Effects of a Mild and Prolonged Restriction in Sodium or Food Intake on the Circadian Rhythm of Aldosterone and Related Variables

The effect of a mild reduction in dietary sodium intake (-30 mEq/24 hr) and body weight (-2 kg/2 months) on circadian rhythms of urinary aldosterone (UA), sodium (UNa), potassium (UK), creatinine (UC) and volume (UV) have been investigated in nine clinically healthy subjects. The mild reduction in dietary sodium is associated with: (1) a decrease in the 24-hr excretion rate of UNa, UK and UV, and an increased mesor of UA and UC; (2) a lowered extent of the circadian variation for UNa, UK, UV and a greater amplitude for UA and UC (3) a later crest in the temporal phase for UK, UA, UC, an earlier phasic wave for UNa. The mild reduction in calorie intake resulting in a body weight loss is associated with a more pronounced decrease in the 24-hr excretion rate of UNa and UK, and in the extent of circadian fluctuation for UNa. Peculiar events are: (1) the decreased 24-hr excretion rate for UA, and the increased mesor for UV; (2) the extent variability increased for UV, decreased for UC. Such effect may have a practical resonance for heuristic physiology since the role of dietary sodium and food intake has been better clarified. Dietary sodium and food can be regarded as 'chronomodulatory agents' for the adrenal cortex since their adrenotropic influence is extended to the tonic as well as phasic secretion of aldosterone.     

Effects of a Mild and Prolonged Restriction in Sodium or Food Intake on the Circadian Rhythm of Aldosterone and Related Variables

The effect of a mild reduction in dietary sodium intake (?30 mEq/24 hr) and body weight (?2 kg/2 months) on circadian rhythms of urinary aldosterone (UA), sodium (UNa), potassium (UK), creatinine (UC) and volume (UV) have been investigated in nine clinically healthy subjects. The mild reduction in dietary sodium is associated with: (1) a decrease in the 24-hr excretion rate of UNa, UK and UV, and an increased mesor of UA and UC; (2) a lowered extent of the circadian variation for UNa, UK, UV and a greater amplitude for UA and UC (3) a later crest in the temporal phase for UK, UA, UC, an earlier phasic wave for UNa. The mild reduction in calorie intake resulting in a body weight loss is associated with a more pronounced decrease in the 24-hr excretion rate of UNa and UK, and in the extent of circadian fluctuation for UNa. Peculiar events are: (1) the decreased 24-hr excretion rate for UA, and the increased mesor for UV; (2) the extent variability increased for UV, decreased for UC. Such effect may have a practical resonance for heuristic physiology since the role of dietary sodium and food intake has been better clarified. Dietary sodium and food can be regarded as ‘chronomodulatory agents’ for the adrenal cortex since their adrenotropic influence is extended to the tonic as well as phasic secretion of aldosterone.     

Ten-Year-Replicated Circadian Profiles for 36 Physiological,Serological and Urinary Variables in Healthy Men

At 3-hr intervals over a 24-hr span, 36 systemic, serologic and urinary variables were examined in 7 men in their mid 20's in the Spring of 1969, and again in the same 7 men in the Spring of 1979 under a similar chronobiologic protocol, using the same chemical and numerical analytical procedures. The variables examined for rhythms by cosinor were: vital signs—blood pressure (systoliC., diastoliC., pulse pressure and mean arterial pressure), heart rate, intraocular pressure (left and right), oral temperature; serum components—albumin, albumin/globulin ratio, total bilirubin, calcium, carbon dioxide, chlorides, bilirubin, cholesterol, globulin, glucose, potassium, sodium, sodium/potassium ratio, transaminase, triglycerides, total protein, urea nitrogen; and urine components—calcium, calcium/magnesium ratio, creatinine, magnesium, pH, potassium, sodium, sodium/potassium ratio, urea clearance, urea nitrogen, volume and zinc. Although all subjects appeared clinically healthy in 1969 and in 1979, certain inter-study differences were observed in a number of rhythm parameters of different variables. Statistically significant increases in mesor for the group as a whole were observed forserum Ca, cholesterol, Cl, CO₂, K, Na, and while statistically significant mesor decreases for a group as a whole were noted in serum glucose and transaminase. Statistically significant increases in amplitude for the group as a whole were observed in serum chloride and urinary Na/K ratio, while statistically signficiant decreases were observed in amplitude for blood pressure, heart rate, serum albumin, A/G ratio, globulin, glucose, protein, sodium and transaminase. For the group as a whole, a statistically significant advance in acrophase was observed in serum transaminase, while a statistically significant delay in acrophase was observed for serum A/G ratio, globulin, glucose, potassium, protein, sodium and for urinary magnesium. Statistically significant by sign test, but not by cosinor, was a numerical mesor increase for urinary urea clearance, a numerical decrease in mesor for urinary zinc; a numerical amplitude decrease for serum cholesterol; and a numerical delay in acrophase for oral temperature and serum cholesterol, CO², and globulin in all men examined. Only mesor changes in serum cholesterol and urinary Ca/Mg were positively correlated with the change in body size over the 10-year span between studies.

