Seasonal and circadian fluctuations in blood biochemical indicators in mice in natural conditions and exposed to constant light]

The fluctuations of activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and those of the levels of protein, glucose, cholesterol, bilirubin, creatinine, blood urea nitrogen, K+, Cl-, Na+ in blood plasma of mice in natural conditions (NC) and exposed to constant light (CL) were studied in different seasons of the year (in January, April, July, October) on days 18, 24, 6 (at 12 o'clock). Most indices both in NC and CL animals had seasonal rhythm similar for each of them. This proves a primary effect of environmental geoclimatic factors of formation of circadian periodicals as compared to desynchronization in constant light revealed by Kosinor analysis in winter (acrophase from 14.16 till 16.32 o'clock) and autumn (acrophase from 23.03 til 4.40 o'clock). During the same seasons one can observe the maximum desynchronization influences of constant light, which leads to abrupt falling (to the 10-fold and more) of the fluctuations amplitude and in some cases to stabilization of circadian rhythm.     

Circadian variation of rectal temperature in newborn sheep

In adult animals, body temperature shows a 24 h rhythm that is endogenously generated. We examined the existence of 24 h rhythms of temperature in 10 newborn sheep. Four newborns, aged 5 to 28 days were kept with their mothers under nycthemeral conditions, and the remaining 6 lambs, aged 21 to 43 days, were kept with their mothers in constant light from day 3 after birth. Experiments were performed with both groups of lambs in the laboratory. Additional experiments were performed with the 6 lambs kept under constant light while they were in the pen with their mothers to rule out artifacts due to manipulation or artificial feeding. During the experiments done in the laboratory, the lambs were kept blindfolded in a canvas sling and were fed baby formula approximately every four hours (lambs kept under nycthemeral conditions) or every hour (constant light lambs). Lights were on in the room during the whole experiment. Temperature in the room was maintained at 18 +/- 0.1 degrees C (mean +/- SEM). In the experiments done in the pen, animals remained with the mother and room temperature was not controlled. In all experiments, rectal temperature was hourly measured for 24 h with a thermocouple inserted in the lamb's rectum and connected to a Philipp Schenk digital recorder. Lambs kept under nycthemeral conditions show a variation of mean rectal temperature (t degree) with a period of 24 h, that fits a cosine function (P less than 0.001): Rectal t degree (degree C) = 40.6 + 0.4 cos [15 (t-16.22)]. The mesor is 40.6, the amplitude 0.4, and the acrophase expressed in h is 16.22 (n = 4). Lambs kept under constant light show a variation of rectal temperature with a period of 24 h, independently of whether the measurements were done in the laboratory or in the pens. The acrophases varied widely in these animals, when the acrophase were synchronized so theta = 2400, mean rectal temperature showed a variation with a period of 24 h that fits the equation (P less than 0.001): Rectal t degree (degree C) = 39.5 + 0.18 cos [15 (t-0.23)]. The presence of a 24 h rhythm of rectal t degree in lambs kept under nycthemeral conditions, and its persistence in lambs kept under constant light suggests that the rhythm of rectal temperature observed in the newborn lamb is a true circadian rhythm.(ABSTRACT TRUNCATED AT 400 WORDS)     

Chronotoxicity of Sodium Valproate and Its Mechanisms in Mice: Dose-Concentration-Response Relationship

A significant circadian rhythm of acute toxicity was demonstrated in mice with intraperitoneal (i.p.) injection of sodium valproate (VPA). The role of pharmacokinetics on the rhythms of the toxicity and electroshock seizure (ES) threshold was investigated. ICR male mice, housed under a light-dark (12 :12) cycle, were injected intraperitoneally 1200 mg/kg for the acute toxicity study and 300 mg/kg for the anticonvulsant effect study. In the acute toxicity, the highest mortality was found when VPA was injected at 1700 and the lowest at 0900 or 0100. The time course of mean plasma and brain VPA concentrations after an injection of VPA was not different between mice injected at 1700 and mice injected at 0100. In the anticonvulsant effect, no significant circadian rhythm was demonstrated for both the ES threshold and the plasma VPA concentrations after i.p. Injection, although a significant rhythm has been reported for them after oral administration. The results suggest that the circadian rhythm in the mortality after an i.p. Injection of VPA may be due to the rhythm in the sensitivity of the central nervous system to the drug and that the mechanism underlying the rhythm of VPA acute toxicity is different from that of the anticonvulsant action of VPA. The route and the time of drug administration are essentially important to study the anticonvulsant effect and acute toxicity of VPA in mice.     

