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| 2. |
- Danfors, Torsten, et al.
(författare)
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Tetrahydrobiopterin in the treatment of children with autistic disorder. A double-blind placebo-controlled crossover study
- 2005
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Ingår i: Journal of Clinical Psychopharmacology. - 0271-0749 .- 1533-712X. ; 25:5, s. 485-489
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Tidskriftsartikel (refereegranskat)abstract
- Twelve children, all boys, aged 4 to 7 years, with a diagnosis of autistic disorder and low concentrations of spinal 6R-l-erythro-5,6,7,8-tetrahydrobiopterin (tetrahydrobiopterin) were selected to participate in a double-blind, randomized, placebo-controlled, crossover study. The children received a daily dose of 3 mg tetrahydrobiopterin per kilogram during 6 months alternating with placebo. Treatment-induced effects were assessed with the Childhood Autism Rating Scale every third month. The results showed small nonsignificant changes in the total scores of Childhood Autism Rating Scale after 3- and 6-month treatment. Post hoc analysis looking at the 3 core symptoms of autism, that is, social interaction, communication, and stereotyped behaviors, revealed a significant improvement of the social interaction score after 6 months of active treatment. In addition, a high positive correlation was found between response of the social interaction score and IQ. The results indicate a possible effect of tetrahydrobiopterin treatment.
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| 3. |
- Doi, Hisashi, et al.
(författare)
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Synthesis of 11C-labelled N,N’-diphenylurea and ethyl phenylcarbamate by rhodium-promoted carbonylation reaction via [11C]-isocyanatobenzene using phenyl azide and [11C]carbon monoxide
- 2004
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Ingår i: Organic and biomolecular chemistry. - 1477-0520 .- 1477-0539. ; 2:21, s. 3063-3066
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Tidskriftsartikel (refereegranskat)abstract
- The reaction with phenyl azide and [11C]carbon monoxide to give N,N'-diphenyl[11C]urea and ethyl phenyl[11C]carbamate has been studied with the aim of development of a new methodology for carbonylation using [11C]carbon monoxide with high specific radioactivity. The synthesis of 11C-labelled N,N'-diphenylurea from phenyl azide and [11C]carbon monoxide, with 1,2-bis(diphenylphosphino)ethane-bound Rh(I) complex at 120 degrees C at a pressure of 35 MPa in the presence of aniline was accomplished in 82% trapping efficiency and 82% conversion yield. This approach was also useful for the synthesis of ethyl phenyl[11C]carbamate with lithium ethoxide as a nucleophilic reagent giving 90% trapping efficiency and 76% conversion yield. These reactions can be considered to proceed via a [11C]isocyanate or a [11C]isocyanate-coordinated Rh complex to give the corresponding 11C-products. This protocol provides the chemical basis for the synthesis of [11C]urea and [11C]carbamate derived from [11C]isocyanates.
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| 4. |
- Dubol, Manon, et al.
(författare)
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Acute nicotine exposure blocks aromatase in the limbic brain of healthy women : A [11C]cetrozole PET study
- 2023
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Ingår i: Comprehensive Psychiatry. - : Elsevier. - 0010-440X .- 1532-8384. ; 123
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Tidskriftsartikel (refereegranskat)abstract
- Background: Of interest to women's mental health, a wealth of studies suggests sex differences in nicotine addiction and treatment response, but their psychoneuroendocrine underpinnings remain largely unknown. A pathway involving sex steroids could indeed be involved in the behavioural effects of nicotine, as it was found to inhibit aromatase in vitro and in vivo in rodents and non-human primates, respectively. Aromatase regulates the synthesis of oestrogens and, of relevance to addiction, is highly expressed in the limbic brain.Methods: The present study sought to investigate in vivo aromatase availability in relation to exposure to nicotine in healthy women. Structural magnetic resonance imaging and two [11C]cetrozole positron emission tomography (PET) scans were performed to assess the availability of aromatase before and after administration of nicotine. Gonadal hormones and cotinine levels were measured. Given the region-specific expression of aromatase, a ROI -based approach was employed to assess changes in [11C]cetrozole non-displaceable binding potential.Results: The highest availability of aromatase was found in the right and left thalamus. Upon nicotine exposure, [11C]cetrozole binding in the thalamus was acutely decreased bilaterally (Cohen's d =-0.99). In line, cotinine levels were negatively associated with aromatase availability in the thalamus, although as non-significant trend.Conclusions: These findings indicate acute blocking of aromatase availability by nicotine in the thalamic area. This suggests a new putative mechanism mediating the effects of nicotine on human behaviour, particularly relevant to sex differences in nicotine addiction.
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| 5. |
- Fernell, Elisabeth, 1948, et al.
(författare)
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Possible effects of tetrahydrobiopterin treatment in six children with autism--clinical and positron emission tomography data: a pilot study.
- 1997
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Ingår i: Developmental Medicine and Child Neurology. - 0012-1622. ; 39:5, s. 313-318
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Tidskriftsartikel (refereegranskat)abstract
- Six children, between 3 and 5 years of age, having infantile autism according to DSM-III-R, were treated for 3 months with 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-BH4), a cofactor for tyrosine hydroxylases in the biosynthetic pathway of catecholamines and serotonin. A criterion for inclusion in the study was a relatively low level of R-BH4 in the cerebrospinal fluid. For clinical evaluation, the Parental Satisfaction Survey (PASS) was used every fourth week and the Griffiths Developmental Scales were used before starting and 3 months after completing the treatment. During the treatment period, all parents reported improvements in the child's social functioning-mainly eye contact and desire to interact-and in the number of words or sounds which the child used. Small positive changes were noted on the Griffiths Developmental Scales between the two testing occasions. R-BH4 levels in CSF increased significantly after treatment. The positron emission tomography (PET) study showed that the high value of dopamine D2 receptor binding in the caudate and putamen decreased by about 10% towards the normal level after treatment with R-BH4. The observations in this open study indicate that the drug might be useful for a subgroup of children with autism, but there is a need for a larger double-blind study with a longer treatment period.
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| 6. |
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| 7. |
- Immenschuh, Jana, et al.
(författare)
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Multimodal neuroimaging reveals neural correlates of aromatase availability in the female brain
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Estrogens extend their influence beyond reproduction, having been associated with neural plasticity and therefore the potential to shape the brain. It is unknown if the availability of aromatase, which is responsible for local estrogen synthesis in the brain, is associated with neural morphology. Here the correlation between in vivo brain availability of aromatase, grey and white matter structure, and peripheral levels of estradiol in healthy, young women was investigated.Methods: [11C]cetrozole positron emission tomography was performed together with structural and diffusion magnetic resonance imaging to assess the availability of aromatase, grey and white matter volumes, cortical surface architecture and white matter microstructure, respectively. Bioavailable gonadal hormone levels were measured. Results: Aromatase availability was notably high in the thalamus, hypothalamus, and amygdala, positively correlating with the grey matter volume of these regions. Cortical thickness and gyrification of the prefrontal cortex, as well as white matter properties of the fornix, were associated with aromatase availability. This suggests the impact of estrogens on the grey matter areas to which high aromatase-expressing regions are connected, and projecting white matter tracts, all part of the limbic brain that is often involved in mental disorders. Brain aromatase availability did not correlate with peripheral bioavailable hormone levels, pointing to a unique role of brain-derived estrogens. Conclusions: These findings provide the first evidence of brain morphological characteristics being associated with aromatase availability, shedding light on the impact of estrogens on brain structure.
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| 8. |
- Jonasson, My, et al.
(författare)
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Quantification of aromatase binding in the female human brain using [11 C]cetrozole positron emission tomography.
- 2020
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Ingår i: Journal of Neuroscience Research. - : Wiley. - 0360-4012 .- 1097-4547. ; 98:11, s. 2208-2218
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Tidskriftsartikel (refereegranskat)abstract
- Aromatase, the enzyme that in the brain converts testosterone and androstenedione to estradiol and estrone, respectively, is a putative key factor in psychoneuroendocrinology. In vivo assessment of aromatase was performed to evaluate tracer kinetic models and optimal scan duration, for quantitative analysis of the aromatase positron emission tomography (PET) ligand [11 C]cetrozole. Anatomical magnetic resonance and 90-min dynamic [11 C]cetrozole PET-CT scans were performed on healthy women. Volume of interest (VOI)-based analyses with a plasma-input function were performed using the single-tissue and two-tissue (2TCM) reversible compartment models and plasma-input Logan analysis. Additionally, the simplified reference tissue model (SRTM), Logan reference tissue model (LRTM), and standardized uptake volume ratio model, with cerebellum as reference region, were evaluated. Parametric images were generated and regionally averaged voxel values were compared with VOI-based analyses of the reference tissue models. The optimal reference model was used for evaluation of a decreased scan duration. Differences between the plasma-input- and reference tissue-based methods and comparisons between scan durations were assessed by linear regression. The [11 C]cetrozole time-activity curves were best described by the 2TCM. SRTM nondisplaceable binding potential (BPND ), with cerebellum as reference region, can be used to estimate [11 C]cetrozole binding and generated robust and quantitatively accurate results for a reduced scan duration of 60 min. Receptor parametric mapping, a basis function implementation of SRTM, as well as LRTM, produced quantitatively accurate parametric images, showing BPND at the voxel level. As PET tracer, [11 C]cetrozole can be employed for relatively short brain scans to measure aromatase binding using a reference tissue-based approach.
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| 9. |
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| 10. |
- Marklund, Niklas, et al.
(författare)
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Increased Cerebral Uptake of [18F]Fluoro-Deoxyglucose but not [1-14C]Glucose Early following Traumatic Brain Injury in Rats
- 2009
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 26:8, s. 1281-1293
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Tidskriftsartikel (refereegranskat)abstract
- Following experimental and clinical traumatic brain injury (TBI), the local cerebral metabolic rate of glucose (lCMRGlc) is commonly estimated using the 2-[18F]fluoro-2-deoxy-D-glucose (FDG) method. The adequate estimation of lCMRGlc using FDG requires a correction factor, the lumped constant (LC), to convert FDG net uptake into lCMRGlc. The LC, and thus lCMRGlc calculations, requires a "steady state" that may be disrupted following TBI. In the present report, we hypothesized that [1-14C]glucose uptake would accurately reflect glucose dynamics early post-injury and was compared to the regional uptake of FDG in 44 rats subjected to moderate (2.4-2.6 atm) lateral fluid percussion brain injury (FPI) or sham injury. Cortical energy state and adenylate (ATP, ADP, AMP) levels were also measured. Early (7-42 min) after FPI, FDG uptake was increased in the ipsilateral cortex and hippocampus (p<0.05). In contrast, no change in [1-14C]glucose uptake (7 and 17 min) or cortical adenylate content (42 min post-injury) was observed. At 12 hours following FPI, the ipsilateral FDG and [1-14C]glucose uptake was decreased in the cortex and hippocampus and the ipsilateral cortical ATP concentration was decreased in comparison to sham-injured controls (p<0.05). Under the present experimental conditions, the rate of cerebral uptake of FDG and of [1-14C]glucose differs, and indicate that following TBI, regional changes in the LC may occur in the immediate, but not in the late, post-injury phase. These results should be considered when interpreting results obtained using FDG for the estimation of lCMRGlc early following experimental TBI.
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