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1.
Nat Commun ; 12(1): 658, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33510169

RESUMO

A microneedle array is an attractive option for a minimally invasive means to break through the skin barrier for efficient transdermal drug delivery. Here, we report the applications of solid polymer-based ion-conductive porous microneedles (PMN) containing interconnected micropores for improving iontophoresis, which is a technique of enhancing transdermal molecular transport by a direct current through the skin. The PMN modified with a charged hydrogel brings three innovative advantages in iontophoresis at once: (1) lowering the transdermal resistance by low-invasive puncture of the highly resistive stratum corneum, (2) transporting of larger molecules through the interconnected micropores, and (3) generating electroosmotic flow (EOF). In particular, the PMN-generated EOF greatly enhances the transdermal molecular penetration or extraction, similarly to the flow induced by external pressure. The enhanced efficiencies of the EOF-assisted delivery of a model drug (dextran) and of the extraction of glucose are demonstrated using a pig skin sample. Furthermore, the powering of the PMN-based transdermal EOF system by a built-in enzymatic biobattery (fructose / O2 battery) is also demonstrated as a possible totally organic iontophoresis patch.


Assuntos
Sistemas de Liberação de Medicamentos/instrumentação , Sistemas de Liberação de Medicamentos/métodos , Epiderme/metabolismo , Pele/metabolismo , Administração Cutânea , Animais , Dextranos/administração & dosagem , Dextranos/metabolismo , Dextranos/farmacocinética , Eletro-Osmose , Fluoresceína-5-Isotiocianato/administração & dosagem , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/metabolismo , Fluoresceína-5-Isotiocianato/farmacocinética , Glucose/administração & dosagem , Glucose/metabolismo , Glucose/farmacocinética , Humanos , Iontoforese/instrumentação , Iontoforese/métodos , Masculino , Microinjeções , Agulhas , Padrões Moleculares Associados a Patógenos/administração & dosagem , Padrões Moleculares Associados a Patógenos/metabolismo , Padrões Moleculares Associados a Patógenos/farmacocinética , Porosidade , Suínos
2.
Life Sci ; 271: 119114, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33513399

RESUMO

AIMS: Epidemiological studies indicate diabetes mellitus and hyperglycemia as risk factors of cancers including cholangiocarcinoma (CCA). How high glucose promotes cancer development and progression, however, is still unrevealed. In this study, insight into the molecular pathway of high glucose promoting progression of CCA cells was investigated. MAIN METHODS: Human CCA cell lines, KKU-213A and KKU-213B were cultured in normal glucose (NG; 5.56 mM) or high glucose (HG; 25 mM) and used as NG and HG cells. Forkhead box M1 (FOXM1) expression was transiently suppressed using siFOXM1. Western blotting and image analysis were employed to semi-quantitatively determine the expression levels of the specified proteins. The migration and invasion of CCA cells were revealed using Boyden chamber assays. KEY FINDINGS: All HG cells exhibited higher expression of FOXM1 than the corresponding NG cells in a dose dependent manner. Suppression of FOXM1 expression by siFOXM1 significantly reduced migration and invasion abilities of CCA cells by suppression of Slug and MMP2 expression. Inhibition of STAT3 activation using Stattic, significantly suppressed expression of FOXM1 and Slug and decreased migration and invasion abilities of HG cells. In addition, EGFR expression was significantly higher in HG cells than NG cells and increased dependently with glucose concentration. Inhibition of EGFR activation by cetuximab significantly suppressed STAT3 activation and FOXM1 expression. SIGNIFICANCE: The mechanism of high glucose promoting progression of CCA cells was revealed to be via in part by upregulation of FOXM1 expression under EGF/EGFR and STAT3 dependent activation.


Assuntos
Neoplasias dos Ductos Biliares/metabolismo , Colangiocarcinoma/metabolismo , Proteína Forkhead Box M1/biossíntese , Glucose/toxicidade , Fator de Transcrição STAT3/metabolismo , Neoplasias dos Ductos Biliares/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Colangiocarcinoma/genética , Progressão da Doença , Relação Dose-Resposta a Droga , Receptores ErbB/metabolismo , Proteína Forkhead Box M1/genética , Regulação Neoplásica da Expressão Gênica , Glucose/administração & dosagem , Humanos , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia
3.
Food Chem ; 339: 127813, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32916401

RESUMO

Bisphenol S (BPS), a structural analog of Bisphenol A (BPA), has been widely used as a substitute for epoxy resin, food packaging materials, and other products due to the limited application of BPA. Studies in vivo and in vitro have indicated that BPA could induce fat accumulation like an obesogen. The main goal of this study was to investigate the role and mechanism of BPS in lipid metabolism using Caenorhabditis elegans (C. elegans) as a model. Results showed that both the overall fat deposition and the triglyceride level were significantly increased in a non-monotonically increasing trend, and the low dose of BPS (0.01 µM) exhibited a stronger influence. Additionally, BPS enhanced fat synthesis depending on daf-16, fat-5, fat-6 and fat-7, and inhibited fatty acid oxidation via nhr-49 and acs-2. This study further indicate that fat accumulation induced by BPS requires nhr-49, which also mediated the nuclear hormone signaling pathway.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Glucose/efeitos adversos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fenóis/toxicidade , Sulfonas/toxicidade , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Dieta/efeitos adversos , Gorduras/metabolismo , Ácidos Graxos/metabolismo , Glucose/administração & dosagem , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Triglicerídeos/metabolismo
4.
Medicine (Baltimore) ; 99(46): e23201, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33181700

RESUMO

OBJECTIVES: Prolotherapy or proliferative therapy is a treatment option for damaged connective tissues involving the injection of a solution (proliferant) which theoretically causes an initial cell injury and a subsequent "proliferant" process of wound healing via modulation of the inflammatory process. Nonetheless, the benefits of dextrose prolotherapy have not been adequately evaluated. Therefore, the present study assesses the effectiveness and superiority of prolotherapy separately in treating dense fibrous connective tissue injuries. METHODS: PubMed, Scopus, and Embase were searched from the earliest record to February 18, 2019. This study included randomized controlled trials whichBoth analysis at individual studies level and pooled meta-analysis were performed. RESULTS: Ten trials involving 358 participants were included for review. At study level, the majority of comparisons did not reveal significant differences between dextrose prolotherapy and no treatment (or placebo) regarding pain control. The meta-analysis showed dextrose prolotherapy was effective in improving activity only at immediate follow-up (i.e., 0-1 month) (standardized mean difference [SMD]: 0.98; 95% confidence interval [CI]: 0.40-1.50; I = 0%); and superior to corticosteroid injections only in pain reduction at short-term follow-up (i.e., 1-3 month) (SMD: 0.70; 95% CI: 0.14-1.27; I = 51%). No other significant SMDs were found in this analysis. CONCLUSIONS: There is insufficient evidence to support the clinical benefits of dextrose prolotherapy in managing dense fibrous tissue injuries. More high-quality randomized controlled trials are warranted to establish the benefits of dextrose prolotherapy. REVIEW REGISTRATION: PROSPERO (CRD42019129044).


Assuntos
Fáscia/efeitos dos fármacos , Glucose/uso terapêutico , Ligamentos/efeitos dos fármacos , Proloterapia/métodos , Tendinopatia/tratamento farmacológico , Fáscia/lesões , Glucose/administração & dosagem , Humanos , Ligamentos/lesões , Metanálise como Assunto , Proloterapia/instrumentação , Revisões Sistemáticas como Assunto
6.
Gene ; 760: 144992, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32721474

RESUMO

BACKGROUND AND AIM: Diabetic retinopathy is a severe diabetic complication and a major cause of blindness. In this study, we explored the role of circ_0001879 in retinal vascular dysfunction under diabetic conditions. METHODS: Human retinal microvascular endothelial cells (HRMECs) were divided into normal glucose group (NG, 5.5 mmol/L d-glucose), high glucose group (HG, 25 mmol/L d-glucose), and osmotic control group (5.5 mmol/L d-glucose + 19.5 mmol/L mannitol). The expression of circ_0001879 and miR-30-3p was assessed via qRT-PCR. The circ_0001879/miR-30-3p roles in retinal vascular dysfunction were investigated through Cell Counting Kit-8 and Transwell assay. Bioinformatics analysis and luciferase reporter assays were applied to examine interactions between circ_0001879 and miR-30-3p in HRMECs. RESULTS: The relative circ_0001879 expression was remarkably increased in diabetic retinas group than that in the control group. Silencing circ_0001879 suppressed the proliferation and migration of HRMECs under high-glucose conditions. In addition, circ_0001879 acted as a binding platform and miRNA sponge for miR-30-3p. Circ_0001879 modulated the function of HRMECs via targeting miR-30-3p. CONCLUSION: Silencing circ_0001879 inhibited the proliferation and migration of HRMECs under high-glucose conditions via modulating miR-30-3p, which might shed new light on a novel potentially marker and molecular therapeutic target for diabetic retinopathy.


Assuntos
Retinopatia Diabética/patologia , Glucose/administração & dosagem , MicroRNAs/genética , Vasos Retinianos/patologia , Animais , Linhagem Celular , Movimento Celular/genética , Proliferação de Células/genética , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Glucose/metabolismo , Humanos , Masculino , MicroRNAs/metabolismo , Ratos , Ratos Sprague-Dawley , Retina/efeitos dos fármacos , Retina/metabolismo , Retina/patologia , Vasos Retinianos/efeitos dos fármacos , Vasos Retinianos/metabolismo
7.
Obstet Gynecol ; 136(2): 411-416, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32649492

RESUMO

OBJECTIVE: To examine whether an insulin protocol for intrapartum glucose control among parturients with diabetes was associated with improved outcomes. METHODS: This is a retrospective cohort study of women with pregestational or gestational diabetes delivering a liveborn neonate at Northwestern Memorial Hospital. Before 2011, women with diabetes were given intravenous (IV) insulin or glucose during labor at the discretion of the on-call endocrinologist. In 2011, a standardized protocol was designed to titrate insulin and glucose infusions. Outcomes were compared between two time periods: January 2005-December 2010 (before implementation) and January 2012-December 2017 (after implementation) with 2011 excluded to account for a phase-in period. Maternal outcomes included intrapartum hyperglycemia (blood glucose greater than 125 mg/dL) and hypoglycemia (blood glucose less than 60 mg/dL). Neonatal outcomes included hypoglycemia (blood glucose less than 50 mg/dL), intensive care admission, and IV dextrose therapy. t tests, Wilcoxon rank sum tests, and χ tests were used for bivariable analyses. Linear and logistic multivariable regression were used to account for confounding factors. RESULTS: Of 3,689 women, 928 (25.2%) delivered before 2011. After protocol implementation, frequencies of both maternal intrapartum hyperglycemia (51.3% vs 37.9%) and hypoglycemia decreased (6.1% vs 2.5%), both P<.001; respective adjusted odds ratio [aOR] 0.64, 95% CI 0.54-0.77 and 0.50, 95% CI 0.33-0.78. The frequency of neonatal hypoglycemia, however, increased (36.6% vs 49.2%, P<.001; aOR 1.73, 95% CI 1.45-2.07). Admission to the neonatal intensive care unit and need for IV dextrose therapy were similar across time periods. CONCLUSION: A formal protocol to manage insulin and glucose infusions for parturients with diabetes was associated with improved intrapartum maternal glucose control, but an increased frequency of neonatal hypoglycemia.


Assuntos
Diabetes Gestacional/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Trabalho de Parto , Gravidez em Diabéticas/tratamento farmacológico , Adulto , Glicemia/análise , Protocolos Clínicos/normas , Diabetes Mellitus/tratamento farmacológico , Feminino , Glucose/administração & dosagem , Humanos , Hiperglicemia/epidemiologia , Hipoglicemia/epidemiologia , Infusões Intravenosas , Unidades de Terapia Intensiva Neonatal , Gravidez , Estudos Retrospectivos
8.
Medicine (Baltimore) ; 99(24): e20283, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541452

RESUMO

RATIONALE: There is an increasing and compelling need for early recognition of features of osmotic demyelination syndrome (ODS), and a further attempt at correcting this even where presentation is late. PATIENT CONCERNS: A 49-year-old male admitted into the emergency department with a complaint of lethargy and severe hyponatremia, with subsequent ODS supervening on initial attempts at correction. DIAGNOSIS: Rapid rise in serum sodium concentration (121 mmol/L in 8 hours from a nadir of 101 mmol/L), concomitant deterioration in patient's conscious level support the diagnosis of ODS. INTERVENTION: Concomitant administration of 5% dextrose water with desmopressin with a therapeutic objective of gradual relowering of serum sodium concentration. OUTCOMES: Significant improvement in patients' conscious level and motor function with the commencement of sodium relowering therapy. The patient was eventually discharged home. LESSONS: Regardless of the temporal profile of neurologic sequelae following ODS due to hyponatremia, its worthwhile attempting initial sodium relowering with dextrose 5% and desmopressin and then monitoring of biochemical and neurologic markers.


Assuntos
Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/terapia , Hiponatremia/complicações , Antidiuréticos/administração & dosagem , Antidiuréticos/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Desamino Arginina Vasopressina/administração & dosagem , Desamino Arginina Vasopressina/uso terapêutico , Doenças Desmielinizantes/sangue , Doenças Desmielinizantes/diagnóstico , Quimioterapia Combinada/métodos , Glucose/administração & dosagem , Glucose/uso terapêutico , Humanos , Hiponatremia/terapia , Doença Iatrogênica , Letargia/etiologia , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Solução Salina Hipertônica/efeitos adversos , Sódio/sangue , Edulcorantes/administração & dosagem , Edulcorantes/uso terapêutico , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
9.
J Vasc Access ; 21(6): 945-952, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32364801

RESUMO

BACKGROUND: Administering a separator fluid between incompatible solutions can optimize the use of intravenous lumens. Factors affecting the required separator fluid volume to safely separate incompatible solutions are unknown. METHODS: An intravenous tube (2-m, 2-mL, 6-French) containing methylene blue dye was flushed with separator fluid until a methylene blue concentration ⩽2% from initial was reached. Independent variables were administration rate, dye solvent (glucose 5% and NaCl 0.9%), and separator fluid. In the second part of the study, methylene blue, separator fluid, and eosin yellow were administered in various administration profiles using 2- and 4-mL (2 × 2 m, 4-mL, 6-French) intravenous tubes. RESULTS: Neither administration rate nor solvent affected the separator fluid volume (p = 0.24 and p = 0.12, respectively). Glucose 5% as separator fluid required a marginally smaller mean ± SD separator fluid volume than NaCl 0.9% (3.64 ± 0.13 mL vs 3.82 ± 0.11 mL, p < 0.001). Using 2-mL tubing required less separator fluid volume than 4-mL tubing for methylene blue (3.89 ± 0.57 mL vs 4.91 ± 0.88 mL, p = 0.01) and eosin yellow (4.41 ± 0.56 mL vs 5.63 ± 0.15 mL, p < 0.001). Extended tubing required less separator fluid volume/mL of tubing than smaller tubing for both methylene blue (2 vs 4 mL, 1.54 ± 0.22 vs 1.10 ± 0.19, p < 0.001) and eosin yellow (2 vs 4 mL, 1.75 ± 0.22 vs 1.25 ± 0.03, p < 0.001). CONCLUSION: The separator fluid volume was neither affected by the administration rate nor by solvent. Glucose 5% required a marginally smaller separator fluid volume than NaCl 0.9%, however its clinical impact is debatable. A larger intravenous tubing volume requires a larger separator fluid volume. However, the ratio of separator fluid volume to the tubing's volume decreases as the tubing volume increases.


