Metabolomics network characterization of resuscitation after normocapnic hypoxia in a newborn piglet model supports the hypothesis that room air is better.

Perinatal asphyxia is attributed to hypoxia and/or ischemia around the time of birth and may lead to multiorgan dysfunction. Aim of this research article is to investigate whether different metabolomic profiles occurred according to oxygen concentration administered at resuscitation. In order to perform the experiment, forty newborn piglets were subjected to normocapnic hypoxia and reoxygenation and were randomly allocated in 4 groups resuscitated with different oxygen concentrations, 18%, 21%, 40%, and 100%, respectively. Urine metabolic profiles at baseline and at hypoxia were analysed by (1)H-NMR spectroscopy and metabolites were also identified by multivariate statistical analysis. Metabolic pathways associations were also built up by ingenuity pathway analysis (IPA). Bioinformatics analysis of metabolites characterized the effect of metabolism in the 4 groups; it showed that the 21% of oxygen is the most "physiological" and appropriate concentration to be used for resuscitation. Our data indicate that resuscitation with 21% of oxygen seems to be optimal in terms of survival, rapidity of resuscitation, and metabolic profile in the present animal model. These findings need to be confirmed with metabolomics in human and, if so, the knowledge of the perinatal asphyxia condition may significantly improve.

Clinical metabolomics and hematic ADMA predict the future onset of cardiorenal syndrome in young grown-up subjects who were born preterm.

OBJECTIVES: To look for differences in the urinary metabolic profile and in the hematic asymmetric dimethylarginine (ADMA) levels between a group of young adults born preterm with an extremely low birthweight (<1000 g; ex-ELBW; n=19) and a control group of subjects born at term with a weight appropriate for their gestational age (AGA; n=13); and to look for a possible correlation between the urinary metabolic profile in ex-ELBW and their hematic levels of ADMA. DESIGN AND METHODS: Urine samples were analyzed by (1)H nuclear magnetic resonance spectroscopy, and then submitted to unsupervised and supervised multivariate analysis. Samples of blood were collected and ADMA concentration was assessed by high-performance liquid chromatography. RESULTS: Using supervised PLS-DA (partial least squares discriminant analysis) model, the authors were able to discriminate between ex-ELBW and AGA. Statistically significant differences were detected in the ADMA levels between ex-ELBW and AGA (p<0.02). Ex-ELBW metabolic profile correlated with ADMA concentrations (r=0.456, p<0.05). Conversely, ADMA levels in AGA did not correlated with their metabolic profiles. CONCLUSIONS: This study demonstrates the relevance of the metabolomic technique as a predictive tool of the metabolic status in ex-ELBW. The relationship between ex-ELBW urinary metabolic profile and their blood ADMA levels suggests the presence of a subclinical cardio-renal involvement in these subjects.

[Hospital-based internal medicine: year 2011 in chief resident's perspective]. / Médecine interne générale en pratique hospitalière: l'année 2011 mise en perspective par les chefs de clinique.

The year 2011 was full of significant advances in all areas of medicine. Whether small or large issues, they all have an impact on daily practice in general internal medicine. For example, intravenous administration of diuretics in heart failure shows no benefit. But double dose may improve symptoms faster. Direct Xa inhibitors are emerging as alternative to anti-vitamin K. beta-blockers reduce overall mortality in COPD and do not worsen lung function significantly. Each year, the chief residents from the Department of internal medicine at the University hospital of Lausanne meet to share their readings. Twelve new therapeutic considerations of 2011 are reviewed here.

[An experimental model for assessing the risk factors for work-related stress in four Italian universities]. / Un modello sperimentale di valutazione del rischio stress lavoro-correlato: risultati ottenuti in ambito universitario.

This study, a collaborative effort among the Local Health Authority 2 of Perugia, Italy, the National Coordination of Worker's Safety Representatives for University and Research Institutions and the National Coordination for Protection and Prevention Services for Universities and Research Institutions, describes the results of a method used to evaluate work-related stress. Personnel from four Italian universities, which we call University I, II, III and IV geographically distributed in nord (1), center (2) and south (1) of Italy, responded to a questionnaire regarding risk evaluation of work-related stress in response to the Italian Law 81/2008. The methodology includes a preliminary analysis of the physical/technological and organizational/relational aspects of the company in order to determine a risk factor of work-related stress. This is followed by an evaluation by agencies competent in the areas of prevention and protection, (Administrative personnel of the company, Medical support persons, heads of the Prevention and Protection Service, employee representatives, and others) that apply a specific algorithm and by the employees through the completion of a questionnaire. The employees, mostly men, of the various universities, completed 510 questionnaires. Based on the results of the questionnaires and on a comparison between the expectations of the administration and the employees, the preventative measures that need to be adopted were identified. The results of this study show that there is not complete agreement between the administration and the employees regarding the work-related expectations. This difference in viewpoints could be a source of work-related stress. Some aspects of the study were shown to be of common concern in the various universities, while for other aspects, there were significantly different perceptions between male and female employees. An immediate response is needed with respect to some aspects in the work context and to plan further investigations where the results are not clear. The method used provides an adequate response to the legislative requirements and labor principles, in evaluating the risk of work related stress. In addition the method allows employees to contribute directly to the evaluation process.

Biochemical activity and multiple locations of particulate guanylate cyclase in Rhyacophila dorsalis acutidens (Insecta: Trichoptera) provide insights into the cGMP signalling pathway in Malpighian tubules.

In insect renal physiology, cGMP and cAMP have important regulatory roles. In Drosophila melanogaster, considered a good model for molecular physiology studies, and in other insects, cGMP and cAMP act as signalling molecules in the Malpighian tubules (MTs). However, many questions related to cyclic nucleotide functions are unsolved in principal cells (PC) and stellate cells (SC), the two cell types that compose the MT. In PC, despite the large body of information available on soluble guanylate cyclase (sGC) in the cGMP pathway, the functional circuit of particulate guanylate cyclase (pGC) remains obscure. In SC, on the other side, the synthesis and physiological role of the cGMP are still unknown. Our biochemical data regarding the presence of cyclic nucleotides in the MTs of Rhyacophila dorsalis acutidens revealed a cGMP level above the 50%, in comparison with the cAMP. The specific activity values for the membrane-bound guanylate cyclase were also recorded, implying that, besides the sGC, pGC is a physiologically relevant source of cGMP in MTs. Cytochemical studies showed ultrastructurally that there was a great deal of pGC on the basolateral membranes of both the principal and stellate cells. In addition, pGC was also detected in the contact zone between the two cell types and in the apical microvillar region of the stellate cells bordering the tubule lumen. The pGC signal is so well represented in PC and, unexpectedly in SC of MTs, that it is possible to hypothesize the existence of still uncharacterized physiological processes regulated by the pGC-cGMP system.

Metabolomics: the "new clinical chemistry" for personalized neonatal medicine.

Metabolomics is a new approach based on the systematic study of the full complement of metabolites in a biological sample. This technology consists of two sequential steps: (1) an experimental technique, based on mass spectrometry or nuclear magnetic resonance (NMR) spectroscopy, designed to profile low molecular weight compounds, and (2) multivariate data analysis. Metabolomic analysis of biofluids or tissues has been successfully used in the fields of physiology, diagnostics, functional genomics, pharmacology, toxicology and nutrition. Recent studies have evaluated how physiological variables or pathological conditions can affect metabolomic profiles of different biofluids in pediatric populations. Little is known about the overall metabolic status of the term and preterm neonate. On the other hand, the management of sick or preterm newborns might be improved if more information on perinatal/neonatal maturational processes and their metabolic background were available. At present, the use of metabolomics in Neonatology is still in the pioneering phase. Meaningful diagnostic information and simple, non-invasive collection techniques make urine a particularly suitable biofluid for metabolomic approach in neonatal medicine. Using NMR-based metabolomic analysis of urine, distinct metabolic patterns have been shown to be associated with different classes of gestational age in a population of preterm and term infants. Together with genomics and proteomics, metabolomics appears to be a promising tool in Neonatology for the monitoring of postnatal metabolic maturation, the identification of biomarkers as early predictors of outcome, the diagnosis and monitoring of various diseases and the "tailored" management of neonatal disorders.

