Formulation And In Vivo Evaluation Of Chronomodulated Drug Delivery Of Nimodipine

Chronotherapy has been emerging as a novel technology in the field of pharmaceutical research. Delivery of drugs with respect to the circadian rhythm has gained greater importance in the diseases such as diabetes, asthma and hypertension in producing maximum therapeutic action. Present study focus on the formulation and evaluation of Nimodipine pulsatile release tablets with the incorporation of Eudragit pH sensitive polymers used for the chronotherapy of hypertension. Pharmacologically Nimodipine is an anti-hypertensive agent that acts by blocking the L and N-type calcium channels. Evaluation parameters for Nimodipine tablets included friability, drug content, bulk and tapped density, angle of repose and Carr’s index and drug release in vitro and in vivo.

The prevalence of hypertension in patients with obstructive sleep apnea hypopnea syndrome and their relationship / 天津医药

Objective To investigate the prevalence of hypertension in patients with obstructive sleep apnea hypopnea syndrome (OSA) and the relationship between blood pressure (BP) with respiratory ventilation function. Methods Patients with OSA (n=3 607) were included in this study and divided into 4 groups based on their apnea-hypopnea index (AHI) scores:control group (control, n=354) with AHI<5;mild OSAHS (mild, n=658) with 5≤AHI<15;moderate OSAHS (moder?ate, n=753) with 15≤AHI<30;and severe OSA (severe, n=1 842) with AHI≥30. BP were measured at 4 time points (daytime, evening, midnight, and morning). The midnight/ daytime average BP (RN/D) and morning/evening average BP (RM/E) ratios were calculated. Finally, the general profiles, prevalence of hypertension and average BP of 4 time points were compared among 4 groups. The correlations of MBP with AHI and LSaO2 were also analyzed. Results The prevalence of hypertension as well as MBP at daytime and in the morning in the mild group (34.65%), moderate group (39.04%) and severe group (55.37%) were all higher than that in control group (22.32%)(all P<0.05). The prevalence of hypertension as well as MBP at daytime and in the morning were both higher in severe group than those in mild and moderate groups. MPB in the evening and at midnight was higher in severe group than that in moderate group than that in mild group than in control group (P<0.05). Average MBP of all four time points rise with increasing AHI (all P<0.05). The ratios of nighttime to daytime MBP (RN/D) and of morning to evening MBP (RM/E) increased with the severity of the illness (F=9.821, 18.957;P<0.001). The day? time BP correlated well with AHI and lowest oxygen saturation (LSaO2;systolic BP, r=0.195,-0.206;diastolic BP, r=0.248,-0.251, P<0.01). Daytime MBP increased gradually with increasing AHI until MPB reached 61-65, at which point it either plateaued or dropped slightly. Conclusion OSA patients have a significant increase in midnight and morning BP and lose normal BP nycterohemeral rhythm. OSA is an independent risk factor for hypertension.

Circadian Variation in Frequency of Stroke in Bangladesh: a Hospital Based Cross Sectional Study.

A hospital based cross sectional study was carried out to analyze diurnal variation of stroke and their association to sleep awake cycle. Four hundred and two patients of stroke admitted in different Medicine Units of Faridpur Medical College and Dhaka Medical College Hospitals from July 2012 to June 2013 were chosen using purposive sampling technique. Enrolled patients were with their first stroke, subsequently proved by CT scan of brain. The initial clinical diagnosis of stroke was made from history and examination obtained from the patient himself or from his/her attendant. The time of onset of stroke was recorded by attending doctor at the time of assessment and recorded on a fixed proforma. Patient who could not give history properly or had no responsible attendant and who had history of head injury, intracranial space occupying lesion or bleeding disorder were excluded from the study. Age ranged from 25 years to 98 years with mean age of 62.02 years (+_SD 11.75 years). Out of 402 patients 59.7% suffered from ischemic stroke. Highest incidence of stroke (26.9%) occurred between 4:01am to 8:00 am and lowest (7.5%) between 8:01 pm to 12:00 am. Among the subtypes, ischaemic stroke has shown a single peak incidence at 4:01 to 8:00 am and lowest between 8:01 pm to 12:00 am. 50 % of ischaemic stroke cases developed between 0:01 am to 8:00 am. In this study, maximum number of patients developed hemorrhagic stroke between 4:01 am to 8:00 am (25.9%) and lowest number developed hemorrhagic stroke between 12:01 pm to 4:00 pm (9.3%). This study confirms the diurnal variation of both hemorrhagic and ischaemic stroke in Bangladesh and most of them occurs in early morning after wakening.

