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Hypertension is a well-known cardiovascular risk. Patients with end-stage renal diseases frequently suffer hypertension, and their blood pressure elevates in winter. However, seasonal changes in daily variations of blood pressure are poorly assessed in patients treated with hemodialysis. Thirty hypertensive patients with end-stage renal diseases were enrolled in the study. Dry weight and antihypertensive medications were altered when they were necessary. Home blood pressure measurements were performed at least for 1 week in each season; April-May 2008, July-August 2008, October-November 2008, and January-February 2009. Both morning and evening systolic blood pressures (SBPs) showed significant seasonal changes ( p < 0.01), with the highest blood pressure in winter (162 +/- 18 and 135 +/- 22 mmHg in morning and evening). Morning diastolic blood pressure (DBP) also exhibited seasonal changes ( p < 0.05), with the highest blood pressure in fall ( 78 +/- 8 mmHg). Evening DBP did not manifest seasonal deviations. Morning-evening differences in SBP and DBP were the greatest in winter (28 +/- 21 and 10 +/- 9 mmHg in SBP and DBP, p < 0.01), and the smallest in summer (16 +/- 12 and 6 +/- 5 mmHg). Daily variations of SBP and DBPs in spring (19 +/- 12 and 7 +/- 6 mmHg) and fall (20 +/- 13 and 9 +/- 8 mmHg) were between those of summer and winter. Our results indicate that not only averaged blood pressure but also variations of blood pressure in winter are larger than the other seasons, and suggest that these blood pressure variations participate in cardiovascular events in hypertensive patients with end-stage renal diseases.

Although the patients with diabetic nephropathy suffered high cardiovascular risk, augmentation index (AI) in diabetic nephropathy has been poorly characterized. Cross-sectional studies were performed on 26 diabetic and 27 nondiabetic nephropathic patients. Home blood pressure was examined. In addition, blood pressure, pulse rate, and AI were measured in both supine and sitting positions. Patient backgrounds such as age, sex, sitting blood pressure, and pulse rate were similar between two groups. Circadian variations of home blood pressure were preserved in nondiabetic patients, but disappeared in diabetes. Changing from supine to sitting position induced greater decrements of systolic blood pressure (DeltaSBP -9 +/- 8 mmHg) and AI (DeltaAI -7 +/- 10) in the diabetic group than in nondiabetic patients (DeltaSBP -4 +/- 12 mmHg, DeltaAI -2 +/- 9). Multivariate regression analysis revealed that AI in a sitting position correlated positively to SBP and inversely to pulse rate. Of interest, AI in supine position related positively to age, the presence of diabetes and SBP, and inversely to pulse rate. The present data indicate autonomic dysfunction in patients with diabetic nephropathy. Furthermore, our findings provide the evidence that autonomic dysfunction elicits an inadequate physiological arterial contraction in response to postural change, thereby reducing AI that results in the fall of SBP. Finally, the present results suggest that AI in supine, but not sitting position, is suited for detecting cardiovascular risk in diabetes.

The influence of interferon-beta (IFN-beta) dosing time on antiviral activity was investigated in ICR male mice under light-dark cycle conditions (lights on at 07:00, off at 19:00) with food and water available ad libitum. There was a significant dosing time-dependent change in 2',5'-oligoadenylate synthetase (2',5'-OAS) activities, as an index of antiviral activity, in liver at 12 h after IFN-beta (15 MIU/kg, i.v.) injection. IFN-beta-induced 2',5'-OAS activity was more potent after the drug injection during the late dark phase. The higher antiviral effect of IFN-beta was observed when the interferon-alpha/beta receptor (IFNAR) expression in the liver increased, and the lower effect was observed when its expression decreased. IFN-beta-induced fever was more serious after IFN-beta injection from the late dark phase to the early light phase. A significant dosing time-dependent change was demonstrated for plasma IFN-beta concentrations, which showed a higher level during the light phase and a lower level during the dark phase. The dosing time-dependent change of plasma IFN-beta concentrations was not associated with that of the antiviral effect or fever induced by IFN-beta. These results suggest that selecting the most suitable dosing time of IFN-beta, associated with the 24-h rhythm of IFNAR expression in the liver, may be important to increase effectively the antiviral activity of the drug in experimental and clinical situations.

The mammalian circadian clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus and in most peripheral tissues. Clock genes drive the biological clock. However, circadian expression variations of the human clock genes are still unclear. In this study, we analyzed the daily variations of mPer2 and mClock mRNA expression in both the mouse SCN and liver to evaluate the central and peripheral alterations in the rodent clock genes. We also examined whether there are the daily variations of the clock genes hPer2 and hClock in human peripheral blood mononuclear cells (PBMCs). The daily variation of mClock and mPer2 mRNA expression in mouse SCN and liver were determined at ZT2, ZT6, ZT10, ZT14, ZT18 or ZT22. We isolated PBMCs from 9 healthy volunteers at 9:00 and 21:00 and examined the expression of hPer2 and hClock mRNA by RT-PCR analysis. The animals exhibited a robust daily rhythm in the RNA levels of mPer2 in the SCN and liver (P<0.01, respectively). In humans, hPer2 mRNA expression also had daily variation, and the hPer2 mRNA levels at 9:00 were significantly larger than those at 21:00 (P<0.01). While, the Clock mRNA in both mice and humans exhibited no daily variation. These findings suggest that the variation in hPer2 mRNA expression may be useful for assessing human peripheral circadian systems.

We determined whether human peripheral blood mononuclear cells (PBMCs) could be used to analyze clock genes by studying their mRNA expressions in human bronchial epithelium (BEAS‐2B) and PBMCs following stimulation by the glucocorticoid homologue dexamethasone (DEX) in vitro. PBMCs were obtained at 10:00 h from two diurnally active (&nvsim;07:00 to 23:00 h) healthy volunteers and were evaluated for h Per1 mRNA expression following DEX stimulation in vitro using real time‐PCR analysis. DEX stimulation of human BEAS‐2B cells and PBMCs in vitro led to a remarkable increase of h Per1 mRNA. The glucocorticoid rapidly affected the expression of h Per1 mRNA in PBMCs, suggesting that human PBMCs may be a useful surrogate marker for the investigation of drug effects on clock genes. [ABSTRACT FROM AUTHOR]

Abstract: Bronchial asthma is characterized by chronic airways inflammation and reversible airflow limitation. In patients with asthma, symptoms generally worsen during the early hours of the morning, and pulmonary function often deteriorates at the same time, suggesting a role for chronopharmacotherapy. Several drugs for asthma have been developed based on chronopharmacology. Most medications employed for the chronotherapy of asthma are administered once at night with the goal of preventing chronic airway inflammation or development of airflow limitation. In addition to bronchodilators, the inhaled glucocorticosteroid ciclesonide is now available with once-daily dosing, which also improves patients'' compliance. Numerous investigations have demonstrated the usefulness of chronotherapy for asthma, especially for patients with nocturnal asthma. This review focuses on chronotherapy of asthma, and also provides a molecular biological explanation for the influence of asthma medications on the clock genes. [Copyright &y& Elsevier]