The Clinical and Economic Impact of Delayed Reperfusion Therapy: Real-World Evidence. / O Impacto Clínico e Econômico do Atraso na Terapia de Reperfusão: Evidências do Mundo Real.

BACKGROUND: Early reperfusion therapy is acknowledged as the most effective approach for reducing case fatality rates in patients with ST-segment elevation myocardial infarction (STEMI). OBJECTIVE: Estimate the clinical and economic consequences of delaying reperfusion in patients with STEMI. METHODS: This retrospective cohort study evaluated mortality rates and the total expenses incurred by delaying reperfusion therapy among 2622 individuals with STEMI. Costs of in-hospital care and lost productivity due to death or disability were estimated from the perspective of the Brazilian Unified Health System indexed in international dollars (Int$) adjusted by purchase power parity. A p < 0.05 was considered statistically significant. RESULTS: Each additional hour of delay in reperfusion therapy was associated with a 6.2% increase (95% CI: 0.3% to 11.8%, p = 0.032) in the risk of in-hospital mortality. The overall expenses were 45% higher among individuals who received treatment after 9 hours compared to those who were treated within the first 3 hours, primarily driven by in-hospital costs (p = 0.005). A multivariate linear regression model indicated that for every 3-hour delay in thrombolysis, there was an increase in in-hospital costs of Int$497 ± 286 (p = 0.003). CONCLUSIONS: The findings of our study offer further evidence that emphasizes the crucial role of prompt reperfusion therapy in saving lives and preserving public health resources. These results underscore the urgent need for implementing a network to manage STEMI cases.

FUNDAMENTO: A terapia de reperfusão precoce é reconhecida como a abordagem mais eficaz para reduzir as taxas de letalidade de casos em pacientes com infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST). OBJETIVO: Estimar as consequências clínicas e econômicas do atraso da reperfusão em pacientes com IAMCSST. MÉTODOS: O presente estudo de coorte retrospectivo avaliou as taxas de mortalidade e as despesas totais decorrentes do atraso na terapia de reperfusão em 2.622 indivíduos com IAMCSST. Os custos de cuidados hospitalares e perda de produtividade por morte ou incapacidade foram estimados sob a perspectiva do Sistema Único de Saúde indexado em dólares internacionais (Int$) ajustados pela paridade do poder de compra. Foi considerado estatisticamente significativo p < 0,05. RESULTADOS: Cada hora adicional de atraso na terapia de reperfusão foi associada a um aumento de 6,2% (intervalo de confiança de 95%: 0,3% a 11,8%, p = 0,032) no risco de mortalidade hospitalar. As despesas gerais foram 45% maiores entre os indivíduos que receberam tratamento após 9 horas em comparação com aqueles que foram tratados nas primeiras 3 horas, impulsionados principalmente pelos custos hospitalares (p = 0,005). Um modelo de regressão linear multivariada indicou que para cada 3 horas de atraso na trombólise, houve um aumento nos custos hospitalares de Int$ 497 ± 286 (p = 0,003). CONCLUSÕES: Os achados do nosso estudo oferecem mais evidências que enfatizam o papel crucial da terapia de reperfusão imediata no salvamento de vidas e na preservação dos recursos de saúde pública. Estes resultados enfatizam a necessidade urgente de implementação de uma rede para gerir casos de IAMCSST.

Comparative effectiveness and cost-effectiveness of cardioprotective glucose-lowering therapies for type 2 diabetes in Brazil: a Bayesian network model.

