Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.161
Filtrar
1.
Medicine (Baltimore) ; 100(39): e27192, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596116

RESUMO

ABSTRACT: The presynaptic dopamine transporter (DAT) modulates the uptake of dopamine by regulating its concentration in the central nervous system. We aimed to evaluate the DAT binding potential (DAT-BP) in a sample of healthy Brazilians through technetium-99 metastable TRODAT-1 single-photon emission computed tomography imaging.We selected 126 healthy individuals comprising 72 men and 54 women, aged 18 to 80 years. We conducted semi-quantitative evaluation in transaxial slices, following which we identified the regions of interest in the striatal region using the occipital lobe as a region of non-specific DAT-BP.We found a decrease in DAT-BP in healthy individuals aged over 30 years, culminating in a 42% mean reduction after 80 years. There was no difference in the decrease by age group between the right (linear regression test [R2] linear = 0.466) and left striatum (R2 linear = 0.510). Women presented a higher DAT-BP than men (women: R2 linear = 0.431; men: R2 linear = 0.457); nonetheless, their decrease by age group was equal to that in men.Our study sheds light on important DAT-BP findings in healthy Brazilian subjects. Our results will facilitate understanding of brain illnesses that involve the dopamine system, such as neuropsychiatric disorders.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tropanos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Adulto Jovem
2.
Adv Ther ; 38(10): 5381-5397, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34528220

RESUMO

INTRODUCTION: Long-acting muscarinic antagonists (LAMAs), long-acting ß2-agonists (LABAs), inhaled corticosteroids (ICS), and their combinations, are recommended for the treatment of chronic obstructive pulmonary disease (COPD). This study aimed to determine whether the safety and efficacy of aclidinium bromide differs by baseline maintenance LABA and ICS therapies. METHODS: ASCENT-COPD was a phase 4, multicenter, double-blind, randomized, placebo-controlled, parallel-group study of patients with moderate-to-very severe COPD and increased cardiovascular risk. Patients were randomized 1:1 to receive aclidinium 400 µg or placebo twice daily, via a multidose dry-powder inhaler for up to 3 years. Outcomes included time to first major adverse cardiovascular events (MACE), all-cause mortality, change from baseline in trough forced expiratory volume in 1 s (FEV1), and COPD assessment test (CAT) total score over 3 years, and annual moderate-to-severe COPD exacerbation rate in patients receiving aclidinium or placebo with maintenance LABA monotherapy, ICS monotherapy, LABA + ICS (fixed/free), or no maintenance therapy (neither LABA nor ICS) at baseline. RESULTS: A total of 3589 patients were included (LABA, n = 227; ICS, n = 290; LABA + ICS, n = 2058; no maintenance, n = 1130). Aclidinium did not increase the risk of MACE or all-cause mortality versus placebo, regardless of baseline maintenance treatment. Reductions in moderate-to-severe exacerbation rates were observed with aclidinium versus placebo in all subgroups [LABA 43% (P = 0.046); ICS 25% (P = 0.202); LABA + ICS 22% (P = 0.003); no maintenance 18% (P = 0.130)]. Aclidinium improved morning trough FEV1 irrespective of baseline therapy and CAT total scores, except for LABA and ICS subgroups, versus placebo at several time points. CONCLUSION: In patients with moderate-to-severe COPD and CV risk factors, the addition of aclidinium to maintenance therapy with LABA or LABA + ICS provided further benefit. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01966107.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2 , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Broncodilatadores/uso terapêutico , Volume Expiratório Forçado , Humanos , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Tropanos/uso terapêutico
3.
Zhongguo Zhong Yao Za Zhi ; 46(17): 4344-4359, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34581037

RESUMO

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.


