Observation and identification of metabolites emerging during postmortem decomposition of brain tissue by means of in situ 1H-magnetic resonance spectroscopy.

Postmortem decomposition of brain tissue was investigated by (1)H-magnetic resonance spectroscopy (MRS) in a sheep head model and selected human cases. Aiming at the eventual estimation of postmortem intervals in forensic medicine, this study focuses on the characterization and identification of newly observed metabolites. In situ single-voxel (1)H-MRS at 1.5 T was complemented by multidimensional homo- and heteronuclear high-resolution NMR spectroscopy of an extract of sheep brain tissue. The inclusion of spectra of model solutions in the program LC Model confirmed the assignments in situ. The first postmortem phase was characterized mainly by changes in the concentrations of metabolites usually observed in vivo and by the appearance of previously reported decay products. About 3 days postmortem, new metabolites, including free trimethylammonium, propionate, butyrate, and iso-butyrate, started to appear in situ. Since the observed metabolites and the time course is comparable in sheep and human brain tissue, the model system seems to be appropriate.     

Interaction between dietary lipids and physical inactivity on insulin sensitivity and on intramyocellular lipids in healthy men

OBJECTIVE: To assess the effect of a possible interaction between dietary fat and physical inactivity on whole-body insulin sensitivity and intramyocellular lipids (IMCLs). RESEARCH DESIGN AND METHODS: Eight healthy male volunteers were studied on two occasions. After 2 days of an equilibrated diet and moderate physical activity, participants remained inactive (bed rest) for 60 h and consumed either a high-saturated fat (45% fat, of which approximately 60% was saturated fat [BR-HF]) or a high-carbohydrate (70% carbohydrate [BR-HCHO]) diet. To evaluate the effect of a high-fat diet alone, six of the eight volunteers were restudied after a 2-day equilibrated diet followed by 60 h on a high-saturated fat diet and controlled physical activity (PA-HF). Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and IMCL concentrations by (1)H-magnetic resonance spectroscopy. RESULTS: Insulin-mediated glucose disposal was decreased by BR-HF condition (-24 +/- 6%, P < 0.05) but did not change with BR-HCHO (+19 +/- 10%, NS). BR-HF and BR-HCHO increased IMCL levels (+32 +/- 7%, P < 0.05 and +17 +/- 8%, P < 0.0011, respectively). Although the increase in IMCL levels with PA-HF (+31 +/- 19%, P = 0.12) was similar to that during BR-HF, insulin-mediated glucose disposal (-7 +/- 9%, NS) was not decreased. CONCLUSIONS: These data indicate that physical inactivity and a high-saturated fat diet may interact to reduce whole-body insulin sensitivity. IMCL content was influenced by dietary lipid and physical inactivity but was not directly associated with insulin resistance.     

A 4-wk high-fructose diet alters lipid metabolism without affecting insulin sensitivity or ectopic lipids in healthy humans

BACKGROUND: High fructose consumption is suspected to be causally linked to the epidemics of obesity and metabolic disorders. In rodents, fructose leads to insulin resistance and ectopic lipid deposition. In humans, the effects of fructose on insulin sensitivity remain debated, whereas its effect on ectopic lipids has never been investigated. OBJECTIVE: We assessed the effect of moderate fructose supplementation on insulin sensitivity (IS) and ectopic lipids in healthy male volunteers (n = 7). DESIGN: IS, intrahepatocellular lipids (IHCL), and intramyocellular lipids (IMCL) were measured before and after 1 and 4 wk of a high-fructose diet containing 1.5 g fructose . kg body wt(-1) . d(-1). Adipose tissue IS was evaluated from nonesterified fatty acid suppression, hepatic IS from suppression of hepatic glucose output (6,6-2H2-glucose), and muscle IS from the whole-body glucose disposal rate during a 2-step hyperinsulinemic euglycemic clamp. IHCL and IMCL were measured by 1H magnetic resonance spectroscopy. RESULTS: Fructose caused significant (P < 0.05) increases in fasting plasma concentrations of triacylglycerol (36%), VLDL-triacylglycerol (72%), lactate (49%), glucose (5.5%), and leptin (48%) without any significant changes in body weight, IHCL, IMCL, or IS. IHCL were negatively correlated with triacylglycerol after 4 wk of the high-fructose diet (r = -0.78, P < 0.05). CONCLUSION: Moderate fructose supplementation over 4 wk increases plasma triacylglycerol and glucose concentrations without causing ectopic lipid deposition or insulin resistance in healthy humans.     

