Therapeutic effects of pegylated-interferon-α2a in a mouse model of multiple sclerosis.

INTRODUCTION: Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS). EAE is mainly mediated by adaptive and innate immune responses that lead to an inflammatory demyelination and axonal damage. The aim of the present research was to examine the therapeutic efficacy of Peg interferon alpha 2a (Peg-IFN α-2a) as a serine protease inhibitor on EAE model. MATERIAL AND METHODS: EAE induction was performed in female C57BL/6 mice by myelin oligodendrocyte glycoprotein (35-55) (MOG35-55) in Complete Freund's Adjuvant (CFA) emulsion, and Peg-IFN α-2a was used for the treatment of EAE. During the course of the study, clinical evaluation was assessed, and on day 21 post-immunisation blood samples were taken from the heart of mice for evaluation of IL-6, and enzymatic and non-enzymatic antioxidants. The mice were sacrificed and the brains and cerebellums were removed for histological analysis. RESULTS: Our findings indicated that Peg-IFN α-2a had beneficial effects on EAE by attenuation of the severity and a delay in the onset of disease. Histological analysis showed that treatment with Peg-IFN α-2a can reduce inflammation criteria. Moreover, in Peg-IFN α-2a-treated mice the serum level of IL-6 was significantly less than in controls, and total antioxidant capacity was significantly more than in the control animals. CONCLUSIONS: These data indicate that Peg-IFN α-2a as an anti-serine protease with immunomodulatory properties may be useful for the treatment of MS.

Preclinical and pharmacotoxicology evaluation of α-l-guluronic acid (G2013) as a non-steroidal anti-inflammatory drug with immunomodulatory property.

CONTEXT: Therapeutic effects of α-l-guluronic acid with the greatest tolerability and efficacy (G2013) have been shown in experimental model of multiple sclerosis and other in vitro and in vivo examinations regarding α-l-guluronic acid; there are no toxicological researches on its safety although the pharmacological impacts have been recorded. OBJECTIVE: This study was designed to determine the acute and sub chronic toxicity of α-l-guluronic acid in healthy male and female BALB/c mice. MATERIALS AND METHODS: For the acute toxicity study, the animals orally received five different single doses of α-l-guluronic acid and were kept under observation for 14 d. In the sub-chronic study, 24 male and female BALB/c mice were divided into four groups and treated daily with test substance preparation at dose levels of 0, 50, 250, and 1250 mg/kg body weight for at least 90 consecutive days. The mortality, body weight changes, clinical signs, hematological and biochemical parameters, gross findings, histopathological, and organs weight determinants were monitored during this study. RESULTS: The results of acute toxicity indicated that the LD50 of α-l-guluronic acid is 4.8 g/kg. We found no mortality or abnormality in clinical signs, body weight, relative organs weight, or necropsy in any of the animals in the subchronic study. Additionally, the results showed no significant difference in hematological, biochemical, and histopathological parameters in rats. CONCLUSIONS: Our results suggest that α-l-guluronic acid has high safety when administered orally in animals.

Effect of Arnebia euchroma ointment on post-laser wound healing in rats.

INTRODUCTION: Arnebia euchroma ointment has been used in Iranian Traditional Medicine for burn wound healing. The aim of this study is to evaluate wound healing efficacy of A. euchroma ointment on wounds induced after fractional CO2 laser in rats. MATERIAL AND METHODS: In this study, after anesthetizing two bilateral burn wounds were induced on dorsal skin of the rat using fractional ablative CO2 laser. After applying laser, A. euchroma ointment, petrolatum, and silver sulfadiazine cream were used topically on wounds twice daily for 10 days. Digital photographs were captured from the wound surfaces every day. At the end of the study, two blinded dermatologists observed the photograph of 3rd, 5th, 7th, and 9th days after laser injury and assessed erythema, crusting/scabbing, epithelial confluence, and general wound appearance to determine the efficacy of wound healing. These wound-healing parameters were assessed using the 5-point scales. RESULTS: This study showed significantly less erythema and crusting (P = 0.024 and P = 0.004, respectively) on 9th day and higher epithelial confluence and general wound appearance scores on 7th (P = 0.037 and p = 0.016, respectively) and 9th days (P = 0.008 and P = 0.016, respectively) in A. euchroma ointment compared with other groups. CONCLUSION: This study showed A. euchroma ointment has good healing effects on post-laser wounds in rats.

Therapeutic effects of dasatinib in mouse model of multiple sclerosis.

BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple sclerosis (MS). EAE is mainly mediated by adaptive and innate immune responses that lead to an inflammatory demyelination and axonal damage. Dasatinib (Sprycel) is a selective protein tyrosine kinase inhibitor with immunomodulatory properties that abrogates multiple signal transduction pathways in immune cells. In the present research, our aim was to test the therapeutic efficacy of dasatinib in experimental model of MS. METHODS: We performed EAE induction in female C57BL/6 mice by myelin oligodendrocyte glycoprotein(35-55) (MOG(35-55)) in Complete Freund's Adjuvant (CFA) emulsion, and used dasatinib for the treatment of EAE. During the course of study, clinical evaluation was assessed, and on day 21 post-immunization blood samples were taken from the heart of mice for tumor necrosis factor-alpha (TNF-α), nitric oxide (NO) and antioxidants capacity evaluation. The mice were sacrificed and brains and cerebellums of mice were removed for histological analysis. Also for in vitro analysis, we used C6 astrocytoma cell line to evaluate the inhibitory effects of dasatinib in cell proliferation and matrix metalloproteinase-2 (MMP-2) activity. RESULTS: Our findings demonstrated that dasatinib had beneficial effects on EAE by lower incidence, attenuation in the severity and a delay in the onset of disease. The serum level of NO and TNF-α in dasatinib treated mice was significantly lower than control mice. In vitro, dasatinib inhibited cell proliferation and MMP-2 activity. CONCLUSION: Dasatinib with its potential therapeutic effects and immunomodulatory properties may be recommended, after additional necessary tests and trials, for the treatment of MS.

Preclinical assessment of ß-d-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug.

CONTEXT: ß-d-Mannuronic acid (M2000) has shown its therapeutic effects with the greatest tolerability and efficacy in various experimental models such as experimental autoimmune encephalomyelitis (EAE), adjuvant induced arthritis (AIA), nephrotic syndrome, and acute glomerulonephritis. Despite pharmacological effects of ß-D-mannuronic acid, there have been no systematic toxicological studies on its safety so far. OBJECTIVE: The study was designed to determine the acute and subchronic toxicity of ß-D-mannuronic acid, an anti-inflammatory agent, in healthy male NMRI mice and Wistar rats, respectively. MATERIALS AND METHODS: For the acute toxicity study, the animals received orally five different single doses of ß-D-mannuronic acid and were kept under observation for 14 d. In the subchronic study, 24 Wistar male rats were divided into four groups and were treated orally (gavage) once daily with test substance preparation at dose levels of 0, 50, 250, and 1250 mg/kg body weight for at least 63 consecutive days (9 weeks). Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histopathological determinations were monitored during the study. RESULTS: The results of acute toxicity indicated that the LD50 of ß-D-mannuronic acid is 4.6 g/kg. We found no mortality and no abnormality in clinical signs, body weight, relative organ weights, or necropsy in any of the animals in the subchronic study. Additionally, the results showed no significant difference in hematological, biochemical, and histopathological parameters in rats. CONCLUSIONS: Our results suggest that ß-D-mannuronic acid is relatively safe when administered orally in animals.

The immunomodulatory effects of Pleurotus florida on cell-mediated immunity and secondary lymphoid tissues in Balb/c mice.

This study aimed to evaluate the immunomodulatory effects of Pleurotus florida on cell-mediated immunity in Balb/c mice. Aqueous extract of P. florida was isolated, lyophilized, and stored in refrigerator until application. Forty female Balb/c mice were randomly divided into seven test and one control groups. Four groups received 10, 20, 50, or 100 mg/kg/day of P. florida extract intraperitoneally, whereas three others received 200, 500, or 1000 mg/kg/day by oral administration. Moreover, the control group received the same volume of normal saline intraperitoneally. The treatments were continued once a day for 2 weeks. Then, delayed type hypersensitivity (DTH), viability of splenic cells, and histology of secondary lymphoid tissues were examined. The results showed that DTH responses were not affected by various doses of the P. florida in different routes. However, a significant decrease in splenic cells viability was observed in groups treated with intraperitoneal injection of 10, 20, and 50 mg/kg of the P. florida extract. In contrast, oral administration of 1000 mg/kg of the extract caused a significant increase in viability of splenic cells. Although atrophic changes in spleen and lymph nodes were observed in some peritoneal injected groups, some doses of oral administration were lead to hyperplastic changes. The results of this study indicated that the effects of P. florida on cellular responses depends on dose and route of administration.

Bovine cysticercosis in feedlot cattle in central region of Iran.

The cestode, Taenia saginata is a zoonotic tapeworm that it's larval stage which known as Cysticercus bovis cause cyst formation in cattle's organs such as heart, lung, liver, tongue, esophagus and diaphragm muscle, despite the infected cattle may show no clinical signs. Antemortem diagnosis of bovine cysticercosis can be made by antigen detecting ELISA. In a feedlot near city of Arak, beef cattle had different degrees of lethargy, dullness, unthriftiness and were reluctant to move. In postmortem examination of cattle, samples were collected from heart tissue and stained by H&E method for light microscopic examination. 10 ml of blood samples were taken from jugular veins of 90 cattle that were going to be sent to slaughterhouse. Serums obtained from blood samples were investigated for presence of C. bovis antigen by ELISA assay. Soils and dusts from farm yard, pen's floor, feed store and both toilets of workers and employer were sampled and evaluated for presence of parasite eggs by floating method. Cysticercus bovis antigen were identified in serums of 18 cattle; and also, samples from workers toilet was contaminated by eggs of T. saginata. This study showed that serologic methods in conjunction with meat inspection can be used for diagnosis of bovine cysticercosis. The aim of this study is to identify infected cattle with C. bovis by serologic methods before slaughter and determine microscopic characteristics of lesions on postmortem examination in central area of Iran.

Diosgenin ameliorates testicular damage in streptozotocin-diabetic rats through attenuation of apoptosis, oxidative stress, and inflammation.

Diabetes mellitus (DM) is a prevalent metabolic disorder that is associated with development of some complications in male reproductive system including testicular damage, sexual dysfunction, abnormal spermatogenesis, and infertility. Diosgenin is a natural steroidal saponin with anti-diabetic, anti-oxidative, and anti-inflammatory effects. This research study was undertaken to explore the protective effect of diosgenin against diabetes-induced testicular damage in the rat. Ten days following streptozotocin (STZ; i.p.), diosgenin was daily administered for 6 weeks (p.o.). Diosgenin administration to diabetic rats significantly improved body weight and lowered serum glucose. In addition, diosgenin-treated diabetic group had a significantly lower level of malondialdehyde (MDA), protein carbonyl, greater level of glutathione (GSH), and higher activity of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) in addition to testicular improvement of ferric reducing antioxidant power (FRAP). Furthermore, diosgenin significantly improved serum insulin and testosterone level and alleviated testicular markers of inflammation including tumor necrosis factor α (TNFα) and interleukin 6 (IL-6) in diabetic rats. Moreover, apoptotic markers including caspase 3 activity, Annexin V, and DNA fragmentation decreased, mitochondrial membrane potential (MMP) accentuated, and myeloperoxidase (MPO) activity as a biomarker of neutrophil infiltration decreased in diosgenin-treated diabetic group. Additionally, diosgenin was capable to improve sperm count, motility, and viability in addition to prevention of damage to seminiferous tubules in diabetic animals. Collectively, diosgenin ameliorates testicular damage in DM, at least via partial suppression of apoptosis, oxidative stress, inflammation, and neutrophil infiltration and also via partial restoration of mitochondrial integrity.

