Assessment of efficacy and safety of the herbal medicinal product BNO 1016 in chronic rhinosinusitis.

BACKGROUND: The objective of this clinical trial (CRS-02) was to assess the efficacy, safety and tolerability of two dosages of the herbal medicinal product BNO 1016 (Sinupret extract) in patients with chronic rhinosinusitis (CRS). METHODOLOGY: 929 patients suffering from CRS were enrolled in this randomised placebo-controlled trial with a treatment period of 12 weeks. The primary endpoint was the mean Major Symptom Score (MSS) in week 8 and week 12 compared to placebo. Secondary endpoints included further MSS related parameters and responder rates over time. Pharmacoeconomic endpoints were also analysed. Finally, safety and tolerability were evaluated. RESULTS: Sinupret extract was not superior over placebo regarding the primary endpoint. However, the results of the secondary endpoints showed a clear trend towards superior efficacy. Therefore, additional post-hoc sensitivity analyses were performed in patients with a baseline MSS over 9 and persistence of disease more than 1 year diagnosed by specialists in otorhinolaryngology. Those patients significantly benefited from Sinupret extract. Therapy was superior for the primary endpoint analysis. Patients were less impaired with respect to work and daily activities. A good safety and tolerability of Sinupret extract was assured in all patients. CONCLUSIONS: Sinupret extract can safely be administered in patients with CRS. Although the primary endpoint of the study was not significant, a post-hoc subgroup analysis in patients whose disease was diagnosed by a specialist revealed a pronounced treatment effect. Effects in that subgroup were even stronger with longer disease persistence and stronger severity.

Clinical efficacy of a dry extract of five herbal drugs in acute viral rhinosinusitis.

OBJECTIVE: A herbal drug combination (Dry Extract BNO 1016) has been assessed for efficacy and tolerability in patients with acute viral rhinosinusitis. METHODOLOGY: In this randomised, controlled trial patients with symptom duration of up to 3 days, mild to moderate facial pain and a Major Symptom Score (MSS) between 8 and 12 were treated for 15 days with BNO 1016 or placebo (coated tablets administered orally). Primary efficacy endpoint was mean MSS at end of treatment. Secondary outcome measures included treatment response and changes in paranasal sinuses assessed by ultrasonography. RESULTS: Treatment resulted in clinically relevant, significant differences in mean MSS for BNO 1016 versus placebo. BNO 1016 provided symptom relief two days earlier than placebo. The number needed to treat for healing is 8. BNO 1016 was superior regarding responder rates at Day 10 and Day 14 and percentage of patients without signs of acute viral rhinosinusitis assessed by ultrasonography at end of treatment. BNO 1016 was well tolerated; no serious adverse events were reported. CONCLUSION: The herbal dry extract BNO 1016 is efficacious and well tolerated in patients with acute viral rhinosinusitis. TRIAL REGISTRATION: ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT01146860; EudraCT: 2009-016682-28).

A broader horizon of Alzheimer pathogenesis: ALZAS--an early serum biomarker?

Recently, a novel risk gene protein expressed in elderly patients with the diagnosis of Alzheimer disease (AD) was discovered on chromosome 21 within the APP (amyloid precursor protein) region. This 79 amino acid protein, ALZAS (Alzheimer Associated Protein) contains the beta-amyloid peptide 1-42 fragment, the APP transmembrane signal, and a unique 12 amino acid c-terminal which is not present in any known allele of the APP gene. Reverse transcription-PCR revealed that the transcript of ALZAS was expressed in cortical and hippocampal regions of human Alzheimer disease brain as well as in leukocytes derived from AD patients. Most specifically, an endogenous antibody was found in patients with confirmed AD, in patients with depression, and in subjects suggested to have presymptomatic AD, where it was directed against epitopes within the intron encoded amino acid c-terminal sequence.

Considerations on the behavior of long-lived radionuclides in the soil.

The migration of radionuclides from waste repositories to the biosphere potentially leads to a contamination of soil. Due to the importance of food production, the mobilisation and accumulation behaviour of long-lived radionuclides in the soil plays a key role in performance assessment studies. In this paper, the main features and processes that control radionuclide behaviour in soil, such as pH, redox potential and sorption to organic and inorganic soil components, are discussed for the radionuclides 36Cl, 79Se, 129I, 99Tc, 237Np and 238U, that are usually most relevant in long-term safety assessments of nuclear waste. The interaction of radionuclide behaviour in soil with environmental factors, such as temperature and humidity as well as farming practices are discussed. The possible impact of future soil development on long-term behaviour in soil are taken into consideration. Due to the physiological constraints of plant growth, appropriate soil conditions for growth will probably not be substantially different from current requirements, bearing in mind that sustainable agriculture strives for optimal plant growth. Against this background, present-day parameters may in general be considered appropriate for roughly estimating the behaviour of radionuclides in the soil-plant system.

Soil-to-plant and plant-to-cow's milk transfer of radiocaesium in alpine pastures: significance of seasonal variability.

Because our present knowledge on the environmental behaviour of fallout radiocaesium in semi-natural environments is rather limited, the transfer of this radionuclide and of natural 40K, from soil-to-plant as well as from plant-to-cow's milk was investigated for a typical alpine pasture (site P). For comparison, a nearby alpine pasture (site K) not used for cattle grazing was also studied. Small seasonal effects were found for 137Cs in the plants, but they were different for the two pastures. Due to the presence of a large variety of different plant species on the pastures and soil adhesion on the vegetation from trampling cattle, the scattering of the data was very large, and the seasonal effects were observable only because of the large number of samples (N approximately 100) collected. The aggregated soil-to-plant transfer factor of 137Cs was for site P, on average, 0.002 +/- 0.001 m2 kg(-1). The plant-to-milk transfer coefficient was, on average, 0.02 day l(-1). The 137Cs concentration in the milk of the cows varied within the grazing period only between 1.4 and 2.9 Bq l(-1), with a significant maximum in the beginning of August. As a result of soil adhesion due to cattle trampling, significantly higher ash- and 137Cs contents of the plants were observed at site P as compared to site K. Possible consequences of the above observations with respect to a representative sampling design of vegetation and milk are discussed.

Variability of water content and of depth profiles of global fallout 137Cs in grassland soils and the resulting external gamma-dose rates.

137Cs from global fallout of nuclear weapon testings in the 1950s and 1960s was determined in successive layers (0-30 cm) of eight undisturbed grassland soils in Bavaria, Germany. The maximum activity concentration was found in soil layers between 4 and 15 cm below the surface. Using the vertical distribution of the cesium activity, which varied considerably from site to site, the mean residence half-time of 137Cs from global fallout in each soil layer was evaluated with a compartment model. These values ranged from 1.0 to 6.3 years/cm. The mean residence half-time averaged over all soil layers and all sites was 2.7 +/- 1.4 years/cm and, thus, about twice the corresponding residence half-time of the Chernobyl-derived 137Cs as determined in the same soil layers (also in 1993). The dose rate of the external gamma-radiation due to 137Cs from global fallout in the soil determined from the depth distributions varied between 0.34 and 0.57 (mean: 0.45 +/- 0.07) nGy/h per kBq/m2. The effect of soil water content on the dose rate was studied by considering four states of the soil, from water content zero to complete water saturation of the total pore volume. It was shown that the difference between the dose rates at the permanent wilting point and the field capacity, which both represent the most relevant water contents of soils, was only 10% of the dose rate at the permanent wilting point for all sites.

Root colonization of different plants by plant-growth-promoting Rhizobium leguminosarum bv. trifolii R39 studied with monospecific polyclonal antisera.

Monospecific polyclonal antisera raised against Rhizobium leguminosarum bv. trifolii R39, a bacterium which was isolated originally from red clover nodules, were used to study the colonization of roots of leguminous and nonleguminous plants (Pisum sativum, Lupinus albus, Triticúm aestivum, and Zea mays) after inoculation. Eight weeks after inoculation of soil-grown plants, between 0.1 and 1% of the total bacterial population in the rhizospheres of all inoculated plants were identified as R. leguminosarum bv. trifolii R39. To characterize the associative colonization of the nonleguminous plants by R.leguminosarum bv. trifolii R39 in more detail, a time course study was performed with inoculated roots of Z. mays. R. leguminosarum bv. trifolii R39 was found almost exclusively in the rhizosphere soil and on the rhizoplane 4 weeks after inoculation. Colonization of inner root tissues was detected only occasionally at this time. During the process of attachment of R. leguminosarum bv. trifolii R39 to the rhizoplane, bacterial lipopolysaccharides were overexpressed, and this may be important for plant-microbe interaction. Fourteen weeks after inoculation, microcolonies of R. leguminosarum bv. trifolii R39 were detected in lysed cells of the root cortex as well as in intracellular space of central root cylinder cells. At the beginning of flowering (18 weeks after inoculation), the number of R. leguminosarum bv. trifolii R39 organisms decreased in the rhizosphere soil, rhizoplane, and inner root tissue.

Association of fallout radiocesium with soil constituents: effect of sterilization of forest soils by fumigation with chloroform.

The effect of soil sterilization by chloroform fumigation on the release of fallout radiocesium incorporated in the fungal biomass of the organic layer of two forest soils was investigated by applying a sequential extraction procedure for radiocesium. The amount of the biomass in all soil samples was estimated by determination of the dissolved organic carbon (DOC) before and after fumigation, and qualitatively also by the ergosterol test. The five fractions obtained by sequential extraction (modified Tessier procedure) were: (I) easily exchangeable, (II) bound to oxides, (III) bound to organic matter, (IV) persistently bound, (V) residual. For the samples from the soil under spruce trees, no significant effects were apparent in any of these five fractions as a result of chloroform fumigation, indicating that the amount of radiocesium in the biomass of this soil was obviously negligibly small compared with the radiocesium associated with other soil constituents. The results obtained for the soil samples from the beech stand, however, reveal that the destruction of the biomass by chloroform fumigation modified considerably the extent of the association (i.e., binding) of radiocesium with the various other soil constituents (especially the clay minerals). As a result of this rapid redistribution of radiocesium released by the fungal biomass, it is not possible, in general, to attribute the observed increase of radiocesium in fraction I (easily exchangeable) after soil sterilization quantitatively to radiocesium released by the biomass. A reliable method to determine the amount of radiocesium incorporated in the fungal biomass of the soil samples which also contain clay minerals has, therefore, still to be developed.