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1.
Nat Commun ; 12(1): 5068, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417460

RESUMO

p53 regulates several signaling pathways to maintain the metabolic homeostasis of cells and modulates the cellular response to stress. Deficiency or excess of nutrients causes cellular metabolic stress, and we hypothesized that p53 could be linked to glucose maintenance. We show here that upon starvation hepatic p53 is stabilized by O-GlcNAcylation and plays an essential role in the physiological regulation of glucose homeostasis. More specifically, p53 binds to PCK1 promoter and regulates its transcriptional activation, thereby controlling hepatic glucose production. Mice lacking p53 in the liver show a reduced gluconeogenic response during calorie restriction. Glucagon, adrenaline and glucocorticoids augment protein levels of p53, and administration of these hormones to p53 deficient human hepatocytes and to liver-specific p53 deficient mice fails to increase glucose levels. Moreover, insulin decreases p53 levels, and over-expression of p53 impairs insulin sensitivity. Finally, protein levels of p53, as well as genes responsible of O-GlcNAcylation are elevated in the liver of type 2 diabetic patients and positively correlate with glucose and HOMA-IR. Overall these results indicate that the O-GlcNAcylation of p53 plays an unsuspected key role regulating in vivo glucose homeostasis.


Assuntos
Acetilglucosamina/metabolismo , Glucose/metabolismo , Fígado/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Sequência de Bases , Restrição Calórica , Linhagem Celular , Colforsina/farmacologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Epinefrina/metabolismo , Glucagon/metabolismo , Glucocorticoides/metabolismo , Gluconeogênese/efeitos dos fármacos , Glicosilação , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Hidrocortisona/metabolismo , Hiperglicemia/complicações , Hiperglicemia/metabolismo , Resistência à Insulina , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fígado/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/complicações , Obesidade/metabolismo , Fosfoenolpiruvato Carboxiquinase (GTP)/metabolismo , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos dos fármacos , Estabilidade Proteica/efeitos dos fármacos , Ácido Pirúvico/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcrição Genética/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética
2.
Sci Rep ; 11(1): 14674, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34282206

RESUMO

To estimate the frequency of headache in patients with confirmed COVID-19 and characterize the phenotype of headache attributed to COVID-19, comparing patients depending on the need of hospitalization and sex, an observational study was done. We systematically screened all eligible patients from a reference population of 261,431 between March 8 (first case) and April 11, 2020. A physician administered a survey assessing demographic and clinical data and the phenotype of the headache. During the study period, 2194 patients out of the population at risk were diagnosed with COVID-19. Headache was described by 514/2194 patients (23.4%, 95% CI 21.7-25.3%), including 383/1614 (23.7%) outpatients and 131/580 (22.6%) inpatients. The headache phenotype was studied in detail in 458 patients (mean age, 51 years; 72% female; prior history of headache, 49%). Headache was the most frequent first symptom of COVID-19. Median headache onset was within 24 h, median duration was 7 days and persisted after 1 month in 13% of patients. Pain was bilateral (80%), predominantly frontal (71%), with pressing quality (75%), of severe intensity. Systemic symptoms were present in 98% of patients. Headache frequency and phenotype was similar in patients with and without need for hospitalization and when comparing male and female patients, being more intense in females.Trial registration: This study was supported by the Institute of Health Carlos III (ISCIII), code 07.04.467804.74011 and Regional Health Administration, Gerencia Regional de Salud, Castilla y Leon (GRS: 2289/A/2020).


