Neurotrophic Factor Mediated Neurorestorative Effect of Pongamia pinnata Against Transient Cerebral Hypoperfusion and Reperfusion in Rats: Preliminary Histological and Molecular Level Evidence / Efecto Neurorestaurador Mediado por Factor Neurotrófico de Pongamia pinnata Contra la Hipoperfusión y Reperfusión Cerebral Transitoria en Ratas: Evidencia Preliminar de un Estudio a Nivel Histológico y Molecular

SUMMARY: Stroke is the leading cause of acquired physical disability in adults and second leading cause of mortality throughout the world. Treatment strategies to curb the effects of stroke would be of great benefit. Pongamia pinnata is a recent attraction in medicine, owing to its abundant medicinal benefits with minimal side effects. The present study aimed to examine acute and subacute effect of Pongamia pinnata leaf extract on transient cerebral hypoperfusion and reperfusion (tCHR) in Wistar rats. 24 adult Wistar rats (12 each for acute and subacute study) were divided in to four groups each viz normal control group, tCHR + NS group, tCHR + 200mg/kg bw and tCHR + 400mg/kg bw groups. Cerebral ischemia induction was carried out by bilateral common carotid artery occlusion and reperfusion. Ethanolic extract of Pongamia pinnata leaves were orally administered for 7 days and 21 days after the surgical procedure for acute and subacute study respectively. Behavioural analysis, histological assessment, and estimation of mRNA levels of HIF-1, GDNF, BDNF and NF-kB were performed. In both acute and subacute study, there was significant improvement in the beam walking assay, neuronal count, decreased neuronal damage in histological sections and higher mRNA expression of BDNF and GDNF in the treatment groups. There was no significant difference in the expression of HIF1 and NF-kB. Thus, Pongamia pinnata has excellent neurorestorative property reversing many of the effects of ischemic stroke induced by tCHR in rats with the underlying mechanism being an improvement in the expression of neurotrophic factors GDNF and BDNF.

El ataque cerebrovascular es la principal causa de discapacidad física adquirida en adultos y la segunda causa de mortalidad en todo el mundo. Las estrategias de tratamiento para frenar los efectos del ataque cerebrovascular serían de gran beneficio. Pongamia pinnata es una atracción reciente en la medicina, debido a sus abundantes beneficios medicinales con mínimos efectos secundarios. El presente estudio tuvo como objetivo examinar el efecto agudo y subagudo del extracto de hoja de Pongamia pinnata sobre la hipoperfusión y reperfusión cerebral transitoria (tCHR) en ratas Wistar. Se dividieron 24 ratas Wistar adultas (12 cada una para el estudio agudo y subagudo) en cuatro grupos, el grupo control normal, el grupo tCHR + NS, los grupos tCHR + 200 mg/kg de peso corporal y tCHR + 400 mg/kg de peso corporal. La inducción de la isquemia cerebral se llevó a cabo mediante oclusión y reperfusión bilateral de la arteria carótida común. El extracto etanólico de hojas de Pongamia pinnata se administró por vía oral durante 7 días y 21 días después del procedimiento quirúrgico para estudio agudo y subagudo respectivamente. Se realizaron análisis de comportamiento, evaluación histológica y estimación de los niveles de ARNm de HIF-1, GDNF, BDNF y NF-kB. Tanto en el estudio agudo como en el subagudo, hubo una mejora significativa en el ensayo de desplazamiento del haz, el recuento neuronal, una disminución del daño neuronal en las secciones histológicas y una mayor expresión de ARNm de BDNF y GDNF en los grupos con tratamiento. No hubo diferencias significativas en la expresión de HIF1 y NF-kB. Por lo tanto, Pongamia pinnata tiene una excelente propiedad neurorestauradora que revierte muchos de los efectos del ataque cerebrovascular isquémico inducido por tCHR en ratas, siendo el mecanismo subyacente una mejora en la expresión de los factores neurotróficos GDNF y BDNF.

Uso de hierro intravenoso en el tratamiento de la anemia ferropénica en niños: a propósito de un caso / Use of intravenous iron for the treatment of iron deficiency anemia in children: clinical case study / Uso de ferro intravenoso no tratamento da anemia ferropriva em crianças: relato de caso

Introducción: el déficit de hierro es la causa más común de anemia debido a carencia nutricional. Su tratamiento consiste en proporcionar alimentos ricos en hierro biodisponible junto con la administración de hierro oral. En circunstancias definidas puede utilizarse el hierro intravenoso. Objetivo: describir el abordaje diagnóstico y terapéutico de un niño portador de anemia ferropénica severa secundaria a mala adherencia al hierro oral en el que se utilizó hierro intravenoso. Caso clínico: niño de 21 meses, raza blanca. Antecedente de anemia ferropénica severa, con repercusión hemodinámica que a los 14 meses requirió transfusión de sangre desplasmatizada. Sin controles de hemoglobina posteriores. Sin adherencia a profilaxis con hierro vía oral. Alto consumo de leche de vaca y bajo consumo de alimentos ricos en hierro. En el contexto de infección respiratoria aguda baja se constata anemia clínica con marcado decaimiento y anorexia, sin repercusión hemodinámica. Se confirma la anemia microcítica, hipocrómica severa, con ancho de distribución eritrocitaria elevado, con metabolismo de hierro alterado. Recibe hierro sacarato, intravenoso, por seis días con buena tolerancia y evolución. Discusión: se identificaron múltiples factores de riesgo para anemia ferropénica. La pobre respuesta al tratamiento con hierro oral debido a efectos adversos y olvidos de administración, junto al antecedente de anemia ferropénica severa, que requirió transfusión de sangre desplasmatizada, motivaron la indicación de hierro intravenoso. Su administración fue programada y monitorizada, sin complicaciones. Es necesario fortalecer la prevención en todos los controles pediátricos y abordar este problema de salud desde una mirada interdisciplinaria.

Introduction: iron deficiency is the most common cause of anemia due to nutritional deficiency. Its treatment consists of providing bioavailable iron rich food together with oral iron. In specific circumstances, intravenous iron may be used. Objective: of this study is to describe the diagnostic and therapeutic approach used with a child with severe iron deficiency anemia secondary to poor adherence to oral iron, in which intravenous iron was used. Clinical case: 21 month-old white patient. History of severe iron deficiency anemia, with hemodynamic repercussions that at 14 months of age required transfusion of deplasmatized blood. Without subsequent hemoglobin controls. No adherence to oral iron prophylaxis. High consumption of cow's milk and low of iron-rich foods. Within the context of acute lower respiratory infection, a clinical anemia with marked decline and anorexia were observed, without hemodynamic repercussions. Severe hypochromic microcytic anemia was confirmed, with an elevated erythrocyte distribution width and altered iron metabolism. He received iron saccharate, intravenously for 6 days with good tolerance and evolution. Discussion: multiple risk factors for iron deficiency anemia were identified. The poor response to treatment with oral iron resulting from adverse effects and lack of proper administration, together with a history of severe iron deficiency anemia, which required transfusion of deplasmatized blood, led to the prescription of intravenous iron. This administration was scheduled and monitored, occurring without complications. It is necessary to strengthen prevention of this condition in all pediatric check-ups and address this health problem from an interdisciplinary perspective.

Introdução: a deficiência de ferro é a causa mais comum de anemia por deficiência nutricional. Seu tratamento consiste no fornecimento de alimentos ricos em ferro biodisponível, juntamente com a administração de ferro por via oral. Em circunstâncias especificas, pode ser utilizado ferro intravenoso. Objetivo: descrever a abordagem diagnóstica e terapêutica de uma criança com anemia ferropriva grave secundária a sua má adesão ao ferro oral, e o uso de ferro intravenoso. Caso clínico: 21 meses, raça branca. História de anemia ferropriva grave, com repercussão hemodinâmica que requiriu de transfusão de sangue desplasmatizada aos 14 meses. Não houve nenhum controle de hemoglobina subsequente. Nenhuma adesão à profilaxia oral com ferro. Alto consumo de leite de vaca e baixo consumo de alimentos ricos em ferro. No contexto de infecção respiratória inferior aguda, observa-se anemia clínica com acentuado emagrecimento e anorexia, sem repercussões hemodinâmicas. É confirmada anemia microcítica e hipocrômica grave, com largura de distribuição eritrocitária elevada e metabolismo alterado do ferro. Recebeu sacarose férrica intravenosa por 6 dias com boa tolerância e evolução. Discussão: foram identificados múltiplos fatores de risco para anemia ferropriva. A má resposta ao tratamento com ferro oral devido aos efeitos adversos e ao esquecimento da administração, aliás da história de anemia ferropriva grave, que exigiu transfusão de sangue desplasmatizada, motivaram a indicação do ferro intravenoso. Sua administração foi programada e monitorada, e aconteceu sem intercorrências. É preciso fortalecer a prevenção em todos os controles pediátricos e abordar este problema de saúde numa persectiva interdisciplinar.

Evaluación de hábitos de medicación sistémica de odontólogos especialistas y no especialistas en endodoncia ante patologías pulpares en Argentina / Evaluation of systemic medication habits of specialists and non-specialists dentists in endodontists in relation to different pulp pathologies in Argentina

Objetivo: Determinar los hábitos de medicación sistémica de odontólogos especialistas y no especialistas en endodoncia ante diferentes patologías pulpares previos al tratamiento en- dodóntico en Argentina. Materiales y métodos: Se diseñó una encuesta para evaluar la prescripción de antibióticos, tipo de antibióticos, tiempo de prescripción, indicación de antinflamatorios no es- teroides y esteroides ante diferentes patologías pulpares. Se envió a 635 odontólogos especialistas y no especialistas en endodoncia a través de SurveyMonkey. Por medio de la prue- ba de Chi cuadrado se evaluaron las diferencias de medica- ción entre los grupos estudiados. Resultados: En pulpitis se medicó con antibióticos en el 3,48% de los casos y con antinflamatorios en un 62,60%. En necrosis pulpar sin fístula no se indicó ninguna medica- ción en un 64,47% de los casos, seguido de antibióticos en un 24,56%. En necrosis con fístula, el 52,38% no indicó nin- guna medicación, seguido de medicación con antibióticos en un 35,49%. En periodontitis apical aguda la principal medica- ción fue con antinflamatorios (52,79%), seguido de antibió- ticos (32,87%); y en el absceso alveolar agudo, un 57,10% indicó antibióticos seguido de antinflamatorios. El antibiótico de elección fue la penicilina en un 65,23% de los casos, y en caso de alergia a la misma, el antibiótico elegido fue azitromi- cina (30,12%). El tiempo de prescripción fue de 7 días. En la comparación entre especialistas y no especialistas hubo dife- rencias estadísticamente significativas para pulpitis y necrosis con fístula (p<0,01) y no las hubo entre necrosis sin fístula, periodontitis apical aguda y absceso alveolar agudo (p> 0,05). Conclusiones: La penicilina fue el antibiótico de elec- ción de la mayoría de los odontólogos argentinos encuestados junto al ibuprofeno como anti-inflamatorio. Existiría una so- bremedicación en patologías endodónticas que podría contri- buir a la resistencia microbiana a los antibióticos (AU)

Aim: Determine the systemic medication habits of den- tists specialists and non-specialists in endodontists in differ- ent pulp pathologies prior to root canal treatment in Argen- tina. Materials and methods: A survey was designed to evaluate the prescription of antibiotics, the type of antibiotics, prescription time, indication of non-steroidal anti-inflamma- tory drugs in different pulp pathologies. It was sent to 635 general dentists and endodontic specialists via SurveyMon- key. A Chi-square test was made to evaluate the differences in medication between the studied groups. Results: In pulpitis, antibiotics were prescribed in 3.48% of cases and anti-inflammatories in 62.60%. In pul- pal necrosis without fistula, no medication was indicated in 64.47% of cases, followed by antibiotics in 24.56%. In ne- crosis with fistula, 52.38% did not indicate any medication, followed by medication with antibiotics in 35.49%. In acute apical periodontitis the main medication was anti-inflamma-tories (52.79%), followed by antibiotics (32.87%); and for acute alveolar abscess, 57.10% indicated antibiotics, fol- lowed by anti-inflammatories. The antibiotic of choice was penicillin in 65.23% of the cases, and in case of allergy to it, the chosen antibiotic was azithromycin (30.12%). The prescription time was 7 days. In the comparison between specialists and non-specialists, there were significant dif- ferences for pulpitis and necrosis with fistula (p<0.01) and there were no significant differences between necrosis without fistula, acute apical periodontitis and acute alveo- lar abscess (p>0.05). Conclusions: Penicillin was the antibiotic of choice for the majority of the surveyed Argentine dentists, as well as ibuprofen as an anti-inflammatory drug. These could reflect an overmedication in endodontics pathologies that could con- tribute to microbial resistance to antibiotics (AU)

Fibrilación auricular una arritmia y un sindrome / Atrial fibrillation, an arrhythmia and a syndrome

Atrial Fibrillation (AF) is the most common sustained arrhythmia and is highly prevalent in elderly patients. It confers a higher risk for ischemic stroke, heart failure and death. The diagnosis and treatment of AF has been extensively studied and remain under constant revision. This article reviews the recent European guidelines and the advances observed with the introduction of direct oral anticoagulants in the last ten years. This new family of drugs has clear benefits in terms of efficacy and safety compared with traditional vitamin K antagonists. Treatment of most common comorbidities in patients with AF such as advanced age, heart failure, diabetes, renal failure, and others are also analyzed. New therapies for AF will be shortly available.

Avaliação do conhecimento sobre a terapêutica medicamentosa de indivíduos em uso de anticoagulantes orais / Evaluation of knowledge about drug therapeutics of individuals using anticoagulants / Evaluación del conocimiento sobre drogoterapéutica de personas que usan anticoagulantes

Objetivo: Avaliar o conhecimento sobre a terapêutica medicamentosa de indivíduos em uso de anticoagulantes orais. Métodos: Estudo transversal, quantitativo, com participação de 90 indivíduos em uso de anticoagulantes orais acompanhados em ambulatório de anticoagulação em Recife-PE. Os dados foram coletados de abril a julho de 2020 através de dois questionários, analisados por estatística descritiva e dispostos em tabelas. Resultados: A maioria dos indivíduos (42,2%) apresentou conhecimento adequado acerca do tratamento. Na associação do conhecimento com outras variáveis, houve significância estatística entre conhecimento adequado com resultados do International Normalized Ratio dentro da faixa indicada (p=0,001) e com idade menor que 60 anos (p=0,018), e entre conhecimento inadequado com baixa escolaridade (p=0,045), hipertensão (p=0,009) e tabagismo (p=0,041). Conclusão: A maioria dos indivíduos apresentou conhecimento adequado acerca do tratamento. Houve associação significativa entre conhecimento adequado e resultados do INR e entre a idade, assim como conhecimento inadequado e baixa escolaridade, não ser tabagista e hipertensão. (AU)

Objective: to assess knowledge about drug therapy using oral anticoagulant drugs. Methods: Cross-sectional, quantitative study, with the participation of 90 users using anticoagulants or followed up in an anticoagulation clinic in Recife-PE. Data were collected from April to July 2020 through two questionnaires, dispersed by descriptive statistics and arranged in tables. Results: Most owners (42.2%) have adequate knowledge of the treatment. In the association of knowledge with other variables, there was significance between adequate knowledge with results of the International Normalized Ratio within the given range (p = 0.001) and aged less than 60 years (p = 0.018), and between inadequate knowledge with low education (p = 0.018) p = 0.045), hypertension (p = 0.009) and smoking (p = 0.041). Conclusion: Most individuals had adequate knowledge about the treatment. There was a significant association between adequate knowledge and INR results and between age, as well as inadequate knowledge and low education, not being a smoker and hypertension. (AU)

Objetivo: Evaluar el conocimiento sobre farmacoterapia de personas que utilizan anticoagulantes orales. Métodos: Estudio transversal, cuantitativo, en el que participaron 90 personas en tratamiento con anticoagulantes orales seguidos en una clínica de anticoagulación en Recife-PE. Los datos fueron recolectados de abril a julio de 2020 a través de dos cuestionarios, analizados por estadística descriptiva y ordenados en tablas. Resultados: La mayoría de los individuos (42,2%) tenía un conocimiento adecuado sobre el tratamiento. En la asociación de conocimiento con otras variables, hubo significancia estadística entre conocimiento adecuado y resultados de la Razón Internacional Normalizada dentro del rango indicado (p = 0.001) y menor de 60 años (p = 0.018), y entre conocimiento inadecuado con baja educación (p = 0,045), hipertensión (p = 0,009) y tabaquismo (p = 0,041). Conclusión: La mayoría de las personas tenían un conocimiento adecuado sobre el tratamiento. Hubo una asociación significativa entre el conocimiento adecuado y los resultados del INR y entre la edad, así como el conocimiento inadecuado y la baja escolaridad, no ser fumador e hipertensión. (AU)

Manejo de hemangioma ulcerado segmentario: combinación de tratamiento sistémico y tópico en dos casos pediátricos / Management of ulcers on a segmental hemangioma: A combination of systemic and topical therapies in two pediatric cases

Los hemangiomas infantiles (HI) son los tumores benignos más frecuentes de la infancia; la variante segmentaria es rara y se asocia con un mal pronóstico. Una de sus principales complicaciones es la ulceración durante la fase de crecimiento del tumor, a pesar de no presentar características macroscópicas compatibles con una lesión agresiva. El manejo en estos casos es dificultoso e impone la necesidad de asociar múltiples estrategias, algunas orientadas específicamente a impedir la proliferación del hemangioma y otras orientadas a la curación de la herida, el manejo del dolor y la prevención de la infección agregada. Presentamos dos casos a fin de comunicar nuestra experiencia respecto del manejo de dicha patología y su evolución final.

Infantile hemangiomas (IHs) are the most common benign tumors of childhood, and segmental ones are rare and associated with a poor prognosis. While these tumors look harmless, one of their main related complications is ulceration during tumor growth. The management in these cases is extremely challenging, requiring a combination of multiple approaches, some specifically aimed at preventing the proliferation of the hemangioma and others aimed at wound care, pain management, and prevention of further infection. Here we discuss two cases to narrate our experience on the management of this condition and its outcome.

