Some specific features of the 24 h blood pressure (BP) pattern are linked to the progressive injury of target tissues and the triggering of cardiac and cerebrovascular events. In particular, many studies show the extent of the nocturnal BP decline relative to the diurnal BP mean (the diurnal/nocturnal ratio, an index of BP dipping) is deterministic of cardiovascular injury and risk. Normalization of the circadian BP pattern is considered to be an important clinical goal of pharmacotherapy because it may slow the advance of renal injury and avert end-stage renal failure. The chronotherapy of hypertension takes into account the epidemiology of the BP pattern, plus potential administration-time determinants of the pharmacokinetics and dynamics of antihypertensive medications, as a means of enhancing beneficial outcomes and/or attenuating or averting adverse effects. Thus, bedtime dosing with nifedipine gastrointestinal therapeutic system (GITS) is more effective than morning dosing, while also reducing significantly secondary effects. The dose-response curve, therapeutic coverage, and efficacy of doxazosin GITS are all markedly dependent on the circadian time of drug administration. Moreover, valsartan administration at bedtime as opposed to upon wakening results in improved diurnal/nocturnal ratio, a significant increase in the percentage of patients with controlled BP after treatment, and significant reductions in urinary albumin excretion and plasma fibrinogen. Chronotherapy provides a means of individualizing treatment of hypertension according to the circadian BP profile of each patient, and constitutes a new option to optimize BP control and reduce risk.
Abstract — — The use of a set of new end points obtained from ambulatory blood pressure monitoring, in addition to the blood pressure values themselves, has been advocated to improve sensitivity and specificity in the diagnosis of hypertension and the evaluation of a patient’s response to treatment. Among these parameters is the use of blood pressure load, the percentage of values above a given constant reference limit or computed by reference to daytime and nighttime limits. We examined the effectiveness of this parameter as a potential screening test for the detection of hypertension in pregnancy. We analyzed 2014 blood pressure series systematically sampled by ambulatory monitoring for 48 consecutive hours every 4 weeks from the first obstetric visit (usually within the first trimester of pregnancy) until delivery of 205 normotensive pregnant women and 123 women who developed gestational hypertension or preeclampsia. The blood pressure load was obtained as the percentage of values >140/110/90 mm Hg (systolic/mean arterial/diastolic blood pressure) during active hours or 120/95/80 mm Hg during resting hours, as well as by comparison with limits obtained by progressively reducing the previous limits by 5 mm Hg, up to a final threshold of 125/95/75 mm Hg (day) and 105/80/65 mm Hg (night). Sensitivity for the blood pressure load computed by reference to the highest limits used here is <55% in all trimesters of pregnancy. The best results were obtained when 130/100/80 mm Hg (day) and 110/85/70 mm Hg (night) were used as references in the third trimester, and when the lowest tested limits of 125/95/75 and 105/80/65 mm Hg were used as references in the first and second trimesters (sensitivity always >73%). The optimum reference limits for calculating the blood pressure load, markedly < \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{140}{90}\) \end{document} mm Hg, must be defined as a function of gestational age, in keeping with the predictable trends in blood pressure along pregnancy previously documented.
Abstract Thermoresponsive nanocomposites comprising a gold nanoparticle core and a poly( N ‐isopropylacrylamide) (pNIPAM) shell are synthesized by grafting the gold nanoparticle surface with polystyrene, which allows the coating of an inorganic core with an organic shell. Through careful control of the experimental conditions, the pNIPAM shell cross‐linking density can be varied, and in turn its porosity and stiffness, as well as shell thickness from a few to a few hundred nanometers is tuned. The characterization of these core–shell systems is carried out by photon‐correlation spectroscopy, transmission electron microscopy, and atomic force microscopy. Additionally, the porous pNIPAM shells are found to modulate the catalytic activity, which is demonstrated through the seeded growth of gold cores, either retaining the initial spherical shape or developing a branched morphology. The nanocomposites also present thermally modulated optical properties because of temperature‐induced local changes of the refractive index surrounding the gold cores.
