Rapid tranquilization is an intervention used in control of agitation or aggression in patients with mental disorders. This study synthesized the available evidence regarding efficacy and safety of ...drugs used for rapid tranquilization in psychiatric patients with psychomotor agitation. It is an overview study of systematic reviews and meta-analysis of randomized controlled trials (RCT) identified in the database MEDLINE, EMBASE, CINAHL, Web of Science, Cochrane Library and LILACS until April 2015. A team of reviewers, in pairs and independently, identified eligible studies and assessed methodological quality using AMSTAR. Data were extracted from four studies (61 RCT, 8021 participants). The association of haloperidol with promethazine (H + P) promoted tranquilization and presented better safety profile, with moderate quality evidence. Olanzapine demonstrated benefit towards tranquilization and good safety profile, but needed additional administration to keep tranquilization. There was no benefit in the use of haloperidol alone or associated to another psychotropic to most outcomes evaluated. The evidence was of low quality to most of the interventions. H + P was considered a good option for rapid tranquilization, however, more RCT are necessary to confirm the efficacy and safety of the available interventions.
Acute kidney injury (AKI) alters renal hemodynamics, leading to tubular injury, activating pathways of inflammation, proliferation, and cell death. The initial damage caused to renal tissue after an ...ischemia/reperfusion (I/R) injury exerts an important role in the pathogenesis of the course of AKI, as well as in the predisposition to chronic kidney disease. Vitamin D deficiency has been considered a risk factor for kidney disease and it is associated with tubulointerstitial damage, contributing to the progression of kidney disease. Obesity is directly related to diabetes mellitus and hypertension, the main metabolic disorders responsible for the progression of kidney disease. Furthermore, the expansion of adipose tissue is described as an important factor for increased secretion of pro-inflammatory cytokines and their respective influence on the progression of kidney disease. We aimed to investigate the influence of vitamin D deficiency and obesity on the progression of renal disease in a murine model of renal I/R. Male Wistar rats underwent renal I/R surgery on day 45 and followed until day 90 of the protocol. We allocated the animals to four groups according to each diet received: standard (SD), vitamin D-depleted (VDD), high fat (HFD), or high fat vitamin D-depleted (HFDV). At the end of 90 days, we observed almost undetectable levels of vitamin D in the VDD and HFDV groups. In addition, HFD and HFDV groups presented alterations in the anthropometric and metabolic profile. The combination of vitamin D deficiency and obesity contributed to alterations of functional and hemodynamic parameters observed in the HFDV group. Moreover, this combination favored the exacerbation of the inflammatory process and the renal expression of extracellular matrix proteins and phenotypic alteration markers, resulting in an enlargement of the tubulointerstitial compartment. All these changes were associated with an increased renal expression of transforming growth factor β and reduced expression of the vitamin D receptor. Our results show that the synergistic effect of obesity and vitamin D deficiency exacerbated the hemodynamic and morphological changes present in the evolution of renal disease induced by I/R.
Background
Tenofovir disoproxil fumarate (TDF), a widely prescribed component in antiretroviral regimens, has been associated with nephrotoxicity. Nebivolol is a third generation selective β-1 ...adrenergic receptor blocker and may protect renal structure and function through the suppression of oxidative stress and enhancement of nitric oxide (NO) synthesis. We aimed to investigate whether nebivolol could be an effective therapeutic strategy to mitigate tenofovir-induced nephrotoxicity.
Methods
We allocated Wistar rats to four groups: control (C), received a standard diet for 30 days; NBV, received a standard diet for 30 days added with nebivolol (100 mg/kg food) in the last 15 days; TDF, received a standard diet added with tenofovir (300 mg/kg food) for 30 days; and TDF+NBV, received a standard diet added with tenofovir for 30 days and nebivolol in the last 15 days.
Results
Long-term exposure to tenofovir led to impaired renal function, induced hypertension, endothelial dysfunction and oxidative stress. Nebivolol treatment partially recovered glomerular filtration rate, improved renal injury, normalized blood pressure and attenuated renal vasoconstriction. Administration of nebivolol contributed to reductions in asymmetric dimethylarginine (ADMA) levels as well as increases in endothelial nitric oxide sintase (eNOS) accompanied by renin-angiotensin-aldosterone system downregulation and decreases in macrophage and T-cells infiltrate. Furthermore, nebivolol was responsible for the maintenance of the adequate balance of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) levels and it was associated with reductions in NADPH oxidase (NOX) subunits.
Conclusion
Nebivolol holds multifaceted actions that promote an advantageous option to slow the progression of kidney injury in tenofovir-induced nephrotoxicity.
Gut microbiota imbalance is associated with the occurrence of metabolic diseases such as obesity. Thus, its modulation is a promising strategy to restore gut microbiota and improve intestinal health ...in the obese. This paper examines the role of probiotics, antimicrobials, and diet in modulating gut microbiota and improving intestinal health. Accordingly, obesity was induced in C57BL/6J mice, after which they were redistributed and fed with an obesogenic diet (intervention A) or standard AIN-93 diet (intervention B). Concomitantly, all the groups underwent a treatment phase with
LG-G12, ceftriaxone, or ceftriaxone followed by
LG-G12. At the end of the experimental period, the following analysis was conducted: metataxonomic analysis, functional profiling of gut microbiota, intestinal permeability, and caecal concentration of short-chain fatty acids. High-fat diet impaired bacterial diversity/richness, which was counteracted in association with
LG-G12 and the AIN-93 diet. Additionally, SCFA-producing bacteria were negatively correlated with high intestinal permeability parameters, which was further confirmed via functional profile prediction of the gut microbiota. A novel perspective on anti-obesity probiotics is presented by these findings based on the improvement of intestinal health irrespective of undergoing antimicrobial therapy or not.
The need for a more sustainable society has prompted the development of bio-based processes to produce fuels, chemicals, and materials in substitution for fossil-based ones. In this context, ...microorganisms have been employed to convert renewable carbon sources into various products. The methylotrophic yeast Komagataella phaffii has been extensively used in the production of heterologous proteins. More recently, it has been explored as a host organism to produce various chemicals through new metabolic engineering and synthetic biology tools. This review first summarizes Komagataella taxonomy and diversity and then highlights the recent approaches in cell engineering to produce renewable chemicals and proteins. Finally, strategies to optimize and develop new fermentative processes using K. phaffii as a cell factory are presented and discussed. The yeast K. phaffii shows an outstanding performance for renewable chemicals and protein production due to its ability to metabolize different carbon sources and the availability of engineering tools. Indeed, it has been employed in producing alcohols, carboxylic acids, proteins, and other compounds using different carbon sources, including glycerol, glucose, xylose, methanol, and even CO2.
Desde o início da pandemia em 2019, a infecção pelo vírus SARS-CoV-2 em pacientes adultos tem se apresentado de forma multissistêmica. Apesar de o acometimento clássico ser o pulmonar, outras ...manifestações clínicas raras têm sido associadas à infecção, como a síndrome inflamatória multissistêmica no adulto, eventos trombóticos e colangiopatia pós covid-19. Nesse contexto, raríssimos casos de rotura esplênica têm sido reportados como complicação pela COVID-19. O objetivo desse trabalho é relatar um caso de rotura esplênica não traumática em paciente com quadro recente de COVID-19. Paciente masculino 42 anos, sem comorbidades, com relato de dor epigástrica iniciada em repouso após escalada de montanha. Houve piora progressiva da dor, buscando atendimento médico na emergência. Realizada tomografia de abdome com contraste venoso que evidenciou rotura esplênica com laceração de parênquima associado a infarto esplênico. Avaliação da cirurgia geral favorável à conduta conservadora com analgesia e reavaliação ambulatorial quanto à realização da esplenectomia. Em história prévia, paciente relatou exame de swab nasofaríngeo com RT-PCR para SARS-CoV-2 positivo 8 dias antes do início do quadro. Negou trauma local. Painel de sorologias virais para diagnóstico diferencial negativo. Imunofenotipagem de sangue periférico para doenças linfoproliferativas também sem alterações. A rotura esplênica atraumática é uma apresentação rara e potencialmente fatal como complicação na infecção pelo SARS-CoV-2. Embora sua completa fisiopatogenia ainda seja desconhecida, em parte dos poucos casos reportados há a presença de trombose de vasos esplênicos visualizados em tomografia de abdome com contraste. A apresentação clínica dos pacientes geralmente é acompanhada de instabilidade hemodinâmica, com presença de hemoperitôneo, o que justifica a indicação de abordagem cirúrgica de emergência. Dessa maneira, o trabalho mostra a necessidade de atenção ao quadro de dor abdominal na apresentação de pacientes no setor de emergência no contexto epidemiológico atual, especialmente em pacientes sabidamente infectados pelo vírus da COVID-19.
Desde o início da pandemia causada pelo vírus SARS-CoV-2, a síndrome respiratória aguda em adultos se tornou a principal preocupação do quadro clínico no paciente com COVID-19. Com o tempo, as ...nuances acerca da infecção e seu amplo espectro de acometimentos sistêmicos alertaram quanto à possibilidade de surgimento de complicações extrapulmonares igualmente graves em pacientes adultos. Nesse contexto, a síndrome inflamatória multissistêmica em adulto (SIM-A) é definida como complicação inflamatória posterior ao quadro de infecção viral potencialmente fatal em adultos, com acometimento multissistêmico associado a disfunções orgânicas. O objetivo desse trabalho é apresentar um relato de caso de paciente com quadro clássico de SIM-A. Paciente de 23 anos, sexo masculino, com relato de infecção leve pelo SARS-CoV-2 diagnosticado por RT-PCR nasofaríngeo, que iniciou cerca de 5 semanas após a infecção aguda quadro de artralgia, febre, linfonodomegalia cervical e hiperemia conjuntival. No setor de emergência, apresentava-se com sinais de hipotensão arterial refratária à reposição volêmica e aumento de creatinina (injúria renal aguda). Apresentava leucocitose, proteína C-reativa e ferritina elevadas. Inicialmente tratado como sepse de foco abdominal, realizou antibioticoterapia e corticoterapia em unidade de terapia intensiva, com melhora progressiva. Posteriormente, após a revisão da história atual da doença, de sistemas e aplicação de critérios diagnósticos, foi feito diagnóstico de SIM-A. Após 10 dias de internação, recebe alta hospitalar para acompanhamento ambulatorial. A SIM-A é uma manifestação tardia rara, porém potencialmente fatal da infecção pelo SARS-CoV-2. Seu diagnóstico, definido através dos critérios do Centers for Disease Control (CDC), dá-se através de RT-PCR positivo para SARS-CoV-2 nas últimas 12 semanas de apresentação do quadro, ausência de acometimento pulmonar, disfunção de um ou mais órgãos, evidência laboratorial de inflamação, em pacientes acima de 21 anos com necessidade de internação. Poucos casos foram relatados desde seu surgimento em meados de 2020. Seu manejo permanece incerto, mas acredita-se que a corticoterapia e a imunoglobulina venosa tenham um importante fator na redução do tempo de internação e melhor prognóstico. Assim, a importância do seu reconhecimento possibilita um manejo direcionado mais eficaz, uma vez que sua apresentação inicial já possui critérios de gravidade como choque circulatório e disfunção orgânica grave.
The international system of drugs’ control implies that drugs’ circulation are confined to the medico-scientific field. This article analyze how this field has been established and stabilized in ...Brazil between the 1920s and the 1950s through the lenses of the commission which organized the control of drugs in the country (CNFE). We study the process of inclusion and exclusion that are linked to the delimitation of this field and show how, during this period, the drugs’ control and regulations focused in particular on those who were their legitimate dealers: the health professions and establishments.
Overweight and obesity are a worldwide public health problem. Obesity prevalence has increased considerably, which indicates the need for more studies to better understand these diseases and related ...complications. Diet induced-obesity (DIO) animal models can reproduce human overweight and obesity, and there are many protocols used to lead to excess fat deposition. So, the purpose of this review was to identify the key points for the induction of obesity through diet, as well as identifying which are the necessary endpoints to be achieved when inducing fat gain. For this, we reviewed the literature in the last 6 years, looking for original articles that aimed to induce obesity through the diet. All articles evaluated should have a control group, in order to verify the results found, and had worked with Sprague-Dawley and Wistar rats, or with C57BL-/-6 mice strain. Articles that induced obesity by other methods, such as genetic manipulation, surgery, or drugs were excluded, since our main objective was to identify key points for the induction of obesity through diet. Articles in humans, in cell culture, in non-rodent animals, as well as review articles, articles that did not have obesity induction and book chapters were also excluded. Body weight and fat gain, as well as determinants related to inflammation, hormonal concentration, blood glycemia, lipid profile, and liver health, must be evaluated together to better determination of the development of obesity. In addition, to select the best model in each circumstance, it should be considered that each breed and sex respond differently to diet-induced obesity. The composition of the diet and calorie overconsumption are also relevant to the development of obesity. Finally, it is important that a non-obese control group is included in the experimental design.
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