Resumo Objetivo: Comparar a progressão da obesidade e do controlo metabólico entre 2017 e 2019, pela terapêutica farmacológica com inibidores da SGLT2 (iSGLT2) em doentes com diabetes mellitus tipo 2 (DM2) na área da Administração Regional de Saúde do Centro (ARS Centro). Métodos: Estudo observacional de coorte retrospetiva em 2021, segundo dados fornecidos pelos serviços informáticos da ARS Centro, após consentimento ético institucional quanto a sexo, idade, ano de classificação DM2, perímetro abdominal (PA), índice de massa corporal (IMC), última avaliação de HbA1c em 2017 e em 2019 e medicamentos assinalados no programa S-Clínico de diabetes. Resultados: De 127.062 doentes com DM2, 16.012 (12,6%) estavam medicados com iSGLT2, 48,8% do sexo masculino, a idade média de 73,5±10,1 anos e o tempo desde classificação DM2 de 8,7±4,2 anos. Para HbA1C, IMC e PA entre ambos os pontos de análise mostraram-se independentes da idade e do tempo desde o diagnóstico: |rS|<0,400. Verificou-se diferença significativa entre os valores medianos de HbA1c em 2017 e 2019 no total e nos subgrupos medicados com SGLT2i, globalmente e por sexo (p<0,001). Nos não medicados com iSGLT2 não foi observada diferença significativa globalmente (p=0,983) e por sexo (M: p=0,932; F: p=0,932). O IMC em sujeitos sob iSGLT2 reduziu significativamente (p<0,001) como no grupo medicado com outros fármacos (p=0,004). O PA aumentou significativamente no grupo não iSGLT2 (p=0,001) e teve redução significativa no grupo sob SGLT2i (<0,001). Discussão: A eficácia dos iSGLT2 observada em ensaios clínicos deve ser verificada em doentes do mundo real, a efetividade. A redução da obesidade por IMC e por PA pode ser fator de futuro controlo de DM2. Conclusão: A terapêutica com iSGLT2 reduziu significativamente o IMC e o PA em comparação com o grupo controlo. O controlo da DM2 pela HbA1c neste espaço de dois anos não revelou crescimento.

Abstract Aim: To compare obesity progression and the type2 diabetes mellitus (T2DM) metabolic control between 2017 and 2019, according to sodium-glucose cotransporter type 2 inhibitors (SGLT2i) or not therapy, in the T2D population of the Central Administrative Portuguese National Health Service Authority, the ARS do Centro. Methods: Observational retrospective cohort study in 2021 of data by the informatic services of ARS do Centro, after ethics consent: gender, age, year of ICPC2 T90 classification, abdominal perimeter (AP), body mass index (BMI), last glycated haemoglobin (HbA1c) in 2017 and 2019 and drugs registered in the e.registration official program, the S-Clínico Diabetes. Results: Out of the 127,062 T2DM patients of the ARS do Centro n=16.012 (12.6%) were on SGLT2i in 2017. The mean age was 73.5±10.1 years, the time since ICPC classification was 8.7±4.2 years and 48.8% were males. HbA1C, BMI and AP values between 2017 and 2019 were independent for age and time since diagnosis, |rS| <0.400. Median HbA1c values between the two moments, in the total sample and the subgroups medicated with SGLT2i and per gender were significantly different (p<0.001) values increasing. No difference was observed in the subgroups not SGLT2i treated, either globally (p=0.983) or per gender (M: p=0.932; F: p=0.932). BMI in SGLT2i treated T2DM showed significant negative variation (p<0.001) also observed in nonSGLT2i treated ones (p=0.004). AP values significantly increased in nonSGLT2i T2DM patients (p=0.001) and significantly decreased in the SGLT2i treated ones (p<0.001). Discussion: The efficacy of SGLT2i in clinical assays and its effectiveness in real-world patients must be ascertained. Obesity decrease in BMI or AP can contribute to future T2DM analytics control. Conclusion: SGLT2i significantly decreased BMI and prevented AP increase, compared to non-SGLT2 T2DM patients. HbA1c control, in a 2-year gap, showed no decrease in growth.

Obstructive sleep apnea (OSA) is classified based on the apnea-hypopnea index (AHI). Another proposed variable for determining the severity of OSA is the total time with oxygen saturation below 90% (T90). Objective: To evaluate the concordance of the severity classification of OSA considering AHI versus T90 in Chilean population. Method: Individuals aged 15 years and older with confirmed OSA by home sleep apnea test (AHI ≥ 5 events/hour) were included. The severity of OSA according to AHI or T90 was determined using the criteria proposed by the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR). Concordance was assessed using weighted kappa statistic. Results: Among 535 cases, considering AHI, 21.3% were classified as mild, 27.9% as moderate, 23.2% as severe, and 27.7% as very severe. According to T90, the percentages were 3.9%, 33.5%, 15.1%, and 47.5%, respectively. The concordance between AHI and T90 in determining the severity of OSA was between fair and moderate (kappa = 0.41, IC 95%: 0.35 - 0.46). Conclusion: The concordance between IAH and T90 in determining the severity of OSA was between fair and moderate (kappa = 0.41, IC 95%: 0.35 - 0.46). T90 would contribute to the evaluation of the severity of obstructive sleep apnea.

Resumen La apnea obstructiva del sueño (AOS) se clasifica según el índice de apnea-hipopnea (IAH). Otra variable propuesta para determinar la gravedad de la AOS es el tiempo acumulado con saturación de oxihemoglobina bajo 90% (CT90). Objetivo: Evaluar la concordancia de la clasificación de gravedad de la AOS considerando IAH versus CT90 en población chilena. Método: Se incluyó a mayores de 15 años con AOS confirmada mediante poligrafía respiratoria (IAH ≥ 5 eventos/hora). La gravedad de la AOS según IAH o CT90 se determinó empleando la propuesta de la Sociedad Española de Neumología y Cirugía Torácica (SEPAR). La concordancia se evaluó con el estadístico kappa. Resultados: 535 pacientes con AOS, considerando el IAH: 21,3% eran leves, 27,9% moderadas, 23,2% graves y 27,7% muy graves; según CT90: 3,9%, 33,5%, 15,1% y 47,5%, respectivamente. La concordancia entre IAH y CT90 para determinar la gravedad de la AOS fue entre débil y moderada (kappa = 0,41; IC 95%: 0,35 - 0,46). Conclusión: La concordancia entre IAH y CT90 para determinar gravedad de la AOS fue entre débil y moderada (kappa = 0,41; IC 95%: 0,35 - 0,46). El CT90 contribuiría en la evaluación de gravedad de la AOS.

Resumo Objetivo: Avaliar a efetividade dos medicamentos inibidores da SGLT2 (iSGLT2) no controlo de pessoa com diabetes tipo 2 (PDM2) pelos valores de hemoglobina A1c (HbA1c), índice de massa corporal (IMC) e perímetro abdominal (PA) após cinco anos de seguimento. Métodos: Estudo observacional de coorte retrospetiva multicêntrica, de 2017 a 2022, efetuado em 2023. Analisaram-se os dados fornecidos pela Administração Regional de Saúde (ARS) do Centro de PDM2 (classificação T90 da ICPC-2) dos Agrupamentos de Centros de Saúde (ACeS) Baixo Mondego e Dão Lafões, de PMD2 escolhidas aleatoriamente e medicadas em 2017 com iSGLT2. Dados de PDM2 em 2017 e 2022, para a data mais próxima do fim do respetivo ano para HbA1c, IMC e PA. Controlo de DM2 para valores de HbA1c: ≤7% e ≤8%. Resultados: Amostra de n=264 pessoas, 59,0% (n=156) homens. Verificaram-se variações de 2017 para 2022 na HbA1c de 7,62±1,21 para 7,56±1,12 (Δ=-0,009) (p=0,951), no IMC de 31,65±8,72 para 29,90±4,56 (Δ=-0,056) (p<0,001) e no PA de 104,90±13,64 para 105,58±11,11 (Δ=+0,007) (p=0,424). Frequência de PMD2 controladas, para HbA1c ≤7% e <65 anos, de 31,1% em 2017 e de 27,1% em 2022, Δ=-12,9 (p>0,05) e para HbA1c ≤8% de 74,8% em 2017 e de 73,3% em 2022, Δ=-0,02 (p=0,002). Discussão: Comparando com valores de um estudo prévio, com seguimento a dois anos, verificaram-se reduções em HbA1c e IMC e aumento do PA, provavelmente pelo facto de a sarcopenia reduzir o IMC, que o aumento do PA não contrabalança. A prescrição de iSGLT2 não reduziu a prevalência de PMD2. Conclusão: Verificou-se efetividade dos iSGLT2 na redução da HbA1c e do IMC, ao contrário do PA e da percentagem de PMDM2 controladas pelo valor de HbA1c.

Abstract Objective: To ascertain the five-year effectiveness of SGLT2 inhibitor (iSGLT2) medicines on Type 2 Diabetes Mellitus Persons (T2DMP) on haemoglobin (HbA1c), body mass index (BMI) and abdominal perimeter (AP) values. Methods: Observational multicentric retrospective cohort study, in 2022, analysing data provided by the Regional Health Administration Authority (RHA) of Central for T2DMP (ICPC-2 - T90 classification) of Baixo Mondego and Dão Lafões, Portuguese NHS Primary Care Units clusters, medicated in 2017 with SGLT2i and re-studied in 2022, for closest date to the end of the year. Two values of HbA1c were taken as control cut-offs: ≤7% and ≤8%. Results: A sample of n=264, 59.0% (n=156) male was studied. From 2017 to 2022: HbA1c, 7.62±1.21 to 7.56±1.12 (Δ=-0.8) (p=0.951); BMI, 31.65±8.72 to 29.90±4.56 (Δ=-5.5) (p<0.001); and AP, 104.90±13.64 to 105.58± 11.11(Δ=+0.6) (p=0.424). The prevalence of controlled PMD2 under 65 years for HbA1c ≤7% in 2017 was 34.0% and in 2022 of 32.1%, Δ=-5.50; and for HbA1c ≤8% for older ones than 65 years of 74.8% in 2017 and of 743.3% in 2022, Δ=-0.02. Discussion: Comparing these values with previous ones, an improvement in HbA1c and BMI, and worsening of AP was verified, sarcopenia possibly reducing BMI not balanced by the AP increase. Conclusion: The effectiveness of iSGLT2 in the reduction of HbA1c and BMI was verified, unlike the AP and the frequency of controlled PDM2.

