RESUMEN
Depression and anxiety are prominent symptoms of withdrawal syndrome, often caused by the abuse of addictive drugs like morphine. N-palmitoylethanolamide (PEA), a biologically active lipid, is utilized as an anti-inflammatory and analgesic medication. Recent studies have highlighted PEA's role in mitigating cognitive decline and easing depression resulting from chronic pain. However, it remains unknown whether PEA can influence negative emotions triggered by morphine withdrawal. This study seeks to explore the impact of PEA on such emotions and investigate the underlying mechanisms. Mice subjected to morphine treatment underwent a 10-day withdrawal period, followed by assessments of the effect of PEA on anxiety- and depression-like behaviors using various tests. Enzyme-linked immunosorbent assay was conducted to measure levels of monoamine neurotransmitters in specific brain regions. The findings indicate that PEA mitigated anxiety and depression symptoms and reduced 5-hydroxytryptamine, noradrenaline, and dopamine levels in the hippocampus and prefrontal cortex. In summary, PEA demonstrates a significant positive effect on negative emotions associated with morphine withdrawal, accompanied with the reduction in levels of monoamine neurotransmitters in key brain regions. These insights could be valuable for managing negative emotions arising from morphine withdrawal.
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An inflammatory response is one of the pathogeneses of depression. The anti-inflammatory and neuroprotective effects of auraptene have previously been confirmed. We established an inflammatory depression model by lipopolysaccharide (LPS) injection combined with unpredictable chronic mild stress (uCMS), aiming to explore the effects of auraptene on depressive-like behaviors in adult mice. Mice were divided into a control group, vehicle group, fluoxetine group, celecoxib group, and auraptene group. Then, behavioral tests were conducted to evaluate the effectiveness of auraptene in ameliorating depressive-like behavior. Cyclooxygenase-2 (COX-2), C-reactive protein (CRP), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) were examined by ELISA. Interleukin-10 (IL-10), interleukin-4 (IL-4), and transforming growth factor-ß (TGF-ß) were examined by protein chip technology. The morphology of microglia was observed by the immunohistochemical method. The data showed that, compared with the control group, the vehicle group mice exhibited a depressive-like behavioral phenotype, accompanied by an imbalance in inflammatory cytokines and the activation of microglia in the hippocampus. The depressive behaviors of the auraptene group's mice were significantly alleviated, along with the decrease in pro-inflammatory factors and increase in anti-inflammatory factors, while the activation of microglia was inhibited in the hippocampus. Subsequently, we investigated the role of auraptene in vitro-cultured BV-2 cells treated with LPS. The analysis showed that auraptene downregulated the expression of IL-6, TNF-α, and NO, and diminished the ratio of CD86/CD206. The results showed that auraptene reduced the excessive phagocytosis and ROS production of LPS-induced BV2 cells. In conclusion, auraptene relieved depressive-like behaviors in mice probably via modulating hippocampal neuroinflammation mediated by microglia.
Asunto(s)
Cumarinas , Citocinas , Depresión , Hipocampo , Lipopolisacáridos , Microglía , Estrés Psicológico , Animales , Microglía/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Masculino , Depresión/tratamiento farmacológico , Depresión/inmunología , Depresión/inducido químicamente , Ratones , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/inmunología , Cumarinas/farmacología , Cumarinas/uso terapéutico , Citocinas/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Modelos Animales de Enfermedad , Conducta Animal/efectos de los fármacos , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/inmunología , Ratones Endogámicos C57BL , Mediadores de Inflamación/metabolismoRESUMEN
Plateau zokor (Myospalax baileyi) is one of the major rodent species at the alpine meadow in Three Rivers Headwater Region. They eat plant roots, excavate many tunnels and deposit soil on the surface, which result in many exposed mounds to cover the aboveground part of plants. Here, taking plateau zokor mound density in a plot as their disturbance degree, we selected seven plots with different plateau zokor mound densities and one control plot which was not disturbed by plateau zokor to explore the effects of M. baileyi disturbance on community composition, species diversity and productivity. The results showed that, with the increases of available mound density, the dominant species were changed from Cyperaceae and Gramineae species to forb species, including Poly-gonum viviparum, Potentilla anserine, and Polygonum sibiricum. The community coverage and height were significantly decreased. Light or intermediate disturbance by plateau zokor improved species diversity, whereas the evenness index showed no significant change. The changes of community productivity did not support the 'intermediate disturbance hypothesis'. With the increases of plateau zokor disturbance, the aboveground biomass, belowground biomass, total biomass of community significantly decreased. Our findings revealed the effects of plateau zokor's activity on plant community at alpine meadow and presented important information for the management and restoration of degraded grassland and the sustainable utilization of grassland in Three Rivers Headwater Region.
