Flavonoid microparticles by spray-drying: Influence of enhancersof the dissolution rate on properties and stability

Naringenin (Nn) and Quercetin (Q) have numerous health benefits particularly due to their antioxidant properties. However, their low solubility, bioavailability and stability limit their use as components for functional foods, nutraceuticals and pharmaceutical agents. In this research, Nn- and Q-microparticles were produced by a spray-drying process using a combination of cellulose acetate phthalate (CAP) as coating gastroresistant polymer and swelling or surfactant agents as enhancers of dissolution rate. Raw materials and microparticles produced were all characterized by particle size analysis, differential scanning calorimetry, X-ray diffraction, and imaged by electron and fluorescence microscopy. During 12 months, storage stability was evaluated by analyzing drug content, HPLC and DSC profiles, as well as antioxidant activity (DPPH test). In vitro dissolution tests, using a pH-change method, were carried out to investigate the influence of formulative parameters on flavonoid release from the microparticles. Presence of a combination of CAP and surfactants or swelling agents in the formulations produced microparticles with good resistance at low pH of the gastric fluid and complete flavonoid release in the intestinal environment. The spray-drying technique and the process conditions selected have given satisfying encapsulation efficiency and product yield. The microencapsulation have improved the technological characteristics of the powders such as morphology and size, have given long-lasting storage stability and have preserved the antioxidant properties

Could antigen presenting cells represent a protective element during sars-cov-2 infection in children?

Antigen Presenting Cells (APC) are immune cells that recognize, process, and present antigens to lymphocytes. APCs are among the earliest immune responders against an antigen. Thus, in patients with COVID-19, a disease caused by the newly reported SARS-CoV-2 virus, the role of APCs becomes increasingly important. In this paper, we dissect the role of these cells in the fight against SARS-CoV-2. Interestingly, this virus appears to cause a higher mortality among adults than children. This may suggest that the immune system, particularly APCs, of children may be different from that of adults, which may then explain differences in immune responses between these two populations, evident as different pathological outcome. However, the underlying molecular mechanisms that differentiate juvenile from other APCs are not well understood. Whether juvenile APCs are one reason why children are less susceptible to SARS-CoV-2 requires much attention. The goal of this review is to examine the role of APCs, both in adults and children. The molecular mechanisms governing APCs, especially against SARS-CoV-2, may explain the differential immune responsiveness in the two populations

Development of a selective and sensitive sensor for urate determination based on tris(1,10-phenantroline)copper(II) bis(tetracyanoquinodimethanide) adsorbed on carbon nanotubes

The present work describes the development of a selective electrochemical sensor for urate based on tris(1,10-phenantroline) copper(II) bis(tetracyanoquinodimethanide) (Cu(phen)(3)(TCNQ)(2)) adsorbed on multi-walled carbon nanotubes (CNT). The composite material was characterized by infrared spectroscopy, scanning electron microscopy, and electrochemical impedance spectroscopy. The composite material showed an excellent electrocatalytic activity toward oxidation of urate. The heterogeneous charge transfer rate constant (k') between the analyte and the sensor was determined using linear sweep voltammetry experiments. The composite material shows a linear range from 5 up to 2500 mu mol L-1 with limit of detection of 1.05 mu mol L-1 and limit of quantification of 3.50 mu mol L-1. The high sensitivity and selectivity of the sensor for urate was sufficient for its determinationThe present work describes the development of a selective electrochemical sensor for urate based on tris(1,10-phenantroline)copper(II) bis(tetracyanoquinodimethanide) (Cu(phen)3(TCNQ)2) adsorbed on multi-walled carbon nanotubes (CNT). The composite materi261020352045FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPEMA - FUNDAÇÃO DE AMPARO A PESQUISA E AO DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO DO MARANHÃOsem informaçãosem informaçãosem informaçãoThe authors are grateful to Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), INCTBio, Rede Mineira de Química, and Fundação de Amparo à Pesquisa do Estado do Maranhão (FAPEMA

