Moderate Toxicity of Potential Boron-containing Therapeutic, Dipotassium-trioxohydroxytetrafl uorotriborate - K2 (B3 O3 F4 OH) in Rats and Mice

Abstract Biological activity of boron-containing compounds (BCCs) has been well-known. Growing interest and numerous applications for BCCs have been reported. Boron and boron-containing acids show low acute toxicity in mammals but data on halogenated boroxine (HB) - dipotassium-trioxohydroxytetrafluorotriborate, K2(B3O3F4OH) acute toxicity have not been reported before. This compound, characterized as a potential therapeutic for skin changes, exhibits no observable genotoxicity in doses lower that 0.1 mg/ml in vitro and 55 mg/kg in vivo. It has also been confirmed as an antitumour agent both in vitro and in vivo as well as an inhibitor of enzymes involved in antioxidant mechanisms. The aim of this study was to assess the acute toxicity of HB and to determine the maximum tolerated dose as well as a dose free of any signs of toxicity in different test organisms. Acute toxicity of HB was tested in Sprague-Dawley and Wistar rats and BALB/c mice after single parenteral application of different doses. We determined doses free of any sign of toxicity and LD50 after single dose administration. LD50 of HB ranges from 63 to 75 mg/kg in different test models, meaning that HB shows moderate toxicity

Preformulation studies for the development of a microemulsion formulation from Ambrosia peruviana All, with anti-inflammatory effect

Abstract Natural products are considered an important source of the therapeutic arsenal currently available. Among these alternatives are the seeds of Ambrosia peruviana (altamisa), whose extract has shown an anti-inflammatory effect. The main objective of this work was to perform a preformulation study of Ambrosia peruviana seeds ethanolic extract, where the main factors that affect the physical, chemical, and pharmacological stability of the extract were evaluated, as well as a compatibility study by differential scanning calorimetry (DSC) analysis against different excipients. A dry extract was obtained by rotary evaporation of the seeds macerated with 96% ethanol. The anti-inflammatory activity was determined by measuring its effect on NO production in RAW 264.7 macrophages, stimulated with LPS. The results showed that the dry extract maintained its stability over time when stored at a temperature of 4 and 25ºC, demonstrating its biological activity, the content of phenolic compounds, and its physicochemical parameters remain practically invariable. However, when exposed to high temperatures (60 ºC) it was affected. The thermal analysis revelated that the behavior of most of the selected excipients and the dry extract was maintained, which indicates that it did not present incompatibilities, therefore they can be candidates for formulating a microemulsion.

Tratamientos y bioterapias para COVID-19 / Therapeutics and biotherapies for covid-19

INTRODUCCIÓN: Un nuevo brote de coronavirus surgió en 2019 en Wuhan, China, causando conmoción en el sistema sanitario de todo el mundo; el Comité Internacional de Taxonomía de Virus lo denominó SARS-CoV-2, agente causante de la enfermedad COVID-19.El espectro de gravedad de la enfermedad es muy amplio: la mayoría de los pacientes no presentan gravedad, pero otros pueden desarrollar neumonías, y la insuficiencia respiratoria aguda es la causa más frecuente de mortalidad. Objetivo: analizar y desarrollar las distintas alternativas terapéuticas aportadas por la Biotecnología para tratar los síntomas de aquellos pacientes con COVID-19. Metodología: se realizó una revisión de la bibliografía disponible, a partir de enero de 2020 en PubMed, acerca de los tratamientos que se encuentran aún en ensayos clínicos y aquellos que cuentan con aprobación bajo uso de emergencia para la enfermedad COVID-19. También se realizaron búsquedas a través de Google y Google Académico para publicaciones de organismos de Salud en referencia a políticas de salud establecidas para la terapéutica durante dicha pandemia. Resultados: este trabajo aborda las nuevas alternativas terapéuticas para COVID-19 derivadas de la Biotecnología, que se encuentran tanto en uso como en etapas de ensayos clínicos comprendidos dentro del segmento de los biofármacos y las bioterapias. Se incluye un breve resumen del estatus regulatorio de entidades de salud, el mecanismo de acción de dichas terapias y características generales de cada uno. Se incluyen novedosas bioterapias que se empezaron a implementar para afrontar la pandemia. Conclusiones: la pandemia de coronavirus está poniendo a prueba el sistema sanitario internacional, para brindar soluciones tanto desde el diagnóstico y prevención como para el tratamiento de la población a fin de disminuir la mortalidad. Esto incluyó, obviamente también, al área de la Biotecnología aplicada a la salud, que ha aportado en los tres aspectos mencionados; el presente trabajo se centra en las respuestas de tipo terapéutico que ha brindado y que están comercializadas o en fases clínicas. (AU)

