Serological patterns and temporal trends of HTLV-1/2 infection in high-risk populations attending public health units in Sao Paulo, Brazil

Background: HTLV-1/2 diagnosis in high-risk populations from Sao Paulo, Brazil has been problematic due a high proportion of seroindeterminate results. Objectives: To confirm and extend previous findings regarding HTLV-1/2 diagnosis in this geographic area. Study design: Sera from 2312 patients were tested for HTLV-1/2 antibodies using enzyme immunoassay (EIA) and Western blot (WB) analysis. Patients were from AIDS Reference Centers (Group 1; 1393 patients) and HTLV out-patient clinics (Group 11; 919 patients). Results were analyzed according to patients` age, gender, and clinic type. Results: HTLV-1 and HTLV-2 were detected in both groups. Among seropositive females, HTLV-2 was slightly more common in Group 1 (54.5%), while HTLV-1 prevailed in Group II (73.9%). Males from Group II had a higher percentage of HTLV-seroindeterminate results. No correlation between HTLV serological results and age was detected. Temporal analyses disclosed a high number of HTLV-seroindeterminate samples, and a large spectrum of indeterminate WB profiles. GD21 and/or rgp46-II bands were detected in 34.6% of sera from Group 1, and a p24 or p19 band was detected in 35.3% of sera from Group II. Conclusions: High rates of HTLV-indeterminate serological patterns during temporal analyses were confirmed in high-risk populations from Sao Paulo, Brazil. (c) 2008 Elsevier B.V. All rights reserved.

Increased expression of monocarboxylate transporters 1, 2, and 4 in colorectal carcinomas

Tumour cells are known to be highly glycolytic, thus producing high amounts of lactic acid. Monocarboxylate transporters (MCTs), by promoting the efflux of the accumulating acids, constitute one of the most important mechanisms in the maintenance of tumour intracellular pH. Since data concerning MCT expression in colorectal carcinomas (CRC) are scarce and controversial, the present study aimed to assess the expressions of MCT1, 2, and 4 in a well characterized series of CRC and assess their role in CRC carcinogenesis. CRC samples (126 cases) were analyzed for MCT1, MCT2, and MCT4 immunoexpression and findings correlated with clinico-pathological parameters. Expression of all MCT isoforms in tumour cells was significantly increased when compared to adjacent normal epithelium. Remarkably, there was a significant gain of membrane expression for MCT1 and MCT4 and loss of plasma membrane expression for MCT2 in tumour cells. Plasma membrane expression of MCT1 was directly related to the presence of vascular invasion. This is the larger study on MCT expression in CRC and evaluates for the first time its clinico-pathological significance. The increased expression of these transporters suggests an important role in CRC, which might justify their use, especially MCT1 and MCT4, as targets in CRC drug therapy.

Non-N-methyl-d-aspartate glutamate receptors in the lateral hypothalamus modulate cardiac baroreflex responses in conscious rats

P>In the present study, we investigated the effects of inhibition of the lateral hypothalamus (LH) neurotransmission with bilateral microinjection of CoCl(2), a non-selective blocker of neurotransmission, on modulation of cardiac baroreflex responses in conscious rats as well as the involvement of LH glutamatergic neurotransmission in this modulation. Reflex bradycardiac and tachycardiac responses to blood pressure increases (following i.v. infusion of phenylephrine) or decreases (following i.v. infusion of sodium nitroprusside) were investigated in conscious male Wistar rats. Responses were evaluated before and after microinjection of 1 nmol/100 nL CoCl(2), 2 nmol/100 nL 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzoquinoxaline-7-sulphonamide (NBQX; a selective non-N-methyl-d-aspartate (NMDA) glutamate receptor antagonist) or different doses (2, 4 or 8 nmol/100 nL) of the selective NMDA glutamate receptor antagonist LY235959. Microinjection of CoCl(2) into the LH had no effect on the tachycardiac baroreflex response, but did evoke a decrease in the reflex bradycardia caused by increases in blood pressure. Microinjection of NBQX into the LH had a similar effect on reflex bradycardia as CoCl(2), but had no effect on the tachycardiac response. Microinjection of increasing doses of LY235959 into the LH had no effect on the cardiac baroreflex response. In conclusion, the data suggest that the LH has a tonic facilitatory influence on the parasympathetic component of the baroreflex. The results also indicate that this facilitatory influence is mediated by local LH glutamatergic neurotransmission through non-NMDA glutamatergic receptors.

