Ismail Gunay

Comparison of nerve conduction blocks by an opioid and a local anesthetic

The experiments were done on frog sciatic nerves, using a sucrose-gap recording technique. The aim of our study was to investigate and to compare the tonic and phasic conduction blocking potency of tramadol and lidocaine on whole nerve and their interactions with Ca(2+). The concentration of a tramadol solution producing the same amount of tonic and phasic conduction blocks was three and six times higher than that needed for lidocaine, respectively. Increasing the Ca(2+) concentration in the test solution enhanced the conduction blocking potency of tramadol, but decreased that of lidocaine. It is concluded that tramadol blocks nerve conduction like a local anesthetic but with a weaker effect than that of lidocaine. Interactions of Ca(2+) and these drugs suggested that these drugs might have either different binding sites or different action mechanisms.

Macrophage depletion delays progression of neuropathic pain in diabetic animals

Despite the fact that it is a frequent diabetic complication, the mechanisms underlying the manifestation of diabetic neuropathic pain remain poorly understood. In this study, we hypothesized that the depletion of peripheral macrophages with liposome-encapsulated clodronate (LEC) can prevent, at least delay, the progression of diabetes-induced neuropathic pain. Therefore, the aim of this study was to evaluate the effects of macrophage depletion on mechanical allodynia and thermal hyperalgesia in the streptozotocin (STZ)-induced rat model of diabetic neuropathy. LEC was intravenously administrated to rats three times with 5-day intervals. A single intravenous injection of STZ caused an increase in the average blood glucose levels and a decrease in body weight. Although LEC treatment did not affect the body weight gain, the blood glucose level was lower and serum insulin level higher in LEC-treated diabetic rats than in that of diabetic rats. In addition, LEC treatment alleviated the excessive damage in beta cells in diabetic rats. Diabetic animals displayed marked mechanical allodynia and thermal hyperalgesia. While the treatment of diabetic rats with LEC did not significantly change the thermal withdrawal latency, diabetes-induced decrease in mechanical paw withdrawal threshold was significantly corrected by the LEC treatment. The results of this study show that thermal hyperalgesia and mechanical allodynia induced by diabetes may be associated with alterations in blood glucose level. Depletion of macrophages with LEC in diabetic rats may reduce mechanical allodynia without affecting thermal hyperalgesia. Taken together, these results suggested that depletion of macrophages in diabetes may partially postpone the development of diabetic neuropathic pain.

Differential effects of lidocaine and tramadol on modified nerve impulse by 4-aminopyridine in rats

We have used the sucrose gap method to measure the effects of drugs on the electrophysiological properties of rat sciatic nerves. The results showed that 4-aminopyridine produced a slight conduction block, prolonged the duration of action potential, enhanced the hyperpolarizing afterpotential, and elicited a hump that followed the action potential. In the presence of 4-aminopyridine, the impulse-blocking activity of lidocaine and tramadol was enhanced. Both lidocaine and tramadol effectively depressed the delayed depolarization generated by 4-aminopyridine. While tramadol decreased the activity-evoked hyperpolarizing afterpotentials, lidocaine completely removed them. These findings indicate that lidocaine may be more effective in blocking the Na+ channels than tramadol. Tramadol may be more effective on the delayed rectifier K+ channels than lidocaine.

Neurobiological effects of pulsed magnetic field on diabetes‐induced neuropathy

In the clinic, although several pharmacological agents or surgical procedures are used to treat diabetes and diabetes-induced neuropathic pain, their success has been limited. Therefore, development of different alternatives in treatments is very important. The purpose of this study was to determine the efficacy of pulsed magnetic field (PMF) in improving signs and symptoms of diabetic neuropathy. In this study, the effects of PMF treatment were investigated in Streptozotocin (STZ)-induced acute and chronic diabetic rats by measuring the thermal latencies, mechanical thresholds, whole blood glucose levels and body weights. After STZ administration to rats, blood glucose level elevated and body weight decreased. Although PMF treatment did not affect changes in body weight, the blood glucose levels of PMF-treated diabetic rats exhibited a decrease during the treatments. Diabetic animals displayed marked decrease in mechanical thresholds and thermal latencies. While treatment of PMF partially restored the mechanical thresholds and thermal latency in acute diabetic rats, PMF caused a corrective effect on only mechanical threshold of chronic diabetic rats. These results suggested that treatment of PMF can potentially ameliorate the painful symptoms of diabetes, such as hyperalgesia and allodynia, by partially preventing the hyperglycemia.

The effects of rosiglitazone on oxidative stress and lipid profile in left ventricular muscles of diabetic rats.

We investigated the effect of rosiglitazone (RSG), a high‐affinity ligand for the peroxisome proliferator‐activated receptor gamma which mediates insulin‐sensitizing actions, on the lipid profile and oxidative status in streptozotocin (STZ)‐induced Type 2 diabetes mellitus (DM) rats. Wistar albino male rats were randomly divided into an untreated control group (C), a C + RSG group which was treated with RSG (4 mg kg−1) two times a day by gavage, a diabetic group (D) that was treated with a single intraperitoneal injection of STZ (45 mgkg−1), D + RSG group which were treated with RSG two times a day by gavage, respectively. Lipid profiles, HbA1c and blood glucose levels in the circulation and malondialdehyde (MDA) and 3‐nitrotyrosine (3‐NT) levels in left ventricular muscle were measured. Treatment of D rats with RSG resulted in a time‐dependent decrease in blood glucose. We found that the lipid profile and HbA1c levels in D + RSG group reached the C rat values at the end of the treatment period. There was a statistically significant difference between the C + RSG and C groups in 3‐NT levels. In group D, 3‐NT and MDA levels were found to be increased when compared with C, C + RSG and D + RSG groups. In the D + RSG group, MDA levels were found to be decreased when compared with C and C + RSG. Our study suggests that the treatment of D rats with RSG for 8 weeks may decrease the oxidative/nitrosative stress in left ventricular tissue of rats. Thus in diabetes‐related vascular diseases, RSG treatment may be cardioprotective. Copyright

Changes in electrophysiological properties of regenerating rat peripheral nerves after crush injury

The conduction of action potential in peripheral nerves requires the coordinated opening and closing of Na(+) and K(+) channels. In the present study, we used the sucrose-gap recording technique to determine the electrophysiological changes of the regenerating nerves after sciatic nerve injury by using 4-aminopyridine (4-AP) and tetraethylammonium (TEA), and lidocaine. 4-AP enhanced the amplitude and duration of the compound action potentials (CAPs) of regenerating sciatic nerve 15 days post crush (15 dpc), and elicited delayed depolarizations (Del-dep) in 38 dpc and intact groups. Hyperpolarizing afterpotentials elicited by 4-AP were completely removed by TEA in both 15 and 38 dpc. Lidocaine effectively blocked the CAP amplitude. This blockage was more pronounced in 15 dpc than 38 dpc. This agent also exhibited a partial blockage on the Del-dep amplitude. These results may indicate that the changes in the activities of 4-AP- and TEA-sensitive K(+) channels and slow Na(+) channels may play critical roles in nerve excitability and conduction.

Effects of alternating magnetic field on the metabolism of the healthy and diabetic organisms

The aim of this study was to determine the effects of alternating magnetic field on the metabolism of the healthy and diabetic rats. The rats were divided into two experimental groups. Magnetic fields of 5 and 8mT intensity was applied to the first group of rats for 3 weeks (C5mT, CMF5mT, C8mT and CMF8mT). The second group was identified as diabetics group and 5mT was applied (D5mT and DMF5mT). The control groups (C5mT, C8mT, D5mT) of applied magnetic fields were placed in the same cage of the rats in experimental groups that have the same conditions but no pass current. The weights of rats exposed to magnetic fields in experimental groups were increased to initial weight; the plasma glucose levels were decreased in the blood parameters of the healthy and diabetic rats that they were exposed to 5mT and 8mT intensity magnetic fields. The decrease of the level of the total cholesterol and triglyceride in the blood plasma of the rats, showed that magnetic fields affected the hormonal systems, directly or indirectly, and slowed down the metabolism or hidratation.

Role of Potassium Channels in the Frequency-Dependent Activity of Regenerating Nerves

After a peripheral nerve injury, ion channel organization and the electrical properties of nerve fibers drastically change during the regeneration process. The present study was designed to compare the frequency-dependent characteristics of regenerating nerves in the presence of 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The results showed that increasing the stimulus frequency produced a greater impulse blockade (frequency-dependent block – FDB) and distinct hyperpolarizing afterpotentials (HAPs) in regenerating nerves. In particular, regenerating sciatic nerves 15 days post-crush (dpc) were more sensitive to the frequency-dependent stimulations than 38-dpc and intact nerves in the presence or absence of drugs. The frequency-dependent effects of TEA on the compound action potentials (CAPs) appeared when TEA was applied to 4-AP-treated nerves. This shows that TEA-sensitive channels may not be masked by the myelin. 4-AP was here found to have more pronounced frequency-dependent effects on regenerating nerves than on intact nerves. Delayed depolarization (in 38-dpc: 22.6 ± 1.3 mV and 47.52 ± 3.63 ms, in intact: 12.0 ± 1.9 mV and 88.51 ± 4.72 ms) elicited by 4-AP resulted in an increase in FDBs and HAP amplitudes. These results suggest that 4-AP-sensitive channels may play important roles in frequency-dependent nerve conduction. Consequently, regenerating or myelin damaged nerves are more sensitive to repetitive firing with or without drug. An understanding of the frequency-dependent properties of regenerating nerves may be of value in the treatment of the nerve diseases.

Effect of pulsed magnetic field on regenerating rat sciatic nerve: an in-vitro electrophysiologic study.

Some experimental studies report that low-frequency pulsed electromagnetic field (PEMF) stimulation may accelerate regeneration in peripheral nerves. In the present study, effects of PEMF on the regeneration of the crushed rat sciatic nerves were investigated with histological and in-vitro electrophysiological methods (sucrose-gap). After crush injury of the sciatic nerves, rats were divided into 5, 15, 25, 38 day-groups and exposed to PEMF (1.5 h/day, intensity; 1.5 mT, consecutive frequency; 10-10-100 Hz). In the 15th day post crush, compound action potential (CAP) amplitude was measured as 5.5 ± 1 mV (crush group) and 5.4 ± 1.2 mV (crush + PEMF group). In addition, half width of CAP extended ∼ 3 fold in both groups and frequency-dependent amplitude inhibition (FDI) decreased -20% at 100 Hz. In the 38th day, amplitude of CAP, half width of CAP and FDI were measured nearly intact nerve values in both groups. In histological examinations, Wallerian degeneration was observed similar progress between both groups. The results were compared between crush and crush + PEMF groups, it was found that the effect of PEMF was not significant. The authors conclude that PEMF were ineffective on rat sciatic nerve regeneration.

Deposition profile of antibacterial anodic silver in root canal systems of teeth

Electrically activated silver was shown to have an antibacterial effect in vitro and in vivo. In this study the effect of placing a silver anode in the root canal systems of teeth was examined to establish a base for treatment of infected teeth. Pure silver wires were placed in the main canals of extracted human teeth (n = 26) whose roots were partly submerged in a lactated Ringers solution. Seventeen microamperes of anodic direct current were applied to one group of silver wires (n = 15) for 4 days. Then the wires were removed and the roots of both group teeth were cut into six sections and demineralized Silver concentrations of the root sections and their bathing solutions were measured with an atomic absorption spectrophotometer. In the anode group, the electrically activated silver concentrations (range, 1-30 micrograms/microL) exceeded the antibacterial levels (minimum inhibitory concentration, 0.1 micrograms/microL Ag) in all sections, particularly in the middle and lower sites of the root. The amount of anodic silver that leaked out of the root was found as to be 0.4 +/- 0.2 micrograms/microL in the fluid medium. This was 10 to 100-fold higher than that found in the nonactivated controls.