Validation of a bioanalytical HPLC-UV method to quantify Α-Bisabolol in rat plasma applied to pharmacokinetic pilot study with the drug nanoemulsion.

α-Bisabolol (α-BIS) is a sesquiterpene alcohol present in chamomile essential oil [Chamomilla recutita (L.) Rauschert]. Despite its numerous pharmacological effects, its pharmacokinetics remain understudied. An analytical method capable of quantifying α-BIS in plasma is crucial to enable pharmacokinetic analysis. Presently, only one study has quantified it using mass spectrometry. Administering α-BIS requires a nanoemulsion for intravenous injection. This study aimed to develop and validate a bioanalytical method using high-performance liquid chromatography with an ultraviolet detector to quantify α-BIS in rat plasma. The method employed acetonitrile and ultrapure water (80:20, v/v) as the mobile phase, with a flow rate of 1 ml/min and concentrations ranging from 465 to 29.625 µg/ml. All US Food and Drug Administration-designated assays were successful, indicating the method's precision, accuracy, sensitivity and linearity in determining α-BIS in rat plasma. The developed nanoemulsion, assessed through dynamic light scattering analysis, the ensemble collection of particles and polydispersity index evaluation, proved safe and effective for intravenous administration. The pharmacokinetic parameters such as volume of distribution, clearance and half-life indicated that α-BIS tends to persist in the body. This study provides a foundation for further research to explore α-BIS's potential pharmaceutical applications in the future.

Detección de SARS-CoV-2 en contactos estrechos asintomáticos de casos confirmados por diagnóstico molecular, provincia de Buenos Aires, Argentina / Detection of SARS-CoV-2 in asymptomatic close contacts of cases confirmed by molecular diagnosis, Buenos Aires province, Argentina

Resumen La detección de SARS-CoV-2 y su implicancia en el diagnóstico de COVID-19 han sido muy debatidas en la pandemia. El objetivo de este estudio fue evaluar el costo/beneficio de la detección de SARS-CoV-2 en contactos estrechos asintomáticos (CE) mediante el uso de distintas pruebas de diagnóstico molecular. Se estudiaron 51 CE de personas con diagnóstico de SARS-CoV-2 confirmado por RTqPCR, clasificadas por el umbral de ciclos (Ct) (<20, entre 20 y 30 y >30) en hospitales públicos de la provincia de Buenos Aires. Del total de contactos estudiados el 15,7% resultó confirmado para SARS-CoV-2; no hubo contactos positivos de casos con Ct>30. La cantidad de contactos positivos de casos con Ct<20 fue significativamente mayor que la de casos con Ct>20. Las muestras con Ct<20 se asociaron a una carga viral estimada de entre uno a cuatro órdenes de magnitud de diferencia con los rangos de Ct>20. Un 13,7% de contactos positivos fueron casos con Ct<20. De las muestras positivas confirmadas por PCR, correspondientes a la semana epidemiológica 1 de 2021 (SE1), sólo un 19,35% correspondían a muestras con Ct<20 y un 50,7% con Ct entre 20 y 30. Estos datos muestran un incremento de sólo un 3,7% de casos detectados. El esfuerzo por parte del sistema de salud pública para esta estrategia, con bajo poder predictivo, puede tener un efecto negativo para el cumplimiento del aislamiento de los contactos y podría generar una demora en los resultados de los casos sospechosos, sin aportar significativamente en el control de la pandemia.

Abstract The detection of SARS-CoV-2 and its implication in the diagnosis of COVID-19 have been highly debated in the pandemic. The objective of this study was to evaluate the cost/benefit of detecting SARS-CoV-2 in asymptomatic close contacts (CC) using different molecular diagnostic tests. A total of 51 CC of people with a diagnosis of SARS-CoV-2 confirmed by RTqPCR, classified by the cycle threshold (Ct) (<20, between 20 and 30 and >30), were studied in public hospitals in the Province of Buenos Aires. Of the total contacts studied, 15.7% were confirmed for SARS-CoV-2; there were no positive contacts of cases with Ct>30 positive. The number of positive contacts of cases with Ct<20 was significantly higher than that of cases with Ct>20. Samples with Ct<20 were associated with an estimated viral load of one to four orders of magnitude difference with Ct ranges >20. A total of 13.7% of positive close contacts were from cases with Ct<20. When studying positive samples with confirmed diagnosis by PCR, corresponding to 1 epidemiological week of 2021 (EW1), only 19.35% corresponded to samples with Ct<20 and 50.7% with Ct between 20 and 30. From these data it is shown that with the CC test only 3.7% of the cases were detected. The effort by the public health system for this strategy, with low predictive power, may have a negative effect on the fulfillment of the isolation of contacts and could generate a delay in the results of suspected cases, without contributing significantly to controlling the pandemic.

