Magnitude Of Metabolic Changes Research Articles

Serum NMR metabolomics uncovers multiple metabolic changes in phenobarbital-treated dogs

IntroductionPhenobarbital is a commonly used anticonvulsant for the treatment of canine epileptic seizures. In addition to its central nervous system (CNS) depressing effects, long-term phenobarbital administration affects liver function. However, broader metabolic consequences of phenobarbital treatment are poorly characterized.ObjectivesTo identify metabolic changes in the sera of phenobarbital-treated dogs and to investigate the relationship between serum phenobarbital concentration and metabolite levels.MethodsLeftovers of clinical samples were used: 58 cases with phenobarbital concentrations ranging from 7.8 µg/mL to 50.8 µg/mL, and 25 controls. The study design was cross-sectional. The samples were analyzed by a canine-specific 1H NMR metabolomics platform. Differences between the case and control groups were evaluated by logistic regression. The linear relationship between metabolite and phenobarbital concentrations was evaluated using linear regression.ResultsIncreasing concentrations of glycoprotein acetyls, LDL particle size, palmitic acid, and saturated fatty acids, and decreasing concentrations of albumin, glutamine, histidine, LDL particle concentration, multiple HDL measures, and polyunsaturated fatty acids increased the odds of the sample belonging to the phenobarbital-treated group, having a p-value < .0033, and area under the curve (AUC) > .7. Albumin and glycoprotein acetyls had the best discriminative ability between the groups (AUC: .94). No linear associations between phenobarbital and metabolite concentrations were observed.ConclusionThe identified metabolites are known to associate with, for example, liver and CNS function, inflammatory processes and drug binding. The lack of a linear association to phenobarbital concentration suggests that other factors than the blood phenobarbital concentration contribute to the magnitude of metabolic changes.

A big-data approach to understanding metabolic rate and response to obesity in laboratory mice.

Maintaining a healthy body weight requires an exquisite balance between energy intake and energy expenditure. To understand the genetic and environmental factors that contribute to the regulation of body weight, an important first step is to establish the normal range of metabolic values and primary sources contributing to variability. Energy metabolism is measured by powerful and sensitive indirect calorimetry devices. Analysis of nearly 10,000 wild-type mice from two large-scale experiments revealed that the largest variation in energy expenditure is due to body composition, ambient temperature, and institutional site of experimentation. We also analyze variation in 2329 knockout strains and establish a reference for the magnitude of metabolic changes. Based on these findings, we provide suggestions for how best to design and conduct energy balance experiments in rodents. These recommendations will move us closer to the goal of a centralized physiological repository to foster transparency, rigor and reproducibility in metabolic physiology experimentation.

Ramadan Fasting and Maternal Perspectives in Healthy Pregnant Women: Systematic Review

Background: Practicing fasting during Ramadan by pregnant women might be risky. Controversies still exist about the nature and the magnitude of metabolic changes in healthy pregnant women who practice fasting. Objectives: To systematically review literature pertaining to the practice of Ramadan fasting and the effect of fasting on maternal health. Methods: Relevant literature was obtained through searches of PubMed, and Cochran's. Incidence and duration of fasting, reasons for non - fasting, dietary changes, physical activity, weight changes, symptoms with fasting, and metabolic parameters for healthy pregnant women who fasted during Ramadan were extracted. Synthesis of data was performed when appropriate.

Short- and long-term quantitation reproducibility of brain metabolites in the medial wall using proton echo planar spectroscopic imaging

Proton echo planar spectroscopic imaging (PEPSI) is a fast magnetic resonance spectroscopic imaging (MRSI) technique that allows mapping spatial metabolite distributions in the brain. Although the medial wall of the cortex is involved in a wide range of pathological conditions, previous MRSI studies have not focused on this region. To decide the magnitude of metabolic changes to be considered significant in this region, the reproducibility of the method needs to be established. The study aims were to establish the short- and long-term reproducibility of metabolites in the right medial wall and to compare regional differences using a constant short-echo time (TE30) and TE averaging (TEavg) optimized to yield glutamatergic information. 2D sagittal PEPSI was implemented at 3T using a 32 channel head coil. Acquisitions were repeated immediately and after approximately 2 weeks to assess the coefficients of variation (COV). COVs were obtained from eight regions-of-interest (ROIs) of varying size and location. TE30 resulted in better spectral quality and similar or lower quantitation uncertainty for all metabolites except glutamate (Glu). When Glu and glutamine (Gln) were quantified together (Glx) reduced quantitation uncertainty and increased reproducibility was observed for TE30. TEavg resulted in lowered quantitation uncertainty for Glu but in less reliable quantification of several other metabolites. TEavg did not result in a systematically improved short- or long-term reproducibility for Glu. The ROI volume was a major factor influencing reproducibility. For both short- and long-term repetitions, the Glu COVs obtained with TEavg were 5-8% for the large ROIs, 12-17% for the medium sized ROIs and 16-26% for the smaller cingulate ROIs. COVs obtained with TE30 for the less specific Glx were 3-5%, 8-10% and 10-15%. COVs for N-acetyl aspartate, creatine and choline using TE30 with long-term repetition were between 2-10%. Our results show that the cost of more specific glutamatergic information (Glu versus Glx) is the requirement of an increased effect size especially with increasing anatomical specificity. This comes in addition to the loss of sensitivity for other metabolites. Encouraging results were obtained with TE30 compared to other previously reported MRSI studies. The protocols implemented here are reliable and may be used to study disease progression and intervention mechanisms.

Prostate cancer: value of magnetic resonance spectroscopy 3D chemical shift imaging

The results of recent studies of magnetic resonance imaging (MRI) combined with three-dimensional magnetic resonance spectroscopic imaging (3D-MRSI) demonstrate that the MRI/3D-MRSI exam is a unique method by which to noninvasively study the cellular metabolism and anatomy of the prostate. 3D-MRSI is emerging as the most specificity tool for non-invasive evaluation of the prostate cancer. The results of current MRI/3D-MRSI studies also provide evidence that the magnitude of metabolic changes in regions of cancer before therapy, as well as the extent of the time course of metabolic changes after therapy, may improve our understanding of cancer aggressiveness. Assessment of cancer spread outside the prostate can be significantly improved by combining MRI findings with estimates of metabolic abnormalities provided by 3D-MRSI. Clinically, combined MRI/3D-MRSI has already demonstrated a potential for improved diagnosis, staging, and treatment planning for patients with prostate cancer. This article reviewed the value of 3D-MRS imaging for the diagnosis, localization, staging, aggressiveness, and treatment planning of prostate cancer.

Effect of dietary l-carnitine and ractopamine-hcl (paylean) on the metabolic response to handling in growing-finishing pigs (2004)

Summary Two experiments (384 pigs) were conducted to determine the interactive effect of dietary L-carnitine and ractopamine·HCl (Paylean) on the metabolic response to handling. Experiments were arranged as split plots, with handling as the main plot and diet as subplots (4 pens/treatment). Dietary Lcarnitine (0 or 50 ppm) was fed from 85 lb to the end of the trials (260 lb) and Paylean (0 or 20 ppm) was fed for the last 4 wk of each trial. At the end of each trial, two pigs per pen were assigned to one of two handling treatments. Gentle-handled pigs were moved at a moderate pace three times through a 164-ft course and up and down a 15° loading ramp. Nongentle-handled pigs were moved at a faster pace, up and down a 30° ramp, and were shocked by an electrical prod. Blood was collected immediately before and after handling in Exp. 1 and immediately after and 1 h after handling in Exp. 2. Feeding Paylean increased (P 0.10) effect of L-carnitine on growth performance in either trial. In Exp. 1 and 2, nongentle handling increased (P 0.96) by 1 h post-handling. Lactate, LDH, cortisol, and temperature changes from immediately posthandling to 1 h post-handling were not different for pigs fed L-carnitine or Paylean, suggesting that L-carnitine did not decrease recovery time of pigs subjected to non-gentle handling. These results demonstrate the importance of proper handling technique to minimize stressful events during the loading and transporting of pigs, regardless of whether either of these feed additives is being fed. This was evident by the large magnitude of the metabolic changes observed for the handling treatments, whereas in general the magnitude of metabolic changes from the dietary treatments was much smaller. Nonetheless, pigs fed Paylean are more susceptible to stress when handled aggressively, compared with pigs not fed Paylean. Dietary L-carnitine did not alleviate the effects of stress when fed in combination with Paylean.

Metabolic and Myoelectrical Effects of Acute Hypoxaemia during Isometric Contraction of Forearm Muscles in Humans: A Combined 31P-Magnetic Resonance Spectroscopy-Surface Electromyogram (MRS—SEMG) Study

1. Failure of muscle force during sustained fatiguing contraction is associated with myoelectrical and metabolic alterations. However, the inter-relationships between these two types of events remain unclear. The purpose of this study was to examine the effects of decreased oxygen availability during sustained contraction on myoelectrical and metabolic changes, thereby addressing the issue of fatigue. 2. 31P-Magnetic resonance spectra and surface electromyograms were simultaneously recorded in six subjects (three women and three men) performing isometric contraction of forearm flexor muscles sustained at 60% maximum value of force under aerobic or acute hypoxaemic conditions (inhalation of a gas mixture containing 12% O2). 3. The 5 min hypoxaemic rest preceding contraction did not affect the phosphocreatine level and pH value. Under both conditions of oxygen availability, the magnitude of metabolic changes remained similar and the duration of contraction was unaffected (similar workload). However, hypoxaemia significantly reduced the rate of changes in integrated surface electromyogram activity measured in the high-frequency band. Correlative analysis of magnetic resonance spectroscopy and surface electromyogram data shows that for a given surface electromyogram change, metabolic variations were always larger under hypoxaemic conditions. 4. These results suggest that hypoxaemia does not alter metabolic changes, i.e. decrease in pH and phosphocreatine during static contraction. The downward shift of the relationships between myoelectrical and metabolic changes under hypoxaemia points to the existence of a better excitation-contraction coupling in acute hypoxaemia compared with normoxia and this is indicative of an adaptative mechanism.