Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 116
Filtrar
1.
J Physiol ; 597(24): 5915-5933, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31598974

RESUMO

KEY POINTS: Xenon (Xe) non-competitively inhibited whole-cell excitatory glutamatergic current (IGlu ) and whole-cell currents gated by ionotropic glutamate receptors (IAMPA , IKA , INMDA ), but had no effect on inhibitory GABAergic whole-cell current (IGABA ). Xe decreased only the frequency of glutamatergic spontaneous and miniature excitatory postsynaptic currents and GABAergic spontaneous inhibitory postsynaptic currents without changing the amplitude or decay times of these synaptic responses. Xe decreased the amplitude of both the action potential-evoked excitatory and the action potential-evoked inhibitory postsynaptic currents (eEPSCs and eIPSCs, respectively) via a presynaptic inhibition in transmitter release. We conclude that the main site of action of Xe is presynaptic in both excitatory and inhibitory synapses, and that the Xe inhibition is much greater for eEPSCs than for eIPSCs. ABSTRACT: To clarify how xenon (Xe) modulates excitatory and inhibitory whole-cell and synaptic responses, we conducted an electrophysiological experiment using the 'synapse bouton preparation' dissociated mechanically from the rat hippocampal CA3 region. This technique can evaluate pure single- or multi-synapse responses and enabled us to accurately quantify how Xe influences pre- and postsynaptic aspects of synaptic transmission. Xe inhibited whole-cell glutamatergic current (IGlu ) and whole-cell currents gated by the three subtypes of glutamate receptor (IAMPA , IKA and INMDA ). Inhibition of these ionotropic currents occurred in a concentration-dependent, non-competitive and voltage-independent manner. Xe markedly depressed the slow steady current component of IAMPA almost without altering the fast phasic IAMPA component non-desensitized by cyclothiazide. It decreased current frequency without affecting the amplitude and current kinetics of glutamatergic spontaneous excitatory postsynaptic currents and miniature excitatory postsynaptic currents. It decreased the amplitude, increasing the failure rate (Rf) and paired-pulse rate (PPR) without altering the current kinetics of glutamatergic action potential-evoked excitatory postsynaptic currents. Thus, Xe has a clear presynaptic effect on excitatory synaptic transmission. Xe did not alter the GABA-induced whole-cell current (IGABA ). It decreased the frequency of GABAergic spontaneous inhibitory postsynaptic currents without changing the amplitude and current kinetics. It decreased the amplitude and increased the PPR and Rf of the GABAergic action potential-evoked inhibitory postsynaptic currents without altering the current kinetics. Thus, Xe acts exclusively at presynaptic sites at the GABAergic synapse. In conclusion, our data indicate that a presynaptic decrease of excitatory transmission is likely to be the major mechanism by which Xe induces anaesthesia, with little contribution of effects on GABAergic synapses.


Assuntos
Anestésicos Inalatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores , Neurônios GABAérgicos/efeitos dos fármacos , Potenciais Pós-Sinápticos Inibidores , Xenônio/farmacologia , Animais , Região CA3 Hipocampal/citologia , Células Cultivadas , Feminino , Neurônios GABAérgicos/fisiologia , Masculino , Ratos , Ratos Wistar , Sinapses/efeitos dos fármacos , Sinapses/fisiologia
2.
Bioconjug Chem ; 30(6): 1642-1648, 2019 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-31180651

RESUMO

Because mitochondria are essential organelles for regulating energy homeostasis and intrinsic apoptosis, the perturbation of mitochondrial functions has been considered as an anticancer treatment. In this study, a new near-infrared (NIR) fluorescent probe, SiR-Mito11 was developed as a theragnostic agent for brain tumor by targeting mitochondria. SiR-Mito11 exhibited potential anticancer activity against glioma cells but tolerance in normal neuronal cells. We further confirmed that the selective accumulation of SiR-Mito11 in glioma cells disrupted mitochondria membrane potential, followed by apoptotic cell death.


Assuntos
Neoplasias Encefálicas/metabolismo , Corantes Fluorescentes/metabolismo , Glioma/metabolismo , Mitocôndrias/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Nanomedicina Teranóstica , Apoptose , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Glioma/patologia , Humanos , Potencial da Membrana Mitocondrial
3.
J Nanosci Nanotechnol ; 19(2): 970-973, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30360182

RESUMO

The purpose of this study was to investigate the bioactive substances and extraction conditions of lipid-soluble green tee extract using supercritical CO extraction from green tea leaves growing in Boseong-gun, Jeollanam-do and to demonstrate cell safety and effects on inflammatory response of the nano-encapsulated lipid-soluble green tee extract. The polyphenol content of green tea extract using supercritical CO2 extraction was analyzed. The highest polyphenol was extracted in the condition of 400 bar/50 °C. A total of polyphenol content was 2.47 mg/g. The lipid-soluble vitamin content of supercritical extracts of lipid-soluble green tea was analyzed. Beta-carotene, a vitamin A precursor (4.131 mg/100 g) and vitamin E (537.9 mg/100 g) were detected. ECG content was the highest of catechin of lipid-soluble green tea extract. For cell safety and NO inhibition, human skin cell-derived HaCaT cells and RBL-2H3 mast cells did not have cytotoxicity in 1% of the nano-encapsulated lipid-soluble green tea leaf extract. RAW 264.7 cells did not show cytotoxicity in 5%. NO production was significantly decreased in RAW 264.7 cells in a concentration-dependent manner and within the concentration range. Based on the findings, this study suggested the extraction standards and ingredients of polyphenol according to temperature and pressure in extracting green tea leaf ingredients using supercritical CO2 extraction. This study also objectively demonstrated the safety and anti-inflammatory effect of the nano-encapsulated lipid-soluble green tea leaf extract which is used as functional materials in the cosmetic industry.


Assuntos
Catequina , Óxido Nítrico , Catequina/análise , Catequina/farmacologia , Humanos , Lipídeos , Extratos Vegetais/farmacologia , Polifenóis , Chá
4.
J Neurophysiol ; 120(3): 1264-1273, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29897859

RESUMO

The current electrophysiological study investigated the functional roles of high- and low-voltage-activated Ca2+ channel subtypes on glutamatergic small mossy fiber nerve terminals (SMFTs) that synapse onto rat hippocampal CA3 neurons. Experiments combining both the "synapse bouton" preparation and single-pulse focal stimulation technique were performed using the conventional whole cell patch configuration under voltage-clamp conditions. Nifedipine, at a high concentration, and BAY K 8644 inhibited and facilitated the glutamatergic excitatory postsynaptic currents (eEPSCs) that were evoked by 0.2-Hz stimulation, respectively. However, these drugs had no effects on spontaneous EPSCs (sEPSCs). Following the use of a high stimulation frequency of 3 Hz, however, nifedipine markedly inhibited eEPSCs at the low concentration of 0.3 µM. Moreover, ω-conotoxin GVIA and ω-agatoxin IVA significantly inhibited both sEPSCs and eEPSCs. Furthermore, SNX-482 slightly inhibited eEPSCs. R(-)-efonidipine had no effects on either sEPSCs or eEPSCs. It was concluded that glutamate release from SMFTs depends largely on Ca2+ entry through N- and P/Q-type Ca2+ channels and, to a lesser extent, on R-type Ca2+ channels. The contribution of L-type Ca2+ channels to eEPSCs was small at low-firing SMFTs but more significant at high-firing SMFTs. T-type Ca2+ channels did not appear to be involved in neurotransmission at SMFTs. NEW & NOTEWORTHY Action potential-evoked glutamate release from small mossy fiber nerve terminals (SMFTs) that synapse onto rat hippocampal CA3 neurons is regulated by high-threshold but not low-threshold Ca2+ channel subtypes. The functional contribution mainly depends on N- and P/Q-type Ca2+ channels and, to a lesser extent, on R-type Ca2+ channels. However, in SMFTs stimulated at a high 3-Hz frequency, L-type Ca2+ channels contributed significantly to the currents. The present results are consistent with previous findings from fluorometric studies of large mossy fiber boutons.


Assuntos
Potenciais de Ação , Região CA3 Hipocampal/fisiologia , Canais de Cálcio/fisiologia , Ácido Glutâmico/fisiologia , Fibras Musgosas Hipocampais/fisiologia , Terminações Pré-Sinápticas/fisiologia , Animais , Estimulação Elétrica , Potenciais Pós-Sinápticos Excitadores , Ratos Wistar
5.
Optom Vis Sci ; 93(3): 259-65, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26760579

RESUMO

PURPOSE: To compare a new optical biometer device, Galilei G6 (Ziemer, Port, Switzerland), with the present optical biometer, Lenstar LS 900 (Haag-Streit, Koeniz, Switzerland), for intraocular lens (IOL) power calculation. METHODS: One hundred forty eyes of 140 cataract patients were evaluated with two optical biometers: the Galilei G6 and the Lenstar. The mean keratometry (K), axial length (AL), anterior chamber depth (ACD), crystalline lens thickness (LT), white-to-white (WTW), and IOL powers using the SRK/T, Holladay 1, Hoffer Q, and Haigis formulas were compared. The intrasession repeatability of the Galilei G6 measurements was assessed in 25 eyes. RESULTS: All ocular parameters measured by the Galilei G6 were highly repeatable (all intraclass correlation coefficients > 0.980). Although K and ACD did not show statistical differences between the two devices (all p > 0.05), the measurements for AL, LT, and WTW were statistically different for the two devices. The K, AL, ACD, LT, and WTW showed good correlations (r = 0.975, 0.998, 0.973, 0.946, and 0.710, respectively; all p < 0.001); however, the agreements of LT and WTW were not good between the two devices. The IOL powers using four formulas did not show statistical differences (all p > 0.05); however, agreements between the IOL powers were not strong. The ranges of 95% limit of agreements were between 1.54 and 1.90D according to the formulas. CONCLUSIONS: The ocular parameters and IOL powers using the Galilei G6 cannot be used interchangeably with those of the Lenstar in clinical practice.


Assuntos
Biometria/instrumentação , Interferometria/instrumentação , Lentes Intraoculares , Óptica e Fotônica/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Câmara Anterior/anatomia & histologia , Comprimento Axial do Olho/anatomia & histologia , Feminino , Humanos , Cristalino/anatomia & histologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes
6.
Del Med J ; 87(4): 117-20, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26027410

RESUMO

We describe a case of an 88-year-old female who presented for needle localization to undergo excisional biopsy of a subtle asymmetry in the left breast, with successful localization achieved using digital breast tomosynthesis. Initial attempts at localization under 2D mammography were inaccurate. Subsequent digital breast tomosynthesis application for triangulation resulted in better visualization of the target, and successful localization. Specimen radiography confirmed the lesion was accurately targeted and pathology revealed ductal carcinoma in situ. Needle localization guided by mammography and inherent limitations of 2D mammography are discussed, along with a literature review of tomosynthesis guided needle localization.


Assuntos
Biópsia por Agulha/métodos , Neoplasias da Mama/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Mamografia , Cuidados Pré-Operatórios , Intensificação de Imagem Radiográfica , Radiografia Intervencionista , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , Mamografia/métodos , Valor Preditivo dos Testes , Intensificação de Imagem Radiográfica/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
7.
Lab Chip ; 24(2): 272-280, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38086678

RESUMO

A cell chip is a microfluidic cell culture device fabricated using microchip manufacturing methods for culturing living cells in a micrometer-sized chamber to model the physiological functions of tissues and organs. It has been extensively investigated in the domain of drug transport and toxicity research. Herein, we developed a cell chip for real-time monitoring of drug release from drug carriers. The proposed system integrates three core functions: cell culture, real-time analysis, and drug delivery tests. This device was designed to be loaded with microparticles for drug release and to enable real-time drug measurement. The efficacy of the developed system was evaluated by measuring the concentration of drugs released from the microparticles prepared with poly(lactic-co-glycolic acid) (PLGA). Doxorubicin, an anticancer drug, was used as a model drug and A549 cells, a type of lung cancer cell, were simultaneously cultured to compare the drug release concentrations in the presence of cells. Furthermore, variations in cell viability with respect to the presence of drug-loaded microparticles were observed and analyzed. Notably, as the proposed system requires an extremely small number of microparticles, it affords simple implementation in a single device, thereby eliminating the need for complex accessories and instruments for analysis. Thus, the analysis process becomes more convenient and cost-efficient. Thus, the proposed method offers an easy analysis of the release behavior of various cells and drugs. The simplicity and low cost of this innovative system without sacrificing analytical precision demonstrate its potential for applications across various fields.


Assuntos
Ácido Láctico , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Liberação Controlada de Fármacos , Sistemas de Liberação de Medicamentos , Portadores de Fármacos , Microesferas , Tamanho da Partícula
8.
Artigo em Inglês | MEDLINE | ID: mdl-38753970

RESUMO

Clopidol is extensively used in livestock farming and residues of this antibiotic can persist in animal tissues, posing a risk to humans and the environment. In this study, we investigated the depletion of clopidol in various edible tissues of chickens (muscle, liver, kidney, fat, and eggs) using liquid chromatography-tandem mass spectrometry after the administration of a clopidol-contaminated diet (at 250 mg kg-1 for the high (1x) dose). After 14 d of exposure, the clopidol concentrations were highest in eggs (median: 9.83 mg/kg), followed by liver (3.56 mg/kg), kidney (3.01 mg/kg), muscle (1.56 mg/kg), and fat (0.727 mg/kg) at low exposure group, indicating that clopidol accumulated primarily in eggs rather than the other edible tissues. In addition, the maternal transfer ratios were estimated, and the transfer efficiencies of clopidol in muscle (egg-to-tissue ratio, ETR:1.81) and fat (2.06-58.2) were higher than those in liver (0.731-31.1) and kidney (0.832-38.9). Furthermore, we conducted a cumulative risk assessment for clopidol in edible chicken tissues using the hazard quotient (HQ) method. This assessment revealed that the exposure levels for Korean consumers pose an acceptable risk. However, for eggs from the 1x dose exposure group, the HQ values were greater than 1 for all age groups, particularly for young children (<18 y), suggesting that the higher daily consumption of eggs combined with the higher clopidol residues in eggs resulted in higher HQ values, which requires further attention. The findings of this study can assist in the management and monitoring of clopidol residues in chicken tissues and eggs.


Assuntos
Galinhas , Contaminação de Alimentos , Animais , Medição de Risco , Contaminação de Alimentos/análise , Humanos , Ovos/análise , Rim/química , Rim/metabolismo , Espectrometria de Massas em Tandem , Fígado/química , Fígado/metabolismo
9.
J Physiol ; 591(4): 1031-43, 2013 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-23109108

RESUMO

Type A botulinum toxin blocks not only ACh release from motor nerve terminals but also central synaptic transmission, including glutamate, noradrenaline, dopamine, ATP, GABA and glycine. Neurotoxins (NTXs) are transported by both antero- and retrogradely along either motor or sensory axons for bidirectional delivery between peripheral tissues or the CNS. A newly developed type A2 NTX (A2NTX) injected into one rat foreleg muscle was transported to the contralateral muscle. This finding was consistent with the NTX traveling retrogradely via spinal neurons and then transsynaptically through motor neurons to the contralateral motor neurons within the spinal cord and on to the soleus muscle. In the present study we found that toxin injection into the rat left soleus muscle clearly induced bilateral muscle relaxation in a dose-dependent fashion, although the contralateral muscle relaxation followed the complete inhibition of toxin-injected ipsilateral muscles. The toxin-injected ipsilateral muscle relaxation was faster and stronger in A2NTX-treated rats than A1LL (BOTOX). A1LL was transported almost equally to the contralateral muscle via neural pathways and the bloodstream. In contrast, A2NTX was mainly transported to contralateral muscles via the blood. A1LL was more successfully transported to contralateral spinal neurons than A2NTX. We also demonstrated that A1LL and A2NTX were carried from peripheral to CNS and vice versa by dual antero- and retrograde axonal transport through either motor or sensory neurons.


Assuntos
Toxinas Botulínicas Tipo A/farmacologia , Músculo Esquelético/efeitos dos fármacos , Animais , Antitoxina Botulínica/farmacologia , Colchicina/farmacologia , Estimulação Elétrica , Feminino , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Contração Isométrica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Músculo Esquelético/inervação , Músculo Esquelético/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Ratos , Ratos Wistar , Substância Gelatinosa/citologia , Nervo Tibial/efeitos dos fármacos , Nervo Tibial/fisiologia
10.
Gen Physiol Biophys ; 32(1): 47-54, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23531834

RESUMO

Selenoprotein P (SeP) not only represents the major selenoprotein in plasma, but also provides more than 50% of the total plasma selenium. However, there is no report concerning the direct action of selenium or selenium-containing compounds on the contraction and relaxation of the airway smooth muscle. Therefore, we investigated the effects of SeP and sodium selenite (SS) on the indirectly induced contraction and relaxation of the cat bronchi, and gel contraction of cultured bovine tracheal smooth muscle cells (BTSMC) induced by ATP. In the present results, SeP or SS suppressed the amplitude of twitch-like contractions of cat bronchiole without affecting the non-adrenergic and non-cholinergic (NANC) relaxations evoked by electrical field stimulation. SeP also suppressed the ATP-induced gel contraction of BTSMC. These results suggest that SeP suppresses the amplitude of twitch-like contraction of cat bronchiole by acting directly on the bronchiolar smooth muscle.


