EXTRAPOLATION METHOD FOR MAXIMAL AND 24-H AVERAGE LTE TDD EXPOSURE ESTIMATION.

The Long-Term Evolution (LTE) system represents the evolution of the Universal Mobile Telecommunication System technology. This technology introduces two duplex modes: Frequency Division Duplex and Time Division Duplex (TDD). Despite having experienced a limited expansion in the European countries since the debut of the LTE technology, a renewed commercial interest for LTE TDD technology has recently been shown. Therefore, the development of extrapolation procedures optimised for TDD systems becomes crucial, especially for the regulatory authorities. This article presents an extrapolation method aimed to assess the exposure to LTE TDD sources, based on the detection of the Cell-Specific Reference Signal power level. The method introduces a ßTDD parameter intended to quantify the fraction of the LTE TDD frame duration reserved for downlink transmission. The method has been validated by experimental measurements performed on signals generated by both a vector signal generator and a test Base Transceiver Station installed at Linkem S.p.A facility in Rome.

The entry of [1-13C]glucose into biochemical pathways reveals a complex compartmentation and metabolite trafficking between glia and neurons: a study by 13C-NMR spectroscopy.

Glial-neuronal interactions were investigated in rats injected intraperitoneally with [1-13C]glucose and killed after 15, 30, 45, or 60 min. Brain extracts were analyzed by 13C-NMR spectroscopy and the fractional 13C-enrichment at individual carbon positions was measured for amino acids, lactate, and N-acetyl-aspartate. [1-13C]Glucose was shown to be metabolized by both neurons and glia, with the anaplerotic pathway through pyruvate carboxylase (PC) accounting for 10% of total cerebral glucose metabolism. The PC-mediated pathway accounted for 39% of the glutamine synthesis, and for 8, 6, 14% of glutamate, GABA, and aspartate synthesis, respectively. These results reflect a compartmentation of the cerebral amino acids synthesis within glial and neuronal cells. The appearance of the 13C-label in C5 of glutamate and glutamine, C1 of GABA and C2 of lactate, is suggestive of pyruvate, formation from TCA cycle intermediates and provides evidence of metabolite trafficking between astrocytes and neurons.

Effect of acetyl-L-carnitine on recovery of brain phosphorus metabolites and lactic acid level during reperfusion after cerebral ischemia in the rat--study by 13P- and 1H-NMR spectroscopy.

The effects of acetyl-L-carnitine (ALCAR) treatment on brain energy state recovery and lactic acid levels following 20 min ischemia and 2, 24 and 48 h reperfusion were investigated by 31P and 1H-NMR spectroscopy. Transient forebrain ischemia was induced by four-vessel occlusion method in fed 6-month-old Fischer rats. ALCAR or saline was administered by intraperitoneal route immediately after 20 min ischemia and again at 1, 4, 24 and 30 h during reperfusion. Twenty-min severe forebrain ischemia was associated with a marked decrease in phosphocreatine (PCr) and ATP levels and a corresponding increase in lactic acid, inorganic phosphate (Pi), AMP, creatine, glycerol 3-phosphate and alanine levels. Following reperfusion, a general tendency to restore pre-ischemic metabolite levels was observed. However, after 2 h reperfusion in saline-treated rats, lactic acid and Pi levels remained significantly higher, while ATP levels were still significantly lower than in non-ischemic controls. On the contrary, in ALCAR-treated animals a complete recovery of all metabolites including Pi and ATP was observed, while PCr levels were even more elevated compared with those in saline-treated rats. Furthermore lactic acid content was significantly lower than that in both saline-treated and non-ischemic control rats. It is concluded that a potential therapeutic role may be claimed for ALCAR in the treatment of cerebral ischemia through mechanisms that include faster recovery and improvement of brain energy production as well as a decreased lactic acid content during early post-ischemic reperfusion.

Aging brain: effect of acetyl-L-carnitine treatment on rat brain energy and phospholipid metabolism. A study by 31P and 1H NMR spectroscopy.

The effects of acetyl-L-carnitine (ALCAR) on metabolites involved in energy and phospholipid metabolism have been evaluated by mean of 31P and 1H NMR spectroscopy on adult (6 months) and old (24 months) rat brains. A significant increase of glycerophosphorylcholin (GroPCho) in aged rat brain has been observed as compared with adult rat brain. No variations in ATP, phosphocreatine (PCr), Cr, lactate, ADP and inorganic phosphate (Pi) levels have been found between aged and adult brains. Treatment with ALCAR caused a significant increase in PCr levels and a decrease in lactate and sugar phosphate in adult and aged rat brain. These results are suggestive of treatment with ALCAR being responsible for a reduction in brain glycolytic flow and for enhancing the utilization of alternative energy sources, such as lipid substrates or ketone bodies. Furthermore, the changes in GroPCho levels observed after treatment with ALCAR may be indicative of a modulating effect on the activity of the enzymes involved in the acylation-re-acylation process of membrane phospholipids.

Acetyl-L-carnitine modulates glucose metabolism and stimulates glycogen synthesis in rat brain.

The effects of acetyl-L-carnitine on cerebral glucose metabolism were investigated in rats injected with differently 14C- and 13C-labelled glucose and sacrificed after 15, 30, 45, and 60 min. Acetyl-L-carnitine was found to reduce total 14CO2 release from [U-14C]glucose along with the decrease in [1-13C]glucose incorporation into cerebral amino acids and tricarboxylic acid cycle intermediates. However the 13C labelling pattern within different carbon positions of glutamate, glutamine, GABA, and aspartate was unaffected by acetyl-L-carnitine administration. Furthermore, the cerebral levels of newly-synthesized proglycogen were higher in rats treated with acetyl-L-carnitine than in untreated ones. These results suggest that acetyl-L-carnitine was able to modulate cerebral glucose utilization and provide new insights on the mechanisms of action of this molecule in the central nervous system.

31Phosphorus magnetic resonance spectroscopy to evaluate medical therapy efficacy in peripheral arterial disease. A pilot study.

BACKGROUND: Human and animal studies have shown that propionyl-L-carnitine, increasing carnitine content, improves the energy metabolism of ischemic skeletal muscle. The aim of the study was to evaluate the accuracy of Doppler continuous wave, Treadmill test and 31Phosphorus magnetic resonance spectroscopy in determining the efficacy of propionyl-L-carnitine in patients with peripheral arterial disease. EXPERIMENTAL DESIGN: Prospective study. SETTING: University hospital. PATIENTS: Eighteen male patients with peripheral arterial disease (category 3) and 8 healthy volunteers form the basis of the study. Patients quit smoking, start physical training (2-3 Km walk per day) and were assigned to medical therapy consisting of propionyl-L-carnitine (8 patients) or placebo (10 patients). Patients were studied with Doppler continuous wave, Treadmill test and 31Phosphorus magnetic resonance spectroscopy at day 0 and at day 90. The following parameters were assessed by the principal component analysis: clinical (absolute claudication, ankle brachial index at rest and at 2, 5 and 10 minutes after completing Treadmill exercises) and biochemical (inorganic phosphorus/phosphocreatine ratio and pH profiles at 20% and 50% of the maximum load, the recovery half time of phosphocreatine, number of exercise steps and slope of linear relationship between muscle power and inorganic phosphorus/phosphocreatine ratio). RESULTS: Final evaluation showed a significant improvement of clinical and biochemical variables (p < 0.05 and p < 0.02 respectively). Breaking down the results on the basis of the two study arms, 31Phosphorus magnetic resonance spectroscopy showed a significant improvement of biochemical variables in the group of patients treated with propionyl-L-carnitine (p < 0.05) and was more sensitive in the evaluation of changes induced by 90-day treatment as compared with the other noninvasive examinations. CONCLUSIONS: 31P-MRS permits the evaluation of muscle metabolic effect induced by PLC after a 90-day-period in patients affected by category 3 of peripheral arterial disease and it is a more sensitive tool in the evaluation of the pharmacological effects of medical therapy.

Improved resolution of 31P nuclear magnetic resonance spectra of phospholipids from brain.

A method is described wherein the resolution of 31P nuclear magnetic resonance spectra of the lipophilic fraction from a Bligh-Dyer extract of rat brain can be enhanced. The lipids are dispersed as micelles in aqueous solution with sodium deoxycholate, and spectral resolution is further optimized by adjusting the pH and by removing ions from the solution. The application of the method to the study of aging in rat brain serves as an example.

Antioxidative effects of sulfurous mineral water: protection against lipid and protein oxidation.

OBJECTIVES: To investigate the antioxidative properties of sulfurous drinking water after a standard hydropinic treatment (500 ml day(-1) for 2 weeks). SUBJECTS/METHODS: Forty apparently healthy adults, 18 men and 22 women, age 41-55 years old. The antioxidant profile and the oxidative condition were evaluated in healthy subjects supplemented for 2 weeks with (study group) or without (controls) sulfurous mineral water both before (T0) and after (T1) treatment. RESULTS: At T1, a significant decrease (P<0.05) in both lipid and protein oxidation products, namely malondialdehyde, carbonyls and AOPP, was found in plasma samples from subjects drinking sulfurous water with respect to controls. Concomitantly, a significant increment (P<0.05) of the total antioxidant capacity of plasma as well as of total plasmatic thiol levels was evidenced. Tocopherols, carotenoids and retinol remained almost unchanged before and after treatment in both groups. CONCLUSIONS: The improved body redox status in healthy volunteers undergoing a cycle of hydropinic therapy suggests major benefits from sulfurous water consumption in reducing biomolecule oxidation, possibly furnishing valid protection against oxidative damage commonly associated with aging and age-related degenerative diseases.

Transient cerebral ischemia in the rat: a study by nuclear magnetic resonance spectroscopy.

The energy state and the levels of metabolites involved in the phospholipid turnover during and following a transient cerebral ischemia have been evaluated with the aids of 31P and 1H nuclear magnetic resonance spectroscopy. Ischemia was induced by electrocoagulation of vertebral arteries in combination with transient occlusion of both common carotid arteries. After 10-min ischemia, the brain energy charge and the levels of high-energy phosphates were reduced, whereas lactic acid levels had undergone an 8-fold increase. Sixty minutes after cerebral blood flow recovery, brain energy charge and levels of high-energy phosphates returned to basal values, whereas lactic acid levels remained persistingly elevated; an increase in phosphocreatine was also observed. At this same time, glycerolphosphorylcholine levels were found to be significantly reduced.

Multivariate data analysis in biochemistry: a new integrative approach to metabolic control in brain aging.

The principal component analysis (PCA) allows to obtain a quantitative measure of the state of metabolism as a whole. In this paper we applied this method to the study of energy metabolism during aging process and of the effect of a drug (Acetyl-1-carnitine, ALCAR) on the aging brain.

31P nuclear magnetic resonance spectroscopy study on kidney preservation. Effect of verapamil.

31P NMR spectroscopy has been used to evaluate the usefulness of verapamil, a calcium channel blocker, in preventing ischemic renal damage. Phosphorylated metabolites have been investigated before, during and after 48 hrs of hypothermic storage. The rapidity in adenosine triphosphate resynthesis and the phosphomonoesters and phosphodiesters levels after reperfusion at the end of the storage period (48 hrs), were significantly higher in verapamil-treated kidneys. Phosphomonoesters to inorganic phosphate ratio, during the storage period, is even higher. These findings suggest that verapamil may protect against ischemic renal damage and so it can be useful for renal preservation. Furthermore, it has been shown that 31P NMR spectroscopy puts into evidence the biochemical recovery and allows the assessment of the viability of organs.

Cellular volume determination of alginate-entrapped hepatocytes by MRI diffusion measurements.

Cellular volume of hepatocytes entrapped in alginate gel beads were evaluated under in vivo conditions in samples having different cell densities by applying mathematical models to the diffusion data obtained by magnetic resonance imaging (MRI). The calculated average volume is in good agreement with the values from the literature-- being closer to the data relative to living tissue than to isolated cells. The non invasive characteristics of magnetic resonance imaging make this method particularly well suited to obtain information from the intact system.

MR spectroscopy: a powerful tool for investigating brain function and neurological diseases.

Magnetic resonance spectroscopy (MRS) has attracted much attention in recent years and has become an important tool to study in vivo particular biochemical aspects of brain disorders. Since the proton is the most sensitive stable nucleus for MRS, and since almost all metabolites contain hydrogen atoms, investigation by in vivo 1H MRS provides chemical information on tissue metabolites, thus enabling a non-invasive assessment of changes in brain metabolism underlying several brain diseases. In this review a brief description of the basic principles of MRS is given. Moreover, we provide some explanations on the techniques and technical problems related to the use of 1H MRS in vivo including water suppression, localization, editing, quantitation and interpretation of 1H spectra. Finally, we discuss the more recent advancement in three major areas of neurological diseases: brain tumors, multiple sclerosis, and inborn errors of metabolism.

Entry of [(1,2-13C2)acetyl]-L-carnitine in liver tricarboxylic acid cycle and lipogenesis: a study by 13C NMR spectroscopy in conscious, freely moving rats.

