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Biomedical subjects

E Karlsson

Publications and source records attributed to E Karlsson.

161 records · Page 9Linked to original sources
PubMed1973

Effects of an isolated toxin from Australian tiger snake (Notechis scutatus scutatus) venom at the mammalian neuromuscular junction.

1. The acute effects of a purified toxin from Australian Tiger snake (Notechis scutatus scutatus) venom have been investigated at the mammalian neuromuscular junction.2. The toxin was injected into the tail vein of mice. Death was due to respiratory paralysis.3. The resting membrane potential, and action potential of muscle fibres in muscles from in vivo intoxicated animals were normal.4. The frequency of miniature end plate potentials (m.e.p.p.s) from intoxicated nerve-muscle preparations was reduced, although m.e.p.p. amplitude was unaltered.5. Nerve stimulation resulted in end plate potentials (e.p.p.s) of quantal amplitude; only rarely was the e.p.p. large enough to give rise to an action potential.6. High (20 mM) K(+) did not increase m.e.p.p. frequency in intoxicated preparations.7. The toxin was largely ineffective in vitro.8. The similarities and differences between this toxin, beta-bungarotoxin and botulinum toxin are discussed.

Action Potentials↗
PubMedDate not supplied

Kinetic evidence for different mechanisms of interaction of black mamba toxins MT alpha and MT beta with muscarinic receptors.

By studying the influence of two toxins from the black mamba Dendroaspis polylepis on the kinetics of [3H]-N-methylscopolamine binding to muscarinic acetylcholine receptors from rat cerebral cortex, it was revealed that these toxins, MT alpha and MT beta, interact with the receptors via kinetically distinct mechanisms. MT beta bound to receptors in a one-step, readily reversible process with the dissociation constant K(d)=5.3 microM. The binding mechanism of MTalpha was more complex, involving at least two consecutive steps. A fast receptor-toxin complex formation (K(T)=3.8 microM) was followed by a slow process of isomerisation of this complex (k(i)=1.8 x 10(-2) s(-1), half-time 39 s). A similar two-step interaction mechanism has been established for a related toxin, MT2 from the green mamba D. angusticeps (K(T)=1.4 microM, k(i)=8.3 x 10(-4) s(-1), half-time 840 s). The slow isomerisation process delays the effect of MT alpha and MT2, but increases their apparent potency compared to toxins unable to induce the isomerisation process.

Animals↗
PubMedDate not supplied

Snake toxins with high selectivity for subtypes of muscarinic acetylcholine receptors.

There are five subtypes of muscarinic acetylcholine receptors (M(1) to M(5)) which control a large number of physiological processes, such as the function of heart and smooth muscles, glandular secretion, release of neurotransmitters, gene expression and cognitive functions as learning and memory. A selective ligand is very useful for studying the function of a subtype in presence of other subtypes, which is the most common situation, since a cell or an organ usually has several subtypes. There are many non-selective muscarinic ligands, but only few selective ones. Mambas, African snakes of genus Dendroaspis have toxins, muscarinic toxins, that are selective for M(1), M(2) and M(4) receptors. They consist of 63-66 amino acids and four disulfides which form four loops. They are members of a large group of snake toxins, three-finger toxins; three loops are extended like the middle fingers of a hand and the disulfides and the shortest loop are in the palm of the hand. Some of the toxins target the allosteric site which is located in a cleft of the receptor molecule close to its extracellular part. A possible explanation to the good selectivity is that the toxins bind to the allosteric site, but because of their size they probably also bind to extracellular parts of the receptors which are rather different in the various subtypes. Some other allosteric ligands also have good selectivity, the alkaloid brucine and derivatives are selective for M(1), M(3) and M(4) receptors. Muscarinic toxins have been used in several types of experiments. For instance radioactively labeled M(1) and M(4) selective toxins were used in autoradiography of hippocampus from Alzheimer patients. One significant change in the receptor content was detected in one region of the hippocampus, dentate gyrus, where M(4) receptors were reduced by 50% in patients as compared to age-matched controls. Hippocampus is essential for memory consolidation. M(4) receptors in dentate gyrus may play a role, since they decreased in Alzheimers disease which destroys the memory. Another indication of the role of M(4) receptors for memory is that injection of the M(4) selective antagonist muscarinic toxin 3 (M(4)-toxin 1) into rat hippocampus produced amnesia.

Amino Acid Sequence↗
PubMedDate not supplied

Tau immunoreactivity detected in human plasma, but no obvious increase in dementia.

Tau proteins are central to the neuropathology of Alzheimer's disease and tau levels in cerebrospinal fluid are elevated in affected individuals. In this study, we investigated the presence of tau in plasma from subjects with Alzheimer's disease (n = 16), frontotemporal dementia (n = 10), vascular dementia (n = 16) and from healthy controls (n = 15). By using an ELISA with monoclonal tau antibodies, tau immunoreactivity was detected in approximately 20% of the subjects. However, no difference between the disease and control groups was seen. After gel filtration of tau immunopositive plasma, the peak reactivity was found in the 160-kD fraction, indicating the source to be tau-like molecules of high-molecular-weight or polymers of low-molecular-weight tau isoforms. We conclude that measurements of tau in plasma cannot be utilized diagnostically for Alzheimer's disease or for the other dementias investigated. Copyrightz1999S.KargerAG,Basel

Aged↗
PubMedDate not supplied

Clinical pharmacokinetics of procainamide.

Procainamide is almost completely absorbed after oral administration and peak plasma concentrations are generally reached within 1 to 2 hours. Upon intravenous administration there is a rapid initial distribution phase, which is completed after about 30 minutes. The pharmacokinetics can be described by a 2-compartment open model. The plasma half-life during the beta-phase averages 3 hours. The apparent volume of distribution is about 2L/kg body weight. At therapeutic plasma levels about 15% is bound to plasma proteins. Approximately 50% of administered procainamide is eliminated as unchanged drug via the kidneys. N-Acetylprocainamide is the main metabolite and is the main metabolite and is pharmacologically active, with a recovery in urine of about 15% (range 7 to 34% in healthy subjects). The acetylation of procainamide seems to be under the same monogenic control as that of isoniazid. At least 2 more metabolites have been found but are not yet identified. The renal clearance of procainamide ranges from 179 to 660ml/min. Glomerular filtration and active tubular secretion seem to be the most important mechanisms. In patients with low-output cardiac and/or renal impairment, the absorption, distribution and elimination of the drug may be significantly altered. Determination of plasma levels is of particular value in these cases and will contribute to more safe and effective therapy in the majority of patients. As N-acetylprocainamide seems to have pharmacological effects comparable with those of procainamide, both agents should be monitored simultaneously in order to optimise therapy.

Acute Kidney Injury↗