Maghemite (γ-Fe2O3) nanoparticles were obtained by coprecipitation of ferrous and ferric salts in an alkaline medium followed by oxidation; the nanoparticles were coated with poly(N,N-dimethylacrylamide) (PDMA) and characterized by transmission electron microscopy, attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering, thermogravimetric and elemental analyses, and magnetic measurements in terms of particle morphology, size, polydispersity, amount of coating, and magnetization, respectively. The effects of α-tocopherol (Toc) and its phenolic (Toc-6-OH) and acetate (Toc-6-Ac) derivatives on Fe2+ release from γ-Fe2O3@PDMA, as well as from γ-Fe2O3 and CuFe2O4 nanoparticles (controls), were examined in vitro using 1,10-phenanthroline. The presence of tocopherols enhanced spontaneous Fe2+ release from nanoparticles, with Toc-6-OH exhibiting more activity than neat Toc. All of the nanoparticles tested were found to initiate blood lipid oxidation in a concentration-dependent manner, as determined by analysis of 2-thiobarbituric acid reactive species. Wistar rats with Walker-256 carcinosarcoma (a model of mammary gland carcinosarcoma) received Toc-6-Ac, magnetic nanoparticles, or their combination per os, and the antitumor activity of each treatment was determined in vivo. γ-Fe2O3@PDMA nanoparticles exhibited increased antitumor activity compared to both commercial CuFe2O4 particles and the antitumor drug doxorubicin. Moreover, increased antitumor activity was observed after combined administration of γ-Fe2O3@PDMA nanoparticles and Toc-6-Ac; however, levels of bilirubin, aspartate aminotransferase, and white bloods normalized and did not differ from those of the intact controls. The antitumor activity of the γ-Fe2O3 nanoparticles strongly correlated with Fe2+ release from the nanoparticles but not with nanoparticle-initiated lipid peroxidation in vitro.

• MeSH
• akrylamidy chemie   MeSH
• alfa-tokoferol aplikace a dávkování   chemie   MeSH
• experimentální nádory mléčných žláz farmakoterapie   MeSH
• karcinosarkom farmakoterapie   MeSH
• lékové transportní systémy metody   MeSH
• magnetické nanočástice aplikace a dávkování   chemie   MeSH
• potkani Wistar MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• transmisní elektronová mikroskopie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• železité sloučeniny chemie   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

In this study we describe the immunogenicity results from a subset of older people (N = 5187) who participated in a Phase 3 randomized, observer-blinded trial of AS03-TIV versus TIV (Fluarix™) (ClinicalTrials.gov, NCT00753272). Participants received one dose of AS03-TIV or TIV in each study year and antibody titers against the vaccine strains were assessed using hemagglutination-inhibition (HI) assay at 21 d and 180 d post-vaccination in each vaccine group in the 2008/09 (Year 1) and 2009/10 (Year 2) influenza seasons. Manufacturing consistency of 3 lots of AS03-TIV for HI antibody responses in Year 1 was a co-primary objective. In a post-hoc analysis, a statistical regression model included 4830 subjects in whom immunogenicity and laboratory-confirmed attack rate data were available; the analysis was performed to assess HI antibody titers against A/H3N2 as a correlate of protection for laboratory-confirmed A/H3N2 influenza. AS03-TIV and TIV elicited strong HI antibody responses against each vaccine strain 21 d post-vaccination in both years. The manufacturing consistency of 3 lots of AS03-TIV was demonstrated. In both years and each vaccine group, HI antibody responses were lower for A/H1N1 than the other vaccine strains. Day 180 seroconversion rates (proportion with ≥4-fold increase in titer compared with pre-vaccination titer) in Year 1 in the AS03-TIV and TIV groups, respectively, were 87.7% and 74.1% for A/H3N2, 69.7% and 59.6% for influenza B, and 58.3% and 47.4% for A/H1N1. The post-hoc statistical model based on A/H3N2 attack rates and HI antibody titers estimated that a 4-fold increase in post-vaccination titers against A/H3N2 was associated with a 2-fold decrease in the odds of A/H3N2 infection.

• MeSH
• alfa-tokoferol aplikace a dávkování   MeSH
• chřipka lidská prevence a kontrola   virologie   MeSH
• fixní kombinace léků MeSH
• inaktivované vakcíny aplikace a dávkování   imunologie   MeSH
• jednoduchá slepá metoda MeSH
• lidé MeSH
• polysorbáty aplikace a dávkování   MeSH
• protilátky virové krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• skvalen aplikace a dávkování   MeSH
• testy inhibice hemaglutinace MeSH
• vakcíny proti chřipce aplikace a dávkování   imunologie   MeSH
• virus chřipky A, podtyp H3N2 imunologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

Pro-apoptotic analogues of vitamin E (VE) exert selective anti-cancer effect on various animal cancer models. Neither suitable formulation of α-tocopheryl succinate (α-TOS), representative semi-synthetic VE analogue ester, nor suitable formulations of the other VE analogues for clinical application have been reported yet. The major factor limiting the use of VE analogues is their low solubility in aqueous solvents. Due to the hydrophobic character of VE analogues, liposomes are predetermined as suitable delivery system. Liposomal formulation prevents undesirable side effects of the drug, enhances the drug biocompatibility, and improves the drug therapeutic index. Liposomal formulations of VE analogues especially of α-TOS and α-tocopheryl ether linked acetic acid (α-TEA) have been developed. The anti-cancer effect of these liposomal VE analogues has been successfully demonstrated in pre-clinical models in vivo. Present achievements in: (i) preparation of liposomal formulations of VE analogues, (ii) physico-chemical characterization of these developed systems and (iii) testing of their biological activity such as induction of apoptosis and evaluation of anti-cancer effect are discussed in this review.

• MeSH
• alfa-tokoferol aplikace a dávkování   MeSH
• apoptóza účinky léků   MeSH
• farmaceutická chemie MeSH
• lékové transportní systémy metody   MeSH
• lidé MeSH
• lipidy chemie   MeSH
• liposomy MeSH
• nádory farmakoterapie   patologie   MeSH
• protinádorové látky aplikace a dávkování   chemie   MeSH
• rozpustnost MeSH
• vitamin E aplikace a dávkování   analogy a deriváty   chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

α-Tocopheryl succinate (TOS), a redox-silent analogue of vitamin E, suppresses cell growth in a number of clinical and experimental cancers, inhibits mitochondrial succinate dehydrogenase (SDH) and activates reactive oxygen species (ROS) generation. The aim of this study was to test whether TOS also inhibits glycerol-3-phosphate dehydrogenase (mGPDH), another flavoprotein-dependent enzyme of the mitochondrial respiratory chain because there are differences between electron transfer pathway from SDH and mGPDH to coenzyme Q pool. For our experiments brown adipose tissue mitochondria with high expression of mGPDH were used. Our data showed that inhibition of glycerol-3-phosphate (GP)-dependent oxygen consumption by TOS was more pronounced than the succinate (SUC)-dependent one (50% inhibition was reached at 10 μmol/l TOS vs. 80 μmol/l TOS, respectively). A comparison of the inhibitory effect of TOS on GP-oxidase, GP-cytochrome c oxidoreductase and GP-dehydrogenase activities showed that TOS directly interacts with the dehydrogenase. After TOS application the GP-dependent generation of ROS was highly depressed. It may thus be concluded that TOS-induced inhibition of mGPDH is more pronounced than TOS-induced inhibition of SDH and that the inhibitory effect of TOS for both substrates is exerted at different locations of the particular dehydrogenases. Our data indicate that the inhibition of mGPDH activity could also play a role in TOS-induced growth suppression in neoplastic cells.

• MeSH
• alfa-tokoferol aplikace a dávkování   MeSH
• glycerolfosfátdehydrogenasa antagonisté a inhibitory   biosyntéza   MeSH
• hnědá tuková tkáň enzymologie   MeSH
• karcinogeneze genetika   MeSH
• křečci praví MeSH
• lidé MeSH
• mitochondrie účinky léků   enzymologie   MeSH
• nádory farmakoterapie   enzymologie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• spotřeba kyslíku účinky léků   MeSH
• zvířata MeSH
• Check Tag
• křečci praví MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Příspěvek nabízí možnosti individuální přípravy nesterilních lékových forem k aplikaci do gastrointestinálního traktu se systémovým účinkem určených pro použití v pediatrii u pěti léčivých látek, které jsou v současnosti nově dostupné pro magistraliter přípravu v lékárnách. Jedná se o domperidon, propranolol-hydrochlorid, sotalol-hydrochlorid, promethazin-hydrochlorid a tokoferol-alfa-acetát. Dochází tak k rozšíření možností terapie uvedenými látkami a velikost dávky lze přizpůsobit individuálním požadavkům dětského pacienta. Článek podává stručné informace o jednotlivých látkách a uvádí příklady magistraliter receptur vhodných pro použití v pediatrii.

This paper offers extemporaneous preparation possibilities of non-sterile dosage forms intended for gastrointestinal application with systemic effect for children in five compounds newly available for magistral preparation in pharmacies. These new substances are domperidon, propranolol hydrochloride, sotalol hydrochloride, promethazine hydrochloride and alpha tocopherol acetate. This increases treatment possibilities with these new substances, and the doses can be customized to the paediatric patient. This article gives brief information about these compounds and presents examples of compounded formulas suitable for use in paediatric practice.

• Klíčová slova
• domperidonová perorální suspenze, infantilní hemangiom, promethazinový sirup, sotalol - sirup, propranolol - roztok,
• MeSH
• alfa-tokoferol aplikace a dávkování   terapeutické užití   MeSH
• aplikace orální MeSH
• aplikace rektální MeSH
• čípky MeSH
• dítě MeSH
• domperidon aplikace a dávkování   terapeutické užití   MeSH
• lékové roztoky MeSH
• lidé MeSH
• pediatrie * MeSH
• příprava léků * MeSH
• promethazin aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• propranolol aplikace a dávkování   terapeutické užití   MeSH
• receptáře jako téma * MeSH
• sotalol aplikace a dávkování   terapeutické užití   MeSH
• tablety MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• přehledy MeSH

• Klíčová slova
• nově dostupné substance, inovativní receptury, možnosti individuální přípravy, legislativa individuální přípravy, problematiky individuální přípravy,
• MeSH
• alfa-tokoferol aplikace a dávkování   terapeutické užití   MeSH
• betamethason analogy a deriváty   aplikace a dávkování   terapeutické užití   MeSH
• dermatologické látky terapeutické užití   MeSH
• dermatologie trendy   MeSH
• fixní kombinace léků MeSH
• fluocinolonacetonid aplikace a dávkování   terapeutické užití   MeSH
• klotrimazol aplikace a dávkování   terapeutické užití   MeSH
• kožní nemoci farmakoterapie   MeSH
• kyselina pantothenová aplikace a dávkování   terapeutické užití   MeSH
• léčivé přípravky zásobování a distribuce   MeSH
• lékové formy MeSH
• lidé MeSH
• nystatin aplikace a dávkování   terapeutické užití   MeSH
• příprava léků metody   MeSH
• promethazin aplikace a dávkování   terapeutické užití   MeSH
• triamcinolonacetonid aplikace a dávkování   terapeutické užití   MeSH
• zákonodárství lékové MeSH
• Check Tag
• lidé MeSH

alpha-Tocopheryl succinate (alpha-TOS) is a semisynthetic analogue of alpha-tocopherol with selective toxicity to the cancer cells and anticancer activity in vivo. Yet, no suitable formulation of alpha-TOS for medical application has been reported. Various formulations, for example, solutions in organic solvents, oil emulsions and vesicules prepared by spontaneous vesiculation, polyethylene glycol conjugates and liposomes of various compositions have been tested. We developed and characterised a stable lyophilised liposome-based alpha-TOS formulation. alpha-TOS (15 mol%) was incorporated into large oligolamellar vesicles (OLVs) composed of soy phosphatidylcholine (SPC) by the method of lipid film hydration followed by extrusion through polycarbonate filters. Stabilised liposomal formulation was prepared by lyophilisation in the presence of sucrose (molar ratio lipid/sucrose, 1:5). The size distribution of the liposomes (130-140 nm, polydispersity index 0.14) as well as the stable lipid and alpha-TOS contents were preserved during storage in the lyophilised form at 2-8 degrees C for at least 6 months. The data indicate good physical and chemical stability of the lyophilised preparation of alpha-TOS liposomes that can be used in clinical medicine.

