Topical application of mycophenolate mofetil in plaque-type psoriasis.
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Administration, Cutaneous↗
Biomedical subjects
K Jahn
Publications and source records attributed to K Jahn.
[The release of forensic patients (63 StGB) and the problem of predicting dangerousness].
This article presents first results of a prospective prediction study with participation of twenty-three forensic institutions from seven states of FRG. Main objective of this study is the determination of valid criteria for predicting recidivism of mentally disordered offenders. This evaluation (n = 188) investigates which patients are presently released from forensic institutions. In comparison to previous studies the releases per annum have decreased significantly. In the last two years there has been an increase in release of schizophrenic patients and a decrease in release of patients with a personality disorder and sexual offenders. In addition it has been analyzed which criteria therapists use to predict dangerousness from a clinical point of view.
Criminal Psychology↗
Investigation of the penetration behaviour of mycophenolate mofetil from a semisolid formulation into human skin ex-vivo.
Mycophenolate mofetil, the morpholinoethylester of mycophenolic acid, is an immunosuppressant used in combination with ciclosporin (cyclosporin) and corticosteroids to prevent organ rejection after heart and kidney transplantations. The drug seems also to be effective in dermal diseases after systemic administration. However, up to date mycophenolate mofetil can be only systemically administered and this is associated with several side effects such as nausea, leucopenia, sepsis, and diarrhoea. The aim of this study was to develop a topical formulation containing mycophenolate mofetil and to investigate in-vitro release and penetration into human skin ex-vivo. HPLC was applied to quantify mycophenolate mofetil after release studies from semisolid formulations using a dodecanol-collodion membrane as a lipophilic acceptor. Penetration studies with an amphiphilic cream using excised human breast skin were carried out in Franz-type diffusion cells. Mycophenolate mofetil and its active metabolite mycophenolic acid were detected by HPLC-MS after microsectioning in different skin layers. In this study the penetration of mycophenolate mofetil from an amphiphilic cream into excised human skin was shown. Additionally, the enzymatic hydrolysis of penetrated mycophenolate mofetil into mycophenolic acid was proven even under ex-vivo conditions. In-vivo a higher extent of metabolism of mycophenolate mofetil to mycophenolic acid would be expected because of the complete enzyme activity. This topical formulation might be a promising alternative to the usual systemic administration of mycophenolate mofetil in the treatment of skin diseases such as psoriasis.
Adult↗
Differential effects of vestibular stimulation on walking and running.
Prompted by our recent observation that an acute vestibular tone imbalance causes less deviation from the intended path when running than when slowly walking, we examined 10 healthy subjects when walking or running at different step frequencies during galvanic vestibular stimulation. Blindfolded subjects were asked to walk (1 Hz step frequency) or run (3 Hz step frequency) straight ahead toward a previously seen target. The mean gait deviation after 10 s was 6.0 +/- 2.4 degrees at 1 Hz and 2.8 +/- 1.8 degrees at 3 Hz step frequency (n = 10; p < 0.001, paired t-test). In a second experiment walking and running in place were investigated. There was no significant difference in body displacement. Walking and running are highly automated processes based on spinal locomotor generators that are under supraspinal control. We conclude that vestibular input is differentially regulated depending on the locomotion speed and pattern used.
Adult↗
Mechanism of block of nicotinic acetylcholine receptor channels by purified IgG from seropositive patients with myasthenia gravis.
OBJECTIVE: To clarify the mechanism of block of nicotinic receptor channels by myasthenic antibodies. BACKGROUND: Nicotinic acetylcholine receptor (nAChR) channel currents are functionally blocked by purified immunoglobulin G (IgG) of patients with myasthenia gravis (MG). METHODS: The molecular mechanism of block of IgG fractions containing antibodies to nAChR channels was tested with the patch-clamp technique in combination with a system for ultrafast solution exchange. For the experiments, outside-out patches from cultured mouse myotubes that express embryonic-type nAChR channels at their surface were used. RESULTS: Incubation of outside-out patches with purified IgG from four myasthenic patients blocked nAChR channel currents activated by the application of 1.0 mM ACh reversibly. The peak current amplitude and the time course of block of nAChR channels decreased with increasing concentrations of IgG. The block became at least partly irreversible if incubation time of outside-out patches exceeded 2 minutes. For the block of nAChR channel currents with a-bungarotoxin, a similar mechanism of block was found. CONCLUSIONS: The reversibility of functional block of nAChR channel currents by myasthenic IgG depended strongly on the incubation time of the receptors with antibodies. Interaction of myasthenic antibodies with nicotinic receptors may proceed in several stages from a low-affinity reversible to a high-affinity irreversible binding.
Adult↗
Introduction and evaluation of a modular seminar system in gross anatomy teaching at the Hannover Medical School.
We present a new modular seminar system which has been introduced into the gross anatomy teaching at the Hannover Medical School. It consists of seven modules with a clinical emphasis. The new modular seminar system was evaluated by an anonymous questionnaire. The results showed that the seminar system as a whole, and the different modules with one exception were highly appreciated by the students. The evaluation also revealed that the main reason for the success of a module is the manner of the teaching and learning rather than the clinical relevance. Taking into account the results of this evaluation we describe the appropriate style of teaching for use in a seminar. The success of this new approach to small group instruction in Germany should encourage other teachers of anatomy and other undergraduate subjects to consider new methods of teaching.
Anatomy↗
[Outcome predictors of intermediate-term treatments in inpatient child and adolescent psychiatry].
Purpose of this study is to identify predictors of the length of stay (LOS) in child and adolescent psychiatry (CAP) and the success of inpatient treatment. All child and adolescent inpatients that had been dismissed over a year's time from a non-university hospital after a medium-length-treatment were rated by their therapists (crisis interventions for < 2 weeks excluded). The group featured a low drop-out-rate (9.8%) and a high percentage of "problematic patients". The ICD-10 diagnoses were irrelevant for the prediction of LOS and success of treatment. The Global Assessment of Function scale (axis VI) correlated significantly with LOS, and functioning in all areas improved with a longer LOS. By the degree of initial psychopathology therapeutic success as well as LOS could be predicted fairly well. Concerning adolescents, motivation for treatment and the degree of cooperation both correlated with LOS and improvement, which implies the importance of their participation. For children under 12, cumulated psychosocial adversities (axis V) predicted a less positive outcome, cooperation of parents and patients raised the chance of success. Shortened lengths of stay will not lead to comparable success. As a system like DRGs for reimbursement of hospitalization in CAP will not prove to be efficient, other variables deserve more attention in future health economy planning. More intervening variables, such as psychosocial adversities, motivation, and cooperation have to be considered.
Adolescent↗
[Cerebral ischemia as initial manifestation of neoplastic low-malignancy changes. 2 case reports and review of the literatures].
Thrombembolic events as paraneoplastic complications in malignant disease account for severe morbidity and mortality in these patients. In some cases disturbance in hemostasis is the first manifestation of a neoplastic process. We report the cases of two patients with cerebral and extracerebral vessel occlusions, in whom epithelial tumors of low malignant potential (borderline-tumors) of ovary and peritoneum were diagnosed later on. In one case the removal of the tumor stopped the coagulation problems. The second patient died a few days after the first symptoms with devastating multiple vessel occlusion. In stroke of unknown aetiology a paraneoplastic process should be kept in mind. The diagnosis is more probable with recurrent thrombembolism in different body regions and when warfarin therapy was ineffective. Thoughtful coagulation studies and a tumor search program is recommended in these cases.
Adult↗
Molecular modulation of recombinant rat alpha1beta2gamma2 GABA(A) receptor channels by diazepam.
Recombinant gamma-aminobutyric acid (GABA(A)) receptor channels containing alpha1beta2gamma2-subunits were transiently expressed in HEK293 cells. Modulation by diazepam (DZ) was investigated using the patch-clamp technique with a device for ultra-fast solution exchange. GABA activated Cl(-)-currents were potentiated when DZ > 0.1 microM was added to non-saturating concentrations of GABA (< 0.1 mM GABA). Maximal potentiation of the peak current amplitude by a factor of 2.5 was observed when 1 microM DZ was added to the test-solution. Deactivation of GABA-activated currents after the end of GABA pulses was best fitted with two time constants. After application of DZ + GABA, increase of time constants of deactivation was measured. It was independent on GABA concentration. We conclude that prolongation of deactivation after application of GABA + DZ may be an important mechanism of the modulatory action of DZ at GABA(A) receptor channels.
Animals↗
Kinetics of AMPA-type glutamate receptor channels in rat caudate-putamen neurones show a wide range of desensitization but distinct recovery characteristics.
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor channels of rat caudate-putamen neurones were studied by ultrafast application of agonists to outside-out vesicles taken from medium-sized spiny neurones in thin slices. Upon application of 10 mM glutamate for 50 ms, fast rising and desensitizing currents were activated. Ten to 90% rise time values were approximately 0.5 ms. Dose-response studies revealed an EC50 of 0.63 mM glutamate. In double logarithmic coordinates, the curve had a maximal slope between 1.33 and 1.85 at low concentrations, indicating at least two binding sites for glutamate. Rise time increased with low agonist concentrations, whereas desensitization kinetics showed only a weak dependence on concentration. The time constant of desensitization was fitted with one exponential and ranged between 2 and 11 ms, with a mean of 6.19+/-2.31 ms (n = 239). Following brief glutamate pulses (1 ms) currents decayed with time constants of 2.7+/-0.23 ms (n = 12). Recovery from desensitization was investigated by double-pulse experiments. Recovery time constants fell in two subgroups with respective mean values of 110.6+/-14.2 ms (n = 8) and 288.6+/-33.2 ms (n = 8). By adding low glutamate concentrations to the bath solution, predesensitization of AMPA-type receptors without channel opening could be shown. A 50% reduction in control amplitude was achieved with 5.2+/-2.1 microM (n = 22) glutamate in the background. We hypothesize a circular reaction scheme with at least two binding sites for glutamate to describe activation, desensitization and recovery from desensitization in rat caudate-putamen neurones.
Animals↗
Activation kinetics and single channel properties of recombinant alpha1beta2gamma2L GABA(A) receptor channels.
Recombinant alpha1beta2gamma2L GABA(A) receptor channels, transiently expressed in HEK 293 cells, were investigated using the patch-clamp technique in combination with a device for ultra-fast solution exchange. The dose-response relationship revealed an EC50 of 11.6 +/- 0.9 microM and saturated with 3 mM GABA. The slope between 0.001 and 0.01 mM GABA was 2.2 +/- 0.4, indicating at least three binding sites for GABA. The rise time decreased from about 120 ms at 0.001 mM GABA to about 0.8 ms at 10 mM GABA. Single channel openings were grouped in bursts with an average duration of 10.3 +/- 3.0 ms. More than 95% of the current was represented by a single channel slope conductance of about 29 pS.
Cell Line↗
[Behavior of thiobarbituric acid reactive substances, alpha-tocopherol, glutathione and selenium during hypertension in pregnancy].
PATIENTS AND METHOD: In a longitudinal study the changes of serum or plasma levels of TBARS, alpha-tocopherol, glutathione and selenium were investigated comparing 46 pregnant women with hypertensive syndrome and 18 women with normal pregnancies. RESULTS AND CONCLUSIONS: A significant increase in TBARS serum level was found in women suffering from hypertension. There was no correlation between the severity of hypertension and the extent of the TBARS rise. An absolute deficiency of the antioxidants alpha-tocopherol, glutathione and the elements selenium, calcium, magnesium, iron and zinc as a cause or a consequence of hypertension in pregnancy could be excluded. Low serum levels of copper and selenium could decrease the activity of glutathione peroxidase (Gpx) resulting in higher levels of TBARS and glutathione during the last trimester of pregnancy and delivery. Increased concentrations of iron in women with hypertensive syndrome may affect the formation of lipid peroxides. The outcome of children was unaffected by increased lipid peroxide levels when an antihypertensive therapy was consequently performed.
Female↗
Distribution of desensitization time constants of mouse embryonic-like nicotinic and homomeric GLUR6 glutamate receptor channels.
The distribution of the desensitization time constant, tauD, of two different, molecular well defined ligand gated receptor channels was analyzed: the embryonic-like nicotinic receptor (nAChR) channel of cultured mouse myotubes and recombinant, homomeric GluR6 receptor channels transiently expressed in HEK293 cells. Experiments were performed using outside-out patches in combination with a system for fast application of agonists which allows solution exchange within 0.1 ms. In response to application of saturating concentrations of acetylcholine (ACh) or glutamate (Glu). the peak current was reached in a submillisecond range and decayed monexponentially in the presence of the agonist, due to desensitization. tauD varied from 10 ms to 100 ms with a mean value of 55.0 +/- 22.6 ms (n = 133) in response to pulses of 10(-4) M ACh for embryonic-like nAChR channels and from 2.6 ms to 8.9 ms with a mean value of 5.0 +/- 1.9 ms (n = 35) in response to pulses of 10(-2) M Glu for homomeric GluR6 receptor channels. The reason for the high variability of the time course of desensitization is at present unclear.
Animals↗
Glutamate receptor editing in the mammalian hippocampus and avian neurons.
RNA editing determines receptor kinetics and permeability of glutamate receptors. This post-transcriptional modification alters single nucleotides within an RNA transcript changing the codon specified by the genome resulting in the incorporation of a different amino acid, profoundly affecting the properties of the protein subunit. We have studied the three sites subject to RNA editing within the kainate-specific subunit GluR6 in the mammalian hippocampus to determine developmental changes and cell-specific variation in editing. GluR6, when measured in the whole rat hippocampus, is predominantly expressed in the unedited form at E18, with a gradual progression to the edited form during the 1st post-natal week, and remains stable from P8 through 30 months. Individual neurons from P0 through P8 rat hippocampal slices analyzed with single-cell PCR show predominant expression of fully edited GluR6, unlike the population profile. In contrast, single astrocytes from P0 hippocampal cultures show that the most common variant is partially edited. Thus, editing in neurons and glia differs, and this difference accounts for part of the disparity between single-neuron and whole-hippocampus data. Editing in astrocytes is affected by conditions in the external environment, as purified astrocytes fail to edit GluR6, although editing occurs in astrocytes from hippocampal cultures. The homogeneity of GluR6 editing between species was also determined by comparing editing in avians and mammals. Genomic and cDNA analysis of chick glutamate receptors demonstrates avian editing of GluR2 but not GluR6.
Animals↗
Synthesis and binding properties of oligodeoxynucleotides containing phenylphosphon(othio)ate linkages.
A method for the synthesis of chimeric oligodeoxynucleotides comprised of phosphodiester and phenylphosphonate [3'-O-P(= O)(C6H5)-O-5'] or phenylphosphono-thioate [3'-O-P(= S)(C6H5)-O-5'] linkages has been developed. Synthesis was performed using suitably protected nucleoside phenylphosphonamidites as building blocks following an adjusted solid-phase phosphoramidite synthesis protocol. The new oligodeoxy-nucleotide analogues were characterized by electrospray ionization- and matrix-assisted laser desorption mass spectrometry, as well as by 31P NMR spectroscopy. Additionally, their binding properties to complementary oligodeoxynucleotides has been studied.
Chromatography, High Pressure Liquid↗
Patch-clamp study on membrane properties and transmitter activated currents of rabbit area postrema neurons.
Using the patch-clamp technique in combination wit sliced tissue preparation the membrane properties of newborn rabbit area postrema neurons were investigated. The neurons responded upon depolarization with a fast Na+-current followed by an inactivating and non-inactivating K+-current. GABA-activated currents were investigated resulting in a large C1-(-)conductance, indicating the expression of GABAA-receptors. The expression of glutamate receptor mRNA was studied by in situ hybridization and electrophysiological measurements of these receptors by means of the patch-clamp technique. As a main result it was found that ionotropic glutamate receptors in the area postrema are composed of "flop" variants of the GluA-, GluB- and GluC-subunits.
Animals↗
Resolution and in vitro and initial in vivo evaluation of isomers of iodine-125-labeled 1-azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate: a high-affinity ligand for the muscarinic receptor.
1-Azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)- alpha-phenylacetate (IQNP, 1), is a highly selective ligand for the muscarinic acetylcholinergic receptor (mAChR). There are eight stereoisomers in the racemic mixture. The optical isomers of alpha-hydroxy-alpha-phenyl-alpha-(1-propyn-3-yl)acetic acid were resolved as the alpha-methylbenzylamine salts, and the optical isomers of 3-quinuclidinol were resolved as the tartrate salts. The E and Z isomers were prepared by varying the reaction conditions for the stannylation of the triple bond followed by purification utilizing flash column chromatography. In vitro binding assay of the four stereoisomers containing the (R)-(-)-3-quinuclidinyl ester demonstrated that each isomer of 1 bound to mAChR with high affinity. In addition, (E)-(-)-(-)-IQNP demonstrated the highest receptor subtype specificity between the m1 molecular subtype (KD, nM, 0.383 +/- 0.102) and the m2 molecular subtype (29.6 +/- 9.70). In vivo biodistribution studies demonstrated that iodine-125-labeled (E)-(-)-(+)-1 cleared rapidly from the brain and heart. In contrast, iodine-125-labeled (E)-(-)-(-)-, (Z)-(-)-(-)-, and (Z)-(-)-(+)-1 have high uptake and retention in mAChR rich areas of the brain. It was also observed that (E)-(-)-(-)-IQNP demonstrated an apparent subtype selectivity in vivo with retention in M1 (m1, m4) mAChR areas of the rain. In addition, (Z)-(-)-(-)-IQNP also demonstrated significant uptake in tissues containing the M2 (m2) mAChR subtype. These results demonstrate that the iodine-123-labeled analogues of the (E)-(-)-(-)- and (Z)-(-)-(-)-IQNP isomers are attractive candidates for single-photon emission-computed tomographic imaging of cerebral and cardiac mAChR receptor densities.
Animals↗
Patch clamp study of histamine activated potassium currents on rabbit olfactory bulb neurons.
Effects of histamine, histamine agonists and antagonists on steady state current in principal neurons and interneurons were investigated in thin slices from the olfactory bulb of newborn rabbits with the nystatin perforated patch-clamp technique and local pipette application. No change in steady state current was observed in mitral cells. In most of the periglomerular, juxtaglomerular and granular cells, however, H1-receptor activation caused an outward current; a similar effect, but mostly not on the same neurons was elicited by 8-bromo-cyclic-AMP. These currents were reversed at the potassium equilibrium potential, indicating block of a potassium current. Specific H3-receptor activation and cyclic GMP were ineffective. Histamine usually caused a combined effect beginning with an inward current. Histaminergic neurons fire with changes in behavioural state and can, by the described mechanisms, markedly influence signal processing in the olfactory bulb.
Animals↗