The success of bottom-up proteomic analysis frequently depends on the efficient removal of contaminants from protein or peptide samples before LC-MS/MS. For a peptide clean-up workflow, single-pot solid-phase-enhanced peptide sample preparation on carboxylate-modified paramagnetic beads (termed SP2) was evaluated for sodium dodecyl sulfate or polyethylene glycol removal from Arabidopsis thaliana tryptic peptides. The robust and efficient 40-min SP2 protocol, tested for 10-ng, 250-ng, and 10-μg peptide samples, was proposed and benchmarked thoroughly against the ethyl acetate extraction protocol. The SP2 protocol on carboxylated magnetic beads proved to be the most robust approach, even for the simultaneous removal of massive sodium dodecyl sulfate (SDS) and polyethylene glycol (PEG) contaminations from AT peptide samples in respect of the LC-MS/MS data outperforming ethyl acetate extraction.
Oleic acid and oleyl alcohol are commonly used permeation and penetration enhancers to facilitate topical drug delivery. Here, we aimed to better understand the mechanism of their enhancing effects in terms of their interactions with the human skin barrier using diclofenac diethylamine (DIC-DEA), a nonsteroidal anti-inflammatory drug for topical pain management. Oleic acid promoted DIC-DEA permeation through ex vivo human skin more rapidly than oleyl alcohol (both applied at 0.75%) due to fluidization of stratum corneum lipids as revealed by infrared spectroscopy. After 12 h, the effect of these enhancers on DIC-DEA permeation leveled off, fluidization was no longer evident, and skin permeabilization was mainly due to the formation of fluid enhancer-rich domains. Contrary to oleyl alcohol, oleic acid adversely affected two indicators of the skin barrier integrity, transepidermal water loss and skin electrical impedance. The content of oleyl alcohol in the stratum corneum was lower than that of oleic acid (even 12 h after the enhancers were removed from the skin surface), but it caused higher DIC-DEA retention in both epidermis and dermis compared to oleic acid. The effects of oleyl alcohol and oleic acid on DIC-DEA permeation and retention in the skin were similar after a single and repeated application (4 doses every 12 h). Thus, oleyl alcohol offers several advantages over oleic acid for topical drug delivery.
- MeSH
- aplikace kožní MeSH
- kožní absorpce * MeSH
- kůže metabolismus MeSH
- kyselina olejová * farmakologie metabolismus MeSH
- lidé MeSH
- mastné alkoholy metabolismus farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- bolest * farmakoterapie MeSH
- dítě MeSH
- fentanyl aplikace a dávkování škodlivé účinky MeSH
- lidé MeSH
- morfin aplikace a dávkování farmakologie škodlivé účinky MeSH
- opioidní analgetika * aplikace a dávkování klasifikace škodlivé účinky MeSH
- oxykodon aplikace a dávkování farmakologie MeSH
- tramadol aplikace a dávkování farmakologie škodlivé účinky MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- přehledy MeSH
Signal transduction by the high-affinity IgE receptor (FcεRI) depends on membrane lipid and protein compartmentalization. Recently published data show that cells treated with 1-heptanol, a cell membrane fluidizer, exhibit changes in membrane properties. However, the functional consequences of 1-heptanol-induced changes on mast cell signaling are unknown. This study shows that short-term exposure to 1-heptanol reduces membrane thermal stability and dysregulates mast cell signaling at multiple levels. Cells treated with 1-heptanol exhibited increased lateral mobility and decreased internalization of the FcεRI. However, this did not affect the initial phosphorylation of the FcεRI-β chain and components of the SYK/LAT1/PLCγ1 signaling pathway after antigen activation. In contrast, 1-heptanol inhibited SAPK/JNK phosphorylation and effector functions such as calcium response, degranulation, and cytokine production. Membrane hyperfluidization induced a heat shock-like response via increased expression of the heat shock protein 70, increased lateral diffusion of ORAI1-mCherry, and unsatisfactory performance of STIM1-ORAI1 coupling, as determined by flow-FRET. Furthermore, 1-heptanol inhibited the antigen-induced production of reactive oxygen species and potentiated stress-induced plasma membrane permeability by interfering with heat shock protein 70 activity. The combined data suggest that 1-heptanol-mediated membrane fluidization does not interfere with the earliest biochemical steps of FcεRI signaling, such as phosphorylation of the FcεRI-β chain and components of the SYK/LAT/PLCγ1 signaling pathway, instead inhibiting the FcεRI internalization and mast cell effector functions, including degranulation and cytokine production.
