Crotoxin down-modulates pro-inflammatory cells and alleviates pain on the MOG35-55-induced experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis.

Multiple sclerosis (MS) is a Central Nervous System inflammatory demyelinating disease that has as primary symptoms losses of sensory and motor functions, including chronic pain. To date, however, few studies have investigated the mechanisms of chronic pain in animal models of MS since locomotor impairments render difficult its evaluation. It was previously demonstrated that in the MOG35-55-induced EAE, an animal model of MS, the hypernociception appears before the onset of motor disability, allowing for the study of these two phenomena separately. Here, we evaluated the effect of crotoxin (CTX), a neurotoxin isolated from the Crotalus durissus terrificus snake venom that displays, at non-toxic dose, antinociceptive, anti-inflammatory and immunomodulatory effects, in the pain and in symptoms progression of EAE. The pain threshold of female C57BL/6 mice decreased at the 4th day after immunization, while the first sign of disease appeared around the 11st-12nd days, coinciding with the onset of motor abnormalities. CTX (40 µg/kg, s.c.) administered in a single dose on the 5th day after immunization, induced a long-lasting analgesic effect (5 days), without interfering with the clinical signs of the disease. On the other hand, when crotoxin was administered for 5 consecutive days, from 5th-9th day after immunization, it induced analgesia and also reduced EAE progression. The antinociceptive effect of crotoxin was blocked by Boc-2 (0.5 mg/kg, i.p.), a selective antagonist of formyl peptide receptors, by NDGA (30 µg/kg, i.p.), a lipoxygenase inhibitor and by atropine sulfate (10 mg/kg, i.p.), an antagonist of muscarinic receptors, administered 30 min before CTX. CTX was also effective in decreasing EAE clinical signs even when administered after its onset. Regarding the interactions between neurons and immunocompetent cells, CTX, in vitro, was able to reduce T cell proliferation, decreasing Th1 and Th17 and increasing Treg cell differentiation. Furthermore, in EAE model, the treatment with 5 consecutive doses of CTX inhibited IFN-γ-producing T cells, GM-CSF-producing T cells, reduced the frequency of activated microglia/macrophages within the CNS and decreased the number of migrating cell to spinal cord and cerebellum at the peak of the disease. These results suggest that CTX is a potential treatment not only for pain alteration but also for clinical progression induced by the disease as well as an useful tool for the development of new therapeutic approaches for the multiple sclerosis control.

Incidence of stroke subtypes, prognosis and prevalence of risk factors in Joinville, Brazil: a 2 year community based study.

BACKGROUND: There have been few population based studies on stroke risk factors and prognosis conducted in Brazil. The objective of this study was to evaluate, over a 2 year period, the incidence of the subtypes of first ever stroke, the prevalence of cardiovascular risk factors and functional prognosis in a city located in the south of Brazil. METHODS: The period from January 2005 to December 2006 was evaluated prospectively by compiling data on first ever stroke cases, medications used prior to the morbidity and the incidence of traditional risk factors. The annual incidence was adjusted for age using the direct method. Patients were monitored for at least 6 months following the event. RESULTS: Of 1323 stroke cases, 759 were first ever stroke cases. Of these, 610 were classified as infarctions, 94 as intracerebral haemorrhage and 55 as subarachnoid haemorrhage. The crude incidence rate per 100 000 inhabitants was 61.8 for infarction (95% CI 57.0 to 66.9), 9.5 for intracerebral haemorrhage (95% CI 7.7 to 11.6) and 5.6 for subarachnoid haemorrhage (95% CI 4.2 to 7.3). The 30 day case fatality was 19.1%. The most prevalent cardiovascular risk factor was arterial hypertension. By post-stroke month 6, 25% had died (95% CI 21.4 to 29.1) whereas 61.5% had regained their independence (95% CI 56.2 to 68.3). CONCLUSIONS: Case fatality rate, prognosis and incidence adjusted for stroke subtypes were similar to those found in other population based studies. The prevalence rates of ischaemic heart disease, dyslipidaemia, arterial hypertension and diabetes suggest that Joinville presents a mixed pattern of cardiovascular risk, a pattern seen in developed and developing countries alike.

Cognitive impairment is frequent among symptomatic carriers of human T-cell lymphotropic virus type 1 (HTLV-1), regardless of their clinical status.