Hesperetin, a citrus flavonoid, attenuates testicular damage in diabetic rats via inhibition of oxidative stress, inflammation, and apoptosis.

AIM: This study was designed to assess the beneficial effect of hesperetin on diabetes-associated testicular injury in the rat. MAIN METHODS: Oral treatment with hesperetin started 10 days after diabetes induction by streptozotocin (60 mg/kg, i.p.) for 46 days. Testicular damage was evaluated by histological evaluation of seminiferous tubules in addition to assessment of epididymal sperm count, motility, and viability. In addition, testicular biomarkers of apoptosis, inflammation, and oxidative stress were also determined. KEY FINDINGS: Hesperetin treatment of diabetic group prevented body weight loss and reduced serum glucose in addition to improvement of serum testosterone. Additionally, hesperetin-treated diabetic group had lower levels of malondialdehyde (MDA), reactive oxygen species (ROS), protein carbonyl, DNA fragmentation, and caspase 3 activity as specific biomarkers of oxidative stress and/or apoptosis. Furthermore, hesperetin augmented testicular antioxidant system as shown by higher levels of glutathione (GSH), mitochondrial membrane potential (MMP), and ferric reducing antioxidant power (FRAP) in addition to improvement of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx). Moreover, hesperetin administration to diabetic rats attenuated testicular indices of inflammation consisting of tumor necrosis factor α (TNFα) and interleukin 17 (IL-17) and prevented damage of seminiferous tubules as revealed by higher levels of sperm count, motility, and viability in diabetic rats. SIGNIFICANCE: Collectively, hesperetin could alleviate testicular damage in DM, at least through inhibition of apoptosis, oxidative stress, and inflammation in addition to its up-regulation of endogenous enzymatic and non-enzymatic antioxidants.

Complementary Diagnostic Value of Heart Type Fatty Acid-binding Protein in Early Detection of Acute Myocardial Infarction.

BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is a novel biomarker for myocardial injury. We compared the use of H-FABP with serum levels of cardiac troponin-T (cTnT) and creatine kinase-MB (CK-MB) in the diagnosis of patients suspicious to acute myocardial infarction (AMI). METHODS: From October 2013 to December 2014, 182 consecutive patients suspicious to acute coronary syndrome were enrolled in this study, who presented within the past 6 hours from the onset of symptoms. Venous blood samples were drawn at baseline to measure serum biochemistry, high-sensitive cardiac troponin T (hs-cTNT), creatine kinase-MB, and H-FABP, and the measurements were repeated after 8 hours. The patients were categorized into 3 groups based on the baseline and second measurements of cTnT and general characteristics, and changes of H-FABP levels were then compared between the groups. Sensitivity and specificity of H-FABP in predicting the presence of AMI was calculated. RESULTS: A total of 91 patients had AMI. Changes of H-FABP through time were also significantly different between the AMI and non-AMI patients (P < 0.001). A cutoff point of 7.15 for H-FABP could predict AMI with a sensitivity of 51.5%, specificity of 96.3%, and diagnostic accuracy of 68.3%. The area under the receiver operating characteristic curve for H-FABP at 8 hours was 79.4% (95% confidence interval: 73.0-85.9; P < 0.001). Positive predictive value and negative predictive value for H-FABP were 85% and 60%, respectively. CONCLUSIONS: H-FABP can be used as an additional cardiac biomarker in the diagnosis of AMI.

Berberine ameliorates intrahippocampal kainate-induced status epilepticus and consequent epileptogenic process in the rat: Underlying mechanisms.

Status epilepticus (SE) is a life-threatening neurologic condition, instigating epileptogenesis to transform normal brain to an epileptic condition. SE is followed by spontaneous recurrent seizures (SRS) and final development of temporal lobe epilepsy (TLE) that is resistant to treatment. Neuroprotective strategies are increasingly put forward as a promising therapy to prevent and/or manage epileptic conditions. In this study, we investigated whether berberis alkaloid, i.e. berberine (BBR), could ameliorate intrahippocampal kainate-induced SE and its consequent epileptogenic process and to explore some underlying mechanisms. BBR was daily administered at doses of 25 or 50mg/kg. Results showed that BBR treatment of kainate-microinjected rats at a dose of 50mg/kg lowered the incidence of SE and SRS. It also significantly restored hippocampal level of reactive oxygen species (ROS), glutathione (GSH), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), activity of catalase and caspase 3, nuclear factor-B (NF-κB), toll-like receptor 4 (TLR4), tumor necrosis factor α (TNFα), interleukin-1ß (IL-1ß), neural cell adhesion molecule (NCAM), glial fibrillary acidic protein (GFAP), cathepsin D, and heme oxygenase 1 (HO-1). Additionally, BBR protected against hippocampal CA3 neuronal loss and prevented development of aberrant mossy fiber sprouting (MFS) as an essential element of chronic epileptogenic circuit. These data suggest that BBR could mitigate SE and SRS in intrahippocampal kainate model of epilepsy and exert neuroprotective effect and its influence is mainly mediated via suppression of oxidative stress, neuroinflammation, and possibly apoptosis.

Acetyl-l-carnitine protects dopaminergic nigrostriatal pathway in 6-hydroxydopamine-induced model of Parkinson's disease in the rat.

Parkinson's disease (PD) is a movement disorder and the second most common neurodegenerative disease worldwide in which nigrostriatal dopaminergic neurons within substantia nigra pars compacta (SNC) are lost, with clinical motor and non-motor symptoms including bradykinesia, resting tremor, rigidity, stooping posture and cognitive deficits. This study was undertaken to evaluate the neuroprotective potential of acetyl-l-carnitine (ALC) against unilateral striatal 6-hydroxydopamine (6-OHDA)-induced model of PD and to explore some involved mechanisms. In this experimental study, intrastriatal 6-OHDA-lesioned rats received ALC at doses of 100 or 200mg/kg/day for 1 week. ALC (200mg/kg) lowered apomorphine-induced rotational asymmetry and reduced the latency to initiate and the total time in the narrow beam test, reduced striatal malondialdehyde (MDA), increased catalase activity and glutathione (GSH) level, prevented reduction of nigral tyrosine hydroxylase (TH)-positive neurons and striatal TH-immunoreactivity, and lowered striatal glial fibrillary acidic protein (GFAP) and its immunoreactivity as an indicator of astrogliosis, and nuclear factor NF-kappa B and Toll-like receptor 4 (TLR4) as reliable markers of neuroinflammation. Meanwhile, ALC at both doses mitigated nigral DNA fragmentation as a valuable marker of apoptosis. The results of this study clearly suggest the neuroprotective effect of ALC in 6-OHDA-induced model of PD through abrogation of neuroinflammation, apoptosis, astrogliosis, and oxidative stress and it may be put forward as an ancillary therapeutic candidate for controlling PD.

Therapeutic effects of D-aspartate in a mouse model of multiple sclerosis.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis. EAE is mainly mediated by adaptive and innate immune responses that leads to an inflammatory demyelization and axonal damage. The aim of the present research was to examine the therapeutic efficacy of D-aspartic acid (D-Asp) on a mouse EAE model. EAE induction was performed in female C57BL/6 mice by myelin 40 oligodendrocyte glycoprotein (35-55) in a complete Freund's adjuvant emulsion, and D-Asp was used to test its efficiency in the reduction of EAE. During the course of study, clinical evaluation was assessed, and on Day 21, post-immunization blood samples were taken from the heart of mice for the evaluation of interleukin 6 and other chemical molecules. The mice were sacrificed, and their brain and cerebellum were removed for histological analysis. Our findings indicated that D-Asp had beneficial effects on EAE by attenuation in the severity and delay in the onset of the disease. Histological analysis showed that treatment with D-Asp can reduce inflammation. Moreover, in D-Asp-treated mice, the serum level of interleukin 6 was significantly lower than that in control animals, whereas the total antioxidant capacity was significantly higher. The data indicates that D-Asp possess neuroprotective property to prevent the onset of the multiple sclerosis.

New therapeutic approach by G2013 in experimental model of multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that leads to an inflammatory demyelination and axonal damage. MS disease often displays a relapsing-remitting course of neurological manifestations that is mimicked by experimental autoimmune encephalomyelitis (EAE) in animal models. The aim of the present research was to test the therapeutic effect of small molecule G2013, a novel designed non-steroidal anti-inflammatory agent in EAE. All experiments were conducted on C57BL/6 male mice aged 10 weeks. To induce the EAE, we performed subcutaneously injection of myelin oligodendrocyte glycoprotein-35-55 (MOG35-55) in Complete Freund's Adjuvant (CFA) emulsion, and for treatment of EAE we used intraperitoneal (IP) injection of G2013. On day 21 post-immunization, for total antioxidant, nitric oxide (NO) and TNF-α assessment, blood samples were taken from the heart and mice were killed, and the brains and cerebellums were then removed for histological analysis. Our findings demonstrated that G2013 had beneficial effects on EAE by lower incidence, attenuation in the severity, and a delay in the onset of disease. Histological analysis showed that inflammation criteria including the number of inflammatory cells and plaques as well as demyelination in G2013 dosed mice were lower than control group. Moreover, the serum level of NO in G2013-treated mice was significantly less than control animals. These data indicate that G2013 therapy can attenuate the disease progression in experimental model of MS.

Effect of Genistein and L-Carnitine and Their Combination on Gene Expression of Hepatocyte HMG-COA Reductase and LDL Receptor in Experimental Nephrotic Syndrome.

BACKGROUND: Nephrotic syndrome is a disorder that leads to hyperlipidemia. L-carnitine and genistein can effect on lipid metabolism and the syndrome. In the present study, we have delved into the separate and the twin-effects of L-carnitine and genistein on the gene expressions of HMG-COA reductase and LDL receptor in experimental nephrotic syndrome. METHODS: In this controlled experimental study, 50 male Sprague-Dawley rats were randomly divided into five groups: NC (normal-control), PC (patient-control), LC (L-carnitine), G (genistein), LCG (L-carnitine-genistein). Adriamycin was used for inducing nephrotic syndrome and the spot urine samples and urine protein-to-creatinine ratio were measured. Hepatocytic RNA was extracted and real-time PCR was used for HMG-COA Reductase and LDL receptor gene Expression measurement. RESULTS: The final weight of the patients groups were lower than the NC group (P=0.001), and weight gain of the NC group was higher than the other groups (P<0.001). The proteinuria and urine protein-to-creatinine ratio showed significant differences between PC group and LC, G and LCG groups at week 7 (P<0.001). The expression of HMGCOA Reductase mRNA down regulated in LC, G and LCG groups in comparison with PC group (P<0.001). ΔCT of LDLr mRNA showed significant differences between the PC group and the other patient groups (P<0.001). CONCLUSION: This study shows a significant decreasing (P<0.001) and non-significant increasing trend in HMG-COA Reductase and LDLr gene expression, respectively, and synergistic effect of L-carnitine and genistein on these genes in experimental nephrotic syndrome.

Neuroprotective effect of thymoquinone, the nigella sativa bioactive compound, in 6-hydroxydopamine-induced hemi-parkinsonian rat model.

Parkinson disease (PD) is the most common movement disorder with progressive degeneration of midbrain dopaminergic neurons for which current treatments afford symptomatic relief with no-prevention of disease progression. Due to the neuroprotective property of the Nigella sativa bioactive compound thymoquinone (TQ), this study was undertaken to evaluate whether TQ could improve behavioral and cellular abnormalities and markers of oxidative stress in an experimental model of early PD in rat. Unilateral intrastriatal 6-hydroxydopamine (6-OHDA)-lesioned rats were daily pretreated p.o. with TQ at doses of 5 and/or 10 mg/Kg three times at an interval of 24 h. After 1 week, apomorphine caused contralateral rotations, a reduction in the number of neurons on the left side of the substantia nigra pars compacta (SNC) was observed, malondialdehyde (MDA) and nitrite level in midbrain homogenate increased and activity of superoxide dismutase (SOD) reduced in the 6-OHDA lesion group. TQ pretreatment significantly improved turning behavior, prevented loss of SNC neurons, and lowered level of MDA. These results suggest that TQ could afford neuroprotection against 6-OHDA neurotoxicity that is partly due to the attenuation of lipid peroxidation and this may provide benefits, along with other therapies, in neurodegenerative disorders including PD.

Effects of imatinib mesylate in mouse models of multiple sclerosis and in vitro determinants.

Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple sclerosis (MS), This autoimmune disease is mainly mediated by adaptive and innate immune responses that lead to an inflammatory demyelination and axonal damage. Imatinib mesylate is a selective protein tyrosine kinase inhibitor with immunomodulatory properties that abrogates multiple signal transduction pathways in immune cells. In the present research, our aim was to test the therapeutic efficacy of imatinib in experimental model of MS. We performed EAE induction in 23 female C57 mice by myelin oligodendrocyte glycoprotein-35-55 (MOG35-55) in Complete Freund's Adjuvant (CFA) emulsion and used imatinib for treatment of EAE. The clinical evaluation and histopathology were assessed. Also for in vitro analysis, we used U-87 MG, C6 and WEHI-164 cell lines to evaluate the inhibitory effects of imatinib in cell proliferation, as well as pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6) and matrix metalloproteinase (MMP) secretion. Our findings demonstrated that this drug had beneficial effects on EAE by attenuation in the severity and a delay in the onset of disease. In vitro, imatinib inhibited cell proliferation, MMP-2 expression and activity and also attenuated the production of proinflammatory cytokines. Imatinib with its potential therapeutic effects and immunomodulatory properties may be considered, after additional necessary tests and trials, for treatment of MS.

Soy protein and genistein improves renal antioxidant status in experimental nephrotic syndrome.

BACKGROUND AND OBJECTIVES: Nephrotic syndrome is a chronic disease especially common in the childhood and adolescence. Reactive oxygen species (ROS) and free radicals have significant role in the pathogenesis of nephrotic syndrome. The aim of this study was to evaluate the effect of soy protein and genistein (main isoflavone of soybean) on renal antioxidant status of nephrotic rats. METHODS: This study was done for 8 weeks on 40 adult male Sprague-Dawley rats divided into four groups of 10 rats each. Study groups included: 1-Control, 2-Nephrotic syndrome, 3-Nephrotic syndrome+soy protein diet and 4-Nephrotic syndrome+soy protein diet+genistein. Urine protein and urine creatinine were measured. After homogenization of kidney, total antioxidant capacities (TAC), activities of catalase enzyme, the concentration of malondialdehydes (MDA) and carbolynated proteins were determined spectrophotometrically. Pathological examination was done on kidneys with light microscope. Cell viability was evaluated with MTT assay on WEHI-164 fibro sarcoma cell line. The MMP2 enzyme activity was evaluated in different concentrations of genistein. RESULTS: Total antioxidant capacity was significantly increased in soy genistein. Catalase activity was significantly increased in soy and soy genistein groups. Protein carbonyl and MDA were significantly lower in soy and soy genistein groups. The scores of pathological examination showed significant improvement in soy and soy genistein groups. Genistein decreased the proliferation of the WEHI-164 fibrosarcoma cell line. CONCLUSION: It seems that soy protein decreases kidney damages in nephrotic syndrome. Adding genistein to soy protein causes improvements in antioxidant status of kidney tissue. Genistein decreases proliferation of cell.

Novel therapeutic approach by nicotine in experimental model of multiple sclerosis.

BACKGROUND: Multiple sclerosis is an autoimmune, neurodegenerative disease of the central nervous system. The cause of multiple sclerosis is still unknown, and there is no cure for multiple sclerosis. Experimental autoimmune encephalomyelitis is considered as an animal model for multiple sclerosis. The therapeutic role of nicotine has been proven to be effective in both Alzheimer's and Parkinson's disease, thus we examined, for the first time, the role of nicotine in the experimental autoimmune encephalomyelitis model. METHODS: Experimental autoimmune encephalomyelitis induction was performed according to Guang-Xian Zhang et al. Treatment with nicotine was started on Day 7 post-immunization. Prevention with nicotine was started on Day 7 pre-immunization. Also for in-vitro analysis, we used U-87 MG cell line to evaluate the inhibitory effect of nicotine in cell proliferation, pro-inflammatory cytokines (TNF-alpha, IL-lbeta, IL-6) and MMP-2 activity by MTT, ELISA, and zymoanalysis methods, respectively. Moreover, the brains of mice were removed for histological analysis. RESULTS: Our findings showed that treatment with nicotine caused a significant reduction in the severity and onset of the experimental autoimmune encephalomyelitis. Histological analysis indicated that there was very mild and mild plaque in the brain sections of nicotine prevention and treatment groups, respectively. CONCLUSION: Our data indicate that nicotine can significantly improve the clinical score and attenuate the demyelinating pathology typically found in experimental autoimmune encephalomyelitis, indicating that nicotine has protective effects in experimental model of multiple sclerosis.

Histopathological and clinical evaluation of Kombucha tea and Nitrofurazone on cutaneous full-thickness wounds healing in rats: an experimental study.

BACKGROUND: Kombucha, a fermented tea (KT) is claimed to possess many beneficial properties. The aim of this study was to evaluate clinical and histopathological alterations of Kombucha tea and Nitrofurazone on cutaneous full-thickness wounds healing in rat. METHODS: In present study 24 Wister -albino rats weighing 150-200 g were selected and divided to two treatment groups as Nitrofurazone ointment (0.2%) and Kombucha tea. Subsequently, the anesthesia was exerted by Ketamin hydrochloride 10% (40 mg/kg) and Xylasine (2 mg/kg) through intra muscular (IM) route. Furthermore, upon preparation of dorsal region of the animal for surgery, a piece of full-thickness skin removed (2 × 2 cm). In order to comparing wounds healing clinically and histologically, once every four days from the commencement, the wounds were photographed and the healed surface was measured by Scion image software. RESULT: The clinical findings indicated that the Kombucha fungus resulted in precipitating healing than Nitrofurazone; however, it was not significant (p > 0.05). In order to pathological comparing of wound healing process, several wound biopsies were taken on 4, 8, 12, 16 and 20th days. Additionally, the histopathological results demonstrated that there was inflammation in Nitrofurazone group through twelveth day, somehow the epithelium was formed and abundant vessels were visible. Although on 16th day and the previous days the healing condition of Kombucha fungus was considered as minimal rate, revealing it is similar to Nitrofurazone group on 20th day. CONCLUSIONS: To wrap up. These observations suggest that the Kombucha fungus healing quality was rapid from 12th day to the end of the research, whereas no significant difference was observed. VIRTUAL SLIDE: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1107407136102196.