Assuntos
Plantas Medicinais , Solanaceae , Vias Biossintéticas , Filogenia , Solanaceae/genética , Tropanos
4.
Harmful Algae ; 108: 102101, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34588122

RESUMO

Water bloom-forming cyanobacteria have a severe impact on freshwater quality. Although some cyanobacterial toxins such as microcystins have been studied extensively, other toxins like anatoxin-a (ATX) and their structural analogs - as well as cyanobacterial taxa producing these toxins remain to be explored in detail. The present study investigated levels of ATX, CYN and their homologs along with the occurrence of anaC and cyrJ genes in water blooms in 16 sites in the Czech Republic that were pre-selected concerning the presence of potential toxin producers. Besides, we also studied toxins and genes in a series of strains available in our laboratories. ATX and its congener HATX were detected in 5 natural biomass samples from the Czech Republic (maximum concentration 2.8 micrograms per gram d.w.). Interestingly, the anaC gene coding for ATX production was not detected in any of these toxin-positive biomass samples. The concentrations of ATX congeners in cyanobacterial laboratory strains were about 10-times higher than those of the original ATX, which calls for further research addressing levels and hazards of ATX analogs. Regarding the CYN and 7-deoxyCYN (other CYN congeners were not analyzed in this study) - these toxins were identified in a single small pond in the Czech Republic at concentrations 4.3 and 2.7 micrograms per gram of biomass d.w., respectively (corresponded to dissolved concentrations higher than 1 microgram per liter). The CYN-positive sample was dominated by CYN-producing taxa Raphidiopsis (basionym Cylindrospermopsis) and Cuspidothrix. We also confirmed the presence of a specific cyrJ gene in this natural bloom sample. To our knowledge, this is the first study pointing to Raphidiopsis (Cylindrospermopsis) and Cuspidothrix as producers of CYN in Europe. This observation calls for further research because of their increasing occurrence in (Central) Europe along with the global change. The present study demonstrates the importance of using combined (taxonomical, analytical, and molecular) approaches in the assessment of hazardous cyanobacteria and their toxins in freshwaters.


Assuntos
Alcaloides , Tropanos , República Tcheca
5.
Biosensors (Basel) ; 11(9)2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34562905

RESUMO

The adoption of electrochemical principles to realize on-field analytical tools for detecting pollutants represents a great possibility for food safety and environmental applications. With respect to the existing transduction mechanisms, i.e., colorimetric, fluorescence, piezoelectric etc., electrochemical mechanisms offer the tremendous advantage of being easily miniaturized, connected with low cost (commercially available) readers and unaffected by the color/turbidity of real matrices. In particular, their versatility represents a powerful approach for detecting traces of emerging pollutants such as cyanotoxins. The combination of electrochemical platforms with nanomaterials, synthetic receptors and microfabrication makes electroanalysis a strong starting point towards decentralized monitoring of toxins in diverse matrices. This review gives an overview of the electrochemical biosensors that have been developed to detect four common cyanotoxins, namely microcystin-LR, anatoxin-a, saxitoxin and cylindrospermopsin. The manuscript provides the readers a quick guide to understand the main electrochemical platforms that have been realized so far, and the presence of a comprehensive table provides a perspective at a glance.


Assuntos
Toxinas Bacterianas/análise , Monitoramento Ambiental/métodos , Análise de Alimentos/métodos , Alcaloides , Técnicas Biossensoriais , Cianobactérias , Água Doce , Toxinas Marinhas , Microcistinas , Tropanos , Uracila
6.
Cogn Behav Neurol ; 34(3): 207-211, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473672

RESUMO

McLeod syndrome is a rare X-linked recessive genetic disorder that is caused by mutations of the XK gene. It is one of the core neuroacanthocytosis syndromes. We report the case of a 67-year-old man who presented to Kyungpook National University Hospital in the Republic of Korea with progressive worsening of generalized chorea and dystonia. He had no recognized family history of neurologic illness. A peripheral blood smear showed increased acanthocytes. His serum creatine kinase levels were 894 U/L. A brain MRI showed atrophy of the bilateral striatal nuclei. An F-18 F-N-(3-fluoropropyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane PET/CT showed moderately decreased dopamine transporter uptake in the putamen and severely decreased uptake in the caudate nucleus. An F-18 fludeoxyglucose PET/CT demonstrated markedly decreased metabolism at the caudate nucleus and the putamen. Whole exome sequencing revealed hemizygous pathogenic mutations of the XK gene (c.856_860delCTCTA;p.Leu286TyrfsTer16). We believe that these findings provide useful information regarding the clinical features of individuals with McLeod syndrome.


