REVISÃO SISTEMÁTICA SOBRE INVESTIGAÇÕES IN VITRO VOLTADAS PARA O TRATAMENTO DA TUBERCULOSE RESISTENTE E MULTIDROGA-RESISTENTE

Introduction: Tuberculosis is caused by variants of the Mycobacterium tuberculosis species, mainly affecting immunocompromised individuals. In this sense, the tuberculosis bacillus in its multi-resistant (MDR) and extremely resistant (XDR) forms has claimed a growing number of victims. Today it is possible to find a vast literature that seeks precisely to expand this spectrum of therapeutic possibilities, however, an overview of current discoveries is needed. Objective: to carry out a systematic review based on the studies developed on the subject, in order to contribute to the construction of a direction for the most promising therapeutic possibilities. Method: Systematized review using in vitro studies with MDR-TB and XDR-TB strains from the MedLine database with the following search: (MDR OR XDR) AND tuberculosis AND (activity OR anti) AND in vitro. Results and Discussion: it was possible to identify a clear and conflicting emphasis on the search for therapeutic possibilities against tuberculosis caused by the MDR strain of Mycobacterium tuberculosis (MTB), when compared to the number of investigations against the XDR strain of MTB. Taking the first position of substances investigated against MDR, we identified the category “new drugs”. Conclusion: The panorama presented in this study was that many in vitro investigations have been carried out in order to seek alternatives for the treatment of MDR-TB, leaving XDR-TB with fewer studies and, consequently, less chance of developing drugs for its treatment.Introducción: La tuberculosis es causada por variantes de la especie Mycobacterium tuberculosis, afectando principalmente a individuos inmunocomprometidos. En este sentido, el bacilo de la tuberculosis en sus formas multirresistentes (MDR) y extremadamente resistentes a los medicamentos (XDR) ha hecho un número creciente de víctimas. Es posible hoy en día encontrar una vasta literatura que busca ampliar exactamente este espectro de posibilidades terapéuticas, sin embargo, es necesaria una visión general de los descubrimientos actuales. Objetivo: Realizar una revisión sistematizada a partir de estudios desarrollados sobre este tema, con el fin de contribuir a la construcción de una dirección de las posibilidades terapéuticas más prometedoras. Método: Revisión sistematizada mediante estudios desarrollados in vitro con cepas MDR-TB y XDR-TB, de la base de datos MedLine con la siguiente frase de investigación: (MDR O XDR) Y tuberculosis Y (actividad O anti) E in vitro. Resultados y Discusión: fue posible identificar un énfasis claro y discrepante en la búsqueda de posibilidades terapéuticas contra la tuberculosis causada por la cepa MDR de Mycobacterium tuberculosis (MTB), en comparación con el número de investigaciones contra la cepa XDR de MTB. Ocupando la primera posición de sustancias investigadas contra MDR, identificamos la categoría "nuevos fármacos". Conclusión: El panorama evidenciado en este estudio fue que las numerosas investigaciones in vitro se han realizado con el fin de buscar alternativas para el tratamiento de la TB-MR, con la TB-XDR con un menor número de estudios y, en consecuencia, una menor probabilidad de desarrollar fármacos para su tratamiento.Introdução: A tuberculose é causada por variantes da espécie Mycobacterium tuberculosis, acometendo principalmente indivíduos imunocomprometidos. Neste sentido, o bacilo da tuberculose em suas formas multidroga-resistente (MDR) e extremamente droga-resistente (XDR) tem feito um número cada vez maior de vítimas. É possível hoje nos depararmos com uma literatura vasta que busca exatamente ampliar esse espectro de possibilidades terapêuticas, entretanto, um panorama sobre as descobertas atuais se faz necessário. Objetivo: Realizar uma revisão sistematizada utilizando estudos desenvolvidos sobre este assunto, a fim de contribuir para a construção de um direcionamento das possibilidades terapêuticas mais promissoras. Método: Revisão sistematizada utilizando estudos desenvolvidos in vitro com cepas MDR-TB e XDR-TB, a partir da base de dados MedLine com a seguinte frase de pesquisa: (MDR OR XDR) AND tuberculosis AND (activity OR anti) AND in vitro. Resultados e Discussão: foi possível identificar uma clara e discrepante ênfase à busca por possibilidades terapêuticas contra a tuberculose causada pela cepa MDR de Mycobacterium tuberculosis (MTB), quando comparada ao número de investigações contra a cepa XDR de MTB. Ocupando a primeira posição de substâncias investigadas contra MDR, identificamos a categoria "novas drogas". Conclusão: O panorama evidenciado neste estudo revelou que as muitas investigações in vitro têm sido realizadas no sentido de se buscar alternativas para o tratamento da TB-MDR, ficando a TB-XDR com menor número de estudos e consequentemente, menor chance de desenvolvimento de drogas para seu tratamento

Standard Electrocardiographic Data of Peccaries (Tayassu tajacu)

Background:Peccaries (Tayassu tajacu, Linnaeus, 1758) are wild suiformes that belong to the Tayassuidae family. Electrocardiography is an important technique for cardiovascular evaluation. Analysis of various intervals, segments, complexes and waveforms of electrocardiographic (ECG) traces aids in the diagnosis of cardiac alterations and in the differentiation of congenital and acquired heart diseases from physiological cases. However, in wild animal medicine, the various patterns of normality and the evaluation of electrical traces associated with heart disease have not yet been sufficiently elucidated. The purpose of this study was to characterize the electrocardiographic (ECG) traces of peccaries sedated using ketamine and xylazine.Materials, Methods & Results:Fourteen healthy adult animals that were subjected to digital ECG examination were used. Animals with evidence of systemic diseases, cardiovascular abnormalities (murmurs or arrhythmias), or any degree of valve insufficiency observed on echocardiogram and animals that exhibited excessive stress during the examination were excluded from the study. All animals presented with a normal sinus rhythm. A combination of 15 mg/kg of ketamine hydrochloride and 3 mg/kg of midazolam maleate was applied intramuscularly for chemical immobilization. The animals were manipulated after 15 min, when the onset of the anaesthetic effect was verified, for a duration of 45 min, and no reinforcement dose was necessary to complete the electrocardiographic examination.  No significant differences were observed in the P-wave duration, PR interval and QT interval between genders (P > 0.05). No significant differences were found between the amplitudes of the P and R waves between males and females (P > 0.05). The observed P waves were small, monophasic and positive. The QRS complex was positive in the DI, DII, DIII, aVF, V4 and V10 derivations and negative in the aVR, aVL, V1 and V2 derivations. In 71% of the animals, the T wave showed negative polarity in the DI, DII, DIII, aVL, aVF, and V10 derivations and positive polarity in the aVR, V1, V2 and V4 derivations. The ST segment was isoelectric in 100% of the animals. GraphPad Prism 7 (La Jolla, CA, USA) software was used to analyze the data, with non-parametric tests used to test for differences in the variables between the sexes. In these tests, a P-value of 0.05 was considered to indicate statistical significance.Discussion:Although studies on the cardiac electrophysiology of wild animals have previously shown good results for several species, this is the first study concerning the standardization ECG traces for peccaries. However, due to the wild nature of these animals, their manipulation for handling and data collection purposes is only feasible under chemical containment, although other studies have used non-anaesthetized agoutis. It is not known to what extent these results may have been influenced by the effects of stress. Drugs used for this function may have direct effects on cardiac function. Therefore, the presumed normal ECG values, as well as the recognition of changes due to drug or iatrogenic interactions, are of fundamental importance.  This protocol provided high-quality anaesthetized peccary ECG traces, allowing reliable measurements of waves and intervals and assessment of the cardiac rhythm and heart rate. The surface registry digital ECG recording technique used with chemical containment allowed good monitoring and rapid acquisition and was well tolerated by the animals. 

Ocular Echobiometry and Resistivity Index of External Ophthalmic Artery in Agoutis (Dasyprocta prymnolopha)

Background: Veterinary Ophthalmology provides complementary information for the diagnosis of ocular pathologies. Studies in wild species are essential. Among the diagnostic techniques in ophthalmology, two-dimensional ultrasonography stands out. The agouti is a rodent belonging to the Dasyproctidae family that has been widely used as an experimental model. For these animals, sight is one of the crucial senses for their survival. The aim of this study was to evaluate the effectiveness of the two-dimensional ocular ultrasound technique to obtain anatomical measurements and the external ophthalmic artery resistivity index, presumably normal in the species Dasyprocta prymnolopha.Materials, Methods & Results: Forty eye bulbs of 20 adult rodents of the species were evaluated by ultrasonography. In these animals, B-mode echobiometry was performed using the transpalpebral approach and the hemodynamic study of the external ophthalmic artery using the color Doppler technique. All examinations were initiated by the left eye bulb and all measurements were performed by only one examiner. The collected data related to echobiometry were analyzed using Bioest 5.0 for Windows. Initially, normality was tested using the Shapiro-Wilk test for each parameter, then the paired t-test was performed, comparing right and left eyes, and a significance level of 5% (P < 0.05) was adopted. Based on the methodology used, the following values were obtained for the right and left eyeballs, respectively: anterior chamber thickness - mean of 1.28 ± 0.3 mm and 1.22 ± 0.1 mm; lens thickness - 8.27 ± 0.9 mm and 8.11 ± 0.9 mm; vitreous chamber thickness - 5.35 ± 0.48 mm and 5.30 ± 0.47 mm and axial length - 12.7 ± 0.9 mm and 13 ± 0.68 mm. The mean external ophthalmic artery resistivity values were 0.4305 ± 0.0390 and 0.4258 ± 0.0387 (right and left eye, respectively), characterizing a low resistance. There was no statistical difference between the right and left eyeballs in any of the studied parameters.Discussion: The use of the convex transducer was feasible, promoting adequate contact with the ocular surface and images of satisfactory quality for obtaining measurements, similar to what was observed in studies evaluating the ocular biometry of primates and dogs. The anterior chamber thickness values in this experiment did not differ statistically between the antimers, as well as observed for dogs. The data obtained for lens thickness did not differ statistically for antimers, like those obtained for other rodent species evaluated with the same methodology. The mean values of vitreous chamber thickness were like those observed in chinchillas but correspond to about half of that obtained for capybaras. In this study, the external ophthalmic artery was characterized in all animals, but obtaining the spectral tracing was difficult due to its fine caliber. In wild animals, and especially in wild rodents, there are few data reporting the resistivity of the ophthalmic artery, and there is a lack of studies, which can be explained by the behavioral characteristics of defense and by the high susceptibility to stress in capture, since the performing the technique requires, as in other procedures, the use of chemical containment.Keywords: Doppler flow, ultrasound, eye, agouti

Educomunicação em Tempos de Pandemia:

Os textos que compõem esta obra são oriundos do VIII Colóquio Ibero-americano de Educomunicação (VIII CIEducom) e IX Colóquio Catarinense de Educomunicação (IX CCEducom), realizados em março de 2021. Em um ano no qual o vírus SARS-CoV-2 e variantes circularam por diversos territórios, Educomunicação em tempos de pandemia: práticas e desafios foi o tema discutido nos eventos. Este livro colocado à disposição do público é um modo de compartilhar caminhos e convidar pessoas curiosas a percorrerem, por meio das palavras e recursos gráficos, desafios identificados e estratégias para o enfrentamento deste inesperado período de pandemia

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure &lt;= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Electrocardiographic Pattern of Agoutis (Dasyprocta prymnolopha) Chemically Contained by the Association of Ketamine and Xylazine

Background: The agouti (Dasyprocta prymnolopha, Wagler, 1831) is an existing wild rodent in almost all of Brazil, used as a biological model in several scientific studies. Veterinary cardiology has showed great advances in the diagnostic area due to the possibility of cardiac evaluation by non-invasive methods. For the practice of scientific or handling procedures in wild animals, chemical containment is essential. Thus, it is important to know the effect of anesthetic protocols on the cardiovascular system, observed through complementary tests, such as the electrocardiogram. The objective of this study was to describe the computerized electrocardiographic tracing of agoutis chemically contained by the association of Ketamine and Xylazine.Materials, Methods & Results: Eighteen male and female clinically healthy animals, aged among 2 years, submitted to digital electrocardiographic examination, were used. The device used to obtain the tracing was the veterinary electrocardiograph (Electrocardiogram Acquisition Module for Computer) - Brazilian Electronic Technology (TEB). The analysis was always made from derivation II (DII). Chemical containment was performed by the combination of Ketamine and Xylazine, intramuscularly. The results showed that the heart rate for males was on average 113.25 bpm, while for females the value of 124.60 bpm was observed, and there was no significant difference between the genders (P > 0.05). The mean weight of males was 2.31 kg and for females 2.28 kg; there was no statistical difference for this variable (P > 0.05). For the QRS duration of 46.14 ± 5.05 ms (males) and 44.66 ± 5.94 ms (females) and PR interval of 79.94 ± 12.01ms (males) and 84.29 ± 12.37ms (females), there was no statistical difference (P > 0.05). The amplitude of the R wave of 0.42 ± 0.31 mV (males) and 0.36 ± 0.22 mV (females) showed no statistical difference (P > 0.05). The T wave showed itself both negative (10 animals) and positive (8 animals), with amplitude measured at 0.24 ± 0.16 mV for males and 0.25 ± 0.10 mV for females (P > 0.05). The anesthetic protocol was well tolerated by the animals of this experiment, and there were no episodes of arrhythmias during the time of their monitoring.Discussion: Wild animals, in general, need chemical containment, with a view to reducing stress during scientific and handling procedures. The protocols established in this work can be used in future experiments which require a longer handling time. The values found for heart rate (HR) of anesthetized agoutis were lower than those for non-anesthetized agoutis, proving the influence of the stress during retention and the depressant cardiovascular effect of the anesthetic drug used. The electrocardiographic parameters and the tracing morphology of the agoutis were like the results found for anesthetized small rodents. The QT interval was higher in males than in females, justifying the fact that it could be influenced by variations in HR, which also showed superior results for males. Taking into consideration the morphological similarity between different individuals, the QT interval in anesthetized agoutis did not present significant differences between the genders, a characteristic also found in ferrets. The animals of this experiment were submitted to food fasting, a fact that contributed to a better standardization of the experiment, preventing alterations in the morphology of the QRS complex, which could lead to changes in the measurements