From a circadian chronobiologic perspective, the immense amount of data uniquely reviewed in this report across a 10-year span in seven healthy individuals serves a useful beginning to the study of the effects of normal aging upon commonly measured physiologic and biochemical variables and, more importantly, upon the circadian rhythm characteristics of these variables. A great deal of supposition about what happens to the mesor, amplitude and acrophase of an individual's circadian rhythms in a variety of endpoints has been based upon transverse studies of short duration and relatively few longterm studies. The further accumulation of data such as presented here and similar long-term longitudinal time series can have no adequate substitute for truly understanding whether reproducible age-related changes in circadian rhythms occur as individuals age.

With these qualifications and with the further qualification that the timing of our observations within the aging process (mid-20's and mid-30's) may be suboptimal for conclusions about aging, very interesting trends definitely appear worth comment. There is some evidence in these data that the flattening of circadian rhythms may really accompany advancing age. In grouped data, this fall in amplitude may be secondary to an isolated fall in predictable swing around the mesor or a combination of this and increased variability of the acrophase with or without amplitude changes. The data are not robust enough to be sure of the relative contribution of these two components. In any event, the circadian amplitude of each and every physiologic variable studied demonstrated a tendency to fall between the mid-20's and mid- 30's. This tendency toward a flattening of circadian variability is also a very prominent property of many of the serum chemistries which were measured. The circadian patterns of excretion of substances in the urine change much less between the mid-20's and mid-30's in our subjects. These findings may indicate a separate effect of aging especially upon metabolic hepatic variables and upon nephrologic circadian rhythms. Cardiovascular rhythms seem to change more in parallel with hepatic metabolic rhythms in contradistinction to the kidney-related serum and urinary rhythms.

Further, ongoing statistical analyses may hopefully turn up interesting and relevant cross-correlations among the individual data themselves in each study year and between the 10-year span, as well as with rhythm (mesor, amplitude and acrophase) and other physiologic characteristics of each subject. Planned re-observation of what happens to the circadian time structure of these seven individuals in their mid-40's will prove invaluable to further sorting out of the effects of aging upon circadian time structure.     

Daily profiles of aldosterone levels during normal, high and low sodium intake in patients with essential hypertension.

The episodic secretion of aldosterone depends on the dietary sodium intake, alterations in posture and follows ACTH circadian rhythm. Aldosterone daily profiles have been studied in 23 supine essential hypertensive patients on normal sodium intake. Secretory pulses at a frequency of two to five pulses per 12 hr have occurred, independent of PRA levels. Among 13 patients with normal PRA two lost pulsatility when sodium was loaded (10 g/24 hr) and the same happened with two others on sodium restricted diet (2 g/24 hr). These results suggest a profound effect of dietary sodium intake on the pulsatile pattern of aldosterone secretion, particularly in normal PRA essential hypertension.     

