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Biomedical subjects

K E Anderson

Publications and source records attributed to K E Anderson.

At least 163 records · Page 9Linked to original sources
PubMed1987

Diet-hormone interactions: protein/carbohydrate ratio alters reciprocally the plasma levels of testosterone and cortisol and their respective binding globulins in man.

The aim of this study was to determine if a change in protein/carbohydrate ratio influences plasma steroid hormone concentrations. There is little information about the effects of specific dietary components on steroid hormone metabolism in humans. Testosterone concentrations in seven normal men were consistently higher after ten days on a high carbohydrate diet (468 +/- 34 ng/dl, mean +/- S.E.) than during a high protein diet (371 +/- 23 ng/dl, p less than 0.05) and were accompanied by parallel changes in sex hormone binding globulin (32.5 +/- 2.8 nmol/l vs. 23.4 +/- 1.6 nmol/l respectively, p less than 0.01). By contrast, cortisol concentrations were consistently lower during the high carbohydrate diet than during the high protein diet (7.74 +/- 0.71 micrograms/dl vs. 10.6 +/- 0.4 micrograms/dl respectively, p less than 0.05), and there were parallel changes in corticosteroid binding globulin concentrations (635 +/- 60 nmol/l vs. 754 +/- 31 nmol/l respectively, p less than 0.05). The diets were equal in total calories and fat. These consistent and reciprocal changes suggest that the ratio of protein to carbohydrate in the human diet is an important regulatory factor for steroid hormone plasma levels and for liver-derived hormone binding proteins.

Adult↗
PubMed1987

Porphyria cutanea tarda associated with the acquired immune deficiency syndrome.

Three male subjects with cutaneous symptoms and biochemical signs typical of porphyria cutanea tarda (PCT) developed acquired immune deficiency syndrome (AIDS). All three were in a classic high risk group for the latter disease and developed a typical progressive illness. Two patients succumbed to opportunistic infections; the third is alive but critically ill. The symptomatic prodrome of AIDS developed concurrently with or followed the onset of symptoms of PCT in all three individuals. PCT and AIDS are both uncommon disorders; their association in three patients is thus of inherent clinical interest. If this association is not coincidental, it raises the possibility that the occurrence of photosensitivity, skin lesions, and evidence of biochemical changes characteristic of PCT may, in certain patients at risk for AIDS, presage the subsequent full clinical expression of the latter disease.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Disposition of tin-protoporphyrin and suppression of hyperbilirubinemia in humans.

Tin (Sn4+)-protoporphyrin, a potent competitive inhibitor of heme degradation to bile pigment, was cleared rapidly from plasma in normal subjects (t1/2 approximately 4 hours for plasma levels greater than 5 nmol/ml, with evidence of dose-dependent pharmacokinetics at lower plasma concentrations). Small amounts were excreted promptly in urine (0.1% to 5.6%) and more gradually in feces (3.7% to 11.3%). The only dose-limiting (greater than 1.0 mumol/kg, single dose) side effect was mild sensitivity to sunlight and long-wave ultraviolet light. Absorption after intramuscular administration was rapid, but there was no absorption after oral dosing. In bile duct-ligated rats treated with Sn-protoporphyrin, there was a substantial (approximately 50%) reduction in plasma bilirubin levels compared with levels in ligated control animals. Seven studies were carried out in four women with moderate to severe cholestasis secondary to primary biliary cirrhosis and in two men with Gilbert's syndrome. In these studies Sn-protoporphyrin (total doses of 0.25 to 2.0 mumol/kg body weight) reduced plasma bilirubin levels to a varying degree (7% to 43%) promptly after its intravenous administration.

Absorption↗
PubMed1986

Effects of type of cage partition, cage shape, and bird density on productivity and well-being of layers.

In Experiment 1 there were no significant differences in rate of lay, egg quality, latency to feeding, and feather condition of hens in cages with wire mesh or solid metal side partitions. Birds in cages with solid metal side partitions had significantly higher mortality (6%) and weight gain (6%) than those in cages with wire side partitions. The deep caged hens had significantly lower mortality (8%) than the shallow caged hens. Hens housed at 464 cm2 of floor area/hen had significantly higher hen-housed egg production (4.9%), lower weight gain (8%), and higher average feather scores (.8 unit) than those housed at 348 cm2. In Experiment 2 type of cage side and back partitions (wire vs. solid metal) significantly affected grams of egg per gram of feed. Birds in deep cages had significantly lower mortality (8.6%) and higher feed consumption (15.2 g/hen/day) than those in shallow cages. Hen-housed rate of lay, mortality, weight gain, feed conversion, and feather scores were significantly affected by bird density: 64.6%, 15%, 24.6%, .384% g egg/g feed, and 4.7 units, respectively, for hens with 464 cm2 floor area vs. 70.8%, 8.3%, 25.2%, .362% g egg/g feed, and 5.8 units for hens with 348 cm2. Data suggest that hens in cages with solid metal sides performed similarly to their sisters in cages with wire mesh sides and backs.

Animals↗
PubMed1985

Role of fatty acid structure in the reversible activation of phosphatidylcholine synthesis in lymphocytes.

Fatty acids rapidly accelerate (1.5-7.0-fold) the incorporation of [methyl-3H]choline chloride into the phosphatidylcholine fraction of bovine lymphocyte lipids. This ability of fatty acids to activate choline phospholipid synthesis has been correlated with certain structural features of fatty acids. Mono- and polyenoic unsaturated fatty acids of 18 and 20 carbons in length are highly active, whereas their saturated analogues are nearly inactive. Among the unsaturated fatty acids, the cis-isomers are active, while the trans-isomers are relatively ineffective. The delayed addition of bovine serum albumin (5 mg/ml) and other lipid-binding proteins to activated cells rapidly counteracts the lipid effects. The activated state of the cell membrane thus appears to be a dynamic one, requiring the continued interaction of the fatty acid with a lipid-sensitive target molecule of the cell surface that in turn appears to coordinate the enzymatic components of this pathway.

Animals↗
PubMed1985

Analysis of the effects of fatty acids and related compounds on the synthesis of phosphatidylcholine in lymphocytes.

Phosphatidylcholine synthesis in cultured bovine lymphocytes is stimulated by cis-unsaturated fatty acids. This stimulation is correlated with an activation of the enzyme cytidyltransferase (EC 2.7.7.15) and its apparent translocation from the cytosol to the membrane/particulate of cells. In addition, these agents increase the levels of cytidine diphosphocholine - a product of the cytidyltransferase reaction and a precursor to phosphatidylcholine. Retinoic acid and 5,8,11,14-eicosatetraynoic acid both activate cytidyltransferase activity and raise cytidine diphosphocholine levels, yet they are ineffective as stimulators of overall phosphatidylcholine synthesis. The effects of all of these lipids are reversed by the delayed addition of bovine serum albumin. The data point to the view that cytidyltransferase activation is required but is not sufficient for stimulation of phosphatidylcholine synthesis: regulation at another step is suggested.

Animals↗
PubMed1985

The liver excretes large amounts of heme into bile when heme oxygenase is inhibited competitively by Sn-protoporphyrin.

TinIV-protoporphyrin IX (Sn-protoporphyrin) potently inhibits heme degradation to bilirubin in vitro and in vivo, and it completely suppresses neonatal hyperbilirubinemia in experimental animals, including primates. It also reduces plasma bilirubin levels in certain naturally occurring or induced forms of jaundice in animals and man. We have examined in this study the fate of that fraction of heme whose degradation to bile pigment is inhibited in vivo by administration of this heme oxygenase (EC 1.14.99.3) inhibitor. In bile-duct-cannulated rats, infused exogenous heme is rapidly converted to biliary bilirubin; a small amount of the infused heme is excreted into bile as well. Sn-protoporphyrin, administered with the exogenous heme, markedly increased (3- to 4-fold) the amount of heme excreted into bile and greatly diminished biliary output of bilirubin. The increase in biliary heme output exceeded the decrease in bilirubin excretion elicited by the inhibitor metalloporphyrin. In the same experimental model, Sn-protoporphyrin substantially decreased the conversion of heme, derived from heat-damaged erythrocytes, to biliary bilirubin. This decrease in biliary bilirubin output was accounted for entirely by a prompt and marked increase in biliary excretion of unmetabolized heme. The enhanced biliary excretion of unmetabolized heme following administration of Sn-protoporphyrin is a newly defined and biologically important response associated with use of this synthetic heme analogue. The features of the action of this compound in vivo--suppression of formation of the potentially neurotoxic metabolite, bilirubin; enhancement of disposal of the untransformed substrate (heme) of the enzyme that it inhibits; and its own elimination without metabolic alteration--define some of the characteristics of a therapeutically useful chemical.

Animals↗
PubMed1985

Studies on the mechanism of Sn-protoporphyrin suppression of hyperbilirubinemia. Inhibition of heme oxidation and bilirubin production.

The synthetic heme analogue Sn-protoporphyrin is a potent competitive inhibitor of heme oxygenase, the rate-limiting enzyme in heme degradation to bile pigment, and can entirely suppress hyperbilirubinemia in neonatal animals and significantly reduce plasma bilirubin levels in a variety of circumstances in experimental animals and man. To further explore the mechanism by which this metalloporphyrin reduces bilirubin levels in vivo, we have examined its effects on bilirubin production in bile duct-cannulated rats, in which bilirubin derived from heme catabolism is known to be rapidly excreted in bile. The administration of Sn-protoporphyrin (10-50 mumol/kg body weight) was followed by prompt (within approximately 1 h) and sustained (up to at least 18 h) decreases in bilirubin output, to levels 25-30 percent below the levels of bilirubin output in control bile fistula animals. The metalloporphyrin had no effect on bile flow or the biliary output of bile acids. Infusions of heme, which is taken up primarily in hepatocytes, or of heat-damaged erythrocytes, which are taken up in reticuloendothelial cells, resulted in marked increases in bilirubin output in bile in control animals; these increases were completely prevented or substantially diminished by Sn-protoporphyrin administration. By contrast, the metalloporphyrin did not alter the high levels of bilirubin in plasma and bile that were achieved in separate experiments by the constant (16 h) infusion of unconjugated bilirubin to bile duct-cannulated rats. Thus, Sn-protoporphyrin exerts no major effects on the metabolic disposition of preformed bilirubin. Heme oxygenase activities were markedly decreased in microsomal preparations from liver, spleen, and kidneys in these experiments, to a degree comparable to the decreases we have observed in the intact rat. We also demonstrated that a substantial proportion (19-35%) of a dose of Sn-protoporphyrin is promptly excreted in bile and that the time course of biliary excretion of this compound more closely reflects plasma concentrations of the metalloporphyrin, which decline rapidly, rather than concentrations in liver, which are considerably more persistent. These results indicate that Sn-protoporphyrin substantially reduces the in vivo production of bilirubin from the degradation of endogenous as well as exogenous heme in the rat. Moreover, this inhibitory effect of the synthetic metalloporphyrin on bilirubin production occurs in both hepatocytes and reticuloendothelial cells, which are the major tissue sites for bilirubin formation. In other studies, we have established that heme oxygenase blockade by Sn-protoporphyrin leads to a marked and rapid excretion of heme into bile presumably because the synthetic metabolism to bile pigment and making it available for excretion via the biliary system in to the gut, These studies strongly suggest that Sn-protoporphyrin diminishes hyperbilirubinemia in animals and man by inhibiting the production of the bile pigment in vivo, and that its principal mode of action involves a potent and sustained competitive inhibition of heme oxygenase.

Animals↗
PubMed1985

Nutrient regulation of chemical metabolism in humans.

Dietary protein, carbohydrate, cruciferous vegetables, and charcoal-broiled beef can markedly alter the patterns of chemical biotransformations in normal subjects. The specific nutritional factors capable of altering the metabolism of drugs and the range of chemicals, including hormones, whose metabolism can be altered by diet in humans merit further study because they have the potential to influence the biological impact of these substances in humans.

Animals↗
PubMed1984

Fluorometric measurement of tin-protoporphyrin in biological samples.

Sn-protoporphyrin is a potent competitive inhibitor of heme oxygenase, can suppress neonatal and other forms of hyperbilirubinemia in laboratory animals, and represents a potential new approach to the treatment of neonatal jaundice in humans. In order to study the disposition of Sn-protoporphyrin in vivo we have developed a sensitive fluorometric method for the quantitation of this metalloporphyrin in biological samples. The method is sensitive to concentrations as low as 0.01 nmol/ml, and is specific for Sn-protoporphyrin even in the presence of other porphyrins such as protoporphyrin.

Animals↗
PubMed1984

The potent induction of intestinal heme oxygenase by the organotin compound, bis(tri-n-butyltin)oxide.

Oral administration of bis(tri-n-butyltin)oxide, an important organotin biocidal agent, produces a substantial elevation in heme oxygenase activity when measured at 16 hours in rat small intestine. An apparent Km for hemin of 100 microM is the same in both control and the organotin-induced 9,000 X g supernatant preparations. Concomitant with elevated heme oxygenase activity there occurs a substantial reduction in benzo(a)pyrene hydroxylase activity (approximately 20% of controls) and cytochrome P-450 concentration (approximately 60% of controls). These perturbations of heme metabolism in intestinal epithelium of the rat define an important new toxicological effect of organotins and raise the possibility that concurrent oral ingestion of environmental pollutants can directly affect the cytochrome P-450-dependent metabolism of other chemicals in the intestine.

Administration, Oral↗
PubMed1984

Effect of brussels sprouts and cabbage on drug conjugation.

Ten healthy subjects were fed three diets for 10 days each: a control diet, a cabbage and brussels sprouts--containing diet, and the control diet a second time. Oxazepam was taken on day 7 and acetaminophen on day 10 of each dietary regimen. The test diet stimulated the metabolism of acetaminophen, at least in part by enhanced glucuronidation, as evidenced by a 16% decrease in mean plasma AUC, a 17% increase in mean metabolic clearance rate, an increased ratio of acetaminophen glucuronide to acetaminophen in plasma from 1 to 11 hr after drug and an 8% increase in mean 24-hr urinary recovery of acetaminophen glucuronide, which returned toward control when the subjects were fed the control diet a second time. There were no comparable changes in the metabolism of acetaminophen to acetaminophen sulfate. When the subjects ate the test diet, 24-hr urinary recovery of the cysteine conjugate and of 3-methoxyacetaminophen sulfate, end-products of minor oxidative pathways, the former involving a toxic intermediate, decreased 13% and 22%. Cabbage and brussels sprouts induced a 17% decrease in mean plasma AUC and a 19% increase in mean metabolic clearance rate for oxazepam, but there was no change in mean plasma t1/2 for this drug, nor was there a change in ratio in plasma of oxazepam glucuronide to oxazepam.

Acetaminophen↗
PubMed1984

The influence of dietary protein and carbohydrate on the principal oxidative biotransformations of estradiol in normal subjects.

Dietary protein, when substituted for carbohydrate or fat, can increase cytochrome P-450-dependent drug oxidation rates in humans. Endogenous estrogens, as well as drugs, are also metabolized by cytochrome P-450 and other enzymes in the hepatic endoplasmic reticulum. Therefore, it was of interest to determine whether variations in diet can alter the major metabolic pathways for estrogens, as assessed by radiometric methods. Eight normal men were fed a high protein diet (44% of calories as protein, and 35% as carbohydrate for 2 weeks), followed by a high carbohydrate diet (70% of calories as carbohydrate and 10% as protein) for an additional 2 weeks. The fat and total energy contents of the two diets were equal. The percent oxidation of [2-3H]estradiol, measured as 3H2O released, which is an in vivo measure of 2-hydroxylation of endogenous estrogen, was greater in all eight men during the high protein dietary period than during the high carbohydrate dietary period (44 +/- 3% and 33 +/- 3%, respectively, means +/- SE, P less than 0.005). In contrast, 16 alpha-hydroxylation of estrogen, as measured using [16 alpha-3H]estradiol, did not change significantly. Our findings demonstrate that dietary components can alter estradiol oxidation in humans and that the 2- and 16 alpha-hydroxylases for estrogen are under separate regulatory control. The influences of specific nutrients on estrogen metabolism may have potential significance for diseases in which these hormones may play a role in clinical expression.

Antipyrine↗
PubMed1984

Tissue distribution and disposition of tin-protoporphyrin, a potent competitive inhibitor of heme oxygenase.

Tin(Sn)-protoporphyrin is a potent competitive inhibitor of heme oxygenase and can also suppress naturally occurring or experimentally induced hyperbilirubinemia in animals. In this study we examined the plasma clearance of Sn-protoporphyrin, its persistence in tissues and the time course of heme oxygenase inhibition up to 7 days after administration of doses up to 50 mumol/kg b.w. to adult male rats. After s.c. doses the metalloporphyrin was rapidly and almost completely absorbed. Initial plasma clearance was log-linear with a T 1/2 of approximately 3 h after either i.v. or s.c. administration. Levels of Sn-protoporphyrin in most tissues rose during the first 2 h and persisted for up to 7 days. Concentrations were highest in kidney and liver, were considerably lower in spleen, lung, intestine, adrenal and testes, and as Sn-protoporphyrin concentrations in plasma declined, concentrations in these tissues eventually exceeded simultaneous plasma concentrations. This suggests a varying degree of uptake and binding of the metalloporphyrin in these tissues. There was little or no uptake of Sn-protoporphyrin in heart, brain and red cells. Markedly decreased heme oxygenase activity in liver, kidney and spleen persisted as did Sn-protoporphyrin up to 7 days. The total amount of Sn-protoporphyrin present in tissues and excreta was a fairly constant fraction of the dose (approximately 50%) at time intervals up to 7 days after injection. These results indicate that single doses of Sn-protoporphyrin are rapidly cleared from plasma and persist in tissues and potently inhibit heme oxygenase activity for prolonged periods.

Animals↗