Assuntos
Sistemas de Liberação de Medicamentos/instrumentação , Amarelo de Eosina-(YS)/administração & dosagem , Bombas de Infusão , Azul de Metileno/administração & dosagem , Desenho de Equipamento , Glucose/administração & dosagem , Infusões Intravenosas , Teste de Materiais , Cloreto de Sódio/administração & dosagem , Solventes/administração & dosagem , Fatores de Tempo
10.
J Dairy Sci ; 103(7): 6218-6232, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32418692

RESUMO

Amino acids and glucose have been shown to regulate protein synthesis in the mammary gland through their effects on cellular signaling pathways. Acetate might also have an effect on protein synthesis via the AMP-activated kinase signaling pathway, because it is the main energy source for the mammary secretory cell. Thus, the objective of this experiment was to evaluate the effects of casein and energy-yielding nutrients (acetate and glucose), and their combination, on performance and mammary metabolism. Six multiparous Holstein cows, averaging 49 kg of milk/d, were used in a 6 × 6 Latin square design with 14-d periods. Cows were fed to 100% National Research Council requirements for metabolizable protein (MP) and energy (ME) for 9 d, after which they were feed-restricted for 5 d to 85% of their individual ad libitum intake and then abomasally infused with 1 of 6 treatments. Treatments were acetate (A), glucose (G), each at 5% of ad libitum ME intake, casein (C) at 15% of ad libitum MP intake, A + C, G + C, or a saline solution (negative control). Casein infused alone increased milk protein yield numerically, with 25% recovery of the infused casein in milk protein. Glucose infused alone increased milk and milk protein yield and promoted the highest efficiency of nitrogen utilization (37%), with an efficiency of MP use for milk protein of 58%. We discovered no effect of treatment on mammary plasma flow, and the increase in milk protein yield with glucose infusion was brought about by greater mammary AA clearance rate. Infusion of casein and glucose together further increased milk protein yield in an additive fashion, and 47% of the infused casein was recovered in milk protein. Acetate infused alone had no effect on milk protein yield but increased milk fat yield numerically, suggesting that the greater amount of acetate taken up by the mammary gland was used for milk fat synthesis. Infusion of acetate and casein together yielded responses similar to those of casein alone. In conclusion, glucose has a major effect on stimulating milk protein synthesis, and the mammary gland has the ability to increase its supply of nutrients to match its synthetic capacity.


Assuntos
Caseínas/administração & dosagem , Bovinos , Glucose/administração & dosagem , Glândulas Mamárias Animais/metabolismo , Proteínas do Leite/biossíntese , Abomaso/metabolismo , Acetatos/análise , Aminoácidos/metabolismo , Animais , Caseínas/metabolismo , Feminino , Hipersensibilidade Alimentar , Trato Gastrointestinal , Glucose/metabolismo , Lactação/fisiologia , Glândulas Mamárias Animais/efeitos dos fármacos , Leite/química , Proteínas do Leite/análise , Biossíntese de Proteínas
11.
Transplant Proc ; 52(6): 1794-1797, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32444123

RESUMO

BACKGROUND AND PURPOSE: The purpose of this study was to identify the quantitative amount of glucose load, which maintained the blood glucose levels between 100 and 180 mg/dL in patients with and without diabetes mellitus (DM) undergoing living donor liver transplantation (LDLT). METHODS AND PATIENTS: The anesthesia records of 477 adult LDLT patients were reviewed retrospectively. The total amount of glucose loads and the changes in blood glucose between groups were compared by using Mann-Whitney U test. One-year patient survival between groups was compared with Pearson's χ2 test. A P value of <.05 was considered statistically significant. RESULTS: Eighty patients diagnosed with DM, who were all type II except one, were placed in group 1 (G1); and 397 patients without DM were placed in group 2 (G2). Table 1 shows that G1 received significantly less glucose loads in comparison to G2, but all the measured blood glucose levels, except in the reperfusion phase, were significantly higher in G1 than in G2. Both groups received glucose loads of 0.342 ± 0.191 and 0.774 ± 0.191 mg/kg/min for G1 and G2, respectively. No difference in 1-year survival between groups was observed. CONCLUSION: Patients with DM required significantly lower glucose loads compared to patients without DM.


Assuntos
Glicemia/análise , Diabetes Mellitus/cirurgia , Glucose/administração & dosagem , Hepatopatias/cirurgia , Transplante de Fígado/métodos , Adulto , Diabetes Mellitus/sangue , Diabetes Mellitus/tratamento farmacológico , Feminino , Humanos , Hepatopatias/sangue , Hepatopatias/mortalidade , Transplante de Fígado/mortalidade , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não Paramétricas , Adulto Jovem
12.
J Nutr ; 150(7): 1790-1798, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32470978

RESUMO

BACKGROUND: Dietary carbohydrate affects intestinal glucose absorption and lipid deposition, but the underlying mechanisms are unknown. OBJECTIVES: We used yellow catfish and their isolated intestinal epithelial cells (IECs) to test the hypothesis that sodium/glucose cotransporters (SGLTs) 1/2 and acetylated carbohydrate response element binding protein (ChREBP) mediated glucose-induced changes in glucose absorption and lipid metabolism. METHODS: Yellow catfish (mean ± SEM weight: 4.68 ± 0.02 g, 3 mo old, mixed sex) were fed diets containing 250 g carbohydrates/kg from glucose (G, control), corn starch (CS), sucrose (S), potato starch (PS), or dextrin (D) for 10 wk. IECs were isolated from different yellow catfish and incubated for 24 h in a control or glucose (15 mM) solution with or without a 2-h pretreatment with an inhibitor [sotagliflozin (LX-4211) or tubastatin A (TBSA)]. Human embryonic kidney cells (HEK293T cells) were transfected with a Flag-ChREBP plasmid to explore ChREBP acetylation. Triglyceride (TG) and glucose concentrations and enzymatic activities were measured in the intestine and IECs of yellow catfish. They also were subjected to immunofluorescence, immunoprecipitation, qPCR, and immunoblotting. Immunoblotting and immunoprecipitation were performed with HEK293T cells. RESULTS: The G group had greater intestine TGs (0.99- to 2.30-fold); activities of glucose 6-phospate dehydrogenase, 6-phosphogluconate dehydrogenase, and isocitrate dehydrogenase (0.12- to 2.10-fold); and expression of lipogenic genes (0.32- to 2.34-fold) than the CS, PS, and D groups. The G group had greater intestine sglt1/2 mRNA and protein expression than the CS, S and D groups (0.35- to 1.12-fold and 0.40- to 4.67-fold, respectively), but lower mRNA amounts of lipolytic genes (48.6%-65.8%) than the CS and PS groups. LX-4211 alleviated the glucose-induced increase in sglt1/2 mRNA (38.2%-47.4%) and SGLT1 protein (48.0%) expression, TGs (29.3%), and lipogenic enzyme activities (27.7%-42.1%) and gene expression (38.0%-55.5%) in the IECs. TBSA promoted the glucose-induced increase in TGs (11.3%), fatty acid synthase activity (32.6%), and lipogenic gene expression (21.6%-34.4%) in the IECs and acetylated ChREBP (10.5%) in HEK293T cells. CONCLUSIONS: SGLT1/2 signaling and acetylated ChREBP mediated glucose-induced changes in glucose absorption and lipid metabolism in the intestine and IECs of yellow catfish.


Assuntos
Peixes-Gato/fisiologia , Dieta/veterinária , Glucose/administração & dosagem , Mucosa Intestinal/efeitos dos fármacos , Transportador 1 de Glucose-Sódio/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Transporte Biológico , Glicemia , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Metabolismo dos Lipídeos , Transdução de Sinais , Transportador 1 de Glucose-Sódio/genética , Transportador 2 de Glucose-Sódio/genética , Triglicerídeos
13.
Invest Ophthalmol Vis Sci ; 61(4): 38, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32340033

RESUMO

Purpose: To test the hypothesis that hyperglycemia perturbs neurovascular\ coupling and compromises retinal vascular response during transition from dark to light in healthy subjects using optical coherence tomography angiography (OCTA). Methods: Ten eyes of 10 healthy subjects were tested, first during fasting and then after receiving a 75-g oral glucose solution. In both sessions, OCTA imaging was done in the dark-adapted state and at 50 seconds, 2 minutes, 5 minutes, and 15 minutes of ambient light. Parafoveal vessel density (VD) and adjusted flow index (AFI) were calculated for the superficial capillary plexus (SCP), middle capillary plexus (MCP), and deep capillary plexus (DCP), and vessel length density was calculated for the SCP. These measurements were compared among conditions after adjusting for age, refractive error, and OCTA scan quality. Results: Hyperglycemia leads to a complete reversal of dark/light adaptation trends in VD and AFI in all layers of the inner retina. In the dark, there is significantly decreased VD in the DCP in hyperglycemia. With a transition to light in hyperglycemia, we observed decreased VD in the SCP, increased vessel density in the MCP and DCP, and decreased AFI in all three layers. Conclusions: Our results show that hyperglycemia significantly disrupts neurovascular coupling in healthy eyes, with potential metabolic deficits affecting photoreceptor oxygen demands during dark adaptation and the inner retina during light exposure. In pathological states, such as diabetic retinopathy, where the vasculature is already attenuated, retinal neurons may be exquisitely vulnerable to intermittent hyperglycemic challenge, which should be the focus of future studies.


Assuntos
Adaptação Ocular/fisiologia , Adaptação à Escuridão/fisiologia , Glucose/efeitos adversos , Hiperglicemia/complicações , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Adulto , Estudos de Coortes , Retinopatia Diabética/diagnóstico por imagem , Retinopatia Diabética/fisiopatologia , Feminino , Glucose/administração & dosagem , Voluntários Saudáveis , Humanos , Modelos Lineares , Masculino , Acoplamento Neurovascular , Variações Dependentes do Observador , Estudos Prospectivos , Vasos Retinianos/patologia , Medição de Risco
14.
Int J Infect Dis ; 96: 61-67, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32339722

RESUMO

OBJECTIVES: To reduce childhood mortality from severe malaria by implementing the World Health Organization's standardized malarial treatment protocol. DESIGN: Observational study comparing the mortality rate from malaria before and after the intervention. SETTING: Inpatient pediatric ward in a district referral hospital of Sierra Leone. PARTICIPANTS: A total of 1298 pediatric patients (ages 0-13 years, male and female) received the intervention, representing 100% of the pediatric patients admitted with severe malaria during the dates of implementation (there were no exclusion criteria). INTERVENTIONS: We implemented the World Health Organization's standardized malarial protocol on September 30, 2015. Based on monthly run reports of mortality and root cause analysis, we adapted the malaria protocol by adding sublingual glucose as a treatment to target hypoglycemia complications in March 2016. MAIN OUTCOME MEASURES: The primary outcome was a change in monthly percent mortality from severe malaria, and the secondary outcome was the percent of mortality attributed to hypoglycemia. RESULTS: The monthly average percent mortality from severe malaria dropped from 9% to 3.6% after the intervention, which was borderline statistically significant (p 0.06, CI 95% 1.5 to 5.6). The secondary outcome, percent of malarial deaths attributable to hypoglycemia via chart reviews, dropped from 83% to 44% across the study period. There was an increase in the average number of admissions for severe malaria from 71 to 153 children per month in the second half of the year (range from 49-212 per month). CONCLUSION: Implementing the WHO malaria treatment protocol with bedside tracking of protocol steps reduced malaria mortality and improved our ward's efficiency without adding any human or medical resources.


Assuntos
Glucose/uso terapêutico , Malária/mortalidade , Administração Sublingual , Adolescente , Criança , Pré-Escolar , Feminino , Glucose/administração & dosagem , Hospitalização , Humanos , Hipoglicemia/complicações , Hipoglicemia/tratamento farmacológico , Hipoglicemia/mortalidade , Lactente , Recém-Nascido , Malária/complicações , Malária/terapia , Masculino , Melhoria de Qualidade , Serra Leoa , Organização Mundial da Saúde
15.
PLoS One ; 15(4): e0231958, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32310996

RESUMO

BACKGROUND: It is reported that postoperative nausea and vomiting, common general anesthesia complications, may be prevented by perioperative intravenous dextrose administration, but with controversial clinical effectiveness. OBJECTIVE: To evaluate perioperative intravenous dextrose for preventing postoperative nausea and vomiting through a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis. DATA SOURCES: MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, clinicaltrials.gov, and the University Hospital Medical Information Network Clinical Trials Registry were searched from inception until 22 June 2019. ELIGIBILITY CRITERIA: Trials investigating intravenous dextrose effects vs. placebos on postoperative nausea and vomiting in patients who underwent general anesthesia. RESULTS: Eleven trials (1,250 patients) were included. All participants were ASA1-2. The nine trials included laparoscopic surgeries, and 92.2% of the participants were women. The timing of dextrose infusion was before, during, and after surgery in three, five, and three trials, respectively. Our results revealed intravenous dextrose administration significantly reduced postoperative nausea, but not vomiting, during early and late postoperative periods (risk ratio [95% confidence interval], early nausea: 0.76 [0.59-0.99], late nausea: 0.65 [0.48-0.89]; early vomiting: 1.00 [0.81-1.25], late vomiting: 0.96 [0.43-2.16]). Evidence quality was downgraded to low because the trial sequential analysis indicated more trials are needed for firm conclusions. CONCLUSIONS: Compared with placebos, perioperative intravenous dextrose administration may decrease postoperative nausea but not vomiting. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (registration number: UMIN000030901).


Assuntos
Glucose/administração & dosagem , Náusea e Vômito Pós-Operatórios/prevenção & controle , Administração Intravenosa , Glicemia/análise , Bases de Dados Factuais , Glucose/efeitos adversos , Humanos , Risco
16.
Arch Phys Med Rehabil ; 101(8): 1296-1303, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32325164

RESUMO

OBJECTIVE: To assess the effects of perineural corticosteroid and 5% dextrose water (D5W) injections in patients with mild to moderate ulnar neuropathy at the elbow (UNE). DESIGN: Prospective, randomized, double-blind, controlled trial (6-month follow-up). SETTING: Outpatients of local medical center settings. PARTICIPANTS: Patients (N=36) with mild to moderate UNE were randomized, and 33 participants were included in the final data analysis. INTERVENTIONS: Patients were administered a single perineural injection with 5 mL D5W and 3 mL corticosteroid (triamcinolone acetonide, 10mg/mL) mixed with 2 mL normal saline under ultrasound guidance in the dextrose and steroid groups, respectively. MAIN OUTCOME MEASURES: The visual analog scale digital pain or paresthesia/dysesthesia score was the primary outcome. The secondary outcomes were the Disabilities of the Arm, Shoulder, and Hand questionnaire, motor nerve conduction velocity, and cross-sectional area (CSA) of the ulnar nerve. The measurement assessment was conducted before and 1, 3, 4, and 6 months after injection. RESULTS: Thirty-three patients completed the study. Both injections were found to be equally effective at most measurement points, although the dextrose group experienced larger reductions in symptom severity and CSA of the ulnar nerve from the third month onward. CONCLUSIONS: We suggest D5W as a more suitable injectate for perineural injection in patients with UNE.


Assuntos
Anti-Inflamatórios/uso terapêutico , Glucose/uso terapêutico , Triancinolona Acetonida/uso terapêutico , Neuropatias Ulnares/tratamento farmacológico , Adulto , Idoso , Anti-Inflamatórios/administração & dosagem , Método Duplo-Cego , Cotovelo , Feminino , Seguimentos , Glucose/administração & dosagem , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Condução Nervosa , Dor/etiologia , Medição da Dor , Parestesia/etiologia , Estudos Prospectivos , Inquéritos e Questionários , Triancinolona Acetonida/administração & dosagem , Nervo Ulnar/diagnóstico por imagem , Neuropatias Ulnares/complicações , Neuropatias Ulnares/fisiopatologia , Ultrassonografia , Extremidade Superior/fisiopatologia
17.
Gen Comp Endocrinol ; 293: 113478, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32243957

RESUMO

This study identified an insulin-like peptide (ILP) in Macrobrachium rosenbergii termed Mr-ILP and further investigated its function through glucose injection and RNAi. With the analysis of five other glucose metabolism related genes, this study shed light on the molecular mechanism of carbohydrate metabolism in crustaceans. Mr-ILP shared the typical skeleton with six conserved cysteine and mainly expressed in neuroendocrine system. In M. rosenbergii, the elevated hemolymph glucose concentration after glucose injection returned to basal levels in short time, implying an efficient regulatory system in carbohydrate metabolism. Hyperglycemic related genes answered the elevated hemolymph glucose concentration quickly with significant decreased expression level, while Mr-ILP showed delayed response. Instead, glycolysis increased after glucose injection, which indicated glycolysis might play an important role in lowering the abnormally high glucose level. In vivo silencing of Mr-ILP, by injecting the prawns with double-stranded RNA (dsRNA) for 21 days reduced its expression by approximately 75%. Accordingly, glycogen synthase decreased and the trehalose and glycogen level in the hepatopancreas were significantly reduced, indicating the function of Mr-ILP in oligosaccharide and polysaccharide accumulation. When Mr-ILP was silenced, the expression of hyperglycemic related genes were enhanced, but the hemolymph glucose level was not elevated significantly, which might attribute to the increased glycolysis to keep a balanced glucose level in hemolymph.


Assuntos
Metabolismo dos Carboidratos , Insulina/metabolismo , Palaemonidae/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Metabolismo dos Carboidratos/genética , DNA Complementar/genética , Feminino , Regulação da Expressão Gênica , Glucose/administração & dosagem , Hemolinfa/metabolismo , Insulina/química , Insulina/genética , Masculino , Palaemonidae/genética , Filogenia
18.
Br J Anaesth ; 124(6): 693-701, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32245569

RESUMO

BACKGROUND: This study assessed whether i.v. sildenafil citrate prevented acute kidney injury in at-risk patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: In a double-blind RCT, adults at increased risk of acute kidney injury undergoing cardiac surgery in a single UK tertiary centre were randomised to receive sildenafil citrate 12.5 mg kg-1 i.v. over 150 min or dextrose 5% at the commencement of surgery. The primary outcome was serum creatinine measured at six post-randomisation time points. The primary analysis used a linear mixed-effects model adjusted for the stratification variables, baseline estimated glomerular filtration rate, and surgical procedure. Secondary outcomes considered clinical events and potential disease mechanisms. Effect estimates were expressed as mean differences (MDs) or odds ratios with 95% confidence intervals. RESULTS: The analysis population comprised eligible randomised patients that underwent valve surgery or combined coronary artery bypass graft and valve surgery, with cardiopulmonary bypass, between May 2015 and June 2018. There were 60 subjects in the sildenafil group and 69 in the placebo control group. The difference between groups in creatinine concentration was not statistically significant (MD: 0.88 µmol L-1 [-5.82, 7.59]). There was a statistically significant increase in multiple organ dysfunction scores in the sildenafil group (MD: 0.54 [0.02, 1.07]; P=0.044). Secondary outcomes, and biomarkers of kidney injury, endothelial function, and inflammatory cell activation, were not significantly different between the groups. CONCLUSIONS: These results do not support the use of i.v. sildenafil citrate for kidney protection in adult cardiac surgery. CLINICAL TRIAL REGISTRATION: ISRCTN18386427.


Assuntos
Lesão Renal Aguda/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Inibidores da Fosfodiesterase 5/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Citrato de Sildenafila/uso terapêutico , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Glucose/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Fosfodiesterase 5/administração & dosagem , Citrato de Sildenafila/administração & dosagem , Reino Unido
19.
J Nutr ; 150(7): 1765-1772, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32297937

RESUMO

BACKGROUND: Fructose ingestion with a high-fat beverage increases postprandial lipemia when compared with glucose. It is unknown whether other sugars, such as galactose, also increase postprandial lipemia. OBJECTIVES: The objective was to assess whether galactose ingestion within a high-fat beverage increases postprandial lipemia relative to glucose or fructose. METHODS: Two experiments were conducted, which contrasted different test drinks under otherwise standardized conditions. In Experiment 1, 10 nonobese men (age: 22 ± 1 y; BMI, 23.5 ± 2.2 kg/2) ingested either galactose or glucose (0.75 g supplemented carbohydrate per⋅kilogram body mass) within a high-fat test drink (0.94 g fat per kilogram body mass). In Experiment 2, a separate group of 9 nonobese men (age: 26 ± 6 y; BMI: 23.5 ± 2.6 kg/m2) ingested either galactose or fructose (identical doses as those in Experiment 1) within the same high-fat test drink. Capillary blood was sampled before and at frequent intervals after ingestion of the test drinks for a 300-min period to determine plasma triacylglycerol, glucose, lactate, nonesterified fatty acid, and insulin concentrations. Paired t tests and 2-way, repeated-measures ANOVA were used to compare conditions within each experiment. RESULTS: The incremental AUC for triacylglycerol was greater following galactose ingestion compared with glucose (127 ± 59 compared with 80 ± 48 mmol⋅L-1 × 300 min, respectively; P = 0.04) but not compared with fructose (136 ± 74 compared with 133 ± 63 mmol⋅L-1 ×300 min, respectively; P = 0.91). Plasma lactate concentrations also increased to a greater extent with galactose compared with glucose ingestion (time-condition interaction: P < 0.001) but not fructose ingestion (time-condition interaction: P = 0.17). CONCLUSIONS: Galactose ingestion within a high-fat beverage exacerbates postprandial lipemia and plasma lactate concentrations compared with glucose but not fructose in nonobese men. These data suggest that galactose metabolism may be more similar to fructose than to glucose, providing a rationale to reassess the metabolic fate of galactose ingestion in humans. This trial was registered at clinicaltrials.gov as NCT03439878.


Assuntos
Bebidas/análise , Gorduras na Dieta/administração & dosagem , Frutose/administração & dosagem , Galactose/administração & dosagem , Glucose/administração & dosagem , Lipídeos/sangue , Adulto , Glicemia , Carboidratos da Dieta/administração & dosagem , Humanos , Masculino , Período Pós-Prandial , Adulto Jovem
20.
Cancer Res ; 80(11): 2243-2256, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32273282

RESUMO

Epigenetic regulation of gene transcription has been shown to coordinate with nutrient availability, yet the mechanisms underlying this coordination remain incompletely understood. Here, we show that glucose starvation suppresses histone 2A K119 monoubiquitination (H2Aub), a histone modification that correlates with gene repression. Glucose starvation suppressed H2Aub levels independently of energy stress-mediated AMP-activated protein kinase activation and possibly through NADPH depletion and subsequent inhibition of BMI1, an integral component of polycomb-repressive complex 1 (PRC1) that catalyzes H2Aub on chromatin. Integrated transcriptomic and epigenomic analyses linked glucose starvation-mediated H2Aub repression to the activation of genes involved in the endoplasmic reticulum (ER) stress response. We further showed that this epigenetic mechanism has a role in glucose starvation-induced cell death and that pharmacologic inhibition of glucose transporter 1 and PRC1 synergistically promoted ER stress and suppressed tumor growth in vivo. Together, these results reveal a hitherto unrecognized epigenetic mechanism coupling glucose availability to the ER stress response. SIGNIFICANCE: These findings link glucose deprivation and H2A ubiquitination to regulation of the ER stress response in tumor growth and demonstrate pharmacologic susceptibility to inhibition of polycomb and glucose transporters.


Assuntos
Estresse do Retículo Endoplasmático/genética , Glucose/metabolismo , Histonas/genética , Histonas/metabolismo , Neoplasias Renais/genética , Neoplasias Pulmonares/genética , Animais , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/metabolismo , Morte Celular/fisiologia , Linhagem Celular Tumoral , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Glucose/administração & dosagem , Glucose/deficiência , Transportador de Glucose Tipo 1/antagonistas & inibidores , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Células HEK293 , Xenoenxertos , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Fosforilação , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 1/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Ubiquitinação
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