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1.
J Steroid Biochem Mol Biol ; 193: 105419, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31255688

RESUMO

Innate immunity plays an important role in pathophysiology of tuberculosis which is influenced by various host factors. One such factor is vitamin D which, along with its associated molecule, can alter the host defense against Mycobacterium Tuberculosis (M.Tb.) via altered production of cathelicidin and nitric oxide, both having bactericidal effect. Therefore, assessment of vitamin D and its associated molecules in tuberculosis patients and household contacts as compared to healthy controls were done and the implication of these findings in susceptibility to tuberculosis (TB) was studied. 80 active TB patients, 75 household contacts and 70 healthy controls were included. Vitamin D receptor (VDR), vitamin D binding protein (VDBP) and inducible nitric oxide synthase (iNOS) mRNA levels were studied using quantitative PCR. Serum VDR, cathelicidin, and iNOS levels were measured using ELISA. Vitamin D and NO levels were measured in serum using chemiluminescence based immunoassay and greiss reaction based colorimetry kit respectively. Decreased serum levels of vitamin D were observed in active TB patients as compared to healthy controls (p < 0.001). VDR and iNOS mRNA levels were found to be significantly lower in active TB patients compared to household contacts and healthy controls (p < 0.0001 and 0.005 respectively). VDBP mRNA expression was found to be lower in active TB group as compared to household contacts and healthy controls however the difference was not found to be significant (p > 0.21). Although, mRNA expression of VDR, VDR protein and iNOS along with vitamin D levels were significantly (p < 0.05) higher in household contacts compared to active TB group. However, levels of iNOS, NO and cathelicidin were found to be higher in TB patients as compared to household contacts and healthy controls (p < 0.01, 0.05 and 0.01 respectively). Higher levels of Vitamin D along with VDR and iNOS expression in household contacts as compared to active TB patients suggest vitamin D might have a protective role against TB plausibly decreasing disease susceptibility. Low vitamin D levels in active TB patients warrants further studies to determine the role of vitamin D supplementation in prevention and treatment of TB.


Assuntos
Tuberculose Pulmonar/sangue , Vitamina D/sangue , Vitaminas/sangue , Adolescente , Adulto , Peptídeos Catiônicos Antimicrobianos/sangue , Estudos Transversais , Características da Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo II/sangue , Óxido Nítrico Sintase Tipo II/genética , Receptores de Calcitriol/sangue , Receptores de Calcitriol/genética , Tuberculose Pulmonar/genética , Proteína de Ligação a Vitamina D/genética , Adulto Jovem
2.
Med Sci Monit ; 25: 4362-4369, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185006

RESUMO

BACKGROUND Ischemia-reperfusion (I/R) leads to kidney injury. Renal I/R frequently occurs in kidney transplantations and acute kidney injuries. Recent studies reported that miR-30 stimulated immune responses and reductions in renal I/R related to anti-inflammation. Our study investigated the effects of miR-30c-5p on renal I/R and the relationship among miR-30c-5p, renal I/R, and macrophages. MATERIAL AND METHODS Sprague Dawley rats received intravenous tail injections of miR-30c-5p agomir. Then a renal I/R model were established by removing the left kidney and clamping the right renal artery. Serum creatinine (Cr) was analyzed using a serum Cr assay kit, and serum neutrophil gelatinase associated lipocalin (NGAL) was measured using a NGAL ELISA (enzyme-linked immunosorbent assay) kit. Rat kidney tissues were analyzed using hematoxylin and eosin staining. THP-1 cells treated with miR-30c-5p agomir and miR-30c-5p antagomir were measured with quantitative reverse transcription-polymerase chain reaction. Protein levels were analyzed by western blot. RESULTS MiR-30c-5p agomir reduced serum Cr, serum NGAL, and renal I/R injury. MiR-30c-5p agomir inhibited the expression of CD86 (M1 macrophage marker), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-alpha (TNF-alpha) and promoted the expression of CD206 (M2 macrophage marker), interleukin (IL)-4, and IL-10 in rat kidneys. MiR-30c-5p agomir reduced the expression of CD86 and iNOS, and increased the expression of CD206 and IL-10 in THP-1 cells. CONCLUSIONS We preliminarily demonstrated that miR-30c-5p agomir might decrease renal I/R through transformation of M1 macrophages to M2 macrophages and resulted in changes in inflammatory cytokines.


Assuntos
Lesão Renal Aguda/sangue , Macrófagos/metabolismo , MicroRNAs/sangue , Traumatismo por Reperfusão/sangue , Lesão Renal Aguda/genética , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/patologia , Animais , Creatina/sangue , Humanos , Inflamação/sangue , Rim/irrigação sanguínea , Rim/patologia , Lipocalina-2/sangue , Macrófagos/patologia , Masculino , MicroRNAs/genética , Óxido Nítrico Sintase Tipo II/sangue , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Células THP-1 , Fator de Necrose Tumoral alfa/sangue
3.
Braz J Psychiatry ; 41(5): 419-427, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30843957

RESUMO

OBJECTIVE: To evaluate whether an animal model of mania induced by lisdexamfetamine dimesylate (LDX) has an inflammatory profile and whether immune activation by lipopolysaccharides (LPS) has a cumulative effect on subsequent stimuli in this model. We also evaluated the action of lithium (Li) on inflammatory and neurotrophic factors. METHODS: Adult male Wistar rats were subjected to an animal model of mania. After the open-field test, they were given LPS to induce systemic immune activation. Subsequently, the animals' blood was collected, and their serum levels of brain-derived neurotrophic factor and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-1ß, IL-10, and inducible nitric oxide synthase [iNOS]) were measured. RESULTS: LDX induced hyperactivity in the animals, but no inflammatory marker levels increased except brain-derived neurotrophic factor (BDNF). Li had no effect on serum BDNF levels but prevented iNOS levels from increasing in animals subjected to immune activation. CONCLUSION: Although Li prevented an LPS-induced increase in serum iNOS levels, its potential anti-inflammatory effects in this animal model of mania were conflicting.


Assuntos
Anti-Inflamatórios/farmacologia , Transtorno Bipolar/imunologia , Modelos Animais de Doenças , Dimesilato de Lisdexanfetamina , Lítio/farmacologia , Fatores de Crescimento Neural/efeitos dos fármacos , Animais , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/sangue , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Lipopolissacarídeos/farmacologia , Locomoção/efeitos dos fármacos , Masculino , Óxido Nítrico Sintase Tipo II/sangue , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
4.
Environ Int ; 126: 184-192, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30798199

RESUMO

Prostatic enlargement might affect up to 30% of men and can cause signs and symptoms in the lower urinary tract in the elderly. Imbalanced estrogen and androgen secretions are important in prostatic physiopathology. Phthalates-environmental endocrine disruptors-affect androgen secretion and disrupt sexual organs, including testes and the prostate, but the underlying mechanisms are unclear. Using European Association of Urology (EAU) guidelines, we recruited from urology clinics in southern Taiwan 207 elderly men diagnosed with benign prostatic hyperplasia (BPH) and prostatic enlargement between 2015 and 2017. We took blood and urine samples from all patients on the same day. We used multivariate linear regression, associations, and potential interactions after we had measured and analyzed oxidative stress (OS) markers, steroidal hormones, and 11 urinary phthalate metabolites, and then we adjusted for confounders. Di(2-ethylhexyl) phthalate (DEHP) metabolite levels, particularly urinary mono-(2-ethylhexyl) phthalate, were positively associated with androgen, estrogen, hormone ratios, inducible nitric oxide synthetase (iNOS), 8-hydroxy-2'-deoxyguanosine (8-OHdG), prostate specific antigen (PSA), and prostate volume (PV) (p < 0.05). PV and PSA were positively associated with androgen, estrogen, hormone ratios and OS markers (p < 0.05). The estimated percentages of exposure to phthalates in prostatic enlargement mediated by androgen, estrogen, and OS markers ranged from 3.5% to 63.1%. Exposure to DEHP promoted the progress of BPH by increasing dihydrotestosterone (DHT), estradiol (E2), the converted enzymes aromatase and 5α reductase, and reactive oxygen species (ROS) (8-OHdG and iNOS) production. Sex hormones and OS might be important hyperplasia-promoters after a patient has been exposed to phthalates, especially to DEHP.


Assuntos
Disruptores Endócrinos/urina , Poluentes Ambientais/urina , Hormônios Esteroides Gonadais/sangue , Estresse Oxidativo , Ácidos Ftálicos/urina , Hiperplasia Prostática/sangue , Hiperplasia Prostática/urina , Androgênios/sangue , Biomarcadores/sangue , Biomarcadores/urina , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Estrogênios/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo II/sangue , Taiwan
5.
Br J Biomed Sci ; 76(1): 29-34, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30379116

RESUMO

OBJECTIVE: An imbalance in oxidant-antioxidant status may impact the severity of sepsis. We hypothesised links between nitrosative stress and pro-inflammatory cytokines and their correlation with the severity of sepsis and associated organ dysfunction. METHODS: The hypothesis was tested in 110 patients with sepsis (in whom a disease severity score (APACHE II) and assessment of organ failure score (SOFA) were determined) and 55 healthy volunteers. Neutrophil inducible nitric oxide synthase (iNOS) expressions at mRNA and protein levels were estimated by real-time PCR and immuno-precipitation followed by Western blotting, respectively. Nitric oxide (NO) content was assessed in neutrophils by confocal microscopy, plasma nitrite by the Griess reaction and inflammatory cytokines (TNF-α, IFN-γ and IL-8) by ELISA (in plasma) and real-time PCR (in neutrophils). Serum bilirubin and creatinine were determined by routine methods and lung function by the PaO2/FiO2 ratio. RESULTS: Increased neutrophil iNOS expression and NO content, plasma total nitrite content and pro-inflammatory cytokines were present in sepsis patients (all P < 0.001). Plasma nitrite correlated with cytokines, APACHE II, SOFA, PaO2/FiO2 ratio, serum bilirubin and creatinine clearance (all r2 0.63-0.85, P < 0.001). Cytokines correlated with nitrite, APACHE II, SOFA, PaO2/FiO2 ratio, serum bilirubin and creatinine clearance (all r2 0.35-0.85, P < 0.001). CONCLUSION: Neutrophils iNOS expression, NO content, plasma nitrite and cytokines have a role in the assessment of the severity of sepsis and organ toxicity.


Assuntos
Interferon gama/sangue , Interleucina-8/sangue , Insuficiência de Múltiplos Órgãos/diagnóstico , Estresse Nitrosativo , Sepse/diagnóstico , Fator de Necrose Tumoral alfa/sangue , APACHE , Adulto , Idoso , Bilirrubina/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Creatinina/sangue , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/fisiopatologia , Neutrófilos/metabolismo , Neutrófilos/patologia , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo II/sangue , Óxido Nítrico Sintase Tipo II/genética , Sepse/sangue , Sepse/fisiopatologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-30529000

RESUMO

Autism spectrum disorder (ASD) is characterized by repetitive behaviors, impaired social communication and stereotyped interests, and often associated with dysregulations in innate/adaptive immune cells. IL-17A has been linked with abnormal behavioral patterns observed in autistic children and animal models of autism. However, it is yet to be investigated if IL-17A and its receptors are implicated in regulation of oxidative and inflammatory mediators in neutrophils of ASD patients. Therefore, we pursued to identify the effect of IL-17 receptor (IL-17R), and its inflammatory potential in neutrophils from ASD (n = 45) and typically developing control (TDC; n = 40) subjects. IL-17A, its receptor (IL-17R), associated signaling pathways [nuclear transcription factor nuclear factor-kappa B (NF-κB), IL-6 and oxidative stress parameters such as NADPH oxidase (NOX2), inducible nitric oxide synthase (iNOS), reactive oxygen species (ROS), and nitrotyrosine] were determined in the neutrophils from TDC and ASD subjects. Our data show that IL-17A expression, and IL-17R are increased in neutrophils of ASD patients. Further, inflammatory signaling pathways such as such as phospho-NFκB, and ROS generating enzymes, i.e. NOX2/iNOS are increased in neutrophils of ASD patients as compared TDC subjects. Furthermore, activation of IL-17A/IL-17R signaling in neutrophils of ASD subjects leads to upregulation of phospho-NFκB, IL-6 and NOX2/ROS, thus suggesting a compelling role of IL-17A in modulation of inflammation. Our study displays for the first time that IL-17A/IL-17R signaling in neutrophils could play a pivotal role in autism through upregulation of oxidative and inflammatory mediators.


Assuntos
Transtorno do Espectro Autista/sangue , Inflamação/sangue , Interleucina-17/sangue , Neutrófilos/metabolismo , Estresse Oxidativo/fisiologia , Transtorno do Espectro Autista/imunologia , Células Cultivadas , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Interleucina-6/sangue , Masculino , NADPH Oxidase 2/sangue , NADPH Oxidases/sangue , Óxido Nítrico Sintase Tipo II/sangue , Receptores de Interleucina-17/sangue , Regulação para Cima
7.
Pharmacol Rep ; 70(6): 1065-1072, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30296742

RESUMO

BACKGROUND: Both major depression and posttraumatic stress disorder (PTSD) are characterized by inflammation, increased concentration levels of proinflammatory cytokines, decreased neurogenesis followed by neuroprogression, as well as mitochondrial and the hypothalamic-pituitary-adrenal axis dysfunction. Elevated levels of oxidative stress caused by an increased activity of prooxidants over antioxidants are also observed. Based on several reports, depressive episodes can lead to the sensitization of immune-inflammatory pathways. Thus, depression, PTSD, and depression comorbid with PTSD are associated with immune-inflammatory markers. The study aimed at evaluating concentration levels of iNOS, HO-1, IL-33, and MIP-1ß in depression with and without PTSD. METHODS: A total number of participants enrolled in the study was 460. Out of them, 420 subjects with various levels of depression severity constituted the study group (210 males and 210 females), and 40 subjects (20 males and 20 females) constituted the control group. Each study group comprised 60 patients (30 males and 30 females) with mild depression (MD), moderate depression (MOD), severe depression (SeD), MD and PTSD (MD+PTSD), MOD and PTSD (MOD+PTSD), SeD and PTSD (SeD+PTSD), and with PTSD alone. At 7:00 a.m., all patients had serum concentrations of iNOS, HO-1, IL-33, MIP-1ß determined using ELISA. RESULTS: Both depression exacerbation and PTSD comorbidity led to elevated levels of iNOS, HO-1, IL-33, and MIP-1ß. CONCLUSION: Depression both with and without PTSD leads to elevated levels of inflammation and an oxidant/antioxidant imbalance. Alterations in both cytokines and oxidative stress are related to the mechanisms responsible for the development of depressive symptoms.


Assuntos
Quimiocina CCL4/sangue , Transtorno Depressivo/sangue , Heme Oxigenase-1/sangue , Interleucina-33/sangue , Óxido Nítrico Sintase Tipo II/sangue , Transtornos de Estresse Pós-Traumáticos/sangue , Adulto , Biomarcadores/sangue , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Feminino , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto Jovem
8.
Free Radic Biol Med ; 129: 227-236, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30248443

RESUMO

Elderly organisms are more susceptible to infectious diseases. However, the impact of aging on antiparasitic mechanisms, especially the nitric oxide pathway, is poorly understood. Using an integrated in vivo and in vitro model, we compared the severity of Trypanosoma cruzi infection in young and elderly (8 or 72 weeks old) mice. Forty C57BL/6 mice were randomized into four groups: Y-inf, young infected; Yn-inf, young uninfected; A-inf, aged infected; An-inf, aged uninfected. Parasitemia was measured daily, and animals were euthanized after 15 days of infection. Trypanosoma cruzi-induced inflammatory processes were analyzed in blood and heart samples, as well as in bone marrow-derived macrophages (BMDMs) co-cultured with splenocytes isolated from young or elderly mice. Our results indicated upregulated IgG2b and IL-17 production in elderly animals, which was not sufficient to reduce parasitemia, parasitic load and myocarditis to levels observed in young animals. The higher susceptibility of elderly mice to T. cruzi infection was accompanied by reduced cardiac inducible nitric oxide synthase (iNOS) gene expression, nitric oxide (NO) and IFN-γ levels, as well as an antagonistic upregulation of arginase-1 expression and arginase activity. The same responses were observed when BMDMs co-cultured with splenocytes from elderly mice were stimulated with T. cruzi antigens. Our findings indicate that elderly mice were more susceptible to T. cruzi infection, which was potentially related to an attenuated response to antigenic stimulation, inhibition of iNOS gene expression and NO production, and antagonistic upregulation of arginase gene expression and activity, which created favorable conditions for heart parasitism and myocarditis development.


Assuntos
Envelhecimento/genética , Arginase/genética , Cardiomiopatia Chagásica/genética , Doença de Chagas/genética , Óxido Nítrico Sintase Tipo II/genética , Parasitemia/genética , Trypanosoma cruzi/patogenicidade , Envelhecimento/imunologia , Animais , Antígenos de Protozoários/farmacologia , Arginase/sangue , Cardiomiopatia Chagásica/imunologia , Cardiomiopatia Chagásica/parasitologia , Doença de Chagas/imunologia , Doença de Chagas/parasitologia , Técnicas de Cocultura , Regulação da Expressão Gênica , Coração/parasitologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/genética , Interferon gama/sangue , Interferon gama/genética , Interleucina-10/sangue , Interleucina-10/genética , Interleucina-17/sangue , Interleucina-17/genética , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/sangue , Parasitemia/imunologia , Índice de Gravidade de Doença , Transdução de Sinais , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/parasitologia , Trypanosoma cruzi/imunologia
9.
J Heart Lung Transplant ; 37(11): 1381-1387, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30139547

RESUMO

BACKGROUND: Brain death elicits microvascular dysfunction and inflammation, and thereby compromises lung viability for transplantation. As 17ß-estradiol was shown to be anti-inflammatory and vascular protective, we investigated its effects on lung injury after brain death in male rats. METHODS: Wistar rats were assigned to: sham-operation by trepanation only (SH, n = 7); brain death (BD, n = 7); administration of 17ß-estradiol (280 µg/kg, iv) at 60 minutes after brain death (BD-E2, n = 7). Experiments were performed 180 minutes thereafter. Histopathological changes in the lung were evaluated by histomorphometry. Gene expression of inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and endothelin-1 was measured by real-time polymerase chain reaction. Protein expression of NO synthases, endothelin-1, platelet endothelial cell adhesion molecule-1 (PECAM-1), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), BCL-2, and caspase 3 was assessed by immunohistochemistry. Cytokines were quantified by enzyme-linked immunosorbent assay. RESULTS: Treatment with 17ß-estradiol after brain death decreased lung edema and hemorrhage (p < 0.0001), and serum levels of cytokine-induced neutrophil chemoattractant-1 (CINC-1; p = 0.0020). iNOS (p < 0.0001) and VCAM-1 (p < 0.0001) also diminished at protein levels, while eNOS accumulated (p = 0.0002). However, gene expression of iNOS, eNOS, and endothelin-1 was comparable among groups, as was protein expression of endothelin-1, ICAM-1, BCL-2, and caspase 3. CONCLUSIONS: 17ß-Estradiol effectively reduces lung injury in brain-dead rats mainly due to its ability to regulate NO synthases. Thus, the drug may improve lung viability for transplantation.


Assuntos
Anti-Inflamatórios/farmacologia , Morte Encefálica/patologia , Estradiol/farmacologia , Lesão Pulmonar/prevenção & controle , Transplante de Pulmão , Animais , Quimiocina CXCL1/sangue , Hemorragia/patologia , Hemorragia/prevenção & controle , Pneumopatias/patologia , Pneumopatias/prevenção & controle , Lesão Pulmonar/patologia , Masculino , Óxido Nítrico Sintase Tipo II/sangue , Óxido Nítrico Sintase Tipo III/sangue , Edema Pulmonar/patologia , Edema Pulmonar/prevenção & controle , Ratos , Ratos Wistar , Molécula 1 de Adesão de Célula Vascular/sangue
10.
Clin Chim Acta ; 484: 278-283, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29885320

RESUMO

BACKGROUND: Pain is a multidimensional condition of multiple origins. Determining both intensity and underlying cause are critical for effective management. Utilization of painkillers does not follow any guidelines relying on biomarkers, which effectively eliminates objective treatment. The aim of this study was to evaluate the use of serum cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as pain biomarkers. This work could significantly advance the diagnosis and treatment of pain. METHODS: We assessed the potential utility of serum COX-2 and iNOS as objective measures of pain in a sample of American patients. Pain was scaled between level 0-5 in accordance with the level reported by the patients. Blood samples were collected from 102 patients in the emergency room. Sandwich ELISA was used to determine the COX-2 and iNOS levels in the blood serum while statistical analysis was performed using Pearson product-moment correlation coefficients, Regression and Receiver Operating Characteristics (ROC) analyses. The biomarker results were also compared with self-reports of pain by the patients using conventional pain ratings and patients were asked to report the cause of the pain. Pain levels were clustered into four groups as 0 [self-reported 0], 1 [self-reported as 1], 2 [self-reported as 2 and 3] and 3 [self-reported as 4 and 5]. Co-expression of COX-2 and iNOS could significantly alter pain development and its sensitization. Therefore, iNOS dependent COX-2 levels were employed as categorized level. RESULTS: Self-reported pain levels did not show a correlation with the serum level of COX-2 and iNOS. The lack of correlation is attributed to multiple reasons including patients' intake of painkillers prior to participation, painkiller intake habit, chronic diseases, and subjectivity of self-reported pain. Increased serum COX-2 levels were reported in relation to the subtypes of these health issues. Further, 83% of the patients who reported pain also showed the presence of COX-2 in serum, while only 53% of the patients showed the presence of iNOS in serum. Moderate relation was found between the clustered pain level and categorized COX-2 and iNOS- levels. CONCLUSIONS: The findings support the requirement of further studies to use COX-2 and iNOS as prognostic biomarkers for objective quantification of pain at the clinical level.


