The effects of oral pseudoephedrine on nasal patency in the common cold: a double-blind single-dose placebo-controlled trial.

A placebo-controlled double-blind randomized trial was carried out to assess the efficacy of pseudoephedrine in relieving nasal congestion in the common cold. Fifty-four previously healthy persons who had a common cold for at least 5 days or less at the start of the study with moderate to severe nasal congestion were recruited, 52 completed the trial. Following a single dose of oral pseudoephedrine (60 mg capsule) or placebo, symptoms of congestion improved significantly compared with placebo at times 60, 90, 120, and 150 min after the dose. Total nasal minimum cross-sectional area and nasal volume measured by acoustic rhinometry increased significantly compared to placebo (P = 0.018 and P = 0.003, respectively) after the dose. There was no significant change in nasal area as measured by active posterior rhinomanometry after pseudoephedrine compared to placebo. We conclude that in the acute common cold, a single 60 mg dose of pseudoephedrine produces significant increases in the dimensions of the nasal cavity compared to placebo and this is associated with a reduction in the symptom of congestion.

Endothelin-1 and insulin activate the steady-state voltage dependent R-type Ca2+ channel in aortic smooth muscle cells via a pertussis toxin and cholera toxin sensitive G-protein.

In single rabbit aortic smooth muscle cells, and at a concentration known to induce a maximum sustained increase of intracellular Ca2+ via activation of the steady-state voltage dependent R-type Ca2+ channels, endothelin-1 (10(-7) M) and insulin (80 microU/ml) were found to induce a sustained increase in cytosolic free Ca2+ ([Ca]i) levels that was significantly attenuated by pre-treatment with either pertussis toxin (PTX), cholera toxin (CTX) or removal of extracellular Ca2+. However, both PTX and CTX failed to inhibit the sustained depolarization-evoked sustained Ca2+ influx and [Ca]i elevation via activation of the R-type Ca2+ channels. Moreover, ET-1 and insulin-evoked sustained increases in Ca2+ influx were not attenuated by the selective PKC inhibitor, bisindolylmaleimide (BIS), or the specific L-type Ca2+ channel blocker, nifedipine, but were completely reversed by the R-type Ca2+ channel blocker, (-) PN 200-110 (isradipine). These data suggest that both insulin and ET-1 activate the nifedipine-insensitive but isradipine-sensitive steady state voltage dependent R-type Ca2+ channels present on rabbit VSMCs and these channels are directly coupled to PTX and CTX sensitive G protein(s).

Bradykinin activates R-, T-, and L-type Ca2+ channels and induces a sustained increase of nuclear Ca2+ in aortic vascular smooth muscle cells.

The mechanism(s) fo Ca2+ entry stimulated by bradykinin (BK) and the receptor subtype responsible for this effect were examined in human and rabbit aortic vascular smooth muscle cells (VSMCs). Using the whole-cell voltage clamp technique, BK (10(-6)M) significantly (p < 0.05) increased both T- and L-type Ca2+ currents (ICa) in rabbit aortic VSMCs. Using the fura-2 total intracellular Ca2+ ([Ca]i) measurement technique, BK (10(-6) M) induced a transient increase of [Ca]i followed by a sustained component. Pretreatment of rabbit VSMCs with sarcoplasmic reticulum (SR) Ca2+ releaser caffeine (1-5 mM) significantly decreased the BK-induced transient increase of [Ca]i without affecting the sustained component induced by this hormone. This sustained phase was blocked by extracellular application of the Ca2+ chelator EGTA. Using the fluo-3 confocal microscopy Ca2+ measurement technique to localize cytosolic ([Ca]c) and nuclear ([Ca]n) free Ca2+ distribution, the resting sustained concentration of Ca2+ in the cytoplasm of rabbit and human aortic VSMCs was less than that in the nucleus. BK (10(-7) M) induced a nonsignificant sustained increase of [Ca]c but significant (p < 0.05) sustained increase of [Ca]n that was reversed but not prevented by the specific B1 receptor antagonist R126 (10(-6) M) as well as by the B2 receptor antagonist R817 (10(-6) M). In both VSMC preparations, the specific B1 agonist R211 (10(-9) to 10(-7) M) rapidly induced a nonsignificant increase of [Ca]c but a significant (p < 0.05) sustained increase of [Ca]n that was prevented but not reversed by the B1 selective antagonist R126 (10(-6) M). The sustained increase of [Ca]c and [Ca]n induced by BK and B1 receptor agonist was blocked by extracellular application of EGTA. These results strongly suggest that B1 and probably B2 receptors are functional in human and rabbit aortic VSMCs. BK-induced transient increase of [Ca]i is mainly due to the stimulation of T- and L-type Ica as well as to Ca2+ release from caffeine- and ryanodine-sensitive Ca2+ pools. The sustained component induced by the hormone or the B1 agonist is mainly nuclear and is due to the stimulation of Ca2+ influx through the R-type Ca2+ channels that are present at the sarcolemma and the nuclear membranes.

Blockade of insulin sensitive steady-state R-type Ca2+ channel by PN 200-110 in heart and vascular smooth muscle.

