Effect of structure on potency and selectivity in 2,6-disubstituted 4-(2-arylethenyl)phenol lipoxygenase inhibitors.

A series of 2,6-disubstituted 4-(2-arylethenyl)phenols with potent human neutrophil 5-lipoxygenase (5-LO) inhibiting activity (IC50S in the 10(-7) M range) and weaker human platelet cyclooxygenase (CO) inhibiting activity (IC50S in the 10(-6) M range) is described. This series evolved from the chemical modification of an antiinflammatory dual CO/5-LO inhibitor, 2,6-di-tert-butyl-4-[2-(3-pyridyl)ethenyl]phenol (BI-L-93 BS). The potency and selectivity for 5-LO inhibition is greatly influenced by the nature of the substituents in the 2- and 6-positions.

Zinc concentrations in mouse embryo and maternal plasma. Effect of valproic acid and nonteratogenic metabolite.

The effect of a single teratogenic dose of the antiepileptic drug valproic acid and its nonteratogenic metabolite, 2-en-valproic acid, on zinc concentrations in mouse plasma, embryo, and decidua on d 9 of gestation was investigated. The substances were injected subcutaneously (sc) as their sodium salts. In this mouse model, valproic acid induced between 20% (400 mg/kg dose) and 60% (600 mg/kg dose) incidence of exencephaly in living fetuses; 2-en-valproic acid was not teratogenic at these dose levels.

Repeated antigen inhalation results in a prolonged airway eosinophilia and airway hyperresponsiveness in primates.

The effects of repeated antigen inhalation on airway cellular composition and airway responsiveness were examined in primates. Airway cellular composition was assessed by bronchoalveolar lavage (BAL), and airway responsiveness was measured as the bronchoconstrictor response to cumulative methacholine dose-response determinations over the course of a 10-wk study. Control animals, exposed to repeated vehicle inhalation challenges, were tested in parallel with the antigen-challenged group.

Intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of asthma.

Airway eosinophilia, epithelial desquamation, and hyperresponsiveness are characteristics of the airway inflammation underlying bronchial asthma. The contribution of intercellular adhesion molecule-1 (ICAM-1) to eosinophil migration and airway responsiveness was studied. ICAM-1 partially mediated eosinophil adhesion to to endothelium in vitro and was upregulated on inflamed bronchial endothelium in vivo.

Asymmetric synthesis and teratogenic activity of (R)- and (S)-2-ethylhexanoic acid, a metabolite of the plasticizer di-(2-ethylhexyl)phthalate.

The stereoselectivity of the teratogenic activity of 2-ethylhexanoic acid (EHXA), a metabolite of the widely-used plasticizer di-(2-ethylhexyl)phthalate, was investigated. The enantiomers of EHXA were prepared via asymmetric synthesis with the aid of the chiral auxiliaries (R)- and (S)-1-amino-2-(methoxymethyl)pyrrolidine (RAMP, SAMP). The aqueous solutions of the sodium salts of (R)- and (S)-EHXA and the racemic EHXA [+/- )-EHXA) were injected each morning and evening of day 7 and 8 of gestation in the NMRI mouse (500 mg/kg, i.

Antigen-coated sepharose beads induce airway eosinophilia and airway hyperresponsiveness in cynomolgus monkeys.

A method of inducing sustained airway eosinophilia and airway hyperresponsiveness in primates has been developed. Our method utilizes a series of intratracheal instillations of Ascaris suum-coated sepharose 4B beads (3 x 10(5] administered once a week for four weeks. Five cynomolgus monkeys (Macaca fascicularis) demonstrating a naturally occurring skin and respiratory sensitivity to Ascaris suum extract were studied.

Evaluation of butylated hydroxytoluene as a cryopreservative added to whole or skim milk diluent for bull semen.

Effect of five concentrations of butylated hydroxytoluene on the percent motility and percent intact acrosomes was evaluated for bull sperm frozen and thawed in whole and skim milk diluents. Twelve ejaculates were frozen in .5-ml straws in moving nitrogen vapor after each ejaculate was split among the five butylated hydroxytoluene treatments within the two diluents.

How adolescents describe pain.

This study assesses how adolescents describe the experience of pain. We queried a convenience sample of 156 adolescents, 13-17 years of age, in two schools and four hospitals. Adolescents answered questions on a questionnaire developed by the investigators.

Acute pulmonary response to cotton bract extract in monkeys: lung function and effects of mediator modifying compounds.

It is well established that cotton dust inhalation can compromise lung function in textile workers. Challenges with a water-soluble extract of cotton bract (CBE) can also induce reversible airway obstruction in healthy volunteers. We have examined the effect of inhaled CBE in nonhuman primates and have attempted to inhibit the bronchoconstrictive response with mediator modifying compounds.

Valproic acid-induced neural tube defects: reduction by folinic acid in the mouse.

Neural tube defects were induced dose-dependently by single injections of the anticonvulsant drug valproic acid (VPA) as sodium salt in mice on gestational day 8. Folinic acid (5-CHO-THF) coadministration by i.p.

Direct determination of folate monoglutamates in plasma by high-performance liquid chromatography using an automatic precolumn-switching system as sample clean-up procedure.

A simple and rapid technique for the simultaneous isolation and analysis of folate monoglutamates (folic acid, 7,8-dihydrofolic acid, 5,6,7,8-tetrahydrofolic acid and 5-formyl-, 5-methyl- and 10-formyl-5,6,7,8-tetrahydrofolic acids) was developed using reversed-phase high-performance liquid chromatography with an automatic precolumn-switching system. The plasma or the dissolved diet samples were directly injected onto a short precolumn flushed with 50 mM phosphate buffer. The folate vitamers absorbed on the precolumn were backflushed onto the analytical column with a 25 mM phosphate buffer containing 5% methanol and then detected by UV absorption at 280 nm.

Linear-lumped-parameter modeling of pulmonary impedance in monkeys.

Pulmonary impedance, ZL, measured from 2 to 32 Hz in anesthetized, intubated and paralyzed bonnet monkeys (Macaca radiata) was fitted to a variety of linear-lumped parameter mechanical networks. Parameter values for each network were obtained by minimizing the average of the percent distance, Dr, between the computed network impedance and measured ZL at all frequencies. Measured resistance, RL, decreased from 2 to 8 Hz and increased from 8 to 32 Hz indicating that a single series resistance-inertance-compliance (RIC) network was not optimal (Dr approximately 19%).

Dynamic respiratory mechanics in monkeys measured by forced oscillations.

We measured impedances of the lungs (ZL) and respiratory system (Zrs) by discrete frequency (f) forced oscillations in adult bonnet monkeys at two lung volumes, FRC and at transrespiratory system pressure (Prs) of -5 cm H2O. Measurements were made from 2 to 32 Hz to study f dependence of effective resistances (Reff) and reactances, and from 1 to 8 Hz to study f dependence of effective pulmonary compliance (Ceff,L). Estimates of resistances (R), inertances (I) and compliances (C) of the lungs (L), chest wall (W) and respiratory system (rs) were obtained by fitting the 2-32 Hz data to a series RIC network model.

Mycetoma or pseudomycetoma? A distinctive mycosis caused by dermatophytes.

A 13-year old black girl presented with an unusual scalp lesion felt to be compatible with mycotic granuloma. She had undergone surgery two years earlier for removal of three similar scalp lesions. Material excised during surgical removal of the cyst-like lesion again revealed histopathology compatible with mycotic granuloma.

How do children describe pain? A tentative assessment.

In a study to determine how children describe the experience of pain, we queried a convenience sample of 100 children in hospitals and 114 children in church and private schools who were between 9 and 12 years old. The questions were designed to seek correlations by age among boys and girls, and between hospitalized and non-hospitalized children that would aid health professionals in strategies that will identify and assist the child who is in pain. The preliminary results show that children clearly describe pain, that there are no appreciable differences by age groups, but that children who are hospitalized describe pain differently from children who are not.

Synthesis of probable and improbable precursors for porphyrin biosynthesis.

Insights into details of the biomechanism by which porphobilinogen (1) cyclotetramerizes to uroporphyrinogen III (2) as well as promising synthetic applications are provided by investigation of this reaction in vitro. The cyclotetramerization of newly prepared norporphobilinogen (5) proved to be extemely specific due to strong conformation control. Advantage was taken of this finding by preparing a N,N,N,N-tetramethyl-porphyrinogen (13a) for the first time.

[Light and electron microscopic studies on the reepithelization of free connective tissue grafts].

1. In mini-pigs epithelium-free connective tissue grafts were transplanted from the cheek to the palate as well as from the palate to the area of the alveolar mucosa. 2.