Nocturnal Rise Research Articles

Dominant mechanism underlying the explosive growth of summer surface O3 concentrations in the Beijing-Tianjin-Hebei Region, China

Despite the implementation of stringent emission reduction measures in China since 2013, ozone (O3) pollution remains a serious concern. Many O3 pollution processes are accompanied by the explosive growth of O3 concentration, meanwhile this explosive growth will trigger O3 pollution with a high probability. This study investigates the chemical and physical mechanisms behind the explosive growth of O3 in the summer within the Beijing-Tianjin-Hebei (BTH) region based on the atmospheric circulation clustering and WRF-CMAQ simulation. Ninety-four instances of O3 explosions from the summer of 2014–2021 were selected based on their day-to-day variation in O3 concentration, and the corresponding meteorological conditions were classified into four clusters using K-means analysis. Cluster 1 revealed that large-scale regional transmission of O3 and its precursors from the southern BTH region led to a renewed burst of O3 growth based on mild pollution. Nighttime reduction in NO2 concentration decreases titration consumption, causing a nocturnal rise in O3 concentration, detectable through observed data and progress analysis. In Cluster 2 and Cluster 3, the BTH region is located in the northeast wind area ahead of the ridge and northly wind area of post-trough situation, respectively. The vertical downward motion with the markable increase in surface solar radiation (SSR), 2-m temperature (T2M), and decrease in relative humidity (RH) contribute to photochemical O3 generation. Additionally, enhancements in boundary layer stability and reductions in dry deposition and vertical diffusion are favorable for the O3 accumulation. Cluster 4 showed the explosive growth after rainfall event, with the largest increment. The post-rain increase in SSR and T2M, coupled with decreased RH, promotes photochemical O3 formation. Moreover, progress analysis reveals the reduced cloud cover slows down O3 removal, contributing to O3 accumulation. The dominant mechanism behind the explosive growth of O3 will provide certain guidance for the prediction of O3.

CARDIOVASCULAR RISK AMONG MEN OF WORKING AGE WITH ARTERIAL HYPERTENSION DEPENDING ON THE ARTERIAL PRESSURE DIURNAL PROFILE

Aim: to investigate the relationship between cardiovascular risk (CVR) and different types of diurnal blood pressure (BP) profile among men of working age with arterial hypertension (AH).
 Materials and methods. The study included 83 men of working age (average age 48±2 years) with II stage, 2 and 3 degrees of AH. The risk of death due to cardiovascular diseases during the next 10 years was assessed using the SCORE scale. All patients underwent ambulatory BP monitoring (ABPM), according to the results of which the following diurnal BP profiles were identified: 23 (28%) patients – normal (optimal) level of nocturnal decrease in BP («dipper»; daily index (DI) 10-20%); 10 (12%) – excessive nocturnal lowering of BP («over-dipper»; DI >20%); 38 (46%) – insufficient nocturnal lowering of BP («non-dipper»; DI <10%); and 12 (14%) patients had an inverted diurnal curve («night-peaker»; DI <0%).
 Results and discussion. According to the SCORE scale, the CVR profile in «dipper» group (n=23) was as follows: low – 6 (26%) patients; moderate – 15 (65%); and high – 2 (9%). Among 10 patients of «over-dipper» group, 7 had low, 2 – moderate, and 1 – high CVR. In «non-dipper» group (n=38), there were 4 (11%) patients with low CVR, 10 (26%) with moderate, 14 (37%) with high, and 10 (26%) with very high CVR. At the same time, 7 out of 12 patients of «night-peaker» group showed very high CVR, 3 – high, and 2 – moderate (overall p<0,001). The frequency of patients with high CVR was higher in the pooled «non-dipper» and «night-peaker» group (pathological BP profile; n=50), as compared to the pooled «dipper» and «over-dipper» group (n=33): 34% vs. 9%, respectively. At the same time, the pooled «dipper» and «over-dipper» group was characterized by the higher frequency of patients with moderate (52%) and low CVR (39%), in contrast to the pooled «non-dipper» and «night-peaker» group (24% and 8%, respectively). Finally, all 17 patients with very high CVR had an abnormal diurnal BP profile (34% in the pooled «non-dipper» and «night-peaker» group) (overall p<0,001).
 Conclusions. It was established that, according to ABPM, 60% of men of working age with the AH of II stage, 2- and 3-degrees, had pathological BP profiles of the «non-dipper» and «night-peaker» types. Individuals diagnosed with nocturnal rise or insufficient diurnal BP decrease have a higher risk of cardiovascular death in the next 10 years according to SCORE. Patients with a «non-dipper» and «night-peaker» diurnal BP profiles require more aggressive drug therapy and re-examination with ABPM to control the normalization of the diurnal BP profile.

