Circadian variation in methotrexate toxicity in streptozotocin-induced diabetes mellitus rats

The effects of diabetes mellitus and circadian rhythm on pharmacokinetics or pharmacodynamics of drugs have been previously separately reviewed. In our previous study, a circadian rhythm has been described in the pharmacokinetics of MTX in streptozotocin-induced diabetes mellitus (SIDM) rats. The aim of the present study was to investigate the effects of circadian rhythm on the toxicity of MTX in SIDM rats. The hematologic parameters and serum folic acid levels were measured in control and SIDM groups before and after MTX administration to evaluate its toxicity. We observed that circadian rhythm in basal peripheral WBC counts disappeared after MTX administration in the first hour and were phase shifted on the fifth day. Circadian variations were not observed in the other blood cells. One hour after MTX administration, folic acid levels were high in both groups. However, a circadian rhythm was present only in the diabetic group. The alteration in the rhythm of WBC counts in diabetic rats may originate not only from the effect of MTX but also physiological alterations due to diabetes and/or the varying cell cycle entry rates in the hematopoetic stem cells.     

The individual development of circadian temperature rhythm in infants

Abstract

The aim of this study was to explore the individual development of the circadian rhythm of human body temperature. Dailyperiodicchanges of body temperature were examined longitudinally in four infants from 3 to 18 months of age. At the 3rd month of life, the day‐night rhythm of the body temperature was obscure but at the 6th month it became moreevident. From the 12th month on, the circadian temperature rhythm with phase similar to that of the adult was discerned. However, the amplitude in circadian rhythm was significantly larger in children between 6 and 18 months of age than in the adult. These findings suggest that the adult type of circadian rhythm of human body temperature is established during the first year of life with regard to phase but not to amplitude.     

The role of the epidermis in the generation of the circadian rhythm of carbon dioxide fixation in leaves of Bryophyllum fedtschenkoi

The role of the epidermis in the generation of the endogenous circadian rhythm of CO₂ exchange in leaves of Bryophyllum fedtschenkoi has been examined. At 25° C the rhythm of CO₂ output exhibited by whole leaves kept in continuous darkness and an initially CO₂-free air stream also occurs in isolated pieces of mesophyll. The sensitivity to light of the rhythms in whole leaves and in isolated mesophyll appears to be identical. At 15° C, however, no rhythm is observed in isolated mesophyll tissue, despite there being a conspicuous rhythm in intact leaves. The rhythm of net CO₂ assimilation in whole leaves kept in continuous light and a stream of normal air at either 25° C or at 15° C is abolished by removal of the epidermis, although at 15° C and under the higher of the two light levels used, there is an indication that rhythmicity may begin to reappear after the third day of the experiment. Thus, only under certain environmental conditions is the rhythm of CO₂ exchange in Bryophyllum leaves independent of the epidermis. The results indicate that the rhythm of carbon dioxide fixation in continuous darkness and CO₂-free air is generated primarily in the mesophyll cells, whereas the rhythm in continuous light and normal air is generated in the stomatal guard cells or in an interaction of these cells with the mesophyll cells.Abbreviation PEPCase phosphoenolpyruvate carboxylase     

生物钟信号调控的营养学

近日节律是生物界普遍存在的一种生理现象,而内源性生物钟是产生近日节律的物质基础,它能使生物体感知并适应环境中的光、温度和食物等周期信号,从而使生物体与外界环境保持周期同步。研究表明,葡萄糖、胆固醇、腺苷、咖啡因、维生素A和视黄酸等营养物质能通过各自不同的方式调控哺乳动物的生物钟,影响其近日节律的信号输出。本文概述了至今为止研究发现的各类与生物钟信号调控相关的营养物质及功能的相关研究进展。     

A rapid circadian rhythm of carbon-dioxide metabolism in Bryophyllum fedtschenkoi

Leaves of Bryophyllum fedtschenkoi Hamet et Perrier maintained in a stream of normal air and at 15° C exhibit a circadian rhythm of CO₂ uptake in continuous light but not in continuous darkness. The rhythm is unusual in that it persists for at least 10 d, and has a short period of approximately 18 h. The mechanism by which this rhythm is generated is discussed.Abbreviation PEPCase phosphoenolpyruvate carboxylase     

