Eficácia da ivermectina e atazanavir no tempo de recuperação dos sintomas de covid-19: uma coorte prospectiva / Effectiveness of ivermectin and atazanavir on time to resolution from covid-19 symptoms: a prospective cohort / Eficacia de ivermectina y atazanavir en el tiempo hasta lá resolución de los síntomas de covid-19: una cohorte prospectiva

Objetivo: avaliar a eficácia da Ivermectina e do Atazanavir em comparação com placebo no tempo de resolução dos sintomas e no tempo de duração da doença por COVID-19. Método: estudo observacional, de coorte prospectivo, longitudinal, descritivo e analítico com pacientes sintomáticos ambulatoriais, acompanhados por 06 meses em duas Unidades Básicas de Saúde para atendimento de COVID-19 em Teresina- Piauí, Brasil, no período de novembro a abril de 2021 identificados por amostragem aleatória 1:1:1. Foram realizados exames Reverse transcription polymerase chain reaction (RT-PCR) para confirmação laboratorial da suspeita de infecção pelo novo coronavírus e avaliação sociodemográfica e clínica. Resultados: dos 87 pacientes randomizados, 62,1% (n=54) eram do sexo masculino, com média de idade de 35,1 anos, possuíam companheira (53,9%), baixa renda (50,6%), eutróficos (40,7%) e sem comorbidades de saúde (78,2%). Não houve diferença entre o tempo médio para resolução dos sintomas, que foi de 21 dias (IQR, 8-30) no grupo atazanavir, 30 dias (IQR, 5-90) no grupo ivermectina em comparação com 14 dias (IQR, 9-21) no grupo controle. No dia 180, houve resolução dos sintomas em 100% no grupo placebo, 93,9% no grupo atazanavir e 95% no grupo ivermectina. A duração mediana da doença foi de 08 dias em todos os braços do estudo. Conclusão: o tratamento com atazanavir (6 dias) e ivermectina (3 dias) não reduziu o tempo de resolução dos sintomas e nem o tempo de duração da doença entre os pacientes ambulatoriais com COVID-19 leve em comparação com o grupo placebo. Os resultados não suportam o uso de ivermectina e atazanavir para tratamento de COVID-19 leve a moderado.

Objective: to evaluate the effectiveness of Ivermectin and Atazanavir compared to placebo in the time to resolution of symptoms and duration of illness due to COVID-19. Method: observational, prospective, longitudinal, descriptive and analytical cohort study with symptomatic outpatients, followed for 06 months in two Basic Health Units for COVID-19 care in Teresina-Piauí, Brazil, from November to April 2021 identified by 1:1:1 random sampling. Reverse transcription polymerase chain reaction (RT-PCR) tests were performed for laboratory confirmation of suspected infection with the new coronavirus and sociodemographic and clinical evaluation. Results: of the 87 randomized patients, 62.1% (n=54) were male, with a mean age of 35.1 years, had a partner (53.9%), low income (50.6%), eutrophic (40.7%) and without health comorbidities (78.2%). There was no difference between the median time to resolution of symptoms, which was 21 days (IQR, 8-30) in the atazanavir group, 30 days (IQR, 5- 90) in the ivermectin group compared with 14 days (IQR, 9- 21) in the control group. At day 180, there was resolution of symptoms in 100% in the placebo group, 93.9% in the atazanavir group, and 95% in the ivermectin group. The median duration of illness was 8 days in all study arms. Conclusion: Treatment with atazanavir (6 days) and ivermectin (3 days) did not reduce the time to symptom resolution or the duration of illness among outpatients with mild COVID-19 compared to the placebo group. The results do not support the use of ivermectin and atazanavir for the treatment of mild to moderate COVID-19.

Objetivo: evaluar la efectividad de Ivermectina y Atazanavir en comparación con placebo en el tiempo de resolución de los síntomas y duración de la enfermedad por COVID-19. Método: estudio de cohorte observacional, prospectivo, longitudinal, descriptivo y analítico con pacientes ambulatorios sintomáticos, seguidos durante 06 meses en dos Unidades Básicas de Salud para atención de COVID-19 en Teresina-Piauí, Brasil, de noviembre a abril de 2021 identificados por 1:1:1 muestreo aleatorio. Se realizaron pruebas de reacción en cadena de la polimerasa con transcriptasa inversa (RT-PCR) para confirmación de laboratorio de sospecha de infección por el nuevo coronavirus y evaluación sociodemográfica y clínica. Resultados: de los 87 pacientes aleatorizados, 62,1% (n=54) eran del sexo masculino, con una edad media de 35,1 años, tenían pareja (53,9%), bajos ingresos (50,6%), eutróficos (40,7%) y sin comorbilidades de salud (78,2%). No hubo diferencia entre la mediana de tiempo hasta la resolución de los síntomas, que fue de 21 días (RIC, 8-30) en el grupo de atazanavir, 30 días (RIC, 5- 90) en el grupo de ivermectina en comparación con 14 días (RIC, 9 - 21) en el grupo control. En el día 180, hubo una resolución de los síntomas del 100 % en el grupo de placebo, del 93,9 % en el grupo de atazanavir y del 95 % en el grupo de ivermectina. La mediana de duración de la enfermedad fue de 8 días en todos los brazos del estudio. Conclusión: El tratamiento con atazanavir (6 días) e ivermectina (3 días) no redujo el tiempo de resolución de los síntomas ni la duración de la enfermedad entre los pacientes ambulatorios con COVID-19 leve en comparación con el grupo placebo. Los resultados no respaldan el uso de ivermectina y atazanavir para el tratamiento de la COVID-19 de leve a moderada.

