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Biomedical subjects

A Safer

Publications and source records attributed to A Safer.

12 recordsLinked to original sources
PubMed1997

MAO-A inhibition in brain after dosing with esuprone, moclobemide and placebo in healthy volunteers: in vivo studies with positron emission tomography.

OBJECTIVE: The aim of the study was to investigate whether or not esuprone binds substantially to MAO-A in the human brain. METHODS: In a randomised double-blind placebo-controlled study 16 male healthy volunteers were examined with positron emission tomography (PET) with [11C]harmine. Eight of the volunteers were given daily doses of 800 mg esuprone, four were given bi-daily doses of 300 mg moclobemide, and four volunteers were given placebo tablets. PET was performed before initiation of a 7-day treatment period. On day 7, one investigation was made immediately before administration of the drug, representing 23 h after the previous day's treatment for esuprone and 11 h after the last tablets of moclobemide. Further investigations were made 4 h and 8 h after the morning dose on day 7. RESULTS: PET showed a high degree of binding of [11C]harmine, a high-affinity ligand for MAO-A, before the start of treatment, and a marked and similar reduction after treatment with esuprone and moclobemide. A slight tendency for normalisation of enzyme binding was observed at the last time point. In the placebo group no change was observed. Plasma kinetics of esuprone showed a rapid elimination with a half-life of about 4 h. CONCLUSION: The study demonstrates that esuprone was comparable to moclobemide in its effect on MAO-A inhibition in the brain at the doses given. This is an illustration of the potential of PET to monitor drug effects directly on target biochemical systems in the brain in human volunteers, and the possibility of using these data, rather than pharmacokinetic data, for the determination of dosing intervals.

Adult↗
PubMed1996

Dietary beta-carotene elevates plasma steady-state and tissue concentrations of beta-carotene and enhances vitamin A balance in preruminant calves.

Preruminant calves are regarded as a model for studying beta-carotene bioavailability in humans. The objectives of this trial were to determine the relationship between multiple beta-carotene doses and plasma steady-state concentration, accumulation in selected tissues, and vitamin A balance in liver. Seventy newborn Holstein calves in six treatments (n = 10/treatment) were fed a complete milk replacer diet low in vitamin A and supplemented with beta-carotene doses of 0, 0.23, 0.46, 0.92, 1.84 or 3.68 mumol/(kg body wt.d) for 28 d. Ten calves were killed on d 1. Plasma beta-carotene increased in relation to log transformations of dose and time (P < 0.05) in all supplemented calves and steady state was attained after 4 wk. For doses up to 0.92 mumol/(kg body wt.d), the dose-response relationship was linear. A dose-dependent accumulation of beta-carotene was found for liver, heart, lungs, adrenals and adipose tissue. All-trans-beta-carotene was the only isomer in plasma and adrenals and the predominant isomer in the remaining tissues. In liver, vitamin A increased with beta-carotene uptake. Hepatic balance between vitamin A accumulation and loss was achieved at beta-carotene intake of 0.36 mumol/(kg body wt.d) for a calf of 45 kg. It is concluded that preruminant calves within 1 mo of age utilize beta-carotene as a source of vitamin A, and that for testing bioavailability of beta-carotene sources, doses up to 0.92 mumol beta-carotene/(kg body wt.d) are most appropriate.

Adipose Tissue↗
PubMed1996

Porous balloon delivery of low molecular weight heparin in the dog coronary artery.

UNLABELLED: The aim of this experimental study was to assess the safety of local delivery of low molecular weight heparin via a porous balloon in the canine coronary artery. In 16 mongrel dogs, percutaneous transluminal coronary angioplasty was performed. In addition, eight of the dogs were given 4 ml Clivarin (1500 IU) delivered locally into the coronary artery immediately after dilatation. The animals were killed after 3 or 14 days. In the animals with local administration, the results of histopathology after 3 days showed the findings to be heterogeneous with marked disruption of the internal elastic lamina in all animals, and varying degrees of medial haemorrhage, medial necrosis, perivascular haemorrhage and signs of myocardial necrosis. Similar changes, but of lesser severity, were present in the animals treated with balloon dilatation only. After 14 days, the severity of vascular and perivascular alterations (medial haemorrhage, perivascular haemorrhage, thrombus formation) was significantly lower in the local delivery group (P < 0.05), but disruption of the internal elastic lamina, as a marker of the initial trauma, was present in all the animals. The presence of residual intracoronary thrombus was only seen in the PTCA group without local delivery. CONCLUSIONS: In this safety study, both groups showed pronounced alterations in the vessel wall 3 days following percutaneous transluminal coronary angioplasty. This changed 14 days following percutaneous transluminal coronary angioplasty when intramural injection of Clivarin resulted in a marked decrease of residual thrombus and medial as well as perivascular haemorrhage. Although the additional vessel trauma by the drug delivery technique did not result in increased complications, a careful approach with this potentially harmful procedure is essential.

Angioplasty, Balloon, Coronary↗
PubMed1988

Protective effect of the new calcium antagonist anipamil against isoprenaline-induced cardionecrosis in rats.

The new calcium antagonist anipamil (1,7-bis-(3-methoxyphenyl)-3-methylaza-7-cyano-nonadecane) exhibited a pronounced protective effect against isoprenaline-induced myocardial necrosis in rats. Anipamil was administered in single doses of 10 or 20 mg/kg daily for 4 days. 30 mg/kg isoprenaline was given by subcutaneous injection on the 3rd and 4th days of the study. The protective effect of anipamil was assessed by histological investigations, and its effect on the activity of the enzymes succinate dehydrogenase, NADH-NBT reductase, acid phosphatase and glucose-6-phosphate dehydrogenase in experimentally-induced myocardial damage was assessed quantitatively by microphotometry. The protective effect of anipamil against isoprenaline-induced myocardial necrosis was definitely dose-dependent: 10 mg/kg anipamil exhibited a partial protective effect, whilst 20 mg/kg anipamil protected the heart completely.

Acid Phosphatase↗
PubMed1978

[Long-term study with the novel cardiac glycoside meproscillarin (author's transl)].

In a multicentre open therapeutic study 64 physicians provided 650 questionnaires of patients who had been treated with the new cardiac glycoside 14-Hydroxy-3beta-[(4-O-methyl-alpha-L-rhamnopyranosyl)oxy]-14beta-bufa-4,20,22-trienolide (meproscillarin, Clift) for more than 3 months; 647 questionnaires had been filled in completely and could be evaluated. The major part of all patients suffering from heart failure of the severity degrees I--III required 2 tablets of 0.25 mg, a smaller part 3 tablets to achieve complete recompensation and/or maintenance of compensation, which was possible in 79% of all cases. The rate of side effects corresponded to that of other cardiac glycosides.

Adult↗
PubMed1978

[A method for describing monotonic dose-effect curves and areas in yes/no reactions (author's transl)].

A method combining a polynomial statistical model and multiple probit regression, is useful in describing nonmonotonic dose-effects in yes/no-reaction variables. An example shows the application of this method to the combination of two substances. The effects can be described with a minimum of polynomial coefficients. The application of a simple X2-test allows to test for additivity of substance effects by testing whether interaction coefficients improve the fit of the model significantly or not.

Computers↗
PubMed1977

[Nephrotic syndrome presumable caused by an complex glomerulonephritis (author's transl)].

The nephrotic syndrome presumably caused by an immune complex glomerulonephritis constitutes a major side effect attendant upon chronic administration of penicillamine. The possible induction of an immune-complex glomerulonephritis by penicillamine and its further development after stopping the drug was investigated in rats. --60 rats were fed perorally 2000 mg D-Penicillamine/kg BW/die resp. for a period of 8--44 days. Following unilateral nephrectomy the animals were observed for further 5 weeks. --Dependent to the time of penicillamine application there was an increasing deposition of IgG and C3 in a granular pattern along the glomerular basement membrane and within the mesangium. The IgG deposits initially were focal and segmental later on diffuse and global in distribution. 5 weeks after stopping the penicillamine the immune globulin deposits had disappeared completely or at least in part as did the mild focal glomerulonephritis and the moderate proteinuria which developed in some animals after a 44 day treatment with penicillamine. --The results confirm the hitherto presumed immune complex pathogenesis of the penicillamine induced nephropathy. The disappearance of the immunoglobulins deposited and of proteinuria stopping penicillamine alludes the good prognosis of this kind of nephropathy.

Animals↗
PubMed1977

[Effects of premedication, narcosis and surgery on the coagulation and fibrinolysis systems and the platelets. The influence of dextran and hydroxyethyl starch (hes) during and after operation (author's transl)].

Patients who had undergone orthopaedic surgery were investigated. The changes attributable to premedication and narcosis were characterized by a primary fibrinolysis which was accompanied by a slight hypercoagulability. This increased fibrinolytic activity was more pronounced immediately after the beginning of the operation. The post operative changes are characterized by increased ADP-induced aggregation, increased release of platelet factors 3 and 4 and hypercoagulability with reduced fibrinolysis. The reduction in platelets during the operation could be prevented due to the influence of dextran and hydroxyethyl starch (HES). It came further to a slight increase in the activity of factor VII, to an increased fibrinogen polymerization and also to an increased release of platelet factor 4.

Adenosine Diphosphate↗