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In 2019, a new coronavirus (SARS-CoV-2) was identified in China and had rapidly spread across the world. Its associated disease, coronavirus disease 2019 (COVID-19), has led to millions of deaths in 2020-2021. Studies have been demonstrating that SARS-CoV-2 induces a systemic hyperinflammatory state, which is associated with a decreased cytotoxic capacity and impaired Type I interferon (IFN) response. Moreover, iron dysfunction/hyperferritinemia in association with hyperinflammation leads to oxidative stress and apoptosis. Altogether, these cellular events contribute to COVID-19 severity. In viral infections, systemic and cellular alterations can promote mitochondrial dysfunction. In this regard, dysfunctional mitochondria can trigger the immune response, leading to the release of mitochondrial damage-associated molecular patterns, including mitochondrial DNA (mtDNA) and reactive oxygen species (mtROS). mtDNA is known to promote a beneficial antiviral response; however, sustained nocive stimuli, such as SARS-CoV-2, could turn this response into oxidative stress and exacerbated inflammation leading to tissue injury. In addition, mtDNA can be released into the extracellular space and induce a proinflammatory state in neighboring cells. Here, we highlight the potential role of mtDNA as an important marker of hyperinflammation in the progress of COVID-19. Furthermore, we briefly discuss the role of mtROS and its interactions with the mitochondrial antiviral signaling (MAVS), which can also contribute to COVID-19 immunopathogenesis.

Introduction After DAA treatment for chronic hepatitis C infection, peripheral monocyte subsets from patients who achieved sustained virological response (SVR) reduced compared to healthy control. Improvement in inflammatory parameters and liver stiffness has been observed. However, little is known about the long-term impact of DAA treatment on peripheral monocyte subsets and immune mediators levels. Objectives We aimed to examine peripheral monocyte subsets and immune mediators levels in Brazilian chronic HCV patients after long-term successful IFN-free SOF-based treatment. Material and methods We analyzed CD14++CD16-, CD14++CD16+ and CD14+CD16++ monocytes and 27 immune mediators by flow cytometry and analysis of multiple secreted proteins assay, respectively, in monoinfected chronic HCV patients receiving IFN-free sofosbuvir-based regimens followed before treatment, at SVR and one year after the end of treatment (1y). Results Twenty-one biomarkers decreased significantly at 1y and 55–80 % of patients this reduction at 1y. Experimented patients presented a greater modulation of immune mediators at 1y. HLA-DR expression significantly decreased on CD14++CD16- and CD14++CD16+ monocytes at 1y when compared to SVR. Conclusions Successful DAA therapy did not modify monocyte subsets frequency but reduced monocyte activation at 1y and sustained the downregulation and restoration of circulating immune mediators, indicating that long-term reversal of inflammation status could occur after HCV eradication.

Objetivo: Avaliar o perfil epidemiológico das gestantes HIV positivo, acompanhadas no Ambulatório do Hospital Municipal Carlos Tortelly de Niterói – RJ. Metodologia: Trata-se de um estudo epidemiológico retrospectivo, quantitativo e descritivo. Consta de 103 gestantes HIV positivo na faixa etária 18 e 45 anos, atendidas no ambulatório de SIDA/Hospital Municipal Carlos Tortelly (HMCT), durante o perí­odo de dezembro de 2009 a dezembro de 2015. Resultados: A faixa etária predominante entre 21 a 30 anos (57,3%), sendo que 40,8% tinham ensino fundamental, 30,1% com renda familiar em torno de um salário mí­nimo, e a maioria 60,2% procedia no Municí­pio de Niterói. A detecção do HIV, majoritariamente, ocorreu antes da gravidez (57,3%), e apenas 14,6% das gestantes não consumia alguma substância quí­mica durante a gestação e 45,6% não sofreram infecção oportunista durante o acompanhamento, 28,2% já tinham dois ou mais filhos. Cesária não eletiva foi a maior forma de escolha para o nascimento (53,4%). Conclusão: O perfil se caracteriza por situação socioeconômica vulnerável, com baixo ní­vel de escolaridade, e o diagnóstico anterior precedem a gestação atual. A realização do pré-natal, e a terapia TARV na gestação e no parto foi alto. Para tanto, faz-se necessário o melhoramento das informações e ações direcionadas í ampliação da atenção í s mulheres, cuja garantia integral e o diagnóstico precoce do HIV constituem artifí­cios importantes na redução da transmissão vertical.

PURPOSE To identify factors associated with the development of adverse drug reactions (ADR) in ribavirin therapeutic regimens. METHODS A multicenter, prospective study was conducted in three public health hospitals in Rio de Janeiro between November 2015 and March 2018. Inclusion criteria were defined by patient follow-up at pharmaceutical consultation at the time of drug dispensing as those who used sofosbuvir in combination with simeprevir, daclatasvir, and/or ribavirin. All patients were invited to participate in the study during the first interview. Adverse drug reactions were reported according to the treatment regimen and frequency of occurrence. Statistical analysis was used to compare adverse reactions between treatments and their associated factors. RESULTS A total of 405 patients were included in the study (mean age 59.6 ± 9.6 years); 61.0% were female, 88.1% were infected with genotype 1, and 65.4% were cirrhotic. The most prescribed treatment was the combination of sofosbuvir, daclatasvir, and ribavirin (55.3%). The majority of patients reported at least one ADR during treatment (83.2%), of which fatigue, anemia, and headache were the most common. Being female (OR = 1.86, [1.08-3.20]) and use of ribavirin (OR: 2.39; 95% CI [1.38-4.13]) were predictors for the development of ADR, which was also associated with development of anemia (OR: 10.28; 95% CI: [5.78-18.30]). Treatment efficacy was 98.1%. CONCLUSIONS Direct-acting antiviral has been shown to be safe and effective. Therefore, use of ribavirin is questionable due to associated adverse reactions and similar efficacy to other treatments.

Yellow fever is an infectious disease of acute evolution, initially non-contagious, transmitted by a ribonucleic acid (RNA) virus that belongs to the Flaviviridae family. In the period from December 2016 until March 17, 2017, 1, 561 suspected cases of wild yellow fever were reported to the Ministry of Health in Brazil. Among these cases, 850 (54.8%) remain under investigation, 448 (28.7%) were confirmed and 263 (16.9%) were discarded. Out of the total cases reported, 264 died, 144 (54.5%) were confirmed for the disease, 110 (41.7%) were investigated and 10 (3.8%) were discarded. The case fatality rate among confirmed cases was 32.2%. The specific diagnosis for determining the etiology of infection can be made by demonstrating the humoral response of the antibodies, virus isolation, or histopathological study of the liver. Only through early laboratory diagnosis and epidemiological data supply can government and cooperative organizations establish public policies to combat future disease epidemics, as well as social awareness campaigns.

Background Hepatitis C virus is known to be highly dependent of lipid metabolism to infect new cells and replicate. Aims To investigate lipid and apolipoprotein profile in chronic HCV patients according to treatment response. Methods Patients recruited from the Hepatitis Treatment Center at Niteroi (Brazil) who received interferon (IFN)-based therapies were separated into two groups, those who achieved sustained virological response (SVR) or not (non-SVR). Another group of patients treated with IFN-free direct-acting antiviral (DAA) therapies was followed from before starting the treatment until one year after therapy. Triglycerides, total cholesterol and fractions were determined by colorimetric and/or electrophoresis techniques. Lecithin cholesterol acyltransferase (LCAT) activity and serum levels of apolipoproteins A1, A2, B, C2, C3 and E were assessed by enzymatic and multiplex assays, respectively. Results We studied 114 patients, and SVR was reached in 28 (39.4%) patients treated with IFN-therapy and in all (100%) patients who received DAA. Non-SVR patients (n = 43) presented altered liver parameters post-treatment. Levels of total cholesterol, LDL-C, VLDL-C and triglycerides were significant higher in SVR group. In contrast, LCAT activity and HDL-C levels were elevated in non-SVR patients. Only apolipoproteins B, C2 and C3 levels were increased in SVR group. The follow-up of SVR-DAA patients (n = 43) revealed a significant and progressive increase in serum levels of total cholesterol, LDL-C, VLDL-C and triglycerides. Conclusions After a successful treatment, chronic hepatitis C patients experienced a reestablishment of lipid metabolism. Our results suggest that the monitoring of serum lipids could be a practical and routine laboratory tool to be applied during the treatment follow-up.

Zika fever can be defined as an acute febrile viral illness, mainly transmitted by the mosquito of the genus Aedes. It makes a differential diagnosis from diseases caused by other flaviviruses, such as chikungunya and dengue fever. Many people with Zika virus (ZIKV) infection will not have symptoms or will only have mild clinical symptoms. The clinical conditions are nonspecific and characterized by low-grade fever, pruritic erythematous maculopapular rash, non-purulent conjunctival hyperemia without pruritus, arthralgia, myalgia, and headache. It is a benign, self-limiting and short-duration condition. Complications such as Guillain-Barre syndrome (GBS), spontaneous abortion and fetal malformations, mainly microcephaly and retinal lesions, may occur. The laboratory investigation is more important in cases suspected of ZIKV infection that have evolved with neurological complications, in pregnant women, abortion or congenital malformations, and is a key part for diagnostic definition. Real-time polymerase chain reaction (RT-PCR) can detect the virus in blood samples about four to seven days after the onset of symptoms. In urine, it is possible to identify viral ribonucleic acid (RNA) up to 15 days after clinical onset, even if viremia has ceased, and it is an alternative for late diagnosis. Serological tests may also be performed, while there may be cross-reactivity with other flaviviruses. Immunoglobulin class M (IgM) can be screened between the 2nd and 12th week after clinical presentation. The immunoglobulin class G (IgG) can be identified after the 15th day, and is present even in the convalescence and cure phase. Non-specific laboratory abnormalities, in general, do not present significant alterations. Patients with GBS must have cerebrospinal fluid (CSF) collection for analysis.

