Gulcin Eskandari

Liver and kidney toxicity in chronic use of opioids: An experimental long term treatment model

In this study, histopathological and biochemical changes due to chronic usage of morphine or tramadol in liver and kidney were assessed in rats. Thirty male Wistar rats (180–220 g) were included and divided into three groups. Normal saline (1 ml) was given intraperitoneally as placebo in the control group (n = 10). Morphine group (n = 10) received morphine intraperitoneally at a dose of 4, 8, 10 mg/kg/day in the first, second and the third ten days of the study, respectively. Tramadol group (n = 10), received the drug intraperitoneally at doses of 20, 40 and 80 mg/kg/day in the first, second and the third ten days of the study, respectively. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatinin, blood urea nitrogen (BUN) and malondialdehyde (MDA) levels were measured in the serum. Liver and kidney specimens were evaluated by light microscopy. Serum ALT, AST, LDH, BUN and creatinin levels were significantly higher in morphine group compared to the control group. Serum LDH, BUN and creatinin levels were significantly increased in the morphine group compared to the tramadol group. The mean MDA level was significantly higher in morphine group compared to the tramadol and control groups (P<0.05). Light microscopy revealed severe centrolobular congestion and focal necrosis in the liver of morphine and tramadol groups, but perivenular necrosis was present only in the morphine group. The main histopathologic finding was vacuolization in tubular cells in morphine and tramadol groups. Our findings pointed out the risk of increased lipid peroxidation, hepatic and renal damage due to long term use of opioids, especially morphine. Although opioids are reported to be effective in pain management, their toxic effects should be kept in mind during chronic usage

Effects of apolipoprotein E genotypes and other risk factors on the development of coronary artery disease in Southern Turkey.

BACKGROUND Apolipoprotein E (apoE) plays a major role in lipoprotein metabolism and lipid transport. Associations between apoE genotypes, coronary artery disease (CAD) and other risk factors have been described by many investigators. The aim of this study was to investigate the role of apoE gene polymorphism and other risk factors in the development of CAD in subjects whose coronary arteries were evaluated by means of coronary angiography. METHODS The study population consisted of 199 subjects (114 male and 55 female). Of the total, 107 had CAD. The apoE gene was amplified by polymerase chain reaction (PCR) and then digested by CfoI restriction enzyme. The plasma lipid levels and other risk factors were also determined in all subjects. RESULTS The epsilon2 and epsilon4 allele frequencies and genotypes carrying epsilon4 allele were significantly higher in CAD (+) patients. Plasma lipids except triglycerides were increased in CAD (+) cases. We found that apoE genotypes, HT, DM, male gender, age and smoking were the independent predictors of CAD. There was no association between apoE alleles and lipids. CONCLUSION We conclude that apoE polymorphism (presence of epsilon4 allele) is associated with the development of CAD in Southern Turkey. In our study, we did not observe any effect of apoE alleles on lipid levels.

Oxidant/antioxidant status in patients with recurrent aphthous stomatitis.

Recurrent aphthous stomatitis (RAS) is recognized as one of the most common oral mucosal diseases worldwide. The aim of this study was to determine the oxidant/antioxidant status in erythrocyte and plasma samples from patients with RAS in comparison with healthy controls. Twenty‐two patients with RAS and 23 healthy controls were recruited. Superoxide dismutase, glutathione peroxidase (GSHPx) and catalase (CAT) activities, and malondialdehyde (MDA) and antioxidant potential (AOP) levels were measured in plasma and erythrocytes from patient with RAS and controls. We found decreased CAT and GSHPx activities and AOP levels in the erythrocytes, and decreased AOP and increased MDA plasma levels in patients with RAS in comparison with control subjects. In summary, this study demonstrated that enzymatic and nonenzymatic antioxidant defence systems are impaired in patients with RAS.

In vivo effects of meloxicam, celecoxib, and ibuprofen on free radical metabolism in human erythrocytes.

Abstract One of the major groups of chemical mediators involved in the inflammatory response is the prostaglandins, which are synthesized from arachidonic acid by the enzyme cyclooxygenase. The aim of this study is to compare the in vivo effects of celecoxib, meloxicam, and ibuprofen on the activities of catalase (CAT), glutathione peroxidase (GSHPx), superoxide dismutase (SOD) as well as malondialdehyde (MDA), and antioxidant potential levels (AOP) in human erythrocytes. Patients diagnosed as osteoarthritis were included in the study. Patients were treated with Celecoxib (200 mg/d) (n = 12), Meloxicam (15 mg/d) (n = 12), and Ibuprufen (1200 mg/d) (n = 9) for 21 days. SOD, CAT, GSHPx activities, MDA, and AOP levels were investigated in human erythrocyte haemolysates. SOD activity and AOP levels were significantly decreased in all NSAID groups when we compared the values before and after 21 days of celecoxib, meloxicam, ibuprofen treatment. There were no significant difference in CAT, GSHPx activities, and MDA levels before and after treatment in each group. Decreased SOD activities are thought to be related with the increased superoxide anion. Decreased AOP levels may indicate impairment in the total antioxidant defence system. These NSAIDs have similar effects on free radical metabolism on human erythrocytes; despite some difference in action mechanisms.

Serum leptin levels in patients with allergic rhinitis

OBJECTIVE: To investigate the serum leptin levels in patients with allergic rhinitis during the symptomatic period. STUDY DESIGN AND SETTING: A randomized, prospective study was performed on 26 adult patients with allergic rhinitis and 20 control subjects with similar age, sex and body mass index in a tertiary otolaryngology center. RESULTS: Leptin levels were 28.8 ± 14.1 ng/mL in the patients with allergic rhinitis, and 20.8 ± 13.5 ng/mL in the control group respectively. The difference between the groups was statistically significant (p = 0.04). CONCLUSION: Serum leptin levels were found to be significantly higher in patients with allergic rhinitis in symptomatic period. SIGNIFICANCE: Apart from its primary role in the regulation of body weight and energy expenditure, leptin may have a role in the inflammatory process of the allergic rhinitis.

Comparison of ischemic and chemical preconditioning in jejunal flaps in the rat.

Jejunum is one of the most frequently used free flaps in esophagus reconstruction. However, the sensitivity of intestinal tissue to ischemia decreases the margin of safety of this donor site while increasing the risk of postoperative complications such as fistula formation and stenosis. Ischemic preconditioning can increase the tolerance of jejunal tissue to ischemia. In this study, the authors investigated the effects of chemical preconditioning with adenosine infusion on ischemia reperfusion injury in the rat jejunum, and evaluated the presence of any additive effects of adenosine administration when used together with ischemic preconditioning. Forty Sprague-Dawley rats weighting 200 to 250 mg were used in the study. Rats were randomly divided into five groups. In group I (sham-operated controls), only laparotomy was performed. In group II (ischemia-reperfusion injury), the superior mesenteric artery was clamped for 40 minutes to induce ischemia in the small bowel, followed by 60 minutes of reperfusion. In group III (ischemic preconditioning), two cycles of 5-minute ischemia and 5-minute reperfusion were performed before implementation of the ischemia-reperfusion protocol used in group II. In group IV (chemical preconditioning), adenosine (1000 &mgr;g/kg) was infused into the internal jugular vein before the group II ischemia-reperfusion schedule was implemented. In group V (adenosine-enhanced ischemic preconditioning), adenosine (1000 &mgr;g/kg) was infused into the internal jugular vein before ischemic preconditioning, followed by 40 minutes of ischemia and 60 minutes of reperfusion. At the end of the reperfusion period, samples from the jejunum were harvested and myeloperoxidase activity was determined as a measure of leukocyte accumulation. Malondialdehyde levels were measured to assess lipid peroxidation. Histopathologic sections stained with hematoxylin-eosin were evaluated for the presence of mucosal damage according to the Chiu scoring method. Immunohistochemical staining by M30 monoclonal antibodies was performed to quantify the number of ischemia-induced apoptotic cells in the intestinal mucosa. The myeloperoxidase and malondialdehyde levels were significantly lower in groups I, III, IV, and V when compared with group II. Although there were no significant differences among myeloperoxidase and malondialdehyde levels in groups III, IV, and V, group I had significantly lower levels of activity compared with the other three groups. Histological scoring reflected significantly less damage in groups I, III, IV, and V compared with group II. Similarly, the number of apoptotic cells was significantly lower in groups I, III, IV, and V when compared with group II. However, no difference was detected among these four groups with regard to either histopathological scoring or apoptosis numbers. This is the first study showing that adenosine administration is as effective as ischemic preconditioning in inducing ischemic tolerance in the rat jejunum. However, there was no enhancement of ischemic preconditioning with prior adenosine infusion.

Effects of venlafaxine and fluoxetine on lymphocyte subsets in patients with major depressive disorder: A flow cytometric analysis

BACKGROUND Studies have yielded conflicting results concerning flow cytometric lymphocyte analyses in patients with depression. Data about the effect of antidepressants on lymphocyte subsets are also contradictory. The aim of this study was to determine effects of venlafaxine versus fluoxetine on lymphocyte subsets in depressive patients. METHODS Sixty-nine patients diagnosed with major depressive disorder (MDD) according to DSM-IV and 36 healthy controls are included in the study. Sixty-nine patients were randomized to take fluoxetine (FLX) (n=33) or venlafaxine (VEN) (n=36). Serum lymphocyte subsets included CD3, CD4, CD8, CD16/56, CD19, CD45, Anti-HLA-DR which were measured by flow cytometric analyses at baseline and 6 weeks after the start of treatment. The severity of depression was evaluated with Hamilton rating scale for depression. RESULTS At baseline, patients with MDD had significantly lower CD16/56 ratio and higher CD45 ratio compared to the controls. Although numerically higher in the VEN treated patients, treatment response rates between the FLX (53%) and the VEN (75%) groups were not different statistically. CD45 values decreased significantly in the VEN group at the end of the 6 week treatment period whereas no difference was observed in the FLX group. By the 6th week, treatment responders showed a significantly higher CD16/56 ratio than non-responders. Baseline severity of depression and anxiety was positively correlated with baseline CD45 ratio and negatively correlated with baseline CD16/56 ratio. We did not observe consistent changes in the absolute number of circulating B or T cells, nor in the helper/inducer (CD4) or suppressor/cytotoxic (CD8) subsets. CONCLUSIONS CD16/56 was lower in patients with MDD and increased in treatment responders at 6th week. CD45 ratio was higher in patients with MDD than healthy subjects; it decreased with antidepressant treatment and was positively correlated with the severity of depression. Antidepressant treatment contributes to immune regulation in patients with major depressive disorder.

Apolipoprotein E polymorphism and lipoprotein compositions in normolipidaemic xanthelasma patients.

Background  Apolipoprotein E (apoE) phenotypes and lipoprotein compositions in xanthelasma patients have been reported in different series.

N‐acetyltransferase 2 polymorphisms in patients with Behcet's disease

It is possible that dietary, environmental factors and/or genetic polymorphisms in xenobiotic‐metabolizing enzymes may contribute to the development of Behcets disease. As N‐acetyltransferase (NAT) 2 is an important xenobiotic‐metabolizing enzyme and theoretically the nonacetylated xenobiotics may induce an autoimmune mechanism, the aim of the present study was to investigate whether the genetic polymorphism of NAT2 plays a role in susceptibility to Behcets disease. Forty Behcets disease patients and 82 control subjects were enrolled in the study. NAT2*5A, NAT2*6A, NAT27*A/B and NAT2*14A polymorphisms were detected by using real time PCR with LightCycler (Roche Diagnostics GmbH, Mannheim, Germany). The NAT2*5A and NAT2*6A mutant genotypes carried an increased risk of developing Behcets disease [odds ratio (OR) = 66.29, 95% confidence interval (CI) = 8.21–535.33; and OR = 24; 95% CI = 2.04–304.98, respectively]. The NAT2*7A/B and NAT2*14A gene polymorphisms were not an increased risk for developing Behcets disease. As a result of this study we conclude the NAT2 slow acetylator status may be a determinant in susceptibility to Behcets disease. This finding may have implications for the theories of the pathogenesis of the disease as well as for therapeutic aspects.

Association of the platelet glycoprotein Ia C807T/G873A gene polymorphism and thrombosis in Behçet patients.

Thrombosis is a common complication of Behçet disease and the pathogenic mechanism of thrombotic tendency in Behçet disease is not well known. Several platelet membrane glycoprotein gene polymorphisms have been identified as risk factors for thrombosis. This study aimed to evaluate the possible role of the GP Ia C807T/G873A polymorphism as a risk factor for thrombosis in Behçet disease. We determined the prevalence of platelet glycoprotein Ia C807T/G873A gene polymorphism in Behçet patients. Genomic DNA was obtained from 20 patients with Behçet disease and 61 controls. All individuals were of Turkish ancestry and were genotyped for the GP Ia C807T/G873A polymorphism with real-time PCR method by LightCycler system. The 807 CC, CT and TT genotypes corresponded with 873 GG, GA and AA genotypes, respectively. Complete linkage between the 807 and 873 sites was found in all samples. The 807CC(873 GG), 807CT(873GA), 807TT(873AA) genotypes found to be 45.9%, 45.9% and 8.1% in controls and 30.0%, 55.0% and 15.0% in patients with Behçet disease, respectively. The Odds Ratio for BD (OR = 1.97; 95% confidence interval (CI): 0.42-9.13) is high for the 807 TT genotype compared with controls. Thrombosis was found in 7 cases of Behçet disease group: five cases have 807CT, one case has 807TT genotype and one case has 807CC genotype. Our data indicate hat patients with BD are affected by the glycoprotein Ia gene 807TT genotypes and carrying 807T allele. The risk of thrombosis is significantly higher in patients who have 807TT and 807CT genotypes than in patients who have 807CC genotype.