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1.
BMC Cardiovasc Disord ; 19(1): 251, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31706288

RESUMO

BACKGROUND: Heart failure (HF) is a major public health problem with increasing prevalence worldwide. It is associated with high mortality and poor quality of life due to recurrent and costly hospital admissions. Several studies have been conducted to describe HF risk predictors in different races, countries and health systems. Nonetheless, understanding population-specific determinants of HF outcomes remains a great challenge. We aim to evaluate predictors of 1-year survival of individuals with systolic heart failure from the GENIUS-HF cohort. METHODS: We enrolled 700 consecutive patients with systolic heart failure from the SPA outpatient clinic of the Heart Institute, a tertiary health-center in Sao Paulo, Brazil. Inclusion criteria were age between 18 and 80 years old with heart failure diagnosis of different etiologies and left ventricular ejection fraction ≤50% in the previous 2 years of enrollment on the cohort. We recorded baseline demographic and clinical characteristics and followed-up patients at 6 months intervals by telephone interview. Study data were collected and data quality assurance by the Research Electronic Data Capture tools. Time to death was studied using Cox proportional hazards models adjusted for demographic, clinical and socioeconomic variables and medication use. RESULTS: We screened 2314 consecutive patients for eligibility and enrolled 700 participants. The overall mortality was 6.8% (47 patients); the composite outcome of death and hospitalization was 17.7% (123 patients) and 1% (7 patients) have been submitted to heart transplantation after one year of enrollment. After multivariate adjustment, baseline values of blood urea nitrogen (HR 1.017; CI 95% 1.008-1.027; p < 0.001), brain natriuretic peptide (HR 1.695; CI 95% 1.347-2.134; p < 0.001) and systolic blood pressure (HR 0.982;CI 95% 0.969-0.995; p = 0.008) were independently associated with death within 1 year. Kaplan Meier curves showed that ischemic patients have worse survival free of death and hospitalization compared to other etiologies. CONCLUSIONS: High levels of BUN and BNP and low systolic blood pressure were independent predictors of one-year overall mortality in our sample. TRIAL REGISTRATION: Current Controlled Trials NTC02043431, retrospectively registered at in January 23, 2014.

2.
PLoS One ; 14(10): e0223838, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31603935

RESUMO

BACKGROUND: Heart failure is associated with exercise intolerance and sleep- disordered breathing; however, studies in patients with chronic constrictive pericarditis are scarce. The purpose of our study was to assess exercise capacity and sleep in patients with chronic constrictive pericarditis (CCP) undergoing a pericardiectomy. METHODS: We studied consecutive patients scheduled for pericardiectomy due to symptomatic CCP. Were performed quality of life (Minnesota Living with Heart Failure Questionnaire-MLHFQ) and sleep questionnaires (Epworth, Pittsburgh Sleep Quality Index-PSQI), serum B-type natriuretic peptide (BNP), serum C-reactive protein, transthoracic echocardiography, cardiopulmonary exercise test and overnight polysomnography immediately before and six months after pericardiectomy. RESULTS: Twenty-five patients (76% males, age: 45.5±13.8 years, body mass index: 24.9±3.7 kg/m2, left ventricular ejection fraction: 60±6%) with CCP (76% idiopathic, 12% tuberculosis) were studied. As compared to the preoperative period, pericardiectomy resulted in reduction in BNP (143 (83.5-209.5) vs 76 (40-117.5) pg/mL, p = 0.011), improvement in VO2 peak (18.7±5.6 vs. 25.2±6.3 mL/kg/min, p<0.001), quality of life (MLHFQ score 62 (43,5-77,5) vs. 18 (8,5-22), p<0,001) and sleep (PSQI score 7.8±4.1 vs. 4.7±3.7, p<0.001) and no significant change in sleep disordered breathing (apnea hypopnea index-AHI 15.6 (8.3-31.7) vs. 14.6 (5.75-29.9) events/h, p = 0.253). CONCLUSION: Patients with symptomatic CCP showed reduced exercise capacity and sleep-disordered breathing. After pericardiectomy, there was improvement in exercise capacity and neutral effect on sleep-disordered breathing.

3.
Chemosphere ; 235: 70-75, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31255767

RESUMO

Some agrochemicals are genotoxic to several organisms. Nevertheless, few protocols are currently available for measuring the toxicogenetic effects of these compounds in target and non-target field-collected species of insects important to agriculture. Herein, we used the species Ceraeochrysa claveri (Neuroptera: Chrysopidae), a non-target predator insect, to investigate the ability of an azadirachtin-based biopesticide (Azamax™) to induce DNA damage. The alkaline version of the comet assay was standardized to evaluate genetic instability caused by the toxicant in somatic (gut) and germ (nurse cells and oocytes) cells of C. claveri. For this, C. claveri larvae were distributed into three groups (10/each) and treated with Azamax™ at 0, 0.3% or 0.5% throughout the larval stage. DNA damage (tail intensity) was measured in adult insects, four days after emerged. The data showed that both doses of Azamax™ (0.3% and 0.5%) were able to significantly (p < 0.05) increase DNA damage in somatic and germ cells of C. claveri. In conclusion, C. claveri (intestinal and ovarian cells) was a sensitive bioindicator for identifying Azamax™ genotoxic potential, whereas the comet assay was a useful tool for detecting the genotoxic hazard of the pesticide in the field-collected insect species. Given that estimation of adverse effects of pollutants on ecosystems is an essential component of environmental risk assessment, the approach used can be recommended to estimate the ecotoxicity of agricultural chemicals.

4.
J Card Surg ; 34(9): 796-802, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31269267

RESUMO

OBJECTIVE: The purpose of this study was to analyze the learning curve effect on hospital mortality, postoperative outcomes, freedom from reintervention in the aorta and long-term survival after frozen elephant trunk (FET) operation. METHODS: From July 2009 to June 2018, 79 patients underwent surgery with the FET technique. They had type A aortic dissection (acute 7.6%, chronic 33%), type B aortic dissection (acute 1.26%, chronic 34.2%), and complex thoracic aortic aneurysm (24%). 27.8% were reoperations and 43% received concomitant cardiac procedures. To compare the results, the sample was divided into group 1 (G1) (first half of the sample - operations from 2009 to 2014) and group 2 (G2) (first half of the sample - operations from 2015 to 2018). RESULTS: The in-hospital mortality was 20.25%, 30.7% for G1 and 10% for G2 (P = .02). The mean cardiopulmonary bypass time, myocardial ischemia time, and selective cerebral perfusion at 25°C time were 154 ± 31, 118 ± 32, and 59 ± 12 minutes, respectively, similar for both groups. Stroke and spinal cord injury occurred in four and two patients, with no difference between groups (P = .61 and P = .24). The necessity for secondary intervention on the downstream aorta for both groups was also similar (P = .136). Five of sixty-three surviving patients died during the follow-up period and the estimated survival rate was different between groups 49% vs 88% (P = .007). CONCLUSION: The learning curve with the FET procedure had a significant impact on hospital mortality and midterm survival over the follow-up period, albeit did not influence the freedom from reintervention on the downstream aorta.

5.
Methods Mol Biol ; 2003: 369-382, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31218626

RESUMO

This chapter addresses the determination of protein-lipid selectivity, here described as the preference of a protein for having a specific type of lipid in its vicinity, from Förster resonance energy transfer methodologies. These allow a quantification of the effect, that is, the determination of the biasing in distribution of the lipid under study around the protein, as compared to its bulk membrane distribution, with advantages over established approaches that have been used for the same purpose, such as electron spin resonance spectroscopy. The experiment can be carried out with steady-state instrumentation, the formalisms are described in detail, and the model can be applied to a membrane protein of any size.

6.
Acta Reumatol Port ; 44(1): 65-70, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249277

RESUMO

BACKGROUND: Rheumatoid Arthritis (RA) is a chronic inflammatory disease with high impact on patients´ quality of life (QoL). The Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL) is a self-completed questionnaire designed to assess QoL in patients with RA. A Portuguese adaptation of the RAQoL was available but required formal validation. AIM: To validate the RAQoL into the Portuguese language. METHODS: Patients with diagnosis of RA were included. The Portuguese RAQoL was administered on two occasions, 14 days apart. Participants also completed the Nottingham Health Profile (NHP) and Health Assessment Questionnaire (HAQ) at Time 1. Internal consistency was assessed using Cronbach's alpha and reliability through Spearman's Correlation Coefficient. Construct validity was evaluated through Spearman's correlation analyses between RAQoL, NHP and HAQ. Known-group validity was tested comparing the RAQoL across different groups, considering self-perceived general health status, flare symptoms and RA severity through non-parametric tests. RESULTS: 178 RA patients (mean age 56.6, 82% female, mean disease duration 13.6 years) were included. The mean score of RAQoL was 11, with low rates of missing data (3.9%), floor (4.5%) and ceiling (2.2%) effects. Cronbach's α was 0.95 and test-retest reliability 0.92. RAQoL scores correlated moderately with scores on the NHP Physical Mobility (r=0.77), Emotional reactions (r=0.69), Pain (r=0.68) and Energy (r=0.65) section scores. RAQoL showed to be discriminative for groups according to self-perceived general health status, flare of arthritis and disease severity. CONCLUSION: The Portuguese version of the RAQoL is a valid, feasible and reliable questionnaire, suitable for use in clinical practice and research purposes.

7.
Arq Bras Cardiol ; 112(5): 649-705, 2019 Jun 06.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31188969
8.
Nat Microbiol ; 4(8): 1368-1377, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31086309

RESUMO

Peptidoglycan (PGN) is the major component of the bacterial cell wall, a structure that is essential for the physical integrity and shape of the cell. Bacteria maintain cell shape by directing PGN incorporation to distinct regions of the cell, namely, through the localization of late-stage PGN synthesis proteins. These include two key protein families, SEDS transglycosylases and bPBP transpeptidases, proposed to function in cognate pairs. Rod-shaped bacteria have two SEDS-bPBP pairs, involved in elongation and division. Here, we elucidate why coccoid bacteria, such as Staphylococcus aureus, also possess two SEDS-bPBP pairs. We determined that S. aureus RodA-PBP3 and FtsW-PBP1 probably constitute cognate pairs of interacting proteins. A lack of RodA-PBP3 resulted in more spherical cells due to deficient sidewall PGN synthesis, whereas depletion of FtsW-PBP1 arrested normal septal PGN incorporation. Although PBP1 is an essential protein, a mutant lacking PBP1 transpeptidase activity is viable, showing that this protein has a second function. We propose that the FtsW-PBP1 pair has a role in stabilizing the divisome at midcell. In the absence of these proteins, the divisome appears as multiple rings or arcs that drive lateral PGN incorporation, leading to cell elongation. We conclude that RodA-PBP3 and FtsW-PBP1 mediate sidewall and septal PGN incorporation, respectively, and that their activity must be balanced to maintain coccoid morphology.

9.
Arq. bras. cardiol ; 112(5): 649-705, May 2019. gráfico, tabela
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1022925

RESUMO

Development: The Department of Geriatric Cardiology of the Brazilian Society of Cardiology (Departamento de Cardiogeriatria da Sociedade Brasileira da Cardiologia) and the Brazilian Geriatrics and Gerontology Society (Sociedade Brasileira de Geriatria e Gerontologia). (AU)


Assuntos
Humanos , Geriatria
10.
J Antimicrob Chemother ; 74(9): 2617-2625, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31127270

RESUMO

OBJECTIVES: To investigate the mechanism of action at the molecular level of pepR, a multifunctional peptide derived from the Dengue virus capsid protein, against Staphylococcus aureus biofilms. METHODS: Biofilm mass, metabolic activity and viability were quantified using conventional microbiology techniques, while fluorescence imaging methods, including a real-time calcein release assay, were employed to investigate the kinetics of pepR activity at different biofilm depths. RESULTS: Using flow cytometry-based assays, we showed that pepR is able to prevent staphylococcal biofilm formation due to a fast killing of planktonic bacteria, which in turn resulted from a peptide-induced increase in the permeability of the bacterial membranes. The activity of pepR against pre-formed biofilms was evaluated through the application of a quantitative live/dead confocal laser scanning microscopy (CLSM) assay. The results show that the bactericidal activity of pepR on pre-formed biofilms is dose and depth dependent. A CLSM-based assay of calcein release from biofilm-embedded bacteria was further developed to indirectly assess the diffusion and membrane permeabilization properties of pepR throughout the biofilm. A slower diffusion and delayed activity of the peptide at deeper layers of the biofilm were quantified. CONCLUSIONS: Overall, our results show that the activity of pepR on pre-formed biofilms is controlled by its diffusion along the biofilm layers, an effect that can be counteracted by an additional administration of peptide. Our study sheds new light on the antibiofilm mechanism of action of antimicrobial peptides, particularly the importance of their diffusion properties through the biofilm matrix on their activity.

11.
Methods Mol Biol ; 1981: 99-115, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31016650

RESUMO

Cholestasis is characterized by impaired secretion of bile flow that can result in the accumulation of highly abnormal levels of bile acids causing hepatocyte and biliary injury. As amphipathic molecules, bile acids can intercalate in lipid membranes, and pathophysiologic concentrations of bile acids have the potential to induce marked changes in the biophysical properties of biomembranes, including membrane ordering. These effects, particularly on the mitochondrial and plasma membranes, have been proposed to trigger toxicity of bile acids. This chapter details different fluorescence-based methods (fluorescence polarization, and spectroscopy/imaging of solvatochromic dyes) to evaluate the impact of different bile acids on membrane order. Protocols are described for the application of these methods to biomimetic vesicles, isolated mitochondria, and hepatocytes, following a bottom-up approach.


Assuntos
Ácidos e Sais Biliares/metabolismo , Hepatócitos/metabolismo , Mitocôndrias/metabolismo , Animais , Ácidos e Sais Biliares/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Polarização de Fluorescência , Hepatócitos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos
12.
Int. j. cardiovasc. sci. (Impr.) ; 32(2): 152-157, mar.-abr. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-988204

RESUMO

Background: Galectin-3 is the designation given to the protein that binds to ß-galactosides, expressed by activated macrophages and described as a cardiac fibrosis mediator. In hypertrophic cardiomyopathy (HCM), myocardial fibrosis is an independent predictor of adverse outcome; however, the association between Galectin-3 and myocardial fibrosis has not been studied in this cardiopathy. Objective: To evaluate the association of Galectin-3 and the presence of myocardial fibrosis in a patient with hypertrophic cardiomyopathy. Methods: Galectin-3 was measured in automated equipment using the Elisa technique in 100 participants divided into two groups: 50 patients with hypertrophic cardiomyopathy and 50 healthy control subjects. All patients with hypertrophic cardiomyopathy underwent magnetic nuclear resonance with the late enhancement technique to investigate myocardial fibrosis. For the statistical analysis, p values < 0.05 were considered statistically significant. Results: Galectin-3 levels were low and did not show significant differences between patients with hypertrophic cardiomyopathy and the control group,10.3 ± 3.1 ng/dL and 11.3 ± 2.6 ng/dL (p = 0.12) respectively. Myocardial fibrosis was a common finding and was identified in 84% (42/50) of patients with HCM, but no differences were observed between Galectin-3 levels when comparing patients with and without fibrosis, 10.3 ± 2.4 ng/dL and 10.1 ± 2.1 ng/dL (p = 0.59). Conclusion: The results did not show an association between Galectin-3 and myocardial fibrosis in patients with hypertrophic cardiomyopathy, suggesting that non-inflammatory mechanisms of myocardial fibrosis formation and cardiac remodeling are involved in this cardiopathy


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Galectina 3 , Fibrose Endomiocárdica , Arritmias Cardíacas/diagnóstico , Diagnóstico por Imagem/métodos , Espectroscopia de Ressonância Magnética/métodos , Biomarcadores , Doenças Cardiovasculares/diagnóstico , Ecocardiografia Doppler/métodos , Análise Estatística
13.
Int. j. cardiovasc. sci. (Impr.) ; 32(2): 152-157, mar.-abr. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-989994

RESUMO

Galectin-3 is the designation given to the protein that binds to ß-galactosides, expressed by activated macrophages and described as a cardiac fibrosis mediator. In hypertrophic cardiomyopathy (HCM), myocardial fibrosis is an independent predictor of adverse outcome; however, the association between Galectin-3 and myocardial fibrosis has not been studied in this cardiopathy. Objective: To evaluate the association of Galectin-3 and the presence of myocardial fibrosis in a patient with hypertrophic cardiomyopathy. Methods: Galectin-3 was measured in automated equipment using the Elisa technique in 100 participants divided into two groups: 50 patients with hypertrophic cardiomyopathy and 50 healthy control subjects. All patients with hypertrophic cardiomyopathy underwent magnetic nuclear resonance with the late enhancement technique to investigate myocardial fibrosis. For the statistical analysis, p values < 0.05 were considered statistically significant. Results: Galectin-3 levels were low and did not show significant differences between patients with hypertrophic cardiomyopathy and the control group, 10.3 ± 3.1 ng/dL and 11.3 ± 2.6 ng/dL (p = 0.12) respectively. Myocardial fibrosis was a common finding and was identified in 84% (42/50) of patients with HCM, but no differences were observed between Galectin-3 levels when comparing patients with and without fibrosis, 10.3 ± 2.4 ng/dL and 10.1 ± 2.1 ng/dL (p = 0.59). Conclusion: The results did not show an association between Galectin-3 and myocardial fibrosis in patients with hypertrophic cardiomyopathy, suggesting that non-inflammatory mechanisms of myocardial fibrosis formation and cardiac remodeling are involved in this cardiopathy


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Galectina 3 , Fibrose Endomiocárdica , Arritmias Cardíacas/diagnóstico por imagem , Diagnóstico por Imagem/métodos , Espectroscopia de Ressonância Magnética/métodos , Biomarcadores , Doenças Cardiovasculares/diagnóstico , Ecocardiografia Doppler/métodos , Análise Estatística
14.
Eur J Med Chem ; 165: 18-30, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30654237

RESUMO

A series of1,2,4- and 1,3,4-oxadiazole derivatives were synthesized and evaluated for their anticancer activity. Halogenated 1,2,4-oxadiazoles were obtained from benzonitrile and coupled either lipophilic amines or with aminoalcohols. Lipophilic 1,3,4-oxadiazole derivatives were obtained through the Mannich reactions between 5-(aryl)-1,3,4-oxadiazole-2-thiol and alkylated or acylated amines. The in vitro cytotoxic effects were evaluated against 4T1- mammary carcinoma and CT26 - colon cancer cells. The best results were obtained for the 1,3,4-oxadiazole coupled to alkylated piperazine with 10-14 carbon chain moiety, with IC50 values ranging from 1.6 to 3.55µΜ for the 4T1 cell line, and from 1.6 to 3.9 µM for the CT26.WT cell line, and selectivity index up to 19. The most potent compounds were investigated with AnnexinV and PI staining as indicative of apoptosis induction.


Assuntos
Antineoplásicos/química , Oxidiazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Interações Hidrofóbicas e Hidrofílicas , Oxidiazóis/síntese química , Oxidiazóis/química , Relação Estrutura-Atividade
15.
Artigo em Inglês | MEDLINE | ID: mdl-30595209

RESUMO

Color Index (C.I.) Disperse Blue 291 (DB291) is an azo dye used by the textile industry. After yarn dyeing, wastewater containing the dye, released into the aquatic environment, may pollute drinking water sources. We investigated the mutagenicity and genotoxicity of DB291 in male Swiss mice, following oral administration. Micronucleated cells, primary DNA damage (comet assay) in blood, liver, and kidney cells, and BAX, BCL2, SMAD4 and TNFA gene expression in leukocytes were evaluated. An increased frequency of micronucleated polychromatic erythrocytes (MNPCEs) was observed in animals treated with 50 mg/kg bw; no other genetic alteration was detected. Neither primary DNA damage nor changes in gene expression were observed.


Assuntos
Compostos Azo/toxicidade , Medula Óssea/efeitos dos fármacos , Corantes/toxicidade , Eritrócitos Anormais/efeitos dos fármacos , Animais , Compostos Azo/farmacologia , Ensaio Cometa , Dano ao DNA/genética , Expressão Gênica/efeitos dos fármacos , Leucócitos/metabolismo , Masculino , Camundongos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteína Smad4/biossíntese , Fator de Necrose Tumoral alfa/biossíntese , Águas Residuárias/química
16.
Can J Physiol Pharmacol ; 97(2): 140-145, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30557036

RESUMO

Metabolic, inflammatory, and autonomic nervous system (ANS) dysfunction are present in patients with heart failure. However, whether these changes are due to left ventricular dysfunction or heart failure etiology is unknown. We evaluated metabolism and inflammatory activity in patients with idiopathic dilated cardiomyopathy (IDC) and Chagas cardiomyopathy (CHG) and their correlation with the ANS. Forty-six patients were divided into 3 groups: IDC, CHG, and control. We evaluated adiponectin, leptin, insulin, interleukin-6, and tumor necrosis factor-alpha. ANS were analyzed by heart rate variability in time and frequency domains on a 24-hour Holter monitor. Levels of glucose, cholesterol, leptin, and adiponectin did not show differences between groups. Insulin levels were lower in CHG group (5.4 ± 3.3 µU/mL) when compared with control (8.0 ± 4.9 µU/mL) and IDC (9.9 ± 5.0 µU/mL) groups (p = 0.007). Insulin was positively associated with LFr/HFr ratio (r = 0.562; p = 0.029) and with the LFr component (r = 0.562; p = 0.029) and negatively associated with adiponectin (r = -0.603; p = 0.017) in CHG group. The addition of an adiponectin unit reduced average insulin by 0.332 µg/mL. Insulin levels were decreased in the CHG group when compared with the IDC group and were associated with ANS indexes and adiponectin levels.


Assuntos
Adipocinas/sangue , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Chagásica/metabolismo , Insulina/sangue , Adipocinas/metabolismo , Adulto , Sistema Nervoso Autônomo/fisiopatologia , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/fisiopatologia , Ecocardiografia Doppler , Eletrocardiografia , Feminino , Coração , Frequência Cardíaca/fisiologia , Humanos , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade
17.
J Org Chem ; 2018 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-30468075

RESUMO

We describe that vinyl-oxadiazoles function as a new and efficient nucleophilic partner for the Morita-Baylis-Hillman (MBH) reaction. The reaction between 5-vinyl-3-aryl-1,2,4-oxadiazoles and aromatic and aliphatic aldehydes, catalyzed by DABCO in absence of solvent, showed high efficiently to afford a new class of heterocyclic MBH adducts with potential biological activity on yields up to 99% and short reaction times. These synthetically attractive adducts bear a heterocyclic scaffold of large pharmaceutical and commercial interest associated to a plethora of biological effects and technological applications. We also demonstrate their synthetic usefulness by a photo-induced addition reaction to a poly-functionalized amino-alcohol.

18.
BMC Pharmacol Toxicol ; 19(1): 74, 2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30446004

RESUMO

BACKGROUND: Oxidative stress is one potential mechanism that explain the direct effects of smoking on cardiac remodeling process. However, no study has compared different myocardial products of macromolecule oxidation after tobacco smoke exposure. Thus, the aim of this study was to investigate the lipid hydroperoxide (LH) levels, protein carbonyl concentrations and DNA damage in cardiac tissue of rats exposed to tobacco smoke. METHODS: Male Wistar rats were divided into two groups: group C (control, n = 14) composed of animals not exposed to cigarette smoke; group ETS (exposed to tobacco smoke, n = 14) composed by animals exposed to cigarette smoke. The animals were exposed to 2 month of ETS and morphological, biochemical and functional analyses were performed. RESULTS: Cardiac cotinine levels were elevated in the ETS group. In addition, the myocyte cross-sectional area was higher in the ETS group. (C = 266.6 ± 23.2 µm2 and ETS = 347.5 ± 15.1 µm2, p <  0.001). Cardiac LH was higher in the ETS group than in group C (C = 196.4 ± 51.5 nmol/g and ETS = 331.9 ± 52.9 nmol/g, p <  0.001). However, there were no between-group differences in cardiac protein carbonyl concentration or DNA damage. CONCLUSIONS: Therefore, our results suggest that, in this model, lipid damage is a good marker of oxidative damage during the cardiac remodeling process induced by 2 months of exposure to tobacco smoke.

20.
Toxicon ; 153: 17-18, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30149042

RESUMO

Accidents involving snakebites constitute a serious public health problem in many regions around the world. However, there are no study about a possible action of snake venom on the reproductive system. Herein we show that Crotalus durissus sp. (Linnaeus) rattlesnake venom (25 µg/kg of body weight) affected chromatin condensation, and increased the number of sperm with abnormal morphology and the sperm count. In conclusion, besides the known hazards of the C. durissus sp. venom to animal health, this study was the first to show its effect also on male germ cells.

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