Circadian variation of essential oil from Piper marginatum Jacq / Variaciones circadiana de aceite esencial de Piper marginatum Jacq

The composition of the essential oil from the leaves of Piper marginatum (Piperaceae) shows circadian variation and a higher yield during high solar incidence. The essential oils samples were investigated by GC-FID and GC-MS, which allowed identification of 29 compounds. Principal component analysis (PCA) and cluster analysis (CA) showed a significant quantitative variability in the chemical composition of the studied samples as well as a correlation between the oil profiles and the collection time. Two main groups were observed, with predominance of phenylpropanoids or sesquiterpenes. The predominant chemical compounds were phenylpropanoids, having as main representative (Z)-asarone and (E)-asarone.

La composición del aceite esencial de hojas de Piper marginatum (Piperaceae) muestra una variación circadiana y un mayor rendimiento durante la mayor incidencia solar. Las muestras de aceites esenciales se investigaron por GC-FID y GC-MS, lo que permitió la identificación de 29 compuestos. El análisis de componentes principales y el análisis de conglomerados mostraron una variación cuantitativa significativa en la composición química de las muestras estudiadas, así como una correlación entre los perfiles del aceite esencial y el tiempo de recolección. Se observaron dos grupos principales, con predominio de fenilpropanoides o sesquiterpenos. Los compuestos predominantes fueron los fenilpropanoides, (Z)-asarona y (E)-asarona.

Relationship between ambulatory blood pressure monitoring and cardiac function / 소아과

It is well known that hemodynamic load is one of the most important determinants of cardiac structure and function. Circadian variations in blood pressure (BP) are usually accompanied by consensual changes in peripheral resistance and/or cardiac output. In recent years, reduction in circadian variations in BP and, in particular, loss of nocturnal decline of BP were observed in hypertensive patients with left ventricular hypertrophy (LVH). The patients with only a slight or no loss of nocturnal decline of BP were considered "non-dippers". Regression of LVH was observed after prolonged antihypertensive therapy. Restoration of the circadian rhythm of BP was also observed. However, the classification of patients into "dippers" and "non-dippers" is arbitrary and poorly standardized and repeatable, and in the recent studies, most hypertensive patients with LVH were "dippers". Therefore, we should be particularly cautious about the conclusions drawn using this index. On the other hand, reduced activity of low-pressure cardiopulmonary baroreceptors and impaired day-to-night modulation of autonomic nervous system activity were observed in patients with only LVH. Therefore, alterations in cardiac structure may impair BP modulation. On the other hand, the reverse can also be trueprimary alterations in BP modulation, through a persistently elevated afterload, can increase cardiac mass. Thus, the interrelationship between cardiac structure and BP modulation is complex. Hence, new and more specific methods of evaluating circadian changes in BP are needed to better clarify the abovementioned reciprocal influences.

Monitorización mmbulatoria de la presión arterial, métodos, indicaciones y utilidades / Ambulatoryblood pressure monitoring. methods, indications and utilities

Introducción. El exámen registra automáticamente la presión arterial en el paciente, en forma intermitente, durante sus actividades habituales, en vigilia y en sueño; es útil para: diagnóstico de hipertensión arterial y valoración del efecto de los antihipertensivos. Objetivos. Mostrar resultados del registro de 24 horas de la presión arterial, sus indicaciones y utilidades y establecer frecuencia y valores de referencia. Métodos. Estudiados 245 pacientes. El registro fue dividido en dos periodos: vigilia y sueño. Se consideraron estudios validos, aquellos mayores a 40. Variables analizadas: edad, sexo, motivos de estudio: sospecha de hipertensión, de hipotensión y evaluación de tratamiento antihipertensivo, caida nocturna, cargas presóricas, alzas tensionales. Criterios de anormalidad: cifras de presión anormales, ausencia de caida nocturna, cargas presóricas mayores de 50%, alzas tensionales mayores a 3, hipotensión arterial. Resultados. Edad media, 52 años. Mujeres 63%. Sospecha de hipertensión 125, de hipotensión 9 y evaluación de tratamiento 111. En 14% no hubo caída nocturna. Cargas presóricas anormales en 27%. Alzas tensionales en 64%. Hipertensión de bata blanca en 33%. Presiones medias anormales en 23%. Tratamiento insuficiente en 69%. Resultados anormales en 70%, por presiones aumentadas en 36% , en 55% por alzas tensionales, en 6%,por hipotensión y en 2% por ausencia de caída nocturna. Conclusiones. Se muestra la experiencia inicial del registro ambulatorio de la presión arterial. Se menciona la utilidad del examen, para definir la variación circadiana y las presiones medias de 24 horas, sistólicas y diastólicas, en vigilia y en sueño.

