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O Arnold

Publications and source records attributed to O Arnold.

11 recordsLinked to original sources
PubMed2005

Double-blind, placebo-controlled pharmacodynamic studies with a nutraceutical and a pharmaceutical dose of ademetionine (SAMe) in elderly subjects, utilizing EEG mapping and psychometry.

In a double-blind, placebo-controlled crossover study, the effects of S-adenosyl-l-methionine (SAMe) on brain function measures of 12 normal elderly volunteers (6 m/6 f, aged 57-73 years, mean: 61 years) were investigated by means of EEG mapping and psychometry. In random order, the subjects were orally administered a pharmaceutical dose of 1600 mg SAMe, a nutraceutical dose of 400 mg SAMe and placebo, each over a period of 15 days, with wash-out periods of 2 weeks in between. EEG recordings, psychometric tests and evaluations of tolerability and side effects were carried out 0, 1, 3 and 6 h after drug administration on days 1 and 15. Multivariate analysis based on MANOVA/Hotelling T2 tests of quantitative EEG data demonstrated significant central effects of SAMe as compared with placebo after acute, subacute and superimposed drug administration of both the nutraceutical and the pharmaceutical dose. EEG changes induced by SAMe were characterized by an increase in total power, a decrease in absolute and relative power in the delta/theta and slow alpha frequencies, an increase in absolute and relative power in the alpha-2 and beta frequencies as well as an acceleration of the alpha centroid and the centroid of the total power spectrum. The delta/theta and the beta centroid showed variable changes over time. The dominant alpha frequency was accelerated, the absolute and relative power in the dominant alpha frequency attenuated after SAMe as compared with placebo. These acute and subacute pharmaco-EEG findings in elderly subjects are typical of activating antidepressants. Time-efficacy calculations showed that acute oral administration of SAMe in both the nutraceutical and the pharmaceutical dose induced the pharmacodynamic peak effect in the first hour with a subsequent decline. The 3rd and 6th hours still showed a significant encephalotropic effect after the 1600 mg dose. The maximum EEG effect was noted after 2 weeks of oral administration of both 1600 mg/die and 400 mg/die. The superimposed dose induced significant encephalotropic effects in the 3rd hour after 400 mg and in the 3rd and 6th hours after 1600 mg as compared with pre-treatment. Dose-efficacy calculations showed that the pharmaceutical dose of 1600 mg had a more pronounced effect on the CNS than the nutraceutical dose of 400 mg, with both doses being superior to placebo. Psychometric tests concerning noopsychic and thymopsychic measures as well as critical flicker fusion frequency generally demonstrated a lack of differences between SAMe and placebo, which reflects a good tolerability of the drug in elderly subjects. This was corroborated by the findings on side effects, pulse and blood pressure.

Aged↗
PubMed2004

EEG-tomographic studies with LORETA on vigilance differences between narcolepsy patients and controls and subsequent double-blind, placebo-controlled studies with modafinil.

The aim of the present study was to identify brain regions associated with vigilance in untreated and modafinil-treated narcoleptic patients by means of low-resolution brain electromagnetic tomography (LORETA). 16 drug-free narcoleptics and 16 normal controls were included in the baseline investigation. Subsequently patients participated in a double-blind, placebo-controlled crossover study receiving a three-week fixed titration of modafinil (200, 300, 400 mg) and placebo. Measurements comprised LORETA, the Multiple Sleep Latency Test (MSLT) and the Epworth Sleepiness Scale (ESS) obtained before and after three weeks' therapy. Statistical overall analysis by means of the omnibus significance test demonstrated significant inter-group differences in the resting (R-EEG), but not in the vigilance-controlled recordings (V-EEG). Subsequent univariate analysis revealed a decrease in alpha-2 and beta 1-3 power in prefrontal, temporal and parietal cortices, with the right hemisphere slightly more involved in this vigilance decrement. Modafinil 400 mg/d as compared with placebo induced changes opposite to the aforementioned baseline differences (key-lock principle) with a preponderance in the left hemisphere. This increase in vigilance resulted in an improvement in the MSLT and the ESS. LORETA provided evidence of a functional deterioration of the fronto-temporo-parietal network of the right-hemispheric vigilance system in narcolepsy and a therapeutic effect of modafinil on the left hemisphere, which is less affected by the disease.

Adult↗
PubMed2002

The key-lock principle in the diagnosis and treatment of nonorganic insomnia related to psychiatric disorders: sleep laboratory investigations.

Nonorganic insomnia is a frequent sleep disorder that has a high comorbidity with other psychiatric illnesses. In our sleep outpatient clinic, 41% of the patients showed neurotic, stress-related and somatoform disorders, 31% affective disorders and 1.6% schizophrenia. Sleep laboratory investigations in patients for diagnostic purposes and in normal subjects for the evaluation of drug effects suggest that changes in the sleep architecture of patients with nonorganic insomnia due to psychiatric disorders, compared with normal controls, are opposite to alterations induced by psychotropic drugs intended for their treatment, compared with placebo (key-lock principle). Evidence for this principle was found regarding nonorganic insomnia related to generalized anxiety disorder or panic disorders and benzodiazepines, depressive episodes, recurrent depression or dysthymia and sedative antidepressants and finally schizophrenia and sedative neuroleptics. Polysomnography (PSG) findings of other mental disorders are rather scarce and often depend upon the subtype and stage of the disease. In conclusion, sleep laboratory studies may be helpful for choosing the right drug for an individual insomniac patient.

Humans↗
PubMed2002

Classification and evaluation of the pharmacodynamics of psychotropic drugs by single-lead pharmaco-EEG, EEG mapping and tomography (LORETA).

Utilizing computer-assisted quantitative analyses of human scalp-recorded electroencephalogram (EEG) in combination with certain statistical procedures (quantitative pharmaco-EEG) and mapping techniques (pharmaco-EEG mapping), it is possible to classify psychotropic substances and objectively evaluate their bioavailability at the target organ: the human brain. Specifically, one may determine at an early stage of drug development whether a drug is effective on the central nervous system (CNS) compared with placebo, what its clinical efficacy will be like, at which dosage it acts, when it acts and the equipotent dosages of different galenic formulations. Pharmaco-EEG profiles and maps of neuroleptics, antidepressants, tranquilizers, hypnotics, psychostimulants and nootropics/cognition-enhancing drugs will be described in this paper. Methodological problems, as well as the relationships between acute and chronic drug effects, alterations in normal subjects and patients, CNS effects, therapeutic efficacy and pharmacokinetic and pharmacodynamic data will be discussed. In recent times, imaging of drug effects on the regional brain electrical activity of healthy subjects by means of EEG tomography such as low-resolution electromagnetic tomography (LORETA) has been used for identifying brain areas predominantly involved in psychopharmacological action. This will be demonstrated for the representative drugs of the four main psychopharmacological classes, such as 3 mg haloperidol for neuroleptics, 20 mg citalopram for antidepressants, 2 mg lorazepam for tranquilizers and 20 mg methylphenidate for psychostimulants. LORETA demonstrates that these psychopharmacological classes affect brain structures differently.

Brain Mapping↗
PubMed2001

The influence of age on the pharmacokinetics and pharmacodynamics of bemetizide and triamterene: a single and multiple dose study.

Diuretics are a frequent cause of adverse drug effects in the elderly, many times involving drug-drug interactions. In addition, multiple chronic diseases, age-dependent pharmacokinetic and pharmacodynamic changes, and a decreased homeostatic capacity often complicate diuretic therapy in the elderly. The pharmacokinetics (area under the plasma concentration-time curve: AUC; peak concentration in plasma: c(max); time to reach peak concentration: t(max); terminal half-life: t(1/2)) and pharmacodynamics (urine flow rates and renal excretion rates of Na(+) at 1, 3, and 6 h after oral administration) of a fixed combination of 25 mg bemetizide and 50 mg triamterene were investigated in 15 elderly patients (age 70-84 years) and 10 young volunteers (age 18-30 years) after a single dose (day 1) and after multiple doses (at steady state, day 8). Compared with the young volunteers, mean plasma concentrations of bemetizide, triamterene, and the active triamterene metabolite were significantly higher in the elderly volunteers. These elevated plasma levels occurred after single dose and were even more pronounced after multiple dose in the elderly. While plasma concentrations and AUC of bemetizide, triamterene, and the active metabolite of triamterene were increasing in correlation to age of subjects and duration of therapy, urine flow and renal Na(+) excretion rates were decreasing at the same degree. At steady state conditions, practically no effect on urine flow and Na(+) excretion rates could be observed in the elderly patients (in contrast to the young volunteers) for the first 8 h after administration of bemetizide and triamterene. The lower the measured (endogenous) creatinine clearance was in all subjects, the higher were the plasma concentrations of bemetizide and triamterene, and the lower was the effect on pharmacodynamics (i.e. urine flow and renal Na(+) excretion rates). The glomerular filtration rate, known to be lower in the elderly (a priori), was apparently decreased at higher levels of bemetizide and triamterene in the elderly, which may explain why there was no diuretic and saluretic effect after multiple dose in the elderly patients.

Journal Article↗
PubMed1999

Effects of L-arginine on endothelial and cardiac function in rats with heart failure.

We examined the effects of chronic oral L-arginine treatment on endothelial and cardiovascular function in rats with heart failure induced by coronary artery ligation. Both heart failure and sham-operated rats were treated with either L-arginine in drinking water (12.5 or 50 g/l) or water placebo for 8 weeks following surgery. Plasma L-arginine levels in heart failure rats (153 +/- 11 microM) were lower than sham rats (201 +/- 13 microM, P < 0.05). The lower dose L-arginine treatment improved endothelium-dependent relaxation of isolated aortic rings of heart failure rats, while the higher dose of L-arginine treatment did not. Neither low nor high dose of L-arginine treatment improved hemodynamic parameters in heart failure rats. Thus, chronic oral L-arginine treatment at a dose of 12.5 g/l in drinking water improves endothelium-dependent relaxation, but fails to improve in vivo cardiac function in rats with heart failure.

Animals↗
PubMed1998

Grapefruit juice-drug interactions.

The novel finding that grapefruit juice can markedly augment oral drug bioavailability was based on an unexpected observation from an interaction study between the dihydropyridine calcium channel antagonist, felodipine, and ethanol in which grapefruit juice was used to mask the taste of the ethanol. Subsequent investigations showed that grapefruit juice acted by reducing presystemic felodipine metabolism through selective post-translational down regulation of cytochrome P450 3A4 (CYP3A4) expression in the intestinal wall. Since the duration of effect of grapefruit juice can last 24 h, repeated juice consumption can result in a cumulative increase in felodipine AUC and Cmax. The high variability of the magnitude of effect among individuals appeared dependent upon inherent differences in enteric CYP3A4 protein expression such that individuals with highest baseline CYP3A4 had the highest proportional increase. At least 20 other drugs have been assessed for an interaction with grapefruit juice. Medications with innately low oral bioavailability because of substantial presystemic metabolism mediated by CYP3A4 appear affected by grapefruit juice. Clinically relevant interactions seem likely for most dihydropyridines, terfenadine, saquinavir, cyclosporin, midazolam, triazolam and verapamil and may also occur with lovastatin, cisapride and astemizole. The importance of the interaction appears to be influenced by individual patient susceptibility, type and amount of grapefruit juice and administration-related factors. Although in vitro findings support the flavonoid, naringin, or the furanocoumarin, 6',7'-dihydroxybergamottin, as being active ingredients, a recent investigation indicated that neither of these substances made a major contribution to grapefruit juice-drug interactions in humans.

Administration, Oral↗
PubMed1986

Salvage of ischaemic myocardium by reperfusion: importance of collateral blood flow and myocardial oxygen demand during occlusion.

Early reperfusion after coronary artery occlusion is used to treat acute myocardial infarction, but the factors that determine whether salvage of ischaemic myocardium actually occurs remain poorly defined. Differences in collateral blood flow to the region at risk, and haemodynamic variables during occlusion, may contribute to uncertainty as to the time beyond which reperfusion no longer reduces infarct size. To clarify this issue, open chest anaesthetised dogs underwent 1, 2, 3, 4, or 6 hours of left anterior descending coronary artery occlusion followed by reperfusion or permanent occlusion (n = 8 per group). Microspheres were injected before occlusion and 15 minutes after occlusion for regional myocardial blood flow determination, and heart rate and arterial blood pressure were measured before occlusion and 10 minutes and 30 minutes after occlusion. At 96 hours after occlusion haemodynamic variables were again measured; the animals were then killed, and occluded bed size was determined by in vitro dye perfusion. The area of necrosis was quantified from histological sections and expressed as a percentage of occluded bed size (AN/OB). If duration of occlusion is considered alone, reperfusion beyond two hours did not salvage ischaemic myocardium in this model. If the results for occlusion equal to and greater than two hours are combined, the mean area of necrosis (27(2)%) was significantly greater than that produced by one hour of occlusion followed by reperfusion (10(4)%). For the animals undergoing occlusion for two or more hours or permanent occlusion, collateral blood flow significantly influenced the area of necrosis. When epicardial flow during occlusion was high (greater than 0.30 ml X min-1 X g-1 tissue) 13 out of 14 dogs undergoing occlusion for two or more hours or permanent occlusion developed small (AN/OB less than 27%) infarcts (mean AN/OB 17(2)%). In contrast, when epicardial collateral flow was low (less than 0.30 ml X min-1 X g-1) 14 out of 23 animals had large (AN/OB greater than 27%) infarcts (mean AN/OB 34(3)%). For the 23 dogs in which epicardial flow was low, heart rate during occlusion significantly influenced infarct size: the 14 dogs that developed large infarcts (AN/OB greater than 27%) had a higher mean heart rate (152(6) beats X min-1) than the nine that developed small infarcts (AN/OB less than 27%) (130(5) beats X min-1; p less than 0.025). Thus reperfusion at one hour after occlusion salvaged ischaemic myocardium.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1981

[Not Available].

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History, Modern 1601-↗