ABSTRACT
Long hydrocarbon chain derivatives with bis-terminal hydroxyl or carboxyl groups and various central moieties (ketone, ether, ester, amide, carbamate, etc.) have been synthesized and evaluated for their effects on the de novo incorporation of radiolabeled acetate into lipids in primary cultures of rat hepatocytes as well as for their effects on lipid, glycemic and body weight variables in female obese Zucker fatty rats following one and two weeks of oral administration. The most active compounds were found to be symmetrical with four to five methylene groups separating the ether or ketone central functionality from the gem dimethyl, cycloalkyl or methyl/aryl substituents. Cycloalkyl substitution alpha to the carboxyl group in keto-acids lowered the in vitro activity to micromolar values. Furthermore, in vivo biological activity was found to be greatest for cyclopropyl-substituted ketone derivatives, particularly the ketodiacid with five methylene groups on each side of the central ketone functionality, which was identified as an HDL elevator and was also found to reduce insulin and glucose.
Subject(s)
Dyslipidemias/drug therapy , Ethers/pharmacology , Hydrocarbons/pharmacology , Ketones/pharmacology , Aging/physiology , Animals , Cholesterol, HDL/blood , Cholesterol, VLDL/blood , Dyslipidemias/blood , Ethers/chemistry , Female , Hepatocytes/drug effects , Hepatocytes/metabolism , Hydrocarbons/chemistry , Hypercholesterolemia/drug therapy , Hyperinsulinism/drug therapy , Hypertriglyceridemia/blood , Hypertriglyceridemia/drug therapy , Ketones/chemistry , Male , Obesity/drug therapy , Obesity/metabolism , Rats , Rats, Sprague-Dawley , Rats, Zucker , Structure-Activity RelationshipABSTRACT
A general and efficient route to the marasmane skeleton is described. Total syntheses of two simple marasmanes (35 and 37) in racemic form were achieved using a MgI2-catalyzed rearrangement-cyclopropanation reaction of trimethylsilyl enol ether 31 derived from naphthalenone 30. The reaction proceeds in high yield with complete diastereoselectivity and does not require the use of special cyclopropanation reagents. Application of this novel route to the marasmane framework was extended to the synthesis of naturally occurring (+)-isovelleral (41).
Subject(s)
Cyclopropanes/chemistry , Sesquiterpenes/chemical synthesis , Basidiomycota/chemistry , Indenes/chemical synthesis , Mesylates/chemistry , Nuclear Magnetic Resonance, Biomolecular , Polycyclic SesquiterpenesABSTRACT
Kangaroo care or skin-to-skin holding of preterm infants requires consistent implementation for best outcomes with infants and families. Successful implementation of a project of this type demands an organized approach. This article describes how a standard of care was developed using research findings and then implemented with a step-by-step approach in the neonatal intensive care unit.
Subject(s)
Infant, Premature , Intensive Care Units, Neonatal , Intensive Care, Neonatal/methods , Intensive Care, Neonatal/organization & administration , Arizona , Humans , Infant, Newborn , Neonatal Nursing , Nursing Staff, Hospital/education , Parents/education , ResearchABSTRACT
A simple method of storing and re-using coil dialysers was used in over 700 dialysers without serious complications but mantaining the efficiency of the dialyser. The method can reduce the expense of coil and tubing by as much as 70%, while the total cost of home or hospital dialysis can be reduced by as much as 15 to 25% even when the coil is re-used only once. Coils were re-used as many as 14 times, making the potential reduction in cost much larger. This technique deserves further evaluation in both hospital and home dialysis programmes.