Electrochemical determination of oncocalyxone A using an iron-phthalocyanine/iron-porphyrin modified glassy carbon electrode

The development of a highly sensitive voltammetric sensor for oncocalyxone A using a glassy carbon electrode modified with a bilayer iron(II) tetrasulfonated phthalocyanine (FeTSPc) and iron(III) tetra-(N-methyl-4-pyridyl)-porphyrin (FeT4MPyP) is described. The modified electrode showed high catalytic activity and stability for the oncocalyxone A reduction, provoking the anodic shift of the reduction peak potentials of ca. 30 mV and presenting much higher peak currents than those obtained on the bare GC electrode. A wide linear response range between 0.005-1.2 µmol L-1, with a sensitivity of 8.11 µA L µmol-1 and limits of detection (LOD) and quantification (LOQ) of 1.5 and 5 nmol L-1 were obtained with this sensor.Descreve-se, no presente trabalho, o desenvolvimento de um sensor voltamétrico altamente sensível para a oncocalixona A, utilizando-se eletrodo de carbono vítreo modificado com uma bi-camada de ftalocianina tetrassulfonada de ferro(II) (FeTSPc) e tetra-(N-metil-4-piridil)-porfirina de ferro(III) (FeT4MPyP). O eletrodo modificado apresentou alta atividade catalítica e estabilidade em relação à redução da oncocalixona, proporcionando deslocamento anódico de ca. de 30 mV e amplificação da corrente de pico, em relação a iguais parâmetros obtidos em eletrodo de carbono vítreo não modificado. Um ampla faixa linear de resposta entre 0.005-1.2 µmol L-1, com sensibilidade de 8.11 µA L µmol-1 e limites de detecção (LOD) e quantificação (LOQ) de 1.5 e 5 nmol L-1 foram obtidos, com o uso desse sensor.697703Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Emerging Evidence and Treatment Perspectives from Randomized Clinical Trials in Systemic Sclerosis: Focus on Interstitial Lung Disease

Systemic sclerosis (SSc) is a complex rare autoimmune disease with heterogeneous clinical manifestations. Currently, interstitial lung disease (ILD) and cardiac involvement (including pulmonary arterial hypertension) are recognized as the leading causes of SSc-associated mortality. New molecular targets have been discovered and phase II and phase III clinical trials published in the last 5 years on SSc-ILD will be discussed in this review. Details on the study design; the drug tested and its dose; the inclusion and exclusion criteria of the study; the concomitant immunosuppression; the outcomes and the duration of the study were reviewed. The two most common drugs used for the treatment of SSc-ILD are cyclophosphamide and mycophenolate mofetil, both supported by randomized controlled trials. Additional drugs, such as nintedanib and tocilizumab, have been approved to slow pulmonary function decline in SSc-ILD. In this review, we discuss the therapeutic alternatives for SSc management, offering the option to customize the design of future studies to stratify SSc patients and provide a patient-specific treatment according to the new emerging pathogenic features of SSc-ILD

Hematopoietic Stem Cell Transplantation in Primary Immunodeficiencies in Brazil-a Survey of the Working Group on Paediatric Transplantation of the Brazilian Society of Bone Marrow Transplantation

Inst Crianca HCFMUSP, Sao Paulo, BrazilHosp Israelita Albert Einstein, Sao Paulo, BrazilInst Oncol Pediat, Sao Paulo, BrazilHosp Clin Porto Alegre, Porto Alegre, RS, BrazilUniv Fed Parana, Bone Marrow Transplantat Unit, BR-80060000 Curitiba, Parana, BrazilCtr Oncol & Hematol, Jau, BrazilUSP Ribeirao Preto, Hosp Clin, Ribeirao Preto, BrazilUniv Fed Minas Gerais, Belo Horizonte, MG, BrazilUniv Fed Rio de Janeiro, Rio De Janeiro, BrazilCtr Nacl Transplate Medula Ossea CEMO, Inst Nacl Canc, Rio De Janeiro, BrazilUniv Fed Parana, Paediat Intens Care Unit, BR-80060000 Curitiba, Parana, BrazilNatl Inst Canc INCA, Rio De Janeiro, BrazilHosp Israelita Albert Einstein, Hematol & Bone Marrow Transplantat Dept, Sao Paulo, BrazilWeb of Scienc

Proteomics Reveals Novel Oxidative and Glycolytic Mechanisms in Type 1 Diabetic Patients' Skin Which Are Normalized by Kidney-Pancreas Transplantation

Background: In type 1 diabetes (T1D) vascular complications such as accelerated atherosclerosis and diffused macro-/microangiopathy are linked to chronic hyperglycemia with a mechanism that is not yet well understood. End-stage renal disease (ESRD) worsens most diabetic complications, particularly, the risk of morbidity and mortality from cardiovascular disease is increased several fold. Methods and Findings: We evaluated protein regulation and expression in skin biopsies obtained from T1D patients with and without ESRD, to identify pathways of persistent cellular changes linked to diabetic vascular disease. We therefore examined pathways that may be normalized by restoration of normoglycemia with kidney-pancreas (KP) transplantation. Using proteomic and ultrastructural approaches, multiple alterations in the expression of proteins involved in oxidative stress (catalase, superoxide dismutase 1, Hsp27, Hsp60, ATP synthase δ chain, and flavin reductase), aerobic and anaerobic glycolysis (ACBP, pyruvate kinase muscle isozyme, and phosphoglycerate kinase 1), and intracellular signaling (stratifin-14-3-3, S100-calcyclin, cathepsin, and PPI rotamase) as well as endothelial vascular abnormalities were identified in T1D and T1D+ESRD patients. These abnormalities were reversed after KP transplant. Increased plasma levels of malondialdehyde were observed in T1D and T1D+ESRD patients, confirming increased oxidative stress which was normalized after KP transplant. Conclusions: Our data suggests persistent cellular changes of anti-oxidative machinery and of aerobic/anaerobic glycolysis are present in T1D and T1D+ESRD patients, and these abnormalities may play a key role in the pathogenesis of hyperglycemia-related vascular complications. Restoration of normoglycemia and removal of uremia with KP transplant can correct these abnormalities. Some of these identified pathways may become potential therapeutic targets for a new generation of drugs

The validity and reliability of the Portuguese versions of three tools used to diagnose delirium in critically ill patients

OBJECTIVES: The objectives of this study are to compare the sensitivity and specificity of three diagnostic tools for delirium (the Intensive Care Delirium Screening Checklist, the Confusion Assessment Method for Intensive Care Units and the Confusion Assessment Method for Intensive Care Units Flowsheet) in a mixed population of critically ill patients, and to validate the Brazilian Portuguese Confusion Assessment Method for Intensive Care Units. METHODS: The study was conducted in four intensive care units in Brazil. Patients were screened for delirium by a psychiatrist or neurologist using the Diagnostic and Statistical Manual of Mental Disorders. Patients were subsequently screened by an intensivist using Portuguese translations of the three tools. RESULTS: One hundred and nineteen patients were evaluated and 38.6% were diagnosed with delirium by the reference rater. The Confusion Assessment Method for Intensive Care Units had a sensitivity of 72.5% and a specificity of 96.2%; the Confusion Assessment Method for Intensive Care Units Flowsheet had a sensitivity of 72.5% and a specificity of 96.2%; the Intensive Care Delirium Screening Checklist had a sensitivity of 96.0% and a specificity of 72.4%. There was strong agreement between the Confusion Assessment Method for Intensive Care Units and the Confusion Assessment Method for Intensive Care Units Flowsheet (kappa coefficient = 0.96) CONCLUSION: All three instruments are effective diagnostic tools in critically ill intensive care unit patients. In addition, the Brazilian Portuguese version of the Confusion Assessment Method for Intensive Care Units is a valid and reliable instrument for the assessment of delirium among critically ill patients