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1.
Wiad Lek ; 72(9 cz 2): 1781-1785, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31622266

RESUMO

OBJECTIVE: Introduction: Polytrauma or multiple organ damage is associated with shock and lead to systemic inflammation, oxidative stress and endothelial dysfunction. A severe mechanical injury causes an increased proinflammatory mediators and cytokines levels. Among them, the overproduction of nitric oxide and its oxidation products play a key role in tissue damage. The aim: To evaluate the changes in dynamics of some ornithine cycle components levels during acute period of polytrauma. PATIENTS AND METHODS: Materials and methods: We measured standard biomechanical parameters and serum levels of NO, sum of nitrite and nitrate (NOx), L-arginine, arginase, and peroxynitrite. According to the ISS, the study included patients with moderate (n=15) to severe (n=15) polytrauma. RESULTS: Results: In 24 hours after polytrauma on the background of intensive care, it was observed significant increasing of NO, NOx, and arginase levels (severe cases) with decreasing of L-arginine and peroxynitrite levels. CONCLUSION: Conclusions: Elevated NO and NOx serum levels in patients with polytrauma is associated with increasing of arginase activity with decreasing of L-arginine and peroxynitrite levels on the background of intensive care.


Assuntos
Traumatismo Múltiplo/diagnóstico , Ornitina/metabolismo , Arginase/sangue , Arginina/sangue , Humanos , Traumatismo Múltiplo/sangue , Nitratos/sangue , Óxido Nítrico/sangue , Nitritos/sangue , Ácido Peroxinitroso/sangue
2.
Cell Physiol Biochem ; 53(2): 388-399, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31403269

RESUMO

BACKGROUND/AIMS: Doxorubicin, a chemotherapy drug used successfully for years, could induce cardiotoxicity. Euterpe oleracea Mart. (açai) is a fruit high in antioxidant properties. The aim of this study was to evaluate doxorubicin-induced cardiotoxicity prevention after açai administration. METHODS: A total of 64 male Wistar rats were allocated into 4 groups: control (C), açai (A), doxorubicin (D) and açai-doxorubicin (DA). Rats received regular chow (C and D groups) or chow supplemented with açai 5% (A and DA groups) for 4 weeks. Subsequently, rats received doxorubicin 20 mg/kg (D and DA groups) or saline (C and A groups). Euthanasia was performed 48 hours after doxorubicin injection. Left ventricular function was evaluated by echocardiography in vivo and by isolated heart study ex vivo. Oxidative stress, myocardial metabolism and nitric oxide metabolite were evaluated by spectrophotometry, MMP-2 activity by zymography and caspase-3 and Bcl-2 protein expression by Western blot. RESULTS: Doxorubicin induced decreases in body weight, food and water ingestion. We observed decreases in left ventricular fractional shortening in rats treated with doxorubicin. Additionally, the same rats showed lower +dP/dt and -dP/dt during isolated heart study than those who did not receive doxorubicin. Doxorubicin injection increased caspase-3 protein expression, myocardium lipid hydroperoxide concentration, MMP-2 activity, phosphofructokinase and lactate dehydrogenase activity, and decreased ß-hydroxyacyl-CoA dehydrogenase, pyruvate dehydrogenase, citrate synthase, complex I, complex II and ATP synthase activity in myocardium. Açai supplementation improved left ventricular fractional shortening, decreased myocardium lipid hydroperoxide concentration, MMP-2 activity, and improved ß-hydroxyacyl-CoA dehydrogenase, phosphofructokinase, citrate synthase, complex II and ATP synthase enzymatic activities. We did not observe differences in nitric oxide metabolite concentrations between groups. CONCLUSION: Doxorubicin induced left ventricular dysfunction, increases in oxidative stress, changes in myocardium metabolism and MMP-2 activation. Açai supplementation was able to prevent these alterations.


Assuntos
Doxorrubicina/toxicidade , Euterpe/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Suplementos Nutricionais , Ecocardiografia , Euterpe/metabolismo , Cardiopatias/etiologia , Cardiopatias/prevenção & controle , Técnicas In Vitro , L-Lactato Desidrogenase/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Miocárdio/metabolismo , Óxido Nítrico/sangue , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Função Ventricular Esquerda/efeitos dos fármacos
3.
Life Sci ; 234: 116753, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31419445

RESUMO

AIMS: Hypertension is a global disease that has been combating the world health for ages. Peristrophe roxburghiana (PR) is used in traditional medicine to treat hypertension and other ailments. The present study examined phytochemical constituents, antioxidant activities and GC-MS analysis of extracts of PR leaf and also evaluated their anti-hypertensive and anti-lipidemic effects in NG-nitro-L-arginine methyl ester (L-NAME) hypertensive rats. METHODS: Wistar rats were grouped into two groups: control and hypertensive. Hypertension was induced in the hypertensive group by oral gavage of 60 mg/kg b.w of L-NAME for 3 weeks. After induction, the hypertensive group was randomly sub-grouped into hypertensive, hypertensive treated and hypertensive untreated groups. These were orally gavaged respectively with 60 mg/kg b.w of L-NAME, 60 mg/kg b.w/day of L-NAME +200 mg/kg b.w of different extracts of PR (aqueous, ethanolic and methanolic extracts) and 60 mg/kg b.w of L-NAME +20 mg/kg b.w ramipril for 3 weeks. The blood pressure was measured by tail-cuff method at the third and sixth weeks. KEY FINDINGS: The results showed that the extracts of PR significantly decrease blood pressure, pro-atherogenic lipids and atherogenic ratios in L-NAME hypertensive rats. White blood cells count, neutrophil count and creatinine level were also effectively decreased by the extracts. Furthermore, the extracts increase serum nitric oxide (NO) level, anti-atherogenic lipid, glutathione level, lymphocyte and platelet count in the rats. SIGNIFICANCE: Extracts of PR leaf decrease blood pressure and increase NO level in L-NAME hypertensive rats and also corrected the hyperlipidemia and inflammatory response arising from the reduction in NO bioavailability.


