Search

We demonstrate the efficiency of the convolution using an optimized Kaiser–Bessel window to resample nonlinear data in wavenumber for Fourier-domain optical coherence tomography (OCT). We extend our previous experimental demonstration that was performed with a specific swept-source nonlinearity. The method is now applied to swept-source OCT data obtained for various simulated swept-source nonlinearities as well as spectral-domain OCT data obtained from both simulations and experiments. Results show that the new optimized method is the most efficient for handling all the different types of nonlinearities in the wavenumber domain that one can encounter in normal practice. The efficiency of the method is evaluated through comparison with common methods using resampling through interpolation prior to performing a fast-Fourier transform and with the accurate but time-consuming discrete Fourier transform for unequally spaced data, which involves Vandermonde matrices.

Photoacoustic tomography (PAT) and ultrasonography (US) of biological tissues usually rely on ultrasonic transducers for the detection of ultrasound. For an optimum sensitivity, transducers require a physical contact with the tissue using a coupling fluid (water or gel). Such a contact is a major drawback in important potential applications such as surgical procedures on human beings and small animal imaging in research laboratories. On the other hand, laser ultrasonics (LU) is a well established optical technique for the non-contact generation and detection of ultrasound in industrial materials. In this paper, the remote optical detection scheme used in industrial LU is adapted to allow the detection of ultrasound in biological tissues while remaining below laser exposure safety limits. Both non-contact PAT (NCPAT) and non-contact US (NCUS) are considered experimentally using a high-power single-frequency detection laser emitting suitably shaped pulses and a confocal Fabry-Perot interferometer in differential configuration. It is shown that an acceptable sensitivity is obtained while remaining below the maximum permissible exposure (MPE) of biological tissues. Results were obtained ex vivo on chicken breast specimens with embedded inclusions simulating blood vessels optical properties. Sub-mm inclusions are readily detected at depths approaching 1 cm. The method is expected to be applicable to living tissues.

The objective of the present study was to investigate the effect of docosahexaenoic acid (DHA), a polyunsaturated fatty acid (omega‐3), on levodopa‐induced dyskinesias (LIDs) in parkinsonian 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)–treated monkeys. We explored the effect of DHA in two paradigms. First, a group of MPTP monkeys was primed with levodopa for several months before introducing DHA. A second group of MPTP monkeys (de novo) was exposed to DHA before levodopa therapy. DHA administration reduced LIDs in both paradigms without alteration of the anti‐parkinsonian effect of levodopa indicating that DHA can reduce the severity or delay the development of LIDs in a nonhuman primate model of Parkinson's disease. These results suggest that DHA can reduce the severity or delay the develoment of LIDs in a nonhuman primate model of Parkinson's disease. DHA may represent a new approach to improve the quality of life of Parkinson's disease patients. Ann Neurol 2006;59:282–288

Monitoring gene expression has been intensively used to identify neurobiological and neuroanatomical substrates associated with administration of antipsychotic drugs. Transcription factors of the Nur family (Nurr1, Nur77, and Nor-1) are orphan nuclear receptors that have been recently associated with dopamine neurotransmission. Nurr1 is involved in midbrain dopamine neuron development. Nur77 and Nor-1 are expressed in dopaminoceptive areas such as the striatum, nucleus accumbens, and prefrontal cortex. To better understand the relationship between Nur and antipsychotic drug effects, we conducted a comprehensive evaluation of the effect of various typical and atypical antipsychotic drugs on the modulation of Nur mRNA levels. We show that differential patterns of Nur expression can be obtained with typical and atypical antipsychotic drugs. Modulation of Nur77 and Nor-1 mRNA expression by antipsychotics can be used to calculate an index that is predictive of the typical or atypical profile of antipsychotic drugs. Inductions of Nur by anti-psychotic drugs are correlated with dopamine D2 receptor in the striatum and D2 and D3 receptor subtypes in the nucleus accumbens. The 5-hydroxytryptamine 2A/D2 affinity ratio of antipsychotics can also predict these patterns of inductions. In addition to classical gene patterns induced in the striatal complex (striatum, accumbens) and cortex, most antipsychotic drugs tested strongly induced Nur77, Nor-1, and increased Nurr1 mRNA levels in the substantia nigra and ventral tegmental area. These data suggest that typical and atypical antipsychotic drugs might induce in multiple brain regions distinct Nur-dependent transcriptional activities, which may contribute to their pharmacological effects.

The performance of a laser ultrasonic system applied to the detection and characterization of stress corrosion cracks and welding discontinuities in stainless steel is reported. A 50 mJ long pulse laser coupled with a confocal Fabry­Perot interferometer and the synthetic aperture focusing technique are used to enhance weak discontinuity related signals. First, stainless steel plates containing stress corrosion cracks with widths of less than 0.03 mm (1.2 × 10-3 in.) and depths ranging from 0.5 to 5 mm (0.02 to 0.2 in.) are tested. Both longitudinal and shear waves are used in synthetic aperture focusing technique processing to detect and characterize these cracks from the surface opposite cracking. Images at the breaking surface reconstructed by shear waves provide very detailed structures of branched tight cracks, which are comparable to results obtained by liquid penetrant testing. This excellent imaging is linked to the presence of crosslike features appearing in B-scans that are interpreted and explained. Secondly, a welded stainless steel plate is tested and various weld discontinuities with sizes of about 1 mm (0.04 in.) are detected. Although the material strongly attenuates ultrasound in this case, laser ultrasonics combined with the synthetic aperture focusing technique successfully detects, locates and sizes these discontinuities. These results are compared with those obtained by X-ray computed tomography. [ABSTRACT FROM AUTHOR]

Dopamine autoreceptors control the synaptic release and turnover of dopamine. Some dopamine agonists display a preference for modulation of autoreceptor functions rather than postsynaptic-driven behaviors. However, the nature of this apparent selectivity is still elusive. To investigate this property, we have used an heterologous expression system in which D2Sreceptors are coupled to both inhibition of cyclic AMP levels and stimulation of inositol triphosphate production. We show that D2-like receptor agonists display distinct potencies on these two second messenger pathways. Moreover, a strong correlation is observed between the potency of agonists to interact with adenylate cyclase and their potency to modulate autoreceptor functions. Such a correlation does not show up with the phospholipase C pathway. This suggests that autoreceptor preference of D2-like receptor agonists may be driven by a preferential interaction with a second messenger system.

The physiological role of the dopamine D3receptor is still unclear. The absence of selective pharmacological tools that can discriminate D3over D2receptor subtype activity is a major drawback in the elucidation of D3‐mediated functions. In order to study D3receptor actions in rat brain, we have developed an antisense strategy, using oligodeoxynucleotide (ODN) directed against the mRNA of the D3receptor. Dopamine D2‐like agents induce a cascade of events that affect numerous genes in the CNS. Transcription factors are among the most dramatically affected. Using the antisense strategy, we explored the involvement of the D3receptor on the expression of two classes of trancription factors, the c‐fosand NGFI‐B. Intracerebroventricular injections of ODNs were made into the lateral ventricle (8 μg/hour, for 5 days). The effect of antisense administration on dopamine D1, D2, and D3 receptor binding was measured by means of receptor autoradiography, whereas transcription factor mRNA levels (c‐fosand NGFI‐B) were evaluated by in situ hybridization using specific complementary RNA probes. Dopamine D3receptor levels were significantly decreased in the shell of nucleus accumbens of rats that received the D3antisense ODN, whereas dopamine D1and D2receptor levels were not affected. Basal c‐fosmRNA levels were concomitantly reduced in both cingulate and medial prefrontal cortices. Basal NGFI‐B mRNA levels were also reduced in the cingulate cortex, shell of nucleus accumbens, and in the dorsomedial striatum, whereas the core of nucleus accumbens and the dorsolateral striatum were not affected after D3antisense ODN treatments. Our results suggest that D3receptors may tonically regulate transcription factor expression in rat forebrain. This supports the hypothesis of a constitutive activity of the D3receptor in vivo. Synapse 32:51–57, 1999. © 1999 Wiley‐Liss, Inc.

