GAMMA RADIATION AS A METHOD FOR STERILIZATION OF ALL-IN-ONE ADMIXTURES BAGS FOR CLINICAL USE: A STUDY OF STABILITY

Objective: The aim of this work was to evaluate the stability of all-in-one (AIO) admixtures exposed to gamma irradiation sterilization.Methods: The samples were divided into four groups with 10 bags each: a) Group I: control samples (bags without sterilization or inoculation with microorganisms); b) Group II: bags sterilized by gamma irradiation; c) Group III: bags inoculated and then irradiated and, d) Group IV: bags only inoculated. The following studies were performed: macroscopic analysis of admixtures; physicochemical stability; degree of lipoperoxidation (LPO), and microbiological tests.Results: Gamma irradiation sterilization was 100% effective, since no irradiated sample showed growth of microorganisms. All groups exhibited similar particle size distribution, but a longer storage time led to a smaller percentage of large particles. In general, irradiated samples showed reduced LPO.Conclusion: Gamma irradiation sterilization of these admixtures can be extended to clinical practice, as it results in physicochemically stable admixtures

Hedera helix L.: uma revisão dos recentes estudos de suas propriedades farmacológicas

Objective: To search the literature for recent scientific evidence corroborating the pharmacological properties of H. helix L. Method: This is an integrative literature review. Searches were carried out in the electronic databases: Virtual Health Library (VHL), EMBASE and SciVerse Scopus. The time interval chosen covered 2013 to 2023. Results: A total of 40 articles were found in the VHL database, 27 in Scopus and 8 in Embase. Given the inclusion and exclusion criteria, which answered the guiding question, 13 articles were selected for full analysis. The use of H. helix extract as a herbal medicine is recognised by the National Health Surveillance Agency (ANVISA) under RE No. 4,287 of 23 September 2011, and this therapeutic use as an expectorant and antitussive agent is scientifically validated by scientific publications. Its proven pharmacological activities include: expectorant, antitussive, anticancer, anti-inflammatory, antioxidant, antiangiogenic, neuroprotective and anti-ulcer preventive. Final considerations: In view of the therapeutic importance of H. helix as a promising medicinal plant with a wide range of pharmacological activities, it can be used in various medical applications due to its efficacy and safety.Objetivo: Buscar na literatura quais evidências científicas recentes corroboram para as propriedades farmacológicas da H. helix L. Método: Trata-se de uma revisão integrativa da literatura. Foram realizadas buscas nas bases de dados eletrônicas: Biblioteca Virtual em Saúde (BVS), EMBASE e SciVerse Scopus. O intervalo temporal escolhido abrangeu de 2013 a 2023. Resultados: Um total de 40 artigos foram encontrados na base de dados BVS, 27 na Scopus e 8 na Embase. Diante dos critérios de inclusão e exclusão, que responderam à questão norteadora, foram selecionados 13 artigos para análise integral. O uso do extrato da H. helix, como medicamento fitoterápico, é reconhecido pela Agência Nacional de Vigilância Sanitária (ANVISA) pela RE Nº 4.287, de 23 de setembro de 2011, e este uso terapêutico como agente expectorante e antitussígeno é validado cientificamente por publicações científicas. Dentre as atividades farmacológicas comprovadas, destacam-se: expectorante, antitussígena, anticancerígena, anti-inflamatória, antioxidante, antiangiogênicas, neuroprotetora e antiúlcera preventivo. Considerações finais: Diante da importância terapêutica da H. helix como uma planta medicinal promissora com ampla gama de atividades farmacológicas, podendo ser utilizada em diversas aplicações médicas devido à sua eficácia e segurança

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 <= 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

The role of HspX protein from Mycobacterium tuberculosis in regulation of genes involved with morphological adaptation to mycobacterial dormancy, with Mycobacterium smegmatis as model organism.