Assuntos
Acanthaceae/química , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Anti-Hipertensivos/química , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/sangue , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Hipolipemiantes/química , Lipídeos/sangue , Masculino , NG-Nitroarginina Metil Éster , Óxido Nítrico/sangue , Extratos Vegetais/química , Folhas de Planta/química , Ratos Wistar
4.
Rev Assoc Med Bras (1992) ; 65(7): 971-976, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31389507

RESUMO

OBJECTIVE: To investigate the relations of T lymphocytes, cytokines, immunoglobulin E, and nitric oxide with otitis media with effusion (OME) in children and their clinical significances. METHODS: Fifty children with OME treated in our hospital were enrolled in the study (observation group). Fifty healthy children were selected as control. The percentages of CD4+ and CD8+ T lymphocyte and CD4+/CD8+ ratio in peripheral blood, and the levels of cytokine (IL)-2, IL-4, IL-6, immunoglobulin E (IgE) and nitric oxide (NO) in peripheral blood and middle ear effusion (MEE) in both groups were detected. The correlations of these indexes with OME were analyzed. RESULTS: The percentage of peripheral blood CD4+ and CD8+ levels, CD4+/CD8 ratio, IgE, and NO levels in the observation group were significantly higher than those in the control group (P < 0.01). In the observation group, the IL-2 and IL-6 levels, and IgE and NO levels in the MEE were significantly higher than those in peripheral blood (P < 0.01). In addition, in the observation group, the MEE IL-2 and IL-6 levels were positively correlated with peripheral blood CD4+/CD8+ ratio, respectively r = 0.366, P = 0.009; r = 0.334, P = 0.018. CONCLUSIONS: The levels of peripheral blood CD4+ and CD8+ lymphocytes and MEE IL-2, IL-6, IgE, and NO levels are increased in children with OME. These indexes have provided significant clues for the diagnosis of OME in children.


Assuntos
Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Citocinas/sangue , Imunoglobulina E/sangue , Óxido Nítrico/sangue , Otite Média com Derrame/sangue , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Humanos , Contagem de Linfócitos , Masculino , Valores de Referência , Membrana Timpânica/metabolismo
5.
Adv Clin Exp Med ; 28(7): 931-936, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31237119

RESUMO

BACKGROUND: Fenofibrate, a peroxisome proliferator-activated receptor-α (PPARα) agonist, is used to treat patients with hypercholesterolemia and hypertriglyceridemia in order to reduce the risk of development of the atherosclerotic cardiovascular disease. However, it exerts pleiotropic effects beyond correcting atherogenic dyslipidemia to treat hypercholesterolemia. OBJECTIVES: The aim of this study was to investigate the potential effects of fenofibrate on endothelial function by analyzing the serum nitric oxide (NO) levels in patients with hypertriglyceridemia. MATERIAL AND METHODS: Lipid profiles and serum NO levels were assessed in 56 healthy adults aged 29 to 84 years, before and after 12 weeks of fenofibrate (250 mg/d; n = 30) or placebo (n = 26). Appropriate dietary suggestions for hypertriglyceridemia were made for all patients. This study was randomized, double-blind and placebo-controlled in design. RESULTS: Total cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) and triglyceride levels significantly decreased; high-density lipoprotein (HDL) and NO levels significantly increased after 12 weeks of fenofibrate therapy. We observed a statistically significant correlation between the increase in serum NO levels and decrease in serum triglyceride levels (r = -0.42, p = 0.02) in the fenofibrate group. CONCLUSIONS: The positive effect of short-term fenofibrate treatments on vascular endothelial functions in patients with hypertriglyceridemia has been demonstrated by increasing the serum NO levels. Agents such as fenofibrate targeting PPARα-associated signaling pathways show promise as an alternative treatment of vascular dysfunction related to advanced age and hyperlipidemia.


Assuntos
Fenofibrato/efeitos adversos , Fenofibrato/farmacologia , Hipertrigliceridemia/tratamento farmacológico , Hipolipemiantes/efeitos adversos , Hipolipemiantes/farmacologia , Óxido Nítrico/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Fenofibrato/uso terapêutico , Humanos , Hipolipemiantes/uso terapêutico , Pessoa de Meia-Idade , Resultado do Tratamento , Triglicerídeos
6.
BMC Complement Altern Med ; 19(1): 127, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196042

RESUMO

BACKGROUND: Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula, which has been reported to exert effective protection against cardiovascular diseases, including hypertension and myocarditis. METHODS: Cultured human umbilical vascular endothelial cells (HUVECs) were treated with angiotensin II (Ang II) and different concentrations of aqueous layer extracts (AqE). Subsequently nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) expression levels were detected. In addition, fifty Kunming mice were randomized into control, Nω-nitro-L-arginine methyl ester (L-NAME), L-NAME+AqE, L-NAME+XJEK and L-NAME+fosinopril treatment groups. Following 8 weeks of treatment, the cardiac hemodynamic index was measured, relaxation of the aorta was examined and pathological changes were observed. Colorimetric analysis and enzyme linked immunosorbent assay (ELISA) were applied to determine the relevant indicators in plasma and cardiac tissues. RESULTS: The in vitro study results demonstrated that AqE could preserve endothelial function (NO, 21.05 ± 2.03 vs. 8.64 ± 0.59; eNOS, 1.08 ± 0.17 vs.0.73 ± 0.06). In addition, the in vivo results demonstrated that compared with the control group, treatment with AqE could enhance a high hemodynamic state (left ventricular systolic pressure, 116.76 ± 9.96 vs.114.5 ± 15.16), improve endothelial function (NO, 7.98 ± 9.64 vs. 1.66 ± 3.11; eNOS, 19.78 ± 3.18 vs.19.38 ± 3.85), suppress oxidative stress (OS) (superoxide dismutase, 178.17 ± 13.78 vs. 159.38 ± 18.86; malondialdehyde, 0.77 ± 0.13 vs.1.25 ± 0.36) and reverse cardiovascular remodeling. CONCLUSION: Polysaccharide from XJEK exerts protective effects against Ang II-induced injury in HUVECs and L-NAME-induced hypertension in mice and the underlying mechanism may be attributed to improving endothelial dysfunction, OS and the inflammation status in mice.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Remodelação Vascular/efeitos dos fármacos , Angiotensina II , Animais , Aorta/efeitos dos fármacos , Arginina/análogos & derivados , Arginina/sangue , Pressão Sanguínea/efeitos dos fármacos , Citocinas/metabolismo , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Hipertensão/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Malondialdeído/sangue , Camundongos , Miocárdio/metabolismo , NG-Nitroarginina Metil Éster , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Superóxido Dismutase/sangue
7.
Wiad Lek ; 72(4): 523-526, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31055525

RESUMO

OBJECTIVE: Introduction: The study increase in the incidence of non-alcoholic steatohepatitis (NASH) on the background of obesity and chronic kidney disease (CKD) in people of working age in Ukraine and in the world necessitates the research into mechanisms of mutual burden and the search for new factors in the pathogenesis of this comorbidity progression . The aim: To establish the role of endothelial dysfunction in the mechanisms of mutual burden and progression of non-alcoholic steatohepatitis and chronic kidney disease in patients with obesity. PATIENTS AND METHODS: Materials and methods: 135 patients were examined: of which 52 patients with non-alcoholic steatohepatitis with obesity I degree (1 group), 53 patients with nonalcoholic steatohepatitis with comorbid obesity of the I degree and chronic kidney disease of the І-ІІ stage (group 2). The control group consisted of 30 practically healthy persons of the corresponding age and sex. The average age of patients was (45.8 ± 3.81) years. RESULTS: Results: The results of the study showed that in patients with NASH, a significant increase in the content of NO in the blood was detected in comparison with the index in PHP (p <0,05) in group 1 - in 2,1 times, in the 2nd group - in 2,6 times (p <0,05). The role of nitrosative stress in the pathogenesis of NASH was proved, the confirmation of which is the increase in the concentration of nitrosothiols, peroxynitrite and other metabolites NO in the blood. Increased peroxynitrite formation due to the generation of NO by leukocytes is an important aspect of the damaging effect and inflammation process in NASH. Pathological hyperproduction of NO by endothelial cells and leukocytes from inflammatory infiltrates in the liver contributes to the development of nitrosative stress in NASH. The established hypernitrate in blood may also be considered compensatory in response to hyperproduction of ET-1 in all observational groups. CONCLUSION: Conclusions: Confirmation of the presence of endothelial dysfunction (ED) in patients with NASH with CKD resulted in a probable growth of the number of desquamated endothelial cells (DEC) in the 2nd group of patients in 1.9 times (p2 <0.05). Generation by neutrophils during the exacerbation of NASH of a significant number of active forms of oxygen and nitrogen and hyperproduction of endothelial cells and endometrial lymphocytes with progressive damage to the endothelium (growth of DEC) leads to significant ED, accompanied by mosaic angiospasm of the arteries due to hyperproduction of ET-1 and parectic vasodilatation of the veins of the portal vein system because of the hyperproduction of NO.


Assuntos
Endotélio Vascular/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Adulto , Estudos de Casos e Controles , Progressão da Doença , Endotelina-1/metabolismo , Humanos , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Ucrânia
8.
BMC Complement Altern Med ; 19(1): 97, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060549

RESUMO

BACKGROUND: Endothelial dysfunction (ED) has been observed in individuals with metabolic syndrome (MetS) and contributes to the initiation and progression of atherosclerosis. The primary management of MetS involves lifestyle modifications and treatment of its individual components with drugs all of which have side effects. Thus, it would be of advantageous if natural products would be used as adjuncts or substitutes for conventional drugs. The aim of the present study was to evaluate the effect of standardized aqueous extract of fruits of Phyllanthus emblica (P. emblica) 250 mg and 500 mg twice daily on ED, oxidative stress, systemic inflammation and lipid profile in subjects with MetS. METHODS: In this randomised, double-blind, placebo-controlled clinical study endothelial function was measured by calculating reflection index (RI) using digital plethysmograph. Oxidative stress biomarkers used were nitric oxide (NO), glutathione (GSH) and malondialdehyde (MDA). Systemic inflammation was measured by determining high sensitivity C-reactive protein (hsCRP) and dyslipidemia by lipid profile. ANOVA, paired and unpaired t-test were used. P-value < 0.05 was considered statistically significant. RESULTS: Out of 65 screened subjects all 59 enrolled completed the study. P. emblica aqueous extract (PEE), 250 mg and 500 mg twice daily dosing, showed significant reduction in mean RI, measure of endothelial function, at 8 and 12 weeks (p <  0.001) compared to baseline and placebo. Significant mean % change was seen in oxidative stress biomarkers, NO (+ 41.89%, + 50.7%), GSH (+ 24.31%, + 53.22%) and MDA (- 21.02%, - 31.44%), and systemic inflammation biomarker, hsCRP (- 39.68%, - 53.77%) (p <  0.001) at 12 weeks with 250 mg and 500 mg twice daily dosage respectively. Significant mean % change was also seen at 12 weeks with TC (- 7.71%, - 11.11%), HDL-C (+ 7.33% + 22.16%, p <  0.05), LDL-C (- 11.39%, - 21.8%) and TG (- 9.81%, - 19.22%) respectively with 250 mg and 500 mg twice daily (p <  0.001). PEE 500 mg twice daily was significantly more efficacious than the 250 mg twice daily and placebo. No participant discontinued the study because of adverse events. CONCLUSIONS: P.emblica aqueous extract significantly improved endothelial function, oxidative stress, systemic inflammation and lipid profile at both dosages tested, but especially at 500 mg twice daily. Thus, this product may be used as an adjunct to conventional therapy (lifestyle modification and pharmacological intervention) in the management of metabolic syndrome. TRIAL REGISTRATION: This study was registered with Clinical Trials Registry - India (CTRI) with the registration number of CTRI/2017/09/009606 . The study was registered retrospectively on 4th September 2017.


Assuntos
Inflamação/tratamento farmacológico , Lipídeos/sangue , Síndrome Metabólica/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Phyllanthus emblica , Extratos Vegetais , Idoso , Método Duplo-Cego , Dislipidemias/metabolismo , Feminino , Frutas/química , Glutationa/sangue , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/sangue , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
9.
Int J Nanomedicine ; 14: 3375-3388, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123402

RESUMO

Background: Magnetic nanoparticles (MNPs) have been successfully tested for several purposes in medical applications. However, knowledge concerning the effects of nanostructures on elderly organisms is remarkably scarce. Purpose: To fill part of this gap, this work aimed to investigate biocompatibility and bio-distribution aspects of magnetic nanoparticles coated with citrate (NpCit) in both elderly and young healthy mice. Methods: NpCit (2.4 mg iron) was administered intraperitoneally, and its toxicity was evaluated for 28 days through clinical, biochemical, hematological, and histopathological examinations. In addition, its biodistribution was evaluated by spectrometric (inductively coupled plasma optical emission spectrometry) and histological methods. Results: NpCit presented age-dependent effects, inducing very slight and temporary biochemical and hematological changes in young animals. These changes were even weaker than the effects of the aging process, especially those related to the hematological data, tumor necrosis factor alpha, and nitric oxide levels. On the other hand, NpCit showed a distinct set of results in the elderly group, sometimes reinforcing (decrease of lymphocytes and increase of monocytes) and sometimes opposing (erythrocyte parameters and cytokine levels) the aging changes. Leukocyte changes were still observed on the 28th day after treatment in the elderly group. Slight evidence of a decrease in liver and immune functions was detected in elderly mice treated or not treated with NpCit. It was noted that tissue damage or clinical changes related to aging or to the NpCit treatment were not observed. As detected for aging, the pattern of iron biodistribution was significantly different after NpCit administration: extra iron was detected until the 28th day, but in different organs of elderly (liver and kidneys) and young (spleen, liver, and lungs) mice. Conclusion: Taken together, the data show NpCit to be a stable and reasonably biocompatible sample, especially for young mice, and thus appropriate for biomedical applications. The data showed important differences after NpCit treatment related to the animals' age, and this emphasizes the need for further studies in older animals to appropriately extend the benefits of nanotechnology to the elderly population.


Assuntos
Envelhecimento/fisiologia , Ácido Cítrico/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Nanopartículas de Magnetita/química , Animais , Feminino , Ferro/química , Pulmão/efeitos dos fármacos , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Óxido Nítrico/sangue , Especificidade de Órgãos/efeitos dos fármacos , Distribuição Tecidual/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue
10.
J Immunol Res ; 2019: 1409383, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31032371

RESUMO

In a recent work, we have described the kinetics among the monocyte subsets in the peripheral blood of hemolytic patients including paroxysmal nocturnal hemoglobinuria (PNH) and sickle cell disease (SCD). After engulfing Hb-activated platelets, classical monocytes (CD14+CD16-) significantly transformed into highly inflammatory (CD14+CD16hi) subsets in vitro. An estimated 40% of total circulating monocytes in PNH and 70% in SCD patients existed as CD14+CD16hi subsets. In this study, we show that the nonclassical (CD14dimCD16+) monocyte subsets are nearly absent in patients with PNH or SCD, compared to 10-12% cells in healthy individuals. In mechanism, we have described the unique role of both free Hb and nitric oxide (NO) in reducing number of nonclassical subsets more than classical monocytes. After engulfing Hb-activated platelets, the monocytes including nonclassical subsets acquired rapid cell death within 12 h in vitro. Further, the treatment to monocytes either with the secretome of Hb-activated platelets containing NO and free Hb or purified free Hb along with GSNO (a physiological NO donor) enhanced rapid cell death. Besides, our data from both PNH and SCD patients exhibited a direct correlation between intracellular NO and cell death marker 7AAD in monocytes from the peripheral blood. Our data together suggest that due to the immune surveillance nature, the nonclassical or patrolling monocytes are encountered frequently by Hb-activated platelets, free Hb, and NO in the circulation of hemolytic patients and are predisposed to die rapidly.


