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Objectives: Dealing with pain is one of the most important issues of medicine. All of the studies aim to find a drug or combination of drugs in order to have more effective analgesia and less side effects. In this study, we aimed to investigate the antinociceptive effects of combination of paracetamol or ketamine with meperidine., Methods: In this study, we evaluated the systemic antinociceptive effects of meperidine, paracetamol, and ketamine one by one with their combinations. We used 50 mice (weighing 25-30 g), which were divided into 5 groups with each group consisting of 10 mice. Meperidine was applied to animals with increasing doses and their tail flick latencies (TFL) were noted at 20, 40, 60, 90, 120, 180, and 240 min. The same protocol was repeated after the combination of meperidine with paracetamol or ketamine., Results: There was no analgesic effect on low doses of ketamine and paracetamol at TFL measurements. But the combination of low doses of these drugs with meperidine significantly increased TFL (p < 0.05)., Conclusion: It was observed that meperidine + ketamine and meperidine + paracetamol combinations have potent analgesic effect., (© The Author(s) 2015.)

Objective: Postoperative adhesions still remain as a common and serious problem leading to morbidity, mortality and economic loss. Adhesions are the major cause of postoperative intestinal obstruction, infertility, and chronic pelvic pain. In this study, we aimed to compare adhesion prevention effects of pentoxyphylline, enoxaparin and methylene blue and to investigate the effects of these agents on angiogenesis, which is suggested as an important step in wound healing, in rat a uterine horn model., Material and Methods: Forty female Wistar albino rats were randomized into four subgroups and underwent laparotomy. Adhesions developed following cauterization at the anti-mesenteric surfaces of both uterine horns. After 14 days, adhesions were investigated by using macroscopic, histopathological and immunohistochemical [vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor (TGF-beta), platelet-derived growth factor (PDGF)] methods., Results: We found that enoxaparin significantly reduced adhesion formation. Pentoxyphylline had no significant effect on adhesion formation, whereas methylene blue had a significant decreasing effect on histopathologically determined adhesion markers and it may affect angiogenesis through PDGF., Conclusion: Among three agents, which were intraperitoneally given by a single dose manner in order to prevent postoperative adhesions, methylene blue and enoxaparin exhibited a positive effect, while no such effect was shown with pentoxyphylline.

Objectives: Adenotonsillar hypertrophy (ATH) is the most common cause of upper airway obstruction in children. Severe upper airway obstruction may have an effect on chronic alveolar hypoventilation, which consequently may lead to right ventricle (RV) dysfunction induced by hypoxemic pulmonary vasoconstriction. The investigators aimed to study RV function and mean pulmonary artery pressure (mPAP) in patients with ATH who were undergoing adenotonsillectomy by using tissue Doppler echocardiography (TDE)., Methods: The study examined 27 children with ATH who had a mean age of 8 ± 2 years. The subjects were comprised 17 (63%) males and 10 (37%) females. Hypertrophy of the tonsils was graded according to the Brodsky scale. Children having either grade 3 or 4 hypertrophied adenotonsils were recruited for the study. Adenotonsillectomy was performed on all subjects in the study group and echocardiographic examination was repeated 3 months postoperatively., Results: Tricuspid Em significantly increased after adenotonsillectomy (17.7 ± 3.6 vs. 19.1 ± 5.5, p=0.04). The RV myocardial performance index (MPI) and mPAP significantly decreased after adenotonsillectomy (RV MPI: 0.57 ± 0.13 vs. 0.40 ± 0.12, p<0.001 and mPAP (mmHg): 31 ± 9 vs. 25 ± 7, p=0.001)., Conclusion: The results of this study, evaluated with the results of previous studies, demonstrated that adenotonsillectomy improved RV performance and reduced mPAP in children with ATH., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: Postoperative adhesions are a serious problem. In this study, we aimed to observe the effects of sorafenib in postoperative adhesions and, to examine the effects of sorafenib on tissue levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF)., Material and Methods: Twenty female Wistar albino rats were randomized into two equal groups; sorafenib group (sorafenib treated) and control group; then all rats underwent laparotomy. Adhesions were developed by scalping on the anti-mesenteric surfaces of the right uterine horns. After 14 days, adhesions were investigated by using macroscopic, histopathological and immunohistochemical (for VEGF and PDGF) methods., Results: The sorafenib group had lower scores of total adhesions [1 (0-2.5) vs 1.5 (1-4); p: 0.037], staining of VEGF [1 (0-1) vs 1 (1-3); p: 0.029] and PDGF [1 (0-2) vs 2 (1-3); p: 0.006], and vascular proliferation [1 (0-2) vs 2 (1-3); p: 0.038] than the control group., Conclusion: The findings of the present study show that sorafenib, a tyrosine kinase inhibitor, significantly reduced postoperative adhesion formation. This effect may be explained by inhibition of VEGF, PDGF, and thus vascular proliferation.

Objective: The objective of the study was to evaluate hypoxia-inducible factor 1 (HIF-1), which plays a major role in the stimulation of angiogenesis in placental tissues, by using immunohistochemical staining in preeclampsia model of rats, developed by N-nitro-L-arginine methyl ester (L-NAME) METHODS: Thirty pregnant rats were randomized into 2 groups (n = 15 in each group) on day 10 of gestation. L-NAME was given to rats in the study group by gavage. On days 0, 10, and 20 of gestation, rats were weighted, and urine protein values and blood pressures were measured. Hypoxia-inducible factor 1 expressions were assessed with immunohistochemical staining by using avidin-biotin peroxidase via selecting preparation., Results: Systolic and diastolic blood pressures and urine protein value of L-NAME group on day 20 of gestation were found to be significantly higher than those obtained on days 0 and 10 of gestation in the same group and those obtained on day 20 of gestation in the sham group (P < 0.05). Maternal weight, number of fetuses, and mean fetal weight of rats in L-NAME group on day 20 of gestation were found to be significantly lower than those obtained from rats in the sham group (P < 0.05). Regarding HIF-1 expression of placental tissues, mild immunohistochemical staining was found in 2 rats (13.4%) and moderate in 13 rats (86.6%) in the L-NAME group. A significant difference was found in terms of HIF-1 positivity in the maternal placentas of both groups (P < 0.05)., Conclusions: L-NAME preeclampsia model of pregnant rats is consistent with human preeclampsia in terms of hypertension, proteinuria, and intrauterine growth retardation; in addition, it also shows evidence of placental hypoxia findings.

The aim of the study was to investigate maternal (hemoglobin, hematocrit, and biochemical parameters of blood and urine) and fetal parameters (number and weight of alive fetus) of preeclampsia in a rat model. Placental oxidative stress markers (protein carbonyl, malondialdehyde) and placental antioxidant values (CuZn-superoxide dismutase, glutathione peroxidase) were also measured. Preeclampsia was induced experimentally in timed-pregnant Sprague-Dawley rats by using the reduced uterine perfusion pressure (RUPP) model. Placental oxidative stress that plays a key role in the pathophysiology of placenta-related disorders, most notably preeclampsia (PE) and intrauterine growth restriction (IUGR) were demonstrated by using RUPP model. On day 14 of gestation, silver clips were placed around the aorta below the renal arteries and on the left and right uterine arcade at the ovarian artery. In the RUPP model animals (n = 15), when compared with the normotensive controls (n = 15), arterial pressure on day 19 of gestation was significantly higher in the RUPP rats (151.7 ± 17.6 mmHg) than normal pregnant rats (113.9 ± 11.4 mmHg). The RUPP rats showed a significant increase in protein excretion when compared with the normal pregnant rats (0.3 ± 0.04 vs 0.47 ± 0.07 g/dL) (p < 0.05). Associated with the hypertension in RUPP rats, placental levels of malondialdehyde (2.4 ± 0.2 vs. 1.6 ± 0.2 umol/gm tissue) and protein carbonyl (1.4 ± 0.3 vs. 0.9 ± 0.3 nmol/mg protein) were increased, while superoxid dismutase (0.03 vs 0.42 U/mg protein) and glutathione peroxidase (1.04 ± 0.31 vs 0.76 ± 0.22 U/g protein) were decreased. Pup number (6.6 ± 3.1 vs. 9.93 ± 2.0) and litter weight (17.4 ± 7.7 vs. 22.9 ± 6.7 g) were lower in the preeclamptic group. None of the complete blood counts and biochemical values other than sodium and chlorine were significantly different in preeclamptic group. Our findings suggest that the RUPP model cannot mimic severe preeclampsia; however, further studies using different settings may be helpful to obtain a preeclampsia model that is capable of successfully producing severe preeclampsia findings., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

We investigated the effect of long-term exposure to modulation magnetic field (MF), insulin, and their combination on blood-brain barrier (BBB) permeability in a diabetic rat model. Fifty-three rats were randomly assigned to one of six groups: sham, exposed to no MF; MF, exposed to MF; diabetes mellitus (DM), DM induced with streptozotocin (STZ); DM plus MF (DMMF); DM plus insulin therapy (DMI); and DM plus insulin therapy plus MF (DMIMF). All the rats underwent Evans blue (EB) measurement to evaluate the BBB 30 days after the beginning of experiments. The rats in MF, DMMF, and DMIMF groups were exposed to MF (B = 5 mT) for 165 min every day for 30 days. Mean arterial blood pressure (MABP), body mass, and serum glucose level of the study rats were recorded. The extravasation of brain EB of the MF, DM, DMMF, DMI, and DMIMF groups was higher than that of the sham group and the extravasation of right hemisphere of the DMIMF group was highest (P < 0.05). The post-procedure body mass of the sham and MF groups were significantly higher than those of the DM and DMMF groups (P < 0.05). In the DM, DMMF, DMI, and DMIMF groups, the baseline glucose was significantly lower than the post-procedure glucose (P < 0.05). DM and MF increase BBB permeability; in combination, they cause more increase in BBB permeability, and insulin decreases their effect on BBB. Improved glucose metabolism may prevent body mass loss and the hypoglycemic effect of MF. DM increases MABP but MF causes no additional effect.

Creatine (Cr) has been shown to increase the total muscle mass. The purpose of this study was to investigate the effect of Cr supplementation on muscle morphology and swimming performance, using an animal model. Each rat was subjected to exercise 15-minute period daily for the 12 weeks. The rats were randomly divided into four groups: no Cr supplementation (CON), no Cr supplementation and incomplete food intake (lacking lysine and methionine in diet for rats) (INCO), Cr supplementation 1 g·kg(-1)·day(-1) (CREAT-I) and Cr supplementation 2 g·kg(-1)·day(-1) (CREAT-II). Three months later, all groups adult rats exercised in swimming pool chambers. Swimming time was recorded as minute for each rat. Following swimming performance period, the animals were killed by cervical dislocation and the gastrocnemius and diaphragm muscles were dissected. Serial slices of 5-7 μm were allocated paraffin wax and histochemical staining procedure of cross-sections was carried out with heamatoxylin-eosin technics. All groups gained body weight at the end of 12 weeks but there was no statistical difference among them. Swimming time values were statistical difference between CREAT-II and CON group as well as between CREAT-I and CON group (p < 0.05). In the INCO group was determined increased connective tissue cell of the muscle sample. In contrast, in the CREAT-I and CREAT-II group, the basic histological changes were large-scale muscle fibers and hypertrophic muscle cells. These results suggest that long-term creatine supplementation increased the number of muscle fibers and enhanced endurance swimming performance in rats. Key pointsThere is no study about the effects of creatine long-term supplementation on muscle morphology and swimming performance in rats.Long-term creatine supplementation increase muscle hypertrophy (but not body weight) and enhance endurance swimming performance in rats.The quantitative analysis indicated that the number of muscle fibers per defined area increased in creatine supplementation groups.