A manutenção da infecção latente pelo M. tuberculosis (TBIL) pode ser atribuída à sua capacidade de sobreviver durante anos no organismo humano em um estado não replicativo (dormente). A proteína HspX do M. tuberculosis, induzida sob condições de hipóxia, está fortemente associada com a manutenção da viabilidade do bacilo na TBIL. O presente estudo tem como objetivo, verificar se a superexpressão da proteína HspX altera a expressão de genes envolvidos com a síntese de componentes da parede celular, replicação do DNA e divisão celular de bacilos, assim como, na expressão de genes envolvidos com a resposta imune inata em macrófagos infectados com esses bacilos. O gene hspX foi amplificado pela PCR a partir do DNA do M. tuberculosis H37Rv, clonado no vetor de expressão pFPCA1GFP, e a proteína HspX expressa em M. smegmatis mc2155. As bactérias, nas quais, a presença da proteína recombinante foi confirmada por Western Blot, foram utilizadas, para a análise de expressão gênica tanto em bactérias quanto em macrófagos infectados. O estudo de expressão gênica foi realizado utilizando a RT-qPCR. Quando comparado aos controles, as bactérias que expressavam a proteína HspX apresentaram uma redução na expressão de genes de replicação do DNA e divisão celular, que foi acompanhado por uma tendência a filamentação das células e uma redução no tamanho das colônias. Além disso, nos macrófagos infectados com a bactéria expressando a proteína HspX, houve um aumento tanto da expressão do mRNA quanto da secreção de IL-1b, citocina importante para estabilização do granuloma, e uma redução na expressão de IRGM, gene relacionado com o processo autofágico, importante mecanismo de defesa do hospedeiro contra bactérias intracelulares. Portanto, em conjunto, essas alterações de expressão gênica, em consequência da presença da proteína HspX sugerem uma contribuição, direta ou indireta, dessa proteína para a adaptação morfológica e metabólica da bactéria dormente durante a TBIL, e consequentemente, para a resposta imune inata dos macrófagos infectados favorecendo a viabilidade intracelular dessas bactérias.The maintenance of Mycobacterium tuberculosis infection latent (TBIL) may be attributed to its ability to persist for years in the host in a non-replicative state (dormant). The HspX protein from M. tuberculosis, induced under hypoxic, is strongly associated with maintaining the bacillus viability in TBIL. This study aims to determine if HspX overexpression chances the expression of genes involved in the synthesis of cell wall components, DNA replication and cell division of bacilli, as well as, the expression of genes involved in innate immune response of macrophages infected. The gene hspX was amplified by PCR from DNA of M. tuberculosis H37Rv, and cloned into the expression vector pFPCA1GFP. The HspX was expressed in M. smegmatis mc2155 and the recombinant protein was confirmed by Western blot. The bacterias expressing HspX were used for gene expression analysis both in bacteria and in infected macrophages by RT-PCRq. In bacterias expressing HspX, it was observed a reduction in expression of genes involved in DNA replication and cell division, and with cells more filamentous and smaller colonies, compared with controls. In addition, in macrophages infected with bacillus expressing HspX, there was an increase in both mRNA expression and secretion of IL-1b, an important cytokine for granuloma stability, and a reduction in expression of IRGM, an autophagic gene, important for host defense mechanism against intracellular bacteria. Together, these results suggest a direct or indirect contribution of HspX protein for metabolic and morphological adaptation of dormant bacteria in TBIL, and for the innate immune response in infected macrophages, improving the bacteria intracellular viability

Dosmetic preparation of medicinal plants used in the treatment for infectious diseases

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgicoA maioria da populaÃÃo de paÃses em desenvolvimento utiliza plantas ou prepara-ÃÃes vegetais em seus cuidados bÃsicos de saÃde. A falta de informaÃÃes sobre os possÃveis riscos e benefÃcios do uso de plantas medicinais à um dos principais fato-res que contribui para automedicaÃÃo da populaÃÃo com ervas. Muitas das espÃcies vegetais utilizadas na medicina popular apresentam propriedades antimicrobianas comprovadas, no entanto, diversos fatores como a preparaÃÃo incorreta das plantas pode interferir na eficÃcia do tratamento. O presente trabalho, teve como objetivo avaliar a utilizaÃÃo de preparaÃÃes caseiras de plantas medicinais, pelas famÃlias das crianÃas assistidas pelo Centro de EducaÃÃo Infantil Aprisco, em Fortaleza. As famÃlias que participaram do estudo responderam a um questionÃrio que permitiu conhecer as principais plantas medicinais utilizadas pela populaÃÃo estudada, suas indicaÃÃes terapÃuticas, modo de preparo, parte da planta utilizada, entre outras questÃes. Num segundo momento, foi realizado um estudo experimental, onde foi testado in vitro o potencial antimicrobiano das preparaÃÃes caseiras das plantas me-dicinais citadas durante as entrevistas. Os dados foram inseridos e analisados no Microsoft Office Excel e no programa estatÃstico Epi Info 3.3.2. Foram entrevistadas 41 famÃlias, das quais 97,6% afirmaram utilizar as plantas medicinais como opÃÃo terapÃutica no tratamento de doenÃas. Num total de 39 questionÃrios foram citadas 97 preparaÃÃes caseiras de plantas, com uma mÃdia de 2,5  1,6 por questionÃrio. Desse total de preparaÃÃes, 71,1% eram usadas buscando solucionar problemas respiratÃrios e digestivos. A principal parte utilizada da planta foi a folha (60%) e a forma de utilizaÃÃo mais citada o chà por decocÃÃo (59,8%). Foram citadas trinta e duas espÃcies vegetais utilizadas nas preparaÃÃes, das quais o eucalipto (Eucalyptus citriodora) teve a maior freqÃÃncia de citaÃÃo (11,9%). Das quarenta e cinco amostras submetidas à avaliaÃÃo da atividade antimicrobiana in vitro, 55,6% (25 amostras) apresentaram atividade inibitÃria sobre o crescimento de pelo menos um dos microrganismos utilizados. A maioria das plantas com propriedade antimi-crobiana conhecida e que foram citadas pelos entrevistados tiveram sua atividade alterada de acordo com a forma com que foram preparadas. Foi verificado ainda o uso de plantas para fins medicinais que apresentam em sua composiÃÃo substÃn-cias com caracterÃsticas tÃxicas. Os resultados obtidos nesse trabalho sugerem que dependendo das condiÃÃes em que as plantas sÃo utilizadas elas podem apresentar ou nÃo a atividade farmacolÃgica que lhe à atribuÃda. Està nas mÃos do profissional farmacÃutico, contribuindo com seu conhecimento, promover o uso eficaz, seguro e racional das plantas medicinais.Most of the people in developing countries use plants or herbal preparations in their basic health care. The lack of information about the possible risks and benefits in the use of medicinal plants is one of the main factors that contribute with herbs automedication. Many plants used in the popular medicine have proved antimicrobial properties; however, several factors for example, incorrect preparation of the plants, can interfere in the efficiency of the treatment. The aim of this study was to assess-ment the use of domestic preparations of medicinal plants by the families of children who study in the Centre of Children Education Aprisco, in Fortaleza. The families that participated of the study answered a questionnaire that allowed knowing the most used medicinal plants by this population, as well as its therapeutic indications, forms of use, parts of the plant used, and other ones. At a second moment, an in vitro ex-perimental study analysed the antimicrobial potential of the domestic preparations of the medicinal plants quoted during the interviews. The data were inserted and ana-lysed in the Microsoftware package Office Excel and in the statistical program Epi Info 3.3.2. Forty one families were interviewed, of which 97,6 % affirmed to use the medicinal plants like therapeutic option in the treatment of diseases. In 39 question-naires were quoted 97 domestic preparations of plants, with an average of 2,5  1,6 preparations. Of this total (97), 71,1 % was used to respiratory and digestive prob-lems. Furthermore, the most used part of the plant was the leaf (60 %) and the de-coction was the main form of the use (59,8 %). Thirty two plants species were used in the preparations, of which the eucalyptus (Eucalyptus citriodora) had the highest fre-quency (11,9 %). From the forty five samples that was submited to the antimicrobial activity in vitro, 55,6 % (25 samples) showed inhibitory activity on the growth at least one of the microorganisms used in the test. Many of the plants that have antimicro-bial properties and that were quoted by the families interviewed, had their activity al-tered in accordance with the form that they were prepared. It was also observed the use of plants for health care that present in their composition toxic substances. The results of this study suggest that the forms of preparation and use of the plants can interfere on the presence or absence of the farmacology activity that is attributed for the plants. Therefore, itâs in the pharmacistâs hands, who can contribute with his knowledge, to promote the efficient, safe and rational use of the medicinal plants

In vitro determination of the antimicrobial potential of homemade preparations based on medicinal plants used to treat infectious diseases

The majority of the population in developing countries uses plants or plant preparations in their basic health care. Many plant species used nowadays in folk medicine have been proved to have antimicrobial properties. However, several factors, such as incorrect preparation of the plants, can interfere with the effectiveness of the treatment. The purpose of this study was to assess the use of homemade preparations of medicinal plants in the treatment of infectious diseases, by in vitro determination of their antimicrobial potential. Based on recipes elicited by questionnaires that were previously applied to a participant population, the samples were prepared in a similar manner and analyzed by the agar diffusion method. Members of 41 families, whose children attend a center of education that serves several needy communities in the city of Fortaleza (Ceará, Brazil), were interviewed; of these, 97.6% said they had used herbal therapy as a means to treat infectious diseases. In replies to a total of 39 questionnaires, 97 different homemade preparations of medicinal plants were cited. Out of 45 samples subjected to an in vitro assessment of antimicrobial activity, 25 (55.6%) had some inhibitory effect on the growth of at least one of the microorganisms used. Most of the plants with known antimicrobial properties and cited by respondents showed variations in their in vitro activity, according to the manner in which they were prepared. Keywords: Medicinal plants. Products with Antimicrobial Action. Traditional Medicine. Homemade preparation. RESUMO Determinação in vitro do potencial antimicrobiano de preparações caseiras de plantas medicinais utilizadas para o tratamento de doenças infecciosas Grande parte da população de países em desenvolvimento utiliza plantas ou preparações vegetais nos cuidados básicos à saúde. Muitas das espécies vegetais utilizadas na medicina popular apresentam propriedades antimicrobianas comprovadas; no entanto, diversos fatores, como a metodologia incorreta de preparo, podem interferir na eficácia do tratamento. O presente trabalho teve como objetivo avaliar a utilização de preparações caseiras de plantas medicinais para o tratamento de doenças infecciosas através da determinação in vitro do potencial antimicrobiano. A partir de informações contidas em questionários que foram previamente aplicados à população participante, as amostras foram preparadas de forma semelhante e analisadas através do método de difusão em ágar. Foram entrevistadas 41 famílias, das quais 97,6% afirmaram utilizar as plantas medicinais como opção terapêutica no tratamento de doenças. Em um total de 39 questionários, foram citadas 97 diferentes preparações caseiras de plantas. Das 45 amostras (indicadas para tratar algum sinal ou sintoma que podem estar relacionado a um quadro infeccioso) submetidas à avaliação da atividade antimicrobiana in vitro, 55,6% (25 amostras) apresentaram atividade inibitória sobre o crescimento de pelo menos um dos microrganismos utilizados. A maioria das plantas com propriedade antimicrobiana conhecida e que foram citadas pelos entrevistados apresentaram variações na sua atividade in vitro de acordo com o modo como foram preparadas. Palavras-chave: Plantas Medicinais. Produtos naturais com ação antimicrobiana. Medicina tradicional

Plasmid-based controls to detect rpoB mutations in Mycobacterium tuberculosis by quantitative polymerase chain reaction-high-resolution melting

Quantitative polymerase chain reaction-high-resolution melting (qPCR-HRM) analysis was used to screen for mutations related to drug resistance in Mycobacterium tuberculosis. We detected the C526T and C531T mutations in the rifampicin resistance-determining region (RRDR) of the rpoB gene with qPCR-HRM using plasmid-based controls. A segment of the RRDR region from M. tuberculosis H37Rv and from strains carrying C531T or C526T mutations in the rpoB were cloned into pGEM-T vector and these vectors were used as controls in the qPCR-HRM analysis of 54 M. tuberculosis strains. The results were confirmed by DNA sequencing and showed that recombinant plasmids can replace genomic DNA as controls in the qPCR-HRM assay. Plasmids can be handled outside of biosafety level 3 facilities, reducing the risk of contamination and the cost of the assay. Plasmids have a high stability, are normally maintained in Escherichia coli and can be extracted in large amounts

Genetic Variant <i>ABCC1</i> rs45511401 Is Associated with Increased Response to Statins in Patients with Familial Hypercholesterolemia

Statins are the first-line treatment for familial hypercholesterolemia (FH), but response is highly variable due to genetic and nongenetic factors. Here, we explored the association between response and genetic variability in 114 Brazilian adult FH patients. Specifically, a panel of 84 genes was analyzed by exon-targeted gene sequencing (ETGS), and the functional impact of variants in pharmacokinetic (PK) genes was assessed using an array of functionality prediction methods. Low-density lipoprotein cholesterol (LDL-c) response to statins (reduction ≥ 50%) and statin-related adverse event (SRAE) risk were assessed in carriers of deleterious variants in PK-related genes using multivariate linear regression analyses. Fifty-eight (50.8%) FH patients responded to statins, and 24 (21.0%) had SRAE. Results of the multivariate regression analysis revealed that ABCC1 rs45511401 significantly increased LDL-c reduction after statin treatment (p ABCC1 rs45511401 possibly impairs statin efflux. Deleterious variants in PK genes were not associated with an increased risk of SRAE. In conclusion, the deleterious variant ABCC1 rs45511401 enhanced LDL-c response in Brazilian FH patients. As such, this variant might be a promising candidate for the individualization of statin therapy

Mechanical ventilation and death in pregnant patients admitted for COVID-19: a prognostic analysis from the Brazilian COVID-19 registry score

Abstract Background The assessment of clinical prognosis of pregnant COVID-19 patients at hospital presentation is challenging, due to physiological adaptations during pregnancy. Our aim was to assess the performance of the ABC2-SPH score to predict in-hospital mortality and mechanical ventilation support in pregnant patients with COVID-19, to assess the frequency of adverse pregnancy outcomes, and characteristics of pregnant women who died. Methods This multicenter cohort included consecutive pregnant patients with COVID-19 admitted to the participating hospitals, from April/2020 to March/2022. Primary outcomes were in-hospital mortality and the composite outcome of mechanical ventilation support and in-hospital mortality. Secondary endpoints were pregnancy outcomes. The overall discrimination of the model was presented as the area under the receiver operating characteristic curve (AUROC). Overall performance was assessed using the Brier score. Results From 350 pregnant patients (median age 30 [interquartile range (25.2, 35.0)] years-old]), 11.1% had hypertensive disorders, 19.7% required mechanical ventilation support and 6.0% died. The AUROC for in-hospital mortality and for the composite outcome were 0.809 (95% IC: 0.641–0.944) and 0.704 (95% IC: 0.617–0.792), respectively, with good overall performance (Brier = 0.0384 and 0.1610, respectively). Calibration was good for the prediction of in-hospital mortality, but poor for the composite outcome. Women who died had a median age 4 years-old higher, higher frequency of hypertensive disorders (38.1% vs. 9.4%, p < 0.001) and obesity (28.6% vs. 10.6%, p = 0.025) than those who were discharged alive, and their newborns had lower birth weight (2000 vs. 2813, p = 0.001) and five-minute Apgar score (3.0 vs. 8.0, p < 0.001). Conclusions The ABC2-SPH score had good overall performance for in-hospital mortality and the composite outcome mechanical ventilation and in-hospital mortality. Calibration was good for the prediction of in-hospital mortality, but it was poor for the composite outcome. Therefore, the score may be useful to predict in-hospital mortality in pregnant patients with COVID-19, in addition to clinical judgment. Newborns from women who died had lower birth weight and Apgar score than those who were discharged alive