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1.
Phytochemistry ; 178: 112458, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32888670

RESUMO

Six previously undescribed tropane alkaloids, designated as erythrobezerrines A-F, were isolated from the EtOH extract from the stem bark of Erythroxylum bezerrae Plowman. Their structures were elucidated based on the interpretation of the NMR and MS data and in some instances, confirmed by X-ray diffraction analysis. The cytotoxicity of the isolated compounds was evaluated against the cancer cell lines L929, PC-3, HCT-116, SNB-19 and NCI-H460, but only erythrobezerrine C showed moderate activity with IC50 values of 3.38 and 5.43 µM for HCT-116 and NCI-H460, respectively.


Assuntos
Erythroxylaceae , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Casca de Planta , Tropanos
2.
Sci Total Environ ; 736: 139515, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32485372

RESUMO

Toxic cyanobacteria are a concern worldwide because they can adversely affect humans, animals, and ecosystems. However, neurotoxins produced by freshwater cyanobacteria are understudied relative to microcystin. Thus, the objective of this critical review was to provide a comprehensive examination of the modes of action, production, fate, and occurrence of the freshwater neurotoxins anatoxin-a and saxitoxin as they relate to human, animal, and ecosystem health. Literature on freshwater anatoxin-a and saxitoxin was obtained and reviewed for both laboratory and field studies. Current (2020) research identifies as many as 41 anatoxin-a producing species and 15 saxitoxin-producing species of freshwater cyanobacteria. Field studies indicate that anatoxin-a and saxitoxin have widespread distribution, and examples are given from every continent except Antarctica. Human and animal health concerns can range from acute to chronic. However, few researchers studied chronic or sublethal effects of freshwater exposures to anatoxin-a or saxitoxin. Ecosystem health also is a concern, as the effects of toxicity may be far reaching and include consequences throughout the food web. Several gaps in knowledge were identified for anatoxin-a and saxitoxin, including triggers of production and release, environmental fate and degradation, primary and secondary exposure routes, diel variation, food web effects, effects of cyanotoxin mixtures, and sublethal health effects on individual organisms and populations. Despite the gaps, this critical review facilitates our current understanding of freshwater neurotoxins and thus can serve to `` guide future research on anatoxin-a, saxitoxin, and other cyanotoxins.


Assuntos
Toxinas Bacterianas , Saxitoxina , Animais , Regiões Antárticas , Ecossistema , Água Doce , Humanos , Microcistinas , Neurotoxinas , Tropanos
3.
Sci Total Environ ; 731: 139014, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32428751

RESUMO

Analytical methods based on direct injection (DI) and solid phase extraction (SPE) coupled with ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC- MS/MS) were developed for the determination of anatoxin-a (ATX-a), cylindrospermopsin (CYN), and homoanatoxin-a (HATX-a) in freshwater samples impacted with cyanobacterial blooms. The presence of CYN in freshwater samples was detected and quantified based on direct injection method, while ATX-a and HATX-a could be determined by both DI and SPE-based methods. Matrix effects (ME) on the signal intensity of the cyanotoxins were systematically evaluated for both direct injection and SPE extract samples. CYN, ATX-a, and HATX-a suffered a significant suppression during UPLC-MS/MS. The selection of internal standards (ISs) for compensating/correcting the losses of target cyanotoxins during sample preparation and matrix effects in UPLC-MS/MS analyses were systematically evaluated. Acetaminophen-d4 (an isotopically labelled acetaminophen) is a suitable internal standard for correcting the ME on the signal intensity of ATX-a and HATX-a, while the use of L-phenylalanine-d5 or caffeine-d9 as IS for correcting ME of these toxins was not efficient, as expected. The method detection limit (MDL) for the target cyanotoxins ranged from 0.6 to 15 ng/L, which is sensitive enough to detect the presence of these toxins in cyanobacterial bloom freshwater. The developed methods were successfully applied for routine monitoring of the occurrence of these cyanotoxins in a local water body. Monitoring results depicted that ATX-a, CYN and HATX-a were ubiquitously detected in water samples, at concentrations ranging from 70 to 24,600 ng/L.


