Chorismate synthase: An attractive target for drug development against orphan diseases

The increase in incidence of infectious diseases worldwide, particularly in developing countries, is worrying. Each year, 14 million people are killed by infectious diseases, mainly HIV/AIDS, respiratory infections, malaria and tuberculosis. Despite the great burden in the poor countries, drug discovery to treat tropical diseases has come to a standstill. There is no interest by the pharmaceutical industry in drug development against the major diseases of the poor countries, since the financial return cannot be guaranteed. This has created an urgent need for new therapeutics to neglected diseases. A possible approach has been the exploitation of the inhibition of unique targets, vital to the pathogen such as the shikimate pathway enzymes, which are present in bacteria, fungi and apicomplexan parasites but are absent in mammals. The chorismate synthase (CS) catalyses the seventh step in this pathway, the conversion of 5-enolpyruvylshikimate-3-phosphate to chorismate. The strict requirement for a reduced flavin mononucleotide and the anti 1,4 elimination are both unusual aspects which make CS reaction unique among flavin-dependent enzymes, representing an important target for the chemotherapeutic agents development. In this review we present the main biochemical features of CS from bacterial and fungal sources and their difference from the apicomplexan CS. The CS mechanisms proposed are discussed and compared with structural data. The CS structures of some organisms are compared and their distinct features analyzed. Some known CS inhibitors are presented and the main characteristics are discussed. The structural and kinetics data reviewed here can be useful for the design of inhibitors. © 2007 Bentham Science Publishers Ltd.

Abordagem initial do paciente com mielopatia aguda não compressiva

Acute myelopathy are characterized by spinal cord dysfunction, developing sensitive, motor and autonomic signs and symptons. Since they are relatively rare, there are some difficulties to early diagnosis and to the beginning of the treatment. So, literature was reviewed to describe the main aetiologies of acute non compressive myelopathy: 1) demyelinating diseases; 2) systemic disease; 3) parainfectious; 4) delayed radiation myelopathy; 5) vascular myelopathy; 6) idiopatic and 7) vitamin B12 deficiency. Besides, we suggest an algorithm to initial approach of these patients and further aethiologic investigation. © Copyright Morelra Jr. Editora.

Teníase: Uma causa rara de apendicite aguda

Acute appendicitis is the most common surgical condition of acute abdomen. Approximately 7 percent of the population will have appendicitis during their lifetime, with the peak incidence occurring between 10 through 30 years-old Obstruction of the appendix lumen with subsequent bacterial infection initiates the pathophysiological sequence of acute appendicitis. Obstruction may have multiple causes, including fecalith, lymphoid hyperplasia (related to viral illnesses, including upper respiratory infection, mononucleosis, and gastroenteritis), foreign bodies, carcinoid tumor and parasites. In Asia, Africa and Latin America, Enterobius vermicularis has been reported as the main parasite that causes appendix obstruction. Rarely, Taenia sp., has been pointed as a cause of parasitic appendicitis. We reported a 30 years-old patient clinically diagnosed with acute appendicitis. The appendectomy was performed through a McBurney incision. The patient's convalescence was uneventful, and he was discharged from hospital 48 hours after operation. Histological examination of the appendix showed acute appendicitis, and it was found aparasite (Taenia sp.) lying inside of the appendix lumen at a transverse section. He has received 10 mg/Kg weight of praziquantel for taeniasis treatment.

Toxicidade de fármacos nitrofurânicos

During the structural designing of new drugs, it is possible predict the influence of specific chemical groups on pharmacological activity. Among these, the nitro group has potential antiparasitic activity, being present in many antimicrobial drugs, such as metronidazole, nitrofurazone, furazolidone, oxamniquine and chloramphenicol. Also, the introduction of the nitro group into a molecule can modify the physicochemical and electronic properties of the substance. Besides antimicrobial drugs, this group is also found in other drug classes, such as antiulcer, anti-inflamatory and anxiolytic. However, the use of the nitro group in drug design has encountered restrictions, due to the associated toxicity. This article is a review of the toxicity of nitrofuran compounds, as well the possible mechanisms involved and the strategy of latentiation by molecular modification to decrease their toxicity.

Dermatoses bolhosas auto-imunes

Autoimmune bullous dermatoses are diseases in which blisters and vesicles are the primary and fundamental types of skin lesion. Their classification is based on the location of the blister: intraepidermal and subepidermal. Patients produce autoantibodies against self-specific structures of the skin detectable by immunofluorescence techniques, immunoblotting and ELISA. Recent advances in molecular and cellular biology have brought to knowledge these self-antigens, against which patients are sensitized, and which are found in epidermis or in the dermo-epidermal junction. These are low incidence, but high morbidity diseases that may be fatal. The aim of this article is to review and describe the progress of four autoimmune vesiculobullous disorders: endemic pemphigus foliaceous (wild fire), pemphigus vulgaris, bullous pemphigoid and dermatitis herpetiformis. ©2009 by Anais Brasileiros de Dermatologia.

Qualidade microbiológica da água e histopatologia de brânquias de peixes provenientes de pisciculturas do município de itapecuru-mirim, Estado do Maranhão

The present study evaluated the microbiological water quality and tissue lesions in gills from Nile tilapia (Oreochromis niloticus) and hybrid tambacu (Colossoma macropomum female x Piaractus mesopotamicus male). For this, water and gills were collected from fish farming at six locations in Itapecuru- Mirim County, Maranhão State. Microbiological water analyses revealed contamination by total coliforms, Escherichia coli and heterotrophic bacteria. In the gills, we observed a diversity of Gram-positive and Gramnegative bacteria. The tissue lesions were: lamellar fusion, interlamellar hyperplasia, sub-epithelial edema and telangiectasia. Inflammatory lesions were not observed. Significant statistical difference (p > 0.05) was not detected when comparing different gills lesions during rainy and dry season. The correlation between lesion and pond type was statistically different (p < 0.05) for lamellar fusion and interlamellar hyperplasia which occurred more frequently at ground ponds. Regarding the frequency of lesions in the different fish species, there was statistical difference (p < 0.05), and the tambacu was more sensitive to lamellar fusion while tilapia was more sensitive for the other lesions. In relation to the sampling stations, there was statistical difference for all the gill lesions. In conclusion, tissue lesions are nonspecific and function as a defense mechanism against polluted aquatic environments, without infectious character.

Nodular dermatofibrosis in a gentian shepherd dog: case report

An 7-year-old male German shepherd dog not neutered was attended presenting several cutaneous nodules ranging from 0.5-3 cm in diameter at least a one year history, located mainly in thoracic and pelvic limbs, with progressive weight loss over two months. Fine needle aspiration biopsy and pelvic and thoracic limbs nodules excision biopsy were performed. After histopathological diagnosis, nodular dermatofibrosis diagnosis was determined and abdominal ultrasound was performed for possible renal cysts evaluation. The animal received treatment to control secondary bacterial infection. It is necessary to carry out histopathological examination and ultraosund to identify possible renal cysts and for definitive diagnosis. There is no specific treatment for nodular dermatofibrosis. © 2013 Asian Network for Scientific Information.

Sustainable production of biologically active molecules of marine based origin

The marine environment offers both economic and scientific potential which are relatively untapped from a biotechnological point of view. These environments whilst harsh are ironically fragile and dependent on a harmonious life form balance. Exploitation of natural resources by exhaustive wild harvesting has obvious negative environmental consequences. From a European industry perspective marine organisms are a largely underutilised resource. This is not due to lack of interest but due to a lack of choice the industry faces for cost competitive, sustainable and environmentally conscientious product alternatives. Knowledge of the biotechnological potential of marine organisms together with the development of sustainable systems for their cultivation, processing and utilisation are essential. In 2010, the European Commission recognised this need and funded a collaborative RTD/SME project under the Framework 7-Knowledge Based Bio-Economy (KBBE) Theme 2 Programme 'Sustainable culture of marine microorganisms, algae and/or invertebrates for high value added products'. The scope of that project entitled 'Sustainable Production of Biologically Active Molecules of Marine Based Origin' (BAMMBO) is outlined. Although the Union is a global leader in many technologies, it faces increasing competition from traditional rivals and emerging economies alike and must therefore improve its innovation performance. For this reason innovation is placed at the heart of a European Horizon 2020 Strategy wherein the challenge is to connect economic performance to eco performance. This article provides a synopsis of the research activities of the BAMMBO project as they fit within the wider scope of sustainable environmentally conscientious marine resource exploitation for high-value biomolecules. © 2013 Elsevier B.V.

Quantificação de proteínas de fase aguda em éguas doadoras de embrião da raça quarto de milha

Pós-graduação em Ciência Animal - FMVA

Perfil genético e fenotípico de Staphylococcus sp isolados de leite de vacas saudáveis e com mastite

Pós-graduação em Biologia Geral e Aplicada - IBB

Efeito da quercetina sobre alguns fatores relacionados com a virulência de Staphylococcus aureus

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Doenças bacterianas em bagres sul americanos: isolamento, caracterização e patogenia

Pós-graduação em Aquicultura - FCAV

Expressão, purificação e estudos estruturais da chaperona molecular Hsp65 de Mycobacterium leprae & caracterização da proteína NUDEL - nuclear distribuition element-like

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

Efeitos da administração tópica per-operatória da mitomicina C, em diferentes concentrações, sobre a cicatrização de mioplastias do reto dorsal do bulbo do olho de coelhos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)