hamed shafaroodi

Antibiotics are medicines that fight against bacterial infections and are usually considered safe drugs. However, they can simultaneously cause several adverse reactions. Nitrofurantoin, which is mainly administered for treatment and prevention of urinary tract infections, causes seizure reportedly. Therefore, further research is required to be conducted to simulate the case report situations and examine whether nitrofurantoin is the main factor leading to seizures. To do this, NMRI male mice (20-30 gr) were chosen and classified into different groups in both acute and chronic phases. Each phase contained mice treated with nitrofurantoin, phenytoin and the combination of both drugs as well as untreated control group. An Electroshock device was used to induce seizure in mice and then the effect of nitrofurantoin and phenytoin was examined in acute and chronic phases. Seizure induction in mice was examined 30 minutes and one week after injection in acute and chronic phases, respectively. Results indicated that THE (Tonic Hind-limb Extension) duration was different among the studied groups. Nitrofurantoin-injected mice were revealed to have a higher THE duration in comparison with control group, while phenytoin-injected group showed a lower THE duration. Furthermore, administration of nitrofurantoin and phenytoin combination reduced THE duration in both acute and chronic phases. Our conclusion is that nitrofurantoin can possess convulsive effects and cause seizure as a side effect.

Macrophages and glial activation contribute to the pathophysiology of spinal cord injury (SCI). Some preclinical studies have shown the anti-inflammatory effects of aripiprazole (ARP). In the current study, we evaluated the anti-inflammatory effects of ARP in a rat SCI model. Forty male Wistar rats underwent either T9 vertebra laminectomy or were used as a sham-operated group without laminectomy. There were four major groups in this study: a sham-operated, three treatments (normal saline [vehicle] control versus ARP 10 and 20 mg/kg/day for three days after surgery, first dose 30 minutes post-surgery) SCI groups. We evaluated locomotor scaling and neuropathic pain behavioral tests over 28 days. On Day 28, tissue samples were investigated for neuroinflammatory and histopathology changes through flow cytometry and ELISA. ARP (10 and 20 mg/kg/day, 3 days) treatment significantly reduced locomotors disability (P<0.01) and mechanical (P<0.01) and thermal allodynia (P<0.001) scores. Additionally, Levels of tumor necrosis factor (TNF)-α level and interleukin (IL)-10 were significantly altered in ARP-treated spinal cord tissues 28 days after SCI (P<0.01). Moreover, spinal cord tissue expression of M1 and M2 macrophages, as well as M1/M2 ratio, were reduced in ARP-treated SCI animals, concurrent with decreased M1 and increased M2 and M1/M2 in dorsal root ganglion (P<0.001). Our study indicates that ARP has therapeutic effects on SCI via the reduction of neuroinflammation and SCI sensory and locomotor abnormalities.

Epileptic seizure is phenomenon of abnormal synchronous neuronal discharge of a set of neurons in brain as a result of neuronal excitation. Evidence shows the nitric oxide (NO) involvement in neuronal excitability. Moreover, the role of NO-mediated cyclic guanosine monophosphate (cGMP) activation in seizure pathogenesis is well-established. Sumatriptan is a selective agonist of 5-Hydroxytryptamine1B/D auto-receptor, has been reassessed for its neuroprotection. This study was aimed to explore the anticonvulsant effect of sumatriptan through possible involvement of NO-cGMP pathway in mice. For this purpose, the protective effect of sumatriptan on PTZ-induced clonic seizure threshold (CST) was measured using NO-cGMP pathway inhibitors including N(G)-nitro-L-arginine (L-NNA, 1, 5, and 10 mg/kg), 7-nitroindazole (7-NI, 30, 45, and 60 mg/kg), aminoguanidine (AG, 30, 50, and 100 mg/kg), methylene blue (MB, 0.1, 0.5, and 1 mg/kg) and sildenafil (5, 10, and 20 mg/kg). The involvement of nitrergic system was further confirmed by measurement of nitrite levels by Griess reaction. The gene expression of neuronal nitric oxide synthase (nNOS) and subunits of soluble guanylyl cyclase (sGC) was studied using qRT-PCR analysis. Acute administration of sumatriptan (1.2 and 0.3 mg/kg) in combination with subeffective doses of NOS, sGC, and phosphodiesterase 5 inhibitors significantly reversed the PTZ-induced CST (P≤0.001). The nitrite level in prefrontal cortex was significantly attenuated by sumatriptan (P≤0.01). Furthermore, sumatriptan downregulated the PTZ-induced mRNA expression of nNOS, and α1, α2, and β1 genes in cerebral cortex of mice (P≤0.0001). In conclusion, the anticonvulsant activity of sumatriptan at least, in part, is mediated through inhibiting NO-cGMP pathway.

Lead may be added to the opium by drug smugglers. It can cause elevated blood lead level (BLL) in opium‑addicted patients. Erythrocyte pyrimidine 5′‑nucleotidase (P5N) activity is susceptible to high BLL. The aim of this study was to fnd out whether opium‑addicted patients show erythropathy and elevated liver enzymes explainable by high BLL and decreased P5N activity. Forty orally opium‑addicted subjects and 40 normal healthy volunteers were enrolled in this study. BLL was measured in whole blood specimens using atomic absorption spectrometry instrumentation. Enzymatic activity, protein amount of P5N, and erythrocyte purine/pyrimidine ratio were determined. Blood flms were analyzed for the presence of basophilic stippling of red cells and hemolytic anemia. The level of liver function enzymes was measured. The mean BLL for opium‑addicted patients was signifcantly higher than control group (P < 0.001). On the contrary, P5N activity showed a valid decrease in opium‑addicted patients when compared with control group (P < 0.001). In line with repressed P5N activity, erythrocyte purine/pyrimidine ratio in patients was lower than control group (P < 0.001). A statistically signifcant reverse correlation was found between BLL and P5N activity (P < 0.05, r = -0.85). The prevalence of both basophilic stippling (P < 0.001, z = 6.62) and hemolytic anemia (P < 0.001, z = 6.52) in study population was signifcantly associated with elevated BLL. We could not fnd any signifcant correlation between serum level of liver enzymes and BLL. Opium‑addicted patients in Tehran, Iran, are at high risk of lead poisoning which may result in hematologic problems and possibly hepatic damage.

Ajuga species(Lamiaceae) are traditionally used in the treatment of jaundice, joint pain, sciatic nerve, and diabetes in different countries. The aim of this study was to investigate the antioxidant and hypoglycemic activities and safety of Ajuga chamaecistus ssp. tomentella.

Antioxidant activity, radical scavenging effect, and total phenolics content of the aqueous and methanol extracts were assessed using ferric reducing antioxidant power (FRAP), 2, 2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging and Folin-Ciocalteu methods. Streptozotocin (STZ) induced diabetic mice were studied in separate groups comprising aqueous and methanol extracts (200, 400, 800 mg/kg), metformin (500 mg/kg) and a negative control group.

The n-butanol fraction showed the most phenolics content (26.5 mg GAE/g of extract) and the highest antioxidant power) 346.7 mmol FeІІ/g of extract) as well as the most considerable radical scavenging activity (IC50=15.34 µg/mL). In STZ-diabetic mice, repeated oral administration of all doses of extracts showed a significant decrease in plasma glucose levels after 3, 14 and 28 days. The results of acute toxicity study showed that the ethanol extract was non-toxic up to the dose of 6000 mg/kg. Based on the sub-chronic toxicity results, a significant decrease in cholesterol and triglyceride was observed after using the extract (1000 mg/kg) for 23rd and 45th days. Histopathology of animal tissues revealed no significant differences in animal tissues between treated and control groups after 23 and 45 days.

our study indicated the antioxidant potential, safety and hypoglycemic effect of A. chamaecistus ssp. tomentella extracts.

The purpose of this research is to provide nanofibers from cellulose with Wheat bran as an agricultural residue and its antimicrobial activity by dipping ciprofloxacin hydrochloride on Staphylococcus aureus. In this experimental study, cellulose disks were prepared from nano-impregnated fiber. Subsequently, these disks were placed on Staphylococcus aureus with standard paper disks and the results were measured as a non-growth zone after 24 hours. The amount of ciprofloxacin hydrochloride adsorbed in cellulose by comparing the effect of cellulosic discs containing different concentrations of antibiotics and standard ciprofloxacin disks was determined. Subsequently, the evaluation of the time of recovery of the ulcer in the skin of the rats was carried out with the drug-mediated formulation and without drug.
Findings: The disk (nano alpha-cellulosic) dipped by ciprofloxacin hydrochloride created a non-growth zone in Staphylococcus aureus. Measuring the size of the wound was done by digital imaging and the ImageJ software. The results of the recovery process were analyzed by ANOVA and pathological tests in five days. The results showed that the nano-fibers disk could be useful in controlling bacteria in the culture medium, and the area of the wounds in rats (rats) dressed with nano-fibers impregnated with the drug was significantly less than the control group (p <0.05)

Epilepsy is a chronic disorder of the brain affecting around 50 million people in the world. Up to 30% of epileptic patients do not respond to available drugs and medical therapies. In this paper, anticonvulsant screening of 10 synthesized new derivatives of 1, 4-dihydropyridine 3, 5-dicarboxamides was performed. Anticonvulsant activity was evaluated by intravenous and intraperitoneal pentylenetetrazole and maximal electroshock induced seizures tests. Nifedipine was used as reference drug. Our pharmacological results revealing the compounds 2, 4, 5, and 6 can be effective in both absence and grandmal seizures in human. These pharmacological studies have displayed that these new dihydropyridine derivatives are capable to inhibiting seizures induced by pentylenetetrazole and maximal electroshock in mice efficiently.

A series of compounds related to ameltolide were studied for anticonvulsant potential in the subcutaneous pentylenetetrazol (sc Ptz) test in mice. These compounds were synthesized and characterized by TLC followed by IR and H1NMR. In vivo screening data acquired indicate that most of analogs have the ability to protect against PTZ-induced seizure. Phenytoin (PHT) was employed as the reference prototype antiepileptic drug. All compounds exerted their maximal effects 30 min after administration. Out of the 6 compounds, compound 2 at 40 mg/kg dose is more potent than phenytoin (reference drug) on clonic seizure. Using a model of the open pore of the Na channel, docking study was performed by AutoDock4.2 program. Docking studies has revealed that these compounds are stabilized through at least one hydrogen bond rises from ketone of phthalimide and residue Thr-87 of domain G of sodium channel.

Phthalimide-based derivatives have anticonvulsant activity like as phenytoin by inhibition of sodium channel. In our previously research we mentioned about some phthalimide derivatives as potent anticonvulsant agents.
Fourteen analogs of 2-substituted phthalimide pharmacophore were synthesized and then were evaluated for the anticonvulsant activities in pentylenetetrazole-induced seizures (PTZ) and maximal electroshock seizure (MES) models.
The in vivo screening results showed that all the analogs have the ability to protect against the maximal electroshock and PTZ. The compounds 3 and 9 elevated clonic seizure thresholds at 30 min which were more active than the standard medicine phenytoin. Compounds 3, 6, 7, 11, 13 and 14 with 100% protection were the most potent ones in tonic seizure. The most potent compound in the both PTZ and MES models was compound 3. Using a model of the open pore of sodium channel, all of the compounds were docked. Results of docking showed that the ligands interacted mainly with residues II-S6 of NaV1.2 by making hydrogen bonds and have additional hydrophobic interactions with other domains in the channel's inner pore.
Some of these compounds are more potent than phenytoin simultaneously in the clonic and tonic seizures.

Cirrhosis has been related with hyperdynamic circulation, manifesting as increased cardiac output and decreased systemic vascular resistance. In the present study we examined the cirrhosis outcome on apoptosis of rat hearts. We also tried to explore the role of nitric oxide (NO) and oxidative stress in the probable changed apoptosis of cirrhotic hearts. Twenty eight days after ligation of bile duct, heart tissues were tested for apoptosis. The extent of malondialdehyde (MDA), and the activities of catalase (CAT), glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) have been calculated in heart tissues. The cirrhotic hearts exhibited structural defects and greater apoptosis. Chronic treatment of cirrhotic rats with L-NAME, a non-selective inhibitor of NO synthase, inhibited heart structural defects and reduced apoptosis of hearts. We also showed that cirrhotic rat hearts had an enhanced level of MDA and reduced activities of CAT, GSHPx and SOD. When the animals were treated by L-NAME chronically, the MDA level reduced and activities of CAT, GSHPx and SOD augmented in cirrhotic heart. In conclusion, increased apoptosis of cirrhotic hearts probably happen due to NO overproduction and increased oxidative stress in hearts of cirrhotic rats.

Creatine exerts beneficial effects on a variety of pathologies in which energy metabolism and oxidative stress play an etiological role. Creatine supplements have shown beneficial effects on neurological disorders including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease and stroke. However, the potential benefits of creatine for patients with convulsive disorders remain poorly defined. While some authors did not suggest any anti- or pro-convulsant roles for creatine treatment, others suggest that creatine may be an anticonvulsant agent. In this study, we investigated the effects of creatine on seizures in mice.
Three models were used to explore the role of creatine on seizures in mice including intravenous pentylenetetrazole (PTZ), intraperitoneal PTZ, and electroshock models.
Acute creatine treatment (10, 20, 40 and 80 mg/kg) significantly increased the clonic seizure threshold in the intravenous PTZ model. Sub-chronic administration of creatine (10 and 20 mg/kg) revealed a significant anticonvulsant effect in intravenous PTZ model. Acute creatine administration (10, 20 and 40 mg/kg) significantly decreased the frequency of clonic seizures in the intraperitoneal PTZ model. Besides that, acute creatine (40 and 80 mg/kg) decreased the incidence of tonic seizures after electroshock.
In conclusion, creatine exerts anticonvulsant effects in three seizure models; therefore it may act as a potential drug to help patients with convulsions. However, further investigations should be done to clarify these results more.

Increased nitric oxide (NO) formation is mechanistically linked to pathophysiology of the extrahepatic complications of cirrhosis. NO is formed by either enzymatic or non-enzymatic pathways. Enzymatic production is catalyzed by NO synthase (NOS) while entero-salivary circulation of nitrate and nitrite is linked to non-enzymatic formation of NO under acidic pH in the stomach. There is no data on salivary excretion of nitrate and nitrite in cirrhosis. This study was aimed to investigate salivary levels of nitrate and nitrite in a rat model of biliary cirrhosis. Cirrhosis was induced by bile duct ligation (BDL). Four weeks after the operation, submandibular ducts of anesthetized BDL and control rats were cannulated with polyethylene microtube for saliva collection. Assessment of pH, nitrite and nitrate levels was performed in our research. We also investigated NOS expression by real time RT-PCR to estimate eNOS, nNOS and iNOS mRNA levels in the submandibular glands. Salivary pH was significantly lower in BDL rats in comparison to control animals. We also observed a statistically significant increase in salivary levels of nitrite as well as nitrate in BDL rats while there was no elevation in the mRNA expression of nNOS, eNOS, and iNOS in submandibular glands of cirrhotic groups. This indicates that an increased salivary level of nitrite/nitrate is less likely to be linked to increased enzymatic production of NO in the salivary epithelium. It appears that nitrate/nitrite can be transported from the blood stream by submandibular glands and excreted into saliva as entero-salivary circulation, and this mechanism may have been exaggerated during cirrhosis.

Sepsis is a systemic inflammatory response syndrome caused by an infection and remains as a major challenge in health care. Many studies have reported that pioglitazone may display anti-inflammatory effects. This study was designed to evaluate the effect of subchronic treatment with pioglitazone on high-grade septic mice survival and nitrergic system involvement. Diffused sepsis was induced by cecal ligation and puncture (CLP) surgery in male NMRI mice (20-30 g). Pioglitazone (5,10 and 20 mg/kg) was administered by gavage daily for 5 days prior to surgery. Nitric oxide involvement was assessed by sub-chronic administration of a non-selective nitric oxide synthase inhibitor, L-NAME and a selective inducible nitric oxide synthase inhibitor, aminoguanidine. TNF-α and IL-1β plasma levels were measured by ELISA. Pioglitazone (10 and 20 mg/kg) significantly improved survival rate in septic mice. The chronic intraperitoneally co-administration of L-NAME (0.5 mg/kg, daily) or aminoguanidine (1 mg/kg, daily) with a daily dose of pioglitazone, 5 mg/kg, significantly increased the survival rate. This survival improving effect was accompanied by a significant reduction in pro-inflammatory cytokines TNF-α and IL-1β plasma levels. In conclusion, sub-chronic pioglitazone treatment can improve survival in mouse sepsis model by CLP. Inhibition of nitric oxide release, probably through inducible nitric oxide synthase at least in part is responsible for this effect. Suppression of TNF-α and IL-1β could be another mechanism in pioglitazone-induced survival improving effect in septic mice.

Methylenedioxymethamphetamine (MDMA),the Ecstasy brand, leads to cell death in many tissues such as kidney because of its oxidative properties. The present study aimed to investigate the possible effects of pentoxifylline as a vasodilators on ecstasy induced renal damage. This experimental study was carried out in four groups of six male wistar rats weighing 250-300 g (n=24). The control group was kept under standard laboratory conditions. Ecstasy was injected as 7.5 mg/kg, q 2 h × 3 doses intraperitoneally (IP) in the treatment group. In PTX(PTX) treated group, 200 mg/kg of PTX was concurrently administered with the third dose of ecstasy injection and in vehicle group, normal saline was injected. The kidneys were evaluated for histomorphological changes by H&E and PAS stainings. Then the degrees of renal damage were scored by Image Tools Version 2 software. Although no significant differences in diameter and number of glomerular cells between control andPTX treated groups was detected, a significant difference was seen between vehicle and Ecstasy groups (P < 0.05). Tubulointerstitial injury was seen in Ecstasy and vehicle groups but it had been decreased in PTX treated group. Findings of this study suggest that PTX can exert asignificant effect on improving the ecstasy induced renal tissue injuries.

Apelin is a recently discovered bioactive peptide, known to be an endogenous high affinity ligand for the previously orphan G protein-coupled receptor APJ. Apelin/APJ as a novel signaling pathway has been shown to play many crucial roles in cardiovascular function, blood pressure regulation, fluid homeostasis, feeding behavior, obesity, type 2 diabetes mellitus, adipoinsular axis regulation, cell proliferation, angiogenesis, neuroprotection and thermoregulation. This ubiquitous peptide opens a new field of research in biology and medicine. In this regard, the aim of this short review is to compile the evidence for the apelin involvement in modulation of cardiovascular system and introduction of this new peptidic pathway as a useful drug target in the treatment of cardiovascular diseases in future.

Ischemia/Reperfusion (I/R)-induced cerebral injury has been reported as a leading cause of death and long-term disabilities. Hippocampus is an area which is more sensitive to be affected by I/R and hypoxic conditions. Coenzyme Q10 is a strong antioxidant which plays a role in membrane stabilization. This study aims to investigate the possible role of CoQ10 in ameliorating the histomorphological changes in the hippocampal CA1 pyramidal cells induced by cerebral I/R. Thirty six adult male wistar rats were divided into six groups, each group consisting of six rats, including control, ischemia, vehicle and CoQ10-treated (10, 50,100 mg/kg). In treatment groups, rats were orally administered CoQ10 during five days before and three days after I/R. Global cerebral ischemia was induced by bilateral common carotid arteries occlusion for about 20 minutes, followed by reperfusion. H&E and Nissl staining were utilized for some qualitative and quantitative studies. Then the histomorphological changes were measured by Image Tools 2 software. The data analysis showed a significant reduction in the number of CA1 pyramidal cells after I/R; whearas, no significant difference was seen in the number of cells in mentioned region between control and 100 mg/kg CoQ10-treated groups. The findings indicate the neurotrophic properties of CoQ10 and support the beneficial effects of CoQ10 as an adjuvant therapy in patients who have risk factor(s) of ischemic stroke.

Cerebral ischemia is known as a main cause of morbidity and mortality in the world and there was no effective treatment yet. Global cerebral ischemia causes loss of pyramidal cells of brain cortex following global ischemic/reperfusion. Recently، using immunophilin ligands has been considered as a potential and appropriate strategy for neuroprotection. Since it was observed that tacrolimus (FK506)، a useful immunosuppressant used in organ transplantation، provides neuroprotection and prevents neuronal damage،the importance of immunophilins in the development of neuroprotectors has emerged. In this study، we investigated the neurotrophic effect of the immunosuppressant agent FK506 in rat after global cerebral ischemia. In this experimental study، 25 Wistar rats were assigned to control (intact)، ischemia and 3 FK506 treated (1،3،6 mg/kg) groups. Both common carotid arteries were occluded for 20 minutes followed by reperfusion. In 3 experimental groups، tacrolimus or FK506 was given as a single dose exactly at the time of reperfusion respectively as 1، 3، 6 mg/kg by intravenous administration (IV). The same doses repeated by intraperitoneally administration (IP) 48 hours after reperfusion. After 4 days، the rats were sacrificed and brain sections were stained by H & E and Nissl. Our findings showed that 20 min ischemia decreased the number of the cortex pyramidal cells. But there were significant differences between number of cortex pyramidal cells in ischemia and FK506 (6mg/kg) groups. Our study suggests that tacrolimus has a neurotrophic effect on pyramidal cells of brain cortex and may candidate for treatment of ischemia brain damage.

The short break in cerebral blood flow causes permanent brain injury and behavioral dysfunction. The hippocampus, specifically the CA1 pyramidal cells, is highly vulnerable to ischemic injuries. There is no effective pharmacological strategy for improving brain tissue damage induced by cerebral ischemia. Previous studies reported that pentoxifylline has a neuroprotective effect on brain trauma and it is well known that endogenous estrogen improves stroke outcome during vascular occlusion. In this study, the possible positive effects of pentoxifylline and estrogen on behavioral deficit and neuronal damage were studied in female Wistar rats in estrous phase subjected to an experimental model of transient global brain ischemia. In this experimental study, female Wistar rats (n= 56) were assigned to control, ischemia, vehicle, and pentoxifylline - treated (200 mg/kg IP) groups and all of them were in their estrous phase. Pentoxifylline was administered at 1 h before and 1 h after ischemia. Global cerebral ischemia was induced by bilateral common carotid artery occlusion, followed by reperfusion.Morris water maze and nissl staining was used for all groups. According to Morris water maze test results, cerebral ischemia could not exert any negative effect on cognitive spatial abilities after reperfusion and there were no significant differences between groups. In Nissl study, there were significant differences between number of pyramidal cells in both control and pentoxifylline - treated groups (P≤0.05), either ischemia and vehicle groups. Our study illustrated that pentoxifylline can reduce CA1 cell damages and in presence of estrogen prevents any cognitive impairment in female rats which were subjected to brain global ischemia.

Indomethacin increases generation of mitochondrial reactive oxygen species (ROS) which have a crucial role in the indomethacin-induced gastric ulcer. Coenzyme Q10 has an antioxidant activity on mitochondria and cell membranes and protects lipids from oxidation and is essential for stabilizing biological membranes. Superoxide dismutase (SOD) acts as one of the defense mechanisms against free radicals. When the generation of ROS overwhelms, the antioxidant defense, lipid peroxiation of cell membrane occurs and cause cell damage. Male adult Wistar rats were divided into A and B groups. The rats in group A were then further divided into three subgroups of 6 animals each and received one of the following treatments: Animals in the first subgroup received saline. Animals in the second subgroup received saline and indomethacin. Animals in the third subgroup received vitamin C and indomethacin. The rats in group B were also further divided into 3 subgroups of 6 rats each and treated with one of the following treatments: Animals in first subgroup received 1% Tween 80 as vehicle. Animals In second subgroup received 1% Tween 80 and indomethacin. Animals in third subgroup received CoQ10 and indomethacin. Four hours after the last treatment, animals were killed and the stomachs removed were cut and gastric mucosal lesions were examined). Ulcer indexes were determined and SOD activity measured in plasma Pretreatment with both vitamin C and coenzyme Q10 was associated with attenuation of ulcer index and increased SOD activity compared with animals treated with indomethacin alone (P<0.001). This effect of CoQ10 may be due to its electron donating property that inhibits the decrease in SOD activity in gastric tissue (replenishment of endogenous SOD) and inhibiting lipid peroxidation.

Ecstasy is a psychoactive, hallucinogen drug and a member of amphetamines family and is used commonly worldwide. Ecstasy overdose leads to restlessness, anxiety, hallucination, cardiovascular disorders and liver toxicity. Recently, the use of vasodilators, such as pentoxifylline (PTX), is one of the new strategies for protection against liver lesions caused by some substances such as alcohol consumption. There are few studies about the protective effect of pentoxifylline on liver damages due to MDMA long administration. Therefore, a comprehensive study on the protective effect of pentoxifylline on liver lesions caused by prolonged use of ecstasy seems to be necessary. This experimental study was performed on five groups: control, Ecstasy (7.5 mg/kg), Experimental 1 (100 mg/kg PTX simultaneously with the last dose of Ecstasy), experimental 2 (100 mg/kg PTX a week before Ecstasy injection), and vehicle (normal saline) groups (n=25). After two weeks, animals were killed and their livers were prepared for histological studies (H&E method) and TUNEL technique for investigating of apoptotic bodies. The apoptotic bodies and hepatocytes lesions in experimental group 1 were lower than the other groupsm except control. It seems that the use of pentoxifylline after consumption of pure ecstasy can decrease tissue damage and prevent the induction of apoptosis in rat liver.

The brief interruption of cerebral blood flow causes permanent brain damage and behavioral dysfunction. The hippocampus is highly vulnerable to ischemic insults, particularly the CA1 pyramidal cell layer. There is no effective pharmacological strategy for improving brain tissue damage induced by cerebral ischemia. Previous studies reported that pentoxifylline (PTX) has a neuroprotective effect on brain trauma. The possible neuroprotector effects of PTX on behavioral deficit were studied in male Wistar rats subjected to a model of transient global brain ischemia. Animals (n= 32) were assigned to control, sham-operated, vehicle, and PTX- treated (200 mg/kg IP) groups. PTX administered at 1hr before and 3 hr after ischemia. Global cerebral ischemia was induced by bilateral common carotid artery occlusion, followed by reperfusion. Morris Water maze testing revealed that PTX administration in cerebral ischemia significantly improved hippocampal-dependent memory and cognitive spatial abilities after reperfusion as compared to sham-operated and vehicle-treated animals. After the behavioral test, the rats were sacrificed and brain sections were stained with Nissl staining. There were no significant differences between number of pyramidal cells in both control and PTX groups.Our study demonstrated that pentoxifylline had a protective effect on rats with transient global ischemia and could reduce cognitive impairment.

Diclofenac sodium has been used for its anti-inflammatory actions for about 28 years, but since all the non-steroidal anti-inflammatory drugs (NSAIDs) suffer from the lethal gastro intestinal (GI) toxicities, diclofenac sodium is not an exception. The free –COOH group is thought to be responsible for the GI toxicity associated with all traditional NSAIDs. In the present research, the main motto was to develop new chemical entities as potential anti-inflammatory agents with no GI toxicities. A new type of 2-(2-phenoxyphenyl) acetohydrazide possessing N-arylidene substituents, was synthesized for evaluation as anti-inflammatory agents. The starting material 2-(2-Phenoxyphenyl) acetohydrazide was synthesized from 2-phenoxybenzoic acid in several steps according to the previous published method. Various substituted arylidene-2-phenoxynicotinic acid hydrazide derivatives were synthesized by the reaction of hydrazide 17 with selected aldehydes and screened for their potential anti-inflammatory activity. The structure of synthesized compounds was confirmed by different nuclear magnetic resonance technique, Fourier transform infrared spectroscopy (FTIR) and Mass-spectrometry data format. Qualitative structure-activity relationship data, acquired using the carrageenan-induced rat paw edema assay, showed that this group of arylidene-2-phenoxybenzoic acid hydrazides exhibit anti-inflammatory activity with significant reduction of rat paw edema (17-58% reduction in inflammation at different time intervals) in comparison with control group and a moderate to good activity range in comparison with diclofenac as the reference drug. Compounds 9a, 9d and 9e exhibited the most prominent and consistent anti-inflammatory activity. The compound, N-(4-Chlorobenzylidene)-2-(2-phenoxyphenyl) acetohydrazide (9d), exhibited the most in-vivo activity (32-58% reduction in inflammation) compared to the reference drug diclofenac (35-74% reduction in inflammation) in a carrageenan induced rat paw-edema assay.

Although there is evidence that diabetes affects seizure susceptibility, the underlying mechanism has not been completely understood. On the other hand, several studies have suggested a pivotal role for KATP channels in the seizure modulation. So, the present study was designed to evaluate the seizure threshold induced by pentylenetetrazole (PTZ) in diabetic mice at different times and to examine the possible role of ATP-sensitive potassium (KATP) channels. In this experimental study, NMRI were diabetic with streptozocine. Then clonic seizure thresholds were determined at different times after induction of diabetes compared with corresponding non-diabetic groups. Each experimental group consisted of ten mice. There was a time-dependent alteration in the threshold in diabetic mice, reaching a peak on week 2 after STZ injection and declining significantly afterwards. The seizure threshold in 8-week diabetic mice was even lower than control levels, though the difference was not significant. The non-effective dose of KATP channel blocker glibenclamide (1 mg/kg,i.p.), but not the voltage-dependent K+ channel blocker 4-aminopyridine (1 mg/kg,i.p.), decreased the seizure threshold in 2-week diabetic mice to the control levels which was blocked by pre-treatment with the KATP channel opener cromakalim (10 μg/kg,i.p.). Moreover, the non-effective dose of cromakalim (10 μg/kg,i.p.) increased significantly the seizure threshold in 8-week diabetic mice which was inhibited by pre-treatment with glibenclamide (1 mg/kg,i.p.) but not with 4-aminopyridine (1 mg/kg,i.p.). This study indicated that the PTZ-induced seizure threshold is altered in diabetic mice in a time-dependent manner which could be due to the probable alteration in the KATP channel functioning during diabetes.