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1.
Temperature (Austin) ; 3(4): 557-566, 2016.
Article in English | MEDLINE | ID: mdl-28090559

ABSTRACT

Fatal hyperthermia as a result of 3,4-methylenedioxymethamphetamine (MDMA) use involves non-esterified free fatty acids (NEFA) and the activation of mitochondrial uncoupling proteins (UCP). NEFA gain access into skeletal muscle via specific transport proteins, including fatty acid translocase (FAT/CD36). FAT/CD36 expression is known to increase following chronic exercise. Previous studies have demonstrated the essential role of NEFA and UCP3 in MDMA-induced hyperthermia. The aims of the present study were to use a chronic exercise model (swimming for two consecutive hours per day, five days per wk for six wk) to increase FAT/CD36 expression in order to: 1) determine the contribution of FAT/CD36 in MDMA (20 mg/kg, s.c.)-mediated hyperthermia; and 2) examine the effects of the FAT/CD36 inhibitor, SSO (sulfo-N-succinimidyl oleate), on MDMA-induced hyperthermia in chronic exercise and sedentary control rats. MDMA administration resulted in hyperthermia in both sedentary and chronic exercise animals. However, MDMA-induced hyperthermia was significantly potentiated in the chronic exercise animals compared to sedentary animals. Additionally, chronic exercise significantly reduced body weight, increased FAT/CD36 protein expression levels and reduced plasma NEFA levels. The FAT/CD36 inhibitor, SSO (40 mg/kg, ip), significantly attenuated the hyperthermia mediated by MDMA in chronic exercised but not sedentary animals. Plasma NEFA levels were elevated in sedentary and exercised animals treated with SSO prior to MDMA suggesting attenuation of NEFA uptake into skeletal muscle. Chronic exercise did not alter skeletal muscle UCP3 protein expression levels. In conclusion, chronic exercise potentiates MDMA-mediated hyperthermia in a FAT/CD36 dependent fashion.

2.
Org Lett ; 17(13): 3256-9, 2015 Jul 02.
Article in English | MEDLINE | ID: mdl-26102589

ABSTRACT

A new class of fluorophores has been developed utilizing an inverse-demand hetero-Diels-Alder reaction with silyl enol ethers and substituted 3-formylchromones. These compounds yield blue to green fluorescence with quantum yields up to 73%. They also exhibit good potential for use as fluorescent probes in biological systems, as they are cell membrane permeable with low cytotoxicity.


Subject(s)
Chromones/chemical synthesis , Fluorescent Dyes/chemical synthesis , Cell Membrane Permeability/drug effects , Chromones/chemistry , Chromones/pharmacology , Cycloaddition Reaction , Ethers/chemistry , Fluorescence , Fluorescent Dyes/chemistry , Fluorescent Dyes/pharmacology , Molecular Structure
3.
J Org Chem ; 78(12): 5817-31, 2013 Jun 21.
Article in English | MEDLINE | ID: mdl-23721508

ABSTRACT

This perspective delineates the history of the National Organic Chemistry Symposium (NOS) and, in doing so, traces the development of organic chemistry over the past 88 years. The NOS is the premier event sponsored by the ACS Division of Organic Chemistry (ORGN) and has been held in odd-numbered years since 1925, with the exceptions of 1943 and 1945. During the 42 symposia, 332 chemists have given 549 plenary lectures. The role the NOS played in the launch of The Journal of Organic Chemistry and Organic Reactions and the initiation of the Roger Adams Award are discussed. Representative examples highlighting the chemistry presented in each era are described, and the evolution of the field is examined by assigning each NOS talk to one of seven subdisciplines and analyzing how the number of talks in each subdiscipline has changed over time. Comparisons of the demographics of speakers, attendees, and ORGN members are made, and superlatives are noted. Personal interest stories of the speakers are discussed, along with the relationships among them, especially their academic lineage. Logistical aspects of the NOS and their historical trends are reviewed. Finally, the human side of science is examined, where over the past century, the NOS has been intertwined with some of the most heated debates in organic chemistry. Conflicts and controversies involving free radicals, reaction mechanisms, and nonclassical carbocations are discussed.

4.
J Org Chem ; 78(10): 4762-78, 2013 May 17.
Article in English | MEDLINE | ID: mdl-23590535

ABSTRACT

A convergent, enantiocontrolled total synthesis of the 15-membered macrolide, amphidinolide P, is described. The synthesis utilizes three nonracemic components for an efficient assembly of the macrolactone in 12 steps via the longest linear pathway. Key developments include studies of the Hosomi-Sakurai reaction for the formation of the C6-C7 bond, a "ligandless" palladium-mediated Stille cross-coupling of the vinylic stannane 4 and the alkenyl bromide 5 to produce a highly functionalized dienol, and a thermally induced, intramolecular lactonization via the late-stage formation of an intermediate α-acylketene.


Subject(s)
Macrolides/chemical synthesis , Macrolides/chemistry , Molecular Conformation
5.
J Pediatr ; 157(4): 684-7, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20580021

ABSTRACT

The short-term outcomes of sodium bicarbonate therapy in preterm infants were investigated by retrospective analysis of 165 of 984 infants who received sodium bicarbonate. The infants treated with sodium bicarbonate were more immature and had greater severity of illness and more adverse outcomes. Sodium bicarbonate therapy did not improve the blood pH.


Subject(s)
Acidosis/drug therapy , Acidosis/metabolism , Hydrogen-Ion Concentration/drug effects , Sodium Bicarbonate/pharmacology , Chronic Disease , Humans , Infant, Newborn , Infant, Premature , Infusions, Intravenous , Severity of Illness Index , Sodium Bicarbonate/administration & dosage
6.
Ann Neurol ; 67(6): 817-23, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20517944

ABSTRACT

OBJECTIVE: Hypernatremia is associated with intracranial hemorrhage in term infants. The etiology of intraventricular hemorrhage in preterm infants is multifactorial. We aimed to characterize the associations between sodium intake, hypernatremia, and intraventricular hemorrhage in preterm infants. METHODS: The charts of 722 preterm infants with a birth weight

Subject(s)
Cerebral Ventricles/physiopathology , Intracranial Hemorrhages/pathology , Intracranial Hemorrhages/physiopathology , Premature Birth/physiopathology , Sodium/blood , Birth Weight , Female , Gestational Age , Humans , Infant Mortality , Infant, Newborn , Intensive Care Units , Intracranial Hemorrhages/epidemiology , Male , Odds Ratio , Premature Birth/epidemiology , Retrospective Studies , Risk Factors
7.
Bioorg Med Chem Lett ; 15(22): 4898-906, 2005 Nov 15.
Article in English | MEDLINE | ID: mdl-16165355

ABSTRACT

A novel class of anthranilic diamides has been discovered with exceptional insecticidal activity on a range of Lepidoptera. These compounds have been found to exhibit their action by release of intracellular Ca2+ stores mediated by the ryanodine receptor. The discovery, synthesis, structure-activity, and biological results are presented.


Subject(s)
Insecticides/chemistry , Insecticides/pharmacology , Ryanodine Receptor Calcium Release Channel/metabolism , ortho-Aminobenzoates/chemistry , ortho-Aminobenzoates/pharmacology , Amination , Animals , Calcium/metabolism , Insecta/drug effects , Molecular Structure , Structure-Activity Relationship , ortho-Aminobenzoates/classification
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