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Bolton MacKinnon posted an update 6 months, 3 weeks ago
Self-emulsifying lipids (SEL) were used as a stabilizer for the preparation of dexamethasone lipid nanoparticles by membrane emulsification employing Shirasu porous glass. The effect of process and formulation parameters on the size and polydispersity and dexamethasone solubility in lipids and its release from lipid nanoparticles were investigated. Lipid phase pressure (40-80 kPa), membrane pore-size (0.1 - 0.4 µm) and agitation speed (300 - 900 rpm) did not affect the size and polydispersity of SEL. However, the size was increased with increasing lipid content and fatty acid chain of the lipid. Sizes of less then 250 nm were achieved from TEGO® careGelucire® blend and it increased to 487 nm by adding 20% w/w of hard fat. The highest solubility of dexamethasone was found in TEGO® care 450 (29 mg/g). Release from the lipid nano-dispersions was extended with no burst effect and the absolute release was increased with increasing lipid content.
We have used a contrast injection scheme termed as “guided catheterization method (guided method).” By using a large-bore 5-Fr catheter and 0.032-in guidewire, a contrast medium could be injected without removing the guidewire. Using a neurovascular phantom, we studied the influence of leaving the guidewire on the contrast injection pressure. Image quality was compared with that obtained using a 4-Fr regular angiography catheter (conventional method).
Actual contrast injection pressure, flow rate, flow volume, and several variables from the time-density curve (TDC) were obtained using the guided method and the conventional method. Catheterization parameters included flow rate, the viscosity of a contrast medium (CM), and catheter length. The pressure limit of a contrast injector was set as 1200 psi. Digital subtraction angiography (DSA) images on the neurovascular phantom were acquired. The DSA images were processed, and TDC on a specific region of interest was obtained. Variables from TDC were calculated and compared between the different catheters.
The ranges of actual contrast injection pressure with the conventional and the guided method were 138-299 psi and 184-451 psi, respectively. A minimal reduction of the actual flow rate was found under some conditions with the guided method. Comparable opacifications in DSA images were achieved in all conditions. Although peak intensity was different by flow rate or CM, all TDC variables did not differ based on the catheter. There were no significant harmful events during the 90 experiments.
With adjustment of the pressure limit, cerebral angiography using the 5-Fr, large-bore catheter without removal of the guidewire is feasible, safe, and expected to provide image quality comparable to that of the 4-Fr regular catheter.
With adjustment of the pressure limit, cerebral angiography using the 5-Fr, large-bore catheter without removal of the guidewire is feasible, safe, and expected to provide image quality comparable to that of the 4-Fr regular catheter.Hypoxia is a frequent occurrence in most solid tumors and associated with multiple cancer progression. Glaucocalyxin A (GLA) has been found to exhibit anti-tumor effect in several types of cancer, except gastric cancer (GC). The present study aimed to evaluate the function of GLA in GC and explore the underlying mechanism under hypoxia condition. Our results showed that GLA suppressed cell viability of MGC-803 cells in both normoxic or hypoxic conditions. MGC-803 cells were more sensitive to GLA in hypoxic condition. GLA attenuated hypoxia-induced migration and invasion of GC cells. Western blot assay proved that GLA elevated E-cadherin expression, as well reduced N-cadherin and vimentin expressions in hypoxia-induced GC cells. Moreover, we also found that GLA suppressed the expression of HIF-1α in both mRNA and protein levels. Furthermore, GLA blocked hypoxia-induced activation of PI3K/Akt pathway in GC cells. Notably, insulin like growth factor 1 (IGF-1), an activator of PI3K/Akt pathway, reversed the effects of GLA on cell migration, invasion and EMT in hypoxia-treated MGC-803 cells. In conclusion, these findings demonstrated that GLA exerted inhibitory effects on cell migration, invasion and epithelial to mesenchymal transition (EMT) via the PI3K/Akt signaling pathway in GC cells.Introduction Positive expiratory pressure (PEP) and oscillating positive expiratory pressure (OscPEP) therapies are often used by people with cystic fibrosis (CF) to facilitate airway clearance. However, suboptimal adherence and poor technique may reduce their effectiveness. Objective To develop a device (PEPtrac) to accurately measure and provide preliminary clinical data of adherence and technique characteristics when airway clearance is performed using PEP/OscPEP devices. Methods This study comprised two distinct phases 1) a benchtop validation study; and 2) clinical study. Benchtop study Accuracy of PEPtrac was measured by comparing it to video analysis for five different PEP/OscPEP devices. Clinical study Clinical data were then collected for 18 adults with CF using one of three PEP/OscPEP devices (PariPEP S®, Acapella DH® or Aerobika®) unsupervised. Results There was 100% agreement between PEPtrac and video analysis data. Clinical data revealed significant variability in expiratory duration and pressure properties between the three PEP/OscPEP devices and between participants. For example, expiratory duration with PariPEP S® (mean = 4.8 sec) was longer (p less then .001) than Acapella DH® (3.7 sec) and Aerobika® (2.9 sec) and Aerobika® had a higher oscillation amplitude than Acapella DH® (6.4 vs 5.3 cmH2O, p less then .001). Discussion Accurate measurement of PEP/OscPEP adherence and technique using a device such as PEPtrac was possible. SAG agonist order Further research is required to investigate the clinical importance of the variability in technique seen in our clinical data.Antiplatelet medications comprise the cornerstone of treatment for diseases that involve arterial thrombosis, including acute coronary syndromes (ACS), stroke and peripheral arterial disease. However, antiplatelet medications may cause bleeding and, furthermore, thrombotic events may still recur despite treatment. The interaction of collagen with GPVI receptors on the surface of platelets has been identified as one of the major players in the pathophysiology of arterial thrombosis that occurs following atherosclerotic plaque rupture. Promisingly, GPVI deficiency in humans appears to have a minimal impact on bleeding. These findings together suggest that targeting platelet GPVI may provide a novel treatment strategy that provides additional antithrombotic efficacy with minimal disruption of normal hemostasis compared to conventional antiplatelet medications. CLEC-2 is gaining interest as a therapeutic target for a variety of thrombo-inflammatory disorders including deep vein thrombosis (DVT) with treatment also predicted to cause minimal disruption to hemostasis.
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