Mustafa Güven

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.

Population-level right-paw preference in rats assessed by a new computerized food-reaching test

We re-studied the distribution of paw preference in rats using a new computerized food-reaching test, which recorded the times and time intervals between the single right- and left-paw entries. Using the traditional food-reaching test, we found that of 144 rats, 72.7% were right-handed, 19.7% left-handed, and 7.6% mixed-handed. This population-level J-shaped right-hand preference did not fit a binomial chance distribution (25:25:50). Of right handers, 99.5% first used their right paw and 0.5% left paw; of left-handers, 98.6% first used their left paw and 1.4% right paw. Of mixed-handers, 59% first used the right paw and 41% left paw for food reaching. The time interval between putting the rat into the test cage and the first right-paw entry was significantly shorter than the first left-paw entry in total sample. Males were faster than females (shorter time intervals between right- or left-paw entries). The distribution of the time intervals between right- or left-paw entries was inverse J-shaped, which exhibited a normal distribution after taking the logarithms of the time intervals. There was no significant difference between time intervals for the left-paw entries; time intervals for the right-paw entries were significantly shorter in males than females, accentuating the role of the left brain for sex differences in motor control. The results suggested that humans are not unique in population-level right-hand preference; our new method would be suitable for new developments in handedness research

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.

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.

Enriched environment has limited capacity for the correction of hippocampal memory-dependent schizoid behaviors in rats with early postnatal NMDAR dysfunction.

Pre‐ and early postnatal stress can cause dysfunction of the N‐methyl‐d‐aspartate receptor (NMDAR) and thereby promote the development of hippocampus memory‐dependent schizoid abnormalities of navigation in space, time, and knowledge. An enriched environment improves mental abilities in humans and animals. Whether an enriched environment can prevent the development of schizoid symptoms induced by neonatal NMDAR dysfunction was the central question of our paper. The experimental animals were Wistar rats. Early postnatal NMDAR dysfunction was created by systemic treatment of rat pups with the NMDAR antagonist MK‐801 at PD10–20 days. During the development period (PD21–90 days), the rats were reared in cognitively and physically enriched cages. Adult age rats were tested on navigation based on pattern separation and episodic memory in the open field and on auto‐hetero‐associations based on episodic and semantic memory in a step‐through passive avoidance task. The results showed that postnatal NMDAR antagonism caused abnormal behaviors in both tests. An enriched environment prevented deficits in the development of navigation in space based on pattern separation and hetero‐associations based on semantic memory. However, an enriched environment was unable to rescue navigation in space and auto‐associations based on episodic memory. These data may contribute to the understanding that an enriched environment has a limited capacity for therapeutic interventions in protecting the development of schizoid syndromes in children and adolescents.

CONDUCTION BLOCKS OF LIDOCAINE ON CRUSHED RAT SCIATIC NERVE: AN IN-VITRO STUDY

The effects of lidocaine on the action potential of crushed sciatic nerves were investigated. The sciatic nerves of the rats were removed 5, 15, 25, and 38 days after the crushing and the compound action potentials were recorded with sucrose gap technique. The nerves were treated with 1 mM lidocaine and the conduction blocks of nonfrequency dependent block (NFDB) and frequency depended block (FDB) at 10, 40, and 100 Hz were determined. In intact nerves, the NFDB effect of lidocaine was 38.4 ± 0.7 %. On the 15th day after the crush, the NFDB was increased to 60.1 ± 1.3%. On the 38th day NFDB was decreased to 46.0 ± 0.8%. The following days after the crushing, lidocaine caused a very high rate of FDB with 10, 40, and 100 Hz stimulation. The high NFDB ratios approached normal levels with the improvement of regeneration, but FDB ratios continued to stay at high levels. The results showed that the ratios of FDB and NFDB were increased on the crushed nerve. It was concluded that, in the regeneration conditions of crushed rat sciatic nerves, the sensitivity to local anesthetic increases more than in intact nerves.

Data cluster analysis-based classification of overlapping nuclei in Pap smear samples.

BackgroundThe extraction of overlapping cell nuclei is a critical issue in automated diagnosis systems. Due to the similarities between overlapping and malignant nuclei, misclassification of the overlapped regions can affect the automated systems’ final decision. In this paper, we present a method for detecting overlapping cell nuclei in Pap smear samples.MethodJudgement about the presence of overlapping nuclei is performed in three steps using an unsupervised clustering approach: candidate nuclei regions are located and refined with morphological operations; key features are extracted; and candidate nuclei regions are clustered into two groups, overlapping or non-overlapping, A new combination of features containing two local minima-based and three shape-dependent features are extracted for determination of the presence or absence of overlapping. F1 score, precision, and recall values are used to evaluate the method’s classification performance.ResultsIn order to make evaluation, we compared the segmentation results of the proposed system with empirical contours. Experimental results indicate that applied morphological operations can locate most of the nuclei and produces accurate boundaries. Independent features significance test indicates that our feature combination is significant for overlapping nuclei. Comparisons of the classification results of a fuzzy clustering algorithm and a non-fuzzy clustering algorithm show that the fuzzy approach would be a more convenient mechanism for classification of overlapping.ConclusionThe main contribution of this study is the development of a decision mechanism for identifying overlapping nuclei to further improve the extraction process with respect to the segmentation of interregional borders, nuclei area, and radius. Experimental results showed that our unsupervised approach with proposed feature combination yields acceptable performance for detection of overlapping nuclei.

The conduction block produced by oxcarbazepine in the isolated rat sciatic nerve: a comparison with lamotrigine

Abstract Objective: Oxcarbazepine is an antiepileptic drug widely used for the treatment of neuropathic pain. In the present study, the effects of oxcarbazepine and lamotrigine on conduction properties in the rat sciatic nerves were examined. Methods: The experiments were conducted with in vitro sucrose-gap technique on the isolated wistar rat sciatic nerves. The compound action potentials were obtained by tonic (single) and phasic (10, 40, and 100 Hz) stimulation. Results: Oxcarbazepine produced a significant concentration- and frequency-dependent reduction in the compound action potential amplitude. When the two drugs were applied at concentrations that produced equal levels of tonic (i.e., non-frequency-dependent) conduction block, oxcarbazepine produced the greatest phasic (i.e., frequency-dependent) conduction block, followed by lamotrigine. Oxcarbazepine and lamotrigine reduced the 4-aminopyridine-induced amplitude of delayed depolarization; however, oxcarbazepine had a significantly greater effect than lamotrigine. Conclusion: These results suggest that oxcarbazepine produces more potent frequency-dependent conduction block than lamotrigine, and suppresses the delayed depolarization which contributes to sensory signaling and may play a role in neuropathic pain. The findings provide insight into the mechanisms of action of oxcarbazepine and lamotrigine and may help in the development of novel therapies for neuropathic pain.