Assuntos
Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Idoso , Encéfalo/diagnóstico por imagem , Humanos , Masculino , Mutação , Neuroacantocitose , Tropanos
7.
Medicine (Baltimore) ; 100(34): e27019, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449475

RESUMO

ABSTRACT: Early and accurate identification of various conditions that can cause parkinsonian symptoms is important for determining treatment policies. Currently dopamine transporter (DAT) imaging using FP-CIT, glucose metabolism imaging using fluorodeoxyglucose, cerebral blood flow image using ethyl cysteinate dimer (ECD), and others are used for differentiation. However, the use of multiple modalities is inconvenient and costly. In the present retrospective study, we evaluated the correlation between regional brain uptake ratios (URs) in perfusion FP-CIT PET and ECD SPECT images.Twenty patients with Parkinson's symptoms underwent perfusion DAT positron emission tomography (18F-FP-CIT PET/CT) and cerebral blood flow tomography (99mTc-ECD SPECT) within a 2-week period. Perfusion 18F-FP-CIT PET/CT and 99mTc-ECD SPECT URs of 19 brain regions (bilateral frontal, temporal, parietal and occipital lobes, bilateral caudate nucleus, bilateral putamen, bilateral insula, bilateral cingulate gyrus, bilateral thalamus, and brainstem) were directly compared and correlations were analyzed.Average 18F-FP-CIT PET/CT regional perfusion URs were higher than 99mTc-ECD SPECT URs. Uptake ratios were well correlated in all 19 regions (except right putamen), and especially in dopamine poor regions (cerebral cortex). In left putamen, URs were significantly correlated, but the correlation coefficient was lower than those of other regions.A single tracer dual phase N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane test seems to be helpful for differential diagnosis of parkinsonian disorders. Large-scale, longitudinal studies on complementary diseases with parkinsonian patterns are required to investigate differences in correlations between perfusion 18F-FP-CIT PET/CT and 99mTc-ECD SPECT over time.


Assuntos
Encéfalo/diagnóstico por imagem , Transtornos Parkinsonianos/diagnóstico por imagem , Transtornos Parkinsonianos/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Idoso , Encéfalo/patologia , Cisteína/análogos & derivados , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Feminino , Radioisótopos de Flúor , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Organotecnécio , Transtornos Parkinsonianos/diagnóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Tropanos
8.
Anal Chem ; 93(32): 11284-11290, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34342436

RESUMO

An effective and precise electrochemiluminescence resonance energy transfer (ECL-RET), including the efficient regulation over the proximity of a donor and an acceptor and the reliable stimuli responsive as well as the avoidance of undesirable probes leakage, etc., is significant for the development of an accurate and sensitive ECL detection method; yet, the current literature in documentation involves only a limited range of such ECL-RET systems. Herein, we propose an ECL-RET strategy with dually quenched ultralow background signals and a dual-stimuli responsive, accurate signal output for the ultrasensitive and reliable detection of anatoxin-a (ATX-a). The dual quenching is accomplished by an integrated ECL-RET probe of metal organic frameworks (MOFs) encapsulated into Ru(bpy)32+ (Ru-MOF) (donor) coated with silver nanoparticles (AgNPs) shell (acceptor 1) and close proximity with DNA-ferrocene (Fc) (acceptor 2). Multistimuli responsive DNAzyme facilitated the accurate signal switch by both target ATX-a and hydrogen peroxide (H2O2). Because of the specific recognition of the aptamer toward ATX-a, an intricate design of the DNA sequence enabled the exposure of the Ag+-dependent DNAzyme sequence and H2O2 in situ generated Ag+ triggering a catalytic cleavage reaction to freely release the two ECL-RET energy acceptors, thus switching the ECL signal significantly and achieving ultrasensitive detection. It is noteworthy that AgNPs are key in this ECL-RET strategy, serving both as the gate-keepers for avoiding ECL probes leakage and also the ECL energy acceptors, and mostly importantly serving as the redox substrate for the subsequent DNAzyme catalytic signal switch. The proposed ECL-RET aptasensor for ATX-a detection displayed splendid monitoring performance with a quite low detection limit of 0.00034 mg mL-1. This sensor not only led to the development of a dual-quenching ECL-RET system but also provided meaningful multistimuli responsive ECL biosensing platform construction, which shows a promising application prospect in complicated sample analysis.


Assuntos
DNA Catalítico , Nanopartículas Metálicas , Técnicas Eletroquímicas , Transferência de Energia , Peróxido de Hidrogênio , Medições Luminescentes , Prata , Tropanos
9.
Clin Nucl Med ; 46(9): 754-755, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34374680

RESUMO

ABSTRACT: Corticobasal syndrome (CBS) is characterized by a slow progressive cognitive decline, apraxia, myoclonus, dystonia, and parkinsonism. We experienced a rapidly progressing CBS patient (onset to bed-ridden within 2 years) presenting only with resting tremor but showing complete unilateral loss of dopamine transporter binding. This case exhibited distinct FDG PET findings involving the unilateral severe anterior frontal cortex, caudate nucleus, and contralateral cerebellum, which is different from classical CBS. However, to date, no detailed serial functional imaging study has been performed in rapidly progressing CBS, so these FDG PET and CIT PET findings may help clinicians to recognize this fulminant type of corticobasal degeneration.


Assuntos
Fluordesoxiglucose F18 , Transtornos Parkinsonianos , Humanos , Tomografia por Emissão de Pósitrons , Tropanos
10.
Sci Rep ; 11(1): 14992, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294739

RESUMO

Delayed phase 18F-FP-CIT PET (dCIT) can assess the striatal dopamine transporter binding to detect degenerative parkinsonism (DP). Early phase 18F-FP-CIT (eCIT) can assess the regional brain activity for differential diagnosis among parkinsonism similar with 18F-FDG PET. We evaluated the diagnostic performance of dual phase 18F-FP-CIT PET (dual CIT) and 18F-FDG PET compared with clinical diagnosis in 141 subjects [36 with idiopathic Parkinson's disease (IPD), 77 with multiple system atrophy (MSA), 18 with progressive supranuclear palsy (PSP), and 10 with non-DP)]. Visual assessment of eCIT, dCIT, dual CIT, 18F-FDG and 18F-FDG PET with dCIT was in agreement with the clinical diagnosis in 61.7%, 69.5%, 95.7%, 81.6%, and 97.2% of cases, respectively. ECIT showed about 90% concordance with non-DP and MSA, and 8.3% and 27.8% with IPD and PSP, respectively. DCIT showed ≥ 88% concordance with non-DP, IPD, and PSP, and 49.4% concordance with MSA. Dual CIT showed ≥ 90% concordance in all groups. 18F-FDG PET showed ≥ 90% concordance with non-DP, MSA, and PSP, but only 33.3% concordance with IPD. The combination of 18F-FDG and dCIT yielded ≥ 90% concordance in all groups. Dual CIT may represent a powerful alternative to the combination of 18F-FDG PET and dCIT for differential diagnosis of parkinsonian disorders.


Assuntos
Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Paralisia Supranuclear Progressiva/diagnóstico por imagem , Tropanos/administração & dosagem , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
11.
J Neural Transm (Vienna) ; 128(11): 1655-1661, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34328563

RESUMO

Glabellar tap or reflex (GR) is an old bedside clinical test used in the diagnostics of Parkinson's disease (PD), but its diagnostic value is unclear. This study examines the diagnostic validity and reliability of GR in PD in relation to brain dopaminergic activity. GR was performed on 161 patients with PD, 47 patients with essential tremor (ET) and 40 healthy controls immediately prior to dopamine transporter (DAT) [123I]FP-CIT SPECT scanning. The binding ratios were investigated with consideration of the GR result (normal/abnormal). In addition, the consistency of the GR was investigated with 89 patients after a mean follow-up of 2.2 years. PD and ET patients had higher GR scores than healthy controls (p < 0.001), but there was no difference in GR between PD and ET patients (p = 0.09). There were no differences in the ratio of abnormal to normal GRs between the PD and ET groups (73% vs. 64% abnormal, respectively, p = 0.13) or in DAT binding between PD patients with abnormal and normal GRs (p > 0.36). Over follow-up, the GR changed from abnormal to normal in 20% of PD patients despite the presence of clinically typical disease. The sensitivity and specificity of GR for differentiating PD from ET were 78.3% and 36.2%, respectively. Although GR has been used by clinicians in the diagnostics of PD, it does not separate PD from ET. It also shows considerable inconsistency over time, and abnormal GR has no relationship with dopamine loss. Its usefulness should be tested for other clinical diagnostic purposes.


