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1.
Int J Cancer ; 146(5): 1261-1267, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31125113

RESUMO

Free thiol groups of intra and extracellular molecules are considered to be antioxidative and to protect cells from damage caused by free radicals. However, the associations of serum total thiol levels (TTL) with the incidences of the four most frequent cancer sites have not yet been investigated in a large population-based, prospective study. TTL was measured in case-cohort design in a sample from the population-based, Norwegian Tromsø 3 study (cancer cases: n = 941; random subcohort: n = 1,000) and was repeatedly measured at Tromsø 5. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by weighted multivariable-adjusted Cox regression with time-dependent modeling of TTL for incident lung, colorectal, breast and prostate cancer. High serum TTL were associated with a reduced risk of all four major cancers. The associations with lung (top vs. bottom tertile: HR, 0.64; 95% CI, 0.41, 0.99) and breast cancer (top vs. bottom tertile: HR, 0.64; 95% CI, 0.42, 0.96) were statistically significant, whereas associations with colorectal (top vs. bottom tertile: HR, 0.79; 95% CI, 0.54, 1.16) and prostate cancer (top vs. bottom tertile: HR, 0.79; 95% CI, 0.53, 1.17) were not statistically significant but pointed in the same protective direction. These findings from a large, prospective Norwegian cohort study suggest a preventive role of thiols against the development of the four most frequent cancers. Whereas associations with breast and lung cancer could be shown with statistical significance, larger studies are needed to corroborate potential associations of TTL with colorectal and prostate cancer.


Assuntos
Neoplasias/sangue , Compostos de Sulfidrila/sangue , Adulto , Idoso , Neoplasias da Mama/sangue , Neoplasias da Mama/epidemiologia , Estudos de Coortes , Neoplasias Colorretais/sangue , Neoplasias Colorretais/epidemiologia , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Noruega/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Risco , Adulto Jovem
2.
J Pharm Biomed Anal ; 177: 112871, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31539712

RESUMO

Osimertinib is a "third-generation'' oral, irreversible, tyrosine kinase inhibitor. It is used in the treatment of non-small cellular lung carcinoma and spares wild-type EGFR. Due to its reactive nature, osimertinib is, in addition to oxidative routes, metabolized through GSH coupling and subsequent further metabolism of these conjugates. The extent of the non-oxidative metabolism of osimertinib is unknown, and methods to quantify this metabolic route have not been reported yet. To gain insight into this metabolic route, a sensitive bioanalytical assay was developed for osimertinib, the active desmethyl metabolite AZ5104, and the thio-metabolites osimertinibs glutathione, cysteinylglycine, and cysteine conjugates was developed. The ease of synthesis of these metabolites was a key-part in the development of this assay. This was done through simple one-step synthesis and subsequent LC-purification. The compounds were characterized by NMR and high-resolution mass spectrometry. Sample preparation was done by a simple protein crash with acetonitrile containing the stable isotopically labeled internal standards for osimertinib and the thio-metabolites, partial evaporation of solvents, and reconstitution in eluent, followed by UHPLC-MS/MS quantification. The assay was successfully validated in a 2-2000 nM calibration range for all compounds except the glutathione metabolite, where the LLOQ was set at 6 nM due to low accuracy at 2 nM. Limited stability was observed for osimertinib, AZ5104, and the glutathione metabolite. The clinical applicability of the assay was demonstrated in samples of patients treated with 80 mg osimertinib once daily, containing all investigated compounds at detectable and quantifiable levels.


Assuntos
Acrilamidas/farmacocinética , Compostos de Anilina/farmacocinética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacocinética , Acrilamidas/administração & dosagem , Acrilamidas/sangue , Acrilamidas/metabolismo , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/administração & dosagem , Compostos de Anilina/sangue , Compostos de Anilina/metabolismo , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , Cromatografia Líquida de Alta Pressão/métodos , Dipeptídeos/sangue , Dipeptídeos/síntese química , Dipeptídeos/metabolismo , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Glutationa/sangue , Glutationa/síntese química , Glutationa/metabolismo , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Pessoa de Meia-Idade , Mutação , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/sangue , Inibidores de Proteínas Quinases/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Compostos de Sulfidrila/sangue , Compostos de Sulfidrila/síntese química , Compostos de Sulfidrila/metabolismo , Espectrometria de Massas em Tandem/métodos
3.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1126-1127: 121738, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31377566

RESUMO

Myocardial Infarction (MI) is one of the most common causes of deaths worldwide. Thiols have been reported to play a key role in physiological and pathological processes of MI. Comprehensive analysis of thiols would be conducive to fully elucidate the relation between thiols and MI. In the current study, we analyze the metabolomic differences of thiols in serum between MI patients (n = 30) and healthy controls (HCs, n = 30) by stable isotope labeling-dispersive solid phase extraction-liquid chromatography-full scan-Orbitrap-mass spectrometry analysis (IL-DSPE-LC-full scan-Orbitrap MS) method. We detected 300 potential thiols in serum of MI patients and HCs, among which, 67 thiols were positively or putatively identified. Furthermore, we found that the levels of 71 thiols in serum exhibited significant difference between MI patients and HCs. In the transsulfuration pathway, we observed that Cys and Hcys were upregulated, while GSH were downregulated. Our results provide a comprehensive understanding of thiols metabolome in human serum between MI patients and HCs.


Assuntos
Metabolômica/métodos , Infarto do Miocárdio/metabolismo , Compostos de Sulfidrila/sangue , Compostos de Sulfidrila/metabolismo , Cromatografia Líquida/métodos , Análise por Conglomerados , Humanos , Marcação por Isótopo/métodos , Espectrometria de Massas , Metaboloma/fisiologia , Infarto do Miocárdio/sangue
4.
Hum Exp Toxicol ; 38(11): 1227-1234, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31451031

RESUMO

Welders' lung disease refers to mixed exposure to different kinds of metals and chemicals from welding fumes, which affect all parts of the respiratory tract including airways and parenchyma together. This study aimed to investigate the oxidative status in patients with welders' lung (PWL) by means of thiol-disulfide homeostasis and ischemia-modified albumin (IMA) levels. The male welder workers diagnosed with welders' lung disease and healthy individuals were recruited in the study. Plasma levels of disulfide, disulfide/native thiol ratio, disulfide/total thiol ratio, IMA, and catalase (CAT) were determined. Pulmonary function test parameters of both groups were compared. The thiol-disulfide homeostasis parameters of PWL and control group were as follows: disulfide (20.5 ± 6.3 vs. 16.2 ± 3.9 µmol L-1, p < 0.001), disulfide/native thiol (4.36 (1.59) vs. 4.0 (1.64), p = 0.024), and disulfide/total thiol (4.01 (1.34) vs. 3.71 (1.41), p = 0.024). IMA levels in PWL were significantly higher than the control group (1.37 (0.27) mg dL-1 vs. 0.49 (0.61) mg dL-1, p < 0.001), whereas CAT activities were significantly higher in the control group (106.6 (54.5) kU L-1 vs. 78.3 (67.8) kU L-1, p = 0.003). The findings of the present study revealed that oxidative stress plays a key role in the pathogenesis of welders' lung disease. Plasma thiol-disulfide homeostasis and IMA levels might be indicators of oxidative stress in PWL.


Assuntos
Dissulfetos/sangue , Pneumopatias/sangue , Doenças Profissionais/sangue , Estresse Oxidativo , Compostos de Sulfidrila/sangue , Soldagem , Adulto , Biomarcadores/sangue , Homeostase , Humanos , Masculino , Pessoa de Meia-Idade , Albumina Sérica Humana , Adulto Jovem
5.
Braz J Cardiovasc Surg ; 34(4): 436-443, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31454197

RESUMO

OBJECTIVE: To investigate the effect of continuous lung ventilation with low tidal volume on oxidation parameters, such as thiol/disulphide homeostasis and albumin-adjusted ischemia-modified albumin (AAIMA), during cardiopulmonary bypass (CBP) in coronary artery bypass grafting (CABG). METHODS: Seventy-four patients who underwent elective CABG with CPB were included in the study. Blood samples were taken in the preoperative period, 10 minutes after CPB, and six and 24 hours postoperatively. Patients were assigned to the continuous ventilation group (Group 1, n=37) and the non-ventilated group (Group 2, n=37). The clinical characteristics, thiol/disulphide homeostasis, ischemia-modified albumin (IMA), and AAIMA levels of the patients were compared. RESULTS: A significant difference was found between the groups regarding native thiol, total thiol, and IMA levels at the postoperative 24th hour (P=0.030, P=0.031, and P=0.004, respectively). There was no difference between the groups in terms of AAIMA. AAIMA levels returned to preoperative levels in Groups 1 and 2, at the 6th and 24th postoperative hours, respectively. Length of hospital stay was significantly shorter in Group 1 (P<0.001) than in Group 2. CONCLUSION: Continuous ventilation during CPB caused an increase in native and total thiol levels, an earlier return of AAIMA levels, and shorter hospital stay. Continuous ventilation may reduce the negative effects of CPB on myocardium (Table 2, Figure 1, and Reference 31).


Assuntos
Ponte Cardiopulmonar/efeitos adversos , Dissulfetos/sangue , Respiração Artificial , Albumina Sérica/análise , Compostos de Sulfidrila/sangue , Idoso , Antioxidantes , Biomarcadores/sangue , Ponte Cardiopulmonar/métodos , Ponte de Artéria Coronária , Método Duplo-Cego , Feminino , Homeostase/fisiologia , Humanos , Lesão Pulmonar/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Albumina Sérica Humana
6.
J Coll Physicians Surg Pak ; 29(9): 843-847, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31455479

RESUMO

OBJECTIVE: To determinate the effects of bilirubin and phototherapy on oxidative stress in newborns. STUDY DESIGN: A case-control study. PLACE AND DURATION OF STUDY: Third level Newborn Intensive Care Unit, Ankara Etlik Zubeyde Hanim Women's Health Teaching and Research Hospital, Turkey, from May to August 2017. METHODOLOGY: Blood samples of 62 term newborns were grouped as control, before and after phototherapy. Total and native thiol, disulfide and ischemia modified albumin values in expressed blood samples were measured. Disulfide-native thiol ratio, disulfide-total thiol ratio and native thiol-total thiol ratio values were computed. RESULTS: Bilirubin levels were positively correlated with native and total thiol levels and negatively correlated with ischemia modified albumin levels (r=0.409 p= 0.001, r= 0.328 p<0.009, r=-0.503 p<0.001). Native and total thiol levels of the control group were lower (p<0.001) and ischemia modified albumin levels were higher than those before and after phototherapy (p<0.001). In jaundiced newborns, native and total thiol values reduced after phototherapy, while IMA levels increased (p=0.001, p<0.001, p<0.001). CONCLUSION: Bilirubin showed antioxidant effect without increasing oxidative stress. Oxidative stress increased after phototherapy. This result was associated with decrease in bilirubin rather than oxidative effect of phototherapy.


Assuntos
Bilirrubina/sangue , Dissulfetos/sangue , Hiperbilirrubinemia/terapia , Estresse Oxidativo/fisiologia , Fototerapia , Compostos de Sulfidrila/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Homeostase , Humanos , Hiperbilirrubinemia/sangue , Recém-Nascido , Masculino , Albumina Sérica Humana
7.
Pediatr Int ; 61(9): 913-918, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31287938

RESUMO

BACKGROUND: Kawasaki disease (KD) is an acute, self-limited, systemic vasculitis of unknown etiology. In the present study, we investigated whether there is a relationship between KD and dynamic thiol/disulphide homeostasis. METHODS: This case-control study involved KD patients and healthy controls. Plasma total, native and disulphide thiol and the disulphide/native, disulphide/total and native thiol/total thiol ratios of all patients and the control group were analyzed simultaneously. RESULTS: A total of 20 patients with KD (male/female, 12/8) and 25 age- and gender-matched healthy controls (male/female, 12/13) were evaluated. Native, total thiol and native thiol/total thiol ratio were significantly lower in KD patients than in the control group (P < 0.001). In contrast, disulphide thiol, disulphide/native thiol and disulphide/total thiol ratios were significantly higher in KD patients than control subjects (P < 0.001). In KD patients with coronary artery lesion (CAL), the native thiol and total thiol were significantly lower than in KD patients without CAL. In KD patients with CAL, the ratios of disulphide/total thiol and disulphide/native thiol were significantly higher than in those without CAL (P = 0.02 and P = 0.02, respectively), whereas the ratio of native/total thiol was significantly lower (P = 0.02). CONCLUSION: The KD patients had lower plasma thiol (native and total) and higher disulphide thiol than controls, indicating that dynamic thiol/disulphide homeostasis might be an important indicator of inflammation in KD. Alteration and shifting of thiol/disulphide homeostasis to the oxidized side are correlated with the pathogenesis of KD and CAL.


Assuntos
Dissulfetos/sangue , Homeostase , Síndrome de Linfonodos Mucocutâneos/etiologia , Compostos de Sulfidrila/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/diagnóstico
8.
Medicina (Kaunas) ; 55(6)2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31207925

RESUMO

Background and objectives: The aim of this study was to research oxidative stress and thiol/disulphide homeostasis in Graves' patients. Materials and Methods: The study included 33 Graves' patients (research group) and 35 healthy subjects (control group). Serum oxidative stress and thiol/disulphide homeostasis (a new and automated spectrophotometric method developed by Erel and Neselioglu) parameters were studied and compared between the groups. Results: The native and total thiol levels and the native thiol/total thiol ratio were lower in patients with Graves' disease compared to the control group (p < 0.001, p < 0.001, and p = 0.006, respectively). TOS (total antioxidant status), PC (protein carbonyl), OSI (Oxidative stress index), and disulphide/native thiol and disulphide/total thiol ratios were determined to be higher in the Graves' disease group than in the control group (p < 0.001, p = 0.001, p = 0.001, p = 0.004, and p = 0.006, respectively). In the Graves' disease group, the free triiodothyronine (FT3) and free thyroxine (FT4) levels were significantly positively correlated with impaired thiol/disulphide homeostasis and oxidative stress parameters (p < 0.05). Conclusion: The results of the current study demonstrated that oxidative stress and thiol/disulphide homeostasis increased towards disulphide formation due to thiol oxidation in Graves' disease. In addition, a positive correlation of FT3 and FT4 was observed with oxidative stress parameters and impaired thiol/disulphide homeostasis.


Assuntos
Dissulfetos/análise , Doença de Graves/sangue , Estresse Oxidativo/fisiologia , Compostos de Sulfidrila/análise , Adolescente , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Dissulfetos/sangue , Feminino , Doença de Graves/fisiopatologia , Homeostase/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Sulfidrila/sangue , Tireotropina/análise , Tireotropina/sangue
9.
An Acad Bras Cienc ; 91(2): e20180547, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31038539

RESUMO

Dynamic thiol-disulfide homeostasis is considered to have critical roles in maintenance of physiological functioning. We aimed to reveal whether there is any specific aberration in thiol-disulfide homeostasis in three distinct categories of individuals, including those who 1) exercise regularly (fitness group), 2) have a sedentary lifestyle (sedentary group) and 3) are overweight or obese (overweight/obese group). 72 male individuals were included in the study, 21 of whom were in fitness group, 28 of whom were overweight or obese and 23 of whom had a sedentary lifestyle. Plasma native thiol (-SH) and total thiol [(-SH) + (-S-S-)] levels were quantitatively determined. Total thiol levels in sedentary group were significantly lower than those in overweight/obese (p<0.05) and fitness groups (p<0.001). Also, disulfide values in fitness group were significantly higher than those in sedentary and overweight/obese groups (p<0.005, p<0.05). On the other hand, disulfide level, reduced and oxidized thiol ratios and oxidation/reduction ratio in fitness group differed significantly from the other groups (p<0.05). Thiol-disulfide homeostasis varies depending on lifestyle. The results of our study indicate that higher total thiol and disulfide levels are conspicuously distinctive features of thiol-disulfide homeostasis in individuals exercising regularly.


Assuntos
Dissulfetos/sangue , Exercício/fisiologia , Obesidade/sangue , Sobrepeso/sangue , Comportamento Sedentário , Compostos de Sulfidrila/sangue , Adulto , Análise de Variância , Antioxidantes/fisiologia , Índice de Massa Corporal , Homeostase/fisiologia , Humanos , Masculino , Estresse Oxidativo/fisiologia , Curva ROC , Valores de Referência , Estatísticas não Paramétricas
10.
PLoS One ; 14(5): e0216359, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31067252

RESUMO

BACKGROUND: Left ventricular hypertrophy (LVH) has been associated with oxidative stress, although not with the protein thiolation index (PTI). This study explored the potential use of PTI as a biomarker of oxidative stress in patients with LVH. METHODS: We recruited 70 consecutive patients (n = 35 LVH and n = 35 non-LVH) based on an echocardiography study in our institution (left ventricular mass indexed to body surface area). Plasma levels of both S-thiolated protein and total thiols were measured as biomarkers of oxidative stress by spectrophotometry, and PTI was calculated as the molar ratio between S-thiolated proteins and the total thiol concentration. RESULTS: Values for plasma S-thiolated proteins were higher in patients with LVH than in the control group (P = 0.01). There were no differences in total thiols between the LVH group and the control group. Finally, PTI was higher in patients with LVH than in the control group (P = 0.001). The area under the ROC curve was 0.75 (95% CI, 0.63-0.86; P<0.001), sensitivity was 70.6%, and specificity was 68.6%, thus suggesting that PTI could be used to screen for LVH. A multivariable logistic regression model showed a positive association (P = 0.02) between PTI and LVH (OR = 1.24 [95% CI, 1.03-1.49]) independently of gender (OR = 3.39 [95% CI, 0.60-18.91]), age (OR = 1.03 [95% CI, 0.96-1.10]), smoking (OR = 5.15 [95% CI, 0.51-51.44]), glucose (OR = 0.99 [95% CI, 0.97-1.01]), systolic arterial pressure (OR = 1.10 [CI 1.03-1.17]), diastolic arterial pressure (OR = 0.94 [CI 0.87-1.02]), dyslipidemia (OR = 1.46 [95% CI, 0.25-8.55]), estimated glomerular filtration rate (OR = 0.98 [95% CI, 0.96-1.01]), body mass index (OR = 1.03 [95% CI, 0.90-1.10]), and valvular and/or coronary disease (OR = 5.27 [95% CI, 1.02-27.21]). CONCLUSIONS: The present study suggests that PTI could be a new biomarker of oxidative stress in patients with LVH.


Assuntos
Proteínas Sanguíneas/metabolismo , Hipertrofia Ventricular Esquerda/diagnóstico , Compostos de Sulfidrila/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Hipertrofia Ventricular Esquerda/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo
11.
Andrologia ; 51(8): e13300, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31058347

RESUMO

Oxidative stress plays an important role in the development of infertility secondary to varicocele. We aimed to investigate the dynamic thiol-disulphide homeostasis as an oxidative stress marker in the spermatic vein of infertility secondary to varicocele. Sixty-one patients with varicocele were included in the study. Blood was drawn from the median cubital vein and the testicular venous return side before the spermatic vein was separated during surgery. Total thiol, native thiol, disulphide, ischaemia modified albumin (IMA) and albumin values were measured from both the dilated spermatic vein and the median cubital vein. The disulphide/native thiol, disulphide/total thiol and native thiol/total thiol ratios were determined. The mean age of the patients was 27.0 ± 6.68 (15-50) years. While the albumin, native thiol and total thiol values and the native thiol/total thiol ratio were significantly lower (p = 0.004, p < 0.001, p < 0.001, p < 0.001 respectively), the IMA value and the disulphide/native thiol and disulphide/total thiol ratios were significantly higher (p < 0.001, p < 0.001, p < 0.001 respectively) in the samples taken from spermatic venous blood. Thiol-disulphide balance had deteriorated towards disulphide formation in the spermatic vein compared with the peripheral vein. Abnormal thiol-disulphide balance may be an independent risk factor for infertility secondary to varicocele.


Assuntos
Dissulfetos/metabolismo , Infertilidade Masculina/metabolismo , Cordão Espermático/irrigação sanguínea , Compostos de Sulfidrila/metabolismo , Varicocele/metabolismo , Adolescente , Adulto , Biomarcadores/sangue , Biomarcadores/metabolismo , Dissulfetos/sangue , Homeostase , Humanos , Infertilidade Masculina/sangue , Infertilidade Masculina/etiologia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Estudos Prospectivos , Fatores de Risco , Albumina Sérica Humana/metabolismo , Compostos de Sulfidrila/sangue , Varicocele/sangue , Varicocele/complicações , Veias , Adulto Jovem
12.
Cutan Ocul Toxicol ; 38(4): 338-343, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31092070

RESUMO

Purpose: Pityriasis rosea (PR) is a common, self-limiting, inflammatory skin disease with an acute onset. The etiology of PR is not yet clearly known but the defect in the oxidation system involved in many papulosquamous skin diseases may play a role. Thiol/disulfide homeostasis is a new marker of oxidative stress and has been studied in many diseases in recent years. The aim of this study to investigate thiol/disulfide homeostasis in PR patients. Material and methods: Thirty-four patients (18 females, 16 males; median age 26 years) that presented to the Dermatology Clinic of Istanbul Medipol Mega University Hospital between November 2017 and December 2018 and were clinically and/or histopathologically diagnosed with PR, and 30 healthy individuals (16 females, 14 males; median age 27 years) were included in the study. The serum native thiol and total thiol were measured by a novel colorimetric, automated method. The disulfide levels and disulfide/native thiol ratios were also calculated from these measured parameters. Results: There was no statistically significant difference in the serum native thiol and total thiol concentration between the PR and control groups (p = 0.711 and 0.788, respectively). Disulfide, disulfide/native thiol, and disulfide/total thiol levels were significantly higher in patients with PR (p = 0.002, 0.006 and 0.006, respectively). Conclusions: The thiol-disulfide balance shifted toward disulfide in patients with PR. This demonstrates the importance of oxidative stress in the etiopathogenesis of PR using a new marker.


Assuntos
Dissulfetos/sangue , Pitiríase Rósea/sangue , Compostos de Sulfidrila/sangue , Adulto , Biomarcadores/sangue , Feminino , Homeostase , Humanos , Masculino , Estresse Oxidativo , Adulto Jovem
13.
Methods Mol Biol ; 1967: 275-283, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31069777

RESUMO

ß2-Glycoprotein I is the major autoantigen in the antiphospholipid syndrome (APS), a prothrombotic disorder characterized by the occurrence of either venous or arterial thrombosis. In women it is also associated with an increased risk of obstetric complications such as recurrent miscarriages. We have identified that the plasma protein ß2-glycoprotein I in healthy individuals exists in an optimal ratio between two distinct forms, an oxidized and free thiol, reduced form. This ratio is disrupted in pathophysiological conditions associated with increased oxidative stress such as the APS, but also in the setting of age-related macular degeneration and gram-negative sepsis. We have developed assays that quantify plasma/serum levels of total and free thiol ß2-glycoprotein I which can potentially be used for risk stratification and prognostic purposes in the early stages of the aforementioned conditions.


Assuntos
Síndrome Antifosfolipídica/sangue , Testes Diagnósticos de Rotina/métodos , Trombose/sangue , beta 2-Glicoproteína I/sangue , Aborto Habitual/sangue , Aborto Habitual/patologia , Síndrome Antifosfolipídica/patologia , Feminino , Humanos , Gravidez , Prognóstico , Compostos de Sulfidrila/sangue , Compostos de Sulfidrila/química , Trombose/patologia , beta 2-Glicoproteína I/isolamento & purificação
14.
Ital J Pediatr ; 45(1): 59, 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31072373

RESUMO

BACKGROUND: Free radicals found in cigarette smoke can harm all tissues and cellular structures in the human body. Passive smoking increases free radical production, leads to the depletion of antioxidants and increases oxidative stress which causes lipid peroxidation. Many studies have been conducted to determine the effects of passive smoking on antioxidant enzymes and lipid levels in adults, but pediatric studies on this topic are few. In our study, we compared the levels of antioxidants, oxidants, total and LDL cholesterol in children exposed to passive cigarette smoking with a healthy control group that was not exposed to passive smoking. METHODS: A total of 41 children (4-17 years of age, 24 girls and 17 boys) exposed to passive smoking and 18 healthy girls and 12 healthy boys were included in this study. Secondhand smoking was confirmed via measurement of the cotinine/creatinine ratio. Various sociodemographic characteristics of patients were recorded. The levels of catalase, thiol, myeloperoxidase were measured to determine the antioxidant and oxidant levels in children, while the levels of total cholesterol and LDL cholesterol were measured to determine the alterations in lipid profile. RESULTS: The groups were similar in regard to demographic characteristics. Myeloperoxidase levels were significantly higher in the passive cigarette smoking group compared to the non-exposure group; however, catalase and thiol levels were similar. In regard to lipid profile, the levels of total cholesterol and LDL cholesterol were also similar in those with and without exposure to passive smoking. CONCLUSIONS: Our findings suggest that the effects of passive smoking initially influence oxidants (MPO), but not antioxidants (thiol and catalase). However, it is apparent that passive smoking adversely affects oxidative balance in children and this may lead to the development of various diseases which could cause significant morbidity and mortality.


Assuntos
Catalase/sangue , Colesterol/sangue , Peroxidase/sangue , Compostos de Sulfidrila/sangue , Poluição por Fumaça de Tabaco/efeitos adversos , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Fatores Socioeconômicos
15.
Acta Medica (Hradec Kralove) ; 62(1): 12-18, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30931891

RESUMO

BACKGROUND: Fibromyalgia syndrome (FMS) is an extra-articular rheumatological disease, characterized by widespread pain and somatic symptoms. The etiology has not yet been clarified. Oxidative stress may play an important role in FMS etiology. Thiol group is a very strong antioxidant. We aimed to investigate whether thiol/disulfide homeostasis in FMS is altered or not. MATERIAL AND METHODS: A total of 80 female FMS patients and 64 healthy female control individuals were included in this study. Thiol and disulfide values were measured by Erel's novel methods. RESULTS: Native thiol (330.6 ± 46.1 vs. 356.8 ± 55.5 µmol/L, p = 0.005) and native thiol/total thiol (89.4 ± 3.2 vs. 93.3 ± 4.0, p < 0.001) levels of FMS patients were significantly lower when compared to the values of control group. However, disulfide (19.4 ± 6.3 vs. 12.2 ± 6.3 µmol/L, p < 0.001) levels of FMS patients were significantly higher than healthy individuals. A negative correlation was found between the native thiol/total thiol and fibromyalgia impact questionnaire (FIQ) score among the FMS patients. A positive correlation was found between disulfide values and FIQ score among the patients. CONCLUSIONS: In FMS patients, there was a significant correlation between the decrease in the thiol levels and an increase in the disulfide levels with the FIQ scores. We determined that thiol-disulfide rate was deteriorated in FMS patients and it increases in favor of disulfide amounts.


Assuntos
Dissulfetos/sangue , Fibromialgia/sangue , Fibromialgia/fisiopatologia , Homeostase , Compostos de Sulfidrila/sangue , Adulto , Antioxidantes/metabolismo , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia
16.
Cardiol Young ; 29(4): 499-504, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30932800

RESUMO

Oxidative stress may contribute to the pathogenesis of congenital heart defects, but the role of dynamic thiol/disulphide homeostasis has not been evaluated. The objective of this study was to assess whether there are changes in thiol/disulphide homeostasis and nitric oxide levels in children with tetralogy of Fallot (TOF) and ventricular septal defect (VSD). A total of 47 children with congenital heart defects (24 TOF and 23 VSD) and 47 healthy age- and sex-matched controls were included in this study. Serum total thiol and native thiol levels were measured using a novel automatic spectrophotometric method. The amount of dynamic disulphide bonds and related ratios were calculated from these values. Serum nitric oxide levels were detected using a chemiluminescence assay. We found that the average native thiol, total thiol, and disulphide levels were decreased in patients with VSD when compared with healthy individuals (p < 0.001, p < 0.001, and p < 0.01, respectively). While native thiol levels were decreased (p < 0.01), disulphide levels were elevated in the TOF group (p < 0.05). We observed marked augmentation of disulphide/native thiol (p < 0.001) and disulphide/total thiol ratios (p < 0.01) in the TOF group. However, there was a significant decrease in native thiol/total thiol ratio in patients with TOF. No significant changes in these ratios were noted in the VSD group. We detected significant elevations in serum nitric oxide levels in children with TOF and VSD (p < 0.001 for all). These results are the first to demonstrate that thiol/disulphide homeostasis and nitric oxide are associated with TOF and VSD in children.


Assuntos
Dissulfetos/sangue , Comunicação Interventricular/sangue , Estresse Oxidativo , Compostos de Sulfidrila/sangue , Tetralogia de Fallot/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Homeostase , Humanos , Lactente , Masculino , Óxido Nítrico/sangue , Turquia
17.
Medicina (Kaunas) ; 55(4)2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30986917

RESUMO

Background and objectives: Oxidative stress signalling plays a monumental role in inflammatory bowel disease (IBD). Reduction of oxidative stress might control inflammation, block tissue damage, and reverse natural history of IBD. We assessed the serum concentrations of free thiols (FT) and uric acid (SUA), together constituting a large part of nonenzymatic serum antioxidant capacity, as well as total antioxidant status (TAS) with reference to IBD phenotype, activity, co-occurrence of anemia, and treatment with azathioprine (AZA) and corticosteroids (CS). Additionally, we appraised the potential of uric acid, thiol stress, and TAS as mucosal healing (MH) markers in ulcerative colitis. Materials and methods: SUA, FT, and TAS were measured colorimetrically using, respectively, uricase, Ellman's and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) methods. Results: The study group consisted of 175 individuals: 57 controls, 71 ulcerative colitis (UC), and 47 Crohn's disease (CD) patients. When compared to controls, SUA levels were significantly lower in patients with CD, and FT and TAS levels were significantly lower in patients with CD and UC. In UC patients, SUA, FT, and TAS inversely correlated with the severity of bowel inflammation. As MH markers, SUA displayed better overall accuracy and higher specificity than FT. In active CD, FT, and SUA were significantly lower in patients with anemia. FT was significantly lower in patients treated with corticosteroids. Conclusions: IBD patients, regardless the disease phenotype, have systemic thiol stress, depleted total antioxidant capacity, and reduced concentrations of uric acid, reflecting, to various degrees, clinical and local disease activity as well as presence of anaemia, the most common extraintestinal manifestation of IBD. Evaluation of systemic total antioxidant status may be useful in noninvasive assessment of mucosal healing. Our findings on thiol stress provide an additional aspect on adverse effects of corticosteroids therapy.


Assuntos
Corticosteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/sangue , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/sangue , Doença de Crohn/tratamento farmacológico , Estresse Oxidativo , Corticosteroides/efeitos adversos , Adulto , Análise de Variância , Anemia/sangue , Anemia/complicações , Anti-Inflamatórios/efeitos adversos , Azatioprina/uso terapêutico , Biomarcadores/sangue , Estudos de Casos e Controles , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Feminino , Hospitais Universitários , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polônia , Estatísticas não Paramétricas , Compostos de Sulfidrila/sangue , Ácido Úrico/sangue
18.
Artigo em Inglês | MEDLINE | ID: mdl-30834829

RESUMO

BACKGROUND: Epilepsy is a serious clinical condition characterized by recurrent seizures. Oxidative stress plays an important role in the etio-pathogenesis of epilepsy. Measurements of serum thiol and disulfide levels were used to evaluate the antioxidant status of the body. OBJECTIVE: The aim of this study was to determine serum levels of thiol and disulfide in epileptic pediatric patients. METHODS: Ninety patients, 54 epilepsy and 36 controls were included in the study. Serum levels of native thiol total thiol and disulfide were measured and disulfide/native, disulfide / total thiol and native thiol/ total thiol ratios were calculated. Hence, the ratios of disulfide/ native thiol, disulfide / total thiol and native thiol/ total thiol were calculated. RESULTS: Serum levels of native thiol, total thiol and disulfide were significantly lower in the epilepsy group than the control group. The ratio of disulfide/native thiol and disulfide / total thiol were significantly higher in the study group than the control group. As well as, the native thiol / total thiol ratio was lower in the epilepsy group than the control group. Native thiol, total thiol and disulfide were significantly lower in the epilepsy group who were taking anti-epileptic drugs than those who were not taking anti-epileptic drugs. CONCLUSION: We demonstrated a meaningful relationship between oxidative stress markers and epilepsy in pediatric patients.


Assuntos
Dissulfetos/sangue , Epilepsia/sangue , Compostos de Sulfidrila/sangue , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos
19.
Acta Neurol Belg ; 119(3): 419-422, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30820867

RESUMO

Neurofibromatosis type 1 (NF1) and tuberous sclerosis (TSC) are autosomal dominant neurocutaneous diseases. Epilepsy, malignancy and other neurological complications are common in both diseases. We aimed to investigate the thiol/disulphide balance as an oxidative stress marker in children who suffer from NF1 and TSC. Twenty-two patients with NF1, 20 TCS, and 22 healthy control subjects were included in the study. The total thiol, native thiol, and disulphide levels were measured and the disulphide/native thiol, disulphide/total thiol and native thiol/total thiol ratios were calculated and compared in three groups. The mean age and sex distribution of the patients with TSC and NF1 and the healthy control were similar. The total thiol, native thiol, and disulfide level was lower in TSC and NF1 group than the healthy control group. There were no significant differences among disulphide/native thiol and disulphide/total thiol ratios of three groups. We detected that the total thiol, native thiol, and disulfide levels were lower in TSC and NF1 group than the healthy control group. These results indicate that dynamic thiol-disulphide homeostasis can be used as a marker of oxidative stress in clinical trials with TSC and NF1.


Assuntos
Dissulfetos/sangue , Homeostase , Neurofibromatose 1/sangue , Estresse Oxidativo , Compostos de Sulfidrila/sangue , Esclerose Tuberosa/sangue , Adolescente , Criança , Feminino , Humanos , Masculino
20.
Curr Med Sci ; 39(1): 52-58, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30868491

RESUMO

This work is aimed at exploring the clinical efficacy of continuous positive airway pressure (CPAP) in treatment of patients with arrhythmias combined with obstructive sleep apnea (OSA). Through evaluating serum native thiol, malonaldehyde (MDA) and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) in these patients and describing the effects on oxidative parameters of CPAP therapy for 3 months, we confirmed the impact of oxidative stress on arrhythmias. A total of 64 patients with OSA combined with arrhythmias were collected from April 2014 to April 2017 with full clinical information. Patients were divided into two groups (paired experiment design): 32 patients in group A (control group), who received unchanged anti-arrhythmia treatment and 32 patients in group B, who were subjected to unchanged pharmacological anti-arrhythmia therapy combined with CPAP. OSA related parameters were compared between the two groups after 3-month therapy. And the levels of parameters of oxidative stress in patients were measured before and after CPAP therapy. After 3 months of CPAP therapy, compared with the control group, the percentage of sage N3 (NREM 3) and stage R (REM) in total sleep time was significantly increased, while apnea-hypopnea index (AHI) and the Epworth Sleepiness Scale (ESS) score were evidently decreased. Meanwhile, the lowest oxygen saturation (LSpO2) was also elevated after CPAP treatment for 3 months. The CPAP therapy significantly prevented the occurrence of arrhythmias (P<0.05). Both the MDA level and NADPH oxidase levels were significantly lower in the group B than in the group A (P<0.05). But serum native thiol was improved by CPAP treatment (P<0.05). In conclusion, proper use of CPAP therapy provides significant benefits for the treatment of arrhythmia in patients with OSA.


Assuntos
Arritmias Cardíacas/prevenção & controle , Pressão Positiva Contínua nas Vias Aéreas/métodos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia , Adulto , Idoso , Arritmias Cardíacas/sangue , Arritmias Cardíacas/etiologia , Feminino , Humanos , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , NADPH Oxidases/sangue , Estresse Oxidativo , Cooperação do Paciente , Apneia Obstrutiva do Sono/sangue , Fases do Sono , Compostos de Sulfidrila/sangue , Resultado do Tratamento , Adulto Jovem
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