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Abstract Background Inflammasomes are a group of molecules that are strongly involved in causing inflammation. This study aimed to evaluate the expression of NLR family pyrin domain containing 1 (NLRP1), NLRP3, and Apoptosis-associated speck-like protein containing a CARD (ASC) as well as their association with serum level of interleukin (IL)-1β in patients with coronavirus disease 2019 (COVID-19). Methods Thirty COVID-19 patients and 30 healthy subjects (HS) were recruited. Peripheral blood specimens were collected from subjects to assess NLRP1, NLRP3, and ASC gene expression by Real time-PCR technique. Serum levels of IL-1β were also measured via the enzyme-linked immunosorbent assay (ELISA). Results The findings showed no significant differences in serum IL-1β level between COVID-19 patients and the HS group. mRNA expression of ASC (P = 0.008) and NLRP1 (P = 0.03) gene had a significant increase in COVID-19 patients compared to HS, while there was no significant increase in the expression of NLRP3 between the studied group. There were significant correlations between patient’s data and expression levels of NLRP1, NLRP3, IL-1β, and ACS. Conclusions NLRP1 and ASC may have a more critical role in the generation of the active form of IL-1β in COVID-19 patients compared to NLRP3. However, serum levels of IL-1β in patients did not show a significant increase, which may be due to the patient’s condition and the application of virus escape mechanisms through impaired NLRP3 expression and its malfunction.

Abstract Background Obesity has become a major health issue in both high and middle-income countries, increasing the risk of cardiovascular diseases and all-cause mortality. Risk of obesity is related to both unchangeable factors such as genetics and gender, and modifiable lifestyle factors. Most importantly, finding the major modifiable lifestyle factors which contribute to obesity may provide valuable benefits to every society. This study aimed to determine the association of demographic and lifestyle parameters with overweight/obesity and abdominal obesity in a population of Iranian adults. Methods In this cross-sectional study, adult participants of Rafsanjan Cohort Study (RCS) (as one of the district areas of the PERSIAN cohort (Prospective Epidemiological Research Studies in IrAN) included the study population. RCS is a population-based prospective cohort of men and women aged 35–70 years, launched in August 2015. Individuals were recruited from four urban and suburban areas of Rafsanjan, south-eastern of Iran. Trained experts interviewed each participant and completed the related questionnaires about his/her socioeconomic status, demography, anthropometric features, personal habits, physical activity and medical history. Multinomial logistic regression models were used to examine the relationships between overweight/obesity/abdominal obesity and associated factors. Results From 9980 participants, 1974 (42.42%) males and 2115 (39.70%) females were overweight, 784 (16.85%) males, 2223 (41.73%) females were obese and 1895 (40.73%) males and 989 (18.57%) females were normal weight. Also, 832 (17.9%) males and 4548 (85.4%) females had abdominal obesity and 3819 (82.1%) males and 778 (14.6%) females didn’t have abdominal obesity. Based on the adjusted multiple logistic regression, overweight/obesity (BMI > 25) was associated with age > 45, female gender, education ≥ 13 years, heavy physical activity, wealth status index (WSI), alcohol consumption, current cigarette smoking and opium consumption compared to reference group. Also, odds of abdominal obesity displayed a significant association with age > 45, female gender, education > 5 years, physical activity, WSI, current cigarette smoking, alcohol and opium consumption compared to reference group. Conclusions Our results recommend local public health strategies that promote training the society on the health benefits of avoiding alcohol, getting more physical exercise and gaining more personal education on the health-threatening lifestyle.

Oral health status can be affected by some factors including drug abuse, systemic conditions and environmental pollutants. The present study was designed to investigate the most important and prevalent dental and oral conditions in adult population of Rafsanjan with the age of 35–70 years. Dental and oral health cohort center as part of the Rafsanjan Cohort Study (RCS) included in the prospective epidemiological research studies in IrAN was established in 2015. Of 9991 subjects enrolled in the RCS, 8682 people participated in the Oral Health Branch of Rafsanjan Cohort Study (OHBRCS).The OHBRCS included 4021 men and 4661 women with the mean age of 49.94 ± 9.51. The most prevalent of oral lesion in total population was candidiasis and the least was aphthous lesion. The prevalence of candidiasis, white and red lesions, periodontal pocket, dental calculus, CAL and the mean of DMFT were higher in the male group than that of female group (p

Introduction: Lack of high-quality sleep causes severe side effects like anxiety and changes in plasma concentration of oxalate. The current study investigated the impact of local extremely low-frequency magnetic fields (ELF-MFs) on inducing sleep (sleepiness) and anxiety in male rats. Methods: In this experimental study, 40 male rats were divided into four groups (n=10 for each group). The ELF-MF exposure (0, 10, and 18 Hz) was applied with an intensity of 200µT for three days (10 min/d). The sham-treated animal did not receive ELF-MF. Serum levels of oxalic acid (OA) and sleepiness were measured before and after the last exposure to ELF-MF or sham. Anxiety, sleepiness, and OA were measured using the elevated plus maze, open-field test (OFT), and ELISA test. Results: A comparison of oxalate levels before and after exposure to ELF-MF revealed that ELF-MF (10 Hz) decreased the serum level of oxalate (P

Background and Objectives: Nurses are at higher risk of insomnia due to changes in their work shifts. This study aims to investigate the effect of extremely low-frequency magnetic field (ELF-MF) exposure on the sleepiness of night-shift nurses during rest time. Methods: This is a randomized crossover clinical trial that was conducted on 28 night-shift nurses, randomly divided into two groups of exposure (n=14) and sham (n=14). The central areas of the brain of nurses in the exposure group was exposed to a magnetic field with 200-μT intensity at a frequency of 10Hz for 10 minutes after each night shift for eight night shifts and four weeks. The executive protocol for the sham group was the same, except that the nurses were not exposed to a magnetic field. After exposure, there was no intervention for two weeks to wash out the effects. Then, the groups exchanged their roles and the protocol was repeated. Stanford sleepiness scale (SSS) was used to measure the sleepiness of nurses. Findings were analyzed in SPSS software. Results: No significant difference was observed in the mean SSS score in the first and second periods between the two groups (P=0.30). No significant difference was observed in the mean SSS score between the periods and the order of placement in each period, either (carryover effect=0.97, period effect=0.96). Conclusion: The local ELF-MF exposure has no significant effect on the sleepiness of night-shift nurses during rest time. It may be due to their disturbed circadian rhythm or the disturbance by the noise and light (not by work-related anxiety). Further investigation is needed.

Objective(s): Delayed tissue plasminogen activator (tPA) thrombolysis is accompanied by different complications in stroke patients. Studies reported sex differences in stroke therapy. Ischemic postconditioning (PC) unveils neuroprotection in stroke models. In this study, we investigate the combined effect of delayed tPA therapy and PC procedure during an embolic stroke experimental model in female rats. Materials and Methods: Female Wistar rats were randomly divided into control (saline), tPA, PC, and tPA+PC groups after stroke induction via clot injection to the middle cerebral artery. tPA treatment was initiated 6 hr after stroke, and PC procedure was performed 6.5 hr post-ischemia induction (occlusion: 10 sec; reopening: 30 sec; 5 cycles). The cerebral blood flow (CBF) was recorded up to 60 min from IV tPA injection time. The parameters of brain edema, infarct volume, disruption of the blood-brain barrier (BBB), behavioral tests, and matrix metalloproteinases-9 (MMP-9) were evaluated.Results: This study revealed that PC conduction prevents excessive CBF increase by tPA and played a protective role in infarct volume reduction (P

Introduction: Memantine as N-Methyl-D-Aspartic Acid (NMDA) receptor antagonist is used in some neurological disorders. Moreover, memantine presents modulatory effects on the somatosensory information processing in healthy subjects. This study investigated the effects of memantine on electrophysiological properties of barrel cortex neurons in male rats. Methods: Single unit recording was used to evaluate the electrophysiological properties of barrel cortex neurons. The neural responses to the Principal Whisker (PW), Adjacent Whisker (AW), and combined displacement of two whiskers [20 ms Inter-Stimulus Intervals (ISIs)] were recorded before and 2 hours after memantine gavage (10 mg/kg). A Condition Test Ratio (CTR) was calculated for assessing inhibitory interactions. Results: Two hours after memantine gavage, neuronal ON and OFF responses to PW deflection were decreased. Furthermore, CTR for both ON and OFF responses was decreased following memantine administration. Conclusion: The current study demonstrated that memantine modified neural response properties in the rat barrel cortex.

Unilateral ureteral obstruction (UUO) as a clinical disorder can cause renal damage. The permanent injury occurs if the obstruction is not relieved. Renal injury can be reversed with UUO removal (RUUO). RUUO attenuates the renal hemodynamic and functional impairment and decreases the renal fibrosis and apoptosis. Nevertheless, kidney injury may continue after RUUO, and synchronous medication therapy seems necessary. However, UUO and post-RUUO periods are also important in final renal recovery. To date, various therapeutic strategies have been applied to develop renal recoverability after RUUO. In animal studies, the effect of some pharmacological agents such as mesenchymal stem cells, anti-inflammation drugs, L-arginine, bone morphogenetic protein-7, epidermal growth factor, allopurinol, renin-angiotensin system antagonists, and endothelin A/B receptor blocker were surveyed in RUUO model. Also, post-RUUO renal recoverability has been studied in human researches. In these studies, the effective strategies have focused on surgery for RUUO creation via urethrotomy, urethroplasty, stent balloon dilatation, and stenting. Accordingly, in this review, we focused on the therapeutic procedure of renal recovery after the RUUO situation in human and animal studies.

Introduction: Stroke is one of the leading causes of death and disability worldwide. Propolis, a polyphenol-rich resinous product processed by honeybees from a variety of plant sources, has a set of biological activities. We investigated the neuroprotective effect of Iranian brown propolis (IBP) in a mouse model of permanent middle cerebral artery occlusion (MCAO). Methods: Experimentally, water extracts of propolis (WEPs) were obtained from Kerman (KeWEP) and Khorasan Razavi (KhWEP) provinces, Iran. The chemical characterization and total polyphenol content of WEPs were determined using the Folin–Ciocalteu assay and gas chromatography-mass spectrometry (GC-MS). Animals were divided into eight experimental groups including: sham, control, and three groups each of which KeWEP- and KhWEP-treated mice. The drugs were administered at doses of 30, 100 and 200 mg/kg, intraperitoneally (IP), during four different time points. Infarct volume and brain edema were measured at 48 h. Behavioral tests were evaluated at 4, 24 and 48-hour post stroke. Results: The total polyphenol content was 1100 and 1400 mg/L in KhWEP and KeWEP respectively. Compared to the control group, the doses of 100 and 200 mg/kg in both samples decreased infarct volume. Brain edema was also reduced in all treatment groups. The dose of 200 mg/kg in both samples and 100 mg/kg in the KeWEP-treated group significantly increased grasping ability. Sensory-motor function was improved in all groups, too. Conclusion: These results suggest that IBP may reduce ischemic brain injury by its neuroprotective effect on focal cerebral ischemia.

Objective(s): Ceftriaxone (Cef), a beta-lactam antibiotic, is accompanied by antioxidant and anti-inflammatory properties. It has been shown that Cef has beneficial effects on Alzheimer’s disease. In the current investigation, the effect of Cef in a mice model of aging was investigated. Materials and Methods: Forty male mice were equally aliquoted into four groups as follows: Control (as healthy normal animals), D-galactose (DG) group (treated with 500 mg/kg/day DG for 6 weeks), DG + Cef group (treated with DG plus Cef 200 mg/kg/day for 6 weeks), and Cef group (treated with Cef 200 mg/kg/day for 6 weeks). A battery of behavioral tests was done to evaluate age-related neurocognitive changes. The activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), as well as the level of malondialdehyde (MDA) in the brain, were measured by biochemical methods. Also, to determine the brain damage, histopathological alterations in the hippocampus were measured using hematoxylin and eosin (H&E) staining. Results: Our results indicate that neurobehavioral dysfunctions of DG can be prevented by co-administration of Cef. We also found that Cef increases the activity of SOD, GPx, and CAT as well as decreasing the level of MDA in the brain of aged mice. Conclusion: Based on our findings, Cef declines neurocognitive dysfunctions in the DG-induced model of aging, possibly through its antioxidative properties.

Objective(s): This study investigated the role of locus coeruleus (LC) nucleus TRPV1 receptors (TRPV1r) in the expression and development of morphine physical dependence by intra-LC administration of AMG9810 (selective TRPV1r antagonist) in male Wistar rats. Materials and Methods: For assessing the development of morphine dependence, AMG9810 (0.03 and 0.3 mM in 10% DMSO, 0.2 µl; intra-LC microinjection) was administered before each morphine administration for seven continues days (once daily; 6, 16, 26, 36, 46, 56, and 66 mg/kg; sc). Furthermore, for evaluating the expression of morphine dependence, a single dose of AMG9810 (0.03 and 0.3 mM in 10% DMSO, 0.2 µl; intra-LC microinjection) was administered to morphine-dependent rats on day 8 of the experiment. Results: Obtained data demonstrated that co-administration of TRPV1r antagonist with morphine reduced the development of morphine withdrawal syndrome somatic signs induced by naloxone. Moreover, single intra-LC administration of TRPV1r antagonist on the final day of the examination period significantly decreased the expression of some signs of morphine withdrawal in rats. Conclusion: The results showed that LC TRPV1r might be participating in the expression and development of morphine dependence.

Objective(s): Cisplatin (Cis) is an anticancer compound, which is used for the treatment of various cancers. Sumatriptan (Suma) is a selective agonist of 5-hydroxytryptamine 1B/1D (5HT1B/1D) receptor, which is prescribed for the management of migraine. It is well-established that Suma has anti-inflammatory and antioxidant properties. We have explored the protective effects of Suma in the mitigation of Cis-induced nephrotoxicity. Materials and Methods: The mice received a single IP injection of Cis (20 mg/kg) on the first day of the experiment. Suma treatment (0.1 and 0.3 mg/kg/day, IP) was started on day 1 and continued for 3 consecutive days. Results: Creatinine (Cr), blood urea nitrogen (BUN) and malondialdehyde (MDA) levels were elevated and glutathione peroxidase (GPx) as well as superoxide dismutase (SOD) activities were decreased in Cis-treated mice. Suma (more potently 0.3 mg/kg) reduced Cr, BUN and MDA levels and increased SOD and GPx levels. Suma also reduced the acute renal injury (tubular degeneration, tubular cells vacuolation, tubular necrosis and cast), which corresponded to kidney damage in Cis-treated mice. Conclusion: These findings demonstrate that Suma mitigates Cis-induced renal injury by inhibition of oxidative stress and enhancing the antioxidant enzymes activities.

Abstract Background Current antiepileptic drugs are not able to prevent recurrent seizures in all patients. Orexins are excitatory hypothalamic neuropeptides that their receptors (Orx1R and Orx2R) are found almost in all major regions of the brain. Pentylenetetrazol (PTZ)-induced kindling is a known experimental model for epileptic seizures. The purpose of this study was to evaluate the effect of Orx2 receptor antagonist (TCS OX2 29) on seizures and anxiety of PTZ-kindled rats. Results Our results revealed that similar to valproate, administration of 7 µg/rat of TCS OX2 29 increased the latency period and decreased the duration time of 3rd and 4th stages of epileptiform seizures. Besides, it significantly decreased mean of seizure scores. However, TCS OX2 29 did not modulate anxiety induced by repeated PTZ administration. Conclusion This study showed that blockade of Orx2 receptor reduced seizure-related behaviors without any significant effect on PTZ-induced anxiety.

Objective(s): Growing evidence suggests that dysfunction of the glutamatergic system and α-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptors are involved in pathology of Alzheimer’s disease (AD). Because AMPA receptors play a key role in plasticity synaptic regulation, positive modulation of these receptors may rescue the cognitive deficits in the AD. The aim of this study was to explore the effect of CX691, a specific positive allosteric modulator of the AMPA-type glutamate receptors (Ampakine), on spatial learning and memory in a rat model of AD. Materials and Methods: For induction of AD, amyloid-beta 1-42 (Aβ1-42) was microinjected into the hippocampus of male Wistar rats (250-300 g). The Morris water maze (MWM) test was used to evaluate the effect of CX691 (0.03 and 0.3 mg/kg, twice a day for 10 days, orally) on spatial learning and memory of rats. In order to evaluate the protein expression of brain-derived neurotrophic factor (BDNF) in hippocampus tissue, ELISA test was used. Results: The obtained data showed that treatment with CX691 (0.3 mg/kg) improves the impairment of spatial learning and memory in AD rats. Also, treatment with CX691 (0.3 mg/kg), increased the BDNF protein level in hippocampus tissue of AD rats compared to non-treated animals.Conclusion: The CX691 can improve the BDNF protein expression as well as spatial performance of learning and memory in AD rats.

Opiate tolerance and dependence is a worldwide public health problem and gives a significant burden to society. The aim of this study was to evaluate the effects of metformin (MET) on development and expression of morphine tolerance and dependence in rats. For induction of tolerance, morphine sulfate was injected (10 mg/kg, twice a day, s.c.) for 7 days. Animals received metformin (5 and 50 mg/kg, orally, daily) during the examination period for assessing the development of morphine tolerance and dependence. In order to evaluate the expression of morphine tolerance and dependence, single doses of MET (5 and 50 mg/kg, orally) were administered on day 7. Tail flick test was performed to assess the induction of morphine tolerance. For evaluation of morphine dependence, naloxone-induced jumping (5 mg/kg, s.c.) was monitored. Our results showed that 7 days coadministration of 50 mg/kg of MET significantly reduced the development of morphine analgesic tolerance versus morphine + saline treated rats (P < 0.001). Treatment with 50 mg/kg MET reduced the incidence and frequency of jumping in naloxone injected animals (P < 0.01). It is notable that single dose administration of MET, did not prevent the expression of analgesic tolerance and physical dependence to morphine. Based on these results, it can be concluded that MET attenuates the development of morphine analgesic tolerance and dependence in rats.

Objective(s): Metformin (Met), an antidiabetic biguanide, reduces hyperglycemia via improving glucose utilization and reducing the gluconeogenesis. Met has been shown to exert neuroprotective, antioxidant and anti-inflammatory properties. The present study investigated the possible effect of Met on the D-galactose (D-gal)-induced aging in mice. Materials and Methods: Met (1 and 10 mg/kg/p.o.), was administrated daily in D-gal-received (500 mg/kg/p.o.) mice model of aging for six weeks. Anxiety-like behavior, cognitive function, and physical power were evaluated by the elevated plus-maze, novel object recognition task (NORT), and forced swimming capacity test, respectively. The brains were analyzed for the level of superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF). Results: Met decreased the anxiety-like behavior in D-gal-treated mice. Also, Met treated mice showed significantly improved learning and memory ability in NORT compared to the D-gal-treated mice. Furthermore, Met increased the physical power as well as the activity of SOD and BDNF level in D-gal-treated mice. Conclusion: Our results suggest that the use of Met can be an effective strategy for prevention and treatment of D-gal-induced aging in animal models. This effect seems to be mediated by attenuation of oxidative stress and enhancement of the neurotrophic factors.

Objective(s): Stroke is known as a main cause of mortality and prolonged disability in adults. Both transient receptor potential V1 (TRPV1) channels and toll-like receptors (TLRs) are involved in mediating the inflammatory responses. In the present study, the effects of TRPV1 receptor activation and blockade on stroke outcome and gene expression of TLR2 and TLR4 were assessed following permanent middle cerebral artery occlusion in rats Materials and Methods: Eighty male Wistar rats were divided into four groups as follows: sham, vehicle, AMG9810 (TRPV1 antagonist) -treated and capsaicin (TRPV1 agonist) -treated. For Stroke induction, the middle cerebral artery was permanently occluded and then behavioral functions were evaluated 1, 3 and 7 days after stroke. Results: TRPV1 antagonism significantly reduced the infarct volume compared to the stroke group. Also, neurological deficits were decreased by AMG9810 seven days after cerebral ischemia. In the ledged beam-walking test, the slip ratio was enhanced following ischemia. AMG9810 decreased this index in stroke animals. However, capsaicin improved the ratio 3 and 7 days after cerebral ischemia. Compared to the sham group, the mRNA expression of TLR2 and TLR4 was significantly increased in the stroke rats. AMG9810 Administration significantly reduced the mRNA expression of TLR2 and TLR4. However, capsaicin did not significantly affect the gene expression of TLR2 and TLR4. Conclusion: Our results demonstrated that TRPV1 antagonism by AMG9810 attenuates behavioral function and mRNA expression of TLR2 and TLR4. Thus, it might be useful to shed light on future therapeutic strategies for the treatment of ischemic stroke.

The Achillea millefolium L. (Yarrow) is a common herb which is widely being used, worldwide. Achillea is being used for treatment of many disorders since centuries. It is considered safe for supplemental use and flavonoids such as kaempferol, luteolin and apigenin are of main constituents present in Achillea. Most of both antioxidant and anti-inflammatory properties of this herb have been attributed to its flavonoid content. Oxidative and inflammatory processes play important roles in pathogenesis of neurodegenerative diseases. Present review was aimed to review the latest literature evidences regarding application of Achillea and/or its three main flavonoid constituents on epilepsy, Alzheimer's disease, multiple sclerosis, Parkinson's disease and stroke.

Context: Oxidative stress has a critical role in the development of physical fatigue and activation of matrix metalloproteinases-9 (MMP-9). Naringin (Nar) is a bioflavonoid that has antioxidant activity and suppresses MMP-9 expression. Objective: The present study evaluates the anti-fatigue activity of Nar on physical fatigue and serum MMP-9 concentration in rats. Materials and methods: Fifty female Wistar rats were randomly divided into five groups (n = 10); a control group, vehicle group and three Nar treatment groups. The Nar treated groups received different doses of Nar (40, 80 and 160 mg/kg/day) for 30 days. On the 30th day, rats were sacrificed immediately after exhaustive swimming test. Serum MMP-9 concentration and several biochemical parameters related to fatigue were measured. Results: Exhaustive swimming time in the Nar-80 group significantly increased 1.78-, 1.53-, 1.5- and 1.3-fold compared with the control, vehicle, Nar-40 and Nar-160 groups, respectively. In addition, exhaustive swimming time in the Nar-160 group significantly increased 1.36-fold compared with the control group. Nar-80 significantly decreased LDH activity by 60.45% and 57.47% compared with the vehicle and control groups, respectively. Furthermore, Nar-80 and Nar-160 increased blood glucose levels by 19.56% and 18.38% compared with the control group, respectively. Nar-80 and Nar-160 significantly decreased serum MMP-9 concentration by 61.57% and 83.39% compared with the control group, respectively. Conclusion: Based on our data, Nar has anti-fatigue effects which may be attributed to its property in modulating energy metabolism and reducing serum MMP-9 concentration. Thus, Nar may be a promising agent for the treatment of physical fatigue.

Objective: The main function of IL-12 is differentiation of naive T cells intoTh1 cells and TGF-β is a powerful immunoregulatory cytokine. The immunomodulatory and anti-inflammatory properties of ginger have also been reported in some studies. The aim of this study was to evaluate the effects of ginger extract on the expression of IL-12 and TGF-β in a model of experimental autoimmune encephalomyelitis (EAE).Materials and Methods: EAE was induced in C57BL/6 mice by immunization with myelin oligodendroglial glycoprotein emulsified in complete Freund's adjuvant. The mice were administered intra-peritoneally with ginger extracts or PBS, from day +3 to +30. On day 31, mice were scarified and the expression of IL-12 and TGF-β mRNA in the spinal cord were determined by using real time-PCR. The serum levels of cytokines were measured by ELISA.Results: In PBS-treated EAE mice, the expression of IL-12 P35 and IL-12 P40 mRNA in the CNS and the mean serum levels of IL-12 were significantly higher than those of healthy group (p

Objective: At present, there are many antiepileptic drugs with a wide range of side effects on the human body. It was assumed that Zataria multiflora Boiss (Z. multiflora) with sedative, anti-spasmodic and anti-inflammatory activity may be effective in the treatment of epilepsy. The aim of the present study was to elucidate the effect of Z. multiflora hydroalcoholic extract and its fraction extracts on pentylenetetrazole (PTZ)-induced chemical kindling. Materials and Methods: In this experimental study, eight separate groups of male albino mice were used. All groups received 11 separate intraperitoneal injections of PTZ (35 mg/kg) with two-day intervals. 30 min before the injection of PTZ, mice received vehicle, Z. multiflora hydroalcoholic extract (300 and 600 mg/kg), n-hexane, acetone, methanol fraction extracts (150 mg/kg), or diazepam (10 mg/kg). Results: The kindled mice that were pretreated with vehicle showed a gradual increase in their seizure scores up to the end of the study. The hydroalcoholic extract of Z. multiflora (300 and 600 mg/kg) reduced seizure scores significantly. However, n-hexane, acetone and methanol extracts did not affect seizure scores significantly. Conclusion: The present findings demonstrate that the hydroalcoholic extract of Z. multiflora did reduce the severity of seizure attacks in PTZ-induced chemical kindling in mice.

Background and Aim: Endogenous opioids and addictive opiate drugs change many body functions. . Previous studies have referred to the effects of morphine on smooth and pulmonary muscles ., but the effects of opioids on skeletal muscles is not known well. Thus, the current study aimed at assessing the effect of a single dose of morphine on muscle fatigue in male rats. Materials and Methods: In this experimental study, 40 male Wistar rats weighing 220-270 g were randomly divided into four equal groups: control (the mice were kept in their cages and received food and water), morphine receiving group, fatigue group (the mice in this group were kept running on a treadmill . for120 minutes at a rate of 20 meters per minute), and morphine plus fatigue group. At the end of the experiments, blood samples were obtained from the corner of their eyes and were sent to the laboratory for measurement of muscle fatigue indexes including lactate dehydrogenase (LDH) and creatine phosphokinase (CPK). Results: Administration of morphine to the fatigue group decreased running time compared with the control group (P=0.009). Furthermore, administration of morphine to the fatigue group significantly increased serum levels of LDH (P=0.009) and CPK (P=0.008). Conclusion: The present study showed that administration of a single dose of morphine in rats increases muscle fatigue biomarkers (LDH, CPK).

Introduction: Dimethyl sulfoxide (DMSO) is a chemical often used as a solvent for waterinsoluble drugs. In this study, we evaluated the effect of intracerebroventricular (ICV) administration of DMSO on neural response characteristics (in 1200–1500 μm depth) of the rat barrel cortex. Methods: DMSO solution was prepared in 10% v/v concentration and injected into the lateral ventricle of rats. Neuronal spontaneous activity and neuronal responses to deflection of the principal whisker (PW) and adjacent whisker (AW) were recorded in barrel cortex. A condition test ratio (CTR) was used to measure inhibitory receptive fields in barrel cortex. Results: The results showed that both PW and AW evoked ON and OFF responses, neuronal spontaneous activity and inhibitory receptive fields did not change following ICV administration of DMSO. Conclusion: Results of this study suggest that acute ICV administration of 10% DMSO did not modulate the electrophysiological characteristics of neurons in the l deep ayers of rat barrel cortex.

Objective(s): Intracerebroventricular injection of orexin-A (hypocretin-1) antagonist has been shown to inhibit stress-induced analgesia. However the locations of central sites that may mediate these effects have not been totally demonstrated. This study was performed to investigate the role of rostral ventromedial medulla (RVM) orexin receptor 1 in stress-induced analgesia (SIA). Materials and Methods: Forced swim stress in water was employed to adult male rats (200-250 g). Nociceptive responses were measured by formalin test (50 µl injection of formalin 2% subcutaneously into hind paw) and, pain related behaviors were monitored for 90 min following intra-microinjection of SB-334867 (orexin receptor 1 antagonist) into RVM. Results: Exposure to swimming stress test after administration of SB-334867 into RVM significantly reduces the formalin-induced nociceptive behaviors in phase1, interphase, and phase 2 in rats. Conclusion: The result demonstrated the involvement of OXR1 in antinociceptive behaviors induced by swim stress in RVM.

Background & Aims: Stroke is the third leading cause of death. Oxidative stress has a principal role in the complications of stroke. Due to this fact and the antioxidant effects of ascorbic acid, this study was designed to evaluate the effect of ascorbic acid on reduction of stroke complications in a permanent model of middle cerebral artery (MCA) occlusion in male rats. Methods: In this experimental study, the rats were divided into 3 groups of control, ascorbic acid, and surgicalsham. Stroke wasinduced by cauterization of MCA. The animals' brain wassliced and stained using tetrazolium chloride (TTC) 48 hours after stroke induction. Then, infarction volume was determined using image processing software. In addition, behavioral tests, such as neurologic deficits, were evaluated 24 and 48 hours afterstroke induction. Data were statistically analyzed using One-way ANOVA test. Results: The infarct volume significantly reduced in the ascorbic acid treated group in comparison with control group (P < 0.010). Moreover, blood-brain barrier (BBB) breakdown, brain edema volume (P < 0.001), and the level of matrix metallopeptidase-9 (MMP-9) (P < 0.050) significantly reduced following treatment by ascorbic acid. Neurologic deficits, which were assessed using the Bederson Grading System, showed relative improvement in the ascorbic acid treated group (P < 0.050). Conclusion:Thisstudy showed that ascorbic acid, due to its neuroprotective effects, can significantly reduce the complications ofstroke.

Introduction: Lower level of estrogen hormone is considered as an important factor for loss of learning and memory in postmenopausal women. Although estrogen replacement therapy is used for compensation, but long-term usage of estrogen is associated with a higher risk of hormonedependent cancers. Phytoestrogens, due to fewer side effects, have been proposed to prevent menopause-related cognitive decline. Methods: 24 female Wistar rats weighing 180-220 g were used in this study. The animals were ovariectomized and randomly divided into four groups including, control and two groups which received 8 and 80 mg/kg Vitex agnus castus (VAC) ethanolic extract orally. The last groups were treated with 40 μg/kg of estradiol valerat. Step-through passive avoidance (STPA) test was used for the evaluation of learning and memory. The hippocampal estrogen receptor α (ERα) expression was measured using Real-Time PCR. Results: The results demonstrated that VAC extract or estradiol had better performance on stepthrough passive avoidance test than control group (all P

Background and Aim: Oxidative stresses are involved in neuronal degeneration of substantia nigra and thereby induction of Parkinson's disease. It is reported that Foeniculum Vulgare L. can affect lactating and modulating dopaminergic system activity and antioxidant activity as well. In the present study, the effects of methanolic extract of Foeniculum Vulgare seeds on a Parkinson’s disease model induced by ICV injection of 6-hydroxydopamin (6-OHDA) in female rats were investigated. Materials and Methods: In this experimental study, 60 female rats were randomly divided into 6 equal groups including saline, Parkinson’s disease and Parkinson’s groups which were treated by different doses of the extract. Parkinson’s disease was induced by i.c.v injection of 6-OHDA. Methanolic extract of Foeniculum Vulgare seeds (100 and 200 mg/kg) was gavaged through two ways including repeated gavage (14 days before and 14 days after 6-OHDA injection) and acute gavage (once every day for 14 days after 6-OHDA injection). The induced Parkinson`s disease. was evaluated using Rotarod and Wire grasping tests on the day 14th after 6-OHDA injection. Results: The findings of the study demonstrated that repeated gavage of Foeniculum Vulgare extract improved motility and muscle tone in Parkinson’s animals (Pp

Background: Chronic use of opioids usually results in physical dependence. The underlying mechanisms for this dependence are still being evaluated. Transient receptor potential vanilloid type 1 (TRPV1) are important receptors of pain perception. Their role during opioid dependence has not been studied well. The aim of this study was to evaluate the effect of morphine-dependence on the expression of TRPV1 receptors in the amygdala and CA1 region of the hippocampus. Methods: This study used four groups of rats. Two groups of rats (morphine and morphine+naloxone) received morphine based on the following protocol: 10 mg/kg (twice daily, 3 days) followed by 20, 30, 40 and 50 mg/kg (twice daily), respectively, for 4 consecutive days. Another group received vehicle (1 ml/kg) instead of morphine given using the same schedule. The morphine+naloxone group of rats additionally received naloxone (5 mg/kg) at the end of the protocol. The control group rats received no injections or intervention. The amygdala and CA1 regions of the morphine, saline-treated and intact animals were isolated and prepared for real-time PCR analysis. Results: Administration of naloxone induced withdrawal signs in morphine-treated animals. The results showed a significant decrease in TRPV1 gene expression in the amygdala (P

Objective(s): There are many reports about the role of rostral ventromedial medulla (RVM) in modulating stress-induced analgesia (SIA). In the previous study we demonstrated that temporal inactivation of RVM by lidocaine potentiated stress-induced analgesia. In this study, we investigated the effect of permanent lesion of the RVM on SIA by using formalin test as a model of acute inflammatory pain. Materials and Methods: Three sets of experiments were conducted: (1) Application of stress protocol (2) Formalin injection after exposing the animals to the swim stress (3) Either the relevant vehicle or dopamine receptor 1 (D1) agonist R-SKF38393 was injected into the RVM to cause a lesion. For permanent lesion of RVM, R-SKF38393 was injected into the RVM. Forced swim stress in water was employed in adult male rats. Nociceptive responses were measured by formalin test (50µl injection of formalin 2% subcutaneously into hind paw) and pain related behaviors were monitored for 90 min. Results: In the unstressed rats, permanent lesion of the RVM by R-SKF38393 decreased formalin-induced nociceptive behaviors in phase 1, while in stressed rats, injection of R-SKF38393 into the RVM potentiated swim stress-induced antinociception in phase 1 and interphase, phase 2A of formalin test. Furthermore, R-SKF38393 had pronociceptive effects in phase2B whereas injections of R-SKF38393 resulted in significant difference in nociceptive bahaviours in all phases of formalin test (P

Objectives: Toxoplasma gondii is a worldwide prevalent zoonotic parasite which causes toxoplasmosis. An appropriate vaccine for animals could interrupt the circle between animals and humans. Our previous study showed that excreted/secreted antigens (E/SA), derived from the peritoneum of mice infected with T. gondii tachyzoites could be considered as a good candidate for animal vaccination. Interleukin-10 (IL-10) inhibits proliferation of B and T lymphocytes and induces homeostasis in immune system responses. However, since IL-10 has also been shown to suppress the killing of T. gondii by human macrophages, the aim of this study was to evaluate IL-10 serum levels after vaccination with T. gondii E/SA prepared in vivo.Methods: T. gondii tachyzoites were inoculated in the peritoneum of mice and harvested E/SA were used as a vaccine, with and without adjuvant, in T. gondii infected and un-infected mice. IL-10 serum levels were evaluated using the ELISA technique.Results: The data showed that although serum levels of IL-10 were not changed at the early phases, they were elevated at the end phases of vaccination with T. gondii E/SA.Conclusion: Based on these and our previous results, it can be concluded that in vivo prepared T. gondii E/SA could be considered as a good candidate for animal vaccination.

Orexin A and B are hypothalamic peptides with a wide variety of effects such as anti-inflammation and neuroprotection. Impaired function of orexin system has been reported in some neurodegenerative diseases like Parkinson, Huntington and Alzheimer. In this study, the mRNA expression levels of some hypothalamic peptides were investigated in C57BL/6 female mice with experimental autoimmune encephalomyelitis (EAE). Animals were randomly divided into two control and EAE groups. EAE was induced by administration of myelin oligodendrocyte glycoprotein (MOG) with complete Ferund’s adjuvant and pertussis toxin. Twenty-first days following immunization, mice were decapitated to remove the brains. Then, the expression profiles of prepro-orexin, orexin 1 receptors (OX1R) and orexin 2 receptors (OX2R) in hypothalamic region were assessed using real-time PCR method. In this study, we found a considerable increase in the mRNA expression of OX1R and OX2R following EAE induction in C57BL/6 mice. Elevation levels of OX1R and OX2R following EAE induction suggest that alteration in orexinergic system may involve in pathogenesis of multiple sclerosis.

Introduction: Morphine addiction and morphine withdrawal syndrome are the two main problems of today’s human society. The present study has investigated the effects of nicotine on the strength of physical and psychological dependency in single and repeated doses morphine administrated rats. Methods: Male Wistar rats were subjected to morphine consumption with single or frequent dose protocols. In the single dose protocol, rats received only one dose of morphine and 24hrs later they also received one dose of nicotine 30 min prior to injection of naloxone. In the repeated dose protocol, rats received incremental doses of morphine for 7 days and 24hr after the last dose (the 8th day) were given naloxone. However, the nicotine regimen of this group was injected 15 min before the morphine injection, for 4 days, from the 4th to the 7th day. Five minutes after naloxone injection, each rat′s behavior was captured for 30 min, and then physical and psychological signs of withdrawal syndrome were recorded. Data were analyzed by ANOVA followed by Tukey tests and p

Introduction. Morphine addiction and morphine withdrawal syndrome are the two main problems of today’s human society. The present study has investigated the effects of nicotine on the strength of physical and psychological dependency in single and repeated doses morphine administrated rats. Materials and methods. Male Wistar rats were subjected to morphine consumption with single or frequent dose protocols. In the single dose protocol, rats received only one dose of morphine and 24hrs later they also received one dose of nicotine 30 min prior to injection of naloxone. In the repeated dose protocol, rats received incremental doses of morphine for 7 days and 24hr after the last dose (the 8th day) were given naloxone. However, the nicotine regimen of this group was injected 15 min before the morphine injection, for 4 days, from the 4th to the 7th day. Five minutes after naloxone injection, each rat′s behavior was captured for 30 min, and then physical and psychological signs of withdrawal syndrome were recorded. Data were analyzed by ANOVA followed by Tukey tests and p

Background/Aim: Occult hepatitis B infection (OBI) is identified as a form of hepatitis in which despite the absence of detectable HBsAg, HBV-DNA is observed in peripheral blood of patients. The main aim of this study has been to investigate the association between polymorphisms in +874 of IFN-γ and +1188 of IL-12 with their serum level in patients suffering from OBI. Materials and Methods: In this experimental study, plasma samples of 3700 blood donors were tested for the presence of hepatitis B surface antigen (HBsAg) and anti-HBc by ELISA. The HBsAg - /anti-HBc + samples were selected and screened for HBV-DNA by PCR. HBV-DNA positive samples were assigned as OBI cases and ARMS-PCR techniques were performed to examine the two known polymorphisms within IL-12 and IFN-γ. In addition, the serum levels of IL-12 and IFN-γ were also determined by ELISA. Results: Results of this study demonstrated that, 352 (9.5%) out of 3700 blood samples were HBsAg - /anti-HBc + and HBV-DNA was detected in 57/352 (16.1%) of HBsAg - /anti-HBc + samples. Our results showed that groups showed significant difference in CC allele of +1188 region of IL-12 and no difference was observed in the other evaluated genes. Our results also showed that the alleles of +1188 region of IL-12 and alleles of +874 of IFN-γ were also not associated with serum level of cytokines. Conclusion: According to the results of this study, it may be concluded that the polymorphisms in +1188 region of IL-12 and +874 region of IFN-γ would not affect the expression of both cytokines at serum level in OBI patients.

(Received 5 Oct, 2008; Accepted 14 Feb, 2009)AbstractBackground and purpose: Occult hepatitis B infection (OBI) is defined as a form of hepatitis B that despite absence of detectable HBsAg, HBV-DNA is present in patient’s peripheral blood. Genetic and immunological differences appear to play important roles in producing OBI. Therefore, this project was aimed to examine the expression of a chemokine receptor (CCR5) on CD8 T cells of OBI patients.Materials and methods: In this experimental study, 3,700 HBsAg- plasma samples were collected. Samples were tested for anti-HBc antibody and all of HBsAg-/anti-HBc+ samples were screened for HBV-DNA by PCR. HBV-DNA positive samples were assigned as OBI cases. Also, flow cytometry analysis was performed to examine the expression of CCR5 on CD8 T cells of OBI patients.Results: Results of current study showed that 352 (9.5%) cases of samples were positive for anti-HBc. Examination of HBsAg-/anti-HBc+ samples for HBV-DNA by PCR showed that 57 (16.1%) cases had HBV-DNA. Flow cytometric studies indicated lymphocytosis in these patients; however, the number of cells which expressed CD8 and CCR5 is decreased significantly in patients, compared to healthy control. In addition to CD8 T cells, the expression of CCR5 is also decreased on all immune cells.Conclusion: One of the chemokine receptors which are expressed by CD8+ T cells is CCR5 and these cells are recruited to infected tissues, including liver by CCR5. Therefore, based on results of this investigation, one may conclude that due to the decreased expression of CCR5, the CD8+ T cells are unable to respond to the chemokines (CCR5 ligands) and, hence, can not immigrate to the infected liver and incorporate in clearance of hepatitis B virus.J Mazand Univ Med Sci 2009; 19(68): 11-18 (Persian)

(Received 25 May, 2009 ; Accepted 10 August, 2009)AbstractBackground and purpose: In the present study, we compared the intensity of physical dependency, mortality rate and weight changes in some common methods for inducing morphine dependency.Materials and methods: Six common different methods for morphine dependency were chosen in wistar rats. In all methods, morphine dependency was induced by repeated morphine injection. Precipitation of morphine withdrawal signs were performed on the last day in each method, 4 hours after the last morphine injection for 20 minutes. The withdrawal signs included: vertical jumping, wet dog shakes, diarrhea, teeth chattering, ptosis, head shakes and rearing.Results: Our results demonstrated that all groups of treated rats showed withdrawal signs following naloxone challenge. However, the intensities of withdrawal signs (vertical jumping, wet dog shakes, diarrhea, teeth chattering, head shakes and rearing) were significantly different among these methods. Also, mortality rate and amount of weight loss were significantly different among the different methods.Conclusion: This study demonstrates that different experimental methods of morphine dependency can induce different intensities of withdrawal signs, mortality rate and weight loss. J Mazand Univ Med Sci 2009; 19(71): 20-26 (Persian)

Increased levels of proinflammatory cytokines have been recorded after the onset of transient or permanent brain ischemia and are usually associated with exacerbation of ischemic injury. Embolic stroke model is more relevant to the pathophysiological situation in such patients, because the majority of ischemic injuries in humans are induced by old thrombi that originate from the heart and carotid arteries. Therefore, the aim of the present study was to investigate changes of inflammatory cytokines after embolic stroke. Rats were subjected to embolic stroke, induced by a natural old clot which was injected in Middle Cerebral Artery (MCA), or sham stroke, which the same volume of saline was injected into the MCA. At 48 h after stroke induction, the levels of 5 cytokines (IL-1α and β, IL-6, IFN-γ and TNF-α) were determined in 500 µg of total protein using the Bio-Plex Rat Cytokine Array (BioRad), according to the manufacturer’s instructions in ischemic and non- ischemic cortices. While stroke animals showed infarctions and neurological deficits, we did not observe any cerebral infarction and neurological deficits in sham-operated animals. The levels of IL-1α (p=0.000) and -β (p =0.004), IL-6 (p =0.008), TNF-α (p =0.000) and IFN-γ (p =0.044) were significantly increased compared to sham treated animals. The findings of the present study suggest that part of ischemic injury in the embolic stroke may be mediated through the increased levels of inflammatory cytokines.

Cardiovascular morbidity and mortality are potentiated with smoking and hypertension. The aim of this study was to investigate the effects of morphine and nicotine co-administration on cardiovascular function in two-kidney one-clip hypertensive (2K1C) rats. Thirty-two male rats were divided into four groups as follow: Vehicle, morphine, nicotine and nicotine + morphine. All drugs were administered for 8 weeks. Baroreflex sensitivity (BRS), heart rate and blood pressure were measured using a Power Lab data acquisition. Plasma rennin activity (PRA) and serum concentration of nitric oxide (NO) were measured using Elisa method. To induce hypertension, the renal artery of left kidney was clipped for 8 weeks. A significant decrease in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) was observed in nicotine + morphine group compared to vehicle and nicotine groups (p

Objective(s)Opioid abuse is still remained a major mental health problem, a criminal legal issue and may cause ischemic brain changes including stroke and brain edema. In the present study, we investigated whether spontaneously withdrawal syndrome might affect stroke outcomes.Materials and MethodsAddiction was induced by progressive incremental doses of morphine over 7 days. Behavioral signs of withdrawal were observed 24, 48 and 72 hr after morphine deprivation and total withdrawal score was determined. Cerebral ischemia was induced 18-22 hr after the last morphine injection by placing a natural clot into the middle cerebral artery (MCA). Neurological deficits were evaluated at 2, 24 and 48 hr after ischemia induction, and infarct size and brain edema were determined at 48 hr after stroke.ResultsMorphine withdrawal animals showed a significant increase in total withdrawal score and decrease of weight gain during the 72 hr after the last morphine injection. Compared to the addicted and control animals, infarct volume and brain edema were significantly increased in the morphine deprived animals (P< 0.05) at 48 hr after cerebral ischemia. Also, neurological deficits were higher in the morphine-withdrawn rats at 48 hr after stroke (P< 0.05). ConclusionOur data indicates that spontaneous withdrawal syndrome may worsen stroke outcomes. Further investigations are necessary to elucidate mechanisms of opiate withdrawal syndrome on stroke.

Objective(s)Although, type 2 diabetes is the most frequent type of diabetes, its main cause is yet to be clarified. Severalenvironmental and genetic parameters are believed to be involved in diabetes. It has also been establishedthat cytokines play key roles in pathogenesis of diabetes. Expression of cytokines is different from person toperson and in different societies. Several studies showed that polymorphisms of +874 of interferon-gamma(IFN-γ) and -590 of interleukin-4 (IL-4) are associated with the regulation of expression of these genes. Thisstudy was aimed to find polymorphisms of these regions in type 2 diabetes patients.Materials and MethodsIn this experimental study peripheral blood samples were collected from 160 type 2 diabetic patients and 160healthy controls. DNA was extracted by salting out method. Polymorphisms of +874 of IFN-γ and -590 ofIL-4 were analyzed by ARMS-PCR and RFLP-PCR.ResultsOur findings indicated that TT genotype of IFN-γ was increased in type 2 diabetic patients compared to thecontrol but difference was not significant. Our results didn’t show any significant difference between IL-4genotype in diabetic and healthy controls either.ConclusionOur results suggested that TT genotype of IFN-γ can be associated with diabetes. This association can bedescribed by the fact that over expression of IFN-γ shifts immune system to Th1; therefore, pancreatic cellscan be miscarried by immune cells.Keywords: Interferon-gamma, Interleukin-4, Polymorphism, Type 2 diabetes