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Full-Text Articles in Medicine and Health Sciences

Efficacy Of Female Rat Models In Translational Cardiovascular Aging Research, Kevin M. Rice, J. C. Fannin, C. Gillette, Eric Blough Dec 2014

Efficacy Of Female Rat Models In Translational Cardiovascular Aging Research, Kevin M. Rice, J. C. Fannin, C. Gillette, Eric Blough

Pharmaceutical Science and Research

Cardiovascular disease is the leading cause of death in women in the United States. Aging is a primary risk factor for the development of cardiovascular disease as well as cardiovascular-related morbidity and mortality. Aging is a universal process that all humans undergo; however, research in aging is limited by cost and time constraints. Therefore, most research in aging has been done in primates and rodents; however it is unknown how well the effects of aging in rat models translate into humans. To compound the complication of aging gender has also been indicated as a risk factor for various cardiovascular diseases. …


3,4,5-Trichloroaniline Nephrotoxicity In Vitro: Potential Role Of Free Radicals And Renal Biotransformation, Christopher Racine, Dakota Ward, Dianne K. Anestis, Travis Ferguson, Deborah Preston, Gary O. Rankin Nov 2014

3,4,5-Trichloroaniline Nephrotoxicity In Vitro: Potential Role Of Free Radicals And Renal Biotransformation, Christopher Racine, Dakota Ward, Dianne K. Anestis, Travis Ferguson, Deborah Preston, Gary O. Rankin

Pharmaceutical Science and Research

Chloroanilines are widely used in the manufacture of drugs, pesticides and industrial intermediates. Among the trichloroanilines, 3,4,5-trichloroaniline (TCA) is the most potent nephrotoxicant in vivo. The purpose of this study was to examine the nephrotoxic potential of TCA in vitro and to determine if renal biotransformation and/or free radicals contributed to TCA cytotoxicity using isolated renal cortical cells (IRCC) from male Fischer 344 rats as the animal model. IRCC (~4 million cells/mL; 3 mL) were incubated with TCA (0, 0.1, 0.25, 0.5 or 1.0 mM) for 60–120 min. In some experiments, IRCC were pretreated with an antioxidant or a …


Management Of Severe Hyponatremia: Infusion Of Hypertonic Saline And Desmopressin Or Infusion Of Vasopressin Inhibitors?, Antonios H. Tzamaloukas Md, Joseph I. Shapiro Md, Dominic S. Raj Md, Glen H. Murata Md, Robert H. Glew Phd, Deepak Malhotra Md, Phd Nov 2014

Management Of Severe Hyponatremia: Infusion Of Hypertonic Saline And Desmopressin Or Infusion Of Vasopressin Inhibitors?, Antonios H. Tzamaloukas Md, Joseph I. Shapiro Md, Dominic S. Raj Md, Glen H. Murata Md, Robert H. Glew Phd, Deepak Malhotra Md, Phd

Pharmaceutical Science and Research

Rapid correction of severe hyponatremia carries the risk of osmotic demyelination. Two recently introduced methods of correction of hyponatremia have diametrically opposite effects on aquaresis. Inhibitors of vasopressin V2 receptor (vaptans) lead to the production of dilute urine, whereas infusion of desmopressin causes urinary concentration. Identification of the category of hyponatremia that will benefit from one or the other treatment is critical. In general, vaptans are effective in hyponatremias presenting with concentrated urine and, with the exception of hypovolemic hyponatremia, can be used as their primary treatment. Desmopressin is effective in hyponatremias presenting with dilute urine or developing urinary dilution …


Ho-1 Upregulation Attenuates Adipocyte Dysfunction, Obesity, And Isoprostane Levels In Mice Fed High Fructose Diets, Zeid Khitan, Mohit Harsh, Komal Sodhi, Joseph I. Shapiro Md, Nader G. Abraham Sep 2014

Ho-1 Upregulation Attenuates Adipocyte Dysfunction, Obesity, And Isoprostane Levels In Mice Fed High Fructose Diets, Zeid Khitan, Mohit Harsh, Komal Sodhi, Joseph I. Shapiro Md, Nader G. Abraham

Pharmaceutical Science and Research

Background. Fructose metabolism is an unregulated metabolic pathway and excessive fructose consumption is known to activate ROS.HO-1 is a potent antioxidant gene that plays a key role in decreasing ROS and isoprostanes.We examinedwhether the fructosemediated increase in adipocyte dysfunction involves an increase in isoprostanes and that pharmacological induction ofHO-1would decrease both isoprostane levels and adipogenesis. Methods and Results. We examined the effect of fructose, on adipogenesis in human MSCs in the presence and absence of CoPP, an inducer of HO-1. Fructose increased adipogenesis and the number of large lipid droplets while decreasing the number of small lipid droplets (𝑃 < 0.05). Levels of heme and isoprostane in fructose treated MSC-derived adipocytes were increased. CoPP reversed these effects andmarkedly increasedHO-1 and theWnt signaling pathway. Thehigh fructose diet increased heme levels in adipose tissue and increased circulating isoprostane levels (𝑃 < 0.05 versus control). Fructose diets decreasedHO-1 and adiponectin levels in adipose tissue. Induction ofHO-1 by CoPP decreased isoprostane synthesis (𝑃 < 0.05 versus fructose). Conclusion. Fructose treatment resulted in increased isoprostane production and adipocyte dysfunction, which was reversed by the increased expression of HO-1.


In Vitro Metabolic Stability Study Of New Cyclen Based Antimalarial Drug Leads Using Rp-Hplc And Lc-Ms/Ms, Apoorva V. Rudraraju, Mohammad F. Hossain, Anjuli Shrestha, Prince N.A. Amoyaw, Babu L. Tekwani, M. O. Faruk Khan Jul 2014

In Vitro Metabolic Stability Study Of New Cyclen Based Antimalarial Drug Leads Using Rp-Hplc And Lc-Ms/Ms, Apoorva V. Rudraraju, Mohammad F. Hossain, Anjuli Shrestha, Prince N.A. Amoyaw, Babu L. Tekwani, M. O. Faruk Khan

Pharmaceutical Science and Research

Metabolic stability of the new antimalarial drug leads is determined using Human Liver Microsome (HLM) and specific cytochrome P450 enzyme (CYP2C8) taking the clinically used antimalarial drug chloroquine as a positive control. Experiment is done using standard methods. All the assays were conducted in 0.5 M phosphate buffer at pH 7.4. In general the metabolic reaction was initiated by adding 1 mM NADPH and 0.5 mg of enzyme. Incubations were done with time frequency of 0 hr, 1 hr, and 2 hrs at 37°C and the reactions were terminated by adding acetonitrile in the equal amounts of the assay mixture …


Honokiol Enhances Paclitaxel Efficacy In Multi-Drug Resistant Human Cancer Model Through The Induction Of Apoptosis, Xu Wang, Jonathan J. Beitler, Hong Wang, Michael J. Lee, Wen Huang, Lydia Koenig, Sreenivas Nannapaneni, Arm R. Amin, Michael Bonner, Hyung Ju C. Shin, Zhuo Georgia Chen, Jack L. Arbiser, Dong M. Shin Apr 2014

Honokiol Enhances Paclitaxel Efficacy In Multi-Drug Resistant Human Cancer Model Through The Induction Of Apoptosis, Xu Wang, Jonathan J. Beitler, Hong Wang, Michael J. Lee, Wen Huang, Lydia Koenig, Sreenivas Nannapaneni, Arm R. Amin, Michael Bonner, Hyung Ju C. Shin, Zhuo Georgia Chen, Jack L. Arbiser, Dong M. Shin

Pharmaceutical Science and Research

Resistance to chemotherapy remains a major obstacle in cancer therapy. This study aimed to evaluate the molecular mechanism and efficacy of honokiol in inducing apoptosis and enhancing paclitaxel chemotherapy in pre-clinical multi-drug resistant (MDR) cancer models, including lineage-derived human MDR (KB-8-5, KB-C1, KB-V1) and their parental drug sensitive KB-3-1 cancer cell lines. In vitro analyses demonstrated that honokiol effectively inhibited proliferation in KB-3-1 cells and the MDR derivatives (IC50 ranging 3.35±0.13 µg/ml to 2.77±0.22 µg/ml), despite their significant differences in response to paclitaxel (IC50 ranging 1.66±0.09 ng/ml to 6560.9±439.52 ng/ml). Honokiol induced mitochondria-dependent and death receptor-mediated apoptosis in …