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Thioredoxin plays an essential role in bacterial antioxidant machinery and virulence; however, its regulatory actions in the host are less well understood. Reduced human Trx activates transient receptor potential canonical 5 (TRPC5) in inflammation, but there is no evidence of whether these receptors mediate bacterial thioredoxin effects in the host. Importantly, TRPC5 can form functional complexes with other subunits such as TRPC4. Herein, E. coli-derived thioredoxin induced mortality in lipopolysaccharide- (LPS-) injected mice, accompanied by reduction of leukocyte accumulation, regulation of cytokine release into the peritoneum, and impairment of peritoneal macrophage-mediated phagocytosis. Dual TRPC4/TRPC5 blockade by ML204 increased mortality and hypothermia in thioredoxin-treated LPS mice but preserved macrophage's ability to phagocytose. TRPC5 deletion did not alter body temperature but promoted additional accumulation of peritoneal leukocytes and inflammatory mediator release in thioredoxin-administered LPS mice. Thioredoxin diminished macrophage-mediated phagocytosis in wild-type but not TRPC5 knockout animals. TRPC5 ablation did not affect LPS-induced responses. However, ML204 caused mortality associated with exacerbated hypothermia and decreased peritoneal leukocyte numbers and cytokines in LPS-injected mice. These results suggest that bacterial thioredoxin effects under LPS stimuli are mediated by TRPC4 and TRPC5, shedding light on the additional mechanisms of bacterial virulence and on the pathophysiological roles of these receptors.

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Rheumatoid arthritis is a chronic disease of the joints, which causes joint pain and disability. Anaemia is a frequent extra-articular manifestation in rheumatoid arthritis, affecting 30-70% of the patients; presenting a negative impact on patient´s quality of life. Some of the drugs used in rheumatoid arthritis treatment improve anaemia; but little is known on the beneficial effects of the anti-rheumatic leflunomide or the anti-TNFα adalimumab, in this parameter. We investigated the incidence of anaemia in rheumatoid arthritis patients treated or not with leflunomide or adalimumab. We also assessed whether anaemia correlates with disease activity. Anaemia was present in patients who had just been diagnosed with rheumatoid arthritis and had never taken disease modifying agents or biologicals (non-specific therapy group), but not in those taking either leflunomide or adalimumab. The erythrocyte sedimentation rate was increased in patients with non-specific therapy in comparison with those taking either leflunomide or adalimumab. Anaemia correlated with increased erythrocyte sedimentation rate. We suggest that leflunomide and adalimumab may be useful in treating anaemia in patients with rheumatoid arthritis.

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Patients with rheumatoid arthritis (RA) suffer from pain and joint disability. The transient receptor potential ankyrin 1 (TRPA1) channel expressed on sensory neurones and non-neuronal cells mediates pain transduction and inflammation and it has been implicated in RA. However, there is little information on the contribution of TRPA1 for human disease. Here, we investigated the expression of TRPA1 on peripheral blood leukocytes and the circulating levels of its endogenous activators 4-hydroxynonenal (4-HNE) and hydrogen peroxide (H2O2) in RA patients treated or not with the anti-rheumatic leflunomide (LFN) or the anti-TNFα adalimumab (ADA). We also assessed whether TRPA1 expression correlates with joint pain and disability, in addition to the immune changes in RA. TRPA1 expression on peripheral blood leukocytes correlated with pain severity and disability. TRPA1 levels on these cells were associated with the numbers of polymorphonuclear and the activation of CD14+ cells. No correlations were found between the lymphocyte population and TRPA1 expression, pain or disability. Patients recently diagnosed with RA expressed increased levels of TRPA1 on their leukocytes whilst treatment with either LFN or ADA down-regulated this receptor probably by reducing the numbers of polymorphonuclears and the activation of CD14+ cells. We suggest that the activation levels of CD14+ cells, the numbers of PMNs in the peripheral blood and the expression of TRPA1 on peripheral blood leukocytes correlate with RA progression, affecting joint pain sensitivity and loss of function.

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Cinnamaldehyde is a natural essential oil suggested to possess anti-bacterial and anti-inflammatory properties; and to activate transient receptor potential ankyrin 1 (TRPA1) channels expressed on neuronal and non-neuronal cells. Here, we investigated the immunomodulatory effects of cinnamaldehyde in an in vivo model of systemic inflammatory response syndrome (SIRS) induced by lipopolysaccharide. Swiss mice received a single oral treatment with cinnamaldehyde 1 h before LPS injection. To investigate whether cinnamaldehyde effects are dependent on TRPA1 activation, animals were treated subcutaneously with the selective TRPA1 antagonist HC-030031 5 min prior to cinnamaldehyde administration. Vehicle-treated mice were used as controls. Cinnamaldehyde ameliorated SIRS severity in LPS-injected animals. Diminished numbers of circulating mononuclear cells and increased numbers of peritoneal mononuclear and polymorphonuclear cell numbers were also observed. Cinnamaldehyde augmented the number of peritoneal Ly6C(high) and Ly6C(low) monocyte/macrophage cells in LPS-injected mice. Reduced levels of nitric oxide, plasma TNFα and plasma and peritoneal IL-10 were also detected. Additionally, IL-1ß levels were increased in the same animals. TRPA1 antagonism by HC-030031 reversed the changes in the number of circulating and peritoneal leukocytes in cinnamaldehyde-treated animals, whilst increasing the levels of peritoneal IL-10 and reducing peritoneal IL-1ß. Overall, cinnamaldehyde modulates SIRS through TRPA1-dependent and independent mechanisms.

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JUSTIFICATIVA E OBJETIVOS: A hepatite B é uma doença de distribuição universal que afeta ambos os sexos, podendo ser adquirida por meio de contato sexual, compartilhamento de seringas, exposição ocupacional e transfusão de sangue contaminado. O padrão de transmissão do vírus da hepatite B (VHB) está relacionado com a taxa de prevalência. O objetivo deste estudo foi determinar a prevalência de marcadores do VHB, de acordo com o índice de proteção vacinal. MÉTODO: A partir dos registros dos exames realizados em um laboratório público do município de São Luís, no ano de 2008, foram pesquisados os resultados para os marcadores de infecção com VHB: o anti-antígeno de superfície do VHB (HBsAg), os anticorpos anti-antígeno do core (anti-HBc) e anti-antígeno de superfície (anti-HBs).RESULTADOS: Dos 894 pacientes com sorologia positiva para VHB, 5,6% apresentaram marcador sorológico para fase aguda (HBsAg) prevalente em mulheres e pessoas com idade acima de 40 anos. Os anticorpos anti-HBc foram divididos em três tipos: anti-HBc (total), anti-HBc (IgG) e anti-HBc (IgM). Os índices de fase aguda e crônica utilizando estes marcadores foram similares (1,9% e 1,5%, respectivamente), com prevalência em mulheres e em pessoas com mais de 20 anos. O anti-antígeno de superfície anti-HBs foi detectado em 47,3% dos pacientes quando analisado isoladamente, indicando boa cobertura vacinal. CONCLUSÃO: Os dados do presente estudo indicam baixa prevalênciado VHB na população estudada.

BACKGROUND AND OBJECTIVES: Hepatitis B is a disease of worldwide distribution that affects both genders and can be acquired through sexual contact, needle sharing, occupational exposure and transfusion of contaminated blood. The pattern of transmission of hepatitis B virus (HBV) is related to the prevalence rate. The aim of this study was to determine the prevalence of HBV markers according to the rate of vaccine protection. METHOD: From the patient's records of a public laboratory of the city of São Luis (2008) the prevalence of three HBV infection markers, i.e., hepatitis B virus surface antigen (HBsAg), core anti-antigen (anti-HBc), and surface antigen antibody (anti-HBs) were studied. RESULTS: Of the 894 patients with positive serology for hepatitis B, 5.6% had prevalence of serologic marker for acute HBsAg in women and people over 40 years of age. The anti-HBc antibodies were divided into three types: anti-HBc (total), anti-HBc (IgG) and anti-HBc (IgM). The rates of acute and chronic use of these markers were similar (1.9% and 1.5% respectively) with the prevalence in women and in people over 20 years. The surface antigens anti-HBs were detected in 47.3% of patients when analyzed alone, indicating good vaccine coverage. CONCLUSION: The data from this study indicate low prevalence of hepatitis B virus among the studied population.

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