inhibit their activities. Molecular cloning, gene knockout, protein expression and purification, N-terminal sequencing, and mass spectrometry are the methods of choice to provide homogeneous drug targets for immobilization by optimized chemical reactions. Plant extract preparations, fractionation of promising plant extracts, propagation protocols and definition of in planta studies to maximize product yield of plant species producing active compounds have to be performed to provide a continuing supply of bioactive materials. Chemical characterization of natural compounds, determination of mode of action by kinetics and other spectroscopic methods (MS, X-ray, NMR), as well as in vitro and in vivo biological assays, chemical derivatization, and structure-activity relationships have to be carried out to provide a thorough knowledge on which to base the search for natural compounds or their derivatives with biological activity.

The neurotoxicological effects of mastoparan Polybia-MPII at the murine neuromuscular junction: an ultrastructural and immunocytochemical study

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeito de um programa de treinamento de facilitação neuromuscular proprioceptiva sobre a mobilidade torácica

A proposta deste estudo foi analisar o efeito de um programa de treinamento de membros superiores baseado nas técnicas de facilitação neuromuscular proprioceptiva (FNP) sobre a mobilidade torácica. Foram estudadas 24 voluntárias sedentárias, idade 22,9 ± 2,9 anos, divididas em grupo controle (GC), que não participou do treinamento, e grupo treinado (GT). O protocolo de treinamento físico foi constituído por um programa de exercícios de FNP, realizado três vezes por semana, durante quatro semanas. Os dois grupos foram submetidos à avaliação da mobilidade torácica por meio de cirtometria, antes e após o período de treinamento. Os dados colhidos foram analisados estatisticamente, com nível de significância α = 5%. Os valores da cirtometria axilar e xifoideana do GC antes e após o período de intervenção não apresentaram alterações significativas (p>0,05). No GT os valores das variáveis foram significantemente maiores após a intervenção (p<0,05). em conclusão, o protocolo de FNP utilizado parece ser um programa de exercícios eficiente, por promover aumento na cirtometria em um curto período de tempo, sugerindo que pode ser utilizado como recurso fisioterapêutico para o desenvolvimento da mobilidade torácica.

PHYSIOLOGICAL and NEUROMUSCULAR PROFILE DURING A BODYPUMP SESSION: ACUTE RESPONSES DURING A HIGH-RESISTANCE TRAINING SESSION

Oliveira, AS, Greco, CC, Pereira, MP, Figueira, TR, de Araujo Ruas, VD, Goncalves, M, and Denadai, BS. Physiological and neuromuscular profile during a Bodypump session: acute responses during a high-resistance training session. J Strength Cond Res 23(2): 579-586, 2009-The main purposes of this study were 1) to describe and to compare blood lactate ([La]), heart rate (HR), and electromyographic (EMG) parameters during high-repetition training sessions (HRTSs), 2) to analyze the influence of physical fitness levels in these parameters, and, 3) to analyze the relationship between metabolic ([La]) and neuromuscular (EMG) responses during the HRTS. Fifteen healthy untrained women (21.7 +/- 2.1 years) performed an HRTS called Bodypump for 1 hour, which incorporated the use of variable free weights and high repetitions in a group setting. This session involved 10 music selections (M1-M10) containing resistive exercises for different muscle groups. After music selections 2 (M2), 4 (M4), 6 (M6), 7 (M7), and 9 (M9), [La], HR, and EMG (vastus medialis [VM], vastus lateralis [VL], iliocostalis lumborum [IC], and longissimus thoracis <) were determined. The [La] (M2, 4.00 +/- 1.45 mM; M7, 5.02 +/- 1.73 mM) and HR (M2, 153.64 +/- 18.89 bpm; M7, 16.14 +/- 20.14 bpm) obtained at M2 and M7 were similar but were significantly higher than the other moments of the session. However, EMG (root mean square [RMS]) at M2 (VL, VM, and LT) was lower than at M7. There was no significant correlation of strength and aerobic physical fitness with [La], RMS. In the same way, there was no significant correlation of [La] with RMS at M2 and M7. on the basis of our data, we can conclude that metabolic, cardiovascular, and EMG variables present different and independent behavior during an HRTS. Accordingly, for neuromuscular conditions during HRTS, it seems to be enough to induce improvement in the muscular strength of inferior limbs in untrained subjects.

Early physical activity promotes lower prevalence of chronic diseases in adulthood

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of a single habituation session on neuromuscular isokinetic profile at different movement velocities

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

IMPROVEMENTS IN METABOLIC and NEUROMUSCULAR FITNESS AFTER 12-WEEK BODYPUMP (R) TRAINING

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Emerging infectious diseases in cetaceans worldwide and the possible role of environmental stressors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Skin diseases in Guiana dolphins (Sotalia guianensis) from the Paranagua estuary, Brazil: A possible indicator of a compromised marine environment

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of neuromuscular electrical stimulation, laser therapy and LED therapy on the masticatory system and the impact on sleep variables in cerebral palsy patients: a randomized, five arms clinical trial

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Relative antioxidant activity of Brazilian medicinal plants for gastrointestinal diseases

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of nandrolone decanoate on the neuromuscular junction of rats submitted to swimming

This study addressed the effects of nandrolone decanoate (ND) on contractile properties and muscle fiber characteristics of rats submitted to swimming. Male Wistar rats were grouped in sedentary (S), swimming (Sw), sedentary+ND (SND), and swimming+ND (SwND), six animals per group. ND (3 mg/kg) was injected (subcutaneously) 5 days/week, for 4 weeks. Swimming consisted of 60-min sessions (load 2%), 5 days/week, for 4 weeks. After this period, the sciatic nerve extensor digitorum longus (EDL) muscle was isolated for myographic recordings. Fatigue resistance was assessed by the percent (%) decline of 180 direct tetanic contractions (30 Hz). Safety margin of synaptic transmission was determined from the resistance to the blockade of indirectly evoked twitches (0.5 Hz) induced by pancuronium (5 to 9 x 10(-7) M). EDL muscles were also submitted to histological and histochemical analysis (haematoxylin-eosin (HE); nicotinamide adenine dinucleotide-tetrazolium reductase (NADH-TR)). Significant differences were detected by two-way ANOVA (p<0.05). ND did not change body mass, fatigue resistance or kinetic properties of indirect twitches in either sedentary or swimming rats. In contrast, ND reduced the safety margin of synaptic transmission in sedentary animals (SND=53.3+/-4.7% vs. S=75.7+/-2.0%), but did not affect the safety margin in the swimming rats (SwND=75.81+/-3.1% vs. Sw=71.0+/-4.0%). No significant difference in fiber type proportions or diameters was observed in EDL muscle of any experimental group. These results indicate that ND does not act as an ergogenic reinforcement in rats submitted to 4 weeks of swimming. on the other hand, this study revealed an important toxic effect of ND, that it reduces the safety margin of synaptic transmission in sedentary animals. Such an effect is masked when associated with physical exercise. (C) 2004 Elsevier B.V. All rights reserved.