Reduced Red Cell 2,3-Diphosphoglycerate Concentrations in Critical Illness without Decreased In Vivo P50

We investigated whether red cell 2,3-diphosphoglycerate (2,3-DPG) concentrations are reduced in critical illness, whether acidaemia, hypophosphataemia or anaemia influence 2,3-DPG, and whether there is any net effect on in vivo P50. Twenty healthy, non-smoking, male volunteers were compared with 20 male intensive care patients with APACHE 2 scores > 20 on the preceding day. Those transfused in this time were excluded. Venous red cell 2,3-DPG concentrations were measured in both groups. In the patient group, routine multichannel biochemical profile and arterial blood gas analysis were also performed and in vivo P50 calculated. The mean 2,3-DPG concentration was significantly lower in the patient group than in the controls (4.2 +/-1.3 mmoll/l vs 4.9 +/-0.5 mmol/l, P=0.016). The patients were well oxygenated (lowest arterial PO2=75 mm Hg) and showed a tendency to acidaemia (median pH 7.37, range 7.06 to 7.48) and anaemia (median haemoglobin concentration 113 g/l, range 89 to 154 g/l). By linear regression of patient data, pH had a significant effect on 2,3-DPG concentrations (r=0.6, P=0.011). Haemoglobin and phosphate concentrations did not, but there were few abnormal phosphate values. There was no correlation between 2,3-DPG concentrations and in vivo P50 (r(2) less than or equal to 0.08). We conclude that 2,3-DPG concentrations were reduced in a broad group of critically ill patients. Although this would normally reduce the P50, the reduction was primarily linked with acidaemia, which increases the P50. Overall, there was no net effect on the P50 and thus no affinity-related decrease in tissue oxygenation.

Aplicação do método de comparação dos índices de neutralização à identificação intratípica de poliovírus dos tipos 1 e 3, utilizando culturas de células Hep-2

Foram estudadas culturas primárias de células renais de macaco rhesus (RMK) e culturas de células contínuas Hep-2, comparativamente em provas de identificação sorológica intratípica de 28 estirpes de poliovírus dos tipos 1 e 3, pelo método da "comparação dos índices de neutralização". A correlação entre os índices foi elevada -0,953 e 0,986 após incubação de três e cinco dias, respectivamente, e todas as estirpes examinadas mostraram o mesmo resultado de identificação nos dois sistemas celulares estudados. Disto se conclui que as culturas de células Hep-2 podem ser utilizadas como alternativa ás culturas primárias de rim de macaco rhesus, na identificação intratípica de poliovírus dos tipos 1 e 3, pelo método mencionado, com as vantagens inerentes às linhagens de células contínuas.

Soroprevalência de anticorpos contra vírus herpes simples 1-2 no Brasil

OBJETIVO: Estimar a soroprevalência de anticorpos por vírus herpes simples (HSV-1 e HSV-2) e analisar fatores associados no Brasil. MÉTODOS: Estudo transversal realizado entre 1996 e 1997 em 1.090 indivíduos com idade entre um e 40 anos da população geral, em quatro diferentes regiões geográficas no Brasil. Foram analisadas amostras sangüíneas para detecção de anticorpos para HSV-1 e HSV-2 com teste tipo-específico Elisa. Foram descritas freqüências e proporções, comparadas entre grupos utilizando o teste de Fisher bilateral exato. Foi realizada análise de regressão logística para avaliar influência das variáveis sociodemográficas e histórico de DST, sobre a soroprevalência de HSV-1 e/ou HSV-2. RESULTADOS: As soroprevalências de anticorpos para HSV-1 e HSV-2, ajustadas por idade, foram 67,2% e 11,3% respectivamente, sem diferença quanto ao sexo e maiores na Região Norte. As soroprevalências aumentaram com a idade, e para HSV-2 o maior aumento ocorreu na adolescência e entre adultos jovens. Indivíduos soropositivos para HSV-1 apresentaram maior risco de serem positivos para HSV-2 (15,7%) quando comparados com os negativos para HSV-1 (4,7%). Na análise multivariada, o histórico de DST aumentou significativamente (OR=3,2) a probabilidade de soropositividade para HSV-2. CONCLUSÕES: As soroprevalências para HSV-1 e para HSV-2 variam com a idade e entre as regiões do Brasil. História pregressa de DST é importante fator de risco para aquisição de infecção por HSV-2.

