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SB‐334867, an orexin receptor 1 antagonist,decreased seizure and anxiety in pentylenetetrazol‐kindled rats
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Elham Kordi Jaz Ali Moghimi Masoud Fereidoni Saeedeh Asadi Ali Shamsizadeh Ali Roohbakhsh 《Fundamental & clinical pharmacology》2017,31(2):201-207
Convulsive seizures are due to abnormal synchronous and repetitive neuronal discharges in the central nervous system (CNS). Finding new therapeutics to overcome the side effects of the current drug therapies and to increase their effectiveness is ongoing. Orexin‐A and orexin‐B are brain neuropeptides originating from postero‐lateral hypothalamic neurons. Studies show that orexins, through activation of OX1 and OX2 receptors, have excitatory effects in the CNS. Accordingly, this study was designed to evaluate the effect of OX1 receptor antagonist (SB‐334867) on seizure‐ and anxiety‐related behaviors of pentylenetetrazol (PTZ)‐kindled rats. Kindling was induced by repeated intraperitoneal (IP) injections of PTZ (32 mg/kg) with two‐day intervals for 24 days in male Wistar rats. Three groups received intracerebroventricular (ICV) injections of SB‐334867 (2.5, 5, and 10 μg/rat) before PTZ injections. Two control groups received vehicle (2 μL/rat, ICV) and valproate (26 μg/rat, ICV) before PTZ injections. An extra group of control animals received saline both ICV and IP. Seizure‐related behaviors were monitored for 30 min following PTZ administration. The anxiety‐like behaviors were also assessed using elevated plus‐maze in the first and last days of the study. The results revealed that ICV injection of SB‐334867, mainly at the dose of 10 μg/rat, decreased the median of seizure stages, prolonged the latency and reduced the duration of different seizure stages, and reversed the PTZ‐induced anxiety‐like behaviors. Based on the presented results, it is suggested that pharmacological blockade of the OX1 receptor is a potential target in the treatment of seizure and concomitant anxiety disorders. 相似文献
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Ehsan Hejazi Maryam Tavakoli Mahmood Jeddi-Tehrani Masoud Kimiagar Jalal Hejazi Mohammad Houshyari 《Nutrition and cancer》2017,69(7):1036-1042
Background: One major concern in the treatment of cancer patients during chemotherapy is drug resistance. Here we investigated the effects of soy isoflavone extracts alone or in combination with Docetaxel on the drug resistance, angiogenesis, apoptosis, and tumor volume in mouse 4T1 breast tumor model. Methods: Sixty female BALB/c mice were randomly divided into 4 groups: control, dietary soy isoflavone extract [Iso, 100 mg/kg diet (0.01%)], Docetaxel (10 mg/kg) injection, and the combination of dietary soy isoflavone extract and intravenous Docetaxel injection (Docetaxel + Iso). One week after the third injection, the breast tumors of eight mice from each group were excised to analyze NF-κBp65′ vascular endothelial growth factor receptor-2 (VEGFR2) and Pgp gene and protein expressions and the other seven mice were monitored for survival rate analysis until they died. Results: NF-κBp65 gene and protein expressions were significantly lower in the Docetaxel + Iso group in comparison with that of the Docetaxel group. VEGFR2 protein expression in the Docetaxel + Iso and Iso groups was significantly lower than that of the Docetaxel group. Conclusion: These findings may indicate that the combined use of isoflavone extracts together with chemotherapeutic agents has more efficient anti-carcinogenic effects than their individual use. 相似文献
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Maged M. Yassin Abed El-Raoof D. Masoud Mohammed M. Yasin 《Diabetes & Metabolic Syndrome: Clinical Research & Reviews》2019,13(3):1865-1870
ObjectiveTo assess serum vitamin D status and its relations to other biochemical parameters in type 2 diabetic patients from Gaza Strip.Materials and methodsThis case-control study included 58 type 2 diabetic patients as well as 58 non-diabetic controls. Patients and controls were matched for age and gender. Data were obtained from questionnaire interview, and biochemical analysis of blood samples.ResultsSerum vitamin D was significantly lower in diabetic patients compared to non-diabetic controls (25.9 ± 11.0 versus 34.6 ± 13.8 ng/dl, % difference = 28.8%, P < 0.001). The number of patients having vitamin D deficient, insufficient and sufficient were 6 (10.4%), 35 (60.3%) and 17 (29.3%) compared to controls of 3 (5.2%), 16 (27.6%) and 39 (67.2%), respectively (χ2 = 14.672, P < 0.001). Serum glucose, glycated hemoglobin (HbA1c), serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglycerides were significantly higher in patients than in controls whereas serum insulin, high density lipoprotein cholesterol (HDL-C) and calcium were significantly lower in patients. Serum vitamin D showed significant negative correlations with HbA1c (r = ? 0.186, P = 0.046), ALT (r = ? 192, P = 0.040) and AST (r = ? 0.188, P = 0.044) whereas significant positive correlations were found with HDL-C (r = 0.188, P = 0.044) and calcium (r = 0.239, P = 0.010).ConclusionThe significant negative and positive correlations of vitamin D with HbA1c and calcium, respectively suggests that vitamin D supplementation would be of potential therapeutic value in clinical settings for controlling of type 2 diabetes and more importantly its complications. However, a well-designed clinical trials are needed to define the contribution of vitamin D status and therapy in the global diabetes problem. 相似文献
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Maciej Kmieciak Kyle K Payne Michael O Idowu Margaret M Grimes Laura Graham Maria-Libera Ascierto Ena Wang Xiang-Yang Wang Harry D Bear Masoud H Manjili 《Journal of translational medicine》2011,9(1):35
Background
Emerging data from pre-clinical and clinical studies suggest that HER-2/neu-specific T cell responses could induce HER-2/neu antigen loss in the tumor cells. These data suggest that patients with HER-2/neu negative breast cancer might have had HER-2/neu positive premalignant lesions in the past that progressed to HER-2/neu negative breast cancer under HER-2/neu-specific immune pressure. 相似文献29.
Rezaei N Farhoudi A Pourpak Z Aghamohammadi A Ramyar A Moin M Gharagozlou M Movahedi M Mohammadpour B Mirsaeid Ghazi B Izadyar M Mahmoudi M 《Iranian journal of allergy, asthma, and immunology》2004,3(1):37-40
Cyclic neutropenia is a rare immunodeficiency syndrome, characterized by regular periodic oscillations in the circulating neutrophil count from normal to neutropenic levels through 3 weeks period, and lasting for 3-6 days. In order to determine the clinical features of cyclic neutropenia, this study was performed. Seven patients with cyclic neutropenia (3 males and 4 females), who experienced neutropenic periods every 3 weeks (5 with severe and 2 with moderate neutropenia), were investigated in this study. They had been referred to Iranian Primary Immunodeficiency Registry during 23 years (1980-2003). The range of patients' ages was from 7 to 13 years (median 11 years). The median age at the onset of the disease was 12 months (1 month- 2 years) and the median age of diagnosis was 2 (1.5-5) years, with a median diagnosis delay of 1 year (2 months- 5 years). Neutropenia was associated with leukopenia (3 patients), anemia (3 patients), and thrombocytopenia (1 patient). Patients were asymptomatic in healthy phase, but during the episode of neutropenia suffered from aphthous ulcers, abscesses and overwhelming infections. The most commonly occurred manifestations were: otitis media (6 cases), oral ulcers (5 cases), abscesses (4 cases), pneumonia (3 cases), diarrhea (3 cases), oral candidiasis (3 cases), cutaneous infections (2 cases), and periodontitis (2 cases). One of these patients subsequently died because of recurrent infections. Unusual, persistent or severe infections should be the initiating factors to search for an immune deficiency syndrome such as cyclic neutropenia, because a delay in diagnosis may result in chronic infection, irretrievable end-organ damage or even death of the patient. 相似文献
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Nahavandi M Tavakkoli F Wyche MQ Perlin E Winter WP Castro O 《British journal of haematology》2002,119(3):855-857
Recent studies suggest that nitric oxide (NO) may partly be responsible for the beneficial effect of hydroxyurea (HU) in sickle cell disease (SCD) patients. NO stimulates cyclic guanosine monophosphate (cGMP) production, which mediates vasodilatation. We investigated the association between NO, cGMP and fetal haemoglobin (HbF) levels after HU administration. Our data showed that chronic HU significantly increased NO, cGMP, and HbF levels in SCD. Recently it was shown that HbF production was stimulated by cGMP-dependent protein kinase. Our results suggest that NO stimulates cGMP production, which then activates a protein kinase and increases the production of HbF. 相似文献