A. Ivanov

Single Intravenous Injection of Coenzyme Q10 Protects the Myocardium after Irreversible Ischemia

Experiments were performed on the model of irreversible myocardial ischemia in Wistar rats. Coenzyme Q10 was injected intravenously 10 min after coronary artery occlusion. On day 21 after myocardial infarction the content of coenzyme Q10 in the left ventricle, liver, and plasma from animals of the treatment group was higher than that in untreated rats by 23, 1042, and 87%, respectively (p<0.05). The area of the necrotic zone was lower, and postinfarction hypertrophy of the left ventricle was less pronounced in coenzyme-receiving rats. Right ventricular hypertrophy did not develop in these animals. These rats were characterized by greater stroke volume (by 24.6%, p<0.05), stroke work (by 34.9%), cardiac output (by 37.8%, p<0.05), ejection fraction (by 35.7%, p<0.05), and contractility (by 22.5%, p<0.05), but lower end-diastolic pressure (by 25.8%, p<0.05) than untreated animals. These data indicate that the development of parenteral ubiquinone preparations holds much promise for urgent therapy of acute cardiovascular disorders.

Cardioprotection with Intravenous Injection of Coenzyme Q10 is limited by Time of Administration after Onset of Myocardial Infarction in Rats

Objective: Coenzyme Q 10 (CoQ 10 ) levels are decreased in patients with cardiovascular diseases. The bioavailability of orally ingested CoQ 10 is limited to 2–3%, and long-term administration is required to increase the level of CoQ10 in myocardium for cardioprotection. Intravenous (IV) administration of solubilized CoQ10 immediately after coronary occlusion has been shown to increase myocardial levels rapidly and to protect against cardiac ischemia. The aim of this study was to determine the length of time following onset of myocardial infarction (MI) for which a single IV administration of CoQ 10 was cardioprotective. Methods: A single IV injection of solubilized CoQ10 (30 mg/kg, 1 ml/kg) or saline (1 ml/kg) was administered at either minute 60 or minute 180 after the onset of MI induced by coronary artery ligation in rats. Results: Twenty-one days after injection, CoQ 10 levels were still high in both the 60 and 180 minute groups. Rats treated with CoQ10 60 min after ligation had a significantly larger mass of viable left ventricle (LV) myocardium, limited LV dilatation, and improved cardiac contractile and relaxation capacity compared with controls. CoQ10 levels were significantly correlated with LV end-systolic volume (r=-0.65), end-diastolic volume (r=-0.56), ejection fraction (r-=0.67), and LV relaxation (r=-0.64) (p<0.001). IV administration of CoQ 10 180 min after occlusion prevented signs of right ventricle hypertrophy but did not limit LV damage. Conclusion: A single IV injection of solubilized CoQ 10 (30 mg/kg) at minute 60 effectively limited LV damage and deterioration of function after coronary ligation in rats; however, the same protective effects were not seen with CoQ 10 injection administered at minute 180.

The role of pharmacokinetic studies in development of drugs, containing endogenous compounds