Introduction. The test automatically recorded blood pressure in the patient, intermittently, during their usual activities in wakefulness and sleep and is useful for diagnosing hypertension arterial and assessing the effect of the antihypertensive drugs. Objetives. Show, results of 24 hour record of blood pressure, indications, Utilities and to establish frecuency an reference values. For study: suspicion of hypertension, hypotension and evaluation of antihypertensive treatment: sleeping blood pressure declines, blood pressure load, pressures peaks. Criteria of abnormality: Abnormal pressure levels, absence of sleeping blood pressure declines, pressure loads greater than 50%, pressure peaks greater than 3, low blood pressure. Results. Average age: 52. Women 63%. Suspected hipertensión 125, hypotension 9 and evaluation treatment 111. In 14% there was no sleeping blood pressure decline. Blood pressure loads abnormal 27%. Pressure peaks 64%. White coat hypertension 33%. Mean pressures abnormal 23%. Insufficient treatment 69%. Abnormal results 70%, increased presures in 36%, in 55% pressure peaks, hypotension in 6% and 2% for lack sleeping blood pressure declines. Conclusions. Shows the initial experience of the ambulatory recording arterial blood pressure. The usefulness of the test is mentioned, to define the circadian variation and the average pressures of 24 hours, systolic an diastolic, in waking and sleep.

Impact of Circadian Variations on Efficacy of Thrombolytic Therapy for Acute Myocardial Infarction / 中国循环杂志

Objective:To study the impact of circadian variations on the efficacy of urokinase (UK) therapy in patients with acute myo- cardial infarction (AMI). Methods:Ninety-five AMI patients presenting with chest pain≤3 hours were given UK theerapy.They were divided into two groups according to their symptom onset time:late morning group (6:01—12:00,n=42) and other time group (12:01—6:00 next day,n=53).We obtained elbow venous blood samples at 3 time points:before UK therapy,30 and 60 minutes after UK ini- tiation respectively.Serum levels of AT-Ⅲ,PAI-1 Ag,PAI-1 activity,D-D,?_2-APL Ag were examined.The repatency of culprit vessels was also determined 120 minutes after UK administration. Results:①UK therapy in the late morning group(23 out of 42 patients) had lower repatency rate compared with the other time group(40 out of 53 patients) (P＜0.05).②The late morning group had a higher serum levels of PAI-1 Ag before UK thera- py (39.822?4.737 versus 37.406?4.696,P＜0.05).③The serum level of PAI-1 antigen at aforementioned three time points was 36.054?4.456,35.242?4.143 and 35.355?4.135 in reperfused patients compared with 42.7822?3.277,42.398? 4.565 and 42.395?5.223 in nonnperfused patients.The activity of PAI-1 was 15.234?2.671,13.256?4.532 and 11.830? 3.905 in reperfused patients versus 17.0743?3.665,16.447?4.469 and 16.928?4.248 in nonreperfused patients at three time points.Both of PAI-1 antigen and its activity was consistently lower in reperfused AMI patients as compared with the nonper- fused patients before and 30,120 minutes after UK therapy(P＜0.05).There was no significant difference in the serum levels of ?_2-APL Ag,D-D,and AT-Ⅲ activity between the two populations (P＞0.05). Conclusion:Our data showed circadian variations have an impact on the efficacy of UK therapy in patients with AMI,which suggests that there may exist a phenomenon of “morning resistance to thrombolysis therapy” due to increased level of PAI-1 Ag and activity.

Circadian Rhythm of Peak Expiratory Flow Rate in Asymptomatic Childhood Asthma / 소아알레르기및호흡기학회지