- MeSH
- cholesterol MeSH
- cytokiny MeSH
- heptanol MeSH
- mastocyty * MeSH
- signální transdukce * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Pregabalin je široce předepisované léčivo ze skupiny antiepileptik s prokázanými protiúzkostnými a analgetickými účinky. V zahraniční literatuře je popisováno jeho zneužívání, a to včetně rozvoje závislosti. Ve dvou kazuistikách popisují autoři příklady z tuzemské praxe. Je popsána jak závislost vzniklá iatrogenně u pacientky bez předchozí psychiatrické komorbidity, tak závislost u polymorfně závislého pacienta s komorbidní depresivní poruchou.
Pregabalin is a widely prescribed antiepileptic medication with anxiolytic and analgetic effect. Pregabalin abuse and pregabaline addiction are described and studied in literature. In two case studies the authors present cases from the Czech republic. A case of iatrogenic addiction is presented as well as a case of a patient with combined addiction and a comorbid depressive disorder.
- MeSH
- anxiolytika MeSH
- dospělí MeSH
- lidé MeSH
- nežádoucí účinky léčiv MeSH
- opioidní analgetika MeSH
- poruchy spojené s užíváním psychoaktivních látek etiologie terapie MeSH
- pregabalin * aplikace a dávkování farmakologie terapeutické užití MeSH
- tramadol škodlivé účinky terapeutické užití MeSH
- závislost (psychologie) MeSH
- zneužívání léčiv * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- dospělí MeSH
- lidé MeSH
- péče o pacienty v kritickém stavu MeSH
- pokus o sebevraždu MeSH
- tukové emulze intravenózní terapeutické užití MeSH
- venlafaxin hydrochlorid * otrava MeSH
- výsledek terapie MeSH
- zneužívání léků na předpis MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
x
x
- MeSH
- bolest farmakoterapie MeSH
- dospělí MeSH
- fixní kombinace léků MeSH
- lidé MeSH
- paracetamol * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- senioři MeSH
- tolerance léku MeSH
- tramadol * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
An important feature of orodispersible tablets (ODTs) is the convenient administration of the drugs, in some cases, faster onset of action, stability maintenance, and dose precision. This work focused on the preparation of ODTs containing mannitol-based co-processed excipients Prosolv® ODT G2, Ludiflash® and Parteck® ODT in combination with tramadol, captopril, and domperidone by direct compression. Prosolv® ODT G2 showed high energy of plastic deformation due to the content of microcrystalline cellulose. Parteck® ODT provided compact tablets due to the content of granulated mannitol. All drugs decreased tensile strength, increased friability, prolonged disintegration time, and decreased the porosity of tablets. Tablets containing Prosolv® ODT G2 with captopril, domperidone, and tramadol; and Parteck® ODT with domperidone met the requirements for ODTs production, i.e., friability ≤ 1% and disintegration time ≤ 180 s, fast wetting time, high water absorption ratio, and adequate tensile strength. The disintegration time was tested using both the pharmacopeial method and the BJKSN-13 apparatus. The results indicate the significant difference between these methods, with the disintegration time being longer when tested with the BJKSN-13 instrument.
Pharmaceutical nanocrystals represent a promising new formulation that combines the benefits of bulk crystalline materials and colloidal nanoparticles. To be applied in vivo, nanocrystals must meet several criteria, namely colloidal stability in physiological media, non-toxicity to healthy cells, avoidance of macrophage clearance, and bioactivity in the target tissue. In the present work, curcumin, a naturally occurring poorly water-soluble molecule with a broad spectrum of bioactivity has been considered a candidate substance for preparing pharmaceutical nanocrystals. Curcumin nanocrystals in the size range of 40-90 nm were prepared by wet milling using the following combination of steric and ionic stabilizers: Tween 80, sodium dodecyl sulfate, Poloxamer 188, hydroxypropyl methylcellulose, phospholipids (with and without polyethylene glycol), and their combination. Nanocrystals stabilized by a combination of phospholipids enriched with polyethylene glycol proved to be the most successful in all evaluated criteria; they were colloidally stable in all media, exhibited low macrophage clearance, and proved non-toxic to healthy cells. This curcumin nanoformulation also exhibited outstanding anticancer potential comparable to commercially used cytostatics (IC50 = 73 μM; 24 h, HT-29 colorectal carcinoma cell line) which represents an improvement of several orders of magnitude when compared to previously studied curcumin formulations. This work shows that the preparation of phospholipid-stabilized nanocrystals allows for the conversion of poorly soluble compounds into a highly effective "solution-like" drug delivery system at pharmaceutically relevant drug concentrations.
- MeSH
- deriváty hypromelózy MeSH
- dodecylsíran sodný chemie MeSH
- fosfolipidy MeSH
- kurkumin * chemie farmakologie MeSH
- léčivé přípravky MeSH
- makrofágy MeSH
- nanočástice * chemie MeSH
- poloxamer chemie MeSH
- polyethylenglykoly chemie MeSH
- polysorbáty MeSH
- rozpustnost MeSH
- velikost částic MeSH
- voda MeSH
- Publikační typ
- časopisecké články MeSH
