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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 265: 120385, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536885

RESUMO

In this work, a strong blue-emitting fluorescent biosensor based on graphite carbon nitride nanoparticles (GCNNs) (Ex = 340 nm and Em = 435 nm) was synthesized by a facile one-step hydrothermal method. With the aid of hydrogen peroxide and horseradish peroxidase, pyrocatechol structure of dopamine (DA) was oxidized to o-quinone structure of polydopamine (PDA) by hydroxyl radical. PDA was able to rapidly and significantly quench fluorescence of GCNNs. In the meanwhile, oxidative self-polymerization from DA to PDA would be blocked by antioxidants, such as glutathione (GSH) and ascorbic acid (AA). Thus, the fluorescence of GCNNs@DA sensor would be recovered owing to the decrease of o-quinone. Based on above-mentioned dual recognition strategy of "turn-off" and "turn off-on", a fast, simple and ultrasensitive method was developed to measure DA and antioxidants. Under the optimal experimental conditions, the detection limits of DA, GSH and AA were 0.064 µmol L-1, 0.11 µmol L-1 and 0.16 µmol L-1 with relative standard deviations of 1.7%, 9.3% and 8.0%, respectively. As one of metal-free quantum dots, our GCNNs-based sensors were also successfully applied to the determination of DA as well as GSH and AA in human serum. The recoveries for the spiked samples were in the range of 93.8%-109% and 95.0%-110% of DA and antioxidants, which shows great promise to clinicalapplication.


Assuntos
Grafite , Pontos Quânticos , Antioxidantes , Carbono , Dopamina , Humanos , Limite de Detecção , Nitrilas , Soro
2.
Talanta ; 237: 122986, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736705

RESUMO

A highly sensitive cationic polyfluorinated azobenzene/reduced graphene oxide (C3F7-azo+/RGO) nanocomposite electrochemical sensor for simultaneous detection of dopamine (DA), ascorbic acid (AA) and uric acid (UA) was successfully synthesized using a facile exfoliation/restacking method. The nanocomposite is self-assembled from oppositely charged graphene oxide nanosheets (GO) and polyfluorinated azobenzene cations (C3F7-azo+), and then obtained by electrochemical reduction. The structure and electrochemical properties were characterized by X-ray diffraction (XRD), energy dispersive spectrometer analysis (EDS), transmission electron microscope (TEM) and scanning electron microscope (SEM). The electrochemical property of C3F7-azo+/RGO was characterized by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV). It can be clearly seen from experimental results that C3F7-azo+/RGO-modified electrode (C3F7-azo+/RGO/GCE) can detect DA, AA and UA simultaneously, and has good stability and anti-interference performance. The detection limits are 65 nM, 8 nM and 11 nM for DA, AA and UA in the ranges 57.28-134.28 µM, 0.04-6.01 µM, 9.23-23.45 µM, respectively.


Assuntos
Grafite , Ácido Úrico , Ácido Ascórbico , Compostos Azo , Cátions , Dopamina , Técnicas Eletroquímicas , Eletrodos
3.
Chemosphere ; 287(Pt 3): 132284, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34563782

RESUMO

Among polychlorinated naphthalenes (PCNs), listed by the Stockholm convention as Persistent Organic Pollutants (POPs), hexachloronaphthalenes are considered the most toxic and raise the highest concern. Of these, 1,2,3,5,6,7-hexachloronaphthalanene (PCN67) is considered the main congener affecting human health due to its hepatotoxicity and its ability to disturb the reproductive, endocrine, and hematological systems. It is also prevalent in human serum/plasma, milk, and adipose tissue. However, little is known about its neurotoxicity, despite the fact that anorectic effects have been observed in workers occupationally exposed to PCNs and in animal research on PCN67. Since dopamine is involved in many aspects of food intake, the aim of this study was to confirm whether PCN67 affects dopamine synthesis in differentiated PC12 cells, a widely used model of neurosecretion. Our results show that exposure to PCN67 resulted in diminished dopamine content and release. Moreover, PCN67 also affected the expression of tyrosine hydroxylase and lowered the expression of vesicular monoamine transporter 1 (VMAT1). In addition, significantly lower expression of antioxidant enzymes, including catalase, glutathione peroxidase and copper/zinc superoxide dismutase, was observed in comparison to the vehicle. In conclusion, PCN67 appears to disturb dopaminergic transmission by altering tyrosine hydroxylation, reducing VMAT1 expression and impairing antioxidant protection. Our study provides a potential mechanism for how PCN67 may cause dopamine deficiency and contribute to neuronal death by affecting cellular antioxidant potency; however, this conclusion requires further research.


Assuntos
Dopamina , Síndromes Neurotóxicas , Animais , Humanos , Naftalenos/toxicidade , Células PC12 , Ratos
4.
Handb Exp Pharmacol ; 271: 401-417, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33483878

RESUMO

Activation of the kappa opioid receptor (KOR) induces antinociception, anti-pruritic activity, diuresis, sedation, and dysphoria. KOR agonist-induced diuresis is characterized as water diuresis, in which water excretion with urine is increased without altering electrolyte excretion. Both centrally and peripherally acting KOR agonists promote diuresis. KOR antagonists block KOR agonist-evoked diuresis suggesting that the diuretic effect is through activation of the KOR. Studies in different experimental animal species and in humans indicate that KOR agonists decrease antidiuretic hormone (ADH) secretion and release from the hypothalamus and posterior pituitary; decrease response to ADH in kidneys; increase renal sympathetic nerve activity; and increase adrenaline, noradrenaline, and dopamine release from the adrenal medulla. The therapeutic potentials of KOR agonists as water diuretics have been studied in animal models of cerebral edema due to ischemia and intracranial mass, hypertension, and cirrhosis. This chapter reviews characteristics, possible mechanisms, as well as therapeutic potentials of KOR agonist-induced diuresis.


Assuntos
Analgésicos Opioides , Receptores Opioides kappa , Analgésicos Opioides/farmacologia , Animais , Diurese , Dopamina , Humanos , Antagonistas de Entorpecentes
5.
Handb Exp Pharmacol ; 271: 97-112, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34136961

RESUMO

Dynorphin (DYN) is an endogenous neurosecretory peptide which exerts its activity by binding to the family of G protein-coupled receptors, namely the kappa opioid receptor (KOR). Opioids are associated with pain, analgesia, and drug abuse, which play a central role in mood disorders with monoamine neurotransmitter interactions. Growing evidence demonstrates the cellular signaling cascades linked to KOR-mediated monoamine transporters regulation in cell models and native brain tissues. This chapter will review DYN/KOR role in mood and addiction in relevance to dopaminergic and serotonergic neurotransmissions. Also, we discuss the recent findings on KOR-mediated differential regulation of serotonin and dopamine transporters (SERT and DAT). These findings led to a better understanding of the role of DYN/KOR system in aminergic neurotransmission via its modulatory effect on both amine release and clearance. Detailed knowledge of these processes at the molecular level enables designing novel pharmacological reagents to target transporter motifs to treat mood and addiction and reduce unwanted side effects such as aversion, dysphoria, sedation, and psychomimesis.


Assuntos
Receptores Opioides kappa , Transtornos Relacionados ao Uso de Substâncias , Dopamina , Dinorfinas , Humanos , Serotonina
6.
Rev. colomb. anestesiol ; 49(4): e200, Oct.-Dec. 2021. tab, graf
Artigo em Inglês | LILACS, COLNAL | ID: biblio-1341236

RESUMO

Abstract Introduction Vasopressors are essential in the management of various types of shock. Objective To establish the trend of vasopressors use in the intensive care units (ICU) in a population of patients affiliated with the Colombian Health System, 2010-2017. Methods Observational trial using a population database of patients hospitalized in eleven ICUs in various cities in Colombia. The drugs dispensed to hospitalized patients over 18 years old, from January 2010 until December 2017 were considered. A review and analysis of the vasopressors dispensed per month was conducted, taking into account sociodemographic and pharmacological variables (vasopressor used and daily doses defined per 100/beds/day (DBD). Results 81,348 dispensations of vasopressors, equivalent to 26,414 treatments in 19,186 patients receiving care in 11 hospitals from 7 cities were reviewed. The mean age of patients was 66.3±18.1 years and 52.6 % were males. Of the total number of treatments recorded, 17,658 (66.8 %) were with just one vasopressor. Norepinephrine was the most frequently prescribed drug (75.9 % of the prescriptions dispensed; 60.5 DBD), followed by adrenaline (26.6 %; 41.6 DBD), dopamine (19.4%), dobutamine (16.0 %), vasopressin (8.5 %) and phenylephrine (0.9 %). The use of norepinephrine increased from 2010 to 2017 (+6.19 DBD), whilst the use of other drugs decreased, particularly the use of adrenaline (-60.6 DBD) and dopamine (-10.8 DBD). Conclusions Norepinephrine is the most widely used vasopressor showing a growing trend in terms of its use during the study period, which is supported by evidence in favor of its effectiveness and safety in patients with shock.


