67 research outputs found
Hemolytic vascular inflammation: an update
Made available in DSpace on 2016-11-10T13:31:43Z (GMT). No. of bitstreams: 1
pmed_26969775.pdf: 607909 bytes, checksum: c33e900140de01738d42c6807067a943 (MD5)
Previous issue date: 201638555
COVID-19: Time for precision epidemiology
The global COVID-19 (SARS-CoV2, COVID-19) tsunami caused by SARSCoV2 is inundating and often-overwhelming health care systems in most countries and regions..
Prominent Role Of Platelets In The Formation Of Circulating Neutrophil-red Cell Heterocellular Aggregates In Sickle Cell Anemia.
99e214-
Understanding the impact of heavy ions and tailoring the optical properties of large-area Monolayer WS2 using Focused Ion Beam
Focused ion beam (FIB) has been used as an effective tool for precise
nanoscale fabrication. It has recently been employed to tailor defect
engineering in functional nanomaterials such as two-dimensional transition
metal dichalcogenides (TMDCs), providing desirable properties in TMDC-based
optoelectronic devices. However, the damage caused by the FIB irradiation and
milling process to these delicate atomically thin materials, especially in the
extended area, has not yet been elaboratively characterised. Understanding the
correlation between lateral ion beam effects and optical properties of 2D TMDCs
is crucial in designing and fabricating high-performance optoelectronic
devices. In this work, we investigate lateral damage in large-area monolayer
WS2 caused by the gallium focused ion beam milling process. Three distinct
zones away from the milling location are identified and characterised via
steady-state photoluminescence (PL) and Raman spectroscopy. An unexpected
bright ring-shaped emission around the milled location has been revealed by
time-resolved PL spectroscopy with high spatial resolution. Our finding opens
new avenues for tailoring the optical properties of TMDCs by charge and defect
engineering via focused ion beam lithography. Furthermore, our study provides
evidence that while some localised damage is inevitable, distant destruction
can be eliminated by reducing the ion beam current. It paves the way for the
use of FIB to create nanostructures in 2D TMDCs, as well as the design and
realisation of optoelectrical devices on a wafer scale
Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications
This work was supported by a restricted research grant of Bayer AG
Prospects For Early Investigational Therapies For Sickle Cell Disease
Sickle cell disease (SCD) is a genetic disorder characterized by the production of abnormal hemoglobin that polymerizes at low oxygen concentrations, causing the erythrocyte to adopt a sickle-shaped morphology. SCD pathophysiology is extremely complex and can lead to numerous clinical complications, including painful vaso-occlusive crises (VOC), end-organ damage, and a shortened lifespan. An impressive number of investigational drugs are currently in early stages of clinical development with prospects for use either as chronic therapies to reduce VOC frequency and end-organ damage in SCD or for use at the time of VOC onset. Many of these agents have been developed using a pathophysiological-based approach to SCD, targeting one or more of the mechanisms that contribute to the disease process. It is plausible that a multi-drug approach to treating the disease will evolve in the coming years, whereby hydroxyurea (HU) (the only drug currently FDA-approved for SCD) is used in combination with drugs that amplify nitric oxide signaling and/or counteract hemolytic effects, platelet activation and inflammation.24559560
cGMP modulation therapeutics for sickle cell disease
Sickle cell disease (SCD) is an inherited disease caused by the production of abnormal hemoglobin (Hb) S, whose deoxygenation-induced polymerization results in red blood cell (RBC) sickling and numerous pathophysiological consequences. SCD affects approximately 300,000 newborns worldwide each year and is associated with acute and chronic complications, including frequent painful vaso-occlusive episodes that often require hospitalization. Chronic intravascular hemolysis in SCD significantly reduces vascular nitric oxide (NO) bioavailability, consequently decreasing intracellular signaling via cyclic guanosine monophosphate (cGMP), in turn diminishing vasodilation and contributing to the inflammatory mechanisms that trigger vaso-occlusive processes. Oxidative stress may further reduce NO bioavailability in SCD and can oxidize the intracellular enzyme target of NO, soluble guanylate cyclase (sGC), rendering it inactive. Increasing intracellular cGMP-dependent signaling constitutes an important pharmacological therapeutic approach for SCD with a view to augmenting vasodilation, and reducing inflammatory mechanisms, as well as for increasing the production of anti-polymerizing fetal Hb in erythroid cells. Pharmacological agents under pre-clinical and clinical investigation for SCD include NO-based therapeutics to augment NO bioavailability, as well as heme-dependent sGC stimulators and heme-independent sGC activators that directly stimulate native and oxidized sGC, respectively, therefore bypassing the need for vascular NO delivery. Additionally, the phosphodiesterases (PDEs) that degrade intracellular cyclic nucleotides with specific cellular distributions are attractive drug targets for SCD; PDE9 is highly expressed in hematopoietic cells, making the use of PDE9 inhibitors, originally developed for use in neurological diseases, a potential approach that could rapidly amplify intracellular cGMP concentrations in a relatively tissue-specific manner2442132146FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2018/08010–9; 2017/14594–0; 2014/ 00984–
- …