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Athens, GA, United States

Yi H.,Konkuk University | Shin M.-J.,Konkuk University | Cho S.-M.,Konkuk University | Lee D.-G.,Konkuk University | And 6 more authors.
Archives of Pharmacal Research | Year: 2010

The dose-dependent toxicokinetics of enrofloxacin were studied by administering various single subcutaneous doses (5, 10, 20, 40, 70, 100, 150, 200, 300 and 400 mg/kg) in male Sprague-Dawley rats. The blood samples were collected from the tail veins, and the plasma concentration of enrofloxacin was determined by an HPLC-fluorescence detection (FLD) method. The time-concentration profiles of enrofloxacin were well fitted by an one-compartmental model with first order elimination. The absorption half-lives (t1/2abs) ranged from 0.2-0.8 h, and the mean time to maximum plasma concentration (Tmax) ranged from 0.6-1.8 h. On the other hand, marked disproportionate increases of the area under the curve (AUC) and elimination half-lives (t1/2) were observed from the increase of the doses. This result indicates that the elimination of enrofloxacin has nonlinear pharmacokinetic properties with increasing doses. Therefore, we need to take into consideration the possible occurrence of side effects resulting from greater systemic exposure from high dose therapies.

Messaritakis I.,University of Crete | Christodoulou V.,University of Crete | Mazeris A.,Veterinary Services of Cyprus | Koutala E.,University of Crete | And 3 more authors.
PLoS ONE | Year: 2013

Resistance of pathogens to drugs is a growing concern regarding many diseases. Parasites like Leishmania, Plasmodium and Entamoeba histolytica; and neoplastic cells, present the multidrug-resistant phenotype rendering chemotherapy ineffective. The acquired resistance of Leishmania to antimony has generated intense research on the mechanisms involved but the question has not yet been resolved. To test the hypothesis that drug efflux in Leishmania, as measured by flow cytometry using the fluorescent dye Rhodamine-123, is largely dependent on the number of efflux pumps an isolate can express, the amount of Pgp 170 molecules was assessed in ten field isolates (5 "resistant" and 5 "susceptible") using: Western Blotting, Confocal and Transmission Electron Microscopy, and proteomics. Their survival after exposure to three antileishmanial drugs, in vitro, was evaluated and clinical data were compared to the in vitro results. All isolates were resistant to Glucantime but susceptible to Miltefosine, whilst Amphotericin B was more effective on the "susceptible" isolates. The MDR gene, expressing the transmembrane efflux pump Pgp 170, appears to play a key role in the phenomenon of drug resistance. When "susceptible" versus "resistant" parasites were compared, it was shown that the higher the number of Pgp 170 molecules the higher the Rhodamine-123 efflux from the parasite body and, when exposed to the drug, the number of efflux pumps increased. However, the rate of this increase was not linear and it is possible that there is a maximum number of Pgp 170 molecules an isolate can express. Nevertheless, the phenomenon is a complex one and other factors and proteins are involved in which the HSP-70 group proteins, detected in the "resistant" isolates, may play a significant role. © 2013 Messaritakis et al.

Park S.-W.,Konkuk University | Yi H.,Konkuk University | Cho S.-M.,Konkuk University | Jo K.,Konkuk University | And 6 more authors.
Journal of Animal and Veterinary Advances | Year: 2011

This study was performed to set up a transcriptional database of the intestinal metabolizing enzymes in beagle dogs. The total RNA was isolated from the duodenum and the mRNA expression was measured using GeneChip® oligonucleotide arrays. Detected genes from the intestine were about 47% of 43, 035 sequences and total of 79 genes involved metabolizing enzymes. Among the phase I enzymes, dogs exhibited abundant gene expressions of CYP3A12, CYP2B11, LOC610195 (similar to CYP2J2) followedby LOC489851 (similar to CYP3A4), CYP27A1 andCYP51. For phase II enzymes, acetyltransferase AC ATI, glutathione S-transferases GST A3 and GSTP1, sulfotransferases SULT1A1 and SULT1D, acyltransferases DGAT1 and ACAA1 and glucuronosyltransferase UGCG were highly expressed in duodenum. The dogs expression profiles were compared with those in mice based on gene classification and annotation. Between the two species, the regression of all enzymes (n = 36) with same annotations was 0.496 as andcoefficient of determination (R2) however, two cytochrome P450s including CYP2S1 and CYP4B1 were expressed <5 fold and phase II enzymes including GSTA3, SULT1A1, SULT1D1, TPST1 and UGCG were expressed >5 fold changes in dogs (t-test, p<0.01). In sum, theses data indicated significant differences between beagle dogs and ICR mice in the mRNA expression of both p450s and phase II metabolizing enzymes. These animals are the most widely used species/lines in toxicological and pharmacological screening. Therefore, this database will be useful for predicting and scaling the intestinal drug metabolism between rodents (mice) and non-rodents (dogs). © Medwell Journals, 2011.

Clarkson S.M.,University of Georgia | Newcomer E.C.,Athens Academy | Newcomer E.C.,University of Virginia | Young E.G.,Athens Academy | And 2 more authors.
Journal of Bacteriology | Year: 2010

The gene (sipA) encoding the sulfur-induced protein A (PF2025) is highly upregulated during growth of Pyrococcus furiosus on elemental sulfur (S 0). Expression of sipA is regulated by sulfide, the product of S 0 reduction, but in an iron-dependent manner. SipA is proposed to play a role in intracellular iron sulfide detoxification. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Pafilis C.,National and Kapodistrian University of Athens | Gaitanis A.,Athens Academy | Gatis C.,National and Kapodistrian University of Athens | Kontaxakis G.,Technical University of Madrid | And 4 more authors.
10th International Workshop on Biomedical Engineering, BioEng 2011 | Year: 2011

We have proposed a method for the estimation of the optimal iteration for the Maximum Likelihood Expectation Maximization (MLEM) algorithm used in Positron Emission Tomography (PET) image reconstruction. For the calculation of the transition matrix and the generation of the projection data a PET scanner was simulated using Monte-Carlo techniques. Our preliminary results show that the proposed methodology can estimate the optimal iteration for the MLEM algorithm. © 2011 IEEE.

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