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1.
Niger J Clin Pract ; 23(10): 1401-1406, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33047697

RESUMO

Aims: This study aimed to compare the serum thiol-disulfide homeostasis, total antioxidant status (TAS), and total oxidant status (TOS) in patients with pseudoexfoliation glaucoma (PEG) patients, primary open-angle glaucoma (POAG) patients, and healthy individuals (control). Methods: Ninety subjects were included in this study. Three groups were separated as PEG, POAG, and control. All groups were chosen to be similar in terms of age and gender. Blood samples were obtained following an overnight fasting state and were collected on the ice at 4°C. The serum samples were separated from the cells by centrifugation at 3000 rpm for 15 min and were stored at -80°C. Serum samples analyzed for TAS and TOS, native thiol, total thiol, disulfide, and native thiol/disulfide ratio. Results: TAS and TOS levels of PEG patients were 1.2892 ± 0.0905 mmol/L; 5.0191 ± 2.7722 µmol/L, respectively. TAS and TOS levels of POAG patients were 1.2741 ± 0.1252 mmol/L; 4.1674 ± 1.7723 µmol/L, respectively. TAS and TOS levels of the control group were 2.3414 ± 0.1409 mmol/L; 4.0931 ± 0.1107 µmol/L, respectively. The TAS level was significantly lower in PEG and POAG groups compared to control. TOS level showed no significant differ ¬ ence between PEG, POAG, and control groups (P > 0.05). The mean serum total thiol and native thiol levels were significantly lower in patients with PEG compared to POAG and control group; there was no significant difference between the POAG and control group (P > 0.05). The mean serum disulfide level was significantly lower in patients with PEG compared to POAG (P = 0.018). Conclusion: Low levels of TAS were observed in patients with glaucoma, which was likely a response to the increased oxidative stress observed in these patients. While total thiol and native thiol levels were higher in the PEG group, the disulfide level was higher in the POAG group. TAS and TOS levels showed no significant difference between POAG and PEG groups.


Assuntos
Antioxidantes/metabolismo , Dissulfetos/sangue , Síndrome de Exfoliação/sangue , Glaucoma de Ângulo Aberto/sangue , Homeostase/fisiologia , Compostos de Sulfidrila/sangue , Adulto , Antioxidantes/análise , Estudos de Casos e Controles , Dissulfetos/metabolismo , Síndrome de Exfoliação/metabolismo , Feminino , Glaucoma de Ângulo Aberto/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Oxidantes/sangue , Estresse Oxidativo/fisiologia , Compostos de Sulfidrila/metabolismo
2.
Medicine (Baltimore) ; 99(26): e20872, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590792

RESUMO

PURPOSE: Oxidative stress has been shown to reflect on the development of sepsis and disease severity. In the present study, we evaluated the effects of increased levels of oxidative stress and decreased antioxidant coactivity in patients with sepsis, and the importance of oxidative stress on treatment outcomes. METHODS: Biomarkers of oxidative stress (thiobarbituric acid-reactive substances [TBARS]) and antioxidant capacity (glutathione peroxidase [GPx] and glutathione content [thiol]) were prospectively evaluated along with biochemical and clinical data in 100 patients with sepsis on days 1, 4, and 7 after admission. RESULTS: The TBARS level of the non-survivor group was significantly higher than that of the survivor group on day 1 and day 4 and negatively correlated with thiol upon admission. However, thiol was positively correlated with lactate concentration. The TBARS and lactate levels upon admission were independent predictors of fatality. CONCLUSIONS: We conclude that a TBARS cut-off value of 18.30 µM can be used to predict fatality, and an increase in the TBARS concentration by 1 µM will increase the fatality rate by 0.94%. In the panel of biomarkers, the TBARS assay can be considered as a prognostic biomarker for the treatment of patients with sepsis.


Assuntos
Biomarcadores/análise , Estresse Oxidativo/fisiologia , APACHE , Adulto , Idoso , Análise de Variância , Área Sob a Curva , Biomarcadores/sangue , Feminino , Glutationa Peroxidase/análise , Glutationa Peroxidase/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Compostos de Sulfidrila/análise , Compostos de Sulfidrila/sangue , Sobreviventes/estatística & dados numéricos , Substâncias Reativas com Ácido Tiobarbitúrico/análise
3.
BMC Med ; 18(1): 130, 2020 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-32456645

RESUMO

BACKGROUND: Serum free thiols (R-SH, sulfhydryl groups) reliably reflect systemic oxidative stress. Since serum free thiols are rapidly oxidized by reactive species, systemic oxidative stress is generally associated with reduced serum free thiol levels. Free thiols associate with favorable disease outcomes in many patient cohorts, and the current hypothesis is that oxidative stress might also play an important role in cardiovascular disease. In this study, we aimed to establish the role of serum free thiols in the general population by investigating their relationship with the risk of cardiovascular (CV) events and all-cause mortality. METHODS: Participants (n = 5955) of the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort study from the general population were included. At baseline, serum levels of free thiols were quantified and adjusted to total protein levels. Protein-adjusted serum free thiol levels were studied for their associations with clinical and biochemical parameters, as well as with the risk of CV events and all-cause mortality. RESULTS: The mean protein-adjusted serum free thiol level was 5.05 ± 1.02 µmol/g of protein. Protein-adjusted serum free thiols significantly predicted the risk of CV events, even after adjustment for potential confounding factors (hazard ratio [HR] per doubling 0.68 [95% confidence interval [CI] 0.47-1.00], P = 0.048). Similarly, protein-adjusted serum free thiols were significantly predictive of the risk of all-cause mortality (HR per doubling 0.66 [95% CI 0.44-1.00], P = 0.050). Stratified analyses revealed lower HRs for subjects with a lower body mass index (BMI), without hypertension, and without diabetes. Conversely, HRs were lower in subjects with albuminuria. CONCLUSIONS: In this large population-based cohort study, serum free thiols significantly predicted the risk of CV events and all-cause mortality. Our results highlight the potential significance and clinical applicability of serum free thiols since they are amendable to therapeutic intervention.


Assuntos
Doenças Cardiovasculares/sangue , Estresse Oxidativo/fisiologia , Compostos de Sulfidrila/efeitos adversos , Adulto , Idoso , Doenças Cardiovasculares/mortalidade , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Compostos de Sulfidrila/sangue , Análise de Sobrevida
4.
Ulus Travma Acil Cerrahi Derg ; 26(3): 389-395, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32436977

RESUMO

BACKGROUND: This study aims to investigate the role of thiol/disulfide homeostasis parameters in the diagnosis of acute appendicitis and to determine whether it is beneficial to use these parameters in combination with the modified Alvarado and RIPASA scoring systems. METHODS: This study was prospectively carried out on 265 patients who presented to the emergency department with the complaint of right lower quadrant pain between 01.07.2017 and 31.12.2017, and met the inclusion criteria of this study. Oxidative stress markers were evaluated on two groups. The relationship between these parameters and the modified Alvarado and RIPASA scoring systems was analyzed. RESULTS: The mean levels of disulfide, disulfide/native thiol and disulfide/total thiol were found to be significantly higher in the appendicitis group (p<0.001). The mean levels of native thiol, total thiol and native thiol/total thiol were significantly lower in the same group (p<0.001, 0.001 and 0.007, respectively). The mean levels of disulfide, disulfide/native thiol and disulfide/total thiol were recorded to be significantly higher in the high-risk group according to the results of RIPASA (p=0.016, 0.003 and 0.001, respectively). CONCLUSION: Thiol/disulfide homeostasis parameters can be used with the modified Alvarado and RIPASA scoring systems in the diagnosis of acute appendicitis.


Assuntos
Apendicite/diagnóstico , Regras de Decisão Clínica , Dissulfetos/sangue , Compostos de Sulfidrila/sangue , Doença Aguda , Humanos , Estudos Prospectivos
5.
J Clin Neurosci ; 75: 188-194, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32223973

RESUMO

BACKGROUND: Alzheimer's Disease (AD) is the most common form of dementia seen in advanced age. It is characterized by progressive deterioration in cognitive functions. The prevalence of Alzheimer's disease increasing day by day due to the increase in the share of the elderly population in the general population due to developing health and living conditions, is limited and early diagnosis and effective treatment possibilities are very limited. From this point of view, a specific biomarker for AD is very important. As a new oxidative stress biomarker, the levels of thiol-disulfide balance, ischemia-modified albumin and seroloplazminin were evaluated. The aim of this study was to determine the serum levels of oxidative stress biomarkers in the early stages of the disease and to compare these oxidative stress markers with patients with mild cognitive impairment as a precursor form of Alzheimer's disease and to determine whether these markers develop at an earlier stage. METHODS: 30 volunteers with early stage AD according to NINCDS-ARDRA criteria, 19 volunteers with Midl Cognitive Impairment according to PCA criteria and 30 volunteers with defined criteria were selected from the subjects aged between 55 and 88 who applied to Gazi University Health Research. Statistical analysis of the data showed that there was a significant difference between the endgroups and biomarkers for the early diagnosis of Alzheimer's disease, but this complicated matter has to be investigated in more comprehensive and detailed studie. RESULTS: In the present study, we investigated oxidative stress parameters, thiol-disulphide balance, ischemia modified abumin and seruloplasmin in parallel with the impairment in cognitive dysfunction from control group to Mild Cognitive Impairment (MCD) and AD group by using a newly-developed method. CONCLUSIONS: This is the first study in literature comparing Early Stages Alzheimer Disease (ESAD), MCD and healthy volunteer groups. Our study has revealed that these newly developed tests may be candidates as oxidative stress biomarkers in pathgenesis of AD. However it was concluded that more comprehensive and detailed studies are required to enlighten this issue.


Assuntos
Doença de Alzheimer/sangue , Disfunção Cognitiva/sangue , Estresse Oxidativo/fisiologia , Compostos de Sulfidrila/sangue , Sulfitos/sangue , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Biomarcadores/sangue , Calorimetria/métodos , Cognição/fisiologia , Disfunção Cognitiva/diagnóstico , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Albumina Sérica Humana
6.
Anal Chim Acta ; 1105: 112-119, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32138909

RESUMO

Perturbation of thiol homeostasis in biological fluids are thought to be associated with several diseases, and reliable analytical methods for the determination of low molecular weight (LMW) thiols in human plasma or serum are thus required. In this study, a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method is described for high throughput determination of four LMW thiols (glutathione, cysteine, homocysteine and cysteinylglycine) in human serum. It is based on the use of a bromoacetyl functionalized C60 (Br-C60) as a derivatization reagent to label thiols. The Br-C60 labeling can add an 832-Da tag to thiols, which moves thiol signals to high mass region and effectively avoids the signal interference generated by the traditional MALDI matrix below 800 Da. The labeling can be completed within 5 min under microwave-assisted condition. Thereby, the Br-C60 labeling based MALDI-TOF MS analytical method can achieve high throughput analysis of LMW thiols in serum. Good linearities of the method for the thiols in human serum were obtained in the range of 0.5-500.0 µM with correlation coefficient (R) greater than 0.9960. The limit of detection is in the range of 0.07-0.18 µM for the investigated thiols in human serum with relative standard deviations of lower than 13.5% and recoveries ranging from 81.9 to 117.1%. Using the method, four thiols in microliter serum samples of breast cancer (BC) patients were determined. The result showed that the contents of the four thiols in BC serum samples significantly changed compared to the healthy control (HC).


Assuntos
Acetatos/química , Fulerenos/química , Compostos de Sulfidrila/sangue , Humanos , Estrutura Molecular , Peso Molecular , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
7.
Biomarkers ; 25(3): 274-280, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32091261

RESUMO

Purpose: To examine thiol-disulphide homeostasis auto painters.Materials and methods: A total of 115 male workers, including 60 auto painters workers and 55 reference group, of the painting and assembly line units respectively, were included in the study. Thiol-disulphide parameters and ischaemia-modified albumin (IMA) of groups were determined. Urinary hippuric acid, (HA) phenol, hexanedione, trichloroacetic acid, arsenic and blood lead and manganese were analysed.Results: The median urinary HA level was significantly higher in auto painters when compared to the reference group [(2461 (1212) vs. 520 (513) µgr/L), (p < 0.001)] . The mean disulphide level [19.7 (4.3) vs 0.15.1(4.1) µmol/L, (p < 0.001)], the disulphide/native thiol ratio [4.72 (1.47) vs. 3.13 (1.21, (p < 0.001)] and the disulphide/total thiol ratio [4.31 (1.23) vs. 2.94 (1.06), (p < 0.001)] were higher in auto painters when compared to the reference group. There was a statistically significant positive correlation between urinary HA and disulphide concentrations (r = 0.536 and p < 0.001), disulphide/native thiol ratio (r = 0.564 and p < 0.001) and the disulphide/total thiol ratio (r = 0.564 and p < 0.001) and IMA (r = 0.396 and p < 0.001).Conclusion: The results presented in this study showed that oxidative stress can be associated with occupational exposure to toluene denoted by alteration of thiol disulphide homeostasis and ischaemia-modified albumin levels.


Assuntos
Biomarcadores/sangue , Dissulfetos/sangue , Homeostase , Exposição Ocupacional/análise , Compostos de Sulfidrila/sangue , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Albumina Sérica Humana , Tolueno/química
8.
Int J Mol Sci ; 21(3)2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32033303

RESUMO

α-Lipoic acid, glutathione, cysteine, and cysteinylglycine can be applied as therapeutic agents in civilization diseases such as diabetes mellitus, cardiovascular diseases, and cancers. On the other hand, a higher concentration of homocysteine can result in health problems and has been indicated as an independent risk factor for cardiovascular disease and accelerated atherosclerosis. Here, the first simplified HPLC-UV assay that enables simultaneous determination of α-lipoic acid and low-molecular-mass thiols in plasma, reduces the number of steps, shortens the total time of sample preparation, and limits the amount of single-use polypropylene laboratory materials is described. The assay is based on reversed-phase high performance liquid chromatography with UV detection and simultaneous reduction of disulfide bound with tris(2-carboxyethyl)phosphine and the selective pre-column derivatization of the thiol group with 1-benzyl-2-chloropyridinium bromide. Linearity in the detector responses for plasma samples were observed in ranges: 0.12-5.0 nmol mL-1 for α-lipoic acid; 2.0-20.0 nmol mL-1 for glutathione, cysteinylglycine, and homocysteine; and 40.0-400.0 for cysteine. The LODs for α-lipoic acid and low-molecular-mass thiols were 0.08 and 0.12 nmol mL-1, respectively, while LOQs were 0.12 and 0.16 nmol mL-1, respectively. The usefulness of the proposed method has been proven by its application to real samples.


Assuntos
Plasma/metabolismo , Compostos de Sulfidrila/sangue , Compostos de Sulfidrila/metabolismo , Ácido Tióctico/sangue , Ácido Tióctico/metabolismo , Adulto , Cisteína/metabolismo , Dipeptídeos/metabolismo , Dissulfetos/metabolismo , Feminino , Glutationa/metabolismo , Homocisteína/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Peso Molecular , Oxirredução , Compostos de Piridínio/metabolismo
9.
Taiwan J Obstet Gynecol ; 59(1): 79-84, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32039805

RESUMO

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common hormonal disorder among women of reproductive age characterized by irregular menstruation and hirsutism and is associated with an increased risk for cardiovascular diseases. Increased inflammatory response and oxidative stress may also present in these patients. In this study, we aimed to compare the neutrophil-to-lymphocyte ratio (NLR), mean platelet volume (MPV), and dynamic thiol-disulphide homeostasis (dTDH) between the patients with PCOS and healthy individuals and to investigate the correlation between these parameters and cardiovascular risk factors in patients with PCOS. MATERIALS AND METHODS: A total of 60 participants were included in this study. The patient group consisted of 36 patients who were diagnosed with PCOS and the control group consisted of 24 healthy individuals without PCOS. Complete blood count and hormonal tests were performed using blood samples. The NLR, MPV, and dTDH were compared between the patient and control groups. RESULTS: There was no statistically significant difference in the native thiol, total thiol, disulphide levels and disulfide/native, disulfide/total and native/total thiol ratios between the patient and control groups (p = 0.494, p = 0.446, p = 0.338, p = 0.717, p = 0.723, and p = 0.717, respectively). In addition, there was no statistically significant difference in NLR and MPV between the groups (p = 0.531 and p = 0.196). CONCLUSION: Our study results showed no significant difference in the NLR, MPV, dTDH levels, and inflammatory biomarkers including leukocyte count between the PCOS patients and healthy controls. Based on these findings, we conclude that the diagnosis of PCOS alone in overweight patients has no considerable effect on these biomarkers.


Assuntos
Plaquetas/patologia , Dissulfetos/sangue , Linfócitos/metabolismo , Neutrófilos/metabolismo , Síndrome do Ovário Policístico/sangue , Compostos de Sulfidrila/sangue , Adulto , Biomarcadores/sangue , Contagem de Células Sanguíneas , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Feminino , Homeostase , Humanos , Contagem de Leucócitos , Volume Plaquetário Médio , Estresse Oxidativo , Síndrome do Ovário Policístico/complicações , Fatores de Risco
10.
Microvasc Res ; 130: 103987, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32035919