Circadian Hematologic Time Structure in the Elderly

Twenty-three clinically healthy, diurnally active elderly subjects, 71 ± 5 years of age were studied over a 24-hr span (six samples). Complete blood counts and differential counts were done (Ortho ELT-8, Wright stained smears). The circadian rhythm parameters of the hematologic variables in the elderly subjects were compared with reference values obtained from a larger group of clinically healthy young adult and adult subjects studied independently. The data were analyzed by cosinor and the Bingham test. Circadian rhythms in the number of circulating formed elements in the peripheral blood persist in the aged. In comparison with the young adult, the elderly subjects show differences in the timing (phase advance) of the circadian rhythms in circulating neutrophil leukocytes and lymphocytes, a decrease in the circadian amplitude of circulating platelets, a decrease in circadian rhythm adjusted mean (mesor) in the red cell count, and in the neutrophil band forms.     

Reference Values for Orcadian Rhythms of 98 Variables in Clinically Healthy Men in the Fifth Decade of Life

Nine clinically healthy men, 41-47 yr of age, served as subjects in a 24-hr study conducted at the Edward Hines Jr Veterans Administration Hospital in the Chicago area in May 1988. Physiologic measurements, and blood and urine samples were collected at 3-hr intervals over a single 24-hr period beginning at 1900. The number of variables measured or calculated (total = 98) included: 6 vital signs (oral temperature, pulse, blood- and intraocular pressures); 16 in whole blood (counts and differentials); 50 in serum (SMAC-24, lipids, hormones, electrophoresis of LDH and proteins); and 26 in urine (solids, proteins, creatinine, catecholamines, melatonin, Cortisol, electrolytes and metals). Data were analyzed for time effect by analysis of variance (ANO VA) and for circadian rhythm by single cosinor. Individual rhythm characteristics for each variable were summarized for the group by population mean cosinor. The vast majority of variables revealed statistically significant within-day changes in values as validated by one-way ANOVA. All vital signs (except for intraocular pressures) and all serum hormones displayed a prominent circadian rhythm for the group, as did most variables in whole blood, while only about half of the variables in urine demonstrated a significant group rhythm. The results obtained are meant to: (a) document the circadian time structure; and (b) serve as reference values for circadian rhythm characteristics (range of change, mesor, amplitude and acrophase) for a defined group of individuals: clinically-healthy adult men in the prime of life.     

Reference Values for Orcadian Rhythms of 98 Variables in Clinically Healthy Men in the Fifth Decade of Life

Nine clinically healthy men, 41–47 yr of age, served as subjects in a 24-hr study conducted at the Edward Hines Jr Veterans Administration Hospital in the Chicago area in May 1988. Physiologic measurements, and blood and urine samples were collected at 3-hr intervals over a single 24-hr period beginning at 1900. The number of variables measured or calculated (total = 98) included: 6 vital signs (oral temperature, pulse, blood- and intraocular pressures); 16 in whole blood (counts and differentials); 50 in serum (SMAC-24, lipids, hormones, electrophoresis of LDH and proteins); and 26 in urine (solids, proteins, creatinine, catecholamines, melatonin, Cortisol, electrolytes and metals). Data were analyzed for time effect by analysis of variance (ANO VA) and for circadian rhythm by single cosinor. Individual rhythm characteristics for each variable were summarized for the group by population mean cosinor. The vast majority of variables revealed statistically significant within-day changes in values as validated by one-way ANOVA. All vital signs (except for intraocular pressures) and all serum hormones displayed a prominent circadian rhythm for the group, as did most variables in whole blood, while only about half of the variables in urine demonstrated a significant group rhythm. The results obtained are meant to: (a) document the circadian time structure; and (b) serve as reference values for circadian rhythm characteristics (range of change, mesor, amplitude and acrophase) for a defined group of individuals: clinically-healthy adult men in the prime of life.     

Reference values for circadian rhythms of 98 variables in clinically healthy men in the fifth decade of life

