A noninvasive method to measure splanchnic glucose uptake after oral glucose administration.

We have developed a noninvasive method to estimate splanchnic glucose uptake (SGU) in humans (oral glucose clamp technique [OG-CLAMP]), which combines a hyperinsulinemic clamp with an oral glucose load (oral glucose tolerance test). We validated this method in 12 nondiabetic subjects using hepatic vein catheterization (HVC) during an oral glucose tolerance test. During HVC, splanchnic blood flow increased from 1,395 +/- 64 to 1,935 +/- 109 ml/min, returning to basal after 180 min and accounted for 45 +/- 7% of SGU in lean and 19 +/- 5% in obese subjects (P < 0.05). SGU estimated during the OG-CLAMP was 22 +/- 2% of the glucose load, and this was significantly correlated (r = 0.90, P < 0.0001) with SGU (35 +/- 4%) and with first pass SGU (24 +/- 3%; r = 0.83, P < 0.001) measured during HVC. SGU was higher in obese than in lean subjects during OG-CLAMP (27 +/- 1% vs 18 +/- 3%, P < 0.01) and HVC (44 +/- 4% vs 26 +/- 5%, P < 0.05). In conclusion, SGU during the OG-CLAMP is well correlated to SGU measured during HVC. An increase in splanchnic blood flow is a major contributor to SGU in lean subjects. SGU is increased in obese subjects as measured by both methods.

Evidence for decreased splanchnic glucose uptake after oral glucose administration in non-insulin-dependent diabetes mellitus.

The role of splanchnic glucose uptake (SGU) after oral glucose administration as a potential factor contributing to postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM) has not been established conclusively. Therefore, we investigated SGU in six patients with NIDDM and six weight-matched control subjects by means of the hepatic vein catheterization (HVC) technique. In a second part, we examined the applicability of the recently developed OG-CLAMP technique in NIDDM by comparing SGU and first-pass SGU during HVC with SGU during the OG-CLAMP experiment. The OG-CLAMP method combines a euglycemic, hyperinsulinemic clamp and an oral glucose tolerance test (75 g) during steady state glucose infusion (GINF). During HVC, SGU equals the splanchnic fractional extraction times the total (oral and arterial) glucose load presented to the liver. For OG-CLAMP, SGU was calculated as first-pass SGU by subtracting the integrated decrease in GINF over 180 min from 75 g. Cumulative splanchnic glucose output after oral glucose correlated significantly between both methods and was increased significantly in NIDDM patients (73.1+/-5.1 g for HVC, 76.5+/-5.5 for OG-CLAMP) compared with nondiabetic patients (46.7+/-4.4 g for HVC, 57.5+/-1.9 for OG-CLAMP). Thus, in NIDDM patients, SGU (7.4+/-2.1 vs. 37.8+/-5.9% in nondiabetic patients, P < 0.001) and first-pass SGU (4.7+/-1.7 vs. 26.5+/-5.1% in nondiabetic patients, P < 0.01) were decreased significantly during HVC, as was SGU during OG-CLAMP (3.9+/-1.7 vs. 23.4+/-2.5% in nondiabetic patients, P < 0.0001). SGU measured during OG-CLAMP correlated significantly with SGU (r = 0.87, P < 0.05 for NIDDM patients; r = 0.94, P < 0.01 for nondiabetic patients) and first-pass SGU (r = 0.87, P < 0.05 for NIDDM patients; r = 0.84, P < 0.05 for nondiabetic patients) during HVC. In conclusion, (a) SGU after oral glucose administration is decreased in NIDDM as measured by both methods, and (b) SGU during the OG-CLAMP is well-correlated to SGU and first-pass SGU during HVC in NIDDM. The decrease in SGU in NIDDM might contribute to postprandial hyperglycemia in diabetic subjects.

Effects of insulin infusion on human skeletal muscle pyruvate dehydrogenase, phosphofructokinase, and glycogen synthase. Evidence for their role in oxidative and nonoxidative glucose metabolism.