Assuntos
Extração em Fase Sólida , Espectrometria de Massas em Tandem , Toxinas Bacterianas , Compostos Bicíclicos Heterocíclicos com Pontes , Cromatografia Líquida , Água Doce/análise , Microcistinas , Tropanos , Uracila/análogos & derivados
4.
PLoS One ; 15(4): e0231010, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32240236

RESUMO

PURPOSE: To evaluate the real-world diagnostic performance of high-resolution susceptibility-weighted imaging (HR-SWI) and investigate whether the reader's predictions can be used to find cases where HR-SWI finding and final clinical diagnosis matched. METHODS: This retrospective study enrolled patients with suspected Parkinsonism (n = 48) or volunteers with other intracranial pathologies (n = 31) who underwent brain magnetic resonance imaging (MRI) including HR-SWI, which was used to evaluate nigrosome 1 (NG1). All patients with suspected Parkinsonism underwent N-3-fluoropropyl-2-carbomethoxy-3-4-iodophenyl nortropane (FP-CIT) positron emission tomography and a clinical diagnosis was made by a neurologist. The HR-SWI data were qualitatively analyzed by two independent reviewers. A consensus reading was performed and a diagnostic confidence score was assigned. According to final clinical diagnosis, diagnostic sensitivity, specificity, and accuracy were calculated. Receiver operating characteristic (ROC) curve analysis was used to examine whether the diagnostic confidence score could be used to identify HR-SWI finding-final clinical diagnosis matched cases. RESULTS: Of the 48 patients with suspected Parkinsonism, 31 were diagnosed with idiopathic Parkinson's disease, and three with multiple system atrophy. The remaining 14 patients were included in the disease control group. Of the 31 volunteers, 10 subjects were excluded due to possibility of nigrostriatal degeneration and finally 21 subjects were enrolled as controls with non-Parkinsonism pathology (non-PD control). After consensus reading, 25 subjects were classified as true positive and 28 as true negative, according to HR-SWI findings. The calculated diagnostic sensitivity, specificity, and accuracy were 73.5%, 80.0%, and 76.8%, respectively. With using diagnostic concordance score, the area under the ROC curve for the detection of concordance case was 0.83 (95% CI: 0.72-0.91, p < 0.05). CONCLUSION: The diagnostic performance of NG1 detection using HR-SWI with 3T MRI was within acceptable range. Using the reader's diagnostic confidence could be helpful to find cases which HR-SWI finding and final clinical conclusion match. So HR-SWI may be of added value in the evaluation of suspected Parkinsonism.


Assuntos
Transtornos Parkinsonianos/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/diagnóstico , Doença de Parkinson/diagnóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Tropanos/administração & dosagem
5.
Aquat Toxicol ; 222: 105422, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32112996

RESUMO

The proliferations of cyanobacteria are increasingly prevalent in many rivers and water bodies due especially to eutrophication. This work aims to study in female medaka fish the toxicity, the transfer and the depuration of the anatoxin-a, a neurotoxin produced by benthic cyanobacterial biofilms. This work will provide answers regarding acute toxicity induced by single gavage by anatoxin-a and to the risks of exposure by ingestion of contaminated fish flesh, considering that data on these aspects remain particularly limited. The oral LD50 and NOAEL of a single dose of (±)-anatoxin-a were determined at 11.50 and 6.67 µg.g-1, respectively. Subsequently, the toxico-kinetics of the (±)-anatoxin-a was observed in the guts, the livers and the muscles of female medaka fish for 10 days. Anatoxin-a was quantified by high-resolution qTOF mass spectrometry coupled upstream to a UHPLC chromatographic chain. The toxin could not be detected in the liver after 12 h, and in the gut and muscle after 3 days. Overall, the medaka fish do not appear to accumulate (±)-anatoxin-a and to largely recover after 24 h following a single sub-acute oral liquid exposure at the NOAEL.


Assuntos
Toxinas Marinhas/toxicidade , Neurotoxinas/toxicidade , Oryzias/metabolismo , Tropanos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Cianobactérias/metabolismo , Eutrofização , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Dose Letal Mediana , Fígado/efeitos dos fármacos , Fígado/metabolismo , Toxinas Marinhas/metabolismo , Modelos Teóricos , Músculos/efeitos dos fármacos , Músculos/metabolismo , Neurotoxinas/metabolismo , Nível de Efeito Adverso não Observado , Rios/química , Toxicocinética , Tropanos/metabolismo , Poluentes Químicos da Água/metabolismo
6.
Toxicon ; 177: 52-88, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32217234