哺乳动物昼夜节律生物钟研究进展

昼夜节律生物钟是一种以近似24小时为周期的自主维持的振荡器,在分子水平上,该振荡器是一个由9个基因组成的转录翻译反馈环路系统。它能受外界环境影响重新设置节律,使自身机体活动处于最佳状态。除了进行自我调节外,生物钟基因还能通过调节代谢途径中特定基因表达而影响机体生理生化过程。在过去的几年里,借用遗传学和分子生物学工具,我们对哺乳动物昼夜节律生物钟的分子基础有了新的认识,本文综述了这一进展,并展望了它们在研究人的昼夜节律行为异常领域的前景。     

An investigation of circadian rhythm in Escherichia coli

Background: Persuasive evidence for circadian programs in non-photosynthetic bacteria other than cyanobacteria is still lacking, we aimed to investigate the circadian rhythm of specific growth rate in Escherichia coli ATCC 25922, one of the important prokaryotes. Methods: To grow E. coli under different light and dark conditions. When the growth entered into the stationary phase, we stopped the culture and obtained the viable counts by MTT assay every 3 h. The specific growth rates (SGRs) were calculated and analyzed with cosinor method for potential rhythms. Results: Single cosinor method revealed that the SGR of E. coli displayed rhythmic variations with a period of around 24 h both under light/dark cycles and under constant darkness. The best-fitting periods and best-fitting cosine curves were acquired. Conclusions: The SGR of E. coli (ATCC 25922) in a culture medium with limiting substrates in the stationary and death phases displayed rhythmic variations with a period of around 24 h under light/dark cycles and constant darkness conditions.     

Twofold effect of blue light on a circadian rhythm in Acetabularia

Abstract

The circadian chloroplast migration in Acetabularia mediterranea was monitored by continuously measuring the transmission of the cells near the apex. Under continuous red light the amplitude of the rhythm decreased rapidly within a few days. However, circadian changes of chloroplast density were still detectable even after 28 days of red light, indicating the persistence of the rhythm. When blue light was added after red light preirradiation of several days phase shifts were observed which were expressed as advances as well as delays. The period of the rhythm proved to be strongly dependent on the intensity of the continuous blue light which was given in addition to red light. Different red light intensities did not change the period. The occurrence of both effects indicates that the sensory transduction of blue light photoreception in Acetabularia works in two different ways: quanta counting processes and processes of light intensity measurement.     

A circadian rhythm of locomotor activity in newly emerged Ceratophyllus sciurorum

Abstract Circadian rhythm in newly emerged individuals of the Red Squirrel ( Scuirus vulgaris ) flea C.s. sciurorum was studied in a constant environment, using an insect activity monitor. Trials were run over 7 days using two start times (08.00 and 17.00 hours). The results show that, regardless of start time, the fleas display a 24 h activity rhythm. The presence of a rhythm under constant conditions gives a strong indication that C. s.sciurorum has a self-sustaining clock which is started by disturbance and is most likely to be linked to host activity patterns.     

Insulin restores expression of adenosine kinase in streptozotocin-induced diabetes mellitus rats

The effects of extracellular Mg²⁺ on both dynamic changes of [Ca²⁺]_i and apoptosis rate were analysed. The consequences of spatial and temporal dynamic changes of intracellular Ca²⁺ on apoptosis, in thapsigargin- and the calcium-ionophore 4BrA23187-treated MCF7 cells were first determined. Both 4BrA23187 and thapsigargin induced an instant increase of intracellular Ca²⁺ concentrations ([Ca²⁺]_i) which remained quite elevated (> 150 nM) and lasted for several hours. [Ca²⁺]_i increases were equivalent in the cytosol and the nucleus. The treatments that induced apoptosis in MCF7 cells were systematically associated with high and sustained [Ca²⁺]_i (150 nM) for several hours. The initial [Ca²⁺]_i increase was not determinant in the events triggering apoptosis. Thapsigargin-mediated apoptosis and [Ca²⁺]_i rise were abrogated when cells were pretreated with the calcium chelator BAPTA. The role of the extracellular Mg²⁺ concentration has been studied in thapsigargin treated cells. High (10 mM) extracellular Mg²⁺, caused an increase in basal [Mg²⁺]_i from 0.8 ± 0.3 to 1.6 ± 0.5 mM. As compared to 1.4 mM extracellular Mg²⁺, 1 M thapsigargin induces, in 10 mM Mg²⁺, a reduced percentage from 22 to 11% of fragmented nuclei, a lower sustained [Ca²⁺]_i and a lower Ca²⁺ influx through the plasma membrane. In conclusion, the cell death induced by thapsigargin was dependent on high and sustained [Ca²⁺]_i which was inhibited by high extracellular and intracellular Mg²⁺.     

