8,473 research outputs found
Odorants could elicit repair processes in melanized neuronal and skin cells
No full textThe expression of ectopic olfactory receptors (ORs) in melanized cells, such as the human brain nigrostriatal dopaminergic neurons and skin melanocytes, is here pointed out. ORs are recognized to regulate skin melanogenesis, whereas OR expression in the dopaminergic neurons, characterized by accumulation of pigment neuromelanin, is downregulated in Parkinson's disease. Furthermore, the correlation between the pigmentation process and the dopamine pathway through α-synuclein expression is also highlighted. Purposely, these ORs are suggested as therapeutic target for neurodegenerative diseases related to the pigmentation disorders. Based on this evidence, a possible way of turning odorants into drugs, acting on three specific olfactory receptors, OR51E2, OR2AT4 and VN1R1, is thus introduced. Various odorous molecules are shown to interact with these ORs and their therapeutic potential against melanogenic and neurodegenerative dysfunctions, including melanoma and Parkinson's disease, is suggested. Finally, a direct functional link between olfactory and endocrine systems in human brain through VN1R1 is proposed, helping to counteract female susceptibility to Parkinson's disease in quiescent life
L’estradiolo stimola la vitalità di cellule endoteliali microvascolari cerebrali in vitro isolate da pazienti neurochirurgici
No full textLa selettività della barriera emato-encefalica (BBB) è garantita dalle cellule endoteliali che rivestono le pareti dei microcapillari cerebrali ( hBMEC ). L'ormone 17β estradiolo ha effetti sulla salute vascolare della BBB in entrambi i sessi, per i quali si può prevedere la crioconservazione di cellule endoteliali (hBMEC) autologhe da utilizzare per terapie personalizzate
Heterogeneous patterning of blood-brain barrier and adaptive myelination as renewing key in gray and white matter
No full textDevelopment and homeostasis of the brain are enabled through the precise control of the cell microenvironment by the blood-brain barrier (BBB), which interfaces between the brain parenchyma and the lumen of blood microvessels, and by the blood-cerebrospinal fluid barrier, which separates the cerebrospinal fluid from the blood vessels of the choroid plexus. Here, the focus will be on the BBB, the impairment of which is considered the earliest common denominator in neurovascular diseases
Barbara James
No full textDate:1943Barbara was born in Holdredge, Nebraska in the United States of America in 1943. In 1960 she arrived in Darwin working in a variety of occupations such as a journalist, historian, author, activist, advocate and editor. Barbara wrote 13 books including "No Man's Land" which explored the contributions of women in the Northern Territory. She also received a number of awards including 2001 NT Heritage Award, the 2000 NT Literary Essay Awards and the Chief Minister's Women's Achievement Award in 1999.JournalistHistorianAuthorActivistEditorAmerica
Retinal pigment epithelial cells as a therapeutic tool and target against retinopathies
No full textRetinal pigment epithelium (RPE) is a cell monolayer essential for photoreceptor function and forming the blood–retinal barrier. RPE and retinal neurons share the same origin and a polarized cytoarchitecture. Several factors determine the phagocytosis and permeability of RPE, influencing photoreceptor renewal and drug delivery, efficacy and toxicity. Adult human RPE expresses neuronal markers in vitro, indicating a potential transdifferentiation. Degeneration of the RPE leads to death of photoreceptors and retinal neurons, resulting in the vision loss of retinopathy. Here, we suggest tools for cell engineering to discover new ways for activating the endogenous regeneration of barrier functions and/or of the retinal precursors in RPE cells
Prodrugs and Endogenous Transporters: Are They Suitable Tools for Drug Targeting into the Central Nervous System?
No full textHydrophilic drugs, or neuroactive agents characterized by high molecular weight, do not have the physico-chemical properties required for passive diffusion across the blood brain barrier (BBB). The prodrug approach by lipidization of hydrophilic drugs generally allows to sensibly increase their permeability across BBB, even if this phenomenon is often not associated to an effective entry into the brain of the lipidized drugs. It has been understood that active efflux transporters (AET) can have a very important role in extruding from the brain not only prodrugs obtained by lipidization processes, but also lipophilic drugs. On the other hand, it has been also demonstrated carrier mediated transporters (CMT), able to transport essential nutrients and hormones from the bloodstream to the CNS, can be employed for the brain targeting of appropriated designed prodrugs. This approach consists on the chemical modification of a drug into a “pseudonutrient” or, differently, on drug conjugation to essential nutrients transported by CMT systems. This review focuses the molecular aspects that regulate the activity of the CMT and AET systems for the transport of their substrates, taking into account the in vitro and in vivo studies related to these transporters and, thus, the prodrug approaches useful to target the neuroactive agents in the central nervous systems are described. Among these, the molecular Trojan horses systems are briefly illustrated as carriers for the transport in the brain of large molecular weight neuroactive agents
Nose-to-Brain Delivery of Antiviral Drugs: A Way to Overcome Their Active Efflux?
No full textAlthough several viruses can easily infect the central nervous system (CNS), antiviral drugs often show dramatic difficulties in penetrating the brain from the bloodstream since they are substrates of active efflux transporters (AETs). These transporters, located in the physiological barriers between blood and the CNS and in macrophage membranes, are able to recognize their substrates and actively efflux them into the bloodstream. The active transporters currently known to efflux antiviral drugs are P-glycoprotein (ABCB1 or P-gp or MDR1), multidrug resistance-associated proteins (ABCC1 or MRP1, ABCC4 or MRP4, ABCC5 or MRP5), and breast cancer resistance protein (ABCG2 or BCRP). Inhibitors of AETs may be considered, but their co-administration causes serious unwanted effects. Nasal administration of antiviral drugs is therefore proposed in order to overcome the aforementioned problems, but innovative devices, formulations (thermoreversible gels, polymeric micro- and nano-particles, solid lipid microparticles, nanoemulsions), absorption enhancers (chitosan, papaverine), and mucoadhesive agents (chitosan, polyvinilpyrrolidone) are required in order to selectively target the antiviral drugs and, possibly, the AET inhibitors in the CNS. Moreover, several prodrugs of antiretroviral agents can inhibit or elude the AET systems, appearing as interesting substrates for innovative nasal formulations able to target anti-Human Immunodeficiency Virus (HIV) agents into macrophages of the CNS, which are one of the most important HIV Sanctuaries of the body
Barbara Ras - Sowell Conference 2017
No full textBarbara Ras, San Antonio, Poet, author of "Bite Every Sorrow" and "The Last Skin
Processing of adenosine receptor agonists in rat and human whole blood
No full textA stability study of adenosine receptor agonists in rat and human whole blood was performed. The compounds were incubated at 37 degrees in fresh blood, and aliquots of the incubation mixture were hemolyzed at regular time intervals and analyzed with HPLC. N6-cyclopentyladenosine (CPA) and N6-cyclobutyladenosine (CBA) were degraded, whereas N6-cyclohexyladenosine, N6-cycloheptyladenosine and N6-sulfophenyladenosine were not. 2-Chloroadenosine had a half-life very similar to that of CPA. However, the 2'-, 3'-, and 5'-deoxyribose derivatives of CPA remained intact. The nucleoside transport inhibitor nitrobenzylthioinosine attenuated CBA and CPA metabolism in rat blood as did the inhibitor of adenosine deaminase erythro-9-(2-hydroxy-3-nonyl)adenine, albeit at relatively high concentrations. Complete blockade of CBA and CPA degradation was achieved by a preincubation of rat and human blood with the adenosine kinase (AK) inhibitor 5'-amino-5'-deoxyadenosine. We conclude that the two adenosine analogues are metabolized by AK both in rat and in human whole blood
Exclusive interview with author Barbara Kingsolver
No full textExclusive interview with author Barbara Kingsolver for her 2018 novel *Unsheltered
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