ABSTRACT
The Solanaceae plants distributed in China belong to 105 species and 35 varietas of 24 genera. Some medicinal plants of Solanaceae are rich in tropane alkaloids(TAs), which have significant pharmacological activities. In this paper, the geographical distribution, chemical components, traditional therapeutic effect, pharmacological activities, and biosynthetic pathways of TAs in Solanaceous plants were summarized. Besides, the phylogeny of medicinal plants belonging to Solanaceae was visualized by network diagram. Fourteen genera of Solanaceae plants in China contain TAs and have medical records. TAs mainly exist in Datura, Anisodus, Atropa, Physochlaina, and Hyoscyamus. The TAs-containing species were mainly concentrated in Southwest China, and the content of TAs was closely related to plant distribution area and altitude. The Solanaceae plants containing TAs mainly have antispasmodic, analgesic, antiasthmatic, and antitussive effects. Modern pharmacological studies have proved the central sedative, pupil dilating, glandular secretion-inhibiting, and anti-asthma activities of TAs. These pharmacological activities provide a reasonable explanation for the traditional therapeutic efficacy of tropane drugs. In this paper, the geographical distribution, chemical components, traditional therapeutic effect, and modern pharmacological activities of TAs-containing species in Solanaceae were analyzed for the first time. Based on these data, the genetic relationship of TAs-containing Solanaceae species was preliminarily discussed, which provided a scientific basis for the basic research on TAs-containing solanaceous species and was of great significance for the development of natural medicinal plant resources containing TAs.
Subject(s)
Biosynthetic Pathways , Phylogeny , Plants, Medicinal , Solanaceae/genetics , TropanesABSTRACT
Background: Since alkaloids are nitrogenous compounds, the availability of nitrogen [N] is expected to play an important role in the biosynthesis and accumulation of alkaloids in plants. Nitrogen has been found to increase the content of alkaloids in some of the medicinal plants
Objective: The aim of this study was to compare the effects of nitrogen bio-fertilizers, conventional nitrogen fertilizer, and nitrogen nano-chelate fertilizer on the content of tropane alkaloids in Hyoscyamus niger L
Methods: This experiment was conducted in a randomized complete block design [RCBD] with 8 treatments, and 3 replications. The experimental treatments included 2 L.h[-1] nitroxin, 1 kg.h[-1] Azotobacter, and 10 t.h[-1] vermicompost each as bio-fertilizer, 150 kg.h[-1] urea as a conventional chemical fertilizer of nitrogen, and nitrogen nano-chelate fertilizer with three amounts of 3, 5, and 7 percent, and control treatment [without nitrogen fertilizer]
Results: The results showed that the effects of bio-fertilizers, conventional nitrogen fertilizer, and nitrogen nano-chelate fertilizer were significant on the scopolamine and hyoscyamine content in black henbane at the level of 1%. The highest content of hyoscyamine [HYO] was related to the treatments of 5% per hectare nitrogen nano-chelate, and the maximum amount of scopolamine [SCO] was observed in the treatments of 3 and 5% nitrogen nano-chelate fertilizers. On the other hand, the lowest values of hyoscyamine and scopolamine were related to the treatment of 7% nitrogen nano-chelate fertilizer, and nitroxin treatment, respectively
Conclusion: Generally, the highest yield of alkaloids content in black henbane were obtained by application of 3 and 5% nitrogen nano-chelate fertilizers
Subject(s)
Tropanes , Fertilizers , Nitrogen CompoundsABSTRACT
Atropa belladonna is a medicinal plant and main commercial source of tropane alkaloids (TAs) including scopolamine and hyoscyamine, which are anticholine drugs widely used clinically. Based on the high throughput transcriptome sequencing results, the digital expression patterns of UniGenes representing 9 structural genes (ODC, ADC, AIH, CPA, SPDS, PMT, CYP80F1, H6H, TRII) involved in TAs biosynthesis were constructed, and simultaneously expression analysis of 4 released genes in NCBI (PMT, CYP80F1, H6H, TRII) for verification was performed using qPCR, as well as the TAs contents detection in 8 different tissues. Digital expression patterns results suggested that the 4 genes including ODC, ADC, AIH and CPA involved in the upstream pathway of TAs, and the 2 branch pathway genes including SPDS and TRII were found to be expressed in all the detected tissues with high expression level in secondary root. While the 3 TAs-pathway-specific genes including PMT, CYP80F1, H6H were only expressed in secondary roots and primary roots, mainly in secondary roots. The qPCR detection results of PMT, CYP80F1 and H6H were consistent with the digital expression patterns, but their expression levels in primary root were too low to be detected. The highest content of hyoscyamine was found in tender stems (3.364 mg x g(-1)), followed by tender leaves (1.526 mg x g(-1)), roots (1.598 mg x g(-1)), young fruits (1.271 mg x g(-1)) and fruit sepals (1.413 mg x g(-1)). The highest content of scopolamine was detected in fruit sepals (1.003 mg x g(-1)), then followed by tender stems (0.600 mg x g(-1)) and tender leaves (0.601 mg x g(-1)). Both old stems and old leaves had the lowest content of hyoscyamine and scopolamine. The gene expression profile and TAs accumulation indicated that TAs in Atropa belladonna were mainly biosynthesized in secondary root, and then transported and deposited in tender aerial parts. Screening Atropa belladonna secondary root transcriptome database will facilitate unveiling the unknown enzymatic reactions and the mechanisms of transcriptional control.
Subject(s)
Alkaloids , Genetics , Metabolism , Atropa belladonna , Genetics , Metabolism , Gene Expression Regulation, Plant , Genetics , Hyoscyamine , Genetics , Metabolism , Plants, Medicinal , Genetics , Metabolism , Scopolamine , Metabolism , Tropanes , MetabolismABSTRACT
To assess the effect of homatropine eye drops on pain after photorefractive keratectomy [PRK]. This randomized, double masked, interventional study included 15 patients [30 eyes] who underwent bilateral PRK. After operation, patients received homatropine eye drops, 4 times daily in only one eye [homatropine eye]. The level of pain was evaluated using visual analogue scale [VAS], verbal rating scale [VRS] and pain rating index [PRI] at 0.5, 24 and 48 h after operation. The level of pain was statistically similar between the two eyes half an hour after operation, however, homatropine eyes had significantly less pain 24 h after operation compared to fellow eyes [2.5 +/- 1.9 vs 5.3 +/- 2.5, P = 0.004 for VAS, 2.0 +/- 1.2 vs 3.2 +/- 0.9, P = 0.023 for VRS, and 9.4 +/- 5.7 vs 16.0 +/- 9.0, P = 0.031 for PRI]. Also, 48 h after surgery, the pain scales were less in the homatropine eyes [2.3 +/- 1.7 vs 4.0 +/- 2.1, P = 0.014 for VAS, 1.6 +/- 1.0 vs 2.5 +/- 1.0, P = 0.038 for VRS, and 6.8 +/- 5.7 vs 12.0 +/- 8.9, P = 0.005 for PRI]. No delayed epithelial healing was observed. Homatropine eye drops may be useful for reducing pain after Photorefractive keratectomy
Subject(s)
Humans , Female , Male , Tropanes/administration & dosage , Tropanes , Pain, Postoperative/therapy , Pilot ProjectsABSTRACT
Atropa belladonna L. is the officially medicinal plant species and the main commercial source of scopolamine and hyoscyamine in China. In this study, we reported the simultaneous overexpression of two functional genes involved in biosynthesis of scopolamine, which respectively encoded the upstream key enzyme putrescine N-methyltransferase (PMT; EC 2.1.1.53) and the downstream key enzyme hyoscyamine 6beta-hydroxylase (H6H; EC 1.14.11.11) in transgenic hair root cultures of Atropa belladonna L. HPLC results suggested that four transgenic hair root lines produced higher content of scopolamine at different levels compared with nontransgenic hair root cultures. And scopolamine content increased to 8.2 fold in transgenic line PH2 compared with that of control line; and the other four transgenic lines showed an increase of scopolamine compared with the control. Two of the transgenic hair root lines produced higher levels of tropane alkaloids, and the content increased to 2.7 fold in transgenic line PH2 compared with the control. The gene expression profile indicated that both PMT and H6H expressed at a different levels in different transgenic hair root lines, which would be helpful for biosynthesis of scopolamine. Our studies suggested that overexpression of A. belladonna endogenous genes PMT and H6H could enhance tropane alkaloid biosynthesis.
