Sait Polat

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.

The effect of levetiracetam on neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury

BACKGROUND Hypoxic-ischemic brain injury (HIBI) is a common cause of neonatal mortality and morbidity. The use of levetiracetam (LEV), as a potential neuroprotective in brain ischemia, receives an increasingly high attention, and it could have a crucial role in the regulation of epileptogenesis and neuroprotection. Potential effects of LEV on neuronal apoptosis in HIBI have not previously been reported in literature. OBJECTIVES The aim of this study is to evaluate the possible effects of LEV on neuronal apoptosis in neonatal rat model of HIBI. METHODS Seven-day-old Wistar rat pups were subjected to right common carotid artery ligation and hypoxia (92% nitrogen and 8% oxygen) for 2h. The pups were treated with LEV or saline after hypoxia. In sham group rats, neither ligation, nor hypoxia was performed. Neuronal apoptosis was evaluated by the terminal deoxynucleotidyl-transferase- mediated dUTP nick-end labeling (TUNEL) methods. RESULTS The counts of apoptotic cells in both hippocampus and cerebral cortex were significantly higher in the saline treatment group than in the sham group. The counts of apoptotic cells in both hippocampus and cerebral cortex were similar to those in the sham group and in the LEV treatment group. The number of apoptotic cells decreased significantly in the LEV-treated group compared with the saline group. CONCLUSIONS These results show that LEV administration after hypoxia reduces neuronal apoptosis. Thus, we propose that LEV, as an effective antiepileptic and antiapoptotic drug, may be a viable choice for the control of seizure activity in neonates with HIBI.

Protective effect of Spirulina platensis enriched in phenolic compounds against hepatotoxicity induced by CCl4

Phenolic compounds make up the major secondary metabolites with high pharmaceutical potential. Microalgae were reported to contain low amounts of phenolic compounds. The present study aimed to investigate the hepatoprotective potential of biomass of Spirulina platensis enriched in phenolic compounds. The protective effects of the biomass of S. platensis with low amounts of phenolics (SP1) and with high amounts of phenolics (SP2) against CCl4-induced acute hepatotoxicity were evaluated in rats. The increased levels of ALT, AST and MDA along with decreased activities of SOD and CAT were significantly (p<0.01) ameliorated by SP2. Histological examinations revealed that SP2 was more potent than SP1 in protecting the liver from toxic injury of CCl4 and preserving the hepatocyte ultrastructure. The lesions including necrosis, lymphocyte infiltration, ballooning degeneration and hepatocyte injury as irregular lamellar organisation, dilations in endoplasmic reticulums and the presence of great number of cytoplasmic vacuolization were healed by SP2.

Effects of ketamine on different types of anxiety/fear and related memory in rats with lesions of the median raphe nucleus

The aim of the present study was to determine the involvement of the median raphe serotonergic system in the effects of ketamine on anxiety behaviours and related memory. The effects of ketamine pretreatment (3 and 10 mg/kg, i.p.) on three types of fear-motivated behaviours, unconditioned one-way escape, conditioned avoidance and freezing were tested. Experiments were performed with the inhibitory avoidance apparatus in rats with ibotenic acid lesions of the median raphe nucleus. It was found that 10 mg/kg ketamine had an anxiogenic-like effect on one-way escape type of fear and anxiolytic-like effect on conditioned freezing-related fear; these effects were unaffected by median raphe lesions. Both ketamine doses impaired freezing-related fear memory. Ketamine (10 mg/kg) also produced an anxiolytic-like effect on avoidance type of fear and impaired avoidance memory. The median raphe lesions attenuated the anxiolytic action of the drug on the avoidance type of fear and prevented ketamine-induced avoidance memory impairment. These results suggest that the anxiolytic-like effect of ketamine on avoidance-type fear is mediated through the median raphe serotonergic system.

Effects of trapidil on ATPase, lipid peroxidation, and correlation with ultrastructure in experimental spinal cord injury

Abstract The present study was performed to investigate the effect of trapidil on ischemic damage of cells after spinal cord injury. The injury was produced by extradural clip compression of the exposed spinal cord in rats according to Rivlin and Tator. The ten rats in group 1 were used to determine normal findings without any surgery or medication. On the 15 rats in group 2, only six-level laminectomy was performed to determine the influence of the total laminectomy on the biochemical factors measured and the light and ultrastructural findings. The 15 rats each in groups 3 and 4 were used as trauma and trapidil (40 mg/kg) treatment groups, respectively. The injury actually produced a significant decrease in Na+–K+/Mg+2 ATPase activity of the injured segments as early as 10 min after trauma. Trapidil attenuated Na+–K+/Mg+2 ATPase inactivation in the traumatized rats for 120 min after treatment (P<0.05) and significantly reduced the malone dialdehyde content below that in the traumatized group at all determined times (P<0.05). Light and electron microscopic findings supported the biochemical results.

An Evaluation of the Effects of Long-term Cell Phone Use on the Testes Via Light and Electron Microscope Analysis

OBJECTIVE To investigate whether the low-intensity electromagnetic waves transmitted by cell phones cause histopathological or ultrastructural changes in the testes of rats. MATERIALS AND METHODS Wistar-Kyoto male rats were placed into either a control group or a group that was exposed to an electromagnetic field (EMF). Two cell phones with Specific Absorbation Rate values of 1.58 were placed and left off in cages that housed 15 rats included in the control group, and four cell phones were placed and left on in cages that housed 30 rats included in the experimental group. After 3 months, weights, seminiferous tubule diameters, and spermatogenic cell conditions of all testes of the rats were evaluated. One half of each testis was examined also under an electron microscope. RESULTS No significant differences were observed between the testis weights, seminiferous tubule diameters, and histopathological evaluations between rats that had and had not been exposed to EMF. Electron microscope analysis revealed that the membrana propria thickness and the collagen fiber contents were increased and the capillary veins extended in the experimental group. Common vacuolization in the cytoplasm of the Sertoli cells, growth of electron-dense structures, and existence of large lipid droplets were noted as the remarkable findings of this study. CONCLUSION Although the cells that had been exposed to long-term, low-dose EMF did not present any findings that were contrary to the control conditions, the changes observed during ultrastructural examination gave the impression that significant changes may occur if the study period were to be extended. Longer studies are needed to better understand the effects of EMFs on testis tissue.

Correlation of alterations on Na+-K+/Mg+2 ATPase activity, lipid peroxidation and ultrastructural findings following experimental spinal cord injury with and without intravenous methylprednisolone treatment

The sodium-potassium activated and magnesium dependent adenosine-5′-triphosphatase (Na+−K+/Mg+2 ATPase EC 3.6.1.3.) activity and lipid peroxidation and early ultrastructural findings are determined in rat spinal cord at the early stage of trauma produced by a surgical clip on the thoracal 2–7 segments. The effect of treatment with intravenous methylprednisolone (MP) was evaluated the basis of these biochemical alterations and ultrastructural findings in the same model. The specific activity of the membrane bound enzyme Na+−K+/Mg+2 ATPase was promptly reduced in as early as ten minutes following spinal cord injury and remained at a level lower than the levels in the control group and in the sham-operated group. Methylprednisolone treatment immediately after the trauma attenuated the inactivation of Na+−K+/Mg+2 ATPase. On the other hand, there was significant difference in lipid peroxide content between the sham-operated and the injured animals. Methylprednisolone treatment reduced thiobarbituric acid reactive substance (TBARS) content in Group IV. We determined a positive relationship among membrane-bound enzyme Na+ K+/Mg+2 ATPase activity, malondialdehyde (MDA) content and early ultrastructural changes in the traumatized and treated groups.These data provide evidence for a beneficial effect of methylprednisolone on the activation of Na+−K+/Mg+2 ATPase and lipid peroxidation and early ultrastructural changes in spinal cord injured rats. The possible mechanism of methylprednisolone effects on the membrane function and lipid peroxidation, and the correlation of biochemical changes with ultrastructural findings are briefly discussed.

Changes of Middle Ear Mucosa in Secretory Otitis Media Treated with Ventilation Tubes

The present study was designed to obtain the precise ultrastructural status of the middle ear mucosa of patients to whom ventilation tubes were applied for the treatment of secretory otitis media (SOM). This study comprised 14 children with SOM aged 5-11. Normal epithelium obtained from otosclerotic patients as controls was composed of three main cell types; basal, ciliated, and secretory. Electron microscopic observations revealed that ciliated cells were almost completely absent in the epithelium of patients with SOM. Secretory cells, on the other hand, were noted to be increased in number with cytoplasmic features indicating active secretory phase; abundant secretory granules in these cells featured both serous and mucoid characteristics. Following the application of ventilation tubes, the micrographs exhibited a vast number of ciliated cells. Furthermore, the secretory cells were less conspicuous and the secretory granules were mostly serous in type. The ultrastructural findings of this investigation strongly suggest that the application of ventilation tubes in cases of SOM stimulates ciliated cell regeneration, inhibits secretion of mucoid material, and activates serous secretion; all of which eventually shorten the recovery period.

The effects of the pretreatment of intravenous high dose methylprednisolone on Na(+)-K(+)/Mg(+2) ATPase and lipid peroxidation and early ultrastructural findings following middle cerebral artery occlusion in the rat.

SummaryThe sodium-potassium activated and magnesium dependent adenosine-5′-triphosphatase (Na+-K+/Mg+2 ATPase EC.3.6.1.3.) activity and lipid peroxidation and early ultrastructural findings were determined in rat brain at the acute stage of ischaemia produced by permanent unilateral occlusion of the middle cerebral artery (MCA). The effects of the pretreatment with intravenous high-dose methylprednisolone (MP) on these biochemical indices and ultrastructural findings were also evaluated in the same model. The rats were divided into four groups. In group I, 10 rats were used to determine Na+-K+/Mg+2 ATPase activity and the extent of lipid peroxidation by measuring the malondialdehyde (MDA) content and normal ultrastructural findings. In group II on 20 rats, only subtemporal craniectomy was done in order to determine the effects of the surgical procedure on these indices and findings. This group was treated intravenously with saline solution before occlusion. In group III with MCA occlusion, saline solution was administered intravenously to 20 rats in the same amount of methylprednisolone used in group IV, ten minutes before the occlusion. In Group IV, a single high-dose (30 mg/kg) of methylprednisolone was administered intravenously, ten minutes before occlusion in 20 rats. After occlusion of the middle cerebral artery, Na+-K+/Mg+2 ATPase activity was decreased promptly in the first ten minutes in the ischaemic hemisphere and remained at a lower level than the contralateral hemispheres in the same group and the normal levels in group I, during 120 minutes of ischaemia. A single dose methylprednisolone pretreatment prohibited the inactivation of Na+-K+/Mg+2 ATPase. On the other hand, there was significant difference in malondialdehyde content between group I and group III. Malondialdehyde levels were significantly increased following ischaemia and a non-significant increase was observed in the contralateral hemisphere. Methylprednisolone treatment significantly decreased malondialdehyde content on the side of the ischaemic hemisphere. We conclude that there is a positive relationship between membrane-bound enzyme Na+-K+/Mg+2 ATPase activity, malondialdehyde content and early ultrastructural changes in the treated group with MP.These data suggest that the pretreatment injection of high doses (30 mg/kg) methylprednisolone contribute to the protection of the brain from ischaemia with stabilization of the cell membrane by effecting the lipid peroxidation and the activation of Na+-K+/Mg+2 ATPase.

Effects of Zoledronic Acid on Healing of Mandibular Fractures: An Experimental Study in Rabbits

PURPOSE The purpose of the present study was to evaluate the effects of systemically administered zoledronic acid (ZA) on mandibular fracture healing in a rabbit model using radiodensitometric, biomechanical, histologic, and histomorphometric methods. MATERIALS AND METHODS A total of 36 skeletally mature male New Zealand white rabbits were used. The rabbits were randomly divided into 2 groups. A mandibular corpus fracture was created experimentally in all 36 rabbits. The experimental group was administered an intravenous, single dose of 0.1 mg/kg ZA, and the control group was administered only saline infusion during the procedure. All rabbits were sacrificed on the 21st postoperative day. Digital radiodensitometric analysis, a 3-point bending test, and histologic and histomorphometric examinations were performed on the harvested hemimandibles. The data were analyzed statistically. RESULTS Biomechanical testing data showed that ZA treatment resulted in a significant increase in the healed bone strength. This result was supported by the radiologic, histologic, and histomorphometric findings. CONCLUSIONS The results of the present study have revealed that systemic administration of ZA accelerates and improves the bone healing of mandibular fractures.