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2.
Nefrologia (Engl Ed) ; 2021 Jan 28.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33781578

RESUMO

We present the case of a male patient with severe SARS-CoV-2 pneumonia, with simultaneous onset of p-ANCA positive rapidly progressive glomerulonephritis. We discuss the different therapeutic possibilities, emphasising the appropriateness of their administration according to the time in the course of the infection.

3.
Thromb Res ; 199: 132-142, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33503547

RESUMO

BACKGROUND: Incidence of thrombotic events associated to Coronavirus disease-2019 (COVID-19) is difficult to assess and reported rates differ significantly. Optimal thromboprophylaxis is unclear. OBJECTIVES: We aimed to analyze the characteristics of patients with a confirmed thrombotic complication including inflammatory and hemostatic parameters, compare patients affected by arterial vs venous events and examine differences between survivors and non-survivors. We reviewed compliance with thromboprophylaxis and explored how the implementation of a severity-adjusted protocol could have influenced outcome. METHODS: Single-cohort retrospective study of COVID-19 patients admitted, from March 3 to May 3 2020, to the Infanta Leonor University Hospital in Madrid, epicenter of the Spanish outbreak. RESULTS: Among 1127 patients, 80 thrombotic events were diagnosed in 69 patients (6.1% of the entire cohort). Forty-three patients (62%) suffered venous thromboembolism, 18 (26%) arterial episodes and 6 (9%) concurrent venous and arterial thrombosis. Most patients (90%) with a confirmed thrombotic complication where under low-molecular-weight heparin treatment. Overt disseminated intravascular coagulation (DIC) was rare. Initial ISTH DIC score and pre-event CRP were significantly higher among non-survivors. In multivariate analysis, arterial localization was an independent predictor of mortality (OR = 18, 95% CI: 2.4-142, p < .05). CONCLUSIONS: Despite quasi-universal thromboprophylaxis, COVID-19 lead to a myriad of arterial and venous thrombotic events. Considering the subgroup of patients with thrombotic episodes, arterial events appeared earlier in the course of disease and conferred very poor prognosis, and an ISTH DIC score ≥ 3 at presentation was identified as a potential predictor of mortality. Severity-adjusted thromboprophylaxis seemed to decrease the number of events and could have influenced mortality. Randomized controlled trials are eagerly awaited.


Assuntos
Anticoagulantes/uso terapêutico , COVID-19/complicações , Heparina de Baixo Peso Molecular/uso terapêutico , Trombose/tratamento farmacológico , Trombose/etiologia , Idoso , Idoso de 80 Anos ou mais , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Trombofilia/diagnóstico , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Trombose/diagnóstico , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia
6.
Biology (Basel) ; 9(11)2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33167441

RESUMO

Alzheimer's disease (AD) is the most common form of neurodegeneration and dementia. The endocannabinoid (ECB) system has been proposed as a novel therapeutic target to treat AD. The present study explores the expression of the ECB system, the ECB-related receptor GPR55, and cognitive functions (novel object recognition; NOR) in the 5xFAD (FAD: family Alzheimer's disease) transgenic mouse model of AD. Experiments were performed on heterozygous (HTZ) and homozygous (HZ) 11 month old mice. Protein expression of ECB system components, neuroinflammation markers, and ß-amyloid (Aß) plaques were analyzed in the hippocampus. According to the NOR test, anxiety-like behavior and memory were altered in both HTZ and HZ 5xFAD mice. Furthermore, both animal groups displayed a reduction of cannabinoid (CB1) receptor expression in the hippocampus, which is related to memory dysfunction. This finding was associated with indirect markers of enhanced ECB production, resulting from the combination of impaired monoacylglycerol lipase (MAGL) degradation and increased diacylglycerol lipase (DAGL) levels, an effect observed in the HZ group. Regarding neuroinflammation, we observed increased levels of CB2 receptors in the HZ group that positively correlate with Aß's accumulation. Moreover, HZ 5xFAD mice also exhibited increased expression of the GPR55 receptor. These results highlight the importance of the ECB signaling for the AD pathogenesis development beyond Aß deposition.

7.
Redox Biol ; 37: 101762, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33128998

RESUMO

Friedreich ataxia (FRDA) is a neurodegenerative disorder characterized by neuromuscular and neurological manifestations. It is caused by mutations in the FXN gene, which results in loss of the mitochondrial protein frataxin. Endoplasmic Reticulum-mitochondria associated membranes (MAMs) are inter-organelle structures involved in the regulation of essential cellular processes, including lipid metabolism and calcium signaling. In the present study, we have analyzed in both, unicellular and multicellular models of FRDA, calcium management and integrity of MAMs. We observed that function of MAMs is compromised in our cellular model of FRDA, which was improved upon treatment with antioxidants. In agreement, promoting mitochondrial calcium uptake was sufficient to restore several defects caused by frataxin deficiency in Drosophila Melanogaster. Remarkably, our findings describe for the first time frataxin as a member of the protein network of MAMs, where interacts with two of the main proteins implicated in endoplasmic reticulum-mitochondria communication. These results suggest a new role of frataxin, indicate that FRDA goes beyond mitochondrial defects and highlight MAMs as novel therapeutic candidates to improve patient's conditions.


Assuntos
Ataxia de Friedreich , Animais , Cálcio/metabolismo , Drosophila melanogaster/genética , Retículo Endoplasmático , Ataxia de Friedreich/genética , Ataxia de Friedreich/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo
8.
Sci Rep ; 10(1): 14912, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32913249

RESUMO

The controls that affect the structure and timing of terminations are still poorly understood. We studied a tufa deposit from the Iberian Peninsula that covers Termination II (T-II) and whose chronology was synchronized to speleothem records. We used the same chronology to synchronize ocean sediments from the North Atlantic to correlate major climate events in a common timescale. We identify two stages within T-II. The first stage started with the increase of boreal summer integrated solar insolation, and during this stage three millennial climate oscillations were recorded. These oscillations resulted from complex ocean-atmosphere interactions in the Nordic seas, caused by the progressive decay of Northern Hemisphere ice-sheets. The second stage commenced after a glacial outburst that caused the collapse of the Thermohaline Circulation, a massive Heinrich event, and the onset of the Bipolar Seesaw Mechanism (BSM) that eventually permitted the completion of T-II. The pace of the millennial oscillations during the first stage of T-II controlled the onset of the second stage, when the termination became a non-reversible and global phenomenon that accelerated the deglaciation. During the last the two terminations, the BSM was triggered by different detailed climate interactions, which suggests the occurrence of different modes of terminations.

9.
Int J Mol Sci ; 21(17)2020 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-32842637

RESUMO

Polycystic ovarian syndrome (PCOS) is the main cause of female infertility. It is a multifactorial disorder with varying clinical manifestations including metabolic/endocrine abnormalities, hyperandrogenism, and ovarian cysts, among other conditions. D-Chiro-inositol (DCI) is the main treatment available for PCOS in humans. To address some of the mechanisms of this complex disorder and its treatment, this study examines the effect of DCI on reproduction during the development of different PCOS-associated phenotypes in aged females and two mouse models of PCOS. Aged females (8 months old) were treated or not (control) with DCI for 2 months. PCOS models were generated by treatment with dihydrotestosterone (DHT) on Days 16, 17, and 18 of gestation, or by testosterone propionate (TP) treatment on the first day of life. At two months of age, PCOS mice were treated with DCI for 2 months and their reproductive parameters analyzed. No effects of DCI treatment were produced on body weight or ovary/body weight ratio. However, treatment reduced the number of follicles with an atretic cyst-like appearance and improved embryo development in the PCOS models, and also increased implantation rates in both aged and PCOS mice. DCI modified the expression of genes related to oocyte quality, oxidative stress, and luteal sufficiency in cumulus-oocyte complexes (COCs) obtained from the aged and PCOS models. Further, the phosphorylation of AKT, a main metabolic sensor activated by insulin in the liver, was enhanced only in the DHT group, which was the only PCOS model showing glucose intolerance and AKT dephosphorylation. The effect of DCI in the TP model seemed mediated by its influence on oxidative stress and follicle insufficiency. Our results indicate that DCI works in preclinical models of PCOS and offer insight into its mechanism of action when used to treat this infertility-associated syndrome.


Assuntos
Blastocisto/efeitos dos fármacos , Infertilidade Feminina/tratamento farmacológico , Inositol/farmacologia , Oócitos/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Envelhecimento , Animais , Blastocisto/fisiologia , Células do Cúmulo/efeitos dos fármacos , Di-Hidrotestosterona/toxicidade , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Intolerância à Glucose/tratamento farmacológico , Infertilidade Feminina/etiologia , Infertilidade Feminina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos , Oócitos/fisiologia , Fosforilação/efeitos dos fármacos , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Propionato de Testosterona/toxicidade
11.
Nutrients ; 12(7)2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32650579

RESUMO

To characterize the metabolic actions of D-Pinitol, a dietary inositol, in male Wistar rats, we analyzed its oral pharmacokinetics and its effects on (a) the secretion of hormones regulating metabolism (insulin, glucagon, IGF-1, ghrelin, leptin and adiponectin), (b) insulin signaling in the liver and (c) the expression of glycolytic and neoglucogenesis enzymes. Oral D-Pinitol administration (100 or 500 mg/Kg) resulted in its rapid absorption and distribution to plasma and liver compartments. Its administration reduced insulinemia and HOMA-IR, while maintaining glycaemia thanks to increased glucagon activity. In the liver, D-Pinitol reduced the key glycolytic enzyme pyruvate kinase and decreased the phosphorylation of the enzymes AKT and GSK-3. These observations were associated with an increase in ghrelin concentrations, a known inhibitor of insulin secretion. The profile of D-Pinitol suggests its potential use as a pancreatic protector decreasing insulin secretion through ghrelin upregulation, while sustaining glycaemia through the liver-based mechanisms of glycolysis control.


Assuntos
Fabaceae/química , Grelina/sangue , Inositol/análogos & derivados , Secreção de Insulina/efeitos dos fármacos , Fígado/metabolismo , Administração Oral , Animais , Depressão Química , Grelina/metabolismo , Glucagon/metabolismo , Glicogênio/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Glicólise , Inositol/administração & dosagem , Inositol/isolamento & purificação , Inositol/farmacocinética , Inositol/farmacologia , Masculino , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piruvato Quinase/metabolismo , Ratos Wistar
12.
Nefrología (Madrid) ; 40(3): 345-350, mayo-jun. 2020. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-201535

RESUMO

La relación entre parásitos y glomerulonefritis (GN) está bien documentada en determinadas parasitosis, no así en casos de Strongyloides stercolaris (S. stercolaris), donde hay pocos casos descritos, siendo la mayoría GN de cambios mínimos. Reportamos un caso de hiperinfestación por S. stercolaris en un paciente afectado de una GN membranosa tratado con corticoides por vía oral con resultado fatal para el paciente. Este caso nos aporta una doble enseñanza: en primer lugar, acerca de una asociación rara de estrongiloidiasis y GN membranosa, y en segundo lugar, sobre la importancia de establecer un diagnóstico de sospecha y tratamiento adecuados ante determinadas infecciones o enfermedades con poca expresividad clínica antes de iniciar cualquier tratamiento inmunosupresor


The relationship between parasites and glomerulonephritis (GN) is well documented in certain parasitoses, but not in cases of Strongyloides stercolaris (S. stercolaris) where there are few cases described being the majority GN of minimal changes. We report a case of hyperinfestation by S. stercolaris in a patient affected by a membranous GN treated with oral corticosteroids with fatal outcome for the patient. This case provides a double teaching: first about a rare association of strongyloid and membranous GN and second about the importance of establishing a diagnosis of suspected and appropriate treatment for certain infections or diseases with little clinical expression before starting any immunosuppressive treatment


Assuntos
Humanos , Animais , Masculino , Pessoa de Meia-Idade , Glomerulonefrite Membranosa/complicações , Imunossupressores/efeitos adversos , Prednisona/efeitos adversos , Strongyloides stercoralis , Estrongiloidíase/complicações , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Criptococose/complicações , Diagnóstico Tardio , Quimioterapia Combinada , Equador/etnologia , Enterococcus faecium , Infecções por Escherichia coli/complicações , Evolução Fatal , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/urina , Infecções por Bactérias Gram-Positivas/complicações , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Pneumopatias Fúngicas/complicações , Meningites Bacterianas/complicações , Pneumonia Bacteriana/complicações , Prednisona/uso terapêutico , Choque Séptico/etiologia , Stenotrophomonas maltophilia , Estrongiloidíase/diagnóstico
13.
Cell Rep ; 30(8): 2627-2643.e5, 2020 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-32101741

RESUMO

The conserved Hedgehog signaling pathway has well-established roles in development. However, its function during adulthood remains largely unknown. Here, we investigated whether the Hedgehog signaling pathway is active during adult life in Drosophila melanogaster, and we uncovered a protective function for Hedgehog signaling in coordinating correct proteostasis in glial cells. Adult-specific depletion of Hedgehog reduces lifespan, locomotor activity, and dopaminergic neuron integrity. Conversely, increased expression of Hedgehog extends lifespan and improves fitness. Moreover, Hedgehog pathway activation in glia rescues the lifespan and age-associated defects of hedgehog mutants. The Hedgehog pathway regulates downstream chaperones, whose overexpression in glial cells was sufficient to rescue the shortened lifespan and proteostasis defects of hedgehog mutants. Finally, we demonstrate the protective ability of Hedgehog signaling in a Drosophila Alzheimer's disease model expressing human amyloid beta in the glia. Overall, we propose that Hedgehog signaling is requisite for lifespan determination and correct proteostasis in glial cells.


Assuntos
Drosophila melanogaster/metabolismo , Proteínas Hedgehog/metabolismo , Longevidade , Neuroglia/metabolismo , Proteostase , Transdução de Sinais , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/metabolismo , Sobrevivência Celular , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Homeostase , Humanos , Modelos Biológicos , Mutação/genética , Neurônios/metabolismo , Neuroproteção , Análise de Sobrevida
16.
Nefrologia (Engl Ed) ; 40(3): 345-350, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31351697

RESUMO

The relationship between parasites and glomerulonephritis (GN) is well documented in certain parasitoses, but not in cases of Strongyloides stercolaris (S. stercolaris) where there are few cases described being the majority GN of minimal changes. We report a case of hyperinfestation by S. stercolaris in a patient affected by a membranous GN treated with oral corticosteroids with fatal outcome for the patient. This case provides a double teaching: first about a rare association of strongyloid and membranous GN and second about the importance of establishing a diagnosis of suspected and appropriate treatment for certain infections or diseases with little clinical expression before starting any immunosuppressive treatment.


Assuntos
Glomerulonefrite Membranosa/complicações , Imunossupressores/efeitos adversos , Prednisona/efeitos adversos , Strongyloides stercoralis , Estrongiloidíase/complicações , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Animais , Criptococose/complicações , Diagnóstico Tardio , Quimioterapia Combinada , Equador/etnologia , Enterococcus faecium , Infecções por Escherichia coli/complicações , Evolução Fatal , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/urina , Infecções por Bactérias Gram-Positivas/complicações , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Pneumopatias Fúngicas/complicações , Masculino , Meningites Bacterianas/complicações , Pessoa de Meia-Idade , Pneumonia Bacteriana/complicações , Prednisona/uso terapêutico , Choque Séptico/etiologia , Espanha , Stenotrophomonas maltophilia , Estrongiloidíase/diagnóstico
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