Subject(s)
Atropa belladonna , Genetics , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Plant , Hyoscyamine , Metabolism , Methyltransferases , Genetics , Metabolism , Mixed Function Oxygenases , Genetics , Metabolism , Plant Roots , Genetics , Plants, Genetically Modified , Genetics , Plants, Medicinal , Genetics , Scopolamine , Metabolism , Synthetic Biology , Tropanes , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To study the effects of methyl jasmonate (MJ) on the accumulation and release of main secondary metabolites i. e. scopolamine and hyoscyamine in liquid cultures of Datura stramonium hairy roots.</p><p><b>METHOD</b>After 18 days liquid culture of D. stramonium hairy roots induced by agrobacterium rhizogenes C58C1, the chemical elicitor methyl jasmonate was added into 1/2 MS liquid cultures and scopolamine and hyoscyamine on the day 0, 3, 6, 9 and 12, after dealing with MJ, was determined by HPLC.</p><p><b>RESULT</b>After dealing with MJ on the day 3, 6, 9 and 12,the concentration of scopolamine reached to 0.419, 0.439, 0.431, 0.374 mg x g(-1), respectively, the increase of scopolamine were 1.36, 1.42, 1.17 and 1.12 fold higher than that of the control, respectively. And hyoscyamine reached 1.493, 0.817, 0.723 and 0.698 mg x g(-1), respectively, the increase of hyoscyamine were 2.28, 1.11, 0.63 and 0.70 fold higher than that of the control, respectively.</p><p><b>CONCLUSION</b>MJ could stimulate the accumulation of scopolamine and hyoscyamine (3,6 d) in D. stramonium hairy root and have released them into the culture medium.</p>
Subject(s)
Acetates , Pharmacology , Alkaloids , Metabolism , Cell Culture Techniques , Cyclopentanes , Pharmacology , Datura stramonium , Chemistry , Metabolism , Oxylipins , Pharmacology , Plant Roots , Chemistry , Metabolism , Tropanes , MetabolismABSTRACT
Plants infection with microorganisms as well as physical factors such as osmotic stresses especially drought stress induced particular secondary metabolite production. Plant root and shoot hyoscyamine [HYO] and scopolamine [SCO] variations were investigated under three water deficit stress [WDS] levels as 30 [W1], 60 [W2] and 90% [W3] water depletion of field capacity and Pseudomonas putida [PP] and P. fluoresence [PF] strains inoculation at flowering stage. Seedling radicles and culture media were inoculated with PP and PF [10[9] CFU/ml] strains. Monitoring of soil moisture levels was conducted using gravimetric method. Alkaloids extracted were identified by gas chromatography [GC] and gas chromatography-mass spectrometry [GC-MS] analysis. Results revealed that HYO was the prevalent alkaloid in root and shoot organs. The highest ratio of SCO to HYO [0.53] and the highest alkaloids both HYO and SCO content in root and shoot was observed in W3PF treatment. The largest total alkaloids [HYO+SCO] yield [25.7 mg.plant[-1]] was showed in PP treated plants under W1 conditions. Integrative use of effective Pseudomonades strains and WDS sounds to be an encouraging and eco-friendly strategy for increasing tropane alkaloids yield and content in Hyoscyamus niger root and shoot parts
Subject(s)
Tropanes , Scopolamine , Pseudomonas putida , Chromatography, Gas , Gas Chromatography-Mass Spectrometry , Water , Hyoscyamine , Flowering TopsABSTRACT
The clinical diagnosis of Parkinson's disease (PD) is susceptible to misdiagnosis, especially in the earlier stages of the disease. Recently, in vivo imaging techniques assessing the presynaptic dopamine transporter (DAT) have emerged as a useful tool in PD diagnosis, improving its accuracy. OBJECTIVE: It was to illustrate the clinical usefulness of a brain single-photon emission computed tomography (SPECT) DAT ligand, and highlight relevant aspects of scans without evidence of dopaminergic deficit (SWEDDs) in this context. CASES: We described four representative patients with clinically unclear parkinsonian syndromes who underwent [99mTc]-TRODAT-1 SPECT and reviewed the clinical implications. CONCLUSION: DAT-SPECT is an important, cost-effective, technique for the differential diagnosis of parkinsonian syndromes. Additionally, SWEDD cases present clinical and paraclinical peculiarities that may retrospectively identify them as essential/dystonic tremor. The lack of histopathological data limits further conclusions.