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Pradera , Poaceae , Altitud , Animales , China , Ecosistema , Ríos , SueloRESUMEN
Erucamide (Era) is a bioactive fatty acid amide, which is similar to the classical endocannabinoid analogue oleoylethanolamide (OEA). In the present study, we hypothesized that Era may regulate the central nervous system and may have the potential to antagonize depression and anxiety. Therefore, we investigated the antidepressant and anxiolytic effects of Era in animal models in comparison with fluoxetine (Fxt). Fifty mice were randomly divided into 5 groups, and treated with a vehicle (0.3% methyl cellulose, 20mL/kg, p.o.), Era (5, 10, 20mg/kg, p.o.), or Fxt (20mg/kg, p.o.) for 7days. Immobility was used to evaluate depressive-like behavior in the forced swimming test (FST) and tail suspension test (TST). Animal activity and exploratory behavior as well as anxiety-like behaviors were measured in open field test (OFT) and elevated plus-maze test (EPMT) in mice. Additionally, serum adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) levels were determined using the ELISA method, and the total anti-oxidative capacity (T-AOC) was detected by ultraviolet spectrophotometry. Our data showed that Era (5, 10, or 20mg/kg) induced a significant reduction in mouse immobility time in the TST and FST compared to the normal control group (vehicle group). The positive control, Fxt (20mg/kg group), also induced a significant change in immobility time in the TST and FST compared to the control (vehicle) group. In the OFT, compared with the control group, Fxt (20mg/kg) and Era (5, 10, or 20mg/kg) did not significantly change the locomotive activity (locomotive time, immobility time, or locomotive distance) in mice, but Fxt (20mg/kg) and Era (10, or 20mg/kg) significantly increased the percentage of time spent and squares visited in the OFT central area. In regards to the EPMT, the data showed that Fxt (20mg/kg) and Era (10, 20mg/kg) significantly increased the ratio of time spent and entries in open arms, but did not significantly change the total locomotive distance (including open arms and closed arms) compared to the control group. Biochemical tests found that after 7days of drug treatment, compared with the control group, ACTH and CORT serum levels in mice were significantly decreased, although T-AOC levels did not significantly change. In conclusion, Era (dose range of 5-20mg/kg) administered orally may alleviate depression- and anxiety-like behaviors in mice, and the antidepressant and anti-anxiety effects of Era may be related to the regulation of the hypothalamus-pituitary-adrenal axis (HPA).
Asunto(s)
Ansiolíticos/farmacología , Antidepresivos/farmacología , Ácidos Erucicos/farmacología , Sistema Hipotálamo-Hipofisario/fisiología , Sistema Hipófiso-Suprarrenal/fisiología , Hormona Adrenocorticotrópica/sangre , Animales , Ansiolíticos/uso terapéutico , Antidepresivos/uso terapéutico , Antioxidantes/metabolismo , Corticosterona/sangre , Ácidos Erucicos/uso terapéutico , Fluoxetina/farmacología , Fluoxetina/uso terapéutico , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Actividad Motora/efectos de los fármacos , Distribución Aleatoria , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/psicologíaRESUMEN
Crown ethers, as a kind of heterocycle, have been the subject of great interest over recent decades due to their selective capability to bind to metal cations. The use of a constant crown ether, such as naphtho-15-crown-5 (N15C5), and varied metal cations (Li+, Na+, K+, Be2+, Mg2+, Ca2+, Co2+, Ni2+, Cu2+) makes it possible to determine the contributions of the metal cations to nonlinear optical (NLO) responses and to design an appropriate NLO-based cation detector. N15C5 and its metal cation derivatives have been systematically investigated by density functional theory. It is found that the dependency of the first hyperpolarizability relies on the metal cation, especially for transition metals. The decrease of the first hyperpolarizabilities for alkali metal cation derivatives is due to their relatively low oscillator strengths, whereas the significant increase of the first hyperpolarizabilities for transition metal cation derivatives can be further illustrated by their low transition energies, large amplitudes and separate distributions of first hyperpolarizability density. Thus, the alkali metal and transition metal cations are distinguishable and the transition metal cations are easier to detect by utilizing the variations in NLO responses.