The main goal of this study was to investigate the presence of cognitive impairment in patients infected with HTLV-1 presenting or not TSP/HAM. METHODS: Cross-sectional study including 104 participants: 37 asymptomatic HTLV-1 carriers, 37 patients diagnosed with TSP/HAM and 30 HTLV-1 negative control patients. Within the HTLV-1 positive group, 53 were female and 21 were male, the average age was 46 (SD=13.5) and the average schooling time was 7.7years (SD=3.3).The sociodemographic variables (genre, age and education) were compared between the three groups. The assessment tools used were: Beck Depression Inventory, Lawton's Activities of Daily Life Scale and a complete neuropsychological battery. The application of these assessment tools was carried out in blind. Both HTLV-1 asymptomatic subjects and HAM/TSP patients showed a lower performance on neuropsychological tests and higher depression scores when compared to the control group. HTLV-1 patients performed poorly in several cognitive domains, but only fluid intelligence, estimated intellectual functioning, immediate and delayed recall of visual memory and information processing speed (in the specific case of patients with TSP/HAM) reached statistical significance when compared with controls. Depression was not associated with cognitive impairment. HTLV-1 carriers presented a higher frequency of cognitive impairment than normal controls.

AIDS incidence and survival in a hospital-based cohort of asymptomatic HIV seropositive patients in São Paulo, Brazil.

BACKGROUND: In spite of the high incidence of AIDS in Brazil, few studies have tried to evaluate the prognosis of asymptomatic HIV seropositive Brazilian patients. METHODS: A hospital outpatient facility-based cohort of HIV seropositive asymptomatic subjects was followed to determine their probability of remaining AIDS-free at 2 and 4 years of follow-up, as well as the one-year estimated cumulative probability of survival for the AIDS incident cases. The cohort was made up of all asymptomatic HIV seropositive subjects referred to the Immunology Branch of a large university hospital in São Paulo, Brazil, between 1985 and June 1997. RESULTS: The cumulative probability of remaining free from AIDS was 79% (+/- 3.7% SE) at 2 years, and 64.4% (+/- 5.1% SE) at 4 years after first known positive anti-HIV serology. Women had a marginally significant better probability of remaining AIDS-free after both 2 and 4 years of known seropositivity, as compared with men. There were no significant differences in the prognosis of the infection by age; the only single parameter associated with better prognosis was an initial CD4+ count > or =350/microl. The probability of survival one year after the diagnosis of AIDS was 78%, and the 50% estimated probability of survival was 19 months. Older patients (aged > or =35 years) had a better prognosis, as suggested by their longer survival estimates (P = 0.06). CONCLUSIONS: The probability of survival with AIDS observed in this study was higher than in the few previously published estimates for Brazil. However, since the time frame was so wide, it may not be entirely comparable with earlier studies. Some likely explanations for this possibly better prognosis could include more efficient prophylaxis for opportunistic diseases, as well as an increase in the availability of anti-retroviral drugs. The 8% incidence of AIDS at 2 years observed in this study for those individuals whose initial CD4+ count was > or =350/ml was close to that found in a large international epidemiological study of seroconverters.

CD4+ T-cell recovery and clinical outcome in HIV-1-infected patients exposed to multiple antiretroviral regimens: partial control of viremia is associated with favorable outcome.

The goal of antiretroviral therapy is clinical benefit through the suppression of viral replication and the immunologic reconstitution of HIV-1-infected patients. In spite of the availability of different highly active antiretroviral therapy only some patients sustain undetectable plasma viremia. We performed an observational study from October 1987 to February 2001 on immunologic and clinical outcome of 148 HIV-1-infected patients from an open clinical cohort at São Paulo University, Brazil. The median T CD4+ at starting first monitored regimen was 227 cells per microliter, with 65% of patients previously exposed to antiretroviral regimens, mostly dual therapy. Virologic response to antiretroviral therapy, after a median period of 179 weeks of monitored treatment, allowed classifying patients as aviremic (RNA plasma viremia below 500 copies per milliliter); viremic (current viral load at historic levels), and viremic-attenuated groups (detectable viremia, but > 1 log viral suppression). HIV RNA viral load, T CD4+ cells count, HIV-1 pol sequencing, inflammatory parameters, and clinical events were documented during a median follow-up of 251 weeks. This study observed better clinical and immunologic responses in the aviremic group, but the viremic-attenuated group showed a significant gain in CD4+ cells (p < 0.013) and a decreased number of cases progressing to an AIDS-defining clinical condition (p < 0.001) compared to the viremic group.

