INTRODUCTION AND OBJECTIVES: Release kinetics of high-sensitivity cardiac troponin (hs-cTn) T and I in patients with acute myocardial infarction (AMI) are incompletely understood. We aimed to assess whether hs-cTnT/I release in early AMI is near linear. METHODS: In a prospective diagnostic multicenter study the acute release of hs-cTnT and hs-cTnI within 1 and 2hours from presentation to the emergency department was quantified using 3 hs-cTnT/I assays in patients with suspected AMI. The primary endpoint was correlation between hs-cTn changes from presentation to 1 hour vs changes from presentation to 2hours, among all AMI patients and different prespecified subgroups. The final diagnosis was adjudicated by 2 independent cardiologists, based on serial hs-cTnT from the serial study blood samples and additional locally measured hs-cTn values. RESULTS: Among 2437 patients with complete hs-cTnT data, AMI was the adjudicated diagnosis in 376 patients (15%). For hs-cTnT, the correlation coefficient between 0- to 1-hour change and 0- to 2 hour change was 0.931 (95%CI, 0.916-0.944), P <.001. Similar findings were obtained with hs-cTnI (Architect) with correlation coefficients between 0- to 1-hour change and 0- to 2 hour change of 0.969 and hs-cTnI (Centaur) of 0.934 (P <.001 for both). Findings were consistent among type 1 and type 2 AMI and in the subgroup of patients presenting very early after chest pain onset. CONCLUSIONS: Patients presenting with early AMI showed a near linear release of hs-cTnT and hs-cTnI. This near linearity provides the pathophysiological basis for rapid diagnostic algorithms using 0- to 1-hour changes as surrogates for 0- to 2 hour or 0- to 3 hour changes. Registered at ClinicalTrials.gov (Identifier: NCT00470587).

• Klíčová slova
• Acute myocardial infarction, Cardiac troponin release, Cinética de liberación linear, Infarto agudo de miocardio, Liberación de troponina cardiaca, Linear release kinetics,
• MeSH
• biologické markery MeSH
• infarkt myokardu * diagnóza   MeSH
• kinetika MeSH
• lidé MeSH
• prospektivní studie MeSH
• troponin I MeSH
• troponin T * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• biologické markery MeSH
• troponin I MeSH
• troponin T * MeSH

The application of polymer-based drug delivery systems is advantageous for improved pharmacokinetics, controlled drug release, and decreased side effects of therapeutics for inflammatory disease. Herein, we describe the synthesis and characterization of linear N-(2-hydroxypropyl)methacrylamide-based polymer conjugates designed for controlled release of the anti-inflammatory drug dexamethasone through pH-sensitive bonds. The tailored release rates were achieved by modifying DEX with four oxo-acids introducing reactive oxo groups to the DEX derivatives. Refinement of reaction conditions yielded four well-defined polymer conjugates with varied release profiles which were more pronounced at the lower pH in cell lysosomes. In vitro evaluations in murine peritoneal macrophages, human synovial fibroblasts, and human peripheral blood mononuclear cells demonstrated that neither drug derivatization nor polymer conjugation affected cytotoxicity or anti-inflammatory properties. Subsequent in vivo tests using a murine arthritis model validated the superior anti-inflammatory efficacy of the prepared DEX-bearing conjugates with lower release rates. These nanomedicines showed much higher therapeutic activity compared to the faster release systems or DEX itself.

• Klíčová slova
• Controlled drug release, Dexamethasone, HPMA, Hydrazone bond, Polymer conjugates,
• MeSH
• antiflogistika terapeutické užití   MeSH
• dexamethason MeSH
• doxorubicin chemie   MeSH
• leukocyty mononukleární * MeSH
• lidé MeSH
• myši MeSH
• nanomedicína MeSH
• nosiče léků chemie   MeSH
• polymery chemie   MeSH
• revmatické nemoci * MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika MeSH
• dexamethason MeSH
• doxorubicin MeSH
• nosiče léků MeSH
• polymery MeSH

The development of new drug delivery platforms including the use of nanotechnology has been found of great interest in recent years. Two different loading approaches of the model antimycotic drug clotrimazole into the nanofibrous polycaprolactone and polydioxanone structures including electrospinning of a drug-polymer blend and impregnation of nanofibers with drug have been tested. The final amount of clotrimazole in the nanofibrous materials was determined by HPLC analysis and Raman spectroscopy. The electrospinning of blend approach allowed the adsorption of clotrimazole in a quantity of up to 30 % using mixtures with polymer/clotrimazole ratios from 2:1 to 8:1 (w/w). Ethanolic clotrimazole solutions with concentrations from 2.5 to 3.5 mg L-1 were used for adsorbing clotrimazole in blank nanofibers for 1-3 h with final clotrimazole content ranging from 3.0 to 5.7 %. Furthermore, a comparative liberation study including comparison with commercially available creams was carried out in low pressure flow system. The results obtained confirmed well controlled release of clotrimazole from both types of nanofibers. Compared to commercial pharmaceutical formulations containing 1 % clotrimazole where first-order release kinetics was observed, nanofibrous materials provided linear controlled release (zero-order kinetics) in the tested 3 h period.

• Klíčová slova
• Automation, Drug release, Electrospinning, Nanofibers, Polycaprolactone, Polydioxanone,
• MeSH
• klotrimazol * chemie   MeSH
• léky s prodlouženým účinkem MeSH
• nanovlákna * chemie   MeSH
• polymery chemie   MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• klotrimazol * MeSH
• léky s prodlouženým účinkem MeSH
• polymery MeSH

The aim of this study is to present the possibility of using of co-processed dry binders for formulation of matrix tablets with drug controlled release. Hydrophilic matrix tablets with tramadol hydrochloride, hypromellose and different co-processed dry binders were prepared by direct compression method. Hypromelloses Methocel™ K4M Premium CR or Methocel™ K100M Premium CR were used as controlled release agents and Prosolv® SMCC 90 or Disintequik™ MCC 25 were used as co-processed dry binders. Homogeneity of the tablets was evaluated using scanning electron microscopy and energy dispersive X-ray microanalysis. The release of tramadol hydrochloride from prepared formulations was studied by dissolution test method. The dissolution profiles obtained were evaluated by non-linear regression analysis, release rate constants and other kinetic parameters were determined. It was found that matrix tablets based on Prosolv® SMCC 90 and Methocel™ Premium CR cannot control the tramadol release effectively for >12h and tablets containing Disintequik™ MCC 25 and Methocel™ Premium CR >8h.

• Klíčová slova
• Co-processed dry binders, Dissolution kinetics, Hypromellose, Matrix tablets, Tramadol hydrochloride,
• MeSH
• deriváty hypromelózy chemie   farmakokinetika   MeSH
• farmaceutická chemie metody   MeSH
• hydrofobní a hydrofilní interakce * MeSH
• rozpustnost MeSH
• tablety MeSH
• tramadol chemie   farmakokinetika   MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• deriváty hypromelózy MeSH
• tablety MeSH
• tramadol MeSH

Photoabsorption and subsequent photodissociation of two structural isomers of Ar(3) (+) are studied via semiclassical non-adiabatic dynamics simulations. Several experimental observables are simulated under various plausible experimental conditions with the main emphasis on the differences between the data produced for the two isomers. They include photoabsorption cross section, total kinetic energy released, fragments kinetic energy distributions, and distribution of the total kinetic energy among photofragments represented via Dalitz plots. The ability of the parameters to discriminate between the two isomers is analyzed through a thorough comparison with available experimental data. We show that the recently recorded experimental Dalitz plots [V. Lepère, Y. J. Picard, M. Barat, J. A. Fayeton, B. Lucas, and K. Béroff, J. Chem. Phys. 130, 194301 (2009)] correspond to a hot mixture of distorted linear-like and perpendicular-like structures where linear-like structures prevail.

• Publikační typ
• časopisecké články MeSH

First-order release kinetics is characterized by a linear dependence of the release rate on the released amount of the active ingredient, the triple of the absolute value of the exponent of the exponential function expressing the reactive fractal dimension DR. Scopolamine bromide release from hydroxypropylmethylcellulose hydrogel was first expressed by first-order kinetics with an estimated DR ranging from 2.98-3.00. The employment of an exponential equation with the exponent of release n renders it possible to make an assumption about the mechanism of release. Within a range of n = 0.505-0.550, estimated DR = 2.46-2.94. In this region, release by means of the mechanism of Fick's diffusion prevails. DR = (3/n)-3 generally holds true for the relationship between both variables, which makes it possible to use the knowledge gained in the experimental influencing of the exponent of release in the examination of the relationship between the reactive fractal dimension and the mechanism of release of scopolamine bromide from hydrogel. An increase in the exponent of release markedly decreases the corresponding values of reactive fractal dimension.

• MeSH
• farmaceutická chemie MeSH
• PEG-DMA hydrogel chemie   MeSH
• rozpustnost MeSH
• skopolamin chemie   MeSH
• tablety MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• PEG-DMA hydrogel MeSH
• skopolamin MeSH
• tablety MeSH

As proven in clinical trials, superficial fungal infections can be effectively treated by single topical application of terbinafine hydrochloride (Ter-HCl) in a film forming system (FFS). Poly(lactic-co-glycolic acid) (PLGA) derivatives, originally synthesized with intention to get carriers with optimized properties for drug delivery, and multifunctional plasticizers - ethyl pyruvate, methyl salicylate, or triacetin - were used for formulation of Ter-HCl loaded FFSs. After spraying, a biodegradable, transparent, adhesive, and occlusive thin layer is formed on the skin, representing drug depot. In situ formed films were characterized by thermal, structural, viscoelastic, and antifungal properties as well as drug release and skin penetration. DSC and SEM showed fully amorphous films with Ter-HCl dissolved in PLGA in high concentration (up to 15%). FFSs are viscoelastic fluids with viscosity which can be easily adjusted by the type of plasticizer used and its concentration. The formulations showed excellent bioadhesion properties, thus ensuring persistence on the skin. In situ film based on branched PLGA/A plasticized with 10% of ethyl pyruvate allowed prolonged release of Ter-HCl by linear kinetics for the first 6 days with a total time of almost 14 days. During ex vivo human skin penetration experiment, Ter-HCl was found to be located only in its target layer, the epidermis. According to our results, plasticized branched PLGA derivatives loaded by Ter-HCl are suitable for the development of FFSs for superficial fungal infections treatment.

• Klíčová slova
• Bioadhesion, Drug release, FFS, PLGA, Skin penetration, Terbinafine hydrochloride,
• MeSH
• antifungální látky MeSH
• lidé MeSH
• mykózy * MeSH
• nosiče léků * MeSH
• terbinafin MeSH
• uvolňování léčiv MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antifungální látky MeSH
• nosiče léků * MeSH
• terbinafin MeSH

A second messenger role for arachidonic acid (AA) in the regulation of the high-affinity choline uptake (HACU) was suggested. It was reported that micromolar concentrations of AA applied in vitro decreased the HACU values and increased the specific binding of [3H]hemicholinium-3 ([3H]HCh-3). It was published that L-glutamic acid (GA) applied in vivo produced a fall in the HACU values. In addition, GA liberates free AA. In this study, an ability of GA to influence in vitro the activity of presynaptic cholinergic nerve terminals via its effect on the release of AA is investigated in hippocampal synaptosomes of young Wistar rats. Millimolar concentrations of GA decrease both the high- and low-affinity choline uptake, the specific as well as nonspecific binding of [3H]HCh-3 and the activity of Na+, K(+)-ATPase. Kinetic analysis (Lineweaver-Burk and Scatchard plots) reveals a change in Vmax and Bmax, but not in KM and KD. It appears very likely that under normal conditions GA applied in vitro is not able to change markedly the choline transport via its effect on the release of AA. Results confirm the hypothesis about an indirect inhibitory role for glutamatergic receptors on cholinergic cells.

• MeSH
• biologický transport účinky léků   MeSH
• cholin farmakokinetika   MeSH
• hemicholinium 3 metabolismus   MeSH
• hipokampus cytologie   účinky léků   metabolismus   MeSH
• krysa rodu Rattus MeSH
• kyselina arachidonová metabolismus   farmakologie   MeSH
• kyselina glutamová farmakologie   MeSH
• lineární modely MeSH
• neurony účinky léků   metabolismus   MeSH
• potkani Wistar MeSH
• techniky in vitro MeSH
• vazebná místa MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cholin MeSH
• hemicholinium 3 MeSH
• kyselina arachidonová MeSH
• kyselina glutamová MeSH

A two-compartment disposition model of ascorbic acid (AA) pharmacokinetics with saturable and time-constrained intestinal absorption was developed. The model was fitted to pharmacokinetic data obtained after oral administration to nine healthy volunteers of two effervescent dosage forms differing in AA content: Celaskon 60 mg (CK60) and Celaskon 500 mg (CK500). It was demonstrated that in the case of CK500 less than 30% of the dose was absorbed as compared with CK60. Parameters of the AA nonlinear absorption kinetics were assessed by simultaneous fitting of mean concentration-time data for both doses and placebo. The relatively short duration of absorption found (3.2 h) can explain the failure of past attempts to increase the AA bioavailability using sustained-release dosage forms. Model simulation showed that the ingestion of 60 mg with 3-4 h intervals is optimal for maximal bioavailability of AA.

• MeSH
• biologická dostupnost MeSH
• dospělí MeSH
• kyselina askorbová krev   farmakokinetika   MeSH
• lidé MeSH
• nelineární dynamika MeSH
• tablety MeSH
• teoretické modely MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• kyselina askorbová MeSH
• tablety MeSH

The chemotactic movement of decanol droplets in aqueous solutions of sodium decanoate in response to concentration gradients of NaCl has been investigated. Key parameters of the chemotactic response, namely the induction time and the migration velocity, have been evaluated as a function of the sodium decanoate concentration and the NaCl concentration gradient. The ability of the decanol droplets to migrate in concentration gradients has been demonstrated not only in a linear chemotactic assay but also in a topologically complex environment. Additionally, the ability to reverse the direction of movement repeatedly, to carry and release a chemically reactive cargo, to select a stronger concentration gradient from two options, and to initiate chemotaxis by an external temperature stimulus have been demonstrated.

• MeSH
• časové faktory MeSH
• chlorid sodný chemie   MeSH
• kinetika MeSH
• kyseliny dekanové chemie   MeSH
• mastné alkoholy chemie   MeSH
• mikroskopie MeSH
• pohyb těles MeSH
• povrchové napětí MeSH
• teplota MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chlorid sodný MeSH
• decanoic acid MeSH Prohlížeč
• kyseliny dekanové MeSH
• mastné alkoholy MeSH
• n-decyl alcohol MeSH Prohlížeč