Resumo A detecção do SARS-CoV-2 e seu envolvimento no diagnóstico da COVID-19 têm sido muito discutidos durante a pandemia. O objetivo desse estudo foi avaliar a relação custo/benefício na detecção de SARSCoV- 2 em casos de contatos próximos assintomático (CP), por meio do uso de diferentes testes de diagnóstico molecular. Foram estudados 51 casos de CP de pessoas com diagnóstico de SARS-CoV-2 confirmado pelo RTqPCR, sendo classificados pelo limiar de ciclos (Ct) (<20, entre 20 e 30 e >30), em hospitais públicos da província de Buenos Aires. Do total de contatos estudados, 15,7% foram confirmados para SARS-CoV-2, não houve contatos positivos de casos com Ct>30. O número de contatos positivos de casos com Ct<20, foi significativamente maior que os casos com Ct>20. As amostras com Ct<20 foram associadas a uma carga viral estimada de uma a quatro ordens de magnitude de diferença com os intervalos de Ct>20. Dos casos positivos, 13,7% foram com Ct<20. Das amostras positivas confirmadas por PCR, correspondentes à semana epidemiológica 1 de 2021 (SE1), apenas 19,35% correspondiam a amostras com Ct>20 e 50,7% com Ct entre 20 e 30. Esses dados mostram incremento de apenas 3,7% de casos detectados. O esforço por parte do sistema de saúde pública para essa estratégia, com baixo poder preditivo, pode ter um efeito negativo no cumprimento do isolamento dos contatos e poderia gerar uma demora nos resultados dos casos suspeitos, sem contribuir significativamente para o controle da pandemia.

DETECTION OF SARS-CoV-2 IN ASYMPTOMATIC CLOSE CONTACTS OF CASES CONFIRMED BY MOLECULAR DIAGNOSIS, BUENOS AIRES PROVINCE, ARGENTINA / DETECCIÓN DE SARS-CoV-2 EN CONTACTOS ESTRECHOS ASINTOMÁTICOS DE CASOS CONFIRMADOS POR DIAGNÓSTICO MOLECULAR, PROVINCIA DE BUENOS AIRES, ARGENTINA / DETECÇÃO DE SARS-CoV-2 EM CONTATOS ESTREITOS ASSIMTOMÁTICOS DE CASOS CONFIRMADOS POR DIAGNÓSTICO MOLECULAR, PROVÍNCIA DE BUENOS AIRES, ARGENTINA

The detection of SARS-CoV-2 and its implication in the diagnosis of COVID-19 have been highly debated in the pandemic. Access to molecular diagnosis and its target population was essential in the public policy. The objective of this study was to evaluate the cost / benefit of detecting SARS-CoV-2 in asymptomatic close contacts using different molecular diagnostic tests. 51 close contacts of people with a diagnosis of SARS-CoV-2 confirmed by RTqPCR, classified by Ct (<20, between 20 and 30 and> 30), were studied in public hospitals in Province of Buenos Aires. Of all contacts studied, 15.7% were confirmed for SARS-CoV-2, there were no contacts of cases with Ct> 30 positive. The number of positive contacts of cases with Ct <20 was significantly higher than that of cases with Cts> 20. Samples with Cts <20 were associated with an estimated viral load of 1 to 4 orders of magnitude difference with Ct ranges> 20. 13.7% of positive close contacts were from cases with Ct <20. When studying positive samples with confirmed diagnosis by PCR, corresponding to EW1 of 2021, only 19.35% corresponded to samples with Cts <20 and 50.7% with Cts between 20 and 30. From these data it is shown that with the close contact test we could detect only 3.7% of cases. The effort by the public health system for this strategy, with low predictive power, may have a negative effect on the fulfillment of the isolation of contacts and could generate a delay in the results of suspected cases, without contributing significantly to controlling the pandemic.

La detección de SARS-CoV-2 y su implicancia en el diagnóstico de COVID-19 han sido muy debatidos en la pandemia. El acceso al diagnóstico molecular y su población destinataria fue parte esencial de las políticas públicas. El objetivo de este estudio fue evaluar el costo/beneficio de la detección de SARS-CoV-2 en contactos estrechos asintomáticos mediante el uso de distintas pruebas de diagnóstico molecular. Se estudiaron 51 contactos estrechos de personas con diagnóstico de SARS-CoV-2 confirmado por RTqPCR, clasificadas por Ct (<20, entre 20 y 30 y >30) en hospitales públicos de la Provincia de Buenos Aires. Del total de contactos estudiados el 15,7% resultó confirmado para SARS-CoV-2, no hubo contactos de casos con Ct>30 positivos. La cantidad de contactos positivos de casos con Ct<20 fue significativamente mayor que la de casos con Cts>20. Las muestras con Cts<20 se asociaron a una carga viral estimada de entre 1 a 4 órdenes de magnitud de diferencia con los rangos de Ct >20. Un 13,7% de contactos estrechos positivos fueron de casos con Ct<20. Al estudiar muestras positivas con diagnóstico confirmado por PCR, correspondientes a la SE1 del 2021, sólo un 19,35% correspondían a muestras con Cts<20 y un 50,7% con Cts entre 20 y 30. A partir de estos datos se muestra que con el testeo de contactos estrechos podríamos detectar sólo un 3,7% de casos. El esfuerzo por parte del sistema de salud pública para esta estrategia, con bajo poder predictivo, puede tener un efecto negativo para el cumplimiento del aislamiento de los contactos y podría generar una demora en los resultados de los casos sospechosos, sin aportar significativamente a controlar la pandemia.

A detecção de SARS-CoV-2 e sua implicação no diagnóstico de COVID-19 têm sido altamente debatidos na pandemia. O acesso ao diagnóstico molecular e à sua população-alvo era parte essencial das políticas públicas. O objetivo deste estudo foi avaliar o custo / benefício da detecção da SARS-CoV-2 em contatos próximos assintomáticos usando diferentes testes de diagnóstico molecular. 51 contatos próximos de pessoas com diagnóstico de SARS-CoV-2 confirmado pelo RTqPCR, classificados pelo Ct (<20, entre 20 e 30 e> 30), foram estudados em hospitais públicos da Província de Buenos Aires. Do total de contatos estudados, 15,7% foram confirmados para SARS-CoV-2, não houve contato de casos com Ct> 30 positivo. O número de contatos positivos de casos com Ct <20 foi significativamente maior que o de casos com Ct> 20. As amostras com Cts <20 foram associadas a uma carga viral estimada de 1 a 4 ordens de diferença de magnitude com intervalos de Ct> 20. 13,7% dos contatos próximos positivos eram de casos com Ct <20. Ao estudar amostras positivas com diagnóstico confirmado por PCR, correspondentes a EW1 de 2021, apenas 19,35% corresponderam a amostras com Cts <20 e 50,7% com Cts entre 20 e 30. A partir desses dados, mostra-se que com o teste de contato próximo poderíamos detectar apenas 3,7% dos casos. O esforço do sistema público de saúde por essa estratégia, com baixo poder preditivo, pode repercutir negativamente no cumprimento do isolamento dos contatos e pode gerar atraso nos resultados dos casos suspeitos, sem contribuir significativamente para o controle da pandemia.

Impactos da COVID-19 na aptidão cardiorrespiratória: exercícios funcionais e atividade física / Impacts of COVID-19 on cardiorespiratory fitness: functional exercises and physical activity

Este ensaio busca abordar as alterações causadas pela COVID-19 nas funções cardiorrespiratórias diárias das pessoas que contraíram a patologia e evidenciar a importância dos exercícios físicos antes e depois da contaminação pelo vírus. A infecção causada pelo novo coronavírus mostrou efeitos deletérios em funções cardiovasculares e pulmonares principalmente em pessoas que necessitaram de tratamento intensivo, podendo provocar déficits tanto na frequência cardíaca, quanto complicações no suprimento de oxigênio de outras estruturas, ao ser relacionada aos componentes moleculares do sistema cardiovascular. Ao afetar as funções de cunho cardiorrespiratório, percebe-se que a doença provoca alterações na funcionalidade das atividades diárias das pessoas acometidas com a COVID-19. A melhora da qualidade de vida através dos exercícios físicos já vem sendo evidenciada muito antes da pandemia, porém, neste momento notou-se uma necessidade de adaptação da maioria dos exercícios diante do isolamento social, para assim facilitar a manutenção do condicionamento físico

This essay seeks to address the changes caused by COVID-19 in the daily cardiorespiratory functions of people who contracted the pathology and to highlight the importance of physical exercises before and after contamination by the virus. The infection caused by the new coronavirus showed deleterious effects on cardiovascular and pulmonary functions, especially in people who needed intensive treatment, which can cause changes in both heart rate and complications in the oxygenation of other structures, when related to the molecular structures of the cardiovascular system. When affecting the cardiorespiratory functions, it is noticed that the disease causes a deficit in the functionality of the daily activities of people affected with COVID-19. The improvement in quality of life through physical exercises has already been evident long before the pandemic, however, at this moment there was a need to adapt most exercises in the face of social isolation, and thus facilitate the maintenance of physical conditioning

Does acidic drinks vs. controls differents interfere with the force of orthodontic chain elastics? / Bebidas ácidas versus diferentes controles interferem com a força de elásticos ortodônticos em cadeia?

This study aimed to investigate alterations in physical properties of orthodontic elastomeric chains when in contact with different controls and acidic beverages. Elastomeric chains were divided into 6 groups (n=18) of elastic chain segments, distributed as follows: Group CW (Deionized water) Group CS (Artificial saliva), Group CC (Coca-Cola®) Group SP (Sprite®) Group GA (Guaraná Antártica®) and Group FA(Fanta®). Elastics were stretched in 50% of the initial length and were held for initial, 1, 7, 14, 21 and 28 day time intervals. Force magnitudes were measured at 23.5 mm of activation using a digital meter. Force decay were assessed using analysis of variance(ANOVA) and Tukey's test(p<.05). Control Group CS saliva demonstrated the highest elastic decay values, with statistical difference between time of 24h with time intervals of 14, 21 and 28 days (p<.05). In comparison between groups, there was statistical difference between Group CS and Groups CW and FA in all experimental time-intervals, with group CC in time-intervals 7, 14, 21 and 28 days and with Group GA in time-intervals 7, 14 and 21 days (p<.05). In decreasing order: Coca-cola®, Fanta®, Guarana Antartica® and Sprite® demonstrated capacity to influence elastomeric chain decay, however with less influence than the saliva medium.

Este estudo objetivou investigar as alterações das propriedades físicas de cadeias elastoméricas ortodônticas quando em contato com diferentes controles e bebidas ácidas. Cadeias elastoméricas foram divididas em 6 grupos (n=18) de segmentos de elásticos em cadeia, assim distribuídos: Grupo CW (água deionizada), Grupo CS (saliva artificial), Grupo CC (Coca-Cola®), Grupo SP (Sprite®), Grupo GA (Guaraná Antártica®) e Grupo FA (Fanta®). Os elásticos foram esticados em 50 % do comprimento inicial e mantidos pelos intervalos de tempo inicial, 1, 7, 14, 21 e 28 dias. Magnitudes de força foram medidos em 23.5 mm de ativação usando um medidor digital. Degradação da Força foi avaliada através da análise de variância (ANOVA) e teste de Tukey (p<.05). Grupo Controle CS saliva demonstrou os maiores valores de degradação elástica, com diferença estatística entre o tempo de 24 h com intervalos de tempo de 14, 21 e 28 dias (p<.05). Na comparação entre os grupos, houve diferença estatística entre o Grupo CS e os Grupos CW e FA em todos os intervalos de tempos experimentais, com grupo CC nos intervalos de tempo de 7, 14, 21 e 28 dias e com o Grupo GA nos intervalos de tempo de 7, 14 e 21 dias (p<.05). Em ordem decrescente: Coca-cola®, Fanta®, Guaraná Antartica® e Sprite® demonstraram capacidade de influenciar a degradação da cadeia elastomérica, porém com menos influência do que o meio de saliva.

Mikania glomerata: Phytochemical, Pharmacological, and Neurochemical Study.

The present study primarily aims to identify the relative density and the fatty acids (methyl esters) content present in the standardized ethanol extract of leaves of M. glomerata (EPMG). Meanwhile, in a second moment, this study evaluated the effects of the EPMG on the levels of amino acids in the hippocampus, and the mechanism of sedative and anxiolytic action. Adult mice were treated with doses of 200, 300, and 400 mg/kg and evaluated in open field, elevated plus-maze, light dark, and rotarod tests. Moreover, in the behavioral tests diazepam (GABAergic anxiolytic, 2 mg/kg) as positive control and flumazenil (GABA antagonist, 2.5 mg/kg) were used to identify mechanism of sedative and anxiolytic action produced by EPMG. The EPMG is constituted by the following compounds: methyl cinnamate, 2H-1-benzopyran-2-one, (2-hydroxyphenyl)methyl propionate, (Z)-methyl-hexadec-7-enoate, methyl hexadecanoate, hexadecanoic acid, (Z)-methyl-octadec-9-enoate, octadecanoic acid, and squalene. This extract demonstrated anxiolytic effects, which may be mediated by GABAergic system, and was able to increase GABA levels and reduce of glutamate and aspartate concentrations in mice hippocampus, which can directly and/or indirectly assist in their anxiolytic effect. Although more studies are needed, the EPMG could represent an interesting therapeutical strategy in the treatment of anxiety.

Brazilian brown propolis elicits antileishmanial effect against promastigote and amastigote forms of Leishmania amazonensis.

Propolis is a complex matrix of chemical constituents extracted from plants and produced by bees which is used in folk medicine due to its several pharmacological properties. Its chemical composition varies according to the region where it is produced. This work has studied the antileishmanial activity and cytotoxicity of brown propolis (BP) originating from the semi-arid region of Piauí, Brazil. The BP showed significant inhibition of the Leishmania amazonensis promastigotes growth as well as being effective in reducing infection of murine macrophages and the number of internalised amastigotes in these cells. The dichloromethane fraction was the most active and showed the best selectivity index. The studied samples presented good activity and the fractioning improved the antileishmanial activity without an increase in the cytotoxicity against mammalian cells. Therefore, BP is a potential source for development of apitherapeutic products for the treatment of leishmaniasis.

Cytotoxic and leishmanicidal properties of garcinielliptone FC, a prenylated benzophenone from Platonia insignis.

Garcinielliptone FC (GFC), a natural prenylated benzophenone, was extracted from Platonia insignis Mart. (Clusiaceae), a native plant commonly known as bacuri and used in traditional Brazilian medicine for the treatment of skin diseases. The aim of this study was to evaluate the cytotoxic and leishmanicidal effects of GFC using in vitro models. The experimental data demonstrated that the polyisoprenylated benzophenone GFC possesses cytotoxic and leishmanicidal activities.

The cytotoxic and antileishmanial activity of extracts and fractions of leaves and fruits of Azadirachta indica (A Juss.).

The leishmaniases are severe parasitic diseases that occur worldwide, caused by protozoa of the genus Leishmania. Studies with medicinal plants can lead to a range of possibilities for treating and improving the patients' quality of life. Research on Azadirachta indica fractions and extracts has shown that they have excellent anti-leishmanial activity based on bioactivity-guided fractionation of ethanolic extracts of leaves and seeds and in vitro activity against promastigotes. In this research the most efficient extracts and fractions were selected for tests on intracellular amastigotes of Leishmania amazonensis. The ethanolic extract of the leaves and dichloromethane and chloroform fractions had IC(50) values of 38, 3.9 and 1.2 µg/mL for promastigotes and 9.8, 1.1 and 0.6 µg/mL for amastigotes, respectively, at 72 hours. For the ethanolic extract and dichloromethane fraction from nut tegument, the IC(50) was 2.7 and 2.1 µg/mL for promastigotes and 0.4 and 0.6 µg/mL for amastigotes. The cytotoxicity of the fractions presented selectivity that was between 8 to 32 times more toxic to promastigotes and 15 to 72 times to amastigotes than to macrophages. The extracts and fractions from leaves and fruits were more effective against amastigotes, and the fractionation increased activity against both promastigotes and amastigotes, enabling us to obtain potentially active fractions with low toxicity.

The cytotoxic and antileishmanial activity of extracts and fractions of leaves and fruits of Azadirachta indica (A Juss.)

The leishmaniases are severe parasitic diseases that occur worldwide, caused by protozoa of the genus Leishmania. Studies with medicinal plants can lead to a range of possibilities for treating and improving the patients' quality of life. Research on Azadirachta indica fractions and extracts has shown that they have excellent anti-leishmanial activity based on bioactivity-guided fractionation of ethanolic extracts of leaves and seeds and in vitro activity against promastigotes. In this research the most efficient extracts and fractions were selected for tests on intracellular amastigotes of Leishmania amazonensis. The ethanolic extract of the leaves and dichloromethane and chloroform fractions had IC50 values of 38, 3.9 and 1.2 μg/mL for promastigotes and 9.8, 1.1 and 0.6 μg/mL for amastigotes, respectively, at 72 hours. For the ethanolic extract and dichloromethane fraction from nut tegument, the IC50 was 2.7 and 2.1 μg/mL for promastigotes and 0.4 and 0.6 μg/mL for amastigotes. The cytotoxicity of the fractions presented selectivity that was between 8 to 32 times more toxic to promastigotes and 15 to 72 times to amastigotes than to macrophages. The extracts and fractions from leaves and fruits were more effective against amastigotes, and the fractionation increased activity against both promastigotes and amastigotes, enabling us to obtain potentially active fractions with low toxicity.

A própolis no combate a tripanossomatídeos de importância médica: uma perspectiva terapêutica para doença de chagas e leishmaniose / Propolis activity against trypanosomatids of medical relevance: a therapeutic perspective for chagas disease and leishmaniasis

Protozoonoses tais como leishmaniose e doença de Chagas, consideradas doenças negligenciadas, afetam milhões de pessoas em todo o mundo, por isso são constantes as pesquisas para o desenvolvimento de terapias mais eficazes. O interesse pela fitoterapia como fonte alternativa para o tratamento de inúmeras enfermidades tem crescido e merece destaque o uso da própolis, amplamente utilizada na prática médica popular. São atribuídas à própolis, principalmente às variedades encontradas no Brasil, diversas propriedades farmacológicas por sua complexa composição. Estudos in vivo e in vitro com extratos de própolis contra Trypanosoma cruzi e Leishmania vêm sendo realizados nos últimos anos com resultados promissores, embora sejam necessários estudos complementares. Este trabalho traz uma revisão sobre os aspectos clínicos e epidemiológicos da leishmaniose e doença de Chagas, assim como a aplicabilidade da própolis como um recurso terapêutico eficaz e seguro para o tratamento dessas protozoonoses.

Beneficios del pinzamiento umbilical tardío desde el punto de vista fisiológico adaptativo neonatal / Benefits from late umbilical locking from the physiological, adaptive, neonatal point of view

Este trabajo analiza la fisiología adaptativa del neonato con el fin de resaltar las bases cognitivas en las que se apoyan los estudios a favor del pinzamiento umbilical tardío, cuyas hipótesis sugieren que el extra de volumen proporcionado por este procedimiento produce una mejor transición cardiopulmonar y sistémica. Revisando el esquema actual fisiológico, la erección capilar pulmonar es un paso esencial en la adaptación neonatal, sugiriendo en teoría que un mayor flujo sanguíneo pulmonar aceleraría la reabsorción de líquido pulmonar y oxigenación alveolar, además de elevar el hematocrito y aumentar las reservas de hierro.