The activity of transdermal permeation enhancers is usually evaluated in vitro on human or animal skin, but skin samples can be hard to source and highly variable. To provide a more consistent basis for evaluating the activity of permeation enhancers, we prepared relatively simple and inexpensive artificial membranes that imitate the stratum corneum (SC) lipid matrix. Our membranes were composed of stearic acid, cholesterol, cholesterol sulfate and a ceramide (CER) component consisting of N-2-hydroxystearoyl phytosphingosine (CER[AP]) and/or N-stearoyl phytosphingosine (CER[NP]). First, the permeation of theophylline (TH) and indomethacin (IND) through these membranes was compared with their permeation through porcine skin. Because the mixed CER[AP]/[NP] membrane gave the closest results to skin, this membrane was then used to test the effects of two permeation enhancers: N-dodecyl azepan-2-one (Azone) and (S)-N-acetylproline dodecyl ester (L-Pro2). Both enhancers significantly increased the flux of TH and IND through the skin and, even more markedly, through the lipid membrane, L-Pro2 having a stronger effect than Azone. Thus, our simplified model of the SC lipid membrane based on phytosphingosine CERs appears to be suitable for mimicking skin permeation.

• MeSH
• aplikace kožní MeSH
• azepiny farmakologie   MeSH
• ceramidy metabolismus   MeSH
• cholesterol metabolismus   MeSH
• indomethacin farmakologie   MeSH
• kožní absorpce účinky léků   MeSH
• kůže metabolismus   MeSH
• kyseliny stearové metabolismus   MeSH
• lidé MeSH
• membránové lipidy metabolismus   MeSH
• membrány umělé MeSH
• permeabilita účinky léků   MeSH
• prasata MeSH
• theofylin farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The immunoregulatory properties of mesenchymal stem cells (MSCs) have been well documented in various models in vitro and in vivo. Furthermore, a population of regulatory B cells (Bregs) that produce relatively high concentrations of IL-10 has been recently described. To study the relationship between MSCs and Bregs, we analyzed the effects of MSCs on IL-10 production by lipopolysaccharide (LPS)-activated mouse B cells. The production of IL-10 by B cells remained preserved in the presence of MSCs and was even significantly enhanced by IFN-γ. However, the production of IL-10 was strongly suppressed in cultures containing MSCs and IFN-γ. Preincubation of MSCs, but not of B cells, with IFN-γ induced the suppression of IL-10 secretion in cultures containing MSCs and B cells. The supernatants from IFN-γ-treated MSCs had no inhibitory effect, and the suppression of IL-10 production was abrogated if the MSCs and B cells were separated in a transwell system. Analysis of the gene expression of IFN-γ- or IFN-γ and LPS-treated MSCs revealed a strong upregulation of genes for indoleamine-2,3-dioxygenase (IDO), cyclooxygenase-2 (Cox-2) and programmed cell death-ligand 1 (PD-L1). While the inhibition of IDO activity or the inclusion of the neutralization monoclonal antibody anti-PD-L1 did not abrogate the suppression, indomethacin, an inhibitor of Cox-2, completely inhibited the MSC-mediated suppression of IL-10 production. Accordingly, the production of IL-10 by B cells was inhibited by exogenous prostaglandin E2. The results thus suggest that IFN-γ-treated MSCs strongly inhibit IL-10 production by activated B cells by a mechanism requiring cell contact and involving the Cox-2 pathway.

• MeSH
• aktivace lymfocytů účinky léků   MeSH
• antigeny CD274 antagonisté a inhibitory   genetika   imunologie   MeSH
• B-lymfocyty cytologie   účinky léků   imunologie   MeSH
• cyklooxygenasa 2 genetika   imunologie   MeSH
• difuzní komory kultivační MeSH
• dinoproston farmakologie   MeSH
• indolamin-2,3,-dioxygenasa genetika   imunologie   MeSH
• indomethacin farmakologie   MeSH
• inhibitory cyklooxygenasy farmakologie   MeSH
• interferon gama farmakologie   MeSH
• interleukin-10 antagonisté a inhibitory   genetika   imunologie   MeSH
• kokultivační techniky MeSH
• kultivační média speciální farmakologie   MeSH
• lipopolysacharidy farmakologie   MeSH
• mezenchymální kmenové buňky cytologie   účinky léků   imunologie   MeSH
• mezibuněčná komunikace imunologie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• neutralizující protilátky farmakologie   MeSH
• primární buněčná kultura MeSH
• regulace genové exprese MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The present in vitro experiments demonstrate inhibitory effects of polysubstituted 2-aminopyrimidines on high output production of nitric oxide (NO) and prostaglandin E2 (PGE2) stimulated by interferon-γ and lipopolysaccharide (LPS) in peritoneal macrophages of mouse and rat origin. PGE2 production was inhibited also in LPS-activated human peripheral blood mononuclear cells. A tight dependence of the suppressive activities on chemical structure of pyrimidines was observed. Derivatives containing hydroxyl groups at the C-4 and C-6 positions of pyrimidine ring were devoid of any influence on NO and PGE2. Remarkable inhibitory potential was acquired by the replacement of hydroxyl groups with chlorine, the 4,6-dichloro derivatives being more effective than the monochloro analogues. The effects were further intensified by modification of the amino group at the C-2 position, changing it to the (N,N-dimethylamino)methyleneamino or the formamido ones. There was no substantial difference in the expression of NO-inhibitory effects among derivatives containing distinct types of substituents at the C-5 position (hydrogen, methyl, ethyl, propyl, butyl, phenyl, and benzyl). In contrast to NO, larger substituents then methyl were required to inhibit PGE2 production. Overall, no significant correlation between the extent of NO and PGE2 suppression was observed. The IC50s of derivatives with the strongest effects on both NO and PGE2 were within the range of 2-10 μM. Their NO-inhibitory potential of pyrimidines was stronger than that of non-steroidal anti-inflammatory drugs (NSAIDs) aspirin and indomethacin. The PGE2-inhibitory effectiveness of pyrimidines was about the same as that of aspirin, but weaker as compared to indomethacin. The NO- and PGE2-inhibitory activity of tested pyrimidines has been found associated with decreased expression of iNOS mRNA and COX-2 mRNA, respectively, and with post-translation interactions. Selected NO-/PGE2-inhibitory derivatives decreased severity of intestinal inflammation in murine model of ulcerative colitis.

• MeSH
• antiflogistika nesteroidní aplikace a dávkování   farmakologie   MeSH
• Aspirin farmakologie   MeSH
• cyklooxygenasa 2 genetika   metabolismus   MeSH
• dinoproston antagonisté a inhibitory   biosyntéza   MeSH
• indomethacin farmakologie   MeSH
• interferon gama farmakologie   MeSH
• kolon účinky léků   metabolismus   MeSH
• lidé MeSH
• lipopolysacharidy farmakologie   MeSH
• messenger RNA metabolismus   MeSH
• mitogenem aktivované proteinkinasy metabolismus   MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• oxid dusnatý antagonisté a inhibitory   biosyntéza   MeSH
• peritoneální makrofágy účinky léků   metabolismus   MeSH
• potkani inbrední LEW MeSH
• pyrimidiny aplikace a dávkování   farmakologie   MeSH
• synthasa oxidu dusnatého, typ II genetika   metabolismus   MeSH
• ulcerózní kolitida farmakoterapie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Zidovudine (AZT) is one of the most frequently used antiretroviral drugs in prevention of perinatal transmission of HIV. However, safety concerns on AZT use in pregnancy still persist as severe side effects are associated with AZT exposure in children. In our study we aimed to contribute to current knowledge on AZT transplacental transport and to evaluate potential involvement of the main human drug efflux ATP-binding cassette (ABC) transporters, p-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2) and multidrug resistance-associated proteins 2 and 5 (ABCC2 and ABCC5) in the disposition of AZT between mother and fetus. In order to elucidate this issue we investigated the effect of selected ABC transporters on AZT transepithelial transport across MDCKII cell monolayers. In addition we used the in situ method of dually perfused rat term placenta to further study the role of ABC transporters in AZT transplacental transport. In vitro studies revealed significant effect of ABCB1 and ABCG2 on AZT transport which was subsequently confirmed also on organ level. Lamivudine, an antiretroviral agent commonly co-administered with AZT, did not affect ABC transporter-mediated AZT transfer.

• MeSH
• ABC transportéry antagonisté a inhibitory   metabolismus   MeSH
• akridiny farmakologie   MeSH
• buňky MDCK MeSH
• indomethacin farmakologie   MeSH
• lamivudin farmakologie   MeSH
• látky proti HIV farmakokinetika   MeSH
• lékové interakce MeSH
• placenta metabolismus   MeSH
• potkani Wistar MeSH
• psi MeSH
• techniky in vitro MeSH
• těhotenství MeSH
• tetrahydroisochinoliny farmakologie   MeSH
• zidovudin farmakokinetika   MeSH
• zvířata MeSH
• Check Tag
• psi MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Dna je charakterizována bolestivým zánětem kloubů, nejčastěji prvního metatarzofalangeálního kloubu, vznikajícím v důsledku precipitace krystalů urátu sodného v kloubním prostoru. Obvykle dnu diagnostikujeme na základě klinických kritérií Americké revmatologické společnosti (American College of Rheumatology). Diagnózu lze potvrdit identifikací krystalů urátu sodného v synoviální tekutině postiženého kloubu. Akutní dnu lze léčit nesteroidními antirevmatiky, kortikosteroidy nebo kolchicinem. Aby snížili pravděpodobnost opakování dnavých záchvatů, měli by pacienti omezit konzumaci potravin s vysokým obsahem purinů (např. vnitřností, plodů moře) a vyhýbat se alkoholickým nápojům (zejména pivu) i nápojům slazeným kukuřičným sirupem s vysokým obsahem fruktózy. Konzumace zeleniny a nízkotučných či netučných mléčných výrobků by měla být naopak podporována. Užívání kličkových a thiazidových diuretik může zvyšovat koncentrace kyseliny močové, zatímco užívání losartanu, blokátoru receptorů AT1 pro angiotensin II, zvyšuje exkreci kyseliny močové do moči. Snížení koncentrací kyseliny močové má klíčový význam pro prevenci dnavých záchvatů. Allopurinol a febuxostat jsou léčivy první linie užívanými v prevenci rekurentní dny, kolchicin a/nebo probenecid jsou vyhrazeny pro nemocné, kteří netolerují léčiva první linie nebo u nichž jsou tato léčiva neúčinná. Pacienti léčení farmaky snižujícími koncentrace kyseliny močové by měli zároveň dostávat i nesteroidní antirevmatika, kolchicin nebo nízké dávky kortikosteroidů s cílem omezit výskyt dnavých záchvatů. Léčba by měla pokračovat i poté, co koncentrace kyseliny močové poklesly pod cílovou hodnotu, a to nejméně tři měsíce u osob bez dnavých tofů a nejméně šest měsíců u osob s tofy.

Gout is characterized by painful joint inflammation, most commonly in the first metatarsophalangeal joint, resulting from precipitation of monosodium urate crystals in a joint space. Gout is typically diagnosed using clinical criteria from the American College of Rheumatology. Diagnosis may be confirmed by identification of monosodium urate crystals in synovial fluid of the affected joint. Acute gout may be treated with nonsteroidal anti-inflammatory drugs, corticosteroids, or colchicine. To reduce the likelihood of recurrent flares, patients should limit their consumption of certain purine-rich foods (e.g., organ meats, shellfish) and avoid alcoholic drinks (especially beer) and beverages sweetened with high-fructose corn syrup. Consumption of vegetables and low-fat or nonfat dairy products should be encouraged. The use of loop and thiazide diuretics can increase uric acid levels, whereas the use of the angiotensin receptor blocker losartan increases urinary excretion of uric acid. Reduction of uric acid levels is key to avoiding gout flares. Allopurinol and febuxostat are first-line medications for the prevention of recurrent gout, and colchicine and/or probenecid are reserved for patients who cannot tolerate first-line agents or in whom first-line agents are ineffective. Patients receiving urate-lowering medications should be treated concurrently with nonsteroidal anti-inflammatory drugs, colchicine, or low-dose corticosteroids to prevent flares. Treatment should continue for at least three months after uric acid levels fall below the target goal in those without tophi, and for six months in those with a history of tophi.

• Klíčová slova
• tofy, rekurentní projevy dny,
• MeSH
• akutní nemoc * MeSH
• alopurinol aplikace a dávkování   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• antiflogistika nesteroidní aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• chronická nemoc * MeSH
• dieta * MeSH
• diferenciální diagnóza MeSH
• dna (nemoc) * diagnóza   etiologie   farmakoterapie   klasifikace   patofyziologie   prevence a kontrola   MeSH
• dnavá artritida * diagnóza   etiologie   farmakoterapie   klasifikace   MeSH
• febuxostat MeSH
• hyperurikemie * farmakoterapie   prevence a kontrola   MeSH
• indomethacin aplikace a dávkování   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• injekce intraartikulární MeSH
• ketorolak aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• kolchicin aplikace a dávkování   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• kyselina močová * analýza   krev   moč   MeSH
• lidé MeSH
• probenecid aplikace a dávkování   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• rizikové faktory MeSH
• xanthinoxidasa antagonisté a inhibitory   aplikace a dávkování   farmakologie   kontraindikace   terapeutické užití   MeSH
• záchvaty MeSH
• Check Tag
• lidé MeSH

This study was designed to determine whether inhibition of either cyclooxygenase-2 (COX-2) by indomethacin or progesterone receptor (PR) by PR antagonist, RU486, affects oocyte maturation, progesterone production, and covalent binding between hyaluronan (HA) and heavy chains of inter-α trypsin inhibitor, as well as expression of cumulus expansion-associated proteins (HA-binding protein, tumor necrosis factor α-induced protein 6, pentraxin 3) in oocyte-cumulus complexes (OCCs). The experiments were based on freshly isolated porcine OCC cultures in which the consequences of PR and COX-2 inhibition on the final processes of oocyte maturation were determined. Granulosa cells (GCs) and OCCs were cultured in medium supplemented with FSH/LH (both 100 ng/mL) in the presence/absence of RU486 or indomethacin. Western blot analysis, (3)H-glucosamine hydrochloride assay, immunofluorescence, and radioimmunoassay were performed. Only treatment with RU486 (25 μM) caused a decrease in the number of oocytes that reached germinal vesicle breakdown and metaphase II stage compared with indomethacin (100 μM) or FSH/LH treatment alone after 44 h. All treated OCCs synthesized an almost equal amount of HA. Heavy chains (of inter-α trypsin inhibitor)-HA covalent complexes were formed during in vitro FSH/LH-stimulated expansion in RU486- or indomethacin-treated OCCs. Follicle-stimulating hormone/LH-induced progesterone production by OCCs was increased in the presence of RU486 after 44 h. In contrast, a decrease of FSH/LH-stimulated progesterone production by GCs was detected in the presence of either RU486 or indomethacin after 72 h. We suggest that the PR-dependent pathway may be involved in the regulation of oocyte maturation. Both PR and COX-2 regulate FSH/LH-stimulated progesterone production by OCCs and GCs.

• MeSH
• antagonisté hormonů farmakologie   MeSH
• C-reaktivní protein genetika   metabolismus   MeSH
• extracelulární matrix metabolismus   MeSH
• folikuly stimulující hormon MeSH
• indomethacin farmakologie   MeSH
• inhibitory cyklooxygenasy farmakologie   MeSH
• IVM techniky veterinární   MeSH
• kumulární buňky účinky léků   fyziologie   MeSH
• kyselina hyaluronová MeSH
• luteinizační hormon MeSH
• mifepriston farmakologie   MeSH
• molekuly buněčné adheze genetika   metabolismus   MeSH
• oocyty účinky léků   fyziologie   MeSH
• prasata * MeSH
• progesteron metabolismus   MeSH
• regulace genové exprese účinky léků   MeSH
• sérový amyloidový protein genetika   metabolismus   MeSH
• transportní proteiny genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

A series of gold(III) complexes involving differently substituted derivatives of a plant hormone N6-benzyladenine (HL1-5) is reported. The complexes have the general formula [Au(HL1-5)Cl3]∙nH2O (n=0 for 1, 3-5; and n=1 for 2), where N6-(2-fluorobenzyl)adenine (HL1), N6-(2-chlorobenzyl)adenine (HL2), N6-(3-chlorobenzyl)adenine (HL3), N6-(4-chlorobenzyl)adenine (HL4) and N6-(4-methylbenzyl)adenine (HL5) represent the N9-coordinated ligands. The results of thorough characterization (elemental and thermal analyses, FT-IR, Raman and NMR spectroscopies, ESI+ mass spectrometry, conductivity measurements, DFT calculations) showed that the presented complexes 1-5 involve a central gold(III) atom coordinated in a square-planar geometry by the N9 atom of the purine moiety of HL1-5 and by three chlorido ligands. The complexes (1-5) were studied in vitro for cytotoxicity and anti-inflammatory activity on LPS-activated macrophages (THP-1 cell line), and in vivo for anti-inflammatory effects (1, 2, 5) using the carrageenan-induced hind paw oedema model on rats. Surprisingly, the results on the in vitro level revealed that the complexes show negligible cytotoxicity and anti-inflammatory activity, however, the activity on the in vivo level was found to be significant, fully comparable with the utilized drug Indomethacin, or even better as compared to a gold-containing metallodrug Auranofin.

• MeSH
• antiflogistika nesteroidní chemická syntéza   farmakologie   MeSH
• auranofin farmakologie   MeSH
• chloridy chemie   MeSH
• edém farmakoterapie   patologie   MeSH
• indomethacin farmakologie   MeSH
• kinetin chemie   MeSH
• komplexní sloučeniny chemická syntéza   farmakologie   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• ligandy MeSH
• monocyty cytologie   účinky léků   MeSH
• nádorové buněčné linie MeSH
• potkani Wistar MeSH
• viabilita buněk účinky léků   MeSH
• zadní končetina MeSH
• zlato chemie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

AIM: To evaluate bacteriocinogeny in short-term high-dose indomethacin administration with or without probiotic Escherichia coli Nissle 1917 (EcN) in experimental pigs. METHODS: Twenty-four pigs entered the study: Group A (controls), Group B (probiotics alone), Group C (indomethacin alone) and Group D (probiotics and indomethacin). EcN (3.5×10(10) bacteria/d for 14 d) and/or indomethacin (15 mg/kg per day for 10 d) were administrated orally. Anal smears before and smears from the small and large intestine were taken from all animals. Bacteriocin production was determined with 6 different indicator strains; all strains were polymerase chain reaction tested for the presence of 29 individual bacteriocin-encoding determinants. RESULTS: The general microbiota profile was rather uniform in all animals but there was a broad diversity in coliform bacteria (parallel genotypes A, B1, B2 and D found). In total, 637 bacterial strains were tested, mostly Escherichia coli (E. coli). There was a higher incidence of non-E. coli strains among samples taken from the jejunum and ileum compared to that of the colon and rectum indicating predominance of E. coli strains in the large intestine. Bacteriocinogeny was found in 24/77 (31%) before and in 155/560 (28%) isolated bacteria at the end of the study. Altogether, 13 individual bacteriocin types (out of 29 tested) were identified among investigated strains. Incidence of four E. coli genotypes was equally distributed in all groups of E. coli strains, with majority of genotype A (ranging from 81% to 88%). The following types of bacteriocins were most commonly revealed: colicins Ia/Ib (44%), microcin V (18%), colicin E1 (16%) and microcin H47 (6%). There was a difference in bacteriocinogeny between control group A (52/149, 35%) and groups with treatment at the end of the study: B: 31/122 (25%, P=0.120); C: 43/155 (28%, P=0.222); D: 29/134 (22%, P=0.020). There was a significantly lower prevalence of colicin Ib, microcins H47 and V (probiotics group, P<0.001), colicin E1 and microcin H47 (indomethacin group, P<0.001) and microcins H47 and V (probiotics and indomethacin group, P=0.025) compared to controls. Escherichia fergusonii (E. fergusonii) was identified in 6 animals (6/11 isolates from the rectum). One strain was non-colicinogenic, while all other strains of E. fergusonii solely produced colicin E1. All animals started and remained methanogenic despite the fact that EcN is a substantial hydrogen producer. There was an increase in breath methane (after the treatment) in 5/6 pigs from the indomethacin group (C). CONCLUSION: EcN did not exert long-term liveability in the porcine intestine. All experimental pigs remained methanogenic. Indomethacin and EcN administered together might produce the worst impact on bacteriocinogeny.

• MeSH
• antiflogistika nesteroidní škodlivé účinky   farmakologie   MeSH
• bakteriociny metabolismus   MeSH
• dechové testy MeSH
• Escherichia coli metabolismus   MeSH
• indomethacin škodlivé účinky   farmakologie   MeSH
• lidé MeSH
• metagenom MeSH
• methan metabolismus   MeSH
• probiotika farmakologie   MeSH
• střevní sliznice účinky léků   mikrobiologie   MeSH
• Sus scrofa MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Hypertension is associated with the imbalance of vasoconstrictor and vasodilator systems. Vasodilation is usually evaluated in isolated blood vessels, but except for nitric oxide (NO), relatively little attention is given to the in vivo efficiency of particular vasodilator mechanisms. The aim of our study was to evaluate the contribution of endogenous vasodilator prostanoids, Ca(2+)-activated K(+) channels and NO to blood pressure (BP) maintenance in rats with three different forms of experimental hypertension. Both principal vasopressor systems (the renin-angiotensin system and the sympathetic nervous system) were blocked by captopril and pentolinium in conscious spontaneously hypertensive rats (SHRs), Dahl salt-hypertensive (DS-HS) rats and rats with NO-deficient hypertension, as well as in their normotensive controls. Thereafter, we monitored BP changes in rats subjected to either a sequential or an isolated blockade of prostanoid synthesis by the non-selective cyclooxygenase inhibitor, indomethacin, of Ca(2+)-activated K(+) channels by tetraethylammonium and of NO formation by N(G)-nitro-L-arginine methyl ester. All three forms of experimental hypertension were characterized by augmented sympathetic vasoconstriction. The vasodilatation exerted by endogenous prostanoids and Ca(2+)-activated K(+) channels was enhanced in all forms of hypertension, almost proportionally to BP elevation. On the contrary, NO-dependent vasodilatation was not enhanced in any form of experimental hypertension, and there was a severe relative NO deficiency in both, SHRs and DS-HS rats. In conclusion, our data suggested that there is a compensatory activation of vasodilator prostanoids and Ca(2+)-activated K(+) channels in rats with experimental hypertension, whereas NO-dependent vasodilatation is not augmented. Thus, the overall activity of vasodilator systems failed to compensate for augmented sympathetic vasoconstriction in hypertensive animals.

• MeSH
• draslíkové kanály aktivované vápníkem metabolismus   MeSH
• hypertenze etiologie   metabolismus   patofyziologie   MeSH
• indomethacin farmakologie   MeSH
• inhibitory cyklooxygenasy farmakologie   MeSH
• kaptopril farmakologie   MeSH
• krevní tlak účinky léků   fyziologie   MeSH
• krysa rodu rattus MeSH
• oxid dusnatý metabolismus   MeSH
• potkani inbrední Dahl MeSH
• potkani inbrední SHR MeSH
• prostaglandiny metabolismus   MeSH
• vazodilatace účinky léků   fyziologie   MeSH
• vazokonstrikce účinky léků   fyziologie   MeSH
• vazokonstriktory farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Stratum corneum ceramides play an essential role in the barrier properties of skin. However, their structure-activity relationships are poorly understood. We investigated the effects of acyl chain length in the non-hydroxy acyl sphingosine type (NS) ceramides on the skin permeability and their thermotropic phase behavior. Neither the long- to medium-chain ceramides (8-24 C) nor free sphingosine produced any changes of the skin barrier function. In contrast, the short-chain ceramides decreased skin electrical impedance and increased skin permeability for two marker drugs, theophylline and indomethacin, with maxima in the 4-6C acyl ceramides. The thermotropic phase behavior of pure ceramides and model stratum corneum lipid membranes composed of ceramide/lignoceric acid/cholesterol/cholesterol sulfate was studied by differential scanning calorimetry and infrared spectroscopy. Differences in thermotropic phase behavior of these lipids were found: those ceramides that had the greatest impact on the skin barrier properties displayed the lowest phase transitions and formed the least dense model stratum corneum lipid membranes at 32°C. In conclusion, the long hydrophobic chains in the NS-type ceramides are essential for maintaining the skin barrier function. However, this ability is not shared by their short-chain counterparts despite their having the same polar head structure and hydrogen bonding ability.

• MeSH
• antiflogistika nesteroidní farmakologie   MeSH
• ceramidy chemie   metabolismus   MeSH
• chemické modely MeSH
• indomethacin farmakologie   MeSH
• inhibitory fosfodiesteras farmakologie   MeSH
• kůže chemie   metabolismus   MeSH
• lidé MeSH
• permeabilita účinky léků   MeSH
• sfingosin chemie   metabolismus   MeSH
• theofylin farmakologie   MeSH
• vysoká teplota MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH