Ümit Türkoğlu

The impact of age, vitamin D3 level, and incidental parathyroidectomy on postoperative hypocalcemia after total or near total thyroidectomy

BACKGROUND Hypocalcemia caused by transient or definitive hypoparathyroidism is the most frequent complication after thyroidectomy. We aimed to compare the impact of incidental parathyroidectomy and serum vitamin D(3) level on postoperative hypocalcemia after total thyroidectomy (TT) or near total thyroidectomy (NTT). PATIENTS Two hundred consecutive patients with nontoxic multinodular goiter treated by TT and NTT were included prospectively in the present study. Group 1 (n = 49) consisted of patients with a postoperative serum calcium level < or =8 mg/dL, and group 2 (n = 151) had a postoperative serum calcium level greater than 8 mg/dL. Patients were evaluated according to age, preoperative serum 25-hydroxy vitamin D (25-OHD) levels, postoperative serum calcium levels, incidental parathyroidectomy, and the type of thyroidectomy. RESULTS Patients in group 1 (n = 49) were hypocalcemic, whereas patients in group 2 (n = 151) were normocalcemic. Preoperative serum 25-OHD levels in group 1 were significantly lower than in group 2 (P < .001). The incidence of hypoparathyroidism was significantly higher following TT (13.5%) than following NTT (2.5%) (P < .05). The risk for postoperative hypocalcemia was increased 25-fold for patients older than 50 years, 28-fold for patients with a preoperative serum 25-OHD level less than 15 ng/mL, and 71-fold for patients who underwent TT. Incidental parathyroidectomy did not have an impact on postoperative hypocalcemia. The highest risk of postoperative hypocalcemia was found in the patients with all of the above variables. CONCLUSIONS Age, preoperative low serum 25-OHD, and TT are significantly associated with postoperative hypocalcemia. Patients with advanced age and low preoperative serum 25-OHD levels should be placed on calcium or vitamin D supplementation after TT to avoid postoperative hypocalcemia and decrease hospital stay.

Nitric oxide and radiation enteritis.

OBJECTIVE To investigate the changes in intestinal nitric oxide (NO) and myeloperoxidase (MPO) concentrations, the rate of endotoxaemia, and intestinal mucosal structure in rats after irradiation of the abdomen and to find out the effect of Nomega-nitroarginine methyl ester (L-NAME) inhibition NO synthesis. SETTING Medical school, Turkey. DESIGN Experimental study. MATERIAL 46 Wistar-albino rats. INTERVENTIONS In Group I (n = 12), rats underwent abdominal irradiation alone. In Group II (n = 12), they underwent abdominal irradiation and were given L-NAME orally for 3 days before and 3 days after irradiation. In Group III (n = 12), rats had abdominal irradiation and were given L-NAME orally for 3 days after irradiation. Group IV (n = 10) were controls and were untreated. The irradiation procedure consisted of a single shot of 1000 cGy to the abdomen and L-NAME was given 30 mg/kg/day orally in the drinking water. MAIN OUTCOME MEASURES Intestinal mucosal MPO and nitrite, and plasma endotoxin concentrations. Changes in villous height and number were recorded. RESULTS In groups II and III, MPO and NO2- concentrations decreased significantly compared with group I. Mucosal integrity was protected in both groups treated with L-NAME (groups II and III) in contrast to the group given irradiation without treatment (group I). CONCLUSION These results suggest that the NO pathway contributes to the inflammatory response of radiation enteritis. Inhibition of NO synthesis may have a beneficial effect in the treatment of inflammation caused by irradiation.

Thymosin α1 protects liver and aorta from oxidative damage in atherosclerotic rabbits

Abstract The thymus hormones were reported to be effective on lipid peroxidation and the antioxidant system. Thymus plays a broader role than just regulating the immune system. Thymosin α1 is the first subgroup extracted from thymosin F5 and has higher biological activity than thymosin F5. In the present study, we have examined the effects of thymosin α1 on lipid levels and lipid peroxidation and glutathione (GSH) content in the plasma, liver and aorta tissues of atherosclerotic rabbits. At the end of thymosin α1 treatment, we determined the lipid levels and lipid peroxidation of the plasma, liver and aorta tissues and hepatic subcellular fractions in these rabbits. Our results demonstrated that thymosin α1 might normalize changed lipid levels and increased lipid peroxides and also elevate decreased GSH in the plasma, liver and aorta tissues of atherosclerotic rabbits. Results of this study suggest that thymosin a, may be beneficial to prevent and/or to treat atherosclerosis.

The effect of glutamine on oxidative damage in an experimental abdominal compartment syndrome model in rats

BACKGROUND The aim was to investigate whether or not glutamine, an antioxidant effective amino acid, improves the reperfusion-induced oxidative injury of abdominal hypertension. METHODS Wistar Albino rats were used. Group 1: Abdominal compartment syndrome alone: With the rats under anesthesia, intraabdominal pressure was obtained. Three days later, the rats were sacrificed, and intestine, lung and liver samples were removed for determination of tissue malondialdehyde (MDA) and glutathione (GSH) levels as oxidative injury parameters and of myeloperoxidase (MPO) activity as an inflammatory parameter. Trunk blood was analyzed for the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Group 2: Abdominal compartment syndrome and glutamine: intragastric glutamine was given for seven days before and three days following establishment of the abdominal compartment syndrome model. The same examination procedure was then performed. Group 3: Glutamine administration alone. Group 4: Control group. RESULTS Intraabdominal pressure significantly increased the intestine, lung and liver MDA levels and MPO activities in comparison to the control group. Glutamine was associated with decreased MDA levels and MPO activities and increased GSH levels. CONCLUSION Glutamine appears to have protective effects against reperfusion-induced oxidative damage via its anti-inflammatory and antioxidant effect.

Effect of olive leaf extract treatment on doxorubicin-induced cardiac, hepatic and renal toxicity in rats

Doxorubicin (DOX) is known to increase in oxidative stress in several organs. Olive leaf extract (OLE) has potent antioxidant effects; therefore, we evaluated the ability of OLE to reduce DOX-induced toxicity in the heart, liver, and kidneys of rats. DOX (30mg/kg; i.p.) was administered to rats, which were sacrificed 4 days after DOX. The rats received OLE (6 and 12mL/L in drinking water) for 12 days. Serum cardiac troponin I (cTnI) levels, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities, urea and creatinine levels, as well as prooxidant and antioxidant status in organs were measured. DOX was found to increase serum markers that indicate tissue injury, malondialdehyde (MDA), diene conjugate (DC), and protein carbonyl (PC) levels, and to decrease glutathione (GSH) levels in organs. Histopathologic changes were also evaluated. OLE, especially OLE 1000, led to decreases in serum cTnI and urea levels, ALT and AST activities, and amelioration in histopathologic findings. Decreases in MDA, DC, and PC, and increases in GSH levels were observed in organs of DOX-treated rats due to OLE. We conclude that OLE treatment may be effective in decreasing DOX-induced cardiac, hepatic and renal oxidative stress and injury.

Oxidative Damage in an Experimentally Induced Gastric and Gastroduodenal Reflux Model

The exact pathophysiologic mechanisms of esophageal cell damage and carcinogenesis by gastroesophageal reflux are not clearly understood. The aim of this study was to evaluate the damage to the esophageal epithelium that occurs after acid reflex and mixed acid and bile reflux by assessing histopathology, reactive oxygen species, and DNA damage. Eighty 10-week-old male Sprague-Dawley rats were divided into two groups, an acid reflux group and a mixed (acid/bile) reflux group. Acid reflux was achieved by esophagogastroplasty in which mixed reflux was encouraged via esophagoduodenal anastomosis. Each group contained a control subgroup that underwent sham laparotomy alone. The rats were killed 3, 6, 9, and 12 months after surgery. Malondialdehyde, protein carbonyl content, and DNA damage were determined in lymphocytes. Histopathologic analysis was performed according to the histologic activity index. Inflammation, ulcer, and regeneration in both reflux groups were significantly increased in the esophagus at 3, 6, 9, and 12 months compared with the control group. Mucosal damage was greater in the mixed reflux group compared with the gastric reflux group. Malondialdehyde and carbonyl content in the serum, and DNA damage in lymphocytes, were significantly increased in both reflux groups. At 9 and 12 months, oxidative damage was increased in the mixed reflux group compared with the acid reflux group. Oxygen-derived free radicals seem to be one of the important mediators in the evaluation and generation of reflux esophagitis. The impact of oxygen free radicals, as demonstrated in this study, can be evaluated by assessing the damage that they incur to lipid membranes, serum proteins, and circulating lymphocyte DNA. Serum malondialdehyde and carbonyl content as well as lymphocyte DNA damage were significantly increased in the setting of acid and mixed acid/bile reflux in these rodent models. Further, these serum and lymphocytic changes were associated with esophageal ulceration, inflammation, and regeneration. Evaluation of such markers as serum malondialdehyde and carbonyl content as well as evaluation of lymphocyte DNA might prove to be useful investigations in patients with precancerous and cancerous conditions in addition to conventional methods of diagnosis. Further studies, both animal and human are warranted.

Heme Oxygenase-1 Prevents Hyperthyroidism Induced Hepatic Damage via an Antioxidant and Antiapoptotic Pathway

BACKGROUND The exact pathogenesis of hepatic dysfunction in hyperthyroidism is still unknown. We aimed to investigate the pathogenesis of liver dysfunction caused by hyperthyroidism through inducing heme oxygenase-1 (HO-1) expression, which has antioxidant and anti-apoptotic properties. METHODS Rats were divided into six groups: untreated (group 1), treated with zinc protoporphyrin (ZnPP) (group 2), treated with hemin (group 3), treated with tri-iodothyronine (T3) (group 4), treated with T3 and ZnPP (group 5), and treated with T3 and hemin (group 6). After 22 d, oxidative stress and antioxidant enzymes and the expression of HO-1, mitochondrial permeability transition, cytochrome c, Bax, Bcl-2, caspase-3, caspase-8, and caspase-3 activity, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay were examined. RESULTS Hyperthyroidism induced oxidative stress of liver tissue was ameliorated by HO-1 induction. Administration of hemin (HO-1 inducer) increased Bcl-2 expression. Decreased expression of cytochrome c was accompanied by a decrease in caspase-3, caspase-8, Bax expression, and caspase-3 activity. The apoptotic activity and oxidative damage were found to be increased by the administration of ZnPP (HO-1 inhibitor). Immunohistochemistry findings supported these results. CONCLUSION HO-1 induction plays a protective role in the pathogenesis of the liver dysfunction in hyperthyroidism. This effect is dependent on modulation of the antiapoptotic and antioxidative pathways by HO-1 expression.

Oxidative DNA Damage Is Significantly Correlated With Flow-Mediated Dilation in Patients With Coronary Artery Disease

Background Oxidative DNA damage was increased in patients with coronary artery disease (CAD) and correlated with the severity of the disease. Endothelial dysfunction plays a major role in atherosclerotic process. The aim of this study was to explore a relation between oxidative DNA damage and endothelial function in patients with CAD. Methods Forty patients with CAD and 20 age- and sex-matched healthy controls were included. Endothelial function was assessed by brachial artery ultrasonography. The DNA damage was determined by comet method. Results The DNA damage scores after incubation with repair enzymes were found significantly higher in the patients with CAD (P = 0.04). There was a significant negative correlation between oxidized DNA damage scores and flow-mediated dilation (FMD) measures in the patients with CAD (r = −0.41; P = 0.009). Oxidized DNA damage scores were significantly and independently associated with FMD (standardized β = −0.455; P = 0.009) when adjusted by age, sex, smoking status, blood pressure, and cholesterol levels. Conclusions The DNA damage scores were significantly inversely correlated with FMD measures. To our knowledge, this is the first study showing the presence of a relation between DNA damage scores and FMD. Abbreviations: CAD, coronary artery disease, 8-Ohgua, 7, 8-Dihydro-8-oxo-guanine; Endo III, endonuclease III; FMD, flow-mediated dilation; Fpg, formamidopyrimidine glycosylase; NTG, nitroglycerin

Cord Blood Cardiac Troponin T and Nonprotein-Bound Iron Levels in Newborns of Mild Pre-Eclamptic Mothers

Background: In hypoxic newborns, cardiac troponin T (cTnT) was shown to be an indicator of cardiac damage and increased levels of nonprotein-bound iron (NPBI), an indicator of increased free radical production and perinatal brain damage. Objective: The aim of this study was to determine cord blood cTnT and NPBI levels in neonates of mild pre-eclamptic mothers. Methods: The study included 50 babies of mild pre-eclamptic mothers and 50 babies of healthy mothers. cTnT and NPBI levels were measured in cord blood. Results: The mean gestational age in the pre-eclamptic and healthy groups were 36.1 ± 3.5 and 38.1 ± 1.9 weeks, mean birth weights were 2,456 ± 945 and 3,059 ± 493 g. Cord blood median cTnT level was significantly higher in the pre-eclamptic group (0.024 vs. 0.015 ng/ml). Serum cTnT in the 95th percentile was 0.047 ng/ml in the healthy group. cTnT levels of preterm babies in the pre-eclamptic group was found to be significantly higher compared to term babies in the control group (0.038 vs. 0.013 ng/ml). It could not be demonstrated whether there is a statistically significant relation between cTnT levels and respiratory distress, gestation, type of delivery, sex and birth weight. The median NPBI level was higher in the control group (3.26 vs. 1.86 µmol/l). Conclusions: Increased levels of cTnT may be a biochemical marker of cardiac involvement in babies of mild pre-eclamptic mothers. In this study, no correlation was found between cTnT levels and NPBI levels.

Effect of Statins on Endothelial Function in Patients With Acute Coronary Syndrome: A Prospective Study Using Adhesion Molecules and Flow-Mediated Dilatation

Background Accumulating evidence suggests that inflammatory mechanisms play a central role in the development, progression and outcome of atherosclerosis. Recent evidence suggests that statins improve anti-inflammatory, anti-thrombotic and endothelial functions, along with their lipid-decreasing effects. We examined the effect of statins on endothelial function using biochemical markers of endothelial dysfunction and brachial artery flow-mediated dilatation (FMD). Methods Thirty male patients presenting with acute coronary syndrome (ACS) and 26 age-matched healthy control subjects aged 40 - 60 years who were not on any medication were enrolled in the study. The patient group was started on atorvastatin (40 mg/day) without consideration of their low-density lipoprotein (LDL)-cholesterol levels. Endothelin, sICAM and E-selectin from stored serum samples were measured using commercially available enzyme-linked immunosorbant assays (ELISAs). Endothelial function was assessed using brachial artery FMD. Results Prior to statin treatment, E-selectin, sICAM and endothelin levels, endothelial dysfunction markers, were 99.74 ± 34.67 ng/mL, 568.8 ± 149.0 ng/mL and 0.62 ± 0.33 fmol/mL, respectively in the patient group. E-selectin and sICAM levels were significantly higher in the patients than in the control subjects (P < 0.001); however, endothelin levels were not significantly different between groups. Statin treatment significantly reduced E-selectin and sICAM levels (P < 0.001); however, the decrease in endothelin levels was not statistically significant. %FMD values were significantly increased after statin treatment (P = 0.005), and levels of C-reactive protein (CRP), an inflammation marker, were significantly reduced. Conclusion Our results indicate that statins play an important role in treatment endothelial dysfunction by reducing adhesion of inflammatory cells.