O diagnóstico clínico da doença de Parkinson (DP) pode estar sujeito a erros especialmente nas fases iniciais da doença. Recentemente, técnicas de imagem in vivo que avaliam o transportador de dopamina pré-sináptico (DAT) surgiram como uma ferramenta empregada no diagnóstico da DP, melhorando sua acurácia. OBJETIVO: Foi demonstrar a utilização clínica de um traçador de tomografia computadorizada por emissão de fóton único (SPECT) e destacar importantes aspectos dos casos de SWEDDs (exames sem evidência de déficit dopaminérgico) neste contexto. CASOS: Descrevemos quatro pacientes representativos de síndromes parkinsonianas clinicamente incertas submetidos a [99mTc]-TRODAT-1 SPECT e revisamos suas implicações. CONCLUSÃO: O DAT-SPECT é uma técnica importante e eficiente para o diagnóstico diferencial das síndromes parkinsonianas. Além disso, os casos de SWEDDs apresentam peculiaridades clínicas e paraclínicas que podem retrospectivamente identificá-los como tremor essencial ou tremor distônico. As conclusões têm alcance limitado pela falta de dados histopatológicos.
Subject(s)
Adult , Female , Humans , Middle Aged , Dopamine Plasma Membrane Transport Proteins/metabolism , Organotechnetium Compounds , Parkinsonian Disorders , Radiopharmaceuticals , Tomography, Emission-Computed, Single-Photon , Tropanes , Diagnosis, Differential , Magnetic Resonance Imaging , Tomography, Emission-Computed, Single-Photon/economicsABSTRACT
OBJECTIVE@#To investigate the therapeutic effects of co-transplantation with Schwann cells (SCs) and human embryonic nerve stem cells (NSCs) on macaque Parkinson's disease (PD).@*METHODS@#Macaque autologous SCs and human embryonic NSCs were adopted for the treatment of macaque PD.@*RESULTS@#Six months after transplantation, positron emission computerized tomography showed that (18)F-FP-β-CIT was significantly concentrated in the injured striatum in the co-transplanted group. Immunohistochemical staining of transplanted area tissue showed migration of tyroxine hydroxylase positive cells from the transplant area to the surrounding area was significantly increased in the co-transplanted group.@*CONCLUSIONS@#Co-transplantation of SCs and NSCs could effectively cure PD in macaques. SCs harvested from the autologous peripheral nerves can avoid rejection and the ethics problems, so it is expected to be applied clinically.
Subject(s)
Animals , Female , Humans , Male , Cells, Cultured , Corpus Striatum , Metabolism , Dyskinesias , Embryonic Stem Cells , Transplantation , Immunohistochemistry , Macaca , Motor Activity , Multimodal Imaging , Nerve Tissue , Transplantation , Parkinsonian Disorders , Metabolism , General Surgery , Positron-Emission Tomography , Radiopharmaceuticals , Metabolism , Schwann Cells , Transplantation , Stem Cell Transplantation , Tomography, X-Ray Computed , Tropanes , MetabolismABSTRACT
Plants infection with microorganisms as well as physical factors such as osmotic stresses induced particular secondary metabolite pathways. To investigate the growth promoting effects of two Rhizobacteria strains including Pseudomonas fluoresces [PF] and Putida [PP] in combination with application of water deficit stress on plant biomass of Hyoscyamus niger young roots and variation of tropane alkaloids content and yield in root and shoot parts. Two grams of dried each shoot and root samples was added to appropriate volume of CHCl3: MeOH: NH4OH 25%, [15:5: 1], and sonicated for 20 min. Alkaloids extracted were analyzed by gas chromatographic [GC] method using a Younglin Acme 6000 GC system equipped with a flame ionization detector [FID] and HP-5MS capillary column [30 m x 0.25 mm, film thickness 0.25 micro m]. The identification of alkaloids was based on the comparison of their GC retention time and mass spectra data with their standards substances. Results indicated that the highest alkaloid content values in root [hyoscyamine: 0.26% DW; scopolamine: 0.12% DW] and shoot [hyoscyamine: 0.85% DW; scopolamine: 0.48% DW] were achieved in PF-187 treated plants grown under severe water stress conditions [W3]. By contrast, the maximum alkaloid yield in root [hyoscyamine: 1.92 mg.plant[-1]; scopolamine: 0.83 mg.plant[-1]] and shoot [hyoscyamine: 5.88 mg.plant[-1]; SCO: 3.06 mg.plant[-1]] were obtained in PP-168 treated plants under low water stress conditions [W1]. Rhizobacteria strains can function as environmentally sound tools to increase alkaloids production and counteract growing problems under stress conditions, especially by auxin production
Subject(s)
Pseudomonas putida , Pseudomonas fluorescens , Alkaloids , Tropanes , DehydrationABSTRACT
A prospective study to evaluate the changes in A-Scan axial parameters of phakic normal eyes before and after instillation of 1% topical Tropicamide and 2% Homatropine eye drops. Anterior chamber depth, lens thickness, vitreous chamber length, and ocular axial length were measured in 76 eyes before and after cycloplegia induced by 1% topical Tropicamide, and in 28 eyes with 2% Homatropine eye drops. Anterior chamber depth demonstrated increase from baseline readings with Tropicamide and Homatropine eye drops, while lens thickness showed decrease from the baseline readings with both eye drops. Effect of both the eye drops on over all axial length and vitreous chamber length is statistically seen, but is clinically negligible and not significant. Cycloplegia induced by 1% Tropicamide eye drops and 2% Homatropine eye drops has a significant measurable influence on anterior chamber depth and lens thickness, while vitreous chamber length and overall axial length demonstrated negligible statistical difference on A-Scan parameters of the normal phakic eyes
Subject(s)
Tropicamide/pharmacology , Tropanes/pharmacology , Lens Implantation, Intraocular , Anterior Chamber/drug effects , Prospective StudiesABSTRACT
PURPOSE: We investigated quantification of dopaminergic transporter (DAT) and serotonergic transporter (SERT) on (123)I-FP-CIT SPECT for differentiating between multiple systemic atrophy (MSA) and idiopathic Parkinson's disease (IPD). MATERIALS AND METHODS: N-fluoropropyl-2beta-carbomethoxy-3beta-4-[(123)I]-iodophenylnortropane SPECT ((123)I-FP-CIT SPECT) was performed in 8 patients with MSA (mean age: 64.0+/-4.5yrs, m:f=6:2), 13 with early IPD (mean age: 65.5+/-5.3yrs, m:f=9:4), and 12 healthy controls (mean age: 63.3+/-5.7yrs, m:f=8:4). Standard regions of interests (ROIs) of striatum to evaluate DAT, and hypothalamus and midbrain for SERT were drawn on standard template images and applied to each image taken 4 hours after radiotracer injection. Striatal specific binding for DAT and hypothalamic and midbrain specific binding for SERT were calculated using region/reference ratio based on the transient equilibrium method. Group differences were tested using ANOVA with the postHoc analysis. RESULTS: DAT in the whole striatum and striatal subregions were significantly decreased in both patient groups with MSA and early IPD, compared with healthy control (p<0.05 in all). In early IPD, a significant increase in the uptake ratio in anterior and posterior putamen and a trend of increase in caudate to putamen ratio was observed. In MSA, the decrease of DAT was accompanied with no difference in the striatal uptake pattern compared with healthy controls. Regarding the brain regions where (123)I-FP-CIT binding was predominant by SERT, MSA patients showed a decrease in the binding of (123)I-FP-CIT in the pons compared with controls as well as early IPD patients (MSA: 0.22+/-0.1 healthy controls: 0.33+/-0.19, IPD: 0.29+/-0.19), however, it did not reach the statistical significance. CONCLUSION: In this study, the differential patterns in the reduction of DAT in the striatum and the reduction of pontine (123)I- FP-CIT binding predominant by SERT could be observed in MSA patients on (123)I- FP-CIT SPECT. We suggest that the quantification of SERT as well as DAT using (123)I- FP-CIT SPECT is helpful to differentiate parkinsonian disorders in early stage.
