Efficacy of a single evening dose of syrup containing paracetamol, dextromethorphan hydrobromide, doxylamine succinate and ephedrine sulfate in subjects with multiple common cold symptoms.

OBJECTIVE: The aim of this study was to evaluate the efficacy of a single night-time dose of a syrup containing paracetamol, dextromethorphan hydrobromide, doxylamine succinate and ephedrine sulfate in subjects with multiple cold symptoms. MATERIALS: A syrup containing 15 mg dextromethorphan hydrobromide, 7.5 mg doxylamine succinate, 600 mg paracetamol and 8 mg ephedrine sulfate (Wick MediNait produced by WICK Pharma, Germany, a subsidiary of Procter & Gamble GmbH; test syrup) or placebo (placebo syrup) for oral administration. METHODS: This was a randomized, double-blind, placebo-controlled, multi-center, parallel design study. At enrollment, eligible subjects had to have at least moderate nasal congestion and a runny nose, at least mild cough and at least mild pain with one or more of the following: sore throat, sore chest, headache or body pain/aches. Subjects were randomized into either Group T (test syrup) or Group P (placebo syrup). On the evening of enrollment, subjects rated baseline symptoms, ingested the assigned study product and completed symptom-relief assessments at 3 hours post-dosing. Within one hour of awakening the following morning, subjects completed night-time symptom relief and sleep satisfaction assessments. All symptoms were recorded using an Interactive Voice Response system. Treatment comparisons were made after adjusting for the severity of baseline symptom using analysis of covariance. RESULTS: Of 485 subjects who took the study product, 432 (224 in Group T; 208 in Group P) were evaluable for analysis. For the primary endpoint (composite of nasal congestion/runny nose/cough/pain relief scores 3 hours post-dosing), subjects in Group T had clinically and statistically significantly greater relief than Group P (p = 0.0002). Each individual symptom score also showed statistically significant improvement at this time point (p < or = 0.017). The next morning, Group T continued to show clinically and statistically significant benefits over Group P on the composite score and each of the individual symptoms (p < or = 0.003). Evidence of benefit with the test syrup was also seen in the higher score for overall night-time relief (p < 0.0001) and greater satisfaction on sleep (p = 0.002) compared to placebo syrup. Improvement in individual symptoms after 3 hours was obtained in 16-42% more subjects in Group T than in Group P, whereas the percentage of subjects in Group T having Good or Very Good relief the morning after dosing increased by 25-68% compared to subjects in Group P. 14 subjects (5 in Group T; 9 in Group P) reported AEs but none of these occurred with an incidence greater than 1%. There were no serious AEs. CONCLUSIONS: The results confirm the multisymptom benefit of a single dose of the test syrup containing paracetamol, dextromethorphan hydrobromide, doxylamine succinate and ephedrine sulfate and support its role as an effective and convenient therapy for symptoms of nasal congestion, runny nose, cough and pain/body aches associated with the common cold and for increasing sleep quality disturbed by the common cold.

Cholesterol-lowering effects of psyllium intake adjunctive to diet therapy in men and women with hypercholesterolemia: meta-analysis of 8 controlled trials.

BACKGROUND: Soluble fibers, including those from psyllium husk, have been shown to augment the cholesterol-lowering effects of a low-fat diet in persons with hypercholesterolemia. As evidence of this, the US Food and Drug Administration recently authorized the use of health claims on food products containing soluble fiber from psyllium that state that they are associated with a decreased risk of coronary heart disease. OBJECTIVE: This meta-analysis was conducted to more precisely define the hypolipidemic effects and safety of psyllium when used adjunctive to a low-fat diet in men and women with hypercholesterolemia. DESIGN: The 8 studies in the meta-analysis included a total of 384 and 272 subjects receiving psyllium or cellulose placebo, respectively. All studies evaluated the hypocholesterolemic effects of 10.2 g psyllium/d adjunctive to a low-fat diet for >/=8 wk in individuals with mild-to-moderate hypercholesterolemia after a low-fat diet lead-in phase lasting >/=8 wk. The safety and adverse events associated with psyllium consumption were summarized from pooled data of 19 clinical studies ranging from 6 wk to 6 mo in duration. RESULTS: Consumption of 10.2 g psyllium/d lowered serum total cholesterol by 4% (P < 0.0001), LDL cholesterol by 7% (P < 0.0001), and the ratio of apolipoprotein (apo) B to apo A-I by 6% (P < 0.05) relative to placebo in subjects already consuming a low-fat diet, with no effect on serum HDL or triacylglycerol concentrations. CONCLUSIONS: Psyllium supplementation significantly lowered serum total and LDL-cholesterol concentrations in subjects consuming a low-fat diet. Psyllium is well tolerated and safe when used adjunctive to a low-fat diet in individuals with mild-to-moderate hypercholesterolemia.