Resumen Introducción Los fármacos vasopresores son fundamentales en el manejo de los diferentes tipos de choque. Objetivo Determinar la tendencia de utilización de fármacos vasopresores en unidades de cuidados intensivos (UCI) en una población de pacientes afiliados al Sistema de Salud de Colombia, 2010-2017. Métodos Estudio observacional, a partir de una base de datos poblacional con pacientes hospitalizados en once UCI de diferentes ciudades de Colombia. Se obtuvieron las dispensaciones de pacientes mayores de 18 años hospitalizados desde enero de 2010 hasta diciembre de 2017. Se hizo revisión y análisis de la dispensación mensual de vasopresores. Se consideraron variables sociodemográficas y farmacológicas (medicamento vasopresor usado y dosis diarias definidas por 100 camas/día [DCD]). Resultados Se revisaron 81.348 dispensaciones de vasopresores, equivalentes a 26.414 terapias en 19.186 pacientes atendidos en 11 hospitales de 7 ciudades, cuya edad promedio fue 66,3±18,1 años y el 52,6 % eran hombres. Del total de terapias registradas, 17.658 (66,8 %) fueron con un solo vasopresor. La norepinefrina fue el más comúnmente prescrito (75,9 % de las dispensaciones; 60,5 DCD), seguido por adrenalina (26,6 %; 41,6 DCD), dopamina (19,4 %), dobutamina (16,0 %), vasopresina (8,5 %) y fenilefrina (0,9 %). El uso de norepinefrina se incrementó de 2010 a 2017 (+6,19 DCD), mientras que el de otros fármacos disminuyó, especialmente adrenalina (-60,6 DCD) y dopamina (-10,8 DCD). Conclusiones La norepinefrina es el fármaco vasopresor más utilizado y el que ha demostrado una tendencia de uso incremental durante el periodo de estudio, lo cual está respaldado por evidencia a favor de su efectividad y seguridad en pacientes con choque.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Choque , Vasoconstritores , Vasopressinas , Unidades de Terapia Intensiva , Fenilefrina , Preparações Farmacêuticas , Dopamina , Epinefrina , Norepinefrina , Dobutamina , Uso de Medicamentos , Dosagem , Prescrições
7.
Adv Exp Med Biol ; 1344: 57-69, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34773226

RESUMO

Rhythmic gene expression is found throughout the central nervous system. This harmonized regulation can be dependent on- and independent of- the master regulator of biological clocks, the suprachiasmatic nucleus (SCN). Substantial oscillatory activity in the brain's reward system is regulated by dopamine. While light serves as a primary time-giver (zeitgeber) of physiological clocks and synchronizes biological rhythms in 24-h cycles, nonphotic stimuli have a profound influence over circadian biology. Indeed, reward-related activities (e.g., feeding, exercise, sex, substance use, and social interactions), which lead to an elevated level of dopamine, alters rhythms in the SCN and the brain's reward system. In this chapter, we will discuss the influence of the dopaminergic reward pathways on circadian system and the implication of this interplay on human health.


Assuntos
Ritmo Circadiano , Núcleo Supraquiasmático , Relógios Biológicos , Dopamina , Humanos , Recompensa
8.
Am J Case Rep ; 22: e933995, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34776506

RESUMO

BACKGROUND Multiple system atrophy cerebellar type (MSA-C) is a subtype of MSA that presents with predominant ataxia along with lesser signs of parkinsonism and autonomic dysfunction. Previous studies have shown benefits from carbidopa/levodopa therapy for the MSA parkinsonian subtype but few studies have focused on the MSA-C subtype. We present a video case of MSA-C that demonstrated significant improvement with carbidopa/levodopa therapy. CASE REPORT A right-handed 61-year-old man with a past medical history of chronic microvascular ischemia, mild lower extremity neuropathy, and lumbar and cervical stenosis status after decompression presented with progressive worsening gait changes over several months with acute deterioration before admission. The initial neurological workup demonstrated bilateral cogwheel rigidity; difficulty with movement initiation. including standing up from a seated position; slow saccadic eye movements; masked facies (hypomimia); right ankle clonus; bilateral upper and left lower limb ataxia; and hyperreflexia. A follow-up workup was negative for metabolic, infectious, and paraneoplastic causes, but magnetic resonance imaging demonstrated cerebellar atrophy along with a "hot cross bun sign" suggestive of probable MSA-C according to consensus criteria, and the patient was started on carbidopa-levodopa. He subsequently demonstrated improvement in key motor domains, including his cogwheel rigidity and gait testing, and was discharged shortly thereafter. CONCLUSIONS Through this case report, we highlight a significant response to L-dopa therapy beyond what is normally expected according to diagnostic criteria for MSA. MSA treatment responsiveness can vary significantly across patients, which warrants additional studies into appropriate treatment choices for patients with Parkinson's disease and MSA.


