Endocrine pancreatic cells of postatal “diabetes” (DB) mice in cell culture

Summary Ultrastructural characteristics as well as secretory and biosynthetic behavior of monolayer pancreatic cell cultures established from 4-day-old C57BL/KsJ misty diabetic (m db/ m db) mice have been studied in comparison to normal littermate controls. Hypersecretion of glucagon by α-cells from BL/Ks misty diabetic mice after 2 days in vitro was found to precede any hyperfunction of the insulin-secreting β-cells. The increased level of glucagon-release in BL/Ks cell cultures from diabetic mice was accompanied by a greatly enhanced level of incorporation of [³H] tryptophan into glucagon-like molecules whose specific radioactivity was up to 15-fold higher than that observed in cultures from genetic controls. The finding of an α-cell dysfunction in cultures established from preweaning diabetic BL/Ks mice suggests that glucagon could play an early role in shaping the events that culminate in the expression of frank diabetes in this inbred strain. This study was supported in part by NIH Grants AM 17631 and AM 14461, and a grant from the Juvenile Diabetes Foundation. The Jackson Laboratory is fully accredited by the American Association for Accrediation of Laboratory Animal Care.     

Marine polyprenylated hydroquinones, quinones, and chromenols with inhibitory effects on leukotriene formation

A series of polyprenylated hydroquinones, quinones, and chromenols were isolated from the extracts of the marine sponge Ircinia spinosula and the brown alga Taonia atomaria, which gave rise to the constituents 1-4 and 5-8, respectively. Compounds 1, 2, 6, and 7 are new natural products, which were fully characterized. Their anti-inflammatory activities in terms of leukotriene formation were evaluated in an in vitro assay with pork leukocytes. The new hydroxylated compound, 2'-[28-hydroxy]heptaprenyl-1',4'-hydroquinone (= 2-[(2E,6E,10E,14E,18Z,22E)-19-(hydroxymethyl)-3,7,11,15,23,27-hexamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl]benzene-1,4-diol; 1), the known tetraprenyl benzoquinone sargaquinone (5), and the known polyprenyl chromenols 3 and 4 exhibited the highest anti-inflammatory activities, with IC50 values of 1.9-9.4 microM (Table 3). Potential structure-activity relationships (SAR) are discussed.     

Reduced respiratory-related evoked activity in subjects with obstructive sleep apnea syndrome.

Midlatency respiratory-related evoked potentials were measured during wakefulness by using a 60-electrode array placed over the cortical region of the scalp. We studied the responses evoked by 200-ms pressure pulses at -5 and -10 cmH(2)O applied at inspiratory onset and during control tests (no pressure applied) in 14 subjects with obstructive sleep apnea syndrome (OSAS) and 18 normal subjects. Wavelet decomposition was used to smooth and dissect the respiratory-related evoked potentials in frequency and time in 8 frequency bands. After denoising, selected wavelet scales were used to reconstruct the respiratory-related evoked potentials, which were quantified by using global field power estimates. The time course of the global field power activity in OSAS subjects compared with normal subjects was significantly depressed in the period 55-70 ms poststimulus onset, a time when afferent traffic from upper airway receptors arrives in normal subjects. The reduced evoked response in subjects with OSAS suggests that these subjects receive less afferent input from upper airway mechanoreceptors. This may reflect reduced sensitivity of mechanoreceptors or reduced mechanoreceptor stimulation due to decreased upper airway compliance during wakefulness in OSAS.