Valproic acid has temporal variability in urinary clearance of metabolites

The reasons for the intra- and interindividual variability in the clearance of valproic acid (VPA) have not been completely characterized. The aim of this study was to examine day-night changes in the clearance of 3-oxo-valproate (3-oxo-VPA), 4-hydroxy-valproate (4-OH-VPA), and valproic acid glucuronides under steady state. Six diurnally active healthy male volunteers ingested 200 mg sodium valproate 12 hourly, at 0800 and 2000, for 28 days. On the last study day, two sequential 12-h urine samples were collected commencing at 2000 the evening before. Plasma samples were obtained at the end of each collection. Following alkaline hydrolysis, urine was analyzed for concentrations of VPA, 3-oxo-VPA, and 4-OH-VPA. A separate aliquot was assayed for creatinine (CR). The plasma concentrations of VPA, 3-oxo-VPA, 2-en-VPA, and CR were determined. The analysis of VPA and its metabolites was performed by CC-MS. There was an increase in plasma 3-oxo-VPA concentration at 0800, sampling as compared to 2000 sampling (p < .05). The urinary excretion of 3-oxo-VPA and VPA glucuronides were decreased between 2000 and 0800, compared to between 0800, and 2000, by 30% and 50% respectively (p < .05). These results indicate a nocturnal decrease in renal clearance of 3-oxo-VPA rather than a decrease in the beta -oxidation of VPA at night. These differences were not explained by differences between the sampling periods in CR excretion. These results indicate the importance of collecting samples of 24-h duration when studying metabolic profiles of VPA.

Maternal care and infant behaviour of the bridled nailtail wallaby (Onychogalea fraenata)

Bridled nailtail wallabies Onychogalea fraenata are endangered, medium-sized, nocturnal macropodids that persist at only one location in central Queensland, Australia. Characteristics of juvenile development, shelter use, anti-predator behaviour and maternal care were investigated in the wild using trapping, radio-tracking and spotlighting observations., Timing of developmental stages was identical to the pattern previously found in captivity, except for age at weaning which was much earlier in the wild. After young had left the pouch permanently at 17 weeks of age and weighing c. 800 g, they always spent the day concealed in dense cover, generally > 200 m from their mothers. Juveniles were also alone in > 50% of observations at night, and stayed closer to cover than did adult females. Young became independent of their mothers 7-8 weeks after permanent exit from the pouch and weighing c. 1800 g. Females with dependent juveniles changed their behaviour in ways likely to reduce predation on young. They reduced their home ranges, stayed closer to cover and became more wary than other females. Juveniles differed from adult females in their habitat use, anti-predator behaviour and shelter site preferences. Juveniles were more likely than adults to respond to threats by standing still or lying flat on the ground, whether or not they were in concealing cover. Juveniles used a wider range of smaller shelters than adults, and were less likely to use solid shelters such as hollow logs during the day. Because bridled nailtail wallabies have a 'hider' strategy of maternal care and the young rely on crypsis, successful breeding in the wild requires dense vegetation cover.

Morphine-3-glucuronide's neuro-excitatory effects are mediated via indirect activation of N-methyl-D-aspartic acid receptors: Mechanistic studies in embryonic cultured hippocampal neurones

Indirect evidence indicates that morphine-3-glucuronide (M3G) may contribute significantly to the neuro-excitatory side effects (myoclonus and allodynia) of large-dose systemic morphine. To gain insight into the mechanism underlying M3G' s excitatory behaviors, We used fluo-3 fluorescence digital imaging techniques to assess the acute effects of M3G (5-500 muM) on the cytosolic calcium concentration ([Ca2+](CYT)) in cultured embryonic hippocampal neurones. Acute (3 min) exposure of neurones to M3G evoked [Ca2+](CYT) transients that were typically either (a) transient oscillatory responses characterized by a rapid increase in [Ca2+](CYT) oscillation amplitude that was sustained for at least similar to30 s or (b) a sustained increase in [Ca2+](CYT) that slowly recovered to baseline. Naloxone-pretreatment decreased the proportion of M3G-responsive neurones by 10%-25%, implicating a predominantly non-opioidergic mechanism. Although the naloxone-insensitive M3G-induced increases in [Ca2+](CYT) were completely blocked by N-methyl-D-aspartic acid (NMDA) antagonists and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (alphaamino-3-hydroxy-5-methyl-4-isoxazolepropiordc acid/ kainate antagonist), CNQX did not block the large increase in [Ca2+](CYT) evoked by NMDA (as expected), confirming that N13G indirectly activates the NMDA receptor. Additionally, tetrodotoxin (Na+ channel blocker), baclofen (gamma-aminobutyric acid, agonist), MVIIC (P/Q-type calcium channel blocker), and nifedipine (L-type calcium channel blocker) all abolished M3G-induced increases in [Ca2+](CYT), suggesting that M3G may produce its neuro-excitatory effects by modulating neurotransmitter release. However, additional characterization is required.