Assuntos
Tremor Essencial , Doença de Parkinson , Dopamina , Proteínas da Membrana Plasmática de Transporte de Dopamina , Tremor Essencial/diagnóstico por imagem , Humanos , Doença de Parkinson/diagnóstico por imagem , Reprodutibilidade dos Testes , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos
12.
Expert Rev Respir Med ; 15(9): 1093-1106, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34137664

RESUMO

Introduction: Aclidinium/formoterol is a long-acting muscarinic antagonist (LAMA) and long-acting ß2-agonist (LABA) dual bronchodilator used as a maintenance treatment for patients with chronic obstructive pulmonary disease (COPD). The efficacy of aclidinium/formoterol has been demonstrated consistently in patients with moderate-to-severe COPD versus placebo and monocomponents, with a comparable safety profile.Areas covered: This review examines recent research findings that expand our understanding of the impact of aclidinium/formoterol on the burden of COPD. Reviewed outcomes include improvements in lung function, respiratory symptoms, health-related quality of life, exercise tolerance, exacerbation rates, and clinically important deteriorations. In addition, the reported cardiovascular safety of aclidinium and current LAMA/LABA treatment recommendations are discussed.Expert opinion: Aclidinium/formoterol reduces disease burden in patients with COPD, including those that are treatment-naïve, without a significant increase in safety risk compared with monotherapies. Furthermore, evidence supports an improvement in lung function over a 24-hour period with aclidinium/formoterol treatment versus monotherapy and placebo, which may offer an advantage over some once-daily LAMA/LABA combinations. In summary, the recent evidence discussed in this review adds weight to the use of LAMA/LABA combinations as an initial therapy for certain patients newly diagnosed with COPD.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2 , Broncodilatadores , Fumarato de Formoterol , Doença Pulmonar Obstrutiva Crônica , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Broncodilatadores/uso terapêutico , Combinação de Medicamentos , Fumarato de Formoterol/uso terapêutico , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Qualidade de Vida , Tropanos
13.
Jpn J Radiol ; 39(11): 1097-1102, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34142306

RESUMO

PURPOSE: We aimed to evaluate the white matter hyperintensity (WMH) effect on dopamine transporter availability (DAT) of striatum. MATERIALS AND METHODS: A total of 48 patients who showed visually normal F-18 FP-CIT uptake were included in this study. Each FP-CIT image were pre-processed using SPM12. Co-registration and spatial normalization of FP-CIT image conducted using T1-weighted magnetic resonance imaging (MRI). And then smoothing of normalized FP-CIT image was performed. Intensity normalization was performed using cerebellum as a reference region. With pre-defined volume of interest template, the specific binding ratio (SBR) of both side of caudate nucleus and putamen was calculated. Fluid attenuated inversion recovery MRI scans were used to evaluate WMH number and volume. RESULTS: SBRs of left and right caudate nucleus were correlated with age (r = - 0.615; p < 0.0001; n = 48, r = - 0.607; p < 0.0001; n = 48, respectively), high density lipoprotein cholesterol (r = 0.296; p = 0.041; n = 48, r = 0.29; p = 0.0455; n = 48, respectively), and WMH number (r = - 0.459; p = 0.001; n = 48, r = - 0.481; p = 0.0005; n = 48, respectively) and volume (r = - 0.407; p = 0.0041; n = 48, r = - 0.428; p = 0.0024; n = 48, respectively). CONCLUSION: DAT availability of patients who showed visually normal F-18 FP-CIT uptake was correlated with number and volume of WMH.


Assuntos
Proteínas da Membrana Plasmática de Transporte de Dopamina , Substância Branca , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Humanos , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos , Substância Branca/diagnóstico por imagem
14.
Physiol Plant ; 172(4): 2098-2111, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33942310

RESUMO

Hyoscyamine (HYO) and scopolamine (SCO) are tropane alkaloids acting as anticholinergic factors on the parasympathetic nervous system in humans and are produced by Solanaceous plants. Two strains of Agrobacterium rhizogenes, A4 and LBA9402, were used to infect Atropa acuminata Royle ex Miers and Atropa belladonna L. leaf explants. A. acuminata was inoculated either by direct infection or sonicated-assisted A. rhizogenes-mediated transformation (SAAT) was performed. A. belladonna was inoculated with the A4 strain using a direct method. The selected hairy root lines of both species were elicited with 50 mM methyl-ß-cyclodextrin (ß-CD), 0.5 µM coronatine (Cor) or 50 mM ß-CD + 0.5 µM Cor on Day 14 of culture. The elicitor effect on growth and HYO and SCO content was analyzed after one (T1) and two (T2) weeks of treatment. In A. acuminata explants, the highest transformation percentage (T%) was obtained with strain A4 and the SAAT method (T%: 96.43). Cor significantly reduced the growth of A. acuminata hairy roots (fresh weight and dry weight [DW]: 2.52 and 0.3 g, respectively), whereas ß-CD increased their DW (0.4 g). Also, the combined ß-CD + Cor treatment had a positive significant effect on the DW of A. belladonna hairy roots (0.41 g). In A. acuminata hairy roots, the HYO level was lower under Cor treatment than in the control at both sampling times. In contrast, the SCO content was increased 10-fold by Cor elicitation at T1 compared to the control (10.95 mg g-1 DW) and was also positively affected by ß-CD + Cor. In A. belladonna hairy roots, all the elicitors had a negative effect on both HYO and SCO production. This report is the first assessment of the effect of ß-CD and Cor elicitors on tropane alkaloid production.


Assuntos
Atropa belladonna , Atropa , Agrobacterium , Aminoácidos , Indenos , Raízes de Plantas , Tropanos , beta-Ciclodextrinas
15.
J Neurol Sci ; 426: 117476, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33975190

RESUMO

INTRODUCTION: Although functional imaging is useful for the diagnosis and pathophysiological evaluation of Parkinson's disease (PD), little is known about the relationship between functional imaging findings and PD clinical features. The objective of this study was to determine the relationship between 123I-FP-CIT-SPECT findings and motor symptoms, in particular gait disturbance. METHODS: The study included 46 drug-naive patients with early-stage PD. The specific binding ratios (SBRs) in the striatum and its subregions, namely anterior/posterior putamen and caudate nucleus, were calculated in patients who underwent 123I-FP-CIT-SPECT. Motor symptoms were evaluated using the modified Hoehn and Yahr (HY) stage and the Unified Parkinson's Disease Rating Scale (UPDRS) part III. Gait disturbance was evaluated by the mean gait cycle duration and the mean gait acceleration amplitude measured with a wearable sensor. RESULTS: The mean SBRs of the striatum and anterior putamen were significantly associated with the modified HY stage and UPDRS part III score. The mean SBR of the caudate nucleus was significantly associated with the UPDRS part III score. The mean striatal SBR was also significantly associated with the mean gait cycle duration and mean gait acceleration amplitude. CONCLUSION: The mean striatal SBR, as determined by 123I-FP-CIT-SPECT, was significantly associated with motor severity and gait severity in drug-naive patients with PD.


Assuntos
Doença de Parkinson , Preparações Farmacêuticas , Proteínas da Membrana Plasmática de Transporte de Dopamina , Humanos , Radioisótopos do Iodo , Doença de Parkinson/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos
16.
Toxins (Basel) ; 13(5)2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946510

RESUMO

Cyanobacterial blooms are an omnipresent and well-known result of eutrophication and climate change in aquatic systems. Cyanobacteria produce a plethora of toxic secondary metabolites that affect humans, animals and ecosystems. Many cyanotoxins primarily affect the grazers of phytoplankton, e.g., Daphnia. The neurotoxin anatoxin-α has been reported world-wide; despite its potency, anatoxin-α and its effects on Daphnia have not been thoroughly investigated. Here, we investigated the effects of the anatoxin-α-producing Tychonema on life-history parameters and gene expression of nicotine-acetylcholine receptors (NAR), the direct targets of anatoxin-α, using several D. magna clones. We used juvenile somatic growth rates as a measure of fitness and analyzed gene expression by qPCR. Exposure to 100% Tychonema reduced the clones' growth rates and caused an up-regulation of NAR gene expression. When 50% of the food consisted of Tychonema, none of the clones were reduced in growth and only one of them showed an increase in NAR gene expression. We demonstrate that this increased NAR gene expression can be maternally transferred and that offspring from experienced mothers show a higher growth rate when treated with 50% Tychonema compared with control offspring. However, the addition of further (anthropogenic) stressors might impair Daphnia's adaptive responses to anatoxin-α. Especially the presence of certain pollutants (i.e., neonicotinoids), which also target NARs, might reduce Daphnia's capability to cope with anatoxin-α.


