Changes of Leptin concentration in plasma in patients with spinal cord injury: A Meta-analysis

Objective:The aim of this study was to investigate changes of leptin concentration in plasma in patients with spinal cord injury to come to a single concept by using a Meta-analysis.Setting:Systematic Review.Methods:Searching relevant articles was performed in Ovid data base, Medline (PubMed) EMBASE, Google Scholar, Cochrane and Scopus up to February 2013. Five articles were selected using two independent reviewers. Analysis were performed using SPSS version 18 and Comparative Meta-analysis software version 2.0.Results:The combined analysis with confidence interval of 95 using comprehensive meta-analysis showed significant higher leptin levels in patients with spinal cord injury in comparison with able bodies (P<0.0001). The effect of spinal lesion level on plasma leptin concentration was also statistically significant (P<0.0001). Body mass index was positively related to plasma leptin concentration in both groups (P<0.0001).Conclusion:This Meta analysis approves increased level of leptin in spinal cord injured patients which can be due to fat distribution changes and sympathetic dysfunction in these patients. Our results also showed that patients with higher spinal lesion level have higher plasma leptin concentration. © 2013 International Spinal Cord Society All rights reserved

Clinical grade human adipose tissue-derived mesenchymal stem cell banking

In this study, our aim was to produce a generation of GMP-grade adipose tissue-derived mesenchymal stem cells for clinical applications. According to our results, we fulfill to establish consistent and also reproducible current good manufacturing practice (cGMP) compliant adipose tissue-derived mesenchymal stem cells from five female donors. The isolated cells were cultured in DMEM supplemented with 10 fetal bovine serum and characterized by standard methods. Moreover, karyotyping was performed to evaluate chromosomal stability. Mean of donors� age was 47.6 ± 8.29 year, mean of cell viability was 95.6 ± 1.51, and cell count was between 9�106 and 14�106 per microliter with the mean of 12.2�106 ± 2863564.21 per microliter. The main aim of this project was demonstrating the feasibility of cGMP-compliant and clinical grade adipose tissue-derived mesenchymal stem cells preparation and banking for clinical cell transplantation trials. © 2015 Tehran University of Medical Sciences. All rights reserved

Clinical Grade Human Adipose Tissue-Derived Mesenchymal Stem Cell Banking

In this study, our aim was to produce a generation of GMP-grade adipose tissue-derived mesenchymal stem cells for clinical applications. According to our results, we fulfill to establish consistent and also reproducible current good manufacturing practice (cGMP) compliant adipose tissue-derived mesenchymal stem cells from five female donors. The isolated cells were cultured in DMEM supplemented with 10 fetal bovine serum and characterized by standard methods. Moreover, karyotyping was performed to evaluate chromosomal stability. Mean of donors' age was 47.6 ± 8.29 year, mean of cell viability was 95.6 ± 1.51, and cell count was between 9�106 and 14�106 per microliter with the mean of 12.2�106 ± 2863564.21 per microliter. The main aim of this project was demonstrating the feasibility of cGMP-compliant and clinical grade adipose tissue-derived mesenchymal stem cells preparation and banking for clinical cell transplantation trials

The Effect of Strenuous Endurance Training on Heme Oxygenase-1 and TNF-α in Intestinal and Gastric Tissues in Male Wistar Rats

Background & aim: Intense sports activity, by creating oxidative stress, plays a role in causing some muscle damage and the spread of inflammation after the activity. On the other hand, it has been stated that oxidative stress tolerance can be done by stress proteins such as hemoxygenase. Therefore, the aim of the present study was to determine and investigate the effect of intense endurance training on hemoxygenase-1 and TNF-α enzyme levels in the stomach and intestinal tissues of male Wistar rats. Methods: In the present experimental study conducted in 2017, 16 male Wistar rats aged 8 weeks were randomly divided into 2 groups (control and intense endurance training) after 10 familiarization sessions and weight lifting (mean and the standard deviation of the control group was 203.125 ± 8.18 and intense endurance training was 211.25 ± 7.9). The intense endurance training protocol included running on a treadmill for 8 weeks (5 sessions per week), water and standard food were freely provided to the samples. 48 hours after the last training session and 4-hour fasting, the mice were dissected and tissue samples were collected, and hemoxygenase-1 enzyme concentration and TNF-α level were measured using an ELISA kit. Collected data were analyzed using independent t-test. Results: The results indicated that intense endurance training had no significant effect on the level of hemoxygenase enzyme in the stomach tissue of rats (p=0.88). Moreover, the amount of hemoxygenase-1 enzyme in the intestinal tissue of mice did not change significantly (p=0.79). The amount of TNF-α in the stomach tissue of mice was not meaningfully different between the two groups (p=0.48). The amount of TNF-α in the intestinal tissue of the two groups was not significantly different (p=0.12). Conclusion: Due to the non-change of TNF-α level, probably regular endurance sports training made the stomach and intestinal tissues safe from the destructive effects of intense endurance training by creating a beneficial adaptation in the antioxidant system. On the other hand, there is a possibility that the lack of significant changes in the inflammatory index in the present study could be related to the intensity of the exercise used. Correspondingly, if the intensity of sports activity is suitable for changes in inflammatory index levels, the lack of proper exercise by the samples of the present study was probably a factor in the absence of significant changes

Nitric oxide involvement in additive antidepressant-like effect of agmatine and lithium in mice forced swim test

Lithium is still the main agent in the management of mood disorders such as depression. Likewise, agmatine protects the central nervous system (CNS) against depression. The aim of the present study was to examine the possible additive antidepressant-like effect of agmatine and lithium in mice forced swim test (FST) as well as exploration of the probable involvement of nitric oxide (NO) pathway in this response. Results showed that pretreatment with a subeffective dose of agmatine (0.01 mg/kg) augmented the antidepressant-like effect of lithium subeffective dose (3 mg/kg) (P 0.05). Moreover, pretreatment with subeffective doses of L-arginine (substrate for NOS, 300 and 750 mg/kg) reversed the augmenting antidepressant-like effect of agmatine (0.01 mg/kg) on lithium (3 mg/kg) (P < 0.001). Our results revealed that agmatine enhances the antidepressant-like effects of lithium and the NO pathway might mediate this phenomenon. In addition, constitutive NOS plays a dramatic role in this response. © 201

Nitric oxide involvement in additive antidepressant-like effect of agmatine and lithium in mice forced swim test

Lithium is still the main agent in the management of mood disorders such as depression. Likewise, agmatine protects the central nervous system (CNS) against depression. The aim of the present study was to examine the possible additive antidepressant-like effect of agmatine and lithium in mice forced swim test (FST) as well as exploration of the probable involvement of nitric oxide (NO) pathway in this response. Results showed that pretreatment with a subeffective dose of agmatine (0.01 mg/kg) augmented the antidepressant-like effect of lithium subeffective dose (3 mg/kg) (P 0.05). Moreover, pretreatment with subeffective doses of L-arginine (substrate for NOS, 300 and 750 mg/kg) reversed the augmenting antidepressant-like effect of agmatine (0.01 mg/kg) on lithium (3 mg/kg) (P < 0.001). Our results revealed that agmatine enhances the antidepressant-like effects of lithium and the NO pathway might mediate this phenomenon. In addition, constitutive NOS plays a dramatic role in this response. © 201

Involvement of NMDA receptors and l-arginine/nitric oxide/cyclic guanosine monophosphate pathway in the antidepressant-like effects of topiramate in mice forced swimming test

Topiramate (TPM) is an agent primarily used in the treatment of epilepsy. Using mice model of forced swimming test (FST) the current study was basically aimed to investigate the influence of TPM on depression by inhibiting NMDA receptor and nitric oxide-cGMP production. When TPM was administered in a dose of 20 and 30 mg/kg by i.p. route it reduced the immobility time during FST. However this effect of TPM (30 mg/kg, i.p.) in the FST was abolished when the mice were pretreated either with NMDA (75 mg/kg, i.p.), or l-arginine (750 mg/kg, i.p. NO precursor), or sildenafil (5 mg/kg, i.p. Phosphodiesterase 5 inhibitor). The immobility time in the FST was reduced after administration of L-NAME (10 mg/kg, i.p, a non-specefic NOS inhibitor), 7-nitoinidazol (30 mg/kg, i.p. a nNOS inhibitor) or MK-801 (0.05 mg/ kg, i.p, a NMDA receptor antagonist) in combination with a subeffective dose of TPM (10 mg/kg, i.p.) as compared with single use of either drug. Co-administrated of lower doses of MK-801 (0.01 mg/kg) or L-NAME (1 mg/kg) failed to effect immobility time. However, simultaneous administration of these two agents in the same doses with subeffective dose of TPM (10 mg/kg, i.p.), reduced the immobility time during FST. None of these drugs were found to have a profound effect on the locomotor activity per se during the open field test.Taken together, our data demonstrates that TPM exhibit antidepressant-like effect which is accomplished either due to inhibition of NMDA receptors or NO-cGMP production. © 2016 Elsevier Inc

The role of nitric oxide�cGMP pathway in selegiline antidepressant-like effect in the mice forced swim test

Background: Considering the pivotal role of nitric oxide (NO) pathway in depressive disorders, the aim of the present study was to investigate the antidepressant-like effect of selegiline in mice forced swimming test (FST), and possible involvement of NO-cyclic guanosine monophosphate (cGMP) pathway in this action. Methods: After assessment of locomotor activity in open-field test, mice were forced to swim individually and the immobility time of the last 4 min was evaluated. All drugs were given intraperitoneally (ip). Results: Selegiline (10 mg/kg) decreased the immobility time in the FST similar to fluoxetine (20 mg/kg). Pretreatment with L-arginine (NO precursor, 750 mg/kg) or sildenafil (a phosphodiesterase 5 inhibitor, 5 mg/kg) significantly reversed the selegiline anti-immobility effect. Sub-effective dose of selegiline (1 mg/kg) showed a synergistic antidepressant effect with NG-nitro-L-arginine methyl ester (L-NAME, inhibitor of NO synthase, 10 mg/kg) or 7-nitroindazole (specific neuronal NO synthase inhibitor, 30 mg/kg), but not with aminoguanidine (specific inducible NO synthase inhibitor, 50 mg/kg). Pretreatment of mice with methylene blue (an inhibitor of NO synthase and soluble guanylyl cyclase, 10 mg/kg) significantly produced a synergistic response with the sub-effective dose of selegiline. Neither of the drugs changed the locomotor activity. Also, hippocampal and prefrontal cortex (PFC) nitrite content was significantly lower in selegiline-injected mice compared to saline-administrated mice. Also, co-injection of 7-nitroindazole with selegiline produced a significant reduction in hippocampal or PFC nitrite contents. Conclusions: It is concluded that selegiline possesses antidepressant-like effect in mice FST through inhibition of L-arginine-NO-cyclic guanosine monophosphate pathway. © 2018 Institute of Pharmacology, Polish Academy of Science

Lithium attenuated the behavioral despair induced by acute neurogenic stress through blockade of opioid receptors in mice

Major depressive disorder is disease with high rate of morbidity and mortality. Stressful events lead to depression and they can be used as a model of depression in rodents. In this study we aimed to investigate whether lithium modifies the stressed-induced depression through blockade of opioid receptors in mice. We used foot shock stress as stressor and forced swimming test (FST), tail suspension test (TST) and open field test (OFT) to evaluation the behavioral responses in mice. We also used naltrexone hydrochloride (as opioid receptor antagonist), and morphine (as opioid receptor agonist). Our results displayed that foot-shock stress significantly increased the immobility time in TST and FST but it could not change the locomotor behavior in OFT. When we combined the low concentrations of lithium and naltrexone a significant reduction in immobility time was seen in the FST and TST in comparison with control foot-shock stressed group administered saline only. Despite the fact that our data showed low concentrations of lithium, when administered independently did not significantly affect the immobility time. Also our data indicated that concurrent administration of lithium and naltrexone had no effect on open field test. Further we demonstrated that simultaneous administration of morphine and lithium reverses the antidepressant like effect of active doses of lithium. Our data acclaimed that we lithium can augment stressed-induced depression and opioid pathways are involved in this action. © 201

Assessment of Schwann cell purity cultured in autologous human serum for spinal cord injury repair

Background: Purity of cultured Schwann cell is very important in patients' outcome. The purpose of this study was evaluation of cell purity in a culture without nerve growth factors and fetal bovine serum.Materials and Methods: In this experimental study, for culture of human Schwann cells, nerve growth factors and fetal bovine serum were replaced by human autologous serum. Obtaining a consent from the close relative, nerve grafts were harvested and transported to processing unit where they were cultured in DMEM upon aseptic condition. Then the cultured cells were evaluated with S100 antibody staining for both morphology and purity. Results: Cell purity range was from 97 to 99 (mean=98.11±0.782). Cell count was 14055.56±2480.479 per microliter. There was not significant correlation between cell purity with either the culture period or the age of donors (P>0.05). The Spearman correlation coefficient for the cell purity with the culture period and the age of donors was -0.21 and -0.09, respectively. Conclusion: We found that the replacement of nerve growth factors and fetal bovine serum with human autologous serum improves the cultured Schwann cells for clinical use with more safety and minimum reagents