Perfil clínico-epidemiológico e desfecho de pessoas idosas hospitalizadas por COVID-19 / Clinical-epidemiological profile and outcome of old people hospitalized for COVID-19

Objetivo: Descrever o perfil clínico-epidemiológico e desfecho de pessoas idosas hospitalizados por COVID-19 no Hospital Universitário do Piauí. Métodos: Realizou-se um estudo observacional, transversal, realizado com dados secundários envolvendo 137 prontuários de pacientes idosos internados por COVID-19 no HU durante o período de abril a dezembro de 2020. Os dados foram coletados nos meses de agosto e setembro de 2021. Utilizou-se um formulário formado por questões equivalentes aos dados sociodemográficos e epidemiológicos dos pacientes idosos. Os dados foram analisados utilizando o Software estatístico SPSS versão 25. Resultados Observou-se que o "uso de ventilação mecânica" (Odds Ratio: 35,96 [10,23-126,47]) e "tipo de leito de internação" (Odds Ratio: 9,40 [2,69-32,82]) foram as variáveis que melhor explicam os óbitos sendo preditoras independentes para esse desfecho. Houve associação estatisticamente significativa entre a quantidade de comorbidades (p=0,007), a presença de manifestações clínicas (p=0,003), a quantidade de manifestações clínicas (p=0,003) e óbito. O menor tempo de sobrevida foi associado à internação em UTI e uso de ventilação mecânica (p=0,000). Conclusão: Os resultados do estudo evidenciam que a presença de fatores de risco para a COVID-19, manifestações clínicas da doença, estavam internados em leitos de UTI, em uso de VM e os que apresentavam idade superior tiveram piores desfechos. Descritores: Perfil de saúde; Saúde do idoso; Coronavirus. COVID-19.

Objective: To describe the clinical-epidemiological profile and outcome of old people hospitalized for COVID-19 at the University Hospital of Piauí. Methods:An observational, cross-sectional study was carried out with secondary data involving 137 medical records of old patients hospitalized for COVID-19 in the UH during the period from April to December 2020. Data were collected in August and September 2021. Aform consisting of questions equivalent to the sociodemographic and epidemiological data of old patients was used. Data were analyzed using SPSS statistical software version 25. Results: It was observed that the "use of mechanical ventilation" (Odds Ratio: 35.96 [10.23-126.47]) and "type of hospitalization bed" (Odds Ratio: 9.40 [2.69-32.82]) were the variables that best explain the deaths being independent predictors for this outcome. There was a statistically significant association between the number of comorbidities (p=0.007), the presence of clinical manifestations (p=0.003), the number of clinical manifestations (p=0.003) and death. The shorter survival time was associated with ICU admission and use of mechanical ventilation (p=0.000). Conclusion: The results of the study show that the presence of risk factors for COVID-19, clinical manifestations of the disease, to be admitted to ICU beds, using MV and those who were older had worse outcomes. Descriptors: Health profile; Health of old people; Coronavirus. COVID-19.

Relationship Between Zinc, Selenium, and Magnesium Status and Markers of Metabolically Healthy and Unhealthy Obesity Phenotypes.

Our objective was to investigate the relationship between zinc, selenium, and magnesium status and markers of metabolically healthy and unhealthy obesity phenotypes. This was a cross-sectional study with 140 women: metabolically healthy obese women (n = 35), metabolically unhealthy obese women (n = 28), and normal-weight women (n = 77). We have calculated the body mass index, waist-hip ratio, waist-height ratio and some adiposity indices. Additionally, we evaluated endocrine-metabolic parameters and estimated the dietary intake of energy, macronutrients, zinc, selenium, and magnesium. The mineral concentrations in plasma, erythrocytes, and urine were assessed. In obese patients, there was a significant decrease in dietary zinc, selenium, and magnesium intake per kilogram of body weight, as well as lower mineral concentrations in both plasma and erythrocytes. Additionally, these patients exhibited higher urinary mineral levels compared to the control group, regardless of whether they had healthy or unhealthy phenotypes. We observed a significant correlation between deficiencies in zinc, selenium, and magnesium and obesity-associated metabolic disorders, including dyslipidemias and redox status disturbances. This study highlights a connection between deficiencies in zinc, selenium, and magnesium and metabolic disorders linked to obesity, including dyslipidemias, alterations in redox status, and thyroid hormonal dysfunction.

Profile of hospital admissions and deaths due to severe acute respiratory syndrome caused by COVID-19 in Piauí, Brazil: a descriptive study, 2020-2021. / Perfil de internações e óbitos hospitalares por síndrome respiratória aguda grave causada por COVID-19 no Piauí: estudo descritivo, 2020-2021.

OBJECTIVE: To describe the profile and temporal variation of hospital admissions and deaths due to severe acute respiratory syndrome (SARS) caused by COVID-19 in Piauí, Brazil, according to place of hospitalization. METHODS: We performed a descriptive study using data from the Influenza Surveillance Information System between 2020 and 2021. Case fatality ratio among hospital records with outcome and respective 95% confidence intervals (95%CI) were calculated. RESULTS: We included 12,649 individuals who were mostly male (57.1%), Black (61.2%) and had one or two comorbidities (30.5%). Case fatality ratio among hospital records with outcome was higher in the state's interior region than in its capital, with proportion of 44.1% (95%CI 42.0;46.3) for those who were hospitalized, 82.3% (95%CI 79.7;84.8) for those admitted to intensive care units and 96.6% (95%CI 94.9;97.8) for those undergoing invasive mechanical ventilation. CONCLUSION: The study enabled characterization of the profile of SARS hospitalizations due to COVID-19 in Piauí and demonstrated high case fatality ratio, among hospital records with outcome, which remained high during the study period, especially in the interior of the state.