Entrainment of the circatidal rhythm of the estuarine amphipod Coroph1um volutator (pallas) to non-tidal cycles of inundation and exposure in the laboratory

The endogenous rhythm of swimming activity shown by the estuarine amphipod Corophium volutator (Pallas) has been studied in animals subjected to periodic inundation under controlled laboratory conditions. A rhythm of circatidal frequency which persisted under constant conditions was recorded in animals entrained to cycles of 8-, 12- and 24-h periods, whereas animals entrained to 6-h cycles appeared to follow the entraining regimen directly, although the free running rhythm was less distinct. Cycles of 4-h period failed to induce rhythmicity. The results support the hypothesis that the endogenous oscillator has a circatidal frequency.

The period for which the animals are submerged is important with regard to entrainment but the effective parameters of the imposed regimen are incompletely understood in this respect.     

Circadian mitotic rhythm in representatives of the soybean Glycine L

The circadian mitotic rhythms in representatives of soybean Glycine max (L.) Merr., G. soja Sieb. & Zucc., as well as in homozygote forms of tibia F6 hybrids were studied. We observed three "waves" of the mitotic activity in the cells of apical root meristem with the initial moment of the perfect rest at 24 o'clock; and the legible periods which decreased later on. Beginning from 1 o'clock to 6 o'clock the first maximum mitotic "wave" increased; the second one evolved up to 12 o'clock, the third less legible one arised at 18-21 o'clock. Each of soybean tested forms was distinguished by the peculiarity in periodical processes and the values of mitotic indexes     

Effect of ethanol and ethylene glycol on the circadian rhythm of adenylic nucleotide levels in muscles]

The 24-hour's changes in ATP content in the gastrocnemiuses of intact rast are not significant. Both the ADP and AMP content is subjected to 24-hour's variations. It reaches its maximum within the time period from 12 to 15 o'clock p.m. for ADP and at 18 o'clock p.m. for AMP. Intragastric administration of ethanol and ethylene glycol to rats in a dose of 1/3 LD50 once per 24-hour period at 9 a. m. during a 7-days-long period dramatically changes the 24-hour's rhythm of adenylic nucleotide content in the rat gastrocnemius. It has been found that ethanol increases the average 24-hour's content of ATP, but decreases that of ADP. It increases the range of their 24-hour period variations and changes the acrophase. Ethylene glycol decreases the average 24-hour content of the both ATP and ADP, but it increases that of AMP. It changes their acrophases and increases the ranges of 24-hour-period variations of ATP.     

Influence of Feeding Schedule on Chronopharmacological Aspects of Gentamicin in Mice

The effects of the time of day of drug administration on the subchronic toxicity and pharmacokinetics of gentamicin, as well as the role of feeding schedule on circadian rhythms, were investigated in mice. ICR male mice were housed in a light-dark (LD) cycle (12:12) with food and water ad libitum (ALF) or under a time-restricted feeding (TRF) schedule (feeding time: 8 h during the light phase) for 1 day or 14 days before drug administration. The animals were given a single subcutaneous dose of gentamicin 180 mg/kg for the kinetic studies and subcutaneous doses of gentamicin 180 mg/kg/day for 14 days or 220 mg/kg/day for 18 days for the subchronic toxicity studies. A significant dosing-time dependency was shown for mortality and body weight loss, with higher values at midlight and lower ones at the middark (p > 0.05). A significant circadian rhythm was also found for gentamicin kinetics in ALF mice, with the highest clearance at middark and the lowest one at midlight (p > 0.01). The kinetic rhythm of gentamicin coincided well with the toxicity rhythm of the drug. The TRF schedule had a marked influence on the rhythms of gentamicin kinetics and toxicity, showing lowest clearance and higher toxicity at middark. The rhythm of subchronic toxicity of gentamicin seems to be due, at least in part, to the rhythm in kinetics and is strongly influenced by the feeding schedule. Thus, the timing of dosing is an important factor in the kinetics and the subchronic toxicity of gentamicin administration in mice, and the manipulation of feeding schedule can modify the rhythm of the toxicity by changing the rhythm of gentamicin kinetics.     