To determine whether activation by insulin of glycogen synthase (GS), phosphofructokinase (PFK), or pyruvate dehydrogenase (PDH) in skeletal muscle regulates intracellular glucose metabolism, subjects were studied basally and during euglycemic insulin infusions of 12, 30, and 240 mU/m2 X min. Glucose disposal, oxidative and nonoxidative glucose metabolism were determined. GS, PFK, and PDH were assayed in skeletal muscle under each condition. Glucose disposal rates were 2.37 +/- 0.11, 3.15 +/- 0.19, 6.71 +/- 0.44, and 11.7 +/- 1.73 mg/kg X min; glucose oxidation rates were 1.96 +/- 0.18, 2.81 +/- 0.28, 4.43 +/- 0.32, and 5.22 +/- 0.52. Nonoxidative glucose metabolism was 0.39 +/- 0.13, 0.34 +/- 0.26, 2.28 +/- 0.40, and 6.52 +/- 1.21 mg/kg X min. Both the proportion of active GS and the proportion of active PDH were increased by hyperinsulinemia. PFK activity was unaffected. Activation of GS was correlated with nonoxidative glucose metabolism, while activation of PDH was correlated with glucose oxidation. Sensitivity to insulin of GS was similar to that of nonoxidative glucose metabolism, while the sensitivity to insulin of PDH was similar to that of glucose oxidation. Therefore, the activation of these enzymes in muscle may regulate nonoxidative and oxidative glucose metabolism.

Early MAVEN Deep Dip campaign reveals thermosphere and ionosphere variability.

The Mars Atmosphere and Volatile Evolution (MAVEN) mission, during the second of its Deep Dip campaigns, made comprehensive measurements of martian thermosphere and ionosphere composition, structure, and variability at altitudes down to ~130 kilometers in the subsolar region. This altitude range contains the diffusively separated upper atmosphere just above the well-mixed atmosphere, the layer of peak extreme ultraviolet heating and primary reservoir for atmospheric escape. In situ measurements of the upper atmosphere reveal previously unmeasured populations of neutral and charged particles, the homopause altitude at approximately 130 kilometers, and an unexpected level of variability both on an orbit-to-orbit basis and within individual orbits. These observations help constrain volatile escape processes controlled by thermosphere and ionosphere structure and variability.

MAVEN observations of the response of Mars to an interplanetary coronal mass ejection.

Coupling between the lower and upper atmosphere, combined with loss of gas from the upper atmosphere to space, likely contributed to the thin, cold, dry atmosphere of modern Mars. To help understand ongoing ion loss to space, the Mars Atmosphere and Volatile Evolution (MAVEN) spacecraft made comprehensive measurements of the Mars upper atmosphere, ionosphere, and interactions with the Sun and solar wind during an interplanetary coronal mass ejection impact in March 2015. Responses include changes in the bow shock and magnetosheath, formation of widespread diffuse aurora, and enhancement of pick-up ions. Observations and models both show an enhancement in escape rate of ions to space during the event. Ion loss during solar events early in Mars history may have been a major contributor to the long-term evolution of the Mars atmosphere.

In vivo cerebral incorporation of radiolabeled fatty acids after acute unilateral orbital enucleation in adult hooded Long-Evans rats.

We examined effects of acute unilateral enucleation on incorporation from blood of intravenously injected unsaturated [1-14C]arachidonic acid ([14C]AA) and [1-14C]docosahexaenoic acid ([14C]DHA), and of saturated [9,10-3H]palmitic acid ([3H]PA), into visual and nonvisual brain areas of awake adult Long-Evans hooded rats. Regional cerebral metabolic rate for glucose (rCMRglc) values also were assessed with 2-deoxy-D-[1-14C]glucose ([14C]DG). One day after unilateral enucleation, an awake rat was placed in a brightly lit visual stimulation box with black and white striped walls, and a radiolabeled fatty acid was infused for 5 min or [14C]DG was injected as a bolus. [14C]DG also was injected in a group of rats kept in the dark for 4 h. Fifteen minutes after starting an infusion of a radiolabeled fatty acid, or 45 min after injecting [14C]DG, the rat was killed and the brain was prepared for quantitative autoradiography. Incorporation coefficients k* of fatty acids, or rCMRglc values, were calculated in homologous brain regions contralateral and ipsilateral to enucleation. As compared with ipsilateral regions, rCMRglc was reduced significantly (by as much as -39%) in contralateral visual areas, including the superior colliculus, lateral geniculate body, and layers I, IV, and V of the primary (striate) and secondary (association, extrastriate) visual cortices. Enucleation did not affect incorporation of [3H]PA into contralateral visual regions, but reduced incorporation of [14C]AA and of [14C]DHA by -18.5 to -2.1%. Percent reductions were correlated with percent reductions in rCMRglc in most but not all regions. No effects were noted at any of nine non-visual structures that were examined. These results indicate that enucleation acutely reduces neuronal activity in contralateral visual areas of the awake rat and that the reductions are coupled to reduced incorporation of unsaturated fatty acids into sn-2 regions of phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine. Reduced fatty acid incorporation likely reflects reduced activity of phospholipases A2 and/or phospholipase C.

Impaired morphological development of the dorsal cochlear nucleus in hamsters treated postnatally with alpha-difluoromethylornithine.

The dorsal cochlear nucleus is a highly organized nucleus in the auditory system in which the ramifications of depletion of specific cell types during development can be studied. Granule cells, small interneurons that are located in all layers of the DCN in the adult hamster, proliferate postnatally and are, therefore, potentially vulnerable to anti-mitotic agents that are administered after birth. The present experiments describe the effects of alpha-difluoromethylornithine, a drug that inhibits proliferation of cerebellar granule cells, on the granule cells in the dorsal cochlear nucleus. As in the cerebellum, the density of granule cells in the dorsal cochlear nucleus is reduced after alpha-difluoromethylornithine treatment. In hamsters treated with alpha-difluoromethylornithine (200 or 500 mg/kg subcutaneously (s.c.), twice daily on postnatal days 4-14), the numerical density of granule cells was reduced in the superficial dorsal cochlear nucleus at 15 days; by 40 days this effect was also apparent in the deep layer, suggesting that cells located superficially that would have migrated into the deep dorsal cochlear nucleus had either failed to develop or did not arrive at their final location. This evidence suggests that the cells normally migrate down from the superficial proliferative zone into the deeper layers. In the drug-treated animals, a layer of mixed granule cells and fusiform cells was thinner than in controls probably due to the reduction in interspersed granule cells since the number of fusiform cells was unaffected. There was also a dose-dependent effect on cell growth; fusiform cells were affected at both doses, while giant cells were only affected at the highest dose. Granule cells form a major input to the fusiform cells and their depletion may account for some of the effects on fusiform cell growth. There could also be additional direct actions of alpha-difluoromethylornithine on this population.

Critical development periods for inhibition of ornithine decarboxylase by alpha-difluoromethylornithine: effects on ontogeny of sensorimotor behavior.

The roles of ornithine decarboxylase and the polyamines in behavioral development were examined through the use of alpha-difluoromethylornithine, a specific irreversible inhibitor of ornithine decarboxylase. alpha-Difluoromethylornithine was administered either prenatally during gestation (days 15-17) or postnatally (days 1-20) to examine critical periods of sensitivity. Prenatal alpha-difluoromethylornithine administration resulted in a deficit in early sensorimotor ontogeny: latencies in surface righting reflex (postnatal days 1-5) and negative geotaxis (postnatal days 5-8) were prolonged, and time spent pivoting (postnatal days 7, 9, and 11) was reduced. In contrast, postnatal alpha-difluoromethylornithine primarily influenced later maturing, complex integrative behaviors such as swimming and open field activity. Thus, the behavioral effects of alpha-difluoromethylornithine exposure are highly dependent upon the age at which the drug is administered, a finding in keeping with the participation of the ornithine decarboxylase/polyamine system in cell replication and differentiation during discrete periods of neural development. The behavioral consequences of ornithine decarboxylase inhibition during these critical periods are thus related primarily both to the timetable for cellular maturation in each brain region.

Effects of alpha-difluoromethylornithine, a specific irreversible inhibitor of ornithine decarboxylase, on nucleic acids and proteins in developing rat brain: critical perinatal periods for regional selectivity.

Ornithine decarboxylase and its metabolic products, the polyamines, are known to coordinate macromolecule synthesis in developing neural tissues; consequently, inhibition of this enzyme by alpha-difluoromethylornithine interferes with cellular replication and differentiation. We examined the regional selectivity of the effect of alpha-difluoromethylornithine administered either postnatally (days 1-19) or during gestation (days 15-17), in order to determine whether specific phases of maturation are particularly sensitive to polyamine depletion. In the cerebellum, which undergoes major phases of replication and differentiation after birth, postnatal alpha-difluoromethylornithine administration caused a profound and progressive deficit in tissue weight gain as well as in DNA, RNA and protein content. Although regions which develop earlier (cerebral cortex, midbrain + brain stem) also showed adverse effects of postnatal alpha-difluoromethylornithine, the deficits were of much smaller magnitude and were comparable to the effect of the drug on general body growth. Despite these regional differences, inhibition of DNA synthesis ([3H]thymidine incorporation) was similar in cerebellum and in midbrain + brain stem, indicating that the direct impact of alpha-difluoromethylornithine-induced polyamine depletion is exerted in both; DNA synthesis in cerebral cortex was spared relative to the other two regions. These data suggested that the impact of alpha-difluoromethylornithine on development depends, in part, upon the relative degree of maturation of each brain region at the time of drug exposure. In confirmation of this hypothesis, prenatal alpha-difluoromethylornithine given on gestational days 15-17 resulted in loss of the specificity toward cerebellar development and enhancement of effects on cerebral cortex, the region which had displayed the least sensitivity to postnatal alpha-difluoromethylornithine.

Incorporation of [1-carbon-11]palmitate in monkey brain using PET.

UNLABELLED: We determined regional incorporation coefficients (k*) of plasma [1-11C]palmitate into stable brain lipids of anesthetized monkeys with PET. METHODS: Carbon-11-palmitate was injected intravenously in untreated animals and in animals pretreated with methyl palmoxirate (MEP), an inhibitor of beta-oxidation of palmitate in the brain and periphery. Plasma radioactivity was followed, and brain radioactivity was determined at various times using PET. A least-squares method was used to fit the data to an operational equation to obtain regional values of k* and of cerebral blood volume (Vb) in individual experiments. RESULTS: MEP significantly decreased the integral of plasma [11C]CO2 following 11C-palmitate infusion. Mean values of k* in monkeys not given MEP were 4.9, 4.2, 4.9, 4.0 and 2.9 x 10(-5) ml/sec.g for the temporal, frontal, parietal and occipital cortices and white matter, respectively. With the exception of k* in white matter, which was increased by MEP, k* in the other brain regions was not significantly changed by MEP. The Vb ranged from 0.035 ml/g to 0.048 ml/g in gray matter regions and equaled 0.022 ml/g in white matter. CONCLUSION: PET can be used to determine regional incorporation coefficients of 11C-palmitate into the primate brain in vivo. Combined with MEP, 11C-palmitate could be used with PET to examine regional brain phospholipid metabolism in humans in normal and pathological conditions.

Lack of association of the (AAAT)6 allele of the GXAlu tetranucleotide repeat in intron 27b of the NF1 gene with autism.

A novel allele of the GXAlu tetranucleotide repeat in intron 27b of the neurofibromatosis 1 (NF1) gene has recently been reported to be present in 4.7% of autistic patients but not in controls. We have found the novel GXAlu allele absent in 204 patients from the South Carolina Autism Project and 200 controls. The autism population studied includes a significant number of patients with hypotonia, stereotyped behaviors, or postural, gait, and motor abnormalities similar to those seen in the patients previously reported to possess the novel GXAlu allele. This suggests that the novel (AAAT)6 GXAlu allele is not associated with autism.

Low-carbohydrate diet alters intracellular glucose metabolism but not overall glucose disposal in exercise-trained subjects.

Dietary composition has been strongly implicated as an important determinant of in vivo insulin sensitivity. However, the metabolic alterations associated with extreme changes in diet have not been well described. We compared glucose metabolism after a standard diet ([STD] 35% fat, 51% carbohydrate, and 14% protein) with the effects of a 3-week adaptation to a low-carbohydrate, high-fat diet ([LCD] 75% fat, 8% carbohydrate, and 17% protein). Ten healthy men were studied using the euglycemic clamp technique, indirect calorimetry, and percutaneous vastus lateralis muscle biopsies for analysis of glycogen synthase (GS) and pyruvate dehydrogenase (PDH) activities in the basal and insulin-stimulated states. Insulin-stimulated glucose disposal was unchanged (STD 46.1 +/- 4.3 v LCD 46.0 +/- 4.3 mumol/kg.min, P = NS), but marked alterations in the routes of glucose disposal were noted. Insulin-stimulated glucose oxidation (Gox) was markedly reduced following LCD (STD 18.6 +/- 1.9 v LCD 8.23 +/- 1.9 mumol/kg.min, P = .0001), and nonoxidative glucose metabolism (Gnox) was enhanced by LCD (STD 24.9 +/- 0.9 v LCD 38.9 +/- 4.3 mumol/kg.min, P = .03). Following LCD, both the total and active forms of PDH (PDHt and PDHa) were significantly depressed. After LCD, GS activates (FV0.1, %I, and A0.5) were unaffected in the basal state, but were greater than for STD (P = .004) after insulin stimulation. The apparent increase in the sensitivity of GS to activation by insulin following LCD correlated strongly with maximal O2 consumption ([VO2max] r = .97, P = .001), suggesting that physical conditioning interacted with the metabolic impact of LCD. In summary, LCD did not induce changes in net glucose disposal.(ABSTRACT TRUNCATED AT 250 WORDS)

