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1.
Sci Rep ; 14(1): 6948, 2024 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521816

RESUMO

Catecholamines norepinephrine and dopamine have been implicated in numerous physiological processes within the central nervous system. Emerging evidence has highlighted the importance of tightly regulated monoamine levels for placental functions and fetal development. However, the complexities of synthesis, release, and regulation of catecholamines in the fetoplacental unit have not been fully unraveled. In this study, we investigated the expression of enzymes and transporters involved in synthesis, degradation, and transport of norepinephrine and dopamine in the human placenta and rat fetoplacental unit. Quantitative PCR and Western blot analyses were performed in early-to-late gestation in humans (first trimester vs. term placenta) and mid-to-late gestation in rats (placenta and fetal brain, intestines, liver, lungs, and heart). In addition, we analyzed the gene expression patterns in isolated primary trophoblast cells from the human placenta and placenta-derived cell lines (HRP-1, BeWo, JEG-3). In both human and rat placentas, the study identifies the presence of only PNMT, COMT, and NET at the mRNA and protein levels, with the expression of PNMT and NET showing gestational age dependency. On the other hand, rat fetal tissues consistently express the catecholamine pathway genes, revealing distinct developmental expression patterns. Lastly, we report significant transcriptional profile variations in different placental cell models, emphasizing the importance of careful model selection for catecholamine metabolism/transport studies. Collectively, integrating findings from humans and rats enhances our understanding of the dynamic regulatory mechanisms that underlie catecholamine dynamics during pregnancy. We identified similar patterns in both species across gestation, suggesting conserved molecular mechanisms and potentially shedding light on shared biological processes influencing placental development.


Assuntos
Catecolaminas , Dopamina , Gravidez , Ratos , Humanos , Animais , Feminino , Linhagem Celular Tumoral , Placenta , Norepinefrina
2.
Physiol Rep ; 12(5): e15966, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38444056

RESUMO

Previous studies revealed a controversial role of mechanistic target of rapamycin complex 1 (mTORC1) and mTORC1-regulated macroautophagy in isoproterenol (ISO)-induced cardiac injury. Here we investigated the role of mTORC1 and potential underlying mechanisms in ISO-induced cardiomyocyte necrosis. Two consecutive daily injections of ISO (85 mg/kg, s.c.) or vehicle control (CTL) were administered to C57BL/6J mice with or without rapamycin (RAP, 5 mg/kg, i.p.) pretreatment. Western blot analyses showed that myocardial mTORC1 signaling and the RIPK1-RIPK3-MLKL necroptotic pathway were activated, mRNA expression analyses revealed downregulation of representative TFEB target genes, and Evan's blue dye uptake assays detected increased cardiomyocyte necrosis in ISO-treated mice. However, RAP pretreatment prevented or significantly attenuated the ISO-induced cardiomyocyte necrosis, myocardial inflammation, downregulation of TFEB target genes, and activation of the RIPK1-RIPK3-MLKL pathway. LC3-II flux assays confirmed the impairment of myocardial autophagic flux in the ISO-treated mice. In cultured neonatal rat cardiomyocytes, mTORC1 signaling was also activated by ISO, and inhibition of mTORC1 by RAP attenuated ISO-induced cytotoxicity. These findings suggest that mTORC1 hyperactivation and resultant suppression of macroautophagy play a major role in the induction of cardiomyocyte necroptosis by catecholamine surges, identifying mTORC1 inhibition as a potential strategy to treat heart diseases with catecholamine surges.


Assuntos
Catecolaminas , Miócitos Cardíacos , Animais , Camundongos , Ratos , Camundongos Endogâmicos C57BL , Macroautofagia , Necroptose , Isoproterenol/toxicidade , Alvo Mecanístico do Complexo 1 de Rapamicina , Necrose
3.
Mikrochim Acta ; 191(3): 170, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427110

