Proportion of out-of-hospital adult non-traumatic cardiac or respiratory arrest among calls for seizure.

OBJECTIVES: To measure the proportion of adult non-traumatic cardiac or respiratory arrest among calls for seizure to an emergency medical dispatch centre and to record whether known epileptic patients present cardiac or respiratory arrest together with seizure. METHODS: This 2-year prospective observational investigation involved the collection of tape recordings of all incoming calls to the emergency medical dispatch centre, in which an out-of-hospital non-traumatic seizure was the chief complaint in patients >18 years, in addition to the paramedics' records of all patients who presented with respiratory or cardiac arrest. The authors also recorded whether the bystander spontaneously mentioned to the dispatcher that the victim was known to have epilepsy. RESULTS: During the 24-month period, the call centre received 561 incoming calls for an out-of-hospital non-traumatic seizure in an adult. Twelve cases were classified as cardiac or respiratory arrest by paramedics. In one case, the caller spontaneously mentioned that the victim had a history of epilepsy. The proportion of cardiac or respiratory arrest among calls for seizure was 2.1%. CONCLUSION: Although these cases are rare, dispatchers should closely monitor seizure patients with the help of bystanders to exclude an out-of-hospital cardiac or respiratory arrest, in which case the dispatcher can offer telephone cardiopulmonary resuscitation advice until the paramedics arrive. Whenever the activity of the centre allows it and no new incoming call is on hold, this can be achieved by staying on the line with the caller or by calling back. A history of epilepsy should not modify the type of monitoring performed by the dispatcher as those patients may also have an arrest together with seizure.

Protective effects of maternal nutritional supplementation with lactoferrin on growth and brain metabolism.

Background:Intrauterine growth restriction (IUGR) is a major risk factor for both perinatal and long-term morbidity. Bovine lactoferrin (bLf) is a major milk glycoprotein considered as a pleiotropic functional nutrient. The impact of maternal supplementation with bLf on IUGR-induced sequelae, including inadequate growth and altered cerebral development, remains unknown.Methods:IUGR was induced through maternal dexamethasone infusion (100 μg/kg during last gestational week) in rats. Maternal supplementation with bLf (0.85% in food pellet) was provided during both gestation and lactation. Pup growth was monitored, and Pup brain metabolism and gene expression were studied using in vivo (1)H NMR spectroscopy, quantitative PCR, and microarray in the hippocampus at postnatal day (PND)7.Results:Maternal bLf supplementation did not change gestational weight but increased the birth body weight of control pups (4%) with no effect on the IUGR pups. Maternal bLf supplementation allowed IUGR pups to recover a normalized weight at PND21 (weaning) improving catch-up growth. Significantly altered levels of brain metabolites (γ-aminobutyric acid, glutamate, N-acetylaspartate, and N-acetylaspartylglutamate) and transcripts (brain-derived neurotrophic factor (BDNF), divalent metal transporter 1 (DMT-1), and glutamate receptors) in IUGR pups were normalized with maternal bLf supplementation.Conclusion:Our data suggest that maternal bLf supplementation is a beneficial nutritional intervention able to revert some of the IUGR-induced sequelae, including brain hippocampal changes.

Characterization of a MexAB-OprM efflux system necessary for productive metabolism of Pseudomonas azelaica HBP1 on 2-hydroxybiphenyl.

Pseudomonas azelaica HBP1 is one of the few bacteria known to completely mineralize the biocide and toxic compound 2-hydroxybiphenyl (2-HBP), but the mechanisms of its tolerance to the toxicity are unknown. By transposon mutant analysis and screening for absence of growth on water saturating concentrations of 2-HBP (2.7 mM) we preferentially found insertions in three genes with high homology to the mexA, mexB, and oprM efflux system. Mutants could grow at 2-HBP concentrations below 100 μM but at lower growth rates than the wild-type. Exposure of the wild-type to increasing 2-HBP concentrations resulted in acute cell growth arrest and loss of membrane potential, to which the cells adapt after a few hours. By using ethidium bromide (EB) as proxy we could show that the mutants are unable to expel EB effectively. Inclusion of a 2-HBP reporter plasmid revealed that the wild-type combines efflux with metabolism at all 2-HBP concentrations, whereas the mutants cannot remove the compound and arrest metabolism at concentrations above 24 μM. The analysis thus showed the importance of the MexAB-OprM system for productive metabolism of 2-HBP.

General unknown screening procedure for the characterization of human drug metabolites: application to loratadine phase I metabolism.

This article describes the application of a recently developed general unknown screening (GUS) strategy based on LC coupled to a hybrid linear IT-triple quadrupole mass spectrometer (LC-MS/MS-LIT) for the simultaneous detection and identification of drug metabolites following in vitro incubation with human liver microsomes. The histamine H1 receptor antagonist loratadine was chosen as a model compound to demonstrate the interest of such approach, because of its previously described complex and extensive metabolism. Detection and mass spectral characterization were based on data-dependent acquisition, switching between a survey scan acquired in the ion-trapping Q3 scan mode with dynamic subtraction of background noise, and a dependent scan in the ion-trapping product ion scan mode of automatically selected parent ions. In addition, the MS(3) mode was used in a second step to confirm the structure of a few fragment ions. The sensitivity of the ion-trapping modes combined with the selectivity of the triple quadrupole modes allowed, with only one injection, the detection and identification of 17 phase I metabolites of loratadine. The GUS procedure used in this study may be applicable as a generic technique for the characterization of drug metabolites after in vitro incubation, as well as probably in vivo experiments.

Small RNA-dependent expression of secondary metabolism is controlled by Krebs cycle function in Pseudomonas fluorescens.

Pseudomonas fluorescens CHA0, an antagonist of phytopathogenic fungi in the rhizosphere of crop plants, elaborates and excretes several secondary metabolites with antibiotic properties. Their synthesis depends on three small RNAs (RsmX, RsmY, and RsmZ), whose expression is positively controlled by the GacS-GacA two-component system at high cell population densities. To find regulatory links between primary and secondary metabolism in P. fluorescens and in the related species Pseudomonas aeruginosa, we searched for null mutations that affected central carbon metabolism as well as the expression of rsmY-gfp and rsmZ-gfp reporter constructs but without slowing down the growth rate in rich media. Mutation in the pycAB genes (for pyruvate carboxylase) led to down-regulation of rsmXYZ and secondary metabolism, whereas mutation in fumA (for a fumarase isoenzyme) resulted in up-regulation of the three small RNAs and secondary metabolism in the absence of detectable nutrient limitation. These effects required the GacS sensor kinase but not the accessory sensors RetS and LadS. An analysis of intracellular metabolites in P. fluorescens revealed a strong positive correlation between small RNA expression and the pools of 2-oxoglutarate, succinate, and fumarate. We conclude that Krebs cycle intermediates (already known to control GacA-dependent virulence factors in P. aeruginosa) exert a critical trigger function in secondary metabolism via the expression of GacA-dependent small RNAs.

Cholesterol metabolism is associated with soluble amyloid precursor protein production in Alzheimer's disease.

Disturbances of the cholesterol metabolism are associated with Alzheimer's disease (AD) risk and related cerebral pathology. Experimental studies found changing levels of cholesterol and its metabolites 24S-hydroxycholesterol (24S-OHC) and 27-hydroxycholesterol (27-OHC) to contribute to amyloidogenesis by increasing the production of soluble amyloid precursor protein (sAPP). The aim of this study was to evaluate the relationship between the CSF and circulating cholesterol 24S-OHC and 27-OHC, and the sAPP production as measured by CSF concentrations of sAPP forms in humans. The plasma and the CSF concentrations of cholesterol, 24S-OHC and 27-OHC, and the CSF concentrations of sAPPα, sAPPβ, and Aß1-42 were assessed in subjects with AD and controls with normal cognition. In multivariate regression tests including age, gender, albumin ratio, and apolipoprotein E (APOE)ε4 status CSF cholesterol, 24S-OHC, and 27-OHC independently predicted the concentrations of sAPPα and sAPPβ. The associations remained significant when analyses were separately performed in the AD group. Furthermore, plasma 27-OHC concentrations were associated with the CSF sAPP levels. The results suggest that high CSF concentrations of cholesterol, 24S-OHC, and 27-OHC are associated with increased production of both sAPP forms in AD.

