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Background: Common cold is one of the most prevalent conditions that family doctors encounter. One of the first symptoms to occur is nasal congestion, which can have a negative impact on daily life and prompts many patients to seek treatment for relief. Xylometazoline nasal spray (Otrivin*) is a topical decongestant that has been used successfully for many years and is generally recognized as an effective and safe therapy. However, most studies have investigated its clinical efficacy in healthy patients and few have included patients with common cold. *Otrivin® is a registered trademark of Novartis AG, Basel, Switzerland. Scope: To review the published clinical efficacy and safety of xylometazoline alone and in combination in the management of nasal congestion in patients with common cold. Literature searches of PubMed and the Cochrane Library were conducted to obtain published open or blinded, randomized, placebo- or active-controlled studies on the use of xylometazoline hydrochloride for the symptomatic relief of nasal congestion in patients with common cold. Searches included papers published in English only, up to September 2009. Findings: Despite the small number of studies identified in common cold (n = 4), as per search criteria defined, intranasal xylometazoline quickly and effectively relieved nasal congestion. When used alone, xylometazoline had a clinically relevant decongestant effect that was significantly superior for up to 10 hours compared with placebo. The superior decongestant effect with xylometazoline led to high patient satisfaction with treatment. When used in combination with ipratropium bromide, nasal congestion and rhinorrhoea were treated simultaneously, leading to significantly higher patient general impression scores compared with either agent used alone. Xylometazoline was well tolerated, with generally mild to moderate nasal-related side effects (e.g. epistaxis in 3.4% of patients, and blood-tinged mucus in 10–26% of patients) that were easily resolved; the most frequently reported non-nasal AEs were headache (3.4%) and period pain (10.3%); no cases of sedation were reported. As expected, no rhinitis medicamentosa or rebound congestion was noted with short-term use (

Protein tyrosine phosphatase-alpha (PTPalpha) is a widely expressed receptor-type phosphatase that functions in multiple signaling systems. The actions of PTPalpha can be regulated by its phosphorylation on serine and tyrosine residues, although little is known about the conditions that promote PTPalpha phosphorylation. In this study, we tested the ability of several extracellular factors to stimulate PTPalpha tyrosine phosphorylation. The growth factors IGF-I and acidic FGF induced the highest increase in PTPalpha phosphorylation at tyrosine 789, followed by PMA and lysophosphatidic acid, while EGF had little effect. Further investigation of IGF-I-induced PTPalpha tyrosine phosphorylation demonstrated that this occurs through a novel Src family kinase-independent mechanism that does not require focal adhesion kinase, phosphatidylinositol 3-kinase, or MEK. We also show that PTPalpha physically interacts with the IGF-I receptor. In contrast to IGF-I-induced PTPalpha phosphorylation, this association does not require IGF-I. The interaction of PTPalpha and the IGF-I receptor is independent of PTPalpha catalytic activity, and expression of exogenous PTPalpha does not promote IGF-I receptor tyrosine dephosphorylation, indicating that PTPalpha does not act as an IGF-I receptor phosphatase. However, PTPalpha mediates IGF-I signaling, because IGF-I-stimulated fibroblast migration was reduced by approximately 50% in cells lacking PTPalpha or in cells with mutant PTPalpha lacking the tyrosine 789 phosphorylation site. Our results suggest that PTPalpha tyrosine phosphorylation can occur in response to diverse stimuli and can be mediated by various tyrosine kinases. In the case of IGF-I, we propose that IGF-I-induced tyrosine 789 phosphorylation of PTPalpha, possibly catalyzed by the PTPalpha-associated IGF-I receptor tyrosine kinase, is required for efficient cell migration in response to this growth factor.