RESUMEN
The photoinduced proton-coupled electron transfer chemistry is very crucial to the development of nonlinear optical (NLO) materials with large first hyperpolarizability contrast. We have performed a systematic investigation on the geometric structures, NLO switching, and simulated absorption spectra of rhenium(I) complexes via density functional theory (DFT). The results show that the first hyperpolarizabilities (ßvec) increase remarkably with further extending of the organic connectors. In addition, the solvent leads to a slight enhancement of the hyperpolarizability and frequency dependent hyperpolarizability. Furthermore, the proton abstraction plays an important role in tuning the second-order NLO response. It is found that deprotonation not only increases the absolute value of ßvec but also changes the sign of ßvec from positive to negative. This different sign can be explained by the opposite dipole moments. The efficient enhancement of first hyperpolarizability is attributed to the better delocalization of the π-electron system and the more obvious degree of charge transfer. Therefore, these kinds of complexes might be promising candidates for designed as proton driven molecular second-order NLO switching.
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Complejos de Coordinación/química , Electrones , Fenantrolinas/química , Protones , Piridinas/química , Renio/química , Modelos Moleculares , Dispositivos Ópticos , Teoría Cuántica , TermodinámicaRESUMEN
Oleoylethanolamide (OEA) is an endocannabinoid analog that belongs to a family of endogenous acylethanolamides. Increasing evidence suggests that OEA may act as an endogenous neuroprotective factor and participate in the control of mental disorder-related behaviors. In this study, we examined whether OEA is effective against depression and investigated the role of circulating endogenous acylethanolamides during stress. Mice were subjected to 28days of chronic unpredictable mild stress (CUMS), and during the last 21days, treated with oral OEA (1.5-6mg/kg) or 6mg/kg fluoxetine. Sucrose preference and open field test activity were used to evaluate depression-like behaviors during CUMS and after OEA treatment. Weights of the prefrontal cortex and hippocampus were determined, and the adrenal index was measured. Furthermore, changes in serum adrenocorticotropic hormone (ACTH), corticosterone (CORT) and total antioxidant capacity (T-AOC), brain-derived neurotrophic factor (BDNF), and lipid peroxidation product malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activities in the hippocampus and prefrontal cortex were detected. Our findings indicate that OEA normalized sucrose preferences, locomotion distances, rearing frequencies, prefrontal cortex and hippocampal atrophy, and adrenal indices. In addition, OEA reversed the abnormalities of BDNF and MDA levels and SOD activities in the hippocampus and prefrontal cortex, as well as changes in serum levels of ACTH, CORT, and T-AOC. The antidepressant effects of OEA may be related to the regulation of BDNF levels in the hippocampus and prefrontal cortex, antioxidant defenses, and normalizing hyperactivity in the hypothalamic-pituitary-adrenal axis (HPA).
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Antidepresivos/farmacología , Depresión/tratamiento farmacológico , Endocannabinoides/farmacología , Endocannabinoides/uso terapéutico , Ácidos Oléicos/farmacología , Ácidos Oléicos/uso terapéutico , Estrés Psicológico/tratamiento farmacológico , Hormona Adrenocorticotrópica/sangre , Animales , Antidepresivos/uso terapéutico , Antioxidantes/metabolismo , Atrofia/tratamiento farmacológico , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Corticosterona/sangre , Depresión/sangre , Depresión/complicaciones , Depresión/metabolismo , Modelos Animales de Enfermedad , Fluoxetina/farmacología , Fluoxetina/uso terapéutico , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Masculino , Malondialdehído/metabolismo , Ratones , Actividad Motora/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Corteza Prefrontal/patología , Estrés Psicológico/sangre , Estrés Psicológico/complicaciones , Estrés Psicológico/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Oleoylethanolamide (OEA) is an endocannabinoid analogy that belongs to a family of endogenous acylethanolamides. Increasing evidence suggests that OEA may act as an endogenous neuroprotective factor and participate in the control of mental disorder-related behaviors. In the present study, we investigated the antidepressant- like potential of OEA in mice in comparison with clomipramine (Cp). 50 mice were randomly divided into 5 groups, and treated with a vehicle (0.3% methyl cellulose, 20 mL/kg, p.o.), OEA (2.5, 5-10mg/kg, p.o.), or Cp (10mg/kg, p.o.) for 7 days. The immobility was used to evaluate depressive-like behaviors in tail suspension test (TST) and forced swimming test (FST). ELISA detected changes in cerebral noradrenaline (NE) and serotonin (5-HT) levels. Likewise, in the drug-induced model of depression, OEA was given once daily at 10mg/kg (p.o.) for 7 consecutive days. Then, the mice received reserpine (4 mg/kg, i.p.) and the rectal temperature was measured at different time points. Consequently, head twitch behavior induced by intraperitoneal injection of 5-hydroxy-tryptophan (5-HTP; 300 mg/kg) were determined. The experimental data showed that OEA (2.5-10mg/kg) treatment significantly decreased the immobility as compared to the control group, and OEA (10mg/kg) treatment significantly increased 5-HTP-induced head twitch behavior and reversed reserpine-induced hypothermia and increased cerebral levels of NE and 5-HT. Thus, the antidepressant effects of OEA may be related to regulating central monoamine neurotransmitters.
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Antidepresivos/farmacología , Depresión/tratamiento farmacológico , Norepinefrina/metabolismo , Ácidos Oléicos/farmacología , Serotonina/metabolismo , Animales , Antidepresivos/uso terapéutico , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Depresión/etiología , Depresión/metabolismo , Depresión/psicología , Endocannabinoides , Suspensión Trasera , Hipertermia Inducida , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Ácidos Oléicos/uso terapéuticoRESUMEN
: Thrombosis is a major complication that could be fatal in acute or chronic cardio-cerebral-vascular diseases. Therefore, the development of novel agents for anticlotting and the prevention of thrombosis and cardiovascular diseases are clinically significant. This study aimed to evaluate the anticoagulant and antithrombotic effects of 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine (Q808), a new phthalazine tetrazole derivative. Bleeding time, clotting time, and serum calcium ion (Ca) concentration were assessed in mice, whereas arteriovenous thrombus weight and plasma prothrombin time were evaluated in rats, and platelets Ca influx was determined in rabbit. Daily oral administration of Q808 at 25, 50, or 100 mg/kg for 3 days significantly delayed bleeding time and clotting time in mice compared with controls. Q808 administration at 50 mg/kg significantly reduced experimental thrombus weight by 62.6% and delayed plasma prothrombin time by 58.7% in rats, whereas 50 and 100 mg/kg of Q808 daily significantly increased serum Ca concentration in mice. Q808 at 0.2, 0.4, and 0.8 mg/mL significantly inhibited thrombin-induced Ca influx in rabbit platelets. Our results suggest that Q808 at 25-200 mg/kg daily exerts anticoagulant and antithrombotic effects, and its mechanisms of action may involve both the intrinsic and extrinsic coagulation pathways that inhibit certain coagulation factors and platelet functions.
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Anticoagulantes/farmacología , Coagulación Sanguínea/efectos de los fármacos , Ftalazinas/farmacología , Tetrazoles/farmacología , Trombosis/prevención & control , Administración Oral , Animales , Anticoagulantes/administración & dosificación , Tiempo de Sangría , Calcio/sangre , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Ratones , Ftalazinas/administración & dosificación , Tiempo de Protrombina , Conejos , Ratas , Ratas Wistar , Tetrazoles/administración & dosificación , Trombina/administración & dosificación , Trombosis/patologíaRESUMEN
BACKGROUND: QUAN-0808 (6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine), a new phthalazine tetrazole derivative, was evaluated for the anti-inflammatory and analgesic effects. METHODS: Xylene-induced ear edema, carrageenan (Carr)-induced paw edema, and acetic acid-induced capillary permeability hyperactivity in mice were used to assess the anti-inflammatory effect; acetic acid-induced writhing and hot plate responses for the analgesic activity. RESULTS: In the present study, QUAN-0808 (100, 200, 400 mg/kg) and indomethacin (Indo) significantly decreased xylene-induced ear edema by 33.3, 37.5, 46.6, and 45.1%, respectively, decreased Carr-induced paw edema at 1, 2, 4 h after Carr injection, and decreased the prostaglandin E(2) (PGE(2)) and nitric oxide (NO) levels on the edema paw at 4 h after Carr injection; QUAN-0808 (100, 200, 400 mg/kg), and aspirin (Asp, 200 mg/kg) significantly decreased Evans blue exudation in acetic acid-induced capillary permeability hyperactivity model by 26.7, 28.7, 32.3 and 29.1%, respectively, and decreased the numbers of acetic acid-induced writhing response in 15 min by 40.4, 53.6, 66.4, and 64.5%, respectively. Morphine (10 mg/kg) significantly increased the latency of the hot plate response by 136.5, 117.4, 67.5, and 22.7%, respectively, at 30, 60, 90, 120 min after intraperitoneal injection of morphine; however, QUAN-0808 (100, 200 and 400 mg/kg) did not produce significantly antinociceptive effects in the hot plate test, suggesting that its antinociceptive action occurs via peripheral rather than a central-acting mechanism. CONCLUSIONS: These results show that QUAN-0808 produced potential anti-inflammatory and peripheral antinociceptive effects, and indicated that the antinociceptive effects of QUAN-0808 were related to its anti-inflammatory activity in a dose-dependent manner. Therefore, as inflammation is a peripheral process, it is suggested that QUAN-0808 exerted peripheral effects. The peripheral effect mechanisms of QUAN-0808 may be related to a decrease in the production of PGE(2), NO, bradykinin and other inflammatory mediators.
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Analgésicos/farmacología , Antiinflamatorios/farmacología , Ftalazinas/farmacología , Tetrazoles/farmacología , Animales , Dinoprostona/análisis , Masculino , Ratones , Óxido Nítrico/fisiología , Peritonitis/tratamiento farmacológico , Xilenos/farmacologíaRESUMEN
Endogenous cannabinoid system (ECS) is highly conserved during evolution of the body's endocrine network. It is a regulator of mood, cognitive, autonomic nervous system and movement control system. ECS dysfunction can promote the progress and maintain of depression, phobia, and extreme anxiety. The antidepressant drugs to enhance the activity of ECS may represent a new direction, but rarely reported research in this regard.
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Depresión/fisiopatología , Endocannabinoides/fisiología , Receptores de Cannabinoides/metabolismo , Animales , Antidepresivos/farmacología , Moduladores de Receptores de Cannabinoides/metabolismo , Depresión/metabolismo , HumanosRESUMEN
The antidepressant-like effects of N-palmitoylethanolamide (PEA), a putative endocannabinoid, was investigated in mice using the tail suspension test (TST) and the forced swimming test (FST). In TST, PEA (10, 20, and 40 mg/kg) produced a statistically significant reduction in immobility (50, 32, and 34%, respectively, vs. the control group), whereas fluoxetine (20 mg/kg) reduced immobility by 38%. In FST, PEA (5, 10, and 20 mg/kg) produced a statistically significant reduction in immobility (15, 21, and 36%, respectively), whereas fluoxetine (20 mg/kg) reduced immobility by 18%. Moreover, PEA (20 mg/kg) did not significantly change motor activity in a spontaneous behavioral test. In conclusion, PEA (dose range of 5-40 mg/kg) administered orally reduced immobility in TST and FST, comparable to the antidepressant effect of fluoxetine, and had no effect on spontaneous activity in mice.
