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Abstract Introduction: High mobility group box 1 protein participates in the pathogenesis of allergic rhinitis. Activation of the inflammasome can mediate the release of high mobility group box 1. The role of the absent in melanoma 2 inflammasome in allergic rhinitis remains unclear. Objective: This study aimed to investigate the function of absent in melanoma 2 inflammasome in murine allergic rhinitis and the interaction between high mobility group box 1 and the absent in melanoma 2 inflammasome. Methods: A murine allergic rhinitis model was established using twenty Balb/c mice. Expression of the components of the absent in melanoma 2 inflammasome: absent in melanoma 2, apoptosis-associated speck-like protein containing a CARD (Asc), caspase-1 p20, and additional nod-like receptor family pyrin domain containing 3 (Nlrp3) were detected by western blotting during allergic rhinitis. Alterations of absent in melanoma 2, caspase-1, and high mobility group box 1 after ovalbumin challenge were demonstrated by immunohistochemistry. TdT-mediated dUTP Nick end labeling, TUNEL assay, and cleavage of caspase-3 and PARP-1 were used for the observation of pyroptosis. Results: Eosinophilia and goblet cell infiltration were observed in the nasal mucosa of mice in the allergic rhinitis group. Absent in melanoma 2, Asc, and caspase-1 p20 increased after ovalbumin exposure while Nlrp3 did not. High mobility group box 1 was released in the nasal mucosa of allergic rhinitis mice. TUNEL-positive cells increased in the epithelium and laminae propria, whereas cleavage of caspase-3 and PARP-1 was not observed. Conclusions: The absent in melanoma 2 inflammasome was activated and pyroptosis may occur in the nasal mucosa after ovalbumin treatment. These may contribute to the translocation of high mobility group box 1 and the development of allergic rhinitis.

Resumo Introdução: A proteína do grupo Box-1 de alta mobilidade participa da patogênese da rinite alérgica. A ativação do inflamassoma pode mediar a liberação de proteína do grupo Box-1 de alta mobilidade. O papel do inflamassoma ausente no melanoma 2 na rinite alérgica permanece incerto. Objetivo: Investigar a função do inflamassoma ausente no melanoma 2 em um modelo murino de rinite alérgica e a interação entre a proteína do grupo Box-1 de alta mobilidade e o inflamassoma ausente no melanoma 2. Método: Um modelo murino de rinite alérgica foi estabelecido com 20 camundongos Balb/c. A expressão dos componentes do inflamassoma ausente no melanoma 2, da proteína speck-like associada à apoptose com CARD (Asc), da caspase-1 p20 e do domínio de pirina da família NLR adicional com 3 (Nlrp3) foi detectada por western blotting durante a rinite alérgica. Alterações de inflamassoma ausente no melanoma 2, na caspase-1 e na proteína do grupo Box-1 de alta mobilidade após o teste de provocação com ovalbumina foram demonstradas por imuno-histoquímica. O ensaio dUTP Nick-End Labeling mediado por TdT, TUNEL e clivagem de caspase-3 e PARP-1 foram usados para a observação de piroptose. Resultados: Eosinofilia e infiltração de células caliciformes foram observadas na mucosa nasal de camundongos do grupo rinite alérgica. Inflamassoma ausente no melanoma 2, Asc e caspase-1 p20 aumentou após a exposição à ovalbumina, enquanto Nlrp3 não aumentou. A proteína do grupo Box-1 de alta mobilidade foi liberada na mucosa nasal de camundongos com rinite alérgica. As células TUNEL-positivas aumentaram no epitélio e na lâmina própria, enquanto a clivagem da caspase-3 e a PARP-1 não foram observadas. Conclusão: O inflamassoma ausente no melanoma 2 foi ativado e pode ocorrer piroptose na mucosa nasal após o tratamento com ovalbumina. Esses fatores podem contribuir para a translocação de proteína do grupo Box-1 de alta mobilidade e o desenvolvimento de rinite alérgica.

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INTRODUCTION: High mobility group box 1 protein participates in the pathogenesis of allergic rhinitis. Activation of the inflammasome can mediate the release of high mobility group box 1. The role of the absent in melanoma 2 inflammasome in allergic rhinitis remains unclear. OBJECTIVE: This study aimed to investigate the function of absent in melanoma 2 inflammasome in murine allergic rhinitis and the interaction between high mobility group box 1 and the absent in melanoma 2 inflammasome. METHODS: A murine allergic rhinitis model was established using twenty Balb/c mice. Expression of the components of the absent in melanoma 2 inflammasome: absent in melanoma 2, apoptosis-associated speck-like protein containing a CARD (Asc), caspase-1 p20, and additional nod-like receptor family pyrin domain containing 3 (Nlrp3) were detected by western blotting during allergic rhinitis. Alterations of absent in melanoma 2, caspase-1, and high mobility group box 1 after ovalbumin challenge were demonstrated by immunohistochemistry. TdT-mediated dUTP Nick end labeling, TUNEL assay, and cleavage of caspase-3 and PARP-1 were used for the observation of pyroptosis. RESULTS: Eosinophilia and goblet cell infiltration were observed in the nasal mucosa of mice in the allergic rhinitis group. Absent in melanoma 2, Asc, and caspase-1 p20 increased after ovalbumin exposure while Nlrp3 did not. High mobility group box 1 was released in the nasal mucosa of allergic rhinitis mice. TUNEL-positive cells increased in the epithelium and laminae propria, whereas cleavage of caspase-3 and PARP-1 was not observed. CONCLUSIONS: The absent in melanoma 2 inflammasome was activated and pyroptosis may occur in the nasal mucosa after ovalbumin treatment. These may contribute to the translocation of high mobility group box 1 and the development of allergic rhinitis.

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ABSTRACT Objectives To provide a meta-analysis of the clinical efficacy and safety of sodium glucose co-transporter 2 inhibitors (SGLT2-i), as a combination treatment with metformin in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control with metformin alone. Materials and methods We have searched randomized controlled trials (RCTs) in the database: MEDLINE, Embase and Cochrane Collaborative database. We used mean differences (MD) to assess the efficacy of glycemic and other clinical parameters, and risk ratios (RR) to evaluate the adverse events for safety endpoints. The heterogeneity was evaluated by I2. Results Finally 9 studies were included. SGLT2-i plus metformin had higher reduction level in HbA1C [MD = -0.50, 95% CI (-0.62, -0.38), p < 0.00001], FPG [MD = -1.12, 95%CI (-1.38, -0.87), p < 0.00001], body weight [MD = -1.72, 95% CI (-2.05, -1.39), p < 0.00001], SBP [MD = -4.44, 95% CI (-5.45, -3.43), p < 0.00001] and DBP [MD = -1.74, 95% CI (-2.40, -1.07), p < 0.00001] compared with metformin monotherapy. However, SGLT2-i plus metformin group had higher risk of genital infection [RR = 3.98, 95% CI (2.38, 6.67), p < 0.00001]. No significant difference was found in the risk of hypoglycemia, urinary tract infection or volume related adverse events. Conclusions Although the risk of genital infection may increase, SGLT2-i plus metformin may provide an attractive treatment option to those T2DM patients who are unable to achieve glycemic control with metformin alone, based on its effects on glycemic control, reducing body weight and lowering blood pressure.

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OBJECTIVES: To provide a meta-analysis of the clinical efficacy and safety of sodium glucose co-transporter 2 inhibitors (SGLT2-i), as a combination treatment with metformin in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control with metformin alone. MATERIALS AND METHODS: We have searched randomized controlled trials (RCTs) in the database: MEDLINE, Embase and Cochrane Collaborative database. We used mean differences (MD) to assess the efficacy of glycemic and other clinical parameters, and risk ratios (RR) to evaluate the adverse events for safety endpoints. The heterogeneity was evaluated by I2. RESULTS: Finally 9 studies were included. SGLT2-i plus metformin had higher reduction level in HbA1C [MD = -0.50, 95% CI (-0.62, -0.38), p < 0.00001], FPG [MD = -1.12, 95%CI (-1.38, -0.87), p < 0.00001], body weight [MD = -1.72, 95% CI (-2.05, -1.39), p < 0.00001], SBP [MD = -4.44, 95% CI (-5.45, -3.43), p < 0.00001] and DBP [MD = -1.74, 95% CI (-2.40, -1.07), p < 0.00001] compared with metformin monotherapy. However, SGLT2-i plus metformin group had higher risk of genital infection [RR = 3.98, 95% CI (2.38, 6.67), p < 0.00001]. No significant difference was found in the risk of hypoglycemia, urinary tract infection or volume related adverse events. CONCLUSIONS: Although the risk of genital infection may increase, SGLT2-i plus metformin may provide an attractive treatment option to those T2DM patients who are unable to achieve glycemic control with metformin alone, based on its effects on glycemic control, reducing body weight and lowering blood pressure.

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Sequence analysis can be used to evaluate transmission networks. We have used retrospective samples to examine two HIV-1 transmission networks established by contact tracing. Regions of the HIV-1 region representing segments of gag and env were amplified by RT-PCR from frozen plasma samples and the sequence of each PCR product was determined. Within one of the networks (composed of 38 subjects) we found only a subset of the tested sequence clusters was consistent with the reported epidemiological linkage. Of 15 presumed transmission events where sequence data were available, 9 could be rejected either by subtype mismatch or by phylogenetic tests. In the other network (composed of 89 subjects) we were able to assess sequences for 26 presumed transmission events, 18 of which were rejected based on subtype discordance. Long lags in time between the time of transmission and the time of sequence sampling (ranging from 2 to 18 years) may limit the sensitivity for the detection of sequence linkage. Also, superinfection and incomplete epidemiological information are other factors that will limit the concordance of phylogenetic reconstruction and reported epidemiological linkage.

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Se demostró la eficacia de la enzima transcriptasa inversa SensiScript para obtener material genético útil en la secuenciación de ácido nucleico de VIH-1, a partir de sueros colectados entre 1989 y 1998 y conservados a temperatura subóptima. Con el empleo de la enzima SensiScript se obtuvo amplificación del ARN del VIH-1 en 86,5 % de las muestras estudiadas, comparado con 20 % al utilizar la enzima AMV-RT. En 13,5 % de las muestras no se obtuvo amplificación con ninguna de las 2 enzimas empleadas.

The efficiency of SensiScript reverse transciptase to obtain useful genetic material in the sequencing of the nucleic acid from HIV-1, starting from sera collected between 1989 and 1998 and kept at suboptimal temperatures, was proved. On using the SensiScript enzyme it was obtained an amplification of the RNA of the HIV-1 in 86.5 % of the studied samples, compared with 20 % on using the AMV-RT enzyme . No amplification was obtained in 13.5 % of the studied samples with any of the 2 enzymes used.

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The efficiency of SensiScript reverse transciptase to obtain useful genetic material in the sequencing of the nucleic acid from HIV-1, starting from sera collected between 1989 and 1998 and kept at suboptimal temperatures, was proved. On using the SensiScript enzyme it was obtained an amplification of the RNA of the HIV-1 in 86.5 % of the studied samples, compared with 20 % on using the AMV-RT enzyme . No amplification was obtained in 13.5 % of the studied samples with any of the 2 enzymes used.

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