Acacia senegal inhibits diabetic nephropathy ultrastructure alteration and renal biomarkers changes in rats / Acacia senegal inhibe la alteración de la ultraestructura de la nefropatía diabética y los cambios en los biomarcadores renales en rata

SUMMARY: Diabetic nephropathy (DN) is the most common complication of diabetes. Several studies have been done in a trial to protect against this problem at the ultrastructure level. This study investigates the protective effect of oral administration of Acacia senegal (AS) against the development of DN. Sixty male albino rats were randomly divided into six groups: control, Acacia senegal control, Diabetic untreated, diabetic insulin-treated, Diabetic AS treated, and Diabetic insulin and AS combined treated groups. Plasma glucose, HbA1c, serum Albumin, creatinine, urine creatinine was measured using specific kits. Determinations of creatinine clearance and blood pressure were done. The renal tissues of both kidneys were prepared to investigate under both light (LM) and electron microscope (EM). Ultrastructure examination of renal rats tissue of diabetic untreated rats showed the destruction of the glomerular basement membrane and endothelial cells together with hemorrhage in glomerular capsules (Bowman's capsules). On the other side, both LM and EM revealed improving the endothelial cells and the other glomerular capsules structures, especially with the combined treated group, which confirmed the improvement of the biochemical investigation in the study. In conclusion, from the present study, using the oral AS together with SC insulin could be protected against the development of DN.

RESUMEN: La nefropatía diabética (ND) es la complicación más común de la diabetes. Se han realizado varios estudios de ensayo para abordar esta dificultad a nivel de ultraestructura. Este estudio investiga el efecto protector de la administración oral de Acacia senegal (AS) contra el desarrollo de la ND. Se dividieron sesenta ratas albinas machos aleatoriamente en seis grupos: control, control de Acacia senegal, diabéticos no tratados, diabéticos tratados con insulina, diabéticos tratados con AS y grupos tratados con compuesto de insulina diabética + AS. Se midieron utilizando kits específicos, glucosa plasmática, HbA1c, albúmina sérica, creatinina en sangre y en orina. Se registraron la creatinina y la presión arterial. Los tejidos renales de ambos riñones se prepararon para investigar tanto con microscopio óptico (MO) como electrónico (ME). El examen de la ultraestructura del tejido renal de ratas diabéticas no tratadas mostró la destrucción de la membrana basal glomerular y las células endoteliales junto con hemorragia en las cápsulas glomerulares (cápsulas de Bowman). Por otro lado, tanto MO como ME revelaron una mejora de las células endoteliales y las estructuras capsulares glomerulares, en el grupo tratado con el compuesto, lo que confirmó la mejora de la investigación bioquímica. En conclusión, el uso de AS oral en combinación con insulina podría proteger contra el desarrollo de ND.

Dados de mundo real: o impacto econômico da inclusão de antineoplásicos orais para as operadoras de saúde no Sistema de Saúde Suplementar do Brasil / Real world data: the economic impact of including oral antineoplastic agents for health care providers in the Brazilian Supplementary Health System

Objetivo: Avaliar o incremento mensal do custo por beneficiário da incorporação das terapias antineoplásicas orais se aprovado o PL nº 6.330/2019. Métodos: As características clínicas e dos medicamentos utilizados em pacientes em tratamento oncológico foram coletadas da base de dados de mundo real Auditron®, plataforma de avaliações de solicitações de pré-autorização de procedimentos médicos. Com base nas características dos pacientes, foram avaliadas as possibilidades de uso dos medicamentos antineoplásicos orais, conforme as diretrizes da NCCN e ESMO. O cálculo do custo incremental foi realizado utilizando o número total de pacientes diagnosticados com uma neoplasia específica e o número de pacientes aptos a receber antineoplásicos orais. Foi utilizada lista de preços CMED para cálculo dos custos de aquisição de medicamentos. Resultados: O custo incremental da incorporação de 34 drogas antineoplásicas orais em 2019 foi de R$ 5.362.642.580 (R$ 3.944.321.786- R$ 6.483.413.466), representando impacto mensal de R$ 9,50 por beneficiário. O custo incremental da incorporação de 21 drogas antineoplásicas orais em 2021 era de R$ 2.028.538.791 (R$ 1.485.919.710-R$ 3,016,407,794), representando impacto mensal de R$ 3,59 por beneficiário. Conclusão: A incorporação das drogas antineoplásicas orais acarretariam um baixo incremento mensal por beneficiário.

Objective: To evaluate the monthly increase in the cost per member of incorporating all oral neoplastic therapies if approved the bill 6,330/2019. Methods: The clinical characteristics and medications used by patients undergoing cancer treatment were collected from the real-world Auditron® database, a platform for evaluating requests for pre-authorization of medical procedures. Based on the characteristics of each patient, the possibility of using oral antineoplastic drugs according to the NCCN and ESMO guidelines was evaluated. The incremental cost calculation was performed using the total number of patients diagnosed with a specific neoplasm and the number of patients eligible to receive oral anticancer drugs. CMED price list was used to calculate drug acquisition costs. Results: The incremental cost of incorporating 34 neoplastic drugs in 2019 was R$ 5,362,642,580 (R$ 3,944,321,786- R$ 6,483,413,466), representing a monthly impact of R$ 9.50 per member. The incremental cost of incorporating 21 neoplastic drugs in 2021 was R$ 2,028,538,791 (R$ 1,485,919,710-R$ 3,016,407,794), representing a monthly impact of R$ 3.59 per beneficiary. Conclusion: The incorporation of oral anticancer drugs in the coverage of health plans following international and national treatment guidelines would result in a low monthly increase in the cost per beneficiary.

Estratégias Econômicas e Sociais para Anticoagulação de Pacientes com Fibrilação Atrial / Economy- and Social-Based Strategies for Anticoagulation of Patients with Atrial Fibrillation

Resumo Fundamento: A fibrilação atrial é um problema de saúde pública associado com um risco cinco vezes maior de acidente vascular cerebral e mortalidade. A análise de custos é importante para a introdução de novas terapias, e deve ser reconsiderada em situações especiais, tais como a pandemia do coronavírus em 2020. Objetivo: Avaliar os custos (em um período de um ano) relacionados à terapia anticoagulante e a qualidade de vida de pacientes com fibrilação atrial tratados em um hospital público universitário. Métodos: Os custos do paciente foram aqueles relacionados à anticoagulação e calculados pela média de custos mensais da varfarina ou de anticoagulantes orais diretos (DOACs). As despesas não médicas, como alimentação e transporte, foram calculadas a partir de dados obtidos de questionários. O questionário brasileiro SF-6D foi usado para medir a qualidade de vida. Valores p<0,05 foram considerados estatisticamente significativos. Resultados: A população do estudo consistiu em 90 pacientes, 45 em cada braço (varfarina vs. DOACs). Os custos foram 20% mais altos no grupo dos DOACs (US$55 532,62 vs. US$46 385,88), e principalmente relacionados ao preço dos medicamentos (US$23 497,16 vs. US$1903,27). Os custos hospitalares foram mais altos no grupo da varfarina (US$31 088,41 vs $24 604,74), e relacionados às visitas ao ambulatório. Ainda, as despesas não médicas foram duas vezes maiores no grupo varfarina ($13 394,20 vs $7 430,72). A equivalência de preço entre os dois medicamentos seria alcançada por uma redução de 39% no preço dos DOACs. Não foram observadas diferenças quanto à qualidade de vida. Conclusões: Os custos totais foram mais altos no grupo de pacientes tratados com DOACs que no grupo da varfarina. No entanto, uma redução de cerca de 40% no preço dos DOACs tornaria viável a incorporação desses medicamentos no sistema de saúde público brasileiro.

Abstract Background: Atrial fibrillation is a public health problem associated with a fivefold increased risk of stroke or death. Analyzing costs is important when introducing new therapies and must be reconsidered in special situations, such as the novel coronavirus pandemic of 2020. Objective: This study aimed to evaluate the costs related to anticoagulant therapy in a one-year period, and the quality of life of atrial fibrillation patients treated in a public university hospital. Methods: Patient costs were those related to the anticoagulation and calculated by the average monthly costs of warfarin or direct oral anticoagulants (DOACs). Patient non-medical costs (eg., food and transportation) were calculated from data obtained by questionnaires. The Brazilian SF-6D was used to measure the quality of life. P-values < 0.05 were considered statistically significant. Results: The study population consisted of 90 patients, 45 in each arm (warfarin vs direct oral anticoagulants). Costs were 20% higher in the DOAC group ($55,532.62 vs $46,385.88), and mainly related to drug price ($23,497.16 vs $1,903.27). Hospital costs were higher in the warfarin group ($31,088.41 vs $24,604.74) and related to outpatient visits. Additionally, non-medical costs were almost twice higher in the warfarin group ($13,394.20 vs $7,430.72). Equivalence of price between the two drugs could be achieved by a 39% reduction in the price of DOACs. There were no significant group differences regarding quality of life. Conclusions: Total costs were higher in the group of patients taking DOACs than those taking warfarin. However, a nearly 40% reduction in the price of DOACs could make it feasible to incorporate these drugs into the Brazilian public health system.

Consumption of mate Ilex paraguariensis: a folk beverage with antioxidant power against myocardial ischemic injury

The effects of the aqueous extract of Ilex paraguariensis (Ip)and the flavonoid quercetin were tested during the induction of in vivomyocardial ischemia/ reperfusion in Rattus norvegicus. The antioxidant power of the extract and quercetin were chemically determined. The experimental groups were: control, ischemia/reperfusion induction, Iporal treatment, Iporal treatment and ischemia /reperfusion, quercetin oral treatment, and quercetin oral treatment and ischemia/reperfusion. Rats were anesthetized with sodium thiopental and xylazine via intraperitoneal injection and subsequently underwent 15 minutes of ischemia followed by 15 minutes of reperfusion. Ischemia was promoted by tying the left anterior descending coronary artery. Areas of risk and infarction were stained by intravenous Evans blue and triphenyl tetrazolium chloride. Reactive oxygen species (ROS), antioxidant capacity against peroxylradicals, and lipid peroxidation of the myocardium were quantified. A significant reduction in areas of risk and infarction was detected in the ischemic myocardium treated with Ipand quercetin; ROS generation and lipid peroxidation were significantly reduced, and the antioxidant capacity was elevated. Oral administration of Ippromoted antioxidant benefits in the myocardium during ischemia and reperfusion, which reduced infarction. We suggest that Mate (a hot drink made from steeped dried leaves of Ip) consumption is a potential cardioprotective habit of indigenous people from southern South American countries, which must be better understood scientifically and ethnographically.

Development of monolithic matrix type transdermal patches containing cinnarizine: Physical characterization and permeation studies

To overcome the problems associated with bioavailability and systemic side effects of the drug by oral administration, monolithic matrix type transdermal patches containing cinnarizine (CNZ) were developed. For this purpose, films based on hydroxypropyl methylcellulose and polyvinylpyrrolidone as matrix-forming polymers were designed. Physical characteristics of transdermal films and drug-excipient compatibility were investigated. Factors affecting in vitro drug release and ex vivo skin penetration and permeation of the drug were studied. It was confirmed that films displayed sufficient flexibility and mechanical strength for application onto the skin for a long time period. Ex vivo penetration experiments gave satisfactory results for transdermal drug delivery through rat skin. The parameters determining good skin penetration were also evaluated. The highest drug permeation rate was obtained with incorporation of Transcutol® (0.102 mg/cm2/h) into the base CNZ formulation, followed by propylene glycol (0.063 mg/cm2/h), menthol (0.045 mg/cm2/h), and glycerin (0.021 mg/cm2/h) as penetration enhancers (p < 0.05). As a result, the developed transdermal patches of CNZ may introduce an alternative treatment for various conditions and diseases such as idiopathic urticarial vasculitis, Ménière's disease, motion sickness, nausea, and vertigo. Thus, the risk of systemic side effects caused by the drug can be reduced or eliminated

Development and in vivo evaluation of lipid-based nanocarriers containing Jatropha isabellei dry extract from the dichloromethane fraction intended for oral treatment of arthritic diseases

In this study, a dichloromethane fraction dry extract from the underground parts of Jatropha isabellei (DFJi) was used to prepare lipid nanocarriers (LNCJi) aimed at providing the oral delivery of terpenic compounds in the treatment of arthritis. The lipid nanocarriers were prepared by the spontaneous emulsification method. The lipid nanocarriers displayed sizes ranging from 180 to 200 nm and zeta potential values of around -18 mV. A high value of entrapment efficiency (> 90%) was obtained for jatrophone, which was used as the chemical marker of DFJi. LNCJi stored at 4°C were demonstrated to be stable through measurements of transmitted light after analytical centrifugation of the samples. In vitro drug release studies conducted in biorelevant dissolution media demonstrated that jatrophone release was faster from LNCJi than from free DFJi. When tested in an acute arthritis model, the LNCJi exhibited antinociceptive properties after oral administration of a 50 mg/kg dose, unlike the free DFJi, although no reduction in articular diameter was observed. These results suggest that an increase in the oral absorption of DFJi constituents may have occurred through the carrying of this fraction in LNCJi, thus improving the antinociceptive activity of this compound

Bioavailability augmentation of silymarin using natural bioenhancers: An in vivo pharmacokinetic study

Abstract Pharmacokinetic studies were carried out in male and female rats to quantify silymarin as silybin (A+B) after the oral administration of various silymarin formulations combined with three bioenhancers, namely, lysergol, piperine, and fulvic acid, and compared with plain silymarin formulation (control). A non-compartmental analysis, model independent analysis, was utilized, and various pharmacokinetic parameters (C max, T max, and AUC 0-t) were calculated individually for each treatment group, and the values were expressed as mean ± SEM (n = 6). Plasma samples obtained from the rats were analyzed for the concentration of silymarin through a validated RP-HPLC method and on the basis of data generated from the pharmacokinetic studies. Results indicated that the bioenhancers augmented pharmacokinetic parameters and bioavailability increased 2.4-14.5-fold in all the formulations compared with the control. The current work envisages the development of an industrially viable product that can be further subjected to clinical trials and scientifically supports the development of silymarin as a contemporary therapeutic agent with enhanced bioavailability and medicinal values.

Evaluation of fertility and embryo implantation in rats after the oral administration of Salvia officinalis (sage) extract / Evaluación de la fertilidad y la implantación de embriones en ratas después de la administración oral de extracto de Salvia officinalis (salvia)

SUMMARY: In Saudi Arabia, it is widely believed that women with reproductive problems can use the extract of the sage plant as a tea drink. This study was conducted to investigate the effects of this herb on the fertility of female rats and embryo implantation. Forty-eight Wistar virgin female rats were divided into four groups at random, with 12 rats in each group. The control group received distilled water orally. The three treatment groups received different concentrations of sage extract: 15, 60, or 100 mg/kg for 14 days before mating, then mated with a male and sacrificed on the 7th day of gestation, the uterine horns removed, and photographed. The total body weight of mothers, weight of uteri and ovaries and number of fetuses were determined. Ovarian and uteri tissues were cut into 5 µ sections and stained with hematoxylin and eosin. Serum FSH, LH were determined by the ELISA method. The present study showed that low dose of sage (15 mg/kg) have no effects on serum concentration levels of FSH and LH hormones, also has no effect on the number of growing follicles. The present study showed a significant differences (P≤0.05) in body weight, ovary and uterus weight in the groups treated with high doses of Salvia officinalis as compared to control group. Also a significant differences (P≤0.05) found in FSH, LH hormones. Histological study showed overall histomorphological structural configurations including growing and matured graafian follicular countable changes, besides a number of corpora lutea and regressed follicles in the treated groups with high doses of Salvia officinalis as compared to control group. The researchers concluded that the extract of the sage plant with high doses can stimulate the growth graafian follicles and improve fertility in female rats.

RESUMEN: En Arabia Saudita, se cree ampliamente que las mujeres con problemas reproductivos pueden usar el extracto de la planta de salvia como bebida de té. Este estudio se realizó para investigar los efectos de esta hierba sobre la fertilidad de las ratas hembra y la implantación del embrión. Se dividieron cuarenta y ocho ratas hembra vírgenes Wistar en cuatro grupos al azar, con 12 ratas en cada grupo. El grupo control recibió agua destilada por vía oral. Los tres grupos de tratamiento recibieron diferentes concentraciones de extracto de salvia: 15, 60 o 100 mg/kg durante 14 días antes del apareamiento, luego se aparearon con un macho y se sacrificaron el día 7 de gestación, se extrajeron los cuernos uterinos y se fotografiaron. Se determinó el peso corporal total de las madres, el peso del útero y los ovarios y el número de fetos. Los tejidos ováricos y uterinos se cortaron en secciones de 5 µ y se tiñeron con hematoxilina y eosina. FSH sérica, LH se determinaron por el método ELISA. El presente estudio mostró que dosis bajas de salvia (15 mg/kg) no tienen efectos sobre los niveles de concentración sérica de las hormonas FSH y LH, tampoco tienen efecto sobre el número de folículos en crecimiento. El presente estudio mostró diferencias significativas (P≤0,05) en el peso corporal, peso de ovario y útero en los grupos tratados con altas dosis de Salvia officinalis en comparación con el grupo control. También se encontraron diferencias significativas (P≤0,05) en las hormonas FSH, LH. El estudio histológico mostró configuraciones estructurales histomorfológicas generales que incluyen cambios contables en los folículos maduros (de Graaf) y en crecimiento, además de una cantidad de cuerpos lúteos y folículos en regresión en los grupos tratados con altas dosis de Salvia officinalis en comparación con el grupo de control. Los investigadores concluyeron que el extracto de la planta de salvia en altas dosis puede estimular el crecimiento de los folículos maduros y mejorar la fertilidad en ratas hembra.

