A pilot study to improve sugar and water consumption in Maltese school children.

BACKGROUND: Excessive sugar consumption remains implicated as one of the key dietary factors that has been linked to overweight and obesity in children. Schools have been identified as an important setting for health promotion interventions in children and can be successful in bringing about dietary behavioral change when well designed. OBJECTIVE: The main aim of the study was to conduct a pilot intervention study and assess the possible effects of educational and environmental methodological components on sugar intake and water consumption in Maltese school children. SUBJECTS AND METHODS: Face-to-face educational sessions for children and parents were supported by written materials and provision of free drinking water for children for a 12 week period in the school setting. Two main dietary outcomes were measured: non-milk extrinsic sugars(NMES) intake (measured as g/day) and water consumption (measured as servings/day), measured in the pre- and post-intervention periods. The dietary outcomes were measured at school using the novel online dietary assessment tool, REALITYMALTA™. RESULTS: 55 children, aged 10-11 years, were recruited, and 48 provided diet data at baseline and end. A reduction in mean energy intakes was noted from 7733 kJ/day (SD 2046) to 6809 (SD 2224) kJ/day (p = 0.03), with water servings intake increased and NMES intake decreased but results not statistically significant. Parent attendance at the educational sessions was low. CONCLUSIONS: A larger scale study, including multi-level analysis is recommended. Modifying the content of the intervention and finding ways to increase parent engagement should be considered in future.

Quantum interface of an electron and a nuclear ensemble.

Coherent excitation of an ensemble of quantum objects underpins quantum many-body phenomena and offers the opportunity to realize a memory that stores quantum information. Thus far, a deterministic and coherent interface between a spin qubit and such an ensemble has remained elusive. In this study, we first used an electron to cool the mesoscopic nuclear spin ensemble of a semiconductor quantum dot to the nuclear sideband-resolved regime. We then implemented an all-optical approach to access individual quantized electronic-nuclear spin transitions. Lastly, we performed coherent optical rotations of a single collective nuclear spin excitation-a spin wave. These results constitute the building blocks of a dedicated local memory per quantum-dot spin qubit and promise a solid-state platform for quantum-state engineering of isolated many-body systems.

Mitochondrial involvement in transhemispheric diaschisis following hypoxia-ischemia: Clomethiazole-mediated amelioration.

Mitochondria play a central role in both the physiological and pathophysiological regulation of cell survival/death. Increasing evidence places mitochondrial dysfunction at the center of many neuropathological conditions. The present study investigates the extent of mitochondrial dysfunction in cortical, hippocampal and cerebellar tissues in a rat model of hypoxia-ischemia (HI). We hypothesized that; mitochondrial dysfunction in situ may be prevented by treatment with clomethiazole (CMZ), a GABA(A) receptor agonist. Assessment of mitochondrial FAD-linked respiration at both 1- and 3-day post-HI revealed a marked decrease in activity from ipsilateral cortical and hippocampal regions (P<0.001). In addition, small changes were seen in contralateral cortical and hippocampal tissues as well as in the cerebellum at 3-days (P<0.05). Assessment of the mitochondrial electron transport chain (complexes I-V), and mitochondrial markers of integrity (citrate synthase) and oxidative stress (aconitase) confirmed mitochondrial impairment in ipsilateral regions following HI. Complexes I, II-III, V and citrate synthase were also impaired in contralateral regions and cerebellum 3-days post-HI. Treatment with CMZ (414 mg/kg/day via minipumps) provided marked protection to all aspects of neuronal tissue assessed. Circulating cytokine (interleukin [IL]-1alpha, IL-1beta, tumor necrosis factor [TNF]-alpha, granulocyte macrophage colony-stimulating factor [GM-CSF], IL-4 and IL-10) levels were also assessed in these animals 3-days post-HI. Plasma IL-1alpha, IL-1beta, TNF-alpha and GM-CSF levels were significantly increased post-HI. Treatment with CMZ ameliorated the increases in IL-1alpha, IL-1beta, TNF-alpha and GM-CSF levels while increasing plasma IL-4 and IL-10 levels. This study provides evidence of the extent of mitochondrial damage following an HI-insult. In addition, we have shown that protection afforded by CMZ extends to preservation of mitochondrial function and integrity via anti-inflammatory mediated pathways.

Expression of melanoma-associated antigens by normal and neurofibroma Schwann cells.

The cell surface antigen distribution on traumatic neuroma Schwann cells and neurofibroma Schwann-like cells was characterized using monoclonal antibodies that define melanoma-associated antigens. Immunofluorescence staining of cultured cells, immunoprecipitation of radioiodinated antigens from cells placed in short-term cultures, and immunoperoxidase staining of frozen tissue sections revealed most of the melanoma-associated antigens tested on traumatic neuroma and neurofibroma Schwann cells and on fetal and adult femoral nerve. The cross-reactivity of the antibodies with neural cells may reflect the common neural crest embryological origin of Schwann cells and melanocytes. Cell sorter analysis of neurofibroma cells using a monoclonal antibody directed against the melanoma nerve growth factor receptor resulted in cell cultures highly enriched for Schwann-like cells which may bear the genetic defect responsible for neurofibromatosis. The antigen detected by this monoclonal antibody is the neurofibroma nerve growth factor receptor and the antibody was a potent inhibitor of nerve growth factor binding to neurofibroma cells.

The binding of lipopolysaccharide from Escherichia coli to mammalian cell membranes and its effect on liposomes.

The kinetics of the absorption of 32P- or 14C-labelled lipopolysaccharide from Escherichia coli NCTC 8623, serotype 0 125, chemotype XII, to erythrocytes, leukocytes, peritoneal macrophages and peritoneal lymphocytes was examined. Under variable conditions maximal levels of binding were found due to saturation of receptor sites on the cell membrane or steric hindrance by bound lipopolysaccharide. During adsorption slight leakage of haemoglobin was found but complete lysis of erythrocytes was ruled out after noting the effect of lipopolysaccharide on artificial lipid bilayers. The affinit of lipopolysaccharide to cell membranes revealed a consistent pattern of cyclic fluctuation between adsorption and desorption. A model was proposed to explain this cyclic fluctuation in binding based on membrane reorganization. It was significant that the cycle of lipopolysaccharide adsorption-desorption proceeded to completion even if the process was interrupted. The indication was that, once triggered, membrane reorganization occurred independently without influence from the test environment.

Total energy expenditure and physical activity in young Scottish children: mixed longitudinal study.

Childhood obesity has been attributed to a decline in total energy expenditure (TEE). We measured TEE, physical activity, and sedentary behaviour in a representative sample of young children from Glasgow, UK, at age 3 years (n=78), and we did a follow-up study at age 5 years (n=72). Mean physical activity level (TEE/resting energy expenditure) was 1.56 (SD 0.39) at age 3 years and 1.61 (0.22) at age 5 years. Median time in sedentary behaviour was 79% of monitored hours at age 3 years (IQR 74-84) and 76% (71-80) at age 5 years. Median time spent in moderate to vigorous physical activity represented only 2% of monitored hours at age 3 years (IQR 1-4) and 4% at age 5 years (2-6). Modern British children establish a sedentary lifestyle at an early age.

Dopamine receptors: molecular biology, biochemistry and behavioural aspects.

The description of new dopamine (DA) receptor subtypes, D1-(D1 and D5) and D2-like (D2A, D2B, D3, D4), has given an impetus to DA research. While selective agonists and antagonists are not generally available yet, the receptor distribution in the brain suggests that they could be new targets for drug development. Binding characteristics and second messenger coupling has been explored in cell lines expressing the new cloned receptors. The absence of selective ligands has meant that in vivo studies have lagged behind. However, progress has been made in understanding the function of DA-containing discrete brain nuclei and the functional consequence of the DA's interaction with other neurotransmitters. This review explores some of the latest advances in these various areas.

Expression of the circadian clock genes clock and period1 in human skin.