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Antidepresivos/farmacología , Depresión/tratamiento farmacológico , Ácidos Palmíticos/farmacología , Administración Oral , Amidas , Animales , Antidepresivos/administración & dosificación , Moduladores de Receptores de Cannabinoides/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Endocannabinoides , Etanolaminas , Conducta Exploratoria/efectos de los fármacos , Fluoxetina/farmacología , Suspensión Trasera , Masculino , Ratones , Ácidos Palmíticos/administración & dosificación , NataciónRESUMEN
OBJECTIVE: To explore the surgical treatment of rhinogenous optic function damage (ROFD) through transnasal endoscopic approach. METHODS: Twenty-three patients (25 eyes) with ROFD were retrospectively reviewed. All patients were operated on through transnasal endoscopic approach, and 9 patients underwent endoscopic optic nerve decompression. RESULTS: Four patients had bilateral pansinusitis, 6 patients had unilateral posterior ethmoidal sinusitis and sphenoiditis. One patient had frontal and ethmoidal sinusitis. Five patients had fungal sinusitis occurred in the sphenoid sinus and unilateral posterior ethmoid sinus. Two patients had unilateral pyocyst and cyst of the sphenoid and ethmoid sinus. The preoperative visual acuity preoperative were as follows: 2 patients (2 eyes) no light perception (NLP), 6 patients (7 eyes) hand movement (HM), 7 patients (7 eyes) fingers counting (FC) less than 20 cm and 8 patients (9 eyes) were vision impaired in different degree. One patient (1 eye) was ophthalmoptosis, direct and indirect light reflex vanished. Three patients (3 eyes) diplopia, 2 patients (2 eyes) abduction paralysis, 3 patients (3 eyes) defect of visual field. One patient ptosis of upper lid. The visual acuity postoperative: 2 eyes failed, 10 eyes cured;13 eyes improved from HM or FC to FC (30-60 cm). CONCLUSIONS: The endoscopic sinus surgery combined with appropriate medical therapy are effective to ROFD. Patients who suffered from severe visual damage and either unresponsive or intolerant to medical treatment should be administrated endoscopic sinus surgery including endoscopic optic nerve decompression.
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Endoscopía , Trastornos de la Visión/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Descompresión Quirúrgica , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quírurgicos Nasales , Neuritis Óptica/cirugía , Estudios Retrospectivos , Sinusitis/cirugía , Trastornos de la Visión/etiología , Adulto JovenRESUMEN
Vestibulo-cardiovascular reflexes (VCR) is a complex sensory-motor regulatory system, it refers to changes in body posture, adequate stimulus acting at vestibular receptor and regulation of cardiovascular functions including blood pressure, cardiac rhythm via autonomic center. Excessive vestibular stimulation or unilateral labyrinth lesion may cause paradoxical reaction including vertigo, tachycardia, etc. The evidences, significance, neural circuit, and neurotransmitters of VCR are reviewed in this paper.
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Sistema Cardiovascular , Reflejo , Nervio Vestibular/fisiología , Animales , Humanos , Reflejo/fisiología , Transmisión SinápticaRESUMEN
A series of 1-substituted-N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl) piperidine-4-carboxamides has been synthesized and evaluated for positive inotropic activity by measuring left atrium stroke volume in isolated rabbit-heart preparations. Some of these derivatives exhibited favorable activity compared with the standard drug, milrinone, among which 1-(2-fluorobenzyl)-N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)piperidine-4-carboxamide 6a was the most potent, increasing stroke volume by 11.92+/-0.35% (milrinone: 6.36+/-0.13%) at 1x10(-4)M.
