Cenário da falsificação de medicamentos no Brasil entre os anos de 2015 e 2022 / Scenario of drug counterfeiting in Brazil between 2015 and 2022

A falsificação de medicamentos é uma prática criminosa frequente em situações de alta demanda, carência de produtos e preços elevados no mercado, gerando muitos riscos à saúde da população. Objetivo: Estabelecer o panorama da falsificação de medicamentos no Brasil entre os anos de 2015 e 2022. Método: Trata-se de um estudo descritivo e retrospectivo dos registros de apreensão de medicamentos com indícios de falsificação, disponibilizados pela Agência Nacional de Vigilância Sanitária. Resultados: 30 fármacos diferentes foram mencionados nos registros de falsificação do período estudado, com predomínio de medicamentos biológicos e controlados e das formas farmacêuticas de via parenteral. Os fármacos que apresentaram mais registros de falsificação foram somatropina, imunoglobulina, sofosbuvir/ledispavir, eculizumabe e defibrotida. Conclusão: Por muitos anos, a falsificação de medicamentos no Brasil foi caracterizada principalmente por estimulantes sexuais masculinos, anabolizantes e anorexígenos. Entretanto, nos últimos anos, os medicamentos de alto custo destinados ao tratamento de doenças crônicas e raras se sobressaíram. Este cenário pode estar relacionado a diversos fatores, como gravidade das doenças, avanços das terapias medicamentosas, elevada lucratividade, falta de acesso aos medicamentos e dificuldades sociais e econômicas associadas à pandemia da doença por coronavírus 2019 (COVID-19)

Drug counterfeiting is a common criminal practice in situations of high demand, lack of products and high market prices, which generates risks to the health of the population. Objective: To establish an overview of drug counterfeiting in Brazil between 2015 and 2022. Method: This is a descriptive and retrospective study of data on drugs arrest with evidence of counterfeiting made available by the Brazilian Health Surveillance Agency. Results: 30 different drugs were mentioned in counterfeiting records for the period studied with a predominance of biopharmaceuticals and controlled substances, and parenteral pharmaceutical forms. The drugs with the most falsification records were somatropin, immunoglobulin, sofosbuvir/ledispavir, eculizumab and defibrotide. Conclusion: For many years, drug counterfeiting in Brazil was mainly characterized by male sexual stimulants, anabolic steroids, and anorectic. However, high-cost drugs for treating chronic and rare diseases have recently gained prominence. This scenario may be related to several factors, such as the severity of the diseases, advances in drug therapies, high profitability, lack of access to drugs, and social and economic difficulties associated with the coronavirus disease 2019 (COVID-19) pandemic

Plantas medicinais, saúde bucal e SUS: uma difícil integração das políticas públicas no interior da Bahia? / Medicinal Plants, Oral Health and Brazilian Unified National Health System: a difficult integration of public policies in the inner Bahia State?

Resumo Estudo exploratório de abordagem qualitativa que buscou analisar os conhecimentos, percepções e práticas de equipes de Saúde Bucal e de agentes comunitários de saúde acerca das políticas públicas que regulamentam a utilização de plantas medicinais e fitoterápicos no contexto das práticas integrativas e complementares, incluindo sua incorporação, reconhecimento, desafios e possibilidades no cotidiano local do SUS. Foram selecionadas oito Unidades Básicas de Saúde no município de Itabuna, Bahia, Brasil, com a realização de entrevistas com oito cirurgiões-dentistas, oito auxiliares/técnicos de saúde bucal e oito agentes comunitários de saúde, totalizando 24 participantes. Para a análise da dados, empregou-se a técnica do Discurso do Sujeito Coletivo. Os conhecimentos, percepções e práticas dos atores envolvidos no estudo sobre as políticas públicas de inserção das plantas medicinais no SUS mostraram-se permeados pela cultura hegemônica, pela formação em saúde tradicional e fragmentada, pelo (des)interesse administrativo do município e por subjetividades individuais que são produzidas e reproduzidas nos serviços de saúde bucal da APS local.

Abstract This exploratory and qualitative study aimed to analyze the knowledge, perceptions and practices of Oral Health Teams and Community Health Agents about public health policies that regulate the use of medicinal plants and herbal medicines in the context of integrative and complementary practices, including their incorporation, recognition, challenges and possibilities in the local routine of the Brazilian Unified Health System (SUS). Eight Basic Health Units were selected in the municipality of Itabuna, Bahia, Brazil, and interviews were conducted with 8 dentists, 8 oral health assistants/technicians and 8 community health agents, totaling 24 participants. For data analysis, the Collective Subject Discourse technique was used. The knowledge, perceptions and practices of the actors involved in the study about public policies for the introduction of medicinal plants in the SUS were permeated by the hegemonic culture, traditional and fragmented health education, the administrative (un)interest of the municipal authorities, and individual subjectivities that are produced and reproduced in the local oral health services and the primary care.

Expenditure of biological drugs for rheumatoid arthritis treatment in the Brazilian public health system

ABSTRACT OBJECTIVE This work aims to analyze the quantity and expenses related to biological drugs used for the treatment of rheumatoid arthritis (RA) in outpatient public care within the Brazilian Unified Health System (SUS). METHODS It is a cross-sectional descriptive study based on secondary data from a historical series, referring to the purchase, volume, and the number of patients treated with different biological drugs (infliximabe, etanercept, adalimumab, rituximab, abatacept, tocilizumab, golimumab, and certolizumab pegol) for RA treatment in outpatient care from 2012 to 2017. The data were extracted from the SUS Outpatient Information System database-SIA/SUS and included ten drugs used for RA treatment. The study assessed the quantity and expenditure of these drugs, the number of RA patients treated, and the expenditure by RA subtypes. The National Broad Consumer Price Index was used to adjust the expenditures for December 2017. RESULTS The Ministry of Health allocated approximately $500 million to provide about 2 million units of biological drugs for RA patients from 2012 to 2017. The supply of adalimumab 40 mg and etanercept 50 mg accounted for 68.3% of the total expenditure. The subtypes "other rheumatoid arthritis with rheumatoid factor" (ICD-10 M05.8), "rheumatoid arthritis without rheumatoid factor" (ICD-10 M06.0), and "Felty's syndrome" (M05. 0) represented 84.5% of the total expenditures. The proportion of patients treated with biological drugs increased by 33.0%. There was a significant 83.0% increase in the number of patients using biological drugs compared to the overall number of RA patients treated during the study period. CONCLUSIONS The results obtained allow us to draw a more recent profile of expenditure on RA treatment and indicate trends in the use of biological drugs for this condition, generating data that can support management decisions in public health policies.

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.

Therapeutic potential of Punica granatum in wound healing: An overview

SUMMARY Objective: This review aim to report the results of the most recent research and applications of different extracts of P. granatum in the in vivo wound healing process. Methods: For the survey of articles in literature, a search was conducted in the PubMed, Scopus, Science Direct and Science Citation Index Expanded (Web of Science) databases. Results: Punica granatum is a plant native to Iran and adjacent regions widely used worldwide as a food and medicinal source. Its healing property is closely linked to the presence of phenolic compounds, tannins and flavonoids, and its concentration in treatment formulations seems to be determinant for the acceleration of tissue repair, although few data on the standardization and stability of these formulations are available. Studies on experimental models were able to demonstrate the repair potential of P. granatum; however, human studies are still scarce. Conclusions: This contribution summarizes the use of P. granatum extracts in healing different types of lesions, emphasizing its effects on inflammatory, prolif-erative, and remodeling phases.

Objetivo: Relatar los resultados de investigaciones y aplicaciones más recientes de diferentes extractos de P. granatum en el proceso de cicatrización de heridas in vivo. Métodos: Para encuesta de artículos en la literatura, se realizó búsqueda en las bases de datos PubMed, Scopus, Science Direct y Science Citation Index Expanded (Web of Science). Resultados: Punica granatum es una planta originaria de Irán y regiones adyacentes, ampliamente utilizada en todo el mundo como fuente alimenticia y medicinal. Su propiedad cicatrizante está íntimamente ligada a la presencia de compuestos fenólicos, taninos y flavonoides, y su concentración en las formulaciones de tratamiento parece ser determinante para aceleración de la reparación tisular, aunque se dispone de pocos datos sobre estandarización y estabilidad de estas formulaciones. Estudios sobre modelos experimentales pudieron demostrar el potencial de reparación de P. granatum; sin embargo, los estudios en humanos aún son escasos. Conclusiones: Este aporte resume el uso de extractos de P. granatum en la curación de diferentes tipos de lesiones, enfatizándose sus efectos en las fases inflamatoria, proliferativa y remodeladora.

Objetivo: Relatar os resultados de pesquisas mais recentes e aplicações de diferentes extratos de P. granatum no processo de cicatrização in vivo. Métodos: Para levantamento de artigos na literatura, realizou-se busca nas bases de dados PubMed, Scopus, Science Direct e Science Citation Index Expanded (Web of Science). Resultados: Punica granatum é uma planta nativa do Irã e das regiões adjacentes, amplamente utilizada em todo o mundo como alimento e fonte medicinal. A propriedade cicatrizante está intimamente ligada à presença de compostos fenólicos, taninos e flavo-noides, cuja concentração nas formulações de tratamento parece ser determinante para aceleração do reparo tecidual, embora poucos dados sobre a padronização e estabilidade dessas formulações estejam disponíveis. Estudos em modelos experimentais foram capazes de demonstrar o potencial de reparo de P. granatum. No entanto, estudos em humanos ainda são escassos. Conclusões: Esta contribuição resume o uso de extratos de P. granatum na cicatrização de diferentes tipos de lesões, enfatizando os efeitos nas fases inflamatória, proliferativa e remodelação.

Eritema indurado de Bazin como una reactivación de una tuberculosis latente en una paciente con tratamiento biológico anti-factor de necrosis tumoral / Erythema induratum of Bazin as a reactivation of latent tuberculosis infection in a patient receiving anti-tumor necrosis factor treatment

Resumen El eritema indurado de Bazin es una tuberculosis cutánea rara, considerada una tuberculide o reacción de hipersensibilidad a Mycobacterium tuberculosis. El tratamiento con agentes biológicos es un factor de riesgo conocido para la reactivación de tuberculosis, especialmente en áreas de alta incidencia como Latinoamérica, por lo que existen protocolos de búsqueda y tratamiento antes del inicio de este tipo de terapias. Se presenta un caso clínico de eritema indurado de Bazin como reactivación de una infección tuberculosa latente en una paciente con artritis reumatoide que recibía tratamiento con golimumab.

Abstract Erythema induratum of Bazin is a rare form of cutaneous tuberculosis, considered as part of the spectrum of tuberculids or hipersensitivity reactions to Mycobacterium tuberculosis. Treatment with biologic agents is a known risk factor for tuberculosis reactivation, especially in areas of high incidence like Latin America, which is why screening and treatment protocols must be followed before these therapies are initiated. We present a case of erythema induratum of Bazin as a reactivation of latent tuberculosis infection in a patient with rheumatoid arthritis treated with golimumab.

Analgesic-like activity of perillyl acetate: In vivo and in silico studies

Objective: To evaluate the antinociceptive activity of perillyl acetate in mice and in silico simulations. Methods: The vehicle, perillyl acetate (100, 150 and/or 200 mg/kg, i.p.), diazepam (2 mg/kg, i.p.) or morphine (6 mg/kg, i.p.) was administered to mice, respectively. Rotarod test, acetic acid-induced abdominal writhing, formalin-induced nociception, hot plate test, and tail-flick test were performed. Opioid receptors-involvement in perillyl acetate antinociceptive effect was also investigated. Results: Perillyl acetate did not affect the motor coordination of mice. However, it reduced the number of acetic acid-induced abdominal twitches and licking times in the formalin test. There was an increase of latency time in the tail-flick test of 30 and 60 minutes. Pretreatment with naloxone reversed the antinociceptive effect of perillyl acetate (200 mg/kg). In silico analysis demonstrated that perillyl acetate could bind to μ-opioid receptors. Conclusions: Perillyl acetate has antinociceptive effect at the spinal level in animal nociception models, without affecting the locomotor integrity and possibly through μ-opioid receptors. In silico studies have suggested that perillyl acetate can act as a μ-opioid receptor agonist.

Orofacial antinociceptive effects of perillyl alcohol associated with codeine and its possible modes of action

Abstract This study evaluated the orofacial antinociceptive effect of (S)-(-)-perillyl alcohol (PA) associated with codeine (C) and investigated the possible molecular anchorage mechanisms of PA. Mice (n = 5 per group) were treated with PA alone and associated with codeine and assigned to the following groups: 75.0 mg/kg PA; 75.0 mg/kg PA + C 30 mg/kg; PA 37.5 mg/kg + C 15.0 mg/kg; C 30.0 mg/kg; and control. Nociception was induced by formalin, capsaicin, and glutamate, and was quantified based on the duration (in seconds) of face grooming. The possible mechanisms of action were evaluated by molecular docking study. In the formalin test, PA75/C30 presented an effect in the neurogenic (p < 0.0001) and inflammatory (p < 0.005) phases. Mice treated with PA75 (p < 0.0001) and PA75/C30 (p < 0.0005) showed a reduced nociceptive behavior in the capsaicin test. Glutamate-induced nociception also was blocked by PA75 (p < 0.0005) and C30 (p < 0.0005). The molecular anchorage analysis indicated high negative binding energy values for the evaluated receptors, especially glutamate receptors (AMPA -79.57 Kcal/mol, mGLUR6 -71.25, and NMDA -66.33 Kcal/mol). PA associated with codeine showed orofacial antinociceptive activity, with theoretical evidence of interaction with glutamate receptors.

Desarrollo de artritis reumatoide refractaria al tratamiento convencional / Development of rheumatoid arthritis refractory to conventional treatment

La artritis reumatoide es una enfermedad inflamatoria crónica sistémica que afecta del 0,4 por ciento de América Latina. Sus manifestaciones consisten en dolor crónico, destrucción articular y muerte prematura, afectando principalmente a mujeres. Mediante el puntaje del Health Assesment Questionnaire, se puede realizar un conteo de articulaciones tumefactas, presencia de nódulos reumatoides, factor reumatoide, velocidad de sedimentación globular, proteína C reactiva y erosiones en radiografía, los cuales estaban asociados con la elección del primer tratamiento con medicamentos antirreumáticos modificadores de la enfermedad (DMARD). El propósito de este estudio es determinar los principales estudios sobre el desarrollo de la artritis reumatoide refractaria al tratamiento convencional. Se realizó la búsqueda de literatura mediante una exploración de artículos en PubMed y SciELO; se consideraron artículos originales y de revisión, publicados en idioma inglés y español, haciendo uso de los descriptores. Se realizó una lectura preliminar de los artículos con el objetivo de seleccionar los que se ajustaban a nuestro propósito. Los documentos que tenían información con los aspectos formales se incluyeron en nuestra revisión, es decir, se seleccionó un total de 24 artículos. Es en este punto la observación clínica ha permitido describir que no todos los pacientes tienen el mismo curso de evolución de la enfermedad, incluso con tratamientos estandarizados a nivel mundial, y al evaluar los desenlaces de la enfermedad se sugiere que debe haber características de cada paciente que hacen que su enfermedad cause más daño en su evolución en comparación con otros pacientes(AU)

Rheumatoid arthritis is a systemic chronic inflammatory disease that affects 0.4 percent to 1 percent of Latin America, manifested by chronic pain, joint destruction and premature death, affecting mainly women. Using the Health Assessment Questionnaire score, a count of swollen joints, presence of rheumatoid nodules, rheumatoid factor, erythrocyte sedimentation rate, C-reactive protein and erosions in radiography, were associated with the choice of the first treatment with disease-modifying antirheumatic drugs (DMARDs). To determine the main studies that ensure efficacy towards the development of rheumatoid arthritis refractory to conventional treatment. The literature search was carried out by means of an exploration of articles in PubMed and SciELO; Original and review articles were considered, published in English and Spanish, making use of the descriptors, a preliminary reading of the articles was carried out with the aim ofSelect those that fit our purpose, the documents that had information with the formal aspects, were included in our review, that is, a rigorous reading, which selected a total of 24 articles. It is at this point that clinical observation has made it possible to describe that not all patients have the same course of evolution of the disease, even with standardized treatments worldwide, and when evaluating the outcomes of the disease it is suggested that there must be characteristics of each patients who cause their disease to cause more damage in their evolution compared to other patients(AU)

The role of biologics in eosinophilic esophagitis / O papel dos imunobiológicos na esofagite eosinofílica

Eosinophilic esophagitis (EoE) is a chronic inflammation in the esophageal mucosa driven by an antigen-mediated abnormal immune response with apparent increasing prevalence worldwide. Genetically predisposed individuals present with a dysfunctional esophageal barrier and an abnormal immune response mediated by Th2 and IgE against certain allergens. Consequently, esophageal lesions can cause dysmotility, fibrosis and loss of esophageal barrier function. Clinical manifestations are age-related and include symptoms of esophageal dysfunction. Diagnosis is established by specific histological features associated with the presence of at least 15 eosinophils per high-power field. Management of EoE includes control of allergic diseases with diet restrictions and/or pharmacological treatment with proton-pump inhibitors and corticosteroids, not completely effective and limited by possible side effects and impairment of quality of life. Although immunological mechanisms of EoE are still less clear than other allergic diseases, biologic trials indicate some promising perspectives for EoE management. The purpose of this review is to present the current evidence of biologic drugs as options for EoE treatment.

Esofagite eosinofílica (EOE) é uma inflamação crônica da mucosa esofágica com resposta imune antígeno-mediada anormal e com aparente aumento mundial na prevalência. Indivíduos geneticamente predispostos se apresentam com quadro de disfunção da barreira esofágica e uma resposta imune, mediada por TH2 e IGE, anormal contra certos alérgenos. Consequentemente, lesões esofágicas podem causar dismotilidade, fibrose e perda da função de barreira. O quadro clínico apresenta variação conforme idade e inclui sintomas de disfunção esofágica. O diagnóstico é estabelecido por achados histológicos específicos associados à presença de, ao menos, 15 eosinófilos por campo de alta potência. O manejo inclui controle do quadro alérgico com restrição dietética e/ou tratamento medicamentoso com bloqueadores da bomba de prótons e corticosteroides. São tratamentos sem completa efetividade, com efeitos colaterais e prejuízo na qualidade de vida. Ainda que os mecanismos imunológicos da EOE sejam menos claros que as demais doenças alérgicas, novos ensaios com imunobiológicos salientam uma perspectiva promissora de tratamento para a EOE. O objetivo desta revisão é apresentar as atuais evidências de uso de imunobiológicos como uma nova opção de terapêutica para a esofagite eosinofílica.

Vacinas no Brasil: análise histórica do registro sanitário e a disponibilização no Sistema de Saúde / Vaccines in Brazil: historical analysis of the Sanitary registration and vaccine availability in the Brazilian Unified Health System

Resumo Com a pandemia da COVID-19 e a importância das políticas públicas de proteção social, questões sanitaristas incluindo as imunizações se tornaram destaque. O estudo tem o objetivo de analisar a dinâmica dos registros sanitários de vacinas no país e as vacinas disponibilizadas por meio do Programa Nacional de Imunização (PNI), com destaque para o calendário vacinal no período entre 2004 e 2018. Realizou-se um estudo descritivo, documental e exploratório dos processos de registro sanitário na Agência Nacional de Vigilância Sanitária (Anvisa) e a incorporação dos produtos no PNI. Como base da pesquisa foram utilizados o banco de dados de registro sanitário disponibilizado pela Anvisa, a análise documental de publicações oficiais/normativas e os dados da literatura. Os dados demonstram a incorporação das vacinas no PNI, assim como um país com potencial industrial para a produção das vacinas, no entanto ainda centrado na transferência de tecnologias, necessitando de investimentos e atenção pública no desenvolvimento de novas tecnologias, garantindo a independência do setor.

Abstract Given the COVID-19 pandemic and the importance of public social protection policies, health issues, including immunizations, have gained prominence. This paper aims to analyze the dynamics of vaccine registration in Brazil and the vaccines made available through the National Immunization Program (PNI in Portuguese), with emphasis on the 2004-2018 vaccination schedule. This descriptive, exploratory, documentary research analyzed vaccine registration procedureswith the Brazilian Health Regulatory Agency (ANVISA, in Portuguese) and the incorporation of vaccine products into the PNI. The study drew on information from the national sanitary registration database, made available by ANVISA; a document analysis of official/normative publications; and data from published literature. The data shows the incorporation of vaccines into the PNI, evidencing that Brazil is a country with industrial potential for vaccine production but that is still focused on the transfer of technologies and in need of public attention and investments for developing new technologies as a way to ensure the sector's independence.

Coriandrum sativum (Coriander) in Oral Health: Literature Review / Coriandrum sativum (Coentro) na Saúde Bucal: Revisão de Literatura

Mouthwashes are an effective complementary method in the biofilm prevention and chemical control, when the practice of mechanical removal is insufficient. Among the active compounds most used in antiseptics are chlorhexidine, cetylpyridinium chloride, triclosan and essential oils. In order to reduce undesirable effects, such as teeth and restorations staining and the supragingival calculus formation, observed mainly after use for long periods, natural products of plant origin have been extensively studied and incorporated into oral hygiene formulations. Commonly used as a functional food or spice in world gastronomy, Coriandrum sativum (C. sativum), popularly known as coriander, is a natural therapeutic resource with several properties, including antifungal and antioxidant ones. Thus, the objective of this study was to carry out a literature review of articles published in the last 10 years that relate natural products, dentistry and C. sativum, in order to understand the role of naturally-occurring agents with potential therapeutic applications in the dental fields, as well as to evaluate the application of C. sativum in the treatment of oral diseases. Therefore, a bibliographic search was carried out in the ScienceDirect and PubMed databases, obtaining 20 articles. It was possible to confirm the antifungal properties and the mode of action of the essential oil from C. sativum in Candida species, as well as its relatively low cytotoxicity in human cells. These findings should encourage further studies for the development of mouthwashes based on C. sativum as an alternative to mouthwashes available on the market. (AU)

Os enxaguatórios bucais constituem um método complementar eficaz na prevenção e controle químico do biofilme, quando a prática de remoção mecânica se mostra insuficiente. Dentre os compostos ativos mais utilizados em antissépticos estão a Clorexidina, o cloreto de cetilpiridíneo, o triclosan e os óleos essenciais. Buscando a diminuição de efeitos indesejáveis, como manchamento de dentes e restaurações e a formação de cálculo supragengival, observados principalmente após a utilização por longos períodos, produtos naturais de origem vegetal têm sido amplamente estudados e incorporados nas formulações para higiene bucal. Comumente utilizado como alimento funcional ou especiaria na gastronomia mundial, o Coriandrum sativum (C. sativum), popularmente conhecido por coentro, apresenta-se como um recurso terapêutico natural com diversas propriedades, incluindo antifúngica e antioxidante. Assim, o objetivo deste estudo foi realizar uma revisão de literatura de artigos publicados nos últimos 10 anos que relacionam produtos naturais, a odontologia e o C. sativum, a fim de compreender o papel de agentes de ocorrência natural em aplicações terapêuticas potenciais na área odontológica, bem como avaliar a aplicação do C. sativum no tratamento de doenças bucais. Para isso foi realizada uma busca bibliográfica nas bases de dados ScienceDirect e PubMed, obtendo-se 20 artigos. Foi possível confirmar as propriedades antifúngicas e o modo de ação do óleo essencial de C. sativum em espécies de Candida, bem como sua citotoxicidade relativamente baixa em células humanas. Esses achados devem incentivar novos estudos para o desenvolvimento de enxaguatórios bucais baseados em C. sativum como alternativa aos enxaguatórios bucais disponíveis no mercado. (AU)

La trazabilidad en el sistema logístico de medicamentos en Cuba y el uso de las tecnologías de auto-identificación / Traceability in the logistics system of medicines in Cuba, use of auto-identification

La trazabilidad es la capacidad para rastrear la historia, aplicación o ubicación de un objeto bajo consideración. En el ámbito farmacéutico, el rastreo y seguimiento de los medicamentos, incluyendo las vacunas y otros medicamentos biológicos, a lo largo de la cadena de suministro constituye un requisito obligatorio establecido por las autoridades sanitarias a nivel internacional, que se exige en mayor o menor magnitud en las reglamentaciones vigentes. En este artículo se analiza el sistema de codificación y clasificación en el sector de la salud y su estado actual en la cadena de suministro de medicamentos de Cuba. Se presenta un procedimiento para la implementación de las tecnologías de auto-identificación e intercambio electrónico de datos, mediante el uso de GS1 en el sistema de codificación y clasificación empleado en el sector de salud, que permita la trazabilidad en toda la cadena de suministro en Cuba(AU)

Traceability is the capability to track the history, application or location of an object under consideration. In the pharmaceutical field, the tracking and monitoring of medicines, including vaccines and other biological medicines, along the supply chain constitutes a mandatory requirement established by the sanitary authorities at an international level, which is demanded to a greater or lesser extent in the regulations in force. This research was carried out involving different links in the drug supply chain in Cuba, ranging from drug suppliers, drug distribution company, to healthcare centers and pharmacies. An analysis is carried out on the current coding and classification system, detecting the ineffectiveness of the identification of the drugs as the main deficiency. A procedure is proposed for the implementation of the auto-identification and electronic data interchange technologies using GS1 in the coding and classification system used in the health sector that allows traceability throughout the supply chain in Cuba(AU)

Cinamaldeído e terpineol como inibidores de biofilmes de Candida albicans e Enterococcus faecalis / Cinamaldehído y terpineol como inhibidores de biopelículas de Candida albicans y Enterococcus faecalis / Cinnamaldehyde and terpineol as inhibitors of Candida albicans and Enterococcus faecalis biofilms

Introdução: Os fitoconstituintes são moléculas naturais que apresentam atividade antimicrobiana satisfatória e devem ser estudados quanto ao seu uso como novas substâncias para irrigação dos canais radiculares. Objetivo: Avaliar o efeito inibitório dos fitoconstituintes cinamaldeído e α-terpineol frente a biofilmes monoespécie e duoespécie de microrganismos envolvidos na infecção endodôntica. Métodos: Trata-se de um estudo experimental na área de microbiologia aplicada, in vitro, cego quanto às análises e randomizado. Foram selecionados os fitoconstituintes cinamaldeído e α-terpineol. A atividade antimicrobiana frente Candida albicans e Enterococcus faecalis foi avaliada por meio da análise da capacidade metabólica com o uso da resazurina e análise da viabilidade celular pelo plaqueamento. O meio de cultura e a clorexidina 1 porcento serviram de controle negativo e positivo, respectivamente. Resultados: Observou-se ausência de crescimento para exposição dos biofilmes nas concentrações de 10 e 5 mg/mL de ambos os fitoconstituintes. Na concentração de 2,5 mg/mL de terpineol, constatou-se crescimento somente nos biofilmes monoespécie de C. albicans e duoespécie. Já na concentração de 1mg/mL de terpineol e cinamaldeído, verificou-se crescimento para todos os biofilmes. Conclusão: O cinamaldeído e α-terpineol apresentaram atividade inibitória frente biofilmes monoespécie e duoespécie de Candida albicans e Enterococcus faecalis, nas concentrações de 10 e 5 mg/mL(AU)

Introducción: Los fitoconstituyentes son moléculas naturales que presentan actividad antimicrobiana satisfactoria y deben ser estudiados en cuanto a su uso como nuevas sustancias para irrigación de los canales radiculares. Objetivo: Evaluar el efecto inhibitorio de fitoconstituyentes cinamaldehído y α-terpineol frente a biopelículas monoespecies y duoespecies de microorganismos involucrados en la infección endodóntica. Métodos: Estudio experimental en el campo de la microbiología aplicada, in vitro, ciego al análisis y aleatorizado. Se seleccionaron los fitoconstituyentes cinamaldehído y α-terpineol. La actividad antimicrobiana frente Candida albicans y Enterococcus faecalis fue evaluada por medio del análisis de la capacidad metabólica con el uso de la resazurina y análisis de la viabilidad celular por el plaqueamiento. El medio de cultivo y la clorexidina 1 por ciento sirvieron de control negativo y positivo, respectivamente. Resultados: Se observó ausencia de crecimiento para exposición de las biopelículas en las concentraciones de 10 y 5 mg/mL de ambos fitoconstituyentes. En la concentración de 2,5 mg/mL de terpineol se constató crecimiento solo en los biofilmios monoespecies de C. albicans y duoespecies. En la concentración de 1 mg/mL de terpineol y cinamaldehído se verificó crecimiento para todas las biopelículas. Conclusiones: Cinamaldehído y α-terpineol presentaron actividad inhibitoria frente a biofilmes monoespecies y duoespecies de Candida albicans y Enterococcus faecalis, en las concentraciones de 10 y 5 mg/mL(AU)

Introduction: Phytoconstituents are natural molecules displaying satisfactory antimicrobial activity. Studies should be conducted about their use as new root canal irrigants. Objective: Evaluate the inhibitory effect of the phytoconstituents cinnamaldehyde and α-terpineol against mono- and duo-species biofilms of microorganisms involved in endodontic infection. Methods: An experimental applied microbiology blind randomized in vitro study was conducted. The phytoconstituents selected were cinnamaldehyde and α-terpineol. Antimicrobial activity against Candida albicans and Enterococcus faecalis was evaluated by metabolic capacity analysis with resazurin and cell viability analysis by the plaque. The culture medium and 1 percent chlorhexidine served as negative and positive controls, respectively. Results: An absence of growth was observed for exposure of the biofilms at concentrations of 10 and 5 mg/ml of both phytoconstituents. At a concentration of 2.5 mg/ml terpineol displayed growth only in the mono-species biofilms of C. albicans and duo-species biofilms. At a concentration of 1 mg/ml terpineol and cinnamaldehyde displayed growth in all biofilms. Conclusions: Cinnamaldehyde and α-terpineol displayed inhibitory activity against mono- and duo-species biofilms of Candida albicans and Enterococcus faecalis at concentrations of 10 and 5 mg/ml(AU)

Vacinas COVID-19 e imunobiológicos / COVID-19 vaccines and immunobiological drugs

Os medicamentos imunobiológicos têm sido frequentemente utilizados no tratamento das doenças alérgicas e de natureza imunológica. Esses agentes regulam a resposta imunológica do tipo 2 nas doenças alérgicas ou atuam em diversas vias de ativação alteradas nos erros inatos da imunidade. Com o surgimento da pandemia COVID-19 um crescente número de pacientes em uso de imunobiológicos para essas condições deverão ser vacinados contra o vírus SARS-CoV-2. Dessa forma, existe a necessidade de avaliar a segurança e eficácia destas vacinas nos pacientes em uso de imunobiológicos para asma, dermatite atópica, rinossinusite crônica com pólipos nasais, urticária crônica e erros inatos da imunidade. Foi realizada uma busca de literatura recente relevante sobre imunobiológicos e vacinas COVID-19 no PubMed. Existe um consenso de manutenção desses agentes durante a pandemia COVID-19, embora nas doenças alérgicas os mesmos devam ser suspensos durante a infecção ativa. Por outro lado, dados disponíveis em relação à segurança e eficácia das vacinas contra a COVID-19 nesse grupo de pacientes são escassos. Existem relatos do uso de outras vacinas inativadas em associação com alguns imunobiológicos demonstrando serem eficazes e seguras. Portanto, considerando o risco potencial da infecção COVID-19, especialmente nos pacientes portadores de erros inatos da imunidade, recomendamos que as vacinas contra a COVID-19 sejam utilizadas nos pacientes em uso de imunobiológicos. Desta forma, existe uma necessidade de estudos que avaliem estas questões haja vista que a terapia com diversos imunobiológicos tem sido amplamente utilizada nos pacientes com doenças alérgicas e de natureza imunológica.

Immunobiological drugs have often been used to treat allergic and immunological diseases. These agents regulate the type 2 immune response in allergic diseases or act on different activation pathways altered in inborn errors of immunity. With the emergence of the COVID-19 pandemic, an increasing number of patients with these conditions using these agents should be vaccinated against the SARS-CoV-2 virus. Thus, there is a need to evaluate the safety and efficacy of these vaccines in patients using biologics for asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, chronic urticaria, and inborn errors of immunity. A search for relevant recent literature on biologics and COVID-19 vaccines was conducted on PubMed. There is a consensus on maintaining the use of these agents during the COVID-19 pandemic, although in allergic diseases they must be suspended during active infection. Conversely, the available data regarding the safety and efficacy of the COVID-19 vaccines are scarce. There are reports of the use of other inactivated vaccines with some biologics proving to be effective and safe. Therefore, considering the potential risk of COVID-19 infection, especially in patients with inborn errors of immunity, we recommend that COVID-19 vaccines should be used in patients using biologics. Thus, there is a need for studies to assess these issues, given that therapy with several biologics has been widely used in patients with allergic and immunological diseases.

Drug prices in Latin American countries: the case of rheumatoid arthritis Biosimilars

Abstract Background: The objective of this paper is to analyze the prices of biological drugs in the treatment of Rheumatoid Arthritis (RA) in three Latin American countries (Brazil, Colombia and Mexico), as well as in Spain and the United States of America (US), from the point of market entry of biosimilars. Methods: We analyzed products authorized for commercialization in the last 20 years, in Brazil, Colombia, and Mexico, comparing them to the United States of America (USA) and Spain. For this analysis, we sought the prices and registries of drugs marketed between 1999 and October 1, 2019, in the regulatory agencies' databases. The pricing between countries was based on purchasing power parity (PPP). Results: The US authorized the commercialization of 13 distinct biologicals and four biosimilars in the period. Spain and Brazil marketed 14 biopharmaceuticals for RA, ten original, four biosimilars. Colombia and Mexico have authorized three biosimilars in addition to the ten biological ones. For biological drug prices, the US is the most expensive country. Spain's price behavior seems intermediate when compared to the three LA countries. Brazil has the highest LA prices, followed by Mexico and Colombia, which has the lowest prices. Spain has the lowest values in PPP, compared to LA countries, while the US has the highest prices. Conclusions: The economic effort that LA countries make to access these medicines is much higher than the US and Spain. The use of the PPP ensured a better understanding of the actual access to these inputs in the countries analyzed.(AU)

Beneficial effects of three natural products for the treatment of denture stomatitis: a randomized clinical trial / Efeitos benéficos de três produtos naturais para o tratamento da estomatite protética: um ensaio clínico randomizado

Aim: To evaluate the effect of three natural antifungal agents combined with routine denture care on the treatment of DS, using a quantitative mycological culture analysis. Methods: Thirty denture wearers with denture stomatitis DS were treated using five substances: sterile distilled water (G1), nystatin oral suspension (G2), 20% alcoholic extract propolis (G3), Punica granatumLinné gel (G4), and Uncaria tomentosa gel (G5). The substances were used 3 times a day for 14 days. Quantitative mycological culture analysis of samples collected from the palatal mucosa was performed at three stages: before treatment (T0), after 14 days of treatment (T1), and 30 days after treatment completion (T2). Data were evaluated using Kruskal-Wallis and Friedman tests (p < 0.05). Results: Palatal mucosa intragroup analysis showed a significant reduction of Candida CFU/mL values for all groups at T1 compared to T0 (p < 0.05). However, they did not present statistical differences when comparing T1 and T2 (p > 0.05). The intergroup analysis demonstrated that there are no statistical differences, regardless of the evaluation time (p > 0.05). Conclusion:The natural products tested showed a satisfactory result on DS treatment, which proved to be equivalent to conventional topical therapy with nystatin and to treatment using only regular oral hygiene procedures.

Objetivo: Avaliar o efeito de três antifúngicos naturais combinados com o cuidado rotineiro com próteses dentárias no tratamento da EP, por meio de uma análise quantitativa de cultura micológica. Métodos: Trinta usuários de próteses dentárias com EP foram tratados com cinco substâncias: água destilada estéril (G1), suspensão oral de nistatina (G2), extrato alcoólico de própolis 20% (G3), gel Punica granatum L. (G4) e gel Uncaria tomentosa (G5). As substâncias foram utilizadas 3 vezes ao dia durante 14 dias. A análise micológica quantitativa das amostras coletadas da mucosa palatina foi realizada em três etapas: antes do tratamento (T0), após 14 dias do tratamento (T1) e 30 dias após o término do tratamento (T2). Os dados foram avaliados pelos testes de Kruskal-Wallis e Friedman (p < 0,05). Resultados: A análise intragrupo da mucosa palatina mostrou uma redução significativa dos valores de Candida UFC/mL para todos os grupos em T1 em comparação com T0 (p < 0,05). No entanto, não apresentaram diferenças estatísticas na comparação de T1 e T2 (p > 0,05). A análise intergrupos demonstrou que não há diferenças estatísticas, independentemente do tempo de avaliação (p > 0,05). Conclusão: Os produtos naturais testados apresentaram resultado satisfatório no tratamento da EP, sendo equivalente à terapia tópica convencional com nistatina e ao tratamento apenas com procedimentos rotineiros de higiene bucal.

Gestión de riesgos relativo al cambio de campaña productiva durante la etapa de desarrollo tecnológico en una instalación multiproducto / Risk-management related to the productive campaign change during technological development stage in a multi-product facility

Los nuevos paradigmas de la industria farmacéutica en el siglo XXI incorporan el uso de las técnicas de gestión de la calidad, necesarias en el cumplimiento de las buenas prácticas de fabricación en el sector biotecnológico. En este caso de estudio, se aplicó la gestión de riesgo en el cambio de campaña entre los ingredientes farmacéuticos activos de futuros candidatos inmunoterapeúticos contra el cáncer, en la etapa de desarrollo tecnológico en una instalación multiproducto certificada. Las causas potenciales de mayor influencia en las fallas son: la calificación del personal de la Dirección de Desarrollo Tecnológico en los procedimientos patrones de operación de la planta, la mezcla entre los componentes y materiales no dedicados utilizados en el proceso de purificación cromatográfica, la documentación en elaboración o aprobación y el establecimiento de las técnicas analíticas en función de la etapa del proyecto. Como resultado se proponen acciones que minimizan los riesgos de la contaminación cruzada y hacen viable un adecuado cambio de campaña entre la fabricación de los inmunoterapéuticos, durante el desarrollo tecnológico en una instalación multiproducto de la industria biotecnológica(AU)

The new paradigms of the pharmaceutical industry in the 21st century introduce the use of modern quality management techniques to comply with good manufacturing practices in the biotechnological area. In this paper, it was applied the risk management for the campaign change among the process for obtaining the active pharmaceutical ingredients to future immunotherapeutic candidates at the technological development stage in a certified multi-product facility. Particularly, the training for the development personnel in the standard operating procedures of the facility, the mixture between the components and non-dedicated materials used in the chromatographic purification process, the documentation in the preparation or approval, and the establishment of analytical techniques depending on the stage of the project are the potential causes of greater influence. As a result, actions are proposed to minimize risks and carry out an adequate campaign change feasible between the manufacture of immunotherapeutics during the technological development stage in a biotechnological multi-product facility(AU)