• MeSH
• alfa-tokoferol aplikace a dávkování   chemie   MeSH
• lipidy chemie   MeSH
• liposomy MeSH
• lyofilizace MeSH
• lysofosfolipidy chemie   MeSH
• peroxid vodíku chemie   MeSH
• povrchové vlastnosti MeSH
• příprava léků metody   MeSH
• protinádorové látky aplikace a dávkování   chemie   MeSH
• skladování léků MeSH
• stabilita léku MeSH
• transmisní elektronová mikroskopie MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The vitamin E analogue alpha-tocopheryl succinate (alpha-TOS) is an efficient anti-cancer drug. Improved efficacy was achieved through the synthesis of alpha-tocopheryl maleamide (alpha-TAM), an esterase-resistant analogue of alpha-tocopheryl maleate. In vitro tests demonstrated significantly higher cytotoxicity of alpha-TAM towards cancer cells (MCF-7, B16F10) compared to alpha-TOS and other analogues prone to esterase-catalyzed hydrolysis. However, in vitro models demonstrated that alpha-TAM was cytotoxic to non-malignant cells (e.g. lymphocytes and bone marrow progenitors). Thus we developed lyophilized liposomal formulations of both alpha-TOS and alpha-TAM to solve the problem with cytotoxicity of free alpha-TAM (neurotoxicity and anaphylaxis), as well as the low solubility of both drugs. Remarkably, neither acute toxicity nor immunotoxicity implicated by in vitro tests was detected in vivo after application of liposomal alpha-TAM, which significantly reduced the growth of cancer cells in hollow fiber implants. Moreover, liposomal formulation of alpha-TAM and alpha-TOS each prevented the growth of tumours in transgenic FVB/N c-neu mice bearing spontaneous breast carcinomas. Liposomal formulation of alpha-TAM demonstrated anti-cancer activity at levels 10-fold lower than those of alpha-TOS. Thus, the liposomal formulation of alpha-TAM preserved its strong anti-cancer efficacy while eliminating the in vivo toxicity found of the free drug applied in DMSO. Liposome-based targeted delivery systems for analogues of vitamin E are of interest for further development of efficient and safe drug formulations for clinical trials.

• MeSH
• alfa-tokoferol analogy a deriváty   aplikace a dávkování   farmakologie   MeSH
• farmaceutická chemie MeSH
• lidé MeSH
• liposomy MeSH
• maleimidy aplikace a dávkování   farmakologie   MeSH
• melanom experimentální farmakoterapie   patologie   MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory prsu farmakoterapie   patologie   MeSH
• polyethylenglykoly aplikace a dávkování   farmakologie   MeSH
• protinádorové látky aplikace a dávkování   farmakologie   MeSH
• vitamin E analogy a deriváty   aplikace a dávkování   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• srovnávací studie MeSH

• MeSH
• alfa-tokoferol aplikace a dávkování   farmakologie   metabolismus   MeSH
• hodnocení stavu výživy MeSH
• kardiovaskulární nemoci metabolismus   prevence a kontrola   MeSH
• lidé MeSH
• nedostatek vitaminu E metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH

OBJECTIVE AND BACKGROUND: Asthma is a chronic inflammatory disease in which an oxidant/antioxidant imbalance plays an important role. d-alpha-tocopherol (biologically the most active form of vitamin E) has redox properties and by scavenging the free radicals can act as an antioxidant. The aim of this study was to examine the effects of orally administered alpha-tocopherol in a rat model of allergic asthma. METHODOLOGY: Actively sensitized rats (OA) were treated with alpha-tocopherol (400 mg/kg/day for 10 days) or vehicle; 1 h after the last dose, they were challenged with antigen aerosol. The antigen-induced airway hyperresponsiveness to direct bronchoconstrictor (serotonin), the inflammatory cell infiltrate and histological changes were determined 1 or 24 h after the antigen challenge. RESULTS: Alpha-tocopherol pretreatment was not significantly effective at reducing the studied parameters when compared with controls, even though there was a tendency to a reduction in bronchial responsiveness and in eosinophil and neutrophil infiltration. CONCLUSION: Alpha-tocopherol when administered in the chosen study design in an animal model of asthma had no major effect on airway inflammation. The effect of antioxidants deserves further evaluation.

• MeSH
• aerosoly MeSH
• alfa-tokoferol aplikace a dávkování   terapeutické užití   MeSH
• aplikace orální MeSH
• bronchiální astma farmakoterapie   MeSH
• bronchoalveolární lavážní tekutina cytologie   chemie   MeSH
• financování organizované MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• ovalbumin imunologie   MeSH
• plíce imunologie   patologie   účinky léků   MeSH
• potkani Wistar MeSH
• serotonin farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH