Biomedical subjects

G Kühne

Publications and source records attributed to G Kühne.

At least 19 recordsLinked to original sources

PubMed2005

Measured total cross sections of slow neutrons scattered by solid deuterium and implications for ultracold neutron sources.

The total scattering cross sections for slow neutrons with energies in the range 100 neV to 3 meV for solid ortho-2H2 at 18 and 5 K, frozen from the liquid, have been measured. The 18 K cross sections are found to be in excellent agreement with theoretical expectations and for ultracold neutrons dominated by thermal up scattering. At 5 K the total scattering cross sections are found to be dominated by the crystal defects originating in temperature induced stress but not deteriorated by temperature cycles between 5 and 10 K.

Journal Article↗

PubMed2005

Measured total cross sections of slow neutrons scattered by gaseous and liquid 2H(2).

The total scattering cross sections for slow neutrons with energies E in the range 300 neV to 3 meV for gaseous and liquid ortho-2H2 have been measured. The cross sections for 2H2 gas are found to be in excellent agreement with both the Hamermesh and Schwinger and the Young and Koppel models. For liquid 2H(2), we confirm the existing experimental data in the cold neutron range and the discrepancy with the gas models. We find a clear 1 / square root[E'] dependence at low energies for both states. A simple explanation for the liquid 2H2 cross section is offered.

Journal Article↗

PubMed2004

Neutron capture autoradiographic study of the biodistribution of 10B in tumor-bearing mice.

For the study on boron neutron capture therapy, the whole-body sections of tumor-bearing mice infused with 10B attached to CR-39 plastic track detectors were exposed to thermal and cold neutron beams. Neutron capture autoradiographic images obtained by the cold neutron irradiation were extremely superior in quality to those of the thermal neutron beams. From the autoradiographic images, the 10B reaction dose of the neutron-induced particles was estimated using the differential LET distribution.

Animals↗

PubMed2001

Resynthesis of muscle glycogen after soccer specific performance examined by 13C-magnetic resonance spectroscopy in elite players.

The purpose of this study was to examine using 13C-magnetic resonance spectroscopy whether muscle glycogen (Gly) utilized during a simulation of a fatiguing soccer match followed by repeated sprints would be resynthesized during the next 24 h while players consumed their habitual diet. A group of 12 elite young players [mean age 17.5 (SD 0.8) years, mean body mass 68.9 (SD 6.6) kg, mean height 177.0 (SD 5.4) cm] participated in the study. Average muscle Gly content before the simulation was 134 (SD 16) mmol.(kg wet mass)-1 and decreased during the test (P < 0.001) to 80 (SD 29) mmol.(kg wet mass)-1. The value had increased (P < 0.01) to 122 (SD 33) mmol.(kg wet mass)-1 24 h later but it was not significantly different from the value obtained before the soccer test. Dietary analysis of the food intake during the 24 h after the running test revealed that players consumed an average of 2,681 (SD 970) kcal.day-1. Mean daily protein, fat, and carbohydrate (CHO) intakes were 85 (SD 29), 99 (SD 44), and 327 (SD 116) g, respectively. The mean amounts of CHO intake normalised to body mass were 4.8 (SD 1.8) g.(kg body mass)-1. In conclusion, the results of this study showed that despite a CHO intake of less than 5 g.(kg body mass)-1 the habitual diet of soccer players might be sufficient to replenish in 24 h the muscle Gly utilized during soccer specific performance. However, cumulative deficits of about 10% in Gly replenishment as found in the present study might provoke decrements in performance. Thus, players should pay attention to their habitual diets and add more carbohydrates to replenish their daily deficits and perhaps increase their basal levels of intake.

Adolescent↗

PubMed1999

Noninvasive measurement of muscle high-energy phosphates and glycogen concentrations in elite soccer players by 31P- and 13C-MRS.

