This cross sectional study aims to investigate the associations between ectopic lipid accumulation in liver and skeletal muscle and biochemical measures, estimates of insulin resistance, anthropometry, and blood pressure in lean and overweight/obese children.
Fasting plasma glucose, serum lipids, serum insulin, and expressions of insulin resistance, anthropometry, blood pressure, and magnetic resonance spectroscopy of liver and muscle fat were obtained in 327 Danish children and adolescents aged 8-18 years.
In 287 overweight/obese children, the prevalences of hepatic and muscular steatosis were 31% and 68%, respectively, whereas the prevalences in 40 lean children were 3% and 10%, respectively. A multiple regression analysis adjusted for age, sex, body mass index z-score (BMI SDS), and pubertal development showed that the OR of exhibiting dyslipidemia was 4.2 (95%CI: [1.8; 10.2], p = 0.0009) when hepatic steatosis was present. Comparing the simultaneous presence of hepatic and muscular steatosis with no presence of steatosis, the OR of exhibiting dyslipidemia was 5.8 (95%CI: [2.0; 18.6], p = 0.002). No significant associations between muscle fat and dyslipidemia, impaired fasting glucose, or blood pressure were observed. Liver and muscle fat, adjusted for age, sex, BMI SDS, and pubertal development, associated to BMI SDS and glycosylated hemoglobin, while only liver fat associated to visceral and subcutaneous adipose tissue and intramyocellular lipid associated inversely to high density lipoprotein cholesterol.
Hepatic steatosis is associated with dyslipidemia and liver and muscle fat depositions are linked to obesity-related metabolic dysfunctions, especially glycosylated hemoglobin, in children and adolescents, which suggest an increased cardiovascular disease risk.
Notes
Cites: Child Obes. 2012 Dec;8(6):533-4123181919
Cites: Int J Pediatr Obes. 2011 Aug;6(3-4):188-9621529264
Cites: Int J Obes (Lond). 2014 Jan;38(1):40-523828099
This article summarizes the current status of 1H MRS in detecting and quantifying a boron neutron capture therapy (BNCT) boron carrier, L-p-boronophenylalanine-fructose (BPA-F) in vivo in the Finnish BNCT project. The applicability of 1H MRS to detect BPA-F is evaluated and discussed in a typical situation with a blood containing resection cavity within the gross tumour volume (GTV). 1H MRS is not an ideal method to study BPA concentration in GTV with blood in recent resection cavity. For an optimal identification of BPA signals in the in vivo 1H MR spectrum, both pre- and post-infusion 1H MRS should be performed. The post-infusion spectroscopy studies should be scheduled either prior to or, less optimally, immediately after the BNCT. The pre-BNCT MRS is necessary in order to utilise the MRS results in the actual dose planning.
Hemorrhagic shock (HS) following trauma is a leading cause of death among persons under the age of 40. During HS the body undergoes systemic warm ischemia followed by reperfusion during medical intervention. Ischemia/reperfusion (I/R) results in a disruption of cellular metabolic processes that ultimately lead to tissue and organ dysfunction or failure. Resistance to I/R injury is a characteristic of hibernating mammals. The present study sought to identify circulating metabolites in the rat as biomarkers for metabolic alterations associated with poor outcome after HS. Arctic ground squirrels (AGS), a hibernating species that resists I/R injury independent of decreased body temperature (warm I/R), was used as a negative control.
Male Sprague-Dawley rats and AGS were subject to HS by withdrawing blood to a mean arterial pressure (MAP) of 35 mmHg and maintaining the low MAP for 20 min before reperfusing with Ringers. The animals' temperature was maintained at 37 ? 0.5 ?C for the duration of the experiment. Plasma samples were taken immediately before hemorrhage and three hours after reperfusion. Hydrophilic and lipid metabolites from plasma were then analyzed via 1H-NMR from unprocessed plasma and lipid extracts, respectively. Rats, susceptible to I/R injury, had a qualitative shift in their hydrophilic metabolic fingerprint including differential activation of glucose and anaerobic metabolism and had alterations in several metabolites during I/R indicative of metabolic adjustments and organ damage. In contrast, I/R injury resistant AGS, regardless of season or body temperature, maintained a stable metabolic homeostasis revealed by a qualitative 1H-NMR metabolic profile with few changes in quantified metabolites during HS-induced global I/R.
An increase in circulating metabolites indicative of anaerobic metabolism and activation of glycolytic pathways is associated with poor prognosis after HS in rats. These same biomarkers are absent in AGS after HS with warm I/R.
Notes
Cites: Am J Physiol Regul Integr Comp Physiol. 2010 Feb;298(2):R329-4019923364
Cites: Gerontology. 2010;56(2):220-3019602865
Cites: Am J Physiol Regul Integr Comp Physiol. 2011 Nov;301(5):R1440-5221865542
Cites: Transplantation. 2011 Dec 15;92(11):1215-2122082817
Cites: Am J Respir Crit Care Med. 2011 Sep 15;184(6):647-5521680948
The 1H NMR spectra of the lipid region of human plasma from healthy adults, neonates, and patients with malignant and nonmalignant tumors have been recorded on a JNM-GX400 FT spectrometer operating at 399.6 MHz for protons. The chemical shifts of methylene and methyl groups of plasma lipids were measured with respect to the higher field component of the methyl proton resonance of the lactate molecule. The results show that there are changes in the chemical shifts of the methylene proton resonances among the plasma from healthy adults, adults with tumors, and neonates. The shifts observed in the case of cancer patients and neonates are in the direction opposite to the shift measured from the plasma of healthy adults. Thus, the observed changes cannot be explained by the activity in the cell proliferation of tissues which is high in the cases of both healthy neonates and patients with malignant tumors, but they most probably reflect the different lipoprotein compositions of neonates, healthy adults, and adults with tumors.
To evaluate the energy metabolism of peripheral skeletal muscle during exercise in patients with chronic respiratory impairment, the 31P-nuclear magnetic resonance (NMR) spectra of forearm muscle were investigated in nine patients and nine age-matched control subjects. We calculated the phosphocreatine (PCr) to PCr + inorganic phosphate (PI) ratio, the time constant of PCr recovery and the intracellular pH. The exercise consisted of repetitive hand grips against a 2-kg load every 3 s for 6 min (0.33 W). The patients showed a marked decrease in the PCr/(PCr + PI) ratio and pH in the muscle during exercise in contrast to the control subjects whose PCr/(PCr + PI) showed a minor decrease without any change in pH. The relationship between PCr utilization and pH demonstrated that anaerobic glycolysis switched on earlier in patients with chronic respiratory impairment. A split PI peak was observed in five of nine patients during exercise. The PCr/(PCr + PI) ratio during the last minute of exercise correlated significantly with the vital capacity (% predicted), with the FEV1/FVC, with the body weight, with the maximum strength of hand grip, and with the muscle mass. The results indicate impaired oxidative phosphorylation and the early activation of anaerobic glycolysis in the muscles of patients with chronic respiratory impairment. Several factors related to chronic respiratory impairment, such as disuse, malnutrition and dysoxia, would contribute to the metabolic changes observed in the muscles examined.
Abnormality of energy metabolism in the skeletal muscle of patients with liver cirrhosis and changes under administration of glucose and branched-chain amino acids.
We assessed changes in skeletal muscle energy metabolism by 31P-magnetic resonance spectroscopy (31P-MRS) and oxygen supply by near-infrared spectroscopy (NIR), after exercise and after administration of glucose and a branched-chain amino acids (BCAA), in healthy volunteers and patients with liver cirrhosis. As for the patients with liver cirrhosis, 4 were classified in Child-Pugh Grade A and the other 4 in Grade B. In patients with liver cirrhosis, the intramuscular pH and PCr index (PCr/PCr + Pi) were lower than in healthy subjects after exercise in the fasting state; the deltapH and deltaPCr index were statistically siginificant (p
Quantitative magnetic resonance (QMR) has previously been shown to both overestimate and underestimate average fat mass (FM) in humans. Eight-electrode bioelectrical impedance analysis (BIA) has previously been found biased as well as successfully validated. We report cross-sectional accuracy of QMR and eight-electrode BIA evaluated with air displacement plethysmography (ADP) as reference method.
Fat mass and fat free mass (FFM) by QMR and eight-electrode BIA were evaluated against ADP as reference in 38 normal weight and 30 obese women. Total body water estimates by QMR and eight-electrode BIA were compared.
In a previous study, the methanolic extract as well as the chloroform fraction of the aerial parts of Caralluma quadrangula (Forssk.) N.E.Br. indigenous to Saudi Arabia showed significant in vitro cytotoxic activity against breast cancer (MCF7) cell line. In a biologically-guided fractionation approach, four acylated pregnane glycosides were isolated from the chloroform fraction of C. quadrangula. The structures of the isolated compounds were elucidated by the analysis of their MS and NMR data. The compounds were identified as 12,20-di-O-benzoylboucerin 3-O-ß-D-digitoxopyranosyl-(1?4)-ß-D-canaropyranosyl-(1?4)-ß-D-cymaropyranoside (1), 12,20-di-O-benzoylboucerin 3-O-ß-D-cymaropyranosyl-(1?4)-ß-D-canaropyranosyl-(1?4)-ß-D-cymaropyranoside (2), 12,20-di-O-benzoylboucerin 3-O-ß-D-glucopyranosyl-(1?4)-ß-D-digitoxopyranosyl-(1?4)-ß-D-canaropyranosyl-(1?4)-ß-D-cymaropyranoside (3) and 12,20-di-O-benzoyl-3ß,5a,12ß,14ß,20-pentahydroxy-(20R)-pregn-6-ene 3-O-ß-D-glucopyranosyl-(1?4)-ß-D-digitoxopyranosyl-(1?4)-ß-D-canaropyranosyl-(1?4)-ß-D-cymaropyranoside (4). The isolated compounds were tested for their cytotoxic activity against breast cancer (MCF7) cell line.
Protein disulphide isomerase (PDI) is a key multi-domain protein folding catalyst in the endoplasmic reticulum. The b' domain of PDI is essential for the non-covalent binding of incompletely folded protein substrates. Earlier, we defined the substrate binding site in the b' domain of human PDI by modelling and mutagenesis studies. Here, we show by fluorescence and NMR that recombinant human PDI b'x (comprising the b' domain and the subsequent x linker region) can assume at least two different conformations in solution. We have screened mutants in the b'x region to identify mutations that favour one of these conformers in recombinant b'x, and isolated and characterised examples of both types. We have crystallised one mutant of b'x (I272A mutation) in which one conformer is stabilized, and determined its crystal structure to a resolution of 2.2 A. This structure shows that the b' domain has the typical thioredoxin fold and that the x region can interact with the b' domain by "capping" a hydrophobic site on the b' domain. This site is most likely the substrate binding site and hence such capping will inhibit substrate binding. All of the mutations we previously reported to inhibit substrate binding shift the equilibrium towards the capped conformer. Hence, these mutations act by altering the natural equilibrium and decreasing the accessibility of the substrate binding site. Furthermore, we have confirmed that the corresponding structural transition occurs in the wild type full-length PDI. A cross-comparison of our data with that for other PDI-family members, Pdi1p and ERp44, suggests that the x region of PDI can adopt alternative conformations during the functional cycle of PDI action and that these are linked to the ability of PDI to interact with folding substrates.