THU315 Sleep And Circadian Regulation, And Intrinsically Photosensitive Retinal Ganglion Cells Function In Diabetic Retinopathy

Abstract Disclosure: S. Reutrakul: None. J.J. McAnany: None. J.C. Park: None. F.Y. Chau: None. K.K. Danielson: None. P. Bharati: None. S. Pannain: None. E. Van Cauter: None. E.C. Hanlon: None. Background: Diabetic retinopathy (DR) is associated with a dysfunction of intrinsically photosensitive retinal ganglion cells (ipRGCs), a crucial component of the entrainment of the circadian system and of the photic entrainment of melatonin secretion. We explored ipRGC function, sleep, 24-h melatonin and cortisol profiles in patients with and without DR. Methods: Type 2 diabetes patients with DR (n=10) and without DR (n=7,) participated. ipRGC function was inferred from the post illumination pupil response (PIPR). Sleep was assessed by 14-day actigraphy. Serum was sampled at hourly intervals for 24hrs for melatonin and cortisol measurement. Results: Mean (SD) age (53.8 (8.1) vs (54.0 (8.6) yr) and mean A1C (7.5 (1.7) vs. 7.1 (0.9)%) did not differ between DR and no-DR patients. PIPR was significantly smaller in DR than no-DR patients (0.14 (0.16) vs. 0.33 (0.10), p=0.001). Nightly sleep duration and efficiency were similar, but sleep variability (standard deviation of daily sleep duration over 7 nights) tended to be larger in DR than no-DR patients (84.1 (29.8) vs. 59.5 (21.8) minutes), p=0.08. Twenty four-hour serum melatonin output was significantly lower in DR than no-DR patients (103.1 (95.4) pg/ml vs. 231.1 (131.3) pg/ml, p=0.034). All no-DR patients exhibited the classical 24-h profile of melatonin with consistently low levels during the day time and a clear nocturnal rise peaking around the middle of the night. In contrast, a normal melatonin rhythm was observed only in 3 of the 10 patients with DR. Six DR patients had 24-h mean melatonin level under 3 pg/ml, five without any evident day-night pattern. One DR patient had a shift in melatonin timing. There was a significant correlation between PIPR and 24-h melatonin output, r= 0.726, p<0.001, but not with sleep variability. In contrast, mean 24-h cortisol profiles and levels, however, were not significantly different between the two groups (mean levels DR 6.18 (1.23) vs no-DR 6.18 (0.73) μg/dL), Conclusion: DR is associated with ipRCGs dysfunction, irregular sleep, and with major disruptions of the 24-hour melatonin rhythm while cortisol rhythm was maintained, suggesting circadian dysfunction in those with type 2 diabetes and retinopathy. Whether melatonin supplementation is beneficial in type 2 diabetes with DR should be explored. Presentation: Thursday, June 15, 2023

Temporal optimization of exercise to lower fasting glucose levels.

Exercise stimulates glucose uptake and increases insulin sensitivity acutely. Temporally optimizing exercise timing may minimize the nocturnal rise in glucose levels. This study examined the effect of exercise timing on evening and overnight glucose concentrations in individuals who were non-obese with normal fasting glucose levels (Non-Ob; n=18) and individuals with obesity (OB) with impaired fasting glucose levels (OB+IFG) and without (n=16 and n=18, respectively). Subjects were studied on three occasions (no exercise (NOEX)), morning exercise (AMEX; 0700h) and evening exercise (PMEX; 2000h). The evening meal was provided (1800h) and blood samples were taken from 1740 to 0700h and morning endogenous glucose production (EGP) was measured. Glucose and insulin concentrations increased with the dinner meal with peak concentrations being higher in OB+IFG than in OB and Non-Ob (P=0.04). In OB+IFG, evening glucose concentrations rose above baseline levels at about 2300h, with the glucose concentrations staying somewhat lower with AMEX and PMEX until ∼0500h than with NOEX. In OB+IFG, insulin concentrations decreased following the dinner meal and waned throughout the night, despite the rising glucose concentrations. In the OB and Non-Ob individuals following the dinner meal, no increase in glucose concentrations occurred in the evening period and insulin levels mirrored this. No difference was observed in the morning fasting glucose levels between study days or between groups. Regardless of time of day, exercise delays the evening rise in glucose concentrations in adults with OB+IFG but does not lower morning fasting glucose levels or improve the synchrony between glucose and insulin concentrations. KEY POINTS: Insulin resistance and type 2 diabetes have been linked to disturbances of the core clock, and glucose tolerance demonstrates a diurnal rhythm in healthy humans with better glucose tolerance in the morning than in the afternoon and evening. Skeletal muscle is a primary site for insulin resistance in people with impaired glucose tolerance. In individuals with obesity and impaired fasting glucose levels (OB+IFG), following a dinner meal, glucose concentrations started to rise and continues throughout the night, resulting in elevated glucose levels, while concomitantly, insulin levels are waning. Exercise, regardless of the time of day, suppressed the rise in glucose levels in OB+IFG for many hours during the night but did not lower morning fasting glucose levels. Morning exercise was not quite as effective as evening exercise.

Circulating blood eNAMPT drives the circadian rhythms in locomotor activity and energy expenditure

Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor of critical enzymes including protein deacetylase sirtuins/SIRTs and its levels in mammalian cells rely on the nicotinamide phosphoribosyltransferase (NAMPT)-mediated salvage pathway. Intracellular NAMPT (iNAMPT) is secreted and found in the blood as extracellular NAMPT (eNAMPT). In the liver, the iNAMPT−NAD+ axis oscillates in a circadian manner and regulates the cellular clockwork. Here we show that the hypothalamic NAD+ levels show a distinct circadian fluctuation with a nocturnal rise in lean mice. This rhythm is in phase with that of plasma eNAMPT levels but not with that of hypothalamic iNAMPT levels. Chemical and genetic blockade of eNAMPT profoundly inhibit the nighttime elevations in hypothalamic NAD+ levels as well as those in locomotor activity (LMA) and energy expenditure (EE). Conversely, elevation of plasma eNAMPT by NAMPT administration increases hypothalamic NAD+ levels and stimulates LMA and EE via the hypothalamic NAD+−SIRT−FOXO1−melanocortin pathway. Notably, obese animals display a markedly blunted circadian oscillation in blood eNAMPT−hypothalamic NAD+−FOXO1 axis as well as LMA and EE. Our findings indicate that the eNAMPT regulation of hypothalamic NAD+ biosynthesis underlies circadian physiology and that this system can be significantly disrupted by obesity.

Diurnal variation of pulmonary artery pressure in ambulatory heart failure patients

Background There is limited information on diurnal variation in pulmonary artery pressures (PAP) in ambulatory heart failure (HF) patients. We aimed to study the variation in morning and night-time PAP in HF patients with an implanted CardioMEMS® sensor. Methods In this prospective, single centre study we enrolled patients who had a cardioMEMS sensor and consented to participate (End stage renal disease and recent hospitalisation for acute HF were exclusions). Subjects were asked to transmit PAP and non-invasive blood pressure information in morning and at night-time for 7 consecutive days. Categorical and continuous variables were reported as percentages and mean ± SD respectively. Repeated measure ANOVA was used to compare the diurnal changes in PAP among different subgroups. Pierson correlation coefficient was performed to assess correlation between diurnal variation of PAP and left ventricular ejection fraction Results Thirty subjects were included in analysis. There was a significant nocturnal rise in PASP and mPAP compared to morning readings (+2.59 mmHg, p = 0.003 and +1.24 mmHg with p = 0.02 respectively) while night-time PADP did not change significantly (+0.48 mmHg, p = 0.18) without significant change in systemic blood pressure or pulse rate. Conclusion The described diurnal changes in PAP should be considered when managing ambulatory HF patients based on these readings. PADP can be used reliably without concern for the time of day the readings were recorded. Highlights There is a diurnal variation in PAP in ambulatory heart failure patients Pulmonary artery systolic and mean pulmonary artery pressures are higher at night-time than in morning. Pulmonary artery diastolic pressures do not vary significantly with time of day. These findings should inform clinical decisions in management of these patients about the time of the day readings are taken

Suppression of trabecular meshwork phagocytosis by norepinephrine is associated with nocturnal increase in intraocular pressure in mice

Intraocular pressure (IOP) is an important factor in glaucoma development, which involves aqueous humor (AH) dynamics, with inflow from the ciliary body and outflow through the trabecular meshwork (TM). IOP has a circadian rhythm entrained by sympathetic noradrenaline (NE) or adrenal glucocorticoids (GCs). Herein, we investigated the involvement of GC/NE in AH outflow. Pharmacological prevention of inflow/outflow in mice indicated a diurnal outflow increase, which was related to TM phagocytosis. NE showed a non-self-sustained inhibition in phagocytosis of immortalized human TM cells, but not GC. The pharmacological and reverse genetic approaches identified β1-adrenergic receptor (AR)-mediated exchange proteins directly activated by cyclic adenosine monophosphate (EPAC)-SHIP1 signal activation by ablation of phosphatidylinositol triphosphate, regulating phagocytic cup formation. Furthermore, we revealed the phagocytosis involvement in the β1-AR-EPAC-SHIP1-mediated nocturnal IOP rise in mice. These suggest that TM phagocytosis suppression by NE can regulate IOP rhythm through AH outflow. This discovery may aid glaucoma management.

Circadian Rhythm Of Pulmonary Artery Pressures In HFpEF Assessed With Cardiomem: Preliminary Results

<h3>Purpose</h3> : Systemic blood pressure is known to display a circadian rhythm in most healthy individuals, characterized by a nocturnal fall and a diurnal rise. Dysregulation of this pattern is associated with higher risk of cardiovascular disease. However, the circadian rhythm in the pulmonary arterial circulation and its impact on cardiovascular disease is less established. The aim of this study is to perform a preliminary investigation of any circadian variations of pulmonary artery (PA) pressures in patients with implanted cardiomem devices. <h3>Methods</h3> : Among 15 subjects with heart failure with preserved ejection fraction (HFpEF) and an implanted cardiomem device who were offered participation in this study, four subjects enrolled. Study participants recorded PA pressure signals three times a day: AM (7-9AM), mid-day (Noon-2PM), and PM (7-9PM). We excluded the readings that were preceded by changes in the diuretic regimen (change in dose and/or prn use of metolazone) within 3 days prior to the reading. <h3>Results</h3> : In the first two subjects (#1 and #2), we identified a "steady trend or slight rise" in PA pressures from morning-to-evening. These subjects had clinical stability (defined as no hospitalizations within the last year or medication changes within last 3-months), and relatively well controlled risk factors (diabetes, hypertension, sleep apnea). In the other two subjects (#3 and #4), we identified a "drop" in PA pressures from morning-to-evening. Subjects #3 and #4 have poorly controlled sleep-disordered breathing and DM, respectively. Both of these disease processes have been implicated in circadian misalignment of systemic BP. <h3>Conclusion</h3> : Based on these preliminary findings, a diurnal rise or steady PA pressures may reflect well-controlled risk factors in HFpEF. However, a nocturnal rise may indicate poorly controlled risk factors like sleep apnea or metabolic syndrome. Future studies are needed to confirm the circadian misalignment and its impact on cardiovascular outcomes.

Molecular basis of Period 1 regulation by adrenergic signaling in the heart.

The cardiac circadian clock is responsible for the modulation of different myocardial processes, and its dysregulation has been linked to disease development. How this clock machinery is regulated in the heart remains an open question. Because noradrenaline (NE) can act as a zeitgeber in cardiomyocytes, we tested the hypothesis that adrenergic signaling resets cardiac clock gene expression in vivo. In its anti-phase with Clock and Bmal1, cardiac Per1 abundance increased during the dark phase, concurrent with the rise in heart rate and preceded by an increase in NE levels. Sympathetic denervation altered Bmal1 and Clock amplitude, while Per1 was affected in both amplitude and oscillatory pattern. We next treated mice with a β-adrenergic receptor (β-AR) blocker. Strikingly, the β-AR blockade during the day suppressed the nocturnal increase in Per1 mRNA, without altering Clock or Bmal1. In contrast, activating β-AR with isoproterenol (ISO) promoted an increase in Per1 expression, demonstrating its responsiveness to adrenergic input. Inhibitors of ERK1/2 and CREB attenuated ISO-induced Per1 expression. Upstream of ERK1/2, PI3Kγ mediated ISO induction of Per1 transcription, while activation of β2-AR, but not β1-AR induced increases in ERK1/2 phosphorylation and Per1 expression. Consistent with the β2-induction of Per1 mRNA, ISO failed to activate ERK1/2 and elevate Per1 in the heart of β2-AR-/- mice, whereas a β2-AR antagonist attenuated the nocturnal rise in Per1 expression. Our study established a link between NE/β2-AR signaling and Per1 oscillation via the PI3Ky-ERK1/2-CREB pathway, providing a new framework for understanding the physiological mechanism involved in resetting cardiac clock genes.

Nocturnal blood pressure rise as a predictor of cognitive impairment among the elderly: a retrospective cohort study

BackgroundThis study investigated the different blood pressure patterns that were evaluated by ambulatory blood pressure monitoring (ABPM) among elderly patients and explored the effect of pressure patterns on cognitive impairment and mortality.MethodsA total of 305 elderly participants aged ≥65 years were divided into the cognitive impairment group (CI, n = 130) and the non-cognitive impairment group (NCI, n = 175) according to the MMSE score. All participants underwent ABPM to evaluate possible hypertensive disorder and cerebral MRI for the evaluation of cerebral small vessel disease. Follow-up was performed by telephone or medical records. The primary outcome was all-cause mortality. Secondary endpoints were major adverse cardiac and cerebrovascular events (MACCE).ResultsAmong 305 participants, 130 (42.6%) were identified with cognitive impairment (CI), with average systolic blood pressure (BP) of 127 mmHg and diastolic BP of 66 mmHg. According to ABPM, only 13.1% had a dipper pattern, 45.6% had a nocturnal BP rise, while 41.3% had a non-dipper pattern. Compared with NCI patients, the CI group had significantly higher night-time systolic BP (130.0 ± 18.2 vs. 123.9 ± 15.1, p = 0.011), and more participants had nocturnal BP rise (52.3% vs. 40.6%, p = 0.042). Nocturnal BP rise was associated with greater white matter hyperintensities (WMH) (p = 0.013). After 2.03 years of follow-up, there were 35 all-cause deaths and 33 cases of major adverse cardiac and cerebrovascular events (MACCE). CI was independently associated with all-cause mortality during long-term observation (p < 0.01). Nocturnal BP rise had no significant predictive ability for all-cause mortality in elderly patients (p = 0.178).ConclusionsNocturnal BP rise contributed to greater cognitive impairment in elderly patients. Not nocturnal BP rise, but CI could significantly increase all-cause mortality. Controlling BP based on ABPM is critical for preventing the progression of cognitive dysfunction.

Hypoxia-mediated inhibition of cholesterol synthesis leads to disruption of nocturnal sex steroidogenesis in the gonad of koi carp, Cyprinus carpio.

Reproductively mature koi carps (Cyprinus carpio) showed a prominent diurnal variation of sex steroids with sustained nocturnal rise. Exposure to chronic hypoxia (DO < 0.8mg/l) disrupted nocturnal sex steroid production in koi carp gonads. Inhibition of sex steroidogenesis is linked to the down-regulation of HMG-Co A reductase (p < 0.05), which acts as a rate-limiting enzyme in the mevalonate pathway for cholesterol production. HMG-CoA reductase inhibition was obvious in the gonads and liver of both sexes during 18.00h and 21.00h resulting in hypocholesterolemia (p < 0.05). The levels of sex steroids, such as estradiol, testosterone, and 11-keto-testosterone in gonads were depleted below the optimum levels owing to disruption of de novo cholesterol synthesis along with attenuation of HDL-cholesterol level in serum. Inhibition of melatonin under hypoxic conditions indicates disruption of melatonin effects on the hypothalamus-pituitary-gonadal (HPG) axis of koi carp. Under severe hypoxic stress, koi carp promoted energy conservation by switching over to the triglyceride (TGA) pathway instead of the mevalonate pathway to suppress cholesterol production. Chronic hypoxia inhibited cholesterol synthesis, a prerequisite for gonadal maturation. It promoted TGA production, as an alternative energy source, suggesting a probable mitigation strategy adopted by hypoxia-tolerant fish to deal with low dissolved oxygen frequently occurring in aquatic bodies.

Red light at night permits the nocturnal rise of melatonin production in horses

Exposure to white light at night suppresses melatonin production, impacts circadian rhythms and contributes to ill-health in humans. Human interaction with horses frequently occurs at night. We tested the hypothesis that dim red light would not suppress the nightly rise in serum melatonin levels in horses. In a crossover design, six horses were maintained for consecutive 48h periods under a Light: Red (LR) and a Light: Dark (LD) photo-schedule. Transitions from light (>200lux, polychromatic white light) to red (5lux, peak wavelength 625nm) or dark (<0.5lux), and vice versa, coincided with ambient sunset and sunrise times. Blood was collected at 2h intervals for 24h during each treatment via indwelling jugular catheters. Samples were harvested for serum and stored at −20°C until assayed for melatonin by radioimmunoassay. Repeated measures two-way ANOVA and t-tests analysed for differences in LR and LD melatonin profiles and their circadian rhythm parameters.No time×treatment interaction or effect of treatment on serum melatonin levels were demonstrated (P>0.05). A robust main effect of time (P<0.0001) predominated, with melatonin levels rising at night under both treatments. Statistically significant differences were not observed when LR and LD were compared for circadian rhythm measures of night time peak, area under the curve (AUC), or for times of onset (evening rise), offset (morning decline), or peak duration. Low intensity red light at night did not impact the pattern of melatonin secretion in this study and is, therefore, unlikely to impact the physiology of circadian or seasonal regulation.

Circadian Blood Pressure Variations Computed From 1.7 Million Measurements in an Acute Hospital Setting.

BACKGROUNDKnowledge of the circadian blood pressure (BP) variations in the acute hospital setting is very limited.METHODSThis is a retrospective analysis of BP data for in-hospital patients stratified by age and sex. We used data collected with the help of a standardized electronic health record system between March 2014 and April 2018 on the adult general wards in 4 acute hospitals in Oxford, UK.RESULTSA total of 41,455 unique patient admissions with 1.7 million sets of vital-sign measurements have been included in the study. The typical 24-hour systolic BP profile (dipping pattern during sleep followed by a gradual increase during the day) was only seen in the younger age groups (up to 40–49 for men and 30–39 for women). For older age groups, there was a late nocturnal rise in systolic BP, the amplitude of which increased with age. The late nocturnal BP rise above the age of 50 was seen whether or not the patient was treated for or previously identified with hypertension.CONCLUSIONHospitalized patients’ circadian patterns of BP largely mirror those found in the community. High-quality hospital data may allow for the identification of patients at significant cardiovascular risk through either opportunistic screening or systematic screening.

Nocturnal Dipping of Blood Pressure in Renal Transplant Recipients

Background: There is a marked diurnal variation in blood pressure (BP). Compared with daytime values, BP in most subjects is considerably lower during the night and a ‘non-dipping BP profile’ is usually defined as a nocturnal SBP fall of less than 10%. Association between non-dipper pattern of circadian rhythm of BP and impaired renal capacity was observed in some studies. A circadian non-dipping pattern is often found in renal transplant recipients, and is related to poor allograft function. Materials and Method: In this analytic-cross sectional study, 24 hours ambulatory blood pressure monitoring (ABPM) was performed in 100 renal post-transplant patients, aged >18 years old, with the serum creatinine level <2 mg/dl after one month of transplant. According to the nocturnal reduction of systolic blood pressure (SBP), dipper (SBP ≥ 10%), non-dipper (0 < SBP < 10%) and reverse dipper (SBP nocturnal rise) pattern were defined. Result: Of 100 participants of this study, 56 patients (56%) were male, and 44 patients (44%) were female. Mean age of participants was 43.34 ± 2.442 years overall, 44.27 ± 2.974 years in males and 42.16 ± 4.074 years in females. Non-dipper pattern was found in 58 patients (58%), revers dipper pattern in 35 patients (35%) and dipper pattern was found only in 7 patients (7%). The nocturnal reduction of systolic blood pressure pattern in participants regarding the gender was not significant (p = 0.794). Mean age of patients with non-dipper pattern was significantly lesser than patients with revers dipper pattern (p = 0.009), but mean age of patients with dipper pattern was not significantly different from patients with non-dipper or revers dipper pattern (p = 0.368, p = 0.605). There was no significant correlation between dipper or non-dipper or revers dipper pattern with immunosuppressive drugs(cyclosporine, tacrolimus and non calcineurin inhibitors), duration of dialysis before transplant, and the time past transplant (p = 0.194, p = 0.252, and p = 0.392, respectively). Conclusion: The revers dipper pattern was seen more frequently in older patients than younger, and there was no significant correlation between dipper or non-dipper or revers dipper pattern with immunosuppressive drugs, duration of dialysis before transplant, and the time past transplant. Urology Research Center, Guilan University of Medical Sciences.

Neuropeptide S increases motor activity and thermogenesis in the rat through sympathetic activation

The central role of neuropeptide S (NPS), identified as the endogenous ligand for GPR154, now named neuropeptide S receptor (NPSR), has not yet been fully clarified. We examined the central role of NPS for body temperature, energy expenditure, locomotor activity and adrenal hormone secretion in rats. Intracerebroventricular (icv) injection of NPS increased body temperature in a dose-dependent manner. Energy consumption and locomotor activity were also significantly increased by icv injection of NPS. In addition, icv injection of NPS increased the peripheral blood concentration of adrenalin and corticosterone. Pretreatment with the β1- and β2-adrenergic receptor blocker timolol inhibited the NPS-induced increase of body temperature. The expression of both NPS mRNA in the brainstem and NPSR mRNA in the hypothalamus showed a nocturnal rhythm with a peak occurring during the first half of the dark period. To examine whether the endogenous NPS is involved in regulation of body temperature, NPSR antagonist SHA68 was administered one hour after darkness. SHA68 attenuated the nocturnal rise of body temperature. These results suggest that NPS contributes to the regulation of the sympathetic nervous system.

Correcting delayed circadian phase with bright light therapy predicts improvement in ADHD symptoms: A pilot study

Attention-deficit/hyperactivity disorder (ADHD) is a common condition with comorbid insomnia reported in >70% of children and adults. These patients demonstrate delays in sleep-wake rhythms, nocturnal rise in melatonin, and early morning rise in cortisol. Given that standard psychopharmacologic treatments for ADHD often do not completely control symptoms in participants with circadian rhythm delay, we sought to test whether bright light therapy (BLT) advances circadian rhythms and further reduces ADHD symptoms over standard treatments. In addition to standard of care, participants with ADHD diagnosis underwent 1 week of baseline assessment followed by 2-weeks of 30-min morning 10,000-lux BLT beginning 3 h after mid-sleep time. Participants minimized overhead light after 4 p.m., wore an actigraphy watch, and recorded BLT time on daily sleep logs. Dim Light Melatonin Onset (DLMO) was assessed at baseline and after 2-week treatment. ADHD symptoms were measured by the ADHD-Rating Scales (ADHD-RS). BLT significantly advanced the phase of DLMO by 31 min [mean time (SEM), 20:36 (0:21) advanced to 20:05 (0:20)] and mid-sleep time by 57 min [4:37 (0:22) advanced to 3:40 (0:16); paired t-tests, p = 0.002 and 0.004, respectively). Phase advances (in DLMO or mid-sleep time) were significantly correlated with decreased ADHD-RS total scores (p = 0.027 and 0.044) and Hyperactive-Impulsive sub-scores (p = 0.014 and 0.013, respectively). Actigraphy analysis for a subset of 8 participants with significant DLMO phase advance revealed no significant changes in total sleep time, sleep efficiency, wake after sleep onset, or percent wake during sleep interval. This is the first successful use of BLT for advancing melatonin phase and improving ADHD symptoms in adults. BLT may be a complementary treatment for both delayed sleep timing and ADHD symptoms in adults.

Circulating Zinc-α2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome.

The aim of study was to assess the relationship between zinc-α2-glycoprotein (ZAG) and androgen excess with insulin resistance in polycystic ovary syndrome (PCOS) women. 99 PCOS women and 100 healthy controls were recruited. Euglycemic-hyperinsulinemic clamp (EHC) was preformed to assess their insulin sensitivity. Circulating ZAG was determined with an ELISA kit. In healthy subjects, circulating ZAG levels exhibited a characteristic diurnal rhythm in humans, with a major nocturnal rise occurring between midnight and early morning. Circulating ZAG and M-value were much lower in PCOS women than in the controls. In all population, overweight/obese subjects had significantly lower circulating ZAG levels than lean individuals. Multiple linear regression analysis revealed that only M-value and the area under the curve for glucose were independently related factors to circulating ZAG in PCOS women. Multivariate logistic regression analysis showed that circulating ZAG was significantly associated with PCOS even after controlling for anthropometric variables, blood pressure, lipid profile and hormone levels. The PCOS women with high ZAG had fewer MetS, IGT and polycystic ovaries as compared with the low ZAG PCOS women. Taken together, circulating ZAG levels are reduced in women with PCOS and ZAG may be a cytokine associated with insulin resistance in PCOS women.