Vagal nerve stimulation improves cerebellar tremor and dysphagia in multiple sclerosis.

Vagus nerve stimulation (VNS), an adjunctive approach for the treatment of epilepsy, was performed in three multiple sclerosis (MS) patients displaying postural cerebellar tremor (PCT) and dysphagia. Following VNS, improvement of PCT and dysphagia was manifested over a period of two and three months, respectively. In view of the involvement of the main brainstem visceral component of the vagus, the nucleus tractus solitarius (NTS), in modulating central pattern generators (CPGs) linked to both olive complex pathway and swallowing, improvement is likely to be VNS related. The results obtained suggest an additional therapeutic application for VNS and may represent a novel form of treatment in patients with severe MS.

A novel Cx32 mutation causes X-linked Charcot-Marie-Tooth disease with brainstem involvement and brain magnetic resonance spectroscopy abnormalities.

The objective of this study was to study genetic and phenotypic features of a family with X-linked Charcot-Marie-Tooth consisting of a healthy father, affected mother, two affected sons and one healthy one. A detailed electrophysiological and neuroimaging study, along with sequencing of the Cx32 gene, was performed in all family members. A novel Cx32 123 G>C mutation, determining an aminoacid variation (Glu41Asp), was found in the mother and the affected sons. An alteration in brainstem evoked potentials was found in the mother and one affected son. The affected son, who underwent magnetic resonance imaging, showed symmetrical hyperintensities in paratrigonal white matter, not found in his heterozygous mother, while both subjects exhibited alterations in brain metabolite ratios derived from localised proton-magnetic resonance spectroscopy. These data extend previous findings about central nervous system involvement in Cx32 mutated subjects and further support a functional role of the protein expression in oligodendrocytes.

Increase in 20-50 Hz (gamma frequencies) power spectrum and synchronization after chronic vagal nerve stimulation.

OBJECTIVE: Though vagus nerve stimulation (VNS) is an important option in pharmaco-resistant epilepsy, its mechanism of action remains unclear. The observation that VNS desynchronised the EEG activity in animals suggested that this mechanism could be involved in VNS antiepileptic effects in humans. Indeed VNS decreases spiking bursts, whereas its effects on the EEG background remain uncertain. The objective of the present study is to investigate how VNS affects local and inter regional syncronization in different frequencies in pharmaco-resistant partial epilepsy. METHODS: Digital recordings acquired in 11 epileptic subjects 1 year and 1 week before VNS surgery were compared with that obtained 1 month and 1 year after VNS activation. Power spectrum and synchronization were then analyzed and compared with an epileptic group of 10 patients treated with AEDs only. RESULTS: VNS decreases the synchronization of theta frequencies (P < 0.01), whereas it increases gamma power spectrum and synchronization (< 0.001 and 0.01, respectively). CONCLUSIONS: The reduction of theta frequencies and the increase in power spectrum and synchronization of gamma bands can be related to VNS anticonvulsant mechanism. In addition, gamma modulation could also play a seizure-independent role in improving attentional performances. SIGNIFICANCE: These results suggest that some antiepileptic mechanisms affected by VNS can be modulated by or be the reflection of EEG changes.

Localization of acid phosphatases in the cell fractions of chick liver.

3 molecular forms (P1, P2 and P3) of acid phosphatase (E.C. 3.1.3.2) have been detected in chicken liver homogenate. The different intracellular localization of these molecules has been demonstrated by cellular fractionation and electrophoretic analysis. P1 and P2 phosphatases are both present in the particulate fraction. P3 is present in a pure form in the soluble fraction. The difference between the enzyme molecules present in the particulate fraction and that in the soluble one is confirmed by the different activation-inhibition effect of various ions and substances on the enzymatic activity of subcellular fractions.

Acid and alkaline phosphatase heterogeneity in liver, heart and intestine of the adult chick.

The molecular heterogeneity of acid and alkaline phosphatase from chick liver, intestine and heart is demonstrated by polyacrilamide disc gel electrophoresis. Liver and heart show the same number of molecular forms of acid and alkaline phosphatases. In contrast, the intestine homogenate shows electrophoretic bands different in number and in gel position from those of the liver and of the heart.