Mustafa Yilmaz

Biomarkers of Systemic Inflammation in Stable and Exacerbation Phases of COPD

Apart from the deleterious effects on the lungs, chronic obstructive pulmonary disease (COPD) should be considered a complex, systemic disease involving several organs and systems. The nature and course of systemic inflammation in COPD is important since there is a potential for anti-inflammatory therapy. The objective of the current study was to assess biomarkers of systemic inflammation in stable and exacerbation phases of COPD patients as compared to healthy controls. We also investigated the course of these biomarkers after COPD exacerbation to evaluate their usefulness for disease monitoring. Eighty-three stable patients with moderate to very severe COPD, 20 patients in exacerbation phase, and 30 subjects with normal pulmonary function were included. Serum tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) levels were measured once in stable COPD patients and controls and three times in the COPD exacerbation group during follow-up. TNF-α and IL-6 levels were higher than in controls in both stable and exacerbation groups. Although NO was not higher in the stable COPD group than in controls, it was higher in the exacerbation group. In follow-up after the exacerbation period, significant alteration was not detected in cytokine or NO levels compared to admission. Raised serum levels of TNF-α and IL-6 support their use as biomarkers of the systemic inflammatory response in stable COPD patients. However, the circulating biomarkers we have studied are not found to be useful either as indicators of COPD exacerbation or for monitoring recovery after exacerbation.

Sex hormone alterations and systemic inflammation in chronic obstructive pulmonary disease

Objective:u2002 Decreased anabolic hormone levels are described in chronic obstructive pulmonary disease (COPD), leading to important clinical consequences. The aim of this study was to evaluate the alterations in sex hormone levels in men with COPD to compare with age‐matched control subjects, the determinants of these alterations, the relationship between hypogonadism and markers of systemic inflammation [interleukin‐6 (IL‐6) and tumour necrosis factor alpha (TNF‐α)] and the androgen status during an acute exacerbation of COPD.

Topiramate and vitamin e modulate antioxidant enzyme activities, nitric oxide and lipid peroxidation levels in pentylenetetrazol-induced nephrotoxicity in rats.

Previous studies have shown that generation of free radicals is increased following pentylenetetrazol kindling, due to increased cytosolic Ca2+ concentrations. Topiramate, a voltage-gated calcium channel inhibitor, has an evident effect in the treatment of childhood epilepsy; however, topiramate may cause nephrotoxicity. We investigated the effects of topiramate and vitamin E administration on pentylenetetrazol-induced nephrotoxicity in rats by evaluation of lipid peroxidation, nitric oxide, glutathione peroxidase, catalase and superoxide dismutase values. Forty male Wistar rats were randomly divided into five equal groups. Group 1 was used as control and group II received a single dose of pentylenetetrazol. Fifty and 100 mg/kg topiramate daily were intragastrically administered to rats in groups III and IV for 7 days, respectively. Intragastric 100 mg topiramate (daily for 7 days) and intraperitoneal vitamin E (150 mg/kg, daily for 3 days) combination were given to animals in group V before a single-dose pentylenetetrazol administration. Serum and kidney samples were taken after 3 hr of pentylenetetrazol administration. Pentylenetetrazol resulted in a significant increase in nitric oxide levels of serum and kidney, and lipid peroxidation levels of kidney although superoxide dismutase and catalase activities in the kidney was reduced by pentylenetetrazol administration. The lipid peroxidation levels in serum and kidneys and the nitric oxide levels in kidneys of groups III, IV and V were decreased by topiramate although the superoxide dismutase and catalase activities in the kidneys were increased. Lipid peroxidation and nitric oxide levels were reduced by the topiramate and vitamin E combination compared to only topiramate. Glutathione peroxidase activity was not affect by pentylenetetrazol, topiramate and vitamin E administrations. In conclusion, topiramate and vitamin E have protective effects on pentylenetetrazol-induced nephrotoxicity by inhibition of free radicals and by support of the antioxidant redox system.

Diazinon-induced brain toxicity and protection by vitamins E plus C

Diazinon (DI) is a widely used pesticide in agriculture, resulting in environmental deleterious effects on neural systems. The current study was performed to investigate the effects of treatment with vitamins E plus C on brain toxicity, which is possibly induced by DI. Twenty-one male rats were divided into three groups (n = 7/group) as follows: (1) control group (C); (2) DI-treated group (DI); (3) DI + vitamins E plus C-treated group (DI + Vit). In order to examine lipid peroxidation and antioxidant status in rats, the level of malondialdehyde (MDA), activities of two free radical scavanging enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) have been studied in brain of rat. The results showed that treatment with DI induced significant (p < 0.05) increases in the level of serum MDA in rat brain. The vitamins E plus C combination reduced lipid peroxidation in rat brain. The activity of SOD level was significantly higher in DI + Vit group, compared to the control group. GSH-Px, SOD and CAT values were not significantly different in the DI group than in control. Oxidative stress contributes to DI-induced brain toxicity. Our results suggested that vitamins E plus C combination may have a protective effect on DI-induced brain toxicity.

Calorie restriction modulates hippocampal NMDA receptors in diet-induced obese rats

Calorie restriction (CR) has attracted increased interest since CR enhances lifespan and alters age-related decline in hippocampal-dependent cognitive functions. Obesity is associated with poor neurocognitive outcome including impaired hippocampal synaptic plasticity and cognitive abilities such as learning and memory. N-Methyl-d-aspartate receptors (NMDARs) are linked to hippocampal-dependent learning and memory, which may be stabilized by CR. In the present study, we aimed to establish the effects of CR on NMDARs in CA1 region of hippocampus in obese and non-obese rats. In addition, malondialdehyde (MDA) levels were determined as a marker for lipid peroxidation (LPO) in hippocampus. Four groups were constituted as control group (C, nu2009=u20099), obese group (OB, nu2009=u200910), obese calorie-restricted group (OCR, nu2009=u20099), and non-obese calorie-restricted group (NCR, nu2009=u200910). OCR and NCR were fed with a 60% CR diet for 10 weeks. After 10 weeks of CR, the MDA levels significantly decreased in the calorie-restricted groups. Obesity caused significant decreases in NR2A and NR2B subunit expressions in the hippocampus. The hippocampal NR2A and NR2B levels significantly increased in the OCR group compared with the OB group (Pu2009<u20090.05). In contrast, the hippocampal NR2A and NR2B levels significantly decreased in the NCR group compared with the C group (Pu2009<u20090.05). Oxidative stress can be prevented by CR, and these data may provide a molecular and cellular mechanism by which CR may regulate NMDAR-mediated response against obesity-induced changes in the hippocampus.

Effects of Venlafaxine and Escitalopram Treatments on NMDA Receptors in the Rat Depression Model

Depression may relate to neurocognitive impairment that results from alteration of N-methyl-d-aspartate receptor (NMDAR) levels. Venlafaxine and escitalopram are two drugs commonly used to treat depression. The drugs may affect expression of NMDARs, which mediate learning and memory formation. The aim of the study was to examine whether the effects of venlafaxine and escitalopram treatments are associated with NMDARs in a rat model of depression. Forty male Wistar albino rats were randomly divided into four groups (nxa0=xa010) as follows: control group, chronic mild stress group (CMS), venlafaxine (20xa0mg/kg body weight per day)xa0+xa0CMS, and escitalopram (10xa0mg/kg body weight per day)xa0+xa0CMS. After induction of depression, a decrease in the concentration of NR2B was observed; venlafaxine treatment prevented the reduction of NR2B expression. Escitalopram treatment did not effect the reduced levels of NR2B resulting from depression. There was no significant difference in NR2A concentration among groups. The present data support the notion that venlafaxine plays a role in maintaining NR2B receptor in experimental depression. It may be possible that treatment with escitalopram has no effect on NMDARs in experimental depression.

Biochemical and Histological Effects of Thiamine Pyrophosphate against Acetaminophen-Induced Hepatotoxicity.

The aim of this study was to investigate whether thiamine pyrophosphate (TPP) has biochemical and histological preventive effects on oxidative liver damage induced by paracetamol (APAP). Rats were divided into the following groups: healthy control (HG), APAP (AG, 1500 mg/kg, orally), thiamine pyrophosphate (TPPG, 100 mg/kg, intraperitoneally), APAP+NAC (ANAC, 100 mg/kg, intraperitoneally), APAP+TPP (ATPG) and APAP+NAC+TPP (ANTG). Oxidant, antioxidant parameters, liver function tests and histological assessment were performed between groups. Malondialdehyde levels in the AG, HG, TPPG, ANAC, ATPG and ANTG groups were 0.470 ± 0.210, 0.213 ± 0.004, 0.194 ± 0.001, 0.197 ± 0.06, 0.199 ± 0.008 and 0.173 ± 0.010 μmol/g protein, respectively. Total glutathione levels were 7.787 ± 0.395, 14.925 ± 0.932, 13.200 ± 0.984, 13.162 ± 0.486, 13.287 ± 0.787 and 13.500 ± 0.891 μm/g protein, respectively. In the AG group, marked liver damage occurred with the elevation of liver function tests and oxidative stress markers, such as malondialdehyde, myeloperoxidase and nitric oxide (p < 0.05). Biochemical results were congruent with the histological changes of oxidative damage. Compared to the AG group (p < 0.05), TPP significantly reduced oxidant parameter levels in the ATPG group and simultaneously increased the antioxidant parameter levels of catalase and glutathione. The histological changes were improved to almost normal hepatic structure. Moreover, TPP had nearly the same hepatoprotective effect as NAC, and there was statistically no additional benefit with NAC co‐treatment. There was no statistically significant difference (p > 0.05) among the ANAC, ANTG and ATPG groups in terms of oxidant/antioxidant levels. TPP proved to be as efficacious as standard therapy and may be beneficial in APAP‐induced hepatotoxicity.

Comparison of different methods for measurement of electrolytes in patients admitted to the intensive care unit

Objectives: To investigate whether electrolyte levels measured by using blood gas analyzers (ABG) and auto-analyzers (AA) are equivalent and can be used interchangeably. Methods: This observational prospective study was conducted in 100 patients admitted to the Intensive Care Unit, Adnan Menderes University School of Medicine, Aydin, Turkey, between March and August 2014. Samples for both AA and ABG analyzers were collected simultaneously from invasive arterial catheters of patients. The electrolyte levels were measured by using 2 methods. Results: The mean sodium level measured by ABG was 136.1±6.3 mmol/L and 137.8±5.4 mmol/L for AA (p=0.001). The Pearson’s correlation coefficient was 0.561 (p<0.001). The Bland-Altman 95% limits of agreement were -9.4 to 12.6 mmol/L. The mean potassium levels measured by ABG was 3.4±0.7 mmol/L and AA was 3.8±0.7 mmol/L (p=0.001). The Bland-Altman comparison limits were -0.58 to 1.24 and the associated Pearson’s correlation coefficient was 0.812 (p<0.001). Conclusion: The results of the 2 analyzing methods, in terms of sodium, were not equivalent and could not be used interchangeably. However, according to the statistical analyses results, by including, but not blindly trusting these findings, urgent and vital decisions could be made by the potassium levels obtained from the BGA, but a simultaneous follow-up sample had to be sent to the central laboratory for confirmation.

Comparison of the effect of gel used in two different serum separator tubes for thyroid function tests

Selection and verification of blood collection tubes is an important preanalytical issue in clinical laboratories. Today, gel tubes are commonly used with many advantages, although they are known to cause interference in immunoassay methods. In this study, we aimed to compare SSTs of two different suppliers (Ayset clot activator & Gel and Becton Dickinson (BD) Vacutainer SST II advance) with reference tubes and evaluate the effect of storage time in terms of commonly used endocrine tests such as thyroid‐stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3).

Effect of Ozone in Freund’s Complete Adjuvant-Induced Arthritis

ObjectivesnThis study aims to investigate the effectiveness and reliability of ozone (O3) in Freunds complete adjuvant (FCA)-induced arthritis, an animal model for rheumatoid arthritis.nnnPatients and methodsnThirty-six four- to five-month-old male Wistar rats weighing between 274-420 gr were used in this study. Saline was injected into the hind paws of half of these rats, and FCA was injected into the other half. At the end of two weeks, 40 μg of O3 was administered to nine rats from each group twice a week for seven total doses. The rats were followed-up in terms of clinical findings. At the sixth week, the rats were sacrificed and serum malondialdehyde, glutathione peroxidase, and superoxide dismutase levels were measured. In addition, ankle joints were separated for histopathological examination.nnnResultsnSignificant improvement was observed in terms of hind-paw diameter, severity of arthritis, and histopathological findings of inflammation after O3 treatment in the group with FCA-induced arthritis. Although it was not quite significant, an upward trend was detected in oxidative stress markers with O3 treatment.nnnConclusionnThis study, the first to investigate the effects of systemic O3 on the clinical and histopathological outcomes of rheumatoid arthritis, indicates that O3 is a highly effective and reliable treatment method in FCA-induced arthritis in animal models.