Isolation and Identification of Phytocompounds from Maytenus dhofarensis and Their Biological Potentials.

Maytenus dhofarensis Sebsebe (Celestraceae) is a naturally growing shrub in Oman. It is not a reputed medicinal plant in Oman, but it is regionally endemic and causes shivering attacks on goats that graze on it. The chemical investigation of the hexane and chloroform extracts of the fruits and stems of M. dhofarensis afforded dihydro-ß-agarofuran-type sesquiterpene pyridine alkaloid (1), lupanyl myristoate (2) and lignanolactone (3). Compounds (1-3) are new isolates from M. dhofarensis. The structures of these compounds were assigned through comprehensive IR, NMR, and ESI-MS analyses, and the relative configurations of compounds 1 and 3 were deduced from density function theory (DFT) calculations and NMR experiments. Compound 1 was assayed against the kinase enzyme and showed no inhibition activity for p38 alpha and delta at a 10 µM test concentration. Compound 3 inhibited the 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH) by 69.5%, compared to 70.9% and 78.0% for gallic acid and butylated hydroxyanisole, respectively, which were used as positive controls.

Brain connectome modularity in weight-restored anorexia nervosa and body dysmorphic disorder.

BACKGROUND: Anorexia nervosa (AN) and body dysmorphic disorder (BDD) frequently co-occur, and have several overlapping phenomenological features. Little is known about their shared neurobiology. The aim of the study was to compare modular organization of brain structural connectivity. METHOD: We acquired diffusion-weighted magnetic resonance imaging data on unmedicated individuals with BDD (n = 29), weight-restored AN (n = 24) and healthy controls (HC) (n = 31). We constructed connectivity matrices using whole-brain white matter tractography, and compared modular structures across groups. RESULTS: AN showed abnormal modularity involving frontal, basal ganglia and posterior cingulate nodes. There was a trend in BDD for similar abnormalities, but no significant differences compared with AN. In AN, poor insight correlated with longer path length in right caudal anterior cingulate and right posterior cingulate. CONCLUSIONS: Abnormal network organization patterns in AN, partially shared with BDD, may have implications for understanding integration between reward and habit/ritual formation, as well as conflict monitoring/error detection.

Yoga for reducing perceived stress and back pain at work.

BACKGROUND: Stress and back pain are two key factors leading to sickness absence at work. Recent research indicates that yoga can be effective for reducing perceived stress, alleviating back pain, and improving psychological well-being. AIMS: To determine the effectiveness of a yoga-based intervention for reducing perceived stress and back pain at work. METHODS: Participants were recruited from a British local government authority and randomized into a yoga group who received one 50 min Dru Yoga session each week for 8 weeks and a 20 min DVD for home practice and a control group who received no intervention. Baseline and end-programme measurements of self-reported stress, back pain and psychological well-being were assessed with the Perceived Stress Scale, Roland Morris Disability Questionnaire and the Positive and Negative Affect Scale. RESULTS: There were 37 participants in each group. Analysis of variance and multiple linear regression showed that in comparison to the control group, the yoga group reported significant reductions in perceived stress and back pain, and a substantial improvement in psychological well-being. When compared with the control group at the end of the programme, the yoga group scores were significantly lower for perceived stress, back pain, sadness and hostility, and substantially higher for feeling self-assured, attentive and serene. CONCLUSIONS: The results indicate that a workplace yoga intervention can reduce perceived stress and back pain and improve psychological well-being. Larger randomized controlled trials are needed to determine the broader efficacy of yoga for improving workplace productivity and reducing sickness absence.

The role of extracellular calcium in generating and in phase-shifting the Bulla ocular circadian rhythm.

Since extracellular calcium is known to be involved in the entrainment of the circadian pacemaker in the retina of Bulla gouldiana, we have assessed the requirement for extracellular calcium in the generation of the circadian rhythm. To enable us to assay the state of the pacemaker during low-calcium treatment, which often obscures rhythmicity, long-duration pulses of low-calcium artificial seawater (no added calcium, 10 mM EGTA, calculated calcium concentration = 4.5 x 10(-10) M) were applied, and the phase of the subsequent rhythm was measured. Pulse treatments started at zeitgeber time (ZT) 6, and durations ranged from 4 to 72 hr. Although no phase shifts followed pulses ending before the next projected dawn (ZT 24), phase delays of up to 4 hr followed pulses ending after projected dawn, and delays of up to 8 hr followed pulses spanning two dawns. Some activity records exhibited unequivocal circadian rhythmicity during the long low-calcium treatments, with phases and periods similar to untreated control eye records; this finding suggests that the phase delays observed following long low-calcium pulses are attributable to the pulsatile nature of the treatment. These data suggest that extracellular calcium is not an essential requirement for the pacemaker in generating the circadian rhythm.

Absence of an increase in the duration of the circadian melatonin secretory episode in totally blind human subjects.

The daily rhythm of melatonin influences multiple physiological measures, including sleep tendency, circadian rhythms, and reproductive function in seasonally breeding mammals. The biological signal for photoperiodic changes in seasonally breeding mammals is a change in the duration of melatonin secretion, which in a natural environment reflects the different durations of daylight across the year, with longer nights leading to a longer duration of melatonin secretion. These seasonal changes in the duration of melatonin secretion do not simply reflect the known acute suppression of melatonin secretion by ocular light exposure, but also represent long-term changes in the endogenous nocturnal melatonin episode that persist in constant conditions. As the eyes of totally blind individuals do not transmit ocular light information, we hypothesized that the duration of the melatonin secretory episode in blind subjects would be longer than those in sighted individuals, who are exposed to light for all their waking hours in an urban environment. We assessed the melatonin secretory profile during constant posture, dim light conditions in 17 blind and 157 sighted adults, all of whom were healthy and using no prescription or nonprescription medications. The duration of melatonin secretion was not significantly different between blind and sighted individuals. Healthy blind individuals after years without ocular light exposure do not have a longer duration of melatonin secretion than healthy sighted individuals.

Circadian rhythm generation, expression and entrainment in a molluscan model system.

The Bulla ocular pacemaker provides remarkable opportunities for cellular study of circadian pacemaker systems. The demonstration of circadian oscillations within individual neurons maintained in culture provides us with a first occasion to study the biophysical and biochemical properties of bona fide neuronal circadian pacemakers. The ocular clock is robust and shares formal similarity with other circadian systems. The development of molecular techniques that can be applied to single neurons should allow research on the Bulla retina to continue to progress towards a molecular analysis of circadian timekeeping.

Calcium in phase control of the Bulla circadian pacemaker.

The circadian pacemaker in the retina of the eye of the marine snail Bulla gouldiana was examined using the whole eye in vitro preparation. Phase-response curves were generated to 6-h pulses of a low calcium EGTA solution and to a hyperpolarizing low potassium-low sodium solution. Both treatments yielded similar phase response curves with phages delays in the late subjective night/early subjective day and phase advances in the late subjective day. The similarity of the phase response curves to hyperpolarizing and low calcium solutions and the absence of additivity when both treatments are combined raises the possibility that both treatments affect the underlying pacemaker through a common mechanism. The persistence of phase shifts to low calcium pulses delivered in the presence of depolarizing light suggests that hyperpolarization is not required for low calcium phase shifting. However, it is possible that both treatments act by reducing a transmembrane calcium flux which is postulated to result from the periodic depolarization of the pacemaker cell membrane during the subjective day. Since a transmembrane calcium flux is known to be essential for both light and depolarization-induced phase shifting, we discuss the hypothesis that calcium fluxes play a pivotal role in the entrainment pathway of the circadian pacemaker.

Chloride conductance contributes to period determination of a neuronal circadian pacemaker.

The isolated eye of Bulla gouldiana, a marine mollusc, is a circadian pacemaker. Previous studies have shown that membrane potential changes of neurons at the base of the Bulla retina play a critical role in the expression of the circadian rhythm and that the free-running period can be modified by chronic alteration of the resting membrane potential. We now report that treatments which inhibit CI- conductance shorten the free-running period. Substitution of CI- with the anions SO4(2-), isethionate and glutamate significantly shorten the period of the ocular rhythm in vitro. Furthermore, addition of the CI- channel blocker 9-anthracene-carboxylic acid (9-AC) is also effective at shortening the period of the circadian rhythm. These data suggest that a CI- conductance participates in determining the free-running period of the circadian pacemaker cells. This is the first report of CI- conductance involvement in a circadian system and the effect is remarkable in that few treatments are known which reliably shorten the period of circadian clocks.

