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Hypothalamic adipic hypernatraemia syndrome with normal osmoregulation of vasopressin.

UNLABELLED: Adipsic hypernatraemia is an uncommon disorder in childhood caused by a defect in the osmoregulation of thirst, leading to impairment of water homeostasis and chronic hyperosmolality of body fluids. Adipsia is often associated with an abnormality in osmoregulated vasopressin secretion due to the close proximity of the hypothalamic osmoreceptors that control thirst with those regulating vasopressin secretion. Hypothalamic lesions of diverse aetiology (vascular abnormalities, neoplasms, granulomatous diseases, trauma etc.) have been described in this syndrome. We report a 12-year-old boy with evident weight loss due to hypernatraemic dehydration with a selective defect in osmoregulation of thirst and normal vasopressin secretion with no demonstrable structural lesion. To date, only six paediatric patients with this condition have been described in the literature. CONCLUSION: Hypothalamic adipsic hypernatraemia syndrome must be suspected when a dehydrated patient denies thirst. The study of antidiuretic function is necessary because the osmoregulation of vasopressin secretion could be altered.

Brain↗

Simplified preformed chelate protein radiolabeling with technetium-99m mercaptoacetamidoadipoylglycylglycine (N3S-adipate).

A simplified kiet has been developed for 99mTc protein radiolabeling using an N3S triamide mercaptide bifunctional chelating agent and the preformed chelate approach. The process combined N3S chelating agent, gluconate intermediate transfer agent, stannous reducing agent, and gentisic acid stabilizer into a lyophilized formulation. With sulfur donor atom hemithioacetal protection of the ligand, delta-2,3,5,6-tetrafluorothiophenyl alpha-S-(1-ethoxyethyl)mercaptoacetamido-L-adipoylglycylglycine , optimum 99mTc chelation was achieved in a single step. Subsequent reaction with NR-LU-10 antibody Fab fragment followed by purification via QAE Sephadex anion exchange resin filter afforded 99mTc-N3S-NR-LU-10 Fab conjugate with retained immunoreactivity and effective tumor targeting properties.

Animals↗

Final report of the amended safety assessment of Glyceryl Laurate, Glyceryl Laurate SE, Glyceryl Laurate/Oleate, Glyceryl Adipate, Glyceryl Alginate, Glyceryl Arachidate, Glyceryl Arachidonate, Glyceryl Behenate, Glyceryl Caprate, Glyceryl Caprylate, Glyceryl Caprylate/Caprate, Glyceryl Citrate/Lactate/Linoleate/Oleate, Glyceryl Cocoate, Glyceryl Collagenate, Glyceryl Erucate, Glyceryl Hydrogenated Rosinate, Glyceryl Hydrogenated Soyate, Glyceryl Hydroxystearate, Glyceryl Isopalmitate, Glyceryl Isostearate, Glyceryl Isostearate/Myristate, Glyceryl Isostearates, Glyceryl Lanolate, Glyceryl Linoleate, Glyceryl Linolenate, Glyceryl Montanate, Glyceryl Myristate, Glyceryl Isotridecanoate/Stearate/Adipate, Glyceryl Oleate SE, Glyceryl Oleate/Elaidate, Glyceryl Palmitate, Glyceryl Palmitate/Stearate, Glyceryl Palmitoleate, Glyceryl Pentadecanoate, Glyceryl Polyacrylate, Glyceryl Rosinate, Glyceryl Sesquioleate, Glyceryl/Sorbitol Oleate/Hydroxystearate, Glyceryl Stearate/Acetate, Glyceryl Stearate/Maleate, Glyceryl Tallowate, Glyceryl Thiopropionate, and Glyceryl Undecylenate.