Disturbances in matrix metalloproteinases (MMPs) and corresponding tissue inhibitors (TIMPs) contribute to hepatitis C virus (HCV)-induced fibrosis. This study aimed to determine MMP-9/TIMP-1 levels in addition to MMP-2 and -9 activities; correlating with the improvement of liver fibrosis in patients under direct-acting antiviral (DAA) therapy.Clinical and laboratory follow-up were performed before treatment and after 12 weeks post-treatment, referred as sustained viral response (SVR). We evaluated liver function including non-invasive fibrosis measurements; MMP activity by zymography; and MMP-9/TIMP-1 complex, inflammatory and pro-fibrogenic mediators by immunoenzymatic assays.Cohort included 33 patients (59.5 ± 9.3 years, 60.6% females) whose reached SVR and 11 control-paired subjects (42.5 ± 15 years, 54.5% females). Before treatment, HCV patients presented higher MMP-9/TIMP-1 levels (P 0.05) when compared to controls, and the highest values were observed in patients with fibrosis (P 0.05). In addition, MMP-9/TIMP-1 levels were significantly reduced after DAA therapy (P 0.0001) and were associated with profibrogenic biomarkers. No differences were observed for MMP-2 and -9 activities; however, these biomarkers were significantly associated with inflammatory mediators.Our data suggest that MMP-9/TIMP-1 complex can be a promising biomarker of active fibrogenesis, being able to identify the interruption of fibrosis progression after HCV eradication.

Measles is an acute febrile exanthematic disease of viral etiology, highly contagious, being the cause of morbidity and mortality of children in developing countries, whereas it has become rarer in developed countries due to vaccination. Its differential diagnosis should be made with other childhood viral respiratory diseases such as influenza, rhinovirus and adenovirus, and exanthematic febrile diseases such as rubella, roseola and varicella. In tropical regions, it should be performed with dengue, zika and chikungunya. Its clinical picture presents the following phases: incubation, usually asymptomatic; a prodrome, in which fever, malaise, coryza can occur, besides Koplik’s signs; exanthematic, with presence of maculopapular exanthema after the fever condition that progresses to a craniocaudal evolution, with clinical improvement in uncomplicated cases. Common complications are pneumonia, otitis media, keratitis; the rarest are acute disseminated encephalomyelitis and subacute sclerosing panencephalitis. Nonspecific laboratory alterations are seen in the blood count. The specific laboratory diagnosis is based on the detection of viral ribonucleic acid (RNA) [polymerase chain reaction (PCR) of nasal swab samples, oral mucosa or urine]. Immunoglobulin class M (IgM) can be detected during the exanthematous period by enzyme-linked immunosorbent assay (ELISA), and immunoglobulin class G (IgG) throughout the convalescence period, and the detection of specific IgG by the plaque reduction neutralization test may also be performed. The prophylaxis of the disease is based on vaccination in children from 15 months in order to reach about 85% to 95% of the population, what confers herd immunity. Thus, vaccination is the most effective measure in combating measles, since the treatment consists only of clinical and symptomatic support. RESUMEN El sarampión es una enfermedad exantemática febril aguda de etiología viral altamente contagiosa. Causa morbilidad y mortalidad de niños en países en desarrollo, mientras que se hizo más raro en países desarrollados gracias a la vacunación. El diagnóstico diferencial se hace con otras enfermedades infantiles, como influenza, rinovirus, adenovirus, rubéola, roséola y varicela. En regiones tropicales, incluye dengue, zika y chikungunya. Su cuadro clínico presenta las siguientes fases: incubación - en general asintomática; pródromo - en la cual pueden ocurrir fiebre, malestar y coriza, además de manchas de Koplik; y la exantemática - con presencia de exantema máculo-papular después del cuadro febril, que se disemina desde la cara a tronco y extremidades, con mejora clínica en casos no complicados. Complicaciones comunes son neumonía, otitis media y queratoconjuntivitis; las más raras, encefalomielitis aguda diseminada y panencefalitis esclerosante subaguda. Alteraciones inespecíficas de laboratorio son vistas en el hemograma. El diagnóstico específico de laboratorio se basa en el aislamiento del ácido ribonucleico (ARN) viral (PCR de muestras nasales, mucosa oral u orina). La inmunoglobulina M (IgM) pude ser detectada durante el período exantemático por ensayo por inmunoadsorción ligado a enzimas (ELISA); la inmunoglobulina G (IgG), a lo largo del período de convalecencia, y la detección de IgG específica por la prueba de neutralización por reducción de placa. La profilaxis de la enfermedad se basa en vacunación en niños desde los 15 meses de edad, buscando alcanzar 85%-95% de la población, lo que confiere inmunidad de grupo. La vacunación es la medida más eficaz en el combate al sarampión, puesto que el tratamiento consiste sólo en soporte clínico. RESUMO O sarampo é uma doença exantemática febril aguda de etiologia viral altamente contagiosa. É causa de morbidade e mortalidade de crianças em países em desenvolvimento, ao passo que se tornou mais rara em países desenvolvidos devido à vacinação. O diagnóstico diferencial deve ser realizado em relação a outras doenças da infância, como influenza, rinovírus, adenoviroses, rubéola, roséola e varicela. Já em regiões tropicais, inclui dengue, vírus da zika e chikungunya. Seu quadro clínico apresenta as seguintes fases: a de incubação - em geral assintomática; a prodrômica - na qual podem ocorrer febre, mal-estar e coriza, além de sinais de Koplik; e a exantemática - com presença de exantema maculopapular após o quadro febril, que progride de forma craniocaudal, com melhora clínica em casos não complicados. Complicações comuns são pneumonia, otite média e ceratoconjuntivite; as mais raras, encefalomielite disseminada aguda e panencefalite esclerosante subaguda. Alterações laboratoriais inespecíficas são vistas no hemograma. O diagnóstico laboratorial específico baseia-se na detecção do ácido ribonucleico (RNA) viral [reação em cadeia da polimerase (PCR) de amostras de swab nasal, mucosa oral ou urina]. Imunoglobulina da classe M (IgM) pode ser detectada durante o período exantemático por ensaio de imunoadsorção enzimática (ELISA) e imunoglobulina da classe G (IgG), ao longo do período de convalescença, podendo também ser realizada a detecção de IgG específica pelo teste de neutralização por redução de placas. A profilaxia da doença é baseada na vacinação em crianças a partir dos 15 meses de idade, visando atingir cerca de 85% a 95% da população, o que confere imunidade de rebanho. A vacinação é a medida mais eficaz no combate ao sarampo, visto que o tratamento consiste apenas em suporte clínico.

