Does a circadian variation occur in myocardial ischemia over 48 hours in patients with unstable angina?

OBJECTIVE: To study the incidence of and variation in myocardial ischemia over 48 hours in patients with unstable angina. METHODS: Thirty-nine patients with unstable angina underwent long-term electrocardiography for 48 hours. The number of events and the period of time of ischemia (in minutes) were analyzed for the 48 hours, in two periods of 24 hours, and in periods of 4 hours. RESULTS: We analyzed 1755.8 hours of monitoring tapes, and ischemic episodes were detected in 18 (46.2%) patients, corresponding to 173 ischemic episodes, allowing the evaluation of 1304 minutes of ischemia.only 4 of which were (2.2%) symptomatic, Considering the entire period of time of recording and the predetermined time intervals, we observed a higher number of ischemic episodes (38) and a longer duration of ischemia (315.4 minutes) between 11:00 am and 3:00 pm. However, no significant differences occurred among the values in the different intervals. CONCLUSION: Long-term electrocardiography over 48 hours showed a high incidence (97.8%) of silent ischemic episodes in patients with unstable angina. No evidence of a circadian variation of myocardial ischemia in unstable angina was observed.

Seasonal and diel variation in the fish assemblage of a Neotropical delta in southern Brazil

The objective of this study was to identify the patterns of seasonal and diel variation and the most important abiotic factors that influence variation in the fish assemblage of the Delta of the Jacuí River in southern Brazil. Seventy-two samples were collected over a one year period. Water temperature was the abiotic factor with the greatest influence on the distribution of the assemblage. The structure of the assemblage exhibited significant changes in terms of species abundance and biomass during the year, with the greatest abundance and biomass being observed during the autumn. There was no significant difference between day and night in terms of abundance, but biomass was significantly greater during the night than during the day.

Hatching and larval export of the intertidal crab Neohelice granulata in Mar Chiquita coastal lagoon, Argentina

Synchronization in the events of the reproductive cycle in female Neohelice granulata Dana, 1851 were studied from samples taken weekly and biweekly from September to December 2006 in the Laguna Mar Chiquita. The timing and larval hatching and synchronicity were inferred from numbers of ovigerous females and observing the stages of embryonic development. Synchronization in larval hatching also was observed in females in experiments in dark for a period of 48 hours, at three different salinities (10, 23 and 33 ppm). In addition plankton sampling were performed in order to study larval exportation at the field and its link to the tidal and light/dark cycles. We found that ovigerous females of N. granulata have a marked synchronization in embryonic development which results in that most of berried females are close to hatching within a period of maximum tidal range (days). Within this period, there is a synchronization of hatching at a time scale of hours, governed by environmental conditions. The salinity range used in this study (10-32‰) did not affect hatching synchronicity neither time to hatch. Hatching was synchronized according to endogenous rhythms governed mainly by the tidal cycle and secondarily by the breadth of it. It is also conditioned by the light-dark cycle through an exogenous cycle, so that the hatchings would occur mostly at night high tides.

Renal sodium handling and nighttime blood pressure.

Blood pressure follows a circadian rhythm with a physiologic 10% to 20% decrease during the night. There is now increasing evidence that a blunted decrease or an increase in nighttime blood pressure is associated with a greater prevalence of target organ damage and a faster disease progression in patients with chronic kidney diseases. Several factors contribute to the changes in nighttime blood pressure including changes in hormonal profiles such as variations in the activity of the renin-angiotensin and the sympathetic nervous systems. Recently, it was hypothesized that the absence of a blood pressure decrease during the nighttime (nondipping) is in fact a pressure-natriuresis mechanism enabling subjects with an impaired capacity to excrete sodium to remain in sodium balance. In this article, we review the clinical and epidemiologic data that tend to support this hypothesis. Moreover, we show that most, if not all, clinical conditions associated with an impaired dipping profile are diseases associated either with a low glomerular filtration rate and/or an impaired ability to excrete sodium. These observations would suggest that renal function, and most importantly the ability to eliminate sodium during the day, is indeed a key determinant of the circadian rhythm of blood pressure.

