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Microcomputed tomography and morphometric analysis revealed that a four-week oral administration of LLEP notably decreased trabecular bone loss. Taken together, our results suggest that LLEP can mitigate estrogen deficiency-induced bone loss by suppressing osteoclastogenesis, which makes it an excellent candidate for combating osteoporosis.Objective Finger systolic blood pressure measurement (FSBP) has been shown helpful in the detection of distal arterial insufficiency in upper limbs. This work assesses the possibility to measure FSBP on the 2nd phalanx instead of the first one in order to improve its sensitivity and to verify this would not alter the repeatability of the measurement. Methods In this multicenter study, FSBP was measured twice in all fingers but the thumbs in consecutive systemic sclerosis patients on the first phalanx and the second phalanx in alternate order using laser-Doppler flowmetry. Results Thirty-seven patients were enrolled. The repeatability of FSBP was excellent and similar on the first and 2nd phalanxes with coefficients of variation respectively of 7.1% and 7.6%. While the correlation between the FSBP at the two sites was fair (Pearson coefficient 0.69; p less then 0.001). The agreement was poor, with a mean difference of 14 mm Hg between the two sites. Significantly higher differences were found in fingers with digital ulcers. The ROC curves showed a better prediction of the 2nd phalanx measurements. Conclusion FSBP has an excellent repeatability whatever the site of phalanx. However, measurements performed on the 2nd phalanx have a better sensitivity for the prediction of digital ulcers.Previous studies indicate that sex-related differences exist in the regulation of cutaneous vasodilation, however, the mechanisms remain unresolved. We assessed if sex-differences in young adults exist for cholinergic, nicotinic, and β-adrenergic cutaneous vasodilation with a focus on nitric oxide synthase (NOS), cyclooxygenase (COX), and K+ channel mechanisms. In twelve young men and thirteen young women, four intradermal forearm skin sites were perfused with the following 1) lactated Ringer’s solution (control), 2) 10 mM Nω-nitro-l-arginine, a non-selective NOS inhibitor, 3) 10 mM ketorolac, a non-selective COX inhibitor, or 4) 50 mM BaCl2, a nonspecific K+ channel blocker. At all four sites, cutaneous vasodilation was induced by 1) 10 mM nicotine, a nicotinic receptor agonist, 2) 100 μM isoproterenol, a nonselective β-adrenergic receptor agonist, and 3) 2 mM and 2000 mM acetylcholine, an acetylcholine receptor agonist. Nicotine and isoproterenol were administered for 3 min, whereas each acetylcholine dose was administered for 25 min. Regardless of treatment site, cutaneous vasodilation in response to nicotine and a high dose of acetylcholine (2000 mM) were lower in women than men. By contrast, isoproterenol induced cutaneous vasodilation was greater in women vs. men. Irrespective of sex, NOS inhibition or K+ channel blockade attenuated isoproterenol-mediated cutaneous vasodilation, whereas K+ channel blockade decreased nicotine-induced cutaneous vasodilation. Taken together, our findings indicate that while the mechanisms underlying cutaneous vasodilation are comparable between young men and women, sex-related differences in the magnitude of cutaneous vasodilation do exist and this response differs as a function of the receptor agonist.Amidst the pandemic that has mesmerized the entire world, as it has not spared anyone according to any specific characteristic, some conditions have, in fact, emerged as risk factors for a complicated evolution of COVID-19. Older age, cardiovascular disease including hypertension, diabetes and pulmonary disease, have been associated with more severe presentations and/or adverse prognosis. In this letter to the editor, we propose that the link between cardiovascular and metabolic diseases and the higher incidence and worse prognosis of COVID-19 patients is the (micro) vascular endothelium.The human choroidal vasculature is subject to age-related structural and gene expression changes implicated in age-related macular degeneration (AMD). In this study, we performed both bulk and single-cell RNA sequencing on infant (n = 4 for bulk experiments, n = 2 for single-cell experiments) and adult (n = 13 for bulk experiments, n = 6 for single-cell experiments) human donors to characterize how choroidal gene expression changes with age. Differential expression analysis revealed that aged choroidal samples were enriched in genes encoding pro-inflammatory transcription factors and leukocyte transendothelial cell migration adhesion proteins. Such genes were observed to be differentially expressed specifically within choroidal endothelial cells at the single-cell level. Immunohistochemistry experiments support transcriptional findings that CD34 is elevated in infant choriocapillaris endothelial cells while ICAM-1 is enriched in adults. These results suggest several potential drivers of the pro-inflammatory vascular phenotype observed with advancing age.Cocrystals that are more soluble than the constituent drug, generate supersaturation levels during dissolution and are predisposed to conversion to the less soluble drug. Drug release studies during cocrystal dissolution generally compare several cocrystals and their crystal structures. However, the influence of drug dose and solubility in different dissolution media has been scarcely reported. The present study aims to investigate how drug dose/solubility ratio (Do=Cdose/Sdrug), cocrystal solubility advantage over drug (SA=Scocrystal/Sdrug), and dissolution media affect cocrystal dissolution-drug supersaturation and precipitation (DSP) behavior. SA and Ksp values of 11 cocrystals of meloxicam-salicylic acid (MLX-SLC) and meloxicam-maleic acid (MLX-MLE) were determined at cocrystal/drug eutectic points. Results demonstrate that both cocrystals enhance SA by orders of magnitude (20 to 100 times for the SLC and over 300 times for the MLE cocrystal) in the pH range of 1.6 to 6.5. It is shown that during dissolutstal preceeded formation of the stable MLX polymorph I in bulk solution (in all conditions without FeSSIF), and (2) bulk nucleation of the stable MLX polymorph (in FeSSIF). selleck products The interplay between cocrystal SA, Do, and drug precipitation pathways provide a framework to interpret and understand the DSP behavior of cocrystals.