INTRODUCTION: A new coronavirus outbreak emerged in 2019 in Wuhan, China, causing a shock to the healthcare system around the world; the International Committee on Taxonomy of Viruses named it SARS-CoV- 2, the infectious agent of the COVID-19 disease. The spectrum of severity of the disease is very wide, most patients are not serious, but others can develop pneumonia, with acute respiratory failure being the most frequent cause of mortality. Objective: to analyze and develop the different therapeutic alternatives provided by Biotechnology dedicated to Health, to treat the symptoms of those COVID-19 patients who require it, and thus reduce mortality.Methodology: a review of the available literature from January 2020 in PubMed of the treatments that are still in clinical trials and those that have been approved under emergency use for the disease COVID-19 was performed. Searches were also carried out through Google and Google Scholar for publications of Health organizations in reference to health policies established for therapeutics during the mentioned pandemic. Results: this work addresses the new therapeutic alternatives derived from Biotechnology, which are both in use and in stages of clinical trials, to treat patients who developed COVID-19 included within the segment of biopharmaceuticals and biotherapies. A brief summary of the regulatory status of health entities, the mechanism of action of said therapies and general characteristics of each one is included. Innovative biotherapies that began to be implemented to face the pandemic are included. Conclusions: The coronavirus pandemic has driven the international health system to the test, to provide solutions both from the diagnosis, prevention and treatment of the population to reduce the mortality of patients. This obviously also included the area of Biotechnology applied to health, which has contributed in the three aspects mentioned. The present work focuses on the therapeutic responses that it has provided and that are commercialized or in clinical phases. (AU)

Aplicación de la medicina natural y tradicional por profesionales de la salud en el nivel primario de atención / Use of natural and traditional medicine by health professionals in the primary care level i: en

Introducción: La medicina natural y tradicional es una alternativa terapéutica inocua, económica y de fácil aplicación; sin embargo, aún persiste el poco empleo de sus modalidades. Objetivo: Describir el uso de la medicina natural y tradicional por profesionales de la salud en el nivel primario de atención. Métodos: Se efectuó un estudio observacional, descriptivo y transversal, desde enero hasta marzo de 2022, que incluyó a los 167 médicos y enfermeros que laboraban en los 42 consultorios pertenecientes al Policlínico Docente Ernesto Guevara de la Serna del municipio de Niquero, provincia de Granma. Entre las variables analizadas figuraron: perfil profesional de los integrantes del equipo básico de salud, frecuencia de aplicación de la medicina natural y tradicional, modalidades más empleadas, prescripción según afecciones y fortalezas para garantizar la práctica de este tratamiento. Resultados: Predominaron los residentes de medicina general integral (34,8 %), el uso frecuente del tratamiento (43,1 %), así como la fitoterapia (86,8 %) y la apiterapia (73,6 %) como modalidades más empleadas; asimismo, la mayoría de las prescripciones fueron para los pacientes con enfermedades osteomioarticulares y cardiovasculares (55,7 y 37,1 %, respectivamente). Conclusiones: El empleo de la medicina natural y tradicional en la atención primaria de salud en el municipio de Niquero proporcionó la información necesaria a los profesionales de la salud para confeccionar planes futuros y trazar estrategias relacionadas con las variantes de tratamiento.

Introduction: The natural and traditional medicine is an innocuous, economic therapeutic alternative of easy application; however, the little use of its modalities still persists. Objective: To describe the use of natural and traditional medicine by health professionals in the primary care level. Methods: An observational, descriptive and cross-sectional study was carried out from January to March, 2022, that included the 167 doctors and male nurses that worked in the 42 family doctor offices belonging to Ernesto Guevara de la Serna Teaching Polyclinic of Niquero municipality in Granma. Among the analyzed variables were the following: professional profile of the health basic team, frequency of natural and traditional medicine use, most used modalities, prescription according to affections and strengths to guarantee the practice of this treatment. Results: There was a prevalence of residents in comprehensive general medicine (34.8 %), the frequent use of the treatment (43.1 %), as well as fitotherapy (86.8 %) and apitherapy (73.6 %) as most used modalities; also, most of the prescriptions were for the patients with osteomioarticular and cardiovascular diseases (55.7 and 37.1 %, respectively). Conclusions: The use of natural and traditional medicine in primary health care in Niquero municipality provided the health professionals with the necessary information to make future plans and trace strategies related to the treatment variants.

Ação de dentifrícios antiplaca e anticálculosobre esmalte dentário bovino / The action of antiplaque and anticalculus dentifrices in bovine dental enamel

Introdução: os dentifrícios antiplaca e anticálculo contêm, em sua composição, agentes específicos para o controle e a redução do biofilme dentário, como o citrato de zinco, o óxido de zinco e o pirofosfato tetrassódico, dentre outros. Objetivo: avaliar in vitroa ação de dentifrícios antiplaca e anticálculo na variação da massa e da rugosidade superficial do esmalte bovino submetido à escovação simulada por 6 e 12 meses.Metodologia: 40 corpos de prova (CP) foram randomizados e divididos aleatoriamente em 4 grupos (n=10): grupo controle (GC- água) e 3 grupos teste (GT1 ­ Colgate-Total® 12 Clean Mint, GT2 ­ Colgate-Total® 12 Anti-Tártaro, GT3 ­ Prevent® Antiplaca). Os CP foram submetidos à escovação simulada por 6 e 12 mesese as avaliações da massa e da rugosidade foram realizadas após cada período de escovação. Resultados: a análise da variação da massa demonstrou que não houve diferença significativa entre os grupos e os tempos. A avaliação da rugosidade demonstrou que, após 12 meses de escovação, o GT1 apresentou aumento significativo da rugosidade, quando comparado aos grupos controle e testes, enquanto os grupos GT2 e GT3 apresentaram comportamento semelhante após um ano de escovação, promovendo o polimento superficial do esmalte bovino. Conclusão: a escovação com os dentifrícios antiplaca ou anticálculo não promoveu perda significativa da massa no esmalte bovino e promoveu seu polimento.

