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Biomedical subjects

P Köhler

Publications and source records attributed to P Köhler.

At least 91 records · Page 5Linked to original sources
PubMed1982

The effect of praziquantel on calcium in Hymenolepis diminuta.

Praziquantel (PZ) at concentrations down to 5 x 10(-8) M induced a rapid contraction of Hymenolepis diminuta musculature. This effect was accompanied by a strong inhibition of 45Ca2+ incorporation which showed some dependence on Ca2+ concentration. Ca2+ efflux experiments showed that PZ markedly stimulated the release of Ca2+ from tapeworms preloaded with 45Ca2+, with the effluxed Ca2+ being derived from a small fast pool and a larger slow pool. This stimulatory effect appeared., like PZ-induced muscle contraction, to be independent of external Ca2+. By carrying out 45Ca2+ exchange experiments under near equilibrium conditions and atomic absorption spectroscopy it could be demonstrated that PZ resulted in a net excretion of endogenous Ca2+. In PZ-induced contracted worms adenylate nucleotide levels and the adenylate energy charge were not significantly different from those of untreated control worms. Also, PZ had no effect on Ca2+-stimulated ATPase activity of the tapeworm's tegumental brush border. Nor did the drug alter the activities of Ca2+-ATPases in whole homogenates of worms or mitochondria, microsomal or soluble fractions. Although the mechanism of PZ-induced changes in Ca2+ transport was not elucidated, it is suggested that the sustained release of endogenous Ca2+ may affect the sequence of excitation-contraction coupling and that such interference may cause the observed massive contraction of the tapeworm's musculature.

Adenine Nucleotides↗
PubMed1981

Intestinal tubulin as possible target for the chemotherapeutic action of mebendazole in parasitic nematodes.

In vitro incubation of the parasitic nematode Ascaris suum in the presence of 10 microM mebendazole (MBZ) resulted in a complete loss of colchicine binding ability of extracts obtained from the parasite's intestine. Biochemical evidence supported the identification of the colchicine binding receptor in A. suum intestinal extracts as tubulin. This protein was partially purified and found to comprise approximately 0.8% of the soluble intestinal protein. MBZ inhibited colchicine binding to the partially purified tubulin in a competitive manner, the inhibition constant being 4.22 X 10(-6) M. Colchicine binding to porcine brain tubulin was also competitively inhibited by MBZ, exhibiting an inhibition constant of 8.0 X 10(-6) M. [3H]Colchicine binding studies revealed an apparent association constant of A. suum tubulin of 5.88 X 10(4) M(-1). Similar experiments employing [3H]MBZ showed that the extent of MBZ binding to the tubulin up to 10(-5) M was linearly dependent on MBZ concentration. Due to solubility problems the precise association constant for MBZ could not be determined but is apparently less than 10(5) M(-1). In view of the small difference in drug binding abilities between nematode intestinal and mammalian brain tubulin it still remains unclear whether the selective toxicity of MBZ can be solely explained by its interference with the parasite's microtubular system. Further studies reported in this paper suggest that a differential pharmacokinetic behaviour of MBZ between parasite and host may be the essential basis for the difference in drug susceptibility between both biological systems.

Animals↗
PubMed1981

Cytotoxicity of Echinococcus granulosus cyst fluid in vitro.

In a cytotoxicity assay, using rat spleen cells as target cells, Echinococcus granulosus cyst fluid from cattle exerted a marked degree of cytotoxicity in vitro. When trypan blue exclusion or [3H]thymidine incorporation by concanavalin A stimulated spleen cells was used as a measure of cell viability, dialyzed cyst fluid showed maximum cell destruction up to a 1:8 dilution. The effect was dose and time dependent, cells being affected by 24 h after exposure to cyst fluid. The components responsible for cytotoxicity of cyst fluid were heat stable and could be recovered using gel chromatography on Sephadex G 50 and G 15 as a single low molecular weight fraction. It is assumed that the toxic products released by the living parasite can readily penetrate through the cyst wall into the surrounding host tissue. The interference of such substances with immunocompetent cells might account for the long-term survival of the parasite in the intermediate host.

Animals↗
PubMed1981

Prostacyclin-thromboxane interactions in the platelet-perfused in vitro heart.

A preparation of an isolated platelet-perfused guinea pig heart is described, which was utilized to study prostacyclin-thromboxane interrelationships. Infusion of washed human platelets (4 X 10(8)/min) through the coronary vascular bed stimulated the vascular PGI2 production from 114 +/- 27 to 350 +/- 30 pg/ml (P less than 0.01) and was associated with a significant increase in platelet cAMP from 1.2 +/- 0.4 to 2.6 +/- 0.9 pmol/10(8) platelets (P less than 0.05). Administration of arachidonic acid (AA) (45 micrograms) to the system led to a further increase (eight- to ninefold) of PGI2 and yielded marked thromboxane formation (20-25 ng/ml). Treatment of the hearts with aspirin (1 mM) prevented the PGI2 formation and AA-induced increase in platelet cAMP. Treatment of platelets with aspirin prevented thromboxane formation but did not influence AA-induced changes in platelet cAMP and vascular PGI2 production. Bioassay data of PGI2 and rabbit aortic contracting substance gave results comparable to radioimmunoassay of 6-keto-PGF1 alpha and thromboxane B2. AA always decreased the coronary vascular resistance whether thromboxanes were formed or not.

Animals↗
PubMed1980

[Changes in the serum triglyceride levels following treatment with ovulation inhibitors in tall girls].

The chronological course of serum triglycerides was determined in 12 girls aged 9--10 years, who have been cyclically treated with mestranol (80 microgram/d) and chlormadinonacetate during 3 1/2 years on average, because of constitutional tall stature. A significant increase of the triglycerides level from 80 to 130 mg/100 ml (0.91 to 1.49 mmol/l) could be noted, followed by normalisation within 6 months. Mechanism and metabolic risk of the reversible increase of serum triglycerides are discussed.

Body Weight↗
PubMed1980

[Frequency of lipid metabolism disorders in blood donors].

It is reported on a screening test examination for disturbances of the lipometabolism in 3,714 blood donors by means of the estimation of the beta-lipoproteins. In 240 blood donors (6.5%) increased values of beta-lipoproteins were found. 45 donors with values increased for several times underwent an after-examination by a specialist, by means of which among others in eight of them an asymptomatic diabetes mellitus was found. The estimation of the beta-lipoproteins as screening test examination is ingenious and serves the improved cure for the health of the donors.

Adolescent↗
PubMed1980

Mechanisms of respiration and phosphorylation in Ascaris muscle mitochondria.

In Ascaris muscle mitochondria the major respiratory chain-linked phosphorylation activity is accomplished by a NADH-linked reduction of fumarate to succinate. Oxygen can also be employed as a terminal electron acceptor via a cyanide- and salicyl-hydroxamate-resistant terminal oxidase. As in fumarate-dependent electron transport this process appears to be coupled to energy conservation at phosphorylation site I. The branchpoint from which electrons are taken from the main respiratory chain to either the alternative oxidase or fumarate reductase is likely to be on the oxygen side of the NADH dehydrogenase segment. Malate and succinate are the only substrates which appreciably support respiration in the mitochondrion of the nematode. Regardless of the presence or absence of oxygen malate is utilized by an oxidation-reduction reaction resulting in the formation of pyruvate, acetate, succinate, propionate and CO2. In addition, aerobically, hydrogen peroxide is formed as the product of oxygen reduction. Succinate accumulation was found to be significantly higher in the anaerobic as compared to the aerobic incubation mixtures. This effect was accompanied by an increase in anaerobic malate consumption. ATP generation and the formation of pyruvate, acetate and propionate were found to be similar in the presence and absence of oxygen. In malate-supported respiration of intact Ascaris mitochondria reducing equivalents (NADH) are produced exclusively through pyruvate and acetate formation. These enzymatic reactions are functionally coupled to the electron transport-linked reductions of fumarate to succinate and oxygen to hydrogen peroxide, respectively. In accordance with the position of the redox potentials of the fumarate/succinate and O2/H2O2 couples, anaerobic and aerobic respiration was found to be associated with relatively low energy conservation efficiencies. Thus one molecule of ATP was conserved per 2e- transferred to fumarate or oxygen, respectively. No evidence could be obtained for a significant activity of energy conservation sites II and III and electron transfer through the alternative oxidase pathway was shown not to be coupled to phosphorylation.