Time invested in the global respiratory care of cystic fibrosis paediatrics patients.

INTRODUCTION: Respiratory therapy is a keystone of the treatment for cystic fibrosis (CF) lung disease, but it is time consuming. OBJECTIVES: We aimed to assess the total time spent on respiratory therapy, including chest physiotherapy (CPT) and physical activity (PA), as well as inhalation therapy (IT) and maintenance of materials (MM) to rationalise and optimise treatment. METHODS: A cross-sectional prospective study in a paediatric CF cohort. A questionnaire was developed to look at the time spent on respiratory care over 3 months. Enrolled in this study are all CF patients aged from 6 to 16 years (the exclusion criterion was lung transplantation). RESULTS: Of the 40 enrolled patients, 22 participated (13 boys and 9 girls), with a mean age of 11 years. The patients spent approximately 19.46 h per week (standard deviation ± 7.53, 8.00-35.25 h) on therapy: CPT (30.58%), IT (15.11%), PA (50%) and MM (4.32%), without statistical significance between sexes. CONCLUSION: In our cohort, CF patients spent an average of nearly 20 h a week in respiratory therapy, within a wide range of between 8 h to almost 36 h a week. PA consumes almost half of the time. Physicians have to take into consideration the burden of the treatment, to optimise the therapy.

Changes in insulin secretion and glucose metabolism induced by dexamethasone in lean and obese females

Résumé But: Chez les individus sveltes et en bonne santé, les modifications de la sensibilité à l'insuline secondaires à l'administration de dexaméthasone pendant deux jours sont compensées par une modification de la sécrétion d'insuline, permettant le maintien de l'homéostasie glucidique. Cette étude évalue les modifications du métabolisme glucidique et de la sécrétion d'insuline induites par une administration limitée de dexaméthasone chez les femmes obèses. Méthode de recherche: Onze femmes obèses ayant une tolérance au glucose normale ont été étudiées à deux reprises, 1° sans dexaméthasone et 2° après deux jours d'administration de dexaméthasone à faible dose. Un clamp hyperglycémique comportant deux plateaux (taux plasmatique de glucose à 7.5, respectivement 10 mM) avec du glucose marqué (6.6 ²H2 glc) a été utilisé pour déterminer la sécrétion d'insuline et le métabolisme du glucose du corps entier. Les résultats ont été comparés à ceux d'un groupe de huit femmes sveltes. Résultats : Sans dexaméthasone, les femmes obèses avaient un taux d'insuline plasmatique supérieur à jeun, durant le premier pic de sécrétion d'insuline, et aux deux plateaux hyperglycémiques. Elles avaient toutefois un métabolisme glucidique normal comparé à celui des femmes sveltes, ce qui indique une compensation adéquate. Après administration de la dexaméthasone, les femmes obèses avaient une augmentation du taux d'insuline plasmatique de 66 à 92%, mais une baisse de stockage du glucose de 15.4%. Ceci contrastait avec l'augmentation du taux d'insuline plasmatique de 91 à 113% chez les femmes sveltes et l'absence de changement de stockage du glucose du corps entier. Discussion : L'administration de dexaméthasone conduit à une baisse significative du stockage du glucose du corps entier pour une glycémie fixée chez les femmes obèses mais non chez les femmes sveltes. Ceci indique que les femmes obèses sont incapables d'accroître adéquatement leur sécrétion d'insuline. Abstract: Objective: In healthy lean individuals, changes in insulin sensitivity occurring as a consequence of a 2-day dexamethasone administration are compensated for by changes in insulin secretion, allowing glucose homeostasis to be maintained. This study evaluated the changes in glucose metabolism and insulin secretion induced by short-term dexamethasone administration in obese women. Research Methods and Procedures: Eleven obese women with normal glucose tolerance were studied on two occasions, without and after 2 days of low-dose dexamethasone administration. A two-step hyperglycemic clamp (7.5 and 10 mr1/1 glucose) with 6,6 2H2 glucose was used to assess insulin secretion and whole body glucose metabolism. Results were compared with those obtained in a group of eight lean women. Results: Without dexamethasone, obese women had higher plasma insulin concentrations in the fasting state, during the first phase of insulin secretion, and at the two hyperglycemic plateaus. However, they had normal whole body glucose metabolism compared with lean women, indicating adequate compensation. After dexamethasone, obese women had a 66% to 92% increase in plasma insulin concentrations but a 15.4% decrease in whole body glucose disposal. This contrasted with lean women, who had a 91% to 113% increase in plasma insulin concentrations, with no change in whole body glucose disposal. Discussion: Dexamethasone administration led to a significant reduction in whole body glucose disposal at fixed glycemia in obese but not lean women. This indicates that obese women are unable to increase their insulin secretion appropriately.

Lung fluid movements in hypoxia.

Pulmonary edema is a problem of major clinical importance resulting from a persistent imbalance between forces that drive water into the airspace of the lung and the biological mechanisms for its removal. Here, we will first review the fundamental mechanisms implicated in the regulation of lung fluid homeostasis, namely, the Starling forces and the respiratory transepithelial sodium transport. Second, we will discuss the contribution of hypoxia to the perturbation of this fine balance and the role of such perturbations in the development of high-altitude pulmonary edema, a disease characterized by a very high morbidity and mortality. Finally, we will review possible interventions aimed to maintain/restore lung fluid homeostasis and their importance for the prevention/treatment of pulmonary edema.

Polyamine metabolism and signaling in plant abiotic stress protection

Polyamines (PAs) are small polycationic compounds present in all living organisms. Compelling evidences indicate a role for PAs in plant protection against stress. During the recent years, genetic, molecular and ‘omic’ approaches have been undertaken to unravel the role of PAs in stress signaling. Overall, results point to intricate relationships between PAs, stress hormone pathways and ROS signaling. Such cross-regulations condition stress signaling through the modulation of abscisic acid (ABA) and ROS amplification-loops. In this chapter we compile our recent findings which elucidate molecular mechanisms and signalingpathways by which PAs contribute to stress protection in plants.

Selective ion changes during spontaneous mitochondrial transients in intact astrocytes.

The bioenergetic status of cells is tightly regulated by the activity of cytosolic enzymes and mitochondrial ATP production. To adapt their metabolism to cellular energy needs, mitochondria have been shown to exhibit changes in their ionic composition as the result of changes in cytosolic ion concentrations. Individual mitochondria also exhibit spontaneous changes in their electrical potential without altering those of neighboring mitochondria. We recently reported that individual mitochondria of intact astrocytes exhibit spontaneous transient increases in their Na(+) concentration. Here, we investigated whether the concentration of other ionic species were involved during mitochondrial transients. By combining fluorescence imaging methods, we performed a multiparameter study of spontaneous mitochondrial transients in intact resting astrocytes. We show that mitochondria exhibit coincident changes in their Na(+) concentration, electrical potential, matrix pH and mitochondrial reactive oxygen species production during a mitochondrial transient without involving detectable changes in their Ca(2+) concentration. Using widefield and total internal reflection fluorescence imaging, we found evidence for localized transient decreases in the free Mg(2+) concentration accompanying mitochondrial Na(+) spikes that could indicate an associated local and transient enrichment in the ATP concentration. Therefore, we propose a sequential model for mitochondrial transients involving a localized ATP microdomain that triggers a Na(+)-mediated mitochondrial depolarization, transiently enhancing the activity of the mitochondrial respiratory chain. Our work provides a model describing ionic changes that could support a bidirectional cytosol-to-mitochondria ionic communication.

Effects of beta-blockade on energy metabolism following burns.

The purpose of this study was to compare the effects of propranolol administered either by i.v. infusion or by prolonged oral administration (4 days) during the first 3 weeks following burns. The resting metabolic rate (RMR) of 10 non-infected fasting burned patients (TBSA: 28 per cent, range 18-37 per cent) was determined four times consecutively by indirect calorimetry (open circuit hood system) following: (1) i.v. physiological saline; (2) i.v. propranolol infusion (2 micrograms/kg/min following a bolus of 80 micrograms/kg); (3) oral propranolol (40 mg q.i.d. during 4 +/- 1 days); and (4) in control patients. All patients showed large increases in both RMR (144 +/- 2 per cent of reference values) and in urinary catecholamine excretion (three to four times as compared to control values). The infusion of propranolol induced a significant decrease in RMR to 135 +/- 2 per cent and oral propranolol to 129 +/- 3 per cent of reference values. A decrease in lipid oxidation but no change in carbohydrate and protein oxidation were observed during propranolol administration. It is concluded that the decrease in RMR induced by propranolol was not influenced by the route of administration. The magnitude of the decrease in energy expenditure suggests that beta-adrenergic hyperactivity represents only one of the mediators of the hypermetabolic response to burn injury.

Protein metabolism and postnatal growth in very low birthweight infants.

Due to the development of new 'bedside' investigative methods, relatively abstract physiologic concepts such as energy cost of growth, efficiency of protein gain, metabolic cost of protein gain and protein turnover have been quantified in very low birthweight infants. 'Healthy' premature infants expend about 30% of their energy to cover the metabolic cost of growth. Stable isotope techniques using 15N-(or 13C)-labeled amino acids gave a new insight into this very high energy demanding process represented by the protein accretion in growing tissues. It has been demonstrated that the rate of protein synthesis (10-12 g/kg/day) greatly exceeds that necessary for net protein gain (2 g/kg/day). The postnatal growth and protein metabolism have different characteristics in 'healthy', 'sick' or 'intrauterine undernourished' very low birthweight infants.

Effects of regular insulin or insulin LISPRO on glucose metabolism after an oral glucose load in patients with type 2 diabetes mellitus.

Seven obese Type 2 diabetic patients were studied for two 4-h periods after ingestion of a glucose load to determine the effects of preprandial subcutaneous injection of Insulin Lispro (5 min before the meal) or regular insulin (20 min before the meal) on glucose metabolism. Glucose production and utilisation were measured using a dual isotope method. After Lispro, the mean postprandial increase in plasma glucose was 29% lower and the increase in insulin concentration 25% higher than after regular insulin (p < 0.05). Suppression of endogenous glucose production was similar with both types of insulin. Thus, preprandial injection of Lispro reduced postprandial glucose increments in Type 2 diabetic patients as compared to regular insulin. This effect is best explained by the increased postprandial bioavailability of Lispro.

The use of uniaxial accelerometry for the assessment of physical-activity-related energy expenditure: a validation study against whole-body indirect calorimetry.

Assessing the total energy expenditure (TEE) and the levels of physical activity in free-living conditions with non-invasive techniques remains a challenge. The purpose of the present study was to investigate the accuracy of a new uniaxial accelerometer for assessing TEE and physical-activity-related energy expenditure (PAEE) over a 24 h period in a respiratory chamber, and to establish activity levels based on the accelerometry ranges corresponding to the operationally defined metabolic equivalent (MET) categories. In study 1, measurement of the 24 h energy expenditure of seventy-nine Japanese subjects (40 (SD 12) years old) was performed in a large respiratory chamber. During the measurements, the subjects wore a uniaxial accelerometer (Lifecorder; Suzuken Co. Ltd, Nagoya, Japan) on their belt. Two moderate walking exercises of 30 min each were performed on a horizontal treadmill. In study 2, ten male subjects walked at six different speeds and ran at three different speeds on a treadmill for 4 min, with the same accelerometer. O2 consumption was measured during the last minute of each stage and was expressed in MET. The measured TEE was 8447 (SD 1337) kJ/d. The accelerometer significantly underestimated TEE and PAEE (91.9 (SD 5.4) and 92.7 (SD 17.8) % chamber value respectively); however, there was a significant correlation between the two values (r 0.928 and 0.564 respectively; P<0.001). There was a strong correlation between the activity levels and the measured MET while walking (r(2) 0.93; P<0.001). Although TEE and PAEE were systematically underestimated during the 24 h period, the accelerometer assessed energy expenditure well during both the exercise period and the non-structured activities. Individual calibration factors may help to improve the accuracy of TEE estimation, but the average calibration factor for the group is probably sufficient for epidemiological research. This method is also important for assessing the diurnal profile of physical activity.