The safety of 43 glyceryl monoesters listed as cosmetic ingredients was reviewed in a safety assessment completed in 2000. Additional safety test data pertaining to Glyceryl Rosinate and Glyceryl Hydrogenated Rosinate were received and served as the basis for this amended report. Glyceryl monoesters are used mostly as skin-conditioning agents--emollients and/or surfactant--emulsifying agents in cosmetics. The following 20 glyceryl monoesters are currently reported to be used in cosmetics: Glyceryl Laurate, Glyceryl Alginate, Glyceryl Arachidonate, Glyceryl Behenate, Glyceryl Caprylate, Glyceryl Caprylate/Caprate, Glyceryl Cocoate, Glyceryl Erucate, Glyceryl Hydroxystearate, Glyceryl Isostearate, Glyceryl Lanolate, Glyceryl Linoleate, Glyceryl Linolenate, Glyceryl Myristate, Glyceryl Oleate/Elaidate, Glyceryl Palmitate, Glyceryl Polyacrylate, Glyceryl Rosinate, Glyceryl Stearate/Acetate, and Glyceryl Undecylenate. Concentration of use data received from the cosmetics industry in 1999 indicate that Glyceryl Monoesters are used at concentrations up to 12% in cosmetic products. Glyceryl Monoesters are not pure monoesters, but are mostly mixtures with mono-, di-, and tri-esters. The purity of commercial and conventional Monoglyceride (Glyceryl Monoester) is a minimum of 90%. Glyceryl Monoesters (monoglycerides) are metabolized to free fatty acids and glycerol, both of which are available for the resynthesis of triglycerides. Glyceryl Laurate enhanced the penetration of drugs through cadaverous skin and hairless rat skin in vitro and has been described as having a wide spectrum of antimicrobial activity. A low-grade irritant response was observed following inhalation of an aerosol containing 10% Glyceryl Laurate by test animals. Glyceryl monoesters have little acute or short-term toxicity in animals, and no toxicity was noted following chronic administration of a mixture consisting mostly of glyceryl di- and mono- esters. Glyceryl Laurate did have strong hemolytic activity in an in vitro assay using sheep erythrocytes. Glyceryl Laurate, Glyceryl Isostearate, or Glyceryl Citrate/Lactate/Linoleate/Oleate were not classified as ocular irritants in rabbits. Undiluted glyceryl monoesters may produce minor skin irritation, especially in abraded skin, but in general these ingredients are not irritating at concentrations used in cosmetics. Glyceryl monoesters are not sensitizers, except that Glyceryl Rosinate and Hydrogenated Glyceryl Rosinate may contain residual rosin, which can cause allergic reactions. These ingredients are not photosensitizers. Glyceryl Citrate/Lactate/Linoleate/Oleate was not mutagenic in the Ames test system. Glyceryl Laurate exhibited antitumor activity and Glyceryl Stearate was negative in a tumor promotion assay. At concentrations higher than used in cosmetics, Glyceryl Laurate did cause moderate erythema in human repeat-insult patch test (RIPT) studies, but the other glyceryl monoesters tested failed to produce any significant positive reactions. Glyceryl Rosinate was irritating to animal skin at 50%, but did not produce sensitization in clinical tests at concentrations up to 10% and covered with semioccluded patches. There is reported use of Glyceryl Rosinate at 12%in mascara, which is somewhat higher than the concentration in the clinical testing. It was reasoned that the available data do support the safety of this use because there would be minimal contact with the skin and no occlusion. The safety of Arachidonic Acid was not documented and substantiated for cosmetic product use in an earlier safety assessment and those same safety questions apply to Glyceryl Arachidonate. Based on these data, the Cosmetic Ingredient Review (CIR) Expert Panel found that these glyceryl monoesters are safe as cosmetic ingredients in the present practices of use and concentration: except that the available data are insufficient to support the safety of Glyceryl Arachidonate. Additional data needed to support the safety of Glyceryl Arachidonate include (1) dermal absorption data; and, based on the results of the absorption studies, there may be a need for (2) immunomodulatory data; (3) carcinogenicity and photocarcinogenicity data; and (4) human irritation, sensitization, and photosensitization data.

Animals↗

A prokaryotic gene cluster involved in synthesis of lysine through the amino adipate pathway: a key to the evolution of amino acid biosynthesis.

In previous studies we determined the nucleotide sequence of the gene cluster containing lys20, hacA (lys4A), hacB (lys4B), orfE, orfF, rimK, argC, and argB of Thermus thermophilus, an extremely thermophilic bacterium. In this study, we characterized the role of each gene in the cluster by gene disruption and examined auxotrophy in the disruptants. All disruptants except for the orfE disruption showed a lysine auxotrophic phenotype. This was surprising because this cluster consists of genes coding for unrelated proteins based on their names, which had been tentatively designated by homology analysis. Although the newly found pathway contains alpha-aminoadipic acid as a lysine biosynthetic intermediate, this pathway is not the same as the eukaryotic one. When each of the gene products was phylogenetically analyzed, we found that genes evolutionarily-related to the lysine biosynthetic genes in T. thermophilus were all present in a hyperthermophilic and anaerobic archaeon, Pyrococcus horikoshii, and formed a gene cluster in a manner similar to that in T. thermophilus. Furthermore, this gene cluster was analogous in part to the present leucine and arginine biosyntheses pathways. This lysine biosynthesis cluster is assumed to be one of the origins of lysine biosynthesis and could therefore become a key to the evolution of amino acid biosynthesis.

2-Aminoadipic Acid↗

Bis(dicyclohexylammonium) adipate monohydrate.

In the asymmetric unit of the title compound, 2C(12)H(24)N(+).C(6)H(8)O(4)(2-).H(2)O, the carboxylate ion lies about an inversion center, the water molecule is on a twofold axis and the sec-ammonium cation is in a general position. Cations link the oxygen ends of two adjacent carboxylate anions to form an eight-membered ring [N.O 2.683 (3) and 2.711 (3) A]. The ion pair propagates as a linear chain and adjacent chains are linked through the water molecules [O.O 2.966 (3) A] into layers.

Journal Article↗