RESUMO

Datura stramonium, Atropa belladonna, Hyoscyamus niger, and Scopolia carniolica are all temperate plants from the family Solanaceae, which as a result of their anticholinergic tropane alkaloids, hyoscyamine/atropine and scopolamine, have caused many cases of poisoning around the world. Despite the danger these nightshade plants represent, the literature often presents incomplete cases lacking in details and filled with ambiguity, and reviews on the topic tend to be limited in scope. Many also point to a gap in knowledge of these plants among physicians. To address this, the following review focuses on intoxications involving these plants as reported in the literature between 1966 and 2018, with brief mention to pertinent related plants to contextualise and provide a fuller picture of the situation surrounding the presently discussed temperate plants. Analysis of the literature displays that D. stramonium is largely associated with drug use among teens while A. belladonna is primarily ingested as a result of the berries being mistaken for edible fruits. H. niger was found to be largely ingested when mistaken for other plants, and S. carniolica was the cause of incredibly few intoxications.


Assuntos
Antagonistas Colinérgicos/toxicidade , Extratos Vegetais/toxicidade , Intoxicação por Plantas/epidemiologia , Solanaceae , Alcaloides de Solanáceas/toxicidade , Alcaloides , Atropa belladonna , Europa (Continente) , Humanos , Hyoscyamus , Escopolamina , Scopolia , Tropanos
7.
PLoS One ; 15(3): e0229860, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32134983

RESUMO

PURPOSE: We have evaluated the clinical significance of the washout rate (WR) on I-123 MIBG scans through the analysis of the relationship between the I-123 MIBG scans and autonomic status in patients with Parkinson's disease (PD). MATERIALS AND METHODS: Sixty patients with clinical PD who had decreased HMR were enrolled. An autonomic symptom was evaluated using a head-up tilt test and the Composite Autonomic Severity Score (CASS). An I-123 MIBG scan and F-18 FP-CIT positron emission tomography (PET) were performed. All of the patients were classified into three groups according to the WR. The differences in patient characteristics and the imaging parameters among the three groups were evaluated, and a correlation analysis was also performed. RESULTS: The frequency of orthostatic hypotension was significantly different among the three groups. The difference in systolic pressure (dSysPr) and the difference in diastolic pressure (dDiaPr) of group 3 was significantly larger than those of groups 1 and 2. From the correlation analysis, it can be seen that age, Hoehn and Yahr (H&Y) stage, dSysPr, and dDiaPr had a weak positive correlation with the WR. The total CASS score was significantly higher in group 3 compared with groups 1 and 2. The WR had a moderate positive correlation with the cardiosympathetic score and the total CASS score. CONCLUSION: The WR is related to autonomic dysfunction. An I-123 MIBG cardiac scan is considered to be a good method to evaluate not only the differential diagnosis of Parkinson's disease but also the degree of autonomic dysfunction.


Assuntos
3-Iodobenzilguanidina/administração & dosagem , Sistema Nervoso Autônomo/diagnóstico por imagem , Radioisótopos do Iodo/administração & dosagem , Doença de Parkinson/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/administração & dosagem , 3-Iodobenzilguanidina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Feminino , Radioisótopos de Flúor/administração & dosagem , Radioisótopos de Flúor/metabolismo , Coração/diagnóstico por imagem , Humanos , Hipotensão Ortostática/diagnóstico , Radioisótopos do Iodo/metabolismo , Masculino , Mediastino/diagnóstico por imagem , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/metabolismo , Estudos Retrospectivos , Tropanos/administração & dosagem , Tropanos/metabolismo
8.
Clin Nucl Med ; 45(4): e178-e184, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32108695