Assuntos
COVID-19/complicações , Cefaleia/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor , Fenótipo , Adulto Jovem
3.
Pain Med ; 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34022054

RESUMO

BACKGROUND: Nummular Headache (NH) is defined in the International Classification of Headache Disorders (ICHD) by the presence of localized pain circumscribed to a small round area of the scalp, not better accounted by any other diagnosis. As in many other primary headache disorders, secondary cases might occur. To date, 13 secondary cases have been published. We aim to present a long series of secondary NH and review the literature of symptomatic NH. PATIENTS AND METHODS: Retrospective analysis of an observational prospective cohort in a headache unit located in a tertiary hospital. We included patients that fulfilled ICHD criteria and were attributed to a secondary cause. We describe the clinical characteristics, the underlying causes, and the response to treatment. RESULTS: We included 274 NH patients, 8 of them (2.9%) were considered secondary. In 1 patient the underlying cause was subcutaneous, as for 6 cases the lesion was located in the bone (two hemangiomas, 1 osteoma, 3 different types of cysts), and in one was intracranial but closely related with internal diploe (cavernoma). Among our patients with secondary NH, a preventive therapy was not always needed and, when required, gabapentin or onabotulinumtoxinA were used with positive response. CONCLUSION: Secondary NH phenotype overlaps primary NH. Therefore, we recommend routine imaging study in every NH patient. Concerning treatment, it was not necessary to remove the underlying lesion to control the pain and many cases responded to the same prophylactics as primary NH cases.

4.
iScience ; 24(2): 102071, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33554072

RESUMO

Excessive consumption of high-fructose diets is associated with insulin resistance, obesity, and non-alcoholic fatty liver disease (NAFLD). However, fructose differentially affects hepatic regulation of lipogenesis in males and females. Hence, additional studies are necessary in order to find strategies taking gender disparities in fructose-induced liver damage into consideration. Although the eighth member of facilitated glucose transporters (GLUT8) has been linked to fructose-induced macrosteatosis in female mice, its contribution to the inflammatory state of NAFLD remains to be elucidated. Combining pharmacological, biochemical, and proteomic approaches, we evaluated the preventive effect of targeted liver GLUT8 silencing on liver injury in a mice female fructose-induced non-alcoholic steatohepatitis female mouse model. Liver GLUT8-knockdown attenuated fructose-induced ER stress, recovered liver inflammation, and dramatically reduced fatty acid content, in part, via the omega oxidation. Therefore, this study links GLUT8 with liver inflammatory response and suggests GLUT8 as a potential target for the prevention of NAFLD.

5.
Sci Rep ; 11(1): 599, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436689

RESUMO

Serious intraocular toxicity cases have been reported worldwide after the use of different perfluorocarbon liquids. The current study reports for the first-time the clinical pictures of cases of acute intraocular toxicity caused by MEROCTANE, a perfluoro-octane commercialized by a Turkish company and distributed in many countries. A series of 18 cases from Chile and Spain was retrospectively analysed. To evaluate the impurity profile, a suspicious MEROCTANE sample (lot OCT.01.2013) was analysed by gas chromatography mass spectrometry and compared with a non-suspicious sample of the same commercial perfluoro-octane (lot OCT 722011). Cytotoxicity was tested following a direct-contact method, taking into consideration the high volatility and hydrophobicity of perfluoro-octane and following the ISO 10993 guideline. Cytotoxicity test showed clear cytotoxic effects of the analysed batch (less than 9% of cell viability). Moreover, chemical analysis demonstrated the presence of many contaminants, some highly toxic (acids and alcohols). Perfluorocarbon liquids are useful tools for intraocular surgery but companies and Agencies of Medical Devices must implement measures that guarantee the safety of these products based on both chemical and cytotoxicity analysis for every batch. Medical staff should be encouraged to report any suspected case to their respective National Agencies.


Assuntos
Fluorcarbonetos/efeitos adversos , Descolamento Retiniano/cirurgia , Epitélio Pigmentado da Retina/patologia , Testes de Toxicidade/métodos , Acuidade Visual/efeitos dos fármacos , Cirurgia Vitreorretiniana/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Sobrevivência Celular , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Estudos Retrospectivos
7.
Hepatology ; 73(2): 606-624, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32329085

RESUMO

BACKGROUND AND AIMS: G protein-coupled receptor (GPR) 55 is a putative cannabinoid receptor, and l-α-lysophosphatidylinositol (LPI) is its only known endogenous ligand. Although GPR55 has been linked to energy homeostasis in different organs, its specific role in lipid metabolism in the liver and its contribution to the pathophysiology of nonalcoholic fatty liver disease (NAFLD) remains unknown. APPROACH AND RESULTS: We measured (1) GPR55 expression in the liver of patients with NAFLD compared with individuals without obesity and without liver disease, as well as animal models with steatosis and nonalcoholic steatohepatitis (NASH), and (2) the effects of LPI and genetic disruption of GPR55 in mice, human hepatocytes, and human hepatic stellate cells. Notably, we found that circulating LPI and liver expression of GPR55 were up-regulated in patients with NASH. LPI induced adenosine monophosphate-activated protein kinase activation of acetyl-coenzyme A carboxylase (ACC) and increased lipid content in human hepatocytes and in the liver of treated mice by inducing de novo lipogenesis and decreasing ß-oxidation. The inhibition of GPR55 and ACCα blocked the effects of LPI, and the in vivo knockdown of GPR55 was sufficient to improve liver damage in mice fed a high-fat diet and in mice fed a methionine-choline-deficient diet. Finally, LPI promoted the initiation of hepatic stellate cell activation by stimulating GPR55 and activation of ACC. CONCLUSIONS: The LPI/GPR55 system plays a role in the development of NAFLD and NASH by activating ACC.


Assuntos
Lisofosfolipídeos/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/complicações , Receptores de Canabinoides/metabolismo , Acetil-CoA Carboxilase/antagonistas & inibidores , Acetil-CoA Carboxilase/metabolismo , Adulto , Idoso , Animais , Biópsia , Agonistas de Receptores de Canabinoides/farmacologia , Linhagem Celular , Estudos de Coortes , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Feminino , Técnicas de Silenciamento de Genes , Células Estreladas do Fígado , Hepatócitos , Humanos , Lipogênese/efeitos dos fármacos , Fígado/patologia , Lisofosfolipídeos/sangue , Masculino , Camundongos , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/sangue , Obesidade/metabolismo , Receptores de Canabinoides/genética , Regulação para Cima
8.
Biomedicines ; 8(12)2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33348877

RESUMO

Cerebral cavernous malformations (CCMs) are vascular malformations that can be the result of the deficiency of one of the CCM genes. Their only present treatment is surgical removal, which is not always possible, and an alternative pharmacological strategy to eliminate them is actively sought. We have studied the effect of the lack of one of the CCM genes, CCM3, in endothelial and non-endothelial cells. By comparing protein expression in control and CCM3-silenced cells, we found that the levels of the Epidermal Growth Factor Receptor (EGFR) are higher in CCM3-deficient cells, which adds to the known upregulation of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) in these cells. Whereas VEGFR2 is upregulated at the mRNA level, EGFR has a prolonged half-life. Inhibition of EGFR family members in CCM3-deficient cells does not revert the known cellular effects of lack of CCM genes, but it induces significantly more apoptosis in CCM3-deficient cells than in control cells. We propose that the susceptibility to tyrosine kinase inhibitors of CCM3-deficient cells can be harnessed to kill the abnormal cells of these lesions and thus treat CCMs pharmacologically.

9.
Cephalalgia ; 40(13): 1432-1442, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33146037

RESUMO

INTRODUCTION: Headache is a common symptom of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we aimed to characterize the phenotype of headache attributed to SARS-CoV-2 infection and to test the International Classification of Headache Disorders (ICHD-3) phenotypic criteria for migraine and tension-type headache. METHODS: The study design was a cross-sectional study nested in a cohort. We screened all consecutive patients that were hospitalized and had a positive SARS-CoV-2 test. We included patients that described headache if the headache was not better explained by another ICHD-3 diagnosis. Patients were interviewed by two neurologists. RESULTS: We screened 580 patients and included 130 (mean age 56 years, 64% female). Headache was the first symptom of the infection in 26% of patients and appeared within 24 hours in 62% of patients. The headache was bilateral in 85%, frontal in 83%, and with pressing quality in 75% of patients. Mean intensity was 7.1, being severe in 64%. Hypersensitivity to stimuli occurred in 57% of patients. ICHD-3 criteria for headache attributed to systemic viral infection were fulfilled by 94% of patients; phenotypic criteria for migraine were fulfilled by 25% of patients, and tension-type headache criteria by 54% of patients. CONCLUSION: Headache attributed to SARS-CoV-2 infection in hospitalized patients has severe intensity, frontal predominance and oppressive quality. It occurs early in the course of the disease. Most patients fulfilled ICHD-3 criteria for headache attributed to systemic viral infection; however, the phenotype might resemble migraine in a quarter of cases and tension-type headache in half of the patients.


Assuntos
Infecções por Coronavirus/complicações , Cefaleia/classificação , Cefaleia/diagnóstico , Cefaleia/virologia , Pneumonia Viral/complicações , Adulto , Idoso , Betacoronavirus , COVID-19 , Estudos Transversais , Feminino , Humanos , Classificação Internacional de Doenças , Masculino , Pessoa de Meia-Idade , Pandemias , Fenótipo , SARS-CoV-2
10.
Int J Mol Sci ; 21(20)2020 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-33080976

RESUMO

The human gastrointestinal system has the capacity to metabolize dietary gluten. The capacity to degrade gliadin-derived peptide is present in humans from birth and increases during the first stages of life (up to 6-12 months of age). Fecal samples from 151 new-born and adult non-celiac disease (NCD) volunteers were collected, and glutenase and glianidase activities were evaluated. The capacity of total fecal proteins to metabolize 33-mer, 19-mer, and 13-mer gliadin peptides was also evaluated by high-performance liquid chromatography (HPLC). Feces from new-borns (meconium) showed glutenase and gliadinase activities, and peptidase activity against all three gliadin peptides. Maximal gluten degradative activity was observed in fecal samples from the youngest volunteers (0-12 months old). After the age of nine months, the gluten digestive capacity of gastrointestinal tract decreases and, from ±8 years old, individuals lose the ability to completely degrade toxic peptides. The gastrointestinal proteases involved in gluten digestion: elastase 2A, elastase 3B, and carboxipeptidase A1 are present from earlier stages of life. The human digestive tract contains the proteins capable of metabolizing gluten from birth, even before starting gluten intake. Humans are born with the ability to digest gluten and to completely degrade the potentially toxic gliadin-derived peptides (33-, 19-, and 13-mer).


Assuntos
Trato Gastrointestinal/metabolismo , Glutens/metabolismo , Proteólise , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Digestão , Gliadina/metabolismo , Humanos , Hidrólise , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Peptídeo Hidrolases/metabolismo , Adulto Jovem
11.
Arch. argent. pediatr ; 118(5): 337-342, oct 2020. tab
Artigo em Inglês, Espanhol | LILACS, BINACIS | ID: biblio-1122034

RESUMO

Introducción. Publicaciones internacionales estiman una prevalencia de sensibilización al látex (SL) en el personal de salud del 7 % al 17 %, y se desconocen los valores en la Argentina.Objetivos. Estimar la prevalencia de sensibilización y alergia al látex en médicos residentes de un hospital pediátrico mediante la prueba epicutánea de lectura inmediata y evaluar factores de riesgo asociados en dicha población.Población y métodos. Estudio de corte transversal. Se incluyeron los residentes, jefes e instructores de Pediatría, Ortopedia, Cirugía y Terapia Intensiva entre junio y octubre de 2017. En todos, se realizó un cuestionario (que evaluó enfermedades atópicas y otros factores de riesgo) y la prueba epicutánea de lectura inmediata. En un subgrupo (residentes de 1ero, 4to año, especialidades quirúrgicas y terapia) se dosó inmunoglobulina E total y específica para látex.Resultados. Se incluyeron 113 participantes. La prevalencia de SL fue del 7,96 % (intervalo de confianza del 95 %: 3,70-14,58); 4 participantes resultaron alérgicos al látex. El antecedente de síntomas relacionados con el látex se asoció significativamente con prueba epicutánea de lectura inmediata + (p = 0,0196; odds ratio 6,13; intervalo de confianza del 95 %: 1,44-26,04). No hubo asociación entre SL y año de residencia.Conclusiones. La prevalencia de SL hallada fue del 7,9 %. Se evidenció una relación significativa entre el antecedente de SRL y un resultado de prueba epicutánea de lectura inmediata positiva


Introduction. International publications estimate a 7 %-17 % latex sensitization (LS) prevalence among health care workers, but values in Argentina are unknown.Objectives. To estimate the prevalence of latex sensitization and allergy among residents of a children's hospital using the immediate-reading prick test and to assess associated risk factors in this population.Population and methods. Cross-sectional study. Residents, trainers, and Chief residents of the Departments of Pediatrics, Orthopedics, Surgery and Intensive Care were included between June and October 2017. All of them were administered a questionnaire (assessing atopic diseases and other risk factors) and underwent the immediate-reading prick test. Total and latex-specific immunoglobulin E levels were determined in a subgroup of individuals (first- and fourth-year residents, surgical specialties, and intensive care).Results. A total of 113 participants were included. LS prevalence was 7.96 % (95 % confidence interval: 3.70-14.58); 4 participants were allergic to latex. A history of latex-related symptoms (LRS) was significantly associated with a positive result in the immediate-reading prick test (p = 0.0196; odds ratio: 6.13; 95 % confidence interval: 1.44-26.04). There was no association between LS and the year of the residency program.Conclusions. The observed LS prevalence was 7.9 %. There was a significant relation between a history of LRS and a positive result in the immediate-reading prick tes


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Hipersensibilidade ao Látex , Médicos , Testes Cutâneos , Epidemiologia Descritiva , Prevalência , Estudos Transversais , Inquéritos e Questionários , Fatores de Risco , Internato e Residência
12.
Arch Argent Pediatr ; 118(5): 337-342, 2020 10.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32924397

RESUMO

Introduction: International publications estimate a 7 %-17 % latex sensitization (LS) prevalence among health care workers, but values in Argentina are unknown. Objectives: To estimate the prevalence of latex sensitization and allergy among residents of a children's hospital using the immediate-reading prick test and to assess associated risk factors in this population. Population and methods: Cross-sectional study. Residents, trainers, and Chief residents of the Departments of Pediatrics, Orthopedics, Surgery and Intensive Care were included between June and October 2017. All of them were administered a questionnaire (assessing atopic diseases and other risk factors) and underwent the immediatereading prick test. Total and latex-specific immunoglobulin E levels were determined in a subgroup of individuals (first- and fourth-year residents, surgical specialties, and intensive care). Results: A total of 113 participants were included. LS prevalence was 7.96 % (95 % confidence interval: 3.70-14.58); 4 participants were allergic to latex. A history of latex-related symptoms (LRS) was significantly associated with a positive result in the immediate-reading prick test (p = 0.0196; odds ratio: 6.13; 95 % confidence interval: 1.44-26.04). There was no association between LS and the year of the residency program. Conclusions: The observed LS prevalence was 7.9 %. There was a significant relation between a history of LRS and a positive result in the immediate-reading prick test.


Assuntos
Imunoglobulina E/imunologia , Internato e Residência , Hipersensibilidade ao Látex/epidemiologia , Médicos/estatística & dados numéricos , Adulto , Argentina , Estudos Transversais , Feminino , Hospitais Pediátricos , Humanos , Hipersensibilidade ao Látex/diagnóstico , Masculino , Recursos Humanos em Hospital/estatística & dados numéricos , Prevalência , Fatores de Risco , Testes Cutâneos , Inquéritos e Questionários
13.
Regul Toxicol Pharmacol ; 110: 104527, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31733229

RESUMO

Perfluorocarbon liquids (PFCLs) have been considered safe for intraocular manipulation of the retina, but since 2013 many cases of acute eye toxicity cousing blindness have been reported in various countries when using various commercial PFCLs. All these PFCLs were CE marked (Conformité Européenne), which meant they had been subjected to evaluation complying with the International Organization for Standardization (ISO) guidelines. These dramatic events raised questions about the safety of PFCLs and the validity of some cytotoxicity tests performed under ISO guidelines. Samples from toxic batches were analyzed by gas chromatography-mass spectrometry combined with Raman and infrared spectrometry. Perfluorooctanoic acid, dodecafluoro-1-heptanol, ethylbenzene and tributyltin bromide were identified and evaluated by a direct contact cytotoxicity test using ARPE-19 cell line, patented by our group (EP 3467118 A1). Perfluorooctanoic acid at a concentration of >0.06 mM and tributyltin bromide at a concentration of ≥0.016 mM were shown to be toxic, whereas the concentration found in the toxic samples reached 0.48 mM, and 0.111 mM, respectively. These finding emphasized the idea that determination of partially fluorinated compounds are not enough to guarantee the safety of these medical devices.


Assuntos
Contaminação de Medicamentos , Fluorcarbonetos/toxicidade , Procedimentos Cirúrgicos Oftalmológicos , Compostos de Trialquitina/toxicidade , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Humanos , Retina/citologia
14.
Aten Primaria ; 52 Suppl 2: 70-92, 2020 11.
Artigo em Espanhol | MEDLINE | ID: mdl-33388119

RESUMO

Vaccine development is one of the fastest growing sectors in medicine now and in the future, as we are living with the emergency health care for the SARS-CoV-2 coronavirus. The semFYC PAPPS program biannually publishes the recommendations of the group and, in this edition, special emphasis is placed on the common vaccination proposed by the Ministry of Health, where, at last, it no longer discriminates between paediatrics and adults, and proposes a calendar throughout life. The main novelties in the field of vaccinology today are focused on the consolidation of the nonavalent vaccine against the human papilloma virus and in the change of the dose of monovalent meningitis vaccine C for the tetravalent one, ACWY, at age 12. The pandemic we are experiencing has led to the postponement of most preventive activities. On the return to «normality¼, the vaccination calendar must be examined, and completed if necessary.


Assuntos
Esquemas de Imunização , Atenção Primária à Saúde/normas , Vacinação/normas , Vacinas/normas , Viroses/prevenção & controle , Adulto , COVID-19/prevenção & controle , Criança , Humanos , Atenção Primária à Saúde/métodos , Vacinação/métodos , Vacinas/administração & dosagem
15.
Bioresour Technol ; 292: 121940, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31419707

RESUMO

Spent coffee grounds are a huge residual stream from instant coffee makers. The production of spent coffee oil and molecular weight fractionated hemicellulose hydrolysates via supercritical CO2 and a hydrothermal treatment followed by concentration, separation, and purification through cascade ultrafiltration/diafiltration (30-10-5 kDa) was studied. Hemicelluloses extraction yield reached 3.49 g/100 g of dry defatted spent coffee after 40 min at 160 °C. The ultrafiltration system allowed concentrating up to 5-fold certain groups of hemicellulose, being most of them retained in the first membrane. Hemicellulose concentration and molecular weight of the feed exerted a great influence on the mass transfer through the membrane due to the formation of aggregates. However, purification through diafiltration allowed both to decrease by-products retentions from 45.6% to 8.7%, increasing the molecular weight of each fraction. Six hemicellulose products were obtained with purities between 83.7 and 97.8 wt% and weight-average molecular weights between 1641 and 49,733 Da.


Assuntos
Café , Ultrafiltração , Peso Molecular , Polissacarídeos
16.
Endocrinology ; 160(5): 1111-1118, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30882881

RESUMO

Since the discovery of the mammalian sterile twenty (MST) kinase family of proteins (MST1/STK4, MST2/STK3, MST3/STK24, and SOK1/STK25), much has been done that adds to our knowledge of their structure, regulation, and function. In the last few years, a series of articles has unveiled a previous unknown relation of these kinases with metabolic regulation and the homeostasis of metabolic tissues. The aim of this review is to bring together this body of data to provide a detailed picture of the current knowledge about these proteins, metabolism, and some of the associated diseases.


Assuntos
Tecido Adiposo/enzimologia , Metabolismo Energético , Neoplasias/enzimologia , Proteínas Serina-Treonina Quinases/metabolismo , Tecido Adiposo/metabolismo , Animais , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias/metabolismo
18.
Br J Ophthalmol ; 103(1): 49-54, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29599249

RESUMO

AIMS: To report new information related to acute retinal toxicity of Bio Octane Plus, a mixture of 90% perfluorooctane (PFO) and 10% perfluorohexyloctane. METHODS: This retrospective, descriptive case series reports the occurrence of acute retinal toxicity after vitreoretinal surgery in which Bio Octane Plus (batch number 1605148) was used as an endotamponade. Cytotoxicity biocompatibility tests and chemical analyses by Fourier-transformed infrared (FTIR) spectroscopy and gas chromatography-mass spectrometry (GC-MS) of the presumed toxic product were performed. RESULTS: Four patients presented with acute severe visual loss after uneventful ocular surgery assisted by Bio Octane Plus (batch number 1605148) as endotamponade. Patients experienced extensive retinal vascular occlusion leading to retinal and optic nerve atrophy. The viability of ARPE-19 cells directly exposed to the suspect batch for 30 min was 0%. The agarose overlay method used by the manufacturer according to European Union regulations and International Organization for Standardization (ISO) International Standards failed to detect toxicity. FTIR spectroscopy showed small differences between the non-toxic and toxic batches. GC-MS analysis showed the presence of bromotributyl stannane (whose toxicity was demonstrated in the dose-response curve) only in the toxic batch of Bio Octane Plus. CONCLUSION: This is the third report of retinotoxicity due to PFO in 4 years. The clinical profiles may be missed as they resemble other postsurgical complications; therefore, more cases worldwide could have gone unreported. Protocols to determine cytotoxicity of intraocular medical devices and approved by the ISO International Standards based on indirect methods have failed and should be revised to ensure safety.


Assuntos
Células Epiteliais/efeitos dos fármacos , Fluorcarbonetos/efeitos adversos , Doenças Retinianas/induzido quimicamente , Epitélio Pigmentado da Retina/citologia , Idoso , Sobrevivência Celular/efeitos dos fármacos , Feminino , Fluorcarbonetos/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
Diabetologia ; 60(12): 2453-2462, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28956081

RESUMO

AIMS/HYPOTHESIS: The identification of mediators in the pathogenesis of type 2 diabetes mellitus is essential for the full understanding of this disease. Protein kinases are especially important because of their potential as pharmacological targets. The goal of this study was to investigate whether mammalian sterile-20 3 (MST3/STK24), a stress-regulated kinase, is involved in metabolic alterations in obesity. METHODS: Glucose regulation of Mst3 (also known as Stk24)-knockout mice was analysed both in 129;C57 mixed background mice and in C57/BL6J mice fed normally or with a high-fat diet (HFD). This work was complemented with an analysis of the insulin signalling pathway in cultured human liver cells made deficient in MST3 using RNA interference. RESULTS: MST3 is phosphorylated in the livers of mice subject to an obesity-promoting HFD, and its deficiency lowers the hyperglycaemia, hyperinsulinaemia and insulin resistance that the animals develop with this diet, an effect that is seen even without complete inactivation of the kinase. Lack of MST3 results in activation of the insulin signalling pathway downstream of IRS1, in both cultured liver cells and the liver of animals after HFD. This effect increases the inhibition of forkhead box (FOX)O1, with subsequent downregulation of the expression of gluconeogenic enzymes. CONCLUSIONS/INTERPRETATION: MST3 inhibits the insulin signalling pathway and is important in the development of insulin resistance and impaired blood glucose levels after an HFD.


Assuntos
Glicemia/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Jejum/sangue , Feminino , Gluconeogênese/fisiologia , Células Hep G2 , Humanos , Resistência à Insulina/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Serina-Treonina Quinases/genética
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