Pharmacological effects of vinorelbine on body temperature and locomotor activity circadian rhythms in mice

The effects of vinorelbine (VRL) on the circadian rhythms in body temperature and locomotor activity were investigated in unrestrained B6D2F₁ mice implanted with radio-telemetry transmitters. A single intravenous VRL dose (24 or 12 mg/kg) was given at 7 h after light onset (HALO), a time of high VRL toxicity, and resulted in transient suppression of temperature and activity circadian rhythms in mice kept in light-dark (LD) 12h:12h. Such suppression was dose-dependent. It occurred within 1-5 d after VRL dosing. Recovery of both rhythms was partially complete within 5 d following the high dose and within 2 or 3 d after the low dose and was not influenced by suppression of photoperiodic synchronization by housing in continuous darkness. Moreover, VRL induced a dose-dependent relative decrease in amplitude and phase shift of the temperature circadian rhythm. The mesor and amplitude of the activity rhythm were markedly reduced following the VRL administration. The relevance of VRL dosing time was studied in mice housed in LD 12h:12h. Vinorelbine was injected weekly (20 mg/kg/injection) for 3 wk at 6 or 18 HALO. Vinorelbine treatment ablated the rest-activity and temperature rhythms 3-6 d after each dose, with fewer alterations after VRL dosing at 18 HALO compared to 6 HALO, especially for the body temperature rhythm. There was at least partial recovery 1 wk after dosing, suggesting the weekly schedule of drug treatment is acceptable for therapeutic purposes. Our findings demonstrate that VRL can transiently, yet profoundly, alter circadian clock function. Vinorelbine-induced circadian dysfunction may contribute to the toxicokinetics of this and possibly other anticancer drugs.     

Changes in the mitotic activity and destruction of rat thymus lymphocytes following hydrocortisone administration at different hours of the day]

The 24-hour rhythm of mitoses was identical in the thymus lymphocytes of 30-day rats in control and in experimental animals 4 hours after injection of hydrocortisone. In the control rats the number of degenerating lymphocytes failed to alter in the course of 24 hours. Four hours after the hydrocortisone injection of degenerated cells increased sharply; however, the rate of the lymphocyte destruction was more significant at night and early in the morning than during the day and the evening.     

蛇毒酶制剂出血毒试验方法比较

使用不同稀释度的蛇毒毒素,等体积注射于大鼠背部皮下、皮内和小鼠背部皮下,１８～２４小时剥皮观察比较动物皮下出血程度,经统计学处理,小鼠背部皮下注射对检查出血毒最敏感。选用小鼠背部皮下注射０．２ｕ蛇毒酶成品、半成品,１８～２４小时剥皮观察皮下瘀血或瘀斑,发现４２批成品中８８．１％未见皮下瘀血,２４批半成品７５％未见皮下瘀血。说明选用小鼠背部皮下注射０．２ｕ蛇毒酶来限量检查出血毒的方法是可取的。     

Circadian rhythm of locomotor activity in the Japanese honeybee, Apis cerana japonica

Abstract.  To reveal circadian characteristics and entrainment mechanisms in the Japanese honeybee Apis cerana japonica , the locomotor-activity rhythm of foragers is investigated under programmed light and temperature conditions. After entrainment to an LD 12 : 12 h photoperiodic regime, free-running rhythms are released in constant dark (DD) or light (LL) conditions with different free-running periods. Under the LD 12 : 12 h regime, activity offset occurs approximately 0.4 h after lights-off transition, assigned to circadian time (Ct) 12.4 h. The phase of activity onset, peak and offset, and activity duration depends on the photoperiodic regimes. The circadian rhythm can be entrained to a 24-h period by exposure to submultiple cycles of LD 6 : 6 h, as if the locomotive rhythm is entrained to LD 18 : 6 h. Phase shifts of delay and advance are observed when perturbing single light pulses are presented during free-running under DD conditions. Temperature compensation of the free-running period is demonstrated under DD and LL conditions. Steady-state entrainment of the locomotor rhythm is achieved with square-wave temperature cycles of 10 °C amplitude, but a 5 °C amplitude fails to entrain.     

不同时间服用比索洛尔对非杓型高血压血压的影响

目的:观察不同给药时间分别给予比索洛尔对非杓型原发性高血压患者的降压疗效和血压节律恢复的影响。方法:选取60例非杓型高血压患者,采取随机平行对照试验,观察比索洛尔(n=30)每日早晨(8:00)给药2.5-10mg、比索洛尔(n=30)每日夜间(20:00)给药2.5-10mg治疗8周后的降压疗效。结果:两种给药方法均能降低非杓型高血压患者的全天血压(P<0.05)。两种给药方法在白天的血压控制上无显著性差异(P>0.05),但在夜间血压的控制上夜间服药降压效果具有显著性差异(P<0.05)。夜间服药在血压节律恢复方面优于早晨服药(P<0.05),早晨服药组有10例恢复杓型,夜间服药组有19例恢复杓型。结论:比索洛尔的两种给药方式均能安全有效的降压,但对于非杓型高血压患者夜间服药优于早晨服药,更有利于血压节律的恢复。     

Entrainment of the circadian activity rhythm to the light-dark cycle can be altered by a short-acting benzodiazepine, triazolam

The circadian rhythm of locomotor activity in hamsters maintained in either constant darkness or constant light can be phase-shifted by a single injection of the short-acting benzodiazepine, triazolam. These results suggest that treatment with triazolam may also alter the entrainment pattern of circadian rhythms in animals that are synchronized to a light-dark (LD) cycle. To test this hypothesis, hamsters maintained on an LD 6:18 light cycle received daily injections of triazolam (or vehicle) for 10-12 days, and any subsequent effects on the phase relationship between the onset of activity and the LD cycle were determined. Daily injections of triazolam (but not vehicle) induced pronounced advances or delays in the phase relationship between the entrained activity rhythm and the LD cycle; the direction of the shift was dependent on the time of the injection. Taken together with data from previous studies, these results suggest that triazolam, and perhaps other short-acting benzodiazepines, can be used to manipulate the mammalian circadian clock under a variety of experimental conditions.     

Temporal structuring of delivery in the absence of a photoperiod: preparturient myometrial activity of the rhesus monkey is related to maternal body temperature and depends on the maternal circadian system.

No convincing evidence exists that the shift from myometrial contractures to contractions, which determines the synchronized 24-h rhythm in the dynamics of the primate uterus, may be attributed to an endogenous circadian rhythm. We therefore wished to ascertain whether a 24-h periodic shift would also occur in the myometrial activity of animals kept under constant conditions. We studied five pregnant rhesus monkeys, kept in continuous darkness from 56-77 days gestational age until delivery at 117-167 days gestational age. During the last week before delivery we determined the individual phase, level, and amplitude of circadian changes in maternal body temperature and 24-h myometrial activity patterns in the form of contractions. In all five monkeys, a rhythm with a period of 24-h characterized the temporal incidence of preparturient contraction activity. A consistent phase lag of 6-7 h from the temperature crest was observed in four out of the five animals. The circadian phase of all individual rhythms was idiosyncratic among animals. We conclude that endogenous rhythms in body temperature and preparturient myometrial activity are truly circadian. In addition, these rhythms are either interdependent or subject to the same maternal timekeeping mechanism, supporting the hypothesis that the exact time of the day at which birth occurs in the rhesus monkey depends on the maternal circadian system.     

Pineal synaptic ribbons in blinded rats

Summary To study the effects of bilateral ophthalmectomy on the circadian rhythm of the pineal gland, the number of the synaptic ribbons and ribbon fields in the pineal gland of female rats were determined by electron microscopy. In a preliminary experiment, the pineal gland was taken from rats at 15 days, and 1, 2, 3, 4, and 6 months after bilateral ophthalmectomy. It was found that the numbers of both synaptic ribbons and ribbon fields decreased markedly and reached a minimum at 1 month postoperatively, but recovered completely after 4 months. In the main experiment, the number of these intracellular elements was counted in both control and enucleated animals killed at 4 h intervals between 02:00 h and 22:00 h at either 1 month or 6 months after operation. All animals were kept under a lighting regimen of 12 h of illumination (06:00 to 18:00) and 12h of darkness (18:00 to 06:00). After 1 month, a remarkable decrease in the number of both the synaptic ribbons and ribbon fields was again noted but the circadian rhythm still remained. Complete quantitative and qualitative recovery in the circadian rhythm was obtained 6 months later.Supported by a grant-in-aid from the Japanese Ministry of Education, Science and Culture The authors wish to thank Mrs. Kazuko Moriwaki for her technical assistance     

Changes in phase-angle under light–dark cycles influenced by nonphotic stimulation

ABSTRACT

Most work looking at nonphotic effects on circadian rhythms is conducted when animals are held under freerunning conditions, usually constant darkness. However, for nonphotic effects to be functionally significant, they should be demonstrable under conditions in which most animals live, i.e., a 24-hr light–dark cycle (LD). Syrian hamsters held in LD 6:18 were administered nonphotic stimulation in the form of a 3-hr confinement to a novel wheel starting about 6 hr before the start of their normal nightly activity bout. This resulted in a 2.5-hr advance of their activity rhythm on the next day that gradually receded to about 1.5 hr over the next 10 days. When hamsters held in LD 6:18 were given five novel wheel confinements over 13 days their nightly activity onset advanced 3 hr and remained at that phase for at least 2 weeks. Home cage wheel deprivation experiments indicated that high levels of home cage activity are necessary to maintain the advanced phase. These results show that nonphotic stimulation can have large, long-lasting effects on daily rhythms in LD and suggest a possible mechanism whereby nocturnal rodents might achieve phase flexibility in response to seasonal changes.     

长白山阔叶红松林土壤氮化亚氮和甲烷的通量研究

采用静态箱／气相色谱分析方法对长白山阔叶红松林两个处理的N2O和CH4通量进行了研究．结果表明,凋落物对土壤N2O排放和CH4吸收的影响是显著的,影响程度分别是36．9％和23．4％．两个处理的N2O排放通量季节变化趋势相似：夏季(6～8月)的排放通量最高,春季(3～5月)次之,秋(9～11月)冬(12～1月)两季较低．其日变化趋势也相似：最大值都出现在18：00,最小值都出现在12：00和14：00．CH4吸收通量的季节变化趋势也很相似：夏秋两季的吸收通量明显高于春冬两季的吸收通量．其日变化趋势也相似：从14：00开始持续上升到18：00达到最大值,然后持续下降到早晨6：00达到通量的最小值．研究还发现,长白山阔叶红松林土壤的N2O排放和CH4吸收间存在着一种负线性相关关系．     

Chronopharmacokinetics and Chronotoxicity of Lithium in Mice Eating Normal and Low-Sodium Diets

The temporal aspects of the pharmacokinetics and toxicity of lithium were studied in mice eating normal and low-sodium diets. ICR male mice, housed under a lightrdark (LD; 12:12) cycle, were injected with variable doses of lithium chloride i.p. A circadian rhythm was found in lithium clearance after a single administration in mice eating the normal diet showed the maximum value in the early dark phase and the minimum in the early light phase. The repeated administration of lithium did not affect the rhythm of the pharmacokinetics of the drug under the LD cycle. Although the low-sodium diet significantly decreased the lithium clearance, it did not influence the rhythm of the clearance. Higher toxicity was demonstrated in mice injected with the drug at the time of day with lower lithium clearance in the single-dose study but not in the repeated-doses study, regardless of the diet conditions. The low-sodium diet increased the acute and chronic toxicity of lithium. The results indicate that there is a circadian rhythm of acute toxicity and clearance of lithium after a single dose or repeated administration of the drug in mice eating normal and low-sodium diets and that the low-sodium diet increases lithium toxicity by reducing the clearance of the drug without influencing the rhythm characteristics.     

Chronopharmacokinetics and Chronotoxicity of Lithium in Mice Eating Normal and Low-Sodium Diets

The temporal aspects of the pharmacokinetics and toxicity of lithium were studied in mice eating normal and low-sodium diets. ICR male mice, housed under a lightrdark (LD; 12:12) cycle, were injected with variable doses of lithium chloride i.p. A circadian rhythm was found in lithium clearance after a single administration in mice eating the normal diet showed the maximum value in the early dark phase and the minimum in the early light phase. The repeated administration of lithium did not affect the rhythm of the pharmacokinetics of the drug under the LD cycle. Although the low-sodium diet significantly decreased the lithium clearance, it did not influence the rhythm of the clearance. Higher toxicity was demonstrated in mice injected with the drug at the time of day with lower lithium clearance in the single-dose study but not in the repeated-doses study, regardless of the diet conditions. The low-sodium diet increased the acute and chronic toxicity of lithium. The results indicate that there is a circadian rhythm of acute toxicity and clearance of lithium after a single dose or repeated administration of the drug in mice eating normal and low-sodium diets and that the low-sodium diet increases lithium toxicity by reducing the clearance of the drug without influencing the rhythm characteristics.     

Localization of labelled cells in the islets, acini and periinsular zone of the pancreas of mice undergoing resection]

Thymidine-3H was injected 5 times during 24 hours to mice CBA X C57BL/6 with resected pancreas (about 40 per cent of the organ tissue). The number of labeled cells in the islets and the acini failed to change with the prolongation of the interval after the last injection of thymidine-3H (5 to 18 days). Localization of labeled cells in the pancreatic islets at later periods showed not much difference from the same localization two hours after the isotope injection. Examination of large andmedium-sized islets at the maximal distance from the wound revealed a similar number of labeled cells per square unit in the central, middle andperipheral region of the islets 2 hours and 18 days after the last injection of the isotope. It is concluded that under conditions of this experiment no islet cells are formed due to external sources.