PURPOSE: Asthmatic patients show marked circadian variation in disease severity, with bronchospasm far worse between midnight and 8 a.m. than at other times of the day. And many studies have demonstrated that symptoms are much relieved in the day-time while they worsen at night. Our study was conducted to examine the circadian variation of peak expiratory flow rate (PEFR) in asymptomatic asthmatic children after proper treatment by mini-Wright peak flow meter. METHODS: Thirty four asthmatic patients who have had no respiratory symptoms for the past one month were enrolled to our study. Control group included 25 patients who were admitted to Wonju Christian Hospital for inguinal hernia, aseptic meningitis, etc., but without respiratory symptoms. RESULTS: The mean age was 6.3 years, ranging from 4 to 11 years, in the stable asthmatic group. In control group, the mean age was 8.7 years ranging from 4 to 14 years. PEFR was checked at every 2 hours from 8 a.m. to 10 p.m. for 4 days. There were no significant differences in PEFR checked at all times between the asthma group and the control group except for the PEFR checked at 8 a.m. in moderate persistent asthma group. PEFR reached the nadir at 8 a.m. in both asthma and control groups. It rose to the highest level in the afternoon, then, it slightly fell in the evening and at night. There were significant differences between the PEFR checked at 8 a.m. and the PEFR checked at any other period of the day in each group (P< 0.05). The circadian variation in moderate persistent asthma group is much greater than that of other groups. CONCLUSION: Our study indicates that the moderate persistent asthma group with no current symptoms of asthma has an increased circadian variability. It is recommended, therefore, that special attention be paid to preventive treatment for the moderate persistent asthma group.

The Circadian Variation of the Onset of Myocardial Infarction / 日本農村医学会雑誌

We have studied the circadian variation of the onset of myocardial infarction (MI). The subject were taken from the cases with MI, the onset of which was registered as the Saku Public Health Center, from April 1989 to March 1997, in accordance with the clinical criteria of the WHOMONICA Project. The number of subjects were 309 cases in which the onset time could be associated with circadian disturbance. We classified them into three groups, the <I>midnight and dawn</I> (00: 00-07: 59 hours), the <I>daytime</I> (08: 00-17: 59 hours) and the <I>nighttime</I> (18: 00-23: 59 hours), and the factors which had influenced the onset time were studied. The cases with sudden deaths (deaths out of hospitals and in the emergency room or deaths from post-resuscitation hypoxic encephalopathy) were also included, if autopsy found coronary occlusion or narrowing, and tissue signs suggestive of fresh MI. The t test was used to check the significant differences.<BR>From the circadian variation of 309 cases of MI, circadian rhythm was observed in a dual-peak pattern - morning and evening (morning < evening). As the sharpest peak had appeared in males at a relative young age (69 or under), it was suggested that there existed relations between the onset time of MI and the engagement in work. However, it was considered necessary to further study the impacts of farming work on the onset of ML In a study of deaths in acute phase, no difference was observed in mortality by onset time, but many deaths from cardiogenic shock were witnessed among cases at night. There is the need for the circulatory management of those cases.

Circadian and Seasonal Variations in the Frequency of Onset of Acute Myocardial Infarction / 대한내과학회지

BACKGROUND: The onset of acute myocardial infarctin varies in a circadian and seasonal pattern, with a morning and winter peak. The purpose of this study was to determine whether the frequency of onset of acute myocardial infarction varies circadianly and seasonally in Korean patients. METHODS: We analyzed the time of onset of chest pain in 409 patients with myocardial infarction admitted to our hospital over the past 30 years according to a 24-hour and 12 month period. RESULTS: There notel marked circadian variations in the frequency of onset, with the primary peak from 6 a.m. to noon and the secondary peak from 6 p.m. to midnight (p<0.001). Circadian bimodal rhythmicity of myocardial infarction was demonstrated in this study. By the sex analysis, circadian variations of frequency of acute myocardial infarction were also similar to those of total patients. Interestingly, circadian variations were slightly different in the patients below 50 years of age, showing the highest frequency of onset in the time between 6 pm and midnight (p<0.062). And we also analyzed the frequency of onset of AMI by seasons. The notel a peak incidence in autumn, and followed by winter and spring. But we didn't find any statistical significance (p<0.059). However, comparing summer to other seasons, summer showed the lowest incidence of myocardial infarction with statistical significance (p<0.001). CONCLUSIONS: Ever though the study population in small, this study showed that the frequency of acute myocardial infarction had a circadian and a seasonal variation in Korean patients.

