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Biomedical subjects

L J Machlin

Publications and source records attributed to L J Machlin.

At least 37 records · Page 2Linked to original sources
PubMed1980

A decrease in irreversibly sickled erythrocytes in sicle cell anemia patients given vitamin E.

Patients with sickle cell anemia were given 450 IU of vitamin E (as alpha-tocopherol) per day for 6 to 35 weeks. Plasma tocopherol levels increased from 0.7 +/- 0.2 mg/g lipid pretreatment, to 2.3 +/- 0.3 mg/g lipid. The percentage of circulating irreversibly sickled red cells decreased from 25 +/- 3% pretreatment to 11 +/- 1% after vitamin E administration (P less than 0.001). The percentage of irreversibly sickled red cells remained below pretreatment levels as long as the vitamin was administered (up to 35 weeks). The biochemical and clinical implications of these observations are discussed.

Anemia, Sickle Cell↗
PubMed1980

Effects of aspirin and related drugs in vitamin E-deficient rats.

Evidence from the literature indicates that in vitamin E-deficient animals prostaglandin (PG) synthesis in platelets is enhanced while it is decreased in the muscle and testis. In the present study the effects of aspirin, a known inhibitor of PG biosynthesis, on vitamin E deficiency signs in the rat were investigated. Administration of aspirin to vitamin E-deficient rats had no protective effect on fetal mortality, incisor depigmentation, body weight gain or red blood cell peroxidative hemolysis. Aspirin prevented the anemia and thrombocythemia observed in vitamin E-deficient rats. Aspirin, salicylic acid and a carbazole prostaglandin inhibitor exacerbated testis degeneration in vitamin E-deficient animals. Addition of aspirin to the diet more than doubled the vitamin E requirement for reversal of necrotizing myopathy.

Animals↗
PubMed1980

Influence of age on the vitamin E requirement for resolution of necrotizing myopathy.

Weanling rats were fed either a vitamin E-deficient diet or the deficient diet supplemented with vitamin E or the antioxidant ethoxyquin. Ethoxyquin was not effective in preventing the elevation in platelet number or percent aggregation. However, ethoxyquin was as effective as vitamin E in maintaining body weight, testes weight, pigmentation of the incisors and in preventing myopathy, observed either histologically or by an elevation in plasma glutamic oxalacetic transaminase (GOT) activity. Removal of ethoxyquin from the diet after 19 weeks of feeding resulted in a rapid onset of myopathy. These observations permitted us to study the requirement for vitamin E at various ages without the complication of any cumulative pathological effects of vitamin E deficiency. Ethoxyquin was deleted from the diet at 8, 20, 44 and 64 weeks of age. The requirement for vitamin E to reduce plasma GOT and pyruvate kinase (PK) activity was measured at 12, 24, 48 and 68 weeks of age. The requirement for vitamin E did not change significantly during this time period.

Aging↗
PubMed1980

Relationship between binding affinities to cellular retinoic acid-binding protein and in vivo and in vitro properties for 18 retinoids.

A new rapid assay has been developed for measurement of the binding of [3H]retinoic acid to cellular retinoic acid-binding protein. The assay, which uses activated charcoal for the separation of bound from unbound retinoic acid, was used to determine the concentration required to inhibit the binding of [3H]retinoic acid to cellular retinoic acid-binding protein by 50% for 18 retinoids with free carboxylic acid groups. Partially purified cellular retinoic acid-binding proteins isolated from rat testes and carcinogen-induced rat mammary tumors were used for these determinations. The following parameters were also determined for some or all of the retinoids: hypervitaminosis A doses; activity against carcinogen-induced mouse skin papillomas; inhibition of growth of a rat chondrosarcoma; inhibition of growth of 3T6 cells; and differentiation of the embryonal carcinoma cell line PCC4.azaIR. While all retinoids that are potent in these biological test systems bind tightly to cellular retinoic acid-binding protein, the converse is not true. The lack of a consistent quantitative correlation between 50% inhibitory concentration and biological activity is probably due to insufficient concentrations of the retinoid in the target tissue or celll, which is a consequence of factors such as absorbability, metabolism, tissue distribution, and pharmacokinetics.

Animals↗
PubMed1979

Fluorinated retinoic acids and their analogues. 1. Synthesis and Biological activity of (4-methoxy-2,3,6-trimethylphenyl)nonatetraenoic acid analogues.

(4-Methoyx-2,3,6-trimethylphenyl)nonatetraenoic acids, esters, and amides (analogues of retinoic acid) bearing a fluorine atom(s) or a trifluoromethyl group on the polyene side chain were synthesized. The biological activities of these compounds and of 10-, 12-, and 14-fluororetinoic acid esters were evaluated in vivo in a chemically induced mouse papilloma test; the toxicities were assessed in an in vivo mouse hypervitaminosis A test. Antipapilloma activity greater than the parent nonfluorinated ester was found for 1c (ethyl 12-fluororetinoate) and 23 and 39 (aromatic 4- and 6-fluororetinoid esters, respectively). A similar increase in antipapilloma activity was observed for 71 and 72, the aromatic 4- and 6-fluororetinoic acids, respectively, relative to 2 and for 73 (aromatic 4-fluororetinoid amide) relative to 4.

Animals↗
PubMed1979

Antiscorbutic activity of ascorbic acid phosphate in the rhesus monkey and the guinea pig.

Rhesus monkeys fed an ascorbic acid-free, purified liquid diet, developed scurvy in 70 to 105 days as evidenced by loss of weight, anemia, bleeding gums, inflamed palate, diarrhea, and inability to stand. Oral administration of either 10 mg/kg body weight of ascorbic acid or an equimolar amount of the magnesium salt of 1-ascorbic acid phosphate cured all symptoms of scurvy. Similarly, oral administration of 1-ascorbic acid phosphate cured all symptoms of scurvy in the guinea pig and resulted in liver ascorbate levels equal to those of animals feed ascorbic acid. It is concluded that ascorbic acid phosphate is a readily available source of ascorbic acid activity in vivo.

Animals↗
PubMed1979

Determination of xylitol in human urine by gas-liquid chromatography.

A rapid and specific method for the quantitative determination of xylitol in human urine has been developed. The method consists of the gas-liquid chromatographic analysis of the acetate ester derivative of the alditol in deionized urine using dulcitol as an internal standard. As little as 20 ng xylitol can be detected. At concentrations ranging from 25 to 400 micrograms/ml urine, the accuracy is +/- 4.0%.

Chromatography, Gas↗
PubMed1979

Availability of adipose tissue tocopherol in the guinea pig.

Young guinea pigs were fed a purified diet containing vitamin E for 3 weeks and then fed the diet without vitamin E for 8 weeks. Levels of vitamin E in plasma and liver decreased to low values within a week. Depletion rates for heart and muscle were much slower, whereas the rate of loss from fat was negligible. In experiments with more mature guinea pigs and a depletion period of 4 months, the depletion rate of tocopherol from fat was also barely detectable. Both yound and mature guinea pigs developed myopathy after 8 weeks of depletion. Apparently, tocopherol in adipose tissue is not sufficiently available to maintain plasma tocopherol levels or to prevent signs of vitamin E deficiency. Even during fasting, adipose tissue tocopherol was not mobilized readily. During a 4 day fast, adipose tissue mass diminished considerably, but there was no appreciable loss of tocopherol.

Adipose Tissue↗
PubMed1978

Plasma activity of pyruvate kinase and glutamic oxalacetic transaminase as indices of myopathy in the vitamin E deficient rat.

Weanling rats were fed vitamin E deficient diets for 6 to 15 weeks and then given vitamin E orally for 4 days. Plasma obtained 1 day after the last dose was assayed for glutamic oxalacetic transaminase (GOT) and pyruvate kinase activity (PK). Administration of vitamin E resulted in reduction in activity of both enzymes. Plasma levels of alkaline phosphatase, lactic dehydrogenase, and bilirubin were unaffected by vitamin E and there was no histological evidence of liver degeneration. The number of phagocytized muscle fibers was greatly reduced by vitamin E treatment, but a substantial number of necrotic fibers were still present. With more prolonged (8 days) treatment, plasma PK and GOT levels were reduced to levels found in plasma of vitamin E replete animals and few degenerated muscle fibers could be observed. It was concluded that resolution of the necrotizing myopathy in vitamin E deficient rats is a rapid process and that the decreased activity of PK and GOT in plasma is a sensitive indicator of the resolution process. The decrease in plasma enzyme levels is an easily quantitated and reproducible biological response to vitamin E administration. Thus, this approach provides a basis for a sensitive and accurate bioassay for vitamin E activity.

Animals↗
PubMed1977

Effects of a prolonged vitamin E deficiency in the rat.

Rats fed a vitamin E-deficient diet containing 10% "stripped" corn oil had reduced growth rate and elevated platelet count by 12 weeks of age, and a normocytic anemia with elevated reticulocytes by 16 weeks of age. After 5 months, rats became emaciated and developed kyphoscoliosis. Some rats developed skin ulcers and tremors, and mortality was high. Neuromuscular lesions included a chronic necrotizing myopathy and localized axonal dystrophy. There was also a selective activation of lysosomes in the central nervous system microcirculation. Liver ascorbic acid of deficient rats was the same as in those receiving vitamin E. Urinary excretion of p-hydroxyphenylpyruvate after a tyrosine load was also the same in deficient and control rats. It was concluded that neither vitamin C synthesis or utilization was affected the E-deficient rats.