Introduction: Antiplaque and anticalculus dentifrices contain in their composition specific agents for the control and reduction of dental biofilm, such as zinc citrate, zinc oxide, tetrasodium pyrophosphate, among others. Objective: To evaluate in vitro the action of antiplaque and anticalculus dentifrices on the variation of mass and surface roughness of bovine enamel submitted to simulated brushing for 6 and 12 months. Metodology: 40 specimens (PB) were randomized and randomly divided into 4 groups (n=10): control group (GC ­ water) and 3 test groups (GT1 ­ Colgate-Total® 12 Clean Mint, GT2 ­ Colgate-Total® 12 Anti-Tartar, and GT3 ­ Prevent®Antiplaque). The PB were submitted to simulated brushing for 6 and 12 months and the mass and roughness evaluations were performed after each brushing period. Results: The analysis of mass variation showed that there was no significant difference between groups and times. The roughness evaluation showed that after 12 months of brushing, GT1 showed a significant increase in roughness when compared to the control and test groups, while the GT2 and GT3 groups showed similar behavior after one year of brushing, promoting the surface polishing of bovine enamel. Conclusion: Brushing with antiplaque or anticalculus dentifrices did not promote significant mass loss in bovine enamel and promoted its polishing.

Fibrina rica en plaquetas aplicada en conjunto con biomodificación alveolar en la regeneración ósea guiada. Reporte de caso / Platelet rich fibrin applied in conjunction with alveolar biomodification in guided bone regeneration. Case report

Resumen Debido a los diferentes problemas existentes a la hora de realizar procedimientos implantológicos por la calidad del remanente óseo y el estado de los tejidos periodontales en la zona a rehabilitar, existen opciones de regeneración ósea inducida que muestran tasas de éxito considerablemente favorables al ser empleadas en casos donde es necesario una regeneración ósea extensa capaz de soportar un implante dental. El objetivo del presente estudio es describir el éxito en la regeneración ósea por medio de alternativas combinadas de fibrina rica en plaquetas y modificación biológica con tetraciclina. Reporte del caso clínico: paciente femenina de 67 años que consulta por inflamación, supuración y dolor en la zona antero-superior. Es diagnosticada como absceso periapical crónico, se hace cirugía de extracción de órganos dentales, posterior a eso se hace descontaminación y adaptación de los alveolos con tetraciclina para realizar la regeneración ósea guiada con fibrina rica en plaquetas, hueso tipo Lumina Bone Porous y Lumina Coat, luego se espera el proceso de evolución para colocación de implantes dentales. El éxito obtenido con el uso de fibrina rica en plaquetas y la biomodificacion ósea como coadyuvante en la desinfección de la zona a tratar, logró mostrar resultados altamente favorables en el proceso de regeneración ósea guiada.

Abstract As the different problems that exist when carrying out implant procedures due to the quality of the bone remnant and the state of the existing periodontal tissues in the area to be rehabilitated, there are induced bone regeneration options that show considerably favorable success rates as they are used in cases where extensive bone regeneration is necessary to support a dental implant. The objective of the present study is to describe the success in bone regeneration using combined alternatives of platelet-rich fibrin and biological modification with tetracycline. Report of the clinical case: 67-year-old female patient consulted for inflammation and suppuration and pain in the upper antero-superior area, she was diagnosed as chronic periapical abscess, dental organ extraction surgery was performed, after that decontamination and adaptation of the alveoli was performed with tetracycline to perform guided bone regeneration with platelet-rich fibrin, Coat membrane and Lumina bone criteria, then wait for the evolution process to place dental implants. The success obtained with the use of FRP and bone biomodification as an adjuvant in the disinfection of the area to be treated achieved to show highly favorable results in the guided bone regeneration process.

Estratégias anti-aging baseadas em moléculas químicas naturais como potentes ativadores de telomerase / Anti-aging strategies based on natural chemical molecules as potent telomerase activators / Estrategias antienvejecimiento basadas en moléculas químicas naturales como potentes activadores de la telomerasa

Mesmo em tempos modernos, os grandes avanços tecnológicos não permitem de forma comprovada retardar o envelhecimento nos seres humanos. Neste sentido, uma das estratégias é o uso moléculas químicas naturais que possuem a ação de ativadores de telomerase, uma vez de que a telomerase é uma ribonucleoproteína transcriptase reversa que possui a função de alongar os telômeros e neutralizar a erosão normal dos telômeros. Neste contexto, este estudo de revisão dedicou-se a aprofundar o conhecimento sobre o uso de moléculas químicas naturais derivadas de plantas que possuem função de ativadores de telomerase para atividade anti-aging. Inúmeras moléculas têm sido propostas e, estudas os seus mecanismos com o intuito de desenvolver novas ferramentas para prevenir/retardar e tratar doenças relacionadas a idade e o envelhecimento. Adicionalmente, o uso de moléculas como ativadores da telomerase têm sido um meio de prolongar o encurtamento dos temoleros, como no caso, de moléculas isolada da erva Astragalus membranaceus (TA-65), curcumina, silbinina e alicina; ademais, outras moléculas de origem natural possuem atividade anti-aging comprovadas, conforme reportadas nesta revisão. Sendo assim, a procura por biomarcadores à base de compostos químicos naturais que estimulem a telomerase, a fim de prolongar a vida dos telômero e assim, retardar o processo de envelhecimento do organismo têm despertado o interesse de diversos pesquisadores ao redor do mundo.