Resumo Fundamento: O agravamento da função renal (AFR) é frequentemente observado na terapia agressiva com diuréticos para o tratamento de insuficiência cardíaca aguda descompensada (ICAD) e está associado com piores desfechos em alguns estudos. Objetivo: Avaliar a relação de AFR e congestão na alta hospitalar com ocorrência de eventos (morte cardíaca ou internação por insuficiência cardíaca). Métodos: Oitenta pacientes com ICAD foram estudados. O AFR foi definido por um aumento absoluto (≥0,5 mg/dL) nos níveis séricos de creatinina a partir dos valores obtidos na admissão. Concentrações de peptídeo natriurético do tipo B (BNP) e lipocalina associada à gelatinase neutrofílica (NGAL) foram medidas na admissão e na alta hospitalar. Congestão foi avaliada na alta utilizando a análise vetorial de bioimpedância elétrica (BIVA). O desfecho primário foi o tempo para o primeiro evento, definido como uma combinação de morte cardíaca ou hospitalização por insuficiência cardíaca. Análise de curva Característica de Operação do Receptor (curva ROC) foi realizada para determinar o ponto de corte de IH mais adequado para predição de eventos. Curvas Kaplan-Meier de sobrevida livre de eventos foram construídas e comparadas usando o teste de log-rank. Modelos de riscos proporcionais de Cox foram usados para investigar a associação com eventos. O critério para se estabelecer significância estatística foi um p

Made available in DSpace on 2019-10-04T12:35:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01. Added 1 bitstream(s) on 2019-10-09T18:33:51Z : No. of bitstreams: 1 S0365-05962019000100010.pdf: 353587 bytes, checksum: d25d1c14906ce51e02986763e1147ae4 (MD5) Sociedade Brasileira de Dermatologia BACKGROUND: Most of the organism's vitamin D (VD) is obtained through the cutaneous synthesis after exposure to the sun's UVB radiation. Sunscreens are indicated for the prevention of actinic damage to the skin, however, there are few clinical trials assessing the synthesis of cutaneous VD in real-life situations of sun exposure with ordinary clothing and usual photoprotection. OBJECTIVES: To evaluate the synthesis of VD with suberythemal sun exposure in healthy adults using topical photoprotection (SPF 30). METHODS: Quasi-experimental study, conducted at Rio de Janeiro (Brazil), during winter, with 95 healthy adults who had 25-OH-VD checked twice, 24 hours apart, and were exposed to the sun (UVB=20 mJ/cm2), according to a randomized grouping: SC - use of SPF 30 on the face, neck and chest (n=64), NO - no sunscreens (n=10), CO - confined from sun exposure for 24h (n=21). The groups were matched according to the propensity score related to gender, age, phototype, body mass index, glycosylated hemoglobin and baseline levels of VD. The outcome evaluated was the variation (Delta VD) in serum level of 25-OH-VD (ng/ml) between the groups. RESULTS: A statistically significant difference was identified between CO and SC groups [median (p25-p75)]: Delta VD =1.4 (-0.3-3.6) vs. 5.5 (4.8-6.6); p

Objective: Investigate the prevalence of periodontal disease in individuals with neurofibromatosis 1 (NF1). Study design: This study was conducted on 42 Brazilian individuals diagnosed with NF1; their ages ranged from 18 to 77 years (mean age, 40 years). Of these, 72% (32 out of 42) were female and 28% (10 out of 42) were male. All participants were subjected to anamnesis, oral exam, measurement of oral hygiene index, tongue coat index, community periodontal index (CPI), and periodontal loss of attachment index. The results were compared with a sex- and age-paired control group. Results: According to the CPI, 37% of individuals with NF1 had gingival bleeding and 68% had periodontal loss of attachment of 4 to 5 mm. Compared to the control group, there was a significant statistical difference in CPI (P = .013) and periodontal loss of attachment (P = .001). Comparing the periodontal indexes of patients with NF1 and oral hygiene, there was an association with poor oral hygiene and loss of periodontal insertion (P

