Uso da toxina botulínica tipo A no tratamento da espasticidade em crianças com paralisia cerebral: revisão sistemática / Use of botulinum toxin type A in the treatment of spasticity in children with cerebral palsy: systematic review

Há pouco mais de duas décadas, a toxina botulínica tipo A (TBA) vem sendo utilizada como parte do tratamento multimodal para a redução do tônus muscular em crianças com paralisia cerebral (PC) espástica. Objetivos: determinar a eficácia e segurança, avaliar as doses utilizadas em cada faixa etária e comparar os custos entre as TBA's para tratamento da espasticidade em crianças portadoras de PC. Métodos: foi realizada uma revisão sistemática de estudos publicados nos últimos 6 anos, de 2017 a abril de 2022, através das bases de dados do PubMed, SciELO, Science Direct, Google Acadêmico e Periódicos CAPES, de acordo com os seguintes critérios de inclusão: (1) termos de busca: toxina botulínica, espasticidade e paralisia cerebral; (2) idioma: português, inglês e espanhol; (3) desenho: ensaios clínicos randomizados e duplo-cego, revisões sistemáticas e metanálises; (4) população: crianças e adolescentes com PC espástica; (5) intervenção: TBA; (6) grupo controle com outro tratamento para PC ou sem intervenção; (7) desfecho: alteração na Escala de Ashworth Modificada, efeitos adversos e qualidade de vida. Resultados: foram incluídos 10 artigos nesta revisão, que apresentaram dose mínima terapêutica, o impacto de injeções únicas e repetidas, seleção de músculos e pontos a serem aplicados. Conclusão: a TBA proporcionou uma melhora significativa sobre a espasticidade e funcionalidade da criança com PC espástica, em um período de até 3 meses após sua aplicação. Pode ser considerada uma opção de tratamento segura e eficaz, e a análise econômica da saúde demonstra que essa intervenção possui excelente relação custo-benefício.

For just over two decades, botulinum toxin type A (BoNT-A) has been used as part of a multimodal treatment to reduce muscle tone in children with spastic cerebral palsy (CP). Objectives: to determine the efficacy and safety, to evaluate the doses used in each age group and to compare the costs between the BoNT-A's for the treatment of spasticity in children with CP. Methods: a systematic review of studies published in the last 6 years, from 2017 to april 2022, was carried out through the PubMed, SciELO, Science Direct, Google Scholar and CAPES Periodicals databases, according to the following inclusion criteria: (1) search terms: botulinum toxin, spasticity and cerebral palsy; (2) language: portuguese, english and epanish; (3) design: trials randomized and double-blind clinical trials, systematic reviews and meta-analyses; (4) population: children and adolescents with spastic CP; (5) intervention: BoNT-A; (6) control group with other treatment for CP or without intervention; (7) outcome: change in Modified Ashworth Scale, adverse effects and quality of life. Results: 10 articles were included in this review, which presented the minimum therapeutic dose, the impact of single and repeated injections, selection of muscles and points to be applied. Conclusion: BoNT-A provided a significant improvement in spasticity and functionality in children with spastic CP, within a period of up to 3 months after its application. It can be considered a safe and effective treatment option, and the economic analysis of health demonstrates that this intervention has an excellent cost-benefit ratio.

LASSBio-596: a New Pre-clinical Candidate for Rheumatoid Arthritis?

Pain and inflammatory disorders are significant health problems because of prevalence and associated disabilities. In this context, LASSBio-596 is a hybrid compound able to modulate TNF-α and phosphodiesterases 4 and 5, exhibiting an anti-inflammatory effect in the pulmonary inflammatory model. Aiming at a better description of the activities of LASSBio-596, we initially conducted nociception tests (acetic acid-induced abdominal writhing, glutamate, and formalin-induced nociception and hot plate test) and later inflammatory tests (acute, peritonitis; and chronic, arthritis) that directed us to this last one. In the abdominal writhing test, there was a dose-dependent inhibition, whose response occurred at the maximum dose (50 mg/kg, p.o.), used in the subsequent tests. LASSBio-596 also inhibited nociception induced by chemical (glutamate by 31.9%; and formalin, in both phases, 1st phase: 25.7%; 2nd phase: 23.9%) and thermal agents (hotplate, by increased latency for pain at two different times). These effects were independent of the motor function, legitimated in rotarod. As there was a response in the inflammatory component of nociception, we performed the peritonitis test, in which migration was inhibited by LASSBio-596 by 39.9%. As the inflammatory process is present in autoimmune diseases, we also performed the arthritis test. LASSBio-596 reduced paw edema from the 15th day to the 21st day of treatment (no liver changes and with fewer paw injuries). In addition, LASSBio-596 decreased serum levels of TNF-α by 67.1%. These data demonstrated the antinociceptive effect of LASSBio-596 and reinforces its anti-inflammatory property (i.e., RA), amplifying the therapeutic potential of this molecule.

Costus spiralis (Jacq.) Roscoe leaves fractions have potential to reduce effects of inflammatory diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Since drugs currently used to manage pain and inflammatory conditions present several side effects, the investigation of new anti-inflammatory and antinociceptive agents from folk-medicine plants is an important approach. Costus spiralis (Costaceae) has been used in Brazilian medicinal teas to treat urinary infection, cough, inflammation, arthritis, among others. AIM OF THE STUDY: The current study focused on investigating anti-inflammatory and antinociceptive effects of fractions from C. spiralis leaves using animal models. MATERIALS AND METHODS: Adults Swiss mice were used in the following experimental models: acetic acid-induced abdominal writhing, formalin-induced nociception, hot plate, zymosan-induced peritonitis, and arthritis induced by complete Freund's adjuvant. RESULTS: The presence of steroids was confirmed in all fractions. Flavonoids, condensed tannins and saponins were observed in EFL. In methanolic fraction leaves (MFL), the presence of flavonoids and pentacyclic triterpenoids was confirmed. Orally administered leaf fractions significantly reduced abdominal writhing. Fractions were ineffective in the neurogenic stage of the formalin test, but in the inflammatory stage, ethyl acetate fraction levaes (AcFL), ethanolic fraction leaves (EFL), and MFL significantly reduced paw licking time by 69.6 ± 11.9%, 58.2 ± 9.4%, and 79.6 ± 8.3%, respectively. In the hot plate test, the reaction latency was similar for treated animals and controls. However, in the peritonitis test, cell migration was significantly reduced in animals treated with chloroform fractions leaves ClFL (61.8 ± 11.4%), AcFL (58.7 ± 8.3%), EFL (39.2 ± 5.0%), and MFL (64.8 ± 4.4%). This was similar to the result observed in the chronic inflammation model, this time only the chloroform fraction was able to reduce paw edema. CONCLUSION: Our results show that leaf fractions of Costus spiralis are capable of modulating peripheral nociceptive and inflammatory responses without effects on central nervous system being potential substrates for phytochemical purification, structural and mechanistic studies.

Citrus limon (L.) Burm f. Essential Oil Has Anxiolytic and Sedative Properties by Modulating GABAA-Receptors

Abstract The high prevalence of anxiety disorders associated with pharmacotherapy side effects have motivated the search for new pharmacological agents. Species from Citrus genus, such as Citrus limon (sicilian lemon), have been used in folk medicine as a potential therapy to minimize emotional disorders. In order to searching for new effective treatments with fewer side effects, the present study evaluated the anxiolytic mechanism of action and the hypnotic-sedative activity from the Citrus limon fruit's peels essential oil (CLEO). Adults male Swiss mice were submitted to barbiturate-induced sleep test; elevated plus-maze (EPM) and light-dark box (LDB) (evaluation of the mechanism of action); rotarod; and catalepsy tests. CLEO oral treatment decreased latency and increased the sleep total time; moreover it induced in animals an increased the number of entries and percentage of time spent into open arms of the EPM; an increased the number of transitions and the percentage of time into light compartment in the LDB; which were only antagonized by flumazenil pretreatment, with no injury at motor function. Thus, results suggest that CLEO treatment induced an anxiolytic behavior suggestively modulated by the benzodiazepine binding site of the GABAA receptor or by an increase of GABAergic neurotransmission, without cause impairment in the motor coordination.

The Antinociceptive Effect of the Leaves and Flowers Ethanolic Extracts of Tabebuia aurea (Silva Manso) Benth & Hook. F. ex S. Moore

ABSTRACT In view of the traditional use of Tabebuia aurea for treating pain and inflammation, the antinociceptive pharmacological potential of T. aurea ethanolic extracts (TAEE) was investigated through in vivo experimental models. First, the MTT assay was conducted to determine the potential cytotoxicity of the TAEEs. Afterwards, the acetic acid-induced writhing test and the formalin-, and glutamate-induced nociception tests were performed on Swiss adult mice treated with TAEEs (100 and 200 mg/kg doses, p.o.), or saline solution (control groups, 10mL/kg, p.o.), or standard drugs: dipyrone 40 mg/kg (p.o.), and morphine 5,7 mg/kg (i.p). In the MTT assay, none of the tested concentrations demonstrated signals of cytotoxicity. In the in vivo experimental models of acetic acid-induced writhing and glutamate-induced nociception, all TAEEs doses were able to statistically reduce the nociceptive response. However, the TAEEs did not show significant decrease in the amount of time that the animals spent licking the stimulated paw in the neurogenic phase of formalin-induced nociception test, differently of what was observed in the inflammatory phase. The results showed that T. aurea species induce an antinociceptive effect in rodents, which encourages the study of new drugs and contributes to the research on natural products.

Cytotoxic mechanism of Baccharis milleflora (Less.) DC. essential oil.

The aim of this study was to investigate the cytotoxic activity of the essential oil from cladodes of Bacharis milleflora in relation to Jurkat, Raji and HL-60 cells, as well as exploring the cell mechanisms in order to elucidate how the cytotoxic process occurs. The presence of the following volatile compounds was detected by GC-MS: bicyclogermacrene (12.16%), germacrene D (11.18%), (E)-caryophyllene (9.28%), and α-humulene (8.05%). In general, IC50 values lower than 50µg/mL were obtained for all the tumor cells at 24, 48 and 72h by MTT assay. The decrease in cell DNA content was demonstrated due to the inhibition of the proliferation of Jurkat, Raji and HL-60 cells by B. milleflora essential oil. In particular, Raji cells presented the greatest inhibition of cell proliferation and they were subsequently used to investigate cell death mechanisms. B. milleflora essential oil promoted G0/G1 arrest and also induced cell fragmentation, which was represented by an increase in the sub-G0 population, indicating cell death induced by apoptosis. The selectivity index was 3.97. Necrotic cell death, coupled with low levels of apoptotic cell death, was observed by conventional EB/AO and Hoechst 33342 staining assays, demonstrating that this essential oil acts via both necrotic and apoptotic mechanisms.

Potencial ansiolítico do gênero citrus: revisão integrativa da literatura / Anxiolytic potential of the citrus genus: an integrative literature review

A alta prevalência de pessoas acometidas por algum distúrbio de ansiedade associada aos efeitos colaterais da farmacoterapia a longo prazo tem motivado a procura por novas terapias. Como terapia complementar e alternativa, óleos essenciais e infusos obtidos de folhas, cascas e flores de muitas espécies do gênero Citrus têm sido utilizadas pela população para minimizar distúrbios emocionais e tem sido recomendado no tratamento da ansiedade. O presente estudo buscou analisar a literatura publicada referente ao potencial ansiolítico do gênero Citrus, por meio de uma revisão integrativa nas bases de dados: MEDLINE, PubMed, SciELO e LILACS, no período de Janeiro a Abril de 2014, utilizando os descritores ansiedade e Citrus e selecionados 12 artigos que compuseram a amostra do estudo. Em todos os artigos selecionados foi demonstrado o potencial ansiolítico do gênero Citrus, o qual se atribui à atividade sinérgica ou isolada dos metabólitos presentes nestes extratos e/ou óleos essenciais estudados, que se assemelham. Diante dos resultados satisfatórios já realizados em humanos, observa-se a importância e a necessidade de maiores estudos e investimentos no sentido de tornar possível a utilização desses compostos de origem natural e de fácil acesso à população na terapêutica.

The high prevalence of people suffering from anxiety disorders associated with side effects of long-term pharmacotherapy has motivated the search for new therapies. As a complementary and alternative therapy, essential oils and infusions obtained from leaves, skins and flowers of many species of the Citrus genus have been used by the population to minimize emotional disorders, as well as being recommended in the anxiety treatment. The present study aimed to analyze the published literature regarding the anxiolytic potential of the Citrus genus, through an integrative review in the MEDLINE, PubMed, SciELO and LILACS databases, from January to April 2014, using the keywords anxiety and Citrus. A total of 12 articles were selected, which composed the study sample. All papers demonstrated the anxiolytic potential of the Citrus genus, which is attributed to the synergistic or isolated activity from the metabolites present in these extracts and/or essential oils studied, which are similar among themselves. Given the satisfactory results already achieved in humans, the importance and the need for further studies and investments is observed, in order to make it possible to use such compounds occurring naturally, which are easily accessible to the population in the therapy.

Revisão integrativa sobre uso medicinal e atividades farmacológicas de plantas do gênero Bauhinia / Integrative review on medical use and pharmacological activities Bauhinia genus plant / Revisión integradora sobre el uso medicinal y actividades farmacológicas de plantas del género Bauhinia

Objetivo: identificar a produção do conhecimento sobre plantas do gênero Bauhinia a respeito de seu uso terapêutico popular e estudos farmacológicos em pesquisas brasileiras. Método: revisão integrativa, cujas as bases de dados consultadas foram LILACS, MEDLINE e Scopus e biblioteca virtual SciELO a partir dos descritores: Bauhinia; Brazil; ethnobotany; folk medicine; medicinal plants; bioassay e anti-infective agents. Os critérios de inclusão foram: pesquisas realizadas no Brasil, estudos etnobotânicos e experimentais com atividades comprovadas. Resultados: a análise dos 51 artigos demonstrou um avanço nas pesquisas etnobotânicas e farmacológicas, o que pode estar relacionado às importantes iniciativas governamentais, mas poucos são os estudos que comprovem as inúmeras utilizações populares para as centenas de espécies do referido gênero. Conclusão: a compilação de dessas informações pode oferecer subsídios na realização de futuros estudos farmacológicos de espécies ainda não avaliadas que podem ser incluídas na RENISUS e listadas na RENAME, para assim serem oficialmente prescritas no Sistema Único de Saúde.(AU)

Objective: to identify knowledge production about Bauhinia genus plants on its popular therapeutic use and pharmacological studies in Brazilian research. Method: integrative review, where the databases LILACS, MEDLINE and Scopus and SciELO virtual library were consulted from descriptors: Bauhinia; Brazil; ethnobotany; folk medicine; medicinal plants; bioassay and anti-infective agents. Some of the inclusion criteria were studies conducted in Brazil, ethnobotanical studies and experimental with proven activities. Results: the analysis of 51 articles showed an improvement in the ethnobotanical and pharmacological research, which may be related to major government initiatives, but there are few studies that prove the many popular uses for hundreds of species of that genus. Conclusion: the compilation of this information can help in the realization of future pharmacological studies of not yet evaluated species that can be included in RENISUS and listed on the RENAME, to be officially prescribed in the public health system. (AU)

Objetivo: identificar la producción del conocimiento sobre plantas del género Bauhinia a respecto de su uso terapéutico popular y estudios farmacológicos en investigaciones brasileñas. Método: revisión integradora donde fueron consultadas las bases de datos LILACS, MEDLINE y Scopus y biblioteca virtual SciELO a partir de los descriptores: Bauhinia; Brazil; ethnobotany; folk medicine; medicinal plants; bioassay y anti-infective agents. Algunos de los criterios de inclusión fueron: investigaciones realizadas en Brasil, estudios etnobotánicos y experimentales con actividades comprobadas. Resultados: el análisis de los 51 artículos demostró un avance en las investigaciones etnobotánicas y farmacológicas, lo que puede estar relacionado a las importantes iniciativas gubernamentales, pero pocos son los estudios que comprueben las innúmeras utilizaciones populares para las centenas de especies del referido género. Conclusión: la compilación de esas informaciones puede ofrecer subsidios en la realización de futuros estudios farmacológicos de especies todavía no evaluadas que pueden ser incluidas en RENISUS y listadas en RENAME, para así ser oficialmente prescritas en el sistema único de salud.(AU)

Antinociceptive and anti-inflammatory effects of flavonoids PMT1 and PMT2 isolated from Piper montealegreanum Yuncker (Piperaceae) in mice.

In this study, we identified the antinociceptive and anti-inflammatory effects of two flavonoids (PMT1 and PMT2) from Piper montealegreanum. The antinociceptive effect was evaluated using the classical tests: acetic acid-induced writhing, formalin and hot plate test. PMT1 and PMT2 (0.1, 1, 30 and 100 µmol/kg, i.p.) reduced the writhings, with an ID50 of 0.58 and 0.44 µmol/kg, respectively. Moreover, these flavonoids (100 µmol/kg, i.p.) inhibited paw-licking time in the neurogenic phase of the formalin test, but only PMT2 was active in the inflammatory phase. However, PMT1 and PMT2 (100 µmol/kg, i.p.) did not increase the latency time of the animals in the hot plate. In order to evaluate the anti-inflammatory effect of these flavonoids, capsaicin-induced ear oedema was carried out. Both flavonoids (100 µmol/kg, i.p.) were active in this model. These results suggest that PMT1 and PMT2 have antinociceptive and anti-inflammatory activities.

Estudo comparativo do uso tópico de própolis verde e vermelha na reparação de feridas em ratos / Comparative study of topical green and red propolis in the repair of wounds induced in rats

OBJETIVO: Avaliar a ação cicatrizante de própolis verde e vermelha, correlacionando ao teor de flavonoides MÉTODOS: Foi realizada a quantificação de flavonoides totais dos extratos etanólicos de própolis verde e vermelha para posterior incorporação em pomada base a 20%. Utilizou-se 20 ratos Wistar distribuídos em quatro grupos: solução salina a 0,9% (S), pomada base (B), pomada própolis verde (G), pomada própolis vermelha (R), todos submetidos à confecção de lesões excisivas na região mediana do dorso. Os ratos foram tratados diariamente durante 15 dias. Neste período foram observados peso; temperatura corporal; diâmetro das feridas. Para análise histológica, amostras das feridas foram coletadas. Ao fim do experimento foram realizadas coleta sanguínea e remoção do rim e fígado para análises bioquímica e histológica. RESULTADOS: Os teores de flavonoides totais das própolis verde (4,50 %) e vermelha (5,92 %) foram elevados (>2 %), mas, embora a segunda apresente teor maior que a primeira, a evolução da própolis verde, macro e histologicamente, foi melhor na reparação das feridas. Não foram observadas nefro ou hepatotoxicidade, resultado corroborado pelos ensaios bioquímicos (TGP e albumina). A própolis influiu na redução de colesterol total, triglicerídeos e glicemia. CONCLUSÃO: Não foi possível correlacionar o teor de flavonoides totais com a ação cicatrizante da própolis. O dado revela a necessidade da elucidação dos flavonoides encontrados em cada classe de própolis para desvendar qual (ou quais) flavonoide(s) seria(m) representativo(s) no processo cicatricial.

OBJECTIVE: To evaluate the healing action of green and red propolis, correlating it with the content of flavonoids. METHODS: We performed quantification of total flavonoids of green and red propolis ethanol extracts for subsequent incorporation in ointment base to 20%. We used 20 Wistar rats divided into four groups: 0.9% saline (S), ointment base (B), green propolis ointment (G) and red propolis ointment (R). All animals were submitted to excisional lesions in the midian back region. The rats were treated daily for 15 days. During this period we observed weight, body temperature and diameters of the wounds. For histological analysis, samples were collected from wounds. At the end of the experiment we performed blood collection and removal of the kidney and liver for biochemical and histological analyzes. RESULTS: The levels of total flavonoids of green (4.50%) and red (5.92%) propolis were high (> 2%), but, while the latter showed a content larger than the former, the evolution of green propolis was better in the repair of wounds, both macroscopically and histologically. There were no nephrotoxicity or hepatotoxicity, a result confirmed by biochemical tests (ALT and albumin). Propolis influenced the reduction of total cholesterol, triglycerides and glucose. CONCLUSION: There was no correlation between total flavonoid contents and the healing action of propolis. This reveals the need for elucidation of the flavonoids found in each class of propolis to unravel which one(s) would be important for the healing process.

Fatores que levam a não adesão dos pacientes em tratamento com antirretrovirais / Factors that lead to noncompliance in patients antiretroviral therapy

Os antirretrovirais utilizados no tratamento da AIDS trouxeram benefícios na sobrevida dos pacientes, entretanto a não adesão terapêutica está relacionada com o desenvolvimento de resistência viral, levando a falência da terapia e disseminação de vírus resistente. O objetivo desta pesquisa foi analisar os fatores que levam a não adesão dos pacientes em tratamento. Foram analisados 26 pacientes, através de entrevista estruturada, dados clínicos laboratoriais e fichas de dispensação da farmácia. Houve um predomínio para o sexo masculino, baixa escolaridade, solteiro(a), com renda familiar de 1 salário mínimo, a média da idade foi de 41 anos, o tempo de uso da terapia ART obteve uma média de 51,88 meses, metade dos pacientes já mudaram de esquema terapêutico. Na contagem de linfócitos T CD4+, 11,5% tiveram valores abaixo de 200 e 57,5% apresentaram níveis indetectáveis de carga viral. Na análise dos dados obtidos na farmácia, 16,04% atrasaram a retirada da medicação. Quando correlacionado os dados, 23,1% dos pacientes não apresentaram boa adesão terapêutica. Dentre os fatores relacionados, estão: menor escolaridade, desemprego, achar que não necessita do tratamento, usuários de drogas, complexidade terapêutica, adequação de rotina e estilo de vida. Deve se estabelecer estratégias que melhorem a adesão ao tratamento.

The antiretroviral drugs used in AIDS treatment have benefits on patient survival, but not the adherence therapy is related to the development of viral resistance, leading to failure of therapy and spread of resistant virus. The objective of this research was to analyze the factors leading to non-adherence of patients to treatment. We analyzed 26 patients using a structured interview, clinical laboratory and pharmacy dispensing tokens. There was a predominance of male sex, low education, single (a), with a family income of minimum wage, the average age was 41 years, the time of use of ART therapy achieved an average of 51.88 months, half patients have already changed the treatment regimen. In the CD4 lymphocyte count, 11.5% had values below 200 and 57.5% had undetectable viral load. In analyzing the data obtained in the pharmacy, 16.04% have delayed the withdrawal of medication. When correlated data, 23.1% of patients with poor adherence. Among the related factors include: lower education, unemployment, find that you do not need treatment, drug users, complexity of therapy, fitness routine and lifestyle. Should develop strategies to improve adherence to treatment.

Comparative study of topical green and red propolis in the repair of wounds induced in rats.

OBJECTIVE: To evaluate the healing action of green and red propolis, correlating it with the content of flavonoids. METHODS: We performed quantification of total flavonoids of green and red propolis ethanol extracts for subsequent incorporation in ointment base to 20%. We used 20 Wistar rats divided into four groups: 0.9% saline (S), ointment base (B), green propolis ointment (G) and red propolis ointment (R). All animals were submitted to excisional lesions in the midian back region. The rats were treated daily for 15 days. During this period we observed weight, body temperature and diameters of the wounds. For histological analysis, samples were collected from wounds. At the end of the experiment we performed blood collection and removal of the kidney and liver for biochemical and histological analyzes. RESULTS: The levels of total flavonoids of green (4.50%) and red (5.92%) propolis were high (> 2%), but, while the latter showed a content larger than the former, the evolution of green propolis was better in the repair of wounds, both macroscopically and histologically. There were no nephrotoxicity or hepatotoxicity, a result confirmed by biochemical tests (ALT and albumin). Propolis influenced the reduction of total cholesterol, triglycerides and glucose. CONCLUSION: There was no correlation between total flavonoid contents and the healing action of propolis. This reveals the need for elucidation of the flavonoids found in each class of propolis to unravel which one(s) would be important for the healing process.