The cerebral vessels are innervated by sympathetic, parasympathetic, and sensory nerves. A sensory innervation of the cerebral vessels originating in the trigeminal ganglion has been described in a number of species by several investigations. It has been shown that the electrical stimulation of the trigeminal ganglion causes an increase of cerebral cortical blood flow (CCoBF). The aim of the present study was to determine the effects of dental electrical stimulation the CCoBF in rabbits. A stimulating electrode was located in the upper right incisor tooth of rabbits and trigeminal ganglion was stimulated orthodromically via the infraorbital nerve. Variations in the cortical CCoBF were evaluated by laser-Doppler flowmetry. In experiment group, CCoBF increased together with the beginning of electrical stimulation (5 V, 0.5-ms impulse duration, square-shaped, 10-Hz frequency). The right and left hemisphere CCoBF values of stimulation period at 15s, 30s, 45s, 60s, 75s, and 90s were significantly higher than those of baseline and 105 and 120s (p < 0.05). The maximum increase in right and left CCoBF was 15.6% and 15.1% respectively. In post-stimulation period, the right CCoBF decreased gradually and returned to the baseline values at 120 s. In experiment groups, the CCoBF values of right hemisphere were comparable that of left hemisphereL (p > 0.05). This study demonstrated that the electrical stimulation of the trigeminal nerve's infraorbital branch via dental pulp increases the cortical right and left CCoBF under physiological conditions.

The pathophysiology of pre-eclampsia is still unknown thus effective primary prevention is not possible at the stage. The present study was conducted to research the smooth muscle responses in the pre-eclampsia model with suramin treated rats and the effect of phosphodiesterase-5 (PDE5) inhibitor on these responses. Rats of three groups; control, suramin and suramin+sildenafil were given intraperitoneal injections of saline, suramin or sildenafil citrate. Suramin injections caused increased blood pressure, protein in urine and caused fetal growth retardation. The use of sildenafil citrate straightened significantly both blood pressure and average fetus weight, but did not reach to control values. At the end of pregnancy, thoracic aorta rings were exposed to contractile and relaxant agents. KCl contraction responses, sodium nitroprusside and papaverine relaxation responses were similar in three groups. Contraction responses of phenylephrine, increased significantly in suramin group. Relaxation responses of acethylcholine and bradykinin decreased in suramin group. The use of sildenafil citrate partially straightened both relaxation and contraction responses, but did not reach to control values. In all groups in the presence of L-nitromonomethylarginine (L-NAME), 1H-(1, 2, 4) oxadiazole (4, 3-a) guinoxalin-1-one (ODQ) and indomethacin decreased the relaxation responses of acetylcholine and bradykinin. The cyclic guanosine monophosphate (cGMP) content of thoracic aorta tissue was determined by radioimmunoassay technique. The content of cGMP in suramin group decreased and use of sildenafil citrate increased the cGMP content but did not reach to control values. We conclude that in pre-eclampsia, the increase of contraction responses, the decrease of relaxation responses and the decrease of cGMP content can depend on insufficiency about synthesis or release of relaxant factors which was released from the vessel endothelium. The results in this study show that in pre-eclampsia; PDE5 inhibitors enhance endothelial function and may be used for protection. Further studies are needed to clear the efficiency and safety of PDE5 inhibitors.

The aim of the present study was to investigate the habituation rates of the sympathetic skin response (SSR) in sedentary subjects and trained sportsmen. A total of 52 voluntary male students (30 sedentary subjects and 22 trained sportsmen) participated in the experiment. SSR was recorded with the contralateral electrical stimulation of the ulnar nerve (of the upper extremities). In order to initiate the SSRs, 16 square-wave consecutive electrical shock stimuli were presented to each subject over the left ulnar nerve. In 52 subjects, 16 stimuli were applied at random time intervals (20-50 s). In sedentary subjects, the mean amplitude of the SSRs decreased from 4.83 +/- 0.36 mV at the first stimulus, to 0.80 +/- 0.12 mV at the 16th stimulus. In trained sportsmen, the mean amplitude of the SSRs decreased from 3.95 +/- 0.51 mV at the first stimulus, to 0.80 +/- 0.17 mV at the 16th stimulus. In the sedentary subjects, at the S1-S9 stimuli, the mean amplitudes of SSRs were higher than those of trained sportsmen. Depending upon these findings we can say that the trained sportsmen showed a more rapid habituation than sedentary subjects. In these processes, changes of amplitude and latency values reflect changes in amount of neuronal activation. Amplitude reflects the amount of neuronal activation, which is concerned with number of neuronal populations. Neuroplasticity, known as the habituation of the brain, is the adaptation of autonomic nervous system, which can be reflected by SSRs.

Objective: To determine the association of leptin with insulin resistance, body composition, and lipid parameters in postmenopausal women and men with type 2 diabetes mellitus (T2DM)., Methods: This study was conducted in 158 patients (87 postmenopausal women and 71 men) with T2DM, and 99 healthy controls (52 postmenopausal women and 47 men). Type 2 diabetes mellitus patients were selected consecutively from the outpatient Endocrinology Service of Cumhuriyet University Hospital, Sivas, Turkey from April 2002 to March 2005. We collected demographic, leptin, insulin resistance, and lipid and body composition parameters., Results: Serum leptin levels of females were significantly higher than those of men in both T2DM, and healthy participants. The basal metabolic rate, fat free mass, and total body water of males, were lower than those of females. In both T2DM and healthy participants, leptin was positively correlated with insulin resistance and body composition parameters in both gender. Serum leptin levels of females were higher compared with males in the same BMI, independent of T2DM., Conclusion: Leptin was associated with insulin, insulin resistance, and body composition parameters (body mass index, basal metabolic rate, body weight, %fat, and fat mass) in participants, with or without T2DM in both genders. Type 2 diabetes mellitus seemed more effective on insulin resistance than obesity. We suggest that the female gender, and fat mass, and not T2DM might have significant influence on leptin levels in age.

Background: The autonomic nervous system in Behcet's patients may be affected due to various reasons. This entity may be detected with the measurement of the electrodermal activities, heart rate variability and pupillometric methods. Habituation is one of the implicit forms of learning and memory and the loss of habituation can reveal pathological changes in the synaptic regions., Aim: To determine whether there is a functional decrease in the synaptic effectiveness (habituation) of the pathways to sympathetic neurons that had been repeatedly activated in Behcet's., Materials and Methods: Twelve patients with Behcet's disease and 12 healthy controls were included in the study. Sympathetic skin potential (SSP) records were taken at normal room temperature in a quiet place within a Faraday cage. Sixteen square wave single shock impulses (duration: 1200 ms, strength: 5 mA) were applied on each case., Results: After the 1st stimulus, the SSP amplitudes were lower in the patients compared to the controls (P<0.001, t value=7.69). There was no significant differences among the SSP amplitudes after the 13th impulse in the patients (P>0.05). Whereas there was no significant differences among the SSP amplitudes after the 9th impulse in the controls (P>0.05). The habituation rate of the SSP after consecutive impulses was slowest in the patients compared to controls (P<0.001, t value=12.39)., Conclusions: There is a delayed habituation in Behcet's disease and that may due to pathologic changes with vasculitis through their peripheral nerves.

Iron plays an important role in maintaining normal brain function. However, in many neurodegenerative diseases abnormal iron accumulation in specific brain regions has been consistently reported. In this study, we investigated the neurotoxic effect of the intracerebroventricularly injected iron on the cerebellar Purkinje cells in the rat and the role of nitric oxide (NO) in this process. The role of NO in rats administered iron (FeCl36H2O) was examined with the use of a donor of NO, L-arginine (L-Arg) and a central selective inhibitor of NO synthase, 7-nitroindazole (7-NI). For this reason, rats were divided into 5 groups: control, iron-injected, iron plus L-Arg, iron plus 7-NI, and iron plus L-Arg plus 7-NI. Means (value +/- standard deviation) of the total numbers of Purkinje cells in the cerebellum were estimated as 337 +/- 23, 209 +/- 16, 167 +/- 19, 305 +/- 26, and 265 +/- 14 thousands in the control, iron, iron plus L-Arg, iron plus 7-NI, and iron plus L-Arg plus 7-NI groups, respectively. Iron treatment alone and the combination of iron and L-Arg caused a significant reduction in the total number of cerebellar Purkinje cells. Therefore, L-Arg increased the Purkinje cell loss induced by treatment with iron. These data show that inhibition of the neuronal NOS by 7-NI can prevent some of the deleterious effects of iron on cerebellar Purkinje cells. Presence of L-arginine decreased the neuroprotective effect of 7-NI.

Leptin and zinc are involved in the regulation of appetite. Copper is a trace element regulating the functions of several cuproenzymes that are essential for life. To evaluate the relationship between zinc and copper status and the leptin system in humans, we examined whether leptin concentrations in the mother and the newborn correlate with the weight of mother, placenta and newborn. A total of 88 pregnant women at 38-42 weeks' gestation were studied. All infants were categorized as small for gestational age (SGA) (n = 16), average for gestational age (AGA) (n = 59) or large for gestational age (LGA) (n = 13). Leptin, zinc, and copper levels were measured in maternal and cord serum at birth. Maternal BMI and placental weight of the LGA groups were significantly higher than those of the SGA and AGA groups. Cord and maternal leptin levels of the SGA groups were significantly lower than those of the AGA and LGA groups. Maternal serum leptin levels were positively correlated with BMI and maternal zinc levels in all groups. Cord serum leptin levels of all groups were positively correlated with birth weight and placental weight. Birth weight was negatively correlated with maternal and cord copper level of all groups. Umbilical leptin concentrations of SGA newborns correlated with leptin concentrations of their mothers. In all pregnancies, birth weight increases in association with increase in cord leptin level. Our results suggest that maternal zinc but not copper level has an effect on maternal serum leptin levels. The increase in copper level in both maternal and cord blood may contribute to restriction in fetal growth.

Alterations in vascular responses to beta-adrenoceptor agonists in normotensive pregnancy and pre-eclampsia are not fully understood. Thus, we studied changes in vasodilator responses to beta(2)-adrenoceptor agonist formoterol and beta(3)-adrenoceptor agonist BRL 37344 on umbilical arteries isolated from normotensive (n=12) and pre-eclamptic (n=12) pregnant women. Changes in the relaxant effect of formoterol and BRL 37344 were investigated by measuring isometric tensions in endothelium-denuded strips of umbilical arteries in the presence or absence of metoprolol, ICI 118.551 and SR 59230A (beta(1), beta(2), beta(3)-adrenoceptor antagonists, respectively, 10(-6) mol/L). Effects of formoterol and BRL 37344 on cAMP levels of umbilical arteries were evaluated by radioimmunoassay kits. Formoterol (10(-10)-10(-4) mol/L) and BRL 37344 (10(-10)-10(-4) mol/L) caused concentration-dependent relaxation of the contraction induced by phenylephrine (10(-5) mol/L) in umbilical artery strips isolated from both groups. E(max) values of formoterol and BRL 37344 (for normotensive pregnant women: 87.33+/-0.87 and 53.25+/-1.17 vs. for pre-eclampsia: 73.68+/-1.58 and 43.64+/-1.19, n=12, P>0.05, respectively) were significantly smaller in strips from pre-eclamptic women (P<0.05), with no significant change in pD(2) values. E(max) values of formoterol were significantly higher than those of BRL 37344 in both tissue (P<0.05). ICI 118.551 and SR 59230A, but not metoprolol, antagonized the relaxant effects of formoterol and of BRL 37344 on umbilical artery strips isolated from normotensive and pre-eclamptic pregnant women. Formoterol and BRL 37344 increased cAMP levels in both groups, but less significant in pre-eclamptic strips (P<0.05). These results suggest that the relaxation caused in human umbilical arteries by formoterol and BRL 37344 is mediated by a mixed population of beta(2)- and beta(3)-adrenoceptor subtypes, with contribution of cAMP. Umbilical arteries from subjects with pre-eclampsia showed a weaker beta(2)- and beta(3)-receptor-mediated relaxation to formoterol and BRL 37344, suggesting that the reduced action of formoterol and BRL 37344 may be partly due to a decreased effect of cAMP.

Nimesulide, celecoxib, and DFU (5, 5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone) are nonsteroidal anti-inflammatory drugs (NSAIDs) with selective cyclo-oxygenase (COX)-2 blocking properties and have potent analgesic and anti-inflammatory activities in oral and parenteral administrations. Dexmedetomidine, a highly selective alpha(2)-adrenoceptor agonist, is an extremely potent antinociceptive agent. The present study was conducted to evaluate the antinociception induced by nimesulide, celecoxib, and DFU when topically applied on the tail in the absence or presence of intraperitoneal dexmedetomidine. Antinociception was measured in the radiant tail-flick test after immersion of the tail of rat into a solution of dimethyl sulfoxide (DMSO) containing nimesulide, celecoxib, or DFU. Antinociceptive effect of all drugs peaked at 60 min and decreased gradually to baseline levels at 240 min. Nimesulide had a potency lower than those of celecoxib, and DFU. The antinociceptive effect of dexmedetomidine was blocked by systemic pretreatment of selective alpha(2)-adrenoceptor antagonist, atipamezole. This suggests that antinociceptive effects of dexmedetomidine involve alpha(2)-adrenoceptors. Combination of topical COX-2 inhibitors with intraperitoneal dexmedetomidine yielded additive analgesic effect. These results demonstrate an additive interaction between topical COX-2 inhibitors with intraperitoneal dexmedetomidine. These observations are significant for physicians to combine selective COX-2 inhibitors and dexmedetomidine in the management of pain.

The study was performed to evaluate whether magnesium sulfate could alter the degree of disruption of the blood-brain barrier (BBB) caused by hyperosmotic mannitol. Wistar adult female rats were infused with 25% mannitol into the left internal carotid artery. Each animal received intraperitoneally a 300 mg/kg loading dose of magnesium sulfate, dissolved in 0.9% saline, followed by a further 100 mg/kg dose. In the other group, intracarotid infusion of magnesium sulfate was performed at a dose of 150 mg/kg 10 min before mannitol administration. Evans blue (EB) dye was used as a marker of BBB disruption. The measured serum glucose and magnesium levels increased after mannitol and/or magnesium administration when compared with their initial values before treatment (P < 0.01). Water content of the left hemisphere was significantly increased by hyperosmotic mannitol (P < 0.01). The increased water content in the mannitol-perfused hemisphere was significantly decreased by magnesium treatment (P < 0.05). The content of EB dye in the mannitol-perfused hemisphere markedly increased when compared with the right hemisphere of the same brain (P < 0.01). The EB dye content in the mannitol-perfused hemisphere following both intraperitoneal and intraarterial administration of magnesium decreased when compared with mannitol alone (P < 0.01). We conclude that although magnesium sulfate administration by both intracarotid arterial and intraperitoneal routes attenuates BBB disruption caused by hyperosmolar mannitol, particularly intraperitoneal route of magnesium sulfate administration may provide a useful strategy to limit the transient osmotic opening of the BBB.