RESUMO

Gold nanostructures and a Nafion modified screen-printed carbon electrode (Nafion/AuNS/SPCE) were developed to assess the cell viability of Parkinson's disease (PD) cell models. The electrochemical measurement of cell viability was reflected by catecholamine neurotransmitter (represented by dopamine) secretion capacity, followed by a traditional tetrazolium-based colorimetric assay for confirmation. Due to the  capacity to synthesize, store, and release catecholamines as well as their unlimited homogeneous proliferation, and ease of manipulation, pheochromocytoma (PC12) cells were used for PD cell modeling. Commercial low-differentiated and highly-differentiated PC12 cells, and home-made nerve growth factor (NGF) induced low-differentiated PC12 cells (NGF-differentiated PC12 cells) were included in the modeling. This approach achieved sensitive and rapid determination of cellular modeling and intervention states. Notably, among the three cell lines, NGF-differentiated PC12 cells displayed the enhanced neurotransmitter secretion level accompanied with attenuated growth rate, incremental dendrites in number and length that were highly resemble with neurons. Therefore, it was selected as the PD-tailorable modeling cell line. In short, the electrochemical sensor can be used to sensitively determine the biological function of neuron-like PC12 cells with negligible destruction and to explore the protective and regenerative impact of various substances on nerve cell model.


Assuntos
Neoplasias das Glândulas Suprarrenais , Polímeros de Fluorcarboneto , Doença de Parkinson , Ratos , Animais , Catecolaminas/metabolismo , Células PC12 , Fator de Crescimento Neural , Avaliação Pré-Clínica de Medicamentos , Neurotransmissores
4.
J Med Case Rep ; 18(1): 161, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38500192

RESUMO

BACKGROUND: This report presents a case of cannabinoid-induced hyperemesis syndrome causing repeated violent retching in a patient with a large (8 cm) adrenal pheochromocytoma resulting in hypertensive urgency. CASE PRESENTATION: A 69-year-old white male patient with a previously diagnosed pheochromocytoma presented to the emergency department with nausea and vomiting and was found to have hypertensive urgency. Computed tomography scan did not show any acute abdominal pathology and history was inconsistent with a gastrointestinal etiology. Patient had a history of daily cannabinoid use for many years and repeated self-limited hyperemesis episodes, and thus a diagnosis of cannabinoid-induced hyperemesis syndrome was made. It was concluded that the likely explanation for the hypertensive urgency was from physical compression of his adrenal tumor during the episodes of retching resulting in a catecholamine surge. The patient was given antiemetics and admitted to the intensive care unit for blood pressure management. Blood pressure was initially controlled with phentolamine and a clevidipine infusion, then transitioned to oral doxazosin and phenoxybenzamine. Hyperemesis and abdominal pain resolved after 24 hours, and his blood pressure returned to baseline. The patient was discharged with the recommendation to stop all cannabis use. On follow-up, his blood pressure remained well controlled, and he subsequently underwent adrenalectomy for tumor removal. CONCLUSION: Hyperemesis can cause hypertensive events in patients with pheochromocytoma by increasing abdominal pressure, leading to catecholamine release.


Assuntos
Neoplasias das Glândulas Suprarrenais , Canabinoides , Feocromocitoma , Humanos , Masculino , Idoso , Canabinoides/efeitos adversos , Feocromocitoma/complicações , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/cirurgia , Vômito/induzido quimicamente , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/cirurgia , Catecolaminas/efeitos adversos
5.
Crit Care Med ; 52(4): 596-606, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38483219

RESUMO

OBJECTIVES: We hypothesized that the immunosuppressive effects associated with antibiotics, sedatives, and catecholamines amplify sepsis-associated immune suppression through mitochondrial dysfunction, and there is a cumulative effect when used in combination. We thus sought to determine the impact of the exemplar drugs ciprofloxacin, propofol, and norepinephrine, used alone and in combination, at clinically relevant concentrations, on the ex vivo functionality of peripheral blood mononuclear cells (PBMCs) drawn from healthy, infected, and septic individuals. DESIGN: In vitro/ex vivo investigation. SETTING: University laboratory. SUBJECTS: Healthy volunteers, infected (nonseptic) patients in the emergency department, and septic ICU patients. INTERVENTIONS: PBMCs were isolated from these subjects and treated with ciprofloxacin (100 µg/mL), propofol (50 µg/mL), norepinephrine (10 µg/mL), or all three drugs combined, with and without lipopolysaccharide (100 ng/mL) for 6 or 24 hours. Comparison was made between study groups and against untreated cells. Measurements were made of cell viability, cytokine production, phagocytosis, human leukocyte antigen-DR (HLA-DR) status, mitochondrial membrane potential, mitochondrial reactive oxygen species production, and oxygen consumption. Gene expression in immune and metabolic pathways was investigated in PBMCs sampled from healthy volunteers coincubated with septic serum. MEASUREMENTS AND RESULTS: Coincubation with each of the drugs reduced cytokine production and phagocytosis in PBMCs isolated from septic patients, and healthy volunteers coincubated with septic serum. No effect was seen on HLA-DR surface expression. No cumulative effects were seen with the drug combination. Sepsis-induced changes in gene expression and mitochondrial functionality were not further affected by addition of any of the drugs. CONCLUSION: Drugs commonly used in critical care lead to significant immune dysfunction ex vivo and enhance sepsis-associated immunosuppression. Further studies are required to identify underlying mechanisms and potential impact on patient outcomes.


Assuntos
Propofol , Sepse , Humanos , Catecolaminas , Hipnóticos e Sedativos/farmacologia , Antibacterianos , Leucócitos Mononucleares , Norepinefrina , Terapia de Imunossupressão , Ciprofloxacina , Antígenos HLA-DR , Citocinas
6.
Int J Mol Sci ; 25(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38473855

RESUMO

In order to determine the behavior of the right ventricle, we have reviewed the existing literature in the area of cardiac remodeling, signal transduction pathways, subcellular mechanisms, ß-adrenoreceptor-adenylyl cyclase system and myocardial catecholamine content during the development of left ventricular failure due to myocardial infarction. The right ventricle exhibited adaptive cardiac hypertrophy due to increases in different signal transduction pathways involving the activation of protein kinase C, phospholipase C and protein kinase A systems by elevated levels of vasoactive hormones such as catecholamines and angiotensin II in the circulation at early and moderate stages of heart failure. An increase in the sarcoplasmic reticulum Ca2+ transport without any changes in myofibrillar Ca2+-stimulated ATPase was observed in the right ventricle at early and moderate stages of heart failure. On the other hand, the right ventricle showed maladaptive cardiac hypertrophy at the severe stages of heart failure due to myocardial infarction. The upregulation and downregulation of ß-adrenoreceptor-mediated signal transduction pathways were observed in the right ventricle at moderate and late stages of heart failure, respectively. The catalytic activity of adenylate cyclase, as well as the regulation of this enzyme by Gs proteins, were seen to be augmented in the hypertrophied right ventricle at early, moderate and severe stages of heart failure. Furthermore, catecholamine stores and catecholamine uptake in the right ventricle were also affected as a consequence of changes in the sympathetic nervous system at different stages of heart failure. It is suggested that the hypertrophied right ventricle may serve as a compensatory mechanism to the left ventricle during the development of early and moderate stages of heart failure.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Humanos , Ventrículos do Coração/metabolismo , Insuficiência Cardíaca/metabolismo , Infarto do Miocárdio/metabolismo , Cardiomegalia/metabolismo , Miocárdio/metabolismo , Receptores Adrenérgicos beta/metabolismo , Catecolaminas/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Adenilil Ciclases/metabolismo
7.
Domest Anim Endocrinol ; 87: 106838, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401307

RESUMO

Increased fetal cortisol is associated with catecholamine release, a primary factor for neonatal adaptive responses. However, relationship between canine peripartum cortisol and catecholamine is unknown. We aimed to compare serum adrenaline, noradrenaline and cortisol during peripartum in bitches and neonates of distinct obstetric conditions and to assess amniotic fluid cortisol concentration. Twenty females and maximum of three puppies per litter were allocated into Vaginal Eutocia (10 females; 17 neonates) and Elective C-section (10 females; 20 neonates) groups. Amniotic fluid was collected at delivery for cortisol concentration. Maternal and neonatal blood were collected prepartum, intrapartum, postpartum and 1h postpartum, and at birth, 30 and 60min, 12hs and 24hs, respectively, for cortisol, adrenaline and noradrenaline assessment. C-section determined higher noradrenaline throughout delivery and cortisol concentration from intrapartum through 1h postpartum, compared to vaginal birth. C-section maternal cortisol showed progressive increase from intrapartum onwards, while neonatal cortisol remained unchanged. No difference of maternal cortisol concentration occurred along whelping, whereas a significant decrease was verified for vaginal delivery puppies from birth until the 12hs. Puppies delivered vaginally had higher cortisol concentration at birth and 30min, compared to c-section puppies. There was a higher concentration of amniotic fluid cortisol in vaginal eutocia. In conclusion, c-section induces higher maternal stress during and after surgery, whilst vaginal delivery is a more neonatal physiologically stressful condition, contributing to better adaptation during transition.


Assuntos
Catecolaminas , Hidrocortisona , Gravidez , Feminino , Cães , Animais , Líquido Amniótico , Norepinefrina , Epinefrina
8.
Medicina (Kaunas) ; 60(2)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38399485

RESUMO

Background and Objectives: Paragangliomas of the head and neck are rare neuroendocrine tumors originating from the paraganglia, which might be sympathetic or parasympathetic. Laryngeal paragangliomas are the rarest subtype of these tumors, with only 1.41% of all paragangliomas, arising from the supraglottic or subglottic paraganglia of the larynx. The vast majority of them are benign, but there are some cases in which they turn out to be malignant, and the only way to know with certainty the difference between them is when we identify distant metastases. The aim of this article is to share our experience with a rare case of laryngeal paraganglioma and review the clinical characteristics, methods of diagnostic, necessary investigation prior to the operation, and surgical management of this type of tumor. Materials and Methods: We present the case of a 68-year-old female patient, a non-smoker, who accused dysphagia, dysphonia, foreign body sensation, chronic cough, and hoarseness for six months. We performed a tracheostomy prior to biopsy to secure the airways in case of bleeding and then took a few biopsy samples. The histopathological exam revealed the presence of a laryngeal paraganglioma. An enhanced CT scan was performed in order to describe the localization, size, and invasion of the tumor. We also measured the vanillylmandelic acid from the urine to determine if the tumor produced catecholamines alongside a full cardiology and endocrinology examinations. In order to prevent massive bleeding during the operation, chemoembolization was attempted before surgery, but it was unsuccessful due to an anatomical variation of the left superior thyroid artery. She underwent surgery, first through transoral endoscopic microsurgery; however, we decided to undertake an external approach because of poor bleeding control, even though we had ligated both the superior thyroid artery and the external carotid artery, with a thyrotomy and laryngofissure achieving the complete resection of the tumor. Results: The patient was discharged 10 postoperative days later, with the recommendation of introducing food step-by-step from liquids to solids. She was decannulated after 30 days, with no complications regarding breathing, phonation, or deglutition. Twelve months after the surgery, we did not identify any local relapses of distant metastases. Conclusions: Laryngeal paragangliomas are rare neuroendocrine tumors that arise from the laryngeal paraganglia. Surgery is the best treatment option available, and it can be done by either an external approach or by transoral endoscopy. Enhanced CT or MRI, as well as full cardiological and endocrinological evaluation are mandatory prior to the operation. Measuring the catecholamines levels show the if the tumor is secretory. Controlling the bleeding poses the biggest challenge in performing the resection of the tumor, especially when a transoral endoscopic approach is chosen. Further standardized follow-up guidelines are required in the future.


Assuntos
Neoplasias Laríngeas , Tumores Neuroendócrinos , Paraganglioma , Feminino , Humanos , Idoso , Recidiva Local de Neoplasia , Paraganglioma/diagnóstico , Paraganglioma/cirurgia , Paraganglioma/patologia , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/cirurgia , Neoplasias Laríngeas/patologia , Catecolaminas
9.
Vitam Horm ; 124: 221-295, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38408800

RESUMO

Stress is part of our daily lives and good health in the modern world is offset by unhealthy lifestyle factors, including the deleterious consequences of stress and associated pathologies. Repeated and/or prolonged stress may disrupt the body homeostasis and thus threatens our lives. Adaptive processes that allow the organism to adapt to new environmental conditions and maintain its homeostasis are therefore crucial. The adrenal glands are major endocrine/neuroendocrine organs involved in the adaptive response of the body facing stressful situations. Upon stress episodes and in response to activation of the sympathetic nervous system, the first adrenal cells to be activated are the neuroendocrine chromaffin cells located in the medullary tissue of the adrenal gland. By releasing catecholamines (mainly epinephrine and to a lesser extent norepinephrine), adrenal chromaffin cells actively contribute to the development of adaptive mechanisms, in particular targeting the cardiovascular system and leading to appropriate adjustments of blood pressure and heart rate, as well as energy metabolism. Specifically, this chapter covers the current knowledge as to how the adrenal medullary tissue remodels in response to stress episodes, with special attention paid to chromaffin cell stimulus-secretion coupling. Adrenal stimulus-secretion coupling encompasses various elements taking place at both the molecular/cellular and tissular levels. Here, I focus on stress-driven changes in catecholamine biosynthesis, chromaffin cell excitability, synaptic neurotransmission and gap junctional communication. These signaling pathways undergo a collective and finely-tuned remodeling, contributing to appropriate catecholamine secretion and maintenance of body homeostasis in response to stress.


Assuntos
Medula Suprarrenal , Células Cromafins , Humanos , Medula Suprarrenal/metabolismo , Células Cromafins/metabolismo , Transmissão Sináptica/fisiologia , Catecolaminas/metabolismo , Junções Comunicantes/metabolismo
10.
Int J Mol Sci ; 25(3)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38338864

RESUMO

Orexins are neuronal peptides that play a prominent role in sleep behavior and feeding behavior in the central nervous system, though their receptors also exist in peripheral organs, including the adrenal gland. In this study, the effects of orexins on catecholamine synthesis in the rat adrenomedullary cell line PC12 were investigated by focusing on their interaction with the adrenomedullary bone morphogenetic protein (BMP)-4. Orexin A treatment reduced the mRNA levels of key enzymes for catecholamine synthesis, including tyrosine hydroxylase (Th), 3,4-dihydroxyphenylalanie decarboxylase (Ddc) and dopamine ß-hydroxylase (Dbh), in a concentration-dependent manner. On the other hand, treatment with BMP-4 suppressed the expression of Th and Ddc but enhanced that of Dbh with or without co-treatment with orexin A. Of note, orexin A augmented BMP-receptor signaling detected by the phosphorylation of Smad1/5/9 through the suppression of inhibitory Smad6/7 and the upregulation of BMP type-II receptor (BMPRII). Furthermore, treatment with BMP-4 upregulated the mRNA levels of OX1R in PC12 cells. Collectively, the results indicate that orexin and BMP-4 suppress adrenomedullary catecholamine synthesis by mutually upregulating the pathway of each other in adrenomedullary cells.


Assuntos
Proteínas Morfogenéticas Ósseas , Catecolaminas , Orexinas , Animais , Ratos , Proteínas Morfogenéticas Ósseas/metabolismo , Catecolaminas/metabolismo , Orexinas/farmacologia , Orexinas/metabolismo , RNA Mensageiro , Transdução de Sinais , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo , Células PC12/metabolismo
11.
Hypertension ; 81(4): 927-935, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38334001

RESUMO

BACKGROUND: High circulating DPP3 (dipeptidyl peptidase 3) has been associated with poor prognosis in critically ill patients with circulatory failure. In such situation, DPP3 could play a pathological role, putatively via an excessive angiotensin peptides cleavage. Our objective was to investigate the hemodynamics changes induced by DPP3 in mice and the relation between the observed effects and renin-angiotensin system modulation. METHODS: Ten-week-old male C57Bl/6J mice were subjected to intravenous injection of purified human DPP3 or an anti-DPP3 antibody (procizumab). Invasive blood pressure and renal blood flow were monitored throughout the experiments. Circulating angiotensin peptides and catecholamines were measured and receptor blocking experiment performed to investigate the underlying mechanisms. RESULTS: DPP3 administration significantly increased renal blood flow, while blood pressure was minimally affected. Conversely, procizumab led to significantly decreased renal blood flow. Angiotensin peptides measurement and an AT1R (angiotensin II receptor type 1) blockade experiment using valsartan demonstrated that the renovascular effect induced by DPP3 is due to reduced AT1R activation via decreased concentrations of circulating angiotensin II, III, and IV. Measurements of circulating catecholamines and an adrenergic receptor blockade by labetalol demonstrated a concomitant catecholamines release that explains blood pressure maintenance upon DPP3 administration. CONCLUSIONS: High circulating DPP3 increases renal blood flow due to reduced AT1R activation via decreased concentrations of circulating angiotensin peptides while blood pressure is maintained by concomitant endogenous catecholamines release.


Assuntos
Hemodinâmica , Peptídeos , Humanos , Masculino , Camundongos , Animais , Peptídeos/farmacologia , Angiotensina II/farmacologia , Catecolaminas , Dipeptidil Peptidases e Tripeptidil Peptidases/farmacologia
12.
Exp Neurol ; 374: 114718, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38336285

