Atividade anti-Candida tropicalis dos enantiômeros (R)-(+)- & (S)-(-)-citronelal em associação com cetoconazol

Introdução: aproximadamente 75% das mulheres saudáveis experimentam pelo menos um episódio sintomático de candidíase vulvovaginal (CVV) durante sua vida. Objetivo: avaliar a atividade antifúngica contra cepas de C. tropicalis dos enantiômeros (R)-(+)- e (S)-(-)-citronelal [(R)-(+)- e (S)-(-)-CT] em associação com cetoconazol. Metodologia: o efeito antifúngico de ambos os enantiômeros foram quantificados e classificados como fungicida ou fungistático a partir dos resultados obtidos da microdiluição em meio líquido RPMI-1640 para a obtenção da concentração inibitória mínima (CIM) e da concentração fungicida mínima (CFM). Foram realizados ensaios de associação do antifúngico padrão, cetoconazol com os fitoconstituintes por difusão em Agar e os resultados foram classificados como sinérgicos, antagônicos e indiferentes. Resultados: a CIM50 e a CFM50 dos compostos (R)-(+)- e (S)-(-)-citronelal foram respectivamente 16 e 64µg/mL e 2×CIM. Houve sinergismo para todas as cepas testadas com ambos os compostos, porém com maior efeito do enantiômero (S)-(-)-CT sobre as cepas LM 665 e LM 255 em relação ao enantiômero (R)-(+)-CT. Conclusão: os compostos naturais deste estudo mostraram efeito fungicida sobre as cepas testadas, bem como efeito sinérgico significativo quando associado ao cetoconazol

Enteroparasitological profile of patients assisted in the Lauro Wanderley University Hospital (HULW)

Infections with intestinal parasites represent a worsening public health, given the large number of individuals affected and various organic changes that can be caused. The objective was to conduct a survey of individuals affected by these parasites assisted by the Clinical Laboratory of the HULW from January 2010 to January 2011, as well as characterizing data intrinsic to individuals. Data were obtained through a statistical analysis of 7844 reports of fecal examinations. Among the results was shown that 32.5 % of samples were parasitized, Ascaris lumbricoides being the most frequent in these reports, accounting for 36 %. Female patients were the most affected, comprising 62 % of positive cases. It was detected the existence of multiple parasitism in 30.7 %. Therefore, the high frequency of intestinal parasites detected is a reality that needs to be minimized in the population assisted by the HULW’s Clinical Laboratory.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Estudo do potencial antifúngico e do mecanismo de ação do timol contra cepas de Candida parapsilosis resistentes ao fluconazol e a anfotericina B

Objetivo: Investigar a suscetibilidade antifúngica do timol contra cepas de Candida parapsilosis isoladas de sangue humano, bem como seu possível mecanismo de ação. Métodos: Foram utilizadas técnicas de microdiluição em placas de 96 poços para determinar a concentração inibitória mínima (CIM) e concentração fungicida mínima (CFM). Além disso, foram realizados testes com o sorbitol e o ergosterol para investigar a ação do timol na parede e na membrana celular fúngica respectivamente. Resultados: Nos testes de CIM e CFM, foi observado que as cepas de C. parapsilosis são resistentes ao fluconazol e a anfotericina B, no entanto, o timol desempenhou efeito fungicida com razão CFM/CIM entre 1 e 2. Além disso, a CIM do timol não aumentou quando o sorbitol ou o ergosterol foi adicionado no meio, sugerindo fortemente que este monoterpeno não age na parede celular fúngica ou por ligação ao ergosterol na membrana plasmática. Conclusão: Portanto, esses resultados contribuem para a elucidação do mecanismo de ação do timol, sugerindo outros possíveis alvos de interação fármaco-receptor. No entanto, mais investigações de caráter enzimático e molecular em modelos in vitro são necessários para que se possa elucidar completamente o modo de ação desse promissor monoterpeno

Citral: antifungal activity and mode of action, against Cladosporium oxysporum

Dematiaceous fungi are a group of fungi with dark colonies and pigmented fungal elements. The spectrum of diseases associated with fungi ranges from superficial skin and soft tissue infections to disseminated sepsis with high mortality. Therefore, it is necessary to study molecules with an antifungal action against these fungis. Attention has been drawn to the antimicrobial activity of aromatic compounds because of their promising biological properties. Citral is a monoterpene with known pharmacological properties, including antimicrobial action. Therefore, we investigated the antifungal activity of citral against strains of C. oxysporum, which involved determining its minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC) and effects on mycelial growth and conidial germination. The effects of citral on the cell wall (sorbitol protect effect) and the cell membrane (citral to ergosterol binding) were investigated. Citral inhibited the growth of 50% of C. oxysporum strains employed in this study at an MIC 128μg/mL, as well as mycelial growth and conidia germination

Evaluation of antitumour and antiinflammatory effects and acute toxicity of extracts obtained from Streptomyces spp. isolated from m Soils of Paraiba (Brazil)

Bioactive metabolites produced by Streptomyces spp. commonly exhibit a variety of pharmacological properties such as antibiotic, antitumor, enzymatic and anti-helminthic. The study evaluated the possible antitumor and anti-inflammatory effects and the degree of toxicity of extracts isolated from Streptomyces in experimental models with animals. The extracts Sp-1 and Sp-3 did not have anti-inflammatory effect. In the Sarcoma 180 model the effects of Sp-1 and Sp-3 were significant with decreased average weights of tumors at 10 mg/kg, and reduction of up to 73 % of initial weight of the implanted tumor. For tumors of Ehrlich Carcinoma, the doses showed no significant effect on the average weight of tumors. Stimulant effects, such as exophthalmia, agitation, escape reaction, irritability, tremors and dermatitis were observed after 1 h of administration, depressive reactions were also observed, such as prostration and decreased respiratory rate, and no deaths were highlighted.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Avaliação da citotoxicidade in vitro e genotoxicidade ex-vivo em compostos da Pavonia glazioviana Gürke (Malvaceae)

Introduction: Alternative therapies using medicinal plants and herbal medicines are quite common in Brazil. Among several Brazilian plant species used in therapies, the species of the Malvaceae family stand out. Objetctives: The present study aimed to evaluate the in vitro cytotoxicity and ex-vivo genotoxicity in compounds of the Brazilian Pavonia glazioviana Gürke belonging to the Malvaceae family. Methodology: In vitro methods were used to verify the cytotoxic potential through hemolytic and antihemolytic assays and the ex-vivo genotoxic analysis. The Crude Etanolic Extract (CEE) and Cloroformic Fraction (CF) was obtained in vegetal sample used on this study. Results: The CEE-Pg and CF-Pg products only showed a low cytotoxic effect at the concentrations of 50 and 100 µg/mL. The exposure to the concentrations of 500 and 1000 µg/mL showed a high to moderate hemolytic index with lysis higher than 60%. A moderate anti-hemolytic effect was described in all samples treated with 500 and 1000 µg/mL, with hemolysis <60%. In addition, the compounds showed low ex-vivo genotoxic effect with a general index of normal cells greater than 84% at all concentrations. Conclusion: The results suggest a low toxic profile of the compounds obtained from the Pavonia glazioviana Gürke species belonging to the Malvaceae family, indicating safe limits for the use of these natural products.Introdução: as terapias alternativas que utilizam plantas medicinais e fitoterápicos são bastante comuns no Brasil. Dentre várias espécies vegetais brasileiras utilizadas em terapias destacam-se as espécies da família Malvaceae. Objetivos: o presente estudo teve como objetivo avaliar a citotoxicidade in vitro e a genotoxicidade ex-vivo em compostos da Pavonia glazioviana Gürke espécie brasileira pertencente à família Malvaceae. Metodologia: métodos in vitro foram utilizados para verificar o potencial citotóxico por meio de ensaios hemolíticos e anti-hemolíticos e da análise genotóxica ex-vivo. O Extrato Etanólico Bruto (EEB) e Fração Clorofórmico (FC) foram obtidos na amostra vegetal utilizada neste estudo. Resultados: os produtos EEB-Pg e FC-Pg apresentaram baixo efeito citotóxico apenas nas concentrações de 50 e 100 µg / mL. As amostras expostas às concentrações de 500 e 1000 µg / mL apresentaram índice hemolítico alto a moderado com lise superior a 60%. Foi descrito efeito anti-hemolítico moderado em todas as amostras tratadas com 500 e 1000 µg / mL, com hemólise < 60%. Além disso, os compostos mostraram baixo efeito genotóxico ex-vivo, com um índice geral de células normais superior a 84% em todas as concentrações. Conclusões: os resultados sugerem um baixo perfil tóxico dos compostos obtidos da espécie Pavonia glazioviana, indicando limites seguros para o uso desses produtos naturais

Evaluation of the antibacterial, modulatory and anti-adherent properties of oregano (Origanum vulgare) essential oil against food pathogenic bacteria

There are over 250 types of foodborne diseases, the majority of which are infections caused by bacteria. Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus saprophyticus are considered contaminants of meat products. The use of natural products as antimicrobials to combat these diseases can be an effective and economical approach. This study proposes to assess the antibacterial, modulatory, and anti-adherent activity of the essential oil of Origanum vulgare against strains of Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus saprophyticus isolated from meat products. The assay was conducted in duplicate. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined using the broth microdilution technique. MIC represents the lowest concentration of the product capable of inhibiting the growth of the bacterial strain, whereas MBC represents the lowest concentration capable of inhibiting total growth. The study of association of the product with antimicrobials was undertaken by disk diffusion using ampicillin, gentamicin, ceftazidime, and ciprofloxacin, resulting in synergistic, antagonistic, or indifferent effects. Anti-adherent activity was determined in the presence of sucrose, as the lowest concentration of the agent in contact with sucrose that prevented adherence to the glass tube. Oregano oil exhibited strong inhibitory and bactericidal activity against Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus saprophyticus, with MIC values ranging from 32 to 512 μg mL-1 and MBC values ranging from 128 to 512 μg mL-1. Origanum vulgare oil showed varied interactions when associated with antimicrobials, with modulations for synergism (37.5%), indifference (50%), and antagonism (12.5%). Regarding anti-adherent activity, the test product effectively inhibited the adherence of P. aeruginosa bacterial strains in the presence of sucrose (1:8) but had no effect against K. pneumoniae or S. saprophyticus. Therefore, oregano oil proves to be an antibacterial and modulating agent against different bacteria isolated from meat products. Additionally, it displays anti-adherent properties against P. aeruginosa, making it a natural product that could serve as an interesting alternative in efforts to combat foodborne diseases

Evaluation of the antibacterial effect of (R)-(+)-Limonene against Enterococcus faecalis and Enterobacter cloacae strains isolated from food

The aim of this study was to evaluate the potential antibacterial and anti-adherent activities of the monoterpene (R)-(+)-limonene, as well as its synergistic potential with synthetic antimicrobials against strains of Enterococcus faecalis and Enterobacter cloacae. The antibacterial properties of (R)-(+)-limonene were assessed using the broth microdilution technique to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Additionally, the infusion disc method was employed to explore the association of the compound with antimicrobials, and the test tube method was used to determine the minimum inhibitory concentration of adherence (MICA). It was observed that the MIC for (R)-(+)-limonene was 1000 μg mL-1 for five of the six E. faecalis strains tested, while for E. cloacae, the MIC exceeded 1000 μg mL-1 for all strains tested. Identical values were recorded for the MBC in E. faecalis. In terms of its combination with synthetic antimicrobials, (R)-(+)-limonene demonstrated a synergistic effect with gentamicin and ciprofloxacin for most strains. Regarding the MICA, both (R)-(+)-limonene and 0.12% chlorhexidine digluconate failed to inhibit biofilm formation at the tested concentrations. Given the need for new therapeutic alternatives for treating bacterial infections, this study revealed that the tested monoterpene exhibited moderate bactericidal effects against E. faecalis strains and no antibacterial effect against E. cloacae strains. However, when combined with various classes of antimicrobials, (R)-(+)-limonene showed synergistic effects with gentamicin and ciprofloxacin for most strains. This suggests that (R)-(+)-limonene holds promise for enhancing the treatment of bacterial infections and could support conventional therapies. Nonetheless, further in vitro, ex vivo, and in vivo studies are necessary to confirm and elucidate its efficacy and mechanisms.

Diretriz sobre Diagnóstico e Tratamento da Cardiomiopatia Hipertrófica – 2024

Hypertrophic cardiomyopathy (HCM) is a form of genetically caused heart muscle disease, characterized by the thickening of the ventricular walls. Diagnosis requires detection through imaging methods (Echocardiogram or Cardiac Magnetic Resonance) showing any segment of the left ventricular wall with a thickness > 15 mm, without any other probable cause. Genetic analysis allows the identification of mutations in genes encoding different structures of the sarcomere responsible for the development of HCM in about 60% of cases, enabling screening of family members and genetic counseling, as an important part of patient and family management. Several concepts about HCM have recently been reviewed, including its prevalence of 1 in 250 individuals, hence not a rare but rather underdiagnosed disease. The vast majority of patients are asymptomatic. In symptomatic cases, obstruction of the left ventricular outflow tract (LVOT) is the primary disorder responsible for symptoms, and its presence should be investigated in all cases. In those where resting echocardiogram or Valsalva maneuver does not detect significant intraventricular gradient (> 30 mmHg), they should undergo stress echocardiography to detect LVOT obstruction. Patients with limiting symptoms and severe LVOT obstruction, refractory to beta-blockers and verapamil, should receive septal reduction therapies or use new drugs inhibiting cardiac myosin. Finally, appropriately identified patients at increased risk of sudden death may receive prophylactic measure with implantable cardioverter-defibrillator (ICD) implantation.La miocardiopatía hipertrófica (MCH) es una forma de enfermedad cardíaca de origen genético, caracterizada por el engrosamiento de las paredes ventriculares. El diagnóstico requiere la detección mediante métodos de imagen (Ecocardiograma o Resonancia Magnética Cardíaca) que muestren algún segmento de la pared ventricular izquierda con un grosor > 15 mm, sin otra causa probable. El análisis genético permite identificar mutaciones en genes que codifican diferentes estructuras del sarcómero responsables del desarrollo de la MCH en aproximadamente el 60% de los casos, lo que permite el tamizaje de familiares y el asesoramiento genético, como parte importante del manejo de pacientes y familiares. Varios conceptos sobre la MCH han sido revisados recientemente, incluida su prevalencia de 1 entre 250 individuos, por lo tanto, no es una enfermedad rara, sino subdiagnosticada. La gran mayoría de los pacientes son asintomáticos. En los casos sintomáticos, la obstrucción del tracto de salida ventricular izquierdo (TSVI) es el trastorno principal responsable de los síntomas, y su presencia debe investigarse en todos los casos. En aquellos en los que el ecocardiograma en reposo o la maniobra de Valsalva no detecta un gradiente intraventricular significativo (> 30 mmHg), deben someterse a ecocardiografía de esfuerzo para detectar la obstrucción del TSVI. Los pacientes con síntomas limitantes y obstrucción grave del TSVI, refractarios al uso de betabloqueantes y verapamilo, deben recibir terapias de reducción septal o usar nuevos medicamentos inhibidores de la miosina cardíaca. Finalmente, los pacientes adecuadamente identificados con un riesgo aumentado de muerte súbita pueden recibir medidas profilácticas con el implante de un cardioversor-desfibrilador implantable (CDI).A cardiomiopatia hipertrófica (CMH) é uma forma de doença do músculo cardíaco de causa genética, caracterizada pela hipertrofia das paredes ventriculares. O diagnóstico requer detecção por métodos de imagem (Ecocardiograma ou Ressonância Magnética Cardíaca) de qualquer segmento da parede do ventrículo esquerdo com espessura > 15 mm, sem outra causa provável. A análise genética permite identificar mutações de genes codificantes de diferentes estruturas do sarcômero responsáveis pelo desenvolvimento da CMH em cerca de 60% dos casos, permitindo o rastreio de familiares e aconselhamento genético, como parte importante do manejo dos pacientes e familiares. Vários conceitos sobre a CMH foram recentemente revistos, incluindo sua prevalência de 1 em 250 indivíduos, não sendo, portanto, uma doença rara, mas subdiagnosticada. A vasta maioria dos pacientes é assintomática. Naqueles sintomáticos, a obstrução do trato de saída do ventrículo esquerdo (OTSVE) é o principal distúrbio responsável pelos sintomas, devendo-se investigar a sua presença em todos os casos. Naqueles em que o ecocardiograma em repouso ou com Manobra de Valsalva não detecta gradiente intraventricular significativo (> 30 mmHg), devem ser submetidos à ecocardiografia com esforço físico para detecção da OTSVE.   Pacientes com sintomas limitantes e grave OTSVE, refratários ao uso de betabloqueadores e verapamil, devem receber terapias de redução septal ou uso de novas drogas inibidoras da miosina cardíaca. Por fim, os pacientes adequadamente identificados com risco aumentado de morta súbita podem receber medida profilática com implante de cardiodesfibrilador implantável (CDI)