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Busulfan is known to cause several adverse effects including reproductive toxicity in humans. Garlic (Allium sativum), a widely distributed medicinal plant, is highly regarded for its medicinal activities including antioxidant property. This study was conducted to assess whether garlic extract could serve as protective agents against testicular toxicity during busulfan treatment in a mice model. Seventy-two adult male mice were randomly divided into nine groups. In groups 1,2 and 3, distilled water, busulfan, and dimethyl sulfoxide and in the treatment groups hydro-alcoholic extract of garlic was administered orally at different doses per day (groups 4, 5 and 6; 200, 400, 800 mg kg-1 respectively). Groups 7, 8 and 9 were treated with the extract (200, 400 and 800 mg kg-1, respectively) plus busulfan. Following euthanasia, blood samples and epididymal sperm were collected. The busulfan-treated group showed significant decreases in sperm quality parameters, and serum levels of testosterone, LH and FSH was observed in the busulfan-treated mice. In addition, the TAC levels and antioxidant enzymes activities were reduced and malondialdehyde (MDA) levels were increased in the busulfantreated mice. Notably, garlic extract co-administration caused a considerable recovery in sperm quality parameters, TAC levels, antioxidant enzymes activities, hormonal changes and MDA level. Based on our results, garlic has antioxidant effects against busulfan-induced testicular damages in mice. [ABSTRACT FROM AUTHOR]

Background: Interleukin (IL-12) and the granulocyte-monocyte colony-stimulating factor gene (GM-CSF) have been used as immunotherapeutic agents in cancer gene therapy as they activate dendritic cells and boost anti-tumor immune responses. IL-12 and GM-CSF have different roles in anti-tumor immune response. Objectives: The aim of present study was to investigate the anti-tumor effects of combined gene therapy with GM-CSF and IL-12 in a fibrosarcoma mouse model. Methods: To investigate the combined therapeutic effect of GM-CSF and IL-12, WEHI 164 tumor cells were transfected with Murine GM-CSF (m-GM-CSF) and Murine IL-12 (m-IL-12) genes, using Lipofectamine. The fibrosarcoma mouse model was established by subcutaneous injection of transfected cells to Balb/c mice. Mice were sacrificed and the tumors were extracted. Tumor sizes were measured by caliper. The expression of GM-CSF, IL-12 and IFN-γ was studied by real-time PCR and immunoblotting. The expression of Ki-67 (a proliferation marker) in tumor masses was studied by immunohistochemistry staining. Results: The tumor size was reduced in IL-12 + GM-CSF group (P < 0.0001); the results of western blotting and real-time PCR demonstrated that IL-12, GM-CSF and IFN-γ expression increased in IL-12+GM-CSF group (with a relative expression of: 2.86,1.98, and 2.560). Immunohistochemistry staining indicated that Ki-67 expression was reduced in IL-12 + GM-CSF group. Conclusions: Combination therapy with GM-CSF and IL-12 displayed significant therapeutic effects and represented a promising gene therapy strategy for cancer. [ABSTRACT FROM AUTHOR]

Introduction: Cytokine gene therapy is one of the cancer treatment strategies. Recently, granulocyte-monocyte colony-stimulating factor (GM-CSF), as an important cytokine in activating dendritic cells and boosting the anti-tumor immune responses, has been utilized as an immunotherapeutic agent in cancer gene therapy. The purpose of the present investigation was to study the GM-CSF gene therapy effects in regression of tumor masses in fibrosarcoma mouse model.Materials and Methods: To investigate the therapeutic efficacy of GM-CSF, WEHI-164 tumor cells were transfected with murine GM-CSF plasmid. For cytokine production by transfected cells, enzyme-linked immunosorbent assay test was used. Fibrosarcoma mouse model established with transfected cells which were injected subcutaneously into Balb/c mice. Tumor sizes were measured by caliper. Mice were sacrificed and the tumors were extracted. The expression of GM-CSF was studied by real-time polymerase chain reaction (PCR) and immunoblotting. The expression of Ki-67 (a tumor proliferative marker) in tumor masses was studied by immunohistochemical staining.Results: The group treated with GM-CSF indicated a decrease in tumor mass volume (P = 0.001). The results of western blotting and real-time PCR showed that GM-CSF expression increased in the group treated with GM-CSF (with a relative expression of 1.36). Immunohistochemical staining showed that Ki-67 expression has reduced in the group treated with GM-CSF.Conclusion: Monotherapy with GM-CSF has therapeutic effects on the regression of tumor masses in the fibrosarcoma mouse model. [ABSTRACT FROM AUTHOR]

Purpose: HMGI-C (High Mobility Group protein Isoform I-C) protein is a member of the high-mobility group AT-hook (HMGA) family of small non-histone chromosomal protein that can modulate transcription of an ample number of genes. Genome-wide studies revealed up regulation of the HMGI-C gene in many human cancers. We suggested that HMGI-C might play a critical role in the progression and migration of various tumors. However, the exact role of HMGI-C in breast adenocarcinoma has not been cleared. Methods:The cells were transfected with siRNAs using transfection reagent. Relative HMGI-C mRNA and protein levels were measured by quantitative real-time PCR and Western blotting, respectively. The cytotoxic effects of HMGI-C siRNA, Paclitaxel alone and combination on breast adenocarcinoma cells were determined using MTT assay. The migration after treatment by HMGI-C siRNA, Paclitaxel alone and combination were detected by wound-healing respectively. Results: HMGI-C siRNA significantly reduced both mRNA and protein expression levels in a 48 hours after transfection and dose dependent manner. We observed that the knockdown of HMGI-C led to the significant reduced cell viability and inhibited cells migration in MDA-MB-468 cells in vitro. Conclusion: These results propose that HMGI-C silencing and Paclitaxel treatment alone can inhibit the proliferation and migration significantly, furthermore, synergic effect of HMGI-C siRNA and Paclitaxel showed higher inhibition compared to mono treatment. Taken together, HMGI-C could be used as a promising therapeutic agent in the treatment of human breast adenocarcinoma. Therefore HMGI-C siRNA may be an effective adjuvant in human breast adenocarcinoma. [ABSTRACT FROM AUTHOR]

Objective(s): Transporters have an important role in pharmacokinetics of drugs. Inhibition or induction of drug transporters activity can affect drug absorption, safety, and efficacy. P-glycoprotein (P-gp) is the most important membrane transporter that is responsible for active efflux of drugs. It is important to understand which drugs are substrates, inhibitors, or inducers of P-gp to minimize or avoid unwanted interactions. The aim of this study was to investigate the effects of clemastine on the expression and function of P-gp. Materials and Methods: The effect of clemastine on P-gp function and expression was evaluated in vitro byrhodamine-123 (Rho123) efflux assay in Caco-2 cells and Western blot analysis. Rat in situ single pass intestinal permeability model was used to investigate the clemastine effect on digoxin Peff, as a known P-gp substrate. Digoxin levels in intestinal perfusates were assayed by high performance liquid chromatography (HPLC) method. Results: The Caco-2 intracellular accumulation of Rho123 in clemastine and verapamil treated cells was 90.8 ± 9.8 and 420.6±25.4 pg/mg protein, respectively which was significantly higher than that in control cells (50.2±6.0; P<0.05). Immunoblotting results indicated that clemastine decreased expression of P-gp in Caco-2 cells in vitro. More over effective intestinal permeability (Peff) of digoxin in the presence of clemastine, was significantly increased compare to control group. Conclusion: Findings of our study suggested dose dependent P-gp inhibition activity for clemastine in vitro and in situ. Therefore co-administration of clemastine with P-gp substrates may result in unwanted interactions and side effects. [ABSTRACT FROM AUTHOR]

Purpose: P-glycoprotein (P-gp) plays a major role in oral absorption of drugs. Induction or inhibition of P-gp by drugs contributes to variability of its transport activity and often results in clinically relevant drug-drug interactions. The purpose of this study was to investigate the effect of cetirizine, a second generation H1 antihistamine, on P-gp function and expression in vitro and in situ. Methods: The in-vitro rhodamin-123 (Rho123) efflux assay in Caco-2 cells was used to study the effect of cetirizine on P-gp function. Western blot analysis was used for surveying the effect of cetirizine on expression of P-gp in Caco-2 cells. Rat in situ single-pass intestinal permeability technique was used to calculate the intestinal permeability of a known P-gp substrate (digoxin) in the presence of cetirizine. The amounts of digoxin and cetirizine in intestinal perfusion samples were analyzed using a HPLC method. Results: The results showed significant increase in Rho123 uptake (P < 0.05) and also P-gp band intensity decrease in cetirizine-treated cells in vitro. Furthermore the intestinal permeability of digoxin was also increased significantly in the presence of cetirizine (P < 0.01). Conclusion: Therefore it is concluded that cetirizine is a P-gp inhibitor and this should be considered in co administration of cetrizine with other P-gp substrate drugs. Further investigations are required to confirm our results and to determine the mechanism underlying P-gp inhibition by cetirizine. [ABSTRACT FROM AUTHOR]

Objective: Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent febrile attacks accompanied by serosal and synovial membrane inflammation. FMF is caused by mutations in the MEFV gene and are found usually among Mediterranean populations, Armenians, Turks, Arabs and Jews. The aim of this study was to determine the frequency of MEFV gene mutations among FMF patients in the Azeri Turk population in North-West of Iran. Materials and Methods: In this descriptive study, 130 FMF patients with Azeri Turk origin were screened for mutations in four exons (2, 3, 5 and10) of MEFV gene. Genomic DNA was extracted from whole blood and entered in ARMS-PCR and PCR-RFLP reactions. When cases were negative in ARMS-PCR and PCR-RFLP, the exons were amplified and subjected to direct sequencing. Results: Our results showed that the most common mutations in this study population was M694V (40.19%) followed by E148Q (17.64%), V726A (13.72%), M680I (12.74%) and M694I (2.94%) mutations. Four new mutations including K618N, K716M, S614F and G136E were identified in our study. Conclusion: The prevalence of five common mutations in our study was highly similar to previous studies analysing the Mediterranean basin populations. Investigation by sequencing also revealed four new variants in the study population. The main genotypephenotype correlation finding was the presence of M694V mutation in homozygote or compound heterozygote state in the patients with renal manifestations. [ABSTRACT FROM AUTHOR]

Purpose: In the present study cytotoxic effects of the alcoholic extract of Dorema Glabrum seed on viability of WEHI-164 cells, mouse Fibrosarcoma cell line and L929 normal cells were compared with the cytotoxic effects of Taxol (anticancer and apoptosis inducer drug). Methods: To find out the plant extract cytotoxic effects, MTT test and DNA fragmentation assay, the biochemical hallmark of apoptosis were performed on cultured and treated cells. Results: According to the findings the alcoholic extract of Dorema Glabrum seed can alter cells morphology and because of chromatin condensation and other changes they shrink and take a spherical shape, and lose their attachment too. So the plant extract inhibits cell growth albeit in a time and dose dependent manner and results in degradation of chromosomal DNA. Conclusion: Our data well established the anti-proliferative effect of methanolic extract of Dorema Glabrum seed and clearly showed that the plant extract can induce apoptosis and not necrosis in vitro, but the mechanism of its activities remained unknown. These results demonstrated that Dorema Glabrum seed might be a novel and attractive therapeutic candidate for tumor treatment in clinical practices. [ABSTRACT FROM AUTHOR]

Gene therapy is one of the most attractive fields in medicine. The concept of gene delivery to tissues for clinical applications has been discussed around half a century, but scientist's ability to manipulate genetic material via recombinant DNA technology made this purpose to reality. Various approaches, such as viral and non-viral vectors and physical methods, have been developed to make gene delivery safer and more efficient. While gene therapy initially conceived as a way to treat life-threatening disorders (inborn errors, cancers) refractory to conventional treatment, to date gene therapy is considered for many non-life-threatening conditions including those adversely influence on a patient's quality of life. Gene therapy has made significant progress, including tangible success, although much slower than was initially predicted. Although, gene therapies still at a fairly primitive stage, it is firmly science based. There is justifiable hope that with enhanced pathobiological understanding and biotechnological improvements, gene therapy will be a standard part of clinical practice within 20 years. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate, for the first time, the genotype of hepatitis B virus (HBV) among hepatitis patients in Eastern Azerbaijan Province, Northwest Iran. Methods: A total of 100 HBV-infected patients were enrolled in this study. Among these, 40 samples were positive for both HBsAg and HBeAg, whereas 60 samples were HBsAg positive and HBe Agnegative. Patients' sera were subjected to DNA extraction and the genotype determined by PCR using type-specific primers. Results: The results of genotyping revealed that genotype D was the only identified genotype in both acute and chronic patients in the study region. Analysis of sequencing results showed 98%--99% homology with the previously reported HBV genotype D sequences. Conclusions: Genotype D was recognized as the predominant HBV genotype in the studied area. There was no significant relationship between genotype D of HBV and different types of infections. [ABSTRACT FROM AUTHOR]

Purpose: In the present study cytotoxic effects of the alcoholic extract of Dorema Glabrum seed on viability of WEHI-164 cells, mouse Fibrosarcoma cell line and L929 normal cells were compared with the cytotoxic effects of Taxol (anticancer and apoptosis inducer drug)., Methods: To find out the plant extract cytotoxic effects, MTT test and DNA fragmentation assay, the biochemical hallmark of apoptosis were performed on cultured and treated cells., Results: According to the findings the alcoholic extract of Dorema Glabrum seed can alter cells morphology and because of chromatin condensation and other changes they shrink and take a spherical shape, and lose their attachment too. So the plant extract inhibits cell growth albeit in a time and dose dependent manner and results in degradation of chromosomal DNA., Conclusion: Our data well established the anti-proliferative effect of methanolic extract of Dorema Glabrum seed and clearly showed that the plant extract can induce apoptosis and not necrosis in vitro, but the mechanism of its activities remained unknown. These results demonstrated that Dorema Glabrum seed might be a novel and attractive therapeutic candidate for tumor treatment in clinical practices.

Gene therapy is one of the most attractive fields in medicine. The concept of gene delivery to tissues for clinical applications has been discussed around half a century, but scientist's ability to manipulate genetic material via recombinant DNA technology made this purpose to reality. Various approaches, such as viral and non-viral vectors and physical methods, have been developed to make gene delivery safer and more efficient. While gene therapy initially conceived as a way to treat life-threatening disorders (inborn errors, cancers) refractory to conventional treatment, to date gene therapy is considered for many non-life-threatening conditions including those adversely influence on a patient's quality of life. Gene therapy has made significant progress, including tangible success, although much slower than was initially predicted. Although, gene therapies still at a fairly primitive stage, it is firmly science based. There is justifiable hope that with enhanced pathobiological understanding and biotechnological improvements, gene therapy will be a standard part of clinical practice within 20 years.