Profile of hospital admissions and in-hospital mortality due to severe acute respiratory syndrome caused by COVID-19 in Piauí, Brazil: descriptive study, 2020-2021 / Perfil de ingresos hospitalarios y mortalidad hospitalaria por síndrome respiratorio agudo grave por COVID-19 en Piauí, Brasil: estudio descriptivo, 2020-2021 / Perfil das internações e da mortalidade hospitalar por síndrome respiratória aguda grave causada por COVID-19 no Piauí: estudo descritivo, 2020-2021

Objective: To describe the profile and temporal variation of hospital admissions and hospital mortality by severe acute respiratory syndrome (SARS) related to COVID-19 in Piauí, Brazil, according to the place of admission. Methods: We performed a descriptive study from the Influenza Surveillance Information System between epidemiological weeks 12/2020 and 12/2021. Hospital mortality was calculated with 95% Confidence Interval (95%CI). Results: The hospitalized patients were mostly male (57.1%), black (61.2%) and had one or two comorbidities (30.5%). Hospital mortality was higher in the interior with coefficients of 44.1% (95%CI 42.0;46.3) in hospitalized patients, 82.3% (95%CI 79.7;84.8) in intensive care units and 96.6% (95%CI 94.9;97.8) of those undergoing invasive mechanical ventilation.Conclusion: The study allowed the characterization of the profile of hospitalizations for SARS caused by COVID-19 in Piauí and demonstrated high in-hospital mortality, which remained high during the study period, especially in the interior.

Objetivo: Describir el perfil y variación temporal de los ingresos hospitalarios y la mortalidad por síndrome respiratorio agudo grave (SRAG) causada por COVID-19 en Piauí, Brasil, según el lugar de ingreso. Métodos: Estudio descriptivo con dados del Sistema de Información de Vigilancia Epidemiológica de Influenza en las semanas epidemiológicas 12/2020 a 12/2021. Se calculó la mortalidad hospitalaria con intervalo de confianza del 95% (IC95%). Resultados: Los pacientes hospitalizados eran en su mayoría hombres (57,1%), negros (61,2%) y tenían una o dos comorbilidades (30,5%). La mortalidad hospitalaria fue mayor en el interior con coeficientes de 44,1% (IC95% 42,0;46,3) en pacientes hospitalizados, 82,3% (IC95% 79,7;84,8) en unidades de cuidados intensivos y 96,6% (IC95% 94,9;97,8) de los sometidos a ventilación mecánica invasiva.Conclusión: El estudio permitió caracterizar el perfil de hospitalizaciones por SRAG por COVID-19 en Piauí y mostró una alta mortalidad hospitalaria, que se mantuvo alta durante el período de estudio, especialmente en el interior.

Objetivo: Descrever o perfil e a variação temporal das internações e mortalidade hospitalar por síndrome respiratória aguda grave (SRAG) por COVID-19 no Piauí, Brasil, segundo local de internação. Métodos: Estudo descritivo sobre dados do Sistema de Informação da Vigilância Epidemiológica da Gripe, da 12ª semana epidemiológica de 2020 à 12ª de 2021. Calculou-se a mortalidade hospitalar e respectivos intervalos de confiança de 95% (IC95%). Resultados: Os indivíduos observados eram majoritariamente do sexo masculino (57,1%), negros (61,2%), com uma ou duas comorbidades (30,5%). A mortalidade hospitalar no interior, entre internados (44,1% ­ IC95% 42,0%;46,3%), admitidos em unidades de terapia intensiva (82,3% ­ IC95% 79,7;84,8) e indivíduos submetidos a ventilação mecânica invasiva (96,6% ­ IC95% 94,9;97,8), foi maior do que na capital do estado. Conclusão: O estudo permitiu a caracterização do perfil das internações devidas a SRAG por COVID-19 no Piauí e demonstrou mortalidade hospitalar elevada, mantendo-se alta no período estudado, sobretudo no interior.

Perfil de internações e óbitos hospitalares por síndrome respiratória aguda grave causada por COVID-19 no Piauí: estudo descritivo, 2020-2021 / Perfil de ingresos y fallecimientos hospitalarios por síndrome respiratorio agudo grave por COVID-19 en Piauí, Brasil: estudio descriptivo, 2020-2021 / Profile of hospital admissions and deaths due to severe acute respiratory syndrome caused by COVID-19 in Piauí, Brazil: a descriptive study, 2020-2021

Objetivo: Descrever o perfil e a variação temporal de internações e óbitos hospitalares por síndrome respiratória aguda grave (SRAG) por COVID-19 no Piauí, Brasil, segundo local de internação. Métodos: Estudo descritivo sobre dados do Sistema de Informação da Vigilância Epidemiológica da Gripe de 2020 a 2021. Calculou-se a letalidade entre registros hospitalares com desfecho e respectivos intervalos de confiança de 95% (IC95%). Resultados: Foram incluídos 12.649 indivíduos majoritariamente do sexo masculino (57,1%), negros (61,2%), com uma ou duas comorbidades (30,5%). No interior, entre registros hospitalares com desfecho, a letalidade para internados (44,1%; IC95% 42,0;46,3), admitidos em unidades de terapia intensiva (82,3%; IC95% 79,7;84,8) e indivíduos submetidos a ventilação mecânica invasiva (96,6%; IC95% 94,9;97,8) foi maior do que na capital do estado. Conclusão: O estudo permitiu a caracterização do perfil das internações devidas a SRAG por COVID-19 no Piauí e demonstrou elevada letalidade entre registros hospitalares com desfechos, mantendo-se alta no período estudado, sobretudo no interior.

