Mohammad Sharifzadeh

Ultra-low dose cannabinoid antagonist AM251 enhances cannabinoid anticonvulsant effects in the pentylenetetrazole-induced seizure in mice

Several lines of evidence suggest that cannabinoid compounds are anticonvulsant since they have inhibitory effects at micromolar doses, which are mediated by activated receptors coupling to Gi/o proteins. Surprisingly, both the analgesic and anticonvulsant effects of opioids are enhanced by ultra-low doses (nanomolar to picomolar) of the opioid antagonist naltrexone and as opioid and cannabinoid systems interact, it has been shown that ultra-low dose naltrexone also enhances cannabinoid-induced antinociception. However, regarding the seizure modulating properties of both classes of receptors this study investigated whether ultra-low dose cannabinoid antagonist AM251 influences cannabinoid anticonvulsant effects. The clonic seizure threshold (CST) was tested in separate groups of male NMRI mice following injection of vehicle, the cannabinoid selective agonist arachidonyl-2-chloroethylamide (ACEA) and ultra-low doses of the cannabinoid CB1 antagonist AM251 and a combination of ACEA and AM251 doses in a model of clonic seizure induced by pentylenetetrazole (PTZ). Systemic administration of ultra-low doses of AM251 (10 fg/kg-100 ng/kg) significantly potentiated the anticonvulsant effect of ACEA at 0.5 and 1 mg/kg. Moreover, inhibition of cannabinoid induced excitatory signaling by AM251 (100 pg/kg) unmasked a strong anticonvulsant effect for very low doses of ACEA (100 ng/kg-100 microg/kg), suggesting that a presumed inhibitory component of cannabinoid receptor signaling can exert strong seizure-protective effects even at very low levels of cannabinoid receptor activation. A similar potentiation by AM251 (100 pg/kg and 1 ng/kg) of anticonvulsant effects of non-effective dose of ACEA (0.5 and 1 mg/kg) was also observed in the generalized tonic-clonic model of seizure. The present data suggest that ultra-low doses of cannabinoid receptor antagonists may provide a potent strategy to modulate seizure susceptibility, especially in conjunction with very low doses of cannabinoids.

Effects of subacute lead acetate administration on nitric oxide and cyclooxygenase pathways in rat isolated aortic ring.

Low level exposure to lead increases blood pressure in human and rats. In this study, we investigated the contribution of the nitric oxide (NO) and cyclooxygenase pathways of aortic rings of 28-day lead-treated and control rats, to the responsiveness to phenylephrine and acetylcholine. There were no differences in phenylephrine contractions between the two groups. N(omega)-nitro-L-Arginine-methyl ester (L-NAME), a NO synthase inhibitor, caused attenuation in contraction response to phenylephrine in the aortic rings of the lead-treated rats, while endothelium-denudation caused attenuation in those of controls. This may be due to either endothelium-derived vasoconstrictor(s) (such as reactive oxygen species or endothelins) or a source of NO in smooth muscle cells. There is a left-shift in acetylcholine relaxation response. Indomethacin incubation caused a left-shift in relaxation response to acetylcholine in controls but without any effect on lead-treated ones. Indomethacin incubation caused attenuation in contraction to phenylephrine in both groups. The relaxation response to sodium nitroprusside is not different between the two groups, suggesting that smooth muscle relaxation component is intact. However, the relaxation response to glyceryl trinitrate is impaired in aortic rings of lead-treated rats. It can be concluded that NO and cyclooxygenase pathways are altered in aortic rings of lead-treated rats, with possible involvement of endothelium-derived vasoconstrictors.

Evaluation of wear and corrosion resistance of pure Mg wire produced by friction stir extrusion

A solid-state process—friction stir extrusion (FSE) was applied to produce wires from Mg chips. The FSE process was performed using tool rotational speed of 150, 250 and 355 r/min at a constant plunge rate of 20 mm/min. The microstructural evolution, tribological behavior and corrosion resistance of the reference specimen and the friction stir extruded specimens were investigated. Microstructural characteristics of the specimens were investigated by optical microscopy (OM) and scanning electron microscopy (SEM). The evaluations of mechanical properties include microhardness and dry sliding wear test. The corrosion resistance of the extruded specimens was characterized by potentiodynamic polarization test. The results show that the extruded specimens possess good surface quality and the process is beneficial for the improvement of hardness and wear resistance of the first machined chips. The produced wires are also found to have adequate corrosion resistance. These results demonstrate that FSE is an effective strategy for converting the machined Mg chips into the usable wires.

An experimental dynamic identification & control of an overconstrained 3-DOF parallel mechanism in presence of variable friction and feedback delay

Abstract The closed-loop dynamic control of parallel mechanisms is a challenging field due to the high complexity of their dynamic behavior, especially those with prismatic actuators. Prismatic joints usually provide considerable amount of friction which could vary along its axis. This paper addresses the application of different control algorithms in order to tackle the challenges in closed-loop control of an overconstrained 3-DOF decoupled parallel mechanism which compromises three prismatic actuators with variable frictions along each axis. In addition, a Kinect vision sensor, as the position feedback, is installed. Since the Kinect RGB sensor performs at 30 frame per second, there is a 33 ms delay in the feedback of the control unit which restricts the control loop frequency to maximum value of 30 Hz. Then, based on the models obtained from the identifications of step response, kinetic friction and inverse dynamic model, various attempts have been made in order to obtain a controller with a reasonably performance. First, the conventional PID and sliding mode controllers are applied. Then, the position–velocity controller based on the obtained experience of the mechanism performance is proposed, in which a feedforward unit as the friction compensator is added to the latter feedback-based control units. Eventually, a feedback–feedforward controller based on PID controller and a compensator based on the identified inverse dynamic model is applied to the mechanism which was able to improve the performance of the control unit to a sufficient level.