Sebnem Apaydin

Analysis of the antinociceptive effect of systemic administration of tramadol and dexmedetomidine combination on rat models of acute and neuropathic pain

The aim of the present study was to investigate the possible antinociceptive effect of systemic administration of tramadol and dexmedetomidine either alone or in combination on acute and neuropathic pain models in rats. The antinociceptive effects of intraperitoneal (i.p.) tramadol (5-20 mg/kg) and dexmedetomidine (5-20 microg/kg) and three different combinations of tramadol+dexmedetomidine (5+5, 5+10 and 10+5, mg/kg+microg/kg, respectively) were measured by tail-flick and hot-plate methods in acute pain. The effects on the sciatic nerve ligation-induced neuropathic pain was tested by i.p. administration of tramadol (5 mg/kg), dexmedetomidine (5 microg/kg) and tramadol+dexmedetomidine combination (5+5) using a thermal plantar test. Sedation/motor-incoordination was assessed on rotarod. Tramadol and dexmedetomidine produced dose-related antinociception in tail-flick and hot-plate tests. In both tests, combination of these drugs produced an antinociceptive effect that is greater than that produced by tramadol or dexmedetomidine alone at several time points. In hot-plate test, tramadol+dexmedetomidine combination (5+10) exerted the strongest antinociceptive effect, while tramadol+dexmedetomidine combination (10+5) was significantly most effective in tail-flick test. In the neuropathic pain, the antinociceptive effect exerted by tramadol+dexmedetomidine combination (5+5) was also significantly greater than their applications alone. In rotarod test, tramadol (30 and 40 mg/kg), dexmedetomidine (30 and 40 microg/kg), tramadol+dexmedetomidine combination (10+10, 20+20) produced sedation/motor-incoordination, whereas tramadol (5-20 mg/kg), dexmedetomidine (5-20 microg/kg) and tramadol+dexmedetomidine combination (5+5, 5+10 and 10+5) did not produce any effect on sedation/motor-incoordination. The combination of tramadol and dexmedetomidine was more effective in increasing the pain threshold in acute and neuropathic pain when compared with the administration of either of these drugs alone.

Antispasmodic effect of Achillea nobilis L. subsp. sipylea (O. Schwarz) Bässler on the rat isolated duodenum.

The aim of the present study was to investigate the antispasmodic effect of the total extract of Achillea nobilis L. subsp. sipylea (Schwarz) Bässler (Asteraceae) on rat duodenum. In the first part of experiments, cumulative dose-response curves for acetylcholine (Ach) were obtained and then dose-response curves are repeated after addition of atropine, papaverine and different doses of the extract. In the second part, cumulative dose-response curves to CaCl(2) were obtained in the absence and presence of verapamil and different doses of the extract. In the third part, papaverine and extract were applied to the tissues after contraction with K(+). The extract has exhibited an inhibitory effect on the dose-response curves induced by Ach and CaCl(2) on rat duodenum and significantly reduced the maximal response in a concentration-dependent manner. A similar effect was observed with papaverine but not with atropine on the dose-response curves obtained by ACh. Verapamil also reduced the maximal response in curves induced by CaCl(2). The present results demonstrate that total extract of A. nobilis subsp. sipylea exerts antispasmodic activity on rat duodenum.

The antinociceptive effect of tramadol on a model of neuropathic pain in rats.

The antinociceptive activity of tramadol was investigated on the vocalization threshold to paw pressure in a rat model of unilateral mononeuropathy produced by loose ligatures around the common sciatic nerve. Despite the analgesic activity of tramadol was clearly established in motor and sensory responses of the nociceptive system in rats, the effect of this atypical opioid on experimental neuropathic pain models is not investigated. The intraperitoneally injected tramadol (2.5, 5 and 10 mg/kg) produced a potent and dose-dependent antinociceptive effect on both lesioned and non-lesioned hind paws. However, the analgesic effect on the lesioned paw was significantly more potent than the non-lesioned paw. This effect was partially antagonized by intraperitoneally administered naloxone (0.1 mg/kg) suggesting an additional non-opioid mechanism. Our results suggest that tramadol may be useful for the alleviation of some symptoms in peripheral neuropathic conditions

Hypericum triquetrifolium Turra. extract exhibits antiinflammatory activity in the rat

The aim of the present study was to explore the probable antiinflammatory effect of Hypericum triquetrifolium Turra. in a rat model of carrageenan induced inflammation. Male Wistar rats were treated intraperitoneally with 0.4% dimethylsulphoxide (DMSO) (as control group) and H. triquetrifolium extract (25, 50, 60 mg/kg), 30 min before 0.1 ml 1% carrageenan injection. Paw volume was measured before and 1, 2, 3, 4, 5 and 6 h after the injection of carrageenan. The results are expressed as the mean+/-s.e. mean and the statistical significance of differences between groups was analyzed by One Way Analysis of Variance (ANOVA). The intraplantar injection of carrageenan caused a time-dependent paw edema in the rat although saline injection caused no swelling. Intraperitoneal administration of H. triquetrifolium extract (25, 50, 60 mg/kg) inhibited paw swelling dose-dependently at 2, 3, 4, 5 and 6 h after carrageenan injection (P<0.05). We can conclude that H. triquetrifolium extract may exert an antiinflammatory effect in rats.

Hypericum triquetrifolium Turra. extract exhibits antinociceptive activity in the mouse.

The aim of the present study was to investigate the antinociceptive activity of Hypericum triquetrifolium Turra. extract. The lyophilized extract was administered to male Swiss mice. Formalin paw test and tail flick tests were used for the evaluation of the antinociceptive activity. Plant extract (10, 25, 50 and 60 mg kg(-1), i.p.) (n = 16-24 for each group) or vehicle (n = 27) was administered 30 min before the subplantar formalin injection. In the tail flick test, mice were examined for latency to withdraw their tails from a noxious thermal stimulus using a tail flick meter (n = 8 for each group). The effects of the extract on sensorimotor performance was also assessed (n = 16-24 for each group). The extract caused a significant dose-related inhibition of the first phase (50, 60 mg kg(-1), i.p.) and second phase (10, 25, 50 and 60 mg kg(-1), i.p.) of formalin induced hindpaw licking. Additionally, the extract administration (50, 60 mg kg(-1), i.p.) increased the tail flick latencies. No significant change was observed in any of the treatment groups in the sensorimotor performance test. The observed antinociceptive activity of the extract may be due to its noradrenaline and serotonin reuptake blocking activity. Moreover, the probable antiinflammatory activity of the extract may play a role in the dose-related inhibition of the second phase of formalin paw test.

Antinociceptive and Anti-inflammatory Activities and Acute Toxicity of Achillea nobilis. subsp. neilreichii. Extract in Mice and Rats

Abstract The ethanol extract of Achillea nobilis. L. subsp. neilreichii. (Kerner) Formanék (Asteraceae) flower heads was investigated for its antinociceptive and anti-inflammatory activities and for acute toxicity in mice and rats. While the extract exhibited an antinociceptive effect during the late phase of the formalin test (100, 200, and 400 mg/kg, i.p.) and an anti-inflammatory effect in the paw edema test (100 and 200 mg/kg, i.p.), it did not exert any significant antinociceptive effect in the tail-flick test. Furthermore, administration of 400 mg/kg extract increased the latency to hot-plate test at 60 and 90 min. No significant change was detected in sensory motor performance. The acute LC50 value of the extract was 4456 mg/kg (i.p.) in mice. The current results demonstrate that an ethanol extract of A. nobilis. L. subsp. neilreichii. exerts anti-inflammatory activity.

Evaluation of the Antinociceptive and Anti-inflammatory Activities of Satureja thymbra. L. Essential Oil

Abstract The aim of this study was to investigate the antinociceptive and anti-inflammatory activities of the essential oil of Satureja thymbra. L. (Lamiaceae). Antinociceptive activity of the essential oil was measured by the formalin test in mice and by the light tail-flick and hot-plate methods in rats. The paw-edema test was performed in rats to evaluate the anti-inflammatory effect of the essential oil. Motor coordination was assessed with a rotarod apparatus. Although the essential oil produced an antinociceptive effect during both the early (50 and 100 mg kg−1) and late phases (25, 50, and 100 mg kg−1) of the formalin test, it did not exert any significant antinociceptive and anti-inflammatory effects in tail-flick and paw-edema tests, respectively. In addition, a significant antinociceptive effect was detected in the hot-plate test (100 and 200 mg kg−1). No significant change was detected in sensory motor performance. In conclusion, S. thymbra. L. essential oil does not exert any anti-inflammatory effect while it may have central analgesic activity in mice and rats.

L-CARNITINE DOES NOT EXERT ANY IN VITRO RELAXANT EFFECT IN GUINEA PIG TRACHEA, LUNG PARENCHYMA AND HUMAN BRONCHIAL TISSUE

The aim of the present study was to investigate the probable in vitro relaxant effect of carnitine in guinea pig trachea, guinea pig lung parenchymal strips, and human bronchial tissue. It was suggested by an in vivo study that carnitine pretreatment prevented the subclinic bronchospasm in children who underwent chronic hemodialysis. Tracheal and lung parenchymal preparations of 10 guinea pigs and 5 human bronchial tissues were prepared and mounted in 20-mL organ baths. In the first series of experiments, contractions to carbachol and histamine (10 -9 to 10 -3 M) were compared after the tissues were incubated with different concentrations of L-carnitine (10 -6 to 10 -4 M). pD 2 values were compared with analysis of variance (ANOVA) and P <. 05 was considered as significant. In the second part of experiments, the inhibitory effect of L-carnitine (10 -9 to 10 -3 M) was investigated on the sustained contractions of preparations to carbachol (10 -6 M) and histamine (10 -5 M). In the first part of the study pD 2 values obtained with carbachol were 6.48 ± 0.09, 5.42 ± 0.05, and 6.48 ± 0.02 for guinea pig trachea, guinea pig lung parenchymal strips, and human bronchial tissues, respectively. pD 2 values obtained with histamine were 5.34 ± 0.10, 5.74 ± 0.06, and 6.32 ± 0.03 for guinea pig trachea, guinea pig lung parenchymal strips, and human bronchial tissues, respectively. No significant difference was observed between the pD 2 values before and after incubation with carnitine (P >. 05). In the second part of the study, only 10 -4 M L-carnitine exerted an insignificant relaxant effect (6.16% ± 1.22% on carbachol induced contractions and 4.48% ± 0.85% on histamine induced contractions) in guinea pig trachea. Our results show that L-carnitine exerts no in vitro relaxant effect in guinea pig trachea, guinea pig lung parenchymal strips, and human bronchial preparations.

Enhancing Solubility and Bioavailability of Rosuvastatin into Self Nanoemulsifying Drug Delivery System

OBJECTIVEnThe aim of this study was to develop new Rosuvastatin calcium (RCa) self nanoemulsifying drug delivery system (SNEDDS) and to evaluate the bioavailability and pharmacodynamic effect of RCa-SNEDDS in Yorkshire pigs.nnnMETHODSnFirstly, SNEDDS was developed and prepared then RCa was incorporated into SNEDDS which was evaluated regarding their characterization, stability properties, drug release profiles, permeation and cytotoxicity studies. Finally, in vivo performance of RCa-SNEDDS (F1-RCa-SNEDDS) was examined by pharmacokinetic and pharmacodynamics studies. The average droplet size of RCa- SNEDDS ranged between 200 and 250 nm. RCa-SNEDDS that contained 12.8% Oleic acid, 11 % Labrafil M, 3.3 % Labrasol and 4.4 % Transcutol HP were found to be stable and exhibited approximately 4-fold higher permeation than commercial tablet (Crestor® 20 mg tablet).nnnRESULTSnIn pharmacokinetic studies, when F1-RCa-SNEDDS and commercial tablet were administered orally, F1-RCa-SNEDDS showed higher bioavailability of RCa than commercial tablet. Respectively, in pharmacodynamic studies, triglyceride and total cholesterol levels were significantly reduced with F1- RCa-SNEDDS formulation by 37% and 19% when compared to baseline values.nnnCONCLUSIONnHowever, these decreases with commercial formulation were only 6% and 2% respectively. According to these findings, development formulation could be potentially used to enhance the oral absorption of RCa.

Can yoga have any effect on shoulder and arm pain and quality of life in patients with breast cancer? A randomized, controlled, single-blind trial

OBJECTIVEnTo examine the effects of yoga on shoulder and arm pain, quality of life (QOL), depression, and physical performance in patients with breast cancer.nnnMETHODSnThis prospective, randomized study included 42 patients. The patients in Group 1 underwent a 10-week Hatha yoga exercise program. The patients in Group 2 were included in a 10-week follow-up program. Our primary endpoint was arm and shoulder pain intensity.nnnRESULTSnThe group receiving yoga showed a significant improvement in their pain severity from baseline to post-treatment, and these benefits were maintained at 2.5 months post-treatment. When compared to the control group, there were no statistically significant differences between the 2 groups with respect to the parameters assessed at the end of week 10.nnnCONCLUSIONnYoga was an effective and safe exercise for alleviating shoulder and arm pain, which is a complication with a high prevalence in patients with breast cancer.