Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 34
Filtrar
1.
Pharmaceutics ; 16(9)2024 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-39339269

RESUMO

Background/Objectives: This study developed and characterized hydrogels (HG-CGG) and films (F-CGG) based on cationic guar gum (CGG) for application in wound healing. Methods: HG-CGG (2% w/v) was prepared by gum thickening and evaluated for pH, stability, spreadability, and viscosity. F-CGG was obtained using an aqueous dispersion of CGG (6% w/v) and the solvent casting method. F-CGG was characterized for thickness, weight uniformity, morphology, mechanical properties, hydrophilicity, and swelling potential. Both formulations were evaluated for bioadhesive potential on intact and injured porcine skin, as well as antioxidant activity. F-CGG was further studied for biocompatibility using hemolysis and cell viability assays (L929 fibroblasts), and its wound-healing potential by the scratch assay. Results: HG-CGG showed adequate viscosity and spreadability profiles for wound coverage, but its bioadhesive strength was reduced on injured skin. In contrast, F-CGG maintained consistent bioadhesive strength regardless of skin condition (6554.14 ± 540.57 dyne/cm2 on injured skin), presenting appropriate mechanical properties (flexible, transparent, thin, and resistant) and a high swelling capacity (2032 ± 211% after 6 h). F-CGG demonstrated superior antioxidant potential compared to HG-CGG (20.50 mg/mL ABTS+ radical scavenging activity), in addition to exhibiting low hemolytic potential and no cytotoxicity to fibroblasts. F-CGG promoted the proliferation of L929 cells in vitro, supporting wound healing. Conclusions: Therefore, CGG proved to be a promising material for developing formulations with properties suitable for cutaneous use. F-CGG combines bioadhesion, antioxidant activity, biocompatibility, cell proliferation, and potential wound healing, making it promising for advanced wound treatment.

2.
Pediatr Rep ; 16(3): 724-735, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39311324

RESUMO

BACKGROUND: This study aimed to conduct a narrative review approaching the effects of exclusive breastfeeding on neuropsychomotor development. The goal was to provide evidence-based knowledge to inform healthcare practices and policies and promote optimized infant feeding strategies. METHODS: Our study reviewed the relevant literature from May and June 2024, covering the publication period between 2013 and 2024. The PubMed database was utilized and searched for articles using keywords such as "Brain", "Growth", "Development", and "Breastfeeding", employing Boolean operators such as "AND", "OR", and "NOT." RESULTS: Our search initially screened 15,412 studies, resulting in 600 articles. Eleven studies met our inclusion criteria and provided relevant information on the topic. Several studies have shown that exclusive breastfeeding and its duration are beneficial for neural development. Research suggests that breastfeeding improves brain architecture, white matter development, and cognitive performance. Additionally, studies indicate that the mother's intake of omega-3 fatty acids can enhance infant brain development, and specific micronutrients in breast milk, such as myo-inositol, may contribute to neural connectivity. Some findings also suggest that the child's sex may play a role in how breast milk benefits the brain. Furthermore, there is evidence of the strong influence of epigenetic compounds on the neurodevelopmental benefits of exclusive breastfeeding. CONCLUSIONS: This narrative review revealed findings that indicate breast milk has a positive impact on brain development. This emphasizes that breast milk has a positive impact on brain development. It underscores the importance of conducting additional research to understand how breastfeeding specifically influences neurodevelopment.

3.
Int J Biochem Mol Biol ; 14(4): 51-61, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37736389

RESUMO

Type 1 diabetes mellitus (T1DM), associated with autoimmune destruction of pancreatic ß cells, is observed in children and adolescents. OBJECTIVE: We investigated the potential association of the apolipoprotein M (APOM) polymorphisms rs707921, rs805264, rs805296, rs805297, and rs9404941 in childhood-onset T1DM (n = 144) and compared them to those in healthy (mostly Euro-Brazilian) children (n = 168). METHODS: This project was approved by the Ethics Committee of the Federal University of Parana (CAAE 24676613.6.0000.0102). Genotyping was performed using PCR-restriction fragment length polymorphisms (rs805296 and rs9404941) and TaqMan probes (rs707921, rs805264, and rs805297). RESULTS: All polymorphisms were in Hardy-Weinberg equilibrium. In the codominant model, no significant differences (P > 0.05) were observed in genotype and allele frequencies between healthy controls and children with T1DM. The minor allele frequencies (95% CI) for healthy subjects were rs707921 (A, 10.7%; 7-14%), rs805264 (A, 6.5%; 4-9%), rs805296 (C, 3.6%; 2-6%), rs805297 (A, 22.6%; 22-31%), and rs9404941 (C, 2.7%; 1-4%). The frequencies of the rs805297 A allele and rs805296 C allele were similar to those of other Caucasian populations; both the rs707921 and rs805264 A alleles were similar to American and Latin American populations, whereas that of the rs9404941 C allele was lower than that observed in the Caucasian and Asian populations. CONCLUSIONS: Haplotype analysis suggests that rs805297-C, rs9404941-T, rs805296-T, rs805264-G, and rs707921-C conferred risk (OR: 4.25; 95% CI: 1.81-10.1) to childhood-onset T1DM in the Euro-Brazilian population.

4.
Pharmaceutics ; 15(4)2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-37111745

RESUMO

Inhibition of ABC transporters is a promising approach to overcome multidrug resistance in cancer. Herein, we report the characterization of a potent ABCG2 inhibitor, namely, chromone 4a (C4a). Molecular docking and in vitro assays using ABCG2 and P-glycoprotein (P-gp) expressing membrane vesicles of insect cells revealed that C4a interacts with both transporters, while showing selectivity toward ABCG2 using cell-based transport assays. C4a inhibited the ABCG2-mediated efflux of different substrates and molecular dynamic simulations demonstrated that C4a binds in the Ko143-binding pocket. Liposomes and extracellular vesicles (EVs) of Giardia intestinalis and human blood were used to successfully bypass the poor water solubility and delivery of C4a as assessed by inhibition of the ABCG2 function. Human blood EVs also promoted delivery of the well-known P-gp inhibitor, elacridar. Here, for the first time, we demonstrated the potential use of plasma circulating EVs for drug delivery of hydrophobic drugs targeting membrane proteins.

5.
J Vis Exp ; (191)2023 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-36715403

RESUMO

This paper describes a novel, simple, and low-cost device to perform in vitro photodynamic therapy (PDT) assays, named the PhotoACT. The device was built using a set of conventional programmable light-emitting diodes (LEDs), a liquid crystal display (LCD) module, and a light sensor connected to a commercial microcontroller board. The box-based structure of the prototype was made with medium-density fiberboards (MDFs). The internal compartment can simultaneously allocate four cell culture multiwell microplates. As a proof of concept, we studied the cytotoxic effect of the photosensitizer (PS) verteporfin against the HeLa cell line in two-dimensional (2D) culture. HeLa cells were treated with increasing concentrations of verteporfin for 24 h. The drug-containing supernatant medium was discarded, the adherent cells were washed with phosphate-buffered saline (PBS), and drug-free medium was added. In this study, the effect of verteporfin on cells was examined either without light exposure or after exposure for 1 h to light using red-green-blue (RGB) values of 255, 255, and 255 (average fluence of 49.1 ± 0.6 J/cm2). After 24 h, the cell viability was assessed by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. Experimental results showed that exposure of cells treated with verteporfin to the light from the device enhances the drug's cytotoxic effect via a mechanism mediated by reactive oxygen species (ROS). In addition, the use of the prototype described in this work was validated by comparing the results with a commercial PDT device. Thus, this LED-based photodynamic therapy prototype represents a good alternative for in vitro studies of PDT.


Assuntos
Antineoplásicos , Fotoquimioterapia , Humanos , Verteporfina/farmacologia , Células HeLa , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Técnicas de Cultura de Células
6.
EXCLI J ; 22: 1155-1172, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38204967

RESUMO

A current clinical challenge in cancer is multidrug resistance (MDR) mediated by ABC transporters. Breast cancer resistance protein (BCRP) or ABCG2 transporter is one of the most important ABC transporters implicated in MDR and the use of inhibitors is a promising approach to overcome the resistance in cancer. This study aimed to characterize the molecular mechanism of ABCG2 inhibitors identified by a repurposing drug strategy using antiviral, anti-inflammatory and antiparasitic agents. Lopinavir and ivermectin can be considered as pan-inhibitors of ABC transporters, since both compounds inhibited ABCG2, P-glycoprotein and MRP1. They inhibited ABCG2 activity showing IC50 values of 25.5 and 23.4 µM, respectively. These drugs were highly cytotoxic and not transported by ABCG2. Additionally, these drugs increased the 5D3 antibody binding and did not affect the mRNA and protein expression levels. Cell-based analysis of the type of inhibition suggested a non-competitive inhibition, which was further corroborated by in silico approaches of molecular docking and molecular dynamics simulations. These results showed an overlap of the lopinavir and ivermectin binding sites on ABCG2, mainly interacting with E446 residue. However, the substrate mitoxantrone occupies a different site, binding to the F436 region, closer to the L554/L555 plug. In conclusion, these results revealed the mechanistic basis of lopinavir and ivermectin interaction with ABCG2. See also the Graphical abstract(Fig. 1).

7.
Biometals ; 35(5): 903-919, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35778658

RESUMO

Diabetes mellitus, a complex and heterogeneous disease associated with hyperglycemia, is a leading cause of mortality and reduces life expectancy. Vanadium complexes have been studied for the treatment of diabetes. The effect of complex [VO(bpy)(mal)]·H2O (complex A) was evaluated in a human hepatocarcinoma (HepG2) cell line and in streptozotocin (STZ)-induced diabetic male Wistar rats conditioned in seven groups with different treatments (n = 10 animals per group). Electron paramagnetic resonance and 51V NMR analyses of complex A in high-glucose Dulbecco's Modified Eagle Medium (DMEM) revealed the oxidation and hydrolysis of the oxidovanadium(IV) complex over a period of 24 h at 37 °C to give low-nuclearity vanadates "V1" (H2VO4-), "V2" (H2V2O72-), and "V4" (V4O124-). In HepG2 cells, complex A exhibited low cytotoxic effects at concentrations 2.5 to 7.5 µmol L-1 (IC50 10.53 µmol L-1) and increased glucose uptake (2-NBDG) up to 93%, an effect similar to insulin. In STZ-induced diabetic rats, complex A at 10 and 30 mg kg-1 administered by oral gavage for 12 days did not affect the animals, suggesting low toxicity or metabolic impairment during the experimental period. Compared to insulin treatment alone, complex A (30 mg kg-1) in association with insulin was found to improve glycemia (30.6 ± 6.3 mmol L-1 vs. 21.1 ± 8.6 mmol L-1, respectively; p = 0.002), resulting in approximately 30% additional reduction in glycemia. The insulin-enhancing effect of complex A was associated with low toxicity and was achieved via oral administration, suggesting the potential of complex A as a promising candidate for the adjuvant treatment of diabetes.


Assuntos
Diabetes Mellitus Experimental , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/metabolismo , Insulina/farmacologia , Malatos , Masculino , Ratos , Ratos Wistar , Estreptozocina , Vanadatos/química , Vanádio/química , Vanádio/farmacologia
8.
FEBS Lett ; 596(3): 381-399, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34939198

RESUMO

A promising strategy to overcome multidrug resistance is the use of inhibitors of ABC drug transporters. For this reason, we evaluated the polyoxovanadates (POVs) [V10 O28 ]6- (V10 ), [H6 V14 O38 (PO4 )]5- (V14 ), [V15 O36 Cl]6- (V15 ) and [V18 O42 I]7- (V18 ) as inhibitors of three major multidrug resistance-linked ABC transporters: P-glycoprotein (P-gp), ABCG2 and MRP1. All of the POVs selectively inhibited P-gp. V10 and V18 were the two most promising compounds, with IC50 values of transport inhibition of 25.4 and 22.7 µm, respectively. Both compounds inhibited P-gp ATPase activity, with the same IC50 value of 1.26 µm. V10 and V18 triggered different conformational changes in the P-gp protein with time-dependent inhibition, which was confirmed using the synthesized salt of V10 with rhodamine B, RhoB-V10 . The hydrophilic nature of POVs supports the hypothesis that these compounds target an unusual ligand-binding site, opening new possibilities in the development of potent modulators of ABC transporters.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP
9.
J Diabetes Metab Disord ; 20(1): 611-620, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34222081

RESUMO

PURPOSE: This prospective study aimed to detect and identify plasma proteins differentially expressed between groups of Brazilian diagnosed with type 1 (T1DM), type 2 (T2DM) diabetes with good and poor glycemic control and the non-diabetic group denominated control group (CG). METHODS: Patients with T1DM and T2DM were subdivided according to their glycated haemoglobin (HbA1c) level: ≥ 53 mmol/mol and < 53 mmol/mol. Each subgroup was composed of ten subjects (n = 10). The plasma from each subgroup was pooled and depleted of albumin and IgG. The reminiscent proteins were quantified and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The relative volume of protein bands was determined by densitometry analysis, and those with differential abundance were identified by MALDI-TOF mass spectrometry. RESULTS: Alpha 2 - Macroglobulin (AMG) was 1.3-fold more abundant in T1DM with HbA1c ≥ 53 mmol/mol and < 53 mmol/mol and 1.4-fold more abundant in T2DM with HbA1c ≥ 53 mmol/mol compared to CG. Ceruloplasmin (Cp) and Haptoglobin (Hp) were overexpressed above 1.5-fold in all DM subgroups. Cp in T1DM and Hp in both types of DM were more expressed in HbA1c ≥ 53 mmol/mol than <53 mmol/mol. Apolipoprotein A-I (Apo A-I) was upregulated only in T2DM subgroups. CONCLUSION: In summary, three positive acute-phase proteins, AMG, Cp and Hp were more abundant in diabetic individuals regardless of the diabetes type. The highest Hp abundance in both types of DM with HbA1c ≥ 53 mmol/mol, reinforces Hp as a possible biomarker associated with diabetic complications.

10.
Rev. bras. anal. clin ; 53(2): 138-142, 20210630. ilus
Artigo em Português | LILACS | ID: biblio-1348698

RESUMO

A pandemia da COVID-19 tem tido um impacto devastador em todo o mundo e levou ao rápido desenvolvimento de testes diagnósticos. Diferentes tecnologias vêm sendo utilizadas para a detecção de imunoglobulinas frente à infecção por SARS-CoV-2. Ensaios imunoenzimáticos (ELISA), quimioluminescentes e imunocromatográficos estão disponíveis e, no geral, apresentam poder diagnóstico limitado, principalmente para a detecção de IgA. A citometria de fluxo tem surgido como alternativa para o desenvolvimento de métodos sensíveis e específicos para a COVID-19 aplicados para diagnóstico, triagem e estratificação da doença. A citometria de fluxo é uma tecnologia óptica baseada em laser que detecta características físico-químicas de células ou partículas em um fluido heterogêneo. O artigo explora a citometria de fluxo para o diagnóstico da COVID-19 em duas estratégias para a detecção de anticorpos no soro ou plasma, uma utilizando antígenos virais expressos na superfície de células de mamíferos e outra com estes elementos imobilizados em microesferas (beads). A possibilidade de detecção rápida de múltiplos anticorpos simultaneamente, com pequeno volume de amostra e elevada sensibilidade e especificidade, torna a citometria de fluxo uma metodologia promissora para o laboratório clínico, como ferramenta de referência para auxiliar na contenção do processo pandêmico da COVID-19 e futuros eventos similares.


The COVID-19 pandemic has had a devastating impact around the world and has led to the rapid development of diagnostic tests. Different technologies have been used to detect immunoglobulins produced against SARS-CoV-2 infection. Immunoenzymatic (ELISA), chemiluminescent and immunochromatographic assays are available and, in general, they have limited diagnostic accuracy, especially for the detection of IgA. Flow cytometry has emerged as an alternative for the development of sensitive and specific methods for COVID-19 applied for diagnosis, screening and stratification of the disease. Flow cytometry is a laser-based optical technology that detects physicochemical characteristics of cells or particles in a heterogeneous fluid. The article explores flow cytometry for the diagnosis of COVID-19 in two strategies for detecting antibodies in serum or plasma, the first one using viral antigens expressed on the surface of mammalian cells and the other one with these elements immobilized on microspheres (beads). The possibility of rapid detection of multiple antibodies simultaneously, with a small sample volume and high sensitivity and specificity, makes flow cytometry a promising methodology for the clinical laboratory, as a reference tool to help stop the COVID-19 pandemic process and similar future events.


Assuntos
Imunoglobulina A , Imunoglobulina G , Imunoglobulina M , Citometria de Fluxo , SARS-CoV-2 , COVID-19
11.
Sci Rep ; 11(1): 1788, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33469044

RESUMO

The ATP-binding cassette transporter ABCG2 mediates the efflux of several chemotherapeutic drugs, contributing to the development of multidrug resistance (MDR) in many cancers. The most promising strategy to overcome ABCG2-mediated MDR is the use of specific inhibitors. Despite many efforts, the identification of new potent and specific ABCG2 inhibitors remains urgent. In this study, a structural optimization of indeno[1,2-b]indole was performed and a new generation of 18 compounds was synthesized and tested as ABCG2 inhibitors. Most compounds showed ABCG2 inhibition with IC50 values below 0.5 µM. The ratio between cytotoxicity (IG50) and ABCG2 inhibition potency (IC50) was used to identify the best inhibitors. In addition, it was observed that some indeno[1,2-b]indole derivatives produced complete inhibition, while others only partially inhibited the transport function of ABCG2. All indeno[1,2-b]indole derivatives are not transported by ABCG2, and even the partial inhibitors are able to fully chemosensitize cancer cells overexpressing ABCG2. The high affinity of these indeno[1,2-b]indole derivatives was confirmed by the strong stimulatory effect on ABCG2 ATPase activity. These compounds did not affect the binding of conformation-sensitive antibody 5D3 binding, but stabilized the protein structure, as revealed by the thermostabilization assay. Finally, a docking study showed the indeno[1,2-b]indole derivatives share the same binding site as the substrate estrone-3-sulfate.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Neoplasias da Mama/metabolismo , Indóis/farmacologia , Proteínas de Neoplasias/antagonistas & inibidores , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Sobrevivência Celular/efeitos dos fármacos , Feminino , Células HEK293 , Humanos , Indóis/química , Relação Estrutura-Atividade
12.
Braz. J. Pharm. Sci. (Online) ; 57: e19078, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1345449

RESUMO

1,5-Anhydroglucitol (1,5-AG) is a non-fasting glycemic marker that responds to hyperglycemia excursions. The reduction in serum levels of 1,5-AG is associated with an increase in postprandial glycemia and glycosuria, phenomena that increase the risk and severity of diabetic complications. The objective is to assess the ability of 1,5-AG to discriminate type 2 diabetes (T2D) patients without overt kidney disease, for screening or diagnostic purposes. The Human Research Ethics Committee of Universidade Federal do Paraná (UFPR) approved the project. Serum samples from 567 individuals classified as healthy subjects (n = 291) and T2D (n = 276) with moderate glycemic control (HbA1c of 7-8%), matched by gender, were analyzed. Serum 1,5-AG levels were measured using an automated enzymatic method (GlycoMark, Inc.). Receiver Operating Characteristic (ROC) curve analysis for 1,5-AG showed sensibility of 65.3% and specificity of 91.1% to detect T2D at cut-off point of 92 µmol/L. The results were similar to the groups' discrimination by glycemia (sensibility/specificity, 62.2%; 89.0%) at cut-off point of 6.3 mmol/L. HbA1c was the best discriminator (sensibility/specificity, 87.4%; 94.2%) at a cut-off point of 5.8% (40 mmol/mol). The serum 1,5-AG concentration was not able to discriminate T2D in the presence of moderate glycemic control with no overt nephropathy.


Assuntos
Humanos , Masculino , Feminino , Pacientes/classificação , Curva ROC , Diabetes Mellitus Tipo 2/patologia , Biomarcadores , Complicações do Diabetes , Controle Glicêmico/instrumentação , Hiperglicemia/complicações
13.
Rev. bras. anal. clin ; 52(4): 337-345, 20201230. tab, ilus
Artigo em Português | LILACS | ID: biblio-1223688

RESUMO

Em humanos, o pH sanguíneo é mantido em uma faixa estreita, entre 7,35 e 7,45. Diferentes mecanismos bioquímicos, de forma harmônica, atuam para a manutenção do pH fisiológico. Múltiplos processos patológicos podem promover alterações no pH e nos gases sanguíneos, caracterizando acidose (pH <7,35) ou alcalose (pH >7,45). A ruptura da homeostasia do pH é identificada pela medição do pH, pressão parcial de dióxido de carbono (pCO2), concentração do bicarbonato (HCO3-) e, adicionalmente, com a pressão de oxigênio (pO2) em sangue arterial, processo descrito como gasometria arterial. Este artigo revisa os principais elementos associados a compreensão das alterações e tem como objetivo central apresentar uma abordagem didática e intuitiva para a caracterização destes distúrbios; e também comenta sobre ferramentais digitais destinadas a interpretações das alterações da gasometria arterial que também são abordados, como programas para computadores em ambiente web e aplicativos para telefonia móvel.


In humans, blood pH is kept in a narrow range, between 7.35 to 7.45. Different biochemical mechanisms, in a harmonic way, act to maintain the physiological pH. Multiple pathological processes can promote changes in pH and blood gases, characterizing acidosis (pH <7.35) or alkalosis (pH> 7.45). The rupture of pH homeostasis is identified by measuring pH, partial pressure of carbon dioxide (pCO2), bicarbonate concentration (HCO3 - and, in addition, with the pressure of oxygen (pO2) in arterial blood, a process described as gasometry arterial. This article reviews the main elements associated with the understanding of acid-base changes and aims to present a didactic and intuitive approach to the characterization of these disorders; and also comments on digital tools for the interpretation of alterations in arterial blood gases are also covered, such as programs for computers in a web environment and applications for mobile phone.


Assuntos
Valores de Referência , Desequilíbrio Ácido-Base , Gasometria , Software , Aplicativos Móveis
14.
Rev. bras. anal. clin ; 52(2): 154-159, 20200630.
Artigo em Português | LILACS | ID: biblio-1147061

RESUMO

O mundo enfrenta duas pandemias distintas, mas que guardam alguma relação entre si. O Diabetes mellitus (DM) promove um estado crônico inflamatório que torna os afetados mais propensos a infecções em geral. A doença aguda causada pelo novo coronavírus, COVID-19, assim como o DM, altera o sistema imunológico, podendo ativar uma tempestade de citocinas deletéria ao hospedeiro. O DM tem sido considerado como um fator de risco independente da idade para a gravidade da COVID-19. De fato, pessoas com DM são propensas a um curso clínico de maior severidade da COVID-19 com maior taxa de morbimortalidade. Uma forte relação entre a COVID-19 e o DM reside no fato de que o SARS-CoV-2 utiliza a proteína ACE-2 como receptor para entrar na célula humana, a qual é superexpressa pelas células das ilhotas pancreáticas e ainda mais em pessoas com DM. Depois de invadir a célula do hospedeiro, o vírus degrada a ACE-2, reduzindo sua atividade anti-inflamatória. Somado a isso, acredita-se que o SARS-CoV-2 afete diretamente a parte endócrina do pâncreas, com consequente hiperglicemia. Entretanto, ainda não está claro de que forma as alterações glicêmicas podem estar relacionadas com a severidade da COVID-19; e se o SARS-CoV-2 tem potencial diabetogênico. Todavia, os mecanismos propostos para explicar a associação observada entre DM e a COVID-19 incluem inflamação, alterações na resposta imune, na coagulação e a agressão direta do vírus às células b pancreáticas. Como o diabetes está associado às manifestações graves da COVID-19, o primeiro passo é evitar a contaminação de pessoas com DM pelo SARS-CoV-2. Depois, todo paciente com COVID-19 que tenha DM deve ser considerado grave. E, por fim, a monitoração glicêmica frequente em pacientes com COVID-19 deve ser considerada, uma vez que o controle da hiperglicemia tem se mostrado eficaz na promoção de melhores desfechos clínicos.


The world faces two distinct pandemics, which have some relationship with each other. Diabetes mellitus (DM) promotes a chronic inflammatory state that makes the affected more prone to general infections. The acute disease caused by the new coronavirus, COVID19, as well as DM, alters the immune system, which can activate a harmful cytokine storm in the host. DM has been considered as an age-independent risk factor for the severity of COVID-19. In fact, people with DM are prone to a more severe clinical course of COVID19 with a higher rate of morbidity and mortality. A strong relationship between COVID-19 and DM lies in the fact that SARS-CoV-2 uses the ACE-2 protein as a receptor to enter the human cell, which is overexpressed by pancreatic islet cells, especially in people with DM. After invading the host cell, the virus degrades ACE-2, reducing its anti-inflammatory activity. In addition, SARS-CoV-2 is believed to directly affect the endocrine part of the pancreas, with consequent hyperglycemia. However, it is not clear how glycemic changes may be related to the severity of COVID-19; and, whether SARS-CoV-2 has diabetogenic potential. However, the mechanisms proposed to explain the observed association between DM and COVID-19 include inflammation, changes in the immune response, coagulation and direct aggression of the virus to pancreatic beta cells. As diabetes is associated with severe manifestations of COVID-19, the first step is to avoid contamination of people with DM by SARS-CoV-2. Then, every patient with COVID-19 who has DM should be considered severe. Finally, frequent glycemic monitoring in patients with COVID-19 should be considered, since the control of hyperglycemia has been shown to be effective in promoting better clinical outcomes


Assuntos
Infecções por Coronavirus , Diabetes Mellitus
15.
Arch. endocrinol. metab. (Online) ; 63(5): 524-530, Sept.-Oct. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1038503

RESUMO

ABSTRACT Objective The aim of the study is to describe a portable and convenient software to facilitate the diagnostics of gestational (GDM) and pre-gestational diabetes (PGDM). Materials and methods An open source software, d-GDM, was developed in Java. The integrated development environment Android Studio was used as the Android operational system. The software for GDM diagnosis uses the criteria endorsed by the International Association of Diabetes and Pregnancy Study Group, modified by the World Health Organization. Results GDM diagnosis criteria is not simple to follow, therefore, errors or inconsistencies in diagnosis are expected and could delay the appropriate treatment. The d-GDM, was developed to assist GDM diagnosis with precision and consistency diagnostic reports. The open source software can be manipulated conveniently. The operator requires information regarding the gestational period and selects the appropriate glycaemic marker options from the menu. During operation, pressing the button "diagnosticar" on the screen will present the diagnosis and information for the follow up. d-GDM is available in Portuguese or English and can be downloaded from the Google PlayStore. A responsive web version of d-GDM is also available. The usefulness and accuracy of d-GDM was verify by field tests involving 22 subjects and 5 mobile phone brands. The approval regards user-friendliness and efficiency were 95% or higher. The GDM diagnosis were 100% correct, in this pilot test. d-GDM is a user-friendly, free software for diagnosis that was developed for mobile devices. It has the potential to contribute and facilitate the diagnosis of gestational diabetes for healthcare professionals.


Assuntos
Humanos , Feminino , Gravidez , Técnicas de Apoio para a Decisão , Diabetes Gestacional/diagnóstico , Aplicativos Móveis
16.
Arch Endocrinol Metab ; 63(5): 524-530, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31482958

RESUMO

OBJECTIVE: The aim of the study is to describe a portable and convenient software to facilitate the diagnostics of gestational (GDM) and pre-gestational diabetes (PGDM). MATERIALS AND METHODS: An open source software, d-GDM, was developed in Java. The integrated development environment Android Studio was used as the Android operational system. The software for GDM diagnosis uses the criteria endorsed by the International Association of Diabetes and Pregnancy Study Group, modified by the World Health Organization. RESULTS: GDM diagnosis criteria is not simple to follow, therefore, errors or inconsistencies in diagnosis are expected and could delay the appropriate treatment. The d-GDM, was developed to assist GDM diagnosis with precision and consistency diagnostic reports. The open source software can be manipulated conveniently. The operator requires information regarding the gestational period and selects the appropriate glycaemic marker options from the menu. During operation, pressing the button "diagnosticar" on the screen will present the diagnosis and information for the follow up. d-GDM is available in Portuguese or English and can be downloaded from the Google PlayStore. A responsive web version of d-GDM is also available. The usefulness and accuracy of d-GDM was verify by field tests involving 22 subjects and 5 mobile phone brands. The approval regards user-friendliness and efficiency were 95% or higher. The GDM diagnosis were 100% correct, in this pilot test. d-GDM is a user-friendly, free software for diagnosis that was developed for mobile devices. It has the potential to contribute and facilitate the diagnosis of gestational diabetes for healthcare professionals.


Assuntos
Técnicas de Apoio para a Decisão , Diabetes Gestacional/diagnóstico , Aplicativos Móveis , Feminino , Humanos , Gravidez
18.
Arch Endocrinol Metab ; 61(3): 238-248, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28699988

RESUMO

OBJECTIVE: Gestational diabetes mellitus (GDM) is a metabolic disorder that shares pathophysiologic features with type 2 diabetes mellitus. The aim of this study was to investigate the association of the polymorphisms fat mass and obesity-associated (FTO) rs1421085, leptin receptor (LEPR) rs1137100, rs1137101, peroxisome proliferator-activated receptor gamma (PPARg) rs1801282, and transcription factor 7-like 2 (TCF7L2) rs7901695 with GDM. SUBJECTS AND METHODS: 252 unrelated Euro-Brazilian pregnant women were classified into two groups according to the 2015 criteria of the American and Brazilian Diabetes Association: healthy pregnant women (n = 125) and pregnant women with GDM (n = 127), matched by age. The polymorphisms were genotyped using fluorescent probes (TaqMan®). RESULTS: All groups were in Hardy-Weinberg equilibrium. The genotype and allele frequencies of the studied polymorphisms did not show significant differences between the groups (P > 0.05). In the healthy and GDM groups, the C allele frequencies (95% CI) of the FTO rs1421085 polymorphism were 36.8% [31-43%] and 35.0% [29-41%]; the G allele frequencies (95% CI) of the LEPR rs1137100 polymorphism were 24.8% [19-30%] and 22.8% [18-28%]; the G allele frequencies (95% CI) of the LEPR rs1137101 polymorphism were 43.6% [37-50%] and 42.9% [37-49%]; the G allele frequencies (95% CI) of the PPARg rs1801282 polymorphism were 7.6% [4-11%] and 8.3% [5-12%]; and the C allele frequencies (95% CI) of the TCF7L2 rs7901695 polymorphism were 33.6% [28-39%] and 39.0% [33-45%], respectively. CONCLUSION: The studied polymorphisms were not associated with GDM in a Brazilian population.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Gestacional/genética , PPAR gama/genética , Polimorfismo Genético/genética , Receptores para Leptina/genética , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Adulto , Análise de Variância , Antropometria , Brasil , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/etnologia , Diabetes Gestacional/etnologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Obesidade/genética , Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Estatísticas não Paramétricas
19.
Arch. endocrinol. metab. (Online) ; 61(3): 233-237, May-June 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-887557

RESUMO

ABSTRACT Objectives Advanced glycation end products (AGEs) are involved in the pathogenesis and complications of diabetes mellitus (DM). Gestational DM (GDM) is characterized by increased glycemia and oxidative stress, which are factors associated with high serum AGE concentrations. The aim of this study was to evaluate the utility of a serum fluorescence AGE (F-AGE) method as a screening tool for gestational diabetes. Subjects and methods Serum samples from 225 GDM patients and 217 healthy pregnant women (healthy controls) were diluted 50-fold in phosphate-buffered saline, and the AGEs were estimated by fluorometric analysis (λEx 350 nm/ λEm 440 nm). Results No significant (P > 0.05) differences in AGE concentrations, expressed in Arbitrary Units (UA/mL × 104), were observed in the women with GDM or in the healthy controls. Furthermore, F-AGE concentrations did not change significantly during the pregnancy (12-32 weeks of gestation). Only the GDM group had a positive correlation (r = 0.421; P < 0.001) between F-AGEs and serum creatinine concentrations. Conclusion It was not possible to distinguish women with gestational diabetes from the healthy controls on the basis of serum F-AGE concentrations.


Assuntos
Humanos , Feminino , Gravidez , Adulto , Diabetes Gestacional/sangue , Produtos Finais de Glicação Avançada/sangue , Valores de Referência , Glicemia/análise , Estudos de Casos e Controles , Antropometria , Programas de Rastreamento/métodos , Reprodutibilidade dos Testes , Análise de Variância , Sensibilidade e Especificidade , Idade Gestacional , Diabetes Gestacional/diagnóstico , Estatísticas não Paramétricas , Creatinina/sangue , Fluorometria/métodos
20.
Arch. endocrinol. metab. (Online) ; 61(3): 238-248, May-June 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-887551

RESUMO

ABSTRACT Objective Gestational diabetes mellitus (GDM) is a metabolic disorder that shares pathophysiologic features with type 2 diabetes mellitus. The aim of this study was to investigate the association of the polymorphisms fat mass and obesity-associated (FTO) rs1421085, leptin receptor (LEPR) rs1137100, rs1137101, peroxisome proliferator-activated receptor gamma (PPARg) rs1801282, and transcription factor 7-like 2 (TCF7L2) rs7901695 with GDM. Subjects and methods 252 unrelated Euro-Brazilian pregnant women were classified into two groups according to the 2015 criteria of the American and Brazilian Diabetes Association: healthy pregnant women (n = 125) and pregnant women with GDM (n = 127), matched by age. The polymorphisms were genotyped using fluorescent probes (TaqMan®). Results All groups were in Hardy-Weinberg equilibrium. The genotype and allele frequencies of the studied polymorphisms did not show significant differences between the groups (P > 0.05). In the healthy and GDM groups, the C allele frequencies (95% CI) of the FTO rs1421085 polymorphism were 36.8% [31-43%] and 35.0% [29-41%]; the G allele frequencies (95% CI) of the LEPR rs1137100 polymorphism were 24.8% [19-30%] and 22.8% [18-28%]; the G allele frequencies (95% CI) of the LEPR rs1137101 polymorphism were 43.6% [37-50%] and 42.9% [37-49%]; the G allele frequencies (95% CI) of the PPARg rs1801282 polymorphism were 7.6% [4-11%] and 8.3% [5-12%]; and the C allele frequencies (95% CI) of the TCF7L2 rs7901695 polymorphism were 33.6% [28-39%] and 39.0% [33-45%], respectively. Conclusion The studied polymorphisms were not associated with GDM in a Brazilian population.


Assuntos
Humanos , Feminino , Adulto , Polimorfismo Genético/genética , Diabetes Gestacional/genética , PPAR gama/genética , Diabetes Mellitus Tipo 2/genética , Receptores para Leptina/genética , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Brasil , Estudos de Casos e Controles , Antropometria , Estudos Transversais , Fatores de Risco , Análise de Variância , Diabetes Gestacional/etnologia , Estatísticas não Paramétricas , Diabetes Mellitus Tipo 2/etnologia , Estudos de Associação Genética , Reação em Cadeia da Polimerase em Tempo Real , Frequência do Gene , Genótipo , Obesidade/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA