9 research outputs found

    Intranasal “painless” Human Nerve Growth Factors Slows Amyloid Neurodegeneration and Prevents Memory Deficits in App X PS1 Mice

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    Nerve Growth Factor (NGF) is being considered as a therapeutic candidate for Alzheimer's disease (AD) treatment but the clinical application is hindered by its potent pro-nociceptive activity. Thus, to reduce systemic exposure that would induce pain, in recent clinical studies NGF was administered through an invasive intracerebral gene-therapy approach. Our group demonstrated the feasibility of a non-invasive intranasal delivery of NGF in a mouse model of neurodegeneration. NGF therapeutic window could be further increased if its nociceptive effects could be avoided altogether. In this study we exploit forms of NGF, mutated at residue R100, inspired by the human genetic disease HSAN V (Hereditary Sensory Autonomic Neuropathy Type V), which would allow increasing the dose of NGF without triggering pain. We show that “painless” hNGF displays full neurotrophic and anti-amyloidogenic activities in neuronal cultures, and a reduced nociceptive activity in vivo. When administered intranasally to APPxPS1 mice ( n = 8), hNGFP61S/R100E prevents the progress of neurodegeneration and of behavioral deficits. These results demonstrate the in vivo neuroprotective and anti-amyloidogenic properties of hNGFR100 mutants and provide a rational basis for the development of “painless” hNGF variants as a new generation of therapeutics for neurodegenerative diseases

    Larger head circumference in Icelandic children 0-4 years of age compared to the World Health Organization and Swedish growth charts

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    AIM: The World Health Organization (WHO) published universal growth standards for children below five year of age in 2006. Traditionally, Swedish growth references have been used to monitor growth of children in Iceland, but it is not yet known how they compare with these reference charts. METHODS: A total of 2128 longitudinal measurements of length or height, 2132 of weight and 2126 of head circumference between birth and four years of age were collected in 1996-2000 from 199 healthy children (53% boys) recruited at Landspitali University Hospital. Measurements were converted to z-scores using the WHO growth standards and Swedish growth references for further analysis with mixed-effects models. RESULTS: Length or height, weight and in particular head circumference largely exceeded the WHO standards, with average z-scores that fluctuated between 0.5 and 1.5. Likewise, the proportion of children with a z-score larger than 2 SD increased about 10-fold. Icelandic children were longer and heavier than their Swedish peers during the first six months of life, but differences were less pronounced thereafter. CONCLUSION: The growth of Icelandic children deviated significantly from the WHO growth standards. Although more comparable to the Swedish references, significant differences were found, suggesting that a national growth reference would be more appropriate.status: publishe

    Larger head circumference in Icelandic children 0-4 years of age compared to the World Health Organization and Swedish growth charts.

    No full text
    To access publisher's full text version of this article click on the hyperlink belowAim: The World Health Organization (WHO) published universal growth standards for children below five year of age in 2006. Traditionally, Swedish growth references have been used to monitor growth of children in Iceland, but it is not yet known how they compare with these reference charts. Methods: A total of 2128 longitudinal measurements of length or height, 2132 of weight and 2126 of head circumference between birth and four years of age were collected in 1996-2000 from 199 healthy children (53% boys) recruited at Landspitali University Hospital. Measurements were converted to z-scores using the WHO growth standards and Swedish growth references for further analysis with mixed-effects models. Results: Length or height, weight and in particular head circumference largely exceeded the WHO standards, with average z-scores that fluctuated between 0.5 and 1.5. Likewise, the proportion of children with a z-score larger than 2 SD increased about 10-fold. Icelandic children were longer and heavier than their Swedish peers during the first six months of life, but differences were less pronounced thereafter. Conclusion: The growth of Icelandic children deviated significantly from the WHO growth standards. Although more comparable to the Swedish references, significant differences were found, suggesting that a national growth reference would be more appropriate. Keywords: Growth anthropometry; Iceland; growth reference; growth standards; head circumference

    Secondary metabolites from cetrarioid lichens: Chemotaxonomy, biological activities and pharmaceutical potential

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    Estrogen receptors and human disease: an update

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    The role of melatonin in autoimmune and atopic diseases

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