Assuntos
Daphnia/metabolismo , Tropanos/farmacologia , Animais , Clonagem Molecular , Cianobactérias/metabolismo , Daphnia/efeitos dos fármacos , Daphnia/genética , Expressão Gênica/efeitos dos fármacos
17.
Eur J Pharmacol ; 904: 174182, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34004212

RESUMO

Restraint stress (RS) is an unavoidable stress model that triggers activation of the autonomic nervous system, endocrine activity, and behavioral changes in rodents. Furthermore, RS induces secretion of oxytocin into the bloodstream, indicating a possible physiological role in the stress response in this model. The presence of oxytocin receptors in vessels and heart favors this possible idea. However, the role of oxytocin secreted in RS and effects on the cardiovascular system are still unclear. The aim of this study was to analyze the influence of oxytocin on cardiovascular effects during RS sessions. Rats were subjected to pharmacological (blockade of either oxytocin, vasopressin, or muscarinic receptors) or surgical (hypophysectomy or sinoaortic denervation) approaches to study the functional role of oxytocin and its receptor during RS. Plasma levels of oxytocin and vasopressin were measured after RS. RS increased arterial pressure, heart rate, and plasma oxytocin content, but not vasopressin. Treatment with atosiban (a Gi biased agonist) inhibited restraint-evoked tachycardia without affecting blood pressure. However, this effect was no longer observed after sinoaortic denervation, homatropine (M2 muscarinic antagonist) treatment or hypophysectomy, indicating that parasympathetic activation mediated by oxytocin secreted to the periphery is responsible for blocking the increase in tachycardic responses observed in the atosiban-treated group. Corroborating this, L-368,899 (oxytocin antagonist) treatment showed an opposite effect to atosiban, increasing tachycardic responses to restraint. Thus, this provides evidence that oxytocin secreted to the periphery attenuates tachycardic responses evoked by restraint via increased parasympathetic activity, promoting cardioprotection by reducing the stress-evoked heart rate increase.


Assuntos
Ocitocina/metabolismo , Restrição Física/fisiologia , Estresse Psicológico/fisiopatologia , Animais , Antagonistas dos Receptores de Hormônios Antidiuréticos/farmacologia , Barorreflexo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Masculino , Agonistas Muscarínicos/farmacologia , Ocitocina/sangue , Parassimpatolíticos/farmacologia , Ratos Wistar , Receptor Muscarínico M2/antagonistas & inibidores , Receptores de Vasopressinas/fisiologia , Estresse Psicológico/sangue , Taquicardia/fisiopatologia , Tropanos/farmacologia , Vasopressinas/sangue , Vasotocina/análogos & derivados , Vasotocina/farmacologia
18.
Cells ; 10(3)2021 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-33801135

RESUMO

Cyanotoxins are harmful to aquatic and water-related organisms. In this study, Lemna trisulca was tested as a phytoremediation agent for three common cyanotoxins produced by bloom-forming cyanobacteria. Cocultivation of L. trisulca with Dolichospermum flos-aquae in BG11 medium caused a release of the intracellular pool of anatoxin-a into the medium and the adsorption of 92% of the toxin by the plant-after 14 days, the total amount of toxin decreased 3.17 times. Cocultivation with Raphidopsis raciborskii caused a 2.77-time reduction in the concentration of cylindrospermopsin (CYN) in comparison to the control (62% of the total pool of CYN was associated with the plant). The greatest toxin limitation was noted for cocultivation with Microcystis aeruginosa. After two weeks, the microcystin-LR (MC-LR) concentration decreased more than 310 times. The macrophyte also influenced the growth and development of cyanobacteria cells. Overall, 14 days of cocultivation reduced the biomass of D. flos-aquae, M. aeruginosa, and R. raciborskii by 8, 12, and 3 times, and chlorophyll a concentration in comparison to the control decreased by 17.5, 4.3, and 32.6 times, respectively. Additionally, the macrophyte stabilized the electrical conductivity (EC) and pH values of the water and affected the even uptake of cations and anions from the medium. The obtained results indicate the biotechnological potential of L. trisulca for limiting the development of harmful cyanobacterial blooms and their toxicity.


Assuntos
Alcaloides/isolamento & purificação , Araceae/metabolismo , Toxinas Marinhas/isolamento & purificação , Microcistinas/isolamento & purificação , Tropanos/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação , Biodegradação Ambiental , Biomassa , Clorofila A/metabolismo , Cianobactérias/metabolismo , Condutividade Elétrica , Concentração de Íons de Hidrogênio , Íons , Cinética , Fotossíntese
19.
Tomography ; 7(2): 95-106, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33810475

RESUMO

[123I]FP-CIT SPECT has been valuable for distinguishing Parkinson disease (PD) from essential tremor. However, its performance for quantitative assessment of motor dysfunction has not been established. A virtual reality (VR) application was developed and compared with [123I]FP-CIT SPECT/CT for detection of severity of motor dysfunction. Forty-four patients (21 males, 23 females, age 64.5 ± 12.4) with abnormal [123I]FP-CIT SPECT/CT underwent assessment of bradykinesia, activities of daily living, and tremor with VR. Support vector machines (SVM) machine learning models were applied to VR and SPECT data. Receiver operating characteristic (ROC) analysis demonstrated greater area under the curve (AUC) for VR (0.8418, 95% CI 0.6071-0.9617) compared with brain SPECT (0.5357, 95% CI 0.3373-0.7357, p = 0.029) for detection of motor dysfunction. Logistic regression identified VR as an independent predictor of motor dysfunction (Odds Ratio 326.4, SE 2.17, p = 0.008). SVM for prediction of the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) demonstrated greater R-squared of 0.713 (p = 0.008) for VR, compared with 0.0764 (p = 0.361) for brain SPECT. This study demonstrates that VR can be safely used in patients prior to [123I]FP-CIT SPECT imaging and may improve prediction of motor dysfunction. This test has the potential to provide a simple, objective, quantitative analysis of motor symptoms in PD patients.


Assuntos
Realidade Virtual , Atividades Cotidianas , Idoso , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Neuroimagem , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos
20.
Neurology ; 96(23): e2801-e2811, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-33883238

RESUMO

OBJECTIVE: To provide evidence that cardiac I-123-metaiodobenzylguanidine sympathetic innervation imaging (MIBG) scintigraphy differentiates probable mild cognitive impairment with Lewy bodies (MCI-LB) from mild cognitive impairment due to Alzheimer disease (MCI-AD), we scanned patients with MCI and obtained consensus clinical diagnoses of their MCI subtype. We also performed baseline FP-CIT scans to compare the accuracy of MIBG and FP-CIT. METHODS: We conducted a prospective cohort study into the accuracy of cardiac MIBG scintigraphy in the diagnosis of MCI-LB. Follow-up clinical assessment was used to diagnose MCI-AD (no core features of MCI-LB and normal FP-CIT), probable MCI-LB (2 or more core features, or 1 core feature with abnormal FP-CIT), or possible MCI-LB (1 core feature or abnormal FP-CIT). For the comparison between MIBG and FP-CIT, only core clinical features were used for diagnosis. RESULTS: We recruited 95 people with mild cognitive impairment. Cardiac MIBG was abnormal in 22/37 probable and 2/15 possible MCI-LB cases and normal in 38/43 MCI-AD cases. The sensitivity in probable MCI-LB was 59% (95% confidence interval [CI], 42%-75%), specificity 88% (75%-96%), and accuracy 75% (64%-84%). The positive likelihood ratio was 5.1 and negative likelihood ratio 0.46. With symptom-only diagnoses, the accuracies were 79% for MIBG (95% CI, 68%-87%) and 76% for FP-CIT (95% CI, 65%-85%). CONCLUSIONS: Cardiac MIBG appears useful in early disease, with an abnormal scan highly suggestive of MCI-LB. Validation in a multicenter setting is justified. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that cardiac MIBG distinguishes MCI-LB from MCI-AD.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Doença por Corpos de Lewy/diagnóstico por imagem , Imagem de Perfusão do Miocárdio/normas , Tomografia Computadorizada de Emissão de Fóton Único/normas , 3-Iodobenzilguanidina , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Doença de Alzheimer/fisiopatologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Diagnóstico Diferencial , Feminino , Seguimentos , Coração/inervação , Humanos , Doença por Corpos de Lewy/complicações , Doença por Corpos de Lewy/fisiopatologia , Masculino , Sensibilidade e Especificidade , Tropanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...