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Biomedical subjects

R Bachmann

Publications and source records attributed to R Bachmann.

At least 55 records · Page 3Linked to original sources
PubMed1985

Respiration and energy conservation in the filarial worm Litomosoides carinii.

The average rate of endogenous respiration of intact Litomosoides carinii was 2.24 muatom O min-1 g-1 worm wet wt. No significant difference was observed in respiration capacities between male and female worms. Rates of oxygen uptake decreased progressively during disruption and fractionation of the parasite tissue and very few respiration capabilities remained in the mitochondrial fraction. Added substrates increased the respiratory rates of the intact filariid and cell-free extracts by a factor of 1.4 to 2.3, depending on the tissue system and substrate species used. Rotenone and cyanide strongly inhibited respiration in all incubations, whereas antimycin A, in most cases, suppressed oxygen consumption only partially. ATP conservation in cell-free extracts of L. carinii, as determined by the incorporation of 32Pi into the organic phosphate fraction, was twice as high in the presence of air as under an atmosphere of nitrogen. Anaerobically, rates of phosphorylation in these extracts were similar to the amounts of lactate. Phosphorylation in mitochondria isolated from the filarial worm was supported by malate, succinate, pyruvate and TMPD/ascorbate, whereas L-glutamate and beta-hydroxybutyrate exhibited only little or no effect, respectively. P/O ratios for pyruvate-supported oxidative phosphorylation were found to approach a value of 3. Electron transport inhibitors, oligomycin and 2,4-dinitrophenol strongly inhibited substrate-dependent mitochondrial phosphorylation. The data of the present investigation, together with other recent findings made by the same authors, have provided evidence that in L. carinii mitochondria a mammalian-type of respiratory system capable of carrying out oxidative phosphorylation is functional. It seems likely that this respiration-dependent chemical energy, proceeding in addition to that generated through fermentation processes, may be vital for muscular contraction and survival of this filarial parasite.

Adenosine Triphosphate↗
PubMed1985

Dynamic responses to intravenous urapidil and dihydralazine in normal subjects.

Hemodynamic responses after urapidil were compared with those after dihydralazine in placebo-controlled, double-blind studies after cumulative intravenous doses. We recorded heart rate, blood pressure, systolic time intervals corrected for heart rate (electromechanical systole and preejection period), electrical impedance cardiography [(dZ/dt)/RZ index and mean electrical thorax impedance], and M-mode echocardiogram (end-systolic and -diastolic diameters, end-systolic wall stress, fractional shortening, and cardiac output). Both drugs induced dose-dependent reductions in total peripheral resistance, which resulted in reduction in left ventricular end-systolic wall stress and increases in heart rate (limited at +10 bpm with urapidil), fractional shortening, cardiac output, and the (dZ/dt)/RZ index. With each drug, diastolic blood pressure fell by 5 mm Hg, the corrected preejection period shortened (dihydralazine greater than urapidil), the corrected electromechanical systole did not change, and mean electrical thorax impedance rose with urapidil. The spectrum of effects indicates that both drugs reduce left ventricular afterload, thereby increasing left ventricular pump performance. Urapidil also exerts some preload reduction.

Adult↗
PubMed1983

The localization of fumarase and malic enzyme in muscle mitochondria of Ascaris suum.

The distribution of fumarase and malic enzyme in Ascaris suum muscle mitochondria was investigated by employing digitonin fractionation techniques. The ability of these procedures to resolve the various submitochondrial fractions (intracristal space, inner membrane, matrix and inner membrane-matrix particles) was verified by electron microscopy and the distribution of appropriate marker enzymes. From the data obtained, it is concluded that fumarase in Ascaris muscle mitochondria is located solely within the matrix compartment and is not present within the intracristal space as reported earlier by other authors (Rew and Saz (1974) J. Cell. Biol. 63, 125-135). In agreement with previous findings malic enzyme in the nematode organelle appears to be associated with both soluble compartments. The implications of these findings to the parasites' mitochondrial metabolism are discussed.

Animals↗
PubMed1983

Essential laboratory determinations for monitoring high-dose methotrexate treatment with citrovorum factor rescue.

The use of high-dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) has considerably improved the prognosis of some pediatric malignancies. Massive doses of methotrexate (mtx) may lead to severe or even lethal toxicity. Safe administration of this regimen requires a wide pattern of laboratory tests as well as clinical supervision. One hundred and eighteen courses of HDMTX (12 gm/m2 over 6 hours iv) with CFR administered to 12 patients were analysed for changes of routine laboratory tests 0, 6, 24, 48, and 72 hours following infusion. Hgb, WBC, and platelets on average showed no change during the 72 hours follow-up period. Serum SGOT and SGPT were elevated with a maximum 24 hours following infusion and slowly returned to normal. The increase of serum LDH values were less marked and reached a maximum at 48 hours; changes of serum y-GT values were not significant. Evaluation of the elimination of mtx from serum in each individual patient throughout 14 sequential mtx courses gave no evidence of a prolonged serum half life due to impaired renal mtx clearance. There was also no evidence of enzyme induction in the liver resulting in a shortened serum half-life. Changes of serum enzymes also were not increasing throughout treatment. Careful monitoring of serum mtx levels is mandatory when HDMTX with CFR treatment is administered. Elevation of blood urea nitrogen and creatinine levels within 24 hours following mtx treatment identify the patient at risk for slow mtx elimination and severe toxicity requiring salvage by adequate doses of citrovorum factor.

Adolescent↗
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↗
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↗