The circadian clock is a cellular machine composed of proteins with regulated expression that gives rise to circadian rhythms. Two main new concepts have arisen from recent research in the field in the last few years: (i) at least three to five key genes are involved in maintaining the basic circadian cellular rhythms, and (ii) their expression is fairly ubiquitous, extending beyond the traditionally considered pacemaker in mammals, the suprachiasmatic nucleus. We have demonstrated the expression of two circadian clock genes, clock and period1, in human skin cells. Reverse transcriptase polymerase chain reaction revealed the presence of clock and period1 mRNA in cultured human keratinocytes, melanocytes, and dermal fibroblasts, as well as in the human keratinocyte cell line HaCaT and the human melanoma line A375. In addition, antibodies to these two proteins produced immuno-positive staining in these cell types. Our investigations demonstrate for the first time that skin cells express circadian clock proteins constitutively although regulation of their expression and activity has not been elucidated. These proteins may have a role in cutaneous and/or systemic circadian biology and the skin and skin cells may provide an attractive model for the study of circadian rhythms.

Bromocriptine enhances the behavioural effects of apomorphine and dopamine after systemic or intracerebral injection in rats.

The ergot alkaloid bromocriptine, given intraperitoneally produced dose-dependent, long-lasting stereotyped behaviour in rats which was partly antagonised by the injection of trifluoperazine into the caudate nucleus. The stereotyped behaviour produced by apomorphine (s.c.) in both naïve and catecholamine-depleted rats was significantly enhanced by prior treatment with bromocriptine (i.p.). The bilateral application of bromocriptine (2.5-40 micrograms/side in either 0.5% tartaric acid or 50% propylene glycol aqueous vehicles) to the nucleus accumbens (NAC) of rats had no effect on locomotion over a 12 hr period after injection. In contrast, another ergot alkaloid, ergometrine, dissolved in the propylene glycol vehicle, and dopamine (DA) dissolved in either of the vehicles or in saline, produced marked stimulation of locomotion. As well as being inactive after direct application to the nucleus accumbens, bromocriptine (10-160 micrograms/side) did not induce stereotyped behaviour after bilateral injection into the caudate nucleus. However, the local application of bromocriptine (10 micrograms/side) to the nucleus accumbens, while itself inactive, significantly enhanced the locomotor stimulant effect of DA (5 micrograms/side) applied to the same nucleus. The data suggest that bromocriptine is able to enhance the effects of agonists such as DA and apomorphine at DA receptors, even under conditions where bromocriptine itself is inactive.

GABA potentiation: a logical pharmacological approach for the treatment of acute ischaemic stroke.

It has been shown that enhancing the function of the major inhibitory neurotransmitter GABA decreases glutamatergic activity in the brain. Since increased glutamatergic activity is the major primary event that results in cell death following an acute hypoxic-ischaemic stroke, GABAmimetic drugs might therefore be expected to be neuroprotective. This review examines the evidence that GABAergic function is acutely depressed following an ischaemic insult, and also reviews the data that suggest that increasing cerebral GABA concentration has a neuroprotective effect, as does the administration of some (but not all) GABAmimetic agents. The GABA uptake inhibitor CI-966, the GABA(A) agonist muscimol and the GABA(A)mimetic clomethiazole have all been shown to be neuroprotective in animal models of stroke when given after the ischaemic insult. In contrast, benzodiazepines and particularly barbiturates, although potent GABA(A) potentiators, have shown little promise as neuroprotectants. The diversity of GABA(A) receptor subtypes and the in vivo efficacy of certain GABA(A) receptor ligands in animal models of stroke suggests that GABAmimetic drugs are an undervalued approach to stroke therapy.

Efficacy of disodium 4-[(tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (NXY-059), a free radical trapping agent, in a rat model of hemorrhagic stroke.