RESUMO

INTRODUCTION: Symptom laterality is one of the main characteristics of Parkinson disease (PD) and reported to be associated with motor and nonmotor symptom severity and prognosis. This study aimed to evaluate the changes of laterality after deep brain stimulation (DBS) and the association between dopamine transporter SPECT using I FP-CIT (DAT SPECT) and symptom laterality in PD before and after DBS. METHODS: Nineteen patients with PD who received bilateral subthalamic nucleus DBS were enrolled. The clinical scores including Unified Parkinson Disease Rating Scale (UPDRS) and Hoehn and Yahr were evaluated at baseline, 6 months, and 1 year after DBS. Also, the patients underwent DAT SPECT before and 6 months and 1 year after DBS. Symptom and DAT laterality indices were determined based on the UPDRS part 3 and DAT SPECT, respectively. The association between DAT and symptom laterality was assessed at baseline and 6 months and 1 year after DBS. RESULTS: At baseline, 11, 6, and 2 among 19 patients had left-side-dominant, right-side-dominant, and symmetric motor symptom, respectively. Among 19 patients, there were 10 patients who showed changed symptom laterality within 1 year after DBS. The agreement between symptom laterality and DAT laterality was good to excellent at baseline and 6 months and 1 year after DBS (weighted κ = 0.742, 0.736, and 0.813). Furthermore, symptom and DAT laterality indices showed significant correlation at baseline (r = 0.542, P = 0.02), 6 months (r = 0.579, P = 0.01), and 1 year after DBS (r = 0.689, P = 0.02). Symptom laterality could be determined by DAT laterality index with areas under curve of 0.833 (P = 0.045), 0.982 (P < 0.001), and 1.000 (P < 0.001) at baseline and 6 and 12 months after DBS, respectively. CONCLUSIONS: The symptom laterality could be altered after DBS and was well correlated with laterality evaluated by DAT SPECT. An objective evaluation of laterality using DAT SPECT would be helpful for the management of patients with PD especially for adjusting the DBS programming for fine balancing of the asymmetric symptom after DBS. The large-scale study is warranted for validation of this result.


Assuntos
Estimulação Encefálica Profunda , Lateralidade Funcional , Doença de Parkinson/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Compostos Radiofarmacêuticos , Tropanos
9.
Expert Rev Clin Pharmacol ; 13(2): 103-113, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31951778

RESUMO

Introduction: Treatment options for COPD have evolved rapidly in the last decade and inhaled bronchodilators have largely supplanted the use of oral bronchodilators because of their increased efficacy and excellent safety with topical delivery to the lung. Recently added to the therapeutic armamentarium are fixed-dose combinations (FDC) of two long acting bronchodilators. LAMAs (long acting muscarinic antagonists) and LABAs (long acting beta agonists) are the main classes available and use different pathways to effectively produce bronchial smooth muscle relaxation.Areas covered: The most recent inhaled FDC LAMA/LABA to come to market is Aclidinium Bromide and Formoterol Fumarate. We searched databases of PubMed, Cochrane Library, and manufacturers' websites and retrieved all the randomized-controlled trials (RCTs) conducted with these drugs up to September 2019.Expert opinion: It is likely that FDCs will become the core of our COPD pharmacotherapy for all but the mildest COPD patients. These individual drugs have excellent efficacy and safety records for the maintenance treatment of COPD. Studies have demonstrated that twice daily treatment with aclidinium/formoterol resulted in significant improvement in lung function and an improved exercise tolerance when compared to placebo. Adverse effects are within the range of what is seen with other LAMA/LABA combinations.


Assuntos
Fumarato de Formoterol/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Tropanos/administração & dosagem , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Broncodilatadores/farmacologia , Combinação de Medicamentos , Fumarato de Formoterol/efeitos adversos , Fumarato de Formoterol/farmacologia , Humanos , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/efeitos adversos , Antagonistas Muscarínicos/farmacologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Tropanos/efeitos adversos , Tropanos/farmacologia
10.
Clin Nucl Med ; 45(2): 95-99, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31876812

RESUMO

PURPOSE: The present study investigated possible associations between cortical dysfunction/degeneration as measured by F-FDG PET and nigrostriatal degeneration according to the specific I-FP-CIT binding ratio (SBR) in striatal subregions defined by striato-cortical anatomical connectivity in Parkinson disease (PD) patients. MATERIALS AND METHODS: The study included 41 patients (61.4 ± 12.8 years) with PD-typical reduction of striatal FP-CIT SBR and no sign of atypical parkinsonian syndrome on FDG PET. FP-CIT SBR was determined separately in the cognitive (composite of executive and limbic) and sensorimotor part of the striatum according to the Oxford-GSK-Imanova Striatal Connectivity Atlas. Scaled FDG uptake was tested voxelwise for correlation with FP-CIT SBR (familywise error corrected P < 0.05). RESULTS: A large cluster (17.6 mL) of significant correlation of scaled FDG uptake with FP-CIT SBR in the cognitive part of the striatum, corrected for SBR in the sensorimotor part, was detected in the bilateral medial frontal cortex and the anterior cingulate cortex (partial correlation coefficient R = 0.767); small clusters were detected in ipsilateral caudate and ipsilateral thalamus. There was a small contralateral occipital cluster (3.0 mL) of significant correlation between FDG uptake and sensorimotor SBR corrected for cognitive SBR (R = 0.709). CONCLUSIONS: The correlation between nigrostriatal degeneration in the cognitive striatum and reduced cerebral glucose metabolism in the medial parts of the frontal cortex including the anterior cingulate suggests that nigrostriatal degeneration is specifically involved in the pathogenesis of cognitive deficits associated with medial frontal dysfunction such as impaired inhibitory control.


