PubMed Health⌕ Search

Biomedical subjects

A Langner

Publications and source records attributed to A Langner.

At least 19 recordsLinked to original sources
PubMed2005

Biophysical and biochemical properties of a binary lipid mixture for DNA transfection.

The phase and miscibility behavior of a triple-chain phosphatidylcholine (TPHPC) and a single-chain surfactant (CTAB) were investigated in aqueous dispersions and in monolayers at the air/water interface. CTAB can be incorporated in the TPHPC monolayer because of its complementary molecule shape and reduces the tilt angle of TPHPC. The type of phases and the phase sequence (L2 - LS) are the same in the pure TPHPC monolayer and in the TPHPC/CTAB (80:20 mol:mol) mixture. No indication of any ordering of adsorbed DNA was observed. In the aqueous dispersions, TPHPC exhibits an inverted hexagonal phase above the chain melting. The addition of 30 mol% CTAB leads to the appearance of a lamellar Lalpha phase. The binding of DNA to the mixture is obvious but this is accompanied by a separation of the two lipids what is supported by monolayer experiments. The system has no long-term stability. The main reason seems to be not only the stronger interaction of DNA with CTAB, but also especially the unexpected weak interaction between CTAB and TPHPC. The transfection efficiency is lower compared with lipofectamine. The main disadvantage of this system is the cytotoxicity of CTAB, which could not be lowered by incorporation of CTAB in the TPHPC bilayer.

Animals↗
PubMed2001

Efficacy and tolerance of topical calcitriol 3 microg g(-1) in psoriasis treatment: a review of our experience in Poland.

Although topical vitamin D3 derivatives have been used in the treatment of patients with psoriasis for the past 15 years, questions remain about the indications and limitations of application. Extensive personal experience gained during the development of calcitriol (1alpha25-dihydroxyvitamin D3) is therefore reviewed. Three double-blind, vehicle-controlled trials have revealed that calcitriol 3 microg g(-1) ointment (Silkis ointment, Galderma Laboratories) has very good clinical efficacy. In a left-right comparison with vehicle ointment, complete clearance of psoriatic lesions was achieved in 48% of sites treated with calcitriol and a further 41% showed considerable or definite improvement. The clinical response to calcitriol in another study was as good as, or even better than, that achieved with betamethasone valerate 0.1% ointment. A preparation containing calcitriol 15 microg g(-1) did not show any clinical superiority to the lower dose but was associated with a higher risk of hypercalciuria, particularly when applied to extensive skin lesions. These results suggest that calcitriol 3 microg g(-1) ointment is an effective and safe treatment for chronic plaque psoriasis.

Administration, Cutaneous↗
PubMed2001

Long-term safety of topical calcitriol 3 microg g(-1) ointment.

To assess the topical and systemic safety and tolerance of twice-daily application of 3 microg g(-1) 1alpha25-dihydroxyvitamin D3 (calcitriol) ointment (Silkis ointment, Galderma Laboratories) in the long-term treatment of patients suffering from chronic plaque psoriasis, we performed an open-design, multicentre study. Two hundred and fifty-three patients (155 males, 98 females) treated all their psoriatic lesions, except for those on the head and scalp, for up to 78 weeks. No serious adverse events were reported: 37 patients (14.6%) had a transient skin irritation reaction on one or more occasions during the study that resulted in study withdrawal for seven of them. The baseline/endpoint analyses showed no clinically relevant changes in measures of calcium and phosphorus homeostasis and renal function. Slight hypercalcaemia was observed in five (2%) patients: in four of these patients, serum albumin-adjusted total calcium levels normalized during treatment. In conclusion, twice-daily calcitriol 3 microg g(-1) ointment is safe and well tolerated in the long-term treatment of chronic plaque psoriasis.

Administration, Cutaneous↗
PubMed2001

Cytochrome P450 1A1 and 4A activities in isolated rat spleen lymphocytes.

In this study the activity of Cytochrome P 450 (CYP) enzymes in isolated spleen lymphocytes of Wistar rats was estimated. 7-Ethoxyresorufin-O-deethylase was analysed to determine the activity of CYP 1A1/2. The activity was increased 2.2-fold by pretreating the animals with 3-methylcholanthrene, and 1.3-fold after the addition of the mitogen concanavalin A to the lymphocyte culture. Pretreatment of the rats with phenobarbitone did not enhance the basal enzyme activity. To estimate reductive activities the azoreduction of 4-(N,N-dimethyl-amino)azobenzene was analysed. Again detectable turnovers were found which could be increased 4-fold after the addition of concanavalin A. Azo-reductase activity could also be increased 2-fold after clofibrate was added to the lymphocyte cultures, and was decreased by adding metyrapone so that it was concluded that azoreduction may be partly due to the CYP 4A-family.

Animals↗
PubMed2000

First bioanalytical evaluation of nonpeptidic cage dimeric HIV-1 protease inhibitor N-benzyl 4-aryl-1,4-dihydropyridine H17: biotransformation and toxicity on Hep G2 cells.

Cage dimeric N-benzyl 4-aryl-1,4-dihydropyridine H17 is a moderate inhibitor of HIV-1 protease. As representative of an innovative and promising class of nonpeptidic HIV-1 protease inhibitors H17 was selected for the characterization of the biochemical profile of the cage dimers concerning metabolic and toxic aspects. In the first bioanalytical evaluation of H17 on Hep G2 monolayers no phase-I metabolites were found and the extent of conjugation on phase-II of biotransformation was poor due to steric hindrance of the hydroxymethylene groups. H17 was found to be nearly non-toxic. A slight noticeable influence on cell proliferation, however, did not result from apoptotic activities. Thus, first biochemical evaluation of H17 practically suggests no decrease of an in-vivo bioavailability by metabolization.

Biotransformation↗
PubMed2000

Bioanalysis of syn dimeric HIV-1 protease inhibitor N-benzyl 4-aryl-1,4-dihydropyridine H19: metabolic and cytotoxic properties in Hep G2 cells.

Syn dimeric N-benzyl 4-aryl-1,4-dihydropyridine H19 is a nonpeptidic HIV-1 protease inhibitor of the dihydroxyethylene type representing novel C2-symmetric inhibitors. Great interest was focussed on the extent of metabolism of these novel inhibitory structures as their functional groups are similar to certain peptidic and non-peptidic HIV-1 protease inhibitors with poor bioavailability due to extensive metabolism. Thus, early characterization of metabolic and toxic properties decisively determines the future prospects of those novel HIV-1 protease inhibitors. Both metabolism and toxicity were evaluated in Hep G2 monolayers. While no phase-I metabolites were found the extent of conjugation in phase-II of biotransformation was poor. Moreover, cytotoxic evaluation of protein and DNA decrease and, furthermore, of membrane toxicity characterized the novel inhibitors as non-toxic. Consequently, the favourable poor metabolism and non-toxic properties encourage further development of these novel HIV-1 protease inhibitors.

Cell Division↗
PubMed1999

Nitroxide metabolism in the human keratinocyte cell line HaCaT.

Metabolism of different nitroxides with piperidine structure used as spin labels in electron spin resonance (ESR) studies in vitro and in vivo was investigated in human keratinocytes of the cell line HaCaT by GC and GC-MS technique combined with S-band ESR. Besides the well known reduction of the nitroxyl radicals to the ESR silent hydroxylamines as primary products our results indicate the formation of the corresponding secondary amines. These reductions are inhibited by the thiol blocking agent N-ethylmaleimide and by the strong inhibitors of the thioredoxin reductase (TR) 2-chloro-2,4-nitrobenzene and 2,6-dichloroindophenol. The competitive inhibitor TR inhibitor azelaic acid and the cytochrome P-450 inhibitor metyrapone lack any effects. The rates of reduction to the hydroxylamines and secondary amines were dependent on the lipid solubility of the nitroxides. Therefore, it can be assumed that the nitroxides must enter the cells for their bioreduction. The mostly discussed intracellular nitroxide reducing substances ascorbic acid and glutathione were unable to form the secondary amines. In conclusion, our results suggest that the secondary amine represents one of the major metabolites of nitroxides besides the hydroxylamine inside keratinocytes formed via the flavoenzyme thioredoxin reductase most probably. Further metabolic conversions were detected with 4-oxo-2,2,6,6-tetramethylpiperidine-1-oxyl and the benzoate of 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl as substrates.

Cell Line↗
PubMed1996

[Biotransformation of the lipoxygenase inhibitor 2-hydroxy-5-methyl-laurophenone-oxime (FLM 5011)].

2-Hydroxy-5-methyl-laurophenone-oxime (FLM 5011, 1) is an inhibitor of the lipoxygenase with antiinflammatory and antiallergic actions. The studies on the biotransformation using in vivo investigations and in vitro test systems resulted in finding of at least eight metabolites. Four of these compounds have been detected and identified in urine and faeces after p.o. administration in male Wistar rats. By means of cultures of hepatocytes, lymphocytes and myeloma cells additional metabolites were found and the main pathways of metabolism could be suggested. Furthermore it was possible to confirm the sequence of the metabolic reactions. First of all, 1 is hydroxylated in the omega-position of the lauryl side chain by the cytochrome P-450 system. The further oxidation to the carboxylated compound is followed by the stepwise degradation of the side chain by beta-oxidation similarly to the pathways of fatty acid metabolism. Simultaneously the oxime group is converted to the keto group. The metabolites and 1 partly occur as sulfate or glucuronide conjugates. Additionally all compounds produced by beta-oxidation are conjugated with other partners, probably amino acids. By omega-oxidation, compounds with higher inhibitory potency on the lipoxygenase than the parent compound are formed. These results suggest that the activity of 1 is partly caused by the initial metabolites.

Animals↗
PubMed1996

A long-term multicentre assessment of the safety and tolerability of calcitriol ointment in the treatment of chronic plaque psoriasis.

Calcitriol (1 alpha,25-dihydroxyvitamin D3), applied topically in an ointment base, has been shown to be effective in the treatment of chronic plaque psoriasis. This open study was designed to assess the safety and tolerability of 3 micrograms/g calcitriol ointment applied twice daily over treatment periods of up to 78 weeks. In the 253 evaluable patients with chronic plaque psoriasis no clinically relevant changes were observed in the baseline/end-point analyses of mean serum levels of total calcium, albumin-adjusted total calcium, phosphorus and creatinine, and plasma calcitriol levels. Mean values of 24-h urinary calcium, phosphorus, creatinine and hydroxyproline excretions, creatinine clearance and mean urinary calcium/creatinine ratio also did not show clinically relevant changes in the baseline/end-point analyses. The treatment was well tolerated, with no serious adverse events occurring during the course of the study. Eight patients withdrew from the study due to adverse events which, although not serious, were thought to be treatment-related: in seven patients skin irritation reactions and in one case a transient asymptomatic slight hypercalcaemia was observed. In addition, assessments of global severity, global improvement and Psoriasis Area and Severity Index scores confirmed the therapeutic efficacy of twice daily 3 micrograms/g calcitriol ointment demonstrated in an earlier controlled study. In conclusion, this study demonstrated that twice daily application of 3 micrograms/g calcitriol ointment is safe and well-tolerated in the treatment of chronic plaque psoriasis.

Adult↗
PubMed1995

[The use of lymphocyte cultures for the investigation of drug biotransformation].

In the present paper the rat lymphocytes and mouse myeloma cell culture are developed as in vitro test systems and used for the investigation on the biotransformation of drugs. The rat lymphocyte culture was established as a suspension culture after the isolation of the cells from the spleen of male wistar rats by mechanical disaggregation and density gradient centrifugation with a yield of 10(7) cells per spleen and a viability of 80%. The addition of the mitogens PHA and Con A to the culture stimulated the proliferation of the lymphocytes leading to a doubling of the number of cells comparing with control cultures. Myeloma cells are a permanent cell line of B-lymphocytes. The cultivation was carried out as stationary suspension. The marked proliferation of the cells could be increased by addition of Con A. The biochemical properties of both kinds of cells are qualitatively comparable. Cytochrome P-450 mediated demethylase activities could be detected, which were 5-10 fold higher in myeloma cells. The pretreatment with the enzyme inductors phenobarbitone and 3-methylcholanthrene as well as the addition of the mitogens PHA and Con A increased these turnover rates. Reductive and conjugating activities were not present in the cultures. The established and characterized in vitro systems were applied for the investigation on the biotransformation of 4 potential drugs. The cardiac effective Trapidil (Rocornal) derivative AR 12463 (5-piperidino-7-[N-pentyl-N-(beta-hydroxyethyl)]- amino-s-triazolo[1,5-a]pyrimidine) is transformed in lymphocyte and myeloma cell cultures in two compounds. These substances revealed as the hydroxypentyl- and the hydroxypyrimidine derivative.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopyrine↗
PubMed1993

Topical calcitriol in the treatment of chronic plaque psoriasis: a double-blind study.

A randomized, double-blind, left-right, vehicle-controlled study to assess the therapeutic efficacy and safety of twice daily application of 15 micrograms/g calcitriol ointment for a period of 6 weeks was performed in 32 patients suffering from bilateral, symmetrical, severe chronic plaque psoriasis. Twice daily 15 micrograms/g calcitriol ointment significantly improved erythema, induration, scaling and global severity of psoriatic plaques, and was much more effective than vehicle ointment. The difference in overall clinical efficacy between calcitriol and vehicle was statistically significant from week 1 onwards, and was maintained over the entire study. On completion of the study, clearance of psoriatic lesions was found in 47% of calcitriol-treated sides and in 13% of vehicle-treated sides. Skin histopathology of calcitriol-treated sides revealed a return to normal keratinization, with decreased inflammatory cell infiltration in the dermis and disappearance of the inflammatory infiltrate from the epidermis. Three patients had asymptomatic hypercalcaemia during the study. Mean serum levels of total calcium, albumin-adjusted total calcium, phosphorus, 25-hydroxyvitamin D and calcitriol did not show statistically significant changes in the baseline/end-point comparisons.

Administration, Topical↗
PubMed1993

[The biotransformation of the anticonvulsant 4-p-chlorophenylpyrrol-3-morpholino-2-carboxylic acid methyl ester (AWD 140-076)].

4-p-Chlorphenylpyrrole-3-morpholino-2-carboxylic acid methylester (1; AWD 140-076) is a substance with anticonvulsive properties. After p.o. administration in male wistar rats many metabolites in relatively small concentration are excreted in urine and faeces, six of them could be isolated and identified as quantitative dominating compounds. Compound 1 is attacked in different sites of the molecule by the cytochrome P-450 system. At the morphine ring N- and O-dealkylation reactions take place leading to the cleavage of the ring. After that a stepwise degradation by oxidative and reductive processes occurs. Further reactions concern the N-oxidation of the morpholine nitrogen as well as the hydroxylation of the pyrrole skeleton forming the main metabolites. 5 metabolites are also present as sulfate or glucuronide conjugates. The quantity ratio of the phase I to phase II metabolites amounts to 9:1. In the in vitro test system isolated perfused rat liver and rat hepatocytes culture solely the two main metabolites are formed. Compound 1 is characterized by enzyme inducing activities. The oxidative demethylation of p-nitroanisole is increased 4-fold after pretreatment.

Animals↗
PubMed1991

Efficacy and safety of CD 271 alcoholic gels in the topical treatment of acne vulgaris.

CD 271, a naphthoic acid, is a powerful modulator of epidermal differentiation. This double-blind, randomized study compared the efficacy and safety of two concentrations (0.03% w/w and 0.1% w/w) of CD 271 alcoholic gel, with 0.025% w/w tretinoin gel in 72 male patients with acne vulgaris over a period of 12 weeks. Efficacy was measured by counting facial inflammatory and non-inflammatory lesions and by grading the severity of the acne at each visit. Skin tolerance was assessed with subjective symptoms, such as burning and pruritus, as well as clinical assessment of erythema, dryness and scaling on the treated areas. The alcoholic 0.1% CD 271 gel was as effective as 0.025% tretinoin gel in reducing total comedone counts (83% reduction for both products after 12 weeks' treatment). The reduction in the number of inflammatory lesions and the total number of acne lesions were significantly greater with 0.1% CD 271 gel than with tretinoin gel (69% and 79% for 0.1% CD 271, 50% and 73% for tretinoin gel, respectively, P less than 0.05). All three treatments were well tolerated and there were no changes in any major blood parameters. No CD 271 could be detected in blood plasma at the end of the study (detection limit = 1 ng/ml).

Acne Vulgaris↗