PubMed Health⌕ Search

Biomedical subjects

C H Gleiter

Publications and source records attributed to C H Gleiter.

At least 19 recordsLinked to original sources
PubMed2000

Measurement of free and bound malondialdehyde in plasma by high-performance liquid chromatography as the 2,4-dinitrophenylhydrazine derivative.

We established a method for the detection of free and total (free and bound) malondialdehyde (MDA) in human plasma samples after derivatisation with 2,4-dinitrophenylhydrazine (DNPH). Free MDA was prepared by perchloric acid deproteinisation whereas an alkaline hydrolysation step for 30 min at 60 degrees C was introduced prior to protein precipitation for the determination of total MDA. Derivatisation was accomplished in 10 min at room temperature subsequently chromatographed by HPLC on a reversed-phase 3 microm C(18) column with UV detection (310 nm). The detection limit was 25 pmol/ml for free and 0.3 nmol/ml for total MDA. The recovery of MDA added to different human plasma samples was 93.6% (n=11; RSD 7.1%) for the hydrolysation procedure. In samples from 12 healthy volunteers who underwent a hypoxic treatment (13% O2 for 6 h) we estimated a baseline value of total MDA of 2.16 nmol/ml (SD 0.29) (ambient air) with a significant increase to 2.92 (nmol/ml, SD 0.57; P=0.01) after the end of this physiological oxidative stress challenge. Plasma values of free MDA in these samples were close to our detection limit. The presented technique can easily performed with an isocratic HPLC apparatus and provides highly specific results for MDA as do sophisticated GC-MS methods.

Adolescent↗
PubMed2000

Dose-dependent effect of angiotensin II on human erythropoietin production.

Current evidence suggests that angiotensin II may be involved in the regulation of renal erythropoietin (EPO) production. The present study assessed the role of angiotensin II (A II) in different doses in the control of EPO production in humans. In a parallel, randomized, placebo-controlled open design, 60 healthy male volunteers received a 6-h intravenous infusion of: placebo (placebo, electrolyte solution), a pressor dose of A II (1-3 microg/min; A II press), a combination of a pressor dose of A II and the selective AT1-receptor blocker losartan, 50 mg (A II press + L), a subpressor dose of A II (0.0375-0.15 microg/min; A II subpress) and a combination of a subpressor dose of A II and losartan (A II subpress + L). A II press treatment resulted in a significant increase of the maximum EPO concentration (CmaxEPO, 41% higher versus placebo) and the amount of EPO produced in 24 h (AUCEPO(0-24 h), 61% larger versus placebo), A II subpress treatment increased CmaxEPO (35% higher versus placebo) and AUC(EPO)(0-24 h) (34% larger versus placebo). A II press + L and A II subpress + L treatments did not significantly increase CmaxEPO and AUCEPO(0-24 h) compared to placebo. A II affects EPO production in a dose-dependent manner. The signal seems to be mediated via AT1-receptors. A II appears to be one modulator EPO production in humans.

Adolescent↗
PubMed2000

Creutzfeldt-Jakob disease and oxidative stress.

OBJECTIVES: Substantial evidence supports the hypothesis that oxygen free radicals are involved in various neurodegenerative disorders. To assess the presence of oxidative stress in Creutzfeldt-Jakob disease (CJD) we examined the concentrations of malondialdehyde (MDA) as an established marker of lipid peroxidation. MATERIAL AND METHODS: MDA was quantified by high performance liquid chromatography (HPLC) in cerebrospinal fluid (CSF; n=12) and in serum (n=11) samples of CJD patients and healthy controls (n = 15). RESULTS: Mean values in healthy controls: 2.56 nmol/ml +/- 0.46 (CSF) and 1.94 nmol/ ml +/- 0.67 (serum); mean values in CJD patients: 2.64 nmol/ml +/- 0.67 (CSF) and 1.68 nmol/ml +/- 0.79 (serum). No significant (P>0.05) difference between CJD patients and controls was observed. CONCLUSIONS: The results indicated that the CSF and serum of CJD patients showed no higher endogenous levels of MDA as compared to normal healthy controls. These findings provide no evidence for an additional role of oxidative stress in the pathogenetic mechanism underlying CJD neurodegeneration.