Background: Heart rate (HR) reduction with ivabradine has been proved to reduce hospitalization and death from heart failure (HF). We sought to investigate whether pyridostigmine would effectively reduce HR in patients with chronic HF as compared with ivabradine. Methods: Twenty-one patients with HF who were in sinus rhythm with a resting HR over 70 bpm, despite optimal medical treatment, were included in a randomized, double-blind study comparing pyridostigmine versus ivabradine. The initial dose of ivabradine was 5 mg twice daily to reach a target HR between 50 and 60 bpm and could be titrated to a maximum of 7.5 mg twice daily. Pyridostigmine was used in a fixed dose of 30 mg 3 times daily. Results: The baseline HR for ivabradine and pyridostigmine groups was 89.1 (13.5) and 80.1 (7.2) bpm, respectively ( P = .083). After 6 months of treatment, HR was significantly reduced to 64.8 (8.3) bpm in the ivabradine group ( P = .0014) and 63.6 (5.9) bpm in the pyridostigmine group ( P = .0001). The N-terminal pro-B-type natriuretic peptide was reduced in the ivabradine group (median: 1308.4 [interquartile range: 731-1896] vs 755.8 [134.5-1014] pg/mL; P = .027) and in the pyridostigmine group (132.8 [89.9-829] vs 100.7 [38-360] pg/mL; P = .002). Inflammatory markers interleukin-1, interleukin-6, and tumor necrosis factor were reduced in both groups. Exercise capacity was improved in both groups, with increments in volume of oxygen utilization ([Formula: see text]O2; ivabradine: 13.1 vs 15.6, P = .048; pyridostigmine: 13.3 vs 16.7, P = .032). Heart rate recovery in the first minute postexercise was improved with pyridostigmine (11.8 [3.9] vs 18 [6.5]; P = .046), but not with ivabradine (13.3 [6.9] vs 14.1 [8.2]; P = .70). No differences in either group were observed in the myocardial scintigraphy with 123-iodine-metaiodobenzylguanidine. Conclusion: Both drugs significantly reduced HR, with improvements in exercise capacity and in neurohormonal and inflammatory profiles.

Adenosine deaminase (ADA) and cytokeratin 19 (CK19) are known pleural biomarkers. Although ADA in humans functions mainly in the immune system, it also appears to be associated with the differentiation of epithelial cells. Keratin filaments are important structural stabilizers of epithelial cells and potent biomarkers in epithelial differentiation. This study aimed to investigate the simultaneous presence of the ADA enzyme and CK19 fragments to assess epithelial differentiation in malignant and benign pleural fluids. Diagnosis of the cause of pleural effusion syndrome was confirmed by means of standard examinations and appropriate surgical procedures. An ADA assay, in which ADA irreversibly catalyzes the conversion of adenosine into inosine, was performed using a commercial kit. The CK19 assay was performed using a CYFRA 21-1 kit, developed to detect quantitative soluble fragments of CK19 using an electrochemiluminescence immunoassay. One hundred nineteen pleural fluid samples were collected from untreated individuals with pleural effusion syndrome due to several causes. ADA levels only correlated with CK19 fragments in adenocarcinomas, with high significance and good correlation (rho = 0.5145, P=0.0036). However, further studies are required to understand this strong association on epithelial differentiation in metastatic pleural fluids from adenocarcinomas.

Introduction: The nutritional profile of the Brazilian population has changed in recent years. Therefore, this study aimed to assess the prevalence of nutritional status among Brazilian school adolescents during the period from January 2014 to December 2014. Methods: This study employed an observational design with a cohort of school adolescents. Anthropometric measurement was assessed by nutritionists in government schools. The cut-off points for body mass index according to Brazilian criteria for adolescents of both sexes between 10 years and 19 years old were underweight (≤17.5 kg/m2), overweigh (≥25.0 kg/m2), and obesity (≥30.0 kg/m2). Results: The number of students included in the analysis was 2162, of which 71.0% were males and 29% were females (P = 0.00001). The mean age (years) was 13.14 ± 2.17 for boys and 12.66 ± 1.85 for girls (P = 0.0001). The prevalence of underweight, overweight, and obesity observed in our population of school adolescents according to the Brazilian criteria was 2.8%, 8.1%, and 2.4% for males, respectively, and 23.0%, 10.7%, and 3.6% for females, respectively. For both sexes, there was no statistically significant difference between overweight (P = 0.5469) and obesity (P = 0.7863), but there was for underweight (P = 0.001). Conclusions: The occurrence of excess weight among Brazilian school adolescents is similar to the international prevalence, but the prevalence of underweight was very high among girls. The nutritional status of adolescents must be considered a public health problem in Brazil.

This study aimed at analyzing circulating levels of inflammatory and profibrogenic cytokines in patients with hepatitis C virus (HCV) chronic infection undergoing therapy with direct-acting antiviral agents (DAA) and correlating these immune biomarkers with liver disease status. We studied 88 Brazilian monoinfected chronic hepatitis C patients receiving interferon- (IFN-) free sofosbuvir-based regimens for 12 or 24 weeks, followed-up before therapy initiation and three months after the end of treatment. Liver disease was determined by transient elastography, in addition to APRI and FIB-4 indexes. Analysis of 30 immune mediators was carried out by multiplex or enzymatic immunoassays. Sustained virological response rate was 98.9%. Serum levels of cytokines were increased in HCV-infected patients when compared to control group. CCL-2, CCL-3, CCL-4, CXCL-8, CXCL-10, IL-1β, IL-15, IFN-γ, IL-4, IL-10, TGF-β, FGFb, and PAI-1 decreased significantly after antiviral therapy, reaching values similar to noninfected controls. TGF-βand suPAR levels were associated with fibrosis/cirrhosis. Also, we observed amelioration in hepatic parameters after DAA treatment. Together, our results suggest that viral control induced by IFN-free DAA therapy restores inflammatory mediators in association with improvement in liver function.

Introduction: Various studies have indicated an association between modifi cation in dietary macronutrient composition and liver apoptosis. Objective: To explain how changes in metabolic pathways associated with a high-protein, high-fat, and low-carbohydrate diet causes liver apoptosis. Methods: Two groups of rats were compared. An experimental diet group (n = 8) using a high-protein (59.46%), high-fat (31.77%), and low-carbohydrate (8.77%) diet versus a control one (n = 9) with American Institute of Nutrition (AIN)-93-M diet. Animals were sacrificed after eight weeks, the adipose tissue weighed, the liver removed for flow cytometry analysis, and blood collected to measure glucose, insulin, glucagon, IL-6, TNF, triglycerides, malondialdehyde, and β-hydroxybutyrate. Statistical analysis was carried out using the unpaired and parametric Student’s t-test and Pearson’s correlation coeffi ents. Significance was set at p < 0.05. Results: Animals from the experimental group presented less adipose tissue than dose of the control group. Percentage of nonviable hepatocytes in the experimental group was 2.18 times larger than the control group (p = 0.001). No statistically significant differences were found in capillary glucose, insulin, glucagon, IL-6, or TNF-α between two groups. Plasmatic β-hydroxybutyrate and malondialdehyde of the experimental group expressed higher levels and triglycerides lower levels compared with the control group. The results show a positive and significant correlation between the percentage of nonviable hepatocytes and malondialdehyde levels (p = 0.0217) and a statistically significant negative correlation with triglycerides levels (p = 0.006). Conclusion: Results suggest that plasmatic malondialdehyde and triglyceride levels are probably good predictors of liver damage associated with an experimental low-carbohydrate diet in rats.

To determine whether high-protein, high-fat, and low-carbohydrate diets can cause lesions in rat livers.We randomly divided 20 female Wistar rats into a control diet group and an experimental diet group. Animals in the control group received an AIN-93M diet, and animals in the experimental group received an Atkins-based diet (59.46% protein, 31.77% fat, and 8.77% carbohydrate). After 8 wk, the rats were anesthetized and exsanguinated for transaminases analysis, and their livers were removed for flow cytometry, immunohistochemistry, and light microscopy studies. We expressed the data as mean ± standard deviation (SD) assuming unpaired and parametric data; we analyzed differences using the Student's t-test. Statistical significance was set at P0.05.We found that plasma alanine aminotransferase and aspartate aminotransferase levels were significantly higher in the experimental group than in the control group. According to flow cytometry, the percentages of nonviable cells were 11.67% ± 1.12% for early apoptosis, 12.07% ± 1.11% for late apoptosis, and 7.11% ± 0.44% for non-apoptotic death in the experimental diet group and 3.73% ± 0.50% for early apoptosis, 5.67% ± 0.72% for late apoptosis, and 3.82% ± 0.28% for non-apoptotic death in the control diet group. The mean percentage of early apoptosis was higher in the experimental diet group than in the control diet group. Immunohistochemistry for autophagy was negative in both groups. Sinusoidal dilation around the central vein and small hepatocytes was only observed in the experimental diet group, and fibrosis was not identified by hematoxylin-eosin or Trichrome Masson staining in either group.Eight weeks of an experimental diet resulted in cellular and histopathological lesions in rat livers. Apoptosis was our principal finding; elevated plasma transaminases demonstrate hepatic lesions.

We have previously shown in in vivo experiments that adipose tissue glyceroneogenesis is increased in rats adapted to a high-protein, carbohydrate-free (HP) diet. The objectives of the present study were (1) to verify if the increased glyceroneogenic activity is also observed in isolated adipocytes and (2) to investigate the role of preformed fatty acids in the production of the increased adipose tissue glyceroneogenesis. Control rats received a balanced diet, with the same lipid content of the HP diet. Glyceroneogenic activity was found to be higher in adipocytes from HP rats than in controls, as evidenced by increased rates of conversion of pyruvate and lactate to triacylglycerol (TAG)-glycerol. Administration of Triton WR 1339, which blocks the removal of TAG incorporated into circulating lipoproteins, to HP diet–adapted rats caused a significant reduction in the incorporation of 14 C-pyruvate into TAG-glycerol by adipose tissue, which was accompanied by a marked inhibition of phosphoenolpyruvate carboxykinase activity, the key enzyme of glyceroneogenesis. The inhibitory effect of Triton on TAG-glycerol synthesis by adipose tissue was also observed in vivo, after administration of 3 H 2 O. Adaptation to the HP diet induced a marked increase in the activity of retroperitoneal and epididymal fat LPL, which was restored to control values 24 hours after replacement of the HP diet by the balanced diet. The data suggest that in rats adapted to a carbohydrate-free diet, adipose tissue glyceroneogenesis is activated by an increased use of diet-derived fatty acids.

