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1.
Exp Parasitol ; 220: 108034, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33188795

RESUMO

Eimeria ninakohlyakimovae represents a highly pathogenic coccidian parasite causing severe haemorrhagic typhlocolitis in goat kids worldwide. NETosis was recently described as an efficient defense mechanism of polymorphonuclear neutrophils (PMN) acting against different parasites in vitro and in vivo. In vitro interactions of caprine PMN with parasitic stages of E. ninakohlyakimovae (i. e. oocysts and sporozoites) as well as soluble oocyst antigens (SOA) were analyzed at different ratios, concentrations and time spans. Extracellular DNA staining was used to illustrate classical molecules induced during caprine NETosis [i. e. histones (H3) and neutrophil elastase (NE)] via antibody-based immunofluorescence analyses. Functional inhibitor treatments with DPI and DNase I were applied to unveil role of NADPH oxidase (NOX) and characterize DNA-backbone composition of E. ninakohlyakimovae-triggered caprine NETosis. Scanning electron microscopy (SEM)- and immunofluorescence-analyses demonstrated that caprine PMN underwent NETosis upon contact with sporozoites and oocysts of E. ninakohlyakimovae, ensnaring filaments which firmly entrapped parasites. Detailed co-localization studies of E. ninakohlyakimovae-induced caprine NETosis revealed presence of PMN-derived DNA being adorned with nuclear H3 and NE corroborating molecular characteristics of NETosis. E. ninakohlyakoimovae-induced caprine NETosis was found to be NOX-independent since DPI inhibition led to a slight decrease of NETosis. Exposure of caprine PMN to vital E. ninakohlyakimovae sporozoites as well as SOA resulted in up-regulation of IL-12, TNF-α, IL-6, CCL2 and iNOS gene transcription in stimulated PMN. Since vital E. ninakohlyakimovae-sporozoites induced caprine NETosis, this effective entrapment mechanism might reduce initial sporozoite epithelial host cell invasion during goat coccidiosis ultimately resulting in less macromeront formation and reduced merozoites I production.


Assuntos
Coccidiose/veterinária , Citocinas/genética , Eimeria/imunologia , Doenças das Cabras/parasitologia , Neutrófilos/parasitologia , Análise de Variância , Animais , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Coccidiose/imunologia , Coccidiose/parasitologia , Colite/parasitologia , Colite/veterinária , Citocinas/metabolismo , Eimeria/genética , Eimeria/ultraestrutura , Hemorragia Gastrointestinal/parasitologia , Hemorragia Gastrointestinal/veterinária , Doenças das Cabras/imunologia , Cabras , Interleucina-12/genética , Interleucina-12/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Microscopia Eletrônica de Varredura/veterinária , NADPH Oxidases/metabolismo , Neutrófilos/imunologia , Neutrófilos/ultraestrutura , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Oocistos/genética , Oocistos/imunologia , Reação em Cadeia da Polimerase/veterinária , Esporozoítos/genética , Esporozoítos/imunologia , Transcrição Gênica , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Tiflite/parasitologia , Tiflite/veterinária , Regulação para Cima
2.
J Eur Acad Dermatol Venereol ; 35(9): 1865-1873, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34013600

RESUMO

BACKGROUND: Descriptions of cutaneous findings associated with COVID-19 have not been consistently accompanied by histopathology or confirmatory testing for SARS-CoV-2. OBJECTIVE: To describe and classify the cutaneous findings with supporting histopathology of confirmed COVID-19 inpatients. METHODS: We included consecutive inpatients with a confirmed diagnosis of COVID-19 for whom a dermatology consult was requested. A skin biopsy was performed in all cases. Skin findings were classified as being compatible with a cutaneous manifestation of COVID-19 or as representing a distinct clinical entity. RESULTS: Twenty-eight patients were studied in whom thirty-one dermatologic diagnoses were made. Twenty-two of the dermatoses were compatible with a cutaneous manifestation of COVID-19; nine entities were not associated with infection by SARS-CoV-2. The most common COVID-19-associated pattern was an exanthematous presentation. In four patients, a new pattern was observed, characterized by discrete papules with varied histopathological findings including a case of neutrophilic eccrine hidradenitis. No cases of pernio-like lesions were identified. Skin findings not associated with COVID-19 represented 29% of diagnoses and included Malassezia folliculitis, tinea, miliaria and contact dermatitis. LIMITATIONS: There is no gold-standard test to distinguish between viral exanthems and drug reactions. CONCLUSION: A histopathological study is critical before attributing skin findings to a manifestation of COVID-19.


Assuntos
COVID-19 , Pérnio , Dermatopatias , Humanos , SARS-CoV-2 , Pele
3.
Phys Rev Lett ; 125(26): 266802, 2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33449729

RESUMO

The persistence of ferroelectricity in ultrathin layers relies critically on screening or compensation of polarization charges which otherwise destabilize the ferroelectric state. At surfaces, charged defects play a crucial role in the screening mechanism triggering novel mixed electrochemical-ferroelectric states. At interfaces, however, the coupling between ferroelectric and electrochemical states has remained unexplored. Here, we make use of the dynamic formation of the oxygen vacancy profile in the nanometer-thick barrier of a ferroelectric tunnel junction to demonstrate the interplay between electrochemical and ferroelectric degrees of freedom at an oxide interface. We fabricate ferroelectric tunnel junctions with a La_{0.7}Sr_{0.3}MnO_{3} bottom electrode and BaTiO_{3} ferroelectric barrier. We use poling strategies to promote the generation and transport of oxygen vacancies at the metallic top electrode. Generated oxygen vacancies control the stability of the ferroelectric polarization and modify its coercive fields. The ferroelectric polarization, in turn, controls the ionization of oxygen vacancies well above the limits of thermodynamic equilibrium, triggering the build up of a Schottky barrier at the interface which can be turned on and off with ferroelectric switching. This interplay between electronic and electrochemical degrees of freedom yields very large values of the electroresistance (more than 10^{6}% at low temperatures) and enables a controlled switching between clockwise and counterclockwise switching modes in the same junction (and consequently, a change of the sign of the electroresistance). The strong coupling found between electrochemical and electronic degrees of freedom sheds light on the growing debate between resistive and ferroelectric switching in ferroelectric tunnel junctions, and moreover, can be the source of novel concepts in memory devices and neuromorphic computing.

4.
Trop Anim Health Prod ; 51(2): 465-468, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30083862

RESUMO

Bituminaria bituminosa (C.H. Stirt.) is a drought tolerant legume that grows spontaneously in subtropical areas: Canary Islands (Spain) and in North African and Mediterranean regions, traditionally used as forage for ruminants. The aim of this research was to investigate the potential of B. bituminosa as a high protein resource for poultry feed by means of feed intake, growth, feed conversion rate (FCR), protein efficiency ratio (PER), and the influence of B. bituminosa feed form (fresh green and dried) on the preference by chicks. B. bituminosa showed higher crude protein content (CP), neutral detergent fiber (NDF), and gross energy than commercial feed. Average daily feed intake (ADFI) for the commercial feed group (control group) was higher than ADFI of the B. bituminosa group (experimental group). However, both groups had no significant differences in total crude protein intake, total NDF intake, average daily gain (ADG), FCR, and PER. The poultry's preference for fresh green B. bituminosa was higher than for dry B. bituminosa. Our results suggest that B. bituminosa (tedera) could be an alternative feedstuff in tropical countries or where protein sources are scarce and costly.


Assuntos
Fabaceae/química , Aves Domésticas/crescimento & desenvolvimento , Ração Animal/análise , Animais , Galinhas/metabolismo , Fibras na Dieta/análise , Proteínas Alimentares/análise , Fabaceae/metabolismo , Aves Domésticas/metabolismo , Espanha
6.
Parasitol Res ; 114(11): 4327-31, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26341796

RESUMO

Eimeria ninakohlyakimovae is an important coccidian parasite of goats which causes severe diarrhoea in young animals. Specific molecules that mediate E. ninakohlyakimovae host interactions and molecular mechanisms involved in the pathogenesis are still unknown. Although strong circumstantial evidence indicates that E. ninakohlyakimovae sporozoite interactions with caprine endothelial host cells (ECs) are specific, hardly any information is available about the interacting molecules that confer host cell specificity. In this study, we describe a novel method to identify surface proteins of caprine umbilical vein endothelial cells (CUVEC) using a phage display library. After several panning rounds, we identified a number of peptides that specifically bind to the surface of CUVEC. Importantly, caprine endothelial cell peptide 2 (PCEC2) and PCEC5 selectively reduced the infection rate by E. ninakohlyakimovae sporozoites. These preliminary data give new insight for the molecular identification of ligands involved in the interaction between E. ninakohlyakimovae sporozoites and host ECs. Further studies using this phage approach might be useful to identify new potential target molecules for the development of anti-coccidial drugs or even new vaccine strategies.


Assuntos
Coccidiose/veterinária , Eimeria/fisiologia , Células Endoteliais/imunologia , Doenças das Cabras/imunologia , Biblioteca de Peptídeos , Peptídeos/imunologia , Animais , Coccidiose/genética , Coccidiose/imunologia , Coccidiose/parasitologia , Eimeria/crescimento & desenvolvimento , Células Endoteliais/parasitologia , Doenças das Cabras/genética , Doenças das Cabras/parasitologia , Cabras , Interações Hospedeiro-Parasita , Ligantes , Peptídeos/genética , Esporozoítos/crescimento & desenvolvimento , Esporozoítos/fisiologia
7.
Radiologia ; 57(5): 419-27, 2015.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-25535030

RESUMO

OBJECTIVE: To determine the degree of tumor necrosis in surgical specimens of hepatocellular carcinomas treated with microspheres preloaded with doxorubicin and to analyze the relationship between the degree of necrosis and a) morphologic factors and b) imaging biomarkers. MATERIAL AND METHODS: We studied the livers of 21 patients who had undergone selective arterial chemoembolization with DC beads (Biocompatibles, UK) before receiving liver transplants. RESULTS: Imaging techniques detected 43 nodules (mean size, 25 mm). Angiography showed 25 hypervascularized nodules, 12 slightly vascularized nodules, and 6 avascular nodules. A total of 81 hepatocellular carcinomas (mean size, 15 mm) were detected in the specimens: two were capsular and two had vascular infiltration. The mean degree of necrosis after chemoembolization was 39%; necrosis was greater than 60% in 28 hepatocellular carcinomas and less than 60% in 52. The degree of necrosis correlated significantly with the time elapsed between the last chemoembolization treatment and liver transplantation (the degree of necrosis decreased as time increased), with the number of nodules in the specimen, and with capsular infiltration. When imaging techniques detected 1 or 2 nodules, there was a greater probability of achieving greater than 90% necrosis. No relation with the degree of necrosis achieved was found for the size of the nodules detected at imaging, the enhancement pattern, or the number of chemoembolization treatments. CONCLUSION: The degree of necrosis achieved depends on the time spent on the waiting list, on the number of nodules in the specimen, and on whether capsular infiltration is present.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Doxorrubicina/administração & dosagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Adulto , Idoso , Carcinoma Hepatocelular/cirurgia , Portadores de Fármacos , Feminino , Humanos , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Rev Esp Anestesiol Reanim (Engl Ed) ; 68(10): 597-601, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34810152

RESUMO

Iatrogenic tracheal rupture (ITR) is a serious complication secondary to procedures such as emergent orotracheal intubation or tracheostomy, among others. The management of ITR depends on the size, extension and location of the injury, along with the patient's respiratory status and comorbidities. The priority of treatment is to keep the airway permeable to ensure adequate ventilation. We present the case of a tracheal rupture after performing a percutaneous tracheostomy, in a patient diagnosed with severe acute respiratory distress syndrome secondary to bilateral interstitial pneumonia due to SARS-Cov-2. The issues are discussed, such as the management (conservative vs. surgical) depending on the features of the injury and the patient, in the extraordinary context that the COVID-19 pandemic has entailed.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Humanos , Doença Iatrogênica , Pandemias , Síndrome do Desconforto Respiratório/etiologia , Ruptura , SARS-CoV-2 , Traqueia/diagnóstico por imagem
9.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33845992

RESUMO

Iatrogenic tracheal rupture is a serious complication secondary to procedures such as emergent orotracheal intubation or tracheostomy, among others. The management of iatrogenic tracheal rupture depends on the size, extension and location of the injury, along with the patient's respiratory status and comorbidities. The priority of treatment is to keep the airway permeable to ensure adequate ventilation. We present the case of a tracheal rupture after performing a percutaneous tracheostomy, in a patient diagnosed with severe acute respiratory distress syndrome secondary to bilateral interstitial pneumonia due to SARS-CoV-2. The issues are discussed, such as the management (conservative vs. surgical) depending on the features of the injury and the patient, in the extraordinary context that the COVID-19 pandemic has entailed.

10.
Science ; 268(5208): 265-7, 1995 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-17814788

RESUMO

The compound [Fe(tvp)(2)(NCS)(2)] . CH(3)OH, where tvp is 1,2-di-(4-pyridyl)-ethylene, has been synthesized and characterized by x-ray single-crystal diffraction. It consists of two perpendicular, two-dimensional networks organized in parallel stacks of sheets made up of edge-shared [Fe(II)](4) rhombuses. The fully interlocked networks define large square channels in the [001] direction. Variable-temperature magnetic susceptibility measurements and Mössbauer studies reveal that this compound shows low-spin to high-spin crossover behavior in the temperature range from 100 to 250 kelvin. The combined structural and magnetic characterization of this kind of compound is fundamental for the interpretation of the mechanism leading to the spin crossover, which is important in the development of electronic devices such as molecular switches.

11.
Nefrologia ; 29(5): 464-73, 2009.
Artigo em Espanhol | MEDLINE | ID: mdl-19820759

RESUMO

INTRODUCTION: Introduction Patients with Chronic renal Disease (CRD) often have cardiovascular disease that is the main cause of morbidity and mortality. Oxidative stress and a subclinical inflammation are crucial factors in its development. The aim of this study was to asses the oxidation of the main molecular lines in patients with advanced renal disease without dialysis and to determinate the best biomarker to asses this stress. PATIENTS AND METHODS: We performed an observational study to measure the most important oxidative biomarkers in 32 patients with stage 4 CRD (MDRD = 22.1 +/- 1.08 ml/min) compared with the values obtained in a control group. In peripheral lymphocytes we measured, the lipid peroxidation by Malondialdehyde (MDA) and F2 Isoprostanes in plasma; protein oxidation by glutathione oxidized/reduced ratio (GSSG/GSH) in peripheral lymphocytes and protein carbonyls in plasma and the oxidative damage in genetic material by modified nucleotide base 8-deoxiguanosina oxo -(8-oxo-dG), after isolating nuclear and mitochondrial DNA. We also studied the antioxidant defenses with superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GSR) and catalase (CAT) in peripheral lymphocytes. We studied the correlation between oxidative stress and the renal function and oxidative stress and co-morbidity factors. RESULTS: All biomarkers showed important differences in comparison with the control subjects. 821.89 +/- 300.47 ng/ml vs. 270 (95.66) * ng/ml (p < 0.000), MDA 0.11 (0.11) * vs. 0.7 +/- 0.31 nmol/mg prot (p <0.000). GSSG / GSH: 6.89 +/- 1.91 vs. 1.39 +/- 0.75 (p <0.000), protein carbonyls: 7.41 +/- 0.84 vs. 3.63 (1.12) *. Nuclear 8-oxo-dG 7.88 (2.32) vs. 2.96 (1.78) * mitochondrial 8-oxo-dG: 15.73 +/- 2.28 vs. 13.85 +/- 1.44 (p <0.05). The Antioxidant enzymes also showed differences. Nuclear 8-oxo-dG demonstrated an important relationship with the rest of biomarkers, homocysteine (r = 0.305, p <0.05), lipoprotein (a) (r = 0.375, p <0.01), mitochondrial 8-oxo-dG (r = 0.411, p <0.05), GSSH/GSH (r = 0.595, p <0.001) and protein carbonyls (r = 0.489, p <0.05). There was an inverse correlation with total protein (r = -0.247, p <0.01), GSH (r = -0.648, p <0.000), GSR (r = -0.563, p <0.001) and SOD (r = -0.497, p <0.000). We did not find any correlation between these parameters and renal function. The presence of diabetes or the treatment with statins did not showed significant differences. * Median (Interquartile range). CONCLUSION: There is an important oxidative stress in patients with advanced renal disease, probably established during early stages of disease. Of the studied parameters, the nuclear 8-oxo-dG is the best marker for oxidative stress in CRD.


Assuntos
Nefropatias/metabolismo , Estresse Oxidativo , Idoso , Doença Crônica , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Res Vet Sci ; 118: 155-163, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29482176

RESUMO

Both the immune response developed in ruminants against Eimeria spp. and the ability to bear patent infections seems to be dependent on the age of the host. In the present study we have evaluated the influence of the age in the development of protective immune responses against Eimeria ninakohlyakimovae. For this purpose, 3, 4 and 5-week-old goat kids were infected with sporulated oocysts and subjected to a homologous challenge 3 weeks later. Goat kids primary infected at 6, 7 and 8 weeks of age served as challenge controls, and uninfected animals were used as negative controls. The protective immunity was assessed by clinical, haematological, parasitological, immunological and pathological parameters. Altogether, the results demonstrate that goat kids of either 3, 4 or 5 weeks of age are able to develop patent infections and immunoprotective responses against E. ninakohlyakimovae, as all age groups: (i) released significantly less oocysts after challenge, which was associated to milder clinical signs; (ii) displayed a local immune response, with significant increase of numerous cellular populations; and (iii) had increased levels of IgG and IgM, and mainly of local IgA. Nevertheless, detailed analysis of the data showed some differences between the three age groups, related both to the Eimeria infection outcome and the resulting immune response, suggesting that youngest goat kids are not fully immunocompetent. This finding may be of interest for the design of immunoprophylactic approaches and/or prophylactic/methaphylactic treatments against goat coccidiosis.


Assuntos
Envelhecimento/imunologia , Coccidiose/veterinária , Eimeria , Doenças das Cabras/imunologia , Animais , Animais Recém-Nascidos , Coccidiose/imunologia , Cabras , Imunoglobulinas , Oocistos
13.
Vet Parasitol ; 242: 1-9, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28606316

RESUMO

During the first schizogony, the goat coccidia Eimeria ninakohlyakimovae develops macroschizonts in lacteal duct endothelial cells, whose rupture leads to severe ileal damage and clinical signs during the prepatent period. The immune response elicited against early stages of the parasite development still requires to be investigated. In the present study we have evaluated immune reactions in goat kids primary- and challenged-infected with Eimeria ninakohlyakimovae, and sacrificed during prepatency (7days after challenge). The oocyst output during the primary infection, body weight and clinical condition of all the animals were examined and, at the end of the experiment, all the goat kids were euthanized and subjected to necropsy. Samples were taken from different sections of the ileum, colon and mesenteric lymph nodes (MLN) of primary- and challenged E. ninakohlyakimovae-infected animals. Intestinal leukocyte subpopulations were characterized in E. ninakohlyakimovae-infected mucosa and counts of lymphocytes, eosinophils, polymorphonuclear neutrophils (PMN), globular leukocytes and mast cells were recorded. Additionally, gene expression of caprine IL-2, IL-4, IL-10 and INFγ of ileal, colonic and MLN tissues were performed, as well as the immunohistochemical characterization of immune cells. The E. ninakohlyakimovae primary infection resulted in moderate to severe enteritis with different degrees of diarrhoea and was accompanied by high OPG counts and an increase of most immune cells analyzed when compared to uninfected control animals. Furthermore, eosinophil-, lymphocyte-, globular leukocyte- and mast cell-counts were significantly higher in the challenge group compared to the primary infected animals, whilst the opposite was true for PMN counts. The challenge infection was also associated with moderate increased levels of local mucosal IgA. Interestingly, the number of immature schizonts found at the ileal mucosa was statistically higher in the challenge infected group compared to the challenged control animals. Furthermore, in the challenged E. ninakohlyakimovae-infected animals a significantly higher number of mucosal CD4+ and CD8+ lymphocytes were observed, indicating that these T cell subpopulations might be involved in protective host immune response elicited against early stages of parasite development. The immune response was however very complex, as antigen presenting cells and other effector cell populations of the innate immune system, as well as certain cytokines, were involved. In summary, the results of this study contribute to the better understanding of local cellular and humoral immune responses against caprine E. ninakohlyakimovae, particularly during the prepatency.


Assuntos
Coccidiose/veterinária , Eimeria/classificação , Doenças das Cabras/parasitologia , Animais , Anticorpos Antiprotozoários/sangue , Coccidiose/parasitologia , Citocinas/genética , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Regulação da Expressão Gênica/imunologia , Cabras , Imunidade Celular , Imunoglobulina G/sangue , Imunofenotipagem
14.
Peptides ; 88: 37-45, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27979738

RESUMO

The renin-angiotensin system modulates insulin action. Angiotensin type 1 receptor exerts a deleterious effects while the angiotensin type 2 receptor (AT2R) appears to have beneficial effects providing protection against insulin resistance and type 2 diabetes. Although recent reports indicate that agonism of AT2R ameliorates diabetes and insulin resistance, the phenotype of AT2R-knockout mice seems to be controversial relating this aspect. Thus, in this study we have explored the role of AT2R in the control of insulin action. To that end, C57Bl/6 mice were administered the synthetic AT2R antagonist PD123319 for 21days (10mg/kg/day ip); vehicle treated animals were used as control. Glucose tolerance, metabolic parameters, in vivo insulin signaling in main insulin-target tissues as well as levels of adiponectin, TNF-α, MCP-1 and IL-6 in adipose tissue were assessed. AT2R blockade with PD123319 induced a marginal effect on glucose homeostasis but an important reduction in the insulin-induced phosphorylation of the insulin receptor and Akt in both liver and adipose tissue. Insulin signaling in skeletal muscle remained unaltered after treatment with PD123319, which could explain the minimal effect on glucose homeostasis induced by PD123319. Our current results reinforce the notion that the AT2R has a physiological role in the conservation of insulin action.


Assuntos
Bloqueadores do Receptor Tipo 2 de Angiotensina II/administração & dosagem , Diabetes Mellitus Tipo 2/genética , Hipertensão/genética , Receptor Tipo 2 de Angiotensina/genética , Adiponectina/genética , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Angiotensina II/metabolismo , Animais , Quimiocina CCL2/genética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/patologia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/patologia , Imidazóis/administração & dosagem , Insulina/genética , Insulina/metabolismo , Resistência à Insulina/genética , Interleucina-6/genética , Losartan/administração & dosagem , Camundongos , Camundongos Knockout , Piridinas/administração & dosagem , Receptor Tipo 2 de Angiotensina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética
15.
Sci Rep ; 7: 44922, 2017 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-28322343

RESUMO

Dense (>98 th%) and homogeneous ceramic/metal composites were obtained by spark plasma sintering (SPS) using ZrO2 and lamellar metallic powders of tantalum or niobium (20 vol.%) as starting materials. The present study has demonstrated the unique and unpredicted simultaneous enhancement in toughness and strength with very high flaw tolerance of zirconia/Ta composites. In addition to their excellent static mechanical properties, these composites also have exceptional resistance to fatigue loading. It has been shown that the major contributions to toughening are the resulting crack bridging and plastic deformation of the metallic particles, together with crack deflection and interfacial debonding, which is compatible with the coexistence in the composite of both, strong and weak ceramic/metal interfaces, in agreement with predictions of ab-initio calculations. Therefore, these materials are promising candidates for designing damage tolerance components for aerospace industry, cutting and drilling tools, biomedical implants, among many others.

16.
Vet Parasitol ; 227: 143-50, 2016 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-27523951

RESUMO

Extracellular trap (ET) formation has been demonstrated as novel effector mechanism against diverse pathogens in polymorphonuclear neutrophils (PMN), eosinophils, mast cells, macrophages and recently also in monocytes. In the current study, we show that E. ninakohlyakimovae triggers the deliverance of monocyte-derived ETs in vitro. Fluorescence illustrations as well as scanning electron microscopy (SEM) analyses showed that monocyte-derived ET formation was rapidly induced upon exposure to viable sporozoites, sporocysts and oocysts of E. ninakohlyakimovae. Classical features of monocyte-released ETs were confirmed by the co-localization of extracellular DNA adorned with myeloperoxidase (MPO) and histones (H3) in parasite-entrapping structures. The treatment of caprine monocyte ET structures with NADPH oxidase inhibitor diphenylene iodondium (DPI) significantly reduced ETosis confirming the essential role of reactive oxygen species (ROS) in monocyte mediated ETs formation. Additionally, co-culture of monocytes with viable sporozoites and soluble oocyst antigen (SOA) induced distinct levels of cytokine and chemokine gene transcription. Thus, the transcription of genes encoding for IL-12 and TNF-α was significantly upregulated after sporozoite encounter. In contrast IL-6 and CCL2 gene transcripts were rather weakly induced by parasites. Conversely, SOA only induced the up-regulation of IL-6 and CCL2 gene transcription, and failed to enhance transcripts of IL-12 and TNF-α in vitro. We here report on monocyte-triggered ETs as novel effector mechanism against E. ninakohlyakimovae. Our results strongly suggest that monocyte-mediated innate immune reactions might play an important role in early host immune reactions against E. ninakohlyakimovae in goats.


Assuntos
Citocinas/metabolismo , Eimeria/classificação , Regulação da Expressão Gênica/imunologia , Monócitos/fisiologia , NADPH Oxidases/metabolismo , Animais , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Citocinas/genética , Doenças das Cabras/parasitologia , Cabras , Interleucina-12/genética , Interleucina-12/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Monócitos/ultraestrutura , NADPH Oxidases/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
18.
Diabetes ; 50(1): 131-8, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11147778

RESUMO

Tungstate was orally administered to 7.5-week-old male Zucker diabetic fatty (ZDF) rats that already showed moderate hyperglycemia (180 +/- 16 mg/dl). The animals became normoglycemic for approximately 10 days. Then, glycemia started to rise again, although it did not reach the initial values until day 24, when levels stabilized at approximately 200 mg/dl for the duration of the experiment. Untreated ZDF rats showed steadily increased blood glucose levels between 7.5 and 10 weeks of age, when they reached a maximum value of 450 +/- 19 mg/dl, which was maintained throughout the experiment. In addition, tolerance to intraperitoneal glucose load improved in treated diabetic rats. Serum levels of triglycerides were elevated in untreated diabetic rats compared with their lean counterparts (ZLC). In the liver of diabetic animals, glucokinase (GK), glycogen phosphorylase a (GPa), liver-pyruvate kinase (L-PK), and fatty acid synthase (FAS) activities decreased by 81, 30, 54, and 35%, respectively, whereas phosphoenolpyruvate carboxykinase (PEPCK) levels increased by 240%. Intracellular glucose-6-phosphate (G6P) decreased by 40%, whereas glycogen levels remained unaffected. Tungstate treatment of these rats induced a 42% decrease in serum levels of triglycerides and normalized hepatic G6P concentrations, GPa activity, and PEPCK levels. GK activity in treated diabetic rats increased to 50% of the values of untreated ZLC rats. L-PK and FAS activity increased to higher values than those in untreated lean rats (1.7-fold L-PK and 2.4-fold FAS). Hepatic glycogen levels were 55% higher than those in untreated diabetic and healthy rats. Tungstate treatment did not significantly change the phosphotyrosine protein profile of primary cultured hepatocytes from diabetic animals. These data suggest that tungstate administration to ZDF rats causes a considerable reduction of glycemia, mainly through a partial restoration of hepatic glucose metabolism and a decrease in lipotoxicity.


Assuntos
Diabetes Mellitus/fisiopatologia , Hipoglicemiantes/farmacologia , Obesidade , Compostos de Tungstênio/farmacologia , Administração Oral , Animais , Diabetes Mellitus/sangue , Glucose-6-Fosfato/metabolismo , Glicogênio/metabolismo , Hiperglicemia/induzido quimicamente , Ilhotas Pancreáticas/fisiopatologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Fosforilação/efeitos dos fármacos , Ratos , Ratos Zucker , Tirosina/metabolismo
19.
Free Radic Res ; 39(9): 943-8, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16087475

RESUMO

The therapeutical beneficial effect of estrogen-derived metabolites or catecholestrogens is controversial. These molecules are produced during estrogen therapy based on 17-beta-estradiol treatment. The metabolization of 17-beta-estradiol is carried out in brain, kidney or liver, and triggers different products such as 2- and 4- hydroxyestradiol (2OH and 4OH). These products have shown antioxidant properties against oxidative stress (OS) in several experimental models. Different noxious side effects related to those metabolites have also been observed upon estrogen therapy. In this sense, catecholestrogens seem to be implicated in tumoral and mutagenic process after long treatment with estrogens substitutive therapy. In our study, we have verified that 2OH and 4OH have antioxidant and cardioprotective effects against adriamycin (AD)-induced cardiomyopathy in ovariectomized (OVX) rats. Catecholestrogens diminished the lipid peroxides and carbonyl protein (CO) content, and different enzymes related to cell injury (creatinine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase) in cardiac tissue from OVX-, AD-, and OVX+AD-treated rats. All these changes were correlated to a recovery on reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) in heart tissue. The present study showed that 2OH and 4OH reduced all the parameters related to OS, antioxidant depletion and cardiac injury in OVX rats treated or not with AD.


Assuntos
Cardiomiopatias/tratamento farmacológico , Estradiol/análogos & derivados , Estrogênios de Catecol/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Cardiomiopatias/sangue , Cardiomiopatias/induzido quimicamente , Catalase/metabolismo , Creatina Quinase/sangue , Doxorrubicina , Estradiol/administração & dosagem , Estradiol/farmacologia , Estrogênios de Catecol/administração & dosagem , Feminino , Glutationa Peroxidase/metabolismo , Hemodinâmica/efeitos dos fármacos , L-Lactato Desidrogenase/sangue , Ovariectomia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
20.
An Med Interna ; 22(12): 579-85, 2005 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-16454597

RESUMO

UNLABELLED: FUNDAMENTALS AND OBJECTIVES: [corrected] Diabetes is the disease that has suffered a greater increase in his incidence in the last years. Obesity is the most important risk factor to develop this disease and metformin is considered as a first line drug in overweighted diabetic patients. The aim of this study is to evaluate the use of metformin and the degree of control of the associated cardiovascular risk factors (CVRF) in patients suffering of type 2 diabetes and overweight or obesity. PATIENTS AND METHODS: This is a transversal descriptive study over a random chosen group of 308 patients followed at primary care level. They were classified in four different groups depending on the treatment used to control them (diet, insulin, metformin and other oral antidiabetic drugs). They were evaluated upon the degree of control of the modifiable CVRF, the presence of complications and the metabolic control. RESULTS: The average age was 69.6 years, 54% of the patients female. 36.6% followed treatment with metformin and 40.5% with sulfonylureas. The macrovascular percentage of affection was 19.4%. The most frequent CVRF was arterial hypertension (76%). The goal levels of control that were less in range were the levels of cLDL < 100 mg/dl and systolic blood pressure < 130 mmHg. Diabetic patients only treated with diet had a better control of fasten glycemia and HbA1c% than those ones treated with metformin (p < 0.001). The group treated with metformin showed levels of triglycerides (TG) significantly higher than those of the diet controlled group (p = 0.009) and insulin group (p < 0.001). CONCLUSIONS: Metformin and sulfonylureas are used in a similar proportion in type 2 diabetics with overweight or obesity. There is a poor control of the majority of the CVRF in the diabetic population studied.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Obesidade/complicações , Sobrepeso , Idoso , Doenças Cardiovasculares/epidemiologia , Feminino , Humanos , Masculino , Fatores de Risco , Compostos de Sulfonilureia/uso terapêutico
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