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OBJECTIVES: Although use of AUC-guided vancomycin dosing was recommended in the revised 2020 consensus guideline, collection of multiple vancomycin serum samples to calculate AUC may cause clinical complications. AUC calculated from trough-only data (one-point AUC-guided dosing) has not been sufficiently validated. The aim of the present study was to compare the incidence of nephrotoxicity following the change from trough-guided to one-point AUC-guided dosing. METHODS: We conducted a single-centre, prospective cohort study to compare the incidence of nephrotoxicity between a trough-guided dosing group and one-point AUC-guided dosing group. RESULTS: One-point AUC-guided dosing significantly decreased the incidence of acute kidney injury (AKI) compared with trough-guided dosing (2.8% versus 17.4%, Pâ=â0.002). Further, Kaplan-Meier plots for cumulative incidence of the AKI-free rate indicated that the onset of AKI was significantly longer in the one-point AUC-guided dosing group than in trough-guided dosing (HR, 6.5; 95% CI, 1.5-27.4; Pâ=â0.011). Moreover, multivariate Cox proportional hazard analysis indicated that implementation of one-point AUC-guided dosing was a significant protective factor against the incidence of AKI (age-adjusted HR, 0.164; 95% CI, 0.04-0.69; Pâ=â0.014). CONCLUSIONS: Compared with trough concentration-guided dosing, AUC-guided dosing using one-point sampling markedly reduced the incidence of AKI, without additional serum sampling.
Assuntos
Injúria Renal Aguda , Vancomicina , Humanos , Vancomicina/efeitos adversos , Antibacterianos , Incidência , Estudos Prospectivos , Área Sob a Curva , Estudos Retrospectivos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/tratamento farmacológicoRESUMO
BACKGROUND: The coronavirus infection 2019 (COVID-19) is associated with microvascular endothelial injury. Here, we report that syndecan-1, a component of endothelial glycocalyx, may reflect the disease state of COVID-19 related to endothelial injury. CASE PRESENTATION: A patient with COVID-19 was transferred to the intensive care unit of our hospital. Computed tomography of the chest showed bilateral ground glass opacities, which was diagnosed as acute respiratory syndrome. The PaO2/FIO2 ratio gradually increased from 158 on hospitalization to 300 on Day 11, on which day the ventilator was withdrawn. However, serum syndecan-1 (SDC-1) level gradually decreased from 400.5 ng/ml at hospitalization to 165.1 ng/ml on Day 5. On Day 6, serum SDC-1 level increased to 612.9 ng/ml owing to a systemic thrombosis with an increase in D-dimer. Serum SDC-1 level then decreased until 206.0 ng/ml on Day 11 after a decrease in D-dimer. The patient was transferred to another hospital on Day 21 after hospitalization. CONCLUSIONS: In this case report, changes in serum SDC-1 level closely reflected the change in disease condition in a patient with COVID-19. Serum SDC-1 may be a useful biomarker for monitoring the disease state of critically ill patients with COVID-19.
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Background: Several clinical studies have suggested that N-acetylaspartate and N-acetylaspartylglutamate levels in the human brain are associated with various psychiatric disorders, including major depressive disorder. We have previously identified Shati/Nat8l, an N-acetyltransferase, in the brain using an animal model of psychosis. Shati/Nat8l synthesizes N-acetylaspartate from L-aspartate and acetyl-coenzyme A. Further, N-acetylaspartate is converted into N-acetylaspartylglutamate, a neurotransmitter for metabotropic glutamate receptor 3. Methods: Because Shati/Nat8l mRNA levels were increased in the dorsal striatum of mice following the exposure to forced swimming stress, Shati/Nat8l was overexpressed in mice by the microinjection of adeno-associated virus vectors containing Shati/Nat8l gene into the dorsal striatum (dS-Shati/Nat8l mice). The dS-Shati/Nat8l mice were further assessed using behavioral and neurochemical tests. Results: The dS-Shati/Nat8l mice exhibited behavioral despair in the forced swimming and tail suspension tests and social withdrawal in the 3-chamber social interaction test. These depression-like behaviors were attenuated by the administration of a metabotropic glutamate receptor 2/3 antagonist and a selective serotonin reuptake inhibitor. Furthermore, the metabolism of N-acetylaspartate to N-acetylaspartylglutamate was decreased in the dorsal striatum of the dS-Shati/Nat8l mice. This finding corresponded with the increased expression of glutamate carboxypeptidase II, an enzyme that metabolizes N-acetylaspartylglutamate present in the extracellular space. Extracellular serotonin levels were lower in the dorsal striatum of the dS-Shati/Nat8l and normal mice that were repeatedly administered a selective glutamate carboxypeptidase II inhibitor. Conclusions: Our findings indicate that the striatal expression of N-acetylaspartate synthetase Shati/Nat8l plays a role in major depressive disorder via the metabotropic glutamate receptor 3-mediated functional control of the serotonergic neuronal system.
Assuntos
Corpo Estriado/metabolismo , Depressão/genética , Depressão/patologia , Regulação da Expressão Gênica/genética , Receptores de Glutamato Metabotrópico/metabolismo , Serotonina/metabolismo , Acetiltransferases/genética , Acetiltransferases/metabolismo , Animais , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Depressão/metabolismo , Dipeptídeos/metabolismo , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Elevação dos Membros Posteriores , Humanos , Relações Interpessoais , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microdiálise , Microinjeções , Natação/psicologia , Transdução GenéticaRESUMO
A novel N-acetyltransferase, Shati/Nat8l, was identified in the nucleus accumbens (NAc) of mice with methamphetamine (METH) treatment. Previously we reported that suppression of Shati/Nat8l enhanced METH-induced behavioral alterations via dopaminergic neuronal regulation. However, the physiological mechanisms of Shati/Nat8l on the dopaminergic system in the brain are unclear. In this study, we injected adeno-associated virus (AAV) vector containing Shati/Nat8l into the NAc or dorsal striatum (dS) of mice, to increase Shati/Nat8l expression. Overexpression of Shati/Nat8l in the NAc, but not in the dS, attenuated METH-induced hyperlocomotion, locomotor sensitization, and conditioned place preference in mice. Moreover, the Shati/Nat8l overexpression in the NAc attenuated the elevation of extracellular dopamine levels induced by METH in in vivo microdialysis experiments. These behavioral and neurochemical alterations due to Shati/Nat8l overexpression in the NAc were inhibited by treatment with selective group II metabotropic glutamate receptor type 2 and 3 (mGluR2/3) antagonist LY341495. In the AAV vector-injected NAc, the tissue contents of both N-acetylaspartate and N-acetylaspartylglutamate (NAAG), endogenous mGluR3 agonist, were elevated. The injection of peptidase inhibitor of NAAG or the perfusion of NAAG itself reduced the basal levels of extracellular dopamine in the NAc of naive mice. These results indicate that Shati/Nat8l in the NAc, but not in the dS, plays an important suppressive role in the behavioral responses to METH by controlling the dopaminergic system via activation of group II mGluRs.
Assuntos
Acetiltransferases/metabolismo , Condicionamento Psicológico/efeitos dos fármacos , Corpo Estriado/metabolismo , Metanfetamina/antagonistas & inibidores , Metanfetamina/farmacologia , Atividade Motora/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Acetiltransferases/genética , Aminoácidos/farmacologia , Animais , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Corpo Estriado/efeitos dos fármacos , Dipeptídeos/metabolismo , Dipeptídeos/farmacologia , Dopamina/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Xantenos/farmacologiaRESUMO
Various molecules are involved in drug addiction induced by drugs of abuse. Therefore, the mechanism of drug addiction is still not clear, and it has been a difficulty in the development of preventive and curative drugs for drug dependence. We tried to identify the molecules associated with drug dependence, and found three molecules including shati/nat81. Recently, it has been demonstrated that the substrate for shati/nat81 is aspaltate and shati/nat8l biosynthesizes N-acetylaspartate, which exists abundantly in the mammalian brain. In this study, we investigated the physiological function of shati/nat81 and the role of shati/nat81 in drug dependence. The overexpression of shati/nat81 in the dorsal striatum of mice led to social abnormality and depression-like behavior, and worsened a part of the motor dysfunction induced by Ca2+ channel agonist BAY-K 8644. The overexpression of shati/nat81 in the nucleus accumbens of mice inhibited methamphetamine-induced behavioral and biochemical abnormalities. These findings suggest that the shati/nat81-associated system could play a role in the regulation of mental activity and motor action, and be a new target in the development of therapeutic drugs for drug dependence.
Assuntos
Acetiltransferases/metabolismo , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Animais , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Humanos , Metanfetamina/farmacologia , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/fisiopatologiaRESUMO
Depression is a frequent and serious illness, and stress is considered the main risk factor for its onset. First-line antidepressants increase serotonin (5-hydroxytryptamine; 5-HT) levels in the brain. We previously reported that an N-acetyltransferase, Shati/Nat8l, is upregulated in the dorsal striatum (dSTR) of stress-susceptible mice exposed to repeated social defeat stress (RSDS) and that dSTR Shati/Nat8l overexpression in mice (dSTR-Shati OE) induces stress vulnerability and local reduction in 5-HT content. Male mice were used in this study, and we found that dSTR 5-HT content decreased in stress-susceptible but not in resilient mice. Moreover, vulnerability to stress in dSTR-Shati OE mice was suppressed by the activation of serotonergic neurons projecting from the dorsal raphe nucleus (dRN) to the dSTR, followed by upregulation of 5-HT content in the dSTR using designer receptors exclusively activated by designer drugs (DREADD). We evaluated the role of GABA in modulating the serotonergic system in the dRN. Stress-susceptible after RSDS and dSTR-Shati OE mice exhibited an increase in dRN GABA content. Furthermore, dRN GABA content was correlated with stress sensitivity. We found that the blockade of GABA signaling in the dRN suppressed stress susceptibility in dSTR-Shati OE mice. In conclusion, we propose that dSTR 5-HT and dRN GABA, controlled by striatal Shati/Nat8l via the dSTR-dRN neuronal circuitry, critically regulate stress sensitivity. Our study provides insights into the neural processes that underlie stress and suggests that dSTR Shati/Nat8l could be a novel therapeutic target for drugs against depression, allowing direct control of the dRN serotonergic system.
Assuntos
Núcleo Dorsal da Rafe , Serotonina , Camundongos , Masculino , Animais , Núcleo Dorsal da Rafe/metabolismo , Corpo Estriado/metabolismo , Neostriado/metabolismo , Ácido gama-Aminobutírico , Acetiltransferases/metabolismoRESUMO
Intradialytic hypotension and arrhythmias are complications of hemodialysis. They are associated with decreased intravascular volume due to reduced ultrafiltration volume, cardiac function, and arterial tone. The vascular endothelial glycocalyx, which exists on the surface of healthy vascular endothelial cells and maintains vascular permeability, has been suggested to be impaired by hemodialysis. This single-center retrospective study evaluated the association between syndecan-1, an endothelial glycocalyx dysfunction marker, and complications of hemodialysis. We enrolled 92 patients who underwent outpatient hemodialysis at Gifu Seiryu Hospital from April to July 2022 (346 hemodialysis sessions). The median duration and time of hemodialysis were 40 months and 4.1 h, respectively. Median serum syndecan-1 levels were 67.7 ng/mL before and 98.3 ng/mL after hemodialysis. Hemodialysis complications were noted in 68 sessions, all of which were hypotension. No correlation between pre-hemodialysis syndecan-1 levels and the incidence of complications was observed. However, a positive correlation between the amount of change in syndecan-1 levels before and after hemodialysis and the incidence of hemodialysis complications was noted. Conversely, syndecan-1 levels did not correlate with brain or atrial natriuretic peptides, suggesting that impairment of the vascular endothelial glycocalyx may be a possible cause of intradialytic hypotension and may be useful in preventing intradialytic hypotension.
Assuntos
Hipotensão , Sindecana-1 , Humanos , Estudos Retrospectivos , Células Endoteliais , Diálise Renal/efeitos adversos , Hipotensão/etiologiaRESUMO
Tissue injury and hemorrhage induced by trauma lead to degradation of the endothelial glycocalyx, causing syndecan-1 (SDC-1) to be shed into the blood. In this study, we investigated whether serum SDC-1 is useful for evaluating trauma severity in patients. A single-center, retrospective, observational study was conducted at Gifu University Hospital. Patients transported to the emergency room for trauma and subsequently admitted to the intensive care unit from January 2019 to December 2021 were enrolled. A linear regression model was constructed to evaluate the association of serum SDC-1 with injury severity score (ISS) and probability of survival (Ps). A total of 76 trauma patients (54 men and 22 women) were analyzed. ISS was significantly associated with serum SDC-1 level in trauma patients. Among the six body regions defined in the AIS used to calculate the ISS score, "chest" and "abdominal or pelvic contents" were significantly associated with serum SDC-1 level, and "extremities or pelvic girdle" also tended to show an association with serum SDC-1 level. Moreover, increasing serum SDC-1 level was significantly correlated with decreasing Ps. Serum SDC-1 may be a useful biomarker for monitoring the severity of trauma in patients. Further large-scale studies are warranted to verify these results.
RESUMO
Syndecan-1 (SDC-1) is found in the endothelial glycocalyx and shed into the blood during systemic inflammatory conditions. We investigated organ dysfunction associated with changing serum SDC-1 levels for early detection of organ dysfunction in critically ill patients. To evaluate the effect of SDC-1 on laboratory parameters measured the day after SDC-1 measurement with consideration for repeated measures, linear mixed effects models were constructed with each parameter as an outcome variable. A total of 94 patients were enrolled, and 831 samples were obtained. Analysis using mixed effects models for repeated measures with adjustment for age and sex showed that serum SDC-1 levels measured the day before significantly affected several outcomes, including aspartate aminotransferase (AST), alanine transaminase (ALT), creatinine (CRE), blood urea nitrogen (BUN), antithrombin III, fibrin degradation products, and D-dimer. Moreover, serum SDC-1 levels of the prior day significantly modified the effect between time and several outcomes, including AST, ALT, CRE, and BUN. Additionally, increasing serum SDC-1 level was a significant risk factor for mortality. Serum SDC-1 may be a useful biomarker for daily monitoring to detect early signs of kidney, liver and coagulation system dysfunction, and may be an important risk factor for mortality in critically ill patients.
Assuntos
Estado Terminal , Insuficiência de Múltiplos Órgãos/sangue , Sindecana-1/sangue , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Endothelial disorders are related to various diseases. An initial endothelial injury is characterized by endothelial glycocalyx injury. We aimed to evaluate endothelial glycocalyx injury by measuring serum syndecan-1 concentrations in patients during comprehensive medical examinations. A single-center, prospective, observational study was conducted at Asahi University Hospital. The participants enrolled in this study were 1313 patients who underwent comprehensive medical examinations at Asahi University Hospital from January 2018 to June 2018. One patient undergoing hemodialysis was excluded from the study. At enrollment, blood samples were obtained, and study personnel collected demographic and clinical data. No treatments or exposures were conducted except for standard medical examinations and blood sample collection. Laboratory data were obtained by the collection of blood samples at the time of study enrolment. According to nonlinear regression, the concentrations of serum syndecan-1 were significantly related to age (p = 0.016), aspartic aminotransferase concentration (AST, p = 0.020), blood urea nitrogen concentration (BUN, p = 0.013), triglyceride concentration (p < 0.001), and hematocrit (p = 0.006). These relationships were independent associations. Endothelial glycocalyx injury, which is reflected by serum syndecan-1 concentrations, is related to age, hematocrit, AST concentration, BUN concentration, and triglyceride concentration.
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OBJECTIVE: