Objectives: The present work was designed to studythe role of endocannabinoid system in the obesity associated atherogenesis and trying to clarify its possible mechanism/s of action. Methods: Thirty adult male wistar albino rats were utilized in the present experiment. They were divided into three equal groups (10 rats each); Group 1: Lean control group, which were fed normal laboratory chow diet and gavaged once daily by dimethyl sulfoxide in a dose of 0.6ml/kg /day for 10 weeks. Group 2: Atherogenic diet group which were fed high fat diet and gavaged once daily by dimethyl sulfoxide as group 1. Group 3: Atherogenic diet treated group which were fed high fat diet and gavaged once daily by NIDA-41020 (a selective cannabinoid receptor 1 blocker) in a dose of 10mg/ kg /day for 10 weeks. Then body mass index (BMI), bleeding time, and total clotting time were assessed. After that, the animals were sacrificed and lipid profile, atherogenic index, bleeding time, platelet aggregation percentage, clot retractions, clotting time, prothrombin time (PT), activated partial thromboplastin time (aPTT), total & differential leukocytic counts and serum adiponectin levels were assessed in all groups. The aorta was obtained from each animal dissected and stained by haematoxylin/eosin and oil Red O staining for histological examination and detection of aortic thickness and foam cells deposition. Results: The laboratory investigations and histological examination revealed, significant increases in BMI, lipid profile, atherogenic index, platelet aggregation%, peripheral monocytic count, and aortic thickness in the high fat diet received group versus lean controls which were otherwise associated with significant decreases in total clotting time, PT, aPTT, serum HDL & adiponectin levels. These changes were significantly and profoundly inhibited by the administration of the cannabinoid receptor antagonist. Conclusion: The endocannabinoid system is involved in the atherogenic changes associated with obesity. These effects were attributed to interference with serum adiponectin level, dyslipidemia, hypercoagulability, increased platelet activation & peripheral as well as endothelial recruitment of monocytes. These effects were found to be via activation of cannabinoid 1 receptor.
The motor function of GIT can be modulated by prokinetics or myorelaxant drugs depending on the nature of the disorder. There is a frequent need for facilitation of gastric emptying in treatment of functional dyspepsia. Among prokinetic drugs used there are compounds belonging to cholinergic and adrenolytic classes. In addition, drugs having affinity for serotonin, motilin and opioid receptors, also participate in alleviating delayed gastric emptying. Itopride is a prokinetic that acts via blocking D 2 receptors in addition to inhibition of choline esterase. Metoclopramide prokinetic effect on the other hand is mediated through D 2 receptor blockade. This study was designed to investigate the effect of the two prokinetic drugs (itopride and metoclopramide) on the motility of different parts of GIT. The results of the present work demonstrated that both itopride and metoclopramide produced significant increments in the amplitude of contraction of fundus stomach of rats, pylorus, jejunum and colon of rabbit in a concentrationdependent manner, It was also proved that itopride is more potent as a prokinetic on these parts of GIT which is evident by the low ED50 of itopride compared to that of metoclopramide. In conclusion, itopride is preferred as a prokinetic than metoclopramide because it has higher potency in addition to acceleration of upper and lower GIT motility.
Background: Ivabradine, Hyperpolarization activated cyclic nucleotide gated (HCN) channel blocker, is the most specific blocker of central nervous system Ih current. Valporate is one of the most commonly used antiepileptic drugs. Objectives: investigate the possible anticonvulsant effect of Ivabradine and its interaction with valporate in pentylenetetrazole (PTZ) induced-kindling in mice. Materials& Methods: mice were divided into four groups, "Group 1", "vehicletreated group" "Group 2", "PTZ kindling Control group "Group 3: Ivabradine ", group 4 Valproate (VPA) group 5" Ivabradine and VPA. Kindling was produced by repeated intraperitoneally (i.p). administration of PTZ (40mg/kg), every other day for 9 doses. Both drugs were administered i.p., 30 minutes before each PTZ injection. Seizure score, latency were recorded. Their brains were removed for assessment of oxidant/antioxidant status and anti-inflammatory cascades. Results: Ivabradine and VPA individually significantly decreased seizure score and co administration of both drugs significantly decreased seizure score less than either vaporate or Ivabradine. Both drugs significantly increased latency to seizures. Ivabradine, VPA and their combined administration significantly elevated brain level of GSH, catalase and significantly decreased levels of nitrite, MDA, IL1β, and TNFα as compared to PTZ control group. Co-administration of both drugs resulted in a significant elevation in the brain level of GSH, catalase concomitant with a significant reduction in the brain levels of MDA, IL1β and TNFα as compared to either VPA or ivabradine groups. Conclusion: Ivabradine has anticonvulsant effect and potentiates the effect of VPA which may be attributes to HCN channel blockade, antioxidant and anti-inflammatory effects.
Background: Pain is an unpleasant sensation experienced when tissues are damaged. Therapeutic management of pain requires consideration of many factors due multiplicity of etiopathogenesis. Objectives: The present study was designed to assess and compare the analgesic effects of gabapentin, diclofenac and tizanidine as well as their combinations in acute and chronic pain. Methods: 128 rats were randomly allocated into two main equal categories; one for acute inflammatory and other for chronic neuropathic pain study. The acute category was divided into 8 equal groups; control, carrageenan, diclofenac, gabapentin, tizanidine, gabapentin-diclofenac, gabapentintizanidine and tizanidine-diclofenac groups. Acute inflammatory pain was induced by carrageenan injection in the animals paw. In the chronic category neuropathic pain was induced by right sciatic nerve ligation except for control and sham groups. This category was divided into; control, sham, gabapentin, tizanidine, gabapentin-diclofenac, gabapentin-tizanidine and tizanidinediclofenac groups. The mean reaction time was assessed in all groups. Results: In acute pain the three drugs and their combinations had significant analgesic effects. Tizanidine potentiated the analgesic effects of diclofenac and gabapentin. In chronic neuropathic pain diclofenac and gabapentin had significant analgesic action while, tizanidine had no analgesic effect. Conclusion: Tizanidine didn't show analgesic effect on chronic pain but potentiated the analgesic effect of gabapentin and diclofenac in acute pain model.
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