Influence of Observer Presence on Pacific Damsel Bug Behavior: Who is Watching Whom?

When direct observations are used to study animal behavior the presence of the observer may alter the animal and hence influence the data being collected, yet few studies have quantified this effect. We conducted direct observation studies in the glasshouse to assess the relative influence of observer presence on the behavior of Pacific damsel bugs, Nabis kinbergii, a potentially important predator of crop pests. Comparisons of predator activity, predator distribution, prey (Helicoverpa armigera) mortality and prey distribution between frequently observed and minimally observed treatments, during diurnal and nocturnal observation sessions showed that the frequency of observer presence had no apparent impact on Pacific damsel bug behavior. This is the first documented test of the impact of observer presence in an insect system. To place our results in context, we reviewed 15 papers on the influence of observer presence in a range of animals. We established that just over half of these papers found evidence for an effect. Nevertheless, direct observations should be useful in further studies of Pacific damsel bug behavior, and researchers using direct observations to study the behavior of other animals should be cognizant of observer effects during design and interpretation of their study.

Fractal analysis of pyramidal cells in the visual cortex of the galago (Otolemur garnetti): Regional variation in dendritic branching patterns between visual areas

Previously it has been shown that the branching pattern of pyramidal cells varies markedly between different cortical areas in simian primates. These differences are thought to influence the functional complexity of the cells. In particular, there is a progressive increase in the fractal dimension of pyramidal cells with anterior progression through cortical areas in the occipitotemporal (OT) visual stream, including the primary visual area (V1), the second visual area (V2), the dorsolateral area (DL, corresponding to the fourth visual area) and inferotemporal cortex (IT). However, there are as yet no data on the fractal dimension of these neurons in prosimian primates. Here we focused on the nocturnal prosimian galago (Otolemur garnetti). The fractal dimension (D), and aspect ratio (a measure of branching symmetry), was determined for I I I layer III pyramidal cells in V1, V2, DL and IT. We found, as in simian primates, that the fractal dimension of neurons increased with anterior progression from V1 through V2, DL, and IT. Two important conclusions can be drawn from these results: (1) the trend for increasing branching complexity with anterior progression through OT areas was likely to be present in a common primate ancestor, and (2) specialization in neuron structure more likely facilitates object recognition than spectral processing.

Strength and endurance training lead to different post exercise glucose profiles in diabetic participants using a continuous subcutaneous glucose monitoring system

Background Although both strength training (ST) and endurance training (ET) seem to be beneficial in type 2 diabetes mellitus (T2D), little is known about post-exercise glucose profiles. The objective of the study was to report changes in blood glucose (BG) values after a 4-month ET and ST programme now that a device for continuous glucose monitoring has become available. Materials and methods Fifteen participants, comprising four men age 56.5 +/- 0.9 years and 11 women age 57.4 +/- 0.9 years with T2D, were monitored with the MiniMed (Northridge, CA, USA) continuous glucose monitoring system (CGMS) for 48 h before and after 4 months of ET or ST. The ST consisted of three sets at the beginning, increasing to six sets per week at the end of the training period, including all major muscle groups and ET performed with an intensity of maximal oxygen uptake of 60% and a volume beginning at 15 min and advancing to a maximum of 30 min three times a week. Results A total of 17 549 single BG measurements pretraining (619.7 +/- 39.8) and post-training (550.3 +/- 30.1) were recorded, correlating to an average of 585 +/- 25.3 potential measurements per participant at the beginning and at the end of the study. The change in BG-value between the beginning (132 mg dL(-1)) and the end (118 mg dL(-1)) for all participants was significant (P = 0.028). The improvement in BG-value for the ST programme was significant (P = 0.02) but for the ET no significant change was measured (P = 0.48). Glycaemic control improved in the ST group and the mean BG was reduced by 15.6% (Cl 3-25%). Conclusion In conclusion, the CGMS may be a useful tool in monitoring improvements in glycaemic control after different exercise programmes. Additionally, the CGMS may help to identify asymptomatic hypoglycaemia or hyperglycaemia after training programmes.