Even in modern times, the great technological advances do not allow in a proven way to delay aging in humans. In this sense, one of the strategies is the use of natural chemical molecules that have telomerase activators, since telomerase is a ribonucleoprotein reverse transcriptase that has the function of lengthening telomeres and neutralizing the normal erosion of telomeres. In this context, this review study was dedicated to deepening the knowledge about the use of natural chemical molecules derived from plants that have telomerase activator function for anti-aging activity. Numerous molecules have been proposed and their mechanisms studied in order to develop new tools to prevent/delay and treat aging-related diseases. Additionally, the use of molecules as telomerase activators has been a means of prolonging the shortening of temolers, as in the case of molecules isolated from the herb Astragalus membranaceus (TA-65), curcumin, silbinin and allicin; in addition, other molecules of natural origin have proven anti-aging activity, as reported in this review. Therefore, the search for biomarkers based on natural chemical compounds that stimulate telomerase in order to prolong the life of telomeres and, thus delay the aging process of the organism has aroused the interest of several researchers around the world.

Aún en los tiempos modernos, los grandes avances tecnológicos no permiten de manera comprobada retrasar el envejecimiento en los humanos. En este sentido, una de las estrategias es el uso de moléculas químicas naturales que tengan activadores de la telomerasa, ya que la telomerasa es una ribonucleoproteína transcriptasa inversa que tiene la función de alargar los telómeros y neutralizar la erosión normal de los telómeros. En este contexto, este estudio de revisión se dedicó a profundizar en el conocimiento sobre el uso de moléculas químicas naturales derivadas de plantas que tienen función activadora de la telomerasa para la actividad antienvejecimiento. Se han propuesto numerosas moléculas y se han estudiado sus mecanismos para desarrollar nuevas herramientas para prevenir/retrasar y tratar enfermedades relacionadas con el envejecimiento. Adicionalmente, el uso de moléculas como activadores de la telomerasa ha sido un medio para prolongar el acortamiento de temolers, como es el caso de moléculas aisladas de la hierba Astragalus membranaceus (TA-65), curcumina, silbinina y alicina; además, otras moléculas de origen natural han demostrado actividad antienvejecimiento, como se reporta en esta revisión. Por ello, la búsqueda de biomarcadores basados en compuestos químicos naturales que estimulen la telomerasa para prolongar la vida de los telómeros y así retrasar el proceso de envejecimiento del organismo ha despertado el interés de varios investigadores a nivel mundial.

Impacto de una intervención educativa en el conocimiento y manejo de residuos peligrosos biológico-infecciosos / Impact of an educational intervention on the knowledge and management of infectious biological hazardous waste

Introducción: el personal de enfermería tiene una participación fundamental en el manejo de los residuos peligrosos biológico-infecciosos (RPBI) durante la atención en salud, situación que hace indispensable el conocimiento respecto a la peligrosidad y riesgo en el manejo de estos residuos. Objetivo: evaluar el impacto de una intervención educativa acerca del conocimiento y manejo de RPBI, en el personal de enfermería de un hospital general regional. Metodología: estudio cuasi experimental, pretest/postest, prospectivo y longitudinal. Se realizó una intervención educativa, y antes y después de esta se aplicó un cuestionario para evaluar conocimientos relacionados con RPBI y una lista de cotejo del Modelo Institucional para la Prevención de Infecciones Nosocomiales (MIPRIN) para evaluar el manejo de RPBI. Resultados: la intervención educativa demostró un efecto positivo en los conocimientos del personal de enfermería en relación con el manejo de RPBI. En la evaluación pretest se obtuvo un porcentaje de conocimientos de 65.2% y en la postest fue de 78.3% (p < 0.001). Respecto al cumplimiento en el manejo de RPBI, hubo un incremento; sin embargo, no se puede atribuir a la intervención, puesto que se evaluó por servicio y no de manera directa con los participantes. Conclusión: la intervención educativa mostró cambios significativos en los conocimientos y el manejo de RPBI del personal de enfermería.

Introduction: Nursing staff represent an important percentage in the management of biological hazardous waste (BHW) during health care, a situation that makes this knowledge essential regarding the danger and risk in handling these wastes. Objective: To evaluate the impact of an educational intervention about the knowledge and management of BHW in the nursing staff of a regional general hospital. Methods: quasi-experimental, pre-test/post-test, prospective and longitudinal study. An educational intervention was carried out; before and after this intervention, a questionnaire was administered to evaluate knowledge related to BHW and a checklist of the Institutional Model for the Prevention of Nosocomial Infections (MIPRIN, according to its initials in Spanish) to evaluate the management of BHW. Results: The educational intervention showed a positive effect in the nursing staff's knowledge in relation to BHW. In the pre-test evaluation a knowledge percentage of 65.2% was obtained and in the post-test evaluation it was 78.3% (p < 0.001). Regarding compliance in the management of BHW there was an increase; however, it cannot be attributed to the intervention, since it was evaluated by service and not directly with the participants.

