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1.
Muscle Nerve ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39132869

RESUMO

INTRODUCTION/AIMS: Somatosensory evoked potentials (SSEPs) are described as a supportive tool to diagnose chronic inflammatory demyelinating polyradiculoneuropathy (CIDP); however, there is a lack of studies determining the effectiveness of SSEPs in monitoring the clinical course of individuals with this condition. The aims of this study are to evaluate the utility of SSEPs in monitoring patients with CIDP and to assess their association with clinical outcomes following immunomodulatory therapy. METHODS: This was a single-center retrospective observational study that included patients who met European Federation of Neurological Societies and Peripheral Nerve Society criteria for CIDP between 2018 and 2023. SSEPs were performed at diagnosis and during follow-up after the start of immunomodulatory treatment. Fisher's exact test was employed to assess the association between clinical improvement and SSEP improvement. RESULTS: Eighteen patients were included in the study. Ten patients had a typical CIDP pattern and 11 were male. In 17, SSEPs were abnormal prior to the start of immunomodulatory treatment. In patients who showed clinical improvement with immunomodulatory therapy, we observed that 15/17 had partial or complete improvement in SSEPs. Patients who showed no clinical improvement with first-line treatment exhibited worsening SSEPs. There was a significant association between clinical and SSEPs improvement (p = 0.009). DISCUSSION: We observed a positive association between improvement in SSEPs and clinical improvement in patients with CIDP. Our data suggest that SSEPs may be useful for monitoring the clinical course of patients with CIDP, but additional, larger studies are needed.

2.
Phys Chem Chem Phys ; 23(8): 4491-4499, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33439159

RESUMO

Due to the network flexibility of their BX3 sub-lattice, a manifold of polymorphs with potential multiferroic applications can be found in perovskite-like ABX3 materials under different pressure and temperature conditions. The potential energy surface of these compounds usually presents equivalent off-center positions of anions connected by low energetic barriers. This feature facilitates a competition between the thermodynamic and kinetic control of the transitions from low to high symmetry structures, and explains the relationship between the rich polymorphism and network flexibility. In the rhombohedral phase of iron trifluoride, our first-principles electronic structure and phonon calculations reveal the factors that determine which of the two scenarios dominates the transition. At the experimentally reported rhombohedral-cubic transition temperature, the calculated fluorine displacements are fast enough to overcome forward and backward a barrier of less than 30 kJ mol-1, leading to an average structure with cubic symmetry. In addition, lattice strain effects observed in epitaxial growth and nanocrystallite experiments involving BX3 compounds are successfully mimicked by computing the phase stability of FeF3 under negative pressures. We predict a transition pressure at -1.8 GPa with a relative volume change around 5%, consistent with a first-order transition from the rhombohedral to the cubic structure. Overall, our study illustrates how, by strain tuning, either a thermodynamic or a kinetic pathway can be selected for this transformation.

3.
Phys Chem Chem Phys ; 23(4): 2825-2835, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33470997

RESUMO

Various structural configurations of iron trifluoride appear at the nanoscale and macroscopic size, either in the amorphous or crystalline state. The specific atomic organization in these structures crucially alters the performance of FeF3 as an effective cathode in Li-ion batteries. Our detailed first-principles computational simulations examine the structural strains induced by temperature and stress on the four anhydrous polymorphs observed so far in FeF3 at ambient pressure. A wealth of data covering previous experimental results on their equilibrium structures and extending their characterization with new static and isothermal equations of state is provided. We inform on how porous apertures associated with the six-octahedra rings of the HTB and pyrochlore phases are modified under compressive and expansive strains. A quasi-auxetic behavior at low pressures for the ground state rhombohedral phase is detected, which is in concordance with its anomalous structural anisotropy. In contrast with the effect of temperature, this structure undergoes under negative pressure phase transitions to the other three polymorphs, indicating potential conditions where low-density FeF3 could show a better performance in technological applications.

4.
Eur J Nutr ; 59(2): 621-631, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30788591

RESUMO

PURPOSE: According to the xenohormesis theory, animals receive signals from plants that give clues about the changing environment, and thus, depending on the season of the year, animals develop physiological changes to adapt in advance to the seasonal changes. Our objective was to study how the same fruit cultivated during two different seasons could affect the adipose tissue of rats. METHODS: Thirty-six Fischer 344 rats were acclimated for 4 weeks to long-day or short-day (SD) photoperiods. After adaptation, three groups (n = 6) from each photoperiod were supplemented either with orange from the northern (ON) or southern (OS) hemispheres harvested in the same month or a vehicle (VH) for 10 weeks. Biometric measurements, postprandial plasmatic parameters, gene expression of the inguinal white adipose tissue (IWAT) and brown adipose tissue (BAT), and the histology of the IWAT were analysed. RESULTS: The OSSD group increased its fat content compared to the VHSD, while the ON groups showed no biometric differences. The OS groups were further studied, and the IWAT showed increased levels of Pparγ gene expression and a higher percentage of larger adipocytes compared to the VH group. The BAT showed down-regulation of Lpl, Cpt1b and Pparα in the OSSD group compared to that in the VHSD group, suggesting an inhibition of BAT activity, however, Ucp1 gene expression was up-regulated. CONCLUSIONS: We observed a different effect from both fruits, with the OS promoting a phenotype prone to fat accumulation when consumed in an SD photoperiod, which might be explained by the xenohormesis theory.


Assuntos
Tecido Adiposo/metabolismo , Tecido Adiposo/fisiologia , Citrus sinensis , Dieta/métodos , Expressão Gênica/fisiologia , Estações do Ano , Animais , Dieta/estatística & dados numéricos , Masculino , Ratos , Ratos Endogâmicos F344
5.
Phys Chem Chem Phys ; 21(23): 12585-12596, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31150030

RESUMO

The valence shell electron pair repulsion (VSEPR) model is a demanding testbed for modern chemical bonding formalisms. The challenge consists in providing reliable quantum mechanical interpretations of how chemical concepts such as bonds, lone pairs, electronegativity, or hypervalence influence (or modulate) molecular geometries. Several schemes have been developed thus far to visualize and characterize these effects; however, to the best of our knowledge, no scheme has yet incorporated the analysis of the premises derived from the ligand close-packing (LCP) extension of the VSEPR model. Within the LCP framework, the activity of the lone pairs of the central atom and ligand-ligand repulsions constitute the two key features necessary to explain certain controversial molecular geometries that do not conform to the VSEPR rules. Considering the dynamical picture obtained when electron local forces at different nuclear configurations are evaluated from first-principles calculations, we investigate the chemical pressure distributions in a variety of molecular systems, namely, electron-deficient molecules (BeH2, BH3, BF3), several AX3 series (A: N, P, As; X: H, F, Cl), SO2, ethylene, SF4, ClF3, XeF2, and nonequilibrium configurations of water and ammonia. Our chemical pressure maps clearly reveal space regions that are totally consistent with the molecular and electronic geometries predicted by VSEPR and provide a quantitative correlation between the lone pair activity of the central atom and electronegativity of ligands, which are in agreement with the LCP model. Moreover, the analysis of the kinetic and potential energy contributions to the chemical pressure allows us to provide simple explanations on the connection between ligand electronegativity and electrophilic/nucleophilic character of the molecules, with interesting implications in their potential reactivity. NH3, NF3, SO2, BF3, and the inversion barrier of AX3 molecules are selected to illustrate our findings.

6.
J Radiol Prot ; 38(1): 229-246, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29154260

RESUMO

This paper proposes an analysis methodology based on the spectral windows technique aimed for environmental real-time gamma-ray spectra obtained with scintillation detectors. The method permits us to monitor activity concentrations of selected isotopes, such as anthropogenic radionuclides like 137Cs and 131I, by removing the Compton scattering plus other external contributions and resolving peak overlapping within any window. Activity concentrations are presented for 137Cs, 131I, 214Bi, and 214Pb when applying the method to a monitor using a LaBr3(Ce) detector. The method avoids false-positive and false-negative results of anthropogenic radionuclides in the presence of radiation from natural origins by obtaining activity concentrations that correspond to those obtained by a Gaussian fitting commercial software.


Assuntos
Monitoramento Ambiental/métodos , Espectrometria gama/métodos , Calibragem , Radioisótopos de Césio/análise , Humanos , Radioisótopos do Iodo/análise
7.
Neurologia ; 32(2): 69-73, 2017 Mar.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-25661268

RESUMO

INTRODUCTION: Patients with Down syndrome (DS) who exhibit Alzheimer disease (AD) are associated with age. Both diseases with a common neuropathological basis have been associated with late-onset myoclonic epilepsy (LOMEDS). This entity presents electroencephalogram features as generalized polyspike-wave discharges. METHOD: We present a series of 11 patients with the diagnosis of DS or AD who developed myoclonic seizures or generalized tonic-clonic seizures. In all cases, clinical and neuroimaging studies and polygraph EEG monitoring was performed. RESULTS: In all cases, cognitive impairment progressed quickly after the onset of epilepsy causing an increase in the degree of dependence. The most common finding in the EEG was a slowing of brain activity with theta and delta rhythms, plus intercritical generalized polyspike-waves were objectified in eight patients. In neuroimaging studies was found cerebral cortical atrophy. The most effective drug in this series was the levetiracetam. CONCLUSIONS: The association of generalized epilepsy with elderly DS represents an epiphenomenon in evolution which is associated with a progressive deterioration of cognitive and motor functions. This epilepsy has some electroclinical characteristics and behaves as progressive myoclonic epilepsy, which is probably related to the structural changes that characterize the evolutionary similarity of DS with AD. Recognition of this syndrome is important, since it has prognostic implications and requires proper treatment.


Assuntos
Doença de Alzheimer/complicações , Síndrome de Down/complicações , Epilepsias Mioclônicas/complicações , Adulto , Idoso , Anticonvulsivantes/uso terapêutico , Eletroencefalografia , Epilepsias Mioclônicas/diagnóstico por imagem , Epilepsias Mioclônicas/tratamento farmacológico , Feminino , Humanos , Levetiracetam , Masculino , Pessoa de Meia-Idade , Piracetam/análogos & derivados , Piracetam/uso terapêutico , Estudos Retrospectivos , Ácido Valproico/uso terapêutico
8.
Phys Chem Chem Phys ; 18(11): 8132-9, 2016 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-26922870

RESUMO

The response of 3C-SiC to hydrostatic pressure and to several uni- and bi-axial stress conditions is thoroughly investigated using first principles calculations. A topological interpretation of the chemical bonding reveals that the so-called non-covalent interactions enhance only at high pressure while the nature of the covalent Si-C bonding network keeps essentially with the same pattern. The calculated low compressibility agrees well with experimental values and is in concordance with the high structural stability of this polymorph under hydrostatic pressure. Under uniaxial [001] stress, the c/a ratio shows a noticeable drop inducing a closure of the band gap and the emergence of a metallic state around 40 GPa. This behavior correlates with a plateau of the electron localization function exhibiting a roughly constant and non-negligible value surrounding CSi4 and SiC4 covalent bonded units.

9.
Nucleic Acids Res ; 42(2): 882-92, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24165878

RESUMO

Modulation of miR-33 and miR-122 has been proposed to be a promising strategy to treat dyslipidemia and insulin resistance associated with obesity and metabolic syndrome. Interestingly, specific polyphenols reduce the levels of these mi(cro)RNAs. The aim of this study was to elucidate the effect of polyphenols of different chemical structure on miR-33a and miR-122 expression and to determine whether direct binding of the polyphenol to the mature microRNAs (miRNAs) is a plausible mechanism of modulation. The effect of two grape proanthocyanidin extracts, their fractions and pure polyphenol compounds on miRNA expression was evaluated using hepatic cell lines. Results demonstrated that the effect on miRNA expression depended on the polyphenol chemical structure. Moreover, miR-33a was repressed independently of its host-gene SREBP2. Therefore, the ability of resveratrol and epigallocatechin gallate to bind miR-33a and miR-122 was measured using (1)H NMR spectroscopy. Both compounds bound miR-33a and miR-122 and differently. Interestingly, the nature of the binding of these compounds to the miRNAs was consistent with their effects on cell miRNA levels. Therefore, the specific and direct binding of polyphenols to miRNAs emerges as a new posttranscriptional mechanism by which polyphenols could modulate metabolism.


Assuntos
Catequina/análogos & derivados , MicroRNAs/efeitos dos fármacos , Estilbenos/farmacologia , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Animais , Catequina/química , Catequina/farmacologia , Linhagem Celular Tumoral , Ácido Graxo Sintases/metabolismo , Flavonoides/química , Flavonoides/farmacologia , Humanos , Fígado/citologia , Fígado/metabolismo , MicroRNAs/metabolismo , Extratos Vegetais/química , Polifenóis/química , Polifenóis/farmacologia , Ratos , Resveratrol , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Estilbenos/química , Vitis/química
10.
Neurologia ; 31(8): 550-61, 2016 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-23582371

RESUMO

INTRODUCTION: Lithium was proposed in 2008 as an effective candidate in the treatment of ALS after a report claimed that it was able to delay functional deterioration by 40% and that none of the 16 patients treated with a combination of lithium plus riluzole had died during a 15-month follow-up period. The excellent results of this pilot study engendered considerable optimism among patients, their families, patients' associations, and the scientific community. This report sparked numerous phase ii clinical trials. Many patients who were not included in these studies used all resources at their disposal to access the drug as treatment under a compassionate use programme. OBJECTIVES: To evaluate the effectiveness of lithium in ALS using a meta-analysis of the information reported in 12 studies which were examined for methodological quality. MATERIAL AND METHODS: . Searches were performed using MEDLINE, EMBASE, the Cochrane Neuromuscular Disease Group Trials Register, ClinicalTrials.gov, and EudraCT (January 1996-August 2012). RESULTS: To date, we have information on more 1100 patients treated with lithium. Unfortunately, the results do not confirm the positive effect described in the pilot study, which suggests that this drug is not effective at slowing disease progression. Two trials had to be suspended before the scheduled completion date due to the ineffectiveness of the drug as well as numerous adverse effects. A recently published study also ruled out any possible modest effect. CONCLUSIONS: There is evidence to suggest that lithium has no short-term benefits in ALS. A comparison of the group of patients treated with lithium+riluzole and the control group treated with riluzole alone showed no statistically significant differences in rates of functional decline, deterioration of respiratory function, or survival time. Furthermore, there was no evidence that it was more effective than the placebo.


Assuntos
Esclerose Lateral Amiotrófica/tratamento farmacológico , Compostos de Lítio/uso terapêutico , Humanos , Fármacos Neuroprotetores/uso terapêutico , Riluzol/uso terapêutico , Resultado do Tratamento
11.
Biochim Biophys Acta ; 1837(6): 783-91, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24486445

RESUMO

Skeletal muscle is a key organ of mammalian energy metabolism, and its mitochondria are multifunction organelles that are targets of dietary bioactive compounds. The goal of this work was to examine the regulation of mitochondrial dynamics, functionality and cell energy parameters using docosahexaenoic acid (DHA), epigallocatechin gallate (EGCG) and a combination of both in L6 myocytes. Compounds (at 25µM) were incubated for 4h. Cells cultured with DHA displayed less oxygen consumption with higher ADP/ATP ratio levels concomitant with downregulation of Cox and Ant1 gene expression. The disruption of energetic homeostasis by DHA, increases intracellular reactive oxygen species (ROS) levels and decreases mitochondrial membrane potential. The defence mechanism to counteract the excess of ROS production was by the upregulation of Ucp2, Ucp3 and MnSod gene expression. Moreover myocytes cultured with DHA had a higher mitochondrial mass with a higher proportion of large and elongated mitochondria, whereas the fission genes Drp1 and Fiss1 and the fusion gene Mfn2 were downregulated. In myocytes co-incubated with DHA and EGCG, ROS levels and the adenosine diphosphate (ADP)/adenosine triphosphate (ATP) ratio were similar to untreated myocytes and the decrease of oxygen consumption, higher mitochondrial mass and the overexpression of Ucp2 and Ucp3 genes were similar to the DHA-treated cells with also a higher amount of mitochondrial deoxyribonucleic acid (DNA), and reduced Drp1 and Fiss1 gene expression levels. In conclusion the addition of EGCG to DHA returned the cells to the control conditions in terms of mitochondrial morphology, energy and redox status, which were unbalanced in the DHA-treated myocytes.


Assuntos
Catequina/análogos & derivados , Ácidos Docosa-Hexaenoicos/farmacologia , Músculo Esquelético/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Cálcio/metabolismo , Catequina/farmacologia , Células Cultivadas , Mitocôndrias Musculares/efeitos dos fármacos , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Fosforilação Oxidativa , Espécies Reativas de Oxigênio/metabolismo
12.
Clin Sci (Lond) ; 127(8): 527-37, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-24754522

RESUMO

Hepatic microcirculatory dysfunction due to cold storage and warm reperfusion (CS+WR) injury during liver transplantation is partly mediated by oxidative stress and may lead to graft dysfunction. This is especially relevant when steatotic donors are considered. Using primary cultured liver sinusoidal endothelial cells (LSECs), liver grafts from healthy and steatotic rats, and human liver samples, we aimed to characterize the effects of a new recombinant form of human manganese superoxide dismutase (rMnSOD) on hepatic CS+WR injury. After CS+WR, the liver endothelium exhibited accumulation of superoxide anion (O2-) and diminished levels of nitric oxide (NO); these detrimental effects were prevented by rMnSOD. CS+WR control and steatotic rat livers exhibited markedly deteriorated microcirculation and acute endothelial dysfunction, together with liver damage, inflammation, oxidative stress, and low NO. rMnSOD markedly blunted oxidative stress, which was associated with a global improvement in liver damage and microcirculatory derangements. The addition of rMnSOD to CS solution maintained its antioxidant capability, protecting rat and human liver tissues. In conclusion, rMnSOD represents a new and highly effective therapy to significantly upgrade liver procurement for transplantation.


Assuntos
Fígado/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Superóxido Dismutase/farmacologia , Animais , Fígado Gorduroso/terapia , Humanos , Fígado/patologia , Transplante de Fígado , Masculino , Microcirculação/efeitos dos fármacos , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Proteínas Recombinantes/farmacologia
13.
Arterioscler Thromb Vasc Biol ; 33(8): 1965-72, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23766266

RESUMO

OBJECTIVE: LL-37, the unique cathelicidin expressed in humans, in addition to acting as an endogenous antibiotic, is an important cell-signaling molecule upregulated in ovarian, breast, and lung tumors. However, the role of LL-37 in tumor microenvironment and its specific actions on the endothelial compartment remain elusive. Prostanoids are key regulators of inflammation, and cyclooxygenases (COXs) display proangiogenic activity in vitro and in vivo, mediated principally through prostaglandin E2 (PGE2). Here, we provide evidence for a novel proangiogenic role of LL-37, exerted via activation of endothelial cells and subsequent PGE2 biosynthesis. APPROACH AND RESULTS: LL-37 triggers PGE2 synthesis in endothelial cells in a dose-dependent manner with maximal induction after 4 hours. Endothelial PGE2 biosynthesis was dependent on COX-1, rather than COX-2, as judged by pharmacological inhibition and gene silencing. In vitro matrigel assays supported these findings because LL-37-induced cord formation was abolished by COX-1, but not COX-2, small interfering RNA, and the angiogenic phenotype could be rescued by addition of exogenous PGE2. We find that LL-37 acts on endothelial cells as a potent calcium agonist, inducing phosphorylation and activation of cytosolic phospholipase A2 (cPLA2), promoting a cPLA2→COX-1→PGE2 biosynthetic pathway and subsequent signaling via PGE2 receptor EP3. Moreover, cathelicidin-related antimicrobial peptide, which is the murine ortholog of LL-37, induced prostaglandin-dependent angiogenesis in vivo, which could be blocked by aspirin. CONCLUSIONS: Our results identify a novel proangiogenic role of LL-37, suggesting that the axis LL-37/COX-1/PGE2 followed by EP3 signaling is amenable to therapeutic intervention in pathological angiogenesis, for instance by aspirin.


Assuntos
Peptídeos Catiônicos Antimicrobianos/antagonistas & inibidores , Peptídeos Catiônicos Antimicrobianos/fisiologia , Aspirina/farmacologia , Células Endoteliais/fisiologia , Neovascularização Fisiológica/fisiologia , Transdução de Sinais/fisiologia , Anti-Inflamatórios não Esteroides/farmacologia , Cálcio/metabolismo , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Fosfolipases A2 do Grupo IV/metabolismo , Humanos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/fisiopatologia , Neovascularização Fisiológica/efeitos dos fármacos , Fosforilação/fisiologia , Cultura Primária de Células , Receptores de Prostaglandina E Subtipo EP3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Catelicidinas
14.
J Clin Microbiol ; 50(2): 488-91, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22135258

RESUMO

The aim of this study was to evaluate the reliability of the VersaTREK system for Mycobacterium tuberculosis drug susceptibility testing compared with results obtained with the Bactec MGIT 960 system. A total of 67 strains were evaluated. Overall agreement was at 98.5%. Kappa indexes were 1.0 for isoniazid, rifampin, and ethambutol, 0.937 for pyrazinamide, and 0.907 for streptomycin. The VersaTREK system is validated for M. tuberculosis drug susceptibility testing.


Assuntos
Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana/métodos
15.
FASEB J ; 25(4): 1417-27, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21228223

RESUMO

Cysteinyl leukotrienes (cysLTs) are potent proinflammatory mediators with particular relevance for asthma. However, control of cysLT biosynthesis in the time period after onset of acute inflammation has not been extensively studied. As a model for later phases of inflammation, we investigated regulation of leukotriene (LT) C(4) synthase (LTC(4)S) in differentiating monocytes, exposed for several days to fungal zymosan. Incubations with LTA(4) revealed 20-fold increased LTC(4)S activity during differentiation of monocytic Mono Mac 6 (MM6) cells, which was reduced by 80% in the presence of zymosan (25 µg/ml, 96 h). Zymosan (48 h) similarly attenuated LTC(4)S activity of primary human monocyte-derived macrophages and dendritic cells. Several findings indicate phosphoregulation of LTC(4)S: increased activity during MM6 cell differentiation correlated with reduced phosphorylation of 70-kDa ribosomal protein S6 kinase (p70S6K), which could phosphorylate purified LTC(4)S; the p70S6K inhibitor rapamycin (20 nM) doubled LTC(4)S activity of undifferentiated MM6 cells, and protein kinase A and C inhibitors (H-89, CGP-53353, and staurosporine) reversed the zymosan-induced suppression of LTC(4)S activity. Finally, zymosan (48 h) up-regulated PGE(2) biosynthesis, and aspirin (10 µM) or prostaglandin E(2) (PGE(2)) receptor antagonists counteracted the zymosan effect. Our results suggest a late PGE(2)-mediated phosphoregulation of LTC(4)S during microbial exposure, which may contribute to resolution of inflammation, with implications for aspirin hypersensitivity.


Assuntos
Aspirina/farmacologia , Glutationa Transferase/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Zimosan/farmacologia , Diferenciação Celular , Linhagem Celular , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Dinoprostona/farmacologia , Humanos , Leucotrieno C4/biossíntese , Macrófagos/efeitos dos fármacos , Proteína Quinase C/metabolismo , Receptores de Prostaglandina E/antagonistas & inibidores , Proteínas Quinases S6 Ribossômicas 70-kDa/antagonistas & inibidores , Sirolimo/farmacologia , Estaurosporina/farmacologia , Receptor 2 Toll-Like/fisiologia , Zimosan/antagonistas & inibidores
16.
Br J Nutr ; 108(2): 208-17, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22011563

RESUMO

Proanthocyanidins have been shown to improve postprandial hypertriacylglycerolaemia. The present study aims to determine the actual contribution of chylomicrons (CM) and VLDL in the hypotriacylglycerolaemic action of grape seed proanthocyanidin extract (GSPE) in the postprandial state and to characterise the mechanisms by which the GSPE treatment reduces TAG-rich lipoproteins in vivo. A plasma lipid tolerance test was performed on rats fasted for 14 h and orally loaded with lard containing either GSPE or not. GSPE (250 mg/kg body weight) markedly blocked the increase in plasma TAG induced by lard, with a statistically significant reduction of 22 % in the area under the curve. The VLDL-rich fraction was the major contributor (72 %) after 1 h, whereas the CM-rich fraction was the major contributor (85 %) after 3 h. At 5 and 7 h after treatment, CM-rich and VLDL-rich fractions showed a similar influence. Plasma post-heparin lipoprotein lipase (LPL) activity and LPL mRNA levels in white adipose tissue and muscle were not affected by GSPE. On the contrary, GSPE treatment significantly repressed (30 %) the secretion of VLDL-TAG. In the liver, GSPE treatment induced different effects on the expression of acyl-coenzyme A synthetase long-chain family member 1, Apoc3 and 3-hydroxy-3-methylglutaryl-coenzyme A reductase at 1 h and Cd36 at 5 h, compared to those induced by lard. Furthermore, GSPE treatment significantly increased the activity of carnitine palmitoyltransferase 1a at 1 h. In conclusion, both CM-rich and VLDL-rich fractions contributed to the hypotriacylglycerolaemic action of GSPE, but their influence depended on time. GSPE induces hypotriacylglycerolaemic actions by repressing lipoprotein secretion and not by increasing LPL activity.


Assuntos
Quilomícrons/sangue , Suplementos Nutricionais , Extrato de Sementes de Uva/uso terapêutico , Hipertrigliceridemia/prevenção & controle , Hipolipemiantes/uso terapêutico , Lipoproteínas VLDL/sangue , Proantocianidinas/uso terapêutico , Triglicerídeos/sangue , Ácido 3-Hidroxibutírico/sangue , Animais , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Quilomícrons/química , Ácidos Graxos não Esterificados/sangue , Regulação Enzimológica da Expressão Gênica , Hipertrigliceridemia/sangue , Hipertrigliceridemia/metabolismo , Mucosa Intestinal/enzimologia , Mucosa Intestinal/metabolismo , Gordura Intra-Abdominal/enzimologia , Gordura Intra-Abdominal/metabolismo , Lipase Lipoproteica/sangue , Lipase Lipoproteica/genética , Lipase Lipoproteica/metabolismo , Lipoproteínas VLDL/química , Lipoproteínas VLDL/metabolismo , Fígado/enzimologia , Fígado/metabolismo , Masculino , Especificidade de Órgãos , Período Pós-Prandial , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Triglicerídeos/efeitos adversos , Triglicerídeos/metabolismo
17.
Rev Neurol ; 74(7): 232-241, 2022 04 01.
Artigo em Espanhol | MEDLINE | ID: mdl-35332927

RESUMO

INTRODUCTION: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a clinical entity with significant phenotypic variability both in its onset and in its course. Therefore, it is important to have objective biomarkers with which to monitor its evolution. In this review we present clinical, neurophysiological, neuroimaging, blood and cerebrospinal fluid (CSF) biomarkers for the monitoring and prognosis of CIDP. DEVELOPMENT: Different clinical tools have been developed and validated to monitor CIDP by assessing strength and disability. However, the best parameter for monitoring gait remains to be determined. Monitoring by neurophysiological examination is also widespread and the amplitude of the compound muscle action potential is the most commonly used. More recently, the Motor Unit Number Index sum score has been developed, which is an accurate and reproducible technique. The role of nerve ultrasonography is under development and a correlation between clinical evolution and ultrasound findings has been described. Multiple biomarkers have been described in blood and CSF, including antinodal/paranodal antibodies, neurofilament light chain, serum immunoglobulin G levels and CSF sphingomyelin levels. Genetic variants and cytokines associated with prognosis and response to treatment have also been described. CONCLUSIONS: One of the most important challenges in the management of CIDP is the monitoring of clinical changes after treatment initiation. The combination of biomarkers that allow an accurate understanding of the disease is crucial for the optimal management of CIDP.


TITLE: Biomarcadores pronósticos y de seguimiento en la polineuropatía desmielinizante inflamatoria crónica.Introducción. La polineuropatía desmielinizante inflamatoria crónica (PDIC) es una entidad clínica con una variabilidad fenotípica muy importante tanto en el inicio como en la evolución. Por lo tanto, es importante disponer de biomarcadores objetivos para monitorizar la evolución. En esta revisión presentamos los biomarcadores clínicos, neurofisiológicos, de neuroimagen, y en la sangre y el líquido cefalorraquídeo (LCR) para el seguimiento y el pronóstico de la PDIC. Desarrollo. Se han desarrollado diferentes herramientas clínicas validadas para el seguimiento de la PDIC mediante la evaluación de la fuerza y la discapacidad. No obstante, falta determinar el mejor parámetro para monitorizar la marcha. El seguimiento mediante examen neurofisiológico también está ampliamente extendido, y la amplitud del compound muscle action potential es lo más utilizado. Más recientemente, se ha desarrollado la Motor Unit Number Index sum score, que es una técnica precisa y reproducible. El papel de la ecografía de nervio se encuentra en desarrollo, y se ha descrito correlación entre la evolución clínica y los hallazgos por ecografía. Se han descrito múltiples biomarcadores en sangre y el LCR, entre los que destacan los anticuerpos antinodales/paranodales, los neurofilamentos de cadena ligera, los niveles de inmunoglobulina G en el suero y los niveles de esfingomielina en el LCR. Asimismo, se han descrito variantes genéticas y citocinas relacionadas con el pronóstico y la respuesta a los tratamientos. Conclusiones. Uno de los retos más importante en el manejo de la PDIC es la monitorización de los cambios clínicos tras el inicio del tratamiento. La combinación de biomarcadores que permitan una comprensión exacta de la enfermedad es crucial para el manejo óptimo de la PDIC.


Assuntos
Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Biomarcadores , Humanos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Prognóstico , Ultrassonografia
18.
Rev Neurol ; 75(8): 247-250, 2022 10 16.
Artigo em Espanhol | MEDLINE | ID: mdl-36218255

RESUMO

INTRODUCTION: The massive vaccination against the SARS-CoV-2 virus has demonstrated to be one of the major measures for the reduction of the morbidity and mortality that this virus causes. However, during the last months the administration of the vaccine has been also associated with some rare, but life-threatening, adverse effects. CASE REPORT: In this article we describe the case of a patient that developed a Guillain-Barre syndrome and an Idiopathic thrombocytopenic purpura nine days after the vaccination with the third dose for the SARS-CoV-2 virus (Moderna). He had received previously two doses of the AstraZeneca vaccine. Moreover, the patient was positive for auto-antibodies anti-SSA/Ro60 and auto-antibodies IgG anti-GM1 and IgG anti-GM3. DISCUSSION: Even though it is not possible to stablish a clear relation of causality between the administration of the vaccine booster for SARS-CoV-2 and the diseases developed by the patient, the association of two concomitant autoimmune processes is remarkable. As well as the positivity for the auto-antibodies anti-SSA/Ro60, which have been described in the bibliography in cases of SARS-CoV-2 infection.


TITLE: Síndrome de Guillain-Barré y trombocitopenia tras la vacunación contra el SARS-CoV-2 con Moderna. Descripción de un caso.Introducción. La vacunación masiva contra el virus SARS-CoV-2 constituye una de las principales estrategias en la reducción de la morbimortalidad que presenta dicho virus. No obstante, a lo largo de los últimos meses, su administración también se ha relacionado con diversos efectos adversos raros, pero potencialmente graves. Caso clínico. En el presente artículo describimos el caso de un paciente que desarrolló un síndrome de Guillain-Barré y una púrpura trombocitopénica idiopática nueve días después de la vacunación con la tercera dosis contra el virus SARS-CoV-2 (Moderna), con dos dosis previas de AstraZeneca. Adicionalmente, destaca la presencia de positividad para autoanticuerpos anti-SSA/Ro60 y para anticuerpos inmunoglobulina G anti-GM1 e inmunoglobulina G anti-GM3. Conclusión. Aunque no es posible establecer una relación de causalidad entre la administración del booster de la vacuna y el desarrollo de la enfermedad, es destacable la asociación de dos procesos autoinmunes concomitantes, junto con la positividad en los autoanticuerpos anti-SSA/Ro60, lo cual se ha descrito en la bibliografía en casos de infección del virus SARS-CoV-2.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Síndrome de Guillain-Barré , Trombocitopenia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Síndrome de Guillain-Barré/etiologia , Humanos , Imunoglobulina G , Masculino , SARS-CoV-2 , Trombocitopenia/etiologia , Vacinação/efeitos adversos , Vacinas Virais
19.
Eur J Clin Microbiol Infect Dis ; 30(12): 1551-5, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21491175

RESUMO

The purpose of this study was to report intra- and inter-species spread of carbapenemase genes between gram negative rods isolated from a non-hospitalized patient with bacteremia. The approach included chart review, antibiotic susceptibility testing and phenotypic screening for metallo-ß-lactamase (MBL) detection, PCR and sequencing of bla, aac(6')-Ib and qnr genes, and plasmid analysis by PCR-based replicon typing. The clonal relationships between the isolates were analysed by comparing PFGE profiles. A non-hospitalized patient presented bacteraemia due to wild type Enterobacter cloacae (4.08), a VIM-1-producing E. cloacae (5.08), a VIM-1- and CTX-M-9-producing E. cloacae (7.08), a VIM-2-producing Pseudomonas aeruginosa, and catheter colonization by VIM-1-producing Klebsiella oxytoca. The patient had no previous hospitalization but had recently undergone an ambulatory colonoscopy. In E. cloacae 7.08 and K. oxytoca isolates, the bla(VIM-1) gene was located on a transferable plasmid of 48.5 kb, while in E. cloacae 5.08 the bla(VIM-1) gene was encoded on a 194 kb non-transferable plasmid. The bla(CTX-M-9) gene detected in E. cloacae was encoded on an HI2 plasmid of 290 kb. To date the prevalence of VIM-1 enzymes in the community is low. This molecular finding suggests an intra-species and/or inter-species horizontal spread of the MBL gene in the same non-hospitalized patient.


Assuntos
Proteínas de Bactérias/genética , Transferência Genética Horizontal , Bactérias Gram-Negativas/enzimologia , Bactérias Gram-Negativas/genética , Infecções por Bactérias Gram-Negativas/microbiologia , beta-Lactamases/genética , Idoso , Antibacterianos/farmacologia , Bacteriemia/microbiologia , Catéteres/microbiologia , Análise por Conglomerados , DNA Bacteriano/genética , Eletroforese em Gel de Campo Pulsado , Genótipo , Bactérias Gram-Negativas/classificação , Bactérias Gram-Negativas/isolamento & purificação , Humanos , Masculino , Testes de Sensibilidade Microbiana , Tipagem Molecular , Plasmídeos/análise , Reação em Cadeia da Polimerase , Análise de Sequência de DNA
20.
Eur J Clin Microbiol Infect Dis ; 30(1): 103-8, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20711795

RESUMO

The purpose of this investigation was to compare the risk factors, clinical features and outcomes in cancer patients with bacteraemia caused by vancomycin-susceptible Enterococcus faecalis and E. faecium. A retrospective, observational 7-year study was carried out in a 450-bed, acute-care university-affiliated hospital. We performed univariate comparisons between the two groups and then multivariate analysis to identify patient risk factors for E. faecium isolation. Seventy-three patients were included in the analysis: 54 (74.0%) with bacteraemia caused by E. faecalis and 19 (26.0%) by E. faecium. The Simplified Acute Physiological Score (SAPS) value was significantly greater in E. faecium isolates (40.7 vs. 35.2; p = 0.009). Diabetes mellitus was more frequently diagnosed in patients with E. faecium bacteraemia (52.6% vs. 24.1%; p = 0.021). Prior penicillin exposure was more frequent in patients with E. faecium bacteraemia (68.4% vs. 29.6%; p = 0.003). There was a trend toward higher mortality in E. faecium bacteraemia patients (47.4% vs. 25.9%; p = 0.084). Independent patient risk factors for E. faecium isolation were prior penicillin exposure (odds ratio [OR], 6.479; p = 0.003) and SAPS > 34 (OR, 6.896; p = 0.009). When compared to E. faecalis bacteraemia, E. faecium bacteraemia in cancer patients is independently associated with more severe illness and prior use of penicillins; therefore, empiric treatment which would cover E. faecium should be considered in cancer patients suspected of having bacteraemia.


Assuntos
Antibacterianos/administração & dosagem , Bacteriemia/epidemiologia , Enterococcus faecalis/isolamento & purificação , Enterococcus faecium/isolamento & purificação , Infecções por Bactérias Gram-Positivas/epidemiologia , Neoplasias/complicações , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bacteriemia/patologia , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Feminino , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/patologia , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Espanha/epidemiologia , Resultado do Tratamento
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