Assuntos
Músculo Liso/metabolismo , Selênio/sangue , Selenoproteína P/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Bronquíolos/metabolismo , Gatos , Bovinos , Relação Dose-Resposta a Droga , Eletricidade , Feminino , Técnicas In Vitro , Masculino , Miócitos de Músculo Liso/citologia , Selenoproteína P/metabolismo , Selenito de Sódio/farmacologia , Estresse Mecânico , Fatores de Tempo , Traqueia/metabolismo
11.
Ann Hepatobiliary Pancreat Surg ; 27(2): 217-219, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-36588168

RESUMO

A 50-year-old male presented gradually growing pancreatic body mass. An abdominal computed tomography showed a 9.9-cm mass, larger than the 8.9-cm mass one year ago. As the patient did not have complaints for any symptomatic problems, the gastroenterologist decided to check it with regular follow-up. However, as the tumor grew faster than expected, the patient was recommended for surgical resection. Laparoscopic pylorus preserving pancreaticoduodenectomy was done. Since the tumor abutted to the superior mesenteric vein and the portal vein, wedge resection of vessel was inevitable. Pathology was serous cystadenoma. The patient was discharged without postoperative complications. Herein, we report this case with asymptomatic large serous cystic neoplasm treated by laparoscopic approach. The appropriateness of current guidelines for surgery in serous cystic neoplasm is also discussed.

12.
Korean J Ophthalmol ; 37(6): 477-484, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37899285

RESUMO

PURPOSE: To evaluate the role of performing photocoagulation up to ora serrata during vitrectomy in preventing recurrent vitreous hemorrhage (VH) in patients undergoing pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR). METHODS: This retrospective, nonrandomized study included 60 eyes from 60 patients who had undergone PPV for VH due to PDR. These patients were divided into two groups: group 1, those who underwent photocoagulation up to ora serrata using the scleral indentation technique during surgery; and group 2, those who did not undergo scleral indentation when photocoagulation and underwent photocoagulation up to vortex veins. Their hospital records were analyzed to investigate the recurrence rate of VH, the time until recurrence of VH after surgery, logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) measured before surgery and at 1, 2, and 3 years after surgery, and the occurrence of complications such as neovascular glaucoma (NVG) during follow-up. RESULTS: Group 1 exhibited lower recurrence rate of VH (2 of 30 [6.7%] vs. 10 of 30 [33.3%], p = 0.01) and lower occurrence of postoperative NVG (2 of 30 [6.7%] vs. 8 of 30 [26.7%], p = 0.038) compared with group 2. There were no statistically significant differences in logMAR BCVA measured at 1, 2, and 3 years between the two groups (at 1 year: 0.54 ± 0.43 vs. 0.54 ± 0.44, p = 0.954; at 2 years: 0.48 ± 0.47 vs. 0.55 ± 0.64, p = 0.235; at 3 years: 0.51 ± 0.50 vs. 0.61 ± 0.77, p = 0.200). Logistic regression analysis showed that among several factors that could affect recurrence rate of VH, only range of photocoagulation performed was a statistically significant factor (odds ratio, 0.119; 95% confidence interval, 0.022-0.659; p = 0.015). CONCLUSIONS: Photocoagulation treatment over a wider range with scleral indentation could be a beneficial adjunct procedure for preventing postoperative recurrent VH following diabetic vitrectomy.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Humanos , Vitrectomia/métodos , Hemorragia Vítrea/diagnóstico , Hemorragia Vítrea/prevenção & controle , Hemorragia Vítrea/cirurgia , Estudos Retrospectivos , Retina , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/cirurgia , Retinopatia Diabética/complicações , Fotocoagulação/efeitos adversos
13.
J Exerc Rehabil ; 19(3): 149-162, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37435594

RESUMO

This study aimed to investigate the effect of whole body vibration (WBV) on the sensory and motor nerve components with sciatic nerve injury model rats. Surgery was performed on 21 female Wister rats (6-8 weeks) under intraperitoneal anesthesia. The nerve-crush injuries for the left sciatic nerve were inflicted using a Sugita aneurysm clip. The sciatic nerve model rats were randomly divided into two groups (n=9; control group, n=12; WBV group). The rats in the WBV group walked in the cage with a vibratory stimulus (frequency 50 Hz, 20 min/day, 5 times/wk), while those in the control group walked in the cage without any vibratory stimulus. We used heat stimulation-induced sensory threshold and lumbar magnetic stimulation-induced motor-evoked potentials (MEPs) to measure the sensory and motor nerve components, respectively. Further, morphological measurements, bilateral hind-limb dimension, bilateral gastrocnemius dimension, and weight were evaluated. Consequently, there were no significant differences in the sensory threshold at the injury side between the control and WBV groups. However, at 4 and 6 weeks postoperatively, MEPs latencies in the WBV group were significantly shorter than those in the control group. Furthermore, both sides of the hind-limb dimension at 6 weeks postoperatively, the left side of the gastrocnemius dimension, and both sides of the gastrocnemius weight significantly increased. In conclusion, WBV especially accelerates the functional recovery of motor nerve components in sciatic nerve-crush injury model rats.