RESUMO

Executive function, including working memory, attention and inhibitory control, is crucial for decision making, thinking and planning. Lisdexamfetamine, the prodrug of d-amphetamine, has been approved for treating attention-deficit hyperactivity disorder and binge eating disorder, but whether it improves executive function under non-disease condition, as well as the underlying pharmacokinetic and neurochemical properties, remains unclear. Here, using trial unique non-matching to location task and five-choice serial reaction time task of rats, we found lisdexamfetamine (p.o) enhanced spatial working memory and sustained attention under various cognitive load conditions, while d-amphetamine (i.p) only improved these cognitive performances under certain high cognitive load condition. Additionally, lisdexamfetamine evoked less impulsivity than d-amphetamine, indicating lower adverse effect on inhibitory control. In vivo pharmacokinetics showed lisdexamfetamine produced a relative stable and lasting release of amphetamine base both in plasma and in brain tissue, whereas d-amphetamine injection elicited rapid increase and dramatical decrease in amphetamine base levels. Microdialysis revealed lisdexamfetamine caused lasting release of dopamine within the medial prefrontal cortex (mPFC), whereas d-amphetamine produced rapid increase followed by decline to dopamine level. Moreover, lisdexamfetamine elicited more obvious efflux of noradrenaline than that of d-amphetamine. The distinct neurochemical profiles may be partly attributed to the different action of two drugs to membranous catecholamine transporters level within mPFC, detecting by Western Blotting. Taken together, due to its certain pharmacokinetic and catecholamine releasing profiles, lisdexamfetamine produced better pharmacological action to improving executive function. Our finding provided valuable evidence on the ideal pharmacokinetic and neurochemical characteristics of amphetamine-type psychostimulants in cognition enhancement.


Assuntos
Estimulantes do Sistema Nervoso Central , Dimesilato de Lisdexanfetamina , Ratos , Animais , Dimesilato de Lisdexanfetamina/farmacologia , Função Executiva , Dopamina , Estimulantes do Sistema Nervoso Central/efeitos adversos , Dextroanfetamina/efeitos adversos , Dextroanfetamina/farmacocinética , Anfetamina/farmacologia , Catecolaminas , Cognição
13.
Nano Lett ; 24(7): 2400-2407, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38345220

RESUMO

Neurotransmitters are important signaling molecules in the brain and are relevant in many diseases. Measuring them with high spatial and temporal resolutions in biological systems is challenging. Here, we develop a ratiometric fluorescent sensor/probe for catecholamine neurotransmitters on the basis of near-infrared (NIR) semiconducting single wall carbon nanotubes (SWCNTs). Phenylboronic acid (PBA)-based quantum defects are incorporated into them to interact selectively with catechol moieties. These PBA-SWCNTs are further modified with poly(ethylene glycol) phospholipids (PEG-PL) for biocompatibility. Catecholamines, including dopamine, do not affect the intrinsic E11 fluorescence (990 nm) of these (PEG-PL-PBA-SWCNT) sensors. In contrast, the defect-related E11* emission (1130 nm) decreases by up to 35%. Furthermore, this dual functionalization allows tuning selectivity by changing the charge of the PEG polymer. These sensors are not taken up by cells, which is beneficial for extracellular imaging, and they are functional in brain slices. In summary, we use dual functionalization of SWCNTs to create a ratiometric biosensor for dopamine.


Assuntos
Catecolaminas , Nanotubos de Carbono , Dopamina , Fluorescência , Neurotransmissores
14.
ACS Chem Neurosci ; 15(4): 816-826, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38344810

RESUMO

The two essential fatty acids, alpha-linolenic acid and linoleic acid, and the higher unsaturated fatty acids synthesized from them are critical for the development and maintenance of normal brain functions. Deficiencies of these fatty acids have been shown to cause damage to the neuronal development, cognition, and locomotor function. We combined electrochemistry and imaging techniques to examine the effects of the two essential fatty acids on catecholamine release dynamics and the vesicle content as well as on the cell membrane phospholipid composition to understand how they impact exocytosis and by extension neurotransmission at the single-cell level. Incubation of either of the two fatty acids reduces the size of secretory vesicles and enables the incorporation of more double bonds into the cell membrane structure, resulting in higher membrane flexibility. This subsequently affects proteins regulating the dynamics of the exocytotic fusion pore and thereby affects exocytosis. Our data suggest a possible pathway whereby the two essential fatty acids affect the membrane structure to impact exocytosis and provide a potential treatment for diseases and impairments related to catecholamine signaling.