Methicillin-resistant Staphylococcal aureus evolution in Australia over 35 years.

Australia has a long association methicillin-resistant Staphylococcus aureus (MRSA). Its unique geographic and demographic features have led to the emergence and spread of three types of MRSA over 35 years. Classical multiresistant hospital-acquired MRSA were first noted in Australia in 1965. By the end of the 1970s, strains of this type of MRSA were well established in the complex tertiary care hospitals in the capital cities on the eastern seaboard of mainland Australia. Characterized by resistance to beta-lactams, erythromycin, tetracycline, gentamicin, and trimethoprim-sulfamethoxazole, these strains have persisted and diversified genetically and have acquired a variety of new resistances. They have proven pathogenicity and are a prominent cause of hospital infection in the endemic institutions. More recently they have become endemic in some central state tertiary care hospitals. Community-acquired strains of MRSA first appeared in the north of Western Australia in the mid-1980s. Strains have subsequently appeared in the south of the state and in the two adjacent central states, and are more frequently isolated from Aboriginal patients. Although harboring few or no additional resistances apart from resistance to beta-lactams initially, these strains are also accumulating additional resistances. A different variety of community-acquired MRSA has recently been noted in eastern Australia. It has a similar antibiogram to the western strains, but an entirely different epidemiology, resembling that currently being experienced in parts of New Zealand, and associated with patients of south Pacific island origin.

Validation of a modified Kirby-Bauer disk diffusion method for metronidazole susceptibility testing of Helicobacter pylori.

Triple antimicrobial therapy that includes metronidazole has been recommended as a first-line therapy for Helicobacter pylori because it has the highest eradication rates. However, resistance in H. pylori to metronidazole has been reported worldwide and its presence may reduce the efficacy of triple therapy. Various methods for testing H. pylori against metronidazole have been used including agar dilution, disk diffusion and the Etest but there has been little standardization of methods. One hundred isolates of H. pylori from different patients were tested for susceptibility to metronidazole by agar dilution, Etest and disk diffusion (5 micrograms disk). The agar dilution results confirmed the MIC susceptibility breakpoint to be < or = 8 micrograms/ml. Using this breakpoint there was close agreement (98%) between Etest and agar dilution results. For susceptible strains, MICs by E-test were generally one twofold dilution lower. Using the error-rate bounded method, agreement between disk diffusion zone diameter and MIC was 98% for agar dilution with breakpoints of > or = 12 mm and < or = 8 micrograms/ml and 100% for Etest with breakpoints of > or = 12 mm and < or = 8 micrograms/ml. The Etest discriminated better than agar dilution between susceptible and resistant strains and was simple to perform. The disk diffusion test is a reliable and cheaper alternative to the Etest with susceptibility being a zone diameter > or = 12 mm with a 5 micrograms disk. The prevalence of metronidazole resistance in this study was 40% by Etest.

Clonal chromosome aberrations in a case of nodular fasciitis.

We report a case of nodular fasciitis with clonal chromosome aberrations including a reciprocal t(3;15)(q21;q22) and interstitial deletion (13)(q14q21).

Potential diagnostic implications of breakpoints in the long arm of chromosome 8 in lipoblastoma.

We report a case of lipoblastoma in a 17-month-old male patient with a pseudodiploid karyotype of 46,XY,der(14)t(8;14)(q11.2;q24). The tumor cells show two normal chromosome 8 homologs in addition to the extra 8q11.2-->qter segment, making it trisomic for the region 8q11.2-->qter, and monosomic for 14q24-->qter. Reports of chromosome studies in lipoblastoma are rare; however, a breakpoint in the long arm of chromosome 8q11-13 appears to be emerging as a consistent finding.

Telomeric associations in the progression of chromosome aberrations in pediatric solid tumors.

Telomeric association (tas) is a cytogenetic phenomenon in which chromosome ends fuse to form dicentric, multicentric, and ring chromosomes. We observed clonal tas in six pediatric solid tumors of various types and histological grades studied using short-term in situ culture and G-banding techniques. These tumors included a neurilemoma, an undifferentiated (embryonal) sarcoma of the liver (UESL), two anaplastic astrocytomas (AA), one case of glioblastoma multiforme (GBM), and a neuroblastoma (NB) of the kidney. Cytogenetic data from all six tumors demonstrated multiple numerical and structural aberrations including tas. The tas appeared to be a secondary aberration in these tumors, however, it was possible to follow the progression of the telomeric chromosome aberrations in several cases. In all but one case (UESL) the loss of chromosome segments occurred. Tas of 11p was observed in three of the six tumors, two of which showed the subsequent loss of 11p (AA and AB). In addition, tas of 4p was seen in three tumors, two of which showed clonal tas of 4p with 22q. Tas of 10p, 21p, and 22q were all observed in at least two different tumors. The clonal telomeric fusions of 4p with 22q, recurring tas of 11p, and the subsequent loss of the short arm of 11 demonstrated here, suggests that some chromosome regions are subject to nonrandom instability and sometimes loss.

Effect of inhibition of beta-oxidation on incorporation of [U-14C]palmitate and [1-14C]arachidonate into brain lipids.

The purpose of the present study was to determine the effect of inhibiting the mitochondrial beta-oxidation of free fatty acids on the incorporation of radiolabeled free fatty acids into brain lipids. To this end, methyl 2-tetradecylglycidate (MEP), an irreversible inhibitor of carnitine palmitoyltransferase I, was given orally to male rats 2, 4, and 6 h prior to an intravenous infusion of the saturated fatty acid [U-14C]palmitic acid (PA) or the polyunsaturated fatty acid [1-14C]arachidonate (AA). With [U-14C]PA, MEP (10-25 mg/kg) increased brain organic radioactivity 2-fold and decreased brain aqueous radioactivity 3- to 5-fold relative to control values at all pretreatment times. The effect was due to prolongation of the plasma integral of [U-14C]PA due to peripheral inhibition of beta-oxidation, and to direct inhibition of beta-oxidation of the tracer within the brain. MEP had no effect on brain organic radioactivity after infusion of [1-14C]AA. Increasing the interval between MEP administration and [U-14C]PA infusion from 2 to 6 h resulted in a dramatic redistribution of [U-14C]PA within brain lipids. The percentage of radioactivity in phospholipids decreased from 65 to 33%, whereas that in the free fatty acid fraction increased from 10 to 47% and that in triglycerides was elevated 2-3 fold over control levels. These results indicate that MEP may facilitate the use of radiolabeled PA as an in vivo probe of brain lipid metabolism using quantitative autoradiography or positron emission tomography.

Incorporation of plasma palmitate into the brain of the rat during development.

Jpalm, the rate of incorporation of plasma palmitate into brain, was determined in awake Fischer-344 rats at 15, 20, 25 and 38 days of age, by a modification of the method of Kimes et al. [14C]palmitate was injected intravenously and plasma-specific activity of unesterified palmitate was followed until the animals were killed at 4 h, when radioactivity was determined by quantitative autoradiography in 45 individual brain regions. Jpalm was calculated as the 4 h brain radioactivity divided by integrated plasma palmitate-specific activity to 4 h. Jpalm rose between 15 and 20 days of age in gray and white matter regions, then declined 4-5-fold in gray matter and 7-10-fold in white matter by 38 days and reached adult levels by 3 months. The white/gray ratio for Jpalm declined significantly between 20 and 38 days, and between 38 days and 3 months of age, consistent with a lower rate of turnover of white matter lipids in the mature brain. The results support the use of the Jpalm technique to measure brain lipid synthesis and turnover. They show that Jpalm corresponds to the time course of myelination during development of the rat brain, when there are parallel changes in the rates of palmitate incorporation into gray and white matter regions.

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.