14.
Mol Pain ; 8: 58, 2012 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-22906126

RESUMO

BACKGROUND: 5-hydroxytryptamine (5-HT) is one of the major neurotransmitters widely distributed in the CNS. Several 5-HT receptor subtypes have been identified in the spinal dorsal horn which act on both pre- and postsynaptic sites of excitatory and inhibitory neurons. However, the receptor subtypes and sites of actions as well as underlying mechanism are not clarified rigorously. Several electrophysiological studies have been performed to investigate the effects of 5-HT on excitatory transmission in substantia gelatinosa (SG) of the spinal cord. In the present study, to understand the effects of 5-HT on the inhibitory synaptic transmission and to identify receptor subtypes, the blind whole cell recordings were performed from SG neurons of rat spinal cord slices. RESULTS: Bath applied 5-HT (50 µM) increased the frequency but not amplitudes of spontaneous inhibitory postsynaptic currents (sIPSCs) in 58% of neurons, and both amplitude and frequency in 23% of neurons. The frequencies of GABAergic and glycinergic mIPSCs were both enhanced. TTX (0.5 µM) had no effect on the increasing frequency, while the enhancement of amplitude of IPSCs was eliminated. Evoked-IPSCs (eIPSCs) induced by focal stimulation near the recording neurons in the presence of CNQX and APV were enhanced in amplitude by 5-HT. In the presence of Ba(2+) (1 mM), a potassium channel blocker, 5-HT had no effect on both frequency and amplitude. A 5-HT(2A) receptor agonist, TCB-2 mimicked the 5-HT effect, and ketanserin, an antagonist of 5-HT(2A) receptor, inhibited the effect of 5-HT partially and TCB-2 almost completely. A 5-HT(2C) receptor agonist WAY 161503 mimicked the 5-HT effect and this effect was blocked by a 5-HT(2C) receptor antagonist, N-desmethylclozapine. The amplitudes of sIPSCs were unaffected by 5-HT(2A) or 5-HT(2C) agonists. A 5-HT(3) receptor agonist mCPBG enhanced both amplitude and frequency of sIPSCs. This effect was blocked by a 5-HT(3) receptor antagonist ICS-205,930. The perfusion of 5-HT(2B) receptor agonist had no effect on sIPSCs. CONCLUSIONS: Our results demonstrated that 5-HT modulated the inhibitory transmission in SG by the activation of 5-HT(2A) and 5-HT(2C) receptors subtypes located predominantly at inhibitory interneuron terminals, and 5-HT(3) receptors located at inhibitory interneuron terminals and soma-dendrites, consequently enhanced both frequency and amplitude of IPSCs.


Assuntos
Potenciais Pós-Sinápticos Inibidores/fisiologia , Células do Corno Posterior/fisiologia , Receptores de Serotonina/metabolismo , Animais , Bário/farmacologia , Glicina/metabolismo , Técnicas In Vitro , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Interneurônios/efeitos dos fármacos , Interneurônios/metabolismo , Masculino , Neurotransmissores/metabolismo , Células do Corno Posterior/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Serotonina/farmacologia , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Substância Gelatinosa/efeitos dos fármacos , Substância Gelatinosa/fisiologia , Ácido gama-Aminobutírico/metabolismo
15.
J Pharmacol Exp Ther ; 341(3): 809-19, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22434676

RESUMO

Ethanol (EtOH) has a number of behavioral effects, including intoxication, amnesia, and/or sedation, that are thought to relate to the activation of GABA(A) receptors. However, GABA(A) receptors at different cellular locations have different sensitivities to EtOH. The present study used the "synaptic bouton" preparation where we could stimulate nerve endings on mechanically dissociated single rat hippocampal CA1 and CA3 pyramidal neurons and investigate the effects of EtOH on presynaptic and postsynaptic GABA(A) receptors. Low concentrations of EtOH (10 mM) had no effect on postsynaptic GABA(A) and glutamate receptors or voltage-dependent Na(+) and Ca(2+) channels. Higher concentrations (≥100 mM) could significantly inhibit these current responses. EtOH at 10 mM had no direct effect on inhibitory postsynaptic currents (IPSCs) and excitatory postsynaptic currents (EPSCs) evoked by focal stimulation of single boutons [evoked IPSCs (eIPSCs) and evoked EPSCs (eEPSCs)]. However, coapplication of 10 mM EtOH with muscimol decreased the amplitude of eIPSCs and eEPSCs and increased their paired-pulse ratio. The effects on eEPSCs were reversed by bicuculline. Coapplication of muscimol and EtOH significantly increased the frequency of spontaneous IPSCs and EPSCs. The EtOH effects on the postsynaptic responses and eEPSCs were similar in neurons from neonatal and mature rats. These results revealed that low concentrations of EtOH can potentiate the activation of presynaptic GABA(A) receptors to inhibit evoked GABA and glutamate release. These results indicate a high sensitivity of presynaptic GABA(A) receptor to EtOH, which needs to be accounted for when considering the cellular mechanisms of EtOH's physiological responses.