The dopamine D3receptor is a member of the G protein‐coupled superfamily of receptors. However, its coupling with intracellular events is still not well understood. We have performed chimera constructions in which amino acid residues located in a region of the receptor involved in the coupling with second messengers (the C‐terminal portion of the third intracellular loop) have been exchanged between dopamine D2and D3receptors. Chimera constructions did not modify substantially the pharmacological profiles, nor G protein coupling, as compared to their respective wild‐type receptors. However, the D2receptor chimera, containing the C‐terminal portion of the third intracellular loop of the D3receptor, has a lower potency to inhibit cyclic AMP production. The reciprocal construction generated a D3receptor that is fully coupled to this second messenger pathway whereas, the native D3receptor is uncoupled to this pathway in our transfected cells. These results suggest that the sequence selected is important for specific coupling characteristics shown by these two dopamine receptor homologues.

A radioreceptor assay (RRA) was used to determine the neuroleptic plasma levels of 32 outpatients with schizophrenia receiving a high dose of neuroleptics (the equivalent of 18 mg or more of oral haloperidol per day) and undergoing a 50% partial and progressive reduction (ten percent each month for five months) in their medication. Plasma levels of neuroleptics were measured three times: before (T1) and immediately after the 50% reduction (T2) and five months later (T3). A linear correlation was observed between neuroleptic plasma levels obtained by RRA and the neuroleptic doses prescribed at T1 and T3. Furthermore, neuroleptic plasma levels were significantly lower at T3 than at T1. Concurrent evaluations of psychopathology were done using the Brief Psychiatric Rating Scale, and the results indicated that no correlation exists between neuroleptic plasma levels and the total rating scale scores at T1 but a significant correlation was observed at T3.

THE functional potency of a series of dopamine agonists for increasing mitogenesis, measured by incorporation of [3H]thymidine, was established in transfected cell lines expressing human D2 or D3 receptors. The functional selectivity of agonists markedly differs from their binding selectivity. (+)7-OH-DPAT, pramipexole, quinerolane and PD 128,907, the most D3 receptor-selective compounds in binding studies, were 7, 15, 21 and 54 times more potent, respectively, at the D3 than at the D2 receptor in the functional test. Bromocriptine displayed a 10-fold functional selectivity toward the D2 receptor. The known behavioural actions of D3 selective agonists support a role for the D3 receptor in motor inhibitions, which should be taken into account for the treatment of motor dysfunctions by dopamine agonists.

WE have investigated the effects of a dopamine D3receptor antisense oligodeoxynucleotide (ODN), on neurotensin and dynorphin mRNA levels in rat nucleus accumbens. Intracerebroventricular injections of ODNs were made into the lateral ventricle (5 and 10 μg h−1, for 5 days). Receptor autoradiography of dopamine D2and D3receptor subtypes was performed. Dynorphin and neurotensin mRNA levels were evaluated by in situhybridization. Dopamine D3receptor levels were significantly decreased in nucleus accumbens shell (NAS) of rats that received the D3antisense ODN. Dynorphin and neurotensin mRNA levels were also significantly decreased in the NAS after D3antisense ODN treatments. Our results show that D3receptors may regulate neuropeptide gene expression and demonstrate that an antisense strategy could be useful to identify molecular targets under control of specific dopamine receptor subtypes.

Although oral administration of L-Dopa remains the best therapy for Parkinson disease, its long-term administration causes the appearance of abnormal involuntary movements such as dyskinesia. Although persistent striatal induction of some genes has already been associated with such pathologic profiles in hemiparkinsonian rats, molecular and cellular mechanisms underlying such long-term adaptations remain to be elucidated. In this study, using a rat model of L-Dopa-induced dyskinesia, we report that activity regulated cytoskeletal (Arc)-associated protein is strongly upregulated in the lesioned striatum and that the extent of its induction further varies according to the occurrence or absence of locomotor sensitization. Moreover, Arc is preferentially induced, along with FosB, nur77, and homer-1a, in striatonigral neurons, which express mRNA encoding the precursor of dynorphin. Given the likely importance of Arc in the regulation of cytoskeleton during synaptic plasticity, its upregulation supports the hypothesis that a relationship exists between cytoskeletal modifications and the longlasting action of chronically administrated L-Dopa.