Previous chronotherapy studies have shown that the circadian pattern of blood pressure (BP) remains unchanged after either morning or evening dosing of several calcium channel blockers (CCB), including amlodipine, isradipine, verapamil, nitrendipine, and cilnidipine. This trial investigated the antihypertensive efficacy and safety profile of the slow-release, once-a-day nifedipine gastrointestinal therapeutic system (GITS) formulation administered at different times with reference to the rest-activity cycle of each participant. We studied 80 diurnally active subjects (36 men and 44 women), 52.1+/-10.7 yrs of age, with grade 1-2 essential hypertension, who were randomly assigned to receive nifedipine GITS (30 mg/day) as a monotherapy for eight weeks, either upon awakening in the morning or at bedtime at night. Patients with uncontrolled BP were up-titrated to a higher dose, 60 mg/day nifedipine GITS, for an additional eight weeks. BP was measured by ambulatory monitoring every 20 min during the day and every 30 min at night for 48 consecutive hours before and after therapy with either dose. The BP reduction after eight weeks of therapy with the lower dose of 30 mg/day was slightly, but not significantly, larger with bedtime dosing. The efficacy of 60 mg/day nifedipine GITS in non-responders to the initial 30 mg/day dose was twice as great with bedtime as compared to morning dosing. Moreover, bedtime administration of nifedipine GITS reduced the incidence of edema as an adverse event by 91%, and the total number of all adverse events by 74% as compared to morning dosing (p=0.026). Independent of the time of day of administration, a single daily dose of 30 mg/day of nifedipine GITS provides full 24 h therapeutic coverage. The dose-dependent increased efficacy and the markedly improved safety profile of bedtime as compared to morning administration of nifedipine GITS should be taken into account when prescribing this CCB in the treatment of essential hypertension.
Honeybees produce honey, royal jelly, propolis, bee venom, bee pollen, and beeswax, which potentially benefit to humans due to the bioactives in them. Clinical standardization of these products is hindered by chemical variability depending on honeybee and botanical sources, but different molecules have been isolated and pharmacologically characterized. Major honey bioactives include phenolics, methylglyoxal, royal jelly proteins (MRJPs), and oligosaccharides. In royal jelly there are antimicrobial jelleins and royalisin peptides, MRJPs, and hydroxy-decenoic acid derivatives, notably 10-hydroxy-2-decenoic acid (10-HDA), with antimicrobial, anti-inflammatory, immunomodulatory, neuromodulatory, metabolic syndrome preventing, and anti-aging activities. Propolis contains caffeic acid phenethyl ester and artepillin C, specific of Brazilian propolis, with antiviral, immunomodulatory, anti-inflammatory and anticancer effects. Bee venom consists of toxic peptides like pain-inducing melittin, SK channel blocking apamin, and allergenic phospholipase A2. Bee pollen is vitaminic, contains antioxidant and anti-inflammatory plant phenolics, as well as antiatherosclerotic, antidiabetic, and hypoglycemic flavonoids, unsaturated fatty acids, and sterols. Beeswax is widely used in cosmetics and makeup. Given the importance of drug discovery from natural sources, this review is aimed at providing an exhaustive screening of the bioactive compounds detected in honeybee products and of their curative or adverse biological effects.
Blood pressure (BP) displays predictable large-amplitude circadian variability. Thus, the identification and the proper definition of hypertension are highly ambiguous when based on single time-unspecified measurements. One way to deal with such variability in the diagnosis of hypertension is to replace the commonly used constant limits of BP by a time-specified reference interval based on the normal circadian BP rhythm assessed by ambulatory BP monitoring (ABPM). A proper reference limit can be constructed, for instance, as a tolerance interval computed for every specific time interval throughout the 24 h. Once such a threshold (given by the upper limit of the tolerance interval) is constructed, a hyperbaric index (HBI) can be computed by numerical integration of the total area of any given patient's BP profile above threshold. The HBI plus the duration of excess within the 24h day serves as nonparametric endpoints for assessing hypertension. Both retrospective and prospective evaluation of this tolerance-hyperbaric test validate its high sensitivity and specificity in the diagnosis of hypertension. We describe the theory of the HBI as well as a newly created dedicated software program that automatically derives the tolerance intervals from a reference database of normotensive subjects and calculates the HBI and other potentially valuable parameters based on data obtained by ABPM. The establishment of time-qualified tolerance limits and the assessment of the extent and timing of BP elevation represents a valuable tool for the more accurate diagnosis of hypertension as well as means of gauging response to treatment.
EDITORIAL article Front. Nutr., 17 October 2022Sec. Food Chemistry Volume 9 - 2022 | https://doi.org/10.3389/fnut.2022.1039724
The construction of time-specified reference limits requires systematic sampling in clinical health, in particular for those variables that are characterized by circadian rhythms of large amplitude, as it is the case for blood pressure. For the detection of false negatives, the use of tolerance intervals is indicated. In the case of hybrid data (time series of data collected from a group of subjects), such a tolerance interval could be very difficult to determine by following a parametric approach which is similar to the procedure used for the computation of prediction intervals, if one wanted to consider both intra- and inter-subject variance. Accordingly, we have developed a nonparametric method for the computation of such tolerance intervals on the basis of bootstrap techniques that does not need to assume normality or symmetry in the data. We also used this method to establish time-qualified reference limits for a series of blood pressures and heart rates monitored automatically in healthy individuals of both genders. By the use of these tolerance intervals, many false positive and false negative diagnoses can be eliminated. These limits serve as a reference for comparisons of a given subject's blood pressure series over time, yielding nonparametric measures of the extent and timing of any blood pressure excess or deficit. Such indices can then be used for an objective and positive definition of health, for the screening and diagnosis of disease, and for gauging the subject's response to treatment.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
The use of marine bivalves in metal pollution monitoring is undoubtedly one of the best tools to evaluate metal pollution in coastal areas worldwide. However, since bivalves integrate metal pollution from both the dissolved and the particulate phases, it cannot be assured that metal bioaccumulation in their tissues will predict the risk posed by metals to sensitive organisms such as invertebrate larvae or microalgae, which are known to be mainly affected by the free metal ion fraction. This study aims to test the usefulness of mussel gills–the primary exchange surfaces with dissolved metals–in reflecting dissolved metal bioavailability in the field. For that, we analyzed metal concentrations in environmental samples (whole soft tissues of mussels, mussel gills, sediment, and particulate and dissolved fractions in the water column) collected from 7 sampling sites during a multi-year investigative monitoring survey in the Ría de Vigo. The results showed a different pattern of Cu and Zn accumulation in gills compared to whole soft tissues, and these differences are attributable to the faster response of gills to changes in dissolved metal concentrations and to the regulation of essential metals at the whole body level. In the case of Pb, by contrast, concentrations in gills were very similar to those in the whole body. The use of mussel gills in metal pollution biomonitoring is a promising tool for the detection of changes in bioavailable metals in the environment, especially for essential metals such as Cu and Zn.