Noninvasive assessment of exercise-related intramyocellular acetylcarnitine in euglycemia and hyperglycemia in patients with type 1 diabetes using ¹H magnetic resonance spectroscopy: a randomized single-blind crossover study

OBJECTIVE

Intramyocellular acetylcarnitine (IMAC) is involved in exercise-related fuel metabolism. It is not known whether levels of systemic glucose influence IMAC levels in type 1 diabetes.

RESEARCH DESIGN AND METHODS

Seven male individuals with type 1 diabetes performed 120 min of aerobic exercise at 55–60% of Vo_2max randomly on two occasions (glucose clamped to 5 or 11 mmol/l, identical insulinemia). Before and after exercise, IMAC was detected by ¹H magnetic resonance spectroscopy in musculus vastus intermedius.

RESULTS

Postexercise levels of IMAC were significantly higher than pre-exercise values in euglycemia (4.30 ± 0.54 arbitrary units [a.u.], P < 0.001) and in hyperglycemia (2.44 ± 0.53 a.u., P = 0.01) and differed significantly according to glycemia (P < 0.01). The increase in exercise-related levels of IMAC was significantly higher in euglycemia (3.97 ± 0.45 a.u.) than in hyperglycemia (1.71 ± 0.50 a.u.; P < 0.01).

CONCLUSIONS

The increase in IMAC associated with moderate aerobic exercise in individuals with type 1 diabetes was significantly higher in euglycemia than in hyperglycemia.Intramyocellular acetylcarnitine (IMAC) is involved in the regulation of fat and carbohydrate oxidation in skeletal muscle during moderate aerobic exercise (1). Although carnitine metabolism appears comparable in patients with type 1 diabetes and healthy control subjects (2), it is not known whether IMAC is related to variations in fuel metabolism observed during exercise under differing glycemic levels in type 1 diabetes (3). Given the controversial results from previous studies linking IMAC to increased β-oxidation (4) but also to high glycolytic flux (1), the aim of the present study was to assess exercise-related concentrations of IMAC noninvasively by ¹H magnetic resonance spectroscopy (¹H MRS) (5,6) in patients with type 1 diabetes in euglycemia and hyperglycemia.     

Dynamic non-invasive ASL perfusion imaging of a normal pancreas with secretin augmented MR imaging

Objectives

To investigate prospectively the repeatability of pancreatic perfusion measurements using arterial spin labelling (ASL) and to determine the increase in perfusion due to secretin stimulation.

Material and methods

An (FAIR)-TrueFISP ASL sequence was applied to determine the perfusion of the pancreatic head in a 3T MRI scanner. Ten healthy volunteers (four men, six women: mean age 28.5 ± 4.6 years; age range 25–40 years) were investigated twice within 1 week. The inter-individual variability was calculated using the standard deviation. Intra-individual agreement between the first and second scan was estimated using the Pearson correlation coefficient. A paired Wilcoxon rank-sum test was used to compare perfusion at baseline (BL) and during secretin stimulation.

Results

The mean BL perfusion of the pancreatic head was 285 ± 96 mL/100 g/min with an intra-individual correlation coefficient of 0.67 (strong) for repeated measurements. Secretin stimulation led to a significant increase (by 81%) in perfusion of the pancreatic head to 486 ±156 mL/100 g/min (p=0.002) with an intra-individual correlation of 0.29 (weak). A return to BL values was observed after 239 ± 92 s with a moderate intra-individual correlation coefficient of 0.42 for repeat measurements.

Conclusion

Dynamic non-invasive ASL imaging of the pancreas permitted quantification of pancreatic perfusion in a clinically applicable setting.

Key Points

? ASL imaging of the pancreas permitted quantification of pancreatic perfusion? Secretin stimulation led to a significant increase in pancreatic perfusion? The intra-individual correlation coefficient for baseline perfusion was strong for repeated measurements

     

Does the presence of the fibronectin-aggrecan complex predict outcomes from lumbar discectomy for disc herniation?

Background context

Protein biomarkers associated with lumbar disc disease have been studied as diagnostic indicators and therapeutic targets. Recently, a cartilage degradation product, the fibronectin-aggrecan complex (FAC) identified in the epidural space, has been shown to predict response to lumbar epidural steroid injection in patients with radiculopathy from herniated nucleus pulposus (HNP).

Effect of oral D-tagatose on liver volume and hepatic glycogen accumulation in healthy male volunteers

Standard toxicity tests with high levels of D-tagatose showed a reversible enlargement of the liver in Sprague-Dawley rats without increase of liver enzymes. The present study tests the hypotheses that partial substitution of dietary sucrose by D-tagatose for 28 days increases the volume of human liver and the concentration of liver glycogen. Twelve healthy, male volunteers were studied in a double-blind crossover study with ingestion of D-tagatose (3x15 g daily) and placebo (sucrose, 3x15 g daily) for periods of 28 days each. Liver volume and glycogen concentration have been determined by magnetic resonance (MR) imaging and spectroscopy, which were accompanied by routine medical examinations. MR examinations before and after the treatments revealed no effects (P>0.05) of treatment, period, or subject for changes in liver volume or glycogen concentration. A steady increase of liver volumes, independent of the D-tagatose or placebo intake, has been observed over the study in parallel with a slight increase in body weight. The treatment with D-tagatose was not associated with clinically relevant changes of the examined clinico-chemical and hematological parameters, including liver enzymes and uric acid.     

Preoperative mapping of arterial spinal supply using 3.0-T MR angiography with an intravasal contrast medium and high-spatial-resolution steady-state

Introduction

Preoperative mapping of the arterial spinal supply prior to thoracoabdominal aortic aneurysm repair is highly relevant because of high risk for postoperative ischemic spinal cord injuries such as paraparesis or paraplegia.

Methods

Twenty-four consecutive patients prior to surgical thoracoabdominal aortic aneurysm repair were investigated. All patients underwent steady-state MR angiography (MRA) of the spinal vasculature with 3-T MRI. The sequence used was a steady-state coronary 3D FLASH with 0.7-mm isotropic voxels. MRA was performed using an intravasal contrast agent. Studies were evaluated by three readers including delineation of arterial spinal supply including both aortic origin and spinal canal entry by three readers.

Results

Identification and localization of the Adamkiewicz artery and its spinal canal entry was successful in all patients. Overall depiction of the vascular anatomy was graded as very good in 3 (12.5%), good in 14 (58.4%), sufficient in 5 (20.8%), and poor in 2 (8.3%) patients. Depiction of segmental artery aortic exit level was graded as good in 6 (25.0%), sufficient in 10 (41.7%), poor in 4 (16.7%) and not identifiable in 4 (16.7%) patients. Delineation of segmental artery entry level into the spinal canal was graded as very good in 4 (16.7%), good in 11 (45.8%), sufficient in 6 (25.0%), and poor in 3 (12.5%) patients.

Conclusions

The use of 3-T MRA with an intravascular contrast agent and steady-state enables AKA localization including its segmental arteries with regard to the level of aortic origin and spinal canal entry in most patients.