Recent global hypertension guidelines recommend an early, strict and 24-hour blood pressure (BP) control for the prevention of target organ damage and cardiovascular events. Out-of-office BP measurement such as ambulatory BP monitoring and home BP monitoring is now widely utilized to rule out white-coat hypertension, to detect masked hypertension, to evaluate the effects of antihypertensive medication, to analyze diurnal BP variation, and to increase drug adherence. Nocturnal hypertension has been neglected in the management of hypertension despite of its clinical significance. Nighttime BP and non-dipping patterns of BP are stronger risk predictors for the future cardiovascular mortality and morbidity than clinic or daytime BP. In addition to ambulatory or home daytime BP and 24-hour mean BP, nocturnal BP should be a new therapeutic target for the optimal treatment of hypertension to improve prognosis in hypertensive patients. This review will provide an overview of epidemiology, characteristics, and pathophysiology of nocturnal hypertension and clinical significance, therapeutic implication and future perspectives of nocturnal hypertension will be discussed.
Blood Pressure ; Chronotherapy ; Epidemiology ; Humans ; Hypertension ; Masked Hypertension ; Mortality ; Prognosis

OBJECTIVETo compare the therapeutic effects, toxic side effects and influence on the immune function in patients treated with TPF [docetaxel (DOC) + cisplatin (DDP) + 5-fluorouracil (5-Fu)] induction chronochemotherapy and conventional chemotherapy for locally advanced nasopharyngeal (NPC).

METHODSSeventy patients with locally advanced nasopharyngeal carcinoma were treated in our department at their first visit from April 2013 to December 2013. They were divided randomly into two groups: the chronochemotherapy group (38 patients) and conventional chemotherapy group (32 patients). All of the patients were treated with TPF regimen with 2 cycles of induction chemotherapy in a 21-28-days/cycle. The chronochemotherapy group: DOC: 75 mg/m2, i. v. gtt, d1 (03: 30-04: 30); DDP: 75 mg/m2, 10 am-10 pm, c.i.v, d1-d5; 5-Fu: 750 mg·m(-2)·d(-1), 10 pm-10 am, c. i.v., d1-d5, both chemotherapies were administered by intravenous infusion using an automatic electric pump. The conventional chemotherapy group: Both DOC and DDP were administered intravenously at a dose of 75 mg/m2 on d1. 5-Fu was given at a dose of 750 mg/m2 for 24 hours from d1-d5 with continuous infusion in a total of 120 hours. In this procedure, prescribing the conventional intravenous infusion, intensity modulated radiation therapy was used after the induction chemotherapy. The prescribed nasopharyngeal lesion dose (GTVnx) was 69.96 Gy/33 fractions for the T1-T2 nasopharygeal cancer, while 73.92 Gy/33 fractions nasopharynx lesion dose (GTVnx) for the T3-T4 nasopharyngeal cancer. The planning target volume (PTV) of positive lymph node (PTVnd) dose was 69.96 Gy/33 fractions. Concurrent chemoradiotherapy: cisplatin 100 mg/m2, i. v. gtt. d1-d2, and there were two cycles in total and 21 days each cycle.

RESULTSSixty-six patients were evaluable for the response assessment. There were 36 patients in the chronochemotherapy group and 30 patients in the conventional chemotherapy group. After the induction chemotherapy, no CR case was found in both of the two groups. The PR was 80.6% in the chronochemotherapy group and 50.0% in the conventional chemotherapy group (P=0.009). After concurrent chemoradiotherapy, the CR rate in the chronocheotherapy group was 45.5%, significantly higher than 20.7% in the conventional chemotherapy group (P=0.040). Secondly, the incidence rates of adverse reactions including bone marrow suppression, nausea, vomiting, diarrhea, constipation, oral mucositis, fatigue, anorexia in the chrono-chemotherapy group were significantly lower than that in the conventional group (P<0.05 for all). Finally, compared the two groups, the CD4+ /CD8+ ratio was significantly lower in the chronochemotherapy group than that in the conventional chemotherapy group (P<0.05). The lymphocytes CD19+ and CD4+/CD8+ were decreased and CD3+, CD4+, CD8+, CD16++CD56+ were increased in the chronochemotherapy group, while only CD3+ and CD8+ were increased in the conventional chemotherapy group.

CONCLUSIONSCompared with the conventional chemotherapy, the chronochemotherapy may be more favorable in the treatment of NPC, with a better therapeutic effects and effectiveness than that of conventional chemotherapy after induction chemotherapy, with less side effects, and can improve the immune function in the patients.

Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Carcinoma ; Chemoradiotherapy ; Cisplatin ; administration & dosage ; Drug Chronotherapy ; Fluorouracil ; administration & dosage ; Humans ; Induction Chemotherapy ; methods ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; radiotherapy ; Nausea ; Neoplasm Staging ; Radiotherapy, Intensity-Modulated ; Taxoids ; administration & dosage ; Treatment Outcome

OBJECTIVE: To examine the demographic profile and treatment patterns in patients with rheumatoid arthritis (RA) prescribed low-dose modified-release prednisone (LODOTRA(R)) on a named patient basis in Singapore and to evaluate safety and clinical outcome of the treatment. METHODS: Medical records of adult patients with RA who had inadequate responses to prior RA treatment and were prescribed low-dose modified-release prednisone between January and December 2012 at a specialist clinic were reviewed retrospectively. Demographics, treatment information, relevant laboratory evaluations, and disease condition, prior to and after the start of treatment, were collected. RESULTS: Thirty-eight patients were enrolled. The mean age was 52.8 years and median disease duration was 1.3 years (0.04 to 8.2 years). Patients received a mean daily dose of 5.0+/-1.0 mg of modified-release prednisone for a median period of 4.4 months (0.2 to 11.8 months). Before treatment, the majority of patients received disease-modifying anti-rheumatic drugs (78.9%), glucocorticoids (71.0%), and non-steroidal anti-inflammatory drugs (NSAIDs) (68.4%). After the start of treatment, prescription of NSAIDs declined from 68.4% to 28.9%. Similar laboratory findings were observed before and after treatment. The median C-reactive protein level decreased substantially from 9.8 mg/L (0.2 to 77.7 mg/L) to 3.9 mg/L (0.4 to 27.6 mg/L). High proportions of patients reported improvement or recovery from morning stiffness (94.7%) or joint pain (70.0 to 100.0%) after treatment. The median number of painful joints decreased from 4 (1 to 8) to 0 (0 to 4) after treatment. CONCLUSION: Our clinical experience in Asian patients with RA suggests that low-dose modified-release prednisone chronotherapy is associated with similar treatment patterns, safety profile, and clinical outcomes as in Western populations.
Adult ; Anti-Inflammatory Agents, Non-Steroidal ; Antirheumatic Agents ; Arthralgia ; Arthritis, Rheumatoid* ; Asian Continental Ancestry Group* ; C-Reactive Protein ; Chronotherapy* ; Demography ; Glucocorticoids ; Humans ; Joints ; Medical Records ; Prednisone* ; Prescriptions ; Retrospective Studies ; Singapore* ; Specialization

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Cisplatin ; administration & dosage ; adverse effects ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Drug Chronotherapy ; Female ; Humans ; Leukopenia ; chemically induced ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Staging ; Neutropenia ; chemically induced ; Remission Induction ; Taxoids ; administration & dosage ; adverse effects

This study investigated the effects of benazepril administered in the morning or evening on the diurnal variation of renin-angiotensin-aldosterone system (RAAS) and clock genes in the kidney. The male Wistar rat models of 5/6 subtotal nephrectomy (STNx) were established. Animals were randomly divided into 4 groups: sham STNx group (control), STNx group, morning benazepril group (MB) and evening benazepril group (EB). Benazepril was intragastrically administered at a dose of 10 mg/kg/day at 07:00 and 19:00 in the MB group and EB group respectively for 12 weeks. All the animals were synchronized to the light:dark cycle of 12:12 for 12 weeks. Systolic blood pressure (SBP), 24-h urinary protein excretion and renal function were measured at 11 weeks. Blood samples and kidneys were collected every 4 h throughout a day to detect the expression pattern of renin activity (RA), angiotensin II (AngII) and aldosterone (Ald) by radioimmunoassay (RIA) and the mRNA expression profile of clock genes (bmal1, dbp and per2) by real-time PCR at 12 weeks. Our results showed that no significant differences were noted in the SBP, 24-h urine protein excretion and renal function between the MB and EB groups. There were no significant differences in average Ald and RA content of a day between the MB group and EB group. The expression peak of bmal1 mRNA was phase-delayed by 4 to 8 h, and the diurnal variation of per2 and dbp mRNA diminished in the MB and EB groups compared with the control and STNx groups. It was concluded when the similar SBP reduction, RAAS inhibition and clock gene profile were achieved with optimal dose of benazepril, morning versus evening dosing of benazepril has the same renoprotection effects.
Animals ; Antihypertensive Agents ; administration & dosage ; Benzazepines ; administration & dosage ; CLOCK Proteins ; metabolism ; Circadian Rhythm ; Drug Chronotherapy ; Gene Expression Profiling ; Hypertension, Renal ; drug therapy ; physiopathology ; Kidney ; drug effects ; physiopathology ; surgery ; Male ; Nephrectomy ; Rats ; Rats, Wistar ; Renin-Angiotensin System ; drug effects ; Treatment Outcome