Effect of Sodium SulfateSodim Bicarbonate Bathing on Body Surface Temperature, Cutaneous Blood Flow and Circadian Variation in Blood Pressure / 日本温泉気候物理医学会雑誌

Sodium sulfate·sodium bicarbonate bathing is known to exert stimulatory effect upon an increase in cutaneous circulation after bathing due to its skin-coating and vasodilating action. In the study, authors investigate the change in cutaneous blood flow after artificial sodium sulfate·sodium bicarbonate bathing in the healthy man, and clarify its antihypertensive effect upon diurnal variations in blood pressure in patients with essential hypertension.<br>The results obtained are as follows.<br>1) Changes in cutaneous blood flow after bathing were studied in five healthy volunteers. Sodium sulfate·sodium bicarbonate bathing (40°C, 10 min) resulted in a significant increase in cutaneous blood flow 30 min after the beginning of bathing, comparing with plain water bathing. Thermographic study on body surface revealed the findings corresponding to the change in cutaneous blood flow.<br>2) Diurnal changes in blood pressure after bathing were studied in ten patients with essential hypertension, who had been treated with hypotensive drugs. No significant difference of hyperbaric indici in systolic, diastolic and mean blood pressure (MBP) was observed between sodium sulfate and plain water as a whole. However, six cases out of ten showed the significant decrease in MBP after sodim sulfate·sodium bicarbonate bathing, comparing with the plain water bathing.<br>From these findings it is expected that artificial sodium sulfate·sodium bicarbonate bathing is available as a supportive therapy for refractory hypertension to medicaments.

Variação circadiana dos leucócitos, fibrinogênio e plaquetas no sangue de cães submetidos a processo inflamatório, tratados com escina / Leucocytes, fibrinogen and platelets circadian variation in dogs exposed to an inflamatory process and treated with aescin

Foram utilizados 20 cães machos, sem raça definida, divididos em dois grupos de 10 para análise da variação circadiana dos leucócitos, fibrinogênio e plaquetas. Todos os cães foram submetidos a um processo inflamatório subcutâneo induzido pela administração de Terebentina. Após 24 horas os animais do grupo 1 foram tratados com duas doses de 1,3mg/kg de escina com intervalos de 12 horas e os cães do grupo II mantidos como testemunha. Coletas de sangue foram feitas em todos os animais às 0, 4, 8, 12, 16, 20 e 24 horas do dia para determinação dos leucócitos, fibrinogênio e plaquetas. A escina determinou nos animais do grupo I monocitose às 0, 8, 12, 16 e 24 horas, linfopenia às 12, 16 e 24 horas, leucocitose às 0, 20 e 24 horas, aumento da taxa de fibrinogênio às 16 e 24 horas e uma diminuição das plaquetas durante todo o dia. Conclui-se que a escina determina variações circadiana instáveis do número de leucócitos, plaquetas e quantidade de fibrinogênio em cães com processo inflamatório.

To analyse the circadian variations of the leucocyte, fibrinogen and platelet 20 mongrel male dogs were used divided into two groups of ten animals. The first group was exposed to an inflamatory process induced by the administration of turpentine and after 24 hours the animals were treated with Aesein 1.3mg/kg from 12 to 12 hours. The second group was only exposed to the inflamatory process. Blood samples were performed in all the animals at 0,4am, 8am, 12am, 4pm, 8pm and 12pm hours of the day to examine the parameters. Aescin has determined monocytose at 0,8am, 12am, 4pm and 12pm; linfopenia at 4pm and 12pm; leucocitosis at 0,8pm and 12 pm, as well as an increase in the amount of fibrinogen at 4pm and 12pm; and a decrease in the platelets during all day. Aescin determines unstable circadian variations in the number of leucocyte, platelet and in the amount of fibrinogen in dogs with inflamatory process.

Circadian Variation of Ventricular Premature Complex in Hypertension and Ischemic Heart Disease Patients

BACKGROUND: Circadian rhythms have been described for acute myocardial infarction, sudden cardiac death, cerebrovascular disease, ischemic heart disease, and ventricular arrhythmia. Most of studies reported that the frequency of ventricular permature contractions(VPC's) shows a peak in day time. We tried to see that the circadian rhythm of VPC's in hypertension and ischemic heart disease(IHD) patients. And we will also studied the relationship between heart rate and frequencey of VPC's. METHOD: Twenty four hour holter monitoring was performed in hypertensive patients (N=23), ischemic heart disease patients(N=25), and normal control group(N=30). We tested the circadian pattern of VPC's and heart rates and the relationships of the frequency of VPC's and heart rates. RESULT: In hypertension group, a peak incidence of heart rate is between 5 and 8 P.M., in ischemic heart disease group, between 3 and 6 P.M.. In control group, the heart rate shows a peak beteen 1 and 3 P.M.. The frequency of VPC's in hypertension group shows the first peak between 4 and 10 P.M., and the second peak beteen 7 and 10 A.M.. In ischemic heart disease group, they show a peak between 2 and 8 P.M..In control group, there was no circadian variation for the frequency of VPC;s. Both in hypertension and IHD patients group, there was significant correlation between the frequency of VPC's and the heart rates. CONCLUSION: It seemed that VPC' were more frequently occurred in relation to the increase of heart rate in the afternoon, in hypertensive and ischemic heart disease patients.

Circadian variation in acute myocardial infarction

BACKGROUND: TAn increased occurrence of morning time acute myocardial infarction(AMI) based on subjective self-reports and objective confirmation has been reported in the USA and Europe. We tried to see if the same circadian pattern is found among Korea patients in the regard. We have also studied how various modifying factors such as age, gender, history of congestive heart failure, previous angina pectoris, hypertension and smoking may affect the circadian pattern. METHODS: The onset of chest pain was studied in 471 patients with AMI admitted to four teaching hospitals in Taegu. Korea. We categorized the patients according to the modifying factors described above. RESULTS: The patients with AMI indeed showed bimodal variation at the onset of myocardial infarction with the primary peak between 6 A.M. and 12 noon. The frequency of the onset of pain occurred during this 6 hour period was 1.8 times higher than the average of the remaining period(p<0.001). The secondary peak occurring in the evening was barely noticeable. On the other hand. the sub-group(n=96) with a history of congestive heart failure demonstrated its peak(30%) in the evening(6 pm~12 midnight) and the sub-group with a history of hypertension(n=177) demonstrated its peak(37%) in the afternoon(12noon-6P.M.). However. the rest of the sub-groups smokers, patients with previous angina and patients over the age of 70 revealed typical circadian rhythm with a pronounced primary morning peak. CONCLUSIONS: This study clearly showed that Korean patients with AMI revealed a remarkably similar circadian pattern, primary morning peak of onset of myocardial infarction and that the marked differences in diurnal patterns of myocardial infarction onset occur in sub-groups of patients with modifying factors, particularly previous congestive heart failure and hypertension.

Circadian variation of thermoregulatory responses during rest in water / 体力科学

To observe possible influences of the biological clock on thermoregulatory responses, heat balance was measured 6 healthy students wearing only trunks during 30 min of immersion in water at a temperature of 21°C in both the rising phase (11: 00-13: 00) and the falling phase (23: 00-1: 00) of body temperature.<BR>Heat production was higher in the rising phase than in the falling phase. Duration of shivering was longer in the rising phase than in the falling phase. Dry heat loss was nearly constant, 163 to 166 W/m<SUP>2</SUP> in both phases. Body heat storage was negative in both phases, but higher in the falling phase than in the rising phase.<BR>The mean body temperature, however, changed to a similar extent in the rising phase and in the falling phase when the circadian temperature variation was balanced.<BR>Analysis of these results implies that the increased shivering in the rising phase is brought about by changes in the sensitivity of the thermoregulatory response.

Circadian variation in cardiovascular events and strategies of therapy / 中国药理学通报

Many studies, both retrospective and prospective, have shown that there is a circadian variation in acute cardiovascular events with a peak during the morning and a trough during the night since the mid 1980s. In addition to the morning peak, a secondary less prominent peak has been observed in the late afternoon in many studies. This circadian variation may well be at least partly linked to the known physiological circadian rhythms. Because the duration of the therapeutic effect of many drugs taken at the conventional time will have reached subtherapeutic levels at the time of waking and commencing activity the following morning, timing of medication is discussed to improve the protection of the patients with cardiovascular disease in the morning waking hours.

CIRCADIAN VARIATIONS OF PITUITARY ?-ENDORPHIN-LIKE IMMUNOREACTIVITY AND ITS RELATIONSHIP TO THE PAIN THRESHOLD IN RATS / 解剖学报

Immunohistochemical method, immuno-electron microscopic technique and radioimmunoassay (RIA) were used for the demonstration of ?-endorphin-like immunoreactivity (?-EP-IR) and of the circadian variation of the ?-EP-IR level in rat pituitary. ?-ER-IR was located in all cells of the pituitary intermediate lobe. A few ?-ER-IR-positive cells were scattered in the anterior lobe, and no positive immunoreactivity was found in the posterior lobe. The controls were negative. Under electron microscope, ?-ER-IR-positive dense particles were mostly located in the secretion granules, and a few of them were scattered freely in the cytoplasm of the intermediate lobe cells. Both pituitary ?-EP-IR concentration and the basal pain threshold in rat showed circadian variations in the experiment done at 4-hr intervals over a 24-hr period (P