Assuntos
Cognição , Neostriado/metabolismo , Doença de Parkinson/metabolismo , Idoso , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neostriado/patologia , Neostriado/fisiopatologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos
11.
Clin Nucl Med ; 45(1): e46-e47, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31306206

RESUMO

A 24-year-old woman with an unresectable right mesencephalic pilocytic astrocytoma was treated with stereotaxic radiation therapy. Three months after a radiation therapy-induced bleeding, she presented a severe disabling low frequency rest and kinetic tremor involving the left upper limb, associated with dystonia, and a Holmes tremor was suspected. Thereby, we performed a I-FP-CIT SPECT (DATSCAN) that revealed a normal distribution of radiotracer over the left striatum, whereas no binding was seen in the right caudate and putamen. This pattern was consistent with a right severe nigrostriatal dopaminergic denervation due to an ipsilateral red nucleus injury.


Assuntos
Astrocitoma/complicações , Mesencéfalo/diagnóstico por imagem , Mesencéfalo/patologia , Tomografia Computadorizada de Emissão de Fóton Único , Tremor/diagnóstico por imagem , Tremor/etiologia , Tropanos , Feminino , Humanos , Tremor/patologia , Adulto Jovem
12.
Ideggyogy Sz ; 72(11-12): 381-388, 2019 Nov 30.
Artigo em Húngaro | MEDLINE | ID: mdl-31834681

RESUMO

The 123I-FP-CIT dopamine transporter SPECT imaging is a sensitive method to assess functional dopaminergic neuron terminals in the striatum. The method has also been available in Hungary for years. There are two main indications: (i) to help differentiate essential tremor from clinically uncertain Parkinsonism, including patients with early symptoms and (ii) to help differentiate dementia with Lewy bodies from Alzheimer's disease. The aim of this paper is to review 123I-FP-CIT SPECT imaging based on international data/guidelines and our own experiences, thereby assisting nuclear medicine practitioners and neurologists.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Proteínas da Membrana Plasmática de Transporte de Dopamina , Doença por Corpos de Lewy/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tropanos , Doença de Alzheimer/metabolismo , Humanos , Hungria , Doença por Corpos de Lewy/metabolismo , Sensibilidade e Especificidade
13.
Rinsho Shinkeigaku ; 59(12): 799-805, 2019 Dec 25.
Artigo em Japonês | MEDLINE | ID: mdl-31761832

RESUMO

We studied whether 123I-FP-CIT uptake in the striatum correlates with cognitive performance in patients with Parkinson's disease (PD). Sixty-nine patients with PD (24 men and 45 women, average age = 71.3 years, disease duration = 5.2 years) underwent 123I-FP-CIT SPECT and neuropsychiatric measurements. Cognitive performance was assessed using the MMSE (Mini-mental state examination), TMT (Trail making test), MoCA-J (Japanese version of Montreal cognitive assessment), FAB (Frontal assessment battery), ACE-R (Addenbrooke's cognitive examination revised), BDI-II (Beck depression inventory-II), and RBMT (Rivermead behavioural memory test) in the ON state. The average specific binding ratio (SBR) and AI (Asymmetry index) of striatal 123I-FP-CIT uptake were semi-quantitatively measured using DaTView software. Clinical data and SBR were compared. In addition, participants were divided into four groups according to the visibility of the striatum on 123I-FP-CIT SPECT images, and results of the Eagle Wing (EW) group and the Egg shape (ES) group were compared. SBR was negatively correlated with age (P < 0.001), disease duration (P < 0.001), H-Y stage (P < 0.001), levodopa equivalent dose (P = 0.004), TMT-A (P = 0.001), and TMT-B (P < 0.001), and positively correlated with MMSE (P = 0.021) and FAB (P = 0.029), MoCA-J (P = 0.012),RBMT (P = 0.021). Multiple regression analysis confirmed that age (P = 0.016) and FAB (P = 0.035) were independent predictors for SBR. Furthermore, in the ES group, Movement Disorder Society - Unified Parkinson's disease rating scale part III scores were significantly higher (P = 0.013) and the AI was lower (P < 0.001) than those in the EW group. Conversely, there were no differences in the findings of neuropsychiatric measures between the two groups. Our study results demonstrate that imaging with 123I-FP-CIT SPECT is sensitive for detecting dopaminergic deficits associated with frontal lobe functions in patients with PD.


Assuntos
Cognição , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/metabolismo , Radioisótopos do Iodo/metabolismo , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/psicologia , Compostos Radiofarmacêuticos/metabolismo , Tropanos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único
14.
Sci Total Environ ; 695: 133913, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31756843

RESUMO

The majority of reports on the toxic effect of cyanobacterial metabolites on the freshwater invertebrates is based on determination of two endpoints: mortality or immobilization. However, detection of sub-lethal effects requires more sensitive indicators The aim of the present study was to evaluate the applicability of digital-video analysis for determination of early behavioral and physiological responses in the assessment of effects caused by the cyanobacterial neurotoxin, anatoxin-a (ANTX) at a broad range of its concentration (0.5-50 µg/mL). Swimming speed (SS), heart rate (HR), oxygen consumption (OC), thoracic limb activity (TLA) and abdominal claw movement (ACM) of Daphnia magna were evaluated. Swimming speed and abdominal claw movements were determined by digital analysis of video clips by Tracker® software; OC by Oxygraph Plus System® while HR, TLA and ACM by digital frame-by-frame analysis of video clips of microscopic view with the use of a media player software. The experimental study showed a concentration- and time-dependent decrease of SS, HR, OC, TLA and ACM. SS was inhibited as early as after 10 s of the exposure of Daphnia magna to ANTX, and the other physiological responses after 2 h. Further inhibition of these parameters was also noted after 24 h of the exposure. On the other hand, stimulation of ACM was noted at the lower (0.5 and 2.5 µg/mL) ANTX concentrations after both 2 h and 24 h of exposure. The results indicated that some behavioral and physiological biomarkers measured by video analysis may be a valuable tool for an early determination of toxic effects induced by cyanobacterial metabolites in zooplankters.


Assuntos
Daphnia/fisiologia , Tropanos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Cianobactérias , Água Doce , Natação , Testes de Toxicidade
15.
Nurse Pract ; 44(12): 21-32, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31658218

RESUMO

In 2019, the FDA approved several new drugs for use in primary care. This article highlights the following new drugs: risankizumab-rzaa (Skyrizi); halobetasol and tazarotene (Duobrii); dolutegravir and lamivudine (Dovato); romosozumab-aqqg (Evenity); brexanolone (Zulresso); solriamfetol (Sunosi); aclidinium and formoterol (Duaklir Pressair); and siponimod (Mayzent).


Assuntos
Aprovação de Drogas , Anticorpos Monoclonais/uso terapêutico , Azetidinas/uso terapêutico , Compostos de Benzil/uso terapêutico , Carbamatos/uso terapêutico , Clobetasol/análogos & derivados , Clobetasol/uso terapêutico , Combinação de Medicamentos , Fumarato de Formoterol/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Lamivudina/uso terapêutico , Ácidos Nicotínicos/uso terapêutico , Fenilalanina/análogos & derivados , Fenilalanina/uso terapêutico , Pregnanolona/uso terapêutico , Tropanos/uso terapêutico , Estados Unidos , United States Food and Drug Administration , beta-Ciclodextrinas/uso terapêutico
16.
Hell J Nucl Med ; 22(3): 194-199, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31587029