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Química Orgánica/métodos , Corazón/efectos de los fármacos , Piperidinas/química , Quinolinas/química , Animales , Cardiotónicos/síntesis química , Cardiotónicos/farmacología , Química Farmacéutica/métodos , Diseño de Fármacos , Ácidos Isonipecóticos/química , Milrinona/síntesis química , Milrinona/farmacología , Modelos Químicos , Miocardio/metabolismo , ConejosRESUMEN
To understand the neurochemical mechanisms underlying the vestibular compensation, we determined the levels of amino acids such as aspartate, glutamate, glutamine, glycine, taurine, alanine in the medial vestibular nucleus (MVN) following unilateral labyrinthectomy (UL), by using in vivo brain microdialysis and high-performance liquid chromatography technique. Rats were pretreated by infusing 2% lidocaine 1.2 mL or 10 mg arsanilic acid into the tympanic cavity to obstruct uni-periphery vestibular organ, and then the levels of amino acids were determined in MVN of normal control and ipsilateral or contralateral lesional (ipsi-/contra-lesional) rats. In the control experiment, the levels of aspartate, glutamate, glutamine, glycine, taurine, and alanine were (6.15 +/- 0.59), (18.13 +/- 1.21), (33.73 +/- 1.67), (9.26 +/- 0.65), (9.56 +/- 0.77) and (10.07 +/- 0.83) pmol/8 muL sample, respectively. The concentrations of aspartate and glutamate decreased, while the concentration of taurine increased in the ipsi-lesional MVN of rats 10 min after infusing 2% lidocaine into middle ear to obstruct uni-periphery vestibular organ. Whereas the concentration of glutamate increased, the concentrations of glycine and alanine decreased in the contra-lesional MVN, accompanied by imbalances of glutamate, glycine and alanine in the bilateral nuclei. In contrast, the levels of glutamate and alanine decreased, the level of glutamine increased in the ipsi-lesional MVN, and the level of glutamate decreased in the contra-lesional MVN of rats 2 weeks after infusing 10 mg arsanilic acid into the tympanic cavity to obstruct uni-periphery vestibular organ. Furthermore, the level of glutamine in the ipsi-lesional MVN was obviously higher than that in the contra-lesional MVN. These results demonstrate that an imbalance of different amino acids appeared in bilateral MVN after UL, and this imbalance decreased after the development of vestibular compensation. Whereas the imbalance of glutamine release in bilateral nuclei appeared after vestibular compensation.
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Aminoácidos/metabolismo , Oído Interno/fisiología , Núcleos Vestibulares/metabolismo , Animales , Ácido Aspártico/metabolismo , Oído Interno/cirugía , Ácido Glutámico/metabolismo , Masculino , Ratas , Ratas Wistar , Taurina/metabolismo , Núcleos Vestibulares/fisiopatologíaRESUMEN
In order to understand whether some special amino acids in the medial vestibular nucleus (MVN) of rats are involved in the regulation of blood pressure, we used microdialysis technique and high performance liquid chromatography (HPLC) to measure the changes of glutamate and taurine in this central area. Acute hypotension was induced by hemorrhage from the femoral artery. It was observed that the basal release of glutamate and taurine in the MVN was stable about 90 min after the beginning of microdialysis. The basal release of glutamate was (18.96 +/- 0.27) pmol/sample (8 mul), and that of taurine was (7.73 +/- 0.05) pmol/sample (8 mul). Glutamate release increased (P<0.05) and taurine release reduced (P<0.05) in the MVN in the hemorrhage-induced acute hypotensive rats. Nevertheless, these changes were not observed in the hemorrhage-induced acute hypotensive rats which were pretreated by infusing 2% lidocaine into the middle ear or 100 mg arsanilic acid into the tympanic cavity. These results suggest that the hemorrhage-induced acute hypotention can influence the activity of the neurons in the MVN by the afferent impulses from vestibular organ, and that some special amino acid transmitters in the MVN are involved in this process.