Assuntos
Anti-Infecciosos Locais/farmacologia , Etanol/farmacologia , Neurônios GABAérgicos/metabolismo , Terminações Pré-Sinápticas/efeitos dos fármacos , Receptores de GABA-A/metabolismo , Receptores de Glutamato/metabolismo , Animais , Bicuculina/farmacologia , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/metabolismo , Região CA3 Hipocampal/efeitos dos fármacos , Região CA3 Hipocampal/metabolismo , Estimulação Elétrica , Agonistas de Receptores de GABA-A/farmacologia , Antagonistas de Receptores de GABA-A/farmacologia , Muscimol/farmacologia , Técnicas de Patch-Clamp , Terminações Pré-Sinápticas/metabolismo , Ratos , Ratos Wistar
16.
J Pharmacol Sci ; 118(1): 75-81, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-32092840

RESUMO

Our recent study showed a possibility that newly developed A2 type botulinum toxin (A2NTX) inhibits both spontaneous and evoked transmitter release from inhibitory (glycinergic or GABAergic) and excitatory (glutamatergic) nerve terminals using rat spinal sacral dorsal commissural nucleus neurons. In the present study, to determine the modulatory effect of A2NTX on glycinergic and glutamatergic release probabilities, we tested the effects of A2NTX on a single inhibitory or excitatory nerve ending adherent to a dissociated neuron that was activated by paired-pulse stimuli by using the focal electrical stimulation technique. The results of the present paired-pulse experiments showed clearly that A2NTX enhanced paired-pulse facilitation of evoked glycinergic inhibitory postsynaptic currents and glutamatergic excitatory postsynaptic currents and increased the failure rate (Rf) of the first postsynaptic currents (P1) and both the responses. These effects of A2NTX on the amplitude and Rf of the P1 and the second postsynaptic currents (P2) and paired-pulse ratio were rescued by application of 4-aminophthalimide. In summary, the present results showed that A2NTX acts purely presynaptically and inhibits the release machinery of transmitters such as glycine and glutamate, and the transmitter release machinery became less sensitive to intracellular free-Ca2+ in A2NTX poisoned nerve terminals.

17.
J Pharmacol Sci ; 118(1): 75-81, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22198005

RESUMO

Our recent study showed a possibility that newly developed A2 type botulinum toxin (A2NTX) inhibits both spontaneous and evoked transmitter release from inhibitory (glycinergic or GABAergic) and excitatory (glutamatergic) nerve terminals using rat spinal sacral dorsal commissural nucleus neurons. In the present study, to determine the modulatory effect of A2NTX on glycinergic and glutamatergic release probabilities, we tested the effects of A2NTX on a single inhibitory or excitatory nerve ending adherent to a dissociated neuron that was activated by paired-pulse stimuli by using the focal electrical stimulation technique. The results of the present paired-pulse experiments showed clearly that A2NTX enhanced paired-pulse facilitation of evoked glycinergic inhibitory postsynaptic currents and glutamatergic excitatory postsynaptic currents and increased the failure rate (Rf) of the first postsynaptic currents (P(1)) and both the responses. These effects of A2NTX on the amplitude and Rf of the P(1) and the second postsynaptic currents (P(2)) and paired-pulse ratio were rescued by application of 4-aminophthalimide. In summary, the present results showed that A2NTX acts purely presynaptically and inhibits the release machinery of transmitters such as glycine and glutamate, and the transmitter release machinery became less sensitive to intracellular free-Ca(2+) in A2NTX poisoned nerve terminals.


Assuntos
Toxinas Botulínicas Tipo A/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Neurotoxinas/farmacologia , Terminações Pré-Sinápticas/efeitos dos fármacos , Animais , Região CA3 Hipocampal/citologia , Ácido Glutâmico/fisiologia , Glicina/fisiologia , Técnicas In Vitro , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Ratos , Ratos Wistar , Medula Espinal/citologia , Ácido gama-Aminobutírico/fisiologia
18.
J Pharmacol Sci ; 118(1): 33-42, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-32092836