BACKGROUND: The escalating prevalence of type 2 diabetes (T2DM) poses an unparalleled economic catastrophe to developing countries. Cardiovascular diseases remain the primary source of costs among individuals with T2DM, incurring expenses for medications, hospitalizations, and surgical interventions. Compelling evidence suggests that the risk of cardiovascular outcomes can be reduced by three classes of glucose-lowering therapies (GLT), including SGLT2i, GLP-1A, and pioglitazone. However, an evidence-based and cost-effective protocol is still unavailable for many countries. The objective of the current study is to compare the effectiveness and cost-effectiveness of GLT in individuals with T2DM in Brazil. METHODS: We employed Bayesian Networks to calculate the incremental cost-effectiveness ratios (ICER), expressed in international dollars (Int$) per disease-adjusted life years [DALYs] averted. To determine the effectiveness of GLT, we conducted a systematic review with network meta-analysis (NMA) to provide insights for our model. Additionally, we obtained cardiovascular outcome incidence data from two real-world cohorts comprising 851 and 1337 patients in primary and secondary prevention, respectively. Our cost analysis took into account the perspective of the Brazilian public health system, and all values were converted to Int$. RESULTS: In the NMA, SGLT2i [HR: 0.81 (95% CI 0.69-0.96)], GLP-1A [HR: 0.79 (95% CI 0.67-0.94)], and pioglitazone [HR: 0.73 (95% CI 0.59-0.91)] demonstrated reduced relative risks of non-fatal cardiovascular events. In the context of primary prevention, pioglitazone yielded 0.2339 DALYs averted, with an ICER of Int$7,082 (95% CI 4,521-10,770) per DALY averted when compared to standard care. SGLT2i and GLP-1A also increased effectiveness, resulting in 0.261 and 0.259 DALYs averted, respectively, but with higher ICERs of Int$12,061 (95% CI: 7,227-18,121) and Int$29,119 (95% CI: 23,811-35,367) per DALY averted. In the secondary prevention scenario, all three classes of treatments were deemed cost-effective at a maximum willingness-to-pay threshold of Int$26,700. Notably, pioglitazone consistently exhibited the highest probability of being cost-effective in both scenarios. CONCLUSIONS: In Brazil, pioglitazone presented a higher probability of being cost-effective both in primary and secondary prevention, followed by SGLT2i and GLP-1A. Our findings support the use of cost-effectiveness models to build optimized and hierarchical therapeutic strategy in the management of T2DM. TRIAL REGISTRATION: CRD42020194415.

The framing of time-dependent machine learning models improves risk estimation among young individuals with acute coronary syndromes.

Acute coronary syndrome (ACS) is a common cause of death in individuals older than 55 years. Although younger individuals are less frequently seen with ACS, this clinical event has increasing incidence trends, shows high recurrence rates and triggers considerable economic burden. Young individuals with ACS (yACS) are usually underrepresented and show idiosyncratic epidemiologic features compared to older subjects. These differences may justify why available risk prediction models usually penalize yACS with higher false positive rates compared to older subjects. We hypothesized that exploring temporal framing structures such as prediction time, observation windows and subgroup-specific prediction, could improve time-dependent prediction metrics. Among individuals who have experienced ACS (nglobal_cohort = 6341 and nyACS = 2242), the predictive accuracy for adverse clinical events was optimized by using specific rules for yACS and splitting short-term and long-term prediction windows, leading to the detection of 80% of events, compared to 69% by using a rule designed for the global cohort.

Clinical and economic impact of coronary artery bypass graft and percutaneous coronary intervention in young individuals with acute coronary syndromes and multivessel disease: A real-world comparison in a middle-income country.