RESUMO

OBJECTIVE: We aimed to evaluate the association between the availability of serotonin transporter (SERT) measured by ioflupane-DaTSCAN (123I-FP-CIT) and imaged by single photon emission tomography (SPET) and memory function in healthy subjects. SUBJECTS AND METHODS: Specific binding of 123I-FP-CIT indicating SERT was achieved using a region of interest analysis. Spherical volumes of interest for midbrain and pons were defined. The cerebellum was chosen as a reference region. Specific binding ratios (SBR) in midbrain and pons representing SERT availability were measured as follows: SBR=(target-cerebellum)/cerebellum. A hundred and eighty-one healthy subjects (117 male, 64 female) were included in this study. RESULTS: Specific binding ratios of both midbrain (P=0.025) and pons (P=0.006) of males was higher than that of females. None of the SBR showed a correlation with age both in males: (midbrain; P=0.736, pons; P=0.875) and in females (midbrain; P=0.294, pons; P=0.170). In all our cases, SERT availability of midbrain correlated positively with total recall score (rho=0.159, P=0.033), and delayed recall score (rho=0.149, P=0.046). In females, the correlation between SERT availability in midbrain and delayed recall score was significant (rho=0.320, P=0.010), however, not in males (rho=0.112, P=0.229). CONCLUSION: In conclusion, we demonstrated that SERT availability was associated with memory function in healthy females from the PPMI database. Further studies are needed to clarify underlying mechanisms of this phenomenon.


Assuntos
Voluntários Saudáveis , Memória , Mesencéfalo/fisiologia , Ponte/fisiologia , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Feminino , Humanos , Masculino , Mesencéfalo/diagnóstico por imagem , Mesencéfalo/metabolismo , Pessoa de Meia-Idade , Ponte/diagnóstico por imagem , Ponte/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos
17.
Optom Vis Sci ; 96(9): 706-709, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31479026

RESUMO

SIGNIFICANCE: Ichthyosis is a group of heterogenous inherited skin disorders characterized by abnormal cornification and keratinization of the skin. Autosomal recessive congenital ichthyosis presents with severe lagophthalmos and cicatricial ectropion of both upper and lower lids. Chronic corneal exposure from lid abnormalities may lead to ulcerative keratitis or corneal perforation. PURPOSE: The case highlights a rarely seen condition that presents with potentially serious ocular complications and vision loss. Corneal complications may be avoided or managed with moisture goggles, corneal vaulting with scleral lenses, topical therapeutics, amniotic membrane, and surgical lid repair. CASE REPORT: A 25-year-old woman presented with a painful right eye for 1 week. She had a medical history of autosomal recessive congenital ichthyosis. Her ocular adnexa revealed bilateral lagophthalmos and cicatricial ectropion of both upper and lower lids. The slit lamp of examination revealed an injected eye with corneal ulcer with hypopyon in the right eye and quiet eye with corneal scarring in the left eye. The patient was treated with topical moxifloxacin and polymyxin B sulfate/trimethoprim as well as in-office homatropine 5% in the right eye. The keratitis was treated to resolution, and the patient referred for consultation on lid repair. CONCLUSIONS: Chronic corneal exposure from autosomal recessive congenital ichthyosis may lead to severe dry eye, ulcerative keratitis, or perforation. Patients should be monitored carefully for corneal disease, educated on methods and devices to protect the corneal surface, and referred for surgical repair if indicated. Although rare, this condition presents unique findings that may be visually devastating. Awareness of the condition, as well as the various clinical presentations and appropriate management necessary, will prove beneficial to the patient.


Assuntos
Úlcera da Córnea/etiologia , Ectrópio/etiologia , Ictiose Lamelar/complicações , Adulto , Antibacterianos/uso terapêutico , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/tratamento farmacológico , Quimioterapia Combinada , Ectrópio/diagnóstico , Ectrópio/tratamento farmacológico , Feminino , Humanos , Moxifloxacina/uso terapêutico , Parassimpatolíticos/uso terapêutico , Polimixina B/uso terapêutico , Microscopia com Lâmpada de Fenda , Trimetoprima/uso terapêutico , Tropanos/uso terapêutico
18.
Toxicon ; 171: 20-28, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31542469