Additive hypocholesterolemic effect of psyllium and cholestyramine in the hamster: influence on fecal sterol and bile acid profiles.

Recent findings suggest that the effects of cholestyramine and psyllium in combination could be additive for cholesterol-lowering. We therefore examined the effect of both agents, alone and in combination, on lipoprotein cholesterol and neutral and acidic steroid excretion in the hamster. Animals (n = 8/group) were fed for 21 days, either a basal chow diet supplemented with 10% palm oil and 0.2% cholesterol, or one of four treatments consisting of the basal diet plus: 5.5% cellulose; 5% psyllium with 0.5% cellulose; 0.5% cholestyramine with 5% cellulose; or 5% psyllium with 0.5% cholestyramine. Psyllium and cholestyramine both had significant hypocholesterolemic effects, but in combination produced additive reductions in lipoprotein and hepatic cholesterol. Psyllium, cholestyramine, and the combination increased total bile acid excretion by 26%, 57%, and 79%, respectively. Psyllium affected only unconjugated bile acid excretion while cholestyramine also increased the excretion of conjugated and primary bile acids. Neither agent, nor the combination, affected fecal neutral sterol excretion. We conclude that, while both agents lower cholesterol by a mechanism of increased bile acid excretion, these studies indicate that psyllium does not bind bile acids in vivo and lend further support for the concomitant use of these agents for cholesterol-lowering.

Bismuth subsalicylate suppression of Helicobacter pylori in nonulcer dyspepsia: a double-blind placebo-controlled trial.

Gastritis caused by Helicobacter pylori (HP) is common in patients with nonulcer dyspepsia (NUD), but an etiologic relationship between the histologic lesion and clinical symptoms is unproven. HP is inhibited by bismuth subsalicylate (BSS), a traditional remedy for dyspeptic complaints. The aim of this study was to assess the short- and long-term effects of BSS on HP, gastritis, and symptoms in patients with NUD. One hundred twenty-six patients with NUD who were shown to be infected with H. pylori (HP+) were enrolled. There was a two-week placebo run-in period to eliminate placebo responders. Fifty patients remained symptomatic and were randomly assigned to therapy with either BSS liquid or a matching placebo. EGD, biopsy, and clinical evaluations were performed at entry, at week 5 (end of therapy), at week 9 (four weeks after therapy), or at time of symptomatic relapse. Twenty-seven patients received placebo and 23 patients received BSS. BSS suppressed H. pylori in 15/23 patients (65%) and eradicated it in one patient, whereas the placebo had no effect on H. pylori. Gastritis improved during therapy with BSS but relapsed by week 9. There was no significant change in level of dyspeptic symptoms during or after treatment, although one month after the end of treatment, the patients in the BSS group consistently had lower symptom scores and fewer symptomatic days for all symptoms measured. The study confirms that BSS given for three weeks suppresses but does not usually eradicate H. pylori. Such short-term suppression of H. pylori heals gastritis but does not result in clinical improvement.

Simple noninvasive method to test efficacy of drugs in the eradication of Helicobacter pylori infection: the example of combined bismuth subsalicylate and nitrofurantoin.

Eradication of Helicobacter pylori infections has proved to be difficult. There is a need both for improved therapies and for ways to rapidly identify therapies that show sufficient promise to be worth pursuing. The objectives of this study were to evaluate the value of a therapeutic regimen of a bismuth salt plus nitrofurantoin for eradication of infection by H. pylori and to determine the validity/utility of the urea breath test in monitoring the progress of a clinical trial. We used an 80% eradication rule to define a promising therapeutic regimen, i.e., a regimen that eradicated the infection (no evidence of infection by H. pylori 4 wk after termination of therapy) in at least 80% of the individuals treated. Eighteen men (median age 38) with documented infection by H. pylori completed the study. At the end-of-study evaluation, H. pylori infection was eradicated (negative urea breath test, culture, and histology) in only one of 18 (5.5%) subjects; 15 were positive by the urea breath test, 16 by culture, 15 by Warthin-Starry stain, and 16 by the presence of acute-on-chronic inflammation. Using the 80% eradication rule, any one of these tests alone would have identified that the combination of antimicrobials tested was not effective in the eradication of the infection. We conclude that the urea breath test is a simple, noninvasive, cost-effective method to separate promising from unpromising candidate therapies and for the evaluation of new therapeutic concepts.

Effects of nonapeptide antagonists on oxytocin- and arginine-vasopressin-induced analgesia in mice.

Several peptides, including arginine-vasopressin (AVP), neurotensin, and substance P, produce analgesia that is not mediated by opiate systems. Using the hot plate test, we studied the analgesic effects of intracisternal (i.c.) administration of various doses of the nonapeptide oxytocin (OXY) in Swiss-Webster mice. We found that OXY (1-4 micrograms) significantly increased the latency of animals to jump or lick their paws after placement on a hot plate. This effect was not blocked by naloxone pretreatment, which suggests that it is not opiate dependent. Using the hot plate test, we confirmed that AVP (1 and 4 micrograms) also produces analgesia. We then studied the analgesia produced by OXY and by AVP using 3 nonapeptide analogues with antagonist properties: [Pen1, LpMePhe2, Thr4, Orn8]OXY (PLMPTO-OXY) that has anti-oxytocic properties in the uterine contraction assay, d(CH2)5Tyr(Me)AVP(dTM-AVP) which antagonizes the antidiuretic properties of AVP and d(CH2)5D-Ile2,Abu4-AVP (dIA-AVP) which antagonizes the vasopressor effects of AVP. Simultaneous administration of PLMPTO-OXY completely blocked the analgesia produced by OXY whereas the antidiuretic antagonist dIA-AVP partially blocked OXY-induced analgesia and dTM-AVP had no effect. None of the antagonists used blocked AVP-induced analgesia. We concluded that the neural systems mediating the analgesic effects of i.c. OXY differ from those for AVP.

Alpha 1-adrenergic regulation of TSH-stimulated cyclic AMP accumulation in rat thyroid cells.

Addition of epinephrine to cultured FRTL-5 rat thyroid cells led to a concentration-dependent reduction of TSH- and forskolin-stimulated cAMP accumulation. Clonidine, which preferentially activates the alpha 2-adrenoreceptor, had no effect on cAMP levels. The reduction of cAMP levels by epinephrine was selectively blocked by prazosin, an alpha 1-adrenoreceptor antagonist, but not by yohimbine, an alpha 2-adrenoreceptor antagonist. Pretreatment of FRTL-5 cells with pertussis toxin failed to abolish the inhibitory effect of epinephrine on cAMP accumulation. The bioactivity of the pertussis toxin preparation in this cell line was verified by its ability to ADP-ribosylate the alpha-subunit of the inhibitory guanine nucleotide regulatory protein, Ni, as well as its ability to abolish the inhibitory effect of N6-[L-2-phenylisopropyl]-adenosine on TSH-stimulated cAMP formation. The inhibitory effect of epinephrine on cAMP levels was dependent on Ca2+ and was reversed by 3-isobutyl-1-methylxanthine. Taken together, these results suggest that epinephrine reduces cAMP levels via alpha 1-adrenoreceptors. The failure of pertussis toxin to abolish this alpha-adrenergic effect is consistent with the conclusion that epinephrine-induced attenuation of cAMP accumulation occurs through activation of a Ca2+-calmodulin-sensitive phosphodiesterase and does not involve Ni or Ni-like proteins.