RESUMO

Recent studies have demonstrated that the botulinum neurotoxins inhibit the release of acetylcholine, glutamate, GABA, and glycine in central nerve system (CNS) neurons. The Na+ current (INa) is of major interest because it acts as the trigger for many cellular functions such as transmission, secretion, contraction, and sensation. Thus, these observations raise the possibility that A type neurotoxin might also alter the INa of neuronal excitable membrane. To test our idea, we examined the effects of A type neurotoxins on INa of central and peripheral neurons. The neurotoxins in femtomolar to picomolar concentrations produced substantial decreases of the neuronal INa, but interestingly the current inhibition was saturated at about maximum 50% level of control INa. The inhibitory pattern in the concentration-response curve for the neurotoxins differed from tetrodotoxin (TTX), local anesthetic, and antiepileptic drugs that completely inhibited INa in a concentration-dependent manner. We concluded that A type neurotoxins inhibited membrane Na+-channel activity in CNS neurons and that INa of both TTX-sensitive and-insensitive peripheral dorsal ganglion cells were also inhibited similarly to a maximum 40% of the control by the neurotoxins. The results suggest evidently that A2NTX could be also used as a powerful drug in treating epilepsy and several types of pain.

19.
J Pharmacol Sci ; 118(1): 33-42, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22156364

RESUMO

Recent studies have demonstrated that the botulinum neurotoxins inhibit the release of acetylcholine, glutamate, GABA, and glycine in central nerve system (CNS) neurons. The Na(+) current (I(Na)) is of major interest because it acts as the trigger for many cellular functions such as transmission, secretion, contraction, and sensation. Thus, these observations raise the possibility that A type neurotoxin might also alter the I(Na) of neuronal excitable membrane. To test our idea, we examined the effects of A type neurotoxins on I(Na) of central and peripheral neurons. The neurotoxins in femtomolar to picomolar concentrations produced substantial decreases of the neuronal I(Na), but interestingly the current inhibition was saturated at about maximum 50% level of control I(Na). The inhibitory pattern in the concentration-response curve for the neurotoxins differed from tetrodotoxin (TTX), local anesthetic, and antiepileptic drugs that completely inhibited I(Na) in a concentration-dependent manner. We concluded that A type neurotoxins inhibited membrane Na(+)-channel activity in CNS neurons and that I(Na) of both TTX-sensitive and -insensitive peripheral dorsal ganglion cells were also inhibited similarly to a maximum 40% of the control by the neurotoxins. The results suggest evidently that A2NTX could be also used as a powerful drug in treating epilepsy and several types of pain.


Assuntos
Toxinas Botulínicas Tipo A/farmacologia , Região CA1 Hipocampal/fisiologia , Gânglios Espinais/fisiologia , Neurônios/efeitos dos fármacos , Neurotoxinas/farmacologia , Bloqueadores dos Canais de Sódio/farmacologia , Animais , Região CA1 Hipocampal/citologia , Gânglios Espinais/citologia , Neurônios/fisiologia , Células Piramidais/efeitos dos fármacos , Células Piramidais/fisiologia , Ratos , Ratos Wistar , Canais de Sódio/efeitos dos fármacos , Canais de Sódio/fisiologia , Tetrodotoxina/farmacologia
20.
NPJ Digit Med ; 5(1): 120, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35986059

RESUMO

We introduce a multi-institutional data harvesting (MIDH) method for longitudinal observation of medical imaging utilization and reporting. By tracking both large-scale utilization and clinical imaging results data, the MIDH approach is targeted at measuring surrogates for important disease-related observational quantities over time. To quantitatively investigate its clinical applicability, we performed a retrospective multi-institutional study encompassing 13 healthcare systems throughout the United States before and after the 2020 COVID-19 pandemic. Using repurposed software infrastructure of a commercial AI-based image analysis service, we harvested data on medical imaging service requests and radiology reports for 40,037 computed tomography pulmonary angiograms (CTPA) to evaluate for pulmonary embolism (PE). Specifically, we compared two 70-day observational periods, namely (i) a pre-pandemic control period from 11/25/2019 through 2/2/2020, and (ii) a period during the early COVID-19 pandemic from 3/8/2020 through 5/16/2020. Natural language processing (NLP) on final radiology reports served as the ground truth for identifying positive PE cases, where we found an NLP accuracy of 98% for classifying radiology reports as positive or negative for PE based on a manual review of 2,400 radiology reports. Fewer CTPA exams were performed during the early COVID-19 pandemic than during the pre-pandemic period (9806 vs. 12,106). However, the PE positivity rate was significantly higher (11.6 vs. 9.9%, p < 10-4) with an excess of 92 PE cases during the early COVID-19 outbreak, i.e., ~1.3 daily PE cases more than statistically expected. Our results suggest that MIDH can contribute value as an exploratory tool, aiming at a better understanding of pandemic-related effects on healthcare.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA