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Biomedical subjects

H Askmark

Publications and source records attributed to H Askmark.

17 recordsLinked to original sources
PubMed1992

Leakage of carbonic anhydrase III from normal and denervated rat skeletal muscle following contractile activity.

Skeletal muscle extracellular carbonic anhydrase III was investigated in anesthetized rats by a microdialysis technique. A small dialysis probe was inserted into the tibialis anterior (TA) muscle and perfused continuously. Perfusates were collected before and during muscle contraction, induced by electrical stimulation of the muscle or of the sciatic nerve. In the perfusate of resting normal and denervated muscle, the concentration of CA III was 10 to 12 ng/mL, as measured by a radioimmunosorbent technique. During contractile activity, the concentrations of CA III increased markedly in the normal and denervated muscle. A TA muscle suspended in physiological saline behaved similarly, even though the leakage before and during contraction was higher than in vivo. The results show that skeletal muscle leaks CA III both in vivo and in vitro, a leakage which was markedly increased by contractile activity. The microdialysis technique should also be useful in humans to study the efflux of various proteins from different kinds of diseased or fatigued muscles.

Animals↗
PubMed1992

Increased binding of 3H-L-deprenyl in spinal cords from patients with amyotrophic lateral sclerosis as demonstrated by autoradiography.

The present investigation has applied quantitative autoradiography and histochemistry to study the regional distribution of MAO-B and its relation to the number of cells in respective regions. L-deprenyl binds irreversibly and quantitatively to the B-form of monoamine oxidase, MAO, and is an ideal 3H-ligand to measure the MAO-B enzyme protein in tissues by means of in vitro autoradiography. The investigation is performed on spinal sections from five controls and five cases with amyotrophic lateral sclerosis (ALS) on cervical, thoracic and lumbar level. The highest density of 3H-L-deprenyl binding was found around the central canal (lamina X). MAO-B was markedly increased (up to 2.5 times of values in controls) specifically in regions of neurodegeneration e.g. motor neuron laminae and corticospinal tracts. There was a high correlation between glial cell count and 3H-L-deprenyl binding with a relation indicating enhanced MAO-B protein in glial cells within areas of neurodegeneration. In contrast the increased microglial cell number in ALS did not show any correlation with 3H-L-deprenyl binding.

Aged↗
PubMed1992

No re-expression of high-affinity nerve growth factor binding sites in spinal motor neurons in amyotrophic lateral sclerosis.

Autoradiographic studies of high-affinity nerve growth factor binding sites in the cervical human spinal cord revealed a high density of binding sites in the dorsal horn and in the tract of Lissauer, which is in agreement with investigations in nonprimates. Very low or no binding was found in the motor neuron areas of controls as well as in amyotrophic lateral sclerosis cases, which indicates that the degeneration of motor neurons in this disease is not accompanied by re-expression of high-affinity nerve growth factor receptors.

Aged↗
PubMed1991

Changes in cholinergic and opioid receptors in the rat spinal cord, dorsal root and sciatic nerve after ventral and dorsal root lesion.

Changes in the distribution of 3H-quinuclidinylbenzilate (3H-QNB), 3H-acetylcholine (3H-ACh) and 3H-alpha-bungarotoxin (alpha-BTx) binding sites were studied with the use of quantitative in vitro autoradiography in the L4-L6 segments of rats 7 days after ventral L4-L6-rhizotomies and 24 hours after ligation of the dorsal roots L4-L6. The changes in the binding sites of these ligands and of 3H-etorphine binding sites were also studied in the dorsal roots of the rats operated with dorsal root ligation and in the sciatic nerves (around a ligature) in the rats operated with ventral rhizotomy. After ventral rhizotomy 3H-QNB binding sites in the ipsilateral motor neuron area were decreased by about 25% from 100 +/- 5 to 73 +/- 5 fmol/mg wet weight. After dorsal root ligation 3H-QNB binding sites in the ipsilateral posterior horn were reduced by about 30% from 91 +/- 5 to 64 +/- 7 fmol/mg wet weight. No significant changes in the binding of the other cholinergic ligands in the spinal cords were observed after the operations. In the dorsal root 3H-alpha-Btx and 3H-etorphine binding sites were higher on the distal side of the ligation (3.5 +/- 0.8 and 14 +/- 4 fmol/mg wet weight, respectively) than on the proximal side (0.7 +/- 0.5 and 2.4 +/- 1.2 fmol/mg wet weight, respectively). The same level of 3H-ACh (total, muscarinic and nicotinic) binding was observed on both sides of the ligation. In the sciatic nerve 3H-QNB and total, muscarinic and nicotinic ACh binding sites were higher on the proximal side of the ligation than on the distal side.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Quantification of extrajunctional acetylcholine receptors in human muscle biopsies.

Extrajunctional acetylcholine receptors were quantified in human muscle biopsies by in vitro autoradiography with 3H-alpha-bungarotoxin (alpha-Btx). Specific alpha-Btx binding was found in seven of eight biopsies with histological and/or histochemical signs of denervation. The highest binding (21 fmol/mg) was seen in the biopsy with the most pronounced signs of denervation. The specimens with co-existing signs of innervation had generally lower binding levels. Four of the control biopsies showed low binding (less than or equal to 1 fmol/mg) while no specific binding could be detected in the other six controls. The findings suggest that this method cannot only be used to demonstrate denervation in muscle biopsy specimens, but also to give a quantitative measure of the changes.

Adolescent↗
PubMed1990

Clinical pharmacokinetics of intravenous and oral 9-amino-1,2,3,4-tetrahydroacridine, tacrine.

The pharmacokinetics of 9-amino-1,2,3,4-tetrahydroacridine; tacrine, THA, was studied after intravenous administration and following the first and last oral doses of a seven week clinical trial involving 8 patients with amyotrophic lateral sclerosis, ALS. Two surgical patients given intravenous THA for reversal of postoperative sedation were also included. Plasma concentration of THA and in some cases the metabolite, 1-hydroxy-THA, were assayed using a selective and sensitive method with high performance liquid chromatography. After an intravenous dose of 30 mg THA, the plasma concentrations were fitted to a two-compartment model. Plasma clearance showed a threefold interindividual variation with a mean of 2.42 l.h-1. Volume of distribution, V alpha varied 100-680 l with a mean of 349 l. The plasma half-lives of distribution and elimination were 1.8 and 98.2 min, respectively. Oral bioavailability showed large interindividual differences and ranged 6-36% in the four subjects studied. After seven weeks treatment with oral THA, plasma concentrations immediately prior to medication were below 10 ng/ml in three patients and above 100 ng/ml in two patients. At the same occasion the plasma metabolite concentrations considerably exceeded those of THA. THA medication was associated with side effects in the majority of the patients.

Administration, Oral↗
PubMed1990

Epidemiology of adverse reactions to carbamazepine as seen in a spontaneous reporting system.

A survey was made of 505 reports on 713 adverse reactions to carbamazepine submitted to the Swedish Adverse Drug Reactions Advisory Committee from 1965-1987. For the period after 1972, the relation between the reports and sales statistics could be investigated. The total incidence of reported adverse reactions to carbamazepine was 4.5 per million defined daily doses (DDD), corresponding to 2.7 per million prescribed daily doses (PDD). Most often reported were skin reactions (48%), but reports on haematological (12%) and hepatic disorders (10%) were also frequent. Virtually all hepatic disorders and severe skin reactions, as well as the majority (60%) of the haematological reactions, occurred within the first 2 months of treatment. In view of the very low incidence of reported serious blood dyscrasias, such as pancytopenia (0.04/million PDD) and agranulocytosis (0.06/million PDD), continuous haematological monitoring seems to be of little value. The elderly appear to be at increased risk of developing blood dyscrasias and liver reactions, and alcohol abusers seem to represent a high-risk group for developing serious skin reactions.

Age Factors↗
PubMed1990

Functional and pharmacokinetic studies of tetrahydroaminoacridine in patients with amyotrophic lateral sclerosis.

Assuming the presence of clinically significant cholinergic hypofunction in amyotrophic lateral scleroses (ALS), seven patients with ALS were treated with 100-200 mg tetrahydroaminoacridine (THA) together with 11 g lecithin daily for up to 7 weeks. In a separate experiment pharmacokinetics and effects on muscle strength and neurophysiological parameters were studied following the injection of 30 mg THA intravenously. Following the injection of THA an increase in muscle strength was observed in two patients. There were no consistent pharmacokinetic differences that could explain the effect on intravenous THA on muscle strength in these two patients. The plasma clearance of THA was high and the oral bioavailability low with large interindividual differences (6-36%). No beneficial effect was seen during oral medication and side-effects were common. There were no conclusive changes observed regarding neurophysiological parameters after drug administration. THA has probably no place in the treatment of ALS.

Administration, Oral↗
PubMed1989

Lactation headache--a new form of headache?

The case of a 26-year-old woman suffering from brief attacks of headache occurring on every occasion of nursing is described. Pulse rate and blood pressure are normal during the attacks and serum prolactin responds normally to nursing. Plasma vasopressin increases before each headache attack. Propranolol does not prevent the headache, which disappears only after lactation has ceased. Possible pathophysiological mechanisms related to suckling are discussed.

Adult↗
PubMed1989

Drug-related headache.

A survey was made of 10,506 reports to the WHO Collaboration Centre for International Drug Monitoring from five countries concerning headache, migraine, aggravated migraine and intracranial hypertension associated with drugs. The ten drugs most frequently reported to be associated with headache were indomethacin, nifedipine, cimetidine, atenolol, trimethoprim-sulphamethoxazole, zimeldine, glyceryl trinitrate, isosorbide dinitrate, zomepirac and ranitidine. Regarding migraine, oral contraceptives were also among the most implicated drugs. Most reports of intracranial hypertension concerned tetracyclines, isotretinoin and trimethoprim-sulphamethoxazole. Vasodilatation and salt and water retention with subsequent redistribution of intracranial fluid seem to be common mechanisms underlying drug-related headache. For certain frequently reported drugs, however, the mechanisms of the headache are unknown.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1989

Screening for neurotrophic disturbances in amyotrophic lateral sclerosis.

Neurotrophic activities in human serum and post-mortem muscle and spinal cord of possible relevance to pathophysiological mechanisms in amyotrophic lateral sclerosis (ALS) were studied. Tests included in vitro assays for nerve fibre outgrowth from sympathetic ganglia and for survival promotion of dissociated ciliary neurons, both types of neurons, of chicken embryo origin. Extracts of postmortem biceps muscle promoted survival of ciliary neurons in a dose-dependent manner. Half-maximum effect was found at a protein concentration of about 450 micrograms/ml for both ALS and control muscle. Ventral horn extracts were about 5 times as efficient as muscle in promoting neuron survival, again with no differences seen between control and ALS samples. Sera from patients suffering from ALS as well as normal sera did not enhance survival of ciliary neurons to any considerable extent, nor did they induce fibre outgrowth from sympathetic ganglia. Both groups of sera, if present above 5% in the medium, suppressed fibre outgrowth induced by added nerve growth factor (NGF). Sera from some of the ALS patients impaired survival in dissociated ciliary neurons supported by a trophic activity in choroid extract. The results do not indicate major neurotrophic deficits as the cause of ALS disease but suggest that a neurotoxic mechanism may be involved.

Aged↗
PubMed1988

Induction of carbonic anhydrase III mRNA and protein by denervation of rat muscle.

Carbonic anhydrase III (CAIII) protein and mRNA amounts in fast- and slow-twitch rat muscles were examined after resection of the sciatic nerve. Striking changes occur in the fast-twitch anterior tibialis (AT) and extensor digitorum longus (EDL) muscles, where CAIII protein and mRNA are increased several-fold 16 days after denervation. The data suggest that these changes are regulated in part by changes in gene transcription and that they perhaps signal a fast-to-slow fibre type transition in these denervated muscles. AT and EDL show some differences in the effects of denervation, which are suggestive of variation in the timing of denervation-induced responses and/or the CAIII protein/mRNA turnover rates in the two muscles.

Actins↗
PubMed1987

Induction of rat muscle carbonic anhydrase by denervation demonstrated with immunofluorescence.

Immunofluorescence microscopy of carbonic anhydrase III (CA III) was performed on sections of rat anterior tibialis (AT), extensor digitorum longus (EDL) and soleus after denervation. In contralateral control muscles, CAIII was located only in type I fibres whereas following the operation, CAIII was markedly induced in type II fibers of all the muscles, most strikingly in EDL.

Animals↗
PubMed1986

Large-section cryomicrotomy for in vitro receptor autoradiography.

A method for processing human postmortem material for application of autoradiography to large cryosections is described. Whole organ or tissue slices 5 mm thick are frozen between copper plates cooled with liquid nitrogen. They are subsequently embedded in carboxymethyl-cellulose, and 40- to 80-microns sections are taken up on adhesive tape and paper and transferred to gelatinized glass plates. Two procedures for incubation of large sections are described. The method is exemplified by autoradiographs of human brain hemisphere ([ 3H]quinuclidinylbenzilate) and whole biceps muscle ([ 3H]alpha-bungarotoxin).

Autoradiography↗