The effect of high K+ concentration, insulin and the L-type Ca2+ channel blocker PN 200-110 on cytosolic intracellular free calcium ([Ca2+]i) was studied in single ventricular myocytes of 10-day-old embryonic chick heart, 20-week-old human fetus and rabbit aorta (VSM) single cells using the Ca(2+)-sensitive fluorescent dye, Fura-2 microfluorometry and digital imaging technique. Depolarization of the cell membrane of both heart and VSM cells with continuous superfusion of 30 mM [K+]o induced a rapid transient increase of [Ca2+]i that was followed by a sustained component. The early transient increase of [Ca2+]i by high [K+]o was blocked by the L-type calcium channel antagonist nifedipine. However, the sustained component was found to be insensitive to this drug. PN 200-110 another L-type Ca2+ blocker was found to decrease both the early transient and the sustained increase of [Ca2+]i induced by depolarization of the cell membrane with high [K+]o. Insulin at a concentration of 40 to 80 microU/ml only produced a sustained increase of [Ca2+]i that was blocked by PN 200-110 or by lowering the extracellular Ca2+ concentration with EGTA. The sustained increase of [Ca2+]i induced by high [K+]o or insulin was insensitive to metabolic inhibitors such as KCN and ouabain as well to the fast Na+ channel blocker, tetrodotoxin and to the increase of intracellular concentrations of cyclic nucleotides. Using the patch clamp technique, insulin did not affect the L-type Ca2+ current and the delayed outward K+ current. These results suggest that the early increase of [Ca2+]i during depolarization of the cell membrane of heart and VSM cells with high [K+]o is due to the opening and decay of an L-type Ca2+ channel. However, the sustained increase of [Ca2+]i during a sustained depolarization is due to the activation of a resting (R) Ca2+ channel that is insensitive to lowering [ATP]i and sensitive to insulin.

Apamin, a highly potent fetal L-type Ca2+ current blocker in single heart cells.

Apamin, a bee venom polypeptide, was reported to block the naturally occurring Ca2+ slow action potentials (APs) in cultured cell reaggregates from old chick hearts [Bkaily, G. et al. Am. J. Physiol. 248 (Heart Circ. Physiol. 17): H961-H965, 1985] as well as the tetrodotoxin (TTX)- and Mn(2+)-insensitive slow Na+ current in young embryonic chick heart cells (Bkaily, G. In Vitro Toxicology. Academic, In press; Bkaily et al. J. Mol. Cell. Cardiol. 23: 25-39, 1991). With the use of the whole cell voltage-clamp technique in single ventricular cells from 10-day-old chick embryos and 17- to 20-wk-old human fetuses, two types of Ca2+ currents (ICa), T and L, were found. These two types of slow inward current in both heart preparations were nearly similar in their voltage, kinetics, and pharmacology. Apamin, a slow Ca2+ action potential blocker in old embryonic chick heart, was found to block the L-type ICa (IL) in a dose-dependent manner without affecting the T-type ICa in both heart cell preparations. The blockade of the IL by apamin was completely reversible upon washout with apamin-free solution. Therefore, when compared with nifedipine or to PN 200-110, apamin seems to be a highly potent L-type Ca2+ channel blocker in heart cells.

Analysis of strength and endurance in fast twitch skeletal muscle after an acute in vitro exposure to an anabolic steroid.

Forty extensor digitorum longus (EDL) muscles from adult rats were used in an in vitro experiment to determine the effects of an anabolic steroid on strength and endurance. Experimental muscles, exposed to a 1 x 10(-3) M testosterone propionate, were compared in strength and endurance to control muscles. Multivariate repeated measures analyses of variance and covariance, and univariate pooled variance t-tests showed the control muscles to be significantly (alpha less than or equal to 0.025) stronger and more durable than the steroid exposed muscles. The results failed to support the notion that steroids enhance contractile strength and endurance in skeletal muscle. It is speculated that steroids may block important mechanisms of muscle contraction, resulting in a decrease in force production.

Ontogeny and sexual dimorphism of the sonic motor nucleus in the oyster toadfish.

Male oyster toadfish, Opsanus tau, produce a courtship boatwhistle call and have a larger sound-producing organ than females, who do not boatwhistle . We investigated the possibility of sexual dimorphism in ontogeny of the sonic motor nucleus (SMN) of the toadfish. Brain weight increases for life though the increase decelerates with increasing fish weight. Neuron number, ranging from 760 to 2,888 in the SMN, increases rapidly to about 3 years, more slowly to about 8 years, and then levels off. There are no sexual differences in regressions of brain weight and SMN neuron number against fish size or age. Neuronal soma size in the SMN increases from 8 to 35 micron in average diameter and 67 to 916 micron2 in area over a period of at least 7 years. Males have larger neurons than females (P less than .01). However, males can be separated by inspection into populations with large and small soma sizes. Neuron size is not different between females and males with small somas. Neurons in males with large somas are larger than neurons in females and neurons in males with small somas. Such male dimorphism is reminiscent of other behavioral and morphological dimorphisms , which have led to characterization of males into territorial and satellite forms in certain mating systems.