Metabolomics approaches in experimental allergic encephalomyelitis.

A myelin basic protein (MBP)-induced experimental allergic encephalomyelitis (EAE) involves paraplegia due to a reversible thoracolumbar spinal cord impairment. The aims of this study were thus to find significant metabolic biomarkers of inflammation and identify the site of inflammation in the central nervous system (CNS) during the acute signs in of the disease using metabolomics. All the EAE samples were associated with higher levels of lactate, ascorbate, glucose and amino acids, and decreased level of N-acetyl-aspartate (NAA) compared to the control group. A decreased NAA level has been particularly shown in lumbar spinal cord in relationship with the clinical signs.

Metabolomics approaches in pancreatic adenocarcinoma: tumor metabolism profiling predicts clinical outcome of patients.

BACKGROUND: Pancreatic adenocarcinomas (PAs) have very poor prognoses even when surgery is possible. Currently, there are no tissular biomarkers to predict long-term survival in patients with PA. The aims of this study were to (1) describe the metabolome of pancreatic parenchyma (PP) and PA, (2) determine the impact of neoadjuvant chemotherapy on PP and PA, and (3) find tissue metabolic biomarkers associated with long-term survivors, using metabolomics analysis. METHODS: 1H high-resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy using intact tissues was applied to analyze metabolites in PP tissue samples (n = 17) and intact tumor samples (n = 106), obtained from 106 patients undergoing surgical resection for PA. RESULTS: An orthogonal partial least square-discriminant analysis (OPLS-DA) showed a clear distinction between PP and PA. Higher concentrations of myo-inositol and glycerol were shown in PP, whereas higher levels of glucose, ascorbate, ethanolamine, lactate, and taurine were revealed in PA. Among those metabolites, one of them was particularly obvious in the distinction between long-term and short-term survivors. A high ethanolamine level was associated with worse survival. The impact of neoadjuvant chemotherapy was higher on PA than on PP. CONCLUSIONS: This study shows that HRMAS NMR spectroscopy using intact tissue provides important and solid information in the characterization of PA. Metabolomics profiling can also predict long-term survival: the assessment of ethanolamine concentration can be clinically relevant as a single metabolic biomarker. This information can be obtained in 20 min, during surgery, to distinguish long-term from short-term survival.

Circulating levels of IGF-I in patients with chronic uremia on conservative dietary treatment.

The assessment of nutritional status is a very important step in the clinical management of chronic uremic patients, because of the influences of chronic renal failure and of dietary manipulations on the energy and protein metabolism. In this study some serum biochemical markers of protein nutrition, including IGF-I and pre-albumin, have been measured in chronic renal failure patients treated with two different low-protein diets, according to the residual renal function for several months. Our results showed no significant changes of IGF-I, pre-albumin or albumin serum levels in the patients treated with a very low-protein diet (0.3 g/Kg b.w. per day) supplemented with essential amino acids and ketoacids, in comparison with the patients on a conventional low-protein (0.6 g/Kg b.w. per day) diet.

Laser Doppler flowmeter assessment of skin microcirculation in uremic patients on hemodialysis treatment.

Vascular disease is frequent in uremics and may contribute to tissue malnutrition and damage. The aim of this study was to detect whether uremic patients show also changes of microcirculation and to evaluate the effects induced by hemodialysis (HD) session. Eleven uremics on HD (7 males, 4 females, aged 25-65 years) were studied; 11 healthy subjects, age- and sex-matched, served as controls. Skin microcirculatory basal flow (BF), maximal postischemic flow (PIF-max) and flow motion index (FMI) were determined at the upper limb contralateral to arteriovenous fistula, by means of a laser Doppler flowmeter. The measurements were taken before, at 1 and 2 h after starting HD and 30 min after the end of HD. In uremics, FMI was lower than in controls (mean +/- SD: 15.2 +/- 13.6 vs. 29.1 +/- 7.4%; p < 0.005); just 1 h after the start of HD, a significant improvement (28.4 +/- 17.7%; p < 0.01) versus basal values was observed and it persisted throughout the HD session. No statistical correlation was observed between the changes of FMI and those of plasma levels of Na+, K+, HCO-3, urea, iPTH or rate of ultrafiltration. BF and PIF-max were similar in uremics and controls, and no changes were observed during HD. Our study shows that the physiological flow motion is reduced in the skin microcirculation of uremics on HD. This abnormality is rapidly corrected by HD.