RESUMO

BACKGROUND: Diabetic foot ulcer (DFU) is one of the most devastating diabetic consequences leading to amputations. Oxidative stress, inflammation, vascular insufficiency and neuropathy have been linked to DFU development. Since soluble fms-like tyrosine kinase-1 (sFlt-1) is one of the anti-angiogenic factors regulating vascular endothelial growth factor (VEGF) biological activity. So, we aimed to evaluate its role in pathogenesis of DFU and its correlation with oxidative stress and inflammatory markers. METHODS: 60 type 2 diabetic patients: 30 without DFU and 30 with DFU in addition to 20 healthy controls were enrolled in the study. sFlt-1 and VEGF mRNA relative gene expressions and levels and sFlt-1/VEGF ratio were assessed. Also, Advanced oxidation protein products (AOPPs), malondialdhyde (MDA), Total thiol and, tumor necrosis factor alpha (TNF-α) levels were measured. RESULTS: sFlt-1 expression and level, AOPPs, MDA and TNF-α were significantly higher in diabetic patients as compared with the control group with highest levels in DFU patients. However, there were significant decrease in total thiol level and VEGF expression and level in diabetic patients with DFU. CONCLUSION: This study revealed that sFlt-1 is a major player in DFU pathogenesis and may be considered as a novel diagnostic biomarker for early detection of DFU.


Assuntos
Pé Diabético/sangue , Mediadores da Inflamação/sangue , Neovascularização Fisiológica , Estresse Oxidativo , Fator de Necrose Tumoral alfa/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , Produtos da Oxidação Avançada de Proteínas/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Pé Diabético/enzimologia , Pé Diabético/patologia , Pé Diabético/fisiopatologia , Diagnóstico Precoce , Feminino , Humanos , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Compostos de Sulfidrila/sangue , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética
11.
Int J Mol Sci ; 21(1)2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31906485

RESUMO

Oxidative stress plays a pivotal role in the pathogenesis of cardiovascular diseases (CVD). Postmenopausal women have an increased risk of developing CVD due to decreased estrogen availability, which is accompanied by increased oxidative stress. Serum free thiols (R-SH) provide a robust and powerful read-out of systemic oxidative stress. In this study, we aimed to establish serum levels of free thiols and explore associations between free thiols and demographic, clinical, and biochemical parameters related to obesity and the risk for developing CVD in both pre- and postmenopausal women. Serum free thiols were measured in a cohort consisting of healthy pre- (n = 223) and postmenopausal (n = 118) Omani women. Postmenopausal women had significantly lower levels of serum free thiols as compared to premenopausal women (762.9 ± 85.3 vs. 780 ± 80.9 µM, age-adjusted p < 0.001). Women's age was positively associated with serum free thiol levels in premenopausal women (ß = 0.36, p = 0.002), whereas an inverse association was observed in postmenopausal women (ß = -0.29, p = 0.002). Homocysteine levels were significantly inversely associated with serum free thiol levels in both pre- (ß = -0.19, p = 0.005) and postmenopausal (ß = -0.20, p = 0.032) women, independent from known cardiovascular risk factors. In this study, we show that postmenopausal women are affected by increased systemic oxidative stress, which independently associates with homocysteine levels.


Assuntos
Doenças Cardiovasculares/sangue , Homocisteína/sangue , Estresse Oxidativo/fisiologia , Pós-Menopausa/sangue , Compostos de Sulfidrila/sangue , Adulto , Doenças Cardiovasculares/metabolismo , Estudos de Coortes , Estudos Transversais , Feminino , Homocisteína/metabolismo , Humanos , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/metabolismo , Omã , Pós-Menopausa/metabolismo , Pré-Menopausa/sangue , Fatores de Risco , Compostos de Sulfidrila/metabolismo
12.
Ulus Travma Acil Cerrahi Derg ; 26(1): 37-42, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31942734

RESUMO

BACKGROUND: Acute pancreatitis is a common disease seen in emergency departments because of abdominal pain. The present study aims to evaluate the relation between measurements of thiol-disulfide parameters in patients diagnosed with acute pancreatitis and other blood parameters. METHODS: A total of 56 (56%) patients, who were admitted to the emergency department, and 44 (44%) healthy volunteers participated in this study. A total of 100 samples were taken from the participants. Detailed blood samples were taken from the patients at the time of arrival at the hospital. The thiol-disulfide level in serum was examined using a brand new method that was developed by Erel and Neselioglu in the venous blood samples of the patients who were diagnosed with acute pancreatitis during the admission. The data were evaluated in the computer medium. RESULTS: Gallstones were defined as the etiology of AP in 41 patients (73.2%); in one patient, hypertriglyceridemia (1.7%); in four patients, alcohol use (7.1%), and idiopathic 10 patients (17.8%). While the blood thiol levels were low, the disulfide levels were high at a significant level. No statistically significant relations were detected between the amylase, lipase, neutrophil lymphocyte ratio (NLR), which are other blood parameters, and thiol-disulfide balance parameters. CONCLUSION: The disruption of the thiol-disulfide balance may play a role in the pathogenesis of acute pancreatitis. In acute pancreatitis, since the thiol level is decreased in the blood, administration of the complementary therapies for this thiol deficiency may contribute to the treatment of the disease.


Assuntos
Dissulfetos/sangue , Pancreatite , Compostos de Sulfidrila/sangue , Serviço Hospitalar de Emergência , Cálculos Biliares , Homeostase , Humanos , Pancreatite/sangue , Pancreatite/epidemiologia
13.
Exp Clin Endocrinol Diabetes ; 128(2): 77-81, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29378378

RESUMO

AIM: The purpose of this study was to examine thiol-disulfide balance in patients with type 2 diabetes mellitus. METHODS: This study included 32 subjects with known type 2 diabetes mellitus without complications, 30 patients with type 2 diabetes mellitus with complications, 28 newly diagnosed patients with type 2 diabetes mellitus, and 45 healthy individuals. Thiol-disulfide profile tests were quantified in all groups. RESULTS: Compared to the control group, patients in each of the diabetic groups had significantly lower native and total thiol levels, higher disulfide levels, and higher disulfide/native thiol and disulfide/total thiol ratios (p<0.05 for all). Disulfide levels were significantly lower in the newly diagnosed group than in other diabetic groups (p<0.05). There were significant associations between glycemic parameters and thiol-disulfide tests (p<0.05). CONCLUSIONS: A disequilibrium between thiol-disulfide pairs occurs in patients with type 2 diabetes mellitus, and a gradual increase to disulfide levels may contribute to the disease's severity. Deteriorated thiol-disulfide homeostasis may be relevant to the pathophysiology of type 2 diabetes mellitus.


Assuntos
Complicações do Diabetes/sangue , Diabetes Mellitus Tipo 2/sangue , Progressão da Doença , Dissulfetos/sangue , Homeostase , Estresse Oxidativo , Compostos de Sulfidrila/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Eur J Ophthalmol ; 30(4): 690-699, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30974971

RESUMO

PURPOSE: The aim of this study was to evaluate thiol/disulfide homeostasis and ischemia-modified albumin levels with primary open-angle glaucoma, ocular hypertension, and control group; also to interpret the correlation between these biochemical parameters and retinal nerve fiber layer analysis. MATERIAL AND METHODS: In a prospective cross-sectional study, 30 primary open-angle glaucoma cases, 30 ocular hypertension cases, and 30 control subjects were included in the study. Native thiol, total thiol, and disulfide measurements and disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol ratios were evaluated as thiol-disulfide homeostasis. Albumin and ischemia-modified albumin parameters were also evaluated. All cases underwent detailed ophthalmologic examination including visual acuity, retinal nerve fiber layer via optical coherence tomography, intraocular pressure, and central corneal thickness measurements and visual field analysis by 24-2 Swedish Interactive Threshold Algorithm (SITA) Standard visual field test. RESULTS: Primary open-angle glaucoma group had significantly higher ischemia-modified albumin values than ocular hypertension and control group (p < 0.001). Native thiol and total thiol values of control group were statistically higher than those of primary open-angle glaucoma and ocular hypertension groups. The correlation between the temporal retinal nerve fiber layer value and ischemia-modified albumin, disulfide/native thiol, and disulfide/total thiol values of the primary open-angle glaucoma patients included in the study was moderate correlation in negative direction (r = -0.46, r = -0.39, r = -0.39, respectively), whereas there was a statistically significant moderate correlation in positive direction between the native thiol/total thiol values (r = 0.39) (p < 0.05). CONCLUSION: These findings have reinforced the role of oxidative stress in the etiopathogenesis of primary open-angle glaucoma, suggesting that the thinning retinal nerve fiber layer may be associated with oxidative stress in favor of prooxidant shift.


Assuntos
Dissulfetos/sangue , Glaucoma de Ângulo Aberto/sangue , Fibras Nervosas/patologia , Células Ganglionares da Retina/patologia , Compostos de Sulfidrila/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos Transversais , Feminino , Glaucoma de Ângulo Aberto/fisiopatologia , Homeostase/fisiologia , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/sangue , Hipertensão Ocular/fisiopatologia , Estresse Oxidativo/fisiologia , Estudos Prospectivos , Albumina Sérica Humana , Tomografia de Coerência Óptica/métodos , Tonometria Ocular , Acuidade Visual/fisiologia , Testes de Campo Visual , Campos Visuais/fisiologia
15.
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
16.
Artigo em Inglês | MEDLINE | ID: mdl-31690176

RESUMO

An adequate level of low molecular weight thiols (LMW-SH, especially glutathione (GSH)) protects cellular macromolecules against toxic agents, and is used as a sensitive biomarker of exposure to toxic compounds. During sample collection, storage and preparation, non-enzymatic and enzymatic oxidation of LMW-SH can occur leading to analytical inaccuracy. The aim of this study was to optimize a fast and reliable screening method for the determination of LMW-SH, mainly GSH, in blood and plasma samples as well as to investigate the impact of storage conditions on the LMW-SH stability. Based on our results, the described spectrophotometric method allows fast and reliable determination of LMW-SH in blood and plasma samples. Results on incubation of samples at 37 °C imply that synthesis of LMW-SH (probably GSH) as well as dynamic interexchange among various thiols forms can be induced in blood cells in in vitro conditions. Importantly, the level of LMW-SH in blood and plasma stored at -20 °C was constant, indicating that they can be stored at -20 °C for at least 30 days. Therefore, the method is suitable for assessment of LMW-SH in long-term human biomonitoring as well as environmental field studies, especially those involving a large number of samples such as epidemiological studies.


Assuntos
Monitoramento Biológico/métodos , Compostos de Sulfidrila/sangue , Biomarcadores/sangue , Biomarcadores/química , Glutationa/sangue , Glutationa/química , Humanos , Peso Molecular , Oxirredução , Manejo de Espécimes , Compostos de Sulfidrila/química , Temperatura
17.
J Clin Res Pediatr Endocrinol ; 12(1): 45-54, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-31414586

RESUMO

Objective: There is an association between obesity and several inflammatory and oxidative markers in children. In this study, we analyzed thiol/disulfide homeostasis and serum ischemia-modified albumin (IMA) levels for the first time in order to clarify and determine the oxidant/antioxidant balance in metabolically healthy and unhealthy children. Methods: This study included obese children and healthy volunteers between 4-18 years of age. The obese patients were divided into two groups: metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). Biochemical parameters including thiol/disulfide homeostasis, and IMA concentrations were analyzed. Results: There were 301 recruits of whom 168 (55.8%) were females. The obese children numbered 196 (MHO n=58 and MUO n=138) and healthy controls numbered 105. No statistically significant difference could be found in ages and genders of the patients among all groups (p>0.05, for all). Native thiol (SH), total thiol (SH+SS), and native thiol/total thiol (SH/SH+SS) ratio were statistically significantly lower in the MUO group than the control group (p<0.001, p=0.005, and p=0.005; respectively). Disulfide (SS), disulfide/native thiol (SS/SH), disulfide/total thiol (SS/SH+SS) and IMA levels were statistically significantly higher in the MUO group than the control group (p=0.002, p<0.001, p<0.001, and p=0.001, respectively). Conclusion: Chronic inflammation due to oxidative stress induced by impaired metabolic parameters in MUO children caused impairment in thiol redox homeostasis. Our data suggested that the degree of oxidant imbalance in obese children worsened as obesity and metabolic abnormalities increased. It is hypothesized that thiol/disulfide homeostasis and high serum IMA levels may be reliable indicators of oxidant-antioxidant status in MUO children.


Assuntos
Dissulfetos/sangue , Homeostase/fisiologia , Inflamação/metabolismo , Síndrome Metabólica/metabolismo , Estresse Oxidativo/fisiologia , Obesidade Pediátrica/metabolismo , Compostos de Sulfidrila/sangue , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Doença Crônica , Feminino , Humanos , Inflamação/sangue , Masculino , Síndrome Metabólica/sangue , Obesidade Pediátrica/sangue , Albumina Sérica Humana
18.
Radiat Res ; 193(1): 88-94, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31738662

RESUMO

Radiation-induced cancer is an ongoing and significant problem, with sources that include clinics worldwide in which 3.1 billion radiology exams are performed each year, as well as a variety of other scenarios such as space travel and nuclear cleanup. These radiation exposures are typically anticipated, and the exposure is typically well below 1 Gy. When radiation-induced (actually ROS-induced) DNA mutation is prevented, then so too are downstream radiation-induced cancers. Currently, there is no protection available against the effects of such <1 Gy radiation exposures. In this study, we address whether the new PrC-210 ROS-scavenger is effective in protecting p53-deficient (p53-/-) mice against X-ray-induced accelerated tumor mortality; this is the most sensitive radiation tumorigenesis model currently known. Six-day-old p53-/- pups received a single intraperitoneal PrC-210 dose [0.5 maximum tolerated dose (MTD)] or vehicle, and 25 min later, pups received 4.0 Gy X-ray irradiation. At 5 min postirradiation, blood was collected to quantify white blood cell c-H2AX foci. Over the next 250 days, tumor-associated deaths were recorded. Findings revealed that when administered 25 min before 4 Gy X-ray irradiation, PrC-210 reduced DNA damage (c-H2AX foci) by 40%, and in a notable coincidence, caused a 40% shift in tumor latency/incidence, and the 0.5 MTD PrC210 dose had no discernible toxicities in these p53-/- mice. Essentially, the moles of PrC-210 thiol within a single 0.5 MTD PrC-210 dose suppressed the moles of ROS generated by 40% of the 4 Gy X-ray dose administered to p53-/- pups, and in doing so, eliminated the lifetime leukemia/lymphoma risk normally residing "downstream" of that 40% of the 4 Gy dose. In conclusion: 1. PrC-210 is readily tolerated by the 6-day-old p53-/- mice, with no discernible lifetime toxicities; 2. PrC-210 does not cause the nausea, emesis or hypotension that preclude clinical use of earlier aminothiols; and 3. PrC-210 significantly increased survival after 4 Gy irradiation in the p53-/- mouse model.


Assuntos
Diaminas/farmacologia , Neoplasias Induzidas por Radiação/mortalidade , Protetores contra Radiação/farmacologia , Compostos de Sulfidrila/farmacologia , Proteína Supressora de Tumor p53/deficiência , Animais , Carcinogênese/efeitos dos fármacos , Carcinogênese/efeitos da radiação , Dano ao DNA , Diaminas/sangue , Feminino , Humanos , Recém-Nascido , Masculino , Camundongos , Neoplasias Induzidas por Radiação/genética , Neoplasias Induzidas por Radiação/patologia , Neoplasias Induzidas por Radiação/prevenção & controle , Protetores contra Radiação/metabolismo , Compostos de Sulfidrila/sangue
19.
Blood Transfus ; 18(1): 40-48, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31855151

RESUMO

BACKGROUND: Red blood cells from smoking donors can have more lesions from oxidative stress, decreasing the benefits of blood transfusion. We aimed to explore the effect of cigarette smoking on the oxidative status of packed red blood cells (PRBCs) prior to storage. MATERIALS AND METHODS: We compared serum vitamin C, plasmatic malondialdehyde (MDA), and non-protein thiol groups (GSH) levels in PRBCs, as well glutathione peroxidase (GPx) and glutathione s-transferase (GST) activity in PRBCs from smoking (n=36) and non-smoking (n=36) donors. We also correlated urinary cotinine levels with these parameters. RESULTS: Cigarette smoking was associated with decreased serum levels of vitamin C and GPx, and increased GST activity in PRBCs. We found negative correlations between cotinine, GPx activity and vitamin C levels, and a positive correlation between cotinine and GST activity. DISCUSSION: Cigarette smoking changed antioxidant defences of PRBCs prior to storage and these parameters are correlated with cotinine levels. Increased RBC antioxidants such as GST may reflect an exposure to oxidants during erythropoiesis. Because of the inability of mature RBCs to resynthesise antioxidants, PRBCs from smokers may have higher risk of storage lesions than those from non-smoker donors.


Assuntos
Doadores de Sangue , Fumar Cigarros/sangue , Eritrócitos/metabolismo , Adulto , Idoso , Antioxidantes/análise , Ácido Ascórbico/sangue , Cotinina/urina , Eritrócitos/química , Eritrócitos/enzimologia , Feminino , Glutationa Peroxidase/sangue , Glutationa Transferase/sangue , Humanos , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Compostos de Sulfidrila/sangue
20.
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
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