Low frequency electrical stimulation attenuated the epileptiform activity-induced changes in action potential features in hippocampal CA1 pyramidal neurons

Objective: Electrical low frequency stimulation [LFS] is a new therapeutic method that moderates hyperexcitability during epileptic states. Seizure occurrence is accompanied by some changes in action potential [AP] features. In this study, we investigated the inhibitory action of LFS on epileptiform activity [EA] induced-changes in AP features in hippocampal CA1 pyramidal neurons

Materials and Methods: In this experimental study, we induced EA in hippocampal slices by increasing the extracellular potassium [K+] concentration to 12 mM. LFS [1 Hz] was applied to the Schaffer collaterals at different pulse numbers [600 and 900] at the beginning of the EA. Changes in AP features recorded by whole-cell patch clamp recording were compared using phase plot analysis

Results: Induction of EA depolarized membrane potential, decreased peak amplitude, as well as the maximum rise and decay slopes of APs. Administration of 1 Hz LFS at the beginning of EA prevented the above mentioned changes in AP features. This suppressive effect of LFS depended on the LFS pulse number, such that application of 900 pulses of LFS had a stronger recovery effect on AP features that changed during EA compared to 600 pulses of LFS. The constructed phase plots of APs revealed that LFS at 900 pulses significantly decreased the changes in resting membrane potential [RMP], peak amplitude, and maximum rise and decay slopes that appeared during EA

Conclusion: Increasing the numbers of LFS pulses can magnify its inhibitory effects on EA-induced changes in AP features

Development of an analytical method for dibutyl phthalate determination using surrogate analyte approach

Dibutyl phthalate [DBP] is a phthalic acid ester and is widely used in polymeric products to make them more flexible. DBP is found in almost every plastic material and is believed to be persistent in the environment. Various analytical methods have been used to measure DBP in different matrices. Considering the ubiquitous nature of DBP, the most important challenge in DBP analyses is the contamination of even analytical grade organic solvents with this compound and lack of availability of a true blank matrix to construct the calibration line. Standard addition method or using artificial matrices reduce the precision and accuracy of the results. In this study a surrogate analyte approach that is based on using deuterium labeled analyte [DBP-d4] to construct the calibration line was applied to determine DBP in hexane samples

Interaction between cannabinoid compounds and capsazepine in protection against acute pentylenetetrazole-induced seizure in mice

The pharmacological interaction between cannabinoidergic system and vanilloid type 1 [TRPV1] channels has been investigated in various conditions such as pain and anxiety. In some brain structure including hippocampus, CB1 and TRPV1 receptors coexist and their activation produces opposite effect on excitability of neurons. In this study, we tested the hypothesis that TRPV1 channel is involved in the modulation of cannabinoid effects on pentylenetetrazole [PTZ]-induced seizure threshold. In single therapy, male mice [n = 10 per group] received either TRPV1 receptor antagonist capsazepine, CB1 receptor agonist ACEA or anandamide reuptake inhibitor VDM11. In combination therapy, mice were treated with either capsazepine-ACEA or capsazepine-VDM11 combination prior to seizure test. Thirty min later, mice were submitted to infusion of PTZ [1%, 0.25 mL/min] into tail vein and the dose of PTZ to induce clonic convulsion was considered as seizure threshold. Administration of capsazepine and ACEA per se produced protective effects against PTZ-induced seizure, while administration of VDM11 per se did not produce such a protection effect. The anticonvulsant actions of both capsazepine and ACEA were attenuated after co-administration of these compounds. Moreover, the anticonvulsant action of capsazepine was attenuated after co-administration with VDM11. The results suggest an interaction between cannabinoidergic system and TRPV1 receptors in protection against acute PTZ-induced seizure in mice

effect of paxilline on early alterations of electrophysiological properties of dentate gyrus granule cells in pilocarpine-treated rats

The dentate gyrus of hippocampus has long been considered as a focal point for studies on mechanisms responsible for the development of temporal lobe epilepsy [TLE]. Change in intrinsic properties of dentate gyrus granule cells [GCs] has been considered as an important factor responsible in temporal lobe seizures. In this study, we evaluated the intrinsic properties of GCs, during acute phase of seizure [24 h after i.p. injection of pilocarpine] compared to sham group using whole cell patch-clamp recordings. Our results showed a significant increase in the number of action potentials [APs] after applying depolarizing currents of 200 pA [p < 0.01] and 250pA [p < 0.05] compared to sham group. The evaluation of AP properties revealed a decrease in half-width of AP in GCs of seizure group [1.27 +/- 0.03 ms] compared to sham group [1.60 +/- 0.11]. Moreover, addition of BAPTA to pipette solution prevented changes in AP half-width in seizure group [1.71 +/- 0.11 ms] compared to sham group [1.91 +/- 0.08 ms]. In contrast, an increase in the amplitude of fast afterhyperpolarization was observed in GCs of seizure group [-11.68 +/- 0.72 mV] compared to sham group [-8.28 +/- 0.59 mV]. Also, GCs of seizure group showed a significant increase in both firing rate and instantaneous firing frequency at depolarizing currents of 200 pA [P < 0.01] and 250 pA [P < 0.05] compared to sham group. The changes in electrophysiological properties of GCs were attenuated after bath application of paxilline suggesting possible involvement of large conductance Ca[2+]- activated K[+] channel [BK channel]. Our results suggested the possible involvement of certain potassium channels in early changes of intrinsic properties of GCs which eventually facilitate TLE development

comparison of the effects of acute and repeated morphine administration on fast synaptic transmission in magnocellular neurons of supraoptic nucleus, plasma vasopressin levels, and urine volume of male rats

The activity of the magnocellular neurons [MCNs] of supraoptic nucleus [SON] is regulated by a variety of excitatory and inhibitory inputs. Opioids are one of the important compounds that affect these inputs at SON synapses. In this study, whole-cell patch clamp recording of SON neurons was used to investigate the effect of acute and repeated morphine administration on spontaneous inhibitory and excitatory post synaptic currents [sIPSCs and sEPSCs] in MCNs. While acute bath application of morphine to brain slice of intact rat produced an increase in sEPSCs frequency and a decrease in sIPSCs frequency, repeated in vivo administration of morphine produced opposite effect. Moreover, repetitive i.c.v. administration of morphine for three consecutive days caused significant increase in urine volume, but had no significant alteration in water consumption compared to control group. The increase in urine volume was consistent with a significant decrease in plasma arginine vasopressin [AVP] levels after repetitive i.p. morphine administration. The results suggest that acute administration of morphine stimulates whereas repeated administration of morphine inhibits the MCNs. Morphine-induced MCN inhibition could result in diminished plasma AVP levels and eventually an increase in urine volume of rats

Chronic intracerebroventricular administration of dimethyl sulfoxide attenuates streptozotocin-iduced memory loss in rats

The memory impairment, obtained from intracerebroventricular [i.c.v.] infusion of streptozotocin in rats through activation of oxidative stress, is accepted as sporadic Alzheimer's disease model in most experimental studies. Dimethyl sulfoxide [DMSO] as a solvent is widely used in animal studies to have antioxidant effects as well. However, no report is available about DMSO effect on oxidative stress-induced cognition deficit i.e. Alzheimer's disease. The present work was designed to assess the effect of chronic treatment of DMSO on STZ-treated rats. STZ [3 mg/ kg; i.c.v.; bilateral with 10 micro l volume in either side; days 1 and 3] using a single-day version of Morris water maze. The DMSO [2.5, 5 and 10%v/v in saline], started from the first day, was infused for 14 days. The chronic administration of DMSO 10% improved the distance to hidden platform [P<0.01] in training sessions and time spent in the target quadrant in probe tests [P<0.01]. Neither STZ nor DMSO had any intervention on velocity and visuo-motor coordination in the visible version of MWM. Totally, the results suggest that DMSO may be appropriate as adjuvant therapies for the prevention of memory impairment in the experimental models of Alzheimer's disease. Therefore, use of DMSO as a solvent in Alzheimer's disease animal studies should be considered having beneficial effects on cognitive function

pilot study of polymorphism of adrenergic beta-2 receptor and mild zsthma: z clinical and pharmacogenetic study

Glycine allele at codon 16 has previously been associated with the increase in asthma severity, bronchial hyperresponsiveness and also the increase in inhaled corticosteroid dependence. This study was designed to evaluate the genetic alleles in mild asthma

Thirty-four patients with diagnosis of mild asthma [FEV[1] >/= 80%, positive methacholine test] and body mass index [BMI

Among all, 20 [58.8%] Arg/Gly, 14 [41.2%] Arg/Arg and no Gly/Gly genotype were detected at codon 16. Genotyping at codon 27 revealed 2 [5.9%] Glu/Glu, 13 [38.2%] Glu/Gln and 18 Gln/Gln [52.9%].Based on the obtained results, Arg/Gly mutation had a higher rate among the studied subjects compared to Arg/Arg polymorphism. This is a pilot study which shows a probable usefulness of genotyping for predicting of asthma severity

Evaluation of anti-nociceptive and anti-inflammatory activities of novel chalcone derivatives

Chalcone [1, 3-diarylprop-2-en-1-one] derivatives have been introduced as selective cyclooxygenase-2 inhibitors. In the present study, anti-nociceptive and anti-inflammatory effects of eight novel compounds were evaluated in male mice and Wistar rats by using the writhing and formalin-induced paw edema tests respectively. The activities of the compounds were compared with celecoxib as a reference drug. Then, novel compounds were divided into two regioisomeric groups based on the position of the methyl sulfonyl substitution. Compounds with substituents such as: 1] H, 2] Me, 3] F and 4] Cl at para position of the phenyl ring of [E]-3-[4-Methanesulfonylphenyl]-1-phenylprop-2-en-1-one were selected in the first group. The regioisomer compounds with 5] H, 6] Me, 7] F and 8] OMe substitutions at C-4 of phenyl ring of [E]-1-[4-Methanesulfonylphenyl]-3-phenylprop-2-en-1-one were chosen as second group. All compounds showed dose-dependent anti-nociceptive activity in writhing test. Interestingly, the potency of anti-nociceptive effect of compounds 1, 2, 5 and 6 were significantly higher than celecoxib. The regioisomeric compounds 1 and 5 with high anti-nociceptive effects, showed a significant dose-dependent anti-inflammatory activity in the paw edema test as well. The results showed that compounds with no substituent or small size substituents at para position of the phenyl ring are the most potent compound in writhing test. Our results revealed that the introduction of a bulky group such as methoxy or chlorine at the vicinal aromatic chain of the derivatives decreases the anti-inflammatory/anti-nociceptive effects. The comparison of estimated ED[50] of each pair of the regioisomeric compounds indicates that the relative position of SO[2]Me to carbonyl moiety did not affect the potency