International audience; Diabetes mellitus is a chronic disease that affects over 382 million people worldwide. Type-1 Diabetes (T1D) is classified as an autoimmune disease that results from pancreatic beta-cell destruction and insulin deficiency. Type-2 Diabetes (T2D) is characterized principally by insulin resistance in target tissues followed by decreased insulin production due to beta-cell failure. It is challenging to identify immunological markers such as inflammatory molecules that are triggered in response to changes during the pathogenesis of diabetes. APRIL is an important member of the TNF family and has been linked to chronic inflammatory processes of various diseases since its discovery in 1998. Therefore, this study aimed to evaluate APRIL serum levels in T1D and T2D. For this, we used the ELISA assay to measure serum APRIL levels of 33 T1D and 30 T2D patients, and non-diabetic subjects as control group. Our data showed a decrease in serum APRIL levels in T1D patients when compared with healthy individuals. The same pattern was observed in the group of T2D patients when compared with the control. The decrease of serum APRIL levels in diabetic patients suggests that this cytokine has a role in T1D and T2D. Diabetes is already considered as an inflammatory condition with different cytokines being implicated in its physiopathology. Our data suggest that APRIL can be considered as a potential modulating cytokine in the inflammatory process of diabetes.

Although the conversion of lactate to glycogen (glyconeogenesis) in muscle was demonstrated a long time ago, the biochemical reactions responsible for this process are still a controversial matter. In the present study, advantage was taken from the specific inhibition induced by phenylalanine on muscle pyruvate kinase (PK) to investigate the role of reverse PK activity in muscle glyconeogenesis. Addition of phenylalanine to the incubation medium of a preparation of isolated, intact skeletal muscles that maintain metabolic activity for several hours reduced by 50% the rate of incorporation of [14C]lactate or [14C]bicarbonate into muscle glycogen. Muscle extracts presented high levels of maximal activity of PK in the reverse direction, which was completely blocked in the presence of phenylalanine. In contrast, mercaptopicolinic acid, an inhibitor of phosphoenolpyruvate carboxykinase (PEPCK), did not affect the incorporation of14C from either lactate or bicarbonate into muscle glycogen. Maximal PEPCK activity was much lower in muscle extracts than in gluconeogenic or glyceroneogenic tissues and was suppressed in the presence of mercaptopicolinic acid. The data suggest that a reversal of the metabolic flux through the reaction catalyzed by PK contributes to the accumulation of lactate-derived glycogen that occurs in skeletal muscle under certain physiological conditions.Key words: lactate, glyconeogenesis, skeletal muscle, reverse pyruvate kinase reaction, phenylalanine.

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of kidney injury. We sought to assess the prognostic value of this biomarker in patients with stable chronic heart failure (HF). Methods: We studied 61 patients with chronic systolic HF who had been receiving optimal medical treatment for at least six months. Biomarkers were measured at baseline and included plasma NGAL, microalbuminuria, serum creatinine, and B-type natriuretic peptide (BNP). Estimated glomerular filtration rate (eGFR) was also calculated. Mean follow-up was 10.6±6.6 months. The primary endpoint was time to first cardiovascular event, defined as a combination of cardiovascular death, HF hospitalization or emergency department visit due to HF. Variables independently related to events were determined using a Cox proportional hazards model. Results: Fifteen (24.6%) patients reached the primary endpoint. Patients with events were more likely to have worse renal function at baseline and also higher NGAL levels (median 316 [interquartile range 122–705] vs. 107 [78–170]; p=0.006). NGAL correlated significantly with creatinine (r=0.50; p

Intravenous (IV) administration of angiotensin II (0.95 nmol/100 g body weight) produced a marked increase in plasma glucose of 20 h fasted rats. To investigate the possibility of a stimulation of gluconeogenesis, conscious unrestrained rats were continuously infused with [14C]bicarbonate, 60 microl/min (0.18 microCi/min), and label incorporation into circulating glucose was determined before and after angiotensin injection. The rate of 14C incorporation into blood glucose of fed rats increased significantly after angiotensin II administration, a 279% increase after 20 min (P < 0.01). In conclusion, the results of the present study show that the hyperglycemia induced by intravenous (IV) administration of angiotensin II is accompanied by an activation of gluconeogenesis, as evidenced by a rapid and marked increase in the rate of 14CO2 incorporation into circulating glucose.

A doença pulmonar obstrutiva crônica (DPOC) caracteriza-se por persistente e geralmente progressiva limitação do fluxo de ar associada com uma resposta inflamatória crônica nas vias aéreas e pulmões em resposta a partículas ou gases nocivos. A prescrição de medicamentos como os antimuscarínicos é um item importante para a reabilitação pulmonar em pacientes com DPOC porque melhoram os sintomas, particularmente a dispneia e a capacidade de fazer as atividades diárias. Há evidências de alguns estudos de que também reduzam a tendência a exacerbações. Não há evidências de que broncodilatadores reduzam complicações sistêmicas, comorbidades ou tenham influência sobre a mortalidade.

