Biomedical subjects

D Guilloteau

Publications and source records attributed to D Guilloteau.

At least 19 recordsLinked to original sources

PubMed2006

Comparative analysis of different scintigraphic approaches to assess pulmonary ventilation.

A study was carried out to investigate the predictive value of 81-metastable-krypton (81mKr) distribution, high-size 99-metastable-technetium (99mTc) aerosol deposition and low-size 99mTc aerosol (Technegas) deposition on the pulmonary ventilation evaluated by 133-xenon (133Xe) lung scintigraphy, and to assess the correlation between the 81mKr distribution, the 99mTc aerosols deposition, and the respiratory parameters of patients with chronic obstructive pulmonary disease (COPD). Twenty COPD patients were included. The 81mKr, 133Xe, and 99mTc aerosol lung scintigraphies were successively carried out. The 81mKr distribution and 99mTc deposition were compared to the 133Xe distribution at equilibrium and to the 133Xe clearance. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 81mKr and Technegas lung scintigraphies to detect alterations in ventilation revealed by 133Xe were defined. The 81mKr distribution and 99mTc deposition according to respiratory parameters were described using a principal component analysis. Compared to 133Xe distribution, a significantly higher distribution of 81mKr in the upper parts of the lungs in the more severe patients (p = 0.05), a significantly higher deposition of Technegas in the lower parts of the lungs (p = 0.0008), and a significantly higher deposition in the central parts of the high-size 99mTc aerosol were observed (p = 0.0001). The PPV and the NPV were, respectively, 0.54 and 0.58 for 81mKr and 0.54 and 0.55 for Technegas. There was a significant negative correlation between 81mKr distribution and 133Xe clearance (p = 0.0001) between Technegas deposition and 133Xe clearance (p = 0.0007), and between 99mTc diethylene-triamino-penta-acetate (DTPA) deposition and 133Xe clearance (p = 0.001). Both the 81mKr peripheral distribution and Technegas peripheral deposition correlated negatively with increased obstruction, as measured by forced expiratory volume in 1 sec (FEV1). Peripheral deposition of the high-size 99mTc aerosol deposition correlated with the inspiration/expiration time ratio. In conclusion, 81mKr and 99mTc aerosols' lung scintigraphies do not reflect exactly the pulmonary ventilation as measured by 133Xe scintigraphy.

Aged↗

PubMed2005

Cholinergic nicotinic receptor involvement in movement disorders associated with Lewy body diseases. An autoradiography study using [(125)I]alpha-conotoxinMII in the striatum and thalamus.

The presence of alpha6 subunit containing nicotinic acetylcholine receptors on nigrostriatal dopaminergic neurons has been demonstrated in rodents and monkeys. [(125)I]alpha-conotoxinMII is a radioligand that binds to alpha6, and also alpha3 subunits of nicotinic acetylcholine receptors (nAChRs). In the present study, we have compared the distribution of [(125)I]alpha-conotoxinMII binding in post mortem human tissue from four groups of patients: individuals with dementia with Lewy bodies displaying extra-pyramidal features (DLB + EPF), DLB without extra-pyramidal features (DLB - EPF) Parkinson's disease without dementia (PD) and age-matched controls. Reduced binding was observed in the putamen and caudate in PD and both DLB groups. In DLB patients, the decline was greater in DLB + EPF compared to DLB - EPF group. The declines in nicotinic receptor binding in the striatum were in part paralleled by reductions in the striatal dopamine transporter. In the thalamus, [(125)I]alpha-conotoxinMII binding was significantly reduced in the centromedian nucleus in both DLB groups, and also in the parafascicular nucleus in the DLB - EPF group. In DLB + EPF and PD patients, there was decreased binding in the ventral lateral nucleus. This study demonstrates alterations of alpha6 and/or alpha3 nAChRs binding in DLB and PD, which are likely to relate to extra-pyramidal symptoms.

Aged↗

PubMed2005

PET and SPECT exploration of central monoaminergic transporters for the development of new drugs and treatments in brain disorders.

Membrane and vesicular monoaminergic transporters, responsible for the homeostasis of neurotransmitter pools at nerve endings, are very involved in the physiology and diseases of central nervous system. Recent progresses of cerebral molecular imaging using SPECT and PET methods allow the extend of in vivo exploration of these transporters. For this aim, an increasing number of radiopharmaceuticals labelled with [123I], [99mTc], [11C] or [18F] have been developed such as cocaine derivatives for the DAT, compounds from the diphenyl sulfide family for the SERT, and dihydrotetrabenazine derivatives for the VMAT2. These functional imaging methods can be very useful in several neurological and psychiatric disorders which involve the monoaminergic neurotransmission systems such as Parkinson's disease, ADHD, depression and autism. For example, the DAT is a specific index of the density of dopaminergic endings which progressively degenerate in Parkinson's disease. In vivo exploration of this transporter can therefore be a relevant way (i) to realize an early detection of the loss of dopaminergic neurons, (ii) to assess the progression of the disease, (iii) to validate and improve the efficacy of new therapeutic strategies such as neuroprotection and neuroreparation. In all, the extend of in vivo exploration of monoamine transporters will allow great progress for (1) knowledge of physiopathological mechanisms of brain disorders, (2) early diagnosis of cerebral dysfunctions, allowing early use of new therapies, (3) selection of homogenous classes of subjects for therapeutic assays, (4) objectiveness of drug-molecular target interaction, (5) follow-up of disease evolution and treatment.

Attention Deficit Disorder with Hyperactivity↗

PubMed2003

Motor behaviour deficits and their histopathological and functional correlates in the nigrostriatal system of dopamine transporter knockout mice.

Chronic dysregulation of dopamine homeostasis has been shown to induce behavioural impairment in dopamine transporter knockout mutant mice arising from the dysfunction of the mesolimbic and hypothalamo-infundibular system. Here, we assessed whether there are also any motor consequences of a chronic and constitutive hyperdopaminergia in the nigrostriatal system in dopamine transporter knockout mutant mice. For this, we analysed motor performances using tests assessing balance, coordinated motor skills (rotarod, pole test), stride lengths and locomotor activity. Dopamine transporter knockout mutant mice were markedly hyperactive in the open field with central compartment avoidance, as previously shown. However, sensorimotor integration was also found to be altered in dopamine transporter knockout mutant mice which displayed a reduced fore- and hind-limb mean stride length, impaired motor coordination on the pole test and reduced rearings in the open field. Moreover, dopamine transporter knockout mutant mice showed a slower task acquisition on the rotarod. Six-week-old dopamine transporter knockout wild type mice having the same femur size as adult dopamine transporter knockout mutant mice ruled out a possible size-effect bias. Whilst there was no significant difference in the striatal volume, we found a slight but significant reduction in neuronal density in the striatum but not in the nucleus accumbens of dopamine transporter knockout mutant mice. There was a reduced binding in the striatum and nucleus accumbens of dopamine(1) receptors ([(3)H]SCH 23390) and dopamine(2) receptors ([(3)H]YM-09151-2). There was no significant difference in the number of dopaminergic neurons in the substantia nigra between dopamine transporter knockout mutant mice and dopamine transporter knockout wild type mice. These results suggest an impaired functioning of the nigrostriatal system in dopamine transporter knockout mutant hyperdopaminergic mice, as illustrated by motor and sensorimotor integration deficits, despite their apparent hyperactivity. These dysfunctions may arise from combined striatal cell loss and/or functional changes of dopaminergic neurotransmission.

Animals↗

PubMed2001

Relationship between the appearance of symptoms and the level of nigrostriatal degeneration in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaque model of Parkinson's disease.

The concept of a threshold of dopamine (DA) depletion for onset of Parkinson's disease symptoms, although widely accepted, has, to date, not been determined experimentally in nonhuman primates in which a more rigorous definition of the mechanisms responsible for the threshold effect might be obtained. The present study was thus designed to determine (1) the relationship between Parkinsonian symptom appearance and level of degeneration of the nigrostriatal pathway and (2) the concomitant presynaptic and postsynaptic striatal response to the denervation, in monkeys treated chronically with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine according to a regimen that produces a progressive Parkinsonian state. The kinetics of the nigrostriatal degeneration described allow the determination of the critical thresholds associated to symptom appearance, these were a loss of 43.2% of tyrosine hydroxylase-immunopositive neurons at the nigral level and losses of 80.3 and 81.6% DA transporter binding and DA content, respectively, at the striatal level. Our data argue against the concept that an increase in DA metabolism could act as an efficient adaptive mechanism early in the disease progress. Surprisingly, the D(2)-like DA receptor binding showed a biphasic regulation in relation to the level of striatal dopaminergic denervation, i.e., an initial decrease in the presymptomatic period was followed by an upregulation of postsynaptic receptors commencing when striatal dopaminergic homeostasis is broken. Further in vivo follow-up of the kinetics of striatal denervation in this, and similar, experimental models is now needed with a view to developing early diagnosis tools and symptomatic therapies that might enhance endogenous compensatory mechanisms.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2001

Polyunsaturated fatty acids and cerebral function: focus on monoaminergic neurotransmission.

More and more reports in recent years have shown that the intake of polyunsaturated fatty acids (PUFA) constitutes an environmental factor able to act on the central nervous system (CNS) function. We recently demonstrated that the effects of PUFA on behavior can be mediated through effects on the monoaminergic neurotransmission processes. Supporting this proposal, we showed that chronic dietary deficiency in alpha-linolenic acid in rats induces abnormalities in several parameters of the mesocortical and mesolimbic dopaminergic systems. In both systems, the pool of dopamine stored in presynaptic vesicles is strongly decreased. This may be due to a decrease in the number of vesicles. In addition, several other factors of dopaminergic neurotransmission are modified according to the system affected. The mesocortical system seems to be hypofunctional overall [e.g., decreased basal release of dopamine (DA) and reduced levels of dopamine D2 (DAD2) receptors]. In contrast, the mesolimbic system seems to be hyperfunctional overall (e.g., increased basal release of DA and increased levels of DAD2 receptors). These neurochemical changes are in agreement with modifications of behavior already described with this deficiency. The precise mechanisms explaining the effects of PUFA on neurotransmission remain to be clarified. For example, modifications of physical properties of the neuronal membrane, effects on proteins (receptors, transporters) enclosed in the membrane, and effects on gene expression and/or transcription might occur. Whatever the mechanism, it is therefore assumed that interactions exist among PUFA, neurotransmission, and behavior. This might be related to clinical findings. Indeed, deficits in the peripheral amounts of PUFA have been described in subjects suffering from neurological and psychiatric disorders. Involvement of the monoaminergic neurotransmission function has been demonstrated or hypothesized in several of these diseases. It can therefore be proposed that functional links exist among PUFA status, neurotransmission processes, and behavioral disorders in humans. Animal models are tools of choice for the understanding of such links. Improved prevention and complementary treatment of neurological and psychiatric diseases can be expected from these studies.

Animals↗

PubMed2001

Pallidal border cells: an anatomical and electrophysiological study in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkey.

A dopamine transporter-radioligand binding study demonstrated a dopaminergic innervation around the pallidal complex in the normal monkey (n=5), i.e. where a subpopulation of pallidal neurons known as "border cells" is classically identified. Surprisingly, this peripallidal binding persists in monkeys rendered parkinsonian (n=5) with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment. The border cell electrophysiological activity was then analysed in normal and parkinsonian monkeys (n=2), either in the untreated state or following administration of levodopa. Pallidal border cell firing frequency was significantly decreased after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment (8.9+/-0.7 vs 31.4+/-1.6Hz, P<0.05). This decrease was partly corrected by levodopa administration (19.2+/-1.0Hz, P<0.05 vs both normal and parkinsonian situations). The peripallidal dopaminergic innervation suggests that pallidal border cells are under a direct dopaminergic control, arising from the ventral tegmental area and/or the basal forebrain magnocellular complex, the role of which remains unknown. Moreover, the relative sparing of these dopaminergic fibers in parkinsonian monkeys suggests that they would exhibit specific adaptive properties totally different from those described in the nigrostriatal pathway.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2001

Synthesis of tropane and nortropane analogues with phenyl substitutions as serotonin transporter ligands.

The effects of structural modifications of 2 beta-carbomethoxy-3 beta-phenyl tropane analogues were evaluated on in vitro affinity to the dopamine (DAT) and serotonin (5-HTT) transporters in rat brain tissue. The introduction of a large alkyl group at the 4'-position of the phenyl ring, affording 2 beta-carbomethoxy-3 beta-(4'-alkylphenyl) tropane, diminished the affinity for the DAT whereas moderate 5-HTT affinity was obtained. The introduction of an iodine at the 3'-position of the 4'-alkylphenyl, affording 2 beta-carbomethoxy-3 beta-(3'-iodo-4'-alkylphenyl) tropane, and N-demethylation, affording 2 beta-carbomethoxy-3 beta-(3'-iodo-4'-alkylphenyl) nortropane, improved affinity and specificity for the 5-HTT. It could be assumed from these results that the combination of these three modifications of tropane structure yielded highly selective compounds for the 5-HTT. Of the new compounds synthesized, the most selective cocaine derivative, 2 beta-carbomethoxy-3 beta-(3'-iodo-4'-isopropylphenyl) nortropane (8d) labeled with iodine-123 or carbon-11, could be a potential ligand for exploration of the 5-HT transporter by SPET or PET.

