Immune responses of IL-5 transgenic mice to parasites and aeroallergens

Eosinophils have long been thought to be effectors of immunity to helminths but have also been implicated in the pathogenesis of asthma. Patterns of cytokine production in the host may influence the pathogenesis of these diseases by regulating the activities of eosinophils and other components of the immune response. Mice which constitutively over-express IL-5 have profound and life-long eosinophilia in a restricted number of tissues. Although eosinophils from IL-5 transgenics are functionally competent for a number of parameters considered to be important in inflammation, untreated animals are overtly normal and free of disease. In addition, the responses of these animals when exposed to aeroallergens and helminths present a number of apparent paradoxes. Eosinophil accumulation in tissues adjacent to major airways is rapid and extensive in transgenics exposed to the aeroallergen, but even after treatment with antigen over many months these mice show no evidence of respiratory distress or pathology. Helminth-infected IL-5 transgenics and their non-transgenic littermates develop similar inflammatory responses at mucosal sites and are comparable for a number of T cell and antibody responses, but they differ considerably in their ability to clear some parasite species. The life-cycle of Nippostrongylus brasiliensis is significantly inhibited in IL-5 transgenics, but that of Toxocara canis is not. Our results also suggest that eosinophilia and/or over-expression of IL-5 may actually impair host resistance to Schistosoma mansoni and Trichinella spiralis. The pathogenesis of diseases in which eosinophils are involved may therefore be more complex than previously thought.

Characterization of pupil responses to blue and red light stimuli in autosomal dominant retinitis pigmentosa due to NR2E3 mutation.

PURPOSE: We characterized the pupil responses that reflect rod, cone, and melanopsin function in a genetically homogeneous cohort of patients with autosomal dominant retinitis pigmentosa (adRP). METHODS: Nine patients with Gly56Arg mutation of the NR2E3 gene and 12 control subjects were studied. Pupil and subjective visual responses to red and blue light flashes over a 7 log-unit range of intensities were recorded under dark and light adaptation. The pupil responses were plotted against stimulus intensity to obtain red-light and blue-light response curves. RESULTS: In the dark-adapted blue-light stimulus condition, patients showed significantly higher threshold intensities for visual perception and for a pupil response compared to controls (P = 0.02 and P = 0.006, respectively). The rod-dependent, blue-light pupil responses decreased with disease progression. In contrast, the cone-dependent pupil responses (light-adapted red-light stimulus condition) did not differ between patients and controls. The difference in the retinal sensitivity to blue and red stimuli was the most sensitive parameter to detect photoreceptor dysfunction. Unexpectedly, the melanopsin-mediated pupil response was decreased in patients (P = 0.02). CONCLUSIONS: Pupil responses of patients with NR2E3-associated adRP demonstrated reduced retinal sensitivity to dim blue light under dark adaptation, presumably reflecting decreased rod function. Rod-dependent pupil responses were quantifiable in all patients, including those with non-recordable scotopic electroretinogram, and correlated with the extent of clinical disease. Thus, the chromatic pupil light reflex can be used to monitor photoreceptor degeneration over a larger range of disease progression compared to standard electrophysiology.

Mesophyll conductance to CO2 and leaf morphological characteristics under drought stress during Quercus ilex L resprouting

• Quercus ilex L., the dominant species in Mediterranean forests and one with a great capacity for resprouting after disturbances, is threatened by the expected increase in fire frequency and drought associated with climate change. • The aim of this study was to determine the contribution of photosynthesis limitants, especially mesophyll conductance (gmes ) during this species’ resprouting and under summer drought. • Resprouts showed 5.3-fold increased gmes and 3.8-fold increased stomatal conductance (gs) atmidday with respect to leaves of undisturbed individuals. With increased drought, structural changes (decreased density and increased thickness) in resprouts contributed to the observed higher photosynthesis and increased gmes. However, gmes only partially depended on leaf structure, and was also under physiological control. Resprouts also showed lower non-stomatal limitations (around 50% higher carboxylation velocity (Vc,max) and capacity for ribulose-1,5-bisphosphate regeneration (Jmax)). A significant contribution of gmes to leaf carbon isotope discrimination values was observed. • gmes exhibits a dominant role in photosynthesis limitation in Q. ilex and is regulated by factors other than morphology. During resprouting after disturbances, greater capacity to withstand drought, as evidenced by higher gmes , gs and lower non-stomatal limitants, enables increased photosynthesis and rapid growth.

