Carrier-bound Methotrexate. III.‡ Antiproliferative Activity of Macromolecular MTX Conjugates Against the Human HeLa and Colo Carcinoma Cell Lines

In continuation of studies in these laboratories aiming at the bioevaluation of macromolecular anticancer drug models, in vitro cytotoxicity screens are performed on several series of water-soluble polymer-methotrexate  conjugates. The methotrexate drug in these conjugates is bound through amide or ester linkages to water- soluble polyamide- or polyamidoamine-type carriers by previously developed anchoring techniques.Tests were  conducted against the HeLahumancervical carcinoma cell line generally considered to be drug-sensitive, and  against two variants of the rather refractory Colo 320 DM, a human colon adenocarcinoma line.KEYWORDS: Drug conjugation, Colo cell line, HeLa cell line, methotrexate, polyaspartamide,  polyamidoamine

Carrier-bound Methotrexate. IV. Antiproliferative Activity of Polyaspartamide-MTX Conjugates against Leukemic Lymphoblast Cell Lines

Polymeric conjugates of methotrexate (MTX) with macromolecular carriers, obtained from amine-functionalized polyaspartamides by coupling with one of the drug’s carboxyl groups, are used in this  preliminary screening project for in vitro cytotoxicity assessment. The water-soluble conjugates, crudely fractionated by aqueous dialysis, possess mass-average molecular masses in the range of 20000–30000. Screens are performed by standard procedures against cultured CEM/S human leukemic lymphoblast cells, a drug-sensitive line, and against CEM/E, its drug-resistant subline, for comparison also against  unconjugated MTX. All compounds tested, including the unconjugated drug, display decreasing activity on  going from CEM/S to CEM/E, resistance factors (IC50 [CEM/E]/IC50[CEM/S]) being in the vicinity of 15–20 for MTX as well as for the majority of conjugates. On the other hand, comparisons of IC50 values for conjugates versus free drug, both against CEM/S and CEM/E, show vastly superior antiproliferative performance of the drug in the carrier-anchored state over the free form, with activity factors (IC50[free MTX]/IC50 [conjugate]) typically in the 10–50 range and higher. On the basis of these promising in vitro findings, the polyaspartamide-MTX conjugates are considered to be excellent candidates for further cell culture and extended in vivo tests.KEYWORDS: Methotrexate conjugates, polyaspartamide, CEM leukemic lymphoblasts

Randomized, parallel-group, double-blind, controlled study to evaluate the efficacy and safety of carbohydrate-derived fulvic acid in topical treatment of eczema

Justin J Gandy, Jacques R Snyman, Constance EJ van RensburgDepartment of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South AfricaBackground: The purpose of this study was to evaluate the efficacy and safety of carbohydrate-derived fulvic acid (CHD-FA) in the treatment of eczema in patients two years and older.Methods: In this single-center, double-blind, placebo-controlled, parallel-group comparative study, 36 volunteers with predetermined eczema were randomly assigned to receive either the study drug or placebo twice daily for four weeks.Results: All safety parameters remained within normal limits, with no significant differences in either group. Significant differences were observed for both severity and erythema in the placebo and CHD-FA treated groups, and a significant difference was observed for scaling in the placebo-treated group. With regard to the investigator assessment of global response to treatment, a significant improvement was observed in the CHD-FA group when compared with the placebo group. A statistically significant decrease in visual analog scale score was observed in both groups, when comparing the baseline with the final results.Conclusion: CHD-FA was well tolerated, with no difference in reported side effects other than a short-lived burning sensation on application. CHD-FA significantly improved some aspects of eczema. Investigator assessment of global response to treatment with CHD-FA was significantly better than that with emollient therapy alone. The results of this small exploratory study suggest that CHD-FA warrants further investigation in the treatment of eczema.Keywords: fulvic acid, eczema, anti-inflammatory, efficacy, safet

Investigation of the Anti-HIV properties of Oxihumate

GesondheidswetenskappeGeneeskundige VirologiePlease help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]

A prospective, observational study comparing the PK/PD relationships of generic Meropenem (Mercide®) to the innovator brand in critically ill patients

Mervyn Mer,1 Jacques Rene Snyman,2 Constance Elizabeth Jansen van Rensburg,2 Jacob John van Tonder,3 Ilze Laurens2 1Department of Medicine, Divisions of Critical Care and Pulmonology, University of the Witwatersrand, Johannesburg, South Africa; 2Office of the Dean, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa; 3Scientific Affairs Department, Triclinium Clinical Development (Pty) Ltd, Centurion, South Africa Introduction: Clinicians’ skepticism, fueled by evidence of inferiority of some multisource generic antimicrobial products, results in the underutilization of more cost-effective generics, especially in critically ill patients. The aim of this observational study was to demonstrate equivalence between the generic or comparator brand of meropenem (Mercide®) and the leading innovator brand (Meronem®) by means of an ex vivo technique whereby antimicrobial activity is used to estimate plasma concentration of the active moiety. Methods: Patients from different high care and intensive care units were recruited for observation when prescribed either of the meropenem brands under investigation. Blood samples were collected over 6 hours after a 30 minute infusion of the different brands. Meropenem concentration curves were established against United States Pharmacopeia standard meropenem (Sigma-Aldrich) by using standard laboratory techniques for culture of Klebsiella pneumoniae. Patients’ plasma samples were tested ex vivo, using a disc diffusion assay, to confirm antimicrobial activity and estimate plasma concentrations of the two brands. Results: Both brands of meropenem demonstrated similar curves in donor plasma when concentrations in vials were confirmed. Patient-specific serum concentrations were determined from zones of inhibition against a standard laboratory Klebsiella strain ex vivo, confirming at least similar in vivo concentrations as the concentration curves (90% confidence interval) overlapped; however, the upper limit of the area under the curve for the ratio comparator/innovator exceeded the 1.25-point estimate, i.e., 4% higher for comparator meropenem. Conclusion: This observational, in-practice study demonstrates similar ex vivo activity and in vivo plasma concentration time curves for the products under observation. Assay sensitivity is also confirmed. Current registration status of generic small molecules is in place. The products are therefore clinically interchangeable based on registration status as well as bioassay results, demonstrating sufficient overlap for clinical comfort. The slightly higher observed comparator meropenem concentration (4%) is still clinically acceptable due to the large therapeutic index and should ally fears of inferiority. Keywords: bioequivalence, antimicrobial, multisource products, Meropenem, ­pharmacokinetics, pharmacodynamic

Flow Cytometric Evaluation of Apoptosis and Cell Viability as a Criterion of Anti-tumour Drug Toxicity

GesondheidswetenskappeFarmakologiePlease help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]

Cytotoxicity and Cell Death Pathways Invoked by Two New Rhodium-Ferrocene Complexes in Benign and Malignant Prostatic Cell Lines

GesondheidswetenskappeFarmakologiePlease help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]

Neuroprotective Effect of Humic Acid on Focal Cerebral Ischemia Injury: an Experimental Study in Rats

Guven, Mustafa/0000-0001-8643-9775; Silan, Coskun/0000-0002-8352-6571; silan, coskun/0000-0002-8352-6571WOS: 000349015900005PubMed: 25173888Stroke is still a major cause of death and permanent neurological disability. As humic acids are well-known antioxidant molecules, the purpose of this study was to investigate the potential neuroprotective effects of humic acid in a focal cerebral ischemia model. Twenty-four rats were divided equally into three groups. A middle cerebral artery occlusion model was performed in this study where control (group II) and humic acid (group III) were administered intraperitoneally following an ischemic experimental procedure. Group I was evaluated as sham. Malondialdehyde (MDA), superoxide dismutase (SOD), and nuclear respiratory factor-1 (NRF-1) levels were analyzed biochemically on the right side of the ischemic cerebral hemisphere, while ischemic histopathological studies were completed on the left side to investigate the antioxidant status. Biochemical results showed that SOD and NRF-1 levels were significantly increased in the humic acid group (III) compared with the control group (II) while MDA levels were significantly decreased. on histopathological examination, cerebral edema, vacuolization, degeneration, and destruction of neural elements were decreased in the humic acid group (III) compared with the control group (II). Cerebral ischemia was attenuated by humic acid administration. These observations indicate that humic acid may have potential as a therapeutic agent in cerebral ischemia by preventing oxidative stress