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Malgorzata Dolowy, Alina Pyka-Pajak, Katarzyna Filip and Joanna Zagrodzka

. 8. Liu, L., et al.: A liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of escin Ia and escin Ib in human plasma: application to a pharmacokinetic study after intravenous administration. Biomed. Chromatogr., 24, 1309-1315, 2010. 9. Man, S.: Chemical study and medical application of saponins as anti-cancer agents. Fitoterapia, 81(7), 703-714, 2010. 10. Rao, A. V, Gurfinkel, D. M.: The bioactivity of saponins: triterpenoid and steroidal glycosides. Drug Metabol Drug Interact., 17(1-4), 211

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Alexandra Lazăr, J Szederjesi, Ruxandra Copotoiu, Sanda-Maria Copotoiu and L Azamfirei

References 1. Cuvillon P, Nouvellon E, Ripart J, Boyer JC, Dehour L, Mahamat A, et al. A comparison of the pharmacodynamics and pharmacokinetics of bupivacaine, ropivacaine (with epinephrine) and their equal volume mixtures with lidocaine used for femoral and sciatic nerve blocks: a double-blind randomized study. Anesth Analg. 2009;108:641-649. 2. Ye F, Feng YX, Lin JJ. A ropivacaine-lidocaine combination for caudal blockade in haemorrhoidectomy. J Int Med Res 2007;35:307-313. 3. Hansen TG. Ropivacaine: A

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M. Göböová, I. Vaňo, V. Kissová, T. Fazekaš and M. Kuželová

Abstract

Introduction A gentamicin dose, which the physicians select, frequently does not take any pharmacokinetic parameters into consideration.

Aim To analyse the results of therapeutic drug monitoring (TDM) of gentamicin for those patients who have not had the gentamicin dose adjusted at the beginning of therapy (first group) and for those patients who had the gentamicin dose adjusted at the beginning of therapy (second group).

Methods We acquired the basic data about patients from the requests for laboratory examination of levels of gentamicin. We measured all the gentamicin concentrations mentioned in this work using the FPIA method.

Results The monitored set included 379 hospitalized patients during a 4-year period. We divided the monitored set into 2 groups. First group was composed of patients without dose adjustment of gentamicin at the beginning of therapy, and the second group was composed of patients with dose adjustment of gentamicin by the clinical pharmacist at the beginning of therapy. In addition, the patients in each group were divided according to the body mass index (BMI). In the first group of patients, a low percentage of patients had both optimal levels (trough, peak levels). As for patients with BMI > 25 m2/kg, there were only 17 % such cases, and the patients with BMI ≤ 25 m2/kg were only 18.8 %. In the second group, the patients had all trough and peak levels in optimal therapeutic range at obese patients, overweight patients and also at patients with normal weight (p < 0.001).

Conclusion Adjustment of dosage regimens immediately at the beginning of therapy will provide for administering sufficient doses of antibiotics at the beginning of therapy, which is a pre-condition for a successful anti-infective therapy. Therapeutic monitoring of levels allows for administration of sufficient dose of gentamicin without fear of any undesirable effects.

Open access

S. Đorđe Marjanović, Danica Bogunović, Mirjana Milovanović, Darko Marinković, Nemanja Zdravković, Vladimir Magaš and M. Saša Trailović

Abstract

In the present study we tested the dose andh time dependence of the antinematodal effects of carvacrol and tyhmol on Caenorabditis elegans, and the efficacy of carvacrol, thymol, p-cymene and cinnamaldehyde,which were administrated in the drinking water of rats naturally infected with the pinworm Syphacia muris. The control treatment of the infected rats was carried out with piperazine. Thymol caused a dose and time-dependent mortality in adult C. elegans. The value of the Median Lethal Concentration (LC50) of thymol was 117.9nM after 24h and 62.89 nM after 48h of exposure. Carvacrol exhibited a higher antinematodal efficiency than thymol. The LC50 of carvacrol, after 24 hours of exposure, was 53.03 nM, while after 48 hours it was 33.83 nM. On the other hand, piperazine showed an extremely high efficacy against S. muris infection in rats. Piperazine, at a dose of 625 mg/kg bw, administered in drinking water continuously for 10 days, eliminates the infection completely. However, none of the investigated active ingredients of essential oils were effective against S. muris. The reason for the lack of efficiency may be due to their pharmacokinetic properties. A relatively low amount of, orally administered, active ingredients of essential oils reaches the distal segments of the gastrointestinal tract, where S. muris inhabits the gut (colon and cecum). The obtained results, on C. elegans, indicate a clear dose and time-dependent antinematodal effect of thymol and carvacrol. However, for clinical application, it is necessary to examine the efficacy of microencapsulated formulations with a controlled release of active ingredients of essential oils in certain parts of the gastrointestinal tract.

Open access

Jytte Banner, Christian Bjerre Høyer, Martin Roest Christensen, Alexandra Gheorghe, Anne Bugge, Gyda Lolk Ottesen, Lene Warner Thorup Boel, Jørgen Lange Thomsen, Line Kruckow and Christina Jacobsen

Abstract

Background: Forensic autopsy strategies may improve differential diagnostics both post-mortem and ante-mortem and aid in clinical settings concerning preventive efforts for premature mortality. Excess mortality and reduced life expectancy affect persons with severe mental illnesses (SMI) for multi-faceted reasons that remain controversial. Somatic conditions, medical treatment and lifestyle diseases, which are primarily examined in the living, contribute to premature deaths. The underlying pathophysiological mechanisms are unclear, though, and the benefits of a focused, standardised autopsy remain unproven. We have developed and implemented an optimised molecular–biological autopsy for deceased persons with SMI. Our aim is to map the occurrence of 1) somatic diseases and organ changes; 2) metabolic syndrome; 3) use and abuse of alcohol, pharmaceuticals and psychoactive substances; 4) pharmacokinetic and pharmacodynamic factors in the metabolism of pharmaceuticals; and 5) genetic variations (acquired and/or congenital) in sudden cardiac death. Additionally, we hope to contribute to diagnostic treatments and preventive measures to benefit those living with SMI. Methods: SURVIVE: let the dead help the living is a prospective, autopsy-based study on 500 deceased persons with SMI subjected to forensic autopsies under the Danish Act on Forensic Inquests and Autopsy. The autopsies followed an extended, standardised autopsy protocol comprised of whole-body computed tomography scanning, magnetic resonance imaging of the heart and brain and an extended forensic autopsy, including a wide panel of analyses (toxicology, microbiology, genetics, histology and biochemical analysis). Additionally, post-mortem data were linked to ante-mortem health data extracted from Danish national health registers.

Discussion: The SURVIVE autopsy procedure, including tissue sampling and bio banking, has been shown to be effective. We expect that the SURVIVE study will provide unique opportunities to unravel the mechanisms and causes of premature death in persons with SMI. We also expect that identifying prognostic biomarkers for comorbidities will contribute to prevention of premature deaths and comorbidities in persons with SMI.

Open access

Aura Rusu, G. Hancu and Á. Gyéresi

Abstract

Introduction: Antibacterial quinolones class comprises a series of synthetic antibacterial agents, following the model of nalidixic acid. Because of their common 6-fl uorosubtituent on the quinolone ring, fluroquinolones are the most potent analogues with extended spectrum of activity and great pharmacokinetic properties. The applicability of capillary zone electrophoresis for the separation of fl uoroquinolones in acidic background electrolyte has been studied, our aim being the development of a capillary zone electrophoresis method for the simultaneous separation of six fl uoroquinolones and also to optimize the analytical conditions. The six studied fl uoroquinolones were ciprofloxacin, enoxacin, enrofloxacin, moxifloxacin, ofloxacin and sarafloxacin.

Material and methods: Preliminary, we studied the electrophoretic behavior of six fluoroquinolones in an acidic pH, which highlighted the possibility of developing a separation method in this area of pH. Electrophoretic parameters infl uencing separation performance were studied and optimized.

Results: A fast and reliable method has been developed, using a background electrolyte containing 100 mM phosphoric acid and the following conditions: applied voltage: + 25 kV, temperature: 20°C, injection pressure 30 mbar - 5 sec, UV detection at 280 nm, capillary: 60 cm (52 cm effective length) x 50 μm, analyte concentration: 167 μg/ml. The separation of the studied fl uoroquinolones was achieved in less than 8 minutes.

Conclusions: Capillary zone electrophoresis using an acidic background electrolyte proved to be an efficient tool in the separation of fluoroquinolones from different generations. Also the proposed methods are particular environment-friendly replacement and improvement of a common high performance liquid chromatography determination with rapid analysis time without using any organic solvents.

Open access

Anthony Singer, Eleni Markoutsa, Alya Limayem, Subhra Mohapatra and Shyam S. Mohapatra

Abstract

Biomedical Nanotechnology (BNT) has rapidly become a revolutionary force that is driving innovation in the medical field. BNT is a subclass of nanotechnology (NT), and often operates in cohort with other subclasses, such as mechanical or electrical NT for the development of diagnostic assays, therapeutic implants, nano-scale imaging systems, and medical machinery. BNT is generating solutions to many conventional challenges through the development of enhanced therapeutic delivery systems, diagnostic techniques, and theranostic therapies. Therapeutically, BNT has generated many novel nanocarriers (NCs) that each express specifically designed physiochemical properties that optimize their desired pharmacokinetic profile. NCs are also being integrated into nanoscale platforms that further enhance their delivery by controlling and prolonging their release profile. Nano-platforms are also proving to be highly efficient in tissue regeneration when combined with the appropriate growth factors. Regarding diagnostics, NCs are being designed to perform targeted delivery of luminescent tags and contrast agents that enhance the NC -aided imaging capabilities and resulting diagnostic accuracy of the presence of diseased cells. This technology has also been advancing the ability for surgeons to practice true precision surgical techniques. Incorporating therapeutic and diagnostic NC-components within a single NC can facilitate both functions, referred to as theranostics, which facilitates real-time in vivo tracking and observation of drug release events via enhanced imaging. Additionally, stimuli-responsive theranostic NCs are quickly developing as vectors for tumor ablation therapies by providing a model that facilitates the location of cancer cells for the application of an external stimulus. Overall, BNT is an interdisciplinary approach towards health care, and has the potential to significantly improve the quality of life for humanity by significantly decreasing the treatment burden for patients, and by providing non-invasive therapeutics that confer enhanced therapeutic efficiency and safety

Open access

Artur Drzewiecki, Małgorzata Bulanda, Katarzyna Talaga, Anna Sodo and Paweł Adamski

-75. 11. Cirillo I, Vaccaro N, Turner K et al.: Pharmacokinetics, safety, and tolerability of doripenem after 0.5-, 1-, and 4-hour infusions in healthy volunteers. J Clin Pharmacol 2009; 49: 798-806. 12. Katsube T, Yano Y, Wajima T et al.: Pharmacokinetic / pharmacodynamic modeling and simulation to determine effective dosage regimens for doripenem. J Pharm Sci 2010; 99: 2483-91. 13. Samtani MN , Flamm R, Kaniga K,Nandy P: Pharmacokinetic-pharmacodynamic-model-guided doripenem dosing in critically ill patients. Antimicrob Agents

Open access

Tahere Kashkolinejad-Koohi, Iraj Saadat and Mostafa Saadat

REFERENCES Bibler MR, Peter TF, Hagler DN, Bode RB, Staneck JL, Thamlikitkul V. (1987). Clinical evaluation of efficacy, pharmacokinetics, and safety of teicoplanin for serious Gram-positive infections. Antimicrob Agents Chemother 31 : 207–212. Eggleston M, Ofosu J. (1988). Teicoplanin, a new agent for gram positive bacterial infection. Infect Control Hosp Epidemiol 9 : 209–211. Glupezynski Y, Lagast H, Auwera PV, Thys JP, Crokaert F, Yourassowsky E, Meunier-Carpentier F, Klastersky J, Kains JP, Serruys-Schoutens E. (1986). Clinical

Open access

Krzysztof Fujarewicz

times for pharmacokinetic experiments, Journal of Pharmacokinetics and Biopharmaceutics   9 (6): 739-756. de Jong, H. (2002). Modeling and simulation of genetic regulatory systems: A literature review, Journal of Computational Biology   9 (1): 67-103. DiStefano, J. J. (1981). Optimized blood sampling protocols and sequential design of kinetic experiments, American Journal of Physiology   9 (240): R259-R265. Fedorov, V. V. (1972). Theory of Optimal Experiments , Academic Press, New York