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Biomedical subjects

D Hermann

Publications and source records attributed to D Hermann.

At least 19 recordsLinked to original sources
PubMed2006

Quetiapine in relapse prevention in alcoholics suffering from craving and affective symptoms: a case series.

PURPOSE: Quetiapine is a novel antipsychotic, which is efficacious in the treatment of positive and negative symptoms in schizophrenia. Research has shown that atypical antipsychotic also reduce the craving and consumption for stimulants and alcohol. Due to Quetiapine's particulars and the promising receptor profile concerning addiction medicine, we set out to examine the tolerability and efficacy concerning relapse prevention of withdrawn alcoholics suffering from craving and affective symptoms. SUBJECTS AND METHODS: Our case observations attempted to evaluate nine alcoholics after withdrawal suffering from persisting craving, sleep disorder, excitement, depressive symptoms or anxiety symptoms. The patients were treated with quetiapine as relapse prevention and we followed them up in our outpatient clinic. RESULTS: Eight out of nine patients were abstinent under quetiapine over a period of 2-7 months. One of these patients relapsed after he stopped taking the preparation at his own initiative after 10 weeks. The ninth patient stopped taking the preparation immediately because of swollen nasal mucosae. All target symptoms disappeared in the patients after an average of (mean+/-S.D.) 24.5+/-18.1 days. The overall tolerability was considered to be very good; however, initial sleepiness appeared in four patients. CONCLUSION: Although uncontrolled case observations can only be interpreted with caution quetiapine seems to deserve further investigation and may hold the potential for preventing alcohol relapse in alcoholics suffering from additional above-mentioned symptoms.

Adult↗
PubMed2005

Reduction of side effects by combining clozapine with amisulpride: case report and short review of clozapine-induced hypersalivation-a case report.

Side effects from a high-dose clozapine treatment for a schizophrenic patient led to massive compliance problems. The dose of clozapine could be halved without recurrence of an acute psychotic symptomatology by concomitantly administering amisulpride. The side effects, especially hypersalivation, disappeared almost entirely, which in turn led to good compliance. In a short review we would like to present the pathophysiology and therapeutic options of clozapine-induced hypersalivation.

Adult↗
PubMed2004

[Drug-induced headache and pain reduction medication with amitriptyline in an 11-year old pupil].

We report on an 11-year-old pupil who present-ed to a neurological practice in the company of his parents because of migraine and strong headaches. Precise anamnesis of drugs yielded the diagnosis of a drug-induced headache with underlying migraine disease. The boy was afflict-ed with a hereditary taint, as both parents also suffered from migraine. The mother was also continuously in treatment because of a chronic pain disorder. Therapy with up to 50 mg per day of amitriptyline enabled the boy to stop consuming analgesics without suffering from head-aches. Moreover, under 47.5 mg per day of metoprolol, the migraine symptoms did not re-occur.

Amitriptyline↗
PubMed2002

Development of alcohol-associated cues and cue-induced brain activation in alcoholics.

The objective of this study was to develop new standardized alcohol-associated cues and assess their effects on brain activation with functional magnetic resonance imaging (fMRI). Pictures of alcoholic and neutral beverages and affectively neutral pictures were presented to 44 abstinent alcoholics and 37 age-matched healthy control subjects. We assessed the skin conductance response, and the elicited arousal and valence. Alcoholics and control subjects did not differ in arousal, valence or skin conductance response evoked by alcohol-associated and affectively neutral stimuli, while nonalcoholic beverages were rated as more unpleasant and arousing by alcoholics compared with control subjects. In the fMRI pilot study, alcohol and abstract pictures were presented to six abstinent alcoholics and induced a significant activation of brain areas associated with visual emotional processes such as the fusiform gyrus, parts of the brain reward system (basal ganglia and orbitofrontal gyrus) and further brain regions in the frontal and parietal cortices associated with the attention network. These observations suggest that standardized pictures of alcoholic beverages can be used to assess brain circuits involved in the processing and evaluation of alcohol cues.

Adult↗
PubMed2001

Semliki Forest virus vectors: efficient vehicles for in vitro and in vivo gene delivery.

Rapidly generated high-titer Semliki Forest virus (SFV) vectors can infect numerous mammalian cell lines and primary cell cultures, and result in high levels of transgene expression. SFV-based expression of transmembrane receptors has been characterized by specific ligand-binding activity and functional responses. Adaptation of the SFV technology for mammalian suspension cultures has allowed the production of hundreds of milligrams of recombinant receptor for purification and structural studies. The same SFV stock solutions used for the infection of mammalian cells in culture have also been successfully applied for efficient transgene expression in organotypic hippocampal slices, as well as in vivo in rodent brain.

Animals↗
PubMed2001

Novel mutant Semliki Forest virus vectors: gene expression and localization studies in neuronal cells.

Semliki Forest virus vectors (SFV) are suitable for high-level transgene expression in neuronal tissue, both in vitro and in vivo. Cortical and hippocampal primary neurons in culture are efficiently infected resulting in 75-95% of GFP-positive cells, and injection of SFV vectors into hippocampal slice cultures revealed a highly neuron-specific expression pattern with more than 90% of the infected cells being neurons. Here, we present novel SFV vector mutants and describe their infection patterns obtained in cultures of baby hamster kidney (BHK) cells, dissociated hippocampal neurons, and organotypic hippocampal slices. A less cytotoxic vector SFV(PD), carrying two point mutations in the nsP2 gene, showed much higher GFP expression levels in primary hippocampal neurons compared to the wild-type SFV vector. A triple mutant vector SFV(PDE153) demonstrated a temperature-sensitive phenotype in both BHK cells and primary neurons. In hippocampal slices cultured at 36 degrees C, SFV(PDE153) showed a remarkably higher (ca 250-fold) preference for expression in interneurons rather than in pyramidal cells as compared to wild-type SFV. The quadruple mutant SFV(PDTE) led to substantially increased and prolonged GFP expression in primary neurons. Relative to SFV(PDE153), a more pronounced temperature-sensitive phenotype was found resulting in no virus production and no GFP expression at the non-permissive temperature (36-37 degrees C) in BHK cells, in dissociated neurons, and in organotypic hippocampal slices. The described novel SFV vectors will be useful for several specific applications in neurobiology.

Animals↗
PubMed2001

Alcohol-associated stimuli activate the ventral striatum in abstinent alcoholics.

Alcohol-associated cues may act as conditioned stimuli that activate the brain reward system and motivate alcohol intake in alcoholics. Alcohol-associated visual stimuli were presented during functional magnetic resonance imaging. An activation of the ventral putamen was observed in alcoholics but not in control subjects. Patients with a strong activation of the ventral putamen relapsed during the next three months. This observation supports the hypothesis that alcohol use affects areas involved in brain reward circuits and that their stimulus-induced activation may be associated with an increased risk for relapse.

Adult↗
PubMed2001

Thyroid function test abnormalities in newly admitted psychiatric patients residing in an iodine-deficient area: patterns and clinical significance.

OBJECTIVE: The prevalence of abnormal in-vitro thyroid function tests in psychiatric in-patients may be as high as 24%. Thus far, however, there is only limited data addressing the underlying causes of these abnormal test results, i.e. how often they can be attributed to genuine thyroid disease. METHOD: We conducted an observational study of all in-patients admitted to our institution during 1 calendar year running analyses of total thyroxin (T4), free thyroxin index (FTI) and thyroid-stimulating hormone (TSH). Patients with abnormal test results were classified according to an algorithm which had been established previously. RESULTS: In 243 of 880 patients with in-vitro thyroid function analysis, at least one concentration of either T4, FTI or TSH was found to be outside the reference range. Work-up according to the algorithm was completed in 848 patients; alterations were classified as representing thyroid dysfunction in 100 (41% of patients with abnormal test results), non-specific findings in 92 (38%), influence of ingested drugs in 18 (7%) and of severe physical disease in 1 (0.4%). As measures of T4 and/or FTI provided no essential information in 854 patients (97% of tested), we found that in most cases the determination of TSH alone was sufficient for demonstrating normal thyroid function. CONCLUSION: In 27.6% of newly admitted patients living in an iodine-deficient area, at least one abnormal result in either T4, FTI or TSH values was found. Genuine thyroid disease was found in slightly less than half the patients with an abnormal value.

