Publications

The lack of nocturnal decline in blood pressure (BP) is frequent in patients with type 2 diabetes mellitus (DM). The actual prevalence of a nondipping pattern in DM is, however, highly variable among different studies. Recent results have also indicated that nondipping in treated hypertensive patients is markedly related to the absence of 24-hour therapeutic coverage [J Hypertens. 2002;20:1097–1104]. Accordingly, we have evaluated the incidence of nondipping in treated and untreated hypertensive patients with and without DM. We studied 234 hypertensive patients with DM (129 men), 59.8±11.3 years of age, and 1,184 patients with grade 1–2 essential hypertension (512 men), 52.1±13.9 years of age. Among those patients, 88 with DM and 679 hypertensive controls were untreated at the time of the study. BP was measured by ambulatory monitoring (ABPM) at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours. Physical activity was simultaneously evaluated at 1-min intervals by wrist actigraphy. Diurnal and nocturnal means of BP obtained according to individual resting time determined by actigraphy were used to classify each patient as dipper or nondipper (nocturnal BP decline <10%). Among untreated patients without DM, 40.4% were nondippers, while this percentage was significantly increased to 56.6% among treated patients. In DM, 65% of the untreated and 77% of the treated patients were nondippers. The percentage of risers (patients with nocturnal BP mean above the diurnal mean) increased from 3.7% in untreated controls to 17.1% in untreated patients with DM, and from 11.9% among treated hypertensive patients to a very high 28.1% among treated patients with DM. Results from this study on hypertensive patients with and without DM evaluated by 48-hour continuous ABPM and with nocturnal BP mean calculated individually according to actual resting time determined by actigraphy, indicates the high prevalence of an altered circadian BP pattern in DM. The extremely high prevalence of risers among both treated and untreated patients with DM indicates the need to establish a proper chronotherapeutic antihypertensive scheme that could allow not only to reduce BP but also to modify the altered circadian profile into a dipper pattern with a lower cardiovascular risk. Am J Hypertens (2004) 17, 214A–214A; doi: 10.1016/j.amjhyper.2004.03.570

A systematic study of the optical effects derived from plasmon coupling in mono- and multilayers of gold nanorods is presented. The monolayers were prepared using the standard polyelectrolyte-assisted layer-by-layer (LbL) method and gold nanorods coated with either poly(N-vinyl pyrrolidone) or homogeneous silica shells. Such plasmon coupling leads in general to extensive red-shift and broadening of the longitudinal plasmon bands, which are discussed on the basis of recently reported theoretical modeling. Whereas for PVP-coated rods, strong interactions were observed for high-density monolayers and closely spaced multilayers, increasingly efficient screening is observed for thicker silica shells.

Population-based epidemiology and clinical case studies document a prominent 24-hour pattern in the occurrence of silent and non-silent angina pectoris (AP), acute myocardial infarction (AMI), and sudden cardiac death (SCD). When the data are summarized per 3 - 6 hour intervals of the 24 hours, the temporal pattern of these ischemic heart disease (IHD) events shows a single morning peak between 06: 00 and 12:00 h in incidence. However, when the occurrence of such events is examined according to the hour of their occurrence, several studies reveal a second late-afternoon/early-evening minor peak. The true day - night pattern in AP, AMI, and SCD is unknown because the data represent nothing more than the recorded `"time of day'' of the events. It has been postulated that the day - night pattern in IHD events is at least in part dependent on endogenous circadian rhythms, which are synchronized by the daily routine of sleep in darkness/ activity in light. Approximately 20% of the working population is involved in night and rotating shift employment; thus, "time of day'' studies are not likely to accurately represent the actual "chronorisk'' of vulnerable individuals to IHD events. Moreover, it is likely that the events in the persons comprising the population and clinical case studies were influenced by ongoing treatment with antihypertensive, anticoagulant, and antianginal medications. Details regarding the class, dose, and schedule of such medications are rarely if ever reported in accounts of IHD events. Many of the investigations were conducted decades ago, when short-acting antihypertensive and cardiovascular medications required twice or thrice-a-day dosing, and thus the observed day - night variations could be significantly affected by such multiple treatment timings each day. Thus, the magnitude and nature (single versus multiple peaks) of the reported day - night patterns in AP, AMI, and SCD are suspect, as are their geneses. Presently, it is hypothesized that multiple cyclic exogenous triggers (e. g. posture, physical exertion, emotional stress, and medication scheduling) superimposed upon an endogenous 24-hour susceptibility-resistance pattern that arises from circadian rhythms in heart rate, blood pressure, rate-pressure product, and haemostasis, are major contributory factors.

The development of food fortified with polyphenols and polyphenol-rich foods represents a novel approach to prevent or attenuate type 2 diabetes. It has been reported that type 2 diabetes may affect the pharmacokinetics of various drugs in several animal models. There is powerful evidence linking dietary polyphenols consumption with the risk factors defining type 2 diabetes, even if some opposite results occurred. This mini-review summarizes important advances on diabetes-associated changes in pharmacokinetics of natural polyphenols. The pharmacokinetic behavior between drugs and dietary polyphenols probably may be different due to (i) Ingested dose/amount per day. The dietary polyphenol intake per day is much higher than that of clinical drugs; (ii) Complexity of the components. Clinical drugs are well-characterized and typically small molecules. However, the polyphenols in diet are unimaginably complex; (iii) Interaction with food proteins. Although the effects of food proteins on the bioavailability of polyphenols are still not examined in much detail, direct binding interactions of polyphenols to proteins always occur; (iv) The most common polyphenols in the human diet have a low intrinsic activity and are poorly absorbed from the intestine, highly metabolized, or rapidly eliminated. Although there is very limited information available so far, it is proposed that type 2 diabetes influences the pharmacokinetic behavior of dietary polyphenols including: i) competition of glucose with polyphenols regarding binding to plasma proteins; ii) weakened non-covalent interaction affinities of plasma proteins for natural polyphenols due to protein glycation in type II diabetes; iii) the enhanced clearance of polyphenols in type 2 diabetes. An understanding of diabetes-associated changes in absorption, distribution, metabolism, elimination and bioactivities of natural polyphenols as well as the mechanism of the variability should lead to the improvement of the benefits of these polyphenols and clinical outcomes for diabetics.