Fluticasone propionate compared with zafirlukast in controlling persistent asthma: a randomized double-blind, placebo-controlled trial

OBJECTIVE: The objective of our study was to compare the efficacy and safety of fluticasone propionate (an inhaled corticosteroid) with zafirlukast (a leukotriene modifier) for persistent asthma. STUDY DESIGN: In this randomized placebo-controlled, parallel-group, double-blind, double-dummy trial, patients underwent an 8- to 14-day run-in period followed by 12 weeks of treatment with inhaled fluticasone propionate (88 mg twice daily by metered-dose inhaler), oral zafirlukast (20 mg twice daily), or placebo. POPULATION: We included a total of 338 persistent asthma patients, 12 years of age or older, using short-acting b2-agonists alone. OUTCOMES: measured Efficacy outcomes included changes in pulmonary function, asthma symptoms, rescue albuterol use, nighttime awakenings due to asthma, and quality of life. Safety outcomes included asthma exacerbations, adverse events, and clinically significant laboratory test results. RESULTS: After 12 weeks of treatment, patients taking fluticasone propionate experienced significantly greater improvements in all clinical parameters (symptom scores, percentages of symptom-free and albuterol-free days, albuterol use, and nighttime awakenings) compared with patients taking zafirlukast (P <.05) or placebo (P <.05). Treatment with fluticasone propionate resulted in significantly greater improvements in pulmonary function compared with zafirlukast (P <.05) or placebo (P <.05). Fewer fluticasone propionate patients (4%) had an exacerbation requiring oral corticosteroids compared with those taking zafirlukast (12%) or placebo (10%). CONCLUSIONS: Inhaled fluticasone propionate is more effective than zafirlukast in controlling asthma symptoms, improving pulmonary function, and improving quality of life for patients who are symptomatic with the use of short-acting b2-agonists alone.     

Histopathology of the hypothalamus and the neural lobe of hypophysis in suicide victims

Histologic studies of the hypothalamus and neurohypophysis revealed that in young (17-35 y. o.) suicide victims, there are degenerative changes in the supraoptic and paraventricular nuclei and partial destruction by inflammation of the neurohypophysis. Simultaneously foci of micromalaic and the gatuering of azurophilic material in neuronal perikarya around the cerebral blood vessel and the leptomeninges. The degenerated neurones contain great vacuoles, often filled with lipofuscin. The probable pathogenic mechanism of the observed changes is discussed with its influence on mood-lowering leading to suicide.     

Regional cooling of the extracorporeal blood circuit: a novel anticoagulation approach for renal replacement therapy?

Objective  To test the hypothesis that cooling of blood in the extracorporeal circuit of continuous veno-venous hemofiltration (CVVH) enables to realize the procedure without the need of anticoagulation. Design  Experimental animal study. Methods  We developed the device for selective cooling of extracorporeal circuit (20°C) allowing blood rewarming (38°C) just before returning into the body. Twelve anesthetized and ventilated pigs were randomized to receive either 6 h of CVVH with application of this device (COOL; n = 6) or without it (CONTR; n = 6). Measurements  Before the procedure and in 15, 60, 180, 360 min after starting hemofiltration variables related to: (1) circuit patency [time to clotting (TC), number of alarm-triggered pump stopping (AS), venous and transmembranous circuit pressures (VP, TMP)], (2) coagulation status in the extracorporeal circuit [thrombin-antithrombin complexes (TAT_circ), thromboelastography (TEG)] and (3) animal status (hemodynamics, hemolysis and biochemistry) were assessed. Results  The patency of all circuits treated with selective cooling was well maintained within the observation period. By contrast, five of six sessions were prematurely clotted in the untreated group. As a result, the number of AS was significantly higher in the CONTR group. In-circuit thrombus generation in CONTR group was associated with a markedly increasing TAT_circ. TEG performed at 180 min of the procedure revealed a tendency to a prolonged initial clotting time and a significant decrease in clotting rate of in-circuit blood in the COOL group. No signs of repeated cooling/rewarming-induced hemolysis were observed in animals treated with “hypothermic circuit” CVVH. Conclusion  In this porcine model, regional extracorporeal blood cooling proved effective in preventing in-circuit clotting without the need to use any other anticoagulant. J. Chvojka and R. Sykora have equally contributed to this study.     

Mild hyperhomocysteinaemia is associated with increased aortic stiffness in general population

Total homocysteine (tHcy) level was identified as a strong and independent predictor of cardiovascular events. We investigated the association between tHcy and mechanical properties of large arteries in a random, general population-based sample of 251 subjects (mean age 48 years). Large artery properties, such as aortic and peripheral (lower-limb) pulse wave velocity (PWV), and augmentation index of radial artery were measured using semi-automatic Sphygmocor device. Aortic PWV (APWV) positively correlated with tHcy (r = 0.28, P<0.0001), and a significant increasing trend of APWV was found by tHcy quartiles (P = 0.0003 by ANOVA). This association remained significant after adjustment for conventional cardiovascular risk factors (age, gender, smoking, overweight, hypertension, dyslipidaemia and impaired glucose metabolism) and for usual homocysteine confounders (folate, B12, renal function). Subjects with mild hyperhomocysteinaemia (i.e. with tHcy > or = 15 micromol/l) had 2.74 times higher risk of having their APWV over 8.42 m/s (i.e. in the top quartile). No such association was found either for PWV measured at lower extremity or for radial augmentation index. In conclusion, in our series of subjects from general population, we found a strong and independent relationship between homocysteine concentration and APWV, a parameter of stiffness of central arteries.     

Involvement of serotonergic and opioidergic systems in the antinociceptive effect of ketamine-magnesium sulphate combination in formalin test in rats

BackgroundKetamine and magnesium sulphate showed synergic interaction in the tail-immersion test and additive interaction in the rat formalin test. Aim of study was to evaluate the influence of serotonergic and opioidergic system of this combination in the formalin test in rats.MethodsAntinociceptive activity was assessed by the formalin test in male Wistar rats (200–250 g). Antagonists (naloxone and methysergide) were administrated 5 min before and magnesium sulphate 5 min after ketamine injection. Formalin (2.5%, 100 μL) was injected into the right hind paw surface (intraplantar) of rats 5 min after ketamine/magnesium combination. Data were recorded as the total time spent in pain related behavior after the injection of formalin or vehicle (0.9% NaCl).ResultsIn the intermediate phase of the formalin test, methysergide at a dose of 0.2 mg/kg did not have any effect, but at doses of 0.5 and 1 mg/kg it had a pronociceptive effect. Methysergide (0.2, 0.5 and 1 mg/kg) inhibited the antinociceptive effect of ketamine-magnesium sulphate combination. In the intermediate phase, naloxone at a dose of 0.2 mg/kg did not have any effect, but at a dose of 3 mg/kg it produced a pronociceptive effect. Naloxone (0.2 and 3 mg/kg) antagonized the antinociceptive effect of the ketamine (5 mg/kg)-magnesium sulphate (5 mg/kg) combination.ConclusionThe results of the present study suggest that serotonergic and opioidergic systems are involved, at least in part, in the antinociceptive effect of the ketamine-magnesium sulphate combination in the model of inflammatory pain in rats.     

Efficacy and safety of low-dose fluticasone propionate compared with zafirlukast in patients with persistent asthma

To compare the efficacy and safety of fluticasone propionate and zafirlukast in patients with relatively stable persistent asthma who were previously treated with inhaled corticosteroids and short-acting beta(2)-agonists.A total of 440 patients (> or =12 years of age) previously treated with inhaled corticosteroids (beclomethasone dipropionate or triamcinolone acetonide) and short-acting beta(2)-agonists were included in this randomized double-blind study. After an 8-day run-in period, patients were treated with fluticasone (88 microg) or zafirlukast (20 mg) twice daily for 6 weeks. Outcome measures included pulmonary function (forced expiratory volume in 1 second [FEV(1)], peak expiratory flow [peak flow]), albuterol use, asthma symptoms, withdrawals due to lack of efficacy, and asthma exacerbations.Patients treated with fluticasone (n = 224) experienced greater mean increases in FEV(1) (0.24 L vs. 0.08 L, P <0.001), morning peak flow (30 L/min vs. 6 L/min, P <0.001), and evening peak flow (23 L/min vs. 5 L/min, P <0.001) during the study than did those treated with zafirlukast (n = 216). Fluticasone-treated patients had significantly greater increases in the mean percentages of symptom-free days (22% vs. 8%, P <0.001), rescue-free days (23% vs. 10%, P = 0.002), nights with uninterrupted sleep (<1% vs. -5%, P = 0.006), and fewer asthma exacerbations (1% vs. 6%, P = 0.005). Fewer fluticasone-treated patients were withdrawn due to lack of efficacy (2% vs. 13%, P <0.001).Inhaled fluticasone was more effective than zafirlukast in maintaining or improving asthma control in patients with relatively stable asthma who were switched from low-dose inhaled corticosteroids.     

Elution of monomers from three different bonding systems and their antibacterial effect

The aim of the present study was to evaluate the release of monomers from three bonding systems and to correlate it with their antibacterial effect. Three bonding systems (Optibond FL^®, Xeno III^® and Clearfil? Protect Bond) were tested after storage in ethanol 75 % and human saliva. Twenty samples (n = 10/medium) of each bonding material were prepared and polymerized according to the manufacturers’ instructions. Each sample was stored in 1 ml of the respective storage medium. The medium was renewed after 24 h, 7 days, and 28 days and was analysed by LC–MS/MS for the release of substances. Additionally, the antibacterial effect of the unpolymerized components of each bonding system and their polymerized mixture was tested using agar disc-diffusion test with Streptococcus mutans. Only HEMA was found to be released. The amount of HEMA detected in the ethanol samples was significantly higher compared to the saliva samples (p < 0.0001). The release of HEMA was as follows: Clearfil? Protect Bond < Optibond FL^® < Xeno III^®. According to the agar disc-diffusion test, all materials exhibited certain antibacterial activity. The release of HEMA from all tested materials even after storing in human saliva increases the concerns about their toxicity. Their antibacterial effect seems not be due to the release of substances.