Asunto(s)
Ácido Glutámico/metabolismo , Hipotensión/fisiopatología , Taurina/metabolismo , Núcleos Vestibulares/metabolismo , Animales , Presión Sanguínea/fisiología , Hipotensión/metabolismo , Masculino , Microdiálisis/métodos , Ratas , Ratas Wistar , Núcleos Vestibulares/fisiopatologíaRESUMEN
OBJECTIVE: To investigate the relation between levels of intercellular adhesion molecule-1, interleukin-6 and airway hyperresponsiveness in patients with allergic rhinitis. METHODS: Fifty-four patients with allergic rhinitis (AR) and 20 controls were included in the study. The levels of intercellular adhesion molecule-1 (ICAM-1) and interleukin-6 (IL-6) in nasal lavage fluid, gathered 1 hour after specific allergen nasal provocation test (SANPT), were detected by sandwich enzyme-linked immunosorbent assay (ELISA) technique. The pulmonary function (FEV1) and nonspecific bronchial provocation test were measured in 54 patients with AR, 36 patients with AR and bronchial asthma (BA) and 20 controls. At the same time, the correlation between levels of ICAM-1 and IL-6 in nasal lavage fluid and pulmonary function (FEV1) was studied. RESULTS: The levels of ICAM-1 and IL-6 in nasal lavage fluid from patients with AR were (272.75 +/- 32.25) pg/ml and (52.11 +/- 16.54) pg/ml, significantly higher than those the controls, which were (158.82 +/- 33.88) pg/ml and (25.64 +/- 10.14) pg/ml (P < 0.01). The pulmonary function (FEV1) in patients with AR and BA was (78.82 +/- 7.41)%. It was obviously lower than that in patients with AR [(83.90 +/- 4.87)%], much lower than that in normal controls [(90.25 +/- 4.69)%]. The difference among them was significant. In patients with AR, the positive percentage of bronchial provocation test was 64.81%, in patients with AR and BA, it was 83.33% in normal controls, it was 0. The differences among them had very significant meaning. The levels of ICAM-1 and IL-6 in nasal provocation fluid had closely negative correlation with pulmonary function (FEV1), r = -0.7071, -0.6248, P < 0.01. CONCLUSIONS: The close correlation was observed in upper and lower airway for allergic inflammation. The pulmonary function of patients with AR was lower, and 64. 8% of them had airway hyperresponsiveness, so that they had the potent possibility to have bronchial asthma.
Asunto(s)
Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-6/metabolismo , Líquido del Lavado Nasal/química , Rinitis Alérgica Perenne/metabolismo , Adolescente , Adulto , Anciano , Asma/metabolismo , Asma/patología , Estudios de Casos y Controles , Niño , Femenino , Humanos , Inflamación , Masculino , Persona de Mediana Edad , Rinitis Alérgica Perenne/patología , Rinitis Alérgica Perenne/fisiopatología , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of recombinant tissue plasminogen activator (rt-PA) and to explore the most suitable dosage of rt-PA in the early treatment of the Chinese patients with acute cerebral infarction (ACI). METHODS: The patients who suited for the standard were divided into three groups. Group A received rt-PA at 0.9 mg/kg, group B received rt-PA at 0.7 mg/kg, and group C did not receive any thrombolytic therapy. In thrombolytic groups, rt-PA at 8 mg was injected intravenously in a bolus at first and then the rest was given over 60 minutes. The maximal dosage was 90 mg. The Chinese stroke scale (CSS) and Barthel Index (BI) were used to evaluate the recovery of neurological functions after rt-PA treatment for 24 hours and 90 days. The hemorrhagic rate and 30 days mortality rate were also analysed. RESULTS: In group A the CSS significant effective rate was 41.18 percent at 24 hours and 76.47 percent at 90 days after thrombolysis. At 90 days BI significant effective rate was 58.82 percent. At 30 days hemorrhagic rate was 8.82 percent and mortality rate was 5.88 percent. In group B, the CSS significant effective rate was 39.39 percent at 24 hours and 69.70 percent at 90 days. At 90 days, BI significant effective rate was 54.55 percent, and at 30 days, hemorrhagic rate was 9.09 percent and mortality rate was 9.09 percent. In group C, the CSS significant effective rate was 21.21 percent, at 24 hours and 30.30 percent at 90 days (P>0.05). At 90 days, BI was 21.21 percent the mortality rate was 9.09 percent. At 30 days the mortality rate was no significant difference within three groups At 90 days, significant effective rate was 73.13 percent vs. 30.30 percent in thrombolytic and control groups (P=0.001 7). The significant disability rate was 13.43 percent vs. 24.24 percent. CONCLUSION: For Chinese individuals, with ACI, rt-PA thrombolysis was effective and safe. The dosage of 0.9 mg/kg for foreign people also fitted for Chinese individuals.