PURPOSE: The purpose of this study was to measure noninvasively the absolute concentrations of muscle adenosine triphosphate [ATP], phosphocreatine [PCr], inorganic phosphate (Pi), and glycogen [Gly] of elite soccer players. METHODS: Magnetic resonance spectroscopy (31P- and 13C-MRS) was used to measure the concentrations of metabolites in the calf muscles of 18 young male players [age = 17.5 +/- 1.0 (SD) yr]. RESULTS: Average muscle [PCr] and [ATP] were 17.8 +/- 3.3 and 6.0 +/- 1.2 mmol x (kg wet weight)(-1), respectively. The ratios of Pi/PCr and PCr/ATP were 0.15 +/- 0.05 and 3.00 +/- 0.26, respectively. The muscle [Gly] was 144 +/- 54 mmol x (kg wet weight)(-1). There was a high correlation (r = 0.93, P < 0.0001) between muscle ATP and PCr concentrations, but there was no correlation between [Gly] and [PCr] or [ATP]. The concentrations of the different metabolites determined in the present study with noninvasive MRS methods were within the ranges of values reported in human muscle from biochemical analysis of muscle biopsies. CONCLUSION: MRS methods can be utilized to assess noninvasively the muscle energetic status of elite soccer players during a soccer season. The high correlation between ATP and PCr might be indicative of fiber type differences in the content of these two metabolites.

Adenosine Triphosphate↗

PubMed1998

Identification of the end stage of scrapie using infected neural grafts.

Although the formal pathogenesis of spongiform encephalopathies has been described in detail, it is not known whether the infectious agent targets primarily neurons, glial cells, or both. To address this question, we have transplanted transgenic embryonic neural tissue overexpressing PrP(c) into the forebrain of Prnp -knockout mice, and infected it with scrapie prions. After infection, grafts developed severe spongiform encephalopathy. As the infected hosts were not clinically affected, we were able to prolong the experiment and to assess changes in the graft over periods of time, which vastly exceeded the normal life span of scrapie-infected mice. Sequential contrast-enhanced magnetic resonance imaging (MRI) revealed progressive impairment of blood-brain barrier properties in infected grafts. However, loss of astrocytes was not observed. Subtotal neuronal loss occurred during the progression of the disease in the grafts, reactive astrocytes persisted until the terminal stage of disease. We conclude that scrapie encephalopathy primarily leads to neuronal death, while degeneration of astrocytes does not occur. Functional impairment of the blood-brain barrier suggests involvement of astrocytes and endothelial cells in the pathological process.

Animals↗

PubMed1996

In vivo evaluation of magnetite nanoparticles for use as a tumor contrast agent in MRI.

Magnetite nanoparticles, coated by three different artificial polypeptides, were conjugated to an antibody specific to the carcinoembryonic antigen (CEA). To protect the particles from fast blood elimination, the coats were modified by various sugars, polyethyleneglycol, albumin, and sialoproteins, respectively. The protective effect was determined by using a specific in vitro test and by analyzing the biodistribution of the nanoparticles in nude mice grafted with CEA-tumors. In particular, a prolongation of the blood circulation time has been expected, if a natural modifier is attached to the coated nanoparticles. Although the elimination rate could hardly be decreased by any modifiers, the tumor accumulation is slightly improved by using the specific sialoprotein glycophorin B. The usefulness of nanoparticles as image contrast agents is probably limited by their microdistribution within the tumor tissue. The requirements for a contrast agent to be highly tissue specific are discussed.

Animals↗

PubMed1996

Comparative in vivo and pathological analysis of the blood-brain barrier in mouse telencephalic transplants.

The post-transplantation status of the blood-brain barrier (BBB) is still a matter of debate. In an attempt to define BBB properties after neural transplantation in mice of a defined genetic background, we have used two exogenous markers (horseradish peroxidase and Evans blue), one endogenous marker (immunoglobulins), and in vivo contrast enhanced magnetic resonance imaging (MRI) and compared the results obtained with the different methods. With all four techniques employed, we found the BBB to be reconstituted in 67% of the grafts 3 weeks after grafting, and in more than 90% of all grafts 50 days after grafting. Horseradish peroxidase and contrast enhanced MRI were the most sensitive techniques, the latter offering the unique advantage of repetitive scanning of individual grafts. Our findings provide important information for transplantation studies in mouse models for neurodegenerative diseases.

Animals↗

PubMed1995

The AMOG/beta 2 subunit of Na,K-ATPase is not necessary for long-term survival of telencephalic grafts.

Adhesion molecule on glia (AMOG) represents the beta 2-subunit of murine Na,K-ATPase. Mice carrying a targeted deletion of the AMOG/beta 2 gene exhibit tremor and limb paralysis at postnatal day (P) 15 and die 2 days after the onset of symptoms. The brains of these mice show edema and swelling of astrocytic end feet. However, the cause of death has remained unclear. To identify long-term consequences of AMOG/beta 2 deficiency, we have grafted parts of the embryonic telencephalic anlage of AMOG/beta 2-deficient mice into the caudoputamen of wild-type mice and analyzed the grafts up to 500 days after transplantation. Histological, immunocytochemical, and in situ hybridization techniques were applied to examine histoarchitecture, proliferation, differentiation, and long-term survival of grafts. AMOG/beta 2-deficient telencephalic grafts develop normally and form solid neural tissue that cannot be distinguished from control grafts by morphological features or with immunocytochemical stains for neuronal and glial markers. No signs of degeneration can be found. Expression analysis, however, revealed that no AMOG/beta 2 protein of possible host origin can be detected in AMOG/beta 2-deficient grafts. Graft-borne astrocytes express neither the AMOG/beta 1 nor the AMOG/beta 2 subunit of Na,K-ATPase as examined with immunocytochemistry and in situ hybridization. These findings indicate that AMOG/beta 2 is not necessary for long-term survival of telencephalic graft tissue.

Adenosine Triphosphatases↗

PubMed1995

Circadian plasma level profile of lisuride in rats and mice after continuous administration via the diet.

Lisuride (Dopergin, CAS 18016-80-3), a dopamine D2 agonist, was administered to male and female rats and mice continuously via the diet for 14 days. The doses were 0.2 mg/kg/d in mice and 1 mg/kg/d in mice and rats. Plasma level profiles (0-22 or 24 h) were determined by measuring lisuride concentrations by radioimmunoassay. At all doses a plateau-like plasma level of lisuride was observed. A clear circadian rhythm of lisuride concentrations (highs during night, low levels during day) was found for male rats (1 mg/kg/d) and for male mice (0.2 mg/kg/d). Female animals did not show this phenomenon as pronounced. At the same dose of 1 mg/kg/d rats showed higher plasma levels than mice. For males the ratio of total AUCs was 1.9 and for female animals 8.6.

Animals↗

PubMed1994

Anti-inflammatory activity of rolipram in a rat ear edema model.

In the present study the anti-inflammatory activity of the phosphodiesterase inhibitor rolipram (ZK 62,711, CAS 61413-54-5) was tested in a rat model where edema was induced in the ears of the animals by the epicutaneous application of croton oil in ethanol (5%, by volume). The administration of 0.015, 0.15 and 1.5 mg rolipram per ear dose-dependently inhibited the formation of edema. Concomitantly, the body temperature of the rats was decreased. 4-14% of rolipram was percutaneously absorbed within a 5-h interval. The absorbed proportion, represented by the area under the plasma level-time curve, correlated with the inhibition of edema formation and with the decrease in body temperature.

Administration, Topical↗

PubMed1993

Biotransformation of the antidepressant D,L-rolipram. II. Metabolite patterns in man, rat, rabbit, rhesus and cynomolgus monkey.

1. The metabolism of D,L-rolipram in man was studied by comparison of h.p.l.c. radiochromatograms of plasma and urine obtained at various times following oral and/or s.c. administration to man, rat, rabbit, and rhesus and cynomolgus monkey. 2. Seven metabolites isolated previously from man, rat, and rhesus monkey urine by preparative h.p.l.c. and identified by mass spectrometry and n.m.r. analysis were used for metabolite identification. 3. In plasma, 3-5 metabolites were found in addition to the unchanged drug. In urine, which was the main excretion route for rolipram metabolites, > 10 metabolites were detected but not the parent compound. 4. Between 40 and 70% of the compounds eliminated renally, were identified by reference to isolated metabolites. 5. Biotransformation proceeded by ether cleavage at the methoxy and pentyloxy groups, and by hydroxylation in positions 2 or 3 of the pentyloxy ring followed by sulphation. 6. In man, not in the other species studied, the 5-position of the pyrrolidone ring was also hydroxylated. This compound cross-reacted with the antibody raised against rolipram which was used formerly for the determination of rolipram in biological fluids.

Animals↗

PubMed1992

High-performance liquid chromatographic procedure for specificity testing of radioimmunoassays: rolipram.

A high-performance liquid chromatographic (HPLC) procedure for testing the specificity of radioimmunoassays (RIA) was developed using the same method of extraction as in the RIA, followed by fractionation of the extract by HPLC and subsequent measurement of cross-reactions in all the fractions according to the normal RIA procedure. The RIA of rolipram, an antidepressant drug, was checked in plasma samples obtained from pharmacokinetic studies in rats, rabbits, cynomolgus monkeys and humans. The antibody was shown to be specific in the plasma samples from the laboratory animals, but not in human plasma. This was because in human plasma a metabolite occurred with a structure similar to that used for the hapten in the immunization process. This metabolite was not found in the plasma of the animal species investigated. The test procedure described is generally applicable, making the time-consuming development of an alternative method such as gas chromatography-mass spectrometry unnecessary.

Animals↗

PubMed1991

The pharmacokinetics and pharmacodynamics of lisuride in healthy volunteers after intravenous, intramuscular, and subcutaneous injection.

The plasma concentration of lisuride and prolactin have been measured in twelve healthy male volunteers after IV, IM or SC injection of 25 micrograms lisuride hydrogen maleate as an aqueous solution. After IV administration the plasma lisuride fell in two phases with half-lives of 14 min and 1.5 h. Total clearance was 13 ml.min-1.kg-1. After IM and SC injection the plasma concentrations peaked at 12 to 15 min and the profiles were similar to that found after IV administration. The systemic availabilities were 90% and 94%, respectively. Prolactin concentrations were reduced by a maximum of 60% relative to the normal circadian rhythm after all three routes of administration. The treatments were well tolerated, the only adverse reactions reported by some of the volunteers being mild, transient dizziness, tiredness, and nausea.

Adult↗

PubMed1991

Pharmacokinetics of 3H-terguride in elderly volunteers.

Blood and plasma levels and excretion of labeled compounds and of the unchanged drug were measured after i.v. injection of 54 micrograms and p.o. administration of 540 micrograms of the ergoline derivative, terguride (CAS 37686-84-3), labeled with tritium, in 6 elderly male volunteers. Following i.v. injection plasma levels of terguride declined with a half-life of 0.5 h and those of radiolabeled compounds with half-lives of 0.5 h, 7 h and 19 h. The total clearance was 17 ml/min/kg and the volume of distribution was 0.7 l/kg. After p.o. administration terguride was rapidly and completely absorbed. The bioavailability was around 20%. Elimination of labeled compounds was complete within 7 days and proceeded mainly via the urine. Computer simulation of plasma levels after 4-times-a-day multiple administrations indicated slight accumulation of metabolites (factor 3) and no accumulation of terguride (factor 1).

Aged↗

PubMed1990

Pharmacokinetics and endocrine effects of terguride in healthy subjects.

Plasma levels of the partial dopamine agonist, terguride, were measured by RIA in healthy volunteers after a single i.v. dose of 50 micrograms and on the first and seventh day of an oral treatment with 250 micrograms, 500 micrograms and 750 micrograms b.d. Basal and releasing hormone (TRH, GHRH, CRF, LHRH)-stimulated pituitary hormone secretion (PRL, TSH, GH, FSH, LH) and cortisol were also determined by RIA. Following the i.v. injection, plasma terguride levels declined biphasically, with half-lives of 0.2 and 1.5 h; total clearance was 17 ml.min-1.kg-1. The oral bioavailability of terguride over all doses was about 20%. Basal and TRH-stimulated prolactin levels were dose-dependently depressed, but the secretion of other hormones remained unaffected. Tolerance of terguride was excellent and there was no negative effect on performance or mood, nor on mixed-function oxygenase activity, assessed as urinary 6 beta-OH cortisol.

Adult↗

PubMed1990

Pharmacokinetics of (+)-rolipram and (-)-rolipram in healthy volunteers.

Plasma levels of S-(+)-rolipram and R-(-)-rolipram in six healthy male volunteers were measured by radioimmunoassay after intravenous injection of 0.1 mg and oral administration of 1.0 mg of the pure enantiomers. Following i.v. treatment, plasma levels of both isomers declined in three phases, with half-lives of 0.2 h, 0.6-0.9 h and 6-8 h. Total clearance was 6 ml.min-1.kg-1. Oral administration of 1.0 mg gave a peak concentration of 16 ng.ml-1 after 0.5 h. Bioavailability of (+)-rolipram was 77% and of the (-) enantiomer it was 74%. There was no significant difference in Cmax, half-life, total clearance or bioavailability between the two enantiomers.

Administration, Oral↗

PubMed1989

Pharmacokinetics of the antidepressant rolipram in healthy volunteers.

1. The pharmacokinetics of rolipram were studied in healthy male volunteers using 3H-rolipram and a radioimmunoassay for measurement of unchanged drug. 2. Rolipram was rapidly and completely absorbed after an oral dose of 1 mg. Bioavailability was 73%. 3. Plasma levels of the unchanged drug declined with a terminal half-life of 2 h. The total clearance of rolipram was 2 ml/min per kg. 4. Labelled rolipram was excreted rapidly and completely. The main route of elimination was via the urine.

Administration, Oral↗