Bacteriophage Lambda (λ) has played an historical role as an essential tool in our current understanding of molecular genetics. It’s major capsid protein gpD occurs on each capid at 405 to 420 copies per phage in homotrimeric form and functions to stabilize the head and likely to compact the genomic DNA. Th e interesting conformation of this protein allows for its exploitation through the genetic fusion of peptides or proteins to either the amino or carboxy terminal end, while retaining phage assembly and viability. We endeavoured to design and construct a highly controllable head decoration system governed by two genetic conditional regulation systems; temperature sensitive repressor expression and bacterial conditional amber mutation suppression. We have sequenced an historical amber mutant of D identifying the position of the stop codon, and employing this mutant in combination with our cellular and plasmid constructs, we will endeavour to measure the decoration of the capsid by a D::gfp fusion under varying conditions. Th is controllable system has the ability to establish a variable number of fusions per phage based on genetic and physical environment without compromising viability.This approach has important implications in the design of new therapeutics in which steric hindrance and avidity are important concerns. To this end we have applied this process innovation and are in the process of testing, toward the development and optimization of new Alzheimer’s Disease therapeutic vaccines, S. aureus, M. tuberculosis and P. acnes antibacterials.To design and synthesis a series of novel L-amino acid esters prodrugs of acyclic nucleoside phosphonates with more potent anti-HBV activity, adefovir dipivoxil was used as lead compound, according to the results of enhanced oral bioavailability and antiviral activities of nucleoside L-amino acid ester prodrugs. Eleven novel L-amino acid ester prodrugs of acyclic nucleoside phosphonates were designed and synthesized, their anti-HBV activities were evaluated in HepG2 2.2.15 cells. Eight compounds exhibited antiviral activity, and compound 11 showed the most potent anti-HBV activity and highest selective index in vitro (EC50 0.0952 micromol x L(-1), SI 69523). Moreover, by analyzing the primary structure and activity relationship of these compounds, it could be suggested that L-amino acid ester strategy has significant potential in the acyclic nucleoside phosphonates prodrug design.Soil samples were collected from three sites (Wadi-El-Natrun, Kafr-El-Sheekh and Mallahat Road) located in Cairo-Alexandria Agriculture Road, Egypt. The total fungal counts allover the road was 755 colonies, constituting ten fungal species (Alternaria alternata, Aspergillus flavus, Aspergillus nidulans, Aspergillus niger, Aspergillus terreus, Fusarium moniliforme, Penicillium chrysogenum, Penicillium purpurogenum, Phoma herbarum and Rhizopus oryzae). The most potent fungal species producing pigments along the road were A. nidulans, F. moniliforme, P. purpurogenum and P. herbarum. Comparative sensitivity to different light wave lengths and radiation (laser, gamma and ultraviolet rays) on growth and pigment production in the four selected fungal species was estimated. Optimization of physical and nutritional factors on growth and pigment production was carried out. A steady increase in the antioxidant activities was showed in all four tested pigments producing species with raising the phenol contents. The extracellular pigment of P. purpurogenum was found to be more effective against some pathogenic microbes and might have a potential role in pharmaceutical drug industry. The identification of the structure of unknown P. purpurogenum pigment was detected using UV and FTIR spectra, and indicated that it is an phenolic compound and has broad stretching OH, C=C and C-H groups of the aromatic ring.Biostudy Solutions, USA F too oft en statistics is viewed as a black box into which data enters one side and results exit from the other, with the calculations performed in between considered far too complex or abstract for all but a statistician to understand. Most pharmaceutical scientists have fi nally become comfortable with the 90% confi dence interval approach for average bioequivalence (ABE), at least in non-replicated studies. With the advent of the scaled average bioequivalence (SABE) method, we now have a powerful, but far more confusing statistical approach which requires reference replication. Th e black box associated with this method appears even larger than the one that exists for ABE. To add to the confusion surrounding FDA’s recently disclosed calculations for SABE, the myth continues to spread that all we need to do is calculate the standard 90% confi dence intervals and apply some “scaled” regulatory limit to the results. A simplifi ed explanation of the SABE calculations, how they relateand do not relate to ABEwill be presented.In addition, minimal statistical concepts familiar to most scientists will be used to explain the inner workings of the SABE black box.

Solubilized coenzyme q10 (30mg/kg iv) protects rat myocardium from the subsequent ischemia-reperfusion damage

Objective: It is well known, that period of ischemia-reperfusion evokes an oxidative stress due to the release of a large amounts of reactive oxygen substances (ROS). Such conditions can be produced in clinics during revascularization of the ischemic myocardium. Coenzyme Q10 is powerful antioxidant which may be effective clinically for acute myocardial ischemia. The aim of the study was to examine whether single intravenous administration of coenzyme Q10 (CoQ10) can protect the myocardium from subsequent ischemia-reperfusion. Design and Methods: The experiments were carried out on anaesthetized open-chest male Wistar rats with ECG monitoring. Occlusion of coronary artery for 30 min and the 2 h reperfusion was performed in rats of the first (n = 9) and second (n = 9) groups. 30 min before occlusion the rats of the first group received solubilized CoQ10 (Kudesan solution, “Akvion”, Russia) intravenously in dose 30 mg/kg; the rats of the second group – saline. The ischemic and infarct zones were calculated as % of the total myocardium. The contents of CoQ10 and CoQ9 in the left ventricle myocardium were determined by HPLC with electrochemical detection. Statistical analysis was performed using nonparametric test. Results: At the end of reperfusion in CoQ10 treated rats myocardial level of CoQ10 was 3 times higher than in saline group, myocardial content of CoQ9 was not different between groups. The ischemic zone was the same in both groups of rats: 48 ± 5% in first group and 49 ± 5% in second group. Mean value of infarct size in CoQ10 treated group (30 ± 7%) was significantly smaller than in saline group (47 ± 6%, p < 0,001). Arrhythmias induced by ischemia were not different in both groups of rats. During reperfusion the ventricular tachycardia is observed in two from nine rats in CoQ10 treated group and in eight from nine rats in saline group. Conclusion: Data demonstrate cardioprotective effect of CoQ10. Single intravenous administration of CoQ10 increases its myocardial level resulting in limitation of the myocardial damage and arrhythmias evoked by ischemia-reperfusion.