Neoadjuvant chemotherapy plus radiotherapy is the most common treatment regimen for advanced nasopharyngeal carcinoma (NPC). Whether chronomodulated infusion of chemotherapy can reduce its toxicity is unclear. This study aimed to evaluate the toxic and therapeutic effects of sinusoidal chronomodulated infusion versus flat intermittent infusion of cisplatin (DDP) and 5-fluorouracil (5-FU) followed by radiotherapy in patients with locoregionally advanced NPC. Patients with biopsy-diagnosed untreated stages III and IV NPC (according to the 2002 UICC staging system) were randomized to undergo 2 cycles of sinusoidal chronomodulated infusion (Arm A) or flat intermittent constant rate infusion (Arm B) of DDP and 5-FU followed by radical radiotherapy. Using a "MELODIE" multi-channel programmed pump, the patients were given 12-hour continuous infusions of DDP (20 mg/m2) and 5-FU (750 mg/m2) for 5 days, repeated every 3 weeks for 2 cycles. DDP was administered from 10:00 am to 10:00 pm, and 5-FU was administered from 10:00 pm to 10:00 am each day. Chronomodulated infusion was performed in Arm A, with the peak deliveries of 5-FU at 4:00 am and DDP at 4:00 pm. The patients in Arm B underwent a constant rate of infusion. Radiotherapy was initiated in the fifth week, and both arms were treated with the same radiotherapy techniques and dose fractions. Between June 2004 and June 2006, 125 patients were registered, and 124 were eligible for analysis of response and toxicity. The major toxicity observed during neoadjuvant chemotherapy was neutropenia. The incidence of acute toxicity was similar in both arms. During radiotherapy, the incidence of stomatitis was significantly lower in Arm A than in Arm B (38.1% vs. 59.0%, P = 0.020). No significant differences were observed for other toxicities. The 1-, 3-, and 5-year overall survival rates were 88.9%, 82.4%, and 74.8% for Arm A and 91.8%, 90.2%, and 82.1% for Arm B. The 1-, 3-, and 5-year progression-free survival rates were 91.7%, 88.1%, and 85.2% for Arm A and 100%, 94.5%, and 86.9% for Arm B. The 1-, 3-, and 5-year distant metastasis-free survival rates were 82.5%, 79.1%, and 79.1% for Arm A and 90.2%, 85.2%, and 81.7% for Arm B. Chronochemotherapy significantly reduced stomatitis but was not superior to standard chemotherapy in terms of hematologic toxicities and therapeutic response.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma ; Cisplatin ; administration & dosage ; Disease-Free Survival ; Dose Fractionation ; Drug Chronotherapy ; Female ; Fluorouracil ; administration & dosage ; Humans ; Induction Chemotherapy ; adverse effects ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; radiotherapy ; Neoplasm Staging ; Neutropenia ; chemically induced ; Radiotherapy, High-Energy ; Stomatitis ; etiology ; Survival Rate ; Young Adult

It was impossible to measure the nighttime blood pressure in patients with hypertension for more than one hundred years. The introduction of ambulatory blood pressure monitoring made it possible to evaluate the nighttime blood pressure and clinical significances in recent 40 years. There are tremendous evidences for proving that the nighttime blood pressure is the more powerful predictor in cardiovascular morbidity and mortality than conventional office and ambulatory daytime blood pressure. The cardiovascular mortality can be reduced when 5% of nighttime blood pressure decreased from Ohasama registry report. So investigators should reevaluate the antihypertensive drugs in the view points of nighttime blood pressure reduction. And changing the administration schedule of antihypertensive drugs, so called chronotherapy, is effective for controlling the nighttime blood pressure and modifying the blood pressure circadian rhythm. Korean Ambulatory Blood Pressure (KORABP), nationwide ambulatory blood pressure monitoring registry in Korea, may answer unproved questions for controlling nighttime blood pressure.
Antihypertensive Agents ; Appointments and Schedules ; Blood Pressure ; Blood Pressure Monitoring, Ambulatory ; Chronotherapy ; Circadian Rhythm ; Humans ; Hypertension ; Korea ; Research Personnel

OBJECTIVETo prepare the gastric retenting and chronopharmacologic drug delivery tablets containing sinomenine hydrochloride as a model drug, evaluate the effects of the coating layers formulation and technics on drug release behavior, and to elucidate the mechanism of drug release based on obtained results.

METHODThe gastric retenting and chronopharmacologic drug delivery tablets were prepared by press-coated technics. The types of disintegrants were chosen according to the expanding rate and the lag-time. The effects of formulation and technics of coating layer on the release characteristic of the drug were investigated by dissolution testing. The mechanism of drug release was proved by erosion test.

RESULTThe tablets had typical chronopharmacologic drug delivery properties with a lag time followed by a rapid release phase. CMS-Na was selected as the disintegrant. The lag-time was prolonged with the increase of the ratio of HPMC/carrrageenan and the amount of matrix material in coating layer. The compressing pressure and preparation method of coat material had minor influence on the lag-time of the tablets. Coating layer erosion and tablet core swelling were involved in the mechanism of drug release.

CONCLUSIONThe tablets had typical chronopharmacologic drug delivery properties. A suitable lag-time can be achieved by adjusting formulation of coating layer to meet the requirement of chronotherapy.

Chemistry, Pharmaceutical ; Drug Chronotherapy ; Drug Delivery Systems ; methods ; Humans ; Morphinans ; chemistry ; pharmacokinetics ; Stomach ; drug effects ; Tablets, Enteric-Coated ; chemistry ; pharmacokinetics

The human circadian system is normally synchronised with the solar day, insuring that alertness and performance peak during daytime hours and consolidated sleep occurs during the night. In circadian rhythm sleep disorders, the pattern of sleep-wake is misaligned with the patient's circadian system or the external environment, resulting in insomnia, fatigue, and deterioration in performance. Appropriately-timed exposure to bright light can reset the timing of sleep and wake to the desired times, and improve sleep quality and daytime alertness. The efficacy of bright light therapy, however, is dependent on the time-of-day of the circadian cycle that the light is administered. In this article, we examine the physiological basis for bright light therapy, and we discuss the application of light in the treatment of circadian rhythm sleep disorders including advanced and delayed sleep-phase disorder, free-running disorder (nonentrained type), shiftwork disorder and jet lag disorder. We review the laboratory and field studies which have established bright light therapy as an effective treatment for sleep-wake and circadian misalignment, and we also provide guidelines for the appropriate timing and safe use of bright light therapy.
Chronotherapy ; methods ; Humans ; Jet Lag Syndrome ; therapy ; Phototherapy ; methods ; Sleep Disorders, Circadian Rhythm ; therapy ; Treatment Outcome

OBJECTIVETo study the endogenous hormone of testosterone and cortisol that secretes volume and rhythm in sports fatigued human bodies and animals. To determine secretory volume and rhythm in sports fatigued human bodies and animals when Shixiang yaofa's drug are used.

METHODRadio-immunity method was used to determine secretory volume and rhythm in sports fatigued human bodies and animals and to analyze secretory volume and rhythm. According to the secretory volume and rhythm of testosterone and cortisol, the Shixiang Yaofa's drugs were used. Doses: wenyang jihuo bead 10 g/sack 2 sack, ziyin xiuyang capsule 0.5 g/pill 8 pill pd in human bodies for 28 days. Wenyang jihuo bead 10 g x kg(-1) of crude drug, ziyin xiuyang capsule 4 g x kg(-1) of crude drug pd for hight doses in animals. Other groups for low doses 5 g x kg(-1) and 2 g x kg(-1) of crude drug pd for 15 days. The blood samples were collected for determination.

RESULT(1) In human bodies the peak value of testosterone was appeared in 8:00 and valley value was appeared in 18:00, ranges: 176.93-281.73 x 10(-5) mg x L(-1). The peak value of cortisol was appeared in 8:00 and valley value was appeared in 22:00, ranges: 1.31-16.13 x 10(-3) mg x L(-1). In the same condition, the mouse peak value of testosterone was appeared in 20:00 and valley value was appeared in 0:00, ranges: (0.56 x 10(-5) - 124.0 x 10(-5)) mg x L(-1). The rhythm in animals was compatible with human bodies, howerer, the peak value was delayed for 12 hours. (2) The testosterone was step up and the cortisol was cut down in sports fatigued human bodies and animals when shixiang yaofa's drug were used (P < 0.05, P < 0.01).

CONCLUSIONThe secretion of testosterone and cortisol in sports fatigued human bodies and animals are existed conclusive biologic rhythm. The secretory volume can be available accommodation by shixiang yaofa's drugs.

Adolescent ; Adult ; Animals ; Chronotherapy ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Fatigue ; etiology ; physiopathology ; Female ; Humans ; Hydrocortisone ; secretion ; Male ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred ICR ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sports ; Testosterone ; secretion