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Biomedical subjects

S Hesse

Publications and source records attributed to S Hesse.

At least 109 records · Page 6Linked to original sources
PubMed1989

Collateral nerve sprouting and twitch forces of single motor units in conditions with partial denervation in man.

Single motor units (MUs) were studied in the first dorsal interosseus muscle of 7 patients with slight partial denervation and in 10 controls. MU action potentials were recorded using the macro-EMG technique and their size was taken to assess collateral nerve sprouting. Simultaneously, the muscle force was monitored to determine the voluntary recruitment thresholds of the MUs and spike-triggered-averaging was applied to measure their twitch forces. At comparable force recruitment thresholds, both macro-EMG potentials and twitch forces were increased in the patients. We conclude, that collateral nerve sprouting increases MU force and can compensate for MU loss.

Adult↗
PubMed1989

Effect of urapidil on the performance of ischaemic myocardium in anaesthetized dogs.

The effect of urapidil on the ischaemic myocardium was studied in eight anaesthetized dogs. Stenosis of the left descending coronary artery reduced blood flow and systolic contraction of the post-stenotic myocardium by about 50%; the end-diastolic length of the post-stenotic myocardium and the end-diastolic pressure increased, while aortic pressure slightly decreased. Subsequent administration of urapidil (0.25 + 0.25 + 0.5 + 1.0 mg/kg intravenously) did not affect the systolic shortening and end-diastolic length of the myocardium supplied by the left circumflux coronary artery, while the stroke volume and the systolic shortening of the ischaemic myocardium increased. The latter was correlated with a decrease in the heart rate (r = -0.92), but not with the reduction in aortic pressure. Urapidil by itself does not impair the performance of the ischaemic myocardium, but might be beneficial in decreasing the heart rate or suppressing reflex tachycardia during reduction of the afterload.

Adrenergic alpha-Antagonists↗
PubMed1987

Glutathione depletion suppresses conjugation of benzo[a]pyrene metabolites and (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene metabolites with glutathione but does not affect their binding to DNA in C3H/10T1/2 mouse fibroblasts.

The study was aimed at determining the role of glutathione (GSH) conjugation in the binding of reactive benzo[a]pyrene (BaP) species to DNA of C3H/10T1/2 cells. In order to suppress GSH conjugation cells were depleted of GSH by treatment with buthionine sulfoximine for 18 h and 1-chloro-2,4-dinitrobenzene for 1 h prior to incubation with radiolabelled substrates. Under these conditions GSH levels decreased to less than 1% of the control value. C3H/10T1/2 cells produced GSH conjugates with 7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BaPDE) comprising 6% of the total metabolites formed from BaP or (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BaP-7,8-diol). In GSH-depleted cells formation of GSH conjugates with metabolic products of BaP or BaP-7,8-diol was suppressed to 1% of total metabolites during an 8-h incubation period. Metabolic activation of BaP and BaP-7,8-diol by C3H/10T1/2 cells resulted in the formation of DNA adducts which largely consisted of BaPDE:deoxyguanosine. Depletion of GSH altered neither the degree of DNA binding nor the pattern of DNA adducts to any significant extent. When C3H/10T1/2 cells were co-incubated with microsomes from liver of 3-methylcholanthrene-treated rats for 1 h in order to activate BaP or BaP-7,8-diol extracellularly, the same pattern of GSH conjugates and DNA adducts was generated as by intracellular metabolism of the polycyclic hydrocarbons. No GSH conjugates were detected following co-incubation of microsomes with GSH-depleted C3H/10T1/2 cells. The formation of DNA adducts again remained unaffected by the suppression of conjugation. C3H/10T1/2 cells are apparently capable of conjugating BaPDE with GSH but are not capable of trapping by GSH conjugation those BaPDE moieties which bind to DNA. The results are compatible with the notion that BaPDE is partially contained in a cellular compartment--presumably the lipid environment of membranes--where it is inaccessible to GSH transferases of C3H/10T1/2 cells.

Animals↗
PubMed1984

The capacity of rat hepatoma cell lines for O6-methylguanine-DNA repair correlates with their status of differentiation.

O6-Methylguanine-DNA methyltransferase activity, i.e., the capacity of cells to transfer the methyl group from O6-methylguanine in DNA to protein, was determined in 10 hepatoma cell lines, all derived from Reuber H35 hepatoma but differing in their status of differentiation. Methyltransferase activity of the six differentiated lines tested was at least 4-5 times higher than that of two dedifferentiated lines. The activity of the two poorly differentiated lines examined was low to intermediate. Some of the differentiated lines possessed methyltransferase activities comparable to those in hepatocytes freshly isolated from adult rat. The results suggest that certain differentiated hepatoma lines are capable of mimicking liver in the capacity for repair of O6-methylguanine lesions and in this respect may be useful as model systems for studying liver-specific effects of monofunctional alkylating agents.

Animals↗
PubMed1982

Inactivation of DNA-binding metabolites of benzo[a]pyrene and benzo[a]pyrene-7,8-dihydrodiol by glutathione and glutathione S-transferases.

The binding to DNA of reactive metabolites of trans-7,8-dihydro-7,8-dihydroxybenzo[a]pyrene (BP-7,8-diol) was studied following the incubation of tritiated benzo[a]pyrene (BP) and BP-7,8-diol with nuclei from livers of 3-methylcholanthrene-treated rats. Binding was inhibited to a small extent by glutathione (GSH) alone and to a much greater extent by GSH and cytosol or purified GSH-transferases B and E. In this respect GSH-transferases A and C were also active, but less so. Inhibition of binding of BP-7,8-diol metabolites to DNA mediated by GSH-transferases was associated with the formation of GSH conjugates. The extent of inhibition of binding was similar in incubations of nuclei alone, nuclei and rat liver microsomes, and calf thymus DNA and rat liver microsomes. This indicates that reactive metabolites of BP-7,8-diol, formed either by nuclei or microsomes, are readily accessible to soluble GSH-transferases. GSH and cytosol were also active in inhibiting DNA-binding of reactive metabolites from 9-hydroxybenzo[a]pyrene (9-OH-BP). Thus, in the rat hepatocyte GSH and GSH-transferases may be important in protecting DNA from electrophilic attack by reactive BP-7,8-diol and 9-OH-BP species.

Animals↗
PubMed1981

Threshold levels in toxicology: significance of inactivation mechanisms.

Metabolic inactivation of chemicals may prevent toxic effects of reactive intermediates when present at low levels whereas inactivation may be overcome at high levels changing dose-effect relation. This is demonstrated in various in vitro test systems: a) Monooxygenase-mediated metabolism causes formation of reactive oxygen species which induce DNA repair in lymphoblastoid cells. DNA damage is suppressed in the presence of glutathione (GSH), catalase or superoxide dismutase. b) Chloroprene is mutagenic in Salmonella typhimurium but not carcinogenic, possibly due to inactivation by GSH-conjugations. c) Chlorodinitrobenzene is not mutagenic is Salmonella typhimurium in the presence of GSH. However it is increasingly mutagenic at concentrations exceeding those of the GSH. d) Suppression of glucuronidation and sulfation in isolated hepatocytes highly increases irreversible binding of naphthalene. It is concluded that information on the metabolism of chemicals is essential for interpretation of toxicity studies in animals and their relevance to man.

Animals↗
PubMed1980

Involvement of phenolic metabolites in the irreversible protein-binding of 14C-bromobenzene catalysed by rat liver microsomes.

During microsomal metabolism of 14C-bromobenzene, radioactive material was irreversibly bound to microsomal protein. Although primary monooxygenation of aromatic hydrocarbons leads to the formation of reactive epoxides which may bind to protein, our results indicate that reactive intermediates formed via oxidation of the phenolic metabolites substantially contribute to the overall binding. This conclusion is supported by the following observations: 1) The binding of radioactivity continued to increase even though the primary metabolism was terminated; 2) Addition of UDP-glucuronic acid largely reduced the amount of the free phenols in the incubation mixture and simultaneously decreased the binding; and 3) Inhibition of the epoxide hydratase by 1,1,1-trichloro-2-propene oxide (TCPO) completely prevented the formation of the dihydrodiols, but did not significantly affect the binding. Thus, the results are in agreement with our previous observations on the binding of 14C-naphthalene and 14C-dichlorobiphenyl, and suggest that phenols generated from these aromatic hydrocarbons are further metabolized to protein-binding species.

Animals↗
PubMed1980

Effect of decreased glucuronidation and sulfation on covalent binding of naphthalene in isolated rat hepatocytes.

Isolated hepatocytes metabolize naphthalene to water soluble compounds. During metabolism, reactive intermediates are formed which bind irreversibly to cellular macromolecules. When naphthalene concentrations in the incubation were raised from 400 to 1200 microM the formation of water soluble metabolites of the aromatic hydrocarbon increased about twice from 16 to 37 nmol/mg cellular protein X h, whereas covalent binding increased up to 10 times. This suggests a qualitative shift in the metabolic pattern of naphthalene probably due to the exhaustion of inactivating pathways. Inhibition of glucuronidation and sulfation -- 2 reactions involved in the metabolism of naphthalene -- did not change the amount of water soluble metabolites but dramatically increased binding.

Animals↗
PubMed1978

Activation of [14C] chlorobiphenyls to protein-binding metabolites by rat liver microsomes.

The irreversible binding of [14C] 2,2'-di- and [14C] 2,4,5,2',4',5'-hexachlorobiphenyl ([14C] DCB and [14C] HCB) to protein was studied in the presence of rat liver microsomes and a NADPH-generating system. Protein-bound radioactivity was found with [14C] DCB but not with [14C] HCB. The binding of 14C-metabolites was increased by pretreatment of the rats with phenobarbital or polychlorinated biphenyls. Protein binding was linear for 80 min. In contrast, monohydroxy-metabolites of DCB were formed and degraded within 40 min. Inhibition of secondary oxidation of DCB by scavenging superoxide anions or by glucuronidation of the monophenols markedly decreased the protein binding. Addition of trichloropropene oxide or styrene oxide, both inhibitors of epoxide hydrase, did not significantly stimulate the binding. The results suggest that the majority of reactive metabolites of DCB arise from secondary metabolism, i.e., the subsequent oxidation of the phenolic metabolites. Arene oxides, the primary products, appear to play a minor role in the protein binding of DCB.

Albumins↗