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Biomedical subjects

H Jorgensen

Publications and source records attributed to H Jorgensen.

At least 19 recordsLinked to original sources

Digestion of fat does not differ in growing pigs fed diets containing fish oil, rapeseed oil or coconut oil.

We studied the digestion of fat and fatty acids in diets containing oils with different fatty acid composition. Four barrows (initial weight 35 kg) were fitted with a simple T-cannula at the terminal ileum. Three wheat starch and fish meal-based diets were formulated to contain either 150 g fish oil, rapeseed oil or coconut oil/kg. A basal diet, which did not contain oil, was also prepared. The diets were fed according to a 4 x 4 Latin square design. Each experimental period comprised 5 d adaptation to the diets, 3 d fecal collection and 2 d digesta collection. The apparent ileal and fecal digestibilities of fat were relatively high (88 - 93%). The ileal digestibilities of total, saturated and monounsaturated fatty acids did not differ among the diets. However, the digestibilities of polyunsaturated fatty acids (PUFA) in the fish and rapeseed oil diets were higher (P < 0.05) than in the coconut oil diet. The ileal digestibilities of 18:1, 18:2 and 18:3 in the rapeseed oil diet ranged from 94 to 97%. The ileal digestion of the unsaturated long-chain fatty acids 20:5(n-3) and 22:6(n-3) in the fish oil diet was nearly complete (97 - 98%). Apparent fecal digestibilities of saturated fatty acids (76 - 89%) were lower than apparent ileal digestibilities (89 - 94%). The digestibilities of fat and fatty acids were relatively high when pigs were fed diets containing fish oil, rapeseed oil or coconut oil. There were few differences in the digestibilities of saturated, monounsaturated and PUFA in the fish oil, rapeseed oil or coconut oil diets.

Animals↗

Effect of blockade of postsynaptic H1 or H2 receptors or activation of presynaptic H3 receptors on catecholamine-induced stimulation of ACTH and prolactin secretion.

The effect of inhibition of the neuronal histaminergic system by blockade of postsynaptic H1 or H2 receptors or activation of presynaptic H3 autoreceptors on the ACTH and prolactin responses to the catecholamines epinephrine and norepinephrine was investigated in conscious male rats. Intracerebroventricular infusion of epinephrine and norepinephrine stimulated ACTH and prolactin secretion. Prior intracerebroventricular infusion of the H1 receptor antagonist, mepyramine, or the H2 receptor antagonist, cimetidine, had no effect on the ACTH response to epinephrine or norepinephrine, while these responses were inhibited by pretreatment with the H3 receptor agonist, imetit. The prolactin response to norepinephrine was significantly inhibited by pretreatment with mepyramine, cimetidine or imetit whereas the three histaminergic compounds had no effect on the prolactin response to epinephrine. The findings suggest that the histaminergic system exerts a mediating or permissive action on the norepinephrine-induced stimulation of prolactin secretion, whereas an intact histaminergic system may not be required for catecholamines to stimulate ACTH secretion. The inhibitory effect of imetit on catecholamine-induced release of ACTH may be due to an activation of H3 receptors located presynaptically on non-histaminergic neurons, e.g. aminergic neurons. The study further indicates an important role of histamine in the neuroendocrine regulation of prolactin secretion.

Adrenocorticotropic Hormone↗

Stress-induced release of anterior pituitary hormones: effect of H3 receptor-mediated inhibition of histaminergic activity or posterior hypothalamic lesion.