Cancer incidence in eighteen cities of the State of São Paulo, Brazil.

OBJECTIVE: As in Brazil cancer registries are mostly based on large cities, there are no estimates per state or per region and information on the disease incidence in the vast in-land areas is very scarce. An incidence survey was conducted in 18 major cities of the state of São Paulo, excluding the capital, aiming to collect information about cancer incidence in the state of São Paulo. METHODS: Of the 18 cities in state of São Paulo included in the survey, all had available resources for cancer management. Data from the year of 1991 were collected by the personnel of the Instituto Brasileiro de Geografia e Estatística (Brazilian Institute of Statistics), who were especially trained by the study coordinators at the Fundação Oncocentro de São Paulo (Cancer Center of São Paulo). The collected data were processed and analyzed at the Oncocentro. Data collection, processing, and analyses were performed according to the recommendations of the International Agency for Research on Cancer. RESULTS: Although some discrepancies were observed in cancer incidence rates between the cities, results obtained for all 18 cities combined were remarkably close to those recently found for the city of São Paulo in the year 1993. One remarkable finding was the relatively high cancer incidence rates in both sexes in the city of Santos. CONCLUSIONS: The very similar all-sites cancer incidence rates found in the year 1991, when compared to those for the city of São Paulo in the year 1993, are suggestive that all regions have common cancer-related factors. Nevertheless, other explanations, such as the inclusion in the study of prevalent cases, as well as of non-residents, may have occurred in both studies, biasing the results. There is a need of further studies to confirm the high cancer incidence in Santos.

HIV heterosexual transmission to stable sexual partners of HIV-infected Brazilian hemophiliacs.

Nineteen Brazilian HIV-infected hemophiliacs and their stable heterosexual sexual partners were studied with the aim of assessing the rate of HIV transmission in this at risk group. The mean length of relationship between couples was 7.4 years. The hemophiliac men were Class II (n = 6), III (n = 11) and IVa (n = 2) of the CDC classification. They had decreased CD4+ and elevated CD8+ cell numbers; five had p24 antigenemia. We found 3 HIV-infected women (15.8 percent) by routine and confirmatory tests, a prevalence similar to that seen in other countries. They were asymptomatic and had no detectable p24 antigenemia. The 3 seropositive women's partners were Class II and III-CDC, and had normal CD4+ and CD8+ values and no p24 antigenemia. All seronegative women also had normal CD4+ and CD8+ numbers, except for elevated CD8+ cells in three of them, but immune abnormalities had already been seen in some seronegative partners at high risk for HIV infection. Our results reinforce previous suggestions that heterosexual transmission to stable female partners occurs preferentially early after initiation of sexual exposure, and possibly when the transmitter had high levels of viremia and regular sexual activity.

PIP: In Brazil, hemophiliacs who received coagulation factor concentrates during 1980-85 have rates of HIV exceeding 50% and rates of heterosexual transmission to their partners in the range of 10-20%. This study investigated the clinical course of HIV infection in 19 male patients from a hematology center in Sao Paulo, Brazil, with hemophilia A or B and their stable, asymptomatic female sexual partners. The mean duration of the relationship was 7.4 years. Compared with 15 normal adult subjects used as controls, CD8+ cell counts of hemophiliacs were significantly higher while CD4+ cell values were significantly reduced. Three sexual partners (15.8%) were HIV-positive, implying a transmission rate of 2.1 per 100 person-years. All female partners were in Centers for Disease Control Class II. Their male partners were in Classes II and III and had normal CD4+ and CD8+ levels. Neither males nor females had p24 antigenemia. Fragments of HIV particles were present in several HIV-negative female partners. These findings suggests early HIV transmission, when the transmitter has high levels of viremia, to stable female partners of hemophiliacs.

Prevalência de hipocalcemia e hipomagnesemia em equinos com distúrbios gastrintestinais / Prevalence of hypocalcemia and hypomagnesemia in equines with gastrointestinal diseases

The prevalence of hypocalcemia and hypomagnesemia was evaluated in horses with gastrointestinal diseases. For that, 12 animals were examined at the UVV Veterinary Hospital. Age and gender of the animals, as well breed clinical diagnosis, adopted therapy and outcomes were recorded. Serum determinations of total calcium and magnesium were done on the day of admission and during the period of hospitalization. They revealed the presence of low levels of calcium and magnesium. The comparison between survivals and non-survivals on the admission day had shown a significant result only for serum calcium.