Assuntos
Ciclo-Oxigenase 2/sangue , Óxido Nítrico Sintase Tipo II/sangue , Dor/sangue , Dor/diagnóstico , Adulto , Idoso , Ciclo-Oxigenase 2/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo II/metabolismo , Dor/metabolismo , Estados Unidos , Adulto Jovem
11.
J Obstet Gynaecol Res ; 44(8): 1377-1383, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29956420

RESUMO

AIM: To analyze inducible nitric oxide synthase (iNOS) and neuropeptide Y (NPY) expression in maternal plasma and placentas of human with intrahepatic cholestasis of pregnancy (ICP). METHODS: The plasma and placentas were collected from 35 women with normal pregnancies and 33 women with ICP. Enzyme-linked immunosorbent assays were used to investigate maternal plasma iNOS and NPY levels. The mRNA levels and cell-specific localization of iNOS and NPY were determined by quantitative PCR, Western Blotting and immunohistochemical analysis in placentas. RESULTS: In human placentas, it revealed iNOS and NPY were mainly localized in syncytiotrophoblast, cytotrophoblastin and vascular endothelium cells using immunohistochemistry analysis. iNOS protein and mRNA expression in ICP maternal plasma and placental tissue were significantly lower than in control groups (P <0.01). In maternal plasma and placentas tissue from ICP patients, a marked up-regulation of NPY protein and mRNA expression were observed (P <0.01). CONCLUSION: iNOS and NPY may play a role in the effect of maternal cholestasis on the placenta. The down-regulation of iNOS and up-regulation of NPY in ICP may influence the blood flow of the utero-placental-fetal unit, which may play a significant role in poor fetoplacental vascular perfusion, acute hypoxia and adverse pregnancy outcomes.


Assuntos
Colestase Intra-Hepática/metabolismo , Neuropeptídeo Y/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Placenta/metabolismo , Complicações na Gravidez/metabolismo , Adulto , Colestase Intra-Hepática/sangue , Feminino , Humanos , Neuropeptídeo Y/sangue , Óxido Nítrico Sintase Tipo II/sangue , Gravidez , Complicações na Gravidez/sangue , Adulto Jovem
12.
Clin Exp Med ; 18(3): 363-372, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29644482

RESUMO

Oxidative stress plays a role in the pathophysiology of rheumatoid arthritis (RA). The aim of the present study was to verify the influence of metabolic syndrome (MetS) and disease-modifying antirheumatic drugs on nitrosative and oxidative biomarkers in patients with RA. A total of 177 patients with RA and 150 healthy volunteers participated in this study, which measured lipid hydroperoxides, advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), carbonyl protein, total radical-trapping antioxidant parameter (TRAP), uric acid (UA), and C-reactive protein (CRP). NOx and the NOx/TRAP ratio were significantly increased in RA, while no significant differences in lipid hydroperoxides, AOPP, UA, and TRAP levels were found between both groups. Treatment with leflunomide was associated with increased levels of carbonyl protein, and lowered levels in TRAP and UA, while the NOx/TRAP ratio further increased. NOx and the NOx/TRAP ratio were significantly higher in women than in men, while TRAP and UA were significantly lower in women. MetS was accompanied by increased AOPP and UA levels. RA was best predicted by increased NOx/TRAP ratio, CRP, and BMI. In conclusion, our data demonstrated that NOx and NOx/TRAP are strongly associated with RA physiopathology. Our findings suggest that inhibition of iNOS may become an interesting therapeutic approach for the treatment of RA. In addition, the presence of MetS and a decrease in levels of UA by leflunomide favor redox imbalance in RA patients. More studies are needed to evaluate the impact of antioxidant capacity reduction on RA progression.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Isoxazóis/uso terapêutico , Síndrome Metabólica/tratamento farmacológico , Ácido Úrico/sangue , Adolescente , Adulto , Produtos da Oxidação Avançada de Proteínas/sangue , Produtos da Oxidação Avançada de Proteínas/genética , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Artrite Reumatoide/patologia , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Progressão da Doença , Feminino , Expressão Gênica , Humanos , Leflunomida , Peróxidos Lipídicos/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo II/sangue , Óxido Nítrico Sintase Tipo II/genética , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Carbonilação Proteica , Fatores Sexuais , Ácido Úrico/antagonistas & inibidores
13.
Shock ; 50(3): 273-279, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29189605

RESUMO

INTRODUCTION: We hypothesized that aromatic microbial metabolites (AMM), such as phenyllactic (PhLA), p-hydroxyphenylacetic (p-HPhAA), and p-hydroxyphenyllactic (p-HPhLA) acids, contribute to the pathogenesis of septic shock. METHODS: Clinical and laboratory data of patients with community-acquired pneumonia were obtained on intensive care unit admission and the next day. Patients were divided into two groups based on septic shock presence or absence. The levels of AMM (PhLA, p-HPhAA, p-HPhLA, and their sum, ∑3AMM), catecholamine metabolites (3,4-dihydroxymandelic [DHMA], 3,4-dihydroxyphenylacetic [DOPAC], and homovanillic [HVA] acids), lactate, N-terminal pro-brain natriuretic peptide (NT-proBNP), inducible nitric oxide synthase (iNOS), and procalcitonin (PCT) were compared. Correlations between AMM and clinical and laboratory data were calculated. RESULTS: There were 20 patients in the septic shock group and 21 in the nonseptic shock group. On admission, the septic shock patients demonstrated significantly higher levels of PhLA (2.3 vs. 0.8 µmol/L), p-HPhAA (4.6 vs. 1.4 µmol/L), p-HPhLA (7.4 vs. 2.6 µmol/L), HVA, lactate, and significantly lower levels of iNOS. The next day, the two groups also showed significant differences in the levels of PCT and NT-proBNP. The correlation between ∑3AMM and presence of shock, levels of lactate, HVA, and NT-proBNP on admission was 0.44, 0.67, 0.57, and 0.38, respectively, and the correlation on the next day was 0.59, 0.73, 0.76, and 0.6, respectively (P < 0.01). These findings can be explained by the ability of AMM to reduce tyrosine hydroxylase activity, thus limiting the synthesis of catecholamines. CONCLUSIONS: AMM are involved in the pathogenesis of septic shock.


Assuntos
Pneumonia , Choque Séptico , Ácido 3,4-Di-Hidroxifenilacético/sangue , Acetatos/sangue , Idoso , Feminino , Ácido Homovanílico/sangue , Humanos , Lactatos/sangue , Masculino , Ácidos Mandélicos/sangue , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Óxido Nítrico Sintase Tipo II/sangue , Fragmentos de Peptídeos/sangue , Pneumonia/sangue , Pneumonia/complicações , Choque Séptico/sangue , Choque Séptico/etiologia
14.
Int J Immunopathol Pharmacol ; 30(4): 395-405, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29164949

RESUMO

Pterygium is a common ocular surface disease observed in humans. Chronic ultraviolet (UV) exposure is extensively recognized as an aetiological factor in the pathogenesis of this disease. This hypothesis is sustained by epidemiological and histopathological data in relation to UV injured skin. Although some findings have indicated that genetic factors, anti-apoptotic and immunological mechanisms are involved in the pathogenesis of pterygium, the mechanism by which it develops remains poorly understood. In this study, we analysed the in vivo production of IL-17A, IL-6, IL-10 and nitric oxide (NO) in the tears and sera from Algerian patients. Interestingly, we observed that IL-6, IL-17A and NO production in the tears and sera of all patients was strongly associated with inflammatory infiltration, NOS2, NF-κB and Bcl2 expression in pterygia biopsies. Collectively, our results indicate a relationship between local inflammation and anti-apoptotic processes in pterygium disease, leading to both tissue damage and enhanced cellular proliferation.


Assuntos
Interleucina-17/metabolismo , Interleucina-6/metabolismo , Óxido Nítrico/metabolismo , Pterígio/metabolismo , Adulto , Túnica Conjuntiva/patologia , Feminino , Humanos , Interleucina-10/sangue , Interleucina-10/metabolismo , Interleucina-17/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , NF-kappa B/sangue , NF-kappa B/metabolismo , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo II/sangue , Óxido Nítrico Sintase Tipo II/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/sangue , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Pterígio/sangue , Pterígio/patologia , Lágrimas/metabolismo
15.
Georgian Med News ; (271): 55-61, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29099702

RESUMO

Purpose - to improve antihypertensive therapy on the basis of studying the antioxidant properties of an angiotensin-converting enzyme (ACE) inhibitor (fosinopril sodium) and a diuretic (hydrochlorothiazide), their impact on endothelial dysfunction and pro-inflammatory cytokines activity in hypertensive patients with overweight and obesity. A combination of fosinopril sodium 20 mg/day and hydrochlorothiazid 12.5 mg/day was prescribed to 54 patients with essential hypertension of 1-3 grades, 30 to 65 years old . The control group included 10 healthy subjects matched for age and sex. During the course of combined antihypertensive therapy we observed a significant decrease of i-NOS activity, reduce of TNF-α type I of its soluble receptor (sTNF-αRI), and 8-iso-PgF2α in the patients. Activity of e-NOS, superoxide dismutase and catalase, in contrast, were increased in patients with hypertension and concomitant obesity. Thus, the improvement of endothelial function, a significant decrease autoimmune activation due to lower tension of oxidative stress in the examined patients optimizes use of a combination of fosinopril sodium and hydrochlorothiazid for differentiated therapy in hypertensive patients with obesity.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Diuréticos/uso terapêutico , Hipertensão Essencial/tratamento farmacológico , Fosinopril/uso terapêutico , Hidroclorotiazida/uso terapêutico , Sobrepeso/complicações , Adulto , Idoso , Estudos de Casos e Controles , Dinoprosta/análogos & derivados , Dinoprosta/sangue , Quimioterapia Combinada , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Hipertensão Essencial/complicações , Hipertensão Essencial/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo II/sangue , Obesidade/complicações , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Fator de Necrose Tumoral alfa/metabolismo
16.
Zhonghua Nei Ke Za Zhi ; 56(10): 763-765, 2017 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-29036959

