No abstract

Despite growing interest in humic products as crop amendments, very few field evaluations have considered environmental factors of humic product efficacy. We determined the spatial and temporal variability in the efficacy of a micronized humic product on maize (Zea mays L.) growth and grain yield in two rainfed fields supporting a maize−soybean [Glycine max (L.) Merr.] rotation in 2012–2014, and 2016 in central Iowa, U.S. Crop management in both fields otherwise followed conventional farmer practices. In two dry growing seasons, mechanized combine measurements of grain yield increased significantly (P < 0.10) with humic product application on an eroded hilltop soil, amounting for two application rates to 930 and 1,600 kg ha–1 (11 and 19% of the control grain yield) in 2012, the droughtiest season, and 700 kg ha–1 (7% of the control) for the higher application rate in the somewhat droughty 2013 season. On a fertile side slope soil in the 2012 field, though, only a faint numeric response occurred in 2012, while on a toe slope soil the sole significant increase was in 2012, 870 kg ha–1 (14% increase above the control) for one application rate. With favorable rainfall in 2014 and 2016, significant grain yield increases with product application were small in the upland soil of 2014 and absent in 2016. Yield components analysis on 1-m row lengths of hand-collected samples attributed these yield boosts primarily to increased ear length, especially of the shorter ears. Combine grain yields, yield components, and total leaf area all demonstrated numerically slightly greater values for humic product treatments compared to the control in the vast majority of comparisons across years and soil types, with better distinction in the upland transects. Statistical significance, though, was reached only in the droughtier settings. The humic product had no consistent effects on nutrient concentrations of the grain, stover, or young leaves. Grain quality parameters showed a slight shift from protein to carbohydrates in the droughtier settings. Fifteen soil properties showed no response to the humic product. This humic product demonstrated the capability to improve maize growth in rainfed conditions in a high-yielding region, and its efficacy varied predictably with environmental conditions. This finding provides one potential explanation for inconsistent reports elsewhere of crop responses to humic products.

BackgroundMany drugs are substrates for P-glycoprotein (P-gp) and interactions involving P-gp may be relevant to clinical practice. Co-administration with P-gp inhibitors or inducers changes the absorption profile as well as the risk for drug toxicity, therefore it is important to evaluate possible P-gp alterations. The purpose of this study was to investigate the effect of two novel cholesterol-lowering agents, disodium ascorbyl phytostanol phosphate (DAPP) and nanostructured aluminium silicate (NSAS), a protonated montmorillonite clay, on mdr-1 gene expression and its protein, P-glycoprotein (P-gp) within Caco-2 cells.MethodsThe effects of DAPP and NSAS on the regulation of mdr-1 gene, P-gp protein expression and activity within Caco-2 cells, were determined using cell viability and cytotoxicity tests, RT-PCR, Western Blot analysis and bi-directional transport studies.ResultsWe observed a significant down-regulation of mdr-1 mRNA (e.g. 38.5 ± 17% decrease vs. control at 5 μM DAPP and 61.2 ± 25% versus control at 10 μM DAPP; n = 6, P* < 0.05) within Caco-2 cells. Western Blot analysis of P-gp expression showed that changes in mdr-1 gene expression lead to correlating changes in P-gp protein expression. This down-regulation of P-glycoprotein also resulted in decreased activity of P-glycoprotein compared to untreated control. In contrast, when Caco-2 cells were treated with NSAS, no changes in mdr-1 gene expression, P-gp protein expression nor P-gp activity were observed.ConclusionsDAPP but not NSAS decreases P-gp mediated drug efflux through decreased mdr-1 gene expression and consequently decreased P-gp protein expression. These findings have to be taken into consideration when DAPP is concurrently given with other drugs that are substrates for P-gp since drug-drug interactions harbour a safety issue and alter bioavailability profiles.NSAS does not have any P-gp altering properties and therefore might not affect drug-drug interactions. We conclude from this study that NSAS might make a safer drug candidate compared to DAPP for lowering LDL-cholesterol.

The developed HPLC-UV assay is a simple and sensitive method for the determination of vitamins D3 and K1 in rat plasma. A higher dose of vitamin K1 should be used in future studies for accurate estimation of pharmacokinetic parameters. The data show the suitability of the assay for pharmacokinetic studies in rats.

Atherosclerosis, the gradual formation of a lipid-rich plaque in the arterial wall is the primary cause of Coronary Artery Disease (CAD), the leading cause of mortality worldwide. Hypercholesterolemia, elevated circulating cholesterol, was identified as a key risk factor for CAD in epidemiological studies. Since the approval of Mevacor in 1987, the primary therapeutic intervention for hypercholesterolemia has been statins, drugs that inhibit the biosynthesis of cholesterol. With improved understanding of the risks associated with elevated cholesterol levels, health agencies are recommending reductions in cholesterol that are not achievable in every patient with statins alone, underlying the need for improved combination therapies. The whole body cholesterol pool is derived from two sources, biosynthesis and diet. Although statins are effective at reducing the biosynthesis of cholesterol, they do not inhibit the absorption of cholesterol, making this an attractive target for adjunct therapies. This report summarizes the efforts to target the gastrointestinal absorption of cholesterol, with emphasis on specifically targeting the gastrointestinal tract to avoid the off-target effects sometimes associated with systemic exposure.