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OBJECTIVE: To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19. METHODS: We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1ß, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days. RESULTS: Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1ß. CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19. TRIAL REGISTRATION NUMBERS: RBR-8jyhxh.
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COVID-19 , Inflamassomos , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18 , Proteínas NLR , Colchicina/uso terapêutico , Interleucina-1beta/metabolismoRESUMO
Four bimetallic phases of the thiophosphate family have been synthesized by the cationic exchange reaction using a freshly prepared K0.5Cd0.75PS3 precursor phase and methanolic solutions of nitrates of the divalent cations ZnII, NiII, CoII, and MnII. All the materials were characterized by FTIR, PXRD, SEM-EDXS and (in the case of the diamagnetic compounds) by solid state NMR. For the K0.5Cd0.75PS3 precursor, the X-ray powder diffraction data suggest a modification of the structure, while solid state NMR results confirm that this phase possesses an ordered arrangement of Cd vacancies. The cationic exchange reaction achieves a complete removal of potassium ions (no potassium detected by SEM-EDXS) and re-occupation of the vacancies by divalent cations. Therefore, the obtained compounds have an average composition of M0.25Cd0.75PS3 (M = ZnII, NiII, CoII, MnII) and possess an ordered distribution of the substituent cations. Even with the paramagnetic substitution level of 25%, antiferromagnetic behaviour is present in the phases with MnII, CoII and NiII, as evidenced by dc susceptibility and in the case of the MnII substituted phase by EPR. The cooperative magnetic interactions confirm the conclusion that the paramagnetic ions adopt an ordered arrangement. The analysis by broad band impedance spectroscopy allows to attribute the conductivity in these materials to charge movements in the layers due to the difference in electronegativity of the metal ions. Zn0.25Cd0.75PS3 is the phase that shows the highest conductivity values. Finally, the band gap energies of the bimetallic phases tend to be lower than those of the single-metal phases, probably due to an overlap of the band structures.
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In this work the magnetic properties of bimetallic phases M'0.2Mn0.8PS3·0.25H2O (M' = CoII, NiII, CuII or ZnII) have been explored and compared with those of the pristine phase MnPS3. Magnetic susceptibility, high field magnetization and electron paramagnetic resonance (EPR) studies reveal that the transition temperature between the antiferromagnetic and paramagnetic order for the pristine phase is shifted to lower values in the bimetallic phases. From magnetization measurements the critical field of the spin-flop transition is found to be dependent on the nature of the added secondary transition metal ion. EPR spectra of all compounds in the temperature range of 8-300 K present a single resonance line shape. Temperature dependence of the EPR parameters, like line width, g values and double integrated area (IDIN), are obtained from the spectra and present a scenario compatible with the magnetization results. The temperature dependence of the first derivative of the product (IDINT) shows two maxima for all samples, with exception of the CoII phase, indicating two critical temperatures, while these critical temperatures could not be clearly determined by dc susceptibility.
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Actinobacteria are known to produce various secondary metabolites having antibiotic effects. This study assessed the antimicrobial potential of actinobacteria isolated from the rhizosphere of Caesalpinia pyramidalis Tul. from the Caatinga biome. Sixty-eight actinobacteria isolates were evaluated for antimicrobial activity against different microorganisms by disk diffusion and submerged fermentation, using different culture media, followed by determination of minimum inhibitory concentration (MIC) and chemical prospecting of the crude extract. Of the isolates studied, 52.9% of those isolated at 37°C and 47.05% of those isolated at 45°C had activity against Bacillus subtilis, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Fusarium moniliforme, and Candida albicans. When compared with others actinobacteria, the isolate C1.129 stood out with better activity and was identified by 16S rDNA gene analysis as Streptomyces parvulus. The crude ethanol extract showed an MIC of 0.97 µg/mL for MRSA and B. subtilis, while the ethyl acetate extract showed MIC of 3.9 µg/mL for S. aureus and MRSA, showing the greatest potential among the metabolites produced. Chemical prospecting revealed the presence of mono/sesquiterpenes, proanthocyanidin, triterpenes, and steroids in both crude extracts. This study evaluates S. parvulus activity against multi-resistant microorganisms such as MRSA. Thus, it proves that low-fertility soil, as is found in the Caatinga, may contain important microorganisms for the development of new antimicrobial drugs.