The biochemical pathways involved in acetyl-L-carnitine utilization were investigated in conscious, freely moving rats by 13C NMR spectroscopy. Following 4-h [(1,2-13C2)acetyl]-L-carnitine infusion in fasted animals, the free carnitine levels in serum were increased, and an efflux of unlabelled acetyl-L-carnitine from tissues was observed. [(1,2-13C2)Acetyl]-L-carnitine was found to enter biosynthetic pathways in liver, and the acetyl moiety was incorporated into both cholesterol and 3-hydroxybutyrate carbon skeleton. In accord with the entry of [(1,2-13C2)acetyl]-L-carnitine in the mitochondrial acetylCoA pool associated with tricarboxylic acid cycle, the 13C label was also found in liver glutamate, glutamine, and glutathione. The analysis of the 13C-labelling pattern in 3-hydroxybutyrate and cholesterol carbon skeleton provided evidence that the acetyl-L-carnitine-derived acetylCoA pool used for ketone bodies synthesis in mitochondria was homogeneous, whereas cholesterol was synthesized from two different acetylCoA pools located in the extra- and intramitochondrial compartment, respectively. Furthermore, cholesterol molecules were shown to be preferentially synthesized by the metabolic route involving the direct channelling of CoA-activated mitochondria-derived ketone bodies into 3-hydroxy-3-methylglutarylCoA pathway, prior to equilibration of their acyl groups with extramitochondrial acetylCoA pool via acetoacetylCoA thiolase.

Effect of long-term feeding with acetyl-L-carnitine on the age-related changes in rat brain lipid composition: a study by 31P NMR spectroscopy.

Changes in brain lipid composition have been determined in 24 months-old Fischer rats with respect to 6 months-old ones. The cerebral levels of sphingomyelin and cholesterol were found to be significantly increased in aged rats, whereas the amount of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and phosphatidic acid appear to be unaffected by aging. Long-term feeding with acetyl-L-carnitine was able to reduce the age-dependent increase of both sphingomyelin and cholesterol cerebral levels with no effect on the other measured phospholipids. These findings shown that changes in membrane lipid metabolism and/or composition represent one of the alterations occurring in rat brain with aging, and that long-term feeding with acetyl-L-carnitine can be useful in normalizing these age-dependent disturbances.

Effect of propionyl-L-carnitine in a rat model of peripheral arteriopathy: a functional, histologic, and NMR spectroscopic study.

Propionyl-L-carnitine (PLC) has been shown to exert beneficial effects in experimental models of peripheral arterial diseases, such as ergotamine-induced tail gangrene and bilateral femoral arteries occlusion in rats. These models, however, present some drawbacks. The present study was performed to determine whether repeated oral administration of PLC improves the functional, histologic, and metabolic parameters in rats with long-lasting chemically induced peripheral arteriopathy. Peripheral arteriopathy was induced by injecting Na laurate in both the femoral arteries of rats. The walking capacity of the animals (treadmill test) was evaluated at different times and up to 5 weeks after Na laurate injection. Histological examination of vessels and muscles was performed at the end of the experimental period (5 weeks). In separate experiments the level of high-energy phosphates was determined with 31P NMR methodology in the leg muscles. Injection of Na laurate impaired (p < 0.05) the walking capacity of rats, caused thickening of the intima and marked narrowing of the vasal lumen, and reduced the ATP and PCr levels in muscles by 42% and 25%, respectively. PLC given orally for 7 days at 30, 60, 120, and 250 mg/kg dose-dependently decreased the severity of walking capacity impairment by 19%, 41%, 64%, and 71%, respectively. Long-term administration (4 weeks) of PLC (60 and 250 mg/kg os) caused a significant improvement of walking capacity throughout the entire period. The improvement persisted 1 week after discontinuation of the treatment. The severity of the vascular and muscular damages was markedly reduced, particularly in animals treated with the highest dose. Alterations in ATP and PCr levels were significantly (p < 0.05) diminished by PLC (120 mg/kg os) administered daily for 15 days starting 24 hours after Na laurate injection, or for 11 days starting 4 days after Na laurate. The dextro-isomer of the compound was completely inactive, and L-carnitine improved motor performance to a much lesser degree than an identical dose of PLC. It is suggested that the activity of PLC is linked to its metabolic effects on fatty acid oxidation, with consequent preservation of high-energy phosphate levels.