Perspectivas atuais da engenharia de tecidos da articulação temporomandibular / Perspectivas Actuales de la Ingeniería de Tejidos para la Articulación Temporomandibular / Current Perspectives of Tissue Engineering for the Temporomandibular Joint

Introdução: As limitações das terapias atuais para doenças degenerativas da articulação temporomandibular (ATM) levaram ao aumento do interesse em estratégias regenerativas. A engenharia de tecidos (ET), combinando células-tronco, arcabouços e fatores de crescimento, pode fornecer uma substituição biológica funcional e permanente das estruturas da ATM, além de prevenir o avanço de doenças degenerativas. Objetivo: Este artigo descreve as perspectivas atuais da ET das estruturas da ATM em modelos animais. Metodologia: As abordagens da ET foram categorizadas de acordo com as estruturas primárias da ATM: 1) o disco articular, 2) o côndilo mandibular e 3) a fossa glenóide e eminência articular. Resultados: As áreas com a maior quantidade de estudos são o côndilo mandibular e disco articular, em estudos que abordam o uso de arcabouços tridimensionais, de origem sintética e/ou natural, podendo ou não estar associados a células tronco (diferenciadas ou não) e a fatores de crescimento. Conclusão: A ET da ATM ainda é uma área relativamente nova, em desenvolvimento e em constante avanço. Os avanços tecnológicos desenvolvidos nessa área têm o potencial de auxiliar no desenvolvimento de terapias mais eficientes e menos invasivos... (AU)

Introducción: Las limitaciones de las terapias actuales para las enfermedades degenerativas de la articulación temporomandibular (ATM) han llevado a un mayor interés en las estrategias regenerativas. La ingeniería de tejidos, que combina células, andamios y factores de crecimiento, puede proporcionar un reemplazo biológico funcional y permanente de las estructuras de la ATM, además de prevenir el avance de enfermedades degenerativas. Objetivo: Este artículo describe las perspectivas actuales de la ingeniería de tecidos de las estructuras de la ATM en modelos animales. Metodología: Los enfoques de ingeniería de tejidos se clasificaron según las estructuras primarias de la ATM: 1) el disco articular, 2) el cóndilo mandibular y 3) la fosa glenoidea y la eminencia articular. Resultados: Las áreas con mayor número de estudios son el cóndilo mandibular y el disco articular, en estudios que abordan el uso de estructuras tridimensionales, de origen sintético y/o natural, que pueden o no estar asociadas a células (diferenciadas o no) y con factores de crecimiento. Conclusión: La ingeniería de tejidos de la ATM es todavía un área relativamente nueva, en desarrollo y en constante avance. Los avances tecnológicos desarrollados en esta área tienen el potencial de ayudar en el desarrollo de terapias más eficientes y menos invasivas... (AU)

Introduction: The limitations of current therapies for degenerative diseases of the temporomandibular joint (TMJ) have led to increased interest in regenerative strategies. Tissue engineering (TE), combining stem cells, scaffolds, and growth factors, can provide a functional and permanent biological replacement of TMJ structures, in addition to preventing the advancement of degenerative diseases. Aim: This article describes current TE perspectives of TMJ structures in animal models. Methods: TE approaches were categorized according to the primary TMJ structures: 1) the articular disc, 2) the mandibular condyle, and 3) the glenoid fossa and articular eminence. Results: The areas with the greatest number of studies are the mandibular condyle and articular disc, in studies that address the use of three-dimensional scaffolds, of synthetic and/ or natural origin, which may or may not be associated with stem cells (differentiated or not) and with growth factors. Conclusion: TE of the TMJ is still a relatively new, developing, and constantly advancing area. The technological advances developed in this area have the potential to assist in the development of more efficient and less invasive therapies... (AU)

Chemical composition and larvicidal activity of the essential oil of Pimenta dioica leaves / Composición química y actividad larvicida del aceite esencial de hojas de Pimenta dioica

In this study, we investigated the main constituent, the predominant class and biological activity of the essential oil extracted from the leaves of Pimenta dioica and the pattern of the major constituent against larvae in the third stage of Aedes aegypti. For this reason, we extracted the oil by hydrodistillation, identified its components by gas chromatography coupled with mass spectrometry (GC/MS) and calculated the lethal concentration (LC50) of the larvicidal activity using the Reed-Muench method. The results show that the oil consists mainly of eugenol, in which the phenylpropanoid class predominated and the lethal concentration, LC50, was 38.86 µg mL-1at a confidence level of 2.25 µg mL-1, while the eugenol standard presented LC5079.75 µg mL-1at a confidence level of 2.10 µg mL-1. Given the facts, we conclude that the oil is more active than the standard and that it has the potential to replace chemical larvicides.

En este estudio, investigamos el constituyente principal, la clase predominante y la actividad biológica del aceite esencial extraído de las hojas de Pimenta dioica y el patrón del constituyente principal contra las larvas en la tercera etapa de Aedes aegypti. Por este motivo, extrajimos el aceite por hidrodestilación, identificamos sus componentes mediante cromatografía de gases acoplada a espectrometría de masas (GC/MS) y calculamos la concentración letal (CL50) de la actividad larvicida mediante el método Reed-Muench. Los resultados muestran que el aceite está constituido principalmente por eugenol, en el que predominó la clase fenilpropanoide y la concentración letal, CL50, fue de 38,86 µg.mL-1 a un nivel de confianza de 2,25 µg.mL-1, mientras que el estándar de eugenol presentó CL50 79,75 µg.mL -1 a un nivel de confianza de 2,10 µg.mL-1. Dados los hechos, concluimos que el aceite es más activo que el estándar y que tiene el potencial de reemplazar los larvicidas químicos.

Potencialidades terapéuticas de la ozonoterapia en el Instituto de Hematología e Inmunología / Therapeutic potentialities of Ozone-therapy in the Hematology and Immunology Institute Sobre los autores:

La ozonoterapia permite aprovechar las reacciones del ozono con moléculas del organismo para inducir efectos biológicos deseados facilitando su empleo en el tratamiento de diferentes afecciones, incluidas las sepsis y el cáncer. El objetivo de este trabajo es describir brevemente las acciones atribuidas al empleo terapéutico del Ozono medicinal para incorporarlo a nuestros esquemas de tratamiento. Mediante la revisión de trabajos recientes que tratan el tema, se recopiló esta información que nos condujo a concluir que el uso del ozono médico, en las dosis adecuadas, es ventajoso en el tratamiento de los pacientes que se atienden en la institución(AU)

The Ozone-therapy allows using the potential of ozone reactions with body molecules in order to obtain a desired biological effect treating diseases as cancer and infection. The aim of this work is to shortly describe the attributable actions of therapeutic use of medicinal ozone to put it into the treatment schemes. By means of reviewing recent issues about the topic there was compiled the information that permits to conclude that usage of medical ozone, in appropriated dose, is an advantage in treatment of patients in the institute(AU)

Utilidad de los productos naturales en afecciones hematológicas e inmunológicas / Usefulness of therapeutic plasmapheresis in critical patients with organ dysfunction

Debido a sus metabolitos secundarios, las plantas medicinales presentan diversas acciones farmacológicas que posibilitan la elaboración de productos naturales. En el presente trabajo se describen, brevemente, las actividades con utilidad en las afecciones hematológicas e inmunológicas. Para ello se realizó una revisión actualizada de las investigaciones científicas acerca de esta temática, lo cual permitió concluir que el empleo de productos naturales, como tratamiento adyuvante, favorece adecuadamente a los pacientes con enfermedades hematológicas e inmunológicas(AU)

Due to their secondary metabolites, medicinal plants have various pharmacological actions that enable the development of natural products. In the present work, the activities useful in hematological and immunological conditions are briefly described. For this, an updated review of the scientific research on this subject was carried out, which allowed the conclusion that the use of natural products, as adjuvant treatment, adequately benefits patients with hematological and immunological diseases(AU)

The recent advances in developing gene editing and expression tools and the synthesis of natural products in Yarrowia lipolytica / 生物工程学报

Yarrowia lipolytica, as an important oleaginous yeast, has been widely used in metabolic engineering. Y. lipolytica is considered as an ideal host for the production of natural products such as terpenes, polyketides and flavonoids, due to its ability to utilize a variety of hydrophobic substrates, high stress tolerance to acid and salt, high flux of tricarboxylic acid cycle and the ability in providing abundant the common precursor acetyl-CoA. Recently, more and more tools for genetic editing, gene expression and regulation has been developed in Y. lipolytica, which facilitate the metabolic engineering of Y. lipolytica for bio-manufacturing. In this review, we summarized the recent progresses in developing gene expression and natural product synthesis in Y. lipolytica, and also discussed the challenges and possible solutions in heterologous synthesis of natural products in this yeast.

Protótipos microbianos como candidatos a fármacos para protozooses negligenciadas / Microbial prototypes as drug candidates for neglected protozoa

Doenças tropicais negligenciadas atingem cerca de 1,7 bilhões de pessoas, gerando um forte impacto na economia e problemas na Saúde Pública. Dentre as endemias mais negligenciadas, encontra-se a doença de Chagas, que afeta cerca de 6 milhões de pessoas, e no Brasil, dispõe-se de apenas de um fármaco altamente tóxico contra a infecção. Sendo assim, existe uma necessidade urgente para novos tratamentos. A exploração farmacológica de compostos produzidos por microrganismos é de longa data e contribuiu até hoje, com diversos fármacos aprovados. O presente projeto avaliou o potencial anti-Trypanosoma cruzi de metabólitos de espécies bacterianas marinhas encontradas no litoral paulista. Para isto, foram coletados invertebrados e sedimentos marinhos e isoladas 32 espécies bacterianas, resultando em 12 microrganismos identificados por MALDI-TOF/MS ou sequenciamento genético. Os extratos orgânicos, contendo os metabólitos microbianos, foram avaliados quanto ao potencial anti-T. cruzi em tripomastigotas, apresentando valores de Concentração Efetiva 50% (CE50) entre 1,5 e 59,0 µg/mL. Duas cepas foram submetidas à abordagem One Strain Many Compounds (OSMAC), porém, não se observou aumento da potência antiparasitária. O pré-fracionamento do extrato da Olleya marilimosa, resultou em uma fração (FII) ativa contra os tripomastigotas (CE50 23 µg/mL), com ausência de citotoxicidade em fibroblastos e hemácias até 200 µg/mL. A análise em ressonância magnética nuclear (RMN 1H) e espectrometria de massas de alta resolução, demonstrou a presença de 4 ácidos graxos de cadeia iso, 1 (C19H37O2), 2 (C20H39O2), 3 (C21H41O2) e 4 (C22H43O2)...(AU)

Neglected tropical diseases affects about 1.7 billion people, generating a strong impact on the economy and problems in Public Health. Among the most neglected endemic diseases is Chagas disease, which affects about 6 million people, and in Brazil, only one highly toxic drug is available against it. Therefore, there is an urgent need for new treatments. The pharmacological exploitation of compounds produced by microorganisms is long-standing and has contributed to several approved drugs. The present project evaluated the anti-Trypanosoma cruzi potential of metabolites of marine bacterial species found on the coast of São Paulo. For this, invertebrates and marine sediments were collected and 32 bacterial species were isolated, resulting in 12 microorganisms identified by MALDI-TOF/MS or genetic sequencing. The organic extracts containing the microbial metabolites were evaluated for antiT. cruzi potential. crossed in trypomastigotes, presenting Effective Concentration 50% (EC50) between 1.5 and 59.0 µg/mL. Two strains were submitted to the One Strain Many Compounds (OSMAC) approach, however, there was no increase in antiparasitic potency. Prefractionation of Olleya marilimosa extract resulted in an active fraction (FII) against trypanomastigotes (EC50 23 µg/mL), with no cytotoxicity in fibroblasts or red blood cells up to 200 µg/mL. Nuclear Magnetic Resonance analysis (NMR 1H) and High-Resolution Mass Spectrometry demonstrated the presence of 4 iso chain fatty acids, 1 (C19H37O2), 2 (C20H39O2), 3 (C21H41O2) and 4 (C22H43O2). Using spectrofluorimetry, it was observed that FII induced a change in the permeability of the plasma membrane of the parasite. Analysis in mass spectrometry (MALDI-TOF/MS) also demonstrated changes in the protein profile of parasites after treatment. This study presented in an unprecedented way, the anti-T. cruzi potential metabolites of the marine bacteria studied. The isolation and characterization of these compounds may contribute to new pharmaceutical prototypes for Chagas disease. (AU)

Launching a CDMO in Brazil aiming to develop biopharmaceuticals for clinical trials

The innovation timeline is expensive, risky, competitive, time-consuming, and labor-intensive. In order to overcome such challenges and optimize financial resources, pharmaceutical companies nowadays hire contract development and manufacturing organizations (CDMO) to help them. Based on the experience acquired first from the development of two biopharmaceuticals, the Heterologous Fibrin Sealant and the Apilic Antivenom, and more recently, during their respective clinical trials; the Center for the Study of Venoms and Venomous Animals (CEVAP) proposed to the Ministry of Health the creation of the first Brazilian CDMO. This groundbreaking venture will assist in converting a candidate molecule - from its discovery, proof of concept, product development, up to pilot batch production - into a product. The CDMO impact and legacy will be immense, offering service provision to the public and private sector by producing validated samples for clinical trials and academic training on translational research for those seeking a position in pharmaceutical industries and manufacturing platforms.(AU)

Voracity, reaction to stings, and survival of domestic hens when feeding on the yellow scorpion (Tityus serrulatus)

Scorpionism is a worldwide problem that has already made thousands of victims, and multi-disciplinary approaches for controlling their populations are to be more successful. Hens are often mentioned as tools for controlling scorpions; however, systematic/experimental behavioral studies are not available. Moreover, there is no systematic information on the effect of scorpion venoms on hens. Using the venomous yellow scorpion Tityus serrulatus, the present study aimed to clarify the following aspects: (1) voracity of hens, (2) how hens react when stung, (3) the effect of scorpion stings on hen behavior during attacks, and (4) hen survivorship after feeding on scorpions. Methods: We attracted hens with corn powder, offered them scorpions and then recorded the hen-scorpion interaction. To test the effects of the sting we manually removed the scorpion's telson. Results: We found that some hens ate up to six scorpions within minutes. By means of an ethogram and drawings, we showed that they exhibited several aversive behaviors when capturing scorpions. Removal of the scorpion telson stopped the aversive reactions, which was not observed in the control group. Finally, hens did not exhibit atypical behaviors after 1, 7 and 30 days and were all alive after 30 days. Conclusion: This is the first empirical and video recorded study providing evidence that hens are clearly affected by scorpion venom but do not die. Therefore, they may have potential to be used in biological control of these arthropods.(AU)

Synthesis and Biological Activity of Trolox Amide Derivatives

Abstract A series of Trolox amide derivatives were synthesized by modifying the carboxyl groups of Trolox. Thirty target compounds were obtained and characterized through nuclear magnetic resonance and mass spectrometry. Trolox derivatives were employed to explore the potential structure-antioxidant activity relationships. The antioxidant activities of these compounds were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP) and hydroxyl radical assays. DPPH scavenging activity test results illustrated that compounds exhibited scavenging activities similar to L-ascorbic acid and Trolox, with compounds 14a, 18a, 24a and 26a in particular exhibiting higher scavenging activities than L-ascorbic acid. The results demonstrated that compounds displayed ABTS scavenging activities similar to L-ascorbic acid and Trolox, with compounds 26a and 29a in particular having potency twofold higher. FRAP assay results indicated that compounds 11a, 19a, 25a, 29a and 30a had activity similar to Trolox. The results revealed that compounds 6a and 19a had similarly high hydroxyl radical-scavenging activities as Trolox. The results of α-glucosidase experiments uncovered that compounds 10a, 25a, 28a and 29a had excellent inhibitory activity, which was similar to that of acarbose and different from Trolox. The results of acetylcholinesterase and butyrylcholinesterase experiments demonstrated that some compounds had weak anticholinesterase activities. 26a and 29a are important Trolox derivatives with better biological activity profiles and deserve further study

Estratégias de enfrentamento em acidentes de trabalho com exposição ao material biológico / Coping strategies for workplace accidents involving exposure to biological material / Estrategias de enfrentamiento en accidentes de trabajo con exposición al material biológico

Diferentes trabalhadores estão sujeitos a acidentes com material biológico, que geram não apenas agravos físicos, mas, sobretudo, psicológicos. O coping ocupacional é a tentativa individual de adaptação às situações estressantes no ambiente de trabalho. O estudo analisou as estratégias de enfrentamento utilizadas pelos trabalhadores da área da saúde que se acidentam com material biológico. Adotou como método o estudo descritivo, com abordagem qualitativa, realizado por meio de entrevistas semiestruturadas com dez trabalhadores da área da saúde que trabalham em hospitais e sofreram acidente com exposição a material biológico recentemente, selecionados a partir da estratégia de bola de neve. As entrevistas foram gravadas, transcritas e organizadas, e, para análise do conteúdo, foram utilizadas as etapas da técnica propostas por Bardin. Os resultados mostraram que a estratégia de enfrentamento mais representativa para os trabalhadores pesquisados foi o controle por meio da busca de mudança de atitudes em relação às rotinas de trabalho e do aperfeiçoamento técnico. A metodologia utilizada proporcionou a identificação, ainda, de outras estratégias, caso da autoculpabilização e a da interação social. Aponta para a importância da formação integrada e continuada no espaço de trabalho como forma de prevenção e de condução dos acidentes de trabalho.(AU)

Diverse workers are subject to accidents involving biological material, which cause not only physical injury but, above all, psychological damage. Occupational coping is the individual's attempt to adapt to stressful situations in the workplace. The study analyzed the coping strategies of health professionals who suffered accidents involving biological material. It adopted a descriptive method, with a qualitative approach, carried out by using semi-structured interviews with ten health professionals working in hospitals and who had recently suffered accidents involving exposure to biological material, selected with a snowball sampling strategy. The interviews were recorded, transcribed, and organized, and for the analysis of the content, the technique of content analysis proposed by Bardin was used. The results showed that the most common coping strategy for the workers surveyed was control by seeking a change of attitudes regarding work routines and technical improvements. The methodology also identified other strategies, such as self-blaming and social interaction. These findings point to the importance of integrated and continuous workplace training as a way to prevent and manage workplace accidents.(AU)

Los trabajadores están sujetos a accidentes con material biológico, los cuales ocasionan no solo agravios físicos, sino también psicológicos. El coping ocupacional es el intento individual de adaptación a las situaciones estresantes en el ambiente de trabajo. Este estudio tuvo como objetivo analizar las estrategias de enfrentamiento utilizadas por los trabajadores del área de la salud que sufrieron accidentes con material biológico. El método que se utilizó fue el estudio descriptivo, de naturaleza cualitativa, a partir de la aplicación de entrevistas semiestructuradas a diez trabajadores del área de la salud en hospitales y que sufrieron accidentes con materiales biológicos recientemente, seleccionados por la estrategia de bola de nieve. Las entrevistas fueron grabadas, transcritas y organizadas, y para el análisis del contenido se utilizaron las etapas de la técnica propuestas por Bardin. Los resultados mostraron que el control fue la estrategia de enfrentamiento más utilizada mediante la búsqueda de cambio de actitud con relación a las rutinas de trabajo y al perfeccionamiento técnico. La metodología permitió identificar otras estrategias, como la autoculpabilización y la interacción social. Cabe destacar la importancia de la formación integrada y continua en el espacio de trabajo como medio de prevención y de manejo a accidentes de trabajo.(AU)

A comparative study on biological activities of different solvent extracts from whole seed, seed coat and cotyledon of two Lathyrus species

Abstract The present study was conducted to assess the phenolic content, and antibacterial and antioxidant activities of Lathyrus L. species. The extraction of phenolic compounds from whole seeds, seed coat and cotyledon of Lathyrus hierosolymitanus Boiss. and Lathyrus annuus L. seeds was performed employing different solvents. Total phenolic content (TPC) was measured by Folin- Ciocalteau assay, while the antioxidant activity was determined by DPPH radical scavenging activity, and reducing power assay. It was found that TPC of extracts ranged from 0.12 mg to 6.53 mg GAE/gdw. For each solvent, seed coat extracts were generally observed to render higher TPC and antioxidant activities. There was a correlation between TPC and antioxidant activity. In addition, all extracts were also examined for their antimicrobial activity against Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. Methanol extracts showed the highest antibacterial activity which is consistent with TPC, but there was no correlation between TPC and antibacterial activity. Solvents were observed to have effects on gallic acid, caffeic acid, and epicatechin extractions. HPLC analysis results of extracts confirmed methanol and ethanol as preferred solvents for phenolic extraction from Lathyrus sp. Phenolic content in the extracts could be suggested to contribute to their antioxidant and antibacterial activity.

Pretreatment with water kefir reduces the development of acidified ethanol-induced gastric ulcers

Abstract To evaluate the gastroprotective and antioxidant effects of pretreatment with water kefir on ulcers induced with HCl/ethanol. All pretreatments lasted 14 days. Male mice were separated into five groups: the control (C) group received vehicle without ulcer induction; the ulcerated (U) group received vehicle; the lansoprazole (L) group received 30 mg/kg/day lansoprazole; the water kefir (WK15 and WK30) groups received WK at a dose of 0.15 or 0.30 ml/kg/day, respectively. Gastroprotection was measured by ulcer area, ulcer index and ulcer reduction percentage. Antioxidant effects were quantified by measuring advanced oxidized protein products (AOPPs), superoxide dismutase (SOD), and catalase activity in the stomach. Pretreatment with WK at both doses promoted gastroprotection against HCl/ethanol-induced ulcers much like the pretreatment with lansoprazole. In addition, WK decreased protein oxidation while increasing SOD and catalase activity. We concluded that pretreatment with water kefir increases the activity of antioxidant enzymes, preventing gastric lesions induced by HCl/ethanol by maintaining the antioxidant performance in gastric tissue.