Hyperpolarized 13C Magnetic Resonance Spectroscopy Reveals the Rate-Limiting Role of the Blood-Brain Barrier in the Cerebral Uptake and Metabolism of l-Lactate in Vivo.

The dynamics of l-lactate transport across the blood-brain barrier (BBB) and its cerebral metabolism are still subject to debate. We studied lactate uptake and intracellular metabolism in the mouse brain using hyperpolarized 13C magnetic resonance spectroscopy (MRS). Following the intravenous injection of hyperpolarized [1-13C]lactate, we observed that the distribution of the 13C label between lactate and pyruvate, which has been shown to be representative of their pool size ratio, is different in NMRI and C57BL/6 mice, the latter exhibiting a higher level of cerebral lactate dehydrogenase A ( Ldha) expression. On the basis of this observation, and an additional set of experiments showing that the cerebral conversion of [1-13C]lactate to [1-13C]pyruvate increases after exposing the brain to ultrasound irradiation that reversibly opens the BBB, we concluded that lactate transport is rate-limited by the BBB, with a 30% increase in lactate uptake after its disruption. It was also deduced from these results that hyperpolarized 13C MRS can be used to detect a variation in cerebral lactate uptake of <40 nmol in a healthy brain during an in vivo experiment lasting only 75 s, opening new opportunities to study the role of lactate in brain metabolism.

High regioselective ultrasonic-assisted synthesis of 2,7-diaryl-4,7-dihydropyrazolo[1,5-a]pyrimidine-5-carboxylic acids.

New and high regioselective method of the synthesis of 2,7-diaryl-4,7-dihydropyrazolo[1,5-a]pyrimidine-5-carboxylic acids by reaction of 3-aryl-5-aminopyrazoles with arylidenpyruvic acid at room temperature under ultrasonication was developed and discussed.

Glycolytic metabolism and tumour response to fractionated irradiation.

BACKGROUND AND PURPOSE: To study whether pre-therapeutic lactate or pyruvate predict for tumour response to fractionated irradiation and to identify possible coherencies between intermediates of glycolysis and expression levels of selected proteins. MATERIALS AND METHODS: Concentrations of lactate, pyruvate, glucose and ATP were quantified via bioluminescence imaging in tumour xenografts derived from 10 human head and neck squamous cell carcinoma (HNSCC) lines. Tumours were irradiated with 30 fractions within 6 weeks. Expression levels of the selected proteins in tumours were measured at the mRNA and protein level. Tumour-infiltrating leucocytes were quantified after staining for CD45. RESULTS: Lactate but not pyruvate concentrations were significantly correlated with tumour response to fractionated irradiation. Lactate concentrations in vivo did not reflect lactate production rates in vitro. Metabolite concentrations did not correlate with GLUT1, PFK-L or LDH-A at the transcriptional or protein level. CD45-positive cell infiltration was low in the majority of tumours and did not correlate with lactate concentration. CONCLUSIONS: Our data support the hypothesis that the antioxidative capacity of lactate may contribute to radioresistance in malignant tumours. Non-invasive imaging of lactate to monitor radiation response and testing inhibitors of glycolysis to improve outcome after fractionated radiotherapy warrant further investigations.

Effect of ultrasound stimulation on metabolic modulation of pyruvic acid.

Pyruvic acid lay on the center position of Eremothecium ashbyii metabolic fluxes, during fermentation, a high performance liquid chromatography (HPLC) method is presented for the simultaneous determination of pyruvic acid in the Eremothecium ashbyii cell culture of both with ultrasound stimulation and the control. Dry weight and riboflavin are also mentored. The results of this study show that the ultrasound stimulation can give rise to pyruvic acid change, at the same time; change of pyruvic acid concentration is correlative to that of dry weight of mycelium and content of riboflavin.

[Content of free amino acids in blood plasma of the clean-up personnel at the Chernobyl nuclear power plant accident]. / Vmist vil'nykh aminokyslot u plazmi krovi v likvidatoriv avariï na Chornobyl'skii AES.

In two groups of the persons participating in liquidation of the Chornobyl Power Plant Catastrophe (individuals which suffered from acute radiation sickness and those ones who were exposed to irradiation at doses 0.25-1.0 Gy) in a year after medical treatment the free amino acids, their derivatives, glucose, sodium lactate and pyruvate homeostasis changed in comparison with the control. The causes and possible mechanisms of these substances exchange regulation disorders in the key biochemical reactions ensuring the body organs and systems functioning were estimated. The experimental findings received can be used at planning the further examination and treatment-and-prophylactic measures for the persons which have been affected by ionizing radiation consequently the accident at the Chornobyl Nuclear Power Plant.

Pantothenol protects rats against some deleterious effects of gamma radiation.

Rats were exposed to gamma radiation from a 60Co source, receiving 0.25 Gy at weekly intervals. During 2 d before each irradiation, the animals received daily intragastric doses of 26 mg pantothenol or 15 mg beta-carotene per kg body weight. One hour after the third irradiation session, the animals were killed and their livers were analyzed. In animals not supplied with pantothenol, the irradiation resulted in a significant decrease of total liver lipids and a 50% decrease in phospholipids. Liver cholesterol was decreased by about 20%. Irradiation produced lipid peroxidation as expressed by doubling of the amounts of conjugated dienes and ketone dienes and of thiobarbituric acid reactive compounds. The amount of CoA in liver was decreased by 24% and that of reduced glutathione by 40%. The NAD+/NADH ratio was increased by 60% and the activity of NADP-dependent malate dehydrogenase (decarboxylating) was decreased by 26%. The amount of pantothenic acid and its derivatives (expressed as pantolactone-generating compounds) in blood decreased by about 80%. In rats to which pantothenol was administered, the content of pantothenic acid in blood was tripled compared to nonirradiated (control) rats, and all the biochemical parameters measured in liver were the same as in nonirradiated animals.