Effects of cashew nut shell liquid (CNSL) on the performance of broiler chickens / Efeitos do líquido da casca da castanha de caju (LCC) sobre o desempenho de frangos de corte

The effects of cashew nut shell liquid (CNSL) on growth performance, carcass yield, relative weight of internal organs and microbiology of digestive tract of broiler chickens were investigated. Five hundred and forty male broiler chicks at one day of age were arranged in a completely randomized design with six treatments and six repetitions with 15 broiler chicks each. The treatments were: control (T1 - without growth promoter virginiamycin and CNSL); inclusion levels of 0.10mL (T2), 0.20mL (T3), 0.30mL (T4) and 0.40mL (T5) of CNSL/kg of feed; and commercial promoter virginiamycin (T6). At 21 and 40 days of age, body weight, feed intake, feed conversion and viability of birds were similar in all treatments. Carcass yield was higher in the treatment with the growth promoter when compared to the control treatment. There was a linear increase in carcass yield when the level of CNSL was increased in the diet. The relative weight of the intestine was lower in the treatment containing virginiamycin when compared to the treatment without the inclusion of additives. The relative weight of the intestines decreased when the levels of inclusion of CNSL were increased. There was a gradual reduction of Escherichia coli concentration reaching the lowest number on the CNSL level of 0.30mL/kg. It was concluded that CNSL showed similar performance and slaughter yield as the growth promoter and reduced the concentration of Escherichia coli in the intestinal contents.

Um estudo foi conduzido para investigar os efeitos do líquido da casca da castanha de caju (LCC) sobre o desempenho, o rendimento de carcaça, o peso relativo dos órgãos internos e a microbiologia do trato digestivo de frangos de corte. Foram utilizados 540 pintos machos de um dia de idade, distribuídos num delineamento inteiramente casualizado, com seis tratamentos e seis repetições de 15 aves cada. Os tratamentos consistiram em: controle (T1 - sem promotor comercial e sem LCC), níveis de inclusão de 0,10mL (T2), 0,20mL (T3), 0,30mL (T4) e 0,40mL (T5) de LCC/kg de ração e T6 (promotor comercial - virginiamicina). Aos 21 e 40 dias de idade, o peso corporal, o consumo de ração, a conversão alimentar e a viabilidade das aves foram semelhantes em todos os tratamentos. O rendimento de carcaça foi superior no tratamento com promotor de crescimento em relação ao tratamento-controle. Ocorreu uma resposta linear de incremento no rendimento de carcaça com o aumento do nível de LCC na dieta. O peso relativo dos intestinos foi menor no tratamento com virginiamicina em relação ao tratamento-controle. O peso relativo dos intestinos diminuiu com o aumento do nível de inclusão do LCC. Houve uma redução gradual da concentração de Escherichia coli, cuja menor concentração atingiu o nível de 0,30mL/kg. Conclui-se que o LCC mostrou desempenho e rendimento de abate semelhantes ao promotor de crescimento e reduziu a concentração de Escherichia Coli no conteúdo intestinal.

Influence of chromium supplementation on energy metabolism in horses used in policing activity / Influência da suplementação com cromo sobre o metabolism energético em equinos usados em atividade de policiamento

The influence of chromium supplementation on some blood variables in 11 adult stallions used for policing activities was evaluated. Each animal was treated with 11mg of chromium/400kg body weight, orally, for a period of 30 days. On days 0 (before) and 30 (after) the animals were evaluated and blood samples were obtained before and after exercise. Plasma glucose and lactate and serum cortisol and insulin were analyzed in each of these moments. On day 0, plasma glucose concentrations were 68.4±5.6mg/dL and 78.7±6.5mg/dL; plasma lactate concentrations were 6.2±0.6mg/dL and 13.1±7.6mg/dL; serum cortisol values were 48.5±7.9ng/mL and 42.6±19.7ng/mL; and serum insulin values were 3.0±6.4µUI/mL and 1.9±1.7µUI/mL, respectively, before and after exercise. On day 30, plasma glucose concentrations were 73.3±5.7mg/dL and 78.4±6.7mg/dL; plasma lactate concentrations were 7.3±0.9mg/dL and 7.6±1.2mg/dL; serum cortisol values were 62.9±21.8ng/mL and 40.3±17.0ng/mL; and serum insulin values were 1.4±1.3µUI/mL and 1.7±1.4µUI/mL, respectively, before and after exercise. As an effect of the exercise, a decrease was shown in the concentration of serum insulin and an increase in plasma lactate and glucose. Chromium supplementation resulted in a reduction of lactate values after physical activity, possibly indicating that chromium contributed to a better utilization of plasma glucose and to a better adaptation of animals to physical activity.