Assuntos
Atrofia de Múltiplos Sistemas , Doença de Parkinson , Transtornos Parkinsonianos , Cerebelo , Dopamina , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/diagnóstico , Atrofia de Múltiplos Sistemas/tratamento farmacológico
9.
Alzheimers Res Ther ; 13(1): 187, 2021 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-34772450

RESUMO

BACKGROUND: Preclinical and pathology evidence suggests an involvement of brain dopamine (DA) circuitry in Alzheimer's disease (AD). We in vivo investigated if, when, and in which target regions [123I]FP-CIT-SPECT regional binding and molecular connectivity are damaged along the AD course. METHODS: We retrospectively selected 16 amyloid-positive subjects with mild cognitive impairment due to AD (AD-MCI), 22 amyloid-positive patients with probable AD dementia (AD-D), and 74 healthy controls, all with available [123I]FP-CIT-SPECT imaging. We tested whether nigrostriatal vs. mesocorticolimbic dopaminergic targets present binding potential loss, via MANCOVA, and alterations in molecular connectivity, via partial correlation analysis. Results were deemed significant at p < 0.05, after Bonferroni correction for multiple comparisons. RESULTS: We found significant reductions of [123I]FP-CIT binding in both AD-MCI and AD-D compared to controls. Binding reductions were prominent in the major targets of the ventrotegmental-mesocorticolimbic pathway, namely the ventral striatum and the hippocampus, in both clinical groups, and in the cingulate gyrus, in patients with dementia only. Within the nigrostriatal projections, only the dorsal caudate nucleus showed reduced [123I]FP-CIT binding, in both groups. Molecular connectivity assessment revealed a widespread loss of inter-connections among subcortical and cortical targets of the mesocorticolimbic network only (poor overlap with the control group as expressed by a Dice coefficient ≤ 0.25) and no alterations of the nigrostriatal network (high overlap with controls, Dice coefficient = 1). CONCLUSION: Local- and system-level alterations of the mesocorticolimbic dopaminergic circuitry characterize AD, already in prodromal disease phases. These results might foster new therapeutic strategies for AD. The clinical correlates of these findings deserve to be carefully considered within the emergence of both neuropsychiatric symptoms and cognitive deficits.


Assuntos
Doença de Alzheimer , Dopamina , Doença de Alzheimer/diagnóstico por imagem , Humanos , Neuroimagem , Estudos Retrospectivos , Tomografia Computadorizada de Emissão de Fóton Único
10.
Artigo em Inglês | MEDLINE | ID: mdl-34770047

RESUMO

Alcohol and other substance use disorders share comorbidity with other RDS disorders, i.e., a reduction in dopamine signaling within the reward pathway. RDS is a term that connects addictive, obsessive, compulsive, and impulsive behavioral disorders. An estimated 2 million individuals in the United States have opioid use disorder related to prescription opioids. It is estimated that the overall cost of the illegal and legally prescribed opioid crisis exceeds one trillion dollars. Opioid Replacement Therapy is the most common treatment for addictions and other RDS disorders. Even after repeated relapses, patients are repeatedly prescribed the same opioid replacement treatments. A recent JAMA report indicates that non-opioid treatments fare better than chronic opioid treatments. Research demonstrates that over 50 percent of all suicides are related to alcohol or other drug use. In addition to effective fellowship programs and spirituality acceptance, nutrigenomic therapies (e.g., KB220Z) optimize gene expression, rebalance neurotransmitters, and restore neurotransmitter functional connectivity. KB220Z was shown to increase functional connectivity across specific brain regions involved in dopaminergic function. KB220/Z significantly reduces RDS behavioral disorders and relapse in human DUI offenders. Taking a Genetic Addiction Risk Severity (GARS) test combined with a the KB220Z semi-customized nutrigenomic supplement effectively restores dopamine homeostasis (WC 199).


Assuntos
Comportamento Aditivo , Transtornos Relacionados ao Uso de Substâncias , Suicídio , Dopamina , Humanos , Recompensa
11.
Anal Chim Acta ; 1186: 339086, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34756249

RESUMO

Carbon fiber microelectrode arrays based on diazonium salt and single-walled carbon nanotubes composites (DS-SWCNT/CFMEA) have been fabricated, and it developed for the simultaneous monitoring of dopamine (DA) and serotonin (5-HT) with differential pulse voltammary (DPV). The diazonium salt can improve the water-solubility of single-walled carbon nanotubes and show good selectivity to DA, thus DS-SWCNT/CFMEA exhibits enhanced electrocatalytic activity for the oxidation of DA and 5-HT, and well antifouling ability to the other biomolecules. Moreover, DS-SWCNT/CFMEA shows the wider liner range, and the good performance of precision, reproducibility and biocompatibility. The excellent characteristics of the prepared microsensor array make it to be used to monitor the release of DA and 5-HT in the mouse brain striatum of different group over time. Meanwhile, the results of in vivo on line assay further confirmed the pharmacological effects of Uncaria alkaloid extract solution on DA and 5-HT. This research may provide a new method for monitoring the release of neurobiomolecules, and the microsensor array are expected to be a tool for the study of pharmacological and physiological processes on line in vivo.


Assuntos
Dopamina , Nanotubos de Carbono , Animais , Fibra de Carbono , Camundongos , Microeletrodos , Reprodutibilidade dos Testes , Serotonina
12.
Anal Chim Acta ; 1187: 339124, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34753568

RESUMO

Dopamine is an important neurotransmitter involved in many human biological processes as well as in different neurodegenerative diseases. Monitoring the concentration of dopamine in biological fluids, i.e., blood and urine is an effective way of accelerating the early diagnosis of these types of diseases. Electrochemical sensors are an ideal choice for real-time screening of dopamine as they can achieve fast, portable inexpensive and accurate measurements. In this work, we present electrochemical dopamine sensors based on reduced graphene oxide coupled with Au or Pt nanoparticles. Sensors were developed by co-electrodeposition onto a flexible substrate, and a systematic investigation concerning the electrodeposition parameters (concentration of precursors, deposition time and potential) was carried out to maximize the sensitivity of the dopamine detection. Square wave voltammetry was used as an electrochemical technique that ensured a high sensitive detection in the nM range. The sensors were challenged against synthetic urine in order to simulate a real sample detection scenario where dopamine concentrations are usually lower than 600 nM. Our sensors show a negligible interference from uric and ascorbic acids which did not affect sensor performance. A wide linear range (0.1-20 µm for gold nanoparticles, 0.1-10 µm for platinum nanoparticles) with high sensitivity (6.02 and 7.19 µA µM-1 cm-2 for gold and platinum, respectively) and a low limit of detection (75 and 62 nM for Au and Pt, respectively) were achieved. Real urine samples were also assayed, where the concentrations of dopamine detected aligned very closely to measurements undertaken using conventional laboratory techniques. Sensor fabrication employed a cost-effective production process with the possibility of also being integrated into flexible substrates, thus allowing for the possible development of wearable sensing devices.


Assuntos
Grafite , Nanopartículas Metálicas , Ácido Ascórbico , Dopamina , Técnicas Eletroquímicas , Eletrodos , Ouro , Humanos , Platina , Ácido Úrico
13.
Biomed Khim ; 67(5): 402-410, 2021 Sep.
Artigo em Russo | MEDLINE | ID: mdl-34730553

RESUMO

The closed enriched cross maze test was employed as a new experimental model of the attention deficit disorder (ADD) for evaluation of the behavioral and neurochemical effects of the nootropic drug pantogam (100 mg/kg, intraperitoneally) and atomoxetine hydrochloride (3 mg/kg, intraperitoneally) administered subchronically to CD-1 outbred mice. Two subpopulations of rodents differed spontaneously in attention to enriched compartments (ED-Low and ED-High), were estimated on the basis of time spent by the mice in the empty or enriched compartments. The ED-Low and ED-High mice insignificantly differed in parameters associated with anxiety, exploratory efficacy and motor activity. Subchronic administration of both drugs in selected doses produced corrective effect on animal behavior seen as a selective increase in the ED-ratio values in the ED-Low subpopulation. Differences in the distribution of dopamine D2 and GABAB receptors (Bmax) between placebo-treated ED-Low and ED-High mice were found in the prefrontal cortex using the radioligand binding method. The neuroreceptor effects of atomoxetine were seen in prefrontal cortex of ED-Low mice as decrease in the Bmax values of D2 receptors by 14%. Pantogam in the prefrontal cortex of ED-Low subpopulation showed a decrease in the Bmax values of D2 receptors by 22% and an increase for GABAB receptors by 44%. Therefore, subchronic administration of pantogam had a positive corrective effect on the behavior parameters and the density of the studied receptor subtypes in animals with severe attention deficit.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Animais , Cloridrato de Atomoxetina/farmacologia , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Dopamina , Camundongos , Ácido Pantotênico/análogos & derivados , Ácido gama-Aminobutírico/análogos & derivados
14.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(6): 901-906, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34841751

