Desenvolvimento de sistemas de liberação controlada de fármacos: quitosana / insulina.

A utilização de biomateriais surgiu em função de pessoas que nascem com problemas em órgãos/tecidos ou os adquirem por traumas. Sua demanda foi enfatizada pelo aumento da expectativa de vida dos seres humanos; recentemente, a área de biomateriais encampou muitos estudos, a exemplo da pesquisa com liberação controlada de fármacos, biosensores e dispositivos biomédicos. Uma das doenças crônicas de grande abrangência na contemporaneidade é o Diabetes mellitus tipo 1, cujo tratamento consiste em administração subcutânea diária de insulina. O objetivo deste trabalho foi desenvolver biofilmes compostos de quitosana e insulina, na perspectiva de administrar o fármaco por uma via alternativa a injetável, em sistemas de liberação controlada, contribuindo para uma maior adesão ao tratamento. Os biofilmes foram desenvolvidos a partir da quitosana adquirida em dois fornecedores diferentes e a insulina utilizada foi a NPH em duas concentrações diferentes. A caracterização foi feita pelas técnicas de Molhabilidade, Espectroscopia na Região do Infravermelho com Transformada de Fourier (FTIR), Difração de Raios X (DRX), Calorimetria Exploratória Diferencial (DSC), Termogravimetria (TG), Microscopia Eletrônica de Varredura (MEV), Biodegradação Enzimática, Avaliação da Viabilidade Celular dos Macrófagos e Determinação da Produção de Óxido Nítrico. Foram constatadas pequenas diferenças de hidrofilicidade das amostras, através das análises de molhabilidade. Através dos resultados de FTIR e DRX foi evidenciada a formação do biofilme quitosana/insulina. A morfologia do biofilme não foi modificada consideravelmente, independentemente da presença da insulina, das concentrações e do tipo de quitosana utilizada, sendo a morfologia característica de polímeros de natureza fibrosa, típica da quitosana. Os ensaios realizados por DRX demonstraram variação da cristalinidade nas preparações sendo constatada maior cristalinidade para a preparação de quitosana a 1%, Sigma Aldrich®, GD 75% (B2.1) e menor para a preparação de quitosana a 1,5% Sigma Aldrich®, GD 85% / 50UI de insulina, (B1.4). O DSC acusou três eventos térmicos mostrando que a presença insulina nas preparações de baixa massa molar se equivaleu aos efeitos constatados nas preparações de alta massa molar. A TG constatou maior perda de massa nas preparações de quitosana sem insulina. Os ensaios de biodegradação foram aplicados aos biofilmes de quitosana Sigma Aldrich® a 1%, resultando numa maior degradação para a composição a 1% / 50 UI de insulina (B1.3) e menor para a composição de quitosana a 1 % sem insulina (B1.1). Os ensaios de toxicidade demonstraram nas composições B, a viabilidade da utilização deste sistema como alternativa viável para o tratamento do Diabetes mellitus.The use of biomaterials was induced to help people borned with problems in organs / tissue or people that acquired them by traumas. This demand was increased by the human beings prolonged life expectance. Recently in the area of biomaterials, many studies have been published, such as researches on drug delivery systems, biosensors and biomedical devices. One of the high incidences of chronic diseases in contemporary society is Diabetes mellitus type 1, which treatment consists of daily subcutaneous administration of insulin. The aim of this study was to develop biofilms composed of chitosan and insulin, towards an alternative to the injectable drug administration, using drug delivery systems to increase adherence to the treatment. Biofilms were developed from chitosan from two different suppliers and NPH insulin was used in two different concentrations. The films were characterized by the techniques of Wettability, Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Differential Scanning Calorimetry (DSC), Thermogravimetry (TG), Scanning Electron Microscopy (SEM), Enzymatic Biodegradation, Assessment of Viability and Determination of Macrophage Nitric Oxide Production. We found small differences in hydrophilicity of the samples observing wettability analysis. The results of FTIR and XRD confimed the formation of biofilms chitosan / insulin. The biofilms morphology didn’t change substantially, regardless the presence of insulin concentrations and the type of chitosan used, presenting a nature fibrous polymer characteristic morphology, typical for chitosan. Tests conducted by XRD showed a variation of crystallinity in the samples. The highest crystallinity was found for the chitosan (1%), Sigma Aldrich ®, 75% GD (B2.1) preparation and lowest for the chitosan (1.5%), Sigma Aldrich ®, GD 85%, plus 50 IU of insulin, (B1.4) preparation. The DSC observed three thermal events showing that insulin presence in preparations of low molecular weight was equivalent to the effects of that in preparations of high molecular weight. The TG showed a higher weight loss for preparations of chitosan without insulin. The biodegradation tests were applied to chitosan from Sigma Aldrich® 1% biofilms, and showed the highest degradation for the composition of 1% / 50 IU of insulin (B1.3) and the lowest for the composition of chitosan 1% without insulin ( B1.1). The toxicity tests showed the feasibility to use this system as a viable alternative for the treatment of Diabetes mellitus

ESTUDO DE POLIMORFOS E COCRISTAIS NO DESENVOLVIMENTO DE MEDICAMENTOS:: UMA REVISÃO INTEGRATIVA

A eficácia terapêutica dos fármacos administrados por via oral sólida está relacionada com seu arranjo cristalino, o qual reflete em taxas de dissolução e biodisponibilidade diferentes. A solubilidade dos medicamentos é influenciada pelo polimorfismo e cocristalização, sendo apontada como um dos principais desafios da indústria na fabricação de novos fármacos ou mesmo de fármacos equivalentes. Frente estes temas, essa pesquisa teve por objetivo realizar uma busca ativa de informações nas bases CAPES, LILACS, MEDLINE, PUBMED e SCIELO, publicados em português, inglês e espanhol, entre os anos de 2011 e 2016. Foi verificado que, embora o polimorfismo seja conhecido há séculos, seu contexto se torna ainda mais importante quando se considera a possibilidade da patente de diferentes estados polimorfos. Além disso, recentemente o mesmo ganhou uma nova abordagem da indústria farmacêutica, cuja adaptação em os cocristais garante maior solubilidade dos fármacos e, portanto, aumentam sua biodisponibilidade. Dessa forma, a engenharia de cristais moleculares se apresenta como uma emergente técnica para o aperfeiçoamento das estruturas tridimensionais dos medicamentos, a fim de torná-los mais solúveis e estáveis

ESTUDO COMPARATIVO E CARACTERIZAÇÃO FÍSICO-QUÍMICA DE DISPOSITIVOS A BASE DE QUITOSANA NACIONAL

Os dispositivos a base de quitosana vem despertando uma atenção maior no meio científico, principalmente em aplicações farmacêuticas, na confecção de matrizes carreadoras de fármacos e regeneração tecidual. Neste contexto, este trabalho objetivou desenvolver e caracterizar dispositivos como micropartículas (MPs) e biofilmes, a partir de quitosana comercial de um fornecedor nacional, visando aumentar a efetividade e aplicabilidade. O desenvolvimento dessas MPs ocorreu através de uma secagem por atomização e a formação dos biofilmes pelo método sol-gel. A caracterização envolveu a técnica de Difração de Raios-X (DRX). Os métodos utilizados foram viáveis para produção das matrizes carreadoras de fármacos. A DRX das amostras demonstrou que os produtos obtidos apresentaram perfis mais amorfos quando comparados aos pós e pôde-se evidenciar que o biofilme revelou-se mais amorfo que as Mps. Isso resulta em uma maior facilidade de degradação desse material apontando para uma maior possibilidade de liberação de fármacos, inseridos em sua estrutura

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Núcleos de Ensino da Unesp: artigos 2008

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

General and abdominal adiposity and hypertension in eight world regions: a pooled analysis of 837 population-based studies with 7·5 million participants

International audienceSummaryBackground Adiposity can be measured using BMI (which is based on weight and height) as well as indices of abdominal adiposity. We examined the association between BMI and waist-to-height ratio (WHtR) within and across populations of different world regions and quantified how well these two metrics discriminate between people with and without hypertension.MethodsWe used data from studies carried out from 1990 to 2023 on BMI, WHtR and hypertension in people aged 20–64 years in representative samples of the general population in eight world regions. We graphically compared the regional distributions of BMI and WHtR, and calculated Pearson’s correlation coefficients between BMI and WHtR within each region. We used mixed-effects linear regression to estimate the extent to which WHtR varies across regions at the same BMI. We graphically examined the prevalence of hypertension and the distribution of people who have hypertension both in relation to BMI and WHtR, and we assessed how closely BMI and WHtR discriminate between participants with and without hypertension using C-statistic and net reclassification improvement (NRI).FindingsThe correlation between BMI and WHtR ranged from 0·76 to 0·89 within different regions. After adjusting for age and BMI, mean WHtR was highest in south Asia for both sexes, followed by Latin America and the Caribbean and the region of central Asia, Middle East and north Africa. Mean WHtR was lowest in central and eastern Europe for both sexes, in the high-income western region for women, and in Oceania for men. Conversely, to achieve an equivalent WHtR, the BMI of the population of south Asia would need to be, on average, 2·79 kg/m² (95% CI 2·31–3·28) lower for women and 1·28 kg/m² (1·02–1·54) lower for men than in the high-income western region. In every region, hypertension prevalence increased with both BMI and WHtR. Models with either of these two adiposity metrics had virtually identical C-statistics and NRIs for every region and sex, with C-statistics ranging from 0·72 to 0·81 and NRIs ranging from 0·34 to 0·57 in different region and sex combinations. When both BMI and WHtR were used, performance improved only slightly compared with using either adiposity measure alone.InterpretationBMI can distinguish young and middle-aged adults with higher versus lower amounts of abdominal adiposity with moderate-to-high accuracy, and both BMI and WHtR distinguish people with or without hypertension. However, at the same BMI level, people in south Asia, Latin America and the Caribbean, and the region of central Asia, Middle East and north Africa, have higher WHtR than in the other regions