Nine clinically healthy men, 41-47 yr of age, served as subjects in a 24-hr study conducted at the Edward Hines Jr Veterans Administration Hospital in the Chicago area in May 1988. Physiologic measurements, and blood and urine samples were collected at 3-hr intervals over a single 24-hr period beginning at 1900. The number of variables measured or calculated (total = 98) included: 6 vital signs (oral temperature, pulse, blood- and intraocular pressures); 16 in whole blood (counts and differentials); 50 in serum (SMAC-24, lipids, hormones, electrophoresis of LDH and proteins); and 26 in urine (solids, proteins, creatinine, catecholamines, melatonin, cortisol, electrolytes and metals). Data were analyzed for time effect by analysis of variance (ANOVA) and for circadian rhythm by single cosinor. Individual rhythm characteristics for each variable were summarized for the group by population mean cosinor. The vast majority of variables revealed statistically significant within-day changes in values as validated by one-way ANOVA. All vital signs (except for intraocular pressures) and all serum hormones displayed a prominent circadian rhythm for the group, as did most variables in whole blood, while only about half of the variables in urine demonstrated a significant group rhythm. The results obtained are meant to: (a) document the circadian time structure; and (b) serve as reference values for circadian rhythm characteristics (range of change, mesor, amplitude and acrophase) for a defined group of individuals: clinically-healthy adult men in the prime of life.     

Aminoglutethimide effect on circadian rhythms in urinary variables in a patient with idiopathic hyperaldosteronism

Aminoglutethimide (AG: 750 mg/day) was administered to a patient with idiopathic hyperaldosteronism (IHA) and circadian rhythms in urinary excretion of sodium (UNaV), potassium (UKV), aldosterone (AER) and 17-OHCS were analyzed by the single cosinor method. Urine was collected every 4h for 24h on the day before and on the 1st, 3rd and 7th day of AG administration, and above variables in each sample were determined. Circadian rhythms of 14 patients with primary aldosteronism (PA) who served as controls were also analyzed. In the present case, circadian acrophases in UNaV and AER studied before AG administration occurred at 22(19) and 07(05), respectively. They were similar to those of preoperative PA-patients. Circadian acrophase in UNaV occurred earlier with AG administration and on the 7th day it was at 14(05), a value similar to that of postoperative PA-patients. Circadian mesor in AER decreased remarkably from 4.1 to 0.6 micrograms/4h with AG administration, as did circadian mesor in UKV, whereas circadian mesor and acrophase in 17-OHCS did not change. Thus, the circadian characteristics in urinary variables in the present IHA-case were pathophysiologically similar to those of PA.     

Daily variations of plasma sex hormone-binding globulin binding capacity, testosterone and luteinizing hormone concentrations in healthy rested adult males

In this study the daily variations of plasma sex hormone-binding globulin (SHBG) binding capacity were measured together with plasma testosterone and luteinizing hormone (LH) concentrations in 7 healthy rested adult males. Plasma SHBG-binding capacity demonstrated a significant circadian rhythm (acrophase = 2.06 p.m.; mesor = 0.35 +/- 0.6 ng testosterone bound/100 ml; amplitude = 17% of the mesor). Plasma testosterone also showed a circadian rhythm (acrophase = 7.02 a.m.; mesor = 4.38 +/- 0.67 ng/ml; amplitude = 18% of the mesor). The free testosterone index (or the ratio between plasma testosterone and SHBG-binding capacity) was not correlated with plasma LH levels. In our hands this last parameter did not vary according to a circadian pattern. These data are discussed in terms of a feedback mechanism controlling the pituitary-testis axis regulation.     

Early disturbance of the circadian rhythm of T and B lymphocytes in human immunodeficiency virus infection

Circadian rhythms in circulating B and T (CD3, CD4, CD8) lymphocyte subsets and in plasma cortisol were studied in 13 HIV-infected men and 14 healthy male controls. The circadian maximum (acrophase) of plasma cortisol was similar in both groups, approximately 8.00 A.M., however, a statistically significant increase was found in the 24 hour-mean value (mesor) of infected patients as compared to healthy controls. Circadian rhythms were statistically validated in all lymphocyte subsets of healthy controls, whereas, large alterations were found in patients with acquired immunodeficiency syndrome (AIDS), already in asymptomatic infected individuals. The alterations concern the mesor and the amplitude for B and CD4 lymphocytes and all cycle parameters for CD3 and CD8 lymphocytes.     

Protective effect of atorvastatin on circadian regulation of liver marker enzymes and redox status in hyperlipidemic rats

Hyperlipidemia was induced in rats by administering 2% cholesterol, 20% coconut oil, and 0.125% cholic acid for 10 weeks. Atorvastatin (0.8 mg/kg b.w.) was administered orally to rats together with high-fat diet for 10 weeks. At the end of the experimental period, the circadian characteristics (acrophase, amplitude, and mesor) of liver marker enzymes (aspartate aminotransferase and alanine transferase), lipid peroxidation products (thiobarbituric acid reactive substances (TBARS), and antioxidants (superoxide dismutase, catalase, reduced glutathione, and glutathione peroxidase) were analyzed. Circadian characteristics (mesor, amplitude, and acrophase) of liver marker enzymes, TBARS, and antioxidants were altered in high-fat diet-induced rats, and the diminished amplitude along with decreased mesor levels of antioxidants were observed in high-fat diet-induced rats. Further, oral administration of atorvastatin to high-fat diet-induced rats showed the normalized mesor, amplitude, and acrophase. These findings suggest that the antihyperlipidemic potential of atorvastatin could modulate the circadian patterns of liver marker enzymes and redox status in hyperlipidemic rats.     

Field survey of circadian rhythm in PEF of electronics workers suffering from colophony-induced asthma

Twenty-two British electronics workers suffering from occupationally-induced asthma due to their exposure to colophony fumes self-recorded their peak expiratory flow (PEF) every 1-2 hr throughout the waking span for at least two weeks, both during work and vacation periods. Data were analyzed by a two-step procedure using the statistical techniques of Single and Population Mean Cosinor analyses. The objective endpoints of mesor (24-hr mean), amplitude (measure of 24-hr rhythmic variation) and acrophase (peak time along the scale of 24 hr) for the time-spans of the work-week (Monday-Friday), weekend after work (Saturday-Sunday) and vacation weekdays and vacation weekends were compared. The PEF data of four workers who participated in the study for nearly one year also were evaluated for seasonal variation. A statistically significant difference (P less than 0.04) was detected in the PEF amplitude between work and vacation weeks; the difference in the PEF mesor and acrophase between work-weekdays and work-weekends achieved near or statistical significance (P = 0.07 and 0.05, respectively). The at-work amplitude was higher and the acrophase earlier timed. There was no statistically significant difference between work-week and weekend-after-work PEF mesors. Winter PEF mesors were significantly lower than summer ones in the four subjects self-measuring their bronchial patency over the year. Overall, the findings indicate that data obtained through employee surveys, using lightweight portable and inexpensive PEF Wright meters and analyzed by statistical analyses used in the field of biological rhythm research, yield objective evidence of occupationally associated decrements in pulmonary function resulting from colophony fume exposure.     

Influence of food intake on the 24-hr variations of plasma iron concentration in the rabbit

Circadian variations in plasma iron levels were first reported in humans in 1937. Influences of the sleeping pattern and of plasma cortisol and adrenaline levels on these variations as well as the reproducibility of the phenomenon itself are discussed controversially in the literature. The influence of food intake, however, was not considered in most of the studies and is therefore subject of this investigation. Circadian plasma iron and plasma transferrin variations were determined in rabbits and compared under free access to food and under starvation (caecotrophy was not prevented). Population-mean-cosinor analysis of circadian plasma iron concentrations showed similar variations in the fed and starved condition (mesor: 116.6 micrograms/dl vs 118.1 micrograms/dl, acrophase 0752 hr vs 0728) except for a significant increase of the circadian amplitude under free access to food (30.9 micrograms/dl vs 22.3 micrograms/dl, P less than 0.05). There was no variation in plasma transferrin, which shows that 24 hr variations in plasma iron are not caused by modulation of plasma transferrin. These findings demonstrate a circadian rhythm for plasma iron, the amplitude of which is increased by food intake.     