RESUMO

Epidemiological studies found that the incidence of myopia was increasing year by year and the age of onset of myopia was showing a trend of affecting increasingly younger children. Reducing the occurrence of myopia and controlling the increase of myopia diopter have always been the focus of research on the prevention and control of myopia. Large randomized controlled clinical trials have found that outdoor activities can effectively reduce the incidence of myopia and delay the progression of myopia. Basic experiments also revealed that there were certain connections between light exposure and myopia. We herein review the research progress, limitations and future directions of research on light exposure and myopia. From the perspective of light properties, increasing the intensity of light can slow the progression of myopia and reduce the occurrence of experimentally induced myopia. However, the actual mechanism of action is still unclear. The rhythmic changes of light exposure caused by the light/dark cycle may cause abnormalities in the secretion of melatonin and dopamine, and changes in the circadian rhythm of intraocular pressure and choroidal thickness, thus affecting myopia. The red light, with relatively longer wavelength and forming images behind the retina, tends to induce myopia more easily, while the blue light, with medium and short wavelength and forming images before the retina, tends to delay myopia progression. However, different species respond differently to lights of different wavelengths, and the relationship between light wavelength and myopia needs further investigation. Future research can be done to further explore the mechanism of action of how light exposure changes the progression of myopia, including the following aspects: how light changes dopamine levels, causing changes in downstream signal pathways, and thus controlling the growth of the axial length of the eye; how retinal photoreceptor cells receive light signals of different wavelengths in order to adjust the refractive power of the eyes; and how to design artificial lighting of reasonable intensity, composition and properties, and apply the design in myopia prevention and control.


Assuntos
Miopia , Ritmo Circadiano , Dopamina , Humanos , Miopia/epidemiologia , Miopia/etiologia , Miopia/prevenção & controle , Retina
15.
Nat Rev Dis Primers ; 7(1): 80, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732752

RESUMO

Restless legs syndrome (RLS) is a common sensorimotor disorder characterized by an urge to move that appears during rest or is exacerbated by rest, that occurs in the evening or night and that disappears during movement or is improved by movement. Symptoms vary considerably in age at onset, frequency and severity, with severe forms affecting sleep, quality of life and mood. Patients with RLS often display periodic leg movements during sleep or resting wakefulness. RLS is considered to be a complex condition in which predisposing genetic factors, environmental factors and comorbidities contribute to the expression of the disorder. RLS occurs alone or with comorbidities, for example, iron deficiency and kidney disease, but also with cardiovascular diseases, diabetes mellitus and neurological, rheumatological and respiratory disorders. The pathophysiology is still unclear, with the involvement of brain iron deficiency, dysfunction in the dopaminergic and nociceptive systems and altered adenosine and glutamatergic pathways as hypotheses being investigated. RLS is poorly recognized by physicians and it is accordingly often incorrectly diagnosed and managed. Treatment guidelines recommend initiation of therapy with low doses of dopamine agonists or α2δ ligands in severe forms. Although dopaminergic treatment is initially highly effective, its long-term use can result in a serious worsening of symptoms known as augmentation. Other treatments include opioids and iron preparations.


Assuntos
Síndrome das Pernas Inquietas , Encéfalo , Dopamina , Agonistas de Dopamina/uso terapêutico , Humanos , Qualidade de Vida , Síndrome das Pernas Inquietas/diagnóstico , Síndrome das Pernas Inquietas/epidemiologia
16.
BMC Neurol ; 21(1): 459, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34814867

