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J G Noronha

Publications and source records attributed to J G Noronha.

9 recordsLinked to original sources
PubMed1990

Quantitative brain autoradiography of [9,10-3H]palmitic acid incorporation into brain lipids.

The distribution of radioactivity within brain metabolic compartments was examined following the intravenous injection of [9,10-3H]palmitate into awake rats. Brain radioactivity reached a maximum value by 15 min after [9,10-3H]palmitate injection and remained unchanged for at least 4 hr. Regional differences in radioactivity could be determined with high resolution by quantitative autoradiography, at the level of cell layers within the hippocampus and cerebral cortex, and between striosomes of the caudate nucleus. Regional brain radioactivities were converted to normalized regional radioactivities (k) by dividing them by the integrated plasma fatty acid radioactivity (integrated over the time course of the experiment). These values reflected incorporation mainly into brain phospholipids; radioactivity due to nonlipid components was minimal. Indeed, about 85% of brain radioactivity was within lipids between 5 min and 4 hr postinjection, the remainder being equally divided between protein-associated pellet and aqueous-soluble metabolites. The major lipids labeled were phospholipids, particularly phosphatidylcholine, which contained about 75% of phospholipid radioactivity. The results show that [9,10-3H]palmitate can be used to examine incorporation of plasma palmitate into individual brain regions via quantitative autoradiography. Furthermore, the tracer is a rather selective marker for phosphatidylcholine and can be used to examine turnover and synthesis of this phospholipid. [9,10-3H]palmitate has advantages over [U-14C]palmitate for autoradiographic studies of incorporation; following the 14C-tracer, significant label even at 4 hr after injection is in nonlipid compartments (glutamate and aspartate), and the long path length of 14C limits resolution at the cell layer level.

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PubMed1990

Synthesis of a fluorinated fatty acid, dl-erythro-9,10-[18F]difluoropalmitic acid, and biodistribution studies in rats.

9,10-Difluoropalmitic acid (DFPA) labeled with the cyclotron produced, positron emitting radionuclide 18F has been synthesized as a potential analogue of 9,10-[3H]palmitic acid, a fatty acid which has been used to study lipid metabolism in rat brain and pituitary. [18F]DFPA was prepared by the direct and stereoselective addition of [18F]F2 to the double bond of cis-9,10-palmitoleic acid. The fluorination was carried out in FCCl3 at -70 degrees C using a low concentration of F2 (0.5%) in neon. [18F]DFPA has been obtained in radiochemical yields of 12-16% from end-of-bombardment (EOB) in approx. 2.5 h. Chemical and radiochemical purity exceeded 95%, and specific activities calculated to EOB ranged from 500 to 1000 mCi/mmol. [18F]DFPA crosses the blood-brain barrier and is incorporated into rat brain at about twice the level of that of 9,10-[3H]palmitic acid. The synthesis of [18F]DFPA permits us to study the biological disposition and metabolism of a vicinal-difluoro fatty acid.

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PubMed1989

Incorporation of plasma [14C]palmitate into the hypoglossal nucleus following unilateral axotomy of the hypoglossal nerve in adult rat, with and without regeneration.

Incorporation of plasma [14C]palmitate into the hypoglossal nucleus of the rat following transection, with and without regeneration of the hypoglossal nerve, was studied using quantitative autoradiography. The left hypoglossal nerve of 3-month-old, male Fischer-344 rats was transected using either: (1) an R-operation, which allowed nerve regeneration; or (2) a D-operation, in which regeneration was prevented. One to 84 days after axotomy, [14C]palmitate was injected intravenously and its rates of incorporation into stable structures of the left and right hypoglossal nuclei were measured at 4 h after injection. Following the R-operation, incorporation into the left hypoglossal nucleus was increased during and following axonal regeneration (up to 23% compared to control side), whereas incorporation was decreased 6-7% in the absence of regeneration, using the D-operation. The time courses of incorporation in both cases corresponded to histological changes, especially cell membrane changes following axotomy and suggest that [14C]palmitate incorporation reflects regenerative and degenerative neuronal changes associated with changes in lipid synthesis.

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PubMed1989

Intravenous injection of [1-14C]arachidonate to examine regional brain lipid metabolism in unanesthetized rats.

We examined the metabolic disposition and brain distribution of an unsaturated fatty acid, [1-14C]arachidonate, between 5 and 240 min following its intravenous bolus injection in unanesthetized adult rats. Injected [1-14C]arachidonate was cleared rapidly from plasma, with less than 10% remaining by 2 min. Total brain radioactivity, 0.2% of the injected dose, was near maximal by 5 min, reached a peak by 15 min, then slowly declined. Radioactivity in brain lipids constituted greater than 82% of the total brain radioactivity at all times. Radioactivity in aqueous-soluble metabolites was greatest at 5 min (13% of total) and declined to 5% by 240 min. Protein pellet-associated radioactivity gradually rose to a peak of 7% by 120 min. Within the lipid fraction, more than 92% of radioactivity was in glycerolipids, with greater than 81% in phospholipids. Radioactivity in inositol phosphoglyceride was maximal at 5 min (47% of phospholipid radioactivity); and declined to 34% by 20 min, whereas radioactivity in choline phosphoglyceride peaked at 15 min (41% of phospholipid radioactivity) and was constant thereafter. In contrast, radioactivity in ethanolamine phosphoglycerides increased from 7 to 17% during the course of the experiment. Quantitative autoradiography of brain sections indicated incorporation of [1-14C]arachidonate into gray-matter regions was 1.5- to threefold that into white-matter regions. The data were analyzed in terms of a model for brain fatty acid uptake from plasma. Estimates of unidirectional transfer constants, k, for [1-14]arachidonate from plasma to brain regions with an intact blood-brain barrier ranged from 0.0005 to 0.0015 ml.sec-1.g-1 and were correlated with those for [9,10-3H]palmitate. The results indicate that brain phospholipid metabolism in awake animals can be examined regionally and quantitatively using intravenous injection of [1-14C]-arachidonate combined with quantitative autoradiography and biochemical analysis.

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PubMed1989

Regional cerebral incorporation of plasma [14C]palmitate, and cerebral glucose utilization, in water-deprived Long-Evans and Brattleboro rats.

Regional rates of incorporation into brain of intravenously administered [14C]palmitate and regional cerebral metabolic rates for glucose (rCMRglc) were measured in water-provided (WP) and water-deprived (WD) homozygous (DI) and heterozygous (HZ) Brattleboro rats, a mutant strain unable to synthesize vasopressin, and in the parent Long-Evans (LE) strain. Following 15 h or 4 days of water deprivation, rCMRglc was elevated threefold in the pituitary neural lobe of LE-WD and DI-WD as compared with LE-WP rats, and in the paraventricular nucleus of LE-WD, and the supraoptic nucleus of DI-WD rats. However, incorporation of [14C]palmitate into these regions was not specifically altered. The results indicate that water deprivation for up to 4 days increases rCMRglc in some brain regions involved with vasopressin, but does not alter [14C]palmitate incorporation into these regions. Incorporation of plasma [14C]palmitate is independent of unlabeled plasma palmitate at brain regions which have an intact blood-brain barrier, but at nonbarrier regions falls according to saturation kinetics as cold plasma concentration rises, with a mean half-saturation constant (Km) equal to 0.136 mumol.ml-1.

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PubMedDate not supplied

Brain tumor imaging in rats using the positron emitting fatty acid dl-erythro-9,10-[18F]difluoropalmitate.

Positron emitting dl-erythro-9,10[18F]difluoropalmitate, [18F]DFPA, was synthesized for the in vivo imaging of brain tumors in rats. Male Fischer 344 rats were intracerebrally implanted with Walker 256 carcinosarcoma tumor cells (1 x 10(6) in 5 microliters tissue culture media) and 7 days later were infused with [18F]DFPA (500-1000 mCi/mmol) i.v. for 5 min. Rats were killed after 20 min. Brains were removed and either prepared for autoradiography, or brain and tumor were separated and their radioactivity quantified by gamma spectroscopy. Brain tumors were well demarcated from surrounding and normal brain in autoradiographs, and closely paralleled tumor growth in histological sections. The mean optical density of tumor was significantly greater, by 318 +/- 68 per cent (P less than 0.025, n = 3), than normal brain in autoradiographs, and that of edematous brain surrounding a large tumor was intermediately increased. [18F]DFPA proved of value to image and circumscribe intracerebral tumors in awake rats, and studies are continuing to facilitate its clinical application in brain tumor patients.

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