RESUMO

To explore the functional phenotype of liver macrophages in patients with autoimmune hepatitis (AIH). Compared with patients with nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis B (CHB), the absolute CD(68)(+) cell count in patients with AIH was significantly higher (all P<0.05). It was positively correlated with ALT and IgG levels (the correlation coefficients 0.600 and 0.700, P=0.285 and 0.188 respectively). Additionally, compared with patients with NAFLD, the absolute iNOS positive cell count in patients with AIH and CHB were significantly higher (all P<0.05). The expression of TNFα, iNOS and IL-1ß in patients with AIH and CHB were significantly higher than in patients with NAFLD (all P<0.05). Interestingly, compared with patients with AIH and CHB, the absolute CD(206)(+) cell count in patients with NAFLD were significantly higher (all P<0.05). CD(206) expression in patients with NAFLD was higher than patients with AIH and CHB, but with no statistical significance. M1 type macrophages over-expressed and played a major role in the inflammatory reaction and liver injury in patients with AIH.


Assuntos
Hepatite B Crônica/sangue , Hepatite Autoimune/sangue , Macrófagos , Hepatopatia Gordurosa não Alcoólica/sangue , Fator de Necrose Tumoral alfa/sangue , Humanos , Interleucina-1beta/sangue , Cirrose Hepática/sangue , Óxido Nítrico Sintase Tipo II/sangue , Fragmentos de Peptídeos/sangue , Fenótipo
17.
Microb Pathog ; 112: 38-49, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28939254

RESUMO

The extracellular signal-regulated kinase (ERK) pathway has been shown to regulate pathogenesis of many viral infections, but its role during rabies virus (RV) infection in vivo is not clear. In the present study, we investigated the potential role of MEK-ERK1/2 signalling pathway in the pathogenesis of rabies in mouse model and its regulatory effects on pro-inflammatory cytokines and other mediators of immunity, and kinetics of immune cells. Mice were infected with 25 LD50 of challenge virus standard (CVS) strain of RV by intracerebral (i.c.) inoculation and were treated i.c. with U0126 (specific inhibitor of MEK1/2) at 10 µM/mouse at 0, 2, 4 and 6 days post-infection. Treatment with U0126 resulted in delayed disease development and clinical signs, increased survival time with lesser mortality than untreated mice. The better survival of inhibitor-treated and RV infected mice was positively correlated with reduced viral load and reduced viral spread in the brain as quantified by real-time PCR, direct fluorescent antibody test and immunohistochemistry. CVS-infected/mock-treated mice developed severe histopathological lesions with increased Fluoro-Jade B positive degenerating neurons in brain, which were associated with higher levels of serum nitric oxide, iNOS, TNF-α, and CXCL10 mRNA. Also CVS-infected/U0126-treated mice revealed significant decrease in caspase 3 but increase in Bcl-2 mRNA levels and less TUNEL positive apoptotic cells. CVS-infected/U0126-treated group also showed significant increase in CD4+, CD8+ T lymphocytes and NK cells in blood and spleen possibly due to less apoptosis of these cells. In conclusion, these data suggest that MEK-ERK1/2 signalling pathway play critical role in the pathogenesis of RV infection in vivo and opens up new avenues of therapeutics.


Assuntos
Butadienos/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Nitrilos/antagonistas & inibidores , Vírus da Raiva/efeitos dos fármacos , Vírus da Raiva/patogenicidade , Raiva/tratamento farmacológico , Animais , Apoptose , Encéfalo/patologia , Encéfalo/virologia , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Caspase 3/metabolismo , Córtex Cerebral/patologia , Córtex Cerebral/virologia , Quimiocina CXCL10/sangue , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Expressão Gênica , Imuno-Histoquímica , Imunofenotipagem , Células Matadoras Naturais , Cinética , Masculino , Camundongos , Degeneração Neural , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo II/sangue , RNA Mensageiro/sangue , Raiva/mortalidade , Raiva/virologia , Vírus da Raiva/genética , Transcriptoma , Fator de Necrose Tumoral alfa/sangue , Carga Viral
18.
Int J Med Sci ; 14(7): 680-689, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28824301

RESUMO

Traumatic and nontraumatic rhabdomyolysis can lead to acute renal failure (ARF), and acute alcohol intoxication can lead to multiple abnormalities of the renal tubules. We examined the effect of acute alcohol intoxication in a rat model of rhabdomyolysis and ARF. Intravenous injections of 5 g/kg ethanol were given to rats over 3 h, followed by glycerol-induced rhabdomyolysis. Biochemical parameters, including blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and creatine phosphokinase (CPK), were measured before and after induction of rhabdomyolysis. Renal tissue injury score, renal tubular cell expression of E-cadherin, nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) were determined. Relative to rats in the vehicle group, rats in the glycerol-induced rhabdomyolysis group had significantly increased serum levels of BUN, Cre, GOT, GPT, and CPK, elevated renal tissue injury scores, increased expression of NF-κB and iNOS, and decreased expression of E-cadherin. Ethanol exacerbated all of these pathological responses. Our results suggest that acute alcohol intoxication exacerbates rhabdomyolysis-induced ARF through its pro-oxidant and inflammatory effects.


Assuntos
Lesão Renal Aguda/sangue , Intoxicação Alcoólica/sangue , Alcoolismo/sangue , Rabdomiólise/sangue , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/complicações , Lesão Renal Aguda/patologia , Intoxicação Alcoólica/complicações , Intoxicação Alcoólica/patologia , Alcoolismo/complicações , Alcoolismo/patologia , Alquil e Aril Transferases/sangue , Animais , Nitrogênio da Ureia Sanguínea , Caderinas/metabolismo , Creatinina/sangue , Etanol/toxicidade , Glicerol/toxicidade , Humanos , Rim/metabolismo , Rim/patologia , NF-kappa B , Óxido Nítrico Sintase Tipo II/sangue , Ratos , Espécies Reativas de Oxigênio/metabolismo , Rabdomiólise/induzido quimicamente , Rabdomiólise/complicações , Rabdomiólise/patologia , Transferases (Outros Grupos de Fosfato Substituídos)/sangue
19.
Mediators Inflamm ; 2017: 2515408, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28572711

RESUMO

Buprenorphine is recommended for use as an analgesic in animal models including in murine models of collagen-induced arthritis (CIA). However, the effect of buprenorphine on the expression of disease-associated biomarkers is not well defined. We examined the effect of buprenorphine administration on disease progression and the expression of inflammatory and oxidative stress markers, in a murine model of CIA. Buprenorphine administration altered the expression of cytokines, IFN-γ, IL-6, and MMP-3, and oxidative markers, for example, iNOS, superoxide dismutase (SOD1), and catalase (CAT), in the CIA mice. As buprenorphine is an analgesic, we further monitored the association of expression of these biomarkers with pain scores in a human cohort of early rheumatoid arthritis (RA). Serum MMP-3 levels and blood mRNA expression of antioxidants sod1 and cat correlated with pain scores in the RA cohort. We have demonstrated that administration of buprenorphine alters the expression of inflammatory and oxidative stress-related molecular markers in a murine model of CIA. This caveat needs to be considered in animal experiments using buprenorphine as an analgesic, as it can be a confounding factor in murine studies used for prediction of response to therapy. Furthermore, the antioxidant enzymes that showed an association with pain scores in the human cohort may be explored as biomarkers for pain in future studies.


Assuntos
Analgésicos Opioides/farmacologia , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Buprenorfina/farmacologia , Estresse Oxidativo , Adulto , Idoso , Animais , Antioxidantes/metabolismo , Artrite Experimental/induzido quimicamente , Artrite Reumatoide/tratamento farmacológico , Biomarcadores/sangue , Catalase/sangue , Estudos de Coortes , Colágeno/química , Citocinas/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Inflamação , Masculino , Metaloproteinase 3 da Matriz/sangue , Metaloproteinase 3 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos DBA , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo II/sangue , Reação em Cadeia da Polimerase em Tempo Real , Superóxido Dismutase-1/sangue
20.
BMC Complement Altern Med ; 17(1): 219, 2017 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-28420359

RESUMO

BACKGROUND: Radix Bupleuri (RB) has been popularly used for treating many liver diseases such as chronic hepatic inflammation and viral Hepatitis in China. Increasing clinical and experimental evidence indicates the potential hepatotoxicity of RB or prescriptions containing RB. Recently, Saikosaponins (SS) have been identified as major bioactive compounds isolated from RB, which may be also responsible for RB-induced liver injury. METHODS: Serum AST, ALT and LDH levels were determined to evaluate SS-induced liver injury in mice. Serum and liver total triglyceride and cholesterol were used to indicate lipid metabolism homeostasis. Liver ROS, GSH, MDA and iNOS were used to examine the oxidative stress level after SS administration. Western blot was used to detect CYP2E1 expression. A 8-Plex iTRAQ Labeling Coupled with 2D LC - MS/MS technique was applied to analyze the protein expression profiles in livers of mice administered with different doses of SS for different time periods. Gene ontology analysis, cluster and enrichment analysis were employed to elucidate potential mechanism involved. HepG2 cells were used to identify our findings in vitro. RESULTS: SS dose- and time-dependently induced liver injury in mice, indicated by increased serum AST, ALT and LDH levels. According to proteomic analysis, 487 differentially expressed proteins were identified in mice administrated with different dose of SS for different time periods. Altered proteins were enriched in pathways such as lipid metabolism, protein metabolism, macro molecular transportation, cytoskeleton structure and response to stress. SS enhanced CYP2E1 expression in a time and dose dependent manner, and induced oxidative stress both in vivo and in vitro. CONCLUSION: Our results identified hepatotoxicity and established dose-time course-liver toxicity relationship in mice model of SS administration and suggested potential mechanisms, including impaired lipid and protein metabolism and oxidative stress. The current study provides experimental evidence for clinical safe use of RB, and also new insights into understanding the mechanism by which SS and RB induced liver injury.


Assuntos
Bupleurum/química , Medicamentos de Ervas Chinesas/toxicidade , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatopatias/etiologia , Fígado/efeitos dos fármacos , Ácido Oleanólico/análogos & derivados , Estresse Oxidativo , Saponinas/toxicidade , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Colesterol/sangue , Citocromo P-450 CYP2E1/sangue , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Células Hep G2 , Humanos , L-Lactato Desidrogenase/sangue , Fígado/enzimologia , Fígado/metabolismo , Hepatopatias/sangue , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Masculino , Camundongos , Óxido Nítrico Sintase Tipo II/sangue , Ácido Oleanólico/toxicidade , Raízes de Plantas , Proteômica , Triglicerídeos/sangue
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