Effect of tibolone on the morphology of skeletal muscle, liver enzymes and blood glucose level in castrated female rats

INTRODUÇÃO: O fígado é uma estrutura de elevada complexidade e é fundamental entender como determinadas substâncias podem afetar sua estrutura e suas funções. OBJETIVO: Analisar a influência da tibolona no metabolismo hepático por meio da avaliação de enzimas e metabólitos comumente utilizados em provas de função hepática. MÉTODOS: Foram utilizadas dez ratas Wistar, divididas em dois grupos: controle (n = 4) e tibolona (n = 6), em status de menopausa cirúrgica. A tibolona (1 mg) foi administrada diariamente por gavagem durante 20 semanas, com avaliação periódica do peso corporal. Após sedação, efetuou-se coleta de sangue para avaliação bioquímica de albumina (Alb) sérica, fosfatase alcalina (FA), transaminases (aspartato aminotransferase e alanina aminotransferase [AST/ALT]), gama-glutamiltranspeptidase (GGT) e glicose, mediante espectrofotometria. O músculo esquelético da coxa foi avaliado por histomorfometria em cortes histológicos corados com hematoxilina e eosina (HE). RESULTADOS: Os animais do grupo tibolona mostraram menor peso corporal, alterações musculares esqueléticas e discretas alterações bioquímicas. Além disso, AST e FA estavam diminuídas e GGT estava mais elevada, porém sem significância estatística. A histomorfometria do músculo revelou uma tendência de menor volume celular nesse grupo. CONCLUSÃO: A tibolona, administrada em alta dose e por tempo prolongado, não interfere de forma significativa nas funções metabólicas e de síntese hepáticas, bem como na permeabilidade da membrana celular, entretanto parece modular a expressão genômica da GGT. A tibolona apresenta influência sistêmica associada a menor peso e diminuição da massa muscular e aumento significativo no peso relativo do fígado, além de alteração da glicogenólise hepática e muscular, da gliconeogênese hepática e dos níveis de glicose circulante

Muscarinic receptors and chronic obstructive pulmonary disease: From Biology to clinical practice

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.The chronic obstructive pulmonary disease (COPD) is characterized by persistent and often progressive airflow limitation associated with a chronic severe inflammatory response in the airways and lungs in response to noxious particles or gases. The prescription of drugs such a muscarinic antagonist is an important step for pulmonary rehabilitation in patients with COPD because they improve symptoms, particularly dyspnea and the ability to do daily activities. There is evidence of some studies also tend to reduce exacerbations. There is no evidence that bronchodilators reduce systemic complications, comorbidities or have influence on mortality

Lead Toxicity Risks in Gunshot Victims

<div><p>Background</p><p>Gunshot wounds require surgeons to decide whether to remove or leave bullet fragments in the body. Surgeons also decide how to follow up with patients who have lead fragments retained in their body. Current literature recommends to remove only intra-articular fragments without the need for a follow-up for patients with the metal retained. Therefore, this study investigates chronic lead toxicity for gunshot wounds.</p><p>Methods</p><p>The study was performed in the metropolitan area of Rio de Janeiro/Brazil, between 2013 and 2015. It was a case-control study that included 45 victims of gunshot lesions with metallic fragments retained for more than 6 months. The 45 controls were matched for gender, age, and race. We compared the lead blood levels and frequency of symptoms.</p><p>Results</p><p>The control group had average blood lead levels of 2.17 μg/dL (95% Confidence Interval [CI]; 1.71–2.63) and median 2.1 μg/dL. The case group had average values of 9.01 μg/dL (CI; 6.07–11.96) and median values of 6.5 μg/dL with p-values < = 0.001. The case group reported the following more frequently: irritancy, bad mood, headache, memory losses, daylight drowsiness, myalgia, weakness, abdominal pain, joint pain, trembling, tingling limbs. There was statistical significance for the differences of symptoms frequencies and for odds ratio between groups.</p><p>Conclusions</p><p>Although the mean lead levels found were lower than the current laboratory references, low levels have been associated with both rising morbidity and mortality. The WHO stated: “There is no known level of lead exposure that is considered safe”. In conclusion, this work showed that bullets retained in the body are not innocuous. There are impacts in the blood lead levels and symptoms related to it, even with few fragments, extra-articular located or existing with low blood lead levels.</p></div

A box plot to represent the samples distribution for blood lead levels.

