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Biomedical subjects

S K Sim

Publications and source records attributed to S K Sim.

11 recordsLinked to original sources
PubMed1978

Hydroxyl radical production by free and DNA-bound aminoquinone antibiotics and its role in DNA degradation. Electron spin resonance detection of hydroxyl radicals by spin trapping.

The reduced antitumor antibiotic mitomycin C in aqueous solution exposed to air gives a 36-line electron spin resonance spectrum of the semiquinone identified by computer simulation. Incubation of this radical with the spin trap N-tert-butyl-alpha-phenylnitrone (PBN) gives the PBN.OH nitroxide radical identified by independent generation. This nitroxide radical is also formed from similar treatment of a DNA to which mitomycin C is covalently attached. Incubation of the semiquinone from mitomycin C, mitomycin B, or streptonigrin (SN) with catalase or with superoxide dismutase inhibits the generation of OH, implying the intermediacy of H2O2 and O2 in its formation. The formation of the spin-trapped nitroxide radical is similarly inhibited by EDTA, suggesting the intermediacy of trace metal ions in the generation of hydroxyl radicals from SN. The results are consistent with the generation by the aminoquinone antibiotics in vivo of OH. already implicated in the degradation of DNA.

Catalase↗
PubMed1976

Studies related to antitumor antibiotics. Part VIII. Cleavage of DNA by streptonigrin analogues and the relationship to antineoplastic activity.

A group of substituted 5,8-quinolinequinones which exhibit antineoplastic activity and which are structurally related to the antitumor antibiotic streptonigrin induce single strand cleavage of PM2 covalently-closed circular-DNA (ccc-DNA) when reductively activated. The cleavage which is detected by an ethidium fluorescence assay is specifically enhanced by cuprous and ferrous ion and is selectively inhibited by superoxide dismutase (EC 1.15.1.1) and catalase (EC 1.11.1.6) and by free radical scavengers. Independent generation of the superoxide ion by xanthine-xanthine oxidase (EC 1.2.3.2) also cleaves PM2 DNA and therefore a chemical mechanism for the scission process induced by the streptonigrin analogues is formulated. A correlation between rate of PM2 ccc-DNA cleavage and inhibition of Walker carcinosarcoma 256 is observed.

Animals↗
PubMed1976

Digoxin tablets--a review of the bioavailability problems.

A review is presented of the more significant aspects of recent bioavailability studies on digoxin tablets that have led to the identification of variations among commercially available tablets and of the correlation of the methods commonly used in such bioavailability evaluations. Pharmacopeial requirements for tablet-to-tablet uniformity of content do not automatically yield uniformity of bioavailability. In vitro dissolution rate of digoxin tablets generally has been shown to correlate with in vivo bioavailability, and this has led to new governmental and pharmacopeial requirements for digoxin tablets. However, some recent reports have shown that in vitro dissolution rate may not always correlate well with bioavailability. The relevance and significance of digoxin tablet bioavailability to clinical effects and therapeutics are briefly discussed.

Biological Availability↗
PubMed1975

Chemotherapy of infections in cancer patients: a review.

The factors altering host-defense mechanisms and the nature and significance of the resultant infections in cancer patients by a wide variety of invasive organisms are described. The principle and method of selection of antimicrobial agents as therapy in initial empiric treatment of presumed infection in febrile cancer patients, as well as therapeutic agents fothe therapy of infections by specfic organisms, are discussed. Special emphasis is placed on the more recently developed agents for the therapy of infections by Pseudomonas and other gram-negative bacilli.

Actinomycetales Infections↗
PubMed1973

Methadone.

Methadone and acetylmethadol, although possessing almost all of morphine's pharmacological properties, differ from other morphine-like drugs in their longer action, more gradual and less intense withdrawal syndrome, and blockade of euphoric effect of other opiates in addicts. A high percentage of patients maintained on methadone are better able to hold employment or to be otherwise socially productive than when dependent on heroin or morphine.A review of published results and procedures used in methadone maintenance treatment programs for heroin dependence is presented. Former heroin addicts are usually maintained on 80 to 120 mg. (high dose) or 20 to 60 mg. (low dose) oral methadone daily. Some programs are reported to have produced 80% success (patients employed or otherwise socially productive). Selection of patients, availability of allied therapeutic and rehabilitative facilities, strict control of supply, record keeping and periodic evaluation are considered essential.Different criteria ("drug-free" vs. "socially productive") for judging "success" of treatment of heroin-dependent persons by methadone maintenance and administrative problems in large-scale treatment programs constitute the principal aspects of controversy.

Acetates↗