Background Xylometazoline is a nasal decongestant spray that constricts nasal blood vessels and increases nasal airflow, enabling patients with a blocked nose to breathe more easily. The purpose of this study was to characterize objectively and subjectively the decongestant and additional effects of xylometazoline in the common cold. Methods A double-blind, placebo-controlled, parallel group study was performed. Patients with a common cold (n = 61) were treated with xylometazoline 0.1% (n = 29) or placebo (saline solution; n = 32; 1 spray three times a day for up to 10 days). The primary objective was to determine the decongestant effect (nasal conductance); the secondary objectives were to determine the peak subjective effect (visual analog scale), duration of relief of nasal congestion, total and individual cold symptoms and general well-being (patients’ daily diary), and adverse events (AEs). Results The decongestant effect of xylometazoline was significantly greater than placebo, as shown by the nasal conductance at 1 hour (384.23 versus 226.42 cm3/s; p ≤ 0.0001) and peak subjective effect (VAS, 20.7 mm versus 31.5 mm; p = 0.0298). Nasal conductance was significantly superior for up to 10 hours (p = 0.0009) and there was a trend in favor of xylometazoline for up to 12 hours (not statistically significant). Xylometazoline significantly improved total and some individual common cold symptoms scores (p < 0.05), leading to significantly greater patient general evaluation and satisfaction with treatment (p < 0.05). Nineteen AEs were reported: 8 with xylometazoline (all mild-moderate) and 11 with placebo (1 severe). Conclusion Xylometazoline is an effective and well-tolerated decongestant nasal spray that significantly relieved nasal congestion compared with placebo in the common cold and provided long-lasting relief with just 1 spray, helping patients to breathe more easily for a longer period of time.

Apoptosis repressor with caspase recruitment domain (ARC), an anti-apoptotic protein, is highly expressed in differentiated heart and skeletal muscle. Apoptosis and differentiation share numerous common pathways; therefore, we examined the impact of ARC on H9c2-myoblast differentiation. We demonstrate that ARC expression levels increase and stabilize upon differentiation. ARC-overexpression in pre-differentiated H9c2-cells suppresses differentiation; indicated by increased myotube formation, nuclear fusion and expression of the differentiation markers myogenin and troponin-T. ARC-overexpression inhibited myoblast differentiation associated caspase-3 activation, suggesting ARC inhibits myogenic differentiation through caspase inhibition. In summary, we show a novel role for ARC in the regulation of muscle differentiation.

BACKGROUND Plant sterol esters reduce cholesterol absorption and lower circulating blood cholesterol concentrations when incorporated into the habitual diet. OBJECTIVE This randomized, double-blind, 3-group parallel, controlled study evaluated the influence of esterified plant sterols on serum lipid concentrations in adults with mild-to-moderate primary hypercholesterolemia. DESIGN Subjects incorporated a conventional 50%-fat spread into a National Cholesterol Education Program Step I diet for a 4-wk lead-in period, followed by a 5-wk intervention period of the diet plus either a control reduced-fat spread (40% fat; n = 92) or a reduced-fat spread enriched with plant sterol esters to achieve intakes of 1.1 g/d (n = 92; low-sterol group) or 2.2 g/d (n = 40; high-sterol group). RESULTS Subjects in the low- and high-sterol groups who consumed > or = 80% of the scheduled servings (per-protocol analyses) had total cholesterol values that were 5.2% and 6.6% lower, LDL-cholesterol values that were 7.6% and 8.1% lower, apolipoprotein B values that were 6.2% and 8.4% lower, and ratios of total to HDL cholesterol that were 5.9% and 8.1% lower, respectively, than values for the control group (P < 0.001 for all). Additionally, triacylglycerol concentrations decreased by 10.4% in the high-sterol group. Serum concentrations of fat-soluble vitamins and carotenoids were generally within reference ranges at baseline and postintervention. Serum plant sterol concentrations increased from baseline (0.48% of total sterol by wt) to 0.64% and 0.71% by wt for the low- and high-sterol groups, respectively (P < 0.05 compared with control). CONCLUSION A reduced-fat spread containing plant sterol esters incorporated into a low-fat diet is a beneficial adjunct in the dietary management of hypercholesterolemia.

Effects of butter and 2 types of margarine on blood lipid and lipoprotein concentrations were compared in a controlled diet study with 23 men and 23 women. Table spreads, added to a common basal diet, provided 8.3% of energy as fat. Diets averaged 34.6% of energy as fat and 15.5% as protein. Each diet was fed for 5 wk in a 3 x 3 Latin-square design. One margarine (TFA-M) approximated the average trans monoene content of trans fatty acid-containing margarines in the United States (17% trans fatty acids by dry wt). The other margarine (PUFA-M) was free of trans unsaturated fatty acids; it contained approximately twice the polyunsaturated fatty acid content of TFA-M (49% compared with 27% polyunsaturated fatty acids). The tub-type margarines had similar physical properties at ambient temperature. Fasting blood lipids and lipoproteins were determined in 2 samples taken from the subjects during the fifth week of each dietary treatment. Compared with butter, total cholesterol was 3.5% lower (P=0.009) after consumption of TFA-M and 5.4% lower (P< 0.001) after consumption of PUFA-M. Similarly, LDL cholesterol was 4.9% lower (P=0.005) and 6.7% lower (P< 0.001) after consumption of TFA-M and PUFA-M, respectively. Neither margarine differed from butter in its effect on HDL cholesterol or triacylglycerols. Thus, consumption of TFA-M or PUFA-M improved blood lipid profiles for the major lipoproteins associated with cardiovascular risk when compared with butter, with a greater improvement with PUFA-M than with TFA-M.

Background: Many over-the-counter medications are available to treat common cold nasal symptoms, but patients may be unsure which one to use. Methods: This review assesses two widely used intranasal treatments for nasal congestion and rhinorrhea in the common cold: xylometazoline hydrochloride and ipratropium bromide. Results: Xylometazoline quickly and effectively relieves nasal congestion, while ipratropium is effective at reducing rhinorrhea. When used in combination, a novel approach to treatment, nasal congestion and rhinorrhea are treated simultaneously, providing effective relief from two of the most troublesome symptoms of the common cold Both drugs are well tolerated, with only mild to moderate, nasal-related side effects. Conclusions: The efficacy and safety of the combination product suggest that it should be used first-line in the symptomatic relief of nasal congestion and rhinorrhea, before the use of oral treatments.

We studied the interrelationship of diet and plant sterols (PS) on plasma lipids, lipoproteins and carotenoids. Mildly hypercholesterolemic men (n = 13) and postmenopausal women (n = 9) underwent four randomized, crossover, double-blind, controlled feeding periods of 23 days each. The design consisted of two levels of PS (0 and 3.3 g/day) and two background diets having fat content either typical of the American diet (total and saturated fat at 33.5 and 13.2% of energy, respectively), or a Step 1 type of diet (total and saturated fat at 26.4 and 7.7% of energy, respectively). Plasma total cholesterol (TC), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, Apo A1 and Apo B were 4.3, 5.3, 4.5, 2.8 and 2.5% lower, respectively (P ≤ 0.0001

Protein-tyrosine phosphatase-alpha (PTPalpha) activates Src family kinases (SFKs) to promote the integrin-stimulated early autophosphorylation of focal adhesion kinase (FAK). We report here that integrin stimulation induces tyrosine phosphorylation of PTPalpha. PTPalpha was dephosphorylated upon fibroblast detachment from the substratum and rephosphorylated when cells were plated on the integrin ligand fibronectin. alpha PTP phosphorylation occurred at Tyr789 and required SFKs (Src or Fyn/Yes), FAK, and an intact cytoskeleton. It also required active PTPalpha or constitutively active Src. These observations indicate that PTPalpha activates SFKs and that the subsequently activated SFK.FAK tyrosine kinase complex in turn phosphorylates PTPalpha. Reintroduction of wild-type PTPalpha or unphosphorylatable PTPalpha(Y789F) (but not inactive PTPalpha) into PTPalpha-null fibroblasts restored defective integrin-induced SFK activation, FAK phosphorylation, and paxillin phosphorylation. PTPalpha(Y789F) and inactive PTPalpha could not rescue delayed actin stress fiber assembly and focal adhesion formation or defective cell migration. This study distinguishes two roles of PTPalpha in integrin signaling: an early role as an activator of SFKs and FAK with no requirement for PTPalpha phosphorylation and a later downstream role in cytoskeleton-associated events for which PTPalpha phosphorylation at Tyr789 is essential.

Twelve obligate heterozygotes from two kindreds were ascertained through phytosterolemic probands homozygous for molecular defects in the ATP binding cassette (ABC) half transporter, ABCG8. The response of these heterozygotes to a Step 1 diet low in fat, saturated fat, and cholesterol, and to 2.2 g daily of plant sterols (as esters) was determined in Protocol I (16 weeks) and Protocol II (28 weeks) during three consecutive feeding periods: Step 1/placebo spread; Step 1/plant sterol spread; and Step 1/placebo spread (washout). At baseline, half the heterozygotes had moderate dyslipidemia and one-third had mildly elevated campesterol and sitosterol levels. On the Step 1/placebo spread, mean LDL cholesterol decreased significantly, 11.2% in Protocol I (n = 12), and 16.0% in Protocol II (n = 7). Substitution with plant sterol spread produced a significant treatment effect on LDL levels in Protocols I and II. Conversely, the mean levels of campesterol and sitosterol increased 119% and 54%, respectively, during the use of plant sterol spread for 6 weeks in Protocol I, an effect mirrored for 12 weeks in Protocol II. During the placebo spread washouts, LDL levels increased, while those of plant sterols decreased to baseline levels in both protocols. In conclusion, phytosterolemic heterozygotes respond well to a Step 1 diet, and their response to a plant sterol ester challenge appears similar to that observed in normals.

The ability of plant sterol esters (PSE) in salad dressing to modify plasma lipids and carotenoids was determined in 26 men and 27 women fed controlled, weight-maintaining, isocaloric diets. Diets contained typical American foods that provided 32% of energy from fat. Dressings contained 8 g (ranch) or 4 g (Italian) of fat per serving. PSE (3.6 g/d) were provided in two servings/d of one of the dressings. Diets with ranch or Italian dressing without and with PSE were fed for 3 wk/diet and crossed over randomly within dressings. Diets were adjusted to similar fat and fatty acid concentrations. Type of salad dressing did not affect plasma lipids, lipoproteins, carotenoids, or fat-soluble vitamins (P0.05). Switching from a self-selected baseline diet to the control diet resulted in reduction in low density lipoprotein (LDL) cholesterol of 7.9%, a decrease in high density lipoprotein (HDL) cholesterol of 3.1%, and a decrease in triglycerides (TG) of 9.3%. Consumption of 3.6 g of PSE resulted in further decreases in LDL cholesterol (9.7%) and TG (7.3%) but no additional change in HDL cholesterol. Total plasma carotenoids decreased 9.6% with PSE. An automated stepwise procedure was developed to produce candidate mixed models relating plasma carotenoid response to PSE. These models adjusted for preintervention plasma carotenoid levels and effects of diets on blood lipids. There were significant decreases in beta-carotene, alpha-carotene, and beta-cryptoxanthin (females only) not associated with changes in plasma lipids. Plasma carotenoids on all diets remained within normal ranges. We conclude that low-fat foods, such as salad dressings, are effective carriers for PSE.

Earlier work has shown that increasing concentration of palmitic acid at the sn-2 position of a fat enhances the atherogenic properties of that fat. This effect has been observed with lard, tallow, cottonseed oil, and palm oil. In the experiment reported here, we have studied the atherogenic effects of four synthetic fats fed to rabbits as 58% (w/w) of the total fat (15%) (w/w) of a semipurified diet containing 0.05% cholesterol. The fats being tested were: 1,3-stearoyl-2-oleoylglycerol (SOS); 1,2-stearoyl-3-oleoylglycerol (SSO); 1,3-palmitoyl-2-oleoylglycerol (POP); and 1,2-palmitoyl-3-oleoylglycerol (PPO). After 20 wk on diet there were no differences among the groups in weight gain, liver weight, serum, or liver lipids. These data are consistent with our previous findings. There were significant differences in atherosclerosis. The most severe atherosclerosis was observed in group PPO and the least in groups SSO and POP. Severity of atherosclerosis was graded visually on a 0-4 scale. The average atherosclerosis [(aortic arch and thoracic aorta) divided by 2] was: SOS--1.35; SSO--0.97; POP--0.83; and PPO--1.80. Fecal fat excretion (an indicator of fat absorption) was higher in the two groups fed the stearic acid-rich fats and lower in groups fed the palmitic acid-rich fats. There were no differences in low density lipoprotein particle size. The results confirm previous findings concerning the increased atherogenicity of fats bearing palmitic acid at the sn-2 position. The mechanism underlying these observations is moot but may, in part, reflect greater absorption of the atherogenic fat.

Amphotericin-B, a potent antifungal agent, was found to form an inclusion complex with γ-cyclodextrin both in aqueous solution and in the solid state. Complex formation in the solution state was studied using phase solubility and spectral shift methods. The increase in the solubility of amphotericin-B with added γ-cyclodextrin was observed to show a positive deviation from linearity (type A p phase diagram) indicating the presence of more than one complex in the system. In the γ-cyclodextrin concentration range 0–0.5 M, two complexes, 1:1 and 1:2, with stability constants of 462 and 42 M(−1), respectively, were identified. Using the spectral method, the formation constant for the 1:1 inclusion complex was determined to be 422 M −1 in 25% v/v methanol. A solid complex of amphotericin-B with γ-cyclodextrin was prepared by using the techniques of lyophilization, kneading and coprecipitation. The solid complex prepared showed improved dissolution as well as enhanced amphotericin-B stability in solution over free amphotericin-B.