Assuntos
Catecolaminas , Lipídeos de Membrana , Catecolaminas/metabolismo , Ácidos Graxos Insaturados , Ácidos Graxos Essenciais/farmacologia , Exocitose/fisiologia
15.
ACS Nano ; 18(10): 7485-7495, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38415599

RESUMO

Homovanillic acid (HVA) is a major dopamine metabolite, and blood HVA is considered as central nervous system (CNS) dopamine biomarker, which reflects the progression of dopamine-associated CNS diseases and the behavioral response to therapeutic drugs. However, facing blood various active substances interference, particularly structurally similar catecholamines and their metabolites, real-time and accurate monitoring of blood HVA remains a challenge. Herein, a highly selective implantable electrochemical fiber sensor based on a molecularly imprinted polymer is reported to accurately monitor HVA in vivo. The sensor exhibits high selectivity, with a response intensity to HVA 12.6 times greater than that of catecholamines and their metabolites, achieving 97.8% accuracy in vivo. The sensor injected into the rat caudal vein tracked the real-time changes of blood HVA, which paralleled the brain dopamine fluctuations and indicated the behavioral response to dopamine increase. This study provides a universal design strategy for improving the selectivity of implantable electrochemical sensors.


Assuntos
Catecolaminas , Dopamina , Ratos , Animais , Ácido Homovanílico/metabolismo , Encéfalo/metabolismo
16.
Cancer Sci ; 115(3): 871-882, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38279513

RESUMO

Malignant peripheral nerve sheath tumors (MPNSTs) are malignant tumors that are derived from Schwann cell lineage around peripheral nerves. As in many other cancer types, cancer stem cells (CSCs) have been identified in MPNSTs, and they are considered the cause of treatment resistance, recurrence, and metastasis. As an element defining the cancer stemness of MPNSTs, we previously reported a molecular mechanism by which exogenous adrenaline activates a core cancer stemness factor, YAP/TAZ, through ß2 adrenoceptor (ADRB2). In this study, we found that MPNST cells express catecholamine synthases and that these enzymes are essential for maintaining cancer stemness, such as the ability to self-renew and maintain an undifferentiated state. Through gene knockdown and inhibition of these enzymes, we confirmed that catecholamines are indeed synthesized in MPNST cells. The results confirmed that catecholamine synthase knockdown in MPNST cells reduces the activity of YAP/TAZ. These data suggest that a mechanism of YAP/TAZ activation by de novo synthesized adrenaline, as well as exogenous adrenaline, may exist in the maintenance of cancer stemness of MPNST cells. This mechanism not only helps to understand the pathology of MPNST, but could also contribute to the development of therapeutic strategies for MPNST.


Assuntos
Neoplasias de Bainha Neural , Neurofibrossarcoma , Humanos , Neoplasias de Bainha Neural/patologia , Catecolaminas , Transdução de Sinais , Epinefrina/uso terapêutico
17.
Neurotoxicol Teratol ; 101: 107317, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38199311

RESUMO

Currently, there is a gap in understanding the neurobiological impact early adolescent toluene exposure has on subsequent actions of other drugs. Adolescent (PND 28-32) male Swiss-Webster mice (N = 210) were exposed to 0, 2000, or 4000 ppm of toluene vapor for 30 min/day for 5 days. Immediately following the last toluene exposure (PND 32; n = 15) or after a short delay (PND 35; n = 15), a subset of subjects' brains was collected for monoamine analysis. Remaining mice were assigned to one of two abstinence periods: a short 4-day (PND 36) or long 12-day (PND 44) delay after toluene exposure. Mice were then subjected to a cumulative dose response assessment of either cocaine (0, 2.5, 5, 10, 20 mg/kg; n = 60), ethanol (0, 0.5, 1, 2, 4 g/kg; n = 60), or saline (5 control injections; n = 60). Toluene concentration-dependently increased locomotor activity during exposure. When later challenged, mice exposed previously to toluene were significantly less active after cocaine (10 and 20 mg/kg) compared to air-exposed controls. Animals were also less active at the highest dose of alcohol (4 g/kg) following prior exposure to 4000 ppm when compared to air-exposed controls. Analysis of monoamines and their metabolites using High Pressure Liquid Chromatography (HPLC) within the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), dorsal striatum (dSTR), and ventral tegmental area (VTA) revealed subtle effects on monoamine or metabolite levels following cumulative dosing that varied by drug (cocaine and ethanol) and abstinence duration. Our results suggest that early adolescent toluene exposure produces behavioral desensitization to subsequent cocaine-induced locomotor activity with subtle enhancement of ethanol's depressive effects and less clear impacts on levels of monoamines.