Subject(s)
Humans , Atrophy , Brain , Dopamine Plasma Membrane Transport Proteins , Hypothalamus , Mesencephalon , Multiple System Atrophy , Parkinson Disease , Parkinsonian Disorders , Pons , Putamen , Serotonin Plasma Membrane Transport Proteins , Tomography, Emission-Computed, Single-Photon , TropanesABSTRACT
Dopamine transporter imaging is useful in the diagnosis of Parkinson's disease and the most successful technique in the clinical use of neuroreceptor imaging. Recently, several radiopharmaceuticals including I-123 FP-CIT, Tc-99m TRODAT, and F-18 FP-CIT for dopamine transporter imaging have been approved for the routine clinical use in several European countries, Taiwan and Korea, respectively. This review summarized the practical issue for the routine clinical examination of dopamine transporter imaging.
Subject(s)
Dopamine , Dopamine Plasma Membrane Transport Proteins , Korea , Parkinson Disease , Positron-Emission Tomography , Radiopharmaceuticals , Sensory Receptor Cells , Taiwan , Tomography, Emission-Computed, Single-Photon , TropanesABSTRACT
This study was conducted to evaluate the applicability of 99mTc-2beta-[ N, N'-bis (2-mercaptoethyl) ethylenediamino]methyl,3beta(4-chlorophenyl)tropane(TRODAT-1) dopamine transporter(DAT) SPECT imaging in children with autism, and thus to provide an academic basis for the etiology, mechanism and clinical therapy of autism. Ten autistic children and ten healthy controls were examined with 99mTc-TRODAT-1 DAT SPECT imaging. Striatal specific uptake of 99mTc-TRODAT-1 was calculated with region of interest analysis according to the ratics between striatum and cerebellum [(STR-BKG)/BKG]. There was no statistically significant difference in semiquantitative dopamine transporter between the bilateral striata of autistic children (P=0.562), and between those of normal controls (p=0.573); Dopamine transporter in the brain of patients with autism increased significantly as compared with that in the brain of normal controls (P=0.017). Dopaminergic nervous system is dysfunctioning in the brain of children with autism, and DAT 99mTc-TRODAT-1 SPECT imaging on the brain will help the imaging diagnosis of childhcod autism.
Subject(s)
Child , Child, Preschool , Humans , Male , Autistic Disorder , Diagnostic Imaging , Metabolism , Brain , Diagnostic Imaging , Metabolism , Dopamine Plasma Membrane Transport Proteins , Metabolism , Organotechnetium Compounds , Tomography, Emission-Computed, Single-Photon , TropanesABSTRACT
INTRODUÇÃO: Radiotraçadores para neuroimagem de transportador de dopamina (TDA) foram desenvolvidos para estimar a perda de neurônios dopaminérgicos in vivo na doença de Parkinson (DP). OBJETIVO: Avaliar a densidade de TDA in vivo utilizando [99mTc]-TRODAT-1 (INER-Taiwan) e SPECT em uma população de pacientes brasileiros com DP. MÉTODO: Quinze pacientes com DP e 15 controles saudáveis pareados realizaram exames de SPECT com [99mTc]-TRODAT-1 (INER-Taiwan). Estimativas da densidade de TDA estriatal foram calculadas usando potencial de ligação (PL). Pacientes foram avaliados com escalas para PD. RESULTADOS: Pacientes com DP apresentaram redução significativa do PL-TDA (0,38±0,12) comparado aos controles (0,84±0,16, p<0,01). Foi possível discriminar casos de DP de controles com uma sensibilidade de 100 por cento e especificidade de 100 por cento. Foram obtidas correlações negativas entre PL-TDA e escalas de severidade da DP (rho= -0,7, p<0,001) e disfunção motora (rho= -0,8, p<0,001). CONCLUSÃO: Exames de SPECT com [99mTc]-TRODAT-1 foram capazes de discriminar pacientes com DP de controles. Esta técnica é um instrumento útil para medir a densidade de TDA e pode ser utilizado para clínica e pesquisa no Brasil.