5-HT2A and alpha1b-adrenergic receptors entirely mediate dopamine release, locomotor response and behavioural sensitization to opiates and psychostimulants.

Addictive properties of drugs of misuse are generally considered to be mediated by an increased release of dopamine (DA) in the ventral striatum. However, recent experiments indicated an implication of alpha1b-adrenergic receptors in behavioural responses to psychostimulants and opiates. We show now that DA release induced in the ventral striatum by morphine (20 mg/kg) is completely blocked by prazosin (1 mg/kg), an alpha1-adrenergic antagonist. However, morphine-induced increases in DA release in the ventral striatum were found to be similar in mice deleted for the alpha1b-adrenergic receptor (alpha1b-AR KO) and in wild-type (WT) mice, suggesting the presence of a compensatory mechanism. This acute morphine-evoked DA release was completely blocked in alpha1b-AR KO mice by SR46349B (1 mg/kg), a 5-HT2A antagonist. SR46349B also completely blocked, in alpha1b-AR KO mice, the locomotor response and the development of behavioural sensitization to morphine (20 mg/kg) and D-amphetamine (2 mg/kg). Accordingly, the concomitant blockade of 5-HT2A and alpha1b-adrenergic receptors in WT mice entirely blocked acute locomotor responses but also the development of behavioural sensitization to morphine, D-amphetamine or cocaine (10 mg/kg). We observed, nevertheless, that inhibitory effects of each antagonist on locomotor responses to morphine or D-amphetamine were more than additive (160%) in naïve WT mice but not in those sensitized to either drug. Because of these latter data and the possible compensation by 5-HT2A receptors for the genetic deletion of alpha1b-adrenergic receptors, we postulate the existence of a functional link between these receptors, which vanishes during the development of behavioural sensitization.

IPH response to DHSSPS and Food Standards Agency (NI) Front of Pack Labelling consultation

From 2016, it will be mandatory for most pre-packed food to carry nutrition labelling.  This provides an opportunity to review the provision of additional nutrition labelling that is provided voluntarily on the front of packs.  The Governments across the UK are committed to the provision of nutritional information to help consumers make better informed food choices. Key points from IPH response Obesity and related chronic conditions are already very prevalent and are expected to increase over the next decade, placing greater financial burden on health care services. Helping consumers to make informed choices about their diet is an important aspect of tackling obesity. Providing clear consistent and easy to understand front of pack (FoP) nutrition information is important in helping consumers to make healthy choices. IPH would support FoP nutrition information using the traffic light labelling scheme and High/Medium/Low text. FoP nutrition labelling should be supported by a public information campaign to educate consumers about portion sizes and recommended daily intakes of fat, sugar and salt. IPH would support a nutrition labelling approach which empowers and enables consumers to take responsibility for their own health through informed dietary choices. The FoP traffic light labelling scheme has the potential to encourage healthier product formulation as manufacturers pursue market share. This in turn would contribute to wider availability of healthier products.

Chagas disease: from bush to huts and houses. Is it the case of the Brazilian amazon?

Two of the major problems facing the Amazon - human migration from the other areas and uncontrolled deforestation - constitute the greatest risk for the establishment of endemic Chagas disease in this part of Brazil. At least 18 species of triatomines had been found in the Brazilian Amazon, 10 of them infected with Trypanosoma cruzi, associated with numerous wild reservoirs. With wide-range deforestation, wild animals will perforce be driven into other areas, with tendency for triatomines to become adapted to alternative food sources in peri and intradomicilies. Serological surveys and cross-sectional studies for Chagas disease, carried out in rural areas of the Rio Negro, in the Brazilian Amazon, showed a high level of seropositivity for T. cruzi antibodies. A strong correlation of seroreactivity with the contact of gatherers of piaçava fibers with wild triatomines could be evidenced.

IPH response to Health and Social Care Board and Public Health Agency Community Development Strategy

The Health and Social Care Board (HSCB) and the Public Health Agency (PHA) launched a new Community Development Strategy for public consultation.  The HSCB and PHA want to see strong, resilient communities where everyone has good health and wellbeing, places where people look out for each other and have community pride in where they live. The HSCB and PHA seek a number of benefits from implementing this strategy including; a reduction in health and wellbeing inequalities, which also means addressing the social factors that affect health; strengthening partnership working with service users, the community and voluntary sectors and other organisations; strengthening families and communities; supporting volunteering and making best use of our resources. Key points from the IPH summary include IPH welcome the Community Development Strategy as an approach to enhance health and wellbeing and tackle health inequalities in Northern Ireland.   IPH recommend the current three strategy documents (Full and summary versions and the Performance Management Framework) are merged into one document for greater clarity. Reference to the Performance Management Framework is required in the main body of the text is to ensure good practice is implemented. IPH welcome the focus on tackling health inequalities using community development approaches however the contribution of community development approaches needs to be highlighted. HIA is a tool to support community engagement and provides a mechanism for HSCB and PHA to support the implementation of this strategy.

IPH response to Palliative and End of Life Care Strategy Consultation

Palliative care and end of life care is the active, holistic care of patients with advanced and progressive illness.  It is an integral part of the care delivered by all health and social care professionals, and indeed by families and carers, to those living with, and dying from any advanced, progressive and incurable conditions.  The Department of Health, Social Services and Public Safety (NI) issued a consultation document on a 5 year Strategy in December 2009.

Procedures to characterize and study P2Z/P2X7 purinoceptor: flow cytometry as a promising practical, reliable tool

The expression of P2Z/P2X7 purinoceptor in different cell types is well established. This receptor is a member of the ionotropic P2X receptor family, which is composed by seven cloned receptor subtypes (P2X1 - P2X7). Interestingly, the P2Z/P2X7 has a unique feature of being linked to a non-selective pore which allows the passage of molecules up to 900 Da depending on the cell type. Early studies of P2Z/P2X7 purinoceptor were exclusively based on classical pharmacological studies but the recent tools of molecular biology have enriched the analysis of the receptor expression. The majority of assays and techniques chosen so far to study the expression of P2Z/P2X7 receptor explore directly or indirectly the effects of the opening of P2Z/P2X7 linked pore. In this review we describe the main techniques used to study the expression and functionality of P2Z/P2X7 receptor. Additionally, the increasing need and importance of a multifunctional analysis of P2Z/P2X7 expression based on flow cytometry technology is discussed, as well as the adoption of a more complete analysis of P2Z/P2X7 expression involving different techniques.

Nonclassical measurement error with applications to labor and development issues

Zero correlation between measurement error and model error has been assumed in existing panel data models dealing specifically with measurement error. We extend this literature and propose a simple model where one regressor is mismeasured, allowing the measurement error to correlate with model error. Zero correlation between measurement error and model error is a special case in our model where correlated measurement error equals zero. We ask two research questions. First, we wonder if the correlated measurement error can be identified in the context of panel data. Second, we wonder if classical instrumental variables in panel data need to be adjusted when correlation between measurement error and model error cannot be ignored. Under some regularity conditions the answer is yes to both questions. We then propose a two-step estimation corresponding to the two questions. The first step estimates correlated measurement error from a reverse regression; and the second step estimates usual coefficients of interest using adjusted instruments.

Appendices for Complex Needs - The Nursing Response to Children and Young People with Complex Physical Healthcare Needs (PDF 708 KB)

Appendices to Complex Needs Report

Complex Needs - The Nursing Response to Children and Young People with Complex Physical Healthcare Needs (PDF 832 KB)

Departmental review of nursing services in order to ensure that they are facilitated to fully support and respond to children with complex needs and their families, and for them to work in partnership with other professions and agencies.