RESUMO

BACKGROUND: Dopamine transporter single-photon emission computed tomography (DaT-SPECT) can quantify the functional integrity of the dopaminergic nerve terminals and has been suggested as an imaging modality to verify the clinical diagnosis of Parkinson's disease (PD). Depending on the stage of progression, approximately 5-15% of participants clinically diagnosed with idiopathic PD have been observed in previous studies to have normal DaT-SPECT patterns. However, the utility of DaT-SPECT in enhancing early PD participant selection in a global, multicenter clinical trial of a potentially disease-modifying therapy is not well understood. METHODS: The SPARK clinical trial was a phase 2 trial of cinpanemab, a monoclonal antibody against alpha-synuclein, in participants with early PD. DaT-SPECT was performed at screening to select participants with DaT-SPECT patterns consistent with degenerative parkinsonism. Acquisition was harmonised across 82 sites. Images were reconstructed and qualitatively read at a central laboratory by blinded neuroradiologists for inclusion prior to automated quantitative analysis. RESULTS: In total, 482 unique participants were screened between January 2018 and May 2019; 3.8% (15/398) of imaged participants were excluded owing to negative DaT-SPECT findings (i.e., scans without evidence of dopaminergic deficit [SWEDD]). CONCLUSION: A smaller proportion of SPARK participants were excluded owing to SWEDD status upon DaT-SPECT screening than has been reported in prior studies. Further research is needed to understand the reasons for the low SWEDD rate in this study and whether these results are generalisable to future studies. If supported, the radiation risks, imaging costs, and operational burden of DaT-SPECT for enrichment may be mitigated by clinical assessment and other study design aspects. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03318523 . Date submitted: October 19, 2017. First Posted: October 24, 2017.


Assuntos
Proteínas da Membrana Plasmática de Transporte de Dopamina , Doença de Parkinson , Biomarcadores , Dopamina , Humanos , Doença de Parkinson/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único
17.
Clin Drug Investig ; 41(12): 1067-1073, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34751928

RESUMO

BACKGROUND AND OBJECTIVES: In clinical trials, the safety of drugs is summarized by the incidence of adverse events, while post-marketing reporting systems use disproportionate reporting of adverse drug reactions. Here, we propose a method to evaluate the novelty of a safety profile of a drug in a new class (in clinical trials), against that of those already on the market (using pharmacovigilance data). METHODS: Through Bayesian disproportionality analyses of the US Food and Drug Administration Adverse Event Reporting System (FAERS) data, we identified and ranked Preferred Terms for a pool of 30 antipsychotics. Adverse event rates in randomized, double-blind, placebo-controlled schizophrenia clinical trials were summarized by their class specificity. One study (N = 245) of the trace amine-associated receptor 1 (TAAR1) agonist ulotaront (SEP-363856) was compared with five studies of dopamine D2 receptor-based antipsychotics lurasidone (N = 1041), quetiapine (N = 119), olanzapine (N = 122), and placebo (N = 504). RESULTS: In clinical trials of antipsychotics, cumulative rates for adverse events at and above a threshold of disproportional reporting (Empirical Bayes Geometric Mean 50 > 3 in FAERS) were 52%, 42%, and 60% for lurasidone, quetiapine, and olanzapine, respectively, indicating that over half of the adverse events reported in clinical trials of an atypical antipsychotic are class-specific risks. In contrast, in the clinical trial of ulotaront, the cumulative rate was 23%, indicating a lower rate of antipsychotic class-specific risk. CONCLUSIONS: These results demonstrate a novel approach to summarize adverse events in clinical trials, where the cumulative burden of class-specific risks describes the emerging safety profile of a new drug in clinical development, relative to reactions anticipated for drugs in an established pharmacological class. CLINICALTRIALS. GOV IDENTIFIERS: NCT0296938, NCT00088634, NCT00549718, NCT00615433, NCT00790192.


Assuntos
Antipsicóticos , Dopamina , Antipsicóticos/efeitos adversos , Teorema de Bayes , Humanos , Piranos , Receptores Acoplados a Proteínas G , Estados Unidos , United States Food and Drug Administration
18.
Biosensors (Basel) ; 11(10)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34677324

RESUMO

Dopamine (DA) and ascorbic acid (AA) are two important biomarkers with similar oxidation potentials. To facilitate their simultaneous electrochemical detection, a new voltammetric sensor was developed by modifying a screen-printed carbon electrode (SPCE) with a newly synthesized block copolymer (poly(DMAEMA-b-styrene), PDbS) as a dispersant for reduced graphene oxide (rGO). The prepared PDbS-rGO and the modified SPCE were characterized using a range of physical and electrochemical techniques including Raman spectroscopy, scanning electron microscopy, transmission electron microscopy, cyclic voltammetry, electrochemical impedance spectroscopy, and linear sweep voltammetry. Compared to the bare SPCE, the PDbS-rGO-modified SPCE (PDbS-rGO/SPCE) showed better sensitivity and peak-to-peak separation for DA and AA in mixed solutions. Under the optimum conditions, the dynamic linear ranges for DA and AA were 0.1-300 and 10-1100 µM, and the detection limits were 0.134 and 0.88 µM (S/N = 3), respectively. Furthermore, PDbS-rGO/SPCE exhibited considerably enhanced anti-interference capability, high reproducibility, and storage stability for four weeks. The practical potential of the PDbS-rGO/SPCE sensor for measuring DA and AA was demonstrated using ex vivo brain tissues from a Parkinson's disease mouse model and the control.


Assuntos
Ácido Ascórbico/análise , Encéfalo , Dopamina/análise , Grafite/química , Animais , Carbono , Técnicas Eletroquímicas/métodos , Eletrodos , Camundongos , Oxirredução , Polímeros , Reprodutibilidade dos Testes , Análise Espectral Raman , Ácido Úrico
19.
Nanoscale ; 13(43): 18148-18159, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34709280

RESUMO

Interfacing affinity between grafts and host tissues is an urgent issue that needs to be addressed for the clinical translation of tissue engineered extracellular matrix (ECM) based grafts. Dopamine is known as a universal adhesive, the catechol groups on which could form chelating bonds with metal ions. Herein we developed an adhesive nano-coating on ECM based grafts which could crosslink in situ with ferric ions for fixation with surrounding tissues after implantation without affecting the porous structures of the grafts. Therefore, decellularized living hyaline cartilage graft (dLhCG), a model ECM-based graft, with dopamine based natural biological material adhesive coatings was manufactured to address the interfacing affinity issue between ECM-based grafts and cartilage. A macromolecule backbone was needed for the coating material to avoid the formation of a rigid crosslinking system and adverse effects caused by small molecules of dopamine. Chondroitin sulfate (CS), a cartilage derived sulfated GAG, was chosen as the backbone to fabricate dopamine modified CS (CSD) with no impurities introduced to the joint. Dopamine modified serum albumin (BCD) was also chosen for the favorable biocompatibility of albumin. Both dLhCG coated with CSD and dLhCG coated with BCD showed enhanced adhesive strength with cartilage after chelating with ferric ions in situ compared to dLhCG and further potential in improving the interfacing affinity of dLhCG with cartilage.


Assuntos
Adesivos , Dopamina , Cartilagem , Matriz Extracelular , Engenharia Tecidual
20.
ACS Chem Neurosci ; 12(22): 4336-4349, 2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34704733

RESUMO

Metabolomic reprogramming plays a crucial role in the activation of several regulatory mechanisms including neuronal responses of the host. In the present study, alterations at physiological and biochemical levels were initially assessed to monitor the impact of the candidate pathogen Cronobacter sakazakii on the nematode host Caenorhabditis elegans. The abnormal behavioral responses were observed in infected worms in terms of hyperosmolarity and high viscous chemicals. The microscopic observations indicated reduction in egg laying and internal hatching of larvae in the host. An increased level of total reactive oxygen species and reduction in antioxidant agents such as glutathione and catalase were observed. These observations suggested the severe effect of C. sakazakii infection on C. elegans. To understand the small molecules which likely mediated neurotransmission, the whole metabolome of C. elegans during the infection of C. sakazakii was analyzed using liquid chromatography-mass spectrometry. A decrease in the quantity of methyl dopamine and palmitoyl dopamine and an increase in hydroxyl dopamine suggested that reduction in dopamine reuptake and dopamine neuronal stress. The disordered dopaminergic transmission during infection was confirmed using transgenic C. elegans by microscopic observation of Dat-1 protein expression. In addition, reduction in arachidonic acid and short-chain fatty acids revealed their effect on lipid droplet formation as well as neuronal damage. An increase in the quantity of stearoyl CoA underpinned the higher accumulation of lipid droplets in the host. On the other hand, an increased level of metabolites such as palmitoyl serotonin, citalopram N-oxide, and N-acyl palmitoyl serotonin revealed serotonin-mediated potential response for neuroprotection, cytotoxicity, and cellular damage. Based on the metabolomic data, the genes correspond to small molecules involved in biosynthesis and transportation of candidate neurotransmitters were validated through relative gene expression.


Assuntos
Caenorhabditis elegans , Cronobacter sakazakii , Animais , Animais Geneticamente Modificados , Dopamina , Serotonina
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