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1.
Artigo em Inglês | MEDLINE | ID: mdl-32975242

RESUMO

BACKGROUND: Hepatitis B virus (HBV) infection is one of the most common infections worldwide, having negative impact on world health due to the tendency for chronification with late complications such as liver cirrhosis and hepatocellular carcinoma. Natural killer (NK) cells as part of innate antiviral defense influence the clinical course of HBV infection: elimination of the virus or chronic disease. AIM: Therefore, we investigated the polymorphisms of the main gene systems, regulating NK-cell function: killer cell immunoglobulin-like receptors (KIRs) and their appropriate HLA class I ligands in 144 HBV infected patients (124 chronic carriers and 20 spontaneously recoved) and 126 ethnically matched healthy controls from the Bulgarian population in a case-control study. METHODS: KIRs and HLA ligands were determined by PCR-SSP or PCR high-resolution typing methods. RESULTS: KIR2DL5B allele variant was significantly less frequent in spontaneously recovered (SR) patients compared to healthy controls (10.0% vs. 45.5%, Pcorr=0.006). The presence of KIR3DL1*004 allele was higher in chronic HBV carriers (CH) than in controls (33.1% vs. 17.6%, Pcorr=0.036). Additionally, SR patients differed from healthy individuals by the lower frequency of HLA-Bw4Ile80 group ligands (30.0% vs 63.7%, P=0.015). Three KIR genotypes were found more frequent in healthy in comparison with HBV infected individuals: ID2 (13.5% vs 5.6%, P=0.025), KIR genotype containing 6 activating KIRs (18.0% vs 7.6%, P=0.017), and KIR genotype composed of 4 activating and 5 inhibitory KIRs (23.8% vs 5.6%, P=0.001). CONCLUSION: These data suggest that inherited KIR and HLA class I ligand polymorphisms may influence the clinical course of HBV infection.

2.
ACS Omega ; 4(6): 11205-11214, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31460221

RESUMO

Herein, we report an atomic layer deposition (ALD) process for Cu2O thin films using copper(II) acetate [Cu(OAc)2] and water vapor as precursors. This precursor combination enables the deposition of phase-pure, polycrystalline, and impurity-free Cu2O thin films at temperatures of 180-220 °C. The deposition of Cu(I) oxide films from a Cu(II) precursor without the use of a reducing agent is explained by the thermally induced reduction of Cu(OAc)2 to the volatile copper(I) acetate, CuOAc. In addition to the optimization of ALD process parameters and characterization of film properties, we studied the Cu2O films in the fabrication of photoconductor devices. Our proof-of-concept devices show that approximately 20 nm thick Cu2O films can be used for photodetection in the visible wavelength range and that the thin film photoconductors exhibit improved device characteristics in comparison to bulk Cu2O crystals.

3.
Food Chem Toxicol ; 130: 317-325, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31128217

RESUMO

Triterpenoids are well known modulators of metabolic syndrome. One of the suggested modes of action (MoAs) involves peroxisome proliferator-activated receptor gamma (PPARγ) binding. In this study we aimed to: (i) evaluate in silico potential metabolites and PPARγ-mediated MoA of the sapogenin of the main saponin present in a purified saponins' mixture (PSM) from Astragalus glycyphylloides; (ii) estimate in silico and in vivo PSM's toxicity; and (iii) investigate in vivo antihyperglycaemic, hypolipidaemic, antioxidant and hepatoprotective effects of PSM. Metabolites and toxicity were predicted using Meteor and Derek Nexus expert systems (Lhasa Limited) and PPARγ binding was investigated using the software MOE (CCG Inc.). PSM's acute oral toxicity was evaluated in mice and the pharmacological effects were assessed in streptozotocin-induced diabetic spontaneously hypertensive rats (SHRs). Liver histopathology was studied as well. PPARγ weak partial agonism was predicted in silico for 24 probable/plausible Phase I metabolites which docking poses were clustered in 12 different binding modes with characteristic protein-ligand interactions. PSM's beneficial effects on the levels of blood glucose, triglycerides, and total cholesterol, on oxidative stress markers and liver histology in diabetic SHRs were comparable to those of the PPARγ ligand pioglitazone. PSM's safety profile was confirmed in silico and in vivo.


Assuntos
Astrágalo (Planta)/química , Síndrome Metabólica/tratamento farmacológico , Saponinas/química , Saponinas/farmacologia , Animais , Sítios de Ligação , Pressão Sanguínea/efeitos dos fármacos , Simulação por Computador , Diabetes Mellitus Experimental/tratamento farmacológico , Descoberta de Drogas , Feminino , Masculino , Camundongos , Estrutura Molecular , Estresse Oxidativo , PPAR gama/agonistas , Ligação Proteica , Conformação Proteica , Ratos , Ratos Endogâmicos SHR , Saponinas/toxicidade
4.
Rev. bras. farmacogn ; 29(2): 221-227, Mar.-Apr. 2019. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1003500

RESUMO

ABSTRACT This study investigated the possible antioxidant and neuroprotective effects of alcesefoliside, isolated from Astragalus monspessulanus L., Fabaceae, against carbon tetrachloride (CCl4)-induced brain injury in Wistar rats. Iron sulphate/ascorbic acid lipid peroxidation was induced in rat brain microsomes and pre-incubated with alcesefoliside and silybin. Male rats were treated in vivo with alcesefoliside and with silymarin alone; animals challenged with CCl4; and pre-treated with alcesefoliside or silymarin in respective doses for 7 days, challenged with CCl4, followed by curative treatment (additional 14 days). The activity of acetylcholine esterase and the antioxidant enzymes: superoxide-dismutase, catalase, glutathione-peroxidase, glutathione reductase and glutathione-S-transferase as well as the biomarkers of oxidative stress malondialdehyde and reduced glutathione were measured. The alcesefoliside pre-treatment and consecutive curative treatment normalizes the activity of the antioxidant enzymes as well as levels of malondialdehyde and reduced glutathione. The observed effects on tissue level correlate with the histopathological observations of the brain. They were comparable to the effects of silymarin, used as a positive control. The results showed that alcesefoliside has a neuroprotective effect against CCl4-induced brain toxicity in rats.

5.
Open Access Maced J Med Sci ; 7(3): 458-460, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30834019

RESUMO

BACKGROUND: Over the past two decades, more thorough investigations for hepatitis E virus (HEV) infection have been done in the world. Reports from Southeast European countries have increased. AIM: The current article presents a critical analysis of all studies for HEV in Bulgaria. MATERIAL AND METHODS: A literature search was done using available medical databases. We analysed the literature in PubMed databases and Bulgarian medical databases for English and Bulgarian languages sources. Preference was given to the sources published within the past 24 years (January 1995 - September 2018). RESULTS: Two thousand two hundred and fifty-seven blood serums were tested for the analysed period (1995 - 2018), and 13.1% of them were positive for acute HEV (Mean ± SD: 20.38 ± 25.77%; 95% CI: 1.29 - 39.47%). The following subtypes were established in the country - HEV Subtype 3e, HEV Subtype 3f, HEV Subtype 3c, HEV Subtype 3i, HEV Subtype 3hi and HEV Subtype 1. CONCLUSION: We hope that the National Health Organizations will take adequate and timely measures to increase the knowledge and research for HEV among Bulgarian citizens.

6.
Caspian J Intern Med ; 10(1): 102-106, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30858949

RESUMO

Background: Fever of unknown origin (FUO) is a perplexing medical problem. The causes for FUO are more than 200 diseases. The aim of the study was to present human clinical cases of Coxiella burnetii infection debuting as FUO. Methods: The following methods were conducted in the study: literature search, laboratory, imaging, and statistical methods. Criteria of Durack and Street were applied for FUO definition. For the etiological diagnosis indirect immunoenzyme assay (ELISA) for antibodies detection against Coxiella burnetii was used (cut-off = 0.481-0.519). Results: From 2008 until 2015, nine patients with FUO caused by C. burnetii were hospitalized at the Military Medical Academy of Sofia. Male gender was predominant (male/female - 77.8% /22.2%), mean age was 48.78±14.52 years (range: 26-67), hospital stay was 9.78±2.95 days (range: 5-15), fever duration was 54.33±56.23 days (range: 21-180). Laboratory investigations estimated the elevation of erythrocyte sedimentation rate 49.11±31.74mm/h (95%CI = 13.09-111.31), C-reactive protein 37.68±37.62mg/L (95% CI = 36.07-111.42) and fibrinogen 5.69±1.59g/L (95% CI=2.57-8.81). The mean values of liver enzymes were in reference range. Among imaging tests, abdominal ultrasound and X-ray demonstrated 33.3% contribution to the final diagnosis. Transthoracic echocardiography found 22.2% contribution. Serological methods presented 100% contribution. Conclusion: C. burnetii infection was accepted as a final diagnosis among 9 patients with FUO based on the integrated information from the applied methods. Active search and establishment of this pathogen among FUO should lead to avoiding potential complications and consequences in case of untreated patients infected with C. burnetii.

7.
Acta Clin Croat ; 58(3): 546-549, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31969770

RESUMO

A case of a 66-year-old man with West Nile neuroinvassive disease manifested with fever, weakness, fatigue, consciousness disorders and underlying diabetes mellitus type 2 and cardiovascular diseases is presented. Laboratory data showed elevated erythrocyte sedimentation rate and fibrinogen. Serological tests revealed West Nile virus specific antibodies of class IgM and IgG in serum. West Nile virus RNA was detected in urine sample. Supportive therapy was applied.


Assuntos
Monitoramento Epidemiológico , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/fisiopatologia , Doenças do Sistema Nervoso/terapia , Febre do Nilo Ocidental/fisiopatologia , Febre do Nilo Ocidental/terapia , Idoso , Bulgária/epidemiologia , Humanos , Masculino , Resultado do Tratamento , Febre do Nilo Ocidental/epidemiologia
8.
Folia Med (Plovdiv) ; 59(1): 53-62, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28384114

RESUMO

BACKGROUND: The patient's immune response is one of the major factors influencing HBV eradication or chronification, and it is thought to be responsible for the treatment success. AIM: Our study aimed to investigate whether cellular defense mechanisms are associated with the course of HBV infection (spontaneous recovery [SR] or chronification [CHB]) and with the therapeutic approach. PATIENTS AND METHODS: A total of 139 patients (118 with CHB, 21 SR) and 29 healthy individuals (HI) were immunophenotyped by flowcytometry. Fifty-six patients were treatment-naïve, 20 were treated with interferons and 42 with nucleoside/ nucleotide analogues. RESULTS: Deficiency of T lymphocytes, helper-inducer (CD3+CD4+), suppressorcytotoxic (CD8+CD3+) and cytotoxic (CD8+CD11b-, CD8+CD28+) subsets, activated T cells (CD3+HLA-DR+, CD8+CD38+) and increased CD57+CD8- cells, elevated percentages of B lymphocytes and NKT cells were observed in CHB patients compared with HI. In SR patients, elevated CD8+CD11b+, NKT and activated T cells were found in comparison with controls. The higher values of T cells and their subsets in SR patients than in CHB patients reflect a recovery of cellular immunity in resolved HBV infection individuals. In both groups of treated patients, reduced T lymphocytes, CD3+CD4+ and CD8+CD38+ subsets were found in comparison with HI. Higher proportions of cytotoxic subsets were observed in treated patients compared with treatment-naïve CHB patients, more pronounced in the group with interferon therapy. CONCLUSION: Our data demonstrate that cellular immune profiles may be of prognostic value in predicting the clinical course of HBV infection, and the determination of the therapeutic response.


Assuntos
Subpopulações de Linfócitos B/imunologia , Hepatite B Crônica/imunologia , Subpopulações de Linfócitos T/imunologia , Doença Aguda , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Estudos de Casos e Controles , Progressão da Doença , Feminino , Citometria de Fluxo , Hepatite B/imunologia , Hepatite B Crônica/tratamento farmacológico , Humanos , Imunofenotipagem , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Células T Matadoras Naturais/imunologia , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Remissão Espontânea , Linfócitos T Citotóxicos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Resultado do Tratamento , Adulto Jovem
9.
Srp Arh Celok Lek ; 144(1-2): 63-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27276860

RESUMO

INTRODUCTION: Hepatitis E is one of the leading clinical manifestations of acute viral hepatitis in developing countries. In industrialized countries, during the past several years, sporadic "autochthonous" cases of HEV infection have been increased. OBJECTIVE: The aim of this study was to analyze the epidemiological, clinical and laboratory features of HEV infection among patients hospitalized at the Department of Infectious Diseases in Military Medical Academy, Sofia, Bulgaria. METHODS: A retrospective study of 806 cases of acute viral hepatitis was performed at the Department of Infectious Diseases in Military Medical Academy, Sofia, Bulgaria, between December 2004 and September 2012.The etiological diagnosis was established by ELISA. The statistical analysis was performed using Excel 2007 (Microsoft, Redmond, Washington, USA) and SPSS Statistics 19.0 (IBM Corp., Armonk, NewYork, USA). RESULTS: Specific reaction to anti-HEV-IgM and anti-HEV-IgG antibodies were detected in 20 (2.48%) of 806 patients. The most observed clinical presentations were jaundice (85%), fatigue (85%), anorexia (65%), abdominal discomfort (55%) and fever (40%). The mean values of aspartate transaminase and alanine transaminase were 521 IU/l and 881 IU/l, respectively. The cholestasis was slight, marked with mean values of gamma-glutamyl transferase and alkaline phosphatase, respectively 418 IU/I and 486 IU/I. CONCLUSION: We report twenty autochthonous sporadic cases of acute infection with HEV. The zoonotic etiology of the virus as well as the foodborne transmission of the infection is discussed. We found that aging and pre-existing underlying diseases are risk factors for a severe course of the HEV infection.


Assuntos
Hepatite E , Adulto , Idoso , Bulgária/epidemiologia , Feminino , Hepatite E/diagnóstico , Hepatite E/epidemiologia , Hepatite E/fisiopatologia , Vírus da Hepatite E , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
10.
ACS Omega ; 1(6): 1296-1306, 2016 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-31457197

RESUMO

Hybrid halide perovskite thin films are applicable in a wide range of devices such as light-emitting diodes, solar cells, and photodetectors. The optoelectronic properties of perovskites together with their simple and inexpensive film deposition methods make these materials a viable alternative to established materials in these devices. However, the potential of perovskite materials is compromised by the limitations of the existing deposition methods, which suffer from trade-off among suitability for large-scale industrial production in a batch or roll-to-roll manner, deposition area, film quality, and costs. We addressed these limitations by developing a deposition method that is inexpensive, applicable to large substrate areas, scalable, and yields high-quality perovskite films. In this study, the low-cost electrodeposition (ED) method and sequential exposure to reagent vapors produce CH3NH3PbI3 perovskite films with thickness nonuniformity below 9% on a centimeter scale. PbO2 films are electrodeposited first and then undergo two vapor conversion steps, with HI vapor in the first step and CH3NH3I vapor in the second step. The second step yields CH3NH3PbI3 films that are continuous and consist of micrometer-sized grains. This process allows the preparation of both α- and ß-phase CH3NH3PbI3 films, offers a simple means to control the film thickness, and works over a wide range of film thicknesses. In this work, films with thicknesses ranging from 100 nm to 10 µm were prepared. ED and vapor conversion are inherently scalable techniques and hence the process described herein could benefit application areas in which large device areas and throughput are required, such as the production of solar cells.

11.
Appl Physiol Nutr Metab ; 39(11): 1280-5, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25181356

RESUMO

Vascular bubble formation results from supersaturation during inadequate decompression contributes to endothelial injuries, which form the basis for the development of decompression sickness (DCS). Risk factors for DCS include increased age, weight-fat mass, decreased maximal oxygen uptake, chronic diseases, dehydration, and nitric oxide (NO) bioavailability. Production of NO is often affected by diving and its expression-activity varies between the genders. Little is known about the influence of sex on the risk of DCS. To study this relationship we used an animal model of Nω-nitro-l-arginine methyl ester (l-NAME) to induce decreased NO production. Male and female rats with diverse ages and weights were divided into 2 groups: treated with l-NAME (in tap water; 0.05 mg·mL(-1) for 7 days) and a control group. To control the distribution of nitrogen among tissues, 2 different compression-decompression protocols were used. Results showed that l-NAME was significantly associated with increased DCS in female rats (p = 0.039) only. Weight was significant for both sexes (p = 0.01). The protocol with the highest estimated tissue pressures in the slower compartments was 2.6 times more likely to produce DCS than the protocol with the highest estimated tissue pressures in faster compartments. The outcome of this study had significantly different susceptibility to DCS after l-NAME treatment between the sexes, while l-NAME per se had no effect on the likelihood of DCS. The analysis also showed that for the appearance of DCS, the most significant factors were type of protocol and weight.


Assuntos
Doença da Descompressão/prevenção & controle , NG-Nitroarginina Metil Éster/farmacologia , Animais , Modelos Animais de Doenças , Feminino , Masculino , Óxido Nítrico/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fatores de Risco
13.
Clin Epigenetics ; 2(1): 7-15, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22704266

RESUMO

Considering psychiatry as a medical discipline, a diagnosis identifying a disorder should lead to an effective therapy. Such presumed causality is the basis of evidence-based psychiatry. We examined the strengths and weaknesses of research onto the causality of relationship between diagnosis and therapy of major depressive disorder and suggest what could be done to strengthen eventual claims on causality. Four obstacles for a rational evidence-based psychiatry were recognised. First, current classification systems are scientifically nonfalsifiable. Second, cerebral processes are-at least to some extent-nondeterministic, i.e. they are random, stochastic and/or chaotic. Third, the vague or lack of relationship between therapeutic regimens and suspected pathogenesis. Fourth, the inadequacy of tools to diagnose and delineate a functional disorder. We suggest a strategy to identify diagnostic prototypes that are characterised by a limited number of parameters (symptoms, markers and other characteristics). A prototypical diagnosis that may either support or reject particular elements of current diagnostic systems. Nevertheless, one faces the possibility that psychiatry will remain a relatively weak evidence-based medical discipline.

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