BACKGROUND: Dopamine transporter (DAT) neuroimaging radiotracers were developed to estimate dopamine neuronal loss in vivo in ParkinsonÆs disease (PD). OBJECTIVE: To evaluate DAT density in vivo using [99mTc]-TRODAT-1 and single photon computerized tomography (SPECT) in a population of Brazilian PD. METHOD: Fifteen PD patients and 15 matched healthy controls scanned with [99mTc]-TRODAT-1 (INER-Taiwan) and SPECT. Estimates of striatum DAT density were calculated using binding potential (BP). Patients were assessed with PD scales. RESULTS: PD patients had significantly lower striatal DAT-BP (mean±SD) (0.38±0.12) compared to controls (BP=0.84±0.16; p<0.01). A 100 percent sensitivity and 100 percent specificity was obtained to discriminate PD cases from controls. Negative correlations between striatal DAT-BP and PD severity (rho= -0.7, p<0.001) and motor scales (rho= -0.80, p<0.001) were found. CONCLUSION: [99mTc]TRODAT-1 SPECTs scanning was able to discriminate PD patients from controls. The technique is a powerful instrument to measure DAT density that can be used in clinical and research settings in Brazil.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Dopamine Plasma Membrane Transport Proteins/metabolism , Organotechnetium Compounds , Parkinson Disease , Tomography, Emission-Computed, Single-Photon/methods , Tropanes , Case-Control Studies , Parkinson Disease/metabolism , Reproducibility of Results , Radiopharmaceuticals , Sensitivity and Specificity , Severity of Illness IndexABSTRACT
Introducción: los déficits cognitivos están relacionados con el deterioro funcional y con la baja calidad de vida en la enfermedad de Parkinson (EP). El sistema dopaminérgico de los ganglios basales es importante para el funcionamiento cognitivo y motor. Radiomarcadores de transportador de Dopamina (TAD) han sido utilizados para calcular la pérdida neuronal dopaminérgica en humanos. Objetivos: estudiar la relación entre el deterioro cognitivo y la pérdida neuronal dopaminérgica estriatal en pacientes con EP. Métodos: quince pacientes fueron escaneados con [99mTc]-TRODAT-1 y SPECT. El estriado (STR) y el lóbulo occipital (BKG) fueron definidos como regiones de interés (RIs) para la obtención del potencial de ligación (PL = [STR - BKG] / BKG). Exámenes neurocognitivos fueron aplicados, incluyendo el Rey Auditory Verbal Learning Test (RAVLT), Wisconsin Card Sorting Test (WCST), Ravens Progressive Matrices, Digit Span y Tavis 3. Resultados: El PL fue correlacionado negativamente con los exámenes de RAVLT 4 y 5, que evalúan el aprendizaje verbal. El PL también fue correlacionado negativamente con el artículo de aprendizaje de WCST y los artículos de Tavis 3, el error de acción y el número de aciertos. Conclusiones: este estudio indica que la pérdida de TAD estriatal está asociada con un desempeño mas pobre en tareas de flexibilidad cognitiva y aprendizaje verbal. Estos resultados están de acuerdo con un estudio previo con participantes sanos que encontró una relación entre la densidad de TAD del caudado y el desempeño en tareas de aprendizaje verbal. La segmentación del caudado/putamen en una muestra mayor está en desarrollo y podrá proveer más información sobre déficits cognitivos y pérdida de TAD estriatal.
Subject(s)
Humans , Tomography, Emission-Computed, Single-Photon , Organotechnetium Compounds , Dopamine/analysis , Parkinson Disease , Dopamine/deficiency , Neurodegenerative Diseases , Membrane Transport Proteins , Neuropsychological Tests , Cognition Disorders , Cognition Disorders/etiology , TropanesABSTRACT
Parkinsons disease (PD) is a common neurodegenerative disorder that is mainly caused by dopaminergic neuron loss in the substantia nigra. Several nuclear medicine radiotracers have been developed to evaluate PD diagnoses and disease evolution in vivo in PD patients. Positron emission tomography (PET) and single photon computerized emission tomography (SPECT) radiotracers for the dopamine transporter (DAT) provide good markers for the integrity of the presynaptic dopaminergic system affected in PD. Over the last decade, radiotracers suitable for imaging the DAT have been the subject of most efforts. In this review, we provide a critical discussion on the utility of DAT imaging for ParkinsonÆs disease diagnosis (sensitivity and specificity).
A doença de Parkinson (DP) é uma desordem neurodegenerativa causada por perda de neurônios dopaminérgicos na substância negra. Vários traçadores da medicina nuclear têm sido desenvolvidos para avaliar o diagnóstico e acompanhamento da DP. Traçadores para o transportador de dopamina (TDA) utilizados na tomografia por emissão de pósitrons (PET) e tomografia por emissão de fóton único (SPECT) demonstram boa marcação na integridade de sistema dopaminergico pré-sináptico, afetada na DP. Na última década, radiotraçadores apropriados para imagens de TDA têm sido mais estudados. Nesta revisão, provemos uma discussão crítica sobre a utilidade dessas imagens de TDA para o diagnóstico de DP (sensibilidade e especificidade).
Subject(s)
Humans , Dopamine Plasma Membrane Transport Proteins , Organotechnetium Compounds , Parkinson Disease , Positron-Emission Tomography/standards , Tomography, Emission-Computed, Single-Photon/standards , Tropanes , Dopamine Agents , Sensitivity and SpecificityABSTRACT
<p><b>BACKGROUND</b>Although dopamine transporter (DAT) is essential for addiction, the effect of additive drugs on DAT function is still controversial, especially for opiates. We investigated the functional changes of dopamine transporter in striatum of rhesus monkeys during acute morphine injection and its abstinence.</p><p><b>METHODS</b>Four rhesus monkeys, 6 to 9 years old, two male and two female, were examined for 12 days. Single photon emission computed tomography (SPECT) was performed with (99)T(cm)-TRODAT-1 as the radiopharmaceutical dopamine transporter agent during different stages of acute morphine injection and its abstinence. The ratios of SPECT signal between striatum and cerebellum (ST/CB) were calculated.</p><p><b>RESULTS</b>The ST/CB ratio declined significantly on the first day of morphine injection and continued declining with more morphine injections. After abstinence, the ratio increased with time, but was still significantly lower on the 5th day of abstinence than the normal level.</p><p><b>CONCLUSIONS</b>In rhesus monkey, acute morphine injection has both rapid and lasting effects on DAT by downregulating its function. The decline was partially reversible following morphine abstinence. The results suggest that striatum is one effective target of morphine and that the DAT function in striatum is one indicator for morphine addiction.</p>
Subject(s)
Animals , Female , Male , Acute Disease , Cerebellum , Metabolism , Corpus Striatum , Metabolism , Dopamine Plasma Membrane Transport Proteins , Physiology , Macaca mulatta , Morphine Dependence , Organotechnetium Compounds , Tomography, Emission-Computed, Single-Photon , TropanesABSTRACT
<p><b>OBJECTIVE</b>To investigate the role of 99mTc-TRODAT-1 SPECT in diagnosis and assessing severity of idiopathic Parkinson's disease (PD).</p><p><b>METHODS</b>Thirty-eight patients with primary, tentative diagnosis of PD and eighteen age-matched normal controls were studied with 99mTc-TRODAT-1 SPECT imaging. The regions of interests (ROIs) were drawn manually on cerebellum (CB), occipital cortex (OC) and three transverse plane slice-views of striatums, the semiquantitative BG (background)/[(OC+CB)/2] were then calculated.</p><p><b>RESULTS</b>A lower uptake of 99mTc-TRODAT-1 in striatums were displayed in thirty-six out of thirty-eight PD patients by visual inspection, compared to controls. In twenty-four PD cases with (Hoehn and Yahr scale) HYS stage I, a greater loss of DAT uptake was found in striatum and its subregions contralateral striatum to the affected limbs than in the same regions of the controls, although the striatal uptake was bilaterally reduced. Using Spearman correlation analysis showed that the reduction of the uptake ratios significantly correlated with the UPDRS in striatum and all its subregions in the PD group (P<0.05), a similar change was also found in the putamen by using the rating scale of Hoehn and Yahr (P<0.05). However, analysis of variance (ANOVA) did not show any relationship between the decreasing uptake of 99mTc-TRODAT-1 and increasing severity of PD patients, although the specific uptake of 99mTc-TRODAT-1 was continuously decreased in the striatum by visual inspection with the progress of PD from HYS stage I to III.</p><p><b>CONCLUSION</b>99mTc-TRODAT-1 SPECT imaging may serve as a useful method for improving the correct diagnosis of PD. In assessing the role of 99mTc-TRODAT-1 SPECT in disease severity of PD, UPDRS can offer a comprehensive index, although the Hoehn and Yahr assessment may be available in part.</p>