Objetivo: Describir el perfil y variación temporal de los ingresos y fallecimientos hospitalarios por síndrome respiratorio agudo grave (SRAG) causado por COVID-19 en Piauí, Brasil, según el lugar de ingreso. Métodos: Estudio descriptivo con datos del Sistema de Información de Vigilancia Epidemiológica de la Gripe de 2020 a 2021. Se calculó la letalidad entre los registros hospitalarios con desenlace con intervalo de confianza del 95% (IC95%). Resultados: Se incluyeran 12.649 individuos que eran en su mayoría del sexo masculino (57,1%), negros (61,2%) y tenían una o dos comorbilidades (30,5%). La letalidad entre los registros hospitalarios con desenlace fue mayor en el interior, con proporciones de 44,1% (IC95% 42,0;46,3) en individuos hospitalizados, 82,3% (IC95% 79,7;84,8) en unidades de cuidados intensivos y 96,6% (IC95% 94,9;97,8) de los sometidos a ventilación mecánica invasiva. Conclusión: El estudio permitió caracterizar el perfil de hospitalizaciones por SRAG por COVID-19 en Piauí y mostró una alta letalidad entre los registros hospitalarios con desenlace, que se mantuvo alta durante el período de estudio, especialmente en el interior.

Objective: To describe the profile and temporal variation of hospital admissions and deaths due to severe acute respiratory syndrome (SARS) caused by COVID-19 in Piauí, Brazil, according to place of hospitalization. Methods: We performed a descriptive study using data from the Influenza Surveillance Information System between 2020 and 2021. Case fatality ratio among hospital records with outcome and respective 95% confidence intervals (95%CI) were calculated. Results: We included 12,649 individuals who were mostly male (57.1%), Black (61.2%) and had one or two comorbidities (30.5%). Case fatality ratio among hospital records with outcome was higher in the state's interior region than in its capital, with proportion of 44.1% (95%CI 42.0;46.3) for those who were hospitalized, 82.3% (95%CI 79.7;84.8) for those admitted to intensive care units and 96.6% (95%CI 94.9;97.8) for those undergoing invasive mechanical ventilation. Conclusion: The study enabled characterization of the profile of SARS hospitalizations due to COVID-19 in Piauí and demonstrated high case fatality ratio, among hospital records with outcome, which remained high during the study period, especially in the interior of the state.

Activation of the Adipose Tissue NLRP3 Inflammasome Pathway in Cancer Cachexia.

Background: Cachexia is a paraneoplastic syndrome that accompanies and compromises cancer treatment, especially in advanced stages, affecting the metabolism and function of several organs. The adipose tissue is the first to respond to the presence of the tumor, contributing to the secretion of factors which drive the systemic inflammation, a hallmark of the syndrome. While inflammation is a defensive innate response, the control mechanisms have been reported to be disrupted in cachexia. On the other hand, little is known about the role of NLRP3 inflammasome in this scenario, a multiprotein complex involved in caspase-1 activation and the processing of the cytokines IL-1ß and IL-18. Aim: based on the evidence from our previous study with a rodent model of cachexia, we examined the activation of the NLRP3 inflammasome pathway in two adipose tissue depots obtained from patients with colorectal cancer and compared with that another inflammatory pathway, NF-κB. Results: For CC we found opposite modulation in ScAT and PtAT for the gene expression of TLR4, Caspase-1 (cachectic group) and for NF-κB p50, NF-κB p65, IL-1ß. CD36, expression was decreased in both depots while that of NLRP3 and IL-18 was higher in both tissues, as compared with controls and weight stable patients (WSC). Caspase-1 basal protein levels in the ScAT culture supernatant were higher in WSC and (weight stable patients) CC, when compared to controls. Basal ScAT explant culture medium IL-1ß and IL-18 protein content in ScAT supernatant was decreased in the WSC and CC as compared to CTL explants. Conclusions: The results demonstrate heterogeneous responses in the activation of genes of the NLRP3 inflammasome pathway in the adipose tissue of patients with cancer cachexia, rendering this pathway a potential target for therapy aiming at decreasing chronic inflammation in cancer.

Association between calcium/magnesium ratio and insulin resistance in women with obesity and normal-weight women

ABSTRACT The aim of this study was to evaluate the association between the calcium/magnesium (Ca/Mg) ratio and insulin resistance in women with obesity and normal-weight women. This was a cross-sectional study with 128 women (62 women with obesity and 66 normal-weight women). We measured dietary minerals intake and analyzed magnesium and calcium biomarkers. Ca/Mg ratio in diet, plasma and urine were calculated. We have evaluated glycemic parameters. Women with obesity had low dietary magnesium, reduced plasma and erythrocyte magnesium concentrations, and elevated urinary magnesium excretion. Plasma calcium concentration was lower and urinary calcium excretion was higher in patients with obesity than in the normal-weight group. Dietary magnesium and calcium intake per kilogram of body weight per day was lower in obese women than in the control group. Ca/Mg ratio in plasma and urine were elevated in women with obesity. We found a significant correlation among magnesium biomarkers and calcium parameters. Ca/Mg ratio seems to be associated with insulin resistance in obese women.

RESUMEN El objetivo de este estudio fue evaluar la asociación entre la relación Ca/Mg y la resistencia a la insulina en mujeres con obesidad y en mujeres con peso normal. El diseño del estudio fue transversal y participaron 128 mujeres (62 mujeres con obesidad y 66 mujeres con peso normal). Se analizó la ingesta de minerales en la dieta y se realizaron análisis de biomarcadores de magnesio y calcio. Se calculó la relación Ca/Mg en dieta, plasma y orina y se evaluaron los parámetros glicémicos. Las mujeres con obesidad tenían niveles bajos de magnesio en la dieta, concentraciones reducidas de magnesio en plasma y eritrocitos, y excreción urinaria de magnesio elevada. La concentración plasmática de calcio fue menor en pacientes con obesidad, y la excreción urinaria de calcio fue mayor que en el grupo de mujeres con peso normal. La ingesta dietética de magnesio y calcio por kilogramo de peso corporal por día fue menor en las mujeres con obesidad, que en el grupo control. La relación Ca/Mg en plasma y orina estaba elevada en mujeres con obesidad. Se encontró una correlación significativa entre los biomarcadores de magnesio y los parámetros de calcio. La relación Ca / Mg parece estar asociada con la resistencia a la insulina en mujeres con obesidad.

Effects of glutamine supplementation on inflammatory bowel disease: A systematic review of clinical trials.

CONTEXT: Glutamine supplementation has been applied clinical practice to treat inflammatory bowel disease (IBD). However, scientific evidence about this is still controversial. OBJECTIVE: In this review, we systematically evaluated the effects of glutamine supplementation on IBD, based on evidence from randomized clinical trials. DATA SOURCE: This review was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We used the PubMed and SciVerse Scopus databases. The Cochrane collaboration tool was used to assess the risk of bias in clinical trials. DATA EXTRACTION: The review was carried out by two independent researchers according to the established inclusion criteria. The PICO (patient, intervention, comparison, and outcomes) strategy was used, with the descriptors: "glutamine," "supplementation," "inflammatory bowel diseases," "Crohn's disease," and "ulcerative colitis". DATA SYNTHESIS: Seven research articles were selected for this systematic review. In these studies, glutamine was administered to the participants through oral (21-30g or 0.5g per kg of participant's body weight), enteral (7.87g-8.3 g/100g of the enteral formula), and/or parenteral (0.3  g/kg of the participant's body weight) routes. No changes in anthropometry or biochemical parameters were observed. However, in one study reduced intestinal permeability and morphometry were reported. In two other studies, a slight effect of glutamine on inflammation and oxidative stress was observed. Additionally, two other studies reported an effect of glutamine supplementation on disease activity. CONCLUSIONS: The findings obtained through this systematic review indicate that glutamine supplementation has no effect on disease course, anthropometric measurements, intestinal permeability and morphology, disease activity, intestinal symptoms, biochemical parameters, oxidative stress and inflammation markers in patients with IBD, regardless of the route of administration, either treated at a hospital or as outpatients.

No association between zinc and thyroid activity in obese women.

Obesity is characterized by changes in the metabolism of zinc and thyroid hormones. Studies have also shown the role of zinc in the function and metabolism of thyroid. The present study aimed to evaluate the relationship between serum concentrations of thyroid hormones, dietary zinc intake and zinc distribution in obese women. A case-control study was conducted enrolling 98 women aged between 20 and 50 years old who were divided into case group (BMI ≥ 35 kg/m2) and control group (BMI = 18.5-24.9 kg/m2). Patients underwent anthropometric measurements and analysis of dietary zinc intake, which was performed by a three-day food record. Zinc concentrations in plasma and erythrocytes were determined by inductively coupled plasma optical emission spectrometry. Serum concentrations of thyroid hormones and antibodies were determined by chemiluminescence. Mean values of dietary zinc intake were higher than recommended (10.37 ± 3.12 mg/day and 11.37 ± 4.36 mg/day for control and obeses, respectively). Obese women had reduced plasma (67.22 ± 5.96 µg/dL) and erythrocyte (37.16 ± 3.64 µg Zn/gHb) zinc concentrations when compared to the control group (plasma: 89.71 ± 13.33 µg/dL; erythrocyte: 42.68 ± 3.73 µg Zn/gHb) (p < 0.001). Serum TSH (control: 2.62 ± 1.29 µIU/mL; obeses: 3.08 ± 1.13 µIU/mL), Free T3 (control: 2.19 ± 0.63 pg/dL; obeses: 2.09 ± 0.34 pg/dL), and Free T4 (control: 1.12 ± 0.31 ng/dL; obeses: 1.09 ± 0.19 ng/dL) concentrations were within the normal range in both groups, without significant difference between them (p > 0.05). There was no correlation between thyroid hormone concentrations and zinc parameters (p > 0.05). Although obese women presented hypozincemia, they had normal levels of thyroid hormones and no correlation was found between the studied parameters.

Immediate effects of a real moderate interval-running training session on inflammatory profile.

The study investigated the immediate effect of a moderate interval-running training session on circulating inflammatory cytokines concentration at real conditions of training. Nine recreational runners (5 women and 4 men; 68,33 ± 10,20 kg; 1,65 ± 0,07 m; 28,67 ± 4,24 years) had blood samples collected from antecubital vein before and immediately after a moderate interval-running training session without fasting. Cytokine levels were obtained from blood samples through Multiplex Analysis of Sample Protein Content, performed by Magpix® instrument. The assay detected the cytokines and calculated the plasma cytokine concentrations. Reduced concentration was observed after training session for all cytokines (p < 0.05), except for IP-10. Moderate effect sizes were identified in IL-6, IL-8, TNF-α, IP-10, MCP1 and GM-CSF. In summary, a single moderate interval-running training session at real conditions of training seems not to be stressing enough to increase cytokine levels as a response to the exercise. Results reinforce that immediate biochemical response and inflammatory modulation related to exercise is dose-dependent and may be influenced by other variables.

Win 55,212-2, atenolol and subdiaphragmatic vagotomy prevent acceleration of gastric emptying induced by cachexia via Yoshida-AH-130 cells in rats.

The aim of this study was to investigate the effect of cachexia induced by AH-130 cells on gastrointestinal motility in rats. We evaluated food intake, body weight variation, cachexia index, gastric emptying and in vitro gastric responsiveness of control or cachexia rats. In addition, we evaluated the effect of pretreatment with atenolol (20 mg/kg, p.o.), win 55,212-2 (2 mg/kg, s.c.) or subdiaphragmatic vagotomy on the effects found. Atenolol prevented (P < 0.05) the acceleration of gastric emptying (area under the curve, AUC, 20360.17 ± 1970.9 vs. 12579.2 ± 785.4 µg/min/ml), and increased gastric responsiveness to carbachol (CCh) stimulation in cachectic rats compared to control groups (CCh-6M: 63.2 ± 5.5% vs. 46.5 ± 5.7%). Vagotomy prevented (P < 0.05) increase in gastric emptying acceleration (AUC 20360.17 ± 1970.9 vs. 13414.0 ± 1112.9 µg/min/ml) and caused greater in vitro gastric responsiveness of cachectic compared to control rats (CCh-6M: 63.2 ± 5.5% vs. 31.2 ± 4.7%). Win 55,212-2 attenuated the cachexia index (38.5 ± 2.1% vs. 25.8 ± 2.7%), as well as significantly (P < 0.05) preventing increase in gastric emptying (AUC 20360.17 ± 1970.9 vs. 10965.4 ± 1392.3 µg/min/ml) and gastric responsiveness compared to control groups (CCh-6M: 63.2 ± 5.5% vs. 38.2 ± 3.9%). Cachexia accelerated gastric emptying and increased gastric responsiveness in vitro. These phenomena were prevented by subdiaphragmatic vagotomy and by atenolol and win 55,212-2 treatments, showing vagal involvement of ß1-adrenergic and cannabinoid CB1/CB2 receptors.

Plasma Lipid Profile and Systemic Inflammation in Patients With Cancer Cachexia.

Cancer cachexia affects about 80% of advanced cancer patients, it is linked to poor prognosis and to date, there is no efficient treatment or cure. The syndrome leads to progressive involuntary loss of muscle and fat mass induced by systemic inflammatory processes. The role of the white adipose tissue (WAT) in the onset and manifestation of cancer cachexia gained importance during the last decade. WAT wasting is not only characterized by increased lipolysis and release of free fatty acids (FFA), but in addition, owing to its high capacity to produce a variety of inflammatory factors. The aim of this study was to characterize plasma lipid profile of cachectic patients and to correlate the FA composition with circulating inflammatory markers; finally, we sought to establish whether the fatty acids released by adipocytes trigger and/or contribute to local and systemic inflammation in cachexia. The study selected 65 patients further divided into 3 groups: control (N); weight stable cancer (WSC); and cachectic cancer (CC). The plasma FA profile was significantly different among the groups and was positively correlated with pro-inflammatory cytokines expression in the CC patients. Therefore, we propose that saturated to unsaturated FFA ratio may serve as a means of detecting cachexia.

Role of Zinc in Zinc-α2-Glycoprotein Metabolism in Obesity: a Review of Literature.

Excessive adipose tissue promotes the manifestation of endocrine disorders such as reduction of the secretion of zinc-α2-glycoprotein (ZAG), an adipokine with anti-inflammatory and lipid-mobilizing activity. The molecular structure of this adipokine includes binding sites for zinc, a trace element with important antioxidant and immunological proprieties that also participates in energy metabolism and stimulates the function of ZAG. The objective of this review is to highlight current data on the metabolism of ZAG in obesity and the role of zinc in this process. The identified studies show that subjects with obesity have low serum concentrations of zinc and ZAG, as well as low expression of the genes encoding this protein. Thus, zinc appears to be an important regulator of the homeostasis of ZAG in the body; however, alterations in the metabolism of zinc in obesity appear to compromise the functions of ZAG. Therefore, further studies are needed to clarify the relationship between zinc and ZAG metabolism and its repercussions in obesity.

Cancer cachexia induces morphological and inflammatory changes in the intestinal mucosa.