Abstract This article presents the synthesis and physicochemical behavior of dual‐responsive plasmonic nanoparticles with reversible optical properties based on protein‐coated gold nanoparticles grafted with thermosensitive polymer brushes by means of surface‐initiated atom transfer radical polymerization (SI‐ATRP) that exhibit pH‐dependent thermo‐responsive behavior. Spherical gold NPs of two different sizes (15 nm and 60 nm) and with different stabilizing agents (citrate and cetyltrimethylammonium bromide (CTAB), respectively) were first capped with bovine serum albumin (BSA). The resulting BSA‐capped NPs (Au@BSA NPs) exhibited not only extremely high colloidal stability under physiological conditions, but also a reversible U‐shaped pH‐responsive behavior, similar to pure BSA. The ϵ‐amine of the L‐lysine in the protein coating was then used to covalently bind an ATRP‐initiator, allowing for the SI‐ATRP of thermosensitive polymer brushes of oligo(ethylene glycol) methacrylates with an LCST of 42 °C in pure water and around 37 °C under physiological conditions. Such protein coated nanoparticles grafted with thermosensitive polymers exhibit a smart pH‐dependent thermosensitive behavior.
The inhibitory potential of natural polyphenols for α-amylases has attracted great interests among researchers. The structure-affinity properties of natural polyphenols binding to α-amylase and the structure-activity relationship of dietary polyphenols inhibiting α-amylase were deeply investigated. There is a lack of consistency between the structure-affinity relationship and the structure-activity relationship of natural polyphenols as α-amylase inhibitors. Is it consistent between the binding affinity and inhibitory potential of natural polyphenols as with α-amylase inhibitors? It was found that the consistency between the binding affinity and inhibitory potential of natural polyphenols as with α-amylase inhibitors is not equivocal. For example, there is no consistency between the binding affinity and the inhibitory potential of quercetin and its glycosides as α-amylase inhibitors. However, catechins with higher α-amylase inhibitory potential exhibited higher affinity with α-amylase.
Previous studies have reported sex differences in the pathophysiology of hypertension and responses to blood pressure (BP)-lowering medications. Moreover, men exhibit typically higher BP than women, the differences being greater for systolic (SBP) than diastolic (DBP) BP. These differences become apparent during adolescence and remain significant at least until 55-60 yrs of age. Despite such significant sex-related differences in BP regulation, the current recommended ambulatory BP monitoring (ABPM) thresholds for diagnosis of hypertension do not differentiate between men and women. We aimed to derive separate male and female diagnostic thresholds for the awake and asleep SBP and DBP means based upon cardiovascular disease (CVD) outcome. We prospectively studied 3344 subjects (1718 men/1626 women), 52.6 ± 14.5 yrs of age, during a median follow-up of 5.6 yrs. Those with hypertension at baseline were randomized to ingest all their prescribed hypertension medications upon awakening or the entire daily dose of ≥1 of them at bedtime. At baseline, BP was measured at 20-min intervals from 07:00 to 23:00 h and at 30-min intervals at night for 48 h, and physical activity was simultaneously monitored every minute by wrist actigraphy to accurately derive the awake and asleep BP means. Identical assessment was scheduled annually and more frequently (quarterly) if treatment adjustment was required. Cox regression analysis was used to derive outcome-based reference thresholds for ABPM in men and women. Men exhibited greater event rates than women of CVD death, myocardial infarction, angina pectoris, coronary revascularization, and heart failure; however, event rates of non-CVD death and cerebrovascular events were comparable. The relationship between progressively higher ambulatory BP and CVD risk increased more rapidly in women than men for awake SBP/DBP means ≥125/75 mm Hg and asleep means ≥110/70 mm Hg. The derived outcome-based reference thresholds for men were 135/85 mm Hg for the awake and 120/70 mm Hg for the asleep SBP/DBP means. In terms of CVD outcome, the equivalent cutoff threshold values for women were 125/80 mm Hg for the awake and 110/65 mm Hg for the asleep SBP/DBP means. Outcome-based reference thresholds for the diagnosis of hypertension were 10/5 mm Hg lower for ambulatory SBP/DBP in women than men. This marked sex difference indicates the need for revision of current guidelines that propose diagnostic thresholds for ambulatory BP without differentiation between men and women.