Age Factors↗
PubMed1976

Lack of antiscorbutic activity of ascorbate 2-sulfate in the rhesus monkey.

Oral administration of 10 mg per kilogram of body weight of ascorbic acid (AA) completely prevented development of scurvy in juvenile rhesus monkey (Mucaca mulata) fed an AA-free liquid diet. The same dose cured scurvy when injected intramuscularly. An equimolar dose of ascorbic acid 2-sulfate (AA-2-S) did not prevent or cure scurvy. Neither AA nor AA-2-S altered serum cholesterol. AA but not AA-2-S reduced serum triglyceride. A case of scurvy in an AA-2-S treated monkey is described in detail.

Alkaline Phosphatase↗
PubMed1976

Role of growth hormone in improving animal production.

Pituitary growth hormone (GH) has considerable potential as an anabolic agent in animal production. For example, pigs treated with GH will grow faster (i.e. deposit protein), require less feed per unit of body weight gain, and will have less carcass fat than untreated animals. Lactating cows will produce more milk with less feed. It is likely, though not completely established, that young cattle will also respond to GH treatments. Most of the information on the mode of action of GH has been obtained with laboratory rather than farm animals. The hormone affects almost all aspects of metabolism although the specific mechanism for these effects is still not understood. Stimulation of protein accretion is reflected by increased nitrogen retention and incorporation of radioactive amino-acids into tissue proteins. An increased rate of protein synthesis is thought to be a result of enhanced ability of ribosomes to translate messenger RNA. GH increases polyamine synthesis by increased ornithine decarboxylase activity; RNA synthesis by increasing RNA polymerase and DNA synthesis by increased DNA polymerase. Cell division is stimulated in several tissues (e.g. muscle and lymphoid tissue). In vivo GH lowers the respiratory quotient indicating an increased oxidation of fatty acids. The numbers of fat cells do not change but the fat cells are reduced in size. The stimulating effects of GH on skeletal tissue, and perhaps other tissues as well, is mediated by the formation of at least three peptides called somatomedins. GH is a protein with a molecular weight of about 22,000 and contains 191 amino-acid residues. The amino-acid sequence varies with the species. GH isolated from one species is not always effective in a different species. Use of GH isolated from pituitaries does not appear to be economically feasible. A chemical synthesis for human GH has been accomplished. However, biological activity equivalent to the native hormone has not been unequivocally established. Synthesis of bovine or porcine GH is feasible but will be expensive. A partial sequence of GH with 39 amino-acid residues has some biological activity. Synthesis of this shorter peptide would be considerably less expensive. Since proteins generally are not active orally, an economic procedure for prolonged parenteral administration would have to be devised. Althernative approaches would be the stimulation of endogeneous production of GH with hypothalmic GH releasing factor. This factor has not been identified but is probably a small peptide. Agents such as arginine, DOPA, and prostaglandins, which are known to stimulate GH release under some conditions, could also be considered. Another approach would be the implantation of sparganum from the spirometra family (a flatworm). This treatment is known to mimic GH effects in the rat. Implantation of a GH producing tumour could also be considered. Clearly these latter suggestions are quite speculative and would present some obvious problems...

Animals↗
PubMed1975

Influence of dietary vitamin E on prostaglandin biosynthesis in rat blood.

A vitamin E (alpha-tocopherol) deficient diet stimulated prostaglandin biosynthesis in coagulating rat blood. Prostaglandins were extracted from serum, purified and bioassayed. The identity of prostaglandin E2 was confirmed by gas chromatography-mass spectrometry. Withholding vitamin E from the diet caused a marked increase in PGE2 and a lesser increase in PGF2alpha production in serum. In rats maintained on diets containing different concentrations of vitamin E, serum concentrations of PGE2 and PGF2alpha were inversely related to serum concentrations of alpha-tocopherol. These data suggest that in vitro alpha-tocopherol inhibits the endogenous conversion of arachidonic acid into PGE2 and PGF2alpha. The possibility that alpha-tocopherol may inhibit the formation of endoperoxide intermediates of PGE2 and PGF2alpha biosynthesis and subsequent induction of platelet aggregation is discussed.

Animals↗
PubMed1975

Influence of vitamin E on platelet aggregation and thrombocythemia in the rat.

Collagen-induced platelet aggregation was increased in 9-10 wk old vitamin E deficient rats although there was no difference in platelet count between deficient and control animals. With a more prolonged deficiency (at 15 wk) both platelet aggregation and platelet counts were elevated in the vitamin E deficient animals.

Age Factors↗