BACKGROUND: Cachexia is a multifactorial and multiorgan syndrome associated with cancer and other chronic diseases and characterized by severe involuntary body weight loss, disrupted metabolism, inflammation, anorexia, fatigue, and diminished quality of life. This syndrome affects around 50% of patients with colon cancer and is directly responsible for the death of at least 20% of all cancer patients. Systemic inflammation has been recently proposed to underline most of cachexia-related symptoms. Nevertheless, the exact mechanisms leading to the initiation of systemic inflammation have not yet been unveiled, as patients bearing the same tumour and disease stage may or may not present cachexia. We hypothesize a role for gut barrier disruption, which may elicit persistent immune activation in the host. To address this hypothesis, we analysed the healthy colon tissue, adjacent to the tumour. METHODS: Blood and rectosigmoid colon samples (20 cm distal to tumour margin) obtained during surgery, from cachectic (CC = 25) or weight stable (WSC = 20) colon cancer patients, who signed the informed consent form, were submitted to morphological (light microscopy), immunological (immunohistochemistry and flow cytometry), and molecular (quantification of inflammatory factors by Luminex® xMAP) analyses. RESULTS: There was no statistical difference in gender and age between groups. The content of plasma interleukin 6 (IL-6) and IL-8 was augmented in cachectic patients relative to those with stable weight (P = 0.047 and P = 0.009, respectively). The number of lymphocytic aggregates/field in the gut mucosa was higher in CC than in WSC (P = 0.019), in addition to those of the lamina propria (LP) eosinophils (P < 0.001) and fibroblasts (P < 0.001). The area occupied by goblet cells in the colon mucosa was decreased in CC (P = 0.016). The M1M2 macrophages percentage was increased in the colon of CC, in relation to WSC (P = 0.042). Protein expression of IL-7, IL-13, and transforming growth factor beta 3 in the colon was significantly increased in CC, compared with WSC (P = 0.02, P = 0.048, and P = 0.048, respectively), and a trend towards a higher content of granulocyte-colony stimulating factor in CC was also observed (P = 0.061). The results suggest an increased recruitment of immune cells to the colonic mucosa in CC, as compared with WSC, in a fashion that resembles repair response following injury, with higher tissue content of IL-13 and transforming growth factor beta 3. CONCLUSIONS: The changes in the intestinal mucosa cellularity, along with modified cytokine expression in cachexia, indicate that gut barrier alterations are associated with the syndrome.

Tumour-derived transforming growth factor-ß signalling contributes to fibrosis in patients with cancer cachexia.

BACKGROUND: Cachexia is a paraneoplastic syndrome related with poor prognosis. The tumour micro-environment contributes to systemic inflammation and increased oxidative stress as well as to fibrosis. The aim of the present study was to characterise the inflammatory circulating factors and tumour micro-environment profile, as potentially contributing to tumour fibrosis in cachectic cancer patients. METHODS: 74 patients (weight stable cancer n = 31; cachectic cancer n = 43) diagnosed with colorectal cancer were recruited, and tumour biopsies were collected during surgery. Multiplex assay was performed to study inflammatory cytokines and growth factors. Immunohistochemistry analysis was carried out to study extracellular matrix components. RESULTS: Higher protein expression of inflammatory cytokines and growth factors such as epidermal growth factor, granulocyte-macrophage colony-stimulating factor, interferon-α, and interleukin (IL)-8 was observed in the tumour and serum of cachectic cancer patients in comparison with weight-stable counterparts. Also, IL-8 was positively correlated with weight loss in cachectic patients (P = 0.04; r = 0.627). Immunohistochemistry staining showed intense collagen deposition (P = 0.0006) and increased presence of α-smooth muscle actin (P < 0.0001) in tumours of cachectic cancer patients, characterizing fibrosis. In addition, higher transforming growth factor (TGF)-ß1, TGF-ß2, and TGF-ß3 expression (P = 0.003, P = 0.05, and P = 0.047, respectively) was found in the tumour of cachectic patients, parallel to p38 mitogen-activated protein kinase alteration. Hypoxia-inducible factor-1α mRNA content was significantly increased in the tumour of cachectic patients, when compared with weight-stable group (P = 0.005). CONCLUSIONS: Our results demonstrate TGF-ß pathway activation in the tumour in cachexia, through the (non-canonical) mitogen-activated protein kinase pathway. The results show that during cachexia, intratumoural inflammatory response contributes to the onset of fibrosis. Tumour remodelling, probably by TGF-ß-induced transdifferentiation of fibroblasts to myofibroblasts, induces unbalanced inflammatory cytokine profile, angiogenesis, and elevation of extracellular matrix components (EMC). We speculate that these changes may affect tumour aggressiveness and present consequences in peripheral organs.

Peritumoural adipose tissue pro-inflammatory cytokines are associated with tumoural growth factors in cancer cachexia patients.

BACKGROUND: Cancer cachexia (CC) is a multifactorial syndrome, often irreversible, that affects patients with cancer influenced, in part, by the inflammatory condition. Peritumoural adipose tissue produces adipokines and angiogenic, apoptotic, and growth factors; given the possible crosstalk between the peritumoural adipose tissue and tumour, these may play an important role in cancer biology and carcinogenesis. METHODS: The aim of this study was to evaluate the factors produced by peritumoural adipose tissue in a cohort of 16 colorectal cancer patients with either weight-stable cancer (WSC; n = 7) or CC (n = 9). The study was approved by the Ethics Research Committee (972.914). Samples of peritumoural adipose tissue were analysed for concentrations of TNF-α, IL-1ß, STAT-1, STAT-3, RANTES, IL-1Ra, IP-10, IL-15, MCP-1, IFN-α, GCSF, FADD, and TGF-ß. The cytokines and proteins were measured using Multiplex. Correlations between the proteins and cytokines were evaluated. RESULTS: TNF-α, STAT-1, and FADD, a factor involved in apoptosis, were significantly higher in CC group than in the WSC group. In the peritumoural adipose tissue of the CC group, RANTES showed a significant positive correlation with IL-1Ra and IP-10 and a negative correlation with IFN-α; and GCSF showed significant negative correlations with IL-1Ra, IP-10, IL-15, and MCP-1 and a positive correlation with IFN-α. In the peritumoural adipose tissue of the WSC group, no significant correlations were detected between RANTES, GCSF, IL-3, FADD, and STAT-1 and the cytokines/chemokines analysed. CONCLUSIONS: These results indicated that inflammatory and tumorigenic pathways were altered in peritumoural adipose tissue in CC. Furthermore, inflammatory cytokines were correlated with growth factors in the peritumoural adipose tissue of cachectic patients, suggesting that inflammatory cytokines modulated the proliferative environment closely linked to the tumour.

