2,839 research outputs found

    Angiotensin type 1 receptor antagonist losartan, reduces MPTP-induced degeneration of dopaminergic neurons in substantia nigra

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    BACKGROUND: Recent attention has focused on understanding the role of the brain-renin-angiotensin-system (RAS) in stroke and neurodegenerative diseases. Direct evidence of a role for the brain-RAS in Parkinson's disease (PD) comes from studies demonstrating the neuroprotective effect of RAS inhibitors in several neurotoxin based PD models. In this study, we show that an antagonist of the angiotensin II (Ang II) type 1 (AT(1)) receptor, losartan, protects dopaminergic (DA) neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity both in primary ventral mesencephalic (VM) cultures as well as in the substantia nigra pars compacta (SNpc) of C57BL/6 mice (Fig. 1). RESULTS: In the presence of exogenous Ang II, losartan reduced MPP(+ )(5 ÎĽM) induced DA neuronal loss by 72% in vitro. Mice challenged with MPTP showed a 62% reduction in the number of DA neurons in the SNpc and a 71% decrease in tyrosine hydroxylase (TH) immunostaining of the striatum, whereas daily treatment with losartan lessened MPTP-induced loss of DA neurons to 25% and reduced the decrease in striatal TH(+ )immunostaining to 34% of control. CONCLUSION: Our study demonstrates that the brain-RAS plays an important neuroprotective role in the MPTP model of PD and points to AT(1 )receptor as a potential novel target for neuroprotection

    Fetal and early postnatal lead exposure measured in teeth associates with infant gut microbiota

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    BACKGROUND: Lead (Pb) is an environmentally ubiquitous heavy metal associated with a wide range of adverse health effects in children. Both lead exposure and the early life microbiome- which plays a critical role in human development-have been linked to similar health outcomes, but it is unclear if the adverse effects of lead are partially driven by early life gut microbiota dysbiosis. The objective of this study was to examine the association between in utero and postnatal lead levels (measured in deciduous baby teeth) and early life bacterial and fungal gut microbiota in the first year of life. METHODS: Data from the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS) birth cohort were analyzed. Tooth lead levels during the 2nd and 3rd trimesters and postnatally (age) were quantified using high-resolution microspatial mapping of dentin growth rings. Early life microbiota were measured in stool samples collected at approximately 1 and 6 months of age, using both 16S rRNA (bacterial) and ITS2 (fungal) sequencing. Of the 1,258 maternal-child pairs in WHEALS, 146 had data on both tooth metals and early life microbiome. RESULTS: In utero tooth lead levels were significantly associated with gut fungal community composition at 1-month of age, where higher levels of 2nd trimester tooth lead was associated with lower abundances of Candida and Aspergillus and higher abundances of Malassezia and Saccharomyces; 3rd trimester lead was also associated with lower abundances of Candida. Though lead did not significantly associate with the overall structure of the infant gut bacterial community, it associated with the abundance of some specific bacterial taxa, including the increased abundance of Collinsella and Bilophila and a decreased abundance of Bacteroides taxa. CONCLUSIONS: The observed associations between lead exposure and infant gut microbiota could play a role in the impact of lead on childhood development. Given the paucity of research examining these associations in humans-particularly for fungal microbiota-further investigation is needed

    'Misdiagnosed and Misunderstood': Insights into Rarer Forms of Dementia through a Stepwise Approach to Co-Constructed Research Poetry

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    This study investigated co-constructed research poetry as a way to understand the lived experiences of people affected by rarer dementia and as a means to use poetry to convey those experiences to healthcare professionals. Using mixed methods, 71 people living with rarer dementia and care-partners (stakeholders) contributed to co-constructing 27 poems with professional poets; stakeholders' verbatim words were analysed with descriptive qualitative analysis. Stakeholders were also surveyed and interviewed about their participation. Healthcare professionals (n = 93) were surveyed to elicit their responses to learning through poetry and its acceptability as a learning tool. Poems conveyed a shared narrative of different aspects of lived experience, often owing to atypical symptoms, misunderstandings by professionals, lack of support pathways, and a continuous struggle to adapt. Stakeholder surveys indicated it was a valuable experience to both co-create and respond to the poems, whilst group interviews revealed people's experiences of the research poetry were characterised by reflection on lived experience, curiosity and exploration. Healthcare professionals' responses reinforced poetry's capacity to stimulate cognitive and affective learning specific to rare dementia support and prompt both empathy and critical thinking in practice. As the largest poetry-based study that we are aware of, this novel accessible approach of creating group poems yielded substantial information about the experiences and needs of those affected by rarer dementia and how poetry can contribute to healthcare education and training

    The Updated Zwicky Catalog (UZC)

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    The Zwicky Catalog of galaxies (ZC), with m_Zw<=15.5mag, has been the basis for the Center for Astrophysics (CfA) redshift surveys. To date, analyses of the ZC and redshift surveys based on it have relied on heterogeneous sets of galaxy coordinates and redshifts. Here we correct some of the inadequacies of previous catalogs by providing: (1) coordinates with <~2 arcsec errors for all of the Nuzc catalog galaxies, (2) homogeneously estimated redshifts for the majority (98%) of the data taken at the CfA (14,632 spectra), and (3) an estimate of the remaining "blunder" rate for both the CfA redshifts and for those compiled from the literature. For the reanalyzed CfA data we include a calibrated, uniformly determined error and an indication of the presence of emission lines in each spectrum. We provide redshifts for 7,257 galaxies in the CfA2 redshift survey not previously published; for another 5,625 CfA redshifts we list the remeasured or uniformly re-reduced value. Among our new measurements, Nmul are members of UZC "multiplets" associated with the original Zwicky catalog position in the coordinate range where the catalog is 98% complete. These multiplets provide new candidates for examination of tidal interactions among galaxies. All of the new redshifts correspond to UZC galaxies with properties recorded in the CfA redshift compilation known as ZCAT. About 1,000 of our new measurements were motivated either by inadequate signal-to-noise in the original spectrum or by an ambiguous identification of the galaxy associated with a ZCAT redshift. The redshift catalog we include here is ~96% complete to m_Zw<=15.5, and ~98% complete (12,925 galaxies out of a total of 13,150) for the RA(1950) ranges [20h--4h] and [8h--17h] and DEC(1950) range [-2.5d--50d]. (abridged)Comment: 34 pp, 7 figs, PASP 1999, 111, 43
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