Circadian rhythms in mouse suprachiasmatic nucleus explants on multimicroelectrode plates.

The suprachiasmatic nucleus (SCN) of the mammalian hypothalamus functions as a circadian pacemaker. This study used multimicroelectrode plates to measure extracellular action potential activity simultaneously from multiple sites within the cultured mouse SCN. Neurons within the isolated mouse SCN expressed a circadian rhythm in spontaneous firing rate for weeks in culture.

Phase shifting of the circadian rhythm in the eye of Bulla by inhibition of chloride conductance.

Inhibition of Cl- conductance has been previously found to shorten the free-running period of the circadian eye rhythm of the marine snail Bulla gouldiana. In this study, we describe a phase-response curve for 6-h pulses of Cl(-)-free seawater, consisting only of phase advances with the largest in the late subjective night (1.5 h) and smaller phase shifts in the late subjective day. Intracellular recordings revealed that at both circadian times retinal pacemaker neurons hyperpolarized in response to the removal of extracellular chloride. Since previous studies indicate that membrane potential generates both phase advances and delays it seems unlikely that the action of chloride removal is mediated exclusively by the change in membrane potential.

The anesthetic agents pentobarbital and chloralose block phase shifts of a neuronal in vitro circadian pacemaker.

The anesthetic pentobarbital (6 mM) is capable of blocking light or high K(+)-induced phase shifts of the circadian pacemaker in the isolated eye of Bulla. Pentobarbital alone was effective in generating phase shifts consistent with phase response curves obtained to either extracellular low Ca2+ or hyperpolarizing pulses. Patch clamp recordings from the circadian pacemaker cells indicate that pentobarbital reduces the Ca(2+)-dependent K+ current. Together, these data suggest that pentobarbital acts on the pacemaker by reducing an inward Ca2+ current. Chloralose (3 mM) was effective in blocking light, but not high K(+)-induced phase shifts, and did not generate phase shifts when applied alone, suggesting that chloralose may act as a weak Ca2+ channel inhibitor.

Phase-shifts of the Bulla ocular circadian pacemaker in the presence of calmodulin antagonists.

Previous work has shown that light-induced phase shifts of the Bulla ocular circadian pacemaker require extracellular calcium, suggesting the possibility that the action of calcium as a second messenger via calmodulin is an element in the phase shifting mechanism. The calmodulin antagonists calmidazolium, trifluoperazine (TFP) and W7 were applied with phase shifting light pulses. Light phase shifts were not blocked by calmidazolium or TFP, suggesting that calmodulin does not mediate light-induced phase shifts. Period changes were observed with treatments of both TFP and W7, but not with calmidazolium and are probably not calmodulin-mediated.

The role of extracellular sodium in the mechanism of a neuronal in vitro circadian pacemaker.

In evaluation of whether extracellular ion concentrations or fluxes are involved in the mechanism of the circadian pacemaker in Bulla retinal neurons, previous studies have ruled out obligatory requirements for extracellular calcium and chloride. In this study, it is demonstrated that extracellular sodium and magnesium are also not requirements for and do not contribute to the circadian pacemaker mechanism. Since sodium-free solutions inhibit the output rhythm of compound action potential activity, pacemaker motion during long pulse treatments was evaluated retrospectively from the phase of the circadian rhythm subsequent to the treatment. Although some pulses of sodium-free solutions were capable of affecting pacemaker phase in a manner consistent with the stopping of pacemaker motion, these effects were reversed by elevating extracellular pH, suggesting that sodium-free solutions can only affect pacemaker motion indirectly through a previously demonstrated effect of low pH on pacemaker motion.

The effects of lithium on a neuronal in vitro circadian pacemaker.

Previous studies have suggested a causal connection between abnormalities of the circadian system and affective disorders. The effectiveness of lithium or rubidium as a treatment for affective disorders and the ability of lithium or rubidium to influence circadian pacemakers has stimulated research into the mechanism of lithium's action on circadian systems. In this study we used a neuronal in vitro circadian pacemaker preparation, the eye of the mollusc Bulla, to examine the cellular effects of lithium and rubidium. Continuous extracellular LiCl application lengthens the period of the circadian rhythm of the Bulla pacemaker in a concentration-dependent manner. Rubidium was found to be more effective than lithium in period lengthening. Stable phase delays were generated by 2-h pulses of 395 mM LiCl applied extracellularly from zeitgeber time (ZT) 5-7 (mid subjective day). Concomitant continuous application of 16 mM LiCl and light (a depolarizing agent) generated period lengthening substantially greater than the arithmetic sum of the modest period lengthening of each treatment alone. Furthermore, LiCl pulses, applied together with depolarizing extracellular KCl concentrations, yielded an increasing magnitude of phase delays with increasing KCl concentration. These data suggest that LiCl acts intracellularly on the circadian pacemaker cells by entering through a voltage-dependent channel, most likely a sodium channel.

Cellular mechanisms of entrainment.

This review summarizes our current understanding of the signal transduction cascade by which light causes phase shifts of the circadian oscillators found in the eye of Bulla and Aplysia. The isolated retina of these marine mollusks contains a circadian oscillator, a photoreceptor, and a light transduction pathway sufficient for entrainment. This preparation offers unique advantages for the cellular analysis of entrainment and the generation of circadian oscillations. There is evidence that similar cellular mechanisms may underlie mammalian and molluscan circadian oscillations. Thus, the models developed to explain entrainment in the molluscan retina are likely to have utility in exploring the mammalian suprachiasmatic nucleus.

Secondary vestibular and neck position signals in the vestibular nuclei of alert rhesus monkeys performing active head movements.

Rhesus monkeys were trained to track a visual target with head and eye movements in order to study central vestibular neurons under natural conditions. Single unit recordings of cells in the vestibular nuclei were obtained during active head rotations in the horizontal plane, and also during passive copies of these self-induced movements. Most cells exhibited secondary responses immediately following the primary vestibular responses to active or passive rapid head movements. They were of opposite polarity to the primary responses, and generally rate enhancements of secondary responses were of greater amplitude than rate suppressions. In addition, vestibular nuclei cells also encoded tonic neck position. The corresponding signal consisted of a variation in the basal discharge rate as a function of neck, and thus head, position. These observations prove for the first time that dynamic and static response characteristics recorded earlier from lesioned brains and under anaesthesia are, at least qualitatively, representative for the normally behaving vestibulomotor system in primates.

Efferent vestibular neurons. Electrophysiological evidence for axon collateralization to cristae ampullares in the pigeon (Columba livia).

Extracellular spikes were recorded under general anaesthesia from the cell bodies of efferent vestibular neurons located in the caudal pontine reticular nucleus of the pigeon. Discrete electrical stimuli, applied directly to the three ampullary nerve branches in one labyrinth and to the anterior ramus of the vestibular nerve trunk in the other labyrinth, evoked antidromic spikes which served to identify efferent neurons. Most cells could be antidromically driven only by stimuli to the vestibular nerve trunk (anterior ramus). The majority of cells exhibiting direct axonal connections to one individual semicircular canal crista ampullaris showed axon collateralization to one or two other cristae as well. Sixty percent of the efferent neurons responded with antidromic spikes to ipsilateral labyrinthine stimuli, 34% to contralateral stimuli, and 6% to both. Synaptic activation was observed in a few efferent and adjacent unidentified neurons. It is concluded that efferent neurons often send collaterals to various cristae in one labyrinth, and less frequently, to both labyrinths. Such projections are incompatible with the assumption that vestibular efferents provide a simple control mechanism which is related to the direction of head movement.

Design of a medical image management system: a practical cost-effective approach.

The impact of technology and economics is driving radiology departments into a digital era. There have been significant developments in the design of Medical Image Management System components. However, many important design criteria have been neglected, leading to an ineffective end product. This paper will discuss the more important design criteria. The design will be considered from the user's point of view. The implementation of a prototype Medical Image Management System (MIMS) serving a Medical Intensive Care Unit in our Institution will be presented. The structure and very preliminary results of a clinical evaluation will be discussed. Plans to expand the MIMS beyond the Department and the Hospital will also be briefly discussed. The role of the personal computer in the design of a MIMS will be reviewed.