O presente trabalho avaliou a influência da suplementação com cromo em algumas variáveis sanguíneas em 11 equinos machos, adultos, usados em atividade de policiamento. Cada animal recebeu 11mg de cromo/400kg de peso corpóreo, via oral, durante 30 dias. Nos dias 0 (antes) e 30 (após), os animais foram avaliados e amostras de sangue foram obtidas antes e após o exercício. Glicose e lactato plasmáticos e cortisol e insulina séricas foram determinados. No dia 0, as concentrações de glicose plasmática foram 68,4±5,6mg/dL e 78,7±6,5mg/dL; de lactato plasmático, 6,2±0,6mg/dL e 13,1±7,6mg/dL; de cortisol sérico, 48,5±7,9ng/mL e 42,6±19,7ng/mL; e de insulina sérica, 3,0±6,4µUI/m L e 1,9±1,7µUI/mL, respectivamente, antes e após o exercício. No dia 30, as concentrações de glicose plasmática foram 73,3±5,7mg/dL e 78,4±6,7mg/dL; de lactato plasmático, 7,3±0,9mg/dL e 7,6±1,2mg/dL; de cortisol sérico, 62,9±21,8ng/mL e 40,3±17,0ng/mL; e de insulina sérica, 1,4±1,3µUI/mL e 1,7±1,4µUI/mL, respectivamente, antes e após o exercício. Como efeito do exercício, foi demonstrado redução na concentração sérica de insulina e aumento no lactato e glicose plasmáticas. A suplementação com cromo resulto u em redução dos valores de lactato após a atividade física, possivelmente indicando que o cromo contribuiu para a melhor utilização da glicose plasmática e melhor adaptação ao exercício físico realizado.

Caracteristicas da mortalidade por doenca isquemica do coracao em adultos de 15 a 74 anos no municipio de Sao Paulo. / Characteristics of the mortality due to ischemic heart disease in adults from 15 to 74 years old in the municipality of Sao Paulo

Foi analisada uma amostra de 2.743 obitos de residentes do Distrito da Capital de Sao Paulo de ambos os sexos e de idade de 15 a 74 a nos. Para cada caso, identificado a partir do atestado de obito, foi feito entrevista junto aos familiares para algumas caracterizacoes, bem como junto aos medicos, hospitais clinicas, etc. onde o falecido recebeu assistencia medica. Foi possivel caracterizar a causa basica da morte, comparando-a com aquela declarada no atestado de obito, assim como analisar a mortalidade segundo causas multiplas,a partir de todas as informacoes obtidas A doenca isquemica do coracao (DIC) foi a mais importante causa basica de morte, responsavel por 16,7% do total. Comparando-se os resultados com aqueles obtidos em pesquisa que empregou a mesma metodologia, realizada em 1962/64, verificou-se que a mortalidade por DIC aumentou 41,5% no sexo masculino e 38,6% no sexo feminino. Sao feitas descricoes mais pormenorizadas da mortalidade segundo idade e sexo. O emprego da metodologia de analise segundo causas multiplas de morte permitiu caracterizar as causas basicas de morte naqueles falecidos de 15 a 74 anos que apresentavam DIC, bem como algumas associacoes desta com outras causas

Pancreatitis cronica - resultados do tratamento cirurgico. / Chronic pancreatitis - results of the surgical treatment

Sao analisadas 59 observacoes de um total de 65 doentes com pancreatite cronica tratados cirurgicamente no Servico de Gastroenterologia Cirurgica do Hospital do Servidor Publico Estadual de Sao Paulo. A ingestao prolongada e continua de alcool foi relatada por 47 pacientes. De acordo com a conduta, dividiu-se o material em grupos incluindo resseccoes pancreaticas cefalicas ou de corpo e cauda, derivacoes pancreatointestinais ou operacoes associadas. Os niveis de amilasemia foram estudados antes e depois das intervencoes, tendo revelado serem um bom indice para se apreciar o efeito do tratamento. Os resultados clinicos da cirurgia foram bons em carca de dois tercos dos doentes, cuidando-se que a operacao deve ser planejada de acordo com as caracteristicas clinicas, radiologicas e anatomo-patologicas do pancreas de cada doente