Osman Genç

Effects of cadmium and zinc on plasma levels of growth hormone, insulin-like growth factor I, and insulin-like growth factor-binding protein 3

Humans are constantly exposed to cadmium (Cd) as a result of the increase in air pollution and cigaret use. Zinc (Zn), which is an essential element for the metabolism of and the constituent of many enzymes, causes growth retardation in the deficiency status so at present it is often added to the diet without measuring blood levels of this element. We also aimed to observe the effects of both Cd and Zn on the plasma levels of growth hormone (GH), insulin-like growth factor I(IGF-I), and insulin-like growth factor-binding protein 3 (IGFBP-3) in this study. For this purpose, 27 young Wistar albino male rats were divided into three groups. The first group was given 50 mg/L of CdCl2, the second group received 500 mg/L of ZnSO4, and the third group, as a control, received only drinking water for 1 mo. At the end of this period, plasma GH, IGF-I, and IGFBP-3 of the animals were analyzed in the blood obtained. The significance between groups was evaluated with the Mann-Whitney U-test. According to our results, levels of IGF-I and IGFBP-3 in the Cd-administered group were significantly lower than those of controls (p<0.05 and p<0.01 respectively). No statistically significant difference was observed between Zn administered and control groups in terms of all three parameters. These results show that although the addition of Zn to the diet of healthy rats had no effect on the levels of GH, IGF-I, and IGFBP-3, Cd addition lowered the levels of IGF-I and IGFBP-3 but did not change the levels of GH compared to controls.

Orexins increase penicillin-induced epileptic activity.

Orexins have been implicated with physiological function including sleep-wake cycle, energy homeostasis, drinking behavior, analgesia, attention, learning and memory but their effects on excitability are controversial. We investigated the effects of intracortical injections of orexin A (100 pmol) and B (100 pmol) on the electrophysiological manifestation of epileptic seizures induced by cortical penicillin application in adult male rats. In comparison to saline, orexin A and B enhanced significantly the spike number, spike amplitude and spectral power values induced by cortical penicillin. Our findings indicates that orexins enhances the hyperexcitable and hypersyncronic cortical epileptic activity induced by focal application of penicillin-G.

Orexins cause epileptic activity.

Orexins have been implicated in the regulation of sleep-wake cycle, energy homeostasis, drinking behavior, analgesia, attention, learning and memory but their effects on epileptic activity are controversial. We investigated whether intracortical injections of orexin A (100 pmol) and B (100 pmol) cause epileptic activity in rats. We observed epileptic seizure findings on these two groups rats. Orexin A and B also significantly increased total EEG power spectrum. Our findings indicate that orexins cause epileptic activity.

Effects of the hippocampal deep brain stimulation on cortical epileptic discharges in penicillin - induced epilepsy model in rats.

AIM Experimental and clinical studies have revealed that hippocampal DBS can control epileptic activity, but the mechanism of action is obscure and optimal stimulation parameters are not clearly defined. The aim was to evaluate the effects of high frequency hippocampal stimulation on cortical epileptic activity in penicillin-induced epilepsy model. MATERIAL AND METHODS Twenty-five Sprague-Dawley rats were implanted DBS electrodes. In group-1 (n=10) hippocampal DBS was off and in the group-2 (n=10) hippocampal DBS was on (185 Hz, 0.5V, 1V, 2V, and 5V for 60 sec) following penicillin G injection intracortically. In the control group hippocampal DBS was on following 8 μl saline injection intracortically. EEG recordings were obtained before and 15 minutes following penicillin-G injection, and at 10th minutes following each stimulus for analysis in terms of frequency, amplitude, and power spectrum. RESULTS High frequency hippocampal DBS suppressed the acute penicillin-induced cortical epileptic activity independent from stimulus intensity. In the control group, hippocampal stimulation alone lead only to diffuse slowing of cerebral bioelectrical activity at 5V stimulation. CONCLUSION Our results revealed that continuous high frequency stimulation of the hippocampus suppressed acute cortical epileptic activity effectively without causing secondary epileptic discharges. These results are important in terms of defining the optimal parameters of hippocampal DBS in patients with epilepsy.

The effects of human umbilical cord blood transplantation in rats with experimentally induced spinal cord injury.

OBJECT Even though there have been many efforts to recover neuronal dysfunction following spinal cord injuries, there are limitations to the treatment of these injuries. The purpose of this laboratory investigation was to determine the clinical and neurophysiological effects of human umbilical cord blood (HUCB) transplantation in a rat hemisection model of spinal cord injury. METHODS In this study, experimental hemisection of the thoracic spinal cord was performed in rats. The rats were divided into 4 groups (6 rats in each group). One group of rats (Group 1) underwent thoracic laminectomy only. Rats in Group 2 underwent laminectomy and right hemisection of the thoracic spinal cord. Rats in Group 3 underwent right hemisection and implantation of freshly obtained HUCB on Day 0 postinjury. Rats in Group 4 underwent hemisection and implantation of freshly obtained HUCB on Day 4 postinjury. Clinical evaluations of rat motor function included the following: neurological examination, Rotarod performance, and inclined plane tests. Rats also underwent reflex evaluation. RESULTS The neurological examinations revealed that the frequency of plegic rats was 70.8% at the beginning of the study across all 4 groups; this value decreased to 20.8% by the end of the study. The percentage of rats with a normal examination increased from 25% to 50%. The results of Rotarod performance and 8-week inclined plane performance tests showed statistical significance (p < 0.05) in an overall group comparison across all time points. At the end of the 8 weeks, a statistically significant difference was found in the inclined plane test results between rats in Groups 1 and 2. There were no statistically significant differences between Groups 1, 3, and 4 (p < 0.05). When the reflex responses of the hemisectioned sides were compared, statistically significant differences were detected between groups (p < 0.05). All groups were significantly different with regard to the right-side reflex response score (p < 0.05). Spinal cord preparations of rats in all groups were examined for histopathological changes. CONCLUSIONS Human umbilical cord blood is stem cell rich and easily available, and it carries less risk of inducing a graft-versus-host reaction in the recipient. Human umbilical cord blood serum is also noted to contain stem cell–promoting factors, which is why cell isolation was not used in this study. Freshly obtained cord blood was also used because storage of cord blood has been reported to have some negative effects on stem cells. Transplantation of freshly obtained HUCB into the hemisectioned spinal cord experimental model demonstrated clinical and neurophysiological improvement.

Insulin-like growth factor-I gene and insulin-like growth factor binding protein-3 polymorphism in patients with thyroid dysfunction.

BACKGROUND AND AIMS Thyroid hormones have important roles in normal growth and skeletal muscle development. IGF-I is one of the most important growth factors and is needed for the proliferation and development of thyroid cells. It stimulates fibroblasts, follicular and endothelia cells in thyroid gland. It has been shown that thyroid hormones play an important role in the regulation of IGF-I and IGFBP-3. In this study we proposed that IGF-I (CA)(19) and IGFBP-3-202 A/C gene polymorphism may affect thyroid functions. For this purpose, frequency of IGF-I (CA)(19) and IGFBP-3-202 A/C gene polymorphism in hypo- and hyperthyroid patients and possible role of these polymorphism in thyroid functions were investigated. METHODS This study was performed on 37 volunteer hyperthyroid and 76 hypothyroid patients as well as with 50 healthy subjects as controls. DNA isolation was applied in peripheral blood samples obtained from patients and controls. Required areas were amplified with PCR by using proper primers belonging to these gene areas from the isolated DNA samples. The products were evaluated with visualization by UV gel documentation system. RESULTS Frequency of IGF-I (CA)(19) gene polymorphism among hypothyroidism patients, hyperthyroidism patients and controls were statistically significant (chi(2) = 11.55, df = 4, p = 0.021). Genotypic variations between hyper- and hypothyroid patients were significant (chi(2) = 11.39, df = 2, p = 0.003), whereas there was no difference in IGF-I (CA)(19) gene polymorphism between the patients and controls. Differences in the IGFBP-3-202 A/C gene polymorphism between controls and hypo- as well as hyperthyroid patients were not significant. But IGFBP-3-202 A/C gene polymorphism genotype frequencies showed a significant difference between hypo- and hyperthyroid patients (chi(2) = 6.24, df = 2, p = 0.044). CONCLUSIONS These findings suggests that IGF-I (CA)(19) and IGFBP-3-202 A/C gene polymorphisms may be a risk factor for hypothyroidism.

Protective effects of simvastatin administered in the experimental hepatic ischemia-reperfusion injury rat model

BACKGROUND Hepatic ischemia-reperfusion (I/R) injury is a major complication in clinical practice. Previous studies suggest that statins have pleiotropic effects in addition to cholesterol-lowering effects. In this study, we aimed to investigate the hepatoprotective role of two different doses of simvastatin (SV) pretreatment in rats with experimental hepatic I/R injury. METHODS Adult male Sprague-Dawley rats were divided into four groups (n = 7 in each group) :control, I/R, I/R with 2.5-mg/kg SV, and I/R with 5.0-mg/kg SV. Before hepatic I/R was induced, SV was injected intraperitoneally at doses of 2.5 and 5.0 mg/kg. After 45-min ischemia and a 60-min reperfusion period, the animals were euthanized, and liver tissues were excised. Tissue levels of malondialdehyde and nitric oxide, and activities of superoxide dismutase, glutathione peroxidase, and catalase were measured. Liver tissues were also evaluated histopathologically and immunohistochemically. RESULTS Histopathologic evaluation showed that 5.0-mg/kg SV reduced hepatic damage and apoptosis. Pretreatment with 5.0-mg/kg SV reduced malondialdehyde and nitric oxide levels (P < 0.01) and increased superoxide dismutase, glutathione peroxidase, and catalase activities significantly (P < 0.001, P < 0.01) in I/R with 2.5-mg/kg SV compared with I/R group. In addition, SV decreased Kupffer cell activation, and hypoxia-inducible factor-1α and vascular endothelial growth factor protein levels. CONCLUSIONS The results of this study suggest that 5.0-mg/kg SV pretreatment may be protective against hepatic I/R injury. This effect can be achieved by antioxidant and antiapoptotic activities.

Effects of acute exercise on the levels of iron, magnesium, and uric acid in liver and spleen tissues.

In this study, we investigated the effects of acute exercise on tissue levels of iron, magnesium, and uric acid of rats. Twenty adult Wistar albino rats were used for the study. They were divided into two groups: controls (n=10) and the study group (n=10). The study group was left into a small water pool and allowed to do swimming exercise for 30 min while controls rested. All of the animals were sacrificed, and their livers and spleens removed and homogenized immediately. The iron, magnesium, and uric acid levels of the homogenates were measured by an autoanalyzer (ILAB 900, Italy) with commercial kits from the same company. Results were evaluated by the Mann-Whitney U-test. According to our results, the liver iron levels increased significantly with exercise, whereas spleen iron levels decreased significantly (p<0.05) compared to controls. We found no significant differences in the levels of the other two parameters with exercise. These results show that the iron distribution in organs changes with exercise.

The influence of cervical spinal cord stimulation on induced epileptic discharges in rats

Spinal cord stimulation (SCS), also known as dorsal column stimulation, is a novel technique used widely in pain surgery. However, its effect on other pathologies such as epileptic disorders is unknown. The aim of this study is to evaluate the influence of electrical epidural stimulation of the upper cervical region on epileptic cortical discharges. The long term goal is to elucidate and evaluate a therapeutic central nervous system (CNS) electrical stimulation methodology to treat epilepsy. Twelve Wistar female rats were randomly divided into two groups. In group 1 (six rats under general anesthesia), C2-3 laminectomies were performed and epidural electrodes were placed to perform SCS. To induce epileptic discharges, 1 ml (200 IU) penicillin G was microinjected into the left somatomotor cortex via left stereotactic parietal craniotomies, 0.01 to 0.1 mA at 2 Hz was used to stimulate the spinal cord. In group 2 (the control group, six rats under general anesthesia), C2-3 laminectomies were performed without electrode placement and epileptic discharges were induced with penicillin G microinjections, as described above. Both groups were monitored with digital electroencencephalography (EEG) for 70 min in seven stages and recordings analyzed with power spectral analysis. Spinal cord stimulation decreased penicillin-induced median values of epileptic discharges. Epileptic wave frequencies decreased significantly with increasing intensities of SCS. The results of this study suggest that SCS used for drug resistant epilepsies may be a viable alternative treatment modal.

Blood Pressure Measurement in Freely Moving Rats by the Tail Cuff Method

Inconsistency in consecutive blood pressure values is one of the most frequently observed problems in tail cuff method. The aim of this study was to measure blood pressure using the tail cuff method in rats without heating, anesthesia, and movement restriction. In this study, it has been shown that blood pressure measurement could be obtained without problem using the tail cuff method in freely moving rats in their cage environment. Also, the reliability of consecutive blood pressure values obtained from freely moving rats was higher than ether anesthesia and restricted groups.