Is it time to dismiss calls to ban DDT.
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DDT↗
Biomedical subjects
F M Steinberg
Publications and source records attributed to F M Steinberg.
Acute gastroenteritis in children.
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Acute Disease↗
Influence of oligomer chain length on the antioxidant activity of procyanidins.
The antioxidant activity of catechin monomers and procyanidin (dimers to hexamers) fractions purified from cocoa was studied in two in vitro systems: liposomes and human LDL. Liposome oxidation (evaluated as formation of 2-thiobarbituric acid reactive substances) was initiated with 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH), 2,2'-azobis (2,4-dimethylvaleronitrile) (AMVN), iron/ascorbate, or UV-C; LDL oxidation (evaluated as formation of conjugated dienes) was initiated with Cu(2+) or AAPH. Catechin monomers and procyanidin fractions inhibited both liposome and LDL oxidation. Monomers, dimers, and trimers fractions were the most effective antioxidants when liposome oxidation was initiated in the aqueous phase. When oxidation was initiated in the lipid domains, higher molecular weight procyanidins were the most effective. All fractions significantly inhibited Cu-mediated LDL oxidation; no significant effect of procyanidin molecular weight was observed. The hexamer fraction was the least effective with respect to preventing AAPH initiated LDL oxidation. Results reported herein give further evidence on the influence of the oligomer chain length on the antioxidant protection by procyanidins.
Amidines↗
Antioxidant vitamin supplementation and lipid peroxidation in smokers.
Previous studies have shown that cigarette smoke enhances lipid peroxidation. This study examined the effect of daily consumption of a tomato-based juice supplemented with vitamin C (600 mg), vitamin E (400 IU, or 400 mg), and beta-carotene (30 mg) on various indexes of lipid peroxidation (breath pentane excretion and susceptibility of LDL to copper-mediated oxidation) in smokers. In addition, plasma lycopene and vitamin concentrations and total peroxyl radical trapping potential, a measure of antioxidant defenses, were assessed. Relative to the placebo juice, the vitamin-supplemented juice resulted in a significant decrease in breath-pentane excretion as well as a significant improvement in the resistance of LDL to oxidation. The lag phase of conjugated diene formation lengthened and the propagation rate decreased, indicating a decreased susceptibility of LDL to oxidative modification. Increased concentrations of plasma vitamin C, beta-carotene, and lycopene were found to be significantly correlated with the conjugated diene lag phase and rate of formation. Vitamin E was highly correlated with beta-carotene. Plasma total peroxyl radical trapping potential values did not change in response to supplementation. This study thus indicates that an antioxidant-supplemented drink can reduce lipid peroxidation and susceptibility of LDL to oxidation in smokers and may ameliorate the oxidative stress of cigarette smoke.
Adult↗
Mechanisms of enhanced macrophage apoE secretion by oxidized LDL.
Previous studies have demonstrated that atherosclerotic lesions contain apoE synthesized primarily by macrophages. As oxidized LDL has been implicated in the development of atherosclerosis, its effect on macrophage apoE synthesis and secretion was examined. Human monocytic leukemia cells, THP-1, and human monocyte-derived macrophages were exposed to various forms of oxidatively modified LDL for determination of their effect on apoE mRNA and protein levels. Extensively copper oxidized (Cu-oxidized) LDL resulted in a time- and concentration-dependent increase in apoE mRNA and protein as compared to other forms of oxidized LDL, i.e., LDL modified by soybean lipoxygenase (SLO), azoamidinopropane HCl (AAPH), and hypochlorite (HOCl). Consistent with these results, experiments using THP-1 cells transfected with the apoE promoter linked to a luciferase reporter gene indicated that Cu-oxidized LDL was the most potent stimulator of apoE transgene expression. Enhanced apoE expression due to Cu-oxidized LDL was shown to be due to cholesterol accumulation as well as additional factors. HPLC analysis of the various forms of modified LDL revealed that 7-ketocholesterol was the major oxysterol present in Cu-oxidized LDL. AAPH-oxidized LDL contained significantly less 7-ketocholesterol than Cu-oxidized LDL and virtually no 7-ketocholesterol was detected in SLO- or HOCl-oxidized LDL. Northern blot analysis indicated an increase in apoE mRNA in response to increasing concentrations of 7-ketocholesterol. These results elucidate a potential role of oxidized LDL, and specifically 7-ketocholesterol, in the stimulation of macrophage apoE secretion in atherosclerotic lesions.
Apolipoproteins E↗
Market reforms for the health care system.
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Economic Competition↗
Modulation of lysyl oxidase by dietary copper in rats.
Lysyl oxidase levels were estimated in rat tissues using an enzyme-linked immunosorption assay (ELISA) and a functional assay standardized against known amounts of purified lysyl oxidase. High concentrations of lysyl oxidase (> or = 150 micrograms/g of tissue or packed cells) were detected in connective tissues, such as tendon and skin. Values for aorta, kidney, lung and liver ranged from 30 to 150 micrograms/g of tissue; values for skeletal muscle and diaphragm were < 30 micrograms/g tissue. Purified rat skin lysyl oxidase catalyzed the release of 50-100 Bq of tritium per micrograms enzyme in assays that used 3H-elastin-rich substrates. In dense connective tissues, good agreement was obtained for the values from ELISA and those derived from measurements of functional activity in aorta, lung, skin and tendon (r2 > 0.9). When egg white-based experimental diets containing 2 or 10 micrograms/g added copper were fed to weanling rats, values for skin lysyl oxidase functional activity in the group fed 2 micrograms/g added copper were one-third to one-half the values for skin lysyl oxidase functional activity in rats fed 10 micrograms/g copper. This reduction in lysyl oxidase activity, however, had minimal effect on indices of collagen maturation in rat skin, e.g., collagen solubility in neutral salt and dilute acid or the levels of acid stable cross-links. Moreover, copper deficiency did not influence the steady-state levels of lysyl oxidase specific mRNA in rat skin or the apparent amounts of lysyl oxidase in rat skin as determined by ELISA. These observations underscore that the concentration of lysyl oxidase is relatively high in dense corrective tissues, and although decreasing dietary copper influences functional activity, there is little apparent effect on the production of lysyl oxidase protein.
Administration, Oral↗
ApoE enhances lipid uptake by macrophages in lipoprotein lipase deficiency during pregnancy.
A woman with primary lipoprotein lipase (LPL) deficiency developed marked hypertriglyceridemia, pancreatitis, eruptive xanthomas, and unusual palmar xanthomas during pregnancy. Hypotheses to account for the palmar xanthomas were that oxidative modification of triglyceride (TG)-rich lipoproteins occurred due to increased plasma residence time, or that their apolipoprotein E (apoE) content was abnormally elevated. Indices of oxidation of her TG-rich lipoproteins did not support the hypothesis that oxidative changes were a causative factor for her xanthomata. However, degradation of her TG-rich lipoproteins by macrophages was markedly increased (1844 ng/mg protein) during pregnancy as compared to hypertriglyceridemic (with normal LPL) and normotriglyceridemic controls (352 and 126 ng/mg protein, respectively). Post pregnancy the degradation of the subject's TG-rich lipoproteins fell to 289 ng/mg protein. Compositional analysis showed significant enrichment of the particles with apoE (0.97 mass ratio of apoE:apoB during pregnancy, in contrast to 0.38 for normolipidemic controls), and was correlated with the rate of degradation of the TG-rich lipoproteins. Thus, the increased uptake of the TG-rich lipoproteins by macrophages appears to be the result of an unusual enrichment of these lipoproteins with apoE.
Adult↗
Dietary pyrroloquinoline quinone: growth and immune response in BALB/c mice.
Pyrroloquinoline quinone (PQQ) is proposed as a nutritionally important growth factor, and we provide evidence that PQQ improves reproduction performance in BALB/c mice and stimulates neonatal growth. In the first experiment, weanling female BALB/c mice were adapted to a chemically-defined diet containing 0, 100, 200, 300, 1000, or 5000 ng PQQ/g of diet. The mice were bred and their reproductive performance and surviving offspring were assessed for 20-wk. Reproductive outcome was markedly compromised for the groups most deprived of PQQ. Supplemented groups (> or = 1000 ng PQQ/g diet) had 8 pups/litter compared with 4-5 pups/litter in the PQQ-deprived groups (< or = 300 ng PQQ/g diet). Of the pups surviving to weaning, 8 of 10 survived when PQQ was added to the diet (> or = 300 ng PQQ/g diet) compared with 4 of 10 in the PQQ/deficient group. The apparent requirement for PQQ for optimal growth of surviving neonates was estimated to be > or = 300 ng PQQ/g of diet. Moreover, splenic cell response to the mitogens concanavalin A and lipopolysaccharide, appeared related to PQQ intake. In a second experiment, female BALB/c mice were fed diets containing PQQ added at 0 or 1000 ng/g of diet, and interleukin 1 and 2 production were assessed. In particular, levels of interleukin 2, an autocrine and paracrine growth factor, were reduced in mice fed the deficient diet at a time when T-cell proliferation occurs in neonates. Results suggest that PQQ or similar compounds may play nutritionally important roles at critical stages in development.
Animals↗
Physiologic importance of pyrroloquinoline quinone.
Pyrroloquinoline quinone (PQQ, methoxatin) is a dissociable cofactor for a number of bacterial dehydrogenases. The compound is unusual because of its ability to catalyze redox cycling reactions at a high rate of efficiency and it has the potential of catalyzing various carbonyl amine reactions as well. In methylotrophic bacteria, PQQ is derived from the condensation of L-tyrosine with L-glutamic acid. Whether or not PQQ serves as a cofactor in higher plants and animals remains controversial. Nevertheless, a strong case may be made that PQQ and related quinoids have nutritional and pharmacologic importance. In highly purified, chemically defined diets, PQQ stimulates animal growth. Furthermore, PQQ deprivation appears to impair connective tissue maturation, particularly when initiated in utero and throughout perinatal development.
Bacteria↗
Biotech pharmaceuticals and biotherapy: an overview.
Broadly, the history of pharmaceutical biotechnology includes Alexander Fleming"s discovery of penicillin in a common mold, in 1928, and the subsequent development-prompted by World War II injuries-of large-scale manufacturing methods to grow the organism in tanks of broth. Pharmaceutical biotechnology has since changed enormously. Two breakthroughs of the late 1970s became the basis of the modern biotech industry: the interspecies transplantation of genetic material, and the fusion of tumor cells and certain leukocytes. The cells resulting from such fusion-hybridomas-replicate endlessly and can be geared to produce specific antibodies in bulk. Modern pharmaceutical biotechnology encompasses gene cloning and recombinant DNA technology. Gene cloning comprises isolating a DNA-molecule segment that corresponds to a single gene and synthesizing ("copying") the segment. Recombinant DNA technology, or gene splicing, comprises altering genetic material outside an organism-for example, by inserting into a DNA molecule a segment from a very different DNA molecule-and making the altered material (recombinant DNA) function in living things. Recombinant DNA technology enables modifying microorganisms, animals, and plants so that they yield medically useful substances, particularly scarce human proteins (by giving animals human genes, for example). This review, however, focuses not on pharmaceutical biotechnology"s methods but on its products, notably recombinant pharmaceuticals. It describes various types of biotech pharmaceuticals, their safety and effectiveness relative to the safety and effectiveness of conventionally produced pharmaceuticals, and the regulation of biotech pharmaceuticals.
Animals↗