Animals↗

PubMed2001

Plasma fatty acid levels in autistic children.

Phospholipid fatty acids are major structural components of neuronal cell membranes, which modulate membrane fluidity and hence function. Evidence from clinical and biochemical sources have indicated changes in the metabolism of fatty acids in several psychiatric disorders. We examined the phospholipid fatty acids in the plasma of a population of autistic subjects compared to mentally retarded controls. Our results showed a marked reduction in the levels of 22: 6n-3 (23%) in the autistic subjects, resulting in significantly lower levels of total (n-3) polyunsaturated fatty acids (PUFA) (20%), without significant reduction in the (n-6) PUFA series, and consequently a significant increase in the (n-6)/(n-3) ratio (25%). These variations are discussed in terms of potential differences in PUFA dietary intake, metabolism, or incorporation into cellular membranes between the two groups of subjects. These results open up interesting perspectives for the investigation of new biological indices in autism. Moreover, this might have new therapeutic implications in terms of child nutrition.

Adolescent↗

PubMed2001

D2 receptor imaging in neonates using I-123 iodobenzamide brain SPECT.

PURPOSE: Hypoxic-ischemic injury induces early changes in cerebral energy that later lead to the presence and extension of brain damage and subsequently to severe neurodevelopmental impairments such as the dyskinetic form of cerebral palsy, which is associated with damage to the striatum. The purpose of the current study was to evaluate the viability of D2 receptors in the perinatal period using I-123 iodobenzamide brain SPECT and to correlate this with early neurologic status. METHODS: After obtaining informed parental consent, 12 full-term neonates with hypoxic-ischemic events were included. I-123 iodobenzamide brain SPECT was performed 1 week after birth, corresponding to a gestational age of 39.2+/-1.7 weeks. Images were acquired using a brain-dedicated gamma camera 1 hour after intravenous injection of 30 MBq (0.8 mCi) I-123 iodobenzamide. Magnetic resonance images (T2 weighted sequence: repetition time/echo time: 2,000/30 to 150) of the brains of the same neonates were acquired on the same day. RESULTS: The right and left striatum:cerebellum activity ratios were between 1.28 and 2.25, with the greatest concentration of I-123 iodobenzamide occurring in the striatum area. A tendency of the striatum:cerebellum ratio to decrease was observed as the severity of the perinatal hypoxic-ischemic event increased despite striatal hypersignal on magnetic resonance imaging in only two neonates. CONCLUSIONS: This study, which confirms that I-123 iodobenzamide could be used in the neonatal period, shows the biochemical maturation of D2 receptors as early as 1 week after birth and also suggests the deleterious effect of perinatal hypoxic-ischemic events on D2 receptors.

Brain↗

PubMed2001

Quantitative analysis of striatal dopamine D2 receptors with 123 I-iodolisuride SPECT in degenerative extrapyramidal diseases.

123I-Iodolisuride has high specific affinity for binding on dopamine D2 receptors in the striatum and has been used in a few single photon emission computed tomography (SPECT) studies of extrapyramidal disorders. The diagnosis of Parkinson's disease (PD) is very difficult in the first 5 years of evolution, with 15-25% false positive diagnoses. The aim of this study was therefore to determine the value of iodolisuride SPECT in discriminating Parkinson's from the most frequent Parkinson-plus syndromes (PPS). Seventeen patients with an extrapyramidal syndrome had a SPECT examination 1 h after injection of 180-185 MBq of 123I-iodolisuride. They were followed under dopaminergic treatment for at least 2 years. After 2 years, they were separated in two groups according to specific clinical criteria and sensitivity to dopaminergic treatment: nine patients had PD (age = 59.8+/-8.8 years; Hoehn and Yahr = 1.8+/-0.7; evolution = 4.3+/-3 years) and eight had PPS (age = 71.6+/-7.3 years; Hoehn and Yahr = 2.9+/-2.0; evolution = 4.1+/-1.5 years). The binding potential of iodolisuride in the striatum was assessed by considering the striatum (S)/occipital lobe (O) ratio at the pseudo-equilibrium 1 h after injection. The S/O ratio was statistically different between PD and PPS (1.97+/-0.3 vs. 1.65+/-0.2 (P<0.02)). Iodolisuride SPECT could differentiate both groups with a sensitivity of 88.8% and a specificity of 75%. Iodolisuride is a good specific D2 receptor ligand for SPECT and complements specific clinical criteria for the diagnosis of Parkinson's disease and differentiation between different extrapyramidal disorders.

