Fluctuations and phase symmetry in coordinated rhythmic movements.

Investigated the assertion that pendular, clocking movements typify mammalian terrestrial locomotion, using a procedure in which people swing hand-held pendulums at the wrists, comfortably and rhythmically. Previous work by P. N. Kugler and the 2nd author (1986) suggests that the periodic timing and powering of rhythmic movements in the comfort state follow from different laws. One law guides the assembling of the reference frame for clocking. Another law guides the assembling of the muscular, escapement processes determining the cycle energy. Pendular, clocking behavior was examined in 4 adult males for in-phase and out-of-phase coordinations. A. M. Wing and A. B. Kristofferson's (see record 1974-08195-001) method for parsing periodic-timing variance into independent clock and motor sources was applied. Results show that mean periodicity was unaffected by phase. Clock fluctuations, however, were larger out of phase than in phase. Motor fluctuations were indifferent to phase but reflected the departures of individual wrist-pendulum systems from their preferred periods. It is suggested that an intended phase relation is realized as a constraint on clock states. These states are more stable under the in-phase constraint than under the out-of-phase constraint. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evidence that the TIM light response is relevant to light-induced phase shifts in Drosophila melanogaster

Light is a major environmental signal for the entrainment of circadian rhythms. In Drosophila melanogaster, recent experiments suggest that photic information is transduced to the clock through the timeless gene product, TIM. We provide genetic and spectral evidence supporting the relevance of TIM light responses to clock resetting. A missense mutant TIM, TIM-SL, exhibits greater sensitivity to light in both TIM protein disappearance and locomotor activity phase shifting assays. We show that the wavelength dependence of light-induced decreases in TIM levels and that of light-mediated phase shifting are virtually identical. Analysis of dose response of TIM disappearance in a variety of mutant genotypes suggests cell-autonomous light responses that are largely independent of the canonical visual transduction pathway.     

Nocturnal antral pH rises are related to duodenal phase III retroperistalsis

The mechanisms behind nocturnal rises of gastric pH are unknown. We have analyzed the relation between interdigestive duodenal peristalsis and nocturnal pH in the gastric antrum. Simultaneous recording of antroduodenal pressures and intragastric pH was performed in 11 healthy subjects (six men, five women) overnight for 8 hr, using a catheter with seven pressure recording points and an antral glass pH electrode. Three pressure recording sites were closely spaced in the descending duodenum. Altogether 46 phase III activities were recorded. A retroperistaltic sequence in the last part of phase III was observed in 31 phase III activities (67.4%), while 15 phase III activities lacked retroperistalsis. All subjects had retroperistalsis in at least one phase III at night with a median of 60% (52-100%) (interquartile range). The duration of the whole phase III was 5.1 (3.1-7.0) min, whereas the duration of the retroperistaltic period was 2.0 (1.5-3.2) min, corresponding to 45% (23-64%) of the duration of phase III. The peak of antral pH occurred 7.4 (6.0-13.0) min from the start of the phase III in the duodenum and and the rise in pH lasted for 8.0 (4.8-12.0) min. Measurement of pH for a period of 10 min before and after phase III, demonstrated an increase in median pH from 1.2 (1.1-1.9) to 3.2 (1.6-4.7), respectively (P < 0.001). Phase III activities without duodenal retroperistalsis were not followed by a significant antral pH change (median 1.7 vs 1.8 before and after phase III, respectively). Increases of pH unrelated to phase III were uncommon, only 1.0 (1.0-2.2) events per night were observed and lasted for a short period of time, 2.1 (0.5-3.2) min. The results indicate that the cyclic rise in antral pH at night is due to a physiological duodenogastric reflux, caused by duodenal retroperistalsis in phase III. This reflux may play a role in protection of the antral mucosa.     