Resumo Introdução: A diabetes mellitus é uma das principais causas de morbimortalidade em todo o mundo. Pretende-se verificar se a pandemia COVID-19 teve repercussões no controlo metabólico e cardiovascular dos doentes com diabetes mellitus tipo 2 (DM2) da USF Garcia de Orta (GO), do ACeS Porto Ocidental. Método: Estudo observacional, transversal, analítico. A população do estudo corresponde aos utentes inscritos na USF GO com o diagnóstico de DM (código T89 e T90 da ICPC-2) na lista de problemas ativos. Depois de aplicados os critérios de inclusão e exclusão obteve-se a amostra por aleatorização simples. Foram comparados valores de hemoglobina glicada (HbA1c), colesterol-LDL, índice de massa corporal (IMC), pressão arterial sistólica (PAs) e diastólica (PAd), registados num período pré-pandémico com os de um período pandémico. Resultados: A amostra foi de 218 pacientes, com média de idades de 70,9 ±11,1 anos. Na amostra a mediana de HbA1c (6,75 vs 6,80) e do colesterol-LDL (82,80 vs 91,60) foi inferior no período pandémico. Verificando-se o oposto em relação ao IMC, com a mediana superior no período pandémico (27,03 vs 26,87). Apenas na análise do colesterol-LDL se obteve um resultado estatisticamente significativo. Na análise do controlo tensional, em média, os valores de PAs (134.06 vs 133.41) e PAd (77.97 vs 76.59) foram superiores no período pandémico face ao pré-pandémico, mas sem significado estatístico. Discussão: No estudo encontrou-se, à exceção do IMC, da PAs e da PAd, uma melhoria dos valores no período pandémico. Em relação ao impacto da pandemia nas variáveis estudadas estão descritos na literatura resultados contraditórios. Estes resultados podem refletir a qualidade das teleconsultas realizadas no período pandémico e/ou no esforço dos diabéticos por manter hábitos saudáveis. Conclusão: Não se pode afirmar que, no período avaliado, a pandemia COVID-19 teve impacto negativo no controlo metabólico e cardiovascular dos pacientes com DM2 da população estudada.

Abstract Introduction: Diabetes mellitus is one of the main causes of morbi-mortality worldwide. In this study, we aim to verify if the COVID-19 pandemic had repercussions on the metabolic and cardiovascular control of patients with type 2 diabetes at USF Garcia de Orta, from ACeS Porto-Ocidental. Methods: Cross-sectional observational analytical study. The study’s population consists of patients registered at the USF GO with the diagnosis of DM (ICPC-2 code T89 and T90) in the list of active problems. After applying inclusion and exclusion criteria, the sample was obtained by simple randomization. Glycated hemoglobin (HbA1c), LDL-cholesterol, body mass index (BMI), systolic (BP) and diastolic (DP) blood pressure values recorded in a pre-pandemic period were compared with those in a pandemic period. Results: The sample consisted of 218 patients, with a mean age of 70.9 ± 11.1 years. The median of HbA1c (6.75 vs 6.80) and LDL-cholesterol (82.80 vs 91.60) was lower in the pandemic period. The opposite was verified in relation to the BMI, with the highest median in the pandemic period (27.03 vs 26.87). Only the analysis of cholesterol-LDL obtained a statistically significant result. On average, the values of BP (134.06 vs 133.41) and DP (77.97 vs 76.59) were higher in the pandemic period compared to the pre-pandemic period, although without statistical significance. Discussion: With the exception of BMI, BP and DP, there was an improvement in the pandemic period. In the literature found, there are contradictory results on the impact of the pandemic on the variables studied. These results may reflect the quality of the teleconsultations carried out during the pandemic period and/or the effort of diabetics to maintain healthy habits. Conclusion: We cannot conclude that, in the period evaluated, the COVID-19 pandemic had a negative impact on the metabolic and cardiovascular control of patients with DM2 in our population.

Resumen Introducción: hay poca información sobre el rol de la hipoxemia como factor de riesgo de hipertensión arterial (HTA) en pacientes con apnea obstructiva del sueño. El objetivo de este estudio fue evaluar la hipoxemia como factor de riesgo independiente de HTA en un modelo de trabajo basado en pacientes reales examinados en una unidad de sueño. Métodos: estudio retrospectivo. Modelo predictivo mediante regresión logística múltiple para establecer la relación entre HTA y edad, sexo, índice de masa corporal (IMC), índice de apneas e hipopneas por hora de registro (IAH) y tiempo de saturación de oxígeno debajo de 90% (T90 > 3%). Resultados: incluimos 3854 pacientes (edad mediana 55 años), predominio varones (61.5%). Según el modelo, las variables asociadas con HTA fueron: edad (OR 3.27 - 3.29, IC95% 2.83 - 3.80, p < 0.0001), sexo masculino (OR 1.35, IC95% 1.17 - 1.56, p < 0.001), obesidad (OR 1.83, IC95% 1.59 - 2.11, p < 0.0001), IAH > 15 eventos por hora (OR 1.22, IC95% 1.05 - 1.43, p < 0.01) y T90 > 3% (OR 1.56 - 1.57, IC95% 1.32 - 1.84, p < 0.0001). Conclusiones: en una población clínica con sospecha de apnea obstructiva del sueño, la hipoxemia (T90 > 3%) se asoció con hipertensión arterial.

Abstract Introduction: there is limited information about the role of hypoxemia degree as a risk factor for hypertension (HTN) in patients with obstructive sleep apnea (OSA). The ob-jective of this study is to assess hypoxemia as an independent risk factor for HTN in a work model based on real-life patients examined at sleep unit. Methods: this retrospec-tive study consisted of a predictive model using multiple logistic regression to establish the relationship between HTN and age, sex, body mass index (BMI), apnea/hypopnea index (AHI) and time below SO2 < 90% (T90 > 3%). Results: we included 3.854 patients (median age: 55 years), mostly men (61.5%). According to the model, the variables that were significantly associated with HTN were: age (OR: 3.27- 3.29, CI95% 2.83 - 3.80, p < 0.0001), male sex (OR 1.35, CI95% 1.17 - 1.56, p < 0.001), Obesity (OR 1.83, CI95% 1.59 - 2.11, p < 0.0001), AHI > 15 events per hour (OR 1.22, CI95% 1.05 - 1.43, p < 0.01) and T90 > 3% (OR 1.56 - 1.57, CI95% 1.32 - 1.84, p < 0.0001). Conclusión: in a clinical population of subjects suspected of OSA, nocturnal hypoxemia measure as T90 > 3% was associated with HTN.

RESUMEN SARS-CoV-2 está presente en fluidos corporales de individuos con infecciones sintomáticas y asintomáticas, estos fluidos se depositan en frecuentemente en aguas residuales, por lo tanto, la vigilancia del RNA de SARS-CoV-2 presente en estas matrices acuáticas es una herramienta prometedora como una señal de alerta temprana para detectar futuras pandemias. En la actualidad se sabe que el material genético del virus puede sobrevivir por varios días en agua residual, sin embargo, se necesita generar más información para entender mejor la cinética de la carga viral en matrices acuáticas a través del tiempo. El objetivo de este trabajo fue determinar la cinética de detección de RNA de SARS-CoV-2 a través del tiempo en diferentes matrices acuáticas. Cada una de las matrices acuáticas (Marina, influente, efluente y potable) fue inoculada y evaluada por 62 días para determinar la cinética de decaimiento en la detección de RNA viral por RT-PCR en tiempo real. El RNA de SARS-CoV-2 fue detectado durante la duración del experimento en todas las matrices. El agua de efluente, influente y marina dificultaron la detección de SARS-CoV-2 conforme avanzaba el tiempo con una vida media de 15.24, 43.24, y 32.38 días y T90 de 50.63, 143.64 y 107.54 días, respectivamente. Por otra parte, en el agua potable, la detección fue constante a lo largo del experimento. Este estudio demuestra el impacto de la matriz acuática en la detección de la carga viral probablemente afectada por los parámetros fisicoquímicos, de igual forma, es interesante entender que el SARS-CoV-2 puede detectarse por un largo periodo de tiempo en aguas recreativas y residuales, lo que lo vuelve una herramienta relevante para realizar epidemiología basada en agua como un indicador de la salud de la comunidad.

ABSTRACT SARS-CoV-2 is present in corporal fluids of individuals with symptomatic or asymptomatic infections, these fluids are deposited on different water matrices, including drainage water; therefore, wastewater surveillance of RNA of SARS-CoV-2 has emerged as a promising tool as an early warning of potential outbreaks. It is known that the viral genetic material is present in wastewater for several days. However, more data on SARS-CoV-2 is needed to better understand the viral load kinetics in raw water matrices. This work aimed to assess the viral load decay of SARS-CoV-2 RNA in different raw aquatic matrices to evaluate the RNA stability through time. Each water matrix (seawater, influent wastewater, effluent wastewater, and tap water) was inoculated and evaluated for 62 days to determine the viral load kinetic decay by RT-PCR in real-time. SARS-CoV-2 RNA was detected in all water matrices during the experiment. Effluent, influent, and seawater water matrices harsh conditions constraint SARS-CoV-2 RNA detection, with a half-life of 15.24, 43.24, and 32.38 days, and T90 values of 50.63, 143.64, and 107.54 days respectively. Meanwhile, in tap water, the viral genetic material remained for the longest time without significant changes. This study successfully demonstrates that the viral load is affected by the physicochemical characteristics of the water matrix yet confirms that the surveillance of recreational waters and wastewater for SARS-CoV-2 can be a valuable tool for WBE (Wastewater-based epidemiology) as a leading indicator of changes in COVID-19 burden in a community.

RESUMEN Objetivo : Determinar la variación de la calidad de vida en pacientes con Síndrome de Apnea Hipopnea Obstructiva del Sueño leve moderado, luego del tratamiento con Dispositivo de Avance Mandibular a una altitud de 3259 msnm. Métodos : Estudio prospectivo, cuasi-experimental. Se incluyeron sujetos con índice de Disturbio Respiratorio (IDR) entre 5 y 30 /hora (medido con poligrafía respiratoria), sin tratamientos previos, que presentaban condiciones para el uso del DAM. Se valoró calidad de vida con el FOSQ (Functional Outcomes Sleep Questionnaire) antes y después de 45 días de tratamiento con DAM. Resultados: 26 completaron el estudio (20 varones). La media (DE) de edad fue: 43 (9.6) años, IMC: 29 (8.6) kg/m2 e IDR: 19 (7.6) /h. Luego de 45 días, se observaron cambios significativos, en el FOSQ (total, dimensiones de productividad general, producción social, nivel de actividad, vigilia y relaciones íntimas/actividad sexual) p <0.001. La media del IDR descendió de 19 (7.6) a 7 (3.8) (p <0.001), la desaturación mínima de O2 incrementó de 77 % (5.2) a 83 % (3.9) (p <0.001), el T90 descendió de 73 % (15.4) a 31 % (16.6) (p <0.001) y el Epworth disminuyó de 11.2 (4.6) a 6.4 (3.5) (p <0.001). Conclusiones : En pacientes con SAHOS leve moderado el tratamiento con DAM produce mejoría significativa en su calidad de vida, reduce nivel de enfermedad expresado en descenso del IDR, mejora el nivel oxigenación y reduce la somnolencia diurna expresado en disminución del puntaje Epworth.