Aged↗

PubMed2001

mRNA D(2) dopaminergic receptor expression after hypoxia-ischemia in rat immature brain.

Previous studies have shown a reduction of dopaminergic D(2) receptors (D(2)R) in the striatum after hypoxia-ischemia in newborn rats. We show here an early and transient reduction of mRNA D(2)R in nonatrophic brains following hypoxia-ischemia. The left carotid artery of P7 rats was ligated followed by hypoxia for 2 h. The rats were sacrificed after 24 h, 48 h and 14 days. D(2)R mRNA was studied by in situ hybridization, the cell number by conventional histology, and neuronal and astrocyte differentiation by immunohistochemistry. A 20% reduction of striatal mRNA D(2)R occurred 24 h after hypoxia-ischemia, whereas no reduction was observed after 48 h and 14 days. There were no differences in total cell number and in the expression of neuronal (MAP-1, MAP-2) and astrocyte (GFAP) markers between both brain hemispheres nor between control and hypoxia-ischemia animals. The early decrease in mRNA D(2)R could explain the delayed reduced D(2)R after neonatal hypoxia-ischemia.

Animals↗

PubMed2001

Characterization of 99mTc-DTPA aerosols for lung permeability studies.

BACKGROUND: The interpretation of 99mTc diethylenetriamine pentaacetate (99mTc DTPA) aerosol clearance is based on the hypothesis that the 99mTc-DTPA complex is not altered by the nebulization process. OBJECTIVES: To characterize (1) the radiochemical purity (RCP) of 99mTc-DTPA and the stability of labeling after jet nebulization, and (2) the particle size distribution of the aerosol. METHODS: RCP and stability--the aerosol was driven by oxygen, captured on filters which were eluted and RCP was checked by thin layer chromatography. Particle size distribution--the aerosol was generated using dry air (50 psi) at three different flow rates, i.e. 3 (1 run), 6 (4 runs) and 9 l x min(-1) (4 runs). The mass median aerodynamic diameter (MMAD) and the geometric standard deviation (sigma(g)) were determined using a cascade impactor from the radioactivity counted on each stage. RESULTS: The RCP was more than 95% in all cases. Mean MMAD (+/-SD) was 0.70 microm (+/-0.07) at 9 l x min(-1), 0.93 microm (+/-0.05) at 6 l x min(-1) (p < 0.05) and 1.50 microm at 3 l x min(-1). Mean sigma(g) (+/-SD) was 2.02 (+/-0.08) at 9 l x min(-1), 2.00 (+/-0.16) at 6 l x min(-1) and 1.90 at 3 l x min(-1). CONCLUSION: This study demonstrates (1) that the high RCP of 99mTc-DTPA is not affected by jet nebulization, even when using oxygen at a high flow rate, and (2) that when using a flow rate between 6 and 9 l x min(-1), the MMAD remains optimal for peripheral lung deposition.

Aerosols↗

PubMed2000

Microdialysis as a tool for in vivo study of dopamine transporter function in rat brains.

The role of dopamine as a major modulator of CNS function is well-known, and the homeostasis of dopamine is considered to be of major importance in the pathogenesis of several psychiatric and neurological diseases. Few methods are currently available for in vivo study of dopamine transporter function, which regulates extracellular levels of dopamine. Adapting the 'indicator diffusion' method applied to the microdialysis technique, we present here a suitable method for this functional investigation. We measured the cellular extraction of [3H]-MPP+, which is known to accumulate in the dopaminergic neurones through the DAT in the rat striatum, using [14C]-mannitol as reference substance characterized by absence of cellular accumulation. The cellular extraction was 0.41 and was almost abolished in the presence of the dopamine-uptake inhibitor cocaine, reaching 0.07. This suggested that extraction of [3H]-MPP+ was due to cellular uptake by dopamine transporters. Tissue analysis confirmed that [3H]-MPP+ was internalized in cells and that such transport was stopped by cocaine. Moreover, [3H]-MPP+ extraction was dramatically decreased after lesioning the nigro-striatal pathway with 6-hydroxydopamine, whereas [14C]-mannitol extraction was unchanged. It is concluded that the presented method can be used to study the functioning of the dopamine transporter in live animals.

1-Methyl-4-phenylpyridinium↗

PubMed2000

Neuroprotection of nerve growth factor-loaded microspheres on the D2 dopaminergic receptor positive-striatal neurones in quinolinic acid-lesioned rats: a quantitative autoradiographic assessment with iodobenzamide.

Huntington's disease (HD) results from the degeneration of striatal neurones, mainly gamma-aminobutyric acid (GABA)ergic projection neurones and lately cholinergic interneurones. The use of trophic factors as agents able to prevent such neural degeneration is a promising strategy. The aim of this study was to validate nerve growth factor-loaded (NGF-loaded) poly-D,L-lactide-co-glycolide (PLGA) microspheres for treatment of HD in a rat model with quinolinic acid lesion using autoradiographic study of D2 dopaminergic receptors (D2R). This target is expressed by about half of striatal neurones and its scintigraphic exploration has already been performed for the follow-up of this degenerative process. Ex vivo autoradiography of D2R performed with iodobenzamide, the widely used ligand for single photo emission computerized tomography, revealed slight neuroprotection. Moreover, tolerance of microspheres was demonstrated by in vitro autoradiography with the marker of gliosis, [(3)H]-PK 11195.

Animals↗

PubMed2000

Chronic n-3 polyunsaturated fatty acid deficiency alters dopamine vesicle density in the rat frontal cortex.

We studied the effects of a chronic deficiency in n-3 polyunsaturated fatty acids (n-3 PUFA) on the vesicle dopaminergic compartment in the frontal cortex of rats. Electronic micrographic analysis showed that the synaptic density and the clear vesicle density were similar in deficient and control rats. However, dopaminergic immunolabeling revealed a significantly decreased number of gold-labeled vesicles in the dopaminergic presynaptic terminals of the deficient rats. These findings demonstrate that dopamine cortical vesicles are specifically decreased in n-3 PUFA deficiency. The mechanism leading to this modification could involve several abnormalities (vesicle turn-over, membrane fluidity, vesicular monoamine transporter). This reduction in the dopaminergic vesicle pool constitutes the first structural support for the previously described modifications of dopamine metabolism in the frontal cortex. Such changes in dopamine neurotransmission could be involved in behavioral abnormalities occurring in n-3 PUFA deficient rats.

Animals↗

PubMed2000

[131I]-TYR3-octreotide: clinical dosimetry and use for internal radiotherapy of metastatic paraganglioma and carcinoid tumors.

Dosimetry and therapeutic application of [(131)I]-Tyr3-octreotide were evaluated in three patients with metastatic paraganglioma and carcinoid tumor. The in vitro stability of [(131)I]-Tyr3-octreotide was verified. Tumor uptake and residence time were between 0.02 and 0.1% and 0.5 to 9.8 h, respectively. The calculated tumor radiation doses were between 0.105 and 0.696 mGy.MBq(-1). No intolerance or adverse effects were observed after the therapeutic doses (3.3-6.6 GBq). A partial tumor response was obtained in one patient and no response occurred in two patients.

Adult↗

PubMed2000

Modification of dopamine neurotransmission in the nucleus accumbens of rats deficient in n-3 polyunsaturated fatty acids.

We studied the effects of a diet chronically deficient in alpha-linolenic acid, the precursor of long-chain n-3 polyunsaturated fatty acids, on dopaminergic neurotransmission in the shell region of the nucleus accumbens of rats. In vivo microdialysis experiments showed increased basal levels of dopamine and decreased basal levels of metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in awake rats from the deficient group compared to controls. The release of dopamine under KCl stimulation was similar in both dietary groups. By contrast, the release of dopamine from the vesicular storage pool under tyramine stimulation was 90% lower in the deficient than in the control rats. Autoradiographic studies in the same cerebral region revealed a 60% reduction in the vesicular monoamine transporter sites in the deficient group. Dopamine D(2) receptors were 35% increased in these rats compared to controls, whereas no change occurred for D(1) receptors and membrane dopamine transporters. These results demonstrated that chronic n-3 polyunsaturated fatty acid deficiency modifies several factors of dopaminergic neurotransmission in the nucleus accumbens. These findings are in agreement with the changes in dopaminergic neurotransmission already observed in the frontal cortex, and with the behavioral disturbances described in these deficient rats.

3,4-Dihydroxyphenylacetic Acid↗