INTRODUCAO: O figado e uma estrutura de elevada complexidade e e fundamental entender como determinadas substâncias podem afetar sua estrutura e suas funcoes. OBJETIVO: Analisar a influencia da tibolona no metabolismo hepatico por meio da avaliacao de enzimas e metabolitos comumente utilizados em provas de funcao hepatica. METODOS: Foram utilizadas dez ratas Wistar, divididas em dois grupos: controle (n = 4) e tibolona (n = 6), em status de menopausa cirurgica. A tibolona (1 mg) foi administrada diariamente por gavagem durante 20 semanas, com avaliacao periodica do peso corporal. Apos sedacao, efetuou-se coleta de sangue para avaliacao bioquimica de albumina (Alb) serica, fosfatase alcalina (FA), transaminases (aspartato aminotransferase e alanina aminotransferase [AST/ALT]), gama-glutamiltranspeptidase (GGT) e glicose, mediante espectrofotometria. O musculo esqueletico da coxa foi avaliado por histomorfometria em cortes histologicos corados com hematoxilina e eosina (HE). RESULTADOS: Os animais do grupo tibolona mostraram menor peso corporal, alteracoes musculares esqueleticas e discretas alteracoes bioquimicas. Alem disso, AST e FA estavam diminuidas e GGT estava mais elevada, porem sem significância estatistica. A histomorfometria do musculo revelou uma tendencia de menor volume celular nesse grupo. CONCLUSAO: A tibolona, administrada em alta dose e por tempo prolongado, nao interfere de forma significativa nas funcoes metabolicas e de sintese hepaticas, bem como na permeabilidade da membrana celular, entretanto parece modular a expressao genomica da GGT. A tibolona apresenta influencia sistemica associada a menor peso e diminuicao da massa muscular e aumento significativo no peso relativo do figado, alem de alteracao da glicogenolise hepatica e muscular, da gliconeogenese hepatica e dos niveis de glicose circulante.

To investigate the effects of prolonged dietary sodium restriction on lipid metabolism, male rats weighing 35 to 40 g (just weaned) were fed either a low-salt (LSD) or a normal salt diet (NSD) and used in metabolic experiments after 1, 2, or 3 months of diet consumption. After 2 and 3 months on the diet, LSD rats showed increased amounts of lipid in carcass and retroperitoneal tissue. In both LSD and NSD, extending the feeding period from 2 to 3 months resulted in a marked reduction in the in vivo rates of adipose tissue fatty acid synthesis that was accompanied by increases in liver lipogenesis and in the activity of adipose tissue lipoprotein lipase (LPL). However, these increases were more marked in LSD rats. Thus, in vivo rates of liver fatty synthesis and LPL activity in LSD rats, which were already higher (by about 35% and 20%, respectively) than in controls after 2 months, attained levels 50% higher than those in NSD animals after another month on the diet. Brown adipose tissue (BAT) thermogenic capacity, estimated after 2 and 3 months by the tissue temperature response to norepinephrine (NE) injection and by guanosine diphosphate (GDP) binding to BAT mitochondria, did not change in controls, but was significantly reduced in LSD rats. This raises the possibility that a decrease in overall energy expenditure, together with an LPL-induced increased uptake of preformed fatty acids from the circulation, may account for the excessive lipid accumulation in LSD rats. Taken together, the data indicate that prolonged dietary sodium restriction exacerbates normal, age-related changes in white and BAT metabolism.

COVID-19 is a highly contagious disease caused by the coronavirus of severe acute respiratory syndrome 2 (SARS-CoV-2). In 2020, due to the outbreak, it was considered by the World Health Organization (WHO) as a pandemic. The infection caused by the novel coronavirus has high mortality in a small portion of the infected population, especially in elderly, immunosuppressed, diabetic, cardiac, and hypertensive individuals. Many infected are asymptomatic (and may be carriers) or present mild or moderate flu-like symptoms. The most severe clinical picture of COVID-19 is characterized by an inflammatory cytokine storm, with hematological changes and coagulation dysfunction, which can lead to tissue damage and death. Nonspecific laboratory biomarkers may be either increased or decreased as the course of the disease progresses and are often useful in predicting complications of the disease, such as the use of D-dimer and platelet/lymphocyte ratio. Specific laboratory diagnosis is based on the detection of viral ribonucleic acid (RNA) by real-time polymerase chain reaction (RT-PCR) of nasal and oropharyngeal swab samples; it is more effective when performed in the first days after symptom onset. Serological tests are useful in detecting the immune response, since both class M (IgM) and class G (IgG) immunoglobulin antibodies can be detected seven days after the onset of clinical symptoms, and may extend for more than 25 days, although not exempting the individual from remaining infectious, depending on their viral load and clinical presentation. The rational use of specific laboratory markers must respect the disease chronology, and the correct interpretation may provide subsidies for a better management of affected patients, as well as identifying asymptomatic carriers or those with mild symptoms.