X-ray structure of O-methyl-acrocol and anti-cancer, anti-parasitic, anti-bacterial and anti-Zika virus evaluations of the Brazilian palm tree Acrocomia totai

Acrocomia totai Mart ("macauba") is a palm tree native from Brazil, whose potential for biodiesel production has been widely explored. In spite of the industrial interest in the oil from the nuts, little is known about the potential applications of other parts of the plant, especially in the pharmacological area. A phytochemical study of the plant thorns led to the identification of a new compound 3-(R)-methoxy-21-(R)-H-hop-22(29)-en-30-ol 1, two known triterpenes 2-3, four steroids 4-7 and a stilbene, piceatannol 8. The structures were elucidated by spectroscopic analyses, including 1D and 2D NMR and low and high resolution mass spectrometry. Compound 1 was purified as crystals, which allowed the determination of the absolute configuration of the asymmetric carbons by analysis of the X-ray diffraction spectrum. Biological tests were performed with crude extract (CE), fractions and isolated compound. The assays showed activity for CE against lung carcinoma (GI(50) 59.2 mu g mL(-1)). The ethyl acetate fraction (EAF) showed efficacy against many tumor cell lines, and the tests showed the most prominent activity for breast cancer (GI(50) 10.4 mu g mL(-1)), glioma (GI(50) 77.3 mu g mL(-1)), uterine cervix (SiHa) HPV 16 (IC50 39.8 mu g mL(-1)), (HeLa) HPV 18 (IC50 12.0 pg mL(-1)) and Caco-2 (IC50 40.0 mu g mL(-1)) and showed bacteriostatic action against Staphylococcus aureus (MIC 50 mu g mL(-1)). Piceatannol 8 isolated from EAF showed activity against the protozoan which causes leishmaniosis (IC50 58.4 mu g mL(-1)). For Ttypanosorna cruzi, the methanol fraction (EC50 15.5 mu g mL(-1)), CE (20.5 mu g(-1)), and HEF (43.8 mu g mL(-1)) were the most active, being highly selective for the protozoan and less toxic against Vero cells. The compound 8 was further tested against Zika virus MR 766 strain on MOI 2, however the assays showed no inhibition against virus infection109483492CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO ARAUCÁRIA DE APOIO AO DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO DO ESTADO DO PARANÁ - FAFUNDAÇÃO DE AMPARO À PESQUISA E INOVAÇÃO DO ESTADO DE SANTA CATARINA - FAPESCsem informaçãosem informaçãosem informaçãosem informaçã

Inflammatory Response and Activation of Coagulation after COVID-19 Infection

SARS-CoV-2 (COVID-19) infection is responsible for causing a disease with a wide spectrum of clinical presentations. Predisposition to thromboembolic disease due to excessive inflammation is also attributed to the disease. The objective of this study was to characterize the clinical and laboratory aspects of hospitalized patients, in addition to studying the pattern of serum cytokines, and associate them with the occurrence of thromboembolic events. Methodology: A retrospective cohort study with 97 COVID-19 patients hospitalized from April to August 2020 in the Triângulo Mineiro macro-region was carried out. A review of medical records was conducted to evaluate the clinical and laboratory aspects and the frequency of thrombosis, as well as the measurement of cytokines, in the groups that presented or did not present a thrombotic event. Results: There were seven confirmed cases of thrombotic occurrence in the cohort. A reduction in the time of prothrombin activity was observed in the group with thrombosis. Further, 27.8% of all patients had thrombocytopenia. In the group that had thrombotic events, the levels of IL1b, IL-10, and IL2 were higher (p < 0.05). Conclusions: In the studied sample, there was an increase in the inflammatory response in patients with thrombotic events, confirmed by the increase in cytokines. Furthermore, in this cohort, a link was observed between the IL-10 percentage and an increased chance of a thrombotic event