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• In this article, we describe the current state of affairs with respect to informal care for people with dementia. We focus on the impact of informal care on the caregiver, caregiving strategies and effective ways to support informal caregivers, including e-health and technological support. • Informal care for people with dementia is intense and has consequences, both positive and negative: 78% of informal caregivers has good feelings about the care they give, but 15% feels heavily burdened. • A stimulating and supportive approach creates a positive and safe environment. Person-centred interventions providing several types of support are most effective for people with dementia and their informal caregivers. • E-health and technological interventions have favourable effects on trust, concern and depressive symptoms of informal caregivers. • New interventions should focus more on social health: interactions between people with dementia and their informal caregivers and encouragement of both to use their abilities.

Objective: The aim of our study was to assess the applicability of Parkinson's patients to use a dry powder inhaler correctly during their off periods, when motor function impairments like tremor, bradykinesia and rigidity are present. Background: Because of its expected rapid onset of effect, pulmonary administration of levodopa is an interesting alternative to orally administered levodopa for the rescue treatment of Parkinson's disease patients in an off period. The inspiratory flow manoeuvre performed by a patient is crucial for the performance and the suitability of a dry powder inhaler and is therefore assessed. Methods: After obtaining written informed consent, 15 patients were asked to postpone there scheduled levodopa dose in order to become off. Before the inhalation procedure started, the extent of the off state was scored by a neurologist, by using the (old) UPDRS motor section 3. Patients were asked to simulate an inhalation manoeuvre through a test inhaler (without drug), with three different resistances to air flow, in order to obtain information about their ability to inhale correctly through an inhaler during off periods. The study was approved by the ethics commitee. Results: Two patients did not become off and were therefore not included for analysis. Measurements with the other 13 Parkinson's patients during off periods showed that patients were able to perform an inhalation manoeuvre correctly, hold their breath for an acceptable time to facilitate deep lung deposition and create the pressure drop necessary to achieve a proper dispersion of a dry powder formulation, like levodopa. Conclusions: The inhalation data gathered in this study set the limits within which levodopa dry powder inhalation products for the rescue treatment of Parkinson's disease patients in an off period should effectively disperse and emit the required dose. They are, therefore, essential in any development activities towards such a product. The demonstrated ability of Parkinson's disease patients in an off period to perform an inhalation manoeuvre is expected to be sufficient for the successful development of levodopa dry powder inhalation products for the rescue treatment during an off period of this particular patient group.

The xylem is a long-distance transport system that is unique to higher plants. It evolved into a very sophisticated plumbing system ensuring controlled loading/unloading of ions and water and their effective translocation to the required sinks. The focus of this overview will be the intrinsic interrelations between structural and functional features of the xylem. Taken together the xylem is designed to prevent cavitation (entry of air bubbles), induced by negative pressures under transpiration and to repair the cavitated vessels. Half-bordered pits between xylem parenchyma cells and xylem vessels are on the one hand the gates to the vessels but on the other hand a serious 'bottle-neck' for transport. Hence it becomes evident that special transport systems exist at the interface between the cells and vessels, which allow intensive fluxes of ions and water to and out of the xylem. The molecular identification and biophysical/biochemical characterization of these transporters has just started. Paradigms for the sophisticated mechanism of controlled xylem transport under changing environmental conditions are SKOR, a Shaker-like channel involved in K

Sodium at high millimolar levels in the cytoplasm is toxic to plant and yeast cells. Sequestration of Na

The substitution pattern of anthocyanin pigments is a main determinant of flower color. Flavonoid 3',5'-hydroxylase (F3'5'H) is a cytochrome P450 enzyme (Cyt P450) that catalyzes the 3',5'-hydroxylation of dihydroflavonols, the precursors of purple anthocyanins. Species such as rose and carnation lack F3'5'H activity and are, therefore, unable to generate purple or blue flowers. Petunia, on the other hand, contains two loci, termed hf1 and hf2, that encode a Cyt P450 with F3'5'H activity. Here we report the identification of an additional petunia gene that is required for 3',5' substitution of anthocyanins and purple flower colors. It encodes a cytochrome b

Background: In a previous study it was hypothesised that the effect of mixing time on drug agglomeration and detachment for a coarse lactose carrier is dependent on the presence of large carrier surface discontinuities. To test this hypothesis, experiments were repeated with a fine lactose carrier that contains smaller surface discontinuities. Methods: Mixtures of lactose (63-90 μm) and salmeterol xinafoate or fluticasone propionate were prepared using a Turbula mixer at 90 rpm for 0.5 to 780 minutes. Laser diffraction analysis of undissolved drug clusters in an aqueous suspension after dissolution of the carrier was performed to follow drug agglomeration behaviour in the blends. A classifier based test inhaler was used to determine drug detachment at 20 and 60 L/min. Mixtures were imaged by SEM. Results: Decreasing drug detachment was observed for both drugs at both flow rates with increased mixing time. Until 60-120 minutes of mixing this was accompanied by a decrease in agglomerate size, whereas with prolonged mixing increased dissolution of salmeterol and a gradual film formation by submicron fluticasone particles on the carrier surface were observed. Conclusions: Mechanical forces have a more pronounced negative effect on drug detachment with increased mixing time for a fine lactose carrier of 63-90 μm than for a coarse carrier of 250-315 μm. In addition to drug deagglomeration, continued low shear blending can cause enhanced solubility of salmeterol and film formation by fluticasone. These findings stress the importance of reducing mechanical stress on drug particles during the mixing process, for example, by using carriers with increased macro surface roughness.

Onderzoek van het Sociaal en Cultureel Planbureau (SCP) in samenwerking met de Hogeschool van Amsterdam (lectoraat Community Care) onder twee specifieke groepen mantelzorgers van mensen met psychiatrische problematiek en met een verstandelijke beperking. Onderzoeksvragen: – Wat zijn de aard en de omvang van de mantelzorg aan mensen met een verstandelijkebeperking of psychiatrische problematiek? – Wat is de ondersteuningsbehoefte van mantelzorgers van mensen met eenverstandelijke beperking of psychiatrische problematiek? In het onderzoek is een secundaire analyse uitgevoerd op het datamateriaal uit het door het SCP in 2007 uitgevoerde onderzoek onder mantelzorgers. Ook is er een kwalitatief onderzoek verricht in de vorm van semi-gestructureerde interviews onder vertegenwoordigers van deze twee groepen in Amsterdam en omgeving. Uit het onderzoek wordt geconcludeerd dat mantelzorgers uit deze groepen ontlast kunnen worden door betere aansluiting van het voorzieningenaanbod op de diverse levensterreinen en een volwaardige betrokkenheid bij de hulpverlening.

Purpose: It is widely believed that high resistance dry powder inhalers (DPI's) can not be operated adequately by patients with reduced vital capacity and that a constant lung deposition requires a flow rate independent fine particle output (FPF). These beliefs may result in incorrect use and prescription of DPI's. We aimed to prove that the opposite is true. Methods: Inspiratory manoeuvres by healthy subjects and severe COPD patients were recorded through a series of air flow resistances. FPF's (

Aims: To present new developments in antibiotic aerosol therapy in the treatment of tuberculosis (TB). The purpose and potential advantages of aerosol treatment will be discussed. Finally, technical developments will be discussed in the light of the clinical objective and requirements from the antibiotics and their use. Summary: The rise of multi-drug resistant tuberculosis and extensively-drug resistant tuberculosis strains are a threat to global health. Since the lungs are the main port of entry for the mycobacterium tuberculosis, pulmonary administration of antibioticsseemsanattractive therapeutic option. Potential advantages of pulmonary drug administration in TB encompass: a reduced change of transmission of the disease; a high local exposure, related to an increased therapeutic efficacy; a decreased systemic exposure, which may reduce side effects; the prevention of the development of new drug resistant strains of mycobacteria; and compared to parenteral administration, inhalation does not require medically trained personnel, is free from the injec- tionassociated infection risks and cheaper. So far, only limited information is available from human studies. The increasing lung surface leads to the question whether the drug concentrations attained upon inhalation are sufficient to obtain the antimicrobial effect in the deeper lung. This may shift the purpose of the aerosol therapy to the prevention of transmission. Pulmonary administration of anti-TB drugs is associated with several challenges for the drug delivery system (formulation and inhalation device). These challenges are related to aspects such as: a high dose, prevention of re-infection via the device and world-wide availability. Conclusions: Aerosol therapy of antibiotics offers a number of potential advantages. However, the prevention of transmission may be a more important objective than treatment of the patient. The development of adequate inhalation devices for TB antibiotics is challenging.

Purpose: To study the effect of carrier payload and flow rate on the drug particle detachment from coarse lactose carriers in an air classifier based test inhaler. Methods: Vibratory and air jet sieved lactose with a size fraction of 250-315 /m was used as a carrier. Mixtures of 0.4 to 4% w/w micronised salmeterol xinafoate with this carrier were prepared by mixing for 10 minutes at 90rpm with a Turbula mixer. The residual amount of drug on the carrier particles retained in the classifier based test inhaler (carrier residue, CR) was determined after each inhalation experiment. Results: The amount of salmeterol (in mg per m2carrier surface area) detached in 3 seconds from the lactose carrier surface in the classifier based test inhaler increases linearly with the initial carrier payload. The degree of linearity increases with increasing flow rate from R2= 0.990 at 20 L/min to R2= 1 at 40 to 60 L/min. Only at 10 L/min linearity is less pronounced. The linear relationship comprises low payload mixtures in which drug particles are primarily attached to the carrier surface by adhesive forces as well as high payload mixtures in which drug particles are primarily bound by cohesive forces. Conclusions: The high degree of linearity at higher flow rates for salmeterol detachment from lactose carrier crystals over the range of carrier payloads tested suggests that any difference in adhesive and cohesive forces is irrelevant to drug particle detachment in effective inhalers.

Proteins of the 14-3-3 family have well-defined functions as regulators of plant primary metabolism and ion homeostasis. However, neither their function nor action mechanism in plant hormonal signaling have been fully addressed. Here we show that abscisic acid (ABA) affects both expression and protein levels of five 14-3-3 isoforms in embryonic barley roots. As ABA prolongs the presence of 14-3-3 proteins in the elongating radicle, we tested whether 14-3-3s are instrumental in ABA action using RNA interference. Transient co-expression of 14-3-3 RNAi constructs along with an ABA-responsive promoter showed that each 14-3-3 is functional in generating an ABA response. In a yeast two-hybrid screen, we identified three new 14-3-3 interactors that belong to the ABF protein family. Moreover, using a yeast two-hybrid assay, we show that the transcription factor HvABI5, which binds to cis-acting elements of the ABA-inducible HVA1 promoter, interacts with three of the five 14-3-3s. Our analyses identify two 14-3-3 binding motifs in HvABI5 that are essential for 14-3-3 binding and proper in vivo trans-activation activity of HvABI5. In line with these results, 14-3-3 silencing effectively blocks trans-activation. Our results indicate that 14-3-3 genes/proteins are not only under the control of ABA, but that they control ABA action as well. © 2007 The Authors.