<p>A box plot to represent the samples distribution for blood lead levels.</p

Exploring Urinary Extracellular Vesicles and Immune Mediators as Biomarkers of Kidney Injury in COVID-19 Hospitalized Patients

Kidney injury is an important outcome associated with COVID-19 severity. In this regard, alterations in urinary extracellular vesicles (uEVs) could be detected in the early phases of renal injury and may be reflective of the inflammatory process. This is an observational study performed with a case series of COVID-19 hospitalized patients presenting mild-to-critical disease. Total and podocyte-derived uEVs were identified by nanoscale flow cytometry, and urinary immune mediators were assessed by a multiplex assay. We studied 36 patients, where 24 (66.7%) were considered as mild/moderate and 12 (33.3%) as severe/critical. Increased levels of total uEVs were observed (p = 0.0001). Importantly, total uEVs were significantly higher in severe/critical patients who underwent hemodialysis (p = 0.03) and were able to predict this clinical outcome (AUC 0.93, p = 0.02). Severe/critical patients also presented elevated urinary levels (p < 0.05) of IL-1β, IL-4, IL-6, IL-7, IL-16, IL-17A, LIF, CCL-2, CCL-3, CCL-11, CXCL-10, FGFb, M-CSF, and CTAcK. Lastly, we observed that total uEVs were associated with urinary immune mediators. In conclusion, our results show that early alterations in urinary EVs could identify patients at higher risk of developing renal dysfunction in COVID-19. This could also be relevant in different scenarios of systemic and/or infectious disease

Associations of symptoms and the presence of bullets retained.

<p>* <b>Fisher exact test.</b></p><p>Associations of symptoms and the presence of bullets retained.</p

Examples of volunteers with different number of bullets fragments retained and their respective blood lead levels.

<p>Examples of volunteers with different number of bullets fragments retained and their respective blood lead levels.</p

Descriptive statistics for blood lead levels (μg/dL).

<p>Descriptive statistics for blood lead levels (μg/dL).</p

Restoring Inflammatory Mediator Balance after Sofosbuvir-Induced Viral Clearance in Patients with Chronic Hepatitis C

Submitted by Sandra Infurna ([email protected]) on 2019-01-29T15:33:38Z No. of bitstreams: 1 elizinandesL_azevedo_etal_IOC_2018.pdf: 2422118 bytes, checksum: 5e9a8f1bae99ba96aec2c59a137893df (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-01-29T15:46:12Z (GMT) No. of bitstreams: 1 elizinandesL_azevedo_etal_IOC_2018.pdf: 2422118 bytes, checksum: 5e9a8f1bae99ba96aec2c59a137893df (MD5)Made available in DSpace on 2019-01-29T15:46:12Z (GMT). No. of bitstreams: 1 elizinandesL_azevedo_etal_IOC_2018.pdf: 2422118 bytes, checksum: 5e9a8f1bae99ba96aec2c59a137893df (MD5) Previous issue date: 2018Universidade Federal Fluminense. Hospital Universitário Antônio Pedro. Faculdade de Medicina. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas. Niterói, RJ, Brasil.Universidade Federal Fluminense. Hospital Universitário Antônio Pedro. Faculdade de Medicina. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas. Niterói, RJ, Brasil.Universidade Federal Fluminense. Hospital Universitário Antônio Pedro. Faculdade de Medicina. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas. Niterói, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Ultraestrutura Celular Hertha Meyer. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Hospital Universitário Antônio Pedro. Faculdade de Medicina. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas. Niterói, RJ, Brasil / Universidade Federal Fluminense. Faculdade de Medicina. Departamento de Patologia. Niterói, RJ, Brasil.Universidade Federal Fluminense. Faculdade de Medicina. Departamento de Medicina Clínica. Serviço de Gastroenterologia. Centro de Referência de Tratamento em Hepatites/HUAP. Niterói, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ. Brasil.Université de Montréal. Centre de Recherche du CHUM. Department of Microbiology, Infectiology and Immunology. Montreal, Canada.Universidade Federal Fluminense. Hospital Universitário Antônio Pedro. Faculdade de Medicina. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas. Niterói, RJ, Brasil.Universidade Federal Fluminense. Hospital Universitário Antônio Pedro. Faculdade de Medicina. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas. Niterói, RJ, Brasil / Universidade Federal Fluminense. Faculdade de Medicina. Departamento de Patologia. Niterói, RJ, Brasil..Universidade Federal Fluminense. Hospital Universitário Antônio Pedro. Faculdade de Medicina. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas. Niterói, RJ, Brasil / Universidade Federal Fluminense. Faculdade de Medicina. Departamento de Patologia. Niterói, RJ, Brasil..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-β and 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