Brain scanning with the Anger multiplane tomographic scanner as a second examination evaluation by the ROC method

The disposition kinetics and systemic availability of ketamine, a dissociative anaesthetic agent, was studied in normal domestic cats. A similar dose (25 mg/kg) of ketamine hydrochloride was administered by the i.v. and i.m. routes; drug concentrations in plasma were measured by a gas-liquid chromatographic procedure. A rapid distribution phase (t1/2 (alpha) = 3 min) was followed by a slower first-order elimination phase. The half-life of the drug (66.9 +/- 24.1 min) was independent of the route of parenteral administration. Absorption from i.m. site of administration was rapid, with peak plasma level at 10 min, and ca. 92 per cent of the dose was available systemically. Extent of plasma protein binding, measured in vitro at 5 and 20 mug/ml by equilibrium dialysis technique, was 53 per cent and independent of ketamine concentration. Simulated plasma and tissue level curves, which were generated by an analogue computer programmed with the individual rate constants of the two-compartment open model, showed that 10 and 15 per cent of the dose were present in the central and peripheral compartments, respectively, at 90 min after i.v. administration of the drug. Peak tissue level of 42 per cent of the dose was reached at 12 to 15 min. Parenteral administration of ketamine, at the dosage rate studied, quickly produced an immobilizing effect of variable duration (0.75 to 1.75 hr) in normal cats.     

A neuronal ryanodine receptor mediates light-induced phase delays of the circadian clock

Circadian clocks are complex biochemical systems that cycle with a period of approximately 24 hours. They integrate temporal information regarding phasing of the solar cycle, and adjust their phase so as to synchronize an organism's internal state to the local environmental day and night. Nocturnal light is the dominant regulator of this entrainment. In mammals, information about nocturnal light is transmitted by glutamate released from retinal projections to the circadian clock in the suprachiasmatic nucleus of the hypothalamus. Clock resetting requires the activation of ionotropic glutamate receptors, which mediate Ca2+ influx. The response induced by such activation depends on the clock's temporal state: during early night it delays the clock phase, whereas in late night the clock phase is advanced. To investigate this differential response, we sought signalling elements that contribute solely to phase delay. We analysed intracellular calcium-channel ryanodine receptors, which mediate coupled Ca2+ signalling. Depletion of intracellular Ca2+ stores during early night blocked the effects of glutamate. Activators of ryanodine receptors induced phase resetting only in early night; inhibitors selectively blocked delays induced by light and glutamate. These findings implicate the release of intracellular Ca2+ through ryanodine receptors in the light-induced phase delay of the circadian clock restricted to the early night.     

Generation and entrainment of circadian rhythms

1. The present brief review examines some of the new developments in the area of circadian rhythm research. 2. The discovery of the mouse clock and m-per genes and their similarity to other clock genes like per and tim has provided new insight into the control of rhythms in vertebrates. In mice, these genes are expressed in the site of the biological clock, the suprachiasmatic nucleus (SCN), and so will now become a focus of research into the generation of rhythmicity. 3. Because SCN cells expressing endogenous rhythms have a periodicity different from 24 h, there must be mechanisms in place to reset the rhythms on a daily basis. This is achieved in mammals by retinal light perception and neural transmission through several discrete pathways to the SCN. 4. The nature of the neurotransmitters involved in this transfer of environmental information to the timing system is controversial and may even very between similar species but, in the rat, there is compelling evidence that a serotonergic pathway is pre-eminent in mediating the effects of light. How the re-setting is achieved at the cellular level is not known.     

Increase of heart rate and determination of W170 as a measure of physical working capacity in children 5 to 14 years of age (author's transl)

1. Exercise testing with stepwise increasing workload was performed in 257 healthy children (134 boys, 123 girls) on a bicycle ergometer, which was independent of variations in pedal speed within a certain range. The procedure of exercise was adapted to the children as far as possible. 2. Nomograms and standard values for heart rate during exercise and for physical working capacity at a heart rate of 170/min (W170) were established. The increase of heart rate (from 1.0 to 2.5 Watt/kg) was well correlated to the age, length, body weight and body surface. If heart rate, respectively W170 are related to workload per kg body weight, results are dependent on sex, but not on age. 3. By means of the new standard values a rough evaluation of cardiorespiratory condition is possible, if the heart rate is measured at moderate exercise during steady state. A more precise assessment of the cardio-respiratory fitness is granted by the W170. By this method physical working capacity can be determined in children with heart diseases in a relative simple manner. 4. Normally in stepwise increasing loads the exercise takes 6 minutes per workload. If this time is reduced, an underestimation of the expected heart rate, respectively an overestimation of W170 is observed, which depends on the extent of the shortening of exercise.     

Effect of serum components on the physico-chemical properties of cationic lipid/oligonucleotide complexes and on their interactions with cells

Two behavioral rhythm phenotypes, oviposition and locomotor activity, have been compared in the four period genotypes (per+, pers, per0, and per1) of Drosophila. Period, signal-to-noise ratio, and phase were all analyzed and the genetic penetrance of the two characters was estimated. Significant rhythmicity of both oviposition and locomotor activity was evident in all four genotypes. The entrained and free-running periods of the activity rhythms of per+, pers, and per1 were within the range reported for these flies by previous workers, and rhythmic behavior was also shown by the per0 flies. The free-running period of the oviposition rhythm varied similarly between the four genotypes and showed significant correlation with that of the locomotor activity rhythm. It is suggested that both rhythm phenotypes are determined by the period gene, and estimates of the genetic penetrance of rhythmicity in oviposition and locomotor activity, based on period and signal-to-noise ratios (SNRs) of the different strains, are consistent with this hypothesis. The phase of maximum oviposition and locomotor activity showed greater variability between the genotypes and was not significantly correlated with period, suggesting that this rhythm characteristic is independent of mutations at the period locus.     

The timSL mutant affects a restricted portion of the Drosophila melanogaster circadian cycle

The circadian rhythm genes period (per) and timeless (tim) are central to contemporary studies on Drosophila circadian rhythms. Mutations in these genes give rise to arrhythmic or period-altered phenotypes, and per and tim gene expression is under clock control. per and tim proteins (PER and TIM) also undergo circadian changes in level and phosphorylation state. The authors previously described a period-altering tim mutation, timSL, with allele-specific effects in different per backgrounds. This mutation also affected the TIM phosphorylation profile during the mid-late night. The authors show here that the single amino acid alteration in TIM-SL is indeed responsible for the phenotype, as a timSL transgene recapitulates the original mutant phenotype and shortens the period of perL flies by 3 h. The authors also show that this mutation has comparable effects in a light-dark cycle, as timSL also accelerates the activity offset during the mid-late night of perL flies. Importantly, timSL advances predominantly the mid-late night region of the perL phase response curve, consistent with the notion that this portion of the cycle is governed by unique rate-limiting steps. The authors propose that TIM and PER phosphorylation are normally rate determining during the mid-late night region of the circadian cycle.     

Family coping during critical illness

The suprachiasmatic nuclei (SCN) of the anterior hypothalamus contain the master circadian pacemaker in mammals. On the occasion of the 25th anniversary of the discovery of the SCN as the circadian clock, Charles A. Czeisler and Steven M. Reppert organized a meeting to review milestones and recent developments in the study of the SCN. The discovery that the SCN contain tissue necessary for generation of circadian rhythmicity was established by lesion studies published in 1972. The second phase of study demonstrated unequivocally that the SCN contain an autonomous circadian pacemaker. The principal studies in this period showed the presence of metabolic and electrical activity rhythms in the SCN in vivo and progressed to studies showing that the SCN maintain rhythmicity in vitro, demonstrating that the transplanted SCN can restore circadian function following destruction of the host SCN and ultimately showing that single SCN "clock cells" exhibit independent rhythms in firing rate. The third phase of study, aimed at identifying the biochemical and molecular mechanisms responsible for rhythmicity within the SCN, has begun with the identification of circadian mutants (tau mutant hamsters and Clock mutant mice) and the isolation of the Clock gene. This report traces the important steps forward in our understanding of the suprachiasmatic circadian clock by recounting the information presented at the SCN Silver Anniversary Celebration.     

Circadian rhythm of insulin-induced hypoglycemia in man

Four healthy men were given an insulin tolerance test (0.1 IU/kg BW) six times in different days at the following clock hours: 0400 h, 0800h, 1200 h, 1600 h, 2000 h, and 2400 h, in random order. Four days separated two consecutive tests. The glucose disappearance rate (K value) was calculated for each test between 5 min and 25 min after iv injection of insulin. The statistical evaluation by Cosinor test showed a statistically significant circadian rhythm for the hypoglycemic action of exogenous insulin with a peak at 1030 h (95% condifence limits: 0830 to 1430 h).     

Plasma noradrenaline correlates to sympathetic muscle nerve activity in normotensive man

Recordings of multiunit sympathetic activity were made in muscle branches of the peroneal nerve in 22 healthy subjects at rest in recumbent position. Nerve activity was quantitated in terms of burst incidence (number of pulse synchronous sympathetic bursts per 100 heart beats or per min). In a separate session, 4-45 months later, blood was drawn from an antecubital vein for noradrenaline analysis. Both sympathetic activity and plasma concentrations of noradrenaline varied widely between subjects and both parameters increased with age. There was a significant positive correlation between a subject's level of sympathetic activity and his plasma concentration of noradrenaline. It is suggested that overflow of transmitter from sympathetic terminals in muscles contributes significantly to plasma levels of noradrenaline at rest.     