Age-associated Advance of Sleep Times Relative to the Circadian Phase of Alertness-Sleepiness Rhythm: Can it be Explained by Changes in Ratios Between Strengths of the Underlying Oscillatory Processes?

The aging process is often associated with more or less prominent shifts of the entrained phases of behavioral and physiological rhythms at earlier clock hours, but the oscillatory mechanisms underlying these shifts have to be determined. The analysis of self-reports on home sleep times and self-scorings of sleepiness provided by 130 participants of sleep deprivation experiments revealed the difference between intro-individual (age-related) and inter-individual (gender- and chronotype-related) variation in phase angle between sleep timing and timing of nocturnal rise of sleepiness. A heterochronity of age-related changes in phase characteristics of the circadian rhythms was suggested for explaining this difference. In particular, a rhythm's strength might determine the rate of age-related decline of its entrainment mechanism. In the case of a weak circadian rhythm, such as the homeostatic process underlying oscillations of slow wave activity in the sleep-wake cycle, a decline of the rhythm's strength might be already pronounced in middle aged adults. In contrast, a similar decline might occur much later in the cases of the homeostatic processes underlying stronger rhythms, such as the fluctuations of alertness-sleepiness, body temperature, melatonin secretion, etc. Moreover, the strength of a strong rhythm might become weaker earlier than that of the circadian pacemaker and, especially, earlier than decline of its ability to entrain to the light-dark cycle. Such sequence of changes in the circadian entrainment mechanisms might explain a general tendency to produce advance rather than delay shifts of entrained phases of circadian rhythms with progression of age from middle adulthood to elderly.

Gender Difference in Timing of Nocturnal Rise of Subjective Sleepiness

Abstract. Experimental research of diurnal variations in body temperature and melatonin secretion consistently revealed an earlier entrained circadian phase in women than in men. Since it is well documented that daily fluctuations in self-reported level of sleepiness closely follow the circadian rhythms of melatonin and body temperature, one can predict that gender differences in phase characteristics of the 24-hour fluctuations of subjective sleepiness resemble the differences revealed by research of physiological and hormonal rhythms. Analysis of sleepiness self-scored by 46 male and 54 female participants of sleep deprivation experiments showed that female participants scored significantly higher their midnight sleepiness level. The model-based simulations of sleepiness curves confirmed the prediction of a relatively earlier phase of 24-hour oscillations of sleepiness in women. Such gender differences persisted after accounting for individual variation in habitual sleep times and morning-evening preference. In today’s environment, the earlier circadian phase in women can cause a larger delaying phase shift in response to midnight exposure to artificial light, but, on the other hand, the earlier rise of subjective sleepiness can make them less vulnerable to the delaying shifts.

Early Effect of Bariatric Surgery on the Circadian Rhythms of Adipokines in Morbidly Obese Women.

The circadian pattern of adipokines is blunted in obese subjects, and we tested the hypothesis that bariatric surgery could normalize the 24-hr pattern of adipokines. Therefore, this study was designed to examine the early impact of the newly designed sleeve gastrectomy with transit bipartition (SGTB) surgery on the circadian pattern of leptin, adiponectin, and resistin in morbidly obese subjects. The study group included six morbidly obese women [body mass index (BMI) 41.3 ± 1.53 kg/m(2)] who underwent SGTB and four lean women (BMI 18.61 ± 0.92 kg/m(2)). Blood from all subjects was collected before and 3 months after bariatric surgery every 6 hr throughout the 24-hr period. The circadian pattern of leptin, adiponectin, and resistin was measured by enzyme-linked immunosorbent assay or Luminex techniques. Lean women exhibited rise of plasma leptin levels at nighttime, whereas obese women had an increase in the overall plasma leptin levels throughout the 24-hr period, lacking the physiological rise of nocturnal leptin levels compared to controls. Obese women had a decrease in 24-hr adiponectin levels and similar plasma resistin levels compared to controls. Three months after SGTB, obese women lost 16.0% (P < 0.005) of their initial body weight and had a decrease in overall 24-hr leptin levels. However, there was no recovery of the nocturnal rise in leptin levels 3 months after SGTB. The 24-hr adiponectin levels were still decreased after SGTB surgery compared to controls, while resistin levels were decreased only during night time after SGTB. These results suggested that SGTB is an efficient innovative procedure to rapidly decrease 24-hr leptin levels. However, after 3 months, SGTB was not enough to recover the physiological nocturnal rise of leptin levels present in lean subjects.