Continuous versus single bolus enteral nutrition: comparison of energy metabolism in humans.

Continuous respiratory exchange measurements were performed on five women and five men for 1 h before and 6 h after the administration of a milkshake (53% carbohydrates, 30% lipid, and 17% protein energy) given either as a single bolus dose or continuously during 3 h using a nasogastric tube. The energy administered corresponded to 2.3 times the postabsorptive resting energy expenditure. Resting energy expenditure, respiratory quotient, plasma glucose, and insulin concentrations increased sooner and steeper, and plasma free fatty acids levels decreased earlier with the meal ingested as a single dose than with continuous administration. The magnitude of nutrient-induced thermogenesis was greater (P less than 0.01) with the single dose (means +/- SE, 10.0 +/- 0.6%) than with the continuous administration (8.1 +/- 0.5%). The overall (6 h) substrate balances were not significantly different between the two modes of administration. It is concluded that the mode of enteral nutrient administration influences the immediate thermogenic response as well as changes in respiratory quotient, glycemia, and insulinemia; however, the overall nutrient balance was not affected by the mode of enteral nutrient administration.

Secondary Aural Symptoms in Relation to Cranio-Cervical and General Disorders

The present thesis comprises two study populations. The first study sample (SS1) consisted of 411 adults examined and interviewed at three annual visits. The second study sample (SS2) consisted of 1720 adults who filled in a mailed questionnaire about secondary otalgia, tinnitus and fullness of ears. In the second phase of the SS2, 100 subjects with otalgia were examined and interviewed by specialist in stomatognathic physiology and otorhinolaryngology. In the third phase, 36 subjects participated in a randomized, controlled and blinded trial of effectiveness of occlusal appliance on secondary otalgia, facial pain, headache and treatment need of temporomandibular disorders (TMD). The standardized prevalence of recurrent secondary otalgia was 6%, tinnitus 15% and fullness of ears 8%. Aural symptoms were more frequent among young than old subjects. They were associated with other, simultaneous aural symptoms, TMD pain, head and neck region pain, and visits to a physician. The subjects with aural symptoms more often had tenderness on palpation of masticatory muscles and clinical signs of temporomandibular joint than the subjects without. 85% of the subjects reporting secondary otalgia had cervical spine or temporomandibular disorder or both. In SS1, the final model of secondary otalgia included active need treatment for TMD, elevated level of stress symptoms, and bruxism. In SS2, the final models of aural symptoms included associated aural symptoms, young age, TMD pain, headache and shoulder ache. Stabilization splint more effectively alleviated secondary otalgia and active treatment need for TMD than a palatal control splint. In patients with aural pain, tinnitus or fullness of ears, it is important to first rule out otologic and nasopharyngeal diseases that may cause the symptoms. If no explanation for aural symptoms is found, temporomandibular and cervical spine disorders should be rouled out to minimize unnecessary visits to a physician.

Effects of lactate on glucose metabolism in healthy subjects and in severely injured hyperglycemic patients.

Hepatic glucose production is autoregulated during infusion of gluconeogenic precursors. In hyperglycemic patients with multiple trauma, hepatic glucose production and gluconeogenesis are increased, suggesting that autoregulation of hepatic glucose production may be defective. To better understand the mechanisms of autoregulation and its possible alterations in metabolic stress, lactate was coinfused with glucose in healthy volunteers and in hyperglycemic patients with multiple trauma or critical illness. In healthy volunteers, infusion of glucose alone nearly abolished endogenous glucose production. Lactate increased gluconeogenesis (as indicated by a decrease in net carbohydrate oxidation with no change in total [13C]carbohydrate oxidation) but did not increase endogenous glucose production. In patients with metabolic stress, endogenous glucose production was not suppressed by exogenous glucose, but lactate did not further increase hepatic glucose production. It is concluded that 1) in healthy humans, autoregulation of hepatic glucose production during infusion of lactate is still present when glycogenolysis is suppressed by exogenous glucose and 2) autoregulation of hepatic glucose production is not abolished in hyperglycemic patients with metabolic stress.

In vivo analysis of efavirenz metabolism in individuals with impaired CYP2A6 function.

INTRODUCTION: The antiretroviral drug efavirenz (EFV) is extensively metabolized into three primary metabolites: 8-hydroxy-EFV, 7-hydroxy-EFV and N-glucuronide-EFV. There is a wide interindividual variability in EFV plasma exposure, explained to a great extent by cytochrome P450 2B6 (CYP2B6), the main isoenzyme responsible for EFV metabolism and involved in the major metabolic pathway (8-hydroxylation) and to a lesser extent in 7-hydroxylation. When CYP2B6 function is impaired, the relevance of CYP2A6, the main isoenzyme responsible for 7-hydroxylation may increase. We hypothesize that genetic variability in this gene may contribute to the particularly high, unexplained variability in EFV exposure in individuals with limited CYP2B6 function. METHODS: This study characterized CYP2A6 variation (14 alleles) in individuals (N=169) previously characterized for functional variants in CYP2B6 (18 alleles). Plasma concentrations of EFV and its primary metabolites (8-hydroxy-EFV, 7-hydroxy-EFV and N-glucuronide-EFV) were measured in different genetic backgrounds in vivo. RESULTS: The accessory metabolic pathway CYP2A6 has a critical role in limiting drug accumulation in individuals characterized as CYP2B6 slow metabolizers. CONCLUSION: Dual CYP2B6 and CYP2A6 slow metabolism occurs at significant frequency in various human populations, leading to extremely high EFV exposure.

The peroxisome proliferator-activated receptor alpha regulates amino acid metabolism.

The peroxisome proliferator-activated receptor alpha is a ligand-activated transcription factor that plays an important role in the regulation of lipid homeostasis. PPARalpha mediates the effects of fibrates, which are potent hypolipidemic drugs, on gene expression. To better understand the biological effects of fibrates and PPARalpha, we searched for genes regulated by PPARalpha using oligonucleotide microarray and subtractive hybridization. By comparing liver RNA from wild-type and PPARalpha null mice, it was found that PPARalpha decreases the mRNA expression of enzymes involved in the metabolism of amino acids. Further analysis by Northern blot revealed that PPARalpha influences the expression of several genes involved in trans- and deamination of amino acids, and urea synthesis. Direct activation of PPARalpha using the synthetic PPARalpha ligand WY14643 decreased mRNA levels of these genes, suggesting that PPARalpha is directly implicated in the regulation of their expression. Consistent with these data, plasma urea concentrations are modulated by PPARalpha in vivo. It is concluded that in addition to oxidation of fatty acids, PPARalpha also regulates metabolism of amino acids in liver, indicating that PPARalpha is a key controller of intermediary metabolism during fasting.

Transcriptional regulation of metabolism.

Our understanding of metabolism is undergoing a dramatic shift. Indeed, the efforts made towards elucidating the mechanisms controlling the major regulatory pathways are now being rewarded. At the molecular level, the crucial role of transcription factors is particularly well-illustrated by the link between alterations of their functions and the occurrence of major metabolic diseases. In addition, the possibility of manipulating the ligand-dependent activity of some of these transcription factors makes them attractive as therapeutic targets. The aim of this review is to summarize recent knowledge on the transcriptional control of metabolic homeostasis. We first review data on the transcriptional regulation of the intermediary metabolism, i.e., glucose, amino acid, lipid, and cholesterol metabolism. Then, we analyze how transcription factors integrate signals from various pathways to ensure homeostasis. One example of this coordination is the daily adaptation to the circadian fasting and feeding rhythm. This section also discusses the dysregulations causing the metabolic syndrome, which reveals the intricate nature of glucose and lipid metabolism and the role of the transcription factor PPARgamma in orchestrating this association. Finally, we discuss the molecular mechanisms underlying metabolic regulations, which provide new opportunities for treating complex metabolic disorders.

Correction: Topographical Body Fat Distribution Links to Amino Acid and Lipid Metabolism in Healthy Obese Women.

This corrects the article on p. e73445 in vol. 8.]. This corrects the article "Topographical Body Fat Distribution Links to Amino Acid and Lipid Metabolism in Healthy Non-Obese Women" , e73445. There was an error in the title of the article. The correct version of the title in the article is: Topographical Body Fat Distribution Links to Amino Acid and Lipid Metabolism in Healthy Obese Women The correct citation is: Martin F-PJ, Montoliu I, Collino S, Scherer M, Guy P, et al. (2013) Topographical Body Fat Distribution Links to Amino Acid and Lipid Metabolism in Healthy Obese Women. PLoS ONE 8(9): e73445. doi:10.1371/journal.pone.0073445

Ammonium alters creatine transport and synthesis in a 3D culture of developing brain cells, resulting in secondary cerebral creatine deficiency.

Hyperammonemic disorders in pediatric patients lead to poorly understood irreversible effects on the developing brain that may be life-threatening. We showed previously that some of these NH4+-induced irreversible effects might be due to impairment of axonal growth that can be protected under ammonium exposure by creatine co-treatment. The aim of the present work was thus to analyse how the genes of arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), allowing creatine synthesis, as well as of the creatine transporter SLC6A8, allowing creatine uptake into cells, are regulated in rat brain cells under NH4+ exposure. Reaggregated brain cell three-dimensional cultures exposed to NH4Cl were used as an experimental model of hyperammonemia in the developing central nervous system (CNS). We show here that NH4+ exposure differentially alters AGAT, GAMT and SLC6A8 regulation, in terms of both gene expression and protein activity, in a cell type-specific manner. In particular, we demonstrate that NH4+ exposure decreases both creatine and its synthesis intermediate, guanidinoacetate, in brain cells, probably through the inhibition of AGAT enzymatic activity. Our work also suggests that oligodendrocytes are major actors in the brain in terms of creatine synthesis, trafficking and uptake, which might be affected by hyperammonemia. Finally, we show that NH4+ exposure induces SLC6A8 in astrocytes. This suggests that hyperammonemia increases blood-brain barrier permeability for creatine. This is normally limited due to the absence of SLC6A8 from the astrocyte feet lining microcapillary endothelial cells, and thus creatine supplementation may protect the developing CNS of hyperammonemic patients.

Alteration of glucose metabolism in cultured astrocytes after AQP9-small interference RNA application.

Aquaglyceroporin-9 (AQP9) facilitates diffusion of water and energy substrates such as glycerol and monocarboxylates. AQP9 is present in plasma membrane and mitochondria of astrocytes and catecholaminergic neurons, suggesting that it plays a role in the energetic status of these cells. Using specific small interference RNA directed against AQP9 in astrocyte cultures, we showed that glycerol uptake is decreased which is associated with an increase in glucose uptake and oxidative metabolism. Our results not only confirm the presence of AQP9 in astrocytes but also suggest that changes in AQP9 expression alter glial energy metabolism.

ParA2, a Vibrio cholerae chromosome partitioning protein, forms left-handed helical filaments on DNA.

Most bacterial chromosomes contain homologs of plasmid partitioning (par) loci. These loci encode ATPases called ParA that are thought to contribute to the mechanical force required for chromosome and plasmid segregation. In Vibrio cholerae, the chromosome II (chrII) par locus is essential for chrII segregation. Here, we found that purified ParA2 had ATPase activities comparable to other ParA homologs, but, unlike many other ParA homologs, did not form high molecular weight complexes in the presence of ATP alone. Instead, formation of high molecular weight ParA2 polymers required DNA. Electron microscopy and three-dimensional reconstruction revealed that ParA2 formed bipolar helical filaments on double-stranded DNA in a sequence-independent manner. These filaments had a distinct change in pitch when ParA2 was polymerized in the presence of ATP versus in the absence of a nucleotide cofactor. Fitting a crystal structure of a ParA protein into our filament reconstruction showed how a dimer of ParA2 binds the DNA. The filaments formed with ATP are left-handed, but surprisingly these filaments exert no topological changes on the right-handed B-DNA to which they are bound. The stoichiometry of binding is one dimer for every eight base pairs, and this determines the geometry of the ParA2 filaments with 4.4 dimers per 120 A pitch left-handed turn. Our findings will be critical for understanding how ParA proteins function in plasmid and chromosome segregation.

Secondary Accident Data Fusion for Assessing Long-Term Performance of Transportation Systems, 2007

Secondary accident statistics can be useful for studying the impact of traffic incident management strategies. An easy-to-implement methodology is presented for classifying secondary accidents using data fusion of a police accident database with intranet incident reports. A current method for classifying secondary accidents uses a static threshold that represents the spatial and temporal region of influence of the primary accident, such as two miles and one hour. An accident is considered secondary if it occurs upstream from the primary accident and is within the duration and queue of the primary accident. However, using the static threshold may result in both false positives and negatives because accident queues are constantly varying. The methodology presented in this report seeks to improve upon this existing method by making the threshold dynamic. An incident progression curve is used to mark the end of the queue throughout the entire incident. Four steps in the development of incident progression curves are described. Step one is the processing of intranet incident reports. Step two is the filling in of incomplete incident reports. Step three is the nonlinear regression of incident progression curves. Step four is the merging of individual incident progression curves into one master curve. To illustrate this methodology, 5,514 accidents from Missouri freeways were analyzed. The results show that secondary accidents identified by dynamic versus static thresholds can differ by more than 30%.

Lack of Discipline in Cape Verdean Secondary Schools: The Need to Better Define the Problem and Develop Strategies to Prevent or Manage the Situation

This research paper has been written with the intention to discuss the problem of discipline in Cape Verdean secondary schools. While many of us discuss the effects that student misbehavior has on the student misbehavior has on the student, school and society as a whole, very few of us seek solutions which would impact on the prevention and management of this problem that each day becomes more complicated and harder to handle. This paper will discuss the need to better define discipline at the school level; identify the causes and factors that aggravate the problem, in addition, to provide what I hope to be useful strategies to better manage the problem as we make the effort to reclaim our schools and better educate our students. My research included surveys completed by teachers and student alike as they baffled over the question: what is discipline and how can we better manage discipline problems at our schools?

The use of textbooks in Capeverdean secondary schools: The Relationship between Use, Evaluation and Adaptation of Textbooks

This study examines the relationship between teacher’s use of English textbooks and the way teachers evaluate and adapt them, looking at a particular context, the Capeverdean secondary schools, specifically in Praia. The referred relationship was analyzed through teachers’ responses about how they use, evaluate and adapt their textbooks. The results of the study revealed that, on the one hand, the way teachers use their textbooks influences the way they evaluate the same textbooks; on the other hand, the use of textbooks doesn’t necessarily influence the way teachers adapt them. Moreover, the findings revealed that, in general, due to some particular constraints the Capeverdean English teachers are using their textbooks as resources, in which several textbooks are used in combination with one another. Additionally, although teachers assume that they are doing their best, they still need more confidence concerning the way they use, evaluate and adapt available textbooks. Teachers’ confidence in the way they are using their textbooks can be reinforced by establishing an intensive teacher training module on materials evaluation and adaptation, taking into account that a textbook is one of the most important tools in the process of teaching and learning. I hope that the elements presented may lead to further studies on this matter, specifically regarding textbook evaluation and adaptation.