PHARMACOLOGICAL THERAPEUTIC MONITORING OF MYCOPHENOLATE MOFETIL (MMF) IN AUTOIMMUNE DISEASES AT EHU OF ORAN-ALGERIA : CONTRIBUTION OF PHARMACEUTICAL INTERVENTIONS

Mycophenolate mofetil (MMF) is an immunosuppressant indicated for organ transplantation and other autoimmune diseases. The pharmacological therapeutic monitoring (PTM) of the MMF based on the measurement of the area under the curve (AUC) is justified. Objective: The objective of our study was to evaluate the contribution of pharmaceutical interventions emitted during MMF PTM of patients with autoimmune diseases in the pharmacovigilance service of the EHU of Oran-Algeria. Material and Methods: This is a retrospective descriptive study of 5 years, dealing with patients treated by MMF for all autoimmune diseases in pharmacovigilance service of the EHU of Oran-Algeria. In total, 60 patients were monitored. The average age of the study population was 29.81 years with a female predominance of 56.66% (sex ratio 0.7). Result and Discussion: In our study lupus nephropathy represents the most common pathology with a rate of 51.67%, followed by nephrotic syndrome with 41.67%. 106 AUC were measured,  37.74% were below 30 mg.h / l, 49.06% were between 30 and 60 mg.h / l and 13.20% of the AUC were above 60 mg / h. / l. The signs of intolerance observed were: 60.42% of the disturbances of the hemogram, 16.67% of the various infections, 12.5% of the cutaneous affections and 10.41% of the digestive disorders. Various pharmaceutical opinions have been issued to manage this drug iatrogenic. Conclusion: The results of our study show that PTM has a major interest in predicting of response to MMF in autoimmune diseases. The application of MMF PTM in routine clinical practice should be generalized to adjust the dosage of MMF to improve the efficacy and reduce the adverse effects of this drug.

Potentiometric studies on the influence of poly(N-vinylpyrrolidone) on the thermal degradation behavior of poly(vinyl chloride) blends

The thermal degradation behavior of poly(vinyl chloride) (PVC) and poly(N-vinylpyrrolidone) (PVP) blends was investigated using potentiometric measurements of the released HCl gas during the degradation process, estimating the degree of discoloration of the degraded samples and measuring the thermal stability (Ts) values. The influence of the PVP percentage in the blend and, moreover, of the addition of commercial dibasic lead carbonate stabilizer to the blend was studied with regard to thermal stability. It turned out that the dehydrochlorination rate of the blend was promoted by increasing the PVP concentration in the blend.

Bioinformatics Analysis of Key Genes and Pathways for Medulloblastoma as a Therapeutic Target

One of the major challenges in cancer treatment is the lack of specific and accurate treatment in cancer. Data analysis can help to understand the underlying molecular mechanism that leads to better treatment. Increasing availability and reliability of DNA microarray data leads to increase the use of these data in a variety of cancers. This study aimed at applying and evaluating microarray data analyzing, identification of important pathways and gene network for medulloblastoma patients to improve treatment approaches especially target therapy. Methods: In the current study, Microarray gene expression data (GSE50161) were extracted from Geo datasets and then analyzed by the affylmGUI package to predict and investigate upregulated and downregulated genes in medulloblastoma. Then, the important pathways were determined by using software and gene enrichment analyses. Pathways visualization and network analyses were performed by Cytoscape. Results: A total number of 249 differentially expressed genes (DEGs) were identified in medulloblastoma compared to normal samples. Cell cycle, p53, and FoxO signaling pathways were indicated in medulloblastoma, and CDK1, CCNB1, CDK2, and WEE1 were identified as some of the important genes in the medulloblastoma. Conclusion: Identification of critical and specific pathway in any disease, in our case medulloblastoma, can lead us to better clinical management and accurate treatment and target therapy.

Novel Combination of Mesenchymal Stem Cell-Conditioned Medium with Sorafenib Have Synergistic Antitumor Effect of Hepatocellular Carcinoma Cells

Objective: Hepatocellular carcinoma (HCC) is the most common liver malignancy. Sorafenib is the first-line systemic treatment for advanced HCCs. However, due to safety concerns, researchers are now looking for ways to boost the efficacy of the medication. One approach for reducing toxicity is combining sorafenib with other agents so that a lower dose of sorafenib is required. Mesenchymal stromal cells (MSCs) can have an inhibitory effect on HCC tumor growth. Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) is the substance extracted from MSC culture and contains most of the potential cytokines secreted by MSCs. We, therefore, anticipated a synergistic Antitumor Effect of sorafenib in Combination with MSC-CM. In this study, we used HepG2 as our target cell lines. Methods: HepG2 cells were treated with sorafenib alone and with sorafenib + MSC-CM. CCK-8 assay was used to evaluate and compare the inhibition of cell growth between the two groups with different treatments. Results: The combination treatment of cell lines with sorafenib and MSC-CM had significantly reduced the values of IC50 compared to the use of sorafenib alone (3.4 vs. 2.7 respectively). Conclusion: This study suggests that a combination of sorafenib with MSC-CM can synergistically suppress the growth of HCC cells.

Experiences of Spouses of Women with Breast Cancer: A Content Analysis

In addition to the affected person, diagnosis and treatment of breast cancer also severely affects her husband. Therefore, it is worth paying attention to the needs of husbands of women with breast cancer. Therefore, the aim of the present study was to explain the experiences of spouses of women with breast cancer.

Serum Levels of Zinc, Copper and Ferritin in Patients with Salivary Gland Tumors

Background: Variation in serum levels of trace elements including zinc, copper and ferritin has been reported in cancer patients. The aim of this study was to evaluate these trace elements in the patients’ sera with benign and malignant salivary gland tumors (SGTs) and compare them with normal individuals. Methods: In this cross-sectional study, 60 patients with SGTs including 16 pleomorphic adenoma and 44 malignant SGTs, as well as 28 healthy controls, were enrolled. Serum levels of zinc, copper and ferritin were determined by atomic absorption and ELISA methods. Data were analyzed using one way ANOVA, Chi-square, Kruskal-Wallis and Mann- Whitney tests. Results: The mean concentration of zinc, copper, ferritin was1.5± 2 ppm, 1.2± 0.5 ppm, and 96.7± 65.7 ng/ml in PA, 1.5± 1.4,1.3± 0.4, and 111.2± 112 in malignant SGTs, and1.1±0.3, 1.2± 0.23 and 124±135.8 in normal control groups. There was no statistically significant difference between the patients and control groups, and between benign and malignant SGTs (P>0.05). Conclusion: The serum levels of trace elements in SGTs were not different from normal individuals. The results might have been affected by some interventional factors. Therefore, designing cohort complementary studies might result in obtaining more accurate data.

Comparative Expression of RAGE and SOX2 in Benign and Malignant Prostatic Lesions

Background: Prostate cancer (PCa) is a common health problem in elderly. RAGE (Receptor for advanced glycation end products) is overexpressed in multiple human cancers. SOX2 (Sex-determining region Y box 2) also functions as an oncoprotein and promotes cancer progression but the mechanisms involved remain largely unknown. Aim: The current study investigated the expression patterns of RAGE and SOX2 in benign and malignant prostate samples in correlation with the histopathological findings in order to evaluate their role as prognostic markers or therapeutic targets. Methods: Immunohistochemical staining for RAGE and SOX2 antibodies was applied on 87 prostatic biopsies [16 of prostatitis, 20 of benign prostatic hyperplasia (BPH) and 51 of PCa]. Results: Expression of RAGE and SOX2 (percentage of positive cells) was significantly higher in PCa lesions compared with prostatitis (p<0.01) and BPH (p<0.0001) and was also significantly higher in prostatitis compared with BPH lesions (p<0.01). Also, percentage of positive RAGE and SOX2 cells showed a significant stepwise increase from Gleason Grade 3 to Grade 5 and were significantly higher in high Gleason Scores (≥8) compared to lower Scores (≤7) with statistical significance (p=0.001). Conclusion: RAGE and SOX2 were up-regulated in prostate cancer lesions, mainly in advanced grades, suggesting an active role of both antigens in the development and progression of prostate cancer and expecting the possibility of their use as therapeutic targets.

Clinicopathologic Features of Colorectal Polyps in Shahid Beheshti University of Medical Sciences (SBMU)

Aim: This study was designed to report epidemiologic findings of polyps in Iranian patients, and predict histology of polyp regarding to demographic and colonoscopic findings. Background: Classification of colorectal polyps had been revised in the past two decades and there is a need for polyp categorization in the Iranian Health System. Patients and methods: In this retrospective study, the medical records of patients with colonoscopic diagnosis of polyp in pathology departments of SBMU affiliated teaching hospitals were reviewed. Patient’s slides evaluated and demographics findings were assessed. The anatomical location, macroscopic appearance including size and histological assessment of all polyps were recorded. Results: From total number of 1106 polyps (detected in 862 patients), adenomatous polyps (638 [57.7%]) were the most prevalent findings, followed by colon mucosal tag (184[16.6%]), hyperplastic and serrated polyps (122[11%]), inflammatory polyps (110[9.9%]), hamartomatous (21[1.9%]), and malignant lesions (13[1.2%]). Multivariate logistic regression showed age (each one year increasing age; odds ratio [OR] = 1.026, 95%confidence interval [CI] = 1.016–1.036, p < 0.0001), location of polyp (right colon; OR = 1.905, 95%CI = 1.366–2.656, p < 0.0001), and polyp size of 5-10 mm (OR = 1.662, 95%CI = 1.214–2.276, p = 0.002), and polyp size of >10 mm (OR = 2.778, 95%CI = 1.750–4.411, p< 0.0001) were independently associated with neoplastic polyps. Also, polyp size of >10 mm (OR= 2.613, 95%CI= 1.083-6.307, p=0.033), tubulovillous pattern of polyp (OR= 3.508, 95%CI= 1.666-7.387, p=0.001) and villous pattern of polyp (OR= 10.444, 95%CI= 4.211-25.905, p<0.0001) were associated with high grade dysplasia in neoplastic polyps. Conclusion: Increased age, location of polyp (right colon), increased size of polyp and villous component of polyp could classify patients in high risk groups.

Neuroprotective Effect of Pentoxifylline on 3,4-Methylenedioxymethamphetamine-Induced Apoptosis in CA1 Cells of Wistar Rat Hippocampus

Department of Anatomical Sciences and Cognitive Neuroscience, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

Background: 3,4-Methylenedioxymethamphetamine is psychoactive and hallucinogenic and has been shown to produce neurotoxicity both in animals and in humans. Recently, vasodilator drugs such as pentoxifylline (PTX) have been introduced as an alternative with neuroprotective effects. There is no study about the protective effect of PTX on hippocampal apoptosis due to high-dose administration of 3,4-Methylenedioxymethamphetamine (MDMA), so in this study, the protective effect of PTX on the hippocampus of male Wistar rats following high-dose of the drug has been investigated.Materials and Methods: Twenty-four male Wistar rats weighing 250-300 g were randomly divided into four groups: control, sham (MDMA injection), experimental (MDMA+PTX injection), and vehicle (MDMA+saline) groups. Two weeks later, the brains were removed and prepared for TUNEL and western blot techniques. Concomitantly the hippocampus was removed to study the change in Bcl-2 and BAX mRNA expression with quantitative real-time polymerase chain reaction.Results: Data showed that the number of apoptotic bodies significantly decreased in the experimental group compared to the other groups, except for in control. Also, further investigation revealed that BAX reduced considerably, while Bcl-2 mRNA expression increased dramatically after PTX treatment.Conclusions: Our results suggest that PTX may be a neuroprotective agent, and its neuroprotective potential may contribute to reducing the severity of lesions in the hippocampus following a high dose administration of MDMA.