Assuntos
Hemoglobinas/análise , Hemoglobinúria Paroxística/imunologia , Monócitos/citologia , Óxido Nítrico/sangue , Adolescente , Adulto , Apoptose , Biomarcadores/sangue , Feminino , Humanos , Masculino , Adulto Jovem
11.
BMC Neurol ; 19(1): 56, 2019 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-30954070

RESUMO

BACKGROUND: Dopaminergic neuronal loss begins years before motor symptoms appear in Parkinson disease (PD). Thus, reliable biomarkers for early diagnosis and prognosis of PD are an essential pre-requisite to develop disease modifying therapies. Inflammation-derived oxidative stress is postulated to contribute to nigrostriatal degeneration. We evaluated the role of selected serum immune mediators (IFNγ, TNFα, IL-10, and NOx) in PD progression and estimated their usefulness in preclinical diagnosis. METHODS: This case-control study recruited 72 PD patients with varying disease durations (< 1-year, n = 12 patients; 1-3 years, n = 30; > 3 years, n = 30) and 56 age- and gender-matched controls (26 with other neurological disorders as disease controls, and 30 healthy controls). Serum cytokine levels and NOx quantified using Sandwich Enzyme Linked Immunosorbent Assay kits, and the Griess test, respectively, were evaluated for diagnostic accuracy of optimal marker combinations by the CombiROC method. PD patients were clinically evaluated for motor and non-motor symptoms, and staged based on Hoehn and Yahr (H-Y) scale. RESULTS: A significant increase in serum IFNγ and IL-10 was observed in PD compared to healthy controls (p < 0.001). The Th1: Th2 (IFNγ: IL-10) cytokine ratio was higher in PD of 3-12 years compared with PD < 1 year (p < 0.001). Highest levels of NOx manifested during early PD (1-3 years) through a subsequent decline with disease duration. TNFα level was highest at PD onset. A low serum NOx level was associated with cognitive impairment (p = 0.002). The potential of using multi-biomarker panel, IFNγ, IL-10 and TNFα, for detection of PD onset was evident (sensitivity [SE] = 83.3%, specificity [SP] =80.4%, area under curve [AUC] = 0.868), while for early and late PD the multi-biomarker signature of IFNγ, IL-10 and NOx appeared to be more promising (SE = 93.3%, SP = 87.5%, AUC = 0.924). CONCLUSION: A Th1 cytokine-biased immune response predominates with PD progression. Both IFNγ and IL-10 are involved in disease severity. However, TNFα-mediated neurotoxicity appears to occur in early PD.


Assuntos
Biomarcadores/sangue , Citocinas/sangue , Óxido Nítrico/sangue , Doença de Parkinson/sangue , Idoso , Área Sob a Curva , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Interferon gama/sangue , Interleucina-10/sangue , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Prognóstico , Fator de Necrose Tumoral alfa/sangue
12.
Nutrients ; 11(3)2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30889894

RESUMO

Obesity is intimately related to a chronic inflammatory state, with augmentation of macrophage infiltration and pro-inflammatory cytokine secretion in white adipose tissue (WAT) and mitochondrial dysfunction in skeletal muscle. The specific aim of this study is to evaluate effects of tartary buckwheat extract (TB) on obesity-induced adipose tissue inflammation and muscle peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α/sirtulin 1 (SIRT1) pathway in rats fed a high-fat diet. Sprague-Dawley rats were divided into four groups and fed either a normal diet (NOR), 45% high-fat diet (HF), HF + low dose of TB (TB-L; 5 g/kg diet), or HF + high dose of TB (TB-H; 10 g/kg diet) for 13 weeks. TB significantly reduced adipose tissue mass with decreased adipogenic gene expression of PPAR-γ and aP2. Serum nitric oxide levels and adipose tissue macrophage M1 polarization gene markers, such as iNOS, CD11c, and Arg1, and pro-inflammatory gene expression, including TNF-α, IL-6, and MCP-1, were remarkably downregulated in the TB-L and TB-H groups. Moreover, TB supplementation increased gene expression of PGC-1α and SIRT1, involved in muscle biogenesis and function. These results suggested that TB might attenuate obesity-induced inflammation and mitochondrial dysfunction by modulating adipose tissue inflammation and the muscle PGC-1α/SIRT1 pathway.


Assuntos
Tecido Adiposo/metabolismo , Fagopyrum , Inflamação/prevenção & controle , Músculo Esquelético/metabolismo , Obesidade/complicações , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Sirtuína 1/metabolismo , Animais , Citocinas/metabolismo , Dieta Hiperlipídica , Regulação para Baixo , Inflamação/etiologia , Inflamação/metabolismo , Macrófagos/metabolismo , Masculino , Óxido Nítrico/sangue , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos Sprague-Dawley
13.
J Comp Pathol ; 167: 50-59, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30898298

RESUMO

There is significant evidence that pathology of the microcirculation occurs in African swine fever (ASF); however, the mechanisms by which it develops are largely unknown. In the present experimental infection study, we show that an increase in vascular permeability in the initial stages of acute ASF is dependent on viraemia and elevation of the concentration of serum nitric oxide (NO). Macrophages activated by ASF virus (ASFV) are stimulated to produce NO and simultaneously to sensitize the endothelial cells through the action of vascular endothelial growth factor Β (VEGFΒ), which is followed by an increase in VEGF-mediated endothelial permeability. In the later stages of disease, the endothelial cells undergo DNA proliferation, which may additionally provoke capillary leakage, point haemorrhages and migration of blood cells into tissues. The possible mechanism of a shift in the cell cycle from the G1 to S and G2 stages could be a direct effect of ASFV. The terminal stages of disease are characterized by triggering of compensatory mechanisms such as stimulation of the synthesis of stromal cell-derived factor-1.


Assuntos
Febre Suína Africana/patologia , Quimiocina CXCL12/sangue , Endotélio Vascular/patologia , Óxido Nítrico/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Febre Suína Africana/metabolismo , Animais , Ciclo Celular/fisiologia , Proliferação de Células/fisiologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Endotélio Vascular/metabolismo , Suínos
14.
Niger J Clin Pract ; 22(3): 375-379, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30837426

RESUMO

Objective: The aim of this study was to investigate the effect of oxidative stress and antioxidant situation on chronic otitis media with effusions (COME) and acute otitis media (AOM) in children. Methods: A total of 107 children aged 2 to 13 years were examined. The study included 31 patients with AOM, 39 with COME, and 37 as control subjects. Venous blood samples were collected from all patients and control group. Myeloperoxidase (MPO), glutathione peroxidase (GPx), catalase (CAT), nitric oxide (NO), malondialdehyde (MDA), and superoxide dismutase (SOD) activities were investigated in the blood samples. Results: The mean age was found as 7.3 ± 3.3 in the AOM group, 6.2 ± 3.0 in the COME group, and 6 ± 2.4 in the control group. MPO, NO, and CAT were found to be significantly higher in the AOM and COME groups than the control groups (P = 0.040, P = 0.001, and P = 0.044). Conclusion: In this study, we observed activity of antioxidant and oxidative stress in children with COME and AOM. These results may be important in the diagnosis of these diseases and may affect the theurapeutic approach to the patients with COME and AOM.


Assuntos
Antioxidantes/metabolismo , Otite Média com Derrame/sangue , Otite Média/sangue , Estresse Oxidativo , Doença Aguda , Adolescente , Catalase/sangue , Criança , Pré-Escolar , Doença Crônica , Feminino , Glutationa Peroxidase/sangue , Humanos , Masculino , Malondialdeído/sangue , Óxido Nítrico/sangue , Peroxidase/sangue , Superóxido Dismutase/sangue
15.
Bull Exp Biol Med ; 166(4): 436-439, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30790107

RESUMO

The development of arterial hypertension in male Wistar rats with fructose-induced metabolic syndrome (12.5% of fructose solution as the only drinking source for 10 weeks) along with impaired glucose tolerance and increased serum concentration of triglycerides and LPO products caused a decrease in the content of serum blood calcitonin gene-related peptide (CGRP). Low-frequency transcutaneous electrical nerve stimulation (1 mA, 2 Hz, 10 min daily for 2 weeks) performed in 8 weeks after the beginning of fructose treatment reduced systolic BP and serum concentration of triglycerides and LPO produces and improved glucose tolerance. After stimulation, CGRP content in rats maintained on fructose diet returned to normal values and the content of nitric oxide metabolites increased. We hypothesize that CGRP and nitric oxide are involved in mechanisms mediating the therapeutic effect of low-frequency transcutaneous electrical nerve stimulation on arterial hypertension developing in metabolic syndrome.


Assuntos
Pressão Sanguínea/fisiologia , Peptídeo Relacionado com Gene de Calcitonina/sangue , Hipertensão/sangue , Óxido Nítrico/sangue , Estimulação Elétrica Nervosa Transcutânea , Animais , Frutose/metabolismo , Masculino , Neuropeptídeos/sangue , Ratos , Ratos Wistar
16.
Mol Med Rep ; 19(3): 2449-2457, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30747212

RESUMO

Vascular endothelial dysfunction is the major contributing factor to hypertension. Endothelial progenitor cells (EPCs) are essential for endogenous vascular endothelial renovation. The activity and number of circulating EPCs are preserved in prehypertensive premenopausal females according to our previous research. However, the changes of EPCs in prehypertensive postmenopausal females are poorly understood, and the mechanisms responsible for the loss of the gender protection advantage of cardiovascular disease remain unexplored. In order to determine the effects of EPCs in prehypertensive postmenopausal females, the number and activity of circulating EPCs were tested in the present study. Next, the function of EPCs secreting nitric oxide (NO), vascular endothelial growth factor (VEGF) and granulocyte­macrophage colony­stimulating factor (GM­CSF), as well as their concentration in the plasma, were measured. The association between flow­mediated dilation (FMD) and EPC secretion was also assessed. Attenuation of proliferation and migration of EPCs was observed in prehypertensive patients in comparison with normotensive subjects. In addition, a reduced NO production secreted by EPCs was detected in prehypertensive patients as compared with that in normotensive patients. There was no significant difference in EPC function between postmenopausal females and age­matched males. Finally, the association between FMD and NO production was validated. Collectively, these data indicated that impaired EPCs mediated vasodilation dysfunction via decreasing NO production. Therefore, EPC function enhancement and NO level augmentation are emerging as novel therapeutic strategies for prehypertension therapy.


Assuntos
Células Progenitoras Endoteliais/patologia , Hipertensão/etiologia , Hipertensão/fisiopatologia , Óxido Nítrico/metabolismo , Pós-Menopausa , Vasodilatação , Pressão Sanguínea , Movimento Celular , Proliferação de Células , Células Cultivadas , Células Progenitoras Endoteliais/metabolismo , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Hipertensão/sangue , Hipertensão/metabolismo , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Eur Arch Otorhinolaryngol ; 276(4): 1231-1239, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30758659

RESUMO

PURPOSE: We conduct this study to evaluate the clinical and functional impact of Nitric Oxide Synthase 3 (NOS3) T-786C and G894T genetic variants on nasopharyngeal carcinoma (NPC) risk and progression in a Tunisian population. METHODS: 259 NPC patients and 169 healthy controls were enrolled into our case-control study. Blood samples were genotyped by the RFLP-PCR analysis. The levels of Nitric oxide (NO) were measured by a colorimetric assay kit in the plasma of NPC patients, healthy controls and according to NOS3 genotypes. The correlation between the NOS3 variants and the clinicopathological parameters was examined. RESULTS: We found no linkage disequilibrium between NOS3 T-786C and G894T variants. These results showed that NOS3 variants were genetically independent. In contrast to NOS3 T-786C, a significant association was found between NOS3 G894T polymorphism and NPC risk. The 894T allele decreased significantly in NPC patients and appeared as protective factor (OR = 0.65, CI 95%= 0.48-0.88, p = 0.006). NPC patients had significantly higher levels of plasma NO as compared to healthy controls (p = 0.0011). The T-786C mutation reduced the levels of plasma NO and decreased risk of lymph node metastasis in NPC patients (OR = 0.64, 95% CI = 0.43-0.96; p = 0.03). In contrast, NOS3 G894T polymorphism had no effects neither on NO plasma levels nor clinical parameters. CONCLUSIONS: This is the first study to associate NPC with significantly higher levels of plasma NO. NOS3-derived NO could play key roles in NPC pathogenesis. NOS3 variants differently contribute to NPC risk and progression in a Tunisian population. NOS3 G894T was associated with NPC risk. NOS3 T-786C decreased the levels of plasma NO and reduced the development of regional lymph node metastasis.


Assuntos
Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo Genético/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Criança , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/sangue , Neoplasias Nasofaríngeas/sangue , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo III/sangue , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Tunísia , Adulto Jovem
18.
J Vet Intern Med ; 33(2): 987-998, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30788867

RESUMO

BACKGROUND: Plasma citrulline (CIT) concentration is considered to be a reliable marker of functional enterocyte mass, primarily in humans. However, information about CIT levels along with related metabolites, arginine (ARG), nitric oxide (NO), and ammonia in neonatal calves are lacking. OBJECTIVES: To compare plasma CIT, ARG, NO, and whole blood ammonia concentrations in neonatal calves with acute diarrhea with those in healthy calves and to assess their possible relationships with diarrhea-related criteria. ANIMALS: Seventy neonatal calves (60 with acute diarrhea and 10 healthy). METHODS: Observational case-control study. Diarrheic calves were classified into subgroups on the basis of etiology, severity of diarrhea, degree of dehydration, and systemic inflammatory response syndrome (SIRS) status. Plasma CIT and ARG concentrations were measured by liquid chromatography/tandem mass spectrometry. RESULTS: Plasma CIT (median [range]: 67.5 [61.9-75.4] vs 30.1 [15.0-56.1] µmol/L) and ARG (170.7 [148.5-219.5] vs 106.1 [54.4-190.7] µmol/L) were lower and plasma NO (4.42 [3.29-5.58] vs 6.78 [5.29-8.92] µM) and blood ammonia concentrations (28.7 [26.1-36.9] vs 59.8 [34.6-99.5] µmol/L) were higher in the neonatal calves with diarrhea (P < .001). Plasma CIT (ß = -0.29, P = .02), ARG (ß = -0.33, P = .01), NO (ß = 0.55, P < .001), and blood ammonia (ß = 0.63, P <.001) were affected by SIRS status. Except for ammonia (0.52), the effects sizes for severity of diarrhea and degree of dehydration were small (ηp2 ≤ 0.45) for CIT, ARG, and NO. CONCLUSIONS AND CLINICAL IMPORTANCE: The changes in these variables might have diagnostic, prognostic, and therapeutic value in diarrheic neonatal calves.


Assuntos
Amônia/sangue , Arginina/sangue , Doenças dos Bovinos/sangue , Citrulina/sangue , Diarreia/veterinária , Óxido Nítrico/sangue , Animais , Animais Recém-Nascidos/sangue , Estudos de Casos e Controles , Bovinos , Desidratação/veterinária , Diarreia/sangue , Síndrome de Resposta Inflamatória Sistêmica/veterinária
19.
Chin Med J (Engl) ; 132(3): 319-328, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30681498

RESUMO

BACKGROUND: Eucommia ulmoides Oliv. is a medicinal plant native to China, with its bark (Eucommiae Cortex) traditionally being used for medicinal purposes. Previous research has shown that Eucommia male flowers can exert anti-inflammatory, analgesic, antibacterial, and other pharmacological effects, including immune regulation. This study explored the anti-inflammatory effects of the 70% ethanol extract of male flowers (EF) of E. ulmoides in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and LPS-administered mice. METHODS: Cytotoxicity of EF for RAW 264.7 cells was investigated using Cell Counting Kit-8. The production of proinflammatory mediators, nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 was determined using enzyme-linked immunosorbent assays. IL-17, IL-23, and IL-10 mRNA levels were determined using quantitative real-time polymerase chain reaction. Activation of the nuclear factor (NF)-κB pathway in RAW 264.7 cells was investigated via Western blotting. In vivo anti-inflammatory effects of EF were studied in an LPS-induced acute inflammation mouse model by analyzing lung tissue histopathology, serum TNF-α and IL-6 levels, and myeloperoxidase (MPO) activity in lung tissue. RESULTS: EF showed no significant cytotoxicity at concentrations from 10 to 60 µg/mL (cell viability > 80%) in the CCK-8 cell viability assay. EF inhibited the RAW 264.7 cell proliferation (EF 60 µg/mL, 120 µg/mL, and 250 µg/mL vs. negative control: 87.31 ±â€Š2.39% vs. 100.00 ±â€Š2.50%, P = 0.001; 79.01 ±â€Š2.56 vs. 100.00 ±â€Š2.50%, P < 0.001; and 64.83 ±â€Š2.50 vs. 100.00 ±â€Š2.50%, P < 0.001), suppressed NO (EF 20 µg/mL and 30 µg/mL vs. LPS only, 288.81 ±â€Š38.01 vs. 447.68 ±â€Š19.07 µmol/L, P = 0.004; and 158.80 ±â€Š45.14 vs. 447.68 ±â€Š19.07 µmol/L, P < 0.001), TNF-α (LPS+EF vs. LPS only, 210.20 ±â€Š13.85 vs. 577.70 ±â€Š5.35 pg/mL, P < 0.001), IL-1ß (LPS+EF vs. LPS only, 193.30 ±â€Š10.80 vs. 411.03 ±â€Š42.28 pg/mL, P < 0.001), and IL-6 (LPS+EF vs. LPS only, 149.67 ±â€Š11.60 vs. 524.80 ±â€Š6.24 pg/mL, P < 0.001) secretion, and downregulated the mRNA expression of IL-17 (LPS+EF vs. LPS only, 0.23 ±â€Š0.02 vs. 0.43 ±â€Š0.12, P < 0.001), IL-23 (LPS+EF vs. LPS only, 0.29 ±â€Š0.01 vs. 0.42 ±â€Š0.06, P=0.002), and IL-10 (LPS+EF vs. LPS only, 0.30 ±â€Š0.01 vs. 0.47 ±â€Š0.01, P=0.008) in LPS-stimulated RAW 264.7 cells. EF inhibited the LPS-induced NF-κB p65 (LPS+EF 20 µg/mL and 30 µg/mL vs. LPS only: 0.78 ±â€Š0.06 vs. 1.17 ±â€Š0.08, P < 0.001; and 0.90 ±â€Š0.06 vs. 1.17 ±â€Š0.08, P =0.002) and inhibitor of kappa B (IκBα) phosphorylation (LPS+EF 20 µg/mL and 30 µg/mL vs. LPS only: 0.25 ±â€Š0.01 vs. 0.63 ±â€Š0.03, P < 0.001; and 0.31 ±â€Š0.01 vs. 0.63 ±â€Š0.03, P < 0.001), LPS+EF 30 µg/mL inhibited IκB kinase (IKKα/ß) phosphorylation (LPS+EF 30 µg/mL vs. LPS only, 1.12 ±â€Š0.14 vs. 1.71 ±â€Š0.25, P = 0.002) in RAW 264.7 cells. Furthermore, EF 10 mg/kg and EF 20 mg/kg inhibited lung tissue inflammation in vivo and suppressed the serum TNF-α (LPS+EF 10 mg/kg and 20 mg/kg vs. LPS only, 199.99 ±â€Š186.49 vs. 527.90 ±â€Š263.93 pg/mL, P=0.001; and 260.56 ±â€Š175.83 vs. 527.90 ±â€Š263.93 pg/mL, P = 0.005), and IL-6 (LPS+EF 10 mg/kg and 20 mg/kg vs. LPS only, 41.26 ±â€Š30.42 vs. 79.45 ±â€Š14.16 pg/ ml, P = 0.011; and 42.01 ±â€Š26.26 vs. 79.45 ±â€Š14.16 pg/mL, P = 0.012) levels and MPO (LPS+EF 10 mg/kg and 20 mg/kg vs. LPS only, 3.19 ±â€Š1.78 vs. 5.39 ±â€Š1.51 U/g, P = 0.004; and 3.32 ±â€Š1.57 vs. 5.39 ±â€Š1.51 U/g, P = 0.006) activity in lung tissue. CONCLUSIONS: EF could effectively inhibit the expression of inflammatory factors and overactivation of neutrophils. Further investigation is needed to evaluate its potential for anti-inflammation therapy.


Assuntos
Anti-Inflamatórios/uso terapêutico , Eucommiaceae/química , Flores/química , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Lipopolissacarídeos/toxicidade , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/química , Inflamação/sangue , Interleucina-1beta/sangue , Macrófagos/efeitos dos fármacos , Camundongos , Inibidor de NF-kappaB alfa/sangue , NF-kappa B/sangue , Óxido Nítrico/sangue , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue
20.
Pediatr Int ; 61(3): 252-257, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30597683

RESUMO

BACKGROUND: Alteration in thiol level under oxidative stress may contribute to community-acquired pneumonia (CAP). The goal of this study was to determine whether there are changes in thiol/disulfide homeostasis and nitric oxide (NO) in children with CAP. METHODS: In total, 130 participants were involved in the study. Of these, 65 had been diagnosed with CAP on admission, and the remaining 65 were healthy individuals. Serum total thiol and native thiol were measured in each participant using a novel automated spectrophotometric method. The amount of dynamic disulfide bonds and related ratios were calculated from these values. Serum NO was measured on chemiluminescence assay. RESULTS: Average native thiol, total thiol, and disulfide in the CAP group were significantly lower than in the healthy individuals (P < 0.0001, P < 0.0001, P = 0.0126, respectively). In addition, disulfide/native thiol (P = 0.0002), and disulfide/total thiol ratios (P = 0.0004) were significantly higher, whereas the native thiol/total thiol ratio (P = 0.0004) was lower in the CAP group. High serum NO was noted in the CAP group (P = 0.0003), but there was no marked correlation between thiol/disulfide and NO. CONCLUSION: The changes in endogenous thiol levels under oxidative stress may be associated with the pathogenesis of CAP in pediatric patients.


Assuntos
Dissulfetos/sangue , Estresse Oxidativo/fisiologia , Pneumonia/sangue , Compostos de Sulfidrila/sangue , Pré-Escolar , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/fisiopatologia , Feminino , Homeostase/fisiologia , Humanos , Lactente , Masculino , Óxido Nítrico/sangue , Pneumonia/fisiopatologia , Espectrofotometria
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