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M Rost

Publications and source records attributed to M Rost.

At least 19 recordsLinked to original sources
PubMed2006

Measurement of the Gerasimov-Drell-Hearn Integrand for 2H from 200 to 800 MeV.

A measurement of the helicity dependence of the total inclusive photoabsorption cross section on the deuteron was carried out at MAMI (Mainz) in the energy range 200<Egamma<800 MeV. The experiment used a 4pi detection system, a circularly polarized tagged photon beam and a frozen-spin target which provided longitudinally polarized deuterons. The contribution to the Gerasimov-Drell-Hearn sum rule for the deuteron determined from the data is 407+/-20(stat)+/-24(syst) mu b for 200<Egamma<800 MeV.

Journal Article↗
PubMed2005

Switchability of neoral and equoral according to Food and Drug Administration rules and regulations.

According to the US Food and Drug Administration (FDA), if a drug product contains a drug substance that is chemically identical and is delivered to the site of action at the same rate and extent as another drug product, then it is equivalent and can be substituted (switchable) for that drug product. Methods used to define bioequivalence as stated by the FDA rules (FDA 21 CFR 320, 24) are (1) pharmacokinetic (PK) studies in healthy volunteers, (2) comparative clinical trials, and (3) pharmacodynamic (PD) studies (bioactivity). We evaluated the switchability of Equoral (IVAX-USA) with Neoral (Novartis Switzerland using all FDA rules. In a single oral dose, we undertook a comparative bioavailability study of Equoral (IVAX, USA) Neoral (Novartis, USA), and Neoral (Novartis UK). The pharmacokinetics of Equoral and Neoral were determined with blood levels at 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 42, and 48 hours. The area under curve (AUC), AUC extrapolated to infinity (AUC0-inf), rate of absorption (Tmax), extent of absorption (Cmax), half time (t1/2) of Equoral and Neoral were all within the 90% confidence interval of 80% to 125% boundaries. A comparative multinational multicenter clinical trial in stable renal transplant patients included 70 patients (22 women and 48 men) of mean age of 33 years (range, 26 to 43) was performed in Turkey, Lebanon, and Pakistan. In this study the ratios of LSM and the 90% confidence intervals for the Nontransformed/Parameters (AUC0-t, AUCinf, Tmax, and Cmax) of Equoral and Neoral SGC were 98% and 95%, respectively, which are within the 80% to 125% FDA acceptance range. For immunosuppressive drugs, the site of action is the lymphocyte and the measurable response is the decrease in lymphocyte count caused by the relative concentration of the drug in the lymphocyte. In a controlled switch, fixed-dose study, both Equoral and Neoral achieved the same concentration in the lymphocytes and caused the same degree of lymphocyte count reduction. The results of the testing (bioavailability-bioequivalence, clinical studies, and pharmacodynamic-bioactivity) required by FDA for interchangeability ("switchability") of immunosuppressive agents suggests that Neoral and Equoral are switchable.

Adult↗
PubMed2005

Serum bile acid profile in women during pregnancy and childbed.

Oestrogens produce cholestasis by inhibition of bile acid (BA) transport as well as by inhibition of BA synthesis in the liver. The present work was done to clarify the relevance of altered serum BA profile in 28 healthy pregnant women from the 15th to the 40th weeks of pregnancy with increasing oestrogen serum concentrations in comparison to 6 to 8 weeks after delivery with normalized oestrogen status. For the first time 6 free and 10 taurine- and glycine-conjugated BAs were analysed during the normal pregnancy by HPLC with postcolumn derivatisation and fluorescence detection. The primary BAs cholic (CA) and chenodeoxycholic acid (CDCA) as well as their glycine (G-) and taurine (T-) conjugates amount to nearly 70 % of total BAs in serum and were not changed from the 15th to the 40th weeks of pregnancy, but free and G-CDCA increased significantly after delivery. Among the secondary BAs, which were produced in the intestine by bacteria due to dehydroxylation of the primary bile acids CA and CDCA, only taurine-conjugated deoxycholic acid (T-DCA) decreased significantly after delivery. The free BAs, produced by bacteria in the intestine due to deconjugation, were not changed during pregnancy but had doubled in childbed. Some BAs occurred seldom and in small amounts in the serum, but during pregnancy not more frequent than after delivery. Contrary to expectation the increasing oestrogen concentrations did neither enhance total serum bile acids nor change bile acid profile during pregnancy.

Adult↗
PubMed2005

Pharmacokinetic conversion study of a new cyclosporine formulation in stable adult renal transplant recipients.

Cyclosporine A (CyA) is a standard component of immunosuppressive regimens. It is a critical-dose drug for which a minor change in absorption can have important clinical consequences. The aim of the study was to compare the pharmacokinetics and safety of the new generic CyA formulation, Equoral capsules, after a switch from original formulation, Neoral capsules, in seventy stable adult renal transplant recipients. The extent and rate of pharmacokinetic parameters for bioequivalence were compared in a non-randomized, steady-state clinical study with fixed non-replicate study design. Pharmacokinetic analysis of CyA have shown that both the rate and extent of absorption of Equoral does not differ significantly from that of Neoral. At identical dosing, the new formulation was found to have geometric means of C(max) 717 ng/ml and AUCtau 3108 ng/ml.h, while corresponding results of comparator were 725 ng/ml and AUCtau 3039 ng/ml.h, respectively. The 90 % confidence intervals of C(max) and AUCtau were within 80- 125 % interval of the mean values. The results suggest that Equoral capsules can be used as an alternative treatment to Neoral capsules in CyA regimen.

Absorption↗
PubMed2004

Photoproduction of eta-mesic 3He.

The photoproduction of eta-mesic 3He has been investigated using the TAPS calorimeter at the Mainz Microtron accelerator facility MAMI. The total inclusive cross section for the reaction gamma3He-->etaX has been measured for photon energies from threshold to 820 MeV. The total and angular differential coherent eta cross sections have been extracted up to energies of 745 MeV. A resonancelike structure just above the eta production threshold with an isotropic angular distribution suggests the existence of a resonant quasibound state. This is supported by studies of a competing decay channel of such a quasibound eta-mesic nucleus into pi(0)pX. A binding energy of (-4.4+/-4.2) MeV and a width of (25.6+/-6.1) MeV is deduced for the quasibound eta-mesic state in 3He.

Journal Article↗
PubMed2002

The reaction gammap-->pi0gamma'p and the magnetic dipole moment of the Delta+ 1232 resonance.

The reaction gammap-->pi(0)gamma'p has been measured with the TAPS calorimeter at the Mainz Microtron accelerator facility MAMI for energies between sqrt[s]=1221-1331 MeV. The cross section's differential in angle and energy have been determined for the photon gamma' in three bins of the excitation energy. This reaction channel provides access to the magnetic dipole moment of the Delta(+)(1232) resonance and, for the first time, a value of mu(Delta(+))=[2.7(+1.0)(-1.3)(stat)+/-1.5(syst)+/-3(theor)]mu(N) has been extracted.

Journal Article↗
PubMed2001

Interface pinning in spontaneous imbibition.

Evaporation and gravity induced pinning in spontaneous imbibition are examined within a phase field formalism. Evaporation is introduced via a nonconserving term and gravity through a convective term that constrains the influx of liquid. Their effects are described by dimensionless coupling constants epsilon and g, respectively. From liquid conservation, the early time behavior of the average interface position follows H(t) approximately t1/2 until a crossover time t*(g,epsilon). After that the pinning height Hp(g,epsilon) is approached exponentially in time, in accordance with mean field theory. The statistical roughness of the interface is described by an exponent chi approximately 1.25 at all stages of the rise, but the dynamic length scale controlling roughness crosses over from xi(x) approximately H1/2 to a time independent pinning length scale xi(p)(epsilon,g).

Journal Article↗
PubMed2001

Monooxygenation, conjugation and other functions in cryopreserved rat liver slices until 24 h after thawing.

For the extensive use of precision-cut liver slices (particularly of human origin) for toxicological investigations successful cryopreservation is necessary. But so far, survival of thawed slices was limited to few hours. This was now overcome by modification of previous procedures. The concentration of DMSO as a cryoprotectant was enhanced to 30%, and washing steps after rapid thawing were omitted. The slices were frozen in liquid nitrogen, thawed at 38 degrees C and incubated immediately in Williams medium E. Protein and potassium contents were stable until 24 h. Glutathione content, amounting to nearly 50% of fresh slices, increased during incubation. High initial lactate dehydrogenase leakage dropped after medium change to less than half during 2-24 h. Testosterone hydroxylation and 7-ethoxycoumarin O-deethylation rates were similar to fresh slices, the latter reaction was inducible by beta-naphthoflavone within 24 h. Methylumbelliferone glucuronidation and p-nitrophenol glucuronidation and sulfation were well measurable and either maintained or decreased by about 50% until 24 h.Altogether, the results are encouraging for further experiments to standardise cryopreservation conditions and to investigate the suitability of this cryopreservation protocol with human liver slices.

Animals↗
PubMed2001

Patterns of 2-year population cycles in spatially extended host-parasitoid systems.

Coexisting but temporally separated cohorts of insects with a multiannual life cycle may have dissimilar average abundance, resulting in periodically fluctuating population density. In the case of the boreal moth genus Xestia with a 2-year life cycle and a distinct abundance difference between the two coexisting cohorts, empirical results and a simple model suggest that the oscillatory dynamics are maintained by interaction with a parasitoid wasp. Here we report theoretical results on a spatially extended version of the basic model and relate the modeling results to empirical observations. A spatially extended model may have domains oscillating in different phases as is the case between western and eastern Finnish Lapland. Spatial heterogeneity tends to fix the location of phase boundaries. In contrast, spatially homogeneous temporal fluctuations tend to synchronize populations in large regions.

Animals↗
PubMed2001

Para-nitrophenol glucuronidation and sulfation in rat and human liver slices.

Para-nitrophenol (PNP) is a well-known substrate for both phase I (hydroxylation at cytochrome P450) and phase II reactions (glucuronidation and sulfation). HPLC separation of PNP conjugates has already been described, but not for respective studies with liver slices, which nowadays have proven to be a suitable model for metabolic studies. Therefore we adapted an HPLC method for the simultaneous measurement of PNP glucuronidation (PNP-G) and sulfation (PNP-S) in this in vitro system. Both activities are substantially maintained over an incubation period of 24 h. PNP-G activity, however, seems to be better preserved, as indicated by stable values for PNP-G but reduced PNP-S values after 48 h liver slice preincubation. 24 h exposure of the slices to beta-naphthoflavone or phenobarbital does not change PNP-G or PNP-S activities.

Animals↗
PubMed1999

Fast coarsening in unstable epitaxy with desorption.

Homoepitaxial growth is unstable towards the formation of pyramidal mounds when interlayer transport is reduced due to activation barriers to hopping at step edges. Simulations of a lattice model and a continuum equation show that a small amount of desorption dramatically speeds up the coarsening of the mound array, leading to coarsening exponents between 1/3 and 1/2. The underlying mechanism is the faster growth of larger mounds due to their lower evaporation rate.

Adsorption↗
PubMed1998

Induction of cytochrome P450 1A1 in rat liver slices by 7-ethoxycoumarin and 4-methyl-7-ethoxycoumarin.

7-Ethoxycoumarin (EC) is widely used as a model substrate for monooxygenase function, its O-deethylation representing cytochrome P450 (P450) activity mainly of 1A but also of 2B isoforms. Reports on investigations of its own capacity to induce or suppress P450 activities, however, have not been found in biomedical literature. To avoid the influence of in vivo pharmacokinetics, studies can well be undertaken with liver slice incubation. Therefore in the present investigation precision-cut rat liver slices from male 43-63-day-old male HAN:Wistar outbred rats were incubated at 30 degrees C in carbogen saturated William's Medium E for 24 h. EC was added previously to final concentrations of 10, 25, 50, 75 or 100 microM. After incubation, homogenate was prepared from slices and used for model reactions (7-ethoxyresorufin O-deethylation [EROD] and 7-pentoxyresorufin O-depentylation [PROD]). EROD, indicating activities of 1A isoforms, was enhanced by incubation with EC at 25 and 50 microM to about doublefold but showed control or lower values at 75 and 100 microM. Incubation with beta-naphthoflavone in comparison led to variable increases (3-5-fold of controls). For PROD as an indicator of the phenobarbital inducible P450 isoforms 2B1 and 2B2 no enhancement was found, but a decrease by incubation with 75 and 100 microM EC. To further investigate the correlation between enzyme activity and gene expression after slice incubation, P450 1A1 mRNA content was measured by RT-PCR. Induced gene expression for 1A1 was seen with different EC concentrations to a variable extent, though not as strong as with BNF. Similar incubation with 4-methyl-7-ethoxycoumarin revealed an even stronger induction of EROD activity with maxima at about 10-32 microM, reaching BNF values. In contrast incubation with 7-benzyloxycoumarin had no evident inducing or suppressing effect, neither on EROD nor on PROD activity.

Animals↗
PubMed1998

Monooxygenation, cytochrome P450-mRNA expression and other functions in precision-cut rat liver slices.

Precision-cut rat liver slices (KRUMDIECK slicer, slice thickness 200-250 microm) were incubated in rollers containing modified William's medium E at 37 degrees C for 2, 24 and 48 hrs. Protein, DNA, potassium and glutathione concentrations did not decrease during 48 hrs. Lactate dehydrogenase (LDH) leakage into the medium was relatively marked during the first 2 hrs of incubation, from the 2nd to the 48th hr LDH leakage was very low. The same is true of the release of thiobarbituric acid-reactive substances. Albumin synthesis and transport into the medium decreased to about 70% after 48 hrs. Cytochrome P450 (CYP)-dependent 7-ethoxycoumarin O-deethylation rate was relatively stable up to 48 hrs, whereas testosterone hydroxylation decreased significantly without alterations of the proportions of the 7 quantified hydroxylated metabolites. After exposure of the slices to beta-naphthoflavone for 6 hrs CYP1A1-mRNA expression, measured by competitive RT-PCR, was increased by a factor of at least 1000. Precision-cut liver slices are a useful tool for the study of various hepatic functions, drug metabolism and its induction in vitro.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1998

Luminol and lucigenin amplified chemiluminescence and lipidperoxidation with brain microsomes from rats during ontogenetic development.

The chemiluminescence (CL) amplifiers luminol (LM) and lucigenin (LC) react with different reactive oxygen species (ROS) in dependence on the ROS generating system used. With liver microsomes LMCL indicates predominantly superoxide anion radicals, whereas LCCL is mainly a measure for hydroxyl radical formation or of reactive organic radicals. With brain microsomes only LCCL, but not LMCL could be measured. For both brain microsomes from newborn (both sexes) and 60 day-old (male) rats LCCL is dependent on protein and NADPH concentration, activity in newborns being only 15% compared with young adult rats. As compared with liver microsomes 10-fold higher protein concentrations are needed to obtain comparable LCCL, whereas the NADPH demand is the same as with liver. A distinct ontogenetic development was demonstrated: low activities in the fetus, in newborn and 10-day-old rat are followed by higher activities with increasing age, after a maximum at an age of 60 days a decline was observed. Microsomal lipidperoxidation (LPO) was measured as formation of thiobarbituric acid reactive substances (TBARS) and was also dependent on protein and NADPH concentration. Unexpectedly, LPO with brain microsomes from newborn rats did not show any developmental variation.

Acridines↗
PubMed1996

Contribution to the mechanism of chromate nephrotoxicity in developing rats: EPR investigations.

The effect of 2 mg and 1 mg Na2Cr2O7 (Cr)/100 g body wt. on renal function was investigated in 10- and 55-day-old rats, respectively. These doses were followed by equal Cr concentrations in the renal tissue of both age groups. Confirming previous data we found lower nephrotoxicity in young than in adult rats. The concentration of glutathione (GSH) and the activity of glutathione reductase (GSSG reductase) in renal tissue of adult rats were diminished by buthionine sulfoximine (BSO) and lomustine (CCNU) administration, respectively. In these animals Cr nephrotoxicity was decreased significantly. Lower nephrotoxicity was accompanied by slower disappearance of Cr(VI) from renal tissue homogenate in vitro. The time course of Cr(VI) reduction demonstrated by the signal intensity of Cr(V), as recorded by electron spin resonance (EPR) spectroscopy in the supernatant of renal tissue homogenate, enabled us to follow the reduction of Cr(VI) to Cr(III) via Cr(V). Maximally reached Cr(V) concentrations lowest in young rats, did not differ significantly in adult control and BSO and BSO + CCNU treated rats. Further reduction of Cr(V) to Cr(III) which appeared most rapidly in adult rats, was delayed by pretreatment with BSO and CCNU. From our results we concluded that (1) reduction of Cr(VI) was more related to the concentration of GSH than to the activity of GSSG reductase, (2) the formation of Cr-GSH-complexes with GSH oxidation seemed to be the first step of Cr(VI) metabolism, and (3) the stabilization of reactive Cr(V) by GSH seemed to be decisive for the preventive effect of BSO and CCNU as well as for age differences in chromate nephrotoxicity.

Age Factors↗
PubMed1996

Monooxygenation, cytochrome P4501A1 and P4501A1-mRNA in rat liver slices exposed to beta-naphthoflavone and dexamethasone in vitro.

Precision-cut liver slices (0.5 mm) were incubated at 30 degrees C in a modified William's Medium E for up to 48 hrs. During the incubation, K+ and GSH/GSSG concentrations did not decrease. Cytochrome P450-dependent dealkylation rates of 7-ethoxycoumarin (ECOD), 7-allyloxycoumarin (ACOD) and 7-ethoxyresorufin (EROD) decreased to 1/3, 1/2 or did not change at all, respectively, after a 48 hrs incubation period. Exposure of the slices to 25 microM beta-naphthoflavone (beta NF) resulted in about 3 times higher monooxygenation rates. An exposure to a combination beta NF and dexamethasone (10(-6)M) caused a marked induction (6 times higher rates) after 48 hrs. Simultaneously an increase in P4501A1 content was observed. P4501A1-mRNA expression (measured by RT-PCR) was distinctly increased following beta NF exposure for 6 or 24 hrs. DMSO (0.2%) and dexamethasone alone modified monooxygenation rates, but did not have significant effects on P4501A1 content or, in the case of DMSO, P4501A1 gene expression (for dexamethasone not determined). Liver slices are a useful and simple tool for the detection of a beta NF-like induction within a few hours after preparation of the slices.

Animals↗
PubMed1996

Luminol-and lucigenin-amplified chemiluminescence with rat liver microsomes. Kinetics and influence of ascorbic acid, glutathione, dimethylsulfoxide, N-t-butyl-a-phenyl-nitrone, copper-ions and a copper complex, catalase, superoxide dismutase, hexobarbital and aniline.

For the investigation of luminol (LM)-and lucigenin (LC)-amplified chemiluminescence (CL) in rat liver microsomes using both a liquid-scintillation counter (LKB/Wallac 1219 Rackbeta) and a Berthold luminometer (AutoLumat LB 953) optimal incubation mixtures and conditions and basic kinetics have been established. Whereas calibration curves for both LM- and LC-CL are performed with hydrogenperoxide (LC quantum yield is 6.25 fold higher as that of LM), distinct differences were revealed with microsomes, indicating that different reactive oxygen species (ROS) are determined: Both LM- and LC-CL follow the kinetics of enzymatic reactions in terms of dependence on protein and NADPH or NADH concentration, time course, temperature etc., but with differences. LM-CL does not work without addition of Fe2+, whereas LC-CL does. Both copper ions and copper bound in a complex abolish CL, LC-CL being much more sensitive. Isolated cytochrome P-450 (P450) and NADPH P450 reductase from liver of pheno-barbital treated rats alone proved to be inactive in LM-and LC-CL production, whereas te combination 1:1 without and with addition of lipid was highly active in both LM-and LC-CL. Ascorbic acid and glutathione as scavengers diminish both LM- and LC-CL in concentrations higher then 10(5). Dimethyl-sulfoxide (DMSO) was ineffective in LM-CL up to concentrations of 0.2 M, the very high concentration of 2 M diminished LM-CL only to 1/3. LC-CL was diminished starting at concentrations of 100 mM and at 2 M only 10% of maximum LC-CL was observed. The trap substance N-t-butyl-a-phenylnitrone (BNP) also diminished LC-CL more effectively than LM-CL. Clearcut differences were revealed by the addition of catalase and superoxide dismutase: both enzymes diminished LM-CL only, without any influence on LC-CL. Hexobarbital, a potent uncoupler of P450, enhances LM-CL fivefold, whereas LC-CL is barely influenced. Aniline (without uncoupling capability) decreased both LM-and LC-CL increasingly with increasing concentrations. Therefore the conclusion is drawn that LM-CL measures in liver microsomes predominantly superoxide anion radicals, whereas LC-CL is mainly a measure for microsomal hydroxyl radical formation or of reactive organic radicals. With microsomes of phenobarbital and beta-naphthoflavone treated rats CL was much higher but in principle the same kinetic characteristics could be shown. All results on microsomes were obtained uniformly with the liquid scintillation counter and the Berthold luminometer, the letter being much more effective and more sensitive.

Acridines↗