Síntese de algicidas da família da bacilamida e rearranjos de dióximas-1,3 cíclicas com vista a dessimetrização funcional

Dissertação para obtenção do Grau de Doutor em Química Orgânica

Infecção pelo HTLV 1/2: atuação no pré-natal como estratégia de controle da doença no Estado de Mato Grosso do Sul

Neste estudo, foi estimada a prevalência da infecção pelo HTLV 1/2 em gestantes no Estado de Mato Grosso do Sul, por meio das técnicas ELISA, Western Blot e PCR, em amostras de sangue obtidas por punção venosa periférica. Foram examinadas 116.689 gestantes, sendo diagnosticadas 153 infectadas pelo HTLV 1/2, com prevalência de 0,13%. Deste total, 133 (86,9%) eram do tipo 1 e 20 (11,1%) do tipo 2. Das 153 gestantes, 73,2% eram negras, pardas ou índias, cerca de 90% tinham atividades domésticas e 75,8% (116/153) tinham 7 anos ou menos de escolaridade. As 153 gestantes tiveram 172 gestações, durante o período do estudo, sendo que 164 tiveram acompanhamento. Das gestações acompanhadas, 6,7% (11/164) evoluíram para aborto, 26,8% (41/153) gestantes relataram abortos anteriores, sendo que 31,7% (13/41) apresentaram mais de dois abortos. Co-morbidades foram detectadas em 17% (26/153) sendo 3,3% (5/153) com HIV (p<0,000002). Os autores enfatizam a importância da identificação das gestantes infectadas pelo HTLV1/2 na estratégia de controle e prevenção da doença.

Efeito de doses de nitrapirina (2-cloro-6-triclorometil piridina), na nitrificação do sulfato de amônio e da uréia, em dois solos (LE e Pml) do Estado de São Paulo

Foram adicionados aos solos LE e Pml 36 ppm de N, na forma de sulfato de amonio e uréia, com 0; 1,2; 2,4 e 4,8 ppm de nitrapirina. Os solos foram incubados por 150 dias à temperatura entre 25ºC e 30ºC, com 75% do seu poder de embebição. Aos 50, 100 e 150 dias de incubação, procedeu-se a determinação dos teores de NO-3 e calculou-se a porcentagem de inibição da nitrificação nos tratamentos com nitrapirina Verificou-se que o teor de NO-3 no solo diminui significativamente, quando o sulfato de amonio e a uréia são associados com nitrapirina. A nitrapirina inibe igualmente a nitrificação do sulfato de amonio e da uréia, e apresenta inicialmente porcentagem de inibição da nitrificação (1%) no LE que no Pml. O tempo de ação da nitrapirina no solo ultrapassa 150 dias.

Increased expression of monocarboxylate transporters 1, 2, and 4 in colorectal carcinomas.

Tumour cells are known to be highly glycolytic, thus producing high amounts of lactic acid. Monocarboxylate transporters (MCTs), by promoting the efflux of the accumulating acids, constitute one of the most important mechanisms in the maintenance of tumour intracellular pH. Since data concerning MCT expression in colorectal carcinomas (CRC) are scarce and controversial, the present study aimed to assess the expressions of MCT1, 2, and 4 in a well characterized series of CRC and assess their role in CRC carcinogenesis. CRC samples (126 cases) were analyzed for MCT1, MCT2, and MCT4 immunoexpression and findings correlated with clinico-pathological parameters. Expression of all MCT isoforms in tumour cells was significantly increased when compared to adjacent normal epithelium. Remarkably, there was a significant gain of membrane expression for MCT1 and MCT4 and loss of plasma membrane expression for MCT2 in tumour cells. Plasma membrane expression of MCT1 was directly related to the presence of vascular invasion. This is the larger study on MCT expression in CRC and evaluates for the first time its clinico-pathological significance. The increased expression of these transporters suggests an important role in CRC, which might justify their use, especially MCT1 and MCT4, as targets in CRC drug therapy.

Ampakine CX546 bolsters energetic response of astrocytes: a novel target for cognitive-enhancing drugs acting as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor modulators.

Glutamate was previously shown to enhance aerobic glycolysis i.e. increase glucose utilization and lactate production with no change in oxygen levels, in mouse cortical astrocytes by a mechanism involving glutamate uptake. It is reported here that a similar response is produced in both hippocampal and cerebellar astrocytes. Application of the cognitive-enhancing drug CX546 promoted further enhancement of glucose utilization by astrocytes from each brain area following glutamate exposure. alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors represent the purported molecular target of cognitive-enhancing drugs such as CX546, and the presence of AMPA receptor subunits GluR1-4 was evidenced in astrocytes from all three regions by immunocytochemistry. AMPA itself did not stimulate aerobic glycolysis, but in the presence of CX546, a strong enhancement of glucose utilization and lactate production was obtained in cortical, hippocampal and cerebellar astrocytes. The effect of CX546 was concentration-dependent, with an EC(50) of 93.2 microm in cortical astrocytes. AMPA-induced glucose utilization in the presence of CX546 was prevented by the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the negative modulator GYKI 52466. In addition, the metabolic effect of CX546 in the presence of AMPA was mimicked by the AMPA receptor modulator cyclothiazide. Our data suggest that astrocyte energetics represents a novel target for cognitive-enhancing drugs acting as AMPA receptor modulators.