ABSTRACT Introduction: Chylothorax after thoracic surgery is a severe complication with high morbidity and mortality rate of 0.10 (95% confidence interval [CI] 0.06 – 0.02). There is no agreement on whether nonoperative treatment or early reoperation should be the initial intervention. This systematic review and meta-analysis aimed to evaluate the outcomes of the conservative approach to treat chyle leakage after cardiothoracic surgeries. Methods: A systematic review was conducted in PubMed®, Embase, Cochrane Library Central, and LILACS (Biblioteca Virtual em Saúde) databases; a manual search of references was also done. The inclusion criteria were patients who underwent cardiothoracic surgery, patients who received any nonoperative treatment (e.g., total parenteral nutrition, low-fat diet, medium chain triglycerides), and studies that evaluated chylothorax resolution, length of hospital stay, postoperative complications, infection, morbidity, and mortality. Central Message Nonoperative treatment for chylothorax after cardiothoracic procedures has significant hospital stay, morbidity, mortality, and reoperation rates. Results: Twenty-two articles were selected. Pulmonary complications, infections, and arrhythmia were the most common complications after surgical procedures. The incidence of chylothorax in cardiothoracic surgery was 1.8% (95% CI 1.7 – 2%). The mean time of maintenance of the chest tube was 16.08 days (95% CI 12.54 – 19.63), and the length of hospital stay was 23.74 days (95% CI 16.08 – 31.42) in patients with chylothorax receiving nonoperative treatment. Among patients that received conservative treatment, the morbidity event was 0.40 (95% CI 0.23 – 0.59), and reoperation rate was 0.37 (95% CI 0.27 – 0.49). Mortality rate was 0.10 (95% CI 0.06 – 0.02). Conclusion: Nonoperative treatment for chylothorax after cardiothoracic procedures has significant hospital stay, morbidity, mortality, and reoperation rates.

RESUMO Objetivo: Avaliar mudanças na resposta imunológica (diminuição de citocinas pró-inflamatórias no sangue) e na microbiota fecal (principalmente Bacteroidetes e Firmicutes) após a administração de probióticos em crianças com doença celíaca que seguiam uma dieta livre de glúten. Fontes de dados: Foram utilizadas para esta revisão as bases de dados Medical Literature Analysis and Retrieval System Online (MEDLINE), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Springer e Scientific Electronic Library Online (SciELO), com os descritores “celiac disease AND probiotics”. No fim da busca, foram recuperados 168 artigos, dos quais quatro foram incluídos na síntese qualitativa final. Os critérios de inclusão foram ensaios clínicos randomizados e população pediátrica (1–19 anos) e os critérios de exclusão, intervenções que não fossem com probióticos, estudos com pacientes portadores de outras doenças associadas à doença celíaca, ou que não preenchessem critérios para o diagnóstico. Todos os estudos eleitos foram publicados até setembro de 2020, sem restrição de idioma, com pacientes recebendo cepas de Bifidobacterium breve ou B. longum e em uma dieta livre de glúten. Síntese dos dados: Os estudos demonstram que a administração de probióticos associada a uma dieta livre de glúten pode aproximar a microbiota fecal desses pacientes às condições típicas de um indivíduo saudável ao restaurar a abundância de algumas comunidades microbianas que caracterizam uma condição tipicamente fisiológica. Além disso, a administração de probióticos pode reduzir as citocinas pró-inflamatórias (principalmente TNF-alfa). Conclusões: Apesar da correlação positiva entre probióticos e microbiota fecal/marcadores sorológicos nos pacientes pediátricos portadores de doença celíaca, ressalta-se a necessidade de estudos multicêntricos futuros que abranjam um maior número de pacientes e maior tempo de acompanhamento.%

ABSTRACT Objective: To evaluate changes in peripheral immunological response (decrease in blood proinflammatory cytokines) and fecal microbiota (especially Bacteroidetes and Firmicutes) after administration of probiotics in children with celiac disease on a gluten-free diet. Data source: The databases MEDLINE, LILACS, Springer and SciELO were used for this review, with the descriptors “celiac disease AND probiotics”. At the end of the search, 168 articles were retrieved, four of which were included in the final qualitative synthesis, having as inclusion criteria randomized clinical trials and pediatric population (1–19 years) and, as exclusion criteria, interventions other than probiotics, studies with patients with other diseases associated with celiac disease, or patients who did not meet the diagnostic criteria. All elected studies were published until September 2020, without language restriction, with patients receiving strains of Bifidobacterium breve or B. longum and on a gluten-free diet. Data synthesis: The studies show that the administration of probiotics along with a gluten-free diet, can approximate the fecal microbiota of celiac patients to typical conditions of healthy individuals, by restoring the abundance of some microbial communities that characterize the typical physiological condition. In addition, the administration of probiotics can reduce serum proinflammatory cytokines (mainly TNF-alpha). Conclusions: Despite the positive correlation between probiotics and fecal microbiota/serological markers in pediatric patients with celiac disease, we emphasize the need for future multicentric studies that should include a larger number of patients and a longer follow up period.%

Abstract Because it promotes the lightening of pigment spots, tyrosinase inhibition is one of the mechanisms of depigmenting cosmetic products. Considering the adverse effects produced by synthetic depigmenting actives, the search for new therapeutic options is desirable, and plant extracts are possible candidates for hyperpigmentation treatment. Glycolic extracts of Cecropia pachystachya Trécul are, therefore, the focus of this study. Its chemical characterization, antioxidant activity, tyrosinase inhibition, and cell viability were evaluated. Glycolic extracts were obtained by macerating the leaves of C. pachystachya in grain alcohol and glycerin or propylene glycol. Both had a similar chemical constitution, the glycerin being more efficient in concentrating phenolic compounds and flavonoids. Analyses by UHPLC-MS detected quinic acid, chlorogenic acid isomers, proanthocyanidin dimers type B and C, catechin/epicatechin, orientin/isoorientin, isoorientin 2”-O-xyloside, vitexin/isovitexin, and rutin. 5-O-caffeoylquinic acid was then quantified was then quantified, with predominance in the extract produced with propylene glycol. These extracts showed a high antioxidant capacity by the method of DPPH, β-carotene, and nitric oxide. As for depigmenting activity, both extracts were able to inhibit tyrosinase. Cell viability assay also revealed that the extracts could safely be used in concentrations of ≤ 125 µg/mL. Thus, this study demonstrated for the first time that the glycolic extracts of C. pachystachya have promising chemical and biological characteristics for the development of a multifunctional cosmetic with antioxidant and tyrosinase-inhibition activities.

RESUMO. Zolpidem é um dos agentes hipnóticos (não benzodiazepínicos) mais prescritos para o manejo dos distúrbios do sono. Recentemente, observou-se um aumento na demanda por esse medicamento, principalmente pela população idosa. Objetivo: Este estudo visa analisar o efeito agudo do zolpidem em relação às alterações cognitivas e de equilíbrio na população idosa. Métodos: Uma busca em quatro bases de informação científica virtual foi feita por dois pesquisadores independentes e incluiu ensaios clínicos randomizados. Os estudos avaliaram o uso de zolpidem em pacientes idosos. Alterações cognitivas e de equilíbrio foram analisadas. Resultados: Seis artigos foram incluídos. A média de idade entre os estudos foi de 69 anos. As seguintes posologias foram analisadas: 5; 6,25; 10; e 12,5 mg. Em relação às alterações cognitivas, comparando-se zolpidem com placebo, não há diferença estatisticamente significativa entre os grupos. Entretanto, no desfecho alterações de equilíbrio, há diferença estatisticamente significativa entre intervenção e comparação, a favor do placebo. Conclusões: Zolpidem, mesmo em doses usuais (5 e 10 mg), mostrou aumentar o risco para alterações de equilíbrio, entretanto, isso não ocorre em relação às alterações cognitivas.

ABSTRACT. Zolpidem is one of the most widely prescribed hypnotic (non-benzodiazepine) agents for sleep disorder. Recently, an increase in the demand for this drug has been observed, mainly in the elderly population. Objective: This study aims to analyze the acute effect of zolpidem on cognitive and balance dysfunctions in the elderly population. Methods: A study was conducted by two independent researchers in four virtual scientific information bases and included randomized controlled trials. The studies evaluated elderly patients using zolpidem. Cognitive and balance dysfunctions were analyzed. Results: Six articles were included. The mean age of the participants in the studies was 69 years. The following zolpidem dosages were evaluated: 5, 6.25, 10, and 12.5 mg. Comparing zolpidem and placebo, relating to the cognitive dysfunctions, there is no statistically significant difference between the groups. However, in relation to balance dysfunctions, there is a statistically significant difference between the intervention and the comparison, favoring placebo. Conclusions: Zolpidem, even in usual doses (5 mg and 10 mg), has shown to increase the risk for balance dysfunctions. However, this does not occur in relation to cognitive changes.

Hidroximetilnitrofural (NFOH) é um novo composto que possui atividade leishmanicida e tripanomicida potencial. Um método apropriado foi desenvolvido e validado para a determinação de NFOH em nanopartículas de poli(n-butil cianoacrilato) (PBCA). A separação cromatográfica foi obtida usando uma coluna C18 (5 µm de tamanho de partícula, 4,6 mm de diâmetro e 150 mm de comprimento), mantida a 25 °C, fase móvel composta de água e acetonitrila 80:20 (v/v), fluxo de 1,2 mL min- 1 e detecção por UV a 265 nm. Investigaram-se os seguintes parâmetros de validação: seletividade, linearidade, exatidão, precisão e robustez (mudanças na temperatura de coluna, proporção da fase móvel e fluxo). O método mostrou-se específico, o pico de NFOH não apresentou interferência dos picos provenientes dos excipientes das nanopartículas e separado do principal produto de degradação (nitrofural). A linearidade foi obtida na faixa de 0,94-13,11 μg mL- 1 (r2=0,999). O método mostrou exatidão (recuperação de 100,7%, DPR de 0,4 %) e precisão (intra-dia e inter-dia, 9,98-9,99 μg mL- 1 e DPR 0,3% a 0,5%, respectivamente). A robustez provou que o método pode resistir às mudanças propostas. Aplicação do método otimizado revelou eficiência de encapsulação de 64,4% (n=3). Portanto, o método foi desenvolvido e validado com sucesso para a determinação da eficiência de encapsulação de nanopartículas de NFOH-PBCA.

Hydroxymethylnitrofurazone (NFOH) is a new compound with potential leishmanicidal and trypanocidal activity. Despite its effectiveness, the formulators have to overcome its poor aqueous solubility. Recently, polymeric nano-scale drug delivery systems have proposed for the treatment of neglected diseases. As several studies have confirmed the advantages of such formulations, and this approach provides new analytical challenges, including the need to detect trace amounts of the drug. A suitable method was developed and validated for NFOH determination bound to poly (n-butylcyanoacrylate) (PBCA) nanoparticles. The chromatographic separation was achieved using a C18 column maintained at 25 ºC and an isocratic mobile phase consisting of water and acetonitrile: 80:20 (v/v) at a flow rate of 1.2 mL min-1 and UV-detection at 265 nm. Investigated validation parameters included selectivity, linearity, accuracy, precision and robustness (changes in column temperature, mobile phase composition and flow). The method was specific, the peak of NFOH had no interference with any nanoparticle excipients and no co-elution with main degradation product (nitrofurazone). Linearity was over the range of 0.94 13.11 μg mL-1 (r2=0.999). The method was accurate and precise, recovery of 100.7%, RSD of 0.4%; intra-day and inter-day RSD range 9.98-9.99 μg mL-1 and 0.3% to 0.5%, respectively. Robustness confirmed that method could resist the applied changes. Application of the optimized method revealed an encapsulation efficiency of 64.4% (n=3). Therefore, the method was successfully developed and validated for the determination of the encapsulation efficiency of NFOH-PBCA nanoparticles.

RESUMOO flurbiprofeno, potente anti-inflamatório não esteroidal, é amplamente utilizado no alívio da dor de pacientes que possuem doenças reumáticas, enxaqueca, dores de garganta e dismenorreia primária. Entretanto, apresenta muitos efeitos gastrointestinais indesejáveis quando administrado por via oral como hemorragia gástrica e úlcera péptica. Esses efeitos foram responsáveis por baixa adesão entre os pacientes, o que resulta no comprometimento do tratamento. As propriedades físico-químicas do flurbiprofeno fazem dele um candidato promissor para a administração transdérmica, que pode eliminar os inconvenientes causados durante a administração oral. Neste sentido, provou-se que as microemulsões aumentam a absorção cutânea de fármacos lipofílicos quando comparadas aos sistemas de liberação convencionais. O objetivo desse estudo foi desenvolver e caracterizar géis bases contendo microemulsões de flurbiprofeno. Diferentes géis bases contendo microemulsão e solução hidroalcoólica de flurbiprofeno foram desenvolvidos e comparados. Os estudos in vitroindicaram que os géis contendo microemulsão apresentaram velocidade de permeação superior ao géis contendo as soluções hidroalcoólicas. Adicionalmente, a formulação de Carbopol -I (microemulsão) apresentou maior capacidade de inibição da inflamação em relação às outras bases. Além disso, o estudo demonstrou que formulação de Carbopol -I (microemulsão) não ocasionou irritações cutâneas. Desta forma, o gel base de Carbopol -I contendo microemulsão de flurbiprofeno apresentou características físico-químicas, desempenho in vitro e in vivo adequados para o desenvolvimento de formulação alternativas de liberação transdérmica.

ABSTRACTFlurbiprofen, a potent nonsteroidal anti-inflammatory drug, is widely used for relief of pain in patients suffering from rheumatic diseases, migraine, sore throat and primary dysmenorrheal. However, this drug has many gastrointestinal side effects produced by its oral administration, such as gastric bleeding and peptic ulcer. These effects were responsible for non-compliance among patients, which ultimately results in treatment failure. The physicochemical properties of flurbiprofen, make it a suitable candidate for transdermal drug delivery, which can overcome the drawbacks of oral administration. In this sense, microemulsions have been proved to increase the cutaneous absorption of lipophilic drugs when compared to conventional drug delivery systems. The purpose of this study was to formulate and characterize gel based microemulsions, for topical delivery of flurbiprofen. Different gel bases, containing microemulsion and hydro-alcoholic solution of flurbiprofen, were developed and compared. In vitro study showed that gels containing microemulsion had a higher permeation rate than those containing hydro-alcoholic solutions. Additionally, formulation of Carbopol-I (microemulsion) showed higher percent of inhibition of inflammation than others bases. Further, skin irritation study demonstrated that Carbopol-I was none irritating. Flurbiprofen microemulsion incorporated on Carbopol-I showed physicochemical, in vitro and in vivo characteristics suitable for the development of alternative transdermal delivery formulation.

A degeneração macular relacionada à idade (DMRI) é uma doença ocular inflamatória tratada principalmente por injeção intravítrea de bevacizumabe (Avastin®) ou de ranibizumabe (Lucentis®). Entre os medicamentos citados, apenas o ranibizumabe tem indicação terapêutica específica para uso oftálmico. Considerando essa realidade, o uso off-label na terapia oftálmica parece constituir regra quando deveria ser exceção. Ademais, a apresentação do bevacizumabe consiste em frascos de múltipla-dose, embora esse medicamento não contenha conservante em sua fórmula. A presente revisão da literatura avaliou os riscos ao paciente relativos ao uso indicado off-label e de frascos de múltipla-dose no tratamento de DMRI. Nesse sentido, avaliou-se a proposta relativa à Consulta Pública Brasileira nº 10, de 12 de setembro de 2012, que propõe o Protocolo Clínico e Diretrizes Terapêuticas para o tratamento de DMRI. O levantamento sistemático de trabalhos científicos e de informações relevantes de banco de dados eletrônicos permitiu concluir que a indicação off-label do bevacizumabe acarreta riscos maiores ao paciente, quando comparado ao produto com indicação terapêutica específica para o tratamento de DMRI (ranibizumabe), especialmente quanto ao aumento significativo de eventos adversos. Evidenciaram-se, também, os riscos ao paciente relativos ao uso de frascos de múltipla-dose, quanto à estabilidade microbiológica e à precisão da dose.

Age-related macular degeneration (AMD) is an ocular inflammatory diseases treated mainly by means of a bevacizumab (Avastin®) or ranibizumab (Lucentis®) intravitreal injection. Among these drugs, only ranibizumab has a specific therapeutic indication for AMD. Considering that, the off-label use on ophthalmic therapy seems to become a rule when it should be an exception. Furthermore, bevacizumab presentation consists of multi-dose vials although it does not contain preservatives in its formula. The current literature review aimed at assessing the risks for the patient related to the use of off-label indication and multi-dose vials on AMD treatment. Considering this, the proposal related to the Brazilian Public Consultation no.10, dated September 12, 2012, which proposes the Clinical Protocol and Therapeutic Guidelines for AMD treatment, was evaluated. This systematic review allowed to conclude that the bevacizumab off-label indication results in increased risks for the patient when compared to the product with specific therapeutic indication for AMD treatment (ranibizumab), especially referring to the significant raise in the adverse events. The risks for the patient related to the multi-dose vial use, referring to the microbiological stability and dose precision, were also made clear.

A derivative spectrophotometric method was validated for quantification of acyclovir in poly (n-butylcyanoacrylate) (PBCA) nanoparticles. Specificity, linearity, precision, accuracy, recovery, detection (LOD) and quantification (LOQ) limits were established for method validation. First-derivative at 295.2 nm eliminated interferences from nanoparticle ingredients and presented linearity for acyclovir concentrations ranging from 1.25 to 40.0 µg/mL (r = 0.9999). Precision and accuracy data demonstrated good reproducibility. Recovery ranged from 99.3 to 101.2. LOD was 0.08 µg/mL and LOQ, 0.25 µg/mL. Thus, the proposed method proved to be easy, low cost, and accurate, and therefore, an useful alternative to quantify acyclovir in nanoparticles.

In addition to the usual advantage of an ice calorimeter of being able to measure slow heat changes, the instrument described here is extremely simple to construct and operate. Specific heat of aluminum, copper, lead and tin metals were determined using the ice calorimeter made with easily accessible materials. The values obtained from specific heat are near to those found in the literature and were 0.204; 0.030; 0.086; 0.046 cal/g °C with an error of theoretical values of 6.84; 1,64; 5.49 and 8.00% for aluminum, copper, lead and tin, respectively.