Adenosine Triphosphate↗
PubMed1977

[Spectrophotometric demonstration of poison in the routine clinical chemistry laboratory].

After the chloroform extraction of drugs from the serum the extracts are vaporized. The remaining residues are solved with diluted NaOH or HCl and the solutions are measured spectrophotometrically. This approach gives the possibility of a simultaneous qualitative and quantitative analysis. The results help, to make quickly diagnostic and therapeutic decisions.

Chemistry, Clinical↗
PubMed1976

Demonstration and possible function of NADH:NAD+ transhydrogenase from ascaris muscle mitochondria.

Mitochondria from the muscle of Ascaris lumbricoides var. suis function anaerobically. NADH is generated in the intermembrane space as a consequence of the "malic" enzyme reaction. It has been suggested that this reducing equivalent in the form of hydride ion, would be translocated across the inner membrane in order to mediate ATP generation via the fumarate reductase reaction. In accord with this suggestion, intact Ascaris mitochondria showed appreciable NADH oxidase activity. Sonication resulted in an approximately 2-fold increase in NADH oxidase activity, whereas "malic" enzyme, fumarase, and NADH:NAD+ transhydrogenase activities increased approximately 7- to 14-fold, respectively. Phosphorylation capabilities and permeability toward pyridine nucleotides also indicated the intactness of the mitochondria. Ascaris mitochondria incubated anaerobically in the presence of fumarate, and [14C]NADH catalyzed a rapid reduction of the fumarate to succinate with the concomitant formation of equivalent quantities of extramitochondrial NAD+. However, very little isotope was recovered from the washed mitochondria, indicating the possibility of hydride ion translocation in the absence of nucleotide translocation. NADH:NAD+ transhydrogenase has been isolated from the muscle mitochondria of the intestinal nematode, Ascaris lumbricoides var. suis. The enzyme seems to have been solubilized from the mitochondrial membrane fraction by treatment with sodium deoxycholate followed by dialysis and subsequent adsorption by and elution from alumina C gamma. No NADPH:NAD+ transhydrogenase activity was detectable, making the Ascaris system unique over others reported. Activity was protected by L-cysteine, reduced glutathione and dithioerythritol, but strongly inhibited by low concentrations of p-chloromercuribenzoate or silver nitrate. The thionicotinamide derivative of NAD+ (thioNAD+) was employed to accept hydride ions from NADH in order to assay spectrophotometrically at 398 nm. Apparent Km values for thioNAD+ and NADH were 1 X 10(-4) M and 8 X 10(-6) M, respectively. That the physiological nucleotide, could act as hydride ion acceptor from NADH was indicated by the findings that NAD+ competitively inhibited the reduction of thioNAD+ when assayed at 398 nm. The additional finding of a noncompetitive inhibition between NAD+ and NADH suggested at least two binding sites on the enzyme, one for NADH and another common site for NAD+ and thioNAD+. More conclusive evidence indicating the participation of NAD+ as acceptor was obtained by incubation of the enzyme with NADH and [14C]NAD+ and demonstrating a rapid formation of [14C]NADH. These findings, in conjunction with those discussed above, suggest a physiological function of this enzyme in hydride ion translocation.

Aerobiosis↗