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Mullen Ho posted an update 2 months ago
This study aims to assess the potential effects of zanubrutinib on the activity of cytochrome P450 (CYP) enzymes and drug transporter proteins using a cocktail probe approach.
Patients received single oral doses of probe drugs alone and after at least 8 days of treatment with zanubrutinib 160 mg twice daily in a single-sequence study in 18 healthy male volunteers. Simultaneous doses of 10 mg warfarin (CYP2C9) and 2 mg midazolam (CYP3A) were administered on Day 1 and Day 14, 0.25 mg digoxin (P-glycoprotein ) and 10 mg rosuvastatin (breast cancer resistance protein ) on Day 3 and Day 16, and 20 mg omeprazole (CYP2C19) on Day 5 and Day 18. Pharmacokinetic (PK) parameters were estimated from samples obtained up to 12 h post dose for zanubrutinib; 24 h for digoxin, omeprazole and midazolam; 48 h for rosuvastatin; and 144 h for warfarin.
The ratios (%) of geometric least squares means (90% confidence intervals) for the area under the concentration-time curve from time zero to the last quantifiable concentration in the presence/absence of zanubrutinib were 99.80% (97.41-102.2%) for S-warfarin; 52.52% (48.49-56.88%) for midazolam; 111.3% (103.8-119.3%) for digoxin; 89.45% (78.73-101.6%) for rosuvastatin; and 63.52% (57.40-70.30%) for omeprazole. Similar effects were observed for maximum plasma concentrations.
Zanubrutinib 320 mg total daily dose had minimal or no effect on the activity of CYP2C9, BCRP and P-gp, but decreased the systemic exposure of CYP3A and CYP2C19 substrates (mean reduction <50%).
Zanubrutinib 320 mg total daily dose had minimal or no effect on the activity of CYP2C9, BCRP and P-gp, but decreased the systemic exposure of CYP3A and CYP2C19 substrates (mean reduction less then 50%).Reuse of oilfield-produced water (OPW) for crop irrigation has the potential to make a critical difference in the water budgets of highly productive but drought-stressed agricultural watersheds. This is the first peer-reviewed study to evaluate how trace metals in OPW used to irrigate California crops may affect human health. We modeled and quantified risks associated with consuming foods irrigated with OPW using available concentration data. The probabilistic risk assessment simulated OPW metal concentrations, crop uptake, human exposures, and potential noncancer and carcinogenic health effects. Overall, our findings indicate that there is a low risk of ingesting toxic amounts of metals from the consumption of tree nuts, citrus, grapes, and root vegetables irrigated with low-saline OPW. Results show increased arsenic cancer risk (at 10-6 ) for adult vegetarians, assuming higher consumption of multiple foods irrigated with OPW that contain high arsenic concentrations. All other cancer risks are below levels of concern and all noncancer hazards are far below levels of concern. Arsenic risk concerns could be mitigated by practices such as blending high-arsenic OPW. Future risk assessment research should model the risks of organic compounds in OPW, as our study focused on inorganic compounds. Nevertheless, our findings indicate that low-saline OPW may provide a safe and sustainable alternative irrigation water source if water quality is adequately monitored and blended as needed prior to irrigation.Interleukin-32 (IL-32) is a pro-inflammatory cytokine that induces other cytokines involved in inflammation, including tumour necrosis factor (TNF)-α, IL-6 and IL-1β. Recent evidence suggests that IL-32 has a crucial role in host defence against pathogens, as well as in the pathogenesis of chronic inflammation. Abnormal IL-32 expression has been linked to several autoimmune diseases, such as rheumatoid arthritis and inflammatory bowel diseases, and a recent study suggested the importance of IL-32 in the pathogenesis of type 1 diabetes. However, despite accumulating evidence, many molecular characteristics of this cytokine, including the secretory route and the receptor for IL-32, remain largely unknown. In addition, the IL-32 gene is found in higher mammals but not in rodents. In this review, we outline the current knowledge of IL-32 biological functions, properties, and its role in autoimmune diseases. We particularly highlight the role of IL-32 in rheumatoid arthritis and type 1 diabetes.The aim of this study was to evaluate the protective effect of biodegradable packages made with chickpea flour on the oxidation of sunflower oil. Chickpea flour films were prepared using the casting technique. To study the influence of storage time on films properties, the chickpea flour films were stored during 60 days at 25 °C and 52% relative humidity. click here In addition, sunflower oil samples were packaged in chickpea flour packages (CPs) and stored for 60 days at 25 °C. Lipid oxidation indicators were evaluated. The results showed that puncture force and redness values (a*) of chickpea films did not change significantly during storage. Tensile strength, Young’s modulus (YM), and yellowness (b*) increased and moisture content (MC), elongation (%E), solubility (%S), water vapor permeability (WVP), and luminosity (L*) decreased. Microscopic images showed the presence of a few cracks in the film network at storage day 60. Conjugated dienes and peroxide value increased less for sunflower oil stored in high-barrier plastic pouches and CPs during storage than the control treatment. CPs helped to preserve the chemical quality of sunflower oil samples, proving to be a promising alternative to develop biodegradable packaging to be used in oily food preservation. PRACTICAL APPLICATION Discarded chickpea grains are those split and different color grains that are separated from marketable grains, and represent an industrial byproduct. These grains are currently used for feed, constituting a nutritive biomass of low commercial value. Chickpea flour is a potential material for making biodegradable films. This strategy allows adding value to the chickpea industry, transforming a byproduct into a raw material with the potential to develop economical food packaging material. The use of chickpea packages to preserve sunflower oil may be an alternative to pack vegetable oil or high lipid content food, allowing the use reduction of nonbiodegradable pouches.
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Start with a huge, uncovered box, or even a kiddie pool, and fill with a thick layer (about 6 inches) of unscented clay or fine sand-like particulate clumping/scoopable litter. For Ollie, you may need to play around with the substrate types to make it more natural. Try using soil or peat.