Adipose tissue fibrosis in human cancer cachexia: the role of TGFß pathway.

BACKGROUND: Cancer cachexia is a multifactorial syndrome that dramatically decreases survival. Loss of white adipose tissue (WAT) is one of the key characteristics of cachexia. WAT wasting is paralleled by microarchitectural remodeling in cachectic cancer patients. Fibrosis results from uncontrolled ECM synthesis, a process in which, transforming growth factor-beta (TGFß) plays a pivotal role. So far, the mechanisms involved in adipose tissue (AT) re-arrangement, and the role of TGFß in inducing AT remodeling in weight-losing cancer patients are poorly understood. This study examined the modulation of ECM components mediated by TGFß pathway in fibrotic AT obtained from cachectic gastrointestinal cancer patients. METHODS: After signing the informed consent form, patients were enrolled into the following groups: cancer cachexia (CC, n = 21), weight-stable cancer (WSC, n = 17), and control (n = 21). The total amount of collagen and elastic fibers in the subcutaneous AT was assessed by histological analysis and by immunohistochemistry. TGFß isoforms expression was analyzed by Multiplex assay and by immunohistochemistry. Alpha-smooth muscle actin (αSMA), fibroblast-specific protein (FSP1), Smad3 and 4 were quantified by qPCR and/or by immunohistochemistry. Interleukin (IL) 2, IL5, IL8, IL13 and IL17 content, cytokines known to be associated with fibrosis, was measured by Multiplex assay. RESULTS: There was an accumulation of collagen and elastic fibers in the AT of CC, as compared with WSC and controls. Collagens type I, III, VI, and fibronectin expression was enhanced in the tissue of CC, compared with both WSC and control. The pronounced expression of αSMA in the surrounding of adipocytes, and the increased mRNA content for FSP1 (20-fold) indicate the presence of activated myofibroblasts; particularly in CC. TGFß1 and TGFß3 levels were up-regulated by cachexia in AT, as well in the isolated adipocytes. Smad3 and Smad4 labeling was found to be more evident in the fibrotic areas of CC adipose tissue. CONCLUSIONS: Cancer cachexia promotes the development of AT fibrosis, in association with altered TGFß signaling, compromising AT organization and function.

Pequi (Caryocar brasiliense Camb.) almond oil attenuates carbon tetrachloride-induced acute hepatic injury in rats: Antioxidant and anti-inflammatory effects.

Carbon tetrachloride (CCl4) is a potent hepatotoxin, capable of generating free radicals that lead to oxidative stress and the inflammation process. Pequi almond oil (PAO) has been reported to possess unsaturated fatty acid and antioxidant compounds related to beneficial effects on oxidation and inflammatory conditions. The present study was undertaken to evaluate the hepatoprotective effects of handmade and coldpressed PAO on CCl4-induced acute liver injury. The possible mechanisms underlying the effect on liver injury enzymes, histopathological parameters, lipid profile, lipid peroxidation, and antioxidant and detoxification defense systems, as well as inflammatory parameters, were determined. Rats treated with PAO (3 or 6 mL/kg) for 21 days before CCl4 induction (3 mL/kg, 70%) showed significantly decreased levels of alanine aminotransferase and aspartate aminotransferase, milder hepatic lesions and higher levels of serum high-density lipoprotein compared to CCl4 group. Moreover, PAO enhanced antioxidant capacity by increasing hepatic glutathione peroxidase and glutathione reductase enzyme activities, as well as reducing circulating concentrations of leptin and inflammatory mediators such as interleukin-6, leukotrienes -4 and -5 and the tumor necrosis factor receptor. In summary, PAO, especially cold-pressed oil, attenuated the CCl4-induced alterations in serum and hepatic tissue in rats due to its antioxidant and anti-inflammatory properties.

White adipose tissue cells and the progression of cachexia: inflammatory pathways.

BACKGROUND: Cachexia is a systemic syndrome leading to body wasting, systemic inflammation, and to metabolic chaos. It is a progressive condition, and little is known about its dynamics. Detection of the early signs of the disease may lead to the attenuation of the associated symptoms. The white adipose tissue is an organ with endocrine functions, capable of synthesising and secreting a plethora of proteins, including cytokines, chemokines, and adipokines. It is well established that different adipose tissue depots demonstrate heterogeneous responses to physiological and pathological stimuli. The present study aimed at providing insight into adipocyte involvement in inflammation along the progression of cachexia. METHODS: Eight-weeks-old male rats were subcutaneously inoculated with a Walker 256 carcinosarcoma cell suspension (2 × 10(7) cells in 1.0 mL; tumour-bearing, T) or Phosphate-buffered saline (control, C). The retroperitoneal, epididymal, and mesenteric adipose pads were excised on Days 0, 7, and 14 post-tumour cell injection, and the adipocytes were isolated. RESULTS: Mesenteric and epididymal adipocytes showed up-regulation of IL-1ß protein expression and activation of the inflammasome pathway, contributing for whole tissue inflammation. The stromal vascular fraction of the retroperitoneal adipose tissue, on the other hand, seems to be the major contributor for the inflammation in this specific pad. CONCLUSION: Adipocytes seem to play a relevant role in the establishment of white adipose tissue inflammation, through the activation of the NF-κB and inflammasome pathways. In epididymal adipocytes, induction of the inflammasome may be detected already on Day 7 post-tumour cell inoculation.