Background: In recent decades, the world watched a dramatic increase in the incidence of acute coronary syndromes (ACS) among young individuals (≤55 years-old) and a relative decrease in the elderly. The management of ACS in young patients with multivessel disease still needs to be elucidated, as these individuals maintain a long life expectancy. Research Question: To compare clinical outcomes and care costs in individuals with premature ACS and multivessel disease undergoing coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI). Methods and Results: Participants included all individuals ≤55 years-old admitted with ACS to public hospitals in Brasília (Brazil) between 2013 and 2015 and who underwent cardiac catheterization with SYNTAX score ≥23 or Duke category 6. Outcomes were adjudicated with death certificates and data from medical records. The primary outcome was the occurrence of major adverse cardiovascular events (MACE), defined as death due to cardiovascular causes, recurrent hospitalizations due to cardiovascular ischemic events, and incident heart failure New York Heart Association III-IV. As secondary outcome we assessed indirect and direct costs by evaluating the cost of lost productivity (in international dollars (Int$) per year) due to illness and death, outpatient costs and costs with new hospitalizations. Multivariate and principal components (PC) adjusted analyzes were performed. Results: Among 1,088 subjects (111 CABG and 977 PCI) followed for 6.2 years (IQR: 1.1), 304 primary events were observed. MACE was observed in 20.7% of the CABG group and 28.8% of the PCI group (p = 0.037). In multivariate analyses, PCI was associated with a hazard ratio (HR) = 1.227 (95% CI: 1.004-1.499; p = 0.0457) for MACE, and in PC-adjusted HR = 1.268 (95% CI: 1.048-1.548; p = 0.0271) compared with CABG. Despite direct costs were equivalent, the cost due to the loss of labor productivity was higher in the PCI group (Int$ 4,511 (IQR: 18,062)/year vs Int$ 3,578 (IQR: 13,198)/year; p = 0.049], compared with CABG. Conclusions: Among young individuals with ACS and multivessel disease, surgical strategy was associated with a lower occurrence of MACE and lower indirect costs in the long-term.

Glucose-Lowering and the Risk of Cardiovascular Events With Antidiabetic Therapies: A Systematic Review and Additive-Effects Network Meta-Analysis.

Aim: To assess the impact of the HbA1c levels achieved with antidiabetic therapies (ADTs) on the risk of MACE. Methods: A systematic search was performed in PubMed, Cochrane, and ClinicalTrials. gov for RCTs published up to March 2022 reporting the occurrence of MACE and all-cause mortality in individuals with T2DM treated with all marketed ADTs, including a sample size ≥100 individuals in each study arm and follow-up ≥24 weeks. A systematic review and additive-effects network meta-analysis with random effects and a multivariate meta-regression were utilized to assess the impact of achieved HbA1c on incident MACE. Results: We included 126 RCTs with 143 treatment arms, 270,874 individuals, and 740,295 individuals-years who were randomized to an active treatment vs. control group. Among all ADTs, only therapy with SGLT2i, GLP1-RA, or pioglitazone similarly reduced the risk of MACE compared to placebo. The achievement of HbA1c ≤ 7.0% in RCTs with the 3 drug classes in the active arm was associated with an adjusted HR of 0.91 (95% CI 0.80, 0.97; p = 0.017) compared with HbA1c>7.0%, without affecting all-cause mortality. These results, however, were not maintained among all ADTs. Conclusions: Achieving lower glucose levels with SGLT2i, GLP1-RA, or pioglitazone is linearly associated with a reduced risk of MACEs, without affecting all-cause mortality. Systematic Review Registration: www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020213127, identifier: CRD42020213127.

Glucose-lowering Drugs and Hospitalization for Heart Failure: A Systematic Review and Additive-effects Network Meta-analysis With More Than 500 000 Patient-years.

BACKGROUND: Sodium glucose co-transporter 2 inhibitors (SGLT2is) prevent hospitalization resulting from heart failure (HHF). However, patients with type 2 diabetes mellitus use multiple antihyperglycemic drugs to achieve glycosylated hemoglobin (HbA1c) targets. In these drug combinations, the risk of HHF is unpredictable and so is the parallel effect of glucose-lowering. PURPOSE: To examine the impact of antihyperglycemic drugs and their association on HHF. DATA SOURCES: Forty randomized controlled trials (RCTs) reporting HHF. STUDY SELECTION: Published RCTs were the data source. DATA EXTRACTION: Incidence rates of HHF. DATA SYNTHESIS: Random additive-effects network meta-analysis showed that metformin (P = 0.55), sulfonylureas (P = 0.51), glucagon-like peptide-1 receptor-agonist (P = 0.16), and dipeptidyl peptidase 4 inhibitors (DPP4is; P = 0.54) were neutral on the risk of HHF. SGLT2is and SGLT2is + DPP4is reduced the risk of HHF with a hazard ratio (HR) of 0.68 (95% CI, 0.60-0.76; P < 0.0001) and 0.70 (95% CI, 0.60-0.81; P < 0.0001), respectively. Increased risk of HHF was associated with thiazolidinediones (TZDs) as monotherapy or in combination with DPP4is (HR: 1.45; 95% CI, 1.18-1.78; P = 0.0004) and 1.49 (95% CI, 1.18-1.88; P = 0.0008), respectively. Regardless of the therapy, a 1% reduction in HbA1c reduced the risk of HHF by 31.3% (95% CI, 9-48; P = 0.009). LIMITATIONS: There are no data to verify drug combinations available for clinical use and to discriminate the effect of drugs within each of the therapeutic classes. CONCLUSIONS: The risk of HHF is reduced by SGLT2is as monotherapy or in combination with DPP4is and increased by TZDs as monotherapy or in combination. Glucose-lowering provides an additive effect of reducing HHF.