Assuntos
Cocaína , Etanol , Humanos , Camundongos , Animais , Masculino , Adolescente , Etanol/farmacologia , Encéfalo , Núcleo Accumbens/metabolismo , Catecolaminas/metabolismo , Catecolaminas/farmacologia , Cocaína/farmacologia , Tolueno/toxicidade
18.
J Cardiothorac Vasc Anesth ; 38(3): 724-730, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38182434

RESUMO

OBJECTIVES: The authors investigated the role of early venoarterial extracorporeal membrane oxygenation (VA ECMO) implantation in patients with postcardiotomy cardiogenic shock (PCS) on mortality and morbidity when integrating vasoactive-inotropic score (VIS) and type of catecholamine support. DESIGN: A retrospective, multicenter, observational study with propensity-weight matching. SETTING: Four university-affiliated intensive care units. PARTICIPANTS: Patients with PCS in the operating room. INTERVENTIONS: Early VA ECMO support. MEASUREMENTS AND MAIN RESULTS: Of 2,742 patients screened during the study period, 424 (16%) patients were treated with inotropic drugs, and 75 (3%) patients were supported by VA ECMO in the operating room. Patients supported by VA ECMO had a higher use of vasopressor and inotropic drugs, with a higher VIS score. After propensity matching (integrating VIS and catecholamines type), mortality (56% v 20%, p < 0.001) and morbidity (cardiac, renal, transfusion) were higher in patients supported by VA ECMO than in a matched control group. CONCLUSIONS: When matching integrated the pre-ECMO VIS and the type of catecholamines, VA ECMO remained associated with high mortality and morbidity, suggesting that VIS alone should not be used as a main determinant of VA ECMO implantation.


Assuntos
Oxigenação por Membrana Extracorpórea , Choque Cardiogênico , Humanos , Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Estudos Retrospectivos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Mortalidade Hospitalar , Catecolaminas
19.
Analyst ; 149(4): 989-1001, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38226461

RESUMO

During a stress condition, the human body synthesizes catecholamine neurotransmitters and specific hormones (called "stress hormones"), the most important of which is cortisol. The monitoring of cortisol levels is extremely important for controlling the stress levels. For this reason, it has important medical applications. Common analytical methods (HPLC, GC-MS) cannot be used in real life due to the bulkiness of the instruments and the necessity of specialized operators. Molecular probes solve this problem. This review aims to provide a description of recent developments in this field, focusing on the analytical aspects and the possibility to obtain real practical devices from these molecular probes.


Assuntos
Catecolaminas , Hidrocortisona , Humanos , Sondas Moleculares , Neurotransmissores , Cromatografia Gasosa-Espectrometria de Massas
20.
Int J Biol Macromol ; 260(Pt 2): 129400, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38224799

RESUMO

There is an increasing demand for stable and durable wound dressings to treat burn injuries and infections. Bioactive electrospun nanofibrous mats with antibacterial properties are promising for wound dressing usage. Electrospinning of biopolymers for wound dressing applications needs post-spinning crosslinking to prevent mat dissolution in moist wound environments. Here, we prepared durable wound dressing by using the Dopamine (DA) polymerization crosslinking in Alginate (ALG)/Polyvinyl alcohol (PVA) nanofibrous mats, which are developed by Ciprofloxacin (CIP) and Zinc oxide (ZO). The nanofibrous mats were investigated by FESEM, FTIR, mechanical strength, water contact angle, degradation, degree of swelling, and WVTR tests. The analyses demonstrate the nanofibrous mats with uniform and unbranched fibers, with a hydrophilic nature, which was porous, durable, and stable. Also, it showed the CIP and ZO addition enhanced their durability by crosslinking reinforcement. In addition, the drug release and antibacterial assays demonstrated the pH-sensitive release with more drug release at higher pH (bacterial invasion) and impressive antibacterial activity (up to 99 %). In the burn wound model in rats, the ALG/PVA/DA/CIP/ZO nanofibrous mats displayed excellent wound healing ability in wound closure and tissue regeneration. Also, complete re-epithelization and remodeling and highest collagen synthesis in histological assessment.


Assuntos
Queimaduras , Nanofibras , Óxido de Zinco , Ratos , Animais , Ciprofloxacina/farmacologia , Catecolaminas , Alginatos/química , Polimerização , Antibacterianos/química , Queimaduras/tratamento farmacológico , Álcool de Polivinil/química , Bandagens , Nanofibras/química
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