Apoptotic Activity and Cytotoxic Effect of Convolvulus spicatus on Human Breast Cancer Cell Line (MCF-7).

<b>Background and Objective:</b> Despite advancements in modern therapeutic strategies, breast cancer still the most common cause of the high death rate among women worldwide. Wild plants and their extracts have been used in traditional medicine because of their efficient anti-cancer properties. This study aims to investigate <i>in vitro</i> the anti-cancer, anti-proliferative and potential therapeutic effects of <i>Convolvulus spicatus </i>(<i>C. spicatus</i>) methanolic extract against human breast cancer cell line Michigan Cancer Foundation-7 (MCF-7), besides putting shed on the mechanism of action of this extract. <b>Materials and Methods:</b> MTT (dimethylthiazol-diphenyltetrazolium bromide) cytotoxicity assay was done to evaluate <i>C. spicatus</i> methanolic extract's cytotoxic effects and its therapeutic potentiality against MCF-7 cells. Flow cytometry was used to clarify the potential impact of the different concentrations of the extract against the cell cycle's evolution. Nuclear densification and apoptotic changes were also analyzed and the Annexin V/propidium iodide staining method was used to ensure the anti-proliferative effect of <i>C. spicatus </i>extracts. The expression level of the apoptotic regulatory gene (Bax gene) was evaluated. <b>Results:</b> The results proved that cytotoxicity was significantly elevated in a dose-dependent manner under various concentrations. preG1 apoptosis and cell growth arrest at the G₂/M phase was noticed. Bax gene was upregulated at its mRNA level by a 5.6-fold increase, compared to the untreated MCF-7 cells. <b>Conclusion:</b> This study gives deep insight into evaluating natural extracts and/or bioactive ingredients derived from the <i>C. spicatus</i> plant and eventually exhibited a promising apoptosis-inducing anti-cancer agent.

Metformin Ameliorates Oxidative Stress Induced by Diabetes Mellitus and Hepatocellular Carcinoma in Rats.

BACKGROUND: Several studies have found an association between Diabetes mellitus (DM) and an increased risk for hepatocellular carcinoma (HCC). Evidence suggests that Metformin (Met) may have a therapeutic and protective effect against both DM and HCC. Therefore, the aim of this study was to evaluate the antioxidant effect of Met against DM and HCC-induced oxidative stress in rat model. METHODS: Forty-two male albino rats were randomly divided into six groups. Group 1 (Gp1) was the control group, Gp2 received an intraperitoneal (i.p.) injection with streptozotocin (STZ), Gp3 was injected i.p. with diethyl nitrosamine (DEN), Gp4 received an oral administration of Met, Gp5 and Gp6 received the same injections as Gp2 and Gp3, respectively, then received an additional injection of Met. Oxidative stress biomarkers, including superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA), were examined. Furthermore, biochemical parameters including liver function tests were assessed. Histopathological and immunohistochemical alterations of the liver were also examined. RESULTS: Our results demonstrate that Gp2 and Gp3 had significant signs of liver dysfunction and had elevated levels of MDA and reduced levels of SOD, CAT, and GSH. Additionally, Gp2 and Gp3 showed significant alterations in the liver architecture shown by high PCNA and caspase-3 expression. In the Gp5 and Gp6, treatment with Met showed an improvement in liver function, oxidative stress biomarkers, and reduced histopathological changes in hepatocytes. CONCLUSION: This study offers insight into the potential for Metformin as a novel therapeutic against the oxidative stress induced by DM or HCC.

Comparative safety and efficacy of conventional interferon versus pegylated-interferon based therapy for HCV: A retrospective cohort study from Gujranwala, Pakistan.

Numerous studies on risk factors, clinical presentation and treatment of hepatitis C are known to the world. However, no data is available about the safety and efficacy of anti-hepatitis C therapy among the patients of Gujranwala, Pakistan. This retrospective study compared two dosage forms of interferon; conventional interferon (IR) and Pegylated interferon (PIR) in 370 Hepatitis C patients selected through non probability convenient sampling technique. Clinical data were collected related to therapy outcomes at the start of therapy, after each follow up and at the end of therapy. The study indicated that HCV 3 was the most prevalent genotype of hepatitis C. Main side effects associated with therapies were pain at injection site (PIR; 49%, IR; 48%), inflammation at injection site (PIR; 34%, IR; 48%), fever (PIR; 56.12%, IR; 61.5%), myalgia (PIR; 24.5%,IR; 22.99%), malaise (PIR; 7.14%, IR; 5.75%), anorexia (PIR; 46%, IR; 39%), vomiting (PIR; 43%, IR; 41%), irritability (PIR; 4%, IR; 11.5%) and impaired concentration (PIR; 13%, IR; 21). The sustained viral response rate was significantly better in PIR group as compared to IR group (PIR; 80.61%, IR; 66.67%). In conclusion Pegylated interferon based therapy showed better clinical response with less adverse events as compared to conventional interferon based therapy. However, there is dire need to shift from these intravenous dosage forms to relatively new oral dosage forms for the treatment of hepatitis C to further improve clinical outcome and minimize the risks of adverse events.

Hepatoprotective effect of ketoconazole in chronic liver injury model.

Ketoconazole is a first orally available anti-fungal drug which has been reported as a potent inhibitor of human cytochrome P-450. The present study was designed to examine the heptoprotective effect of ketoconazole in both in vitro and in vivo liver injury models. Hepatocyte injury was induced by 8mM CCl4 while hepatic fibrosis model was established by injecting 1 ml/kg CCl4 followed by treatment with ketoconazole. Effect of ketoconazole treatment on injured hepatocytes was determined by lactate dehydrogenase release and trypan blue assay. Analysis of ketoconazole treatment and prevention on liver fibrosis was assessed by sirius red staining, masson trichome staining, PCR and liver function tests for bilirubin and alanine transaminase (ALAT).A significant reduction (P<0.05) in LDH release and reduced number of dead cells was observed in hepatocytes treated with ketoconazole. Sirus red and masson trichome stainings showed reduced levels of collagen in both treated and preventive groups and down regulation of alpha smooth muscle actin was observed with up-regulations of MMP-2, CK-8 and CK-18. Hepatic functional assessment demonstrated reduced serum levels of bilirubin and ALAT. Treatment of fibrotic liver with ketoconazole improves hepatic microenvironment and enhanced reduction of liver injury after fibrosis. Cytochrome P-450 inhibitors seems a favored therapeutic option in attenuation of liver fibrosis.

Correlation Between Doppler Echocardiography and Right Heart Catheterization Derived Pulmonary Artery Pressures: Impact of Right Atrial Pressures.

OBJECTIVE: To evaluate the correlation between Doppler echocardiography (DE) and right heart catheterization (RHC) derived pulmonary artery pressures and to assess the impact of right atrial (RA) pressures on this correlation. STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: Cardiology Department, Tahir Heart Institute, Chenab Nagar, from June 2013 to December 2014. METHODOLOGY: All patients undergoing RHC were included. Relevant data were collected from hospital database. Continuous variables were expressed as the mean and SD or as the median and interquartile range where the distributions were skewed. Pearson correlation coefficient and Bland-Altman method were used to correlate DE derived right ventricular systolic pressure (RVSP) and RHC derived systolic pulmonary artery pressures (sPAP). Adjusted RVSP was calculated by replacing default value of RA pressure (10 mmHg) with RHC derived mean RA pressure. Receiver operating characteristic curve (ROC) was used to identify the best cut-off value of RVSP in predicting pulmonary hypertension. RESULTS: Fifty-one patients completed the study protocol. Mean age of study population was 45.22 &plusmn;15.25 years with male to female ratio of 1.47:1. Median error was 13 mmHg (7 to 20). Pearson correlation coefficient (r) between RVSP and sPAP was 0.72. Bland-Altman method of correlation showed bias of +4.43 mmHg with 95% limits of agreement ranging from -34.61 to +43.47. Using ROC curve, the best cut-off value of RVSP was greater than 52 mmHg with accuracy of 75% (sensitivity: 81%, specificity: 69%) in predicting pulmonary hypertension. Adjusted RVSP showed only little improvement in correlation (r = 0.75), adjusted error (13.65 &plusmn;13.05) and diagnostic accuracy (79%). CONCLUSION: Doppler echocardiography can frequently overestimate pulmonary artery pressures. Though correctly estimated RA pressure may improve this correlation, yet its contribution is only minimal.