Adolescent↗
PubMed2001

Improved Semliki Forest virus vectors for receptor research and gene therapy.

We have modified Semliki Forest virus (SFV) vectors to broaden their application range. Here we describe a series of site-directed mutagenesis experiments on the SFV subgenomic 26S promoter to down-regulate the heterologous gene expression. Several mutants showed a dramatic effect on transgene expression levels in BHK cells. The luciferase activity was reduced to approximately 30%, 3%, and 1% compared to the wild type promoter. Similarly, a decrease in beta-galactosidase activity was observed in BHK cells and after injection into the striatum of male Wistar rats. Novel non-cytopathogenic and temperature-sensitive SFV vectors have recently been developed by introduction of point mutations in the viral nonstructural genes nsP2 and nsP4. These vectors do not show the typical shut down of host cell protein synthesis after SFV infections and therefore allow for a substantially prolonged survival of host cells. Both the mutant vectors demonstrating lower and more physiological expression levels and the non-cytopathogenic vectors should be valuable tools for various applications within receptor research. Furthermore, recent studies suggest that SFV vectors can be efficient gene delivery vehicles for gene therapy applications.

Amino Acid Sequence↗
PubMed2000

Evolution of energy failure after repeated cerebral ischemia in gerbils.

We have examined the regional differences in the evolution of energy failure in experimental focal cerebral ischemia. In gerbil brain subjected to repeated unilateral common carotid artery occlusion, the tissue ATP content, pH and succinic dehydrogenase activity decreased at different rates after the circulation had been restored in various cerebral regions. Light microscopical infarction became apparent at different rates following the impairment of the energy metabolism in these regions. In brain cortex with selective neuronal necrosis, only minor alterations in energy metabolism were detectable over a 7-day period following the restoration of the circulation. The present data show that the rate of energy failure is significantly different in various cerebral regions after repeated periods of cerebral ischemia in the gerbil. A slowly evolving impairment of the cerebral energy metabolism after circulation of the brain has been restored appears to be indispensable for the delayed formation of infarction after transient cerebral ischemia.

Acid-Base Equilibrium↗
PubMed2000

Regional differences in the rate of energy impairment after threshold level ischemia for induction of cerebral infarction in gerbils.

The development of infarction and/or selective neuronal death in the brain after transient cerebral ischemia depends on the severity of the ischemic episode. After transient cerebral ischemia of the threshold level for the induction of infarction, both changes evolve slowly in various postischemic regions. We examined the relationship of disturbances of energy metabolism to infarction and selective neuronal death in various regions of the postischemic brain subjected to two 10-min occlusions of the unilateral common carotid artery. Our results indicated that in various cerebral regions that developed infarction, the tissue ATP content, in parallel with the succinic dehydrogenase activity, fell to their lowest levels at different times over a 4-day period after circulation had been restored (earliest to latest: dorsolateral thalamus > dorsolateral caudate > chiasmal level cortex > hippocampal CA3 sector > hippocampal CA sector). In the cortex at the infundibular level, disseminated selective neuronal death developed over a 7-day period following restoration of circulation; it was accompanied by only a slight alteration in energy metabolism. The present results indicate that regional differences existed in the rate of energy impairment and evolving infarction in the postischemic gerbil brain. Energy impairment, in association with mitochondrial enzymatic dysfunction, seems to be indispensable for the delayed manifestation of cerebral infarction but not for disseminated selective neuronal death.

Adenosine Triphosphate↗
PubMed2000

One hundred years of alcoholism: the Twentieth Century.

The past 100 years witnessed the formation of a disease concept of alcoholism and a rapid increase in the knowledge of its aetiopathology and treatment options. In the first half of the century, public sanctions aimed at the abolition of alcoholism. In the United States, alcohol prohibition was revoked in the economic turmoil of the Great Depression. In Germany, proposed medical procedures to reduce the fertility of alcoholics had catastrophic consequences during the fascist dictatorship. A revived focus on alcoholics as patients with a right to medical treatment came out of self-organized groups, such as Alcoholics Anonymous. The current disease concept includes the psychosocial and neurobiological foundations and consequences of alcoholism. Neurobiological research points to the dispositional factor of monoaminergic dysfunction and indicates that neuroadaptation and sensitization may play a role in the maintenance of addictive behaviour. New treatment options include pharmacological approaches and indicate that behaviour and motivational therapy and the attendance of patient groups may equally reduce the relapse risk. The task of the future will be to apply scientific discoveries in the best interest of the patients and to support their efforts to be respected like subjects suffering from other diseases.

Alcoholism↗
PubMed2000

Dynamics of regional brain metabolism and gene expression after middle cerebral artery occlusion in mice.

The evolution of brain infarcts during permanent occlusion of the middle cerebral artery (MCA) was studied in mice using multiparametric imaging techniques. Regional protein synthesis and the regional tissue content of ATP were measured on adjacent cryostat sections at increasing intervals after vascular occlusion ranging from 1 hour to 3 days. The observed changes were correlated with the expression of the mRNA of hsp70, c-fos, c-jun, and junB, as well as the distribution of DNA double-strand breaks visualized by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL). One hour after MCA occlusion, the tissue volume with suppressed protein synthesis was distinctly larger than that in which ATP was depleted. With ongoing ischemia time, the ATP-depleted area gradually expanded and, within 1 day, merged with the region of suppressed protein synthesis. Expression of hsp70 mRNA occurred mainly in the penumbra (defined as the region of suppressed protein synthesis but preserved ATP), peaking at 3 hours after vascular occlusion. Expression of the immediate-early genes c-jun, c-fos, and junB increased both in the penumbra and the periinfarct normal tissue already at 1 hour after vascular occlusion, with slightly different regional and temporal patterns for each of these genes. DNA fragmentations were clearly confined to neurons; they appeared after 1 day in the infarct core (defined as the region of suppressed ATP) and never were detected in the penumbra. The late appearance of TUNEL after infarcts had reached their final size and the absence in the penumbra points against a major pathogenetic role of apoptosis. Permanent MCA occlusion in mice thus produces a gradually expanding infarct, the final size of which is heralded by the early inhibition of protein synthesis.

Adenosine Triphosphate↗
PubMed2000

Evolution of brain infarction after transient focal cerebral ischemia in mice.

The evolution of brain infarction after transient focal cerebral ischemia was studied in mice using multiparametric imaging techniques. One-hour focal cerebral ischemia was induced by occluding the middle cerebral artery using the intraluminal filament technique. Cerebral protein synthesis (CPS) and the regional tissue content of adenosine triphosphate (ATP) were measured after recirculation times from 0 hours to 3 days. The observed changes were correlated with the expression of the mRNAs of hsp-70, c-fos, and junB, as well as the distribution of DNA double-strand breaks, visualized by TUNEL. At the end of 1 hour of ischemia, protein synthesis was suppressed in a larger tissue volume than ATP in accordance with the biochemical differentiation between core and penumbra. Hsp70 mRNA was selectively expressed in the cortical penumbra, whereas c-fos and junB mRNAs were increased both in the lateral part of the penumbra and in the ipsilateral cingulate cortex with normal metabolism. During reperfusion after withdrawal of the intraluminal filament, suppression of CPS persisted except in the most peripheral parts of the middle cerebral artery territory, in which it recovered between 6 hours and 3 days. ATP, in contrast, returned to normal levels within 1 hour but secondarily deteriorated from 3 hours on until, between 1 and 3 days, the ATP-depleted area merged with that of suppressed protein synthesis leading to delayed brain infarction. Hsp70 mRNA, but not c-fos and junB, was strongly expressed during reperfusion, peaking at 3 hours after reperfusion. TUNEL-positive cells were detected from 3 hours on, mainly in areas with secondary ATP depletion. These results stress the importance of an early recovery of CPS for the prevention of ischemic injury and suggest that TUNEL is an unspecific response of delayed brain infarction.

Adenosine Triphosphate↗
PubMed1999

Validation of a population pharmacokinetic/pharmacodynamic model for 5 alpha-reductase inhibitors.

A population pharmacokinetic/dynamic model describing the conversion of testosterone to dihydrotestosterone (DHT) by 5alpha-reductases and the irreversible inhibition of 5alpha-reductase(s) by finasteride and dutasteride was validated. The model had been developed using data from a single dose study in healthy volunteers and was validated against data from a 28-day repeat dose study in patients with benign prostatic hyperplasia. Validation was carried out by comparing results of Monte Carlo simulations to the observed data, fitting the model to the repeat dose data and comparing with previously derived parameter values, and examining individual predictions of the model for the individuals in the repeat dose study for any bias. Simulations closely predicted the outcome of the repeat dose study, estimated parameters of the pharmacodynamic modelling were generally close to within 88 to 116% of those from the original model and the individual predictions did not indicate any bias. Thus the model derived from single dose data from healthy volunteers was considered to be valid for the prediction of DHT levels in the patient population after repeated dosing of dutasteride and finasteride.

5-alpha Reductase Inhibitors↗
PubMed1999

Studies on wound healing: effects of calcium D-pantothenate on the migration, proliferation and protein synthesis of human dermal fibroblasts in culture.

The effect of calcium D-pantothenate on the migration, proliferation and protein synthesis of human dermal fibroblasts from three different donors was investigated. The migration of cells into a wounded area was dose-dependently stimulated by Ca D-pantothenate. The number of cells that migrated across the edge of the wound increased from 32 +/- 7 cells/mm without Ca D-pantothenate to 76 +/- 2 cells/mm with 100 mg/ml Ca D-pantothenate. Moreover, the mean migration distance per cell increased from 0.23 +/- 0.05 mm to 0.33 +/- 0.02 mm. The mean migration speed was calculated to be 10.5 mm/hour without and 15 mm/hour with Ca D-pantothenate. Cell proliferation was also dose-dependently stimulated. The final cell densities were 1.2 to 1.6-fold higher in cultures containing 100 mg/ml Ca D-pantothenate. The protein synthesis was modulated, since two unidentified proteins were more strongly expressed in pantothenate supplemented cultures. In conclusion, Ca D-pantothenate accelerates the wound healing process by increasing the number of migrating cells, their distance and hence their speed. In addition, cell division is increased and the protein synthesis changed. These results suggest that higher quantities of pantothenate are locally required to enhance wound healing.

Cell Division↗
PubMed1999

Inhibition of autoimmune deterioration in MRL/lpr mice by vitamin E.

The potential of the antioxidant vitamin E to modulate the progress of the SLE-like (systemic lupus erythematosus) autoimmune disease in MRL/MP-lpr/lpr (MRL/lpr) mice is described. Mice were orally supplemented with 0.4 mg vitamin E per day 5 times per week from week 8 of age onwards and compared with mice on a commercial or a vitamin E-deficient diet. Supplementation with vitamin E extended the mean survival time from 157 to 196 days; the massive spleen and lymph node enlargements were reduced; mitogenic responses of B and T cells were normalized; the abnormal differentiation patterns of thymic and splenic cell sub-populations were changed; titers of anti-double stranded DNA antibodies, concentrations of serum amyloid P component (SAP, an acute phase protein), and proteinuria were reduced. The results indicate that vitamin E beneficially affects the development of the SLE-like disease in MRL/lpr mice suggesting a possible measure to reduce human SLE and probably various other autoimmune diseases in humans as well.

Animals↗