RESUMO

The indolizidine alkaloid swainsonine, found in some Astragalus and Oxytropis (i.e., locoweed) species, is a potent cellular glycosidase inhibitor that often poisons livestock. Other toxic genera such as some Ipomoea species also contain swainsonine as well as calystegines which are similar polyhydroxy alkaloids. The toxicity of calystegines is poorly characterized; however, they are also potent glycoside inhibitors capable of intestinal and cellular glycoside dysfunction. The objective of this study was to directly compare A. lentiginosus and I. carnea poisoning in goats to better characterize the role of the calystegines. Three groups of four goats each were treated with ground alfalfa (control), I. carnea or A. lentiginosus to obtain daily doses of 0.0, 1.5, and 1.5 mg swainsonine/kg bw per day, respectively, for 45 days. Animals were observed daily and weekly body weights, serum enzyme activities, and serum swainsonine concentrations were determined. At day 45 all animals were euthanized and necropsied. Goats treated with A. lentiginosus and I. carnea developed clinical disease characterized by mild intention tremors and proprioceptive deficits. Goats treated with A. lentiginosus developed clinical disease sooner and with greater consistency. No differences in body weight, serum swainsonine concentrations and serum enzyme activity were observed between goats treated with A. lentiginosus and I. carnea. Additionally, there were no differences in the microscopic and histochemical studies of the visceral and neurologic lesions observed between goats treated with A. lentiginosus and I. carnea. These findings suggest that I. carnea-induced clinical signs and lesions are due to swainsonine and that calystegines contribute little or nothing to toxicity in goats in the presence of swainsonine.


Assuntos
Astrágalo (Planta)/envenenamento , Doenças das Cabras/etiologia , Ipomoea/envenenamento , Intoxicação por Plantas/veterinária , Swainsonina/envenenamento , Animais , Doenças das Cabras/enzimologia , Doenças das Cabras/patologia , Cabras , Masculino , Propriocepção/efeitos dos fármacos , Swainsonina/sangue , Tremor/veterinária , Tropanos/envenenamento
19.
Nat Commun ; 10(1): 4036, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492848

RESUMO

The skeleton of tropane alkaloids is derived from ornithine-derived N-methylpyrrolinium and two malonyl-CoA units. The enzymatic mechanism that connects N-methylpyrrolinium and malonyl-CoA units remains unknown. Here, we report the characterization of three pyrrolidine ketide synthases (PYKS), AaPYKS, DsPYKS, and AbPYKS, from three different hyoscyamine- and scopolamine-producing plants. By examining the crystal structure and biochemical activity of AaPYKS, we show that the reaction mechanism involves PYKS-mediated malonyl-CoA condensation to generate a 3-oxo-glutaric acid intermediate that can undergo non-enzymatic Mannich-like condensation with N-methylpyrrolinium to yield the racemic 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoic acid. This study therefore provides a long sought-after biosynthetic mechanism to explain condensation between N-methylpyrrolinium and acetate units and, more importantly, identifies an unusual plant type III polyketide synthase that can only catalyze one round of malonyl-CoA condensation.


Assuntos
Malonil Coenzima A/metabolismo , Proteínas de Plantas/metabolismo , Policetídeo Sintases/metabolismo , Pirróis/metabolismo , Alcaloides de Solanáceas/metabolismo , Tropanos/metabolismo , Sequência de Aminoácidos , Biocatálise , Cromatografia Líquida/métodos , Cristalografia por Raios X , Malonil Coenzima A/química , Modelos Químicos , Estrutura Molecular , Filogenia , Proteínas de Plantas/classificação , Proteínas de Plantas/genética , Policetídeo Sintases/química , Policetídeo Sintases/genética , Pirróis/química , Homologia de Sequência de Aminoácidos , Alcaloides de Solanáceas/química , Espectrometria de Massas em Tandem/métodos , Tropanos/química
20.
Clin Nucl Med ; 44(12): 987-988, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31524680

RESUMO

A 59-year-old man had developed within a few months walking disorders and rigidity of the left upper limb. I-FP-CIT SPECT/CT was performed in response to the suspicion of atypical parkinsonian syndrome. It showed an anomaly in presynaptic dopaminergic transmission on the right striatum and a voluminous expansive process on CT. MRI revealed an atypical meningioma. The patient had surgery for tumor removal. Later I-FP-CIT SPECT/CT showed normalization of presynaptic dopaminergic transmission on the right striatum.


Assuntos
Erros de Diagnóstico , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/diagnóstico , Meningioma/complicações , Meningioma/diagnóstico , Transtornos Parkinsonianos/complicações , Humanos , Imagem por Ressonância Magnética , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Pessoa de Meia-Idade , Neostriado/diagnóstico por imagem , Neostriado/metabolismo , Transtornos Parkinsonianos/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos
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