Physiology and Pharmacology
Volume:19 Issue: 4, Dec 2015

Long-term levodopa treatment of Parkinson’s disease (PD) is frequently complicated by spontaneously occurring involuntary muscle movements called dyskinesia. The exact pathological mechanism of this complication has not yet been elucidated. We have previously demonstrated that in PD patients the vulnerability to develop peripheral but not orofacial dyskinesia is associated with the presence of two variants of the GRIN2A gene. Moreover, we have shown that in tardive dyskinesia (TD) orofacial dyskinesia is associated with other polymorphisms as compared with peripheral dyskinesia. In the present study we investigate whether the peripheral versus orofacial nature of levodopa-induced dyskinesia (LID) in PD can be explained by considering polymorphisms for dopaminergic and serotonergic receptors.
101 Russian patients with PD (38M/63F) were examined. Genotyping was carried out on 19 SNPs for 3 neurotransmitter genes: 10 SNPs for DRD3 gene (rs11721264, rs167770, rs3773678, rs963468, rs7633291, rs2134655, rs9817063, rs324035, rs1800828, rs167771), 1 SNP for DRD4 gene (rs3758653), and 8 SNPs for HTR2C gene (rs6318, rs5946189, rs569959, rs17326429, rs4911871, rs3813929, rs1801412, rs12858300).
Genotyping patients with PD and LID revealed that only rs3773678 (DRD3, dominant, p = 0.042) was associated with orofacial dyskinesia.
The findings of the current study are not related to LID in PD itself, but to other forms of orofacial dyskinesia in this patient group.

To study the effects of exercise, how important it is to choose a posture? We aimed to characterize the possible impact of different body positions on cardiovascular parameters during and after sustained isometric handgrip (IHG) exercise.
Cross sectional study was carried out in 33 young adult males (mean age: 19.21±1.083 years). We recorded Blood Pressure (BP), Heart Rate (HR) and SpO2 at rest, 1st minute of exercise, at 3rd minute of exercise or prior to failure and at 2 minutes after IHG exercise at 30% of Maximum voluntary contraction (MVC) in sitting, supine and standing positions. Mean arterial pressure (MAP), Pulse pressure (PP) and Rate pressure product (RPP) were calculated from BP and HR data.
SBP, DBP, MAP, HR and RPP increased significantly during 1st and 3rd min of exercise and returned to resting level at 2 min after exercise in all three postures. During resting period and at 2 min after IHG exercise SBP and PP were significantly higher in supine compared with sitting and standing position, while DBP, HR and RPP were significantly increased in standing position. DBP, PP, MAP and HR changed significantly in supine, sitting and standing posture with time of exercise (two-way repeated measure ANOVA).
IHG exercise leads to an across the board increase of all the cardiovascular parameters. The effect of posture was more pronounced at rest and during initial duration of exercise. Thus, posture may be a factor to consider in testing initial response during IHG exercise, but not for studying effects of prolonged duration of exercise.

This study evaluated the effects of pretreatments with melatonin (MT), and Alpha Lipoic acid (ALA) on lopinavir/ritonavir (LPV/r) -induced serum levels of creatinine (Cr), urea (U), uric acid (Ua) and kidney levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT) in male albino rats. Effects of treatments with MT and ALA were also evaluated on baseline levels of the above parameters.
Adult male albino rats orally received MT (10mg/kg), ALA (10mg/kg) and LPV/r (22.9/5.71, 45.6/11.4 and 91.4/22.9mg/kg) for 60 days. At the end of drug treatment animals were sacrificed, serum was extracted and evaluated for Cr, U, and Ua. Kidney was harvested and evaluated for MDA, SOD, CAT and GSH.
Treatment with MT and ALA significantly (p Observations in this study may be due to the oxidant effect of LPV/r and the antioxidant effects of MT and ALA. This study, therefore recommends MT and ALA as treatment or prevention for LPV/r induced renal toxicity.

It has been demonstrated that cholecystokinin sulfated octapeptide (CCK-8s) can affect synaptic transmission in the hippocampus. Because one of the major experimental models to understand the events happening in synaptic plasticity is To Study the long-term potentiation (LTP), we decided to investigate the effect of concomitant administration of CCK-8s and tetanic stimulation of Schaffer collateral path-CA1 synapses on LTP induction and maintenance.
Experimental groups were control, CCK-5min and CCK-30min. CCK-8s was injected 5 or 30 min (1.6 μg/kg; i.p.) prior to induction of LTP. The stimulating and the recording electrodes were placed in the Schaffer collateral pathway and hippocampal CA1, respectively. LTP was induced by 100 Hz tetanization and field excitatory postsynaptic potentials (fEPSP) slope, area and amplitude were measured and compared during 30 minutes Interval before, and 90 minutes Interval after LTP induction in each group.
The results showed that maintenance of the induced LTP was significantly improved in the CCK-30min group comparing to the control group. This improvement was particularly visible in the fEPSP slope (p These results indicated that LTP induction and maintenance is carried out effectively, at higher levels of CCK in the brain. The data suggest that CCK-8s has pronounced effects on synaptic plasticity in the hippocampus and the consequent cognitive functions.

Currently, developing new antibacterial drugs as alternative antibiotics is a very active area of research, due to widspreading widespread prevalence of resistant strains of microorganisms. This work intends to investigate of antibacterial properties and influence on immune blood cells of the silver-based compound hexamethylenetetramine (methenamine) silver nitrate with general formula [Ag(CH2)6 N4]NO3.
The antibacterial effect of the silver complex was investigated by agar diffusion and serial dilution methods. Silver complex have been investigated for its impact on the phagocytic activity of neutrophils and on immune cells during the reaction of blast transformation of lymphocytes (RBTL).
Studies have shown that hexamethylenetetramine silver nitrate possesses both bactericidal and bacteriostatic dose-dependent effect on tested bacterial strains, including Staphylococcus aureus, Proteus vulgaris, Pseudomonas aeruginosa, Streptococcus pneumoniae. Escherichia coli were shown to be the most susceptible bacteria. Cytotoxic effect of silver salt on lymphocytes was detected in high dosage in RBTL. No significant immunosuppressive impact on neutrophils phagocytic activity of tested complex was shown.
Agents of nosocomial infections were highly susceptible to the drug. Complex has proved to be promising as a prospective antibacterial drug with wide range of activity.

Neurodegenerative diseases are progressive disorders that could impair neuronal functions and structures. Oxidative stress and mitochondrial dysfunction are involved in the etiology of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and etc. Gemfibrozil is used as a therapeutic drug for hyperlipidemia. It has been shown that gemfibrozil is neuroprotective via modulation of mitochondrial biogenesis pathway under oxidative stress condition and in a sex-dependent manner.
In this study, neuronal-like PC12 cells with were pretreated with different concentrations of gemfibrozil and H2O2, concomitantly.
In gemfibrozil pretreated groups, reduced level of caspase-3 and raised mitochondrial transcription factor A (TFAM) levels were detected. In contrast, adding fulvestrant, an Estradiol receptor antagonist, prevents the impact of gemfibrozil on oxidative stress condition, reducing its efficacy to protect the neurons against stress.
Our results indicated the involvement of estradiol receptors in gemfibrozil neuroprotective mechanism, in diminishing oxidative stress-induced damage via reducing caspase-3 and inducing the level of TFAM that plays a crucial role in the mitochondrial biogenesis.

Hydrogen sulfide (H2S) plays a key role in the regulation of vascular tone and protection of blood vessels against endothelial dysfunction. Since the mechanism of salt impairing H2S-induced vascular relaxation is not fully clear, therefore this study was designed to investigate the role of potassium (K) channels in the vasodilatory effects of exogenous H2S in rat aortic rings.
Isolated thoracic aortic rings of adult male albino rats fed 8% NaCl diet for six weeks were used for isometric tension recording using PowerLab tissue bath system.
The relaxation response to sodium disulfide (Na2S, an H2S donor) was reduced in aortic rings of rats that were either fed high salt (HS) or incubated in a medium containing 1,3 or 5mM/L of extra NaCl compared with control rings. Na2S-induced relaxation was lower in rings precontracted by high K than phenylephrine (PE, a selective α1adrenergic receptor agonist). In addition, incubation of aortic rings of HS loaded rats with inward-rectifier K (KIR) channels blocker individually or simultaneously with either ATP-dependent (KATP) or voltage-sensitive K (KV) channels blockers inhibited Na2S-induced relaxation in PE-precontracted rings; however it had no effects on rings pretreated with KATP channels blocker. In contrast, incubation of aortic rings of HS loaded rats with Ca activated K (KCa) channels blocker individually or in combination with KIR channels blocker significantly enhanced Na2S-induced relaxation.
These results revealed that HS partially impairs aortic relaxation caused by H2S, and that the mechanism of relaxation is mainly mediated by the stimulation of KIR channels and inhibition of KCa channels.

Morphine withdrawal syndrome is mediated via several central and peripheral neurological pathways. In the present study we investigated the role of N-methyl-D aspartic acid (NMDA) glutamate receptor on naloxone-induced withdrawal syndrome in morphine-conditioned mice.
We designed two separate experiments. In experiment one, 30 male NMRI mice were divided into 5 groups, pretreated with memantine (0.1, 1 and 5 mg/kg; I.P.) followed by morphine-dependence period for 3 days. In the other experiment, 48 male NMRI mice distributed into 8 groups, pretreated with intra-accumbens (IAc) memantine (1 and 5 μg/animal) within the right, left and both side of nucleus accumbens (RNAcc, LNAcc and BNAcc) followed by I.P. morphine-dependence (3 days). On day 4, in both experiments, morphine was injected into mice, followed by naloxone. Then naloxone-induced total jumping count, jump height and defecation in morphine-conditioned mice were recorded for 30 min.
Pre-treatment by I.P. injection of memantine significantly attenuated naloxone precipitated jumping count/30 min, jumping height (mm) and fecal material output in morphine dependent mice (P0.05). These findings indicated asymmetric involvement of central and peripheral NMDA glutamate receptors in withdrawal syndrome development in morphine-dependent mice.