Programa de melhoria da qualidade na administração de medicamentos via sonda nasoenteral / Programa de mejora de la calidad en la administración de medicamentos por sonda nasoenteral / Quality improvement program in medication administration through nasogastric tube

Resumo Objetivo Avaliar o impacto de um programa de melhoria da qualidade relacionado aos indicadores de frequência de sondas nasoenterais obstruídas, do tempo despendido pela equipe de enfermagem no preparo e na administração de medicamentos orais por essa via, e dos custos associados ao incidente. Método Estudo de intervenção voltado para a comparação pré (Fase I) e pós (Fase II) implementação de um Programa Melhoria da Qualidade, proposto pelo Institute for Healthcare Improvement . Foram observadas 92 doses de medicamentos na Fase I e 66 doses na Fase II. Foram necessários quatro ciclos Plan-Do-Study-Act (PDSA) para atingir a meta proposta para o programa de melhoria. Resultados Houve redução no tempo médio gasto pelo profissional no preparo e na administração de medicamentos sólidos via sonda nasoenteral em ambas as fases. As frequências de sondas obstruídas reduziram de 33,3% (Fase I) para 7,4% (Fase II) e nenhuma sonda apresentou-se obstruída durante os ciclos 1, 2 e 4. O custo médio da obstrução por paciente foi de R$ 1.251,05 ao mês na Fase I e de R$ 23,31 na Fase II. Após as mudanças testadas, foi verificada economia de tempo para a equipe de enfermagem e de custo para a instituição. Conclusão Os ciclos PDSA foram eficazes na redução de não conformidades no preparo e na administração de medicamentos via sonda nasoenteral. Tal melhoria impactou a frequência de obstrução, os custos relacionados e o tempo médio gasto pelo profissional de enfermagem durante o preparo e a administração das doses.

Resumen Objetivo Evaluar el impacto de un programa de mejora de la calidad relacionado con los indicadores de frecuencia de sondas nasoenterales obstruidas, del tempo invertido por el equipo de enfermería en la preparación y en la administración de medicamentos orales por esa vía y de los costos asociados con el incidente. Métodos Estudio de intervención direccionado para la comparación previa (Fase I) y posterior (Fase II) a la implementación de un Programa Mejora de la Calidad, propuesto por el Institute for Healthcare Improvement . Se observaron 92 dosis de medicamentos en la Fase I y 66 dosis en la Fase II. Se necesitaron cuatro ciclos Plan-Do-Study-Act (PDSA) para alcanzar la meta propuesta para el programa de mejora. Resultados Hubo reducción del tiempo promedio consumido por el profesional en la preparación y en la administración de medicamentos sólidos por sonda nasoenteral en ambas fases. La frecuencia de la obstrucción de las sondas se redujo del 33,3 % (Fase I) para el 7,4 % (Fase II) y ninguna sonda presentó obstrucción durante los ciclos 1, 2 y 4. El costo promedio de la obstrucción por paciente fue de R$ 1.251,05 al mes en la Fase I y de R$ 23,31 en la Fase II. Después de someter a pruebas los cambios, se verificó un ahorro de tiempo para el equipo de enfermería y de costo para la institución. Conclusión Los ciclos PDSA fueron eficaces en la reducción de no conformidades en la preparación y en la administración de medicamentos por sonda nasoenteral. Esa mejora impactó la frecuencia de obstrucción, los costos relacionados y el tiempo promedio consumido por el profesional de enfermería durante la preparación y la administración de las dosis.

Abstract Objective Evaluate the impact of a quality improvement program related to the frequency indicators of obstructed nasogastric tubes, the time the nursing team spent on oral medication preparation and administration through this route, and the costs associated with the incident. Method Intervention study aimed at comparing pre (Phase I) and post (Phase II) implementation of a Quality Improvement Program, proposed by Institute for Healthcare Improvement . Ninety-two medication doses were observed in Phase I and 66 doses in Phase II. Four Plan-Do-Study-Act (PDSA) cycles were needed to achieve the proposed target for the improvement program. Results The average time the professional spent on solid medication preparation and administration through nasogastric tube decreased in both phases. Frequencies of obstructed tubes dropped from 33.3% (Phase I) to 7.4% (Phase II) and no probe was obstructed during cycles 1, 2, and 4. The average cost of the obstruction per patient was R$ 1,251.05 per month in Phase I and R$ 23.31 in Phase II. After testing the changes, time savings for the nursing team and cost savings for the institution were verified. Conclusion The PDSA cycles were effective in reducing non-conformities in medication preparation and administration via nasogastric tube. This improvement influenced the obstruction frequency, related costs, and the average time the nursing professional spent on the preparation and administration of the medication doses.

Cannabis. Usos y aplicaciones en la práctica odontológica diaria: revisión de la literatura / Cannabis. Uses and applications in daily dental practice: a review of the literature

La evidencia científica presente en la literatura indica que el cannabis puede ser utilizado con fines terapéuticos para tratar distintas afecciones odontológicas. Dado el acceso sencillo a la cavidad bucal, las distintas formulaciones de cannabis pueden aplicarse de forma tópica. La aplicación local de dosis bajas de cannabis ha demostrado alta efectividad para tratar distintas afecciones bucales, constituyendo un tratamiento seguro con baja probabilidad de generar repercusiones sistémicas indeseadas. En la actualidad, está siendo incorporado a materiales convencionales de uso e higiene odontológica con la finalidad de aprovechar sus efectos terapéuticos. El cannabis tiene múltiples usos en odontología: como componen-te de enjuagues bucales y soluciones para la desinfección de conductos radiculares, en tratamientos de trastornos de ansiedad bucal, como complemento en terapias oncológicas, como analgésico para atenuar el dolor inflamatorio y el neuropático, como miorrelajante y condroprotector para tratar trastornos de articulación témporomandibular (ATM) y bruxismo, como osteomodulador para el tratamiento de patologías que comprometen la integridad ósea, como la enfermedad periodontal y la osteoporosis, y para la cicatrización ósea asociada a fracturas, extracciones dentarias e implantes, y como inmunomodulador con potencial terapéutico para tratar patologías autoinmunes como las enfermedades reumáticas. El trata-miento local con cannabis es efectivo, bien tolerado por el paciente y con pocos efectos adversos. Por lo tanto, se puede concluir que el cannabis aporta un enorme abanico de posibilidades terapéuticas para tratar distintas afecciones odontológicas, aunque aún se requiere mayor cantidad de estudios científicos que avalen su utilización en cada situación fisiopatológica particular (AU)

The scientific evidence present in the literature indicates that cannabis can be used for therapeutic purposes to treat different dental conditions. Given the easy access to the oral cavity, the different cannabis formulations can be applied topically. The local application of low doses of cannabis has shown high effectiveness in treating different oral conditions, constituting a safe treatment with a low probability of generating unwanted systemic repercussions. It is currently being incorporated into conventional materials for dental use and hygiene in order to take advantage of its therapeutic effects. Cannabis has multiple uses in dentistry: as a component of mouthwashes and solutions for disinfecting root canals, in the treatment of oral anxiety disorders, as a complement in oncological therapies, as an analgesic to reduce inflammatory and neuropathic pain, as a muscle relaxant and chondroprotective to treat temporomandibular joint disorders and bruxism, as an osteomodulator for the treatment of pathologies that compromise bone integrity, such as periodontal disease and osteoporosis, and or bone healing associated with fractures, dental extractions and implants, and as immunomodulator with therapeutic potential to treat autoimmune pathologies such as rheumatic diseases. Local treatment with cannabis is effective, well tolerated by the patient and with few adverse effects. Local treatment with cannabis is effective, well tolerated by the patient and with few adverse effects. Therefore, it can be concluded that cannabis provides an enormous range of therapeutic possibilities to treat different dental conditions, although more scientific studies are still required to support its use in each particular pathophysiological situation (AU)

Necessidades de aprendizagem de familiares de crianças e adolescentes em tratamento com quimioterápicos antineoplásicos orais / Necesidades de aprendizaje de los familiares de niños y adolescentes en tratamiento con quimioterapia antineoplástica oral / Learning needs of relatives of children and teenagers under oral antineoplastic chemotherapy treatment

RESUMO Objetivo descrever as necessidades de aprendizagem de familiares de crianças e adolescentes com câncer quanto ao tratamento com quimioterápicos antineoplásicos orais. Método pesquisa qualitativa descritiva desenvolvida em um hospital federal do Rio de Janeiro, Brasil. Os dados foram coletados nos meses de julho a setembro de 2020 a partir de entrevistas semiestruturadas com vinte e três familiares de crianças e adolescentes com câncer em quimioterapia antineoplásica oral. Os dados foram processados no software Interface de R pour Analyses Multidimensionnelles de Textes et de Questionnaires pela Classificação Hierárquica Descendente. Resultados dentre os temas que demandam aprendizagem pelos familiares estão administração oral, armazenamento e manipulação dos quimioterápicos orais, além dos efeitos adversos e emergências que demandam atendimento hospitalar. Conclusão e implicações para a prática no tratamento com quimioterápicos orais, as necessidades de aprendizagem dos familiares de crianças e adolescentes precisam ser problematizadas em práticas educativas dialógicas para, assim, favorecer a segurança, a adesão e a eficácia do tratamento.

RESUMEN Objetivo describir las necesidades de aprendizaje de familiares de niños y adolescentes con cáncer en cuanto al tratamiento con quimioterápicos antineoplásicos orales. Método investigación cualitativa descriptiva desarrollada en un hospital federal de Río de Janeiro, Brasil. Los datos fueron recogidos en los meses de julio a septiembre de 2020 a partir de entrevistas semiestructuradas con veintitrés familiares de niños y adolescentes con cáncer en quimioterapia antineoplásica oral. Los datos fueron procesados en el software Interface de R pour Analyses Multidimensionnelles de Textes et de Questionnaires por la Clasificación Jerárquica Descendente. Resultados entre los temas que demandan aprendizaje por los familiares están administración oral, almacenamiento y manipulación de los quimioterápicos orales, además de los efectos adversos y emergencias que demandan atención hospitalaria. Conclusión e implicaciones para la práctica en el tratamiento con quimioterápicos orales, las necesidades de aprendizaje de los familiares de niños y adolescentes necesitan ser problematizadas en prácticas educativas dialógicas para, así, favorecer la seguridad, la adhesión y la eficacia del tratamiento.

ABSTRACT Objective to describe the learning needs of family members of children and adolescents with cancer regarding treatment with oral antineoplastic chemotherapies. Method a descriptive qualitative research developed in a federal hospital in Rio de Janeiro, Brazil. Data were collected in the months from July to September 2020 from semi-structured interviews with twenty-three family members of children and adolescents with cancer undergoing oral antineoplastic chemotherapy. Data was processed in the software Interface de R pour Analyses Multidimensionnelles de Textes et de Questionnaires by the Descending Hierarchical Classification. Results among the themes that demand learning by the family members are oral administration, storage and handling of oral antineoplastic drugs, as well as adverse effects and emergencies that require hospital care. Conclusion and implications for practice in oral antineoplastic treatment, the learning needs of family members of children and adolescents need to be problematized in dialogic educational practices in order to favor the safety, adherence, and efficacy of the treatment.

Comparative stomach tissue distribution profiles of four major bio-active components of Radix Astragali in normal and gastric ulcer mice

Numerous studies have demonstrated that Radix Astragali can inhibit gastric ulcers in mice. Anhydrous ethanol (0.01 mL/g) administered to mice by intragastric infusion can induce gastric ulcer injury. This study was performed to compare the stomach tissue distribution profiles of four major bioactive constituents of Radix Astragali(calycosin-7-O-ß-d-glucoside, calycosin, ononin and formononetin) after oral administration of extract of Radix Astragali (ERA)in normal and gastric ulcer mice. The abundance of Radix Astragali constituents was determined using an ultra-pressure liquid chromatograph with a photodiode array detector (UPLC-PDA), after which histograms were drawn. In comparison with normal mice, the contents of calycosin- 7-O-ß-d-glucoside, calycosin, ononin and formononetin in the stomach tissue samples of gastric ulcer mice showed significant differences at the selected time points (P < 0.05).The abundance of each of the four tested constituents in the normal groups was higher than that of the gastric ulcer groups. This study provides an empirical foundation for future studies focused on developing clinical applications of Radix Astragali