A novel GPIHBP1 mutation related to familial chylomicronemia syndrome: A series of cases.

BACKGROUND AND AIMS: GPIHBP1 is an accessory protein of lipoprotein lipase (LPL) essential for its functioning. Mutations in the GPIHBP1 gene cause a deficit in the action of LPL, leading to severe hypertriglyceridemia and increased risk for acute pancreatitis. METHODS: We describe twelve patients (nine women) with a novel homozygous mutation in intron 2 of the GPIHBP1 gene. RESULTS: All patients were from the Northeastern region of Brazil and presented the same homozygous variant located in a highly conserved 3' splicing acceptor site of the GPIHBP1 gene. This new variant was named c.182-1G > T, according to HGVS recommendations. We verified this new GPIHBP1 variant's effect by using the Human Splicing Finder (HSF) tool. This mutation changes the GPIHBP1 pre-mRNA processing and possibly causes the skipping of the exon 3 of the GPIHBP1 gene, affecting almost 50% of the cysteine-rich Lys6 GPIHBP1 domain. Patients presented with severe hypertriglyceridemia (2351 mg/dl [885-20600]) and low HDL (18 mg/dl [5-41). Four patients (33%) had a previous history of acute pancreatitis. CONCLUSIONS: We describe a novel GPIHBP1 pathogenic intronic mutation of patients from the Northeast region of Brazil, suggesting the occurrence of a founder effect.

Synthesis and biological effects of small molecule enhancers for improved recombinant protein production in plant cell cultures.

Histone deacetylases are involved in chromatin remodelling and thus play a vital role in the epigenetic regulation of gene expression. HDAC inhibitors alter the acetylation status of histone and non-histone proteins to regulate various cellular events such as transcription. Novel HDAC inhibitors were designed and synthesised to promote higher levels of recombinant protein production in tobacco cell cultures. The effect of these chemical enhancers on the epigenetic profiles in plant cells has been evaluated by molecular docking, in vitro and in vivo studies. The addition of these novel enhancers led to an increase in histone H3 acetylation levels that promoted an increase in the accumulation levels of the recombinant protein in cell culture. These results can pave the way for the application of these enhancers to improve the production of high value products in plant cell based systems.

Anthelmintic activity of plant aqueous extracts against Panagrellus redivivus in vitro / Atividade anti-helmíntica de extratos aquosos de plantas contra Panagrellus redivivis in vitro

