Lobeline inhibits nicotine-evoked [(3)H]dopamine overflow from rat striatal slices and nicotine-evoked (86)Rb(+) efflux from thalamic synaptosomes.

The present study evaluated the interaction of lobeline with neuronal nicotinic acetylcholine receptors using two in vitro assays, [(3)H] overflow from [(3)H]dopamine ([(3)H]DA)-preloaded rat striatal slices and (86)Rb(+) efflux from rat thalamic synaptosomes. To assess agonist interactions, the effect of lobeline was determined and compared to S(-)-nicotine. To assess antagonist interactions, the ability of lobeline to inhibit the effect of S(-)-nicotine was determined. Both S(-)-nicotine (0.1-1 microM) and lobeline (>1.0 microM) evoked [(3)H] overflow from superfused [(3)H]DA-preloaded striatal slices. However, lobeline-evoked [(3)H] overflow is mecamylamine-insensitive, indicating that this response is not mediated by nicotinic receptors. Moreover, at concentrations (<1.0 microM) which did not evoke [(3)H] overflow, lobeline inhibited S(-)-nicotine (0.1-10 microM)-evoked [(3)H] overflow, shifting the S(-)-nicotine concentration-response curve to the right. S(-)-Nicotine (30 nM-300 microM) increased (EC(50) value=0.2 microM) (86)Rb(+) efflux from thalamic synaptosomes. In contrast, lobeline (1 nM-10 microM) did not evoke (86)Rb(+) efflux, and the lack of intrinsic activity indicates that lobeline is not an agonist at this nicotinic receptor subtype. Lobeline completely inhibited (IC(50) value=0.7 microM) (86)Rb(+) efflux evoked by 1 microM S(-)-nicotine, a concentration which maximally stimulated (86)Rb(+) efflux. Thus, the results of these in vitro experiments demonstrate that lobeline inhibits the effects of S(-)-nicotine, and suggest that lobeline acts as a nicotinic receptor antagonist.

Predilection for frailty remedial strategies among black and white seniors.

BACKGROUND: Frailty prevention and remedial programs based on exercise, hormone replacement, and vitamin supplementation are becoming available for use with older patients, but success of these programs depends largely on seniors' willingness to participate. METHODS: We evaluated preferences for specific aspects of these programs using a sample of 359 older persons recruited from potential delivery sites. Main effects and subgroup analyses were done. RESULTS: Subjects preferred stretching, chair-based, walking, and dynamic balance exercises over lifting weights, dancing, hormone and vitamin therapy; exercising alone in their own homes over exercising in groups; and vitamins over hormones. Preferences were affected to some extent by sex, race, recruitment site, and functional status. However, subjects' willingness even to consider exercise was rarely as high as the desired levels of participation set forth in Healthy People 2000. CONCLUSIONS: Physicians and public health authorities need to educate older persons about effective methods to prevent or treat frailty.

Ocular Halicephalobus (syn. Micronema) deletrix in a horse.

Ocular contents from a horse with a 4-week history of severe unilateral uveitis were submitted for histopathologic examination. A severe unilateral granulomatous chorioretinitis with intralesional Halicephalobus deletrix was diagnosed. The horse developed progressive neurologic signs several days following the surgery to remove ocular contents and implant a prosthesis and was subsequently euthanatized. A severe multifocal granulomatous encephalitis with intralesional H. deletrix, localized primarily to the optic chiasm, thalamus, and brain stem, was diagnosed from tissues acquired at necropsy. The other eye was not affected. This is the first report of ocular parasitism by H. deletrix and suggests possible systemic dissemination from a primary site in the eye.

Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis.

Leukotrienes, the biologically active metabolites of arachidonic acid, have been implicated in a variety of inflammatory responses, including asthma, arthritis and psoriasis. Recently a compound, MK-886, has been described that blocks the synthesis of leukotrienes in intact activated leukocytes, but has little or no effect on enzymes involved in leukotriene synthesis, including 5-lipoxygenase, in cell-free systems. A membrane protein with a high affinity for MK-886 and possibly representing the cellular target for MK-886 has been isolated from rat and human leukocytes. Here, we report the isolation of a complementary DNA clone encoding the MK-886-binding protein. We also demonstrate that the expression of both the MK-886-binding protein and 5-lipoxygenase is necessary for leukotriene synthesis in intact cells. Because the MK-886-binding protein seems to play a part in activating this enzyme in cells, it is termed the five-lipoxygenase activating protein (FLAP).

Identification and isolation of medicarpin and a substituted benzofuran as potent leukotriene inhibitors in an anti-inflammatory Chinese herb.

In a search for new inhibitors of leukotriene formation, a methylene chloride extract of the plant Dalbergia odorifera (Jiangxiang) was found to be a potent inhibitor of LTC4 formation in AB-CXBG Mct-1 mastocytoma cells. Following LH-20 and reverse phase HPLC chromatography, two compounds were isolated that had potent LTC4 inhibitory activity: medicarpin and 6-hydroxy-2-(2-hydroxy-4-methoxyphenyl) benzofuran (IV) with IC50s of 0.5 and 0.05 microM respectively. IV was shown to be a specific inhibitor of 5-lipoxygenase with an IC50 against the soluble rat enzyme of 0.08 microM, whereas it was inactive against cyclooxygenase. In neutrophils IV inhibited LTB4 production at comparable concentrations but had no effect on neutrophil degranulation or adhesion.

Abetalipoproteinemia. Report of an unusual patient.

Abetalipoproteinemia (Bassen-Kornzweig syndrome, acanthocytosis) was diagnosed at age 13 months in a black male. At age 13 months, the electroretinogram was nonrecordable and a pigmentary retinopathy was obvious with ophthalmoscopy. Following dietary modification and vitamin supplementation, the scotopic electroretinogram improved to about 30% of normal.