Continuous glucose monitoring in diabetic long distance runners

Marathon running is growing in popularity, and many diabetic patients are participating in various marathon races all over the world each year. This study aimed to investigate the prevalence and extent of glycemic excursions (hypo- and hyperglycemic) during a marathon run in patients with well-controlled diabetes mellitus using a continuous glucose monitoring system (CGMS). Five subjects with type 1 and one patient with type 2 diabetes mellitus were monitored with the Medtronic MiniMed CGMS during the 2002 Vienna City Marathon (n = 3) or the Fernwarme run (n = 3) long distance runs of 42.19/15.8 km. All six patients finished their course. The CGSM system was well tolerated in all patients over an average duration of 34 +/- 4.0 hours and it did not limit the patients' activities. The mean running time for the Vienna city marathon was 257 +/- 8 min (247 to 274 min) and for the Fernwarme run 134 +/- 118 min (113 to 150 min). A total of 1470 blood glucose measurements (mean 245 readings per subject) were performed. During and after the marathons frequent hypo and hyperglycemic episodes with and without clinical symptoms were measured. Our data confirm that the CGMS may help to identify asymptomatic hypoglycemia or hyperglycemia during and after a long distance run. The system may also be helpful to improve our understanding about the individual changes of glucose during and after a marathon and may protect hypoglycemic or hyperglycemic periods in future races.

Atmospheric boundary layer development over a narrow coastal plain during onshore flow

A study of the structure of the daytime atmospheric boundary layer during onshore flow over a narrow coastal plain is presented. The main emphasis of the study is on the nature and causes of heating and cooling observed in the boundary layer temperature profiles. Measurements included vertical temperature profiles above at least two sites derived from radiosondes and aircraft, as well as surface estimates of radiative and sensible heat fluxes. Surface meteorological and pilot balloon data were also available, providing further evidence of short-term changes in atmospheric boundary layer structure. The Manawatu case was representative of autumnal anticyclonic conditions with weak pressure gradients, and illustrated typical diurnal development of a convective boundary layer over a coastal plain bordered by mountain ranges, with a transition from a stable nocturnal situation to a well-mixed profile in the afternoon. The profiles show surface input of heat propagating upwards through the boundary layer during the day, as well as entrainment of heat at the top associated with shear induced turbulence and/or penetrative convection. Applying a one-dimensional model, estimates of boundary layer heat budget components were obtained for four time periods during the day. Later periods were affected by cumulus cloud development at the top of the boundary layer, resulting in significant changes in individual components. Input of sensible heat from the surface decreased, while the addition of heat to the boundary layer from both cloud condensation and advection increased.

Testosterone secretion and pharmacological spermatozoal recovery in the cane toad (Bufo marinus)

The cane toad (Bufo marinus) was used as a model to study male anuran reproductive endocrinology and to develop a protocol for non-invasive sperm recovery. Circulating testosterone concentrations in 6-hourly samples did not vary significantly (P < 0.05) over a 24 h period although there was a tendency (P = 0.06) for testosterone to be elevated at 19:00 h relative to other times of the day, which may be related to the nocturnal activity pattern of this species. Testosterone secretion after intraperitoneal (IP) injection of either a GnRH agonist (5 mu g IP) or hCG (1000 IU) was also examined. While the GnRH agonist did not produce a significant increase above basal plasma testosterone (0.29, 95% C.I. of 0.05-1.10 ng/ml), injection of hCG resulted in an increase (P < 0.01) of plasma testosterone with peak concentrations at approximately 120 min (4.17, 95% C.I. of 2.69-7.44 ng/ml) after injection. Non-invasive pharmaceutical sperm recovery was attempted following IP injection of graded doses of GnRH agonist, hCG or FSH. Urine was collected at 3, 6 and 12 h after treatment to assess sperm quality and quantity. The optimal protocol for sperm recovery in cane toads was injection of either 1000 or 2000 IU hCG; there was no significant difference in the quality of the spermic urine samples obtained using either dose of hCG or with respect to collection time. The findings indicated that hCG can be used to assess testicular steroidogenic status and also to induce sperm recovery in the cane toad. The hCG protocols developed in this study will have application in studies on the reproductive biology of rare and endangered male anurans. (c) 2005 Elsevier B.V. All rights reserved.

Common causes of sleep disruption and daytime sleepiness: childhood sleep disorders II

There are strong associations between childhood sleep disorders and behavioural, concentration and mood problems. Sleep disorders caused and maintained by behavioural factors (eg, sleep-onset association disorder) are common in young children, and have a significant impact on families. Evaluation should include a medical history, a physical, neurological and developmental examination, a description of any nocturnal events or daytime effects of the child's disturbed sleep, and a good understanding of the family situation and parental management of the child. Management involves recognising the developmental age of the child and the family dynamics, and educating and supporting families in applying behavioural techniques to establish good sleep hygiene. Children with parasomnias (eg, night terrors) also benefit from good sleep hygiene, while those with respiratory or neurological causes of sleep disturbance should be referred for specialist treatment.

Diurnal polyp expansion behavior in stony corals may enhance carbon availability for symbionts photosynthesis

Photosynthesis of zooxanthellate stony corals may be limited by inorganic carbon at high irradiances. We demonstrated that oxygen consumption of expanded corals is higher than that of contracted corals in both night-expanding and day-expanding corals. It is assumed that at the single-polyp level, the expansion of tentacles increases the surface area for solute exchange with the surrounding water, which may alleviate potential carbon limitation and excess oxygen levels in the tissue under high irradiance. We investigated this hypothesis using stable carbon isotope (613 C) analysis of coral species from the Red Sea exhibiting different morphologies. delta C-13 ratios in zooxanthellae of branched coral colonies with small polyp size that extend their tentacles during daytime (diurnal morphs) showed lower delta C-13 values in their zooxanthellae - 13.83 +/- 1.45 parts per thousand, compared to corals from the same depth with large polyps, which are usually massive and expand their tentacles only at night (nocturnal morphs). Their algae delta C-13 was significantly higher, averaging - 11.33 +/- 0.59 parts per thousand. Carbon isotope budget of the coral tissue suggests that branched corals are more autotrophic, i.e., that they depend on their symbionts for nutrition compared to massive species, which are more heterotrophic and depend on plankton predation. (c) 2005 Elsevier B.V. All rights reserved.

Cone photoreceptor oil droplet pigmentation is affected by ambient light intensity

The cone photoreceptors of many vertebrates contain spherical organelles called oil droplets. In birds, turtles, lizards and some lungfish the oil droplets are heavily pigmented and function to filter the spectrum of light incident upon the visual pigment within the outer segment. Pigmented oil droplets are beneficial for colour discrimination in bright light, but at lower light levels the reduction in sensitivity caused by the pigmentation increasingly outweighs the benefits generated by spectral tuning. Consequently, it is expected that species with pigmented oil droplets should modulate the density of pigment in response to ambient light intensity and thereby regulate the amount of light transmitted to the outer segment. In this study, microspectrophotometry was used to measure the absorption spectra of cone oil droplets in chickens (Gallus gallus domesticus) reared under bright (unfiltered) or dim (filtered) sunlight. Oil droplet pigmentation was found to be dependent on the intensity of the ambient light and the duration of exposure to the different lighting treatments. In adult chickens reared in bright light, the oil droplets of all cone types (except the violet-sensitive single cones, whose oil droplet is always non-pigmented) were more densely pigmented than those in chickens reared in dim light. Calculations show that the reduced levels of oil droplet pigmentation in chickens reared in dim light would increase the sensitivity and spectral bandwidth of the outer segment significantly. The density of pigmentation in the oil droplets presumably represents a trade-off between the need for good colour discrimination and absolute sensitivity. This might also explain why nocturnal animals, or those that underwent a nocturnal phase during their evolution, have evolved oil droplets with low pigment densities or no pigmentation or have lost their oil droplets altogether.

Opioids and NMDA receptors: Neuro-excitation and abnormal pain behaviours

In the clinical setting, chronic administration of high doses of systemic morphine may result in neuro-excitatory behaviours such as myoclonus and allodynia in some patients. Additionally, high doses of m-opioid agonists such as morphine administered chronically by the intrathecal route in both rats and humans, as well as DAMGO in rats, have been reported to produce neuro-excitatory behaviours. However, more recently, it has begun to be appreciated that even at normal analgesic doses, opioids such as morphine are capable not only of activating pain inhibitory systems (analgesia/antinociception), but they also activate pain facilitatory systems such that post-opioid allodynia/hyperalgesia may be evident after cessation of opioid treatment. Whilst it is well documented that opioid receptors mediate the inhibitory effects of opioid analgesics, the excitatory and pro-nociceptive effects of opioids appear to involve indirect activation of N-methyl-D-aspartate (NMDA) receptors, such that the extent of pain relief produced may be the net effect of these two opposing actions. Apart from the NMDA-nitric oxide (NO) pro-nociceptive signaling cascade, considerable evidence also implicates dynorphin A as well as the endogenous anti-opioid peptides cholecystokinin (CCK), neuropeptide FF (NPFF) and orphanin FQ/nociceptin, in mediating opioid-induced neuro-excitation and abnormal pain behaviours. Apart from the neuro-excitatory effects that may be produced by the parent opioid, systemic administration of some opioid analgesics such as morphine and hydromorphone in rats and humans results in their rapid conversion to 3-glucuronide metabolites that also contribute significantly to the neuro-excitatory and abnormal pain behaviours produced