Because free radical mechanisms may contribute to brain injury in hemorrhagic stroke, the effect of the free radical trapping agent disodium 4-[(tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (NXY-059) was investigated on outcome following intracerebral hemorrhage (ICH) in rat. ICH was induced in 20 adult rats by infusion of collagenase into the caudate-putamen. Thirty minutes later rats were treated with NXY-059 (50 mg/kg subcutaneous plus 8.8 mg/kg/h for 3 days subcutaneous delivered via implanted osmotic pumps) or saline (equivalent volumes). Magnetic resonance imaging 24 h after ICH confirmed that the hemorrhage was uniform in the two groups, and subsequent imaging at 7 and 42 days post-ICH showed that the hematoma resolved similarly in the two groups. Behavioral testing on days 1, 3, 7, 14, and 21 after ICH showed that rats treated with NXY-059 had significantly decreased neurological impairment at all times. Deficits in skilled forelimb use 4-5 weeks post-ICH, and in striatal function 6 weeks post-ICH, were not reduced by treatment with NXY-059. Treatment with NXY-059 significantly reduced the neutrophil infiltrate observed 48 h post-hemorrhage in the vicinity of the hematoma, and the number of TUNEL-positive cells 48 h post-hemorrhage at the hematoma margin. However, by 6 weeks there were no differences in neuronal densities in treated and control rats.

Development of tolerance to 8-OH-DPAT induced blockade of acquisition of a passive avoidance response.

We examined the effects of manipulating 5-HT1A receptors on the performance of a passive avoidance task in rats. Firstly, we studied the effect of racemic 8-OH-DPAT and compared it to the pure enantiomers (subcutaneous injection, s.c.). Secondly, we investigated the effect (s.c.) of the selective 5-HT1A receptor antagonist (S)-UH-301 [(S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin] both alone and on 8-OH-DPAT-induced disruption of acquisition. Thirdly, we examined whether tolerance occurs to the effects of 8-OH-DPAT on passive avoidance acquisition. Finally, we examined the effects (s.c.) of the selective NMDA receptor antagonist dizocilpine, (+)-MK-801[(5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohe pten-5, 10-imine], on this tolerance development. Different doses of racemic 8-OH-DPAT were injected 10 min before rats were exposed to the acquisition phase of a step through passive avoidance response. When tested for retention 24 h later, 8-OH-DPAT-pretreated rats failed to exhibit any avoidance. R(+) and S(-)-8-OH-DPAT were also active with the R(+)-isomer being more active than the S(-)-isomer. The 5-HT1A antagonist (S)-UH-301 [(S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin] was without effect on avoidance performance but antagonized the effect of 8-OH-DPAT. In a further experiment, rats were pretreated with racemic 8-OH-DPAT (0.3 mg/kg). Twenty four hours later, they received a challenge dose of 8-OH-DPAT and exposed to the acquisition phase of the avoidance response. When tested 24 hr later for retention, 8-OH-DPAT challenged rats failed to show any indication of an avoidance response.(ABSTRACT TRUNCATED AT 250 WORDS)

The interaction of AR-A008055 and its enantiomers with the GABA(A) receptor complex and their sedative, muscle relaxant and anticonvulsant activity.

AR-A008055 [(+/-)-1-(4-methyl-5-thiazolyl)-1-phenylmethylamine] is structurally related to clomethiazole and has been used to probe the mechanism of the neuroprotective effect of clomethiazole. Clomethiazole, (+/-)-AR-A008055 and (S)-(-)-AR-A008055 all displaced [35S]-t-butyl-bicyclophosphorothionate ([35S]TBPS) from rat cerebral cortex tissue (IC50 values: GABA, 8.1+/-0.04 microM; clomethiazole, 130+/-30 microM; (+/-)-AR-A008055, 494+/-7 microM; (S)-(-)-AR-A008055, 221+/-14 microM. (R)-(+)-AR-A008055 was without significant effect (IC50>1000 microM). None of the compounds interacted with NMDA or AMPA receptors or with sodium or calcium (N, P/Q) channels. Brain penetration of both enantiomers following their i.p. administration was excellent, with brain and plasma concentrations being similar. Clomethiazole dose-dependently inhibited spontaneous locomotor activity in rats and was approximately 10 times more sedative than either enantiomer of AR-A008055. Clomethiazole was more potent than (S)-(-)-AR-A008055 in the "pull-up" test (muscle relaxation) and in producing loss of righting reflex, while (R)-(+)-AR-A008055 had little effect. The time animals remained on a Rota-rod was of the order: clomethiazole<(S)-(-)-AR-A008055<(R)-(+)-AR-A008055. (S)-(-)-AR-A008055 (210 micromol/kg) raised seizure threshold to pentylenetetrazole (i.v.) by 119+/-21%. The (R)-(+)- enantiomer was not anticonvulsant. Overall, (S)-(-)-AR-A008055 exhibited a similar pharmacology to clomethiazole. However, its sedative and muscle relaxant effects were substantially less than clomethiazole, emphasising that these properties are not directly related to neuroprotective efficacy. The current data suggest that the proposed GABA uptake inhibitory property of (R)-(+)-AR-A008055 fails to produce significant sedative, myorelaxant or anticonvulsant activity.

