A TNF-α inhibitor abolishes sepsis-induced cognitive impairment in mice by modulating acetylcholine and nitric oxide homeostasis, BDNF release, and neuroinflammation.

Neurodegenerative disorders have a pathophysiology that heavily involves neuroinflammation. In this study, we used lipopolysaccharide (LPS) to create a model of cognitive impairment by inducing systemic and neuroinflammation in experimental animals. LPS was injected intraperitoneally at a dose of 0.5 mg/kg during the last seven days of the study. Adalimumab (ADA), a TNF-α inhibitor, was injected at a dose of 10 mg/kg a total of 3 times throughout the study. On the last two days of the experiment, 50 mg/kg of curcumin was administered orally as a positive control group. Open field (OF) and elevated plus maze tests (EPM) were used to measure anxiety-like behaviors. The tail suspension test (TST) was used to measure depression-like behaviors, while the novel object recognition test (NOR) was used to measure learning and memory activities. Blood and hippocampal TNF α and nitric oxide (NO) levels, hippocampal BDNF, CREB, and ACh levels, and AChE activity were measured by ELISA. LPS increased anxiety and depression-like behaviors while decreasing the activity of the learning-memory system. LPS exerted this effect by causing systemic and neuroinflammation, cholinergic dysfunction, and impaired BDNF release. ADA controlled LPS-induced behavioral changes and improved biochemical markers. ADA prevented cognitive impairment induced by LPS by inhibiting inflammation and regulating the release of BDNF and the cholinergic pathway.

Evaluation of the protective and therapeutic effects of extra virgin olive oil rich in phenol in experimental model of neonatal necrotizing enterocolitis by clinical disease score, inflammation, apoptosis, and oxidative stress markers.

BACKGROUND AND AIM: Necrotizing Enterocolitis (NEC) is an inflammation-associated ischemic necrosis of the intestine. To investigate the effects of extra virgin olive oil (EVOO) on inflammation, oxidative stress, apoptosis, and histological changes in NEC-induced newborn rats. MATERIALS AND METHODS: 24 rats were randomly divided into three groups: control, NEC and NEC + EVOO. NEC induction was performed using hypoxia-hyperoxia, formula feeding, and cold stress. The NEC + EVOO group received 2 ml/kg EVOO with high phenolic content by gavage twice a day for 3 days. 3 cm of bowel including terminal ileum, cecum, and proximal colon was excised. RESULTS: Weight gain and clinical disease scores were significantly higher in the NEC + EVOO group than in the NEC group (p < 0.001). EVOO treatment caused significant decreases in IL1ß, IL6 levels (p = 0.016, p = 0.029 respectively) and EGF, MDA levels (p = 0.032, p = 0.013 respectively) compared to NEC group. Significant decreases were observed in IL6 gene expression in the NEC + EVOO group compared to the NEC group (p = 0.002). In the group NEC + EVOO, the number of Caspase-3 positive cells was found to be significantly reduced (p < 0.001) and histopathological examination revealed minimal changes and significantly lower histopathological scores (p < 0.001). CONCLUSION: Phenol-rich EVOO prevents intestinal damage caused by NEC by inhibiting inflammation, oxidative stress, apoptosis.

The use of calprotectin and other inflammatory parameters in the investigation of pseudoexfoliation syndrome concomitant glaucoma and systemic diseases.

PURPOSE: The present study aimed to investigate the value of calprotectin and other inflammatory parameters in patients with glaucoma and systemic diseases accompanying pseudoexfoliation syndrome (PEX-S). METHODS: This prospective study included 45 PEX-S patients and 45 non-PEX control patients. Patients were investigated for the presence of glaucoma, cardiovascular disease (CVD), ischemic brain disease (IBD), Alzheimer's disease, and neurosensory hearing loss (NSHL). After excluding diseases that may affect inflammatory parameters, a detailed biomicroscopic examination, and blood tests were performed for the patients. RESULTS: Glaucoma, CVD, NVK, Alzheimer's disease, and NSHL were high in the PEX-S group ( P = 0.01, P = 0.01, P = 0.04, P = 0.04, and P = 0.03, respectively). Calprotectin, ferritin, neutrophil-to-platelet ratio, and lymphocyte-to-platelet ratio were found to be high in the PEX-S group ( P < 0.01, P = 0.04, P < 0.01, and P < 0.01, respectively). On evaluating the relationship between PEX-S and glaucoma and systemic diseases, it was found that elevated calprotectin increased the risk of glaucoma by 4.36 times and elevated neutrophil-to-lymphocyte ratio (NLR) increased the risk of CVD by 3.23 times in PEX-S patients ( P = 0.02 and P = 0.03, respectively). CONCLUSION: This study demonstrated the value of calprotectin elevation in detecting concomitant glaucoma in PEX-S patients and, in addition, the value of NLR elevation in detecting concomitant CVD.

Evaluation of vitamin B12 levels among severe obese and obese adolescents.

Obesity, whose prevalence is increasing globally, is malnutrition that causes micro/macronutrients and vitamin deficiencies in adolescents. Vitamin B12 plays a prominent role in the body systems such as remethylation, deoxidation, and DNA synthesis. We aimed to examine the relationship between severe obese/obese adolescents and vitamin B12 levels in this study. This study was conducted as a case-control study consisting of 44 obese and 40 healthy control adolescents aged 11-17 years. Obesity was diagnosed using body mass index (BMI) charts defined by the World Health Organization according to age and gender. Vitamin B12 deficiency was found to be 34.1% in the patient obesity group, while it was 12.5% in the control group (p = 0.02). Homeostatic Model Assessment for Insulin Resistance levels were found to be 3.09 (1.9-5.29) higher in the severely obese group (p < 0.001). The median level of vitamin B12 in the obese group was 173 (122.5-220.7) in the severe obese group, 197 (146.5-302.7) in the obese group, and 252.5 (192.8-302) in the control group (p = 0.021). We found that obesity has a 1.6-fold decreasing effect on vitamin B12 levels. This study shows the clinician the importance of monitoring BMI and vitamin B12 levels in obese adolescents, given the effects of vitamin B12 on neuronal migration, metabolic reactions, and many systems in the body. Further researches are needed to investigate the pathophysiology and effect of low vitamin B12 levels in obese adolescents.

Effect of mode of delivery on neonatal oxidative stress and dynamic thiol-disulfide homeostasis.

OBJECTIVE: To evaluate the effect of the mode of delivery on neonatal oxidative stress and dynamic thiol-disulfide homeostasis. METHODS: Sixty women who were followed up in the Obstetrics and Gynecology clinic were included in this prospective study. Cord blood samples were obtained from women who underwent cesarean section (CS) and vaginal delivery (VD). Total oxidant status and total antioxidant status levels were measured by spectrophotometry. The dynamic thiol-disulfide balance was determined by colorimetry. RESULTS: The total antioxidant status and oxidative stress index levels were higher and total oxidant status levels were lower in the VD group compared with the CS group. Native and total thiol levels were higher while disulfide levels were lower in the VD compared with the CS delivery group, while disulfide levels were higher in the CS group. CONCLUSION: These results indicate that disulfide formation leads to decreased antioxidant capacity in women undergoing CS. Monitoring of dynamic thiol-disulfide levels may thus provide clinicians with important information on the oxidative stress status in newborns.

Thiol/disulfide homeostasis as a new oxidative stress marker in patients with Fabry disease.

This is the first study to show both dynamic thiol-disulfide balance and oxidative stress levels in patients with Fabry disease (FD). This prospective study consists of 30 FD patients and 30 healthy controls. Thiol and disulfide values of the study groups were evaluated using a new, cost-effective and fully automatic colorimetric method. A total of 60 subjects were included in the study. A statistically significant difference was found between the patient and control groups for native and total thiol levels (p < 0.001). In addition, disulfide levels were significantly higher in FD patients compared with the control group (p < 0.003). Native thiol levels showed significantly negative correlation with lysosomal globotriaosylceramide, total oxidant status (TOS), and oxidative stress index (OSI) levels. In addition, a positive correlation was found between disulfide/natural thiol and disulfide/total thiol ratios and TOS, OSI, and blood urea nitrogen. We found total antioxidant status levels were lower in the patient group compared to the control group, while TOS and OSI levels were higher and were statistically significant. This study highlights for the first time a novel, cost-effective and fully automated measurement of thiol-disulfide levels in patients with FD. Determination of thiol levels can make important contributions to understand the etiopathogenesis and follow-up of the disease in FD patients.

Evaluation of Oxidative Stress Levels and Dynamic Thiol-disulfide Balance in Patients with Retinopathy of Prematurity.

PURPOSE: The aim of this study is to evaluate both dynamic thiol-disulfide homeostasis and oxidative stress (OS) levels in patients with retinopathy of prematurity (ROP). METHODS: A total of 129 infants of <34 weeks gestational age were enrolled in the present study. The thiol-disulfide homeostasis was determined by using the new, cost-effective and fully automated colorimetric method. Total antioxidant status (TAS), Total oxidant status (TOS) and Oxidative stress index (OSI) levels were evaluated. RESULTS: We found serum TAS levels were lower while serum TOS and OSI levels were significantly higher in patients with ROP compare to the without ROP group (p < .05). However, native, total and disulfide values were not statistically significant between the groups (p > .05). In addition, we also evaluated the native, total and disulfide levels in patients with ROP according to grades and no statistically significant results were found (p > .05). Low birth weight (p = .001), gestational age (p = .001) and 5-min Apgar score were significantly lower in the ROP group. CONCLUSION: This study revealed that dynamic thiol-disulfide homeostasis was changed in patients with ROP. Increased TOS and decreased TAS levels may be associated with functional reduction of the antioxidant system due to increased OS. This indicate that ROP patients are highly sensitive to OS. The dynamic thiol-disulfide homeostasis may conduce to the pathophysiological mechanism and disease follow-up in patients with ROP. The results of this study show that ROP patients are highly sensitive to oxidative stress.

Oxidative Stress Levels and Dynamic Thiol-Disulfide Balance in Preterm Newborns with Bronchopulmonary Dysplasia.

OBJECTIVE: The aim of this study was to assess the oxidative stress (OS) levels and dynamic thiol-disulfide balance in preterm newborns with bronchopulmonary dysplasia (BPD). METHODS: This prospective study included newborns separated into 2 groups, those with BPD (case) or without BPD (control). The 2 groups were compared by clinical and laboratory findings. The OS parameters total oxidant status (TOS), total antioxidant status (TAS), OS index (OSI), native thiol (NT), and total thiol were measured within the first day after birth. Oxygen requirements were measured using the fraction of inspired oxygen (FIO2) recorded in the first hour after birth/admission and the average FIO2 within 28 days of the birth. RESULTS: Infants diagnosed with BPD had a significantly lower gestational age and birth weight and a lower 5-min Apgar score (P < .05). Infants with BPD also had a higher rate of respiratory distress syndrome, rate of use of surfactant therapy, duration of ventilation therapy, and duration of hospital stay compared with control (P = .001, P = .001, P = .001, and P = .001, respectively). Plasma TAS and NT levels of newborns with BPD were significantly lower than newborns without BPD (P < .05). In the BPD group, plasma TOS and OSI levels were significantly higher than in the control group. CONCLUSION: We found that OS was increased in newborns with BPD. The clinical significance of this study will provide the clinician with a different perspective on BPD by determining the dynamic thiol disulfide balance.

Association between thiol-disulfide hemostasis and transient tachypnea of the newborn in late-preterm and term infants.

BACKGROUND: Transient tachypnea of the newborn (TTN), which is the most common respiratory disease in the neonatal period, increases respiratory workload in newborns. We purposed to evaluate the oxidative stress (OS) status and thiol disulfide hemostasis in late preterm and term newborns with TTN in this study. METHODS: The study was carried out in a single-centre neonatal intensive care unit to investigate the effect of continuous airway positive pressure (CPAP) on the oxidative system in newborns with TTN. Thiol (native and total) and disulfide levels, total antioxidant and oxidant status (TAS/TOS) and Oxidative stress index (OSI) levels were measured. RESULTS: Total thiol levels measured before treatment was 429.5 (369.5-487) µmol/L in the late preterm group and 425 (370-475) µmol/L in the term group (p = 0.741). We found significant changes in TOS, OSI and TAS levels after CPAP treatment in the late preterm group (p < 0.001, p < 0.001, p = 0.012 respectively). It was also found that the disulfide level, which was 26.2 (19.2-31.7) before the treatment, decreased to 19.5 (15.5-28.75) after the treatment (p = 0.001) in late preterms. CONCLUSION: CPAP treatment reduced the OS status burden associated with TTN in neonates. The late preterm newborns with TTN are more affected by OS and increased OS levels decrease with CPAP treatment.

Evaluation of thiol-disulfide homeostasis and oxidative stress parameters in newborns receiving phototherapy.

The aim of our study was to evaluate oxidative stress and thiol-disulfide homeostasis in term newborns receiving phototherapy. The study was planned as a single-blind, intervention study in a single center with level 3 neonatal intensive care unit to investigate the effect of phototherapy on the oxidative system in term newborns with hyperbilirubinemia. Neonates with hyperbilirubinemia were treated with total body exposure phototherapy technique for 18 h using a Novos® device. Blood samples of 28 term newborns were taken before and after phototherapy. Total and native thiol, total antioxidant status (TAS) and total oxidant status (TOS), and oxidative stress index (OSI) levels were measured. The 28 newborn patients included 15 (54%) males and 13 (46%) females with a mean birthweight of 3080.1 ± 366.5 g. Native and total thiol levels were found to be decreased in patients receiving phototherapy (p = 0.021, p = 0.010). Besides, significantly lower TAS and TOS levels were found after phototherapy (p < 0.001, p < 0.001). We found that decreased thiol levels were related to increased oxidative stress. We also determined significantly the lower bilirubin levels after phototherapy (p < 0.001). In conclusion, we found that phototherapy treatment induced decreased oxidative stress associated with hyperbilirubinemia in neonates. Thiol-disulfide homeostasis can be used as a marker of oxidative stress due to hyperbilirubinemia in the early period.

Evaluation of thiol disulfide balance in adolescents with vitamin B12 deficiency.

BACKGROUND: Vitamin B12 is an important vitamin for metabolism and affects many mechanisms in the body including neuronal migration, DNA synthesis, neurotransmitter synthesis, brain and cognitive development. Increased oxidative stress in the body leads to the damage of the child development, but also plays a crucial role in the pathogenesis of many diseases encountered in the childhood period. Our aim is to investigate whether or not B12 deficiency is associated with dynamic thiol/disulfide homeostasis in adolescent patients. METHODS: This is a case-controlled observational study consisting of 45 adolescent patients with vitamin b12 deficiency and a control group consisting of 45 healthy adolescent. Patients between 11 and 18 ages who applied to the outpatient clinic for the first time with one of the complaints of headache were selected due to their decreased school performance, dizziness, and fatigue. Hemogram, vitamin B12, homocysteine levels and oxidative stress parameters such as native and total thiol disulfide levels and ratios of disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol were measured from the patients. RESULTS: Vitamin B12 level was found to be significantly lower in vitamin B12 deficiency group (p < 0.001). The serum disulfide level was found to be 27.5 ± 8.38 in the case group and 20.5 ± 8.36 in the control group (p < 0.001). In the multiple linear regression analysis, it was determined that the independent variables of native thiol, homocysteine and disulfide levels effected of vitamin B12 levels (p < 0.001, p < 0.001, p < 0.005 respectively; R2 = 0.62). CONCLUSION: The results obtained in terms of the effect of vitamin B12 deficiency on oxidative stress in adolescents are remarkable. The increase in oxidative stress parameters in the patient group may also suggest that oxidative stress plays a vital role in vitamin B12 deficiency in adolescence.

Evaluation of dynamic thiol-disulfide homeostasis and ischemia-modified albumin levels in patients with chronic lymphocytic leukemia.

This is the first study to evaluate both the dynamic thiol-disulfide homeostasis and ischemia-modified albumin (IMA) levels in patients with chronic lymphocytic leukemia (CLL). Twenty-nine patients with CLL and 20 controls were included in the study. The dynamic thiol-disulfide balance was determined by the newly developed colorimetric method by Erel. IMA levels were determined by the cobalt binding test. We found that total antioxidant status levels were lower while total oxidant status (TOS) and oxidative stress index (OSI) levels were significantly higher in patients with CLL than controls. Moreover, native and total thiol levels were found to be statistically significant between the study and control groups (p<0.001), whereas no statistically significant difference was noted for IMA levels (p=0.365). A negative correlation was observed between native and total thiol levels, leukocyte, lymphocyte, and TOS. Total bilirubin showed positive correlation with direct bilirubin and alkaline phosphatase. In addition, IMA levels showed a positive correlation with OSI. This study highlights measurement of native and total thiol and IMA levels in patients with CLL for the first time. Dynamic thiol-disulfide homeostasis may contribute in the pathophysiological mechanism, and follow-up to disease in patients with CLL.

Determination of Serum Perfluorooctanoic Acid and Perfluorooctanesulfonic Acid Levels with Different Stages of Chronic Kidney Disease.

The aim of this study is to investigate the perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) levels in patients with different stages of chronic kidney disease (CKD). Sixty-one CKD stage 1-4 patients who applied to the nephrology outpatient clinic were recruited. A control group consisting of 26 age- and sex-matched healthy controls were also included in the study. Concentrations of PFOA and PFOS were determined by comparing their peak areas with their standard curves. All samples were analyzed three times. The average values of blank samples were subtracted from the detected PFOA and PFOS values. PFOA and PFOS levels were significantly higher in CKD group than the controls (11.4 ± 7.47, 0.45 ± 0.55; 0.13 ± 0. 17, 0.19 ± 0.4 ng/mL, respectively) (P = 0.001). Hemoglobin, serum albumin, and estimated glomerular filtration rate (eGFR) levels were significantly lower and potassium and uric acid levels were higher in the CKD group than the controls. PFOA and PFOS levels were significantly higher in all stages of CKD patients than healthy controls. However, there was no correlation between eGFR, and PFOS and PFOA. We have demonstrated significantly increased PFOA and PFOS concentrations in different stages of CKD patients. We could not find an association between eGFR, age, and serum PFOS and PFOA concentrations.

Plasma Ischemia-Modified Albumin Levels and Dynamic Thiol/Disulfide Balance in Sickle Cell Disease: A Case-Control Study

Objective: Sickle cell disease (SCD), described as a group of inherited blood disorders, affects millions of people throughout the world and is particularly common in the southern part of Turkey. We aimed to determine the relationship between ischemia-modified albumin (IMA) and the dynamic thiol/disulfide balance in SCD. Materials and Methods: Fifty-four adult SCD patients and 30 healthy controls were included in the study. The 54 adult patients included 30 (56%) males and 24 (44%) females with a mean age of 28.3±8.4 years (minimum-maximum: 18-46 years). Of the 54 patients, 46 had homozygous sickle cell anemia (HbSS) and 8 had sickle/ß-thalassemia (HbS/ß+-thalassemia). Fasting blood samples were collected. After centrifugation at 1500×g for 10 min, plasma samples were portioned and stored at -80 °C. IMA levels were determined by albumin cobalt binding test, a colorimetric method. Total and native thiols and disulfide were analyzed with a novel spectrophotometric method. Results: We found significantly lower levels of native thiol (-SH) (284.0±86.3 µmol/L), disulfide levels (14.6±7 µmol/L), and total thiols (-SH + -S-S-) (313.0±89.3 µmol/L) in SCD patients compared to healthy controls (respectively 417.0±54.2, 22.7±11.3, and 462.0±58.7 µmol/L). Plasma albumin levels (34.9±7.9 g/L) were lower and IMA levels (13.6±3.1 g/L) were higher in SCD patients compared to controls (respectively 43.5±3.1 and 8.4±1.6 g/L). Plasma albumin levels were strongly correlated with both plasma native (r=0.853; p=0.0001) and total thiols (r=0.866; p=0.0001). Conclusion: Decreased plasma native and total thiol levels and increased IMA levels are related to increased oxidative stress and provide an indirect and quick reflection of the oxidative damage in SCD patients.

The Effect of Pneumatic Tube Systems on the Hemolysis of Biochemistry Blood Samples.

Pneumatic tube systems (PTSs) are widely used in many hospitals because they lead to reduced turnaround times and cost efficiency. However, PTSs may affect the quality of the blood samples transported to the laboratory. The aim of this study was to investigate the effect of the PTS used in our hospital on the hemolysis of the biochemical blood samples transported to the laboratory. METHODS: A total of 148 samples were manually transported to the laboratory by hospital staff, 148 samples were transported with the PTS, and 113 were transported with the PTS without use of sponge-rubber inserts (PTSws). Hemolysis rates and the levels of biochemical analytes for the different transportation methods were compared. RESULTS: No significant difference was found between the samples transported manually and with the PTS with regard to hemolysis rate and the levels of biochemical analytes. However, the samples transported with the PTSws showed a significant difference compared with the samples transported manually and with the PTS with regard to hemolysis rate and potassium and lactate dehydrogenase levels. The percentages of the samples that exceeded the permissible threshold for the hemolysis among the samples transported manually, with the PTS, and with the PTSws were 10%, 8%, and 47%, respectively. DISCUSSION: A PTS can be used safely for transporting biochemistry blood samples to the laboratory. However, a sponge-rubber insert that holds sample tubes must be used with the PTS to prevent the hemolysis of blood samples.

Cancer cell sensing and therapy using affinity tag-conjugated gold nanorods.

Through the developments in controlling the shape of gold nanoparticles, synthesis of gold nanorods (AuNRs) can be considered as a milestone discovery in the area of nanomaterial-based cancer treatments. Besides having tuneable absorption maxima at near infrared (NIR) range, AuNRs have superior absorption cross section at NIR frequencies compared with other gold nanoparticles. When this unique optical property is combined with the specificity against cancer cells used by affinity tag conjugations, AuNRs become one of the most important nanoparticles used in both cancer cell sensing and in therapy. In this review, the impact of size and shape control of nanoparticles, especially AuNRs, on cancer cell treatments and a range of aptamer-conjugated AuNR applications in this regard are reviewed.