The pineal neurohormone melatonin and its physiologic opiatergic immunoregulatory role

The pineal gland functions as a neuroendocrine transducer that coordinate the organism response to changing environmental stimuli such as light and temperature. The main and best known pineal neurohormone is melatonin that is synthesized and released in a circadian fashion with a peak during the night darkness hours. We have recently reported that melatonin exerts important immuno regulatory functions. Here we describe the astonishing property of exogenous melatonin which is able to counteract completely the depressive effect of anxiety-restraint stress and/or of corticosterone on thymus weight, andibody production and antiviral responses. This effect seems to be mediated by antigen-activated T cells via an opiatergic mechanism.

Ambulatory blood pressure measurement and antihypertensive therapy.

The traditional basis for assessing the effect of antihypertensive therapy is the blood pressure reading taken by a physician. However, several recent trials have been designed to evaluate the blood pressure lowering effect of various therapeutic agents during the patients' normal daytime activities, using a portable, semi-automatic blood pressure recorder. The results have shown that in a given patient, blood pressure measured at the physician's office often differs greatly from that prevailing during the rest of the day. This is true both in treated and untreated hypertensive patients. The difference between office and ambulatory recorded pressures cannot be predicted from blood pressure levels measured by the physician. Therefore, a prospective study was carried out in patients with diastolic blood pressures that were uncontrolled at the physician's office despite antihypertensive therapy. The purpose was to evaluate the response of recorded ambulatory blood pressure to treatment adjustments aimed at reducing office blood pressure below a pre-set target level. Only patients with high ambulatory blood pressures at the outset appeared to benefit from further changes in therapy. Thus, ambulatory blood pressure monitoring can be used to identify those patients who remain hypertensive only when facing the physician, despite antihypertensive therapy. Ambulatory monitoring could thus help to evaluate the efficacy of antihypertensive therapy and allow individual treatment.

T-type Ca2+ channels, SK2 channels and SERCAs gate sleep-related oscillations in thalamic dendrites.

T-type Ca2+ channels (T channels) underlie rhythmic burst discharges during neuronal oscillations that are typical during sleep. However, the Ca2+-dependent effectors that are selectively regulated by T currents remain unknown. We found that, in dendrites of nucleus reticularis thalami (nRt), intracellular Ca2+ concentration increases were dominated by Ca2+ influx through T channels and shaped rhythmic bursting via competition between Ca2+-dependent small-conductance (SK)-type K+ channels and Ca2+ uptake pumps. Oscillatory bursting was initiated via selective activation of dendritically located SK2 channels, whereas Ca2+ sequestration by sarco/endoplasmic reticulum Ca2+-ATPases (SERCAs) and cumulative T channel inactivation dampened oscillations. Sk2-/- (also known as Kcnn2) mice lacked cellular oscillations, showed a greater than threefold reduction in low-frequency rhythms in the electroencephalogram of non-rapid-eye-movement sleep and had disrupted sleep. Thus, the interplay of T channels, SK2 channels and SERCAs in nRt dendrites comprises a specialized Ca2+ signaling triad to regulate oscillatory dynamics related to sleep.

In vivo characterization of the circadian clock output gene usp2

Life on earth is subject to the repeated change between day and night periods. All organisms that undergo these alterations have to anticipate consequently the adaptation of their physiology and possess an endogenous periodicity of about 24 hours called circadian rhythm from the Latin circa (about) and diem (day). At the molecular level, virtually all cells of an organism possess a molecular clock which drives rhythmic gene expression and output functions. Besides altered rhythmicity in constant conditions, impaired clock function causes pathophysiological conditions such as diabetes or hypertension. These data unveil a part of the mechanisms underlying the well-described epidemiology of shift work and highlight the function of clock-driven regulatory mechanisms. The post-translational modification of proteins by the ubiquitin polypeptide is a central mechanism to regulate their stability and activity and is capital for clock function. Similarly to the majority of biological processes, it is reversible. Deubiquitylation is carried out by a wide variety of about ninety deubiquitylating enzymes and their function remains poorly understood, especially in vivo. This class of proteolytic enzymes is parted into five families including the Ubiquitin-Specific Proteases (USP), which is the most important with about sixty members. Among them, the Ubiquitin-Specific Protease 2 (Usp2) gene encodes two protein isoforms, USP2-45 and USP2-69. The first is ubiquitously expressed under the control of the circadian clock and displays all features of core clock genes or its closest outputs effectors. Additionally, Usp2-45 was also found to be induced by the mineralocorticoid hormone aldosterone and thought to participate in Na+ reabsorption and blood pressure regulation by Epithelial Na+ Channel ENaC in the kidneys. During my thesis, I aimed to characterize the role of Usp2 in vivo with respect to these two areas, by taking advantage of a total constitutive knockout mouse model. In the first project I aimed to validate the role of USP2-45 in Na+ homeostasis and blood pressure regulation by the kidneys. I found no significant alterations of diurnal Na+ homeostasis and blood pressure in these mice, indicating that Usp2 does not play a substantial role in this process. In urine analyses, we found that our Usp2-KO mice are actually hypercalciuric. In a second project, I aimed to understand the causes of this phenotype. I found that the observed hypercalciuria results essentially from intestinal hyperabsorption. These data reveal a new role for Usp2 as an output effector of the circadian clock in dietary Ca2+ metabolism in the intestine.

A role for clock genes in sleep homeostasis.

The timing and quality of both sleep and wakefulness are thought to be regulated by the interaction of two processes. One of these two processes keeps track of the prior sleep-wake history and controls the homeostatic need for sleep while the other sets the time-of-day that sleep preferably occurs. The molecular pathways underlying the latter, circadian process have been studied in detail and their key role in physiological time-keeping has been well established. Analyses of sleep in mice and flies lacking core circadian clock gene proteins have demonstrated, however, that besides disrupting circadian rhythms, also sleep homeostatic processes were affected. Subsequent studies revealed that sleep loss alters both the mRNA levels and the specific DNA-binding of the key circadian transcriptional regulators to their target sequences in the mouse brain. The fact that sleep loss impinges on the very core of the molecular circadian circuitry might explain why both inadequate sleep and disrupted circadian rhythms can similarly lead to metabolic pathology. The evidence for a role for clock genes in sleep homeostasis will be reviewed here.

Seasonal distribution and diel biting patterns of culicine mosquitoes in Costa Marques, Rondônia, Brazil

A study of peridomestic man-biting culicines in the Amazon Basin was conducted from January through December, 1987. Fifteen species of mosquitoes from six genera were collected by volunters in all-night human-bait indoor and outdoor collections at five hoses in and near the town of Costa Marques, Rondônia, Brazil. Culex quinquefasciatus and members of the Mansonia titillans/indubitans Group comprised 61 and 33%, respectively, of all culcines collected from human-bait outside houses and 62 and 35%, respectively, of those collected from volunteers inside houses in the town. In rural areas, Cx. quinquefasciatus was less abundant and only comprised 2 and 5% of the culcines, respectively, collected inside and outside houses. Mansonia titillans/indubitans Group comprised 75% and 86% of the culicines collected inside and outside houses, respectively, from rural residences. Culex quinquefasciatus and members of Mn. titillans/indubitans Group were more endophilic than other culcines collected. Nocturnal and seasonal biting rhythms for the more common culcines are described

Quantitative genetics of sleep in inbred mice.

The timing and the organization of sleep architecture are mainly controlled by the circadian system, while sleep need and intensity are regulated by a homeostatic process. How independent these two systems are in regulating sleep is not well understood. In contrast to the impressive progress in the molecular genetics of circadian rhythms, little is known about the molecular basis of sleep. Nevertheless, as summarized here, phenotypic dissection of sleep into its most basic aspects can be used to identify both the single major genes and small effect quantitative trait loci involved. Although experimental models such as the mouse are more readily amenable to genetic analysis of sleep, similar approaches can be applied to humans.

Laboratory indicators for monitoring HIV disease

Immunological monitoring of disease progression following HIV infection and seroconversion illness, latency and AIDS, not only helps in the basic investigation of the natural history of the viral infection in man, but also can assist in prognosis and treatment of AIDS-defining illnesses. However, outside clinical trials, these tests should be selected and used in clinical practice only if they are validated as relevant and effective. The absolute CD4+ T-helper lymphocyte count, measured by flow cytometry, has emerged as the best available investigation, but needs care in sampling due to diurnal and circadian rhythms, effects of age, pregnancy, therapy, intercurrent infections and technique. Sampling should provide a baseline and trends - monthly intervals initially, then quarterly in uncomplicated cases. Thresholds may be given for counts (e.g. 200/µl) below which prophylaxis against pneumocystis pneumonia should be administered, and repeating persistently low counts (e.g. below 50/µl) is seldom helpful in practice. Serum levels of beta-2 microglobulin, neopterin and immunoglobulins rarely add information. Physicians and laboratories should have testing guidelines based on clinical audit of best practice, based in turn on scientific understanding of the immunological processes involved.