Modulating effects of vanillic acid on circadian pattern of indices of redox homeostasis in N-Methly-N′-Nitro-N-Nitrosoguanidine induced endometrial carcinoma in rats

The circadian timing system controls drug metabolism and cellular proliferation over the 24-h period through molecular clocks in every cell. Accumulating epidemiological and genetic evidences indicate that the disruption of circadian rhythms might be directly linked to cancer. This study evaluates the effect of vanillic acid on the circadian rhythms of circulatory lipid peroxidation and antioxidant status during N-Methyl-N′-Nitro-N-Nitrosoguanidine (MNNG)-induced endometrial carcinoma in rats. The characteristics of circadian rhythms (acrophase, amplitude and mesor) of lipid peroxidation products – thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH) and enzymatic antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-enzymatic antioxidants such as reduced glutathione (GSH), vitamins C and E were markedly declined in MNNG-treated rats when compared to other groups. Pre and co-treatment of vanillic acid to MNNG-treated animals significantly increased the mesor and altered amplitudes of antioxidants and significantly decreased the mesor values of TBARS and LOOH. Further, delays in acrophase in MNNG-induced rats were reversed by vanllic acid administration. Thus, oral treatment of vanillic acid results in normalization of the altered rhythms of these indices of redox homeostasis (compared to controls) by its anticarcinogenic, cytoprotective and antioxidant effects.     

Circadian Rhythms of Histatin 1, Histatin 3, Histatin 5, Statherin and Uric Acid in Whole Human Saliva Secretion

The circadian rhythms of histatins 1, 3, 5, of statherin and uric acid were investigated in whole human saliva. Histatins showed a rhythm approximately synchronous with salivary flow rate (acrophase around 5 pm), the higher amplitude pertaining to histatin 1 (about 50% of the mesor). Uric acid showed a large rhythm asynchronous with flow rate and histatin concentrations (4.4 ± 1.4 am). Statherin did not show a significant circadian rhythm on five of six volunteers. This finding confirms that the secretion route of statherin is different from that of histatins.     

Comparison of the circadian rhythm in cell proliferation in corneal epithelium of male rats studied under normal and hypobaric (hypoxic) conditions

Groups of 20-45-day-old rats maintained on a light (0600-1800)/dark (1800-0600) regimen with food and water available ad libitum were studied for the effect of hypoxic hypoxia on the circadian rhythm of corneal epithelial mitosis and thymidine incorporation. In experiments conducted during the months of September and November, hypoxic hypoxia was accomplished by the exposure of rats to a simulated altitude of 7500 m in one series of experiments, or to a gaseous mixture of 8% oxygen and 92% nitrogen at sea level atmospheric pressure (760 mmHg) in another series of experiments. Controls were included as well. Statistically significant (P less than 0.05) circadian rhythmicity in the corneal mitotic index was substantiated in the control animals with mesor (M) = 12.4%, amplitude (A) = 9.6% and acrophase (phi) of 0911. In the hypoxic hypoxia situation, the mesor and amplitude were depressed to 8.6 and 5.9%, respectively. In control groups, thymidine incorporation was circadian rhythmic with M = 38.5 and A = 11.3 cpm/microns DNA and acrophase of 2255. In the hypoxic hypoxia situation, the mesor was similar to the controls; whereas the amplitude was suppressed to 6.1% and acrophase was phase advanced by about 7 hr. Changes in the circadian rhythm of corneal mitosis and in thymidine incorporation under hypoxic hypoxia can be explained by programmed-in-time energy requirements during the corneal cell regeneration cycle.     

Effect of octreotide on 24-hour growth hormone and prolactin secretory patterns in acromegalics.

Four adult patients with active acromegaly underwent studies of their 24-hour secretory pattern of hGH and Prl prior to and at the end of 3 months of treatment with the octreotide (somatostatin analog SMS 201-995) 100 micrograms s.c. every 8 h. Blood was withdrawn at 30-min intervals with the aid of a constant withdrawal pump. The best fit cosinor method was used to define the following rhythm parameters: mesor, amplitude, acrophase and periodicity. Prior to treatment, hGH secretion was increased in all patients. The mean 24-hour ranged from 9-47 ng/ml with amplitude 5.2-23 and observed maximal pulse 41-95 ng/ml. Computed rhythms were circadian in 3 patients and ultradian in 1; in 2 patients the acrophases were shifted to daytime. hPrl secretion was altered in 3 of the patients. Two had elevated mean 24-hour of 17.7 and 22.2 ng/ml, while computed rhythms showed semicircadian periodicity in 1 of them and circadian periodicity with a shift of acrophase to daytime in the other. The third patient who had normal hPrl levels, showed ultradian 8-hour periodicity. At the end of treatment there was a marked reduction in hGH secretion in 1 patient and a lesser reduction in the other 3. The rhythm was influenced by the masking effect of the drug, to yield an 8-hour period with acrophases related to injection clock time having equal amplitudes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circadian regulation gene polymorphisms are associated with sleep disruption and duration,and circadian phase and rhythm in adults with HIV

Genes involved in circadian regulation, such as circadian locomotor output cycles kaput [CLOCK], cryptochrome [CRY1] and period [PER], have been associated with sleep outcomes in prior animal and human research. However, it is unclear whether polymorphisms in these genes are associated with the sleep disturbances commonly experienced by adults living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Thus, the purpose of this study was to describe polymorphisms in selected circadian genes that are associated with sleep duration or disruption as well as the sleep–wake rhythm strength and phase timing among adults living with HIV/AIDS. A convenience sample of 289 adults with HIV/AIDS was recruited from HIV clinics and community sites in the San Francisco Bay Area. A wrist actigraph was worn for 72?h on weekdays to estimate sleep duration or total sleep time (TST), sleep disruption or percentage of wake after sleep onset (WASO) and several circadian rhythm parameters: mesor, amplitude, the ratio of mesor to amplitude (circadian quotient), and 24-h autocorrelation. Circadian phase measures included clock time for peak activity (acrophase) from actigraphy movement data, and bed time and final wake time from actigraphy and self-report. Genotyping was conducted for polymorphisms in five candidate genes involved in circadian regulation: CLOCK, CRY1, PER1, PER2 and PER3. Demographic and clinical variables were evaluated as potential covariates. Interactions between genotype and HIV variables (i.e. viral load, years since HIV diagnosis) were also evaluated. Controlling for potentially confounding variables (e.g. race, gender, CD4+ T-cell count, waist circumference, medication use, smoking and depressive symptoms), CLOCK was associated with WASO, 24-h autocorrelation and objectively-measured bed time; CRY1 was associated with circadian quotient; PER1 was associated with mesor and self-reported habitual wake time; PER2 was associated with TST, mesor, circadian quotient, 24-h autocorrelation and bed and wake times; PER3 was associated with amplitude, 24-h autocorrelation, acrophase and bed and wake times. Most of the observed associations involved a significant interaction between genotype and HIV. In this chronic illness population, polymorphisms in several circadian genes were associated with measures of sleep disruption and timing. These findings extend the evidence for an association between genetic variability in circadian regulation and sleep outcomes to include the sleep–wake patterns experienced by adults living with HIV/AIDS. These results provide direction for future intervention research related to circadian sleep–wake behavior patterns.     

Modulating effects of hesperidin on circadian pattern indices of rotenone induced redox homeostasis in clock mutant (cryb) of Drosophila melanogaster

The circadian timing system controls drug metabolism and cellular processes over the 24 h period in every cell. Impaired redox homeostasis is a casual factor for a number of diseases and it is desirable to understand the orchestration of circadian clock under oxidative stress in the model organism, Drosophila melanogaster. This study evaluates the effect of hesperidin on the circadian rhythms of lipid peroxidation products and antioxidants during rotenone-induced oxidative stress in fruit fly. The characteristics of temporal rhythms (acrophase, amplitude, and mesor) of glutathione peroxides (GPx), reduced glutathione (GSH)), were markedly declined in rotenone-treated flies when compared to other groups. Treatment of hesperidin to rotenone-treated flies significantly increased the mesor and modified the amplitudes of antioxidants. Further, delays in acrophase in rotenone-induced flies were reversed by hesperidin treatment. Thus, treatment of hesperidin results in normalization of the altered rhythms of these indices plausibly by its cytoprotective and antioxidant effects. Impairment of 24 h rhythms in oxidative stress markers and antioxidants were observed during rotenone treatment and the impairment is severe in circadian clock mutant cry^b flies. A reversibility of rhythms was prominent consequent to hesperidin treatment in wild-type flies than cry^b flies. These findings revealed a role of circadian clock in redox homeostasis and the use of Drosophila model in screening putative antioxidative phytomedicines earlier to their use in mammalian systems.