Prolactin (PRL) is a peptidic hormone that displays pleiotropic functions in the organism including different actions in the brain. PRL exerts a neuroprotective effect against excitotoxicity produced ...by glutamate (Glu) or kainic acid in both in vitro and in vivo models. It is well known that Glu excitotoxicity causes cell death through apoptotic or necrotic pathways due to intracellular calcium (Ca.sup.2+ i) overload. Therefore, the aim of the present study was to assess the molecular mechanisms by which PRL maintains cellular viability of primary cultures of rat hippocampal neurons exposed to Glu excitotoxicity. We determined cell viability by monitoring mitochondrial activity and using fluorescent markers for viable and dead cells. The intracellular calcium level was determined by a fluorometric assay and proteins involved in the apoptotic pathway were determined by immunoblot. Our results demonstrated that PRL afforded neuroprotection against Glu excitotoxicity, as evidenced by a decrease in propidium iodide staining and by the decrease of the LDH activity. In addition, the MTT assay shows that PRL maintains normal mitochondrial activity even in neurons exposed to Glu. Furthermore, the Glu-induced intracellular Ca.sup.2+ i overload was attenuated by PRL. These data correlate with the reduction found in the level of active caspase-3 and the pro-apoptotic ratio (Bax/Bcl-2). Concomitantly, PRL elicited the nuclear translocation of the transcriptional factor NF-kappaB, which was detected by immunofluorescence and confocal microscopy. To our knowledge, this is the first report demonstrating that PRL prevents Glu excitotoxicity by a mechanism involving the restoration of the intracellular calcium homeostasis and mitochondrial activity, as well as an anti-apoptotic action possibly mediated by the activity of NF-kappaB. Overall, the current results suggest that PRL could be of potential therapeutic advantage in the treatment of neurodegenerative diseases.
In 2019, the EPMA celebrated its 10th anniversary at the 5th World Congress in Pilsen, Czech Republic. The history of the International Professional Network dedicated to Predictive, Preventive and ...Personalised Medicine (PPPM / 3PM) is rich in achievements. Facing the coronavirus COVID-19 pandemic it is getting evident globally that the predictive approach, targeted prevention and personalisation of medical services is the optimal paradigm in healthcare demonstrating the high potential to save lives and to benefit the society as a whole. The EPMA World Congress Supplement 2020 highlights advances in 3P medicine.
Methanol extract, obtained from
Tagetes patula plant, was assayed against three phytopathogenic fungi:
Botrytis cinerea, Fusarium moniliforme and
Pythium ultimum. The antifungal activity was tested ...both in the dark and in the light, using two different lighting systems. The data showed that the extract proved to have a dose-dependent activity on all the fungi with a marked difference between treatments in the light than in the dark. Good growth inhibition was observed in fungi only when these were treated with the highest dose of the extract and irradiated, whereas the same dose gave only a modest inhibition when the experiment was conducted in the dark. At 5 and 10
μg/ml in the dark, growth increased. The results indicated that the presence of a luminous source enhances the antifungal activity, with small differences between UV-A and solar spectrum light. SEM and TEM observations on
Pythium ultimum revealed that the
Tagetes patula extract induced alterations on cell fungal membranes with a photoactivation mechanism possibly involving the production of free radicals and leading to a premature aging of the mycelium.
Inclusion complexes of protonated propiconazole nitrate (PCZH-NO
3
) with three substituted cyclodextrin (CD) derivatives, namely, sulfobutylether-β-CD (SBE7-β-CD), sulfated-β-CD (β-CD-SNa) and ...monochlorotriazinyl-β-CD (MCT-β-CD), were investigated as new antifungal systems and compared with a previously published complex of PCZH-NO
3
with unsubstituted β-CD. The inclusion complexes were prepared by the freeze-drying method and were characterized by
1
H-NMR, 2D Roesy NMR and DSC. This study demonstrates the coexistence of two types of PCZH-NO
3
inclusion into the CD cavity. The complexes with SBE7-β-CD had the highest association constant values and the inclusion efficiency was close to 100%. Comparative
in silico
docking and molecular dynamics simulations were performed. The antifungal activity was assessed on
Candida
spp. and was similar for all four inclusion complexes. The cytotoxicity assessed on normal human dermal fibroblasts (NHDF) was significantly higher for the complex with β-CD than that of the complexes of substituted CDs.
Inclusion complexes with sulfobutylether-β-cyclodextrin, β-cyclodextrin sulphated sodium salt and monochlorotriazinyl-β-cyclodextrin were characterized and assessed for antifungal activity and cytotoxicity.
We assessed the costs and effectiveness of rapid HIV testing services provided to transgender communities in New York City and San Francisco from April 2005 to December 2006. Program costs were ...estimated based on service provider's perspective and included the costs attributable to staff time, incentives, transportation, test kits, office space, equipment, supplies, and utilities. The average annual numbers of persons tested were 195 and 106 persons and numbers notified of new HIV diagnoses were 35 (18.2%) in New York City and 8 (7.3%) in San Francisco, respectively. The estimated annual program costs were $125,879 and $64,323 and average costs per person notified of new diagnosis were $3,563 and $8,284 in New York City and San Francisco, respectively. The primary reason for differences in program costs by site was differences in the proportion of undiagnosed HIV infection among persons tested. Our findings can inform decisions about program planning and allocation of limited HIV testing resources.
Inclusion complexes of protonated propiconazole nitrate (PCZH-NO sub(3)) with three substituted cyclodextrin (CD) derivatives, namely, sulfobutylether- beta -CD (SBE7- beta -CD), sulfated- beta -CD ( ...beta -CD-SNa) and monochlorotriazinyl- beta -CD (MCT- beta -CD), were investigated as new antifungal systems and compared with a previously published complex of PCZH-NO sub(3) with unsubstituted beta -CD. The inclusion complexes were prepared by the freeze-drying method and were characterized by super(1)H-NMR, 2D Roesy NMR and DSC. This study demonstrates the coexistence of two types of PCZH-NO sub(3) inclusion into the CD cavity. The complexes with SBE7- beta -CD had the highest association constant values and the inclusion efficiency was close to 100%. Comparative in silicodocking and molecular dynamics simulations were performed. The antifungal activity was assessed on Candidaspp. and was similar for all four inclusion complexes. The cytotoxicity assessed on normal human dermal fibroblasts (NHDF) was significantly higher for the complex with beta -CD than that of the complexes of substituted CDs.
The production of deuterons and anti-deuterons in pp collisions at s=7and13TeV has been studied as a function of charged-particle multiplicity using the ALICE detector at the LHC. The preliminary ...results are shown here, together with those obtained in heavy-ion collisions. They are presented by focusing the discussion on the comparison with expectations from hadron-coalescence models.
ALICE has measured quarkonium production in p-Pb collisions at backward (−4.46 <ycms < −2.96), mid (−1.37 <ycms < 0.43) and forward (2.03 <ycms < 3.53) rapidity (y) regions down to zero transverse ...momentum (pT). The inclusive J/ψ production has been studied at mid-y in p-Pb interactions at sNN=5.02TeV and at forward and backward y in p-Pb collisions at sNN=5.02TeV and8.16TeV. The comparison of the J/ψ production to the one of the loosely bound ψ(2S) state is discussed, together with new results on the nuclear modification factors of the ϒ(1S) and ϒ(2S) states measured at forward and backward y. All the results will be compared to those obtained at lower energies and with available theoretical calculations.
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