Plasma clearance of cholyl-lysyl-fluorescein: a pilot study in humans

BACKGROUND/AIMS: Cholyl-lysyl-fluorescein is a fluorescent analogue of the natural bile acid, cholyl glycine. In vivo and in vitro studies showed that this analogue has many biological characteristics similar to cholyl glycine. In this study we analysed cholyl-lysyl-fluorescein plasma clearance in six healthy volunteers as a potential quantitative liver function test. METHODS: The compound in water for injection was administered as an i.v. bolus in the dose of 0.02 mg/kg b.w. RESULTS: The plasma elimination curve showed rapid, intermediate and slow phases of clearance. Half-life (T1/2 time) for the first (t1/2 1st phase), second (t1/2 2nd phase) and third (t1/2 3rd phase) phases of elimination was 1.7+/-0.9 min, 6.7+/-1.6 min and 68+/-17 min, respectively. Ninety-minute plasma retention (% dose/l plasma) was 2.2%. Cholyl-lysyl-fluorescein volume of distribution and residual fluorescence after 60 min were similar to the data obtained by others for natural or radiolabelled bile acids. In five out of six healthy volunteers a 25-fold higher dose of cholyl-lysyl-fluorescein (0.5 mg/kg b.w.) was injected to estimate the safety margins of the compound. This dose was eliminated at a disappearance rate similar to that of the dose of 0.02 mg/kg b.w. and did not cause any adverse reactions. Serum liver tests measured before and after injection did not change significantly. CONCLUSIONS: This study showed that cholyl-lysyl-fluorescein clearance is similar to the clearance of endogenous natural bile acids and may potentially offer a new, dynamic test of liver function.     

On the inapplicability of gibbs phase rule to coherent solids

A relationship is derived between the number of degrees of freedom, independent chemical components, and number of phases for a specially constructed nonhydrostatically stressed coherent solid in complete thermodynamic equilibrium. The results obtained are based on the thermodynamics of crystalline solids, and indicate that the degrees of freedom are independent of the number of phases present. This model is used to demonstrate that coherent solids do not obey Gibbs phase rule. It is also shown that domains of what are the same phase in the absence of all stress effects may occupy different states of deformation and hence possess different equilibrium compositions when the system is constrained to behave coherently. The results derived here are in complete agreement with recent work on coherent phase diagrams.     

On the inapplicability of gibbs phase rule to coherent solids

A relationship is derived between the number of degrees of freedom, independent chemical components, and number of phases for a specially constructed nonhydrostatically stressed coherent solid in complete thermodynamic equilibrium. The results obtained are based on the thermodynamics of crystalline solids, and indicate that the degrees of freedom are independent of the number of phases present. This model is used to demonstrate that coherent solids do not obey Gibbs phase rule. It is also shown that domains of what are the same phase in the absence of all stress effects may occupy different states of deformation and hence possess different equilibrium compositions when the system is constrained to behave coherently. The results derived here are in complete agreement with recent work on coherent phase diagrams.     

Clock-face drawing, reading and setting tests in the screening of dementia in Chinese elderly adults

Comprehensive neuropsychological batteries focus on the subtle cognitive deficits in dementia, but a brief screening instrument is also of immense practical value. As the clock-drawing test encompasses a number of cognitive domains frequently disturbed by the dementing process, it is considered to be a suitable screening instrument for the disorder. We documented the usefulness of a new scoring method of the clock-drawing test for screening of dementia in the elderly Chinese in Hong Kong. Fifty-three demented individuals and 53 healthy elderly controls were assessed. At a cutoff score of 3/4, the sensitivity and specificity of the clock-drawing test in screening of dementia was 83% and 79%. With a composite test of clock reading and clock setting, the positive predictive value of the clock face test was 98%. This new scoring method of clock-drawing proved to be a valid measure for screening of dementia. It is applicable in non-English speaking populations and should be a useful adjunct for quick screening assessment of dementia.     

Cutaneous nociceptive facilitation of Ib heteronymous pathways to lower limb motoneurones in humans

The effects of tonic pain stimulation on heteronymous Ib pathways from the gastrocnemius medialis (GM) to the soleus (Sol) and to the quadriceps (Q) muscles were investigated in four healthy human subjects. Tonic pain stimulation was performed by subcutaneous injection of 0.5 mg levo-ascorbic acid or vitamin C (L-LAS) in a volume of 0.5 ml on the dorsal surface of the ipsilateral foot. The mean curve of L-AS-induced pain sensation showed a steep rising phase reaching maximum intensity at 2-3 min, followed by a slow decay phase lasting about 15-20 min. Between about 5 and 20 min after injection, there was evidence of pure pain stimulation due to chemical activation of free nerve endings. During this interval, significant potentiation of Ib inhibition from GM to both Sol and Q motoneurones was observed. The time-course of these Ib heteronymous changes paralleled that of subjective pain sensation. These findings demonstrate that nociceptive discharge modifies the gain of Ib heteronymous effects in humans. Since the man function of these Ib pathways is to coordinate activity of muscles operating at different joints, it is suggested that nociceptive input may change muscle synergies by selecting specific subpopulations of Ib interneurones, thus contributing to establish appropriate adaptive motor strategies.     

Transportin: nuclear transport receptor of a novel nuclear protein import pathway

The main purposes of this study were to investigate the best parameter for describing gallbladder emptying and whether gallbladder bile emptying should be induced with a bolus injection or continuous infusion of cholecystokinin-octapeptide (CCK-8). METHODS: Gallbladder emptying was measured by dynamic cholescintigraphy. Twelve healthy subjects and six patients with gallstones were examined twice with CCK-8 infusion cholescintigraphy, 0.3 ng CCK-8 kg per min for 60 min under identical circumstances. Another six healthy subjects randomly received bolus injection (0.04 microgram/kg) and infusion of CCK-8 (0.3 ng/kg per min for 60 min), respectively, during cholescintigraphy on two separate occasions. The choice of bolus dose was based on recommendations from the CCK-8 manufacturer. The infusion dose was chosen to produce plasma CCK concentrations similar to postprandial plasma CCK levels. RESULTS: A parameter of gallbladder emptying, mean ejection fraction (EF), was defined as 100% minus the area under the time-activity curve normalized to 100% and divided by the time interval from maximum to minimum counts per minute. This parameter proved superior to the well known parameters, EFmax. and EF30, in regard to reproducibility in healthy subjects. The slope of the regression line for the mean EF was 0.998 and the intercept value approximately 0% (p = 0.0001). The mean coefficient of variation was 4%. Apart from a higher mean coefficient of variation, similar reproducibility results were seen in the six patients. The measurements of EF30 in healthy subjects scattered more widely around the mean compared to the mean EF and EFmax, which indicates poorer ability to separate normal from abnormal gallbladder emptying. Intravenous bolus injection of CCK-8 resulted in incomplete gallbladder emptying with a mean EF value of 16% (s.d. 9%; range 7%-32%) compared to 49% (s.d. 7%; range 37%-57%) following CCK-8 infusion (p = 0.004). Abdominal discomfort was observed in all subjects after administration of the bolus injection, whereas no complaints were reported during infusion. CONCLUSION: Mean EF is the best parameter for describing gallbladder emptying. Moreover, slow infusion of a physiological dose of CCK-8 is preferable to induce gallbladder emptying because it results in more complete emptying and has no side effects.     

Aging, rhythms of physical performance, and adjustment to changes in the sleep-activity cycle

OBJECTIVES: Shiftwork causes disturbances of the normal sleep-wake cycle and circadian rhythm. There is concern that aging workers have more problems than younger counterparts when the human body clock is disrupted. This review considers issues relating to aging, the circadian body clock, and adjustment to altered sleep-wake schedules. METHODS: Reports on effects of aging on the human body clock were reviewed. Research concerned with adjustment to circadian phase shifts (as occurs in night work) was considered. RESULTS: With aging there is an increased tendency towards morningness which is linked with difficulties in sleeping. The peak time and amplitude of normal circadian rhythms are altered. Tolerance of shiftwork can be linked with social factors as well as adaptation of the body clock. CONCLUSIONS: People habituated to night work seem to have developed mechanisms which allow them to cope with disruptions to lifestyle and the endogenous body clock. Elderly people are more suited to phase advances, as occur in morning workshifts, than to phase delays such as nocturnal work.