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Actinobacteria/metabolismo , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Produtos Biológicos/farmacologia , Caesalpinia/microbiologia , Rizosfera , Actinobacteria/genética , Actinobacteria/isolamento & purificação , Antibacterianos/química , Antifúngicos/química , Bacillus subtilis/efeitos dos fármacos , Produtos Biológicos/química , Candida albicans/efeitos dos fármacos , Fusarium/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Filogenia , Staphylococcus aureus/efeitos dos fármacosRESUMO
Subjects with chronic liver disease are susceptible to hypovitaminosis A due to several factors. Therefore, identifying patients with vitamin deficiency and a requirement for vitamin supplementation is important. Most studies assessing vitamin A in the context of hepatic disorders are conducted using cirrhotic patients. A cross-sectional study was conducted in 43 non-cirrhotic patients with chronic hepatitis C to evaluate markers of vitamin A status represented by serum retinol, liver retinol, and serum retinol-binding protein levels. We also performed the relative dose-response test, which provides an indirect estimate of hepatic vitamin A reserves. These vitamin A indicators were assessed according to the stage of liver fibrosis using the METAVIR score and the body mass index. The sample study was predominantly composed of male subjects (63%) with mild liver fibrosis (F1). The relative dose-response test was <20% in all subjects, indicating vitamin A sufficiency. Overweight or obese patients had higher serum retinol levels than those with a normal body mass index (2.6 and 1.9 µmol/L, respectively; P<0.01). Subjects with moderate liver fibrosis (F2) showed lower levels of serum retinol (1.9 vs 2.5 µmol/L, P=0.01) and retinol-binding protein levels compared with those with mild fibrosis (F1) (46.3 vs 67.7 µg/mL, P<0.01). These results suggested an effect of being overweight on serum retinol levels. Furthermore, more advanced stages of liver fibrosis were related to a decrease in serum vitamin A levels.
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Hepatite C Crônica/complicações , Deficiência de Vitamina A/diagnóstico , Vitamina A/análise , Adulto , Idoso , Biomarcadores/análise , Biópsia , Índice de Massa Corporal , Estudos Transversais , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Feminino , Humanos , Fígado/química , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Sobrepeso/sangue , Proteínas de Ligação ao Retinol/análise , Deficiência de Vitamina A/complicações , Adulto JovemRESUMO
Subjects with chronic liver disease are susceptible to hypovitaminosis A due to several factors. Therefore, identifying patients with vitamin deficiency and a requirement for vitamin supplementation is important. Most studies assessing vitamin A in the context of hepatic disorders are conducted using cirrhotic patients. A cross-sectional study was conducted in 43 non-cirrhotic patients with chronic hepatitis C to evaluate markers of vitamin A status represented by serum retinol, liver retinol, and serum retinol-binding protein levels. We also performed the relative dose-response test, which provides an indirect estimate of hepatic vitamin A reserves. These vitamin A indicators were assessed according to the stage of liver fibrosis using the METAVIR score and the body mass index. The sample study was predominantly composed of male subjects (63%) with mild liver fibrosis (F1). The relative dose-response test was <20% in all subjects, indicating vitamin A sufficiency. Overweight or obese patients had higher serum retinol levels than those with a normal body mass index (2.6 and 1.9 µmol/L, respectively; P<0.01). Subjects with moderate liver fibrosis (F2) showed lower levels of serum retinol (1.9 vs 2.5 µmol/L, P=0.01) and retinol-binding protein levels compared with those with mild fibrosis (F1) (46.3 vs 67.7 µg/mL, P<0.01). These results suggested an effect of being overweight on serum retinol levels. Furthermore, more advanced stages of liver fibrosis were related to a decrease in serum vitamin A levels.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Hepatite C Crônica/complicações , Deficiência de Vitamina A/diagnóstico , Vitamina A/análise , Biópsia , Índice de Massa Corporal , Biomarcadores/análise , Estudos Transversais , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Cirrose Hepática/patologia , Fígado/química , Escores de Disfunção Orgânica , Sobrepeso/sangue , Proteínas de Ligação ao Retinol/análise , Deficiência de Vitamina A/complicaçõesRESUMO
The emergence of ganciclovir (GCV) resistance during the treatment of human cytomegalovirus (HCMV) infection is a serious clinical challenge, and is associated with high morbidity and mortality. In this case report, we describe the emergence of two consecutive mutations (A594V and L595W) related to GCV resistance in a patient with HCMV retinitis and long-term HIV progression after approximately 240 days of GCV use. Following the diagnosis of retinitis, the introduction of GCV did not result in viral load reduction. The detected mutations appeared late in the treatment, and we propose that other factors (high initial HCMV load, previous GCV exposure, low CD4+ cell count), in addition to the presence of resistance mutations, may have contributed to the treatment failure of HCMV infection in this patient.
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Infecções Oportunistas Relacionadas com a AIDS/genética , Antivirais/uso terapêutico , Retinite por Citomegalovirus/genética , Farmacorresistência Viral/genética , Ganciclovir/uso terapêutico , Mutação , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/virologia , Retinite por Citomegalovirus/tratamento farmacológico , DNA Viral/genética , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Falha de Tratamento , Carga Viral/efeitos dos fármacosRESUMO
O objetivo deste estudo foi relatar um caso de ocorrência de brucelose em um equino manejado juntamente com bovinos em uma propriedade rural na região de Fernandópolis, São Paulo. O animal era uma fêmea, de raça meio-sangue quarto-de-milha, com idade de 4 anos, e manejado juntamente com 40 bovinos destinados à produção de leite e carne, em uma propriedade rural, cuja vacinação contra brucelose em bezerras (3 a 8 meses de idade) e o diagnóstico sorológico desta enfermidade em bovinos adultos não eram realizados na rotina. Ao realizar o exame físico, evidenciou-se a presença de abscesso de cernelha fistulado pelo qual se drenava secreção seropurulenta em moderada quantidade, osteoartrite nos membros pélvicos (jarretes), apresentando relutância ao esforço físico e exaustão, além de infertilidade. Amostras de sangue, sem anticoagulante, foram obtidas através da punção da veia jugular e encaminhadas a um laboratório credenciado para proceder à prova do antígeno acidificado tamponado. O equino obteve resultado positivo ao exame sorológico e os sinais clínicos foram considerados como achados importantes no processo diagnóstico. O proprietário foi informado da importância de sacrificar o animal, seguindo recomendações do Programa Nacional de Controle e Erradicação da Brucelose e da Tuberculose Animal. A transmissão da brucelose equina pode ter ocorrido principalmente pela ingestão de á
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Este trabalho objetivou traçar o nível endêmico de perdas reprodutivas e determinar a positividade para quatro agentes infecciosos relacionados com problemas reprodutivos em um rebanho bovino leiteiro no município de São Carlos-SP. Foram coletadas amostras de soro sanguíneo de 142 animais em reprodução com idades acima de dois anos, dos quais 21,1% apresentaram casos de abortamentos ou natimortos em pelo menos uma gestação. Utilizaram-se os testes sorológicos de imunofluorescência indireta, teste do antígeno acidificado tamponado, virusneutralização e soroaglutinação microscópica, virusneutralizaçãopara detecção de anticorpos anti-Neospora caninum, anti-Brucella abortus, anti-Herpesvírus Bovino Tipo-1(BoHV-1) e anti-Leptospira spp, respectivamente. Os exames sorológicos realizados demonstraram que 28,9% dos animais apresentaram títulos superiores ou iguais a 100 de anticorpos anti-Neospora caninum. Os exames de virusneutralização demonstraram que 26,8% dos animais apresentaram títulos maiores ou iguais a 256 para anticorpos anti-BoHV-1. Apenas 7,7% dos animais estudados apresentaram títulos iguais ou superiores a 100 na soroaglutinação microscópica para diagnóstico de Leptospira spp. Não foram observadas reações positivas ao teste de antígeno acidificado tamponado para diagnóstico de brucelose bovina. O estudo realizado sugere a presença de BoHV-1, N. caninum e Leptospira spp em contato com os animais leiteiros da unidade experimental, podendo estar envolvidos na ocorrência de abortamentos e natimortos no rebanho. As perdas reprodutivas encontram-se de forma endêmica, implicando um possível comportamento crônico das infecções causadas por estes micro-organismos.(AU)
The aim of this work was draw an endemic level of reproductive losses and determine positivity for four infectious agents related to reproductive problems in dairy cattle on a property in São Carlos city. Blood serum samples were collected of 142 breeding animals more than two years old, from which 21.1% showed history of abortions or stillbirths in at least one pregnancy. Immunofluorescent antibody technique, tamponated acidified antigen test, serum neutralization technique and microscopic agglutination test, were used for detection of antibody anti-Neospora caninum, anti- Brucella abortus, anti-Bovine Herpesvirus Type-1 (BoHV-1) and anti-Leptospira spp , respectively. The serological tests carried out showed that 28.9% of the animals had titers greater than or equal to 100 of anti-Neospora caninum. Viral neutralization tests demonstrated that 26.8% of the animals had titers greater or equal to 256 for antibody anti-BoHV-1.Only 7.7% of the animals studied had titers equal to or greater than 100 in the microscopic agglutination test for Leptospira spp. There werent observed positive reactions to the tamponated acidified antigen test for diagnosis of bovine brucellosis. The study suggests the presence of BoHV-1, N. caninum and Leptospira spp in contact with dairy cattle property and could be involved in the occurrence of abortions and stillbirths in cattle. Reproductive losses are endemic and implies a possible behavior of chronic infections caused by these microorganisms.(AU)