An emerging role for Cullin-3 mediated ubiquitination in sleep and circadian rhythm

Although the neurophysiological correlates of sleep have been thoroughly described, genetic mechanisms that control sleep architecture, long surmised from ethological studies, family histories and clinical observations, have only been investigated during the past decade. Key contributions to the molecular understanding of sleep have come from studies in Drosophila, benefitting from a strong history of circadian rhythm research. For instance, a number of recent papers have highlighted the role of the E3 ubiquitin ligase Cullin-3 in the regulation of circadian rhythm and sleep. We propose that different Cullin-3 substrate adaptors may affect specific molecular pathways and diverse aspects of circadian rhythm and sleep. We have previously shown that mutations in BTBD9, a risk factor for Restless Legs Syndrome (RLS) encoding a Cullin-3 substrate adaptor, lead to reduced dopamine, increased locomotion and sleep fragmentation. Here, we propose that Cullin-3 acts together with BTBD9 to limit the accumulation of iron regulatory proteins in conditions of iron deficiency. Our model is consistent with clinical observations implicating iron homeostasis in the pathophysiology of RLS and predicts that lack of BTBD9 leads to misregulation of cellular iron storage, inactivating the critical biosynthetic enzyme Tyrosine Hydroxylase in dopaminergic neurons, with consequent phenotypic effects on sleep.     

The role of glycation in aging and diabetes mellitus

One of the hypotheses trying to explain the process of aging is the idea of glycation of proteins. This reaction, also called the Maillard or browning reaction, may explain age-related symptoms such as cataract, atherosclerosis and modification of collagen-containing tissues. Diabetics, which posses elevated blood sugar levels, show signs of accelerated aging exposing similar complications. The Maillard reaction, which occurs on a large scale in vivo, may play a key role in the initiation of these symptoms.     

The circadian conidiation rhythm inNeurospora crassa

The filamentous fungusNeurospora crassais one of the best organisms for analysing the molecular basis of the circadian rhythm observed in asexual spore formation, conidiation. Many clock mutants in which the circadian conidiation rhythm has different characteristics compared to those in the wild-type strain have been isolated since the early 1970s. With the cloning of one of these clock genes,frq, the molecular basis of the circadian clock inNeurosporahas become gradually clearer. Physiological and pharmacological studies have also contributed to our understanding of the physiological basis of the circadian clock inNeurospora. These studies strongly indicate that the circadian clock is based on or is closely related to a network of metabolic processes for cellular activities. Based on these studies, it may be possible to isolate new types of clock mutants which should contribute to a better understanding of the molecular basis of the circadian clock inNeurospora.     

Characteristics of the circadian activity rhythm in common marmosets (Callithrix j. jacchus)

The circadian activity rhythm of the common marmoset, Callithrix j. jacchus was investigated by long-term recording of the locomotor activity of 15 individuals (5 males, 10 females) from 1.5 to 8 years old, both under constant illumination and under LD 12:12. The mean period of the spontaneous circadian rhythm was 23.2 ± 0.3 h. Neither sex-specific differences nor a systematic influence of light intensity on the spontaneous period were observed, but the period was dependent on the duration of the trial and on the age of the individual. Due to the short spontaneous period, in LD 12:12 there was a distinct advance of the activity phase with respect to the light time and a masking of the true onset of activity by the inhibitory direct effect of low light intensity during the dark time. After an 8 h delay shift of the LD 12:12, re-entrainment of the circadian activity rhythm required an average of 6.8 ± 0.7 days; the average re-entrainment time after an 8 h phase advance of the LD cycle was 8.6 ± 1.3 day. This directional effect is ascribed to characteristics of the phase-response curve. No ultradian components were observed, either in the LD-entrained or the free-running circadian activity rhythm.     

Morphine withdrawal produces circadian rhythm alterations of clock genes in mesolimbic brain areas and peripheral blood mononuclear cells in rats

Previous studies have shown that clock genes are expressed in the suprachiasmatic nucleus (SCN) of the hypothalamus, other brain regions, and peripheral tissues. Various peripheral oscillators can run independently of the SCN. However, no published studies have reported changes in the expression of clock genes in the rat central nervous system and peripheral blood mononuclear cells (PBMCs) after withdrawal from chronic morphine treatment. Rats were administered with morphine twice daily at progressively increasing doses for 7 days; spontaneous withdrawal signs were recorded 14 h after the last morphine administration. Then, brain and blood samples were collected at each of eight time points (every 3 h: ZT 9; ZT 12; ZT 15; ZT 18; ZT 21; ZT 0; ZT 3; ZT 6) to examine expression of rPER1 and rPER2 and rCLOCK . Rats presented obvious morphine withdrawal signs, such as teeth chattering, shaking, exploring, ptosis, and weight loss. In morphine-treated rats, rPER1 and rPER2 expression in the SCN, basolateral amygdala, and nucleus accumbens shell showed robust circadian rhythms that were essentially identical to those in control rats. However, robust circadian rhythm in rPER1 expression in the ventral tegmental area was completely phase-reversed in morphine-treated rats. A blunting of circadian oscillations of rPER1 expression occurred in the central amygdala, hippocampus, nucleus accumbens core, and PBMCs and rPER2 expression occurred in the central amygdala, prefrontal cortex, nucleus accumbens core , and PBMCs in morphine-treated rats compared with controls. rCLOCK expression in morphine-treated rats showed no rhythmic change, identical to control rats. These findings indicate that withdrawal from chronic morphine treatment resulted in desynchronization from the SCN rhythm, with blunting of rPER1 and rPER2 expression in reward-related neurocircuits and PBMCs.     

Time estimation circadian rhythm in shift workers and diurnally active humans

The ability of shift workers to estimate timer intervals of short duration was examined. The study included 22 shift workers and 10 diurnally working control subjects. A circadian rhythm in time estimates was documented in control subjects, but it was found to bed disrupted in shift workers. Spectral analysis revealed frequency or circadian component in time estimates to be lower among the shift workers. Furthermore, an interesting relationship was marked between time estimates and oral temperature in 4 control subjects and 6 shift workers in that the time of the closest estimation coincided with the peak time of their body temperature.     

Tissue antioxidant status in streptozotocin-induced diabetes in rats

Interactions between manganese (Mn) deficiency and streptozotocin (STZ)-diabetes with respect to tissue antioxidant status were investigated in male, Sprague-Dawley rats. All rats were fed either a Mn-deficient (1 ppm) or a Mn-sufficient (45 ppm) diet for 8 wk. Diabetes was then induced by tail-vein injection of STZ (60 mg/kg body weight), after which the rats were kept for an additional 4 or 8 wk. The control groups comprised rats not injected with STZ and fed either Mn-deficient or Mn-sufficient diets for a total of 12 wk. The Mn-deficient diet decreased the activities of manganese superoxide dismutase (MnSOD) in kidney and heart, and of copperzinc superoxide dismutase (CuZnSOD) in kidney, in the non-diabetic animals. In the diabetic rats, the Mn-deficient diet induced more pronounced decreases in activities of these same enzymes, and also increased liver MnSOD activity. Plasma and hepatic vitamin E levels increased progressively with the duration of diabetes, independent of dietary Mn intake. Lipid peroxidation, as measured by H₂O₂-induced production of thiobarbituric acid reactive substances in erythrocytes, also increased, concomitant with decreased liver and kidney glutathione (GSH) levels. These findings demonstrate for the first time an interactive effective between Mn deficiency and STZ-diabetes, resulting in amplification of tissue antioxidant changes seen with either Mn deficiency or STZ-diabetes alone. This effect of Mn deprivation in experimental diabetes suggests a physiological role for Mn as an antioxidant nutrient.