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Antisense oligonucleotides (chemically modified oligonucleotides) are generally 12-30 bases in length and are under intense evaluation as therapeutic agents for the treatment of cancer and viral infections. The stability of these compounds against various endo- and exonucleases in biological media is a critical question in drug development. An automatic CE system with entangled polymer solution...
System suitability tests (SSTs) are essential for ensuring reliability and robustness of HPLC systems, and instil confidence in results obtained. Since the HPLC column is the most important part of a system, both chiral and standard packing phases should be monitored on a regular and frequent basis. In this way an adequate level of performance and integrity of the system (and HPLC column) can be...
Mitogen activated protein kinase plays a key role in cellular processes. Besides regulation of the activity of other serine/threonine kinases, MAP kinases are involved in the regulation of gene expression, cell growth, differentiation and cytoskeletal function.In extracts of U-937 macrophage-like cells mitogen activated protein kinase was stimulated by LDL and oxLDL. A maximum value (161% of the...
Amphiphilic cationic drugs are efficiently taken up by the liver and excreted into bile in a concentrative way. In order to obtain more insight in the potential carrier mechanisms involved we investigated the biliary excretion of the relatively small organic cations tri-n-butyl methylammonium (TBuMA) and azidoprocainamidemethoidide (APM), the bulky cations Rocuronium (Roc) and Vacuronium (Vec), and...
Objective: Negatively charged albumins (NCAs), with the prototypes Suc-HSA and Aco-HSA, are polyanionic proteins with a potent antiviral activity on HIV-1 laboratory strains. In the present study the mechanism of their antiviral action was addressed. Results: Formation of syncytia of infected and uninfected T-lymphocytes was inhibited by the NCAs. Early products of reverse transcription, in cells...
The pharmacokinetics and absolute bioavailability of the enantiomers of diprafenone, a type lc antiarrhythmic drug, were investigated in eight healthy volunteers using a specific enantioselective HPLC procedure. Single doses of diprafenone were administered intravenously (50 mg, 15 minute constant rate infusion) and orally (100 mg tablet).After IV infusion, mean peak plasma levels (C ma ...
For the search of the substances with anti-inflammatory, anti-pyretic and analgetic properties and for definition of the peculiavities of the bound ''structure - action'' based on the amino acids, aromatic and heterocyclic amines and hydrazides of aromatic carboxylic acids, 300 substances - the derivatives of 2-thionethiazolidone-4 - remote structural analogues of acetaminophen and phenazone - were...
Azathioprine (AZA) is an immunosuppressive agent, less toxic and more effective than 6-mercaptopurine (6-MP). Its intracellular metabolites e.g. nucleotides 6-MPN, 6-thioguanine (6-TGN), 6-methylmercaptopurine (6-mMPN) are incorporated into DNA and RNA resulting in cell death. Therefore, AZA and 6-MP itselves are inactive drugs and their monitoring in blood is not worthwhile. The metabolism of...
A modified hepatitis B surface antigen carrying the pre-S2 region (TGP-943) was produced in yeast using recombinant DNA technology and developed as a new type of hepatitis B vaccine.In order to conduct peptide mapping to confirm the amino acid sequence, conditions for enzymatic digestion and cyanogen bromide cleavage were optimized, and an RP-HPLC method that can directly analyze hydrophobic peptides...
Liposomes are a carrier system currently widely investigated for pulmonary drug delivery. Liposome technology offers the means of increasing lung deposition and decreasing the upper respiratory tract distribution as well as prolonging the residence time of active substance within the lower airways. Several cytokines, like IL-1β, IL-6 and TNFα, are intimately involved in initiating and maintaining...
Cationic vesicle-DNA complexes have been shown to exhibit a low to modest transfection in vivo. Because of potential toxicity of such complexes, exposure of DNA to nucleases and inability to incorporate other agents which may promote transfection efficiency, their usefulness may not be as promising as when nucleic acids are incorporated within conventional liposomes. To that end, 10-100 μg of pGL2...
Many terpenes used therapeutically or as flavour and fragrance materials are chiral compounds and are used as components of essential oils.Reports of studies of biological activity of enantiomers have been very scant, but as stereospecifity of drug action is related to the melecular asymmetry of the receptors, differences in biological activity are suspected.The biological action of the enantiomers...
It has been known for a number of years that oligodeoxynucleotides (ODN) form sequence-specific Hoogsteen hydrogen bonds with double helix DNA, resulting in the formation of a triple helix (Hoogsteen 1959). More recently it has been shown by the work of Helene and workers that this can be used to prevent gene transcription (Helene & Toulme 1990), and the attachment of an intercalator to either...
Determination of beta-endorphin in different regions of the brain revealed changes in beta-endorphin levels under the effect of some psychotropic drugs. Changes in beta-endorphin levels and appropriate peptides in some brain regions might be in correlation with disturbances in neuro-endocrine system. The article deals with changes in beta-endorphin level in the brain and serum of rats after the...
The beneficial effects of topical retinoids have been well recognised in different clinical conditions of acne, psoriasis and skin photodamage (Leyden et al, 1989). Skin irritation, however, is an unwanted side effect (Gilchrest, 1991) associated with topical retinoid treatment. Inhibition of the metabolism of endogenous retinoic acid (RA) is a novel approach to exploit the controlling action of...
Previous studies from our laboratory have showed that dopamine participated in the regulation of immune responses.The aim of this study was to investigate the influence of drugs, which have been effective in the treatment of Parkinson's disease, on the concentrations of dopamine (DA), norepinephrine (NE) and epinephrine (E) in the spleen and the thymus of wistar rats. We also examined the influence...
A new pharmacokinetic model of stratum corneum with two parallel pathways: lipophilic and porous hydrophilic, is not well documented yet. The results of our previous studies supported this model - passive transport of zwitterionic species like amino acids and baclofen was described. Examination of pharmacokinetics of baclofen penetrating through the skin from aqueous or ethanolic solutions in the...
Rifampicin is often taken orally over prolonged periods for the treatment of mycobacterial infections. However compliance is poor, resulting in treatment failure and drug resistance. To overcome this problem, biodegradable polylactide(PLA) and polylactide-co-glycolide(PLGA) may be useful in the development of controlled release parenterals containing antimycobacterial drugs. Rifampicin-loaded microspheres...
Levamisole was tested on the rats of Wister strain, previously immunized with BSA (Bovine Serum Alumin) and suppressed by dexamethasone sodium phosphate. Then, two Levamisole doses of 2.2 mg/kg body weight and 4.4 mg/kg body weight were administered. The group of rats treated with 2.2 mg/kg body weight ashowed increased immune response, and that was proved by the test of early skin hypersensitivity...
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