The effect of stress- or lipopolysaccharide (LPS) endotoxin-induced release of ACTH, beta-endorphin (beta-END) and prolactin (PRL) was investigated in two groups of conscious male rats: (1) Rats pretreated with different H3 receptor agonists, which inhibit neuronal histamine (HA) synthesis and release, and (2) rats with bilateral posterior hypothalamic lesion, which destroys the histaminergic perikarya exclusively localized in the mammillary nuclei. The H3 receptor agonists R(alpha)methyl-HA, BP 2-94 or imetit injected intraperitoneally (ip) had no effect on basal secretion of ACTH or PRL but inhibited the ACTH and PRL responses to restraint stress and the ACTH response to LPS endotoxin. LPS had no effect on PRL secretion. The inhibitory effect of the agonists was prevented by prior ip administration of the H3 receptor antagonist thioperamide. Bilateral lesion of the posterior hypothalamus inhibited the ACTH, beta-END and PRL responses to restraint stress, ether stress and LPS endotoxin, whereas sham operation had no effect compared to nonoperated control rats. In addition, posterior hypothalamic lesion inhibited the PRL response but not the ACTH and beta-END responses to activation of serotonergic neurons induced by ip administration of the 5-HT precusor 5-hydroxytryptophan in combination with the 5-HT re-uptake inhibitor fluoxetine. Thus, serotonergic pathways were not damaged by the lesions. The present results support our previous findings that inhibition of neuronal HA synthesis by alpha-fluoromethylhistidine as well as blockade of H1 or H2 receptors inhibit the ACTH, beta-END and PRL responses to stress and LPS endotoxin and further substantiate an important role of histaminergic neurons in the mediation of the stress-induced release of pituitary stress hormones. Furthermore, in accordance with our previous findings, the lesion experiments indicated the existence of an interaction between the histaminergic and serotonergic system in regulation of the stress- and LPS-induced PRL release.

5-Hydroxytryptophan↗

Effect of selective blockade of catecholaminergic alpha and beta receptors on histamine-induced release of corticotropin and prolactin.

We investigated the role of adrenergic receptors in histamine (HA)-induced release of corticotropin (ACTH) and prolactin (PRL) in conscious male rats. Specific alpha- or beta-receptor antagonists were administered intracerebroventricularly in doses of 1 mmol at time -20 min, and HA (270 nmol), the H1 receptor agonist 2-thiazolylethylamine (2-TEA; 2,180 nmol) or the H2 receptor agonist 4-methylHA (4-MeHA; 790 nmol) were administered intracerebroventricularly at -15 min. The animals were decapitated at 0 min, and plasma was analyzed for ACTH and PRL. Administration of HA and the histaminergic agonists stimulated ACTH secretion equally, while only HA and the H2 receptor agonist stimulated PRL secretion. Pretreatment with the adrenergic receptor antagonists had no effect on the ACTH response to the histaminergic compounds. In contrast, the PRL response to HA or 4-MeHA was inhibited or prevented by the alpha-receptor antagonists phenoxybenzamine and phentolamine, the alpha1-receptor antagonist prazocin, the beta-receptor antagonist propranolol and the beta1-receptor antagonist atenolol, whereas the alpha2-receptor antagonist yohimbine or the beta2-receptor antagonist ICI-118-551 had no effect. The study indicates that histaminergic neurons interact with the catecholaminergic neuronal system in regulation of PRL secretion, and that this interaction is dependent upon activation of alpha1- and beta1-receptors. In contrast, histaminergic neurons stimulate ACTH secretion independently of adrenergic receptor activation.

Adrenergic alpha-Antagonists↗

Natural killer cells in peripheral blood after autologous bone marrow transplantation: a combined phenotypic and functional study.

The peripheral blood regeneration of natural killer (NK) cells was studied before and on 5 occasions during the first 6 weeks after autologous bone marrow transplantation (auto-BMT) in 10 patients with hematological malignancies and solid tumors. The number of NK cells (relative as well as absolute), enumerated by their lack of CD3 and their expression of CD56 recovered after a severe decline 1 week posttransplant to increase beyond pretransplantation levels during the next 2 weeks. Similar patterns were seen for the average NK activity against K562 as well as LAK cell lytic activity against Daudi but without the overshoot at weeks 2-3. Moreover, the fraction, but not the absolute numbers, of NK cells was found to correlate to the lytic NK activity. In contrast, no phenotypic marker was correlated to LAK activity. Immunophenotypic studies using three-color flow cytometry revealed that during the first 2 weeks after auto-BMT the phenotype of NK cells changed towards an immature phenotype (decreased CD45RA and CD11a) 1 week after transplant to an activated (increase in CD25, HLA-DR and CD11c) after 2-4 weeks. However, when the absolute number of selected phenotypically defined NK cell subsets(CD45RA, CD45RB, CD11a, CD11c, CD2, CD25, HLA-DR and fibronectin expressing CD56+,CD3- NK cells) were compared to the cytotoxic activity for each patient, we were not able to show any correlations except between the activation-related antigens CD25 and HLA-DR on the one hand, and NK lysis on the other, and only 3 weeks after auto-BMT. We conclude that NK cell function recovers quickly following auto-BMT concomitantly with the emergence of a transiently altered phenotype which increased expression of activation-related antigens.

Adult↗

Molecular dynamics simulation of winter flounder antifreeze protein variants in solution: correlation between side chain spacing and ice lattice.

The solution structure of the 38 amino acid C-terminal region of the precursor for the HPLC-6 antifreeze protein from winter flounder has been investigated with molecular dynamics using the AMBER software. The simulation for the peptide in aqueous solution was carried out at a constant temperature of 0 degree C and at atmospheric pressure. The simulation covered 120 ps and the results were analyzed based on data sampled upon reaching a stable equilibrium phase. Information has been obtained on the quality of constant temperature and pressure simulations, the solution structure and dynamics, the hydrogen bonding network, the helix stabilizing role of terminal charges and the interaction with the surrounding water molecules. The Lys18-Glu22 interactions and the terminal charged residues are found to stabilize a helical structure with the side chains of Thr2, Thr13, Thr24 and Thr35 equally spaced on one side of the helix. The spacing between oxygen atoms in the hydroxyl group of the threonine side chains exhibits fluctuations of the order of 2-3 A during the 120 ps of simulation, but values simultaneously close to the repeat distance of 16.6 A between oxygen atoms along the [0112] direction in ice are observed. Furthermore, two engineered variants were studied using the same simulation protocol.

Amino Acid Sequence↗

The drug research process.

The Department of Dermatology at the Washington Hospital Center conducts research on drugs and products for various drug companies prior to their approval by the Food and Drug Administration. The purpose of this article is to describe this interesting and rewarding process which can give dermatology nurses the opportunity to assist patients who might not have found effective or affordable treatment for their condition.

Clinical Trials as Topic↗

Induction of self-tolerance in mature peripheral B lymphocytes.

In transgenic mice, mature peripheral B lymphocytes in lymphoid follicles, like immature B cells, are rendered tolerant by encounter with self-antigen, provided receptor occupancy by self-antigen exceeds a critical threshold. The tolerant state of the B cell is closely correlated with down-regulation of membrane IgM but not IgD antigen-receptors. Identical changes in antigen-receptor expression occur in a subset of follicular B cells in nontransgenic mice, suggesting that clonally silenced self-reactive cells are common in the peripheral B-cell repertoire.

Animals↗

Elevation of serum triglyceride levels from oral isotretinoin in disorders of keratinization.

Ten patients with disorders of keratinization were treated with oral isotretinoin (13-cis-retinoic acid) on an investigational protocol to test the efficacy, safety, and optimal dosage schedule for using the drug in these rare disorders. Elevations of serum triglyceride levels above the highest normal levels developed in seven of the ten patients, while they maintained normal levels of serum cholesterol. This effect was found to be dose and/or time related and reversible. Moderate elevations of serum triglyceride levels have not been clearly established as a risk factor for the development of coronary artery disease. High levels, however, may precipitate acute pancreatitis. For this reason, the conditions of patients receiving retinoids must be carefully monitored for triglyceride abnormalities throughout their courses of treatment.

Administration, Oral↗

1alpha-hydroxycholecalciferol in the treatment of hypoparathyroidism.

In two patients (father and daughter) with idiopathic hypoparathyroidism, one of whom was resistant to the action of vitamin D2 and AT-10, 1alpha-hydroxycholecalciferol (1alpha-(OH)D3) in doses of 2-5 mug/day restored the serum calcium concentration to the normal range. The calcemic effect of 1alpha (OH)D3 was in both patients due to an increased intestinal calcium absorption and increased calcium mobilization from bone. In one of the patients 1alpha-(OH)D3 also increased the renal tubular calcium reabsorption; in the other it did not have this effect, resulting in hypercalciuria as serum calcium rose. The lack of effect on tubular calcium reabsorption probably accounts for the relative resistance to the action of 1alpha-(OH)C3 in this patient compared with other.

Adult↗