Control of phytonematodes is very hard and requires a combination of techniques to succeed. Alternative control through plant extracts may result in the discovery of nematicide substances. Research aimed at evaluating the effect of 33 plants submitted to aqueous extraction against Panagrellus redivivus in vitro. Concentrations were prepared at 1.25, 2.5, 5, 10, and 20%. Monitoring happened at 0, 6, 12, 24 and 30 hours after preparation. Counting considered dead nematodes subtracted from alive ones. Juveniles were also counted, and extract efficiency was expressed in percentage of control or stimuli. Data were submitted to variance analysis. Significant results got with the Scott-Knott test (5%), and multiple linear regression analysis. Extracts were observed acting as controllers, but also as stimulators to nematode reproduction. The best controlling performance was set by Carica papaya (-66% at 20%; -33.7% at 10%), Euphorbia milii (-37% at 20%), Psychotria carthagenensis (-25.5% at 2.5%), Clusia variegate (-22% at 20%), and Zamioculcas zamiifolia (-21.5% at 20%). Stimulator extracts were Mentha villosa at 10% (+148%) and 2.5% (+131.5%), followed by Aloe vera (+123% at 5%), Schinus molle (+112.5% at 10%), Schefflera arboricola (+93.5% at 5%), C. variegate (+89% at 5%), and S. molle (+88% at 5%). Some extracts kept population stable throughout the experiment, presenting lower control indexes. Besides an additive effect, there was an individual influence of concentration or time on control.(AU)

O controle de fitonematoides é muito difícil e requer uma combinação de técnicas para ter sucesso. O controle alternativo via extrato vegetal pode resultar na descoberta de substâncias nematicidas. Esta pesquisa objetivou avaliar o efeito de 33 plantas submetidas à extração aquosa contra Panagrellus redivivus in vitro. As concentrações foram preparadas a 1,25; 2,5; 5; 10; e 20%. O monitoramento ocorreu em 0, 6, 12, 24 e 30 horas após a preparação. Para a contagem, foram considerados nematoides mortos subtraídos dos vivos. Nematoides jovens também foram contados, e a eficiência dos extratos foi expressa em porcentagem de controle ou de estímulo. Os dados foram submetidos à análise de variância. Resultados significativos foram analisados pelos testes de Scott-Knott (5%) e análise de regressão múltipla. Foram observados extratos agindo como controladores, bem como estimuladores da reprodução de nematoides. A melhor performance de controle foi obtida por Carica papaya (-66% a 20%; -33,7% a 10%), Euphorbia milii (-37% a 20%), Psychotria carthagenensis (-25,5% a 2,5%), Clusia variegate (-22 a 20%) e Zamioculcas zamiifolia (-21,5% a 20%). Os extratos estimuladores foram Mentha villosa a 10% (+148%) e 2,5% (+131,5%), seguido por Aloe vera (+123% a 5%), Schinus molle (+112.5% a 10%), Schefflera arboricola (+93.5% a 5%), C. variegate (+89% a 5%) e S. molle (+88% a 5%). Alguns extratos mantiveram a população estável durante todo o experimento, apresentando menores índices de controle. Além do efeito aditivo houve uma influência individual da concentração e do tempo no controle.(AU)

Perfil dos egressos de Serviço Social do Programa de Residência Multiprofissional em Oncologia do INCA / Profile of the graduates in Social Work from Multidisciplinary Residency Program in Oncology at INCA / El perfil de los graduados de Trabajo Social del Programa de Residencia Multidisciplinar en Oncología del INCA

Esse artigo tem o objetivo de identificar e analisar os perfis acadêmico e profissional dos assistentes sociais egressos no Programa de Residência Multiprofissional em Oncologia do Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA). Trata-se de pesquisa de cunho descritivo-exploratório por meio de aplicação de questionário semi-estruturado para os 12 egressos do Serviço Social matriculados entre 2010 e 2013. Foram estabelecidas três categorias analíticas (Perfil acadêmico; Perfil profissional; Contribuição da residência para inserção profissional) discutidas à luz do referencial crítico-dialético. Os resultados demonstram que o perfil dos egressos coaduna as diretrizes da política de formação em saúde. Nessa perspectiva, a residência se apresenta como um importante espaço de transformação e efetivação do SUS.

This article is intended to identify and analyze the academic and professional profiles of graduate social workers in the Multidisciplinary Residency Program in Oncology at the National Cancer Institute José Alencar Gomes da Silva (INCA). This is a descriptive and exploratory research by applying a semi-structured questionnaire for the 12 graduates of Social Work registered between 2010 and 2013. Three analytical categories were established (academic profile, professional profile; contribution of the residence to the professional insertion) discussed at the light of dialectical historical materialism. The results show that the profile of the graduates meets as guidelines of the health education policy. In this perspective, the residence presents itself as an important space for transformation and realization of SUS.

Este artículo tiene como objetivo identificar y analizar los perfiles académicos y profesionales de los graduados de los trabajadores sociales en el Programa de Residencia Multidisciplinar en Oncología del Instituto Nacional del Cáncer José Alencar Gomes da Silva (INCA). Se trata de una investigación descriptiva y exploratoria mediante la aplicación de un cuestionario semi-estructurado para los 12 graduados de Servicio Social registrados entre 2010 y 2013 se establecieron tres categorías de análisis (perfil académico, perfil profesional, la contribución residencia para la inserción profesional) examinará a la luz del marco crítico-dialéctico. Los resultados muestran que el perfil de los graduados son coherentes con la política de educación para la salud. En esta perspectiva, la residencia se presenta como un espacio importante para la transformación y la realización del SUS.

Avaliação da influência de alterações cardíacas na ultrassonografia vascular periférica de idosos / Assessment of cardiac influence on peripheral vascular Doppler in the elderly

Resumo Contexto As cardiopatias podem causar alterações no formato das ondas da ultrassonografia vascular (UV) em vasos periféricos. Essas alterações, tipicamente bilaterais e sistêmicas, são pouco conhecidas e estudadas. Objetivo Avaliar as ondas periféricas da UV de pacientes idosos para identificar alterações decorrentes de cardiopatias. Métodos Foram estudados 183 pacientes idosos submetidos a UV periférica no ano de 2014. Resultados Foram avaliados 102 mulheres (55,7%) e 81 homens (44,3%) com idade entre 60 e 91 anos (média de 70,4±7,2 anos). Encontraram-se alterações pela UV em 84 pacientes (45,9%). Foram identificadas 138 alterações de oito dos 13 tipos descritos na literatura: arritmia, onda bisferiens de pico sistólico, baixa velocidade de pico sistólico, pulsatilidade em veias femorais, bradicardia, taquicardia, onda de pulso parvus tardus e onda de pulso alternans. Houve baixa concordância entre a presença e a não presença de alterações na UV e na avaliação cardiológica. Na análise específica das alterações, os exames tiveram uma concordância variável, que foi boa para o achado de taquicardia, moderada para arritmia e baixa para bradicardia. Não houve concordância entre a UV e os exames cardiológicos para as demais alterações. Conclusões É possível identificar determinadas alterações cardíacas em idosos por meio da análise do formato das ondas periféricas da UV. É importante reconhecer e relatar a presença dessas alterações, pela possibilidade de alertar para um diagnóstico ainda não identificado nesses pacientes. Entretanto, mais estudos são necessários para que seja definida a importância das alterações no formato das ondas Doppler periféricas no reconhecimento de cardiopatias.

Abstract Background Heart diseases can cause changes to vascular ultrasonography (VUS) waveforms in peripheral vessels. These changes are typically bilateral and systemic, they have been little studied, and little is known about them. Objective To assess peripheral VUS waveforms in elderly patients in order to identify changes caused by heart diseases. Methods During 2014, a total of 183 elderly patients were examined with peripheral VUS and the results were analyzed. Results The sample comprised 102 women (55.7%) and 81 men (44.3%) with ages ranging from 60 to 91 years (mean of 70.4±7.2 years). Abnormalities were identified in VUS waveforms in 84 patients (45.9%). A total of 138 abnormalities were identified and classified into eight of the 13 categories described in the literature, as follows: arrhythmia, systolic pulsus bisferiens, low peak systolic velocity, pulsatile flow in femoral veins, bradycardia, tachycardia, pulsus tardus et parvus and pulsus alternans. There was low agreement between presence/absence of VUS abnormalities and cardiological assessments. Analysis of specific abnormalities revealed variable levels of agreement between VUS and cardiological assessments, ranging from good for tachycardia, moderate for arrhythmia, to low for bradycardia. There was no agreement between VUS and cardiological examinations for the remaining categories of abnormalities. Conclusions Certain cardiac abnormalities can be identified in elderly patients by analysis of peripheral VUS waveforms. It is important to recognize and report the presence of these abnormalities because there is a possibility that they may serve to signal hitherto unidentified diagnoses in these patients. However, further studies are needed to determine the importance of changes to peripheral Doppler waveforms to recognition of heart diseases.

Employing photoacoustic spectroscopy in the evaluation of the skin permeation profile of emulsion containing antioxidant phenolic-rich extract of Melochia arenosa.

CONTEXT: Oxidative stress is an important factor modulating skin alterations. Melochia arenosa Benth. (Malvaceae) is a Brazilian plant with antimicrobial activity and antioxidant potential. OBJECTIVE: The objective of this study is to develop a topical formulation containing antioxidant phenolic-rich extract of M. arenosa and to evaluate its skin permeation profile. MATERIALS AND METHODS: Response surface methodology was used to maximize the total phenolic (TP) content of the extract and its antioxidant activity was evaluated by 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and respiratory burst methods. An emulsion containing 1% optimized extract (OE) was developed and employed photoacoustic spectroscopy (PAS) for the determination of its skin permeation profile. The morphology of the skin was studied in histological sections stained with hematoxylin-eosin. RESULTS AND DISCUSSION: The optimum conditions predicted for the major extractive efficiency of the phenolics with 100% ethanol led extraction time 101 h and plant:solvent proportion 1:13.5 (w/v). OE presented TP = 724.6 ± 8.2 mg GAE/g extract and scavenging capacity of DPPH (IC50 value = 11.43 ± 0.14 µg/mL) and ABTS radicals (IC50 value = 35.42 ± 0.48 µg/mL). The production of ROS by neutrophils after stimulation with phorbol miristate acetate was lower when the OE was present in the reaction medium, endorsing its high antioxidant capacity. The data obtained by PAS indicated that the OE present in the emulsion has permeated and was distributed in the whole skin. No histopathological alterations were observed in the histological analysis. CONCLUSION: The formulation developed is a promising tool for skin care and could prevent the damage caused by oxidative stress.

Nectandra falcifolia: potential phytopharmaceutical for skin damage protection designed by statistical approach and characterized by photoacoustic spectroscopy

AbstractPhytopharmaceutical products are being used in the treatment and prevention of health problems. Nowadays, the development and evaluation of novel pharmaceutical products is expensive and time consuming. A statistical approach is a good tool for optimal development processes. Nectandra falcifolia (Nees) J.A. Castigl. ex Mart. Crov. & Piccinini, Lauraceae, a Brazilian species, is reported as anti-inflammatory, anti-leishmanial and anti-microbial. However, there is little known about its chemical composition. For other species of Nectandra genus, the presence of antioxidant compounds is reported. In order to optimize the process of obtaining extract with high antioxidant activity, different extraction conditions were tested following a statistical approach. Two sequential experimental designs were used – first, a factorial 23 design, followed by central composite 22. The extracts manufactured by these experimental statistical matrixes had their antioxidant activity and phenolic contents quantified and the response surface plots were fitted in quadratic models and they predicted the best extraction condition for the best antioxidant activity. This standardized extract and its antioxidant activity were better evaluated by two complementary tests (ABTS and Burst respiratory). A topical formulation containing 1% (w/w) of standardized extract was prepared and used for an in vivo skin permeation study using a two-dose application. The photoacoustic spectroscopy was used to analyze the samples from the permeation study and the composition profile of standardized extract. In rat skin samples, the data demonstrated that for the higher dose of topical formulation (5 g/cm2), the standardized extract could cross skin and be seen in epidermis and dermis. This was not the case for the lower dose (2 g/cm2) which was only present in the epidermis. This information suggests that this novel standardized extract of N. falcifoliacould be explored for skin damage prevention or treatment for diseases developed by oxidative damage.

Insulin complexation with hydroxypropyl-beta-cyclodextrin: Spectroscopic evaluation of molecular inclusion and use of the complex in gel for healing of pressure ulcers.

The pressure ulcer healing is a complex process and difficult to be achieved. Insulin is known to promote wound healing, and when complexed with cyclodextrin presents improved solubility, stability and biological activity. Complexation of insulin with hydroxypropyl-beta-cyclodextrin (HPßCD) was performed in this work through the coprecipitation method, providing the inclusion complex (HPßCD-I). The spectroscopic techniques used to analyze the complex were H(1) NMR, FT-Raman and FT-IR/ATR. A gel containing the HPßCD-I complex was prepared and a clinical study was conducted in patients with pressure ulcers. The spectroscopic techniques allowed to confirm the complex formation through the inclusion of aromatic amino acids, such as phenylalanine present in the HPßCD cavity. Data obtained from the FT-Raman and FT-IR/ATR techniques, combined with the H(1) NMR results, showed the effectiveness of these techniques in evaluating the inclusion complex of HPßCD with insulin. Clinical studies demonstrated tissue revitalization and a trend (p=0.06) for a significant difference between the healing effect of the control gel and that with HPßCD-I complex. The creation of the gel prepared with insulin and HPßCD-I complex and its use in patients with pressure ulcers appears to be promising in wound healing and its possible use in hospital care.

Curcumin-ß-cyclodextrin inclusion complex: stability, solubility, characterisation by FT-IR, FT-Raman, X-ray diffraction and photoacoustic spectroscopy, and food application.

Curcumin was complexed with ß-CD using co-precipitation, freeze-drying and solvent evaporation methods. Co-precipitation enabled complex formation, as indicated by the FT-IR and FT-Raman techniques via the shifts in the peaks that were assigned to the aromatic rings of curcumin. In addition, photoacoustic spectroscopy and X-ray diffraction, with the disappearance of the band related to aromatic rings, by Gaussian fitting, and modifications in the spectral lines, respectively, also suggested complex formation. The possible complexation had an efficiency of 74% and increased the solubility of the pure colourant 31-fold. Curcumin-ß-CD complex exhibited a sunlight stability 18% higher than the pure colourant. This material was stable to pH variations and storage at -15 and 4°C. With an isothermal heating at 100 and 150°C for 2h, the material exhibited a colour retention of approximately 99%. The application of curcumin-ß-CD complex in vanilla ice creams intensified the colour of the products and produced a great sensorial acceptance.

Formulation and characterization of ethylcellulose microparticles containing .L-alanyl- L-glutamine peptide.

CONTEXT: The L-alanyl-L-glutamine peptide (AGP) has been effective to promote acute glycemia recovery during long-term insulin-induced hypoglycemia (IIH), and the oral administration of AGP is suggested to prevent prolonged hypoglycemia, such as nocturnal hypoglycemia. OBJECTIVE: Considering the ability of AGP on glycemia recovery and AGP's fast metabolism, the aim of current study was to obtain and characterize ethylcellulose microparticles to deliver the drug for a prolonged time. MATERIALS AND METHODS: Microparticles were prepared by simple and double emulsification/hardening method and characterized by scanning electron microscopy, thermogravimetry (TG), differential scanning calorimetry (DSC), Fourier transform infra-red (FTIR) and FT-Raman spectroscopy and in vitro release. RESULTS AND DISCUSSION: Spherical structures with a mean diameter between 9.30 µm and 13.19 µm were formed. TG analysis showed that the thermal stability of AGP was even more increased by encapsulation with ethylcellulose. In addition, TG, DSC, FTIR and FT-Raman analyses proved that AGP was encapsulated in a molecular way. Higher values of encapsulation efficiency were observed for the microparticles prepared by double emulsification (57.83-83.67%) than for those prepared by simple emulsification (18.37%). However, the last ones could release the peptide in a quicker and more extensive manner than those prepared by double emulsification. CONCLUSION: For the first time, microparticles containing AGP were developed and exhibited prolonged in vitro release as well as protection to the drug, and it could be considered as a dosage form for patients who suffer from insulin-induced hypoglycemia and/or nocturnal hypoglycemia.