Biomarkers↗
PubMed2000

[New antidepressive drugs in comparison with classical tricyclics. Mechanism of action and clinical evaluation].

During the last decade several new agents have been introduced in the treatment of depressive disorders. In comparison to classical tricyclic antidepressants, these agents have less side effects and a very low toxicity. Selective inhibitors of serotonin reuptake do not produce sedation; however, in the initial phase of treatment this is not always an advantage. In contrast, receptor antagonists, such as mirtazapin and nefazodone have moderate sleep-inducing properties. Selective agents are also characterized by certain pharmacologic interactions which can lead to considerable inhibition of the metabolism of other drugs. Classical antidepressants still play an important role in the treatment of severe depressive episodes. Different synaptic effects of new antidepressants lead to an increased availability of monoaminergic neurotransmitters. The article summarizes the most important neurobiological consequences of these acute synaptic effects which might be more closely associated with neurobiological correlates of depression. The authors conclude about the advantages and disadvantages of the different classes of antidepressants from a clinical point of view.

Animals↗
PubMed2000

Increased psychological responses and divergent neuroendocrine responses to m-CPP and ipsapirone in patients with panic disorder.

In patients with panic disorder and /or agoraphobia (PDA) an increased sensitivity of central 5-HT2C receptors and a decreased responsiveness of 5-HT1A receptors has been postulated. In the present study, neuroendocrine challenges were performed using oral doses of the non-selective 5-HT2C agonist m-chlorophenylpiperazine (m-CPP) (0.4 mg/kg), the selective 5-HT1A antagonist ipsapirone (0.3 mg/kg), and placebo in 40 patients with PDA and 12 healthy controls in order to compare 5-HT2C and 5-HT1A-specific psychobehavioural and neuroendocrine response patterns. At baseline, all psychobehavioural variables and the plasma concentration of noradrenaline (NE) were significantly increased in the patient group compared to the controls. The administration of m-CPP or ipsapirone was followed by comparable psychological symptoms and, in 55% of all patients, panic attacks. In comparison to the control subjects, patients were characterized by significantly higher psychological reactions to both challenge agents and a significantly higher NE response to m-CPP. In the patient group, there was also a trend towards an increased cortisol response after administration of m-CPP and a decreased cortisol and hypothermia response after administration of ipsapirone compared to the control group. The neuroendocrine findings of our study support earlier reports of opposite changes in the responsiveness of 5-HT2C and 5-HT1A-related receptors in PDA patients. The behavioural hypersensitivity to both, m-CPP and ipsapiron, shows that the provocation of anxiety and other psychological symptoms might be influenced by

Adolescent↗
PubMed1999

Kinetics and characteristics of an acute phase response following cardiac arrest.

OBJECTIVE: Inflammation and hypoxia are frequently associated, but their interaction is poorly understood. In vitro studies have shown that hypoxia stimulates the genes of acute phase proteins (APP) and cytokines known to induce APP. We decided to determine kinetics and potential determinants of an acute phase response after cardiac arrest and to assess whether isolated moderate hypoxia can induce APP in humans in vivo. DESIGN: Prospective, observational study in patients and human experiment. SETTING: Tertiary care university hospital. PATIENTS AND PARTICIPANTS: 22 patients after primarily successful cardiopulmonary resuscitation (CPR) and 7 healthy volunteers. INTERVENTIONS: None in patients; exposure of volunteers to simulated altitude (460 torr/6 h). RESULTS: Following CPR, type-1 APP (C-reactive protein, alpha 1-acidglycoprotein, serum amyloid A) and type-2 APP (haptoglobin, alpha 1-antitrypsin) increased consistently within 1-2 days and the 'negative' APP transferrin was downregulated. This APP response occurred irrespective of the cause of arrest, the estimated time of anoxia, clinical course or patient outcome and was not different in patients with and without infectious complications. Exposure of healthy volunteers to less severe but more prolonged hypoxia did not induce APP, although a time dependent increase of serum erythropoietin (EPO) was measurable under these conditions, indicating the activation of oxygen dependent gene expression. CONCLUSIONS: (i) A marked acute phase response occurs regularly after cardiac arrest, but within the complexity of this situation the severity of hypoxia is not a predominant determinant of this response. (ii) Despite in vitro evidence for similarities in the oxygen dependent regulation of APP and EPO production, the oxygen sensitivity of these proteins in vivo is different. (iii) Measurements of APP are not revealing regarding infectious complications in the early phase after CPR.

Acute-Phase Proteins↗
PubMed1999

Decreased neuroendocrine responses to meta-chlorophenylpiperazine (m-CPP) but normal responses to ipsapirone in marathon runners.

Several clinical studies suggest antidepressive and anxiolytic effects of regular aerobic exercise. To study the effects of exercise on central serotonergic receptor sensitivity, we performed neuroendocrine challenges using oral doses of meta-chlorophenylpiperazine (m-CPP, 0.4 mg/kg), ipsapirone (0.3 mg/kg) and placebo in 12 marathon runners and 12 healthy controls not practicing regular exercise. After administration of the nonselective serotonergic agonist m-CPP, which exerts a number of well-reproducible effects mainly by means of its action on 5-HT2C receptors, marathon runners showed a significantly reduced cortisol response in comparison to the control group. There was also a statistical trend toward a blunted prolactin response after m-CPP in the athlete group. In contrast, the increase of cortisol and the hypothermia observed after administration of the 5-HT1A agonist ipsapirone were of the same magnitude in both groups. The behavioral response to m-CPP or ipsapirone and the mean maximal increases of plasma adrenaline and noradrenaline did not differ between the marathon and the control group. In conclusion, exercise-induced downregulation of 5-HT2C receptors could play an important role in mediating the anxiolytic and antidepressive effects of exercise.

Adult↗
PubMed1999

Fenoterol stimulates human erythropoietin production via activation of the renin angiotensin system.

AIMS: The present study assessed the hypothesis that the beta2 sympathomimetic fenoterol influences the production of erythropoietin (EPO) by activation of the renin angiotensin system (RAS), i.e. angiotensin II. METHODS: In an open, parallel, randomized study healthy volunteers received i.v. either placebo (electrolyte solution), fenoterol or fenoterol in combination with an oral dose of the AT1-receptor antagonist losartan. RESULTS: Compared with placebo treatment AUCEPO(0,24 h) was significantly increased after fenoterol application by 48% whereas no increase in the group receiving fenoterol and losartan could be detected. The rise of PRA was statistically significant under fenoterol and fenoterol plus lorsartan. CONCLUSIONS: Stimulation of EPO production during fenoterol infusion appears to be angiotensin II-mediated. Thus, angiotensin II may be considered as one important physiological modulator of EPO production in humans.

Adrenergic beta-Agonists↗
PubMed1999

Lack of interaction between thioctic acid, glibenclamide and acarbose.

AIMS: Thioctic acid (TA), glibenclamide and acarbose are widely used to either alone or concomitantly treat patients suffering from noninsulin-dependent diabetes (NIDDM). This study systematically investigated drug-drug interactions between TA and glibenclamide and TA and acarbose. METHODS: Fourteen male and 10 female healthy volunteers participated a randomized, open three period cross over trial (treatments A-C) followed by a fourth period (treatment D). A baseline profile for plasma insulin and glucose concentrations, variables which served as pharmacodynamic measures, was assessed before entering the trial. Treatments were A=600 mg TA orally, B=3.5 mg glibenclamide orally, C=600 mg TA+3.5 mg glibenclamide, D=600 mg TA+50 mg acarbose. Time courses of R(+)-TA and S(-)-TA as well as glibenclamide concentrations were measured with specific analytical methods. RESULTS: There was no clinically relevant change of TA enantiomer pharmacokinetics by glibenclamide or acarbose. Also, glibenclamide pharmacokinetics were not altered by TA to a clinically meaningful extent. Plasma insulin and glucose concentrations did not indicate an interaction between TA and glibenclamide or TA and acarbose. Glibenclamide had the expected effect on insulin and glucose levels independent of comedication. There were only minor and short lasting adverse events with the majority being (expected) hypoglycaemic symptoms occurring during the treatments with glibenclamide. CONCLUSIONS: Coadministration of single doses of TA and glibenclamide or TA and acarbose does not appear to cause drug-drug interactions.

Acarbose↗
PubMed1999

Angiotensin II increases erythropoietin production in healthy human volunteers.

BACKGROUND: A number of animal studies and our own clinical trials point towards a possible influence of the renin-angiotensin-system (RAS) on erythropoietin (EPO) production. In this study we investigated the role of angiotensin II in the regulation of EPO production in humans. METHODS: After a hemorrhage of 750 ml as a basic physiological stimulus 72 healthy male volunteers received in a parallel design either placebo (physiologic electrolyte solution) for 6 h, angiotensin II i.v. for 6 h (1-3 microgram min-1, sufficient to increase systolic blood pressure by 20 mmHg), the selective AT1-receptor antagonist losartan, the ACE-inhibitor captopril, angiotensin II + losartan, or angiotensin II + captopril. RESULTS: Administration of angiotensin II alone and in combination with captopril resulted in a significantly higher Cmax EPO (67% higher vs. placebo, P < 0.05) and AUCEPO (0-24h) (40% higher vs. placebo, P < 0.05). In the groups receiving losartan or captopril alone or the combination of angiotensin II + losartan no significant difference of Cmax EPO and AUCEPO(0-24h) compared to placebo could be detected. CONCLUSIONS: This study shows in a model of controlled, basic physiological stimulation of renal EPO production that angiotensin II is able to increase EPO levels in humans. This effect of angiotensin II can be blocked by the specific AT1-receptor antagonist losartan but not by the ACE-inhibitor captopril. The result may be interpreted as a hint that one signal for the control of EPO production in humans may be mediated by angiotensin II (AT1)-receptors.

Adult↗
PubMed1999

Persistence of haloperidol in human brain tissue.

OBJECTIVE: After discontinuation of neuroleptic drugs, their antipsychotic and antiparkinsonian effects are still present for a prolonged period. It is not known whether the extended effects of neuroleptic drugs in humans are due to the continued presence of drug in brain tissue or to long-lasting drug-induced physiologic changes. The aim of this study was to directly examine haloperidol concentrations in human brain tissue in relation to drug-free time. METHOD: Haloperidol concentrations were measured in five regions (temporal cortex, cingulate gyrus, caudate nucleus, dentate nucleus, corpus callosum) of the postmortem brains of 11 patients previously treated with haloperidol. Haloperidol was analyzed by means of high-performance liquid chromatography with ultraviolet detection. The half-life in brain tissue was estimated by a population kinetic analysis. RESULTS: Haloperidol concentrations in the human brain tissue were 10-30 times higher than optimal serum concentrations used in the treatment of schizophrenia. Haloperidol concentrations appeared to be homogeneously distributed across different brain areas within a single patient. There was no apparent relation between duration of treatment and mean haloperidol concentration. Higher doses of haloperidol seemed to be related to higher concentrations in brain tissue. The elimination half-life from brain tissue was calculated to be 6.8 days. CONCLUSIONS: The results may have implications for clinical treatment decisions and the design of clinical research protocols. Patients exposed to haloperidol cannot be considered to be free of residual effects of the drug for a number of weeks after withdrawal.

Antipsychotic Agents↗
PubMed1999

Haematological abnormalities in early abstinent alcoholics are closely associated with alterations in thrombopoietin and erythropoietin serum profiles.

Numerous reports exist on haematological pathology in alcoholism. However, no data are available regarding a potential involvement of haematopoietic growth factors in the recovery from alcohol-induced haematological abnormalities upon abstinence. Therefore, thrombopoietin (TPO) and erythropoietin (EPO) serum levels along with haematological and other routine laboratory parameters were closely followed in 14 thoroughly characterized male alcoholic patients over one to five months of controlled abstention from alcohol. Haematological changes in these early abstinent alcoholics consisted predominantly of (a) the well known rebound surge of platelets, (b) an early reticulocyte peak, and (c) persistently low haematocrit levels over months without signs of recovery. Observations on EPO and TPO during early abstinence can be summarized as follows: (1) Increased TPO levels precede the rebound thrombocytosis by several days, (2) both EPO and TPO concentrations are higher in anaemic than in nonanaemic alcoholics, with (3) nonanaemic subjects exhibiting levels of TPO in the range of healthy controls but levels of EPO below controls and (4) TPO concentrations show a stronger correlation with initial haematocrit values than with thrombocyte counts. To conclude, haematological recovery in early alcohol abstinence appears to be, at least in part, growth factor-driven, involving both TPO and EPO, and may reflect an intense interaction of erythro- and thrombopoiesis.

Adult↗
PubMed1998

When are bioavailability studies required? A German proposal.

The Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), the German drug regulation authority, issued guidelines for determining whether bioavailability/bioequivalence studies are required for certain drugs. This decision tree is based on pharmacodynamic, pharmacokinetic, and physicochemical criteria. Details of this decision tree were worked out by an expert panel, the Bioavailability Commission at the BfArM. The decision tree has been in use by German regulatory authorities for more than 10 years. In the meantime, its essentials were adopted by the European Committee for Proprietary Medicinal Products (CPMP) and by the World Health Organization (WHO) for their "Guidelines on interchangeability of multisource pharmaceutical products." This article reviews the original decision tree of the BfArM and provides examples of drugs that have been assessed according to its rules. The current procedure of the German regulatory authorities for judging the necessity of bioavailability trials, which reflects the status quo of regulatory practice in Germany, is also discussed.

Biological Availability↗
PubMed1998

Assessment of drug accumulation in the evaluation of pharmacokinetic data.

The evaluation of drug accumulation is approached from a practical point of view. Estimates of accumulation indices as obtained from standard estimators-AUC, peak levels, and trough levels (RAUAUC Rmax and Rmin, respectively)-are compared and differences analyzed. The estimators are based on the concentration-time curve characteristics area under the concentration-time curve (AUC), maximum concentration, and trough level. Simulated data are used for the analysis, both noise-free and with random error added. The data are based on pharmacokinetic parameters derived from a clinical study. The numerical procedures can be reproduced by the interested reader with little effort. It is shown empirically that if Rmin, > RAUC then simple kinetic behavior cannot be safely assumed, but accumulation is a complex function of time. Rmax as obtained from the data and an estimate of this value based on time to peak concentration (tmax) and apparent elimination rate constant (lambda(z)) after a single dose and at steady state can then be compared in an attempt to exclude time-dependent kinetics. This new numerical procedure can provide valuable and even pivotal information regarding the accumulation kinetics of a compound under investigation. Recommendations on how to use the available concentration-time information to the best advantage are presented. It is concluded that the assessment of drug accumulation should not be confined to the calculation of just one estimate, because the three estimators RAUC, Rmax. and Rmin reflect different aspects of accumulation. Moreover, all information about accumulation should be carefully analyzed in the clinical context. This way the relevant accumulation can be identified for safe and efficacious drug treatment.

Algorithms↗
PubMed1998

Fenoterol increases erythropoietin concentrations during tocolysis.

AIMS: The present study was carried out to assess the effect of the selective beta2-adrenoceptor agonists on erythropoietin (EPO) production. METHODS: Routine tocolysis with fenoterol (using the regular rate of 2 microg min[-1]) was used as a clinically easily accessible model. RESULTS: EPO concentrations had doubled 24 h after the start of tocolysis (P < 0.001). This increase lasted over the entire observation period of 48 h. Potassium concentrations fell significantly during the first hours of fenoterol infusion. There was no increase of human placenta lactogen during the period of EPO increase. CONCLUSIONS: The data confirm our earlier results that fenoterol increases EPO concentrations following haemorrhage. In this model it was not necessary to stimulate EPO production prior to pharmacological treatment.

Adrenergic beta-Agonists↗
PubMed1998

Influence of urine pH and urinary flow on the renal excretion of memantine.

AIMS: The present study assessed the influence of urinary flow rate and urine pH on the renal excretion of the NMDA-receptor antagonist memantine. METHODS: In a randomized, open, four-period cross-over trial, 12 healthy male volunteers received 10 mg memantine daily for 43 days. After reaching steady state conditions the volunteers were allocated to four different regimens to alter urine pH and urinary flow, which were each separated by a 1 week period while the study medication continued (A: acidification of urine pH, low urinary flow; B: acidification of urine pH, high urinary flow; C: alkalinization of urine pH, low urinary flow; D: alkalinization of urine pH, high urinary flow). RESULTS: The renal clearance of memantine (CL(R)) in regimen A and B was 7-10 fold higher in comparison with regimen C and D (P<0.05). There were small but statistically significant differences of CL(R) between the two regimens with acidic urine pH (A: median: 210.2 ml min(-1) vs B: median: 218.7 ml min(-1)) and between the two regimens with alkaline urine pH (C: median: 19.4 ml min(-1) vs D: median: 30.5 ml min(-1)). The amount of memantine excreted into the urine within one regimen (Ae0-24h) was 5.7-7.4 fold higher in regimens A and B than C and D (P< 0.05). Differences of the AUC(0,24 h) and Cmax/AUC(0,24 h) were significant (P<0.05) between each of the regimens with acidic urine pH (A, B) and regimens (C, D) with alkaline urine pH (A vs C, A vs D, B vs C, B vs D) but not between regimens A vs B or C vs D. CONCLUSIONS: The present study demonstrated a considerable effect of urine pH, whereas no clinically relevant change of the renal excretion of memantine with urinary flow could be detected. As the renal excretion of memantine may have an impact on therapeutic efficacy changes of dietary habits that may alter urine pH should be avoided during treatment with memantine.

Adult↗
PubMed1998

Monoamine oxidase inhibitors. A perspective on their use in the elderly.

Monoamine oxidase inhibitors (MAOIs) are mainly used in psychiatry for the treatment of depressive disorders and in neurology for the treatment of Parkinson's disease. While the classical, nonselective and nonreversible MAOIs, such as phenelzine and tranylcypromine, are characterised by the risk of inducing a hypertensive crisis when dietary tyramine is ingested, the selective monoamine oxidase-B (MAO-B) inhibitor selegiline (deprenyl) and, even more so, the selective and reversible monoamine oxidase-A (MAO-A) inhibitor moclobemide, are free from this potential interaction. Drug tolerability data for the elderly show that moclobemide is one of the most well tolerated compounds. Selegiline, especially when used in combination with levodopa, can cause anorexia, dry mouth, dyskinesia and, most problematic, orthostatic hypotension. For the traditional MAOIs, phenelzine and tranylcypromine, published data are insufficient to be able to give a conclusive tolerability statement regarding the use of these compounds in elderly people. Although orthostatic hypotension occurs in most patients treated with traditional MAOIs, the incidence in elderly patients with depression does not appear to be greater than that reported with tricyclic antidepressants.

Aged↗