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This study aimed to evaluate the effects of firocoxib for controlling experimentally-induced breakdown of the blood-aqueous barrier in healthy and Toxoplasma gondii -seropositive cats. Thirty two cats with no ocular abnormalities were used. Groups (n=8/each) were formed with healthy cats that received 5mg g-1 of oral firocoxib (FH) or no treatment (CH) on day 0; seropositive cats for anti -T. gondii specific immunoglobulin G (IgG) were grouped (n=8/each) and treated in a similar fashion (FT and CT). On day 1, cats of all groups received the same treatment protocol, and 1h later, aqueocentesis was performed under general anesthesia (M0). Following 1h, the same procedure was repeated (M1). Quantitation of aqueous humor total protein and prostaglandin E2 (PGE2) were determined. Aqueous samples of seropositive cats were tested for anti- T. gondii specific IgG. In M0, aqueous samples of CT showed a significantly higher concentration of PGE2 in comparison with other groups (P

Brucellosis is a zoonosis. The aim of this study was to check the health status of felids kept at the zoo of the Federal University of Mato Grosso, Cuiaba, Brazil. Blood samples were taken from seven Puma Puma concolor, five Jaguar Panthera onca, four Ocelot Leopardus pardalis and one Lion Panthera leo. Brucellosis serology and polymerase chain reaction were performed. The presence of antibodies and DNA of Brucella abortus and Brucella canis were not detected in P. leo. The amplification of DNA from B. abortus and B. canis was observed in the four Ocelot. DNA from B. abortus was detected in one Jaguar, and DNA from B. canis in two Puma and one Jaguar. Serology for B. abortus was positive in two Puma and two Jaguar, while B. canis was observed in one Ocelot and two Jaguar. Although not considered a source of infection to staff, multidisciplinary studies should be carried out to elucidate the role of domestic animals in the epidemiology of this zoonosis.

Este estudo teve como objetivo investigar a ocorrência da brucelose causada por Brucella canis em cães no município de Cuiabá, MT, e os possíveis fatores de risco associados durante o período de 2007 a 2008. Foram analisadas 327 amostras baseadas numa amostragem aleatória simples, abrangendo os quatro distritos do município. A ocorrência da B. canis foi de 24,1% (I.C. 95%: 19,7 - 29,0%). A análise estatística dos sinais clínicos demonstrou associação de conjuntivite e ceratite com a positividade por B. canis, com um valor de odds ratio de 4,72 (I.C.95%=1,30-17,76) e Exato de Fisher de 0,0103; e 16,69 (I.C.95%=1,86-385,55) e Exato de Fisher de 0,0036, respectivamente. Os resultados obtidos neste estudo demonstraram a ocorrência da B. canis no município de Cuiabá e sugerem novas pesquisas e monitoramento, além de propor, como diagnóstico molecular para B. canis, a técnica de PCR.

Este estudo teve como objetivo investigar a ocorrência da brucelose causada por Brucella canis em cães no município de Cuiabá, MT, e os possíveis fatores de risco associados durante o período de 2007 a 2008. Foram analisadas 327 amostras baseadas numa amostragem aleatória simples, abrangendo os quatro distritos do município. A ocorrência da B. canis foi de 24,1% (I.C. 95%: 19,7 - 29,0%). A análise estatística dos sinais clínicos demonstrou associação de conjuntivite e ceratite com a positividade por B. canis, com um valor de odds ratio de 4,72 (I.C.95%=1,30-17,76) e Exato de Fisher de 0,0103; e 16,69 (I.C.95%=1,86-385,55) e Exato de Fisher de 0,0036, respectivamente. Os resultados obtidos neste estudo demonstraram a ocorrência da B. canis no município de Cuiabá e sugerem novas pesquisas e monitoramento, além de propor, como diagnóstico molecular para B. canis, a técnica de PCR.This study aimed to investigate the occurrence of brucellosis caused by Brucella canis in dogs in Cuiabá, State of Mato Grosso, and possible risk factors associated during the period of 2007 to 2008. Three hundred twenty seven samples were analized based on simple random sampling, covering the 04(four) districts of the municipality. The occurrence of B. canis was 24.1% (95% CI: 19.7-29.0%). The statiscal analysis showed association of conjunctivitis and keratitis with the positivity of B. canis, with an odds ratio of 4.72(95% CI=1.30-17.76) and 0.0103 for Fisher's Exact, and 16.69(95% CI=1.86-385.55) and 0.0036 for Fisher's Exact, respectively. The results of this study demonstrate the occurrence of B. canis in this city of Cuiabá, and suggest and new research and monitoring and proposes a molecular diagnostics to B. canis, the PCR techinique.

β-Secretase inhibitors are potentially disease-modifying treatments for Alzheimer's disease. Previous efforts in our laboratory have resulted in hydroxyethylamine-derived inhibitors such as 1 with low nanomolar potency against β-site amyloid precursor protein cleaving enzyme (BACE). When dosed intravenously, compound 1 was also shown to significantly reduce Aβ40 levels in plasma, brain, and cerebral spinal fluid. Herein, we report further optimizations that led to the discovery of inhibitor 16 as a novel, potent, and orally efficacious BACE inhibitor.

Leishmaniasis is transmitted naturally in urban and suburban areas, due to the emergence and reemergence of their vectors in these areas. In order to deepen the knowledge about ecological aspects that affect the occurrence of vectors in areas of transmission of leishmaniasis areas in Cuiaba, state of Mato Grosso (MT), Brazil, a survey was carried out of the Zoonosis Control Center database – ZCC serologically positive dogs from Cuiaba municipality within the period 2005-2011. Nine species of the genus Lutzomyia and one of Brumptomyia were identified. The most abundant species were Lutzomyia whitmani (33.2%), followed by L. cruzi (16.8%) longipalpis (13.9%) Brumptomyia brumpti (9.9%), L. saulensis (4.0%) and L. flaviscutellata (3.5%). There was an increase in the number of Leishmaniasis vectors in the municipality of Cuiaba during the years 2005-2011. The presence of infected dogs, the increase in vector’s density and the rate of susceptibility and surveillance interruption may increase the risk of leishmaniasis transmission to humans in the municipality of Cuiaba. Keywords: Dogs. Center for Zoonosis Control. Protozoa. Resumo A leishmaniose e transmitida naturalmente em areas urbanas e periurbanas, devido a emergencia e reemergencia de seus vetores nessas areas. Com o objetivo de aprofundar o conhecimento sobre aspectos ecologicos que afetam a ocorrencia de vetores em areas de transmissao de leishmaniose no municipio de Cuiaba, estado de Mato Grosso (MT), Brasil, foi realizado um levantamento do banco de dados do Centro de controle de Zoonoses - CCZ de Cuiaba de caes sorologicamente positivos do periodo de 2005 a 2011. Nove especies de genero Lutzomyia e uma dos Brumptomyia foram identificadas. As especies mais abundantes foram Lutzomyia whitmani (33,2%), seguido por L. cruzi (16,8%), L. longipalpis (13,9%), Brumptomyia brumpti (9,9%), L. saulensis (4,0%) e L. flaviscutellata (3,5%). Observou-se um aumento no numero de vetores de Leishmanioses no municipio de Cuiaba durante os anos de 2005 a 2011. A presenca de caes infectados, o aumento da densidade do vetor, a taxa de susceptibilidade e a interrupcao de vigilância epidemiologica pode aumentar o risco de transmissao de leishmaniose para o homem no municipio de Cuiaba. Palavras-chave: Caes. Centro de Controle de Zoonoses. Protozoarios.

Detection of disseminated tumor cells in the bone marrow may provide important prognostic information in breast cancer patients. With few exceptions the number of stained cells scored as cancer is very low; there may be only 1 cell per slide. This makes definitive interpretation of cancer in marrow challenging. False-positive staining of marrow cells with cytokeratin (CK) antibody is relatively common and makes interpretation more difficult. In this report we focus on false-positive staining of marrow specimens from breast cancer patients and noncancer controls and demonstrate that the frequency of false-positive events is common. Bone marrow was collected from 23 cancer-free donors and 60 breast cancer patients. Samples were processed by Ficoll density gradient centrifugation and slides were prepared for immunocytochemical staining with CK and irrelevant (IR) antibody. Slides were evaluated manually and positive cells were categorized as tumor cells, hematopoetic cells, or questionable cells. False-positive staining events were commonly observed in noncancer cases stained with CK or IR antibodies and in breast cancer cases stained with IR antibody. There was little difference in the number of breast cancer marrow specimens scored as tumor cells regardless of whether the antibody used was CK or IR. It is important to devise improved criteria and methods for accurate detection and interpretation of disseminated tumor cells in the marrow of breast cancer patients.

Cerebral deposition of amyloid beta peptide (Abeta) is an early and critical feature of Alzheimer's disease. Abeta generation depends on proteolytic cleavage of the amyloid precursor protein (APP) by two unknown proteases: beta-secretase and gamma-secretase. These proteases are prime therapeutic targets. A transmembrane aspartic protease with all the known characteristics of beta-secretase was cloned and characterized. Overexpression of this protease, termed BACE (for beta-site APP-cleaving enzyme) increased the amount of beta-secretase cleavage products, and these were cleaved exactly and only at known beta-secretase positions. Antisense inhibition of endogenous BACE messenger RNA decreased the amount of beta-secretase cleavage products, and purified BACE protein cleaved APP-derived substrates with the same sequence specificity as beta-secretase. Finally, the expression pattern and subcellular localization of BACE were consistent with that expected for beta-secretase. Future development of BACE inhibitors may prove beneficial for the treatment of Alzheimer's disease.

Amyloid beta-proteins (A beta) are proteolytic fragments of the beta-amyloid precursor protein (beta APP) that are secreted by mammalian cells throughout life but also accumulate progressively as insoluble cerebral aggregates in Alzheimer's disease (AD). Because mounting evidence indicates that A beta aggregation and deposition are early, critical features of AD leading to neurotoxicity, many studies of A beta aggregation have been conducted using synthetic peptides under generally nonphysiological conditions and concentrations. We recently described the oligomerization of A beta peptides secreted by beta APP-expressing cells at low nanomolar (20-30 ng/mL) levels into sodium dodecyl sulfate- (SDS-) stable oligomers of 6-16 kDa. Here, we extensively characterize this in vitro system and show that the amyloid binding dye, Congo red, acts to markedly decrease oligomer/monomer ratios by stabilizing the 4 kDa A beta monomers (ID50 approximately equal to 3.4 microM). Addition of radioiodinated synthetic A beta 1-40 to the cultures or to their conditioned media at physiological concentrations (0.25-2.5 nM) reveals that it undergoes progressive aggregation into SDS-stable oligomers of 6-25 kDa during brief (approximately 4 h) incubation at 37 degrees C, and this is inhibitable by Congo red. The level of A beta oligomers can be quantitated in the Chinese hamster ovary (CHO) conditioned medium by size-exclusion chromatography as well as by SDS-polyacrylamide gel electrophoresis (PAGE), and comparison of these two methods suggests that aggregation of A beta into higher molecular weight polymers that are not detectable by SDS-PAGE occurs in the cultures. We conclude that both endogenous and synthetic A beta can assemble into stable oligomers at physiological concentrations in cell culture, providing a manipulable system for studying the mechanism of early A beta aggregation and identifying inhibitors thereof under biologically relevant conditions.

Humans inheriting missense mutations in the presenilin (PS)1 and -2 genes undergo progressive cerebral deposition of the amyloid beta-protein at an early age and develop a clinically and pathologically severe form of familial Alzheimer's disease (FAD). Because PS1 mutations cause the most aggressive known form of AD, it is important to elucidate the structure and function of this multitransmembrane protein in the brain. Using a panel of region-specific PS antibodies, we characterized the presenilin polypeptides in mammalian tissues, including brains of normal, AD, and PS1-linked FAD subjects, and in transfected and nontransfected cell lines. Very little full-length PS1 or -2 was detected in brain and untransfected cells; instead the protein occurred as a heterogeneous array of stable N- and C-terminal proteolytic fragments that differed subtly among cell types and mammalian tissues. Sequencing of the major C-terminal fragment from PS1-transfected human 293 cells showed that the principal endoproteolytic cleavage occurs at and near Met298 in the proximal portion of the large hydrophilic loop. Full-length PS1 in these cells is quickly turned over (T1/2 approximately 60 min), in part to the two major fragments. The sizes and amounts of the PS fragments were not significantly altered in four FAD brains with the Cys410Tyr PS1 missense mutation. Our results indicate that presenilins are rapidly processed to N- and C-terminal fragments in both neural and nonneural cells and that interference with this processing is not an obligatory feature of FAD-causing mutations.