ABSTRACT Objective: To determine the variation of the Quality of Life in patients with mild to moderate Obstructive Sleep Apnea Hypopnea Syndrome, after treatment with the Mandibular Advancement Device at an altitude of 3259 masl. Methods: Prospective, quasi-experimental study. Subjects with respiratory disturbance index (RDI) between 5 and 30 / hour (measured with respiratory polygraphy), without previous treatments, with conditions for the use of MAD were included. The quality of life was assessed with the FOSQ (questionnaire of functional sleep results) before and after 45 days of treatment with MAD. Results: 26 completed the study (20 males). The mean (SD) of the age was 43 (9.6) years, BMI was 29 (8.6) kg / m2, and the RDI was 19 (7.6) / hour. After 45 day, significant changes were observed, with respect to the baseline values, in the FOSQ score (total calculation, general productivity, social outcome, activity level, vigilance and intimate relationships/sexual activity, p <0.001). The mean RDI decreased from 19 (7.6) to 7 (3.8) (p <0.001), the minimum desaturation of O2 increased from 77 (5.2) to 83 (3.9) (p <0.001), the T90 decreased from 73 (15.4) to 31 (16.6) (p <0.001) y Epworth's score decreased from 11.2 (4.6) to 6.4 (3.5) (p <0.001). Conclusions : In patients with mild-moderate OSA, treatment with MAD produces significant improvement in their quality of life, reduces the level of disease expressed in decreased RDI, improves oxygenation level and reduces daytime sleepiness expressed in decreased Epworth score.

Abstract The objective of the present study was to develop time delayed chronotherapeutic formulation of Eplerenone (Ep) to provide rapid drug release after a pre-determined lag time for the treatment of early morning hypertension. Cyclodextrin complexation was used to prepare fast release Ep core tablets. The developed core tablets were then coated with different rate-controlling polymers using compression coating technique. The developed tablets were evaluated for hardness, friability, drug content and swelling index. The in-vitro drug release was carried out to study the effect of different coating materials on drug release and lag time. Tablets selected for stability study were those showing lag time of 5-7 hours followed by complete drug release; F2, F3, F7, F8, and F12. The in-vivo study was carried out on tablets with the highest t90 as compared to commercial tablets after being administered to healthy human volunteers where plasma Ep and urinary Na/K ratio were determined. Results suggested that this approach was able to provide delayed release Ep formulations that will be useful for patients with morning surge in blood pressure.

RESUMO O objetivo deste trabalho foi avaliar a recuperação de espermatozoides epididimários de cães castrados, utilizando as técnicas de fluxo retrógrado (FR) e flutuação (FL) em diluidor Tris-gema, antes e após a criopreservação. Foram coletados 30 complexos testículo-epididímos (CTE), sendo 15 para FR e 15 para FL, e, logo após a recuperação dos espermatozoides, foram analisadas as alterações morfológicas nessas células espermáticas. Após a adição do diluidor, foram avaliados os parâmetros de motilidade total (MOT) e vigor (V) espermáticos. O sêmen pós-criopreservado foi submetido ao teste de termorresistência nos tempos T0, T30, T60 e T90 minutos, além da avaliação das membranas plasmática e acrossomal por sondas fluorescentes. Não houve diferença estatística entre as técnicas quanto à MOT e ao vigor no sêmen diluído (FR-MOT: 82,3% e V: 3,4; FL-MOT: 79,6% e V: 3,2) e pós-criopreservado (FR-MOT: 34% e V: 2,8; FL-MOT: 30% e V: 2,7). A partir do T30, houve diferença significativa quanto à MOT e ao vigor nas técnicas utilizadas, e o tempo também prejudicou o acrossoma espermático a partir do T30. Conclui-se que as técnicas de recuperação de espermatozoides epididimários de cães castrados, testadas neste trabalho, podem ser utilizadas para refrigeração e criopreservação de sêmen.

ABSTRACT The objective of this work was to evaluate the recovery of epididymal spermatozoa from castrated dogs using retrograde flow (FL) and flotation (FL) techniques in Tris-egg yolk diluent, before and after cryopreservation. Thirty testicle-epididymal complexes (CTE) were collected, 15 for FR and 15 for FL and soon after spermatozoid recovery, morphological changes in these spermatic cells were analyzed. After addition of the diluent, the parameters of total motility (MOT) and vigor (V) were evaluated. The post-cryopreserved semen was submitted to thermoresistance (TTR) test at T0, T30, T60 and T90 minutes, as well as the plasma and acrosomal membrane evaluation by fluorescent probes. There was no statistically significant difference between techniques tested for MOT and vigor in the diluted semen (FR-MOT: 82.3% and V: 3.4, FL-MOT: 79.6% and V: 3.2) and post-cryopreserved (FR-MOT: 34% and V: 2.8, FL-MOT: 30% and V: 2.7). From the T30 there was a significant difference regarding MOT and vigor in the used techniques, and the time also damaged the spermatic acrosome from the T30. It is concluded that the epididymal spermatozoa recovering techniques from castrated dogs, tested in this study, can be used for semen refrigeration and cryopreservation.

Abstract Background: Adaptive immune cells, including CD4+CD69+ and CD4+CD25+FoxP3+ regulatory T (Treg) cells, are important for maintaining immunological tolerance. In human systemic lupus erythematosus (SLE), CD4+CD25+FoxP3+ Treg cells are reduced, whereas CD69 expression is increased, resulting in a homeostatic immune imbalance that may intensify autoreactive T cell activity. To analyze the mechanisms implicated in autotolerance failure, we evaluated CD4+CD69+ and CD4+CD25+FoxP3+ T cells and interleukin profiles in a pristane-induced SLE experimental model. Methods: For lupus induction, 26 female Balb/c mice received a single intraperitoneal 0.5 ml dose of pristane, and 16 mice received the same dose of saline. Blood and spleen samples were collected from euthanized mice 90 and 120 days after pristane or saline inoculation. Mononuclear cells from peripheral blood (PBMC), peritoneal lavage (PL) and splenocytes were obtained by erythrocyte lysis and cryopreserved for further evaluation by flow cytometry using the GuavaEasyCyte TM HT. After thawing, cells were washed and stained with monoclonal antibodies against CD3, CD4, CD8, CD25, CD28, CD69, FoxP3, CD14 and Ly6C (BD Pharmingen TM). Interleukins were quantified using Multiplex® MAP. The Mann-Whitney test and the Pearson coefficient were used for statistical analysis, and p < 0.05 considered significant. Results: Compared with the controls, SLE-induced animals presented increased numbers of CD4+CD69+ T cells in the blood on T90 and T120 (p = 0.022 and p = 0.008) and in the spleen on T120 (p = 0.049), but there were decreased numbers in the PL (p = 0.049) on T120. The percentage of Treg was lower in blood (p < 0.005 and p < 0.012) on T90 and T120, in spleen (p = 0.043) on T120 and in PL (p = 0.001) on T90. Increased numbers of CD4+ CD69+ T cells in the PL were positively associated with high IL-2 (p = 0.486) and IFN-γ (p = 0.017) levels, whereas reduced Treg cells in the blood were negatively correlated with TNFα levels (p = 0.043) and positively correlated with TGFβ1 (p = 0.038). Conclusion: Increased numbers of CD4+CD69+ T cells and reduced numbers of CD4+CD25+FoxP3+ Treg cells with an altered interleukin profile suggests loss of autotolerance in pristane-induced lupus mice, which is similar to human lupus. Therefore, this model is useful in evaluating mechanisms of cellular activation, peripheral tolerance and homeostatic immune imbalance involved in human SLE.

A oclusão do ponto lacrimal inferior limita a drenagem da lágrima, mantendo-a sobre a superfície ocular, prolonga a lubrificação e minimiza a posologia de lubrificantes. Objetivou-se, com este estudo, avaliar a efetividade dos adesivos n-butil-cianoacrilato e 2-octil-cianocacrilato, na oclusão do ponto e canalículo lacrimais inferiores de cães e suas repercussões clínicas durante 180 dias. Para tanto, utilizaram-se 11 cães distribuídos em dois grupos: oclusão com n-butil-cianoacrilato (GB, n=6) e com 2-octil-cianoacrilato (GO; n=5). A produção lacrimal foi avaliada previamente ao procedimento e, posteriormente, aos 3, 7, 15, 30, 45, 60, 90, 120, 150 e 180 dias, assim como blefarospasmo, secreção ocular, epífora e hiperemia conjuntival. A produção lacrimal de GB diferiu significativamente de seu controle no momento T90 (P=0,0282). Entre momentos, T7 (p=0,0069) e T180 (P=0,0207), diferiram de T0. Em GO, comparando-se tratamento e controle, T15 (P<0,001) diferiu-se estatisticamente dos demais. Ao se compararem os momentos, verificou-se que T15 diferiu significativamente de T0 (P= 0,0044), T3 (P= 0,0234), T60 (P= 0,0207) e T 90 (P= 0,0482). Não foi observada diferença entre os tratamentos ao longo do tempo. Concluiu-se que ambos os adesivos foram efetivos para a oclusão da drenagem lacrimal por longo período, sendo uma opção factível para animais com deficiência do filme lacrimal

The occlusion of the inferior lacrimal punctum limits tear drainage and thus keeps it over the ocular surface, prolongs lubrication and minimizes the need of ocular lubricants. The aim of this study was to evaluate the effectiveness of n-butyl-cyanoacrylate and 2-octyl-cyanoacrylate adhesives in the occlusion of the inferior lacrimal punctum and canaliculi of dogs and their clinical repercussions over 180 days. Eleven dogs, were divided into two groups: occlusion with n-butyl-cyanoacrylate (GB, n=6) and with 2-octyl-cyanoacrylate (GO, n=5). Tear production, blepharospasm, ocular discharge, epiphora and conjunctival hyperemia were analyzed before the procedure and on days (T) 3,7,15, 30, 45, 60, 90, 120, 150 and 180 after the procedure. Tear production of GB was significantly higher at T90 (P=0.0282) than its control. Variations between days showed that T7 (P=0.0069) and T180 (P=0.0207) varied significantly from T0. In the GO group, when treatment was compared to control, T15 (P<0.001) was significantly different from the rest. Variations between days showed that T15 was significantly different than T0 (P=0.0044), T3 (P=0.0234), T60 (P=0.0207) and T90 (P=0.0482). No significant difference was observed between the treatment groups at any given time. It was concluded that both adhesives were effective in occluding lacrimal drainage for long periods and could thus be considered as therapeutic options in treating animals with lacrimal deficiency

Experiência: Objetivamos investigar os efeitos de metoclopramida e ondansetrona no bloqueio neuromuscular por mivacúrio. Métodos: Foram incluídos no estudo 75 pacientes ASA I-II, com idades entre 18 e 65 anos e agendados para cirurgia eletiva necessitando de intubação traqueal. Os pacientes receberam metoclopramida 10 mg, ondansetrona 4 mg ou salina normal 5 mL; grupo M, grupo O e grupo SN (n = 25) respectivamente. Antes da anestesia, os medicamentos em estudo foram administrados em um volume de 5 mL. O nível de colinesterase plasmática foram obtidos antes e 5 minutos depois da administração dos medicamentos em estudo e 5 minutos depois da administração de mivacúrio. Os tempos até o início e os níveis T25, T75, T25-75 e T90 foram comparados entre si, tendo sido investigadas as diferenças entre cada paciente. Depois de registrar T90, o estudo foi terminado, tendo início a cirurgia. Resultados: O tempo até o início foi significativamente mais breve no Grupo M versus os outros dois grupos. O tempo até o início no Grupo O foi significativamente mais breve versus grupo SN. No grupo M, T25, T75, T90 e os índices de recuperação foram significativamente maiores versus Grupo NS (p < 0,001). No Grupo O, T25 e T75 foram maiores versus Grupo NS (p < 0,01 e p < 0,05,respectivamente). No Grupo M, T75, T90 e índices de retorno da anestesia foram significativamente maiores versus Grupo O (p < 0,001, p < 0,01, p < 0,001, respectivamente). Nos Grupos M e O, os níveis plasmáticos de colinesterase diminuíram significativamente (p < 0,001). Depois da administração dos medicamentos em estudo e de mivacúrio. Houve também redução na colinesterase plasmática no Grupo NS 5 minutos após a administração de mivacúrio (p < 0,001). Conclusão: Consideramos que ondansetrona seja agente mais confiável do que metoclopramida, quando utilizada com mivacúrio.

Background: We aimed to investigate the effects of metoclopramide and ondansetrone on mivacurium neuromuscular blockade. Methods: Seventy five, ASA I-II patients, aged 18-65 and scheduled for elective surgery requiring tracheal intubation were included in the study. The patients received metoclopramide 10 mg, ondansetrone 4 mg or normal saline 5 mL; group M, group O, group NS (n = 25), respectively. Before anesthesia study drugs were administered in a volume of 5 mL. The level of plasma cholinesterase were obtained before and 5 minutes after the administration of study drugs and5 minutes after the administration of mivacurium. Onset time, T25, T75, T25-75, T90 levelswere compared with each other and differences between each patients were investigated. After recording T90, the study was terminated and surgery was started. Results: Onset time was significantly shorter in group M, than the other two groups. Onset time in group O was significantly shorter than in group NS. In Group M T25, T75, T90 and recovery indices were significantly greater than in Group NS (p < 0.001). In Group O T25, T75 were greater than Group NS (p < 0.01 and p < 0.05, respectively). In Group M T75, T90 and emergence indices were significantly higher than Group O (p < 0.001, p < 0.01, p < 0.001, respectively). In Groups M and O, plasma cholinesterase levels decreased significantly (p < 0.001) after administration of study drugs and mivacurium. Plasma cholinesterase also was reduced in Group NS 5 minutes after the administration of mivacurium (p < 0.001). Conclusion: Ondansetrone is believed to be more reliable agent than metoclopramide when used with mivacurium.

Objetivo: Evaluar la relación entre el Síndrome de Apneas-Hipopneas del Sueño (SAHS) e hipertensión arterial (HTA). Material y métodos: Estudio en población clínica de 367 pacientes con sospecha de trastornos respiratorios del sueño. Se realizó historia clínica completa y polisomnografía (PSG) o poligrafía respiratoria (PR). Fueron excluidos 85 pacientes. Se implementaron medidas de resumen, análisis de diferencia de medias, relación entre variables y análisis de regresión logística univariada y multivariada. Resultados: Edad 49,6 ± 12,7 [18-90) años, 247 pacientes (84%) varones, Índice de Masa Corporal (IMC) 29,6 ± 4,7 (20,1-47,6) kg/m2. La tasa de HTA en esta población fue 67%. Se realizaron 229 PSGs (78%) y 65 PRs (22%). Los resultados fueron: índice apnea-hipopnea (IAH) 34,8 ± 27,4 (0-125), desaturación máxima (DesatMax) 81,5 ± 9,5 (38-95) % y porcentaje del tiempo total del estudio con SatO2 < 90% (T90) 8,8 ± 15,2 (0-72) %. Diagnósticos principales: 253 (86%) SAHS, 34 (12%) ronquido primario y 7 (2%) sin trastorno respiratorio del sueño. De los pacientes con SAHS, 45 (18%) fueron de grado leve (IAH de 5 a <15), 57 (22%) moderado (IAH de 15 a <30) y 151 (60%) severo (IAH ≥ 30). Realizamos un modelo de regresión logística univariada de algunas variables del SAHS en relación a HTA. Al analizar el IAH se obtuvo OR 1,029 (IC95% 1,017-1,041 p<0,001), con DesatMax OR 1,072 (IC95% 1,037-1,109 p<0,001) y con T90 OR 1,062 (IC95% 1,029-1,095 p<0,001). Al introducir al modelo la edad, género e IMC el OR ajustado del IAH fue 1,205 (IC95% 1,064 - 1,363 p=0,003), DesatMax 1,693 (IC95% 1,208 - 2,374 p=0,002) y T90 1,517 (IC95% 1,163 - 1,979 p=0,002). Conclusiones: El SAHS esta asociado a la hipertensión arterial independientemente de la edad, género e IMC. Se requiere realizar estudios con mayor tamaño muestral para evaluar el efecto de otras variables en esta asociación. (Rev Med Hered 2009;20:123-132).

Objective: To evaluate the relation between Obstructive Sleep Apnea (OSA) and hypertension (HP). Material and methods: Clinical population-based study in 367 patients with suspected breathing sleep disorder. A complete clinical history and polysomnography (PSG) or respiratory polygraphy (RP) were done. Eighty-five patients were excluded. We did summary measures, median difference analysis, relations between variables, univariate and multivariate logistic regression. Results: Age 49.6 ± 12.7 (18-90) years, 247 patients (84%) males, body mass index (BMI) 29.6 ± 4.7 (20.1-47.6) kg/m2. HP rate was 67%. We made 229 (78%) PSGs and 65 (22%) RPs. Apnea-Hipopnea Index (AHI) 34.8 ± 27.4 (0-125), Maximum Oxygen Desaturation (MaxDesat) 81.5 ± 9.5 (38-95) % and percentage of registry time with SatO2 below 90% (T90) 8.8 ± 15.2 (0-72) %. The main diagnoses were: OSA 253 (86%), primary snoring 34 (12%) and without breathing sleep disorder 7 (2%). From OSA patients, 45 (18%) were mild (AHI 5 to <15), 57 (22%) moderate (AHI 15 to <30) and 151 (60%) severe. We did a univariate logistic regression model of some OSA variables in relation to HP. When analyzing AHI we obtained OR 1.029 (CI 95% 1.017-1.041 p<0.001), with MaxDesat OR 1.072 (CI 95% 1.037-1.109 p<0.001) and T90 OR 1.062 (CI 95% 1.029-1.095 p<0.001). When we introduced to the model age, sex and BMI; the AHI adjusted OR was 1.205 (CI95% 1.064 - 1.363 p=0.003), DesatMax adjusted OR 1.693 (CI95% 1.208 - 2.374 p=0.002) and T90 adjusted OR 1.517 (CI95% 1.163 - 1.979 p=0.002). Conclusions: We concluded that OSA is associated to HP independently of age, sex and BMI. It is required to make studies with greater sample to evaluate the effect of other variables in this association. (Rev Med Hered 2009;20:123-132).

O objetivo deste estudo foi comparar os efeitos da expansão volêmica produzida pelo hidroxietilamido 130/0,4 (HES 130/0,4) ou pelo sangue em gatas com hipovolemia induzida. Foram utilizadas 12 gatas adultas, sem raça definida (SRD), com peso médio de 2,85±0,28kg e hígidas. Os animais foram induzidos à anestesia geral com isofluorano a 5V%, intubados e conectados a um sistema sem reinalação de gases. Após a instrumentação, os animais foram mantidos sob anestesia com isoflurano em 1,3V% e mantidos em ventilação mecânica, ciclada a pressão. Em seguida, foi induzida a hipovolemia por meio da retirada de 30ml kg-1 de sangue da artéria femoral. Após 60 minutos da estabilização do paciente, os tratamentos foram iniciados. No grupo hidroxietilamido (GH, n=06), os animais receberam, como reposição volêmica, o hidroxietilamido 130/0,4 no mesmo volume de sangue retirado e, no grupo sangue (GS, n=06), os animais receberam o próprio sangue retirado, sendo considerado grupo controle. A pressão arterial sistólica, a diastólica e a média e a pressão venosa central aumentaram após a reposição volêmica em ambos os grupos. Observou-se, para o GH, aumento da PaCO2 no T15, no T30 e no T60. Houve redução do pH no T30 e no T45 e de íons Na+ no T90 para GH. A restauração das pressões arteriais com a administração de HES 130/0,4 foi similar ao grupo controle. A reposição volêmica com HES 130/0,4 produz aumento acentuado da PVC; e o uso do HES 130/0,4 em gatas submetidas à hipovolemia não produziu alterações clinicamente significativas no equilíbrio ácido-básico.

The aim of this study was to compare the volemic expansion effects produced by hydroxyethyl starch 130/0.4 (HES 130/0.4) or blood, in female cats with induced hypovolemia. Twelve healthy adult female cats, crossbreed and weighing an average of 2.85±0.28kg were used. They were induced into general anesthesia with isofluorane at 5V%, intubated and connected to a non-rebreathing system. After instrumentation, the animals were maintained under anesthesia with isofluorane at 1.3V% and maintained on pressure cycled mechanic ventilation. Afterwards, hypovolemia was induced by withdrawal of 30ml kg-1 of blood from the femoral artery. After 60 minutes of stabilization of the patient, the treatments were initiated. In the hydroxyethyl starch group (GH, n=06) the animals received hydroxyethyl starch 130/0.4 as volemic expansion at the same volume of blood withdrawed, in the blood group (GS, n=06) the animals received their own withdrawed blood, being considered the control group. The systolic, diastolic and mean arterial pressures and central venous pressure increased after volemic expansion in both groups. An increase of PaCO2 at T15, T30 and T60 in GH was observed. In addition, there was reduction of pH at T30 and T45 and Na+ ions at T90 in GH. The arterial pressure restoration with the use of HES 130/0.4 was similar to the control group; the volemic expansion with HES 130/0,4 produces accentuated increase of CVP; the use of HES 130/0,4 in female cats submitted to hypovolemia did not produce clinically significant alterations in acid-base equilibrium.

In this work an HPLC stability-indicating method was developed and applied to study the hydrolytic behavior of pravastatin in different pHs and temperatures. From the system suitability test, the selected chromatographic conditions were a C-18 column, acetonitrile-30 mmol L-1 phosphate buffer solution pH 2 (28:72) as mobile phase, 40°C temperature column, a flux of 1 mL/min and 239 nm as wavelength detection. The developed method exhibited an adequate repeatability and reproducibility (CV 0.11% and 0.49%, respectively) and a recovery higher than 98%. Furthermore, the detection and quantitation limits were 3.4x10-7mol L-1 and 3.7xl0-6mol L-1. The kinetic degradation of pravastatin fits to a pseudo-first order kinetic. The degradation was pH-dependent: alkaline pH < acid pH and the generation of degradation products was dependent of the media tested (one product in alkaline medium and 4 products in acid medium). Activation energy, kinetic rate constants at different temperatures, t1/2 and t90 values are also reported.