The effect of nedocromil sodium, sodium cromoglycate and codeine phosphate on citric acid-induced cough in dogs.

1. The effects of nedocromil sodium, sodium cromoglycate and codeine phosphate on citric acid-induced cough have been studied in conscious tracheostomised dogs. 2. Nedocromil sodium (approximately 15 mg given as an aerosol) and codeine phosphate (5 mg kg-1, i.v.) significantly increased the time to the first cough when dogs were challenged with citric acid aerosol. The mean number of coughs in the initial period of coughing fell after treatment of dogs with nedocromil sodium or with codeine phosphate, but this reduction in mean cough number was not statistically significant. 3. Neither sodium cromoglycate (approximately 15 mg given as an aerosol) nor saline had significant effect on a citric acid challenge. 4. It is concluded that nedocromil sodium, but not sodium cromoglycate, possesses an anti-tussive action that may result from inhibition of sensory nerve activity in the lung. Nedocromil sodium may prove useful in the treatment of unproductive cough in situations where the use of a centrally-acting antitussive is undesirable.

The effects of sodium cromoglycate on histamine aerosol-induced reflex bronchoconstriction in the anaesthetized dog.

1 The effects have been studied of sodium cromoglycate (SCG), given by aerosol or intravenously, on reflex bronchoconstriction induced by histamine aerosol in the anaesthetized dog. 2 Four breaths of an aerosol generated from a 2% solution of SCG significantly inhibited the vagally mediated increase in total lung resistance (RL) produced by histamine. 3 SCG given intravenously as bolus injections (5-500 microgram/kg) produced a dose-dependent reversal of a sustained reflex bronchoconstriction induced by histamine aerosol. Propranolol (500 microgram/kg) did not prevent this reversal. 4 SCG did not inhibit the increase in RL produced by supramaximal electrical stimulation of a vagus nerve. 5 The possibility is discussed that SCG may reduce the activity of lung irritant receptors in the anaesthetized dog.

The effects of pentobarbitone and chloralose anaesthesia on the vagal component of bronchoconstriction produced by histamine aerosol in the anaesthetized dog.

1 Total lung resistance (R(L)) and dynamic lung compliance (C(dyn)) were measured in dogs anaesthetized with pentobarbitone or chloralose and subjected to aerosols of histamine during 4 successive inspirations.2 Histamine caused concentration-dependent increases in R(L) and decreases in C(dyn). A significant vagal component was involved, but only when chloralose was employed and then only in the R(L) response.3 The resting values of R(L) and C(dyn) were similar regardless of which anaesthetic was used and remained essentially the same if the vagi were cooled.4 Electrical stimulation of the efferent vagi caused large increases in R(L) of dogs given chloralose and these effects were attenuated by the administration of pentobarbitone. Such stimulation was relatively ineffective in dogs given pentobarbitone alone.5In vitro, electrical field stimulation caused contractions of dog trachealis muscle. The responses were reduced by pentobarbitone in concentrations approximating to plasma levels in the anaesthetized dogs (1 to 5 x 10(-4) M), but the effects of exogenous acetylcholine were unaltered. The inhibition was dose-dependent, reversed by washing and unaltered by hexamethonium.6 The results suggest that pentobarbitone inhibits the vagal component of histamine-induced bronchoconstriction in the dog by an action on the efferent pathway. Furthermore, pentobarbitone acts either by blocking transmission along postganglionic parasympathetic nerves or by preventing the release of acetylcholine from the nerve endings in the lung.

The effects of sodium cromoglycate on lung irritant receptors and left ventricular cardiac receptors in the anaesthetized dog.

1 The time from the injection of sodium cromoglycate 10 to 50 mug/kg into a saphenous vein, the cervical carotid arteries, the left ventricle and the aortic arch, to the onset of reflex hypotension has been measured in anaesthetized dogs. The shortest latency was 16.9 s on injection of sodium cromoglycate into the left ventricle.2 Instillation of 2% lignocaine into the pericardium of an anaesthetized dog blocked the reflex hypotensive response to sodium cromoglycate (10 to 50 mug/kg i.v.), and also prevented sodium cromoglycate (100 mug/kg) from reversing reflex bronchoconstriction induced by inhalation of an aerosol of histamine.3 The effect of sodium cromoglycate (100 mug/kg i.v.) on resting discharge and histamine-induced discharge (20 mug/kg i.v.) of five lung irritant receptors in five anaesthetized dogs has been studied. Sodium cromoglycate (100 mug/kg i.v.) did not affect the resting discharge of these receptors or their ability to respond to histamine.4 Sodium cromoglycate (100 mug/kg i.v.) increased the rate of discharge of three receptors found in the endocardium of the left ventricle of the canine heart. A solution of sodium cromoglycate (0.1%) was applied topically to one receptor and its rate of discharge was increased.5 It is suggested that in the dog, sodium cromoglycate produces reflex hypotension and reverses histamine-induced reflex bronchoconstriction by activating receptors in the left ventricle of the heart.

The action of sodium cromoglycate on 'C' fibre endings in the dog lung.

The effect has been studied of sodium cromoglycate (SCG) on the activity of 'C' fibre sensory nerve endings in the canine lung. Pretreatment with SCG (100 microgram/kg i.v.) reduced the excitation of these endings by capsaicin (10 microgram/kg i.v.) for approximately 45 min. This property of SCG may explain its ability to suppress certain types of bronchoconstrictor responses in man.

The effects of H1- and H2-receptor agonists and antagonists on total lung resistance, dynamic lung compliance and irritant receptor discharge in the anaesthetized dog.

1 The effects of histamine and 4 methylhistamine (i.v.) alone, and in the presence of chlorpheniramine or cimetidine, on total lung resistance (RL), dynamic lung compliance (Cdyn) and irritant receptor activity have been studied in dogs anaesthetized with chloralose. 2 Histamine produced dose-related increases in RL and irritant receptor activity with associated falls in Cdyn which were blocked by chlorpheniramine but unaffected by cimetidine. 3 4 Methylhistamine produced small insignificant changes in RL and Cdyn and small significant increases in irritant receptor activity which were reduced with chlorpheniramine but unaffected by cimetidine. 4 The results suggest that histamine increases irritant receptor activity, either directly or indirectly, via H1-receptors.

The pharmacology of the rat ureter in vivo.

1. A method of recording the peristaltic frequency and the rate of transport of fluid (perfusion rate) in the rat ureter in vivo is described.2. Acetylcholine and atropine did not alter ureteral activity. Histamine increased the rate of peristalsis by up to 15% and the rate of perfusion by up to 10%. Low doses of 5-hydroxytryptamine increased peristaltic frequency whereas high doses decreased peristaltic frequency; all doses reduced the rate of perfusion.3. Morphine reduced the rate of perfusion by 5-10% at all dose levels, but only the highest dose used reduced the frequency of ureteral peristalsis.4. (-)-Adrenaline, (-)-noradrenaline and (+/-)-isoprenaline reduced the frequency of peristalsis. The order of potency was isoprenaline>noradrenaline>adrenaline. The response was dose-related and blocked by propranolol, which itself did not affect ureteral activity.