Analysis of composition, morphology, and biosynthesis of cuticular wax in wild type bilberry (Vaccinium myrtillus L.) and its glossy mutant.

In this study, cuticular wax load, its chemical composition, and biosynthesis, was studied during development of wild type (WT) bilberry fruit and its natural glossy type (GT) mutant. GT fruit cuticular wax load was comparable with WT fruits. In both, the proportion of triterpenoids decreased during fruit development concomitant with increasing proportions of total aliphatic compounds. In GT fruit, a higher proportion of triterpenoids in cuticular wax was accompanied by a lower proportion of fatty acids and ketones compared to WT fruit as well as lower density of crystalloid structures on berry surfaces. Our results suggest that the glossy phenotype could be caused by the absence of rod-like structures in GT fruit associated with reduction in proportions of ketones and fatty acids in the cuticular wax. Especially CER26-like, FAR2, CER3-like, LTP, MIXTA, and BAS genes showed fruit skin preferential expression patterns indicating their role in cuticular wax biosynthesis and secretion.

Compositional and morphological analyses of wax in northern wild berry species.

Aerial surfaces of plants are covered by a waxy cuticle protecting plants from excessive water loss and UV light. In the present study, composition and morphology of cuticular waxes of northern wild berry species bilberry (Vaccinium myrtillus L.), lingonberry (V. vitis-idaea L.), bog bilberry (V. uliginosum L.) and crowberry (Empetrum nigrum L.) were investigated. Scanning electron microscopy (SEM) revealed differences in epicuticular wax morphology, and gas chromatography-mass spectrometry (GC-MS) analysis confirmed variation in chemical composition of cuticular waxes between the berry species. The dominant compounds in bilberry and lingonberry cuticular waxes were triterpenoids, while fatty acids and alkanes were the dominant ones in bog bilberry and crowberry, respectively. Wax extracted by supercritical fluid extraction (SFE) from industrial press cakes of bilberry and lingonberry contained linoleic acid and γ-linolenic acid as the dominant compounds. Furthermore, in vitro sun protection factor (SPF) of berry waxes depicted good UV-B absorbing capacities.

A Comparative Review of Marketing Authorization Decisions in Switzerland, the EU, and the USA.

BACKGROUND: In this study we compared Swissmedic's (SMC's) regulatory marketing authorization decisions to those of the US Food and Drug Administration (FDA) and European drug regulatory authorities (EU). We investigated the overall similarity of the regulatory decisions, approval, and postmarketing withdrawal rates in the 3 jurisdictions. In case regulatory decisions diverged, we analyzed the reasons for rejection of marketing authorization applications (MAAs). METHODS: The study comprises 255 new molecular entity (NME) MAAs assessed by SMC by the EU and FDA between 2005 through 2014. Study parameters included the regulatory decision, postmarketing withdrawal rates, and the official reasons for rejection. RESULTS: Regulatory decisions converged to a high degree among all 3 agencies (between 84% and 90%). SMC's average approval rate (84%) was slightly lower than those of the FDA (87%) and the EU (91%). Postmarketing withdrawal rates were generally low (4%-5%) but were 3 to 5 times higher when decisions among the drug regulatory authorities (DRAs) diverged. SMC's primary grounds for rejection were lack of efficacy (45%) and safety (40%). CONCLUSIONS: The 3 investigated DRAs adhere largely to the same scientific principles and regulatory guidelines; therefore, remaining disparities ought to be considered in a cultural, legal and public health priority context.

Second-harmonic response of multilayer nanocomposites of silver-decorated nanoparticles and silica.

We perform a detailed characterisation of the second-order nonlinear optical response of nanocomposites consisting of alternating layers of silver-decorated silica glass nanoparticles and pure silica glass. The samples are fabricated using aerosol techniques and electron-beam dielectric coating, resulting in a bulk-like material with symmetry-breaking induced by the porosity of the alternating layers. The second-order nonlinear response increases with the number of layers. Further, by determining the components of the second-order susceptibility tensor of the samples, we show that the structural properties of the samples are well maintained as the sample thickness is increased. Our results form an important baseline for any further optimization of these types of structures, which can be fabricated using very straightforward methods.

Polymeric slot waveguide at visible wavelength.

Polymeric slot waveguide structure, which pushes the mode field toward the surrounding media, was designed and characterized. The slot waveguide was fabricated by using nanoimprint lithography, and the operation of the slot was demonstrated at 633 nm wavelength with an integrated Young interferometer. The experimental result shows that the nanolithography method provides possibilities to fabricate disposable slot waveguide sensors.

Biosimilars: what clinicians should know.

Biosimilar medicinal products (biosimilars) have become a reality in the European Union and will soon be available in the United States. Despite an established legal pathway for biosimilars in the European Union since 2005 and increasing and detailed regulatory guidance on data requirements for their development and licensing, many clinicians, particularly oncologists, are reluctant to consider biosimilars as a treatment option for their patients. Major concerns voiced about biosimilars relate to their pharmaceutical quality, safety (especially immunogenicity), efficacy (particularly in extrapolated indications), and interchangeability with the originator product. In this article, the members and experts of the Working Party on Similar Biologic Medicinal Products of the European Medicines Agency (EMA) address these issues. A clear understanding of the scientific principles of the biosimilar concept and access to unbiased information on licensed biosimilars are important for physicians to make informed and appropriate treatment choices for their patients. This will become even more important with the advent of biosimilar monoclonal antibodies. The issues also highlight the need for improved communication between physicians, learned societies, and regulators.

The alpha 2-adrenoceptor antagonist atipamezole potentiates anti-Parkinsonian effects and can reduce the adverse cardiovascular effects of dopaminergic drugs in rats.

The present experiments investigated the effects of the specific alpha(2)-adrenoceptor antagonist atipamezole, alone and in combination with a dopamine agonist, on motor function in rats with a unilateral 6-hydroxydopamine lesion of the nigro-striatal pathway and on exploratory behaviour and cardiovascular function in rats equipped with telemetry transmitters. Dexmedetomidine, an alpha(2)-adrenoceptor agonist and the alpha(2)-adrenoceptor antagonists idazoxan and yohimbine were used as reference compounds. In the unilaterally lesioned animals, direct dopamine agonists, such as apomorphine, induce contralateral turning behaviour. Indirect agonists, such as amphetamine, induce ipsilateral circling in the animals. Atipamezole (0.3 mg/kg s.c) potentiated and dexmedetomidine (10 micro g/kg s.c.) decreased contralateral circling evoked by apomorphine (50 micro g/kg s.c.) and by l-3,4-dihydroxyphenylalanine (L-DOPA, 5 mg/kg i.p.). Atipamezole also prolonged the duration of action of L-DOPA. Atipamezole dose-dependently induced ipsilateral turning behaviour and potentiated turning induced by amphetamine (1 mg/kg i.p.). The alpha(1)-adrenoceptor antagonist prazosin (0.1 mg/kg i.p.) partially antagonised the effect of amphetamine and had a strong inhibitory effect on the atipamezole-induced potentiation of the amphetamine response. Prazosin did not have any major effect on either the apomorphine response itself or on the potentiation of the apomorphine response by atipamezole. This suggests that atipamezole can modulate motor function both indirectly, by stimulating the release of noradrenaline and directly, by blocking postsynaptic alpha(2)-adrenoceptors in neurones other than noradrenergic nerves. The alpha(2)-adrenoceptor antagonists, when tested at comparably effective central alpha(2)-adrenoceptor antagonising doses in a rat mydriasis model: atipamezole 0.3 mg/kg s.c., idazoxan 1 mg/kg s.c. and yohimbine 3 mg/kg s.c., all induced ipsilateral turning behaviour and potentiated apomorphine-induced contralateral circling. The effects of the alpha(2)-adrenoceptor antagonists were in general similar in these experiments. In habituated non-lesioned rats equipped with telemetry transmitters, apomorphine (50 micro g/kg s.c.) decreased blood pressure in the home cage and in an open-field test. It also decreased spontaneous motor activity in the open field. Neither atipamezole (0.3 mg/kg s.c.) nor idazoxan (1 mg/kg s.c.) had any effect on blood pressure when given alone, but reversed the apomorphine-induced decrease in blood pressure. Atipamezole also diminished apomorphine-induced sedation in the open-field test. In conclusion, atipamezole improved the efficacy of L-DOPA and apomorphine in an animal model of Parkinson's disease and also reduced adverse dopaminergic effects on vigilance and on cardiovascular function. These results suggest that an investigation of the effects of specific alpha(2)-adrenoceptor antagonists in Parkinson's disease patients is warranted.