Comparison of gabapentin and ketotifen in treatment of uremic pruritus in hemodialysis patients

Objectives: Uremic pruritus is a common problem in hemodialysis patients. Several treatments have been used for decreasing itching in these patients. Gabapentin and ketotifen are two drugs used for treating uremic patients.The aim of this study was to compare gabapentin and ketotifen in treatment of uremic pruritus in hemodialysis patients. Methods: In this double-blind randomized clinical trial, 52 hemodialysis patients with uremic pruritus referred to 5azarTeaching Hospital in Gorgan in 2013 were studied. Patients were randomly assigned to two groups of 26 subjects (groups G and K). In group G, patients treated with gabapentin capsules 100 mg daily for 2 weeks, and in Group K, patients treated with ketotifen 1 mg twice daily for 2 weeks. Before and at the end of study, pruritus severity was determined based on Shiratori›s severity scores. Collected data were analyzed by SPSS-21 statistical software. Results: There was no significant different between two groups in the age and sex. After two weeks of treatment, severity of pruritus was significantly reduced in both groups (88.4 in group G vs. 76.9 in group K). Gabapentin compared with ketotifen had a better effect on improving itching in the age group of 30-60 years and in males. 5 patients (19.2) in both groups suffered from drowsiness and dizziness, but no serious side effects were observed. Conclusions: The results showed that gabapentin and ketotifen significantly improved pruritus in hemodialysis patients, and no significant difference was observed between two groups. © 2016, Professional Medical Publications. All rights reserved

Different expression of extracellular signal-regulated kinases (ERK) 1/2 and phospho-Erk proteins in MBA-MB-231 and MCF-7 cells after chemotherapy with doxorubicin or docetaxel

Objective(s) Curative treatment of breast cancer patients using chemotherapy often fails as a result of intrinsic or acquired resistance of the tumor to the drug. ERK is one of the main components of the Ras/Raf/MEK/ERK cascade, which mediates signal from cell surface receptors to transcription factors to regulate different gene expression. In this study, cytotoxicity and the expression of Erk1/2 and phospho-ERK was compared in MDA-MB-231 (ER-) and MCF-7 (ER+) cell lines after treatment with doxorubicin (DOX) or docetaxel (DOCT). Materials and Methods Cell cytotoxicity of DOX or DOCT was calculated using MTT assay. Immonofluorescent technique was used to show MDR-1 protein in MDA-MB-231 and MCF-7 cells after treatment with DOX or DOCT. The expression of ERK1/2 and phpspho-ERK was assayed with immunoblotting. Results Comparing IC 50 values showed that MDA-MB-231 cells are more sensitive than MCF-7 cells to DOX or DOCT. Immonofluorescent results confirmed the expression of MDR-1 in these two cell lines after DOX or DOCT treatment. In MDA-MB-231 cells the expression of ERK1/2 and phospho-ERK was decreased after DOX treatment in a dose-dependent manner. In contrast in MCF-7 cells the expression of ERK1/2 and phospho-ERK was increased after DOX treatment. DOCT treatment demonstrated the same result with less significant differences than DOX. Conclusion The heterogeneity seen in cell lines actually reflects the heterogeneity of breast cancers. That is why, patients categorized in one group respond differently to a single treatment. These results emphasize the importance of a more accurate classification and a more specific treatment of breast cancer subtypes

The effect of 2 and 8 MT magnetic field on rat spatial memory consolidation

Background: Magnetic fields in human environment can affect on learning and memory. This study was conducted on evaluation the effect of short time exposure to 2 and 8 MT magnetic fields on rat consolidation of spatial memory. Materials and Methods: Thirty-six male Wistar rats (3-4 month old, 235 ±15 g) were randomly allocated in three groups (sham and exposed to 2 and 8 MT magnetic fields). Animals were given 8 trials (one training session) at 2 blocks, with 3 minutes interval between the blocks for one day in Morris Water Maze. Immediately after training, head exposure was performed by a 50 Hz, 2 or 8 MT magnetic fields for 20 minutes. Forty eight hours after training and exposure to magnetic field, animals were given a 60 seconds probe trial.Results: Animals exposed to 8 MT but not to 2 MT magnetic fields spend significantly less time in the platform quadrant during 60 seconds probe trial and had different swimming patterns so that they showed fewer tendencies for finding the platform. Conclusion: The results of this study showed that short time exposure to 50 Hz, 8 MT but not 2 MT magnetic fields can impair consolidation phase of spatial memory

Different interactions of Hsp90Hsp90 and Hsp90Hsp90 with different substrates

Background: The Hsp90 chaperone complex functions in assembly, folding and activation of numerous substrates. The two vertebrate homologues encoded by hsp90 and hsp90 genes are differentially expressed in embryonic and adult tissues and during stress, however, it is not known if they possess identical functional activities in chaperone complexes. This question was addressed by examining potential differences between the Hsp90 isoforms with respect to both co-chaperone and substrate interactions. Materials and Methods: Epitope-tagged proteins were expressed in mammalian cells or Xenopus oocytes and subjected to immunoprecipitation with an array of co-chaperones. Results: Both isoforms were shown to participate equally in multi-chaperone complexes and no significant difference in co-chaperone distribution was observed. The substrates Raf-1, HSF1, Cdc37 and Mek interacted with both Hsp90 and Hsp90, and the relative patterns of these interactions were not affected by heat shock. The substrates kinases c-Src, CKIIB, A-raf, and Erk interacted with both isoforms, however, significantly more Hsp90 was recovered after heat shock. Conclusion: The results demonstrate that the Hsp90 and Hsp90 exhibit similar interactions with co-chaperones, but significantly different behaviors with respect to substrate interactions under stress conditions

Substrate-dependent activity of ERK and MEK proteins in breast cancer (MCF7), and kidney embryonic (Hek-293) cell lines, cultured on different substrates

Background: Breast cancer has been one of the most common types of cancer, as the leading cause of women death in world. Breast cancer has known as a heterogenic disease that the clinical path in different patients would be very different. Since the current classification has not covered the diverse clinical course of breast cancer, lots of efforts has done to find new biological markers. Integrins are hetero dimmer proteins of α and β subunits on cell membrane. After binding to extra cellular matrix (ECM), integrins activate MAPK pathway that regulated different activities like survival, differentiation, migration, immunologic response. The interaction of integrins and ECM have a key role in cancer cell activities like survival and metastasis. Objectives: In this study the expression of αvβ3 integrin, substrate -dependent morphology and ERK and p-ERK activation was compared in MCF7 and Hek-293 cells lines. Materials and Methods: The expression of αvβ3 integrin was assayed by flow cytometry. These cell lines were cultured on pre-covered plates with fibronectin (FN), fibrinogen (Fg) or collagen (Col) and the expression of ERK and p-ERK proteins was assessed in attached and free cells for each substrate after 1 hour incubation. The morphology of the cells have examined under an inverted phase contrast microscope at 15 min, 1 hour, 3 hours, 5 hours and 1 day of incubatioon. Results: Different substrate induced the expression ERK or p-ERK differently in the two cell lines. In MCF7 cells, substrates induced the expression of ERK in all the attached cells but free cells in BSA, collagen and Fg showed a lower expression of ERK. In comparison with Hek-293 cells althought all the attached cells have expressed ERK peotein but only free cells in collagen plates showed the expression of ERK. None of the cell lines has shown any expression of ERK and p-ERK in attached or free cells except for the Hek-293 free cells in collagen platees that have shown a weak signal for p-ERK. Conclusions: Overall the breast cancer cell lines MCF7 and Hek-293 cells have differently responded on similar substrates regarding morpology or ERK and MEK expressions. © 2015, Iranian Journal of Cancer Prevention

Expression of hsp90α and hsp90β during Xenopus laevis embryonic development

Background: Members of the eukaryotic Hsp90 family function as important molecular chaperones in the assembly, folding and activation of cellular signaling in development. Two hsp90 genes, hsp90α and hsp90β, have been identified in fish and homeothermic vertebrates but not in poikilothermic vertebrates. In the present study, the expression of hsp90α and hsp90β genes in Xenopus laevis, which is phylogenetically positioned between zebrafish and mammals, has been addressed. Methods: Partial Xenopus hsp90α and hsp90β cDNA were identified and isolated using RT-PCR, and a full-length Xenopus hsp90β cDNA was isolated from an embryonic cDNA library. Northern-blot analysis was used to study the expression of hsp90α and hsp90β genes in total RNA of the embryos and in situ hybridization was used to compare the expression of these genes with that of hsp70 and MyoD genes in Xenopus embryogenesis. Results: Northern-blot analysis revealed that the hsp90β gene was strongly expressed constitutively at all stages of embryogenesis, but weakly induced following the heat shock. In contrast, the hsp90α gene was weakly expressed in embryos at control temperature, but strongly up-regulated following heat shock. In situ hybridization results showed that hsp90α gene was observed predominantly in cells of the developing somite. Microscopic sections showed that hsp90α and MyoD mRNA are expressed in similar regions in somite and this pattern was distinct from that of hsp70 and hsp90β. Conclusion: These data support the hypothesis that the presence of hsp90α and hsp90β genes is conserved among vertebrates, and these genes are differentially regulated in a tissue, stress, and development stage-specific manner

The Protective Effect of Hydroalcoholic Extract of Rosa canina (Dog Rose) Fruit on Liver Function and Structure in Streptozotocin-Induced Diabetes in Rats

ABSTRACT This study was conducted to evaluate the hepatoprotective effects of Rosa canina (R. canina) extract on streptozotocin- (STZ-) induced diabetes in rats by measuring the fasting blood glucose (FBG), total antioxidant capacity (TAC), and liver enzyme activity, including serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Forty adult male Wistar rats were randomly divided into four groups and treated daily for 42 days as follows: group I (control) received saline as a vehicle; group II (diabetic) received saline; groups III and IV (diabetic) treated with 250 and 500 mg/kg body weight (BW) per day R. canina extract, respectively. Diabetes was induced by a single intraperitoneal (IP) injection of streptozotocin (50 mg/kg BW). At the end of the study, blood samples were collected via heart puncture and sera were used for estimation of the mentioned parameters. Then all the rats were sacrificed and their livers used for histopathological evaluations. In the untreated diabetic group, the results showed a significant increase in FBG, ALT, and AST levels compared to the other groups (p .05). In the treated groups, administration of R. canina extract significantly improved the mentioned parameters in a dose-dependent manner (p < .05). Histological evaluations indicated that R. canina extract ameliorated defective liver caused by STZ. It can be concluded that R. canina extract has a hepatoprotective effect in STZ-induced diabetes in rats. KEYWORDS: diabetes mellitus, hepatoprotective, Rosa canina, streptozotoci

Antidiabetic and Antihyperlipidemic Effects of Ethanol Extract of Rosa canina L. fruit on Diabetic Rats: An Experimental Study With Histopathological Evaluations

Rosa canina L. (Rosaceae) has been traditionally used as a medicinal plant. This study was undertaken to evaluate the antidiabetic and antihyperlipidemic effects of Rosa canina fruit extract in streptozotocin induced diabetic rats. The results showed oral administration of Rosa canina fruit extract significantly ameliorated the high levels of blood glucose compared with the control group. Serum triglyceride levels significantly decreased by the administration of Rosa canina extract compared with control. Histopathological examinations showed that the Rosa canina extract improved islets necrotic and regenerated pancreatic islet cells. Rosa canina extract has the antihyperglycemic and antihyperlipidemic effects in streptozotocin-induced diabetic rats. © 2015, © The Author(s) 2015

ST6Gal1, Cox-2 and HB-EGF mRNA expression in breast cancer samples from Kashan, Iran

Background: ST6Gal1, Cox-2 and HB-EGF genes are involved in different tumors and their enhanced expressions often correlate with poor prognosis. In this study we assay the expressions of these genes by reverse transcriptase-PCR in 54 breast cancer samples. Methods: Tissue samples were either formalin-fixed for histopathological examination or frozen for reverse transcriptase-PCR. Image program was used for the densitometry of the image of the gels and the expression of different genes was normalized with beta actin expression. The student�s t-test and correlation matrix were used for data analyses. Results: We observed significantly higher expressions of ST6Gal1 (P= 0.040), Cox-2 (P= 0.001) and HB-EGF (P= 0.009) in the tumor region compared to the margin samples. A significant correlation was found between HB-EGF and Cox-2 expression (P= 0.001). There was a positive correlation between total score, tumor size, histology grade and nuclear grade but there was a reverse correlation between age and tumor size, histology grade and total score. Conclusion: Expressions of ST6Gal1, Cox-2 and HB-EGF in breast tumor samples in this and a number of other studies emphasize their role as important markers in breast cancer. The use of medications to inhibit either their individual expressions or the possible inhibition of all three genes may improve patient survival and prevent metastasis. © 2015, Shiraz University of Medical Sciences. All rights reserved