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C H Gleiter

Publications and source records attributed to C H Gleiter.

At least 19 recordsLinked to original sources
PubMed2006

Effect of endothelin-1 on erythropoietin production in a rat model under normoxia and functional carbon monoxide-induced hypoxia.

It has been hypothesized that autacoids, such as endothelin-1 (ET), may modulate erythropoietin (Epo) secretion. Therefore, we studied the effect of ET-1 infusion and of a nonselective ET(A/B) receptor antagonist on Epo secretion under carbon monoxide (CO) exposure. Anesthetized rats were supplied with room temperature air containing increasing concentrations of CO by an aerating cap. A CO-Epo dose-response curve over the range of 0.02-0.14 vol% CO was conducted. Subpressor doses of ET-1 (3 pmol/min/kg BW) and the ET(A/B) receptor antagonist LU302872 (LU; 30 mg/kg) were applied to anaesthetized rats under normoxia (controls CON, ET, LU) and following hypoxia (CO exposure; H-CON, H-ET, H-LU). Mean arterial blood pressure (MAP), glomerular filtration rate (GFR, inulin clearance), Epo and ET-1 serum concentrations (ELISA) and renal Epo mRNA (Light Cycler) were determined. The EC50 value for CO was 0.1 vol% with a 70-fold increase in Epo serum concentrations. CO exposure increased Epo serum and Epo mRNA concentrations in the expected range in all groups. None of the treatments with ET or LU influenced the effect of hypoxia on Epo serum concentrations and renal Epo mRNA content. Under hypoxia, administration of ET-1 as well as LU prevented the hypoxia-induced decrease in MAP (p<0.05). Under hypoxia, GFR was reduced by 50% except for H-LU with values comparable to normoxia. Taken together, the influence of hypoxia exceeds by far the effect of ET-1 on Epo production, irrespective of the presence or absence of exogenous ET-1. Thus, ET-1 does not appear to be a major modulator of Epo production.

Animals↗
PubMed2006

Pharmacokinetics and pharmacodynamic action of budesonide in children with Crohn's disease.

BACKGROUND: Budesonide is effective as initial therapy of mild to moderate Crohn's disease in adults. Superior tolerability to conventional corticosteroids might be attributed to extensive first-pass metabolism of budesonide by cytochrome P450 3A. AIM: To evaluate biotransformation and pharmacodynamic action of budesonide in children. METHODS: Drug disposition and effects on endogenous cortisol were evaluated in 12 children with Crohn's disease (5-15 years) after first intake of 3 mg budesonide (single dose), and again after 1 week of thrice daily dosing (steady-state). The parent drug and cytochrome P450 3A-dependent metabolites were analysed in blood and urine. RESULTS: Pharmacokinetic parameters of budesonide following single-dose administration (e.g. AUC(0-infinity) 7.7+/-5.1 h ng/mL, C(max) 1.8+/-1.2 ng/mL) did not change upon multiple dosing. Overall systemic elimination of budesonide reflected by clearance and half-life was not different between children and adults. After 1 week of treatment reversible adrenal suppression was observed - most pronounced in children aged below 12 years. CONCLUSIONS: Disposition of oral budesonide appears to be similar between children and adults, but the doctor has to be aware of an increased risk for adrenal suppression in paediatric patients.

Administration, Oral↗
PubMed2006

Multiple drug prescribing by general practitioners in a German region: Implications for drug interactions and patient safety.

OBJECTIVE: An increased number of drugs used by patients enhances the risk of potentially hazardous drug interactions. So far, no representative data are available about how common this problem is in German general practices. METHODS: We performed a retrospective analysis using a prescription database for a German region. The 50 general practitioners (out of 1,457) who wrote the most prescriptions during January to March 2003 were included. Data on 4,153 patients who were prescribed at least 10 drugs were analyzed for 92 predefined Drug Combinations Prone to Interact (DCPI) to a clinically relevant extent and possible contraindications. RESULTS: From 92 DCPIs, 71 occurred in the analyzed population between 1 and 275 times. The total number of DCPI cases was 1,295, which included 10% (n = 129) of contraindicated combinations. Among 4,153 analyzed patients, 822 patients (19.8%) were affected by at least 1 DCPI. In 268 patients (6.5%), multiple DCPIs occurred. The most frequently found drug pairs were digitalis/diuretics, digitalis/calcium channel blockers, and theophylline/quinolones. Among contraindicated combinations, tricyclic antidepressants, St. John's wort and antiarrhythmic drugs were most frequently involved. In about 1/3 of patients treated for chronic heart failure, pharmacotherapy appeared not to be guideline-adherent. CONCLUSION: Drug interactions, especially in polypharmacotherapy, represent a potential hazard which must be taken into account by the prescribing physician. Our study is the first to use a prescription database for the evaluation of drug prescriptions within a German region.

Databases, Factual↗
PubMed2005

Effect of acute hyperhomocysteinemia on methylation potential of erythrocytes and on DNA methylation of lymphocytes in healthy male volunteers.

Homocysteine is a precursor of S-adenosylmethionine (AdoMet) and a metabolite of S-adenosylhomocysteine (AdoHcy). The ratio of AdoMet to AdoHcy, defined as the methylation potential (MP), indicates the flow of methyl groups within the cells. Chronic elevations of total homocysteine (tHcy) in plasma correlate with increased AdoHcy concentrations, decreased MP, and impaired DNA methylation. However, the influence of acute hyperhomocysteinemia on MP is unknown. We induced acute hyperhomocysteinemia in 14 healthy volunteers by oral administration of l-homocysteine (65.1 micromol/kg body wt) in an open, randomized, placebo-controlled two-period crossover study. The kinetics of tHcy in blood and urine, MP in blood, and global DNA methylation in lymphocytes were studied systematically during 48 h. Plasma tHcy concentrations reached a peak at 34 +/- 11 min after an oral load with l-homocysteine and decreased with a half-life of 257 +/- 41 min (means +/- SD). Only 2.3% of the homocysteine dose were recovered in urine. AdoHcy concentrations and MP in whole blood and erythrocytes were not affected by the oral homocysteine load. Furthermore, global DNA methylation in lymphocytes did not change under these conditions. We found no difference between the genotypes of 5,10-methylenetetrahydrofolate reductase in response to the homocysteine load. However, AdoMet content in erythrocytes was significantly higher in the C677T carriers (CT; n = 7) compared with the CC genotype (n = 7). Although chronic elevation of tHcy has been shown to affect MP and DNA methylation, acute elevation of plasma tHcy above 20 micromol/l for 8 h is not sufficient to change MP and to induce DNA hypomethylation in lymphocytes.

Adult↗
PubMed2005

[Drug research. First into human in phase I].

Phase I clinical trials are of particular importance in drug research. In this phase, a new chemical entity is applied for the first time to humans, normally to young healthy volunteers. The primary aims are safety and tolerability, the pharmacokinetic, and as far as possible the pharmacodynamic behaviour of the new substance in the human body. The effects of age, gender, race, drug interactions, food intake and organ damage are examined in studies of later phase I. This article deals mainly with "first into human" studies during early phase I. We describe the processes before, as well as the technical, medical and regulatory requirements during, the conduct of a "first into human" trial. Furthermore, the choice of galenic formulation, route of application, and study population, and the risks at trial participation are addressed. In addition to different dose escalating schemes, which serve for the identification of the maximum tolerated dose, and other common study designs for "first into human" trials, this article reviews the literature on the determination of the first dose.

Adolescent↗
PubMed2005

Use of nonprohibited hallucinogenic plants: increasing relevance for public health? A case report and literature review on the consumption of Salvia divinorum (Diviner's Sage).

INTRODUCTION: : We want to call attention to a mint plant, called diviner's sage ( Salvia divinorum), originally used in shamanic ceremonies of the Mazatec Indians of Mexico. On numerous websites of the internet, this ancient herbal drug and its extracts are offered as a legal means of widening individual awareness. Regarding its dose-response relationship, the active ingredient, salvinorin A, is one of the most potent naturally occurring hallucinogens. Laws on controlled substances, except for Finland, Denmark and Australia, do not prohibit cultivating, consuming or dealing with Salvia divinorum. Ingestion by smoking, vaporising or chewing, induces a short-lived inebriant state with intense, bizarre feelings of depersonalization. This article wants to be a signal for physicians or psychotherapists to take Salvia into consideration, when exploring young people for drug use. METHODS: We report the individual perceptions of a young man consuming Salvia divinorum. We review the scarce scientific literature and consider relevant internet websites. DISCUSSION: We define open issues for further investigations and try to discuss why Salvia divinorum may be of interest for teenagers and young adults in Europe.

Adult↗
PubMed2005

What do primary care patients think about generic drugs?

OBJECTIVE: To examine the attitude of patients towards generic drugs and prescriptions containing generic drugs as an alternative to brand-name products, with a special focus on information on patients attitude to generic drugs provided by their general practitioners (GPs). METHODS: A total of 804 patients in 31 general practices were surveyed using a self-questionnaire. The influence of age, sex, education, disease, knowledge of generic drugs, experience with generic substitution and information provided by the GP on patient attitudes towards generic drugs and substitutions were examined. RESULTS: Nearly two thirds of the patients (509/804) stated that they knew of the difference between brand-name drugs and generics; of these, one third were not satisfied with the information given by their GPs and 37% of patients expressed general skepticism towards generic drugs because of their lower price. This attitude was more frequent among those who felt that generic prescribing was "invented" to solve the financial crisis in the German health insurance system at their expense (odds ratio (OR): 6.2; 95% confidence interval: 4.0 - 9.8) and those who had not been confronted personally with a generic substitution (OR: 1.8; 1.3 3.0). Patients who had been skeptical when first confronted with a generic substitution were more frequently among those who considered inexpensive drugs to be inferior (OR: 4.5; 2.0 10.4) and they were frequently not satisfied with the information on substitution provided by their GP (OR: 2.7; 1.2 - 5.9). CONCLUSION: GPs are in an ideal position to inform their patients adequately about the equivalence of brand-name and generic drugs. However, the patient view that inexpensive drugs must be inferior may be difficult to rectify in the short term.

Drugs, Generic↗
PubMed2003

[Phytotherapeutic medicines. A possible source of drug interactions].

Herbal drugs are popular. Coming from nature, many people are still reluctant to link them with the risk of adverse effects. Many of these products do not require a prescription. Thus, their use and any potential risks may easily escape the physician's attention. Interactions, causing either adverse effects or treatment failures, with synthetic drugs have attracted increasing interest and recent case reports (e.g. about patients suffering from transplant rejection upon using of St John's wort with subsequently insufficient cyclosporine levels) have triggered some systematic research. As of yet, however, a substantial part of knowledge is based on case reports only. In this situation, the assessment of potential risks arising from herb drug interactions is difficult. More research is needed. This review is a brief account of interactions involving garlic, ginkgo, ginseng, echinacea, and St John's wort.

Drug Interactions↗
PubMed2003

Do alterations of endogenous angiotensin II levels regulate erythropoietin production in humans?

AIMS: Recent evidence suggests a potential role of angiotensin II in the physiological regulation of erythropoietin (Epo) production. While the administration of exogenous angiotensin II (AII) has been used so far to study its effects, the role of endogenous AII has remained unclear. METHODS: To alter endogenous AII in humans experimentally we used furosemide bolus injection as a short-term (study 1) and dietary salt as a long-term modulator (study 2). In an open crossover design, 12 healthy male volunteers received furosemide (F) 0.5 mg kg(-1) intravenously or placebo (P) in random order (study 1). With the same design, 12 volunteers received high-salt (HS), normal-salt (NS) and low-salt (LS) diet (study 2). Plasma renin activity (PRA) was analysed along with AII. Inulin and paraaminohippurate (PAH) clearances were used to indicate glomerular filtration rate (GFR) and renal plasma flow (RPF), respectively. RESULTS: While F stimulated AII and PRA and decreased GFR and RPF significantly, no concomitant alteration of Epo was observed [AUCEpo: placebo 5709 +/- 243 (% of baseline x h), furosemide: 5833 +/- 255 (% of baseline x h); 95% confidence interval (CI) -608.4, 856.0; P = 0.73]. F decreased GFR (from 103.6 +/- 4.0 to 90.6 +/- 4.8 ml min(-1) 1(-1) 73 m-2; 95% CI 1.1, 24.9; P < 0.05), but not RPF (study 1). Correspondingly, LS stimulated and HS decreased AII and PRA significantly. HS increased GFR and RPF. Again, Epo concentrations were not affected (AUCEpo: normal sodium 44 +/- 6.7 mIU x day ml(-1), low sodium 39 +/- 2.4 mIU x day ml(-1), high sodium 48.5 +/- 6.1 mIU x day ml(-1); normal salt/low salt 95% CI -11.9, 21.9, P = 0.54; normal salt/high salt 95% CI -14.4, 23.3, P = 0.63; study 2). CONCLUSIONS: We conclude that, at least in the physiological setting in healthy volunteers, increased concentrations of endogenous AII may not be a major factor of Epo regulation.

Adult↗
PubMed2003

The role of active metabolites in dihydrocodeine effects.

OBJECTIVE: The metabolism of dihydrocodeine to dihydromorphine, a high affinity mu-opioid receptor ligand in membrane homogenates, is catalyzed by CYP2D6. However, it is not clear whether an active CYP2D6 enzyme is required for opioid receptor-mediated effects in man after standard dihydrocodeine doses. METHODS: Whole cell opioid-receptor affinity and effects on cAMP accumulation of dihydrocodeine and its metabolites were determined in differentiated SH-SY5Y neuroblastoma cells. In a double-blind, 2-period, placebo-controlled randomized crossover pilot study the pharmacokinetics of dihydrocodeine (60 mg single dose) and its metabolites were examined in 5 phenotyped extensive (EMs) and 4 poor metabolizers (PMs) for CYP2D6, and pharmacodynamics were evaluated using a pain threshold model and dynamic pupillometry. RESULTS: Displacement binding and cAMP accumulation experiments showed clearly higher affinities (100- and 50-fold) and activities (180- and 250-fold) of dihydromorphine and dihydromorphine-6-glucuronide, respectively, whereas the other metabolites had similar or lower affinities and activities as compared to dihydrocodeine. The clinical study revealed no significant difference in plasma or urine pharmacokinetics between EMs and PMs for dihydrocodeine and its glucuronide. Dihydromorphine and its glucuronides were detectable in EMs only. A clear reduction of initial pupil diameters was observed up to 6 hours postdose in both PMs and EMs, with no obvious differences between CYP2D6 phenotypes. In the pain threshold model no effects were observed in either group. CONCLUSION: CYP2D6 phenotype has no major impact on opioid receptor-mediated effects of a single 60 mg dihydrocodeine dose, despite the essential role of CYP2D6 in formation of highly active metabolites.

Analgesics, Opioid↗
PubMed2002

["Off-label" prescribing of drugs in the ambulatory care of children and adolescents].

BACKGROUND AND OBJECTIVE: Hospitalised children receive up to 90 % of their drug prescriptions without ("unlicensed use") or outside ("off-label use") the terms of their product license. As no data are available for pediatric outpatients in Germany, we determined "off-label" use in a representative cohort of children and adolescents. PATIENTS AND METHODS: We analyzed 1.74 million prescriptions, written from January 1 st through March 31 st, 1999, to 455 661 children and adolescents aged 0 to 16 years by 6886 specialists in pediatric, general or internal medicine. All prescriptions were covered by the public health insurance, Allgemeine Ortskrankenkasse, (AOK) Baden-Wuerttemberg. License status of 1 592 006 identifiable prescriptions comprising more than 10 000 differently branded drugs was determined in 5 age groups and in different groups of the Anatomical Therapeutical Chemical Classification (ATC). As reference documents for licensing status we used the "Fachinformation" (summary of product characteristics), the "Rote" and "Gelbe" Liste, respectively. RESULTS: 13.2 %, i. e. 210 528 of the 1.59 million prescriptions, were "off-label". 75 % of these "off-label" prescriptions were due to a lack of information on pediatric use in the summary of product characteristics. The highest "off-label" fractions were found in drugs topically used in eyes and ears (78.6 %), dermatological (57.9 %), cardiovascular drugs (55.2 %), drugs für musculoskeletal (45.2 %) and urogenital disorders (48.5 %) and antidepressants (36.6 %). CONCLUSION: "Off-label" prescribing in outpatient children is less frequent than in pediatric inpatients. Considering the high absolute number of prescriptions however, 13.2 % cannot be neglected. Doctors prescribing drugs for children and adolescents should be aware of their actual licensing status because of its medical and legal consequences.

Adolescent↗
PubMed2002

Erectile dysfunction: comparison of efficacy and side effects of the PDE-5 inhibitors sildenafil, vardenafil and tadalafil--review of the literature.

Since introduction of the PDE-5 inhibitor sildenafil 4 years ago, there has been a fundamental change in the treatment of erectile dysfunction (ED). Intracavernosal or intraurethral injections of vasoactive substances or penile implants as mechanical aids now play hardly any part in it. - The development of the PDE-5 inhibitors vardenafil and tadalafil prompts the question of whether and how these three substances differ in terms of their efficacy and adverse effects. - Sildenafil has proven to be a very effective medicinal product. Studies with a follow-up period of up to 6 years have been conducted. The success rate of sildenafil varies in the group of ED patients with an organic underlying disease from 43% in patients who have undergone radical prostatectomy to 85% in patients with a neurological underlying disease, and amounts to an average 82% (range 43-85%, 100mg). - In an evaluation of spontaneous reports of deaths associated with sildenafil, the FDA concluded that there was no deducible evidence of an increase in the mortality rate among sildenafil users compared to the general population. In fact, fewer deaths associated in time with the ingestion of sildenafil were reported than might have been expected purely statistically on the basis of the normal mortality rate for men in this age group. - According to the initial studies conducted, vardenafil and tadalafil demonstrate efficacy data approximately comparable to those of sildenafil. As yet, insufficient data are available to evaluate the adverse effects of vardenafil and tadalafil, particularly their long-term use and use in high-risk groups. - Sildenafil has already been used by over 20 million men in over 110 countries and is one of the best-studied pharmacological substances available. This adventage in terms of knowledge and safety data makes sildenafil a safe and reliable treatment for patients with erectile dysfunction.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2002

Pharmacokinetics of doxepin and desmethyldoxepin: an evaluation with the population approach.

OBJECTIVE: Little information on the population pharmacokinetics of the tricyclic antidepressant doxepine and its pharmacologically active metabolite desmethyldoxepine is available. However, a more individualised drug therapy may be feasible if the influence of various patient characteristics on plasma concentration was known. PATIENTS AND METHODS: We retrospectively analysed pharmacokinetic therapeutic drug-monitoring data in 114 psychiatric patients (79 females, 35 males) treated with doxepine for a period of 22-306 days, mostly due to major depression. The data were analysed using the computer program NONMEM. For both, doxepine and its metabolite desmethyldoxepine, a one-compartment model was chosen. Pharmacokinetic parameters clearance (CL/F) and volume of distribution (V/F) of doxepine and desmethyldoxepine were modelled in terms of both random and fixed effects. RESULTS: The fit of the model to the concentration-time data was significantly improved when V/F was expressed as a function of weight ( P<0.05) and CL/F as a function of age ( P<0.05). Co-medication that inhibits P(450) isoenzymes lowered CL/F of doxepine by 15%. CONCLUSION: The analysis indicates that the factors age and, to some extent, body weight may be a guidance for individual doxepine dose regimens, which however needs confirmation in prospective clinical trials linking pharmacokinetics and therapeutic effect. Co-medication may represent only a minor important covariate.

Adult↗
PubMed2002

[Celecoxib].

Explore the source record for details and available documents.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Influence of controlled hypoxia and radical scavenging agents on erythropoietin and malondialdehyde concentrations in humans.

UNLABELLED: The present study was carried out to evaluate a model of a hypoxic stimulus of erythropoietin (EPO) production in humans and to investigate the role of free oxygen radicals in human EPO production. The study was conducted as an open, randomized, parallel, placebo-controlled trial. Thirty-six healthy male volunteers received a hypoxic treatment (13% O(2)) with a respiration mask for 6 h. During the period of hypoxia, the volunteers received as a short-term treatment either 1200 mg thioctic acid, or N-acetylcysteine 600 mg or placebo (0.9% sodium chloride). The EPO concentration in plasma increased up to 290% of the baseline level in all three groups. No statistically significant differences of AUC(EPO(0-48 h)) could be demonstrated between the groups. The malondialdehyde (MDA) concentration in plasma increased significantly (P < 0.001) 2 h after termination of hypoxia (mean 129.8 +/- 6.8% of the baseline) in all three groups. CONCLUSIONS: Taken together, our in-vivo results do not support a gross modulatory effect of a short-term treatment with radical scavenging agents on EPO-production during or after hypoxia in humans, as derived from the detected changes of MDA-concentrations in peripheral plasma.

Acetylcysteine↗
PubMed2001

Effect of aerobic exercise on behavioral and neuroendocrine responses to meta-chlorophenylpiperazine and to ipsapirone in untrained healthy subjects.

RATIONALE: Several clinical studies suggest antidepressive and anxiolytic effects of regular aerobic exercise. OBJECTIVES: The present study examines the effects of a 10-week protocol of moderate aerobic exercise (3-4 miles jogging 3 times per week) on central serotonergic receptor sensitivity. METHODS: Neuroendocrine challenges using oral doses of meta-chlorophenylpiperazine (m-CPP; 0.4 mg/kg), ipsapirone (0.3 mg/kg), and placebo were performed in 12 untrained healthy volunteers before and after 10 weeks of moderate aerobic exercise. RESULTS: Before training, administration of the non-selective serotonergic agonist m-CPP, which exerts a number of well-reproducible effects mainly via its action on 5-HT2C receptors, was associated with a significant increase of cortisol and prolactin (but not adrenaline or noradrenaline) in comparison with the placebo condition. After the 10-week training period, administration of m-CPP was followed by a blunted cortisol response which was not significantly increased in comparison to the placebo challenge. In contrast, the increases of cortisol observed after administration of the 5-HT1A agonist ipsapirone were of the same magnitude during the pre- and post-training challenge sessions. The behavioral response to ipsapirone and the mean maximal increases of plasma adrenaline and noradrenaline did not change during the training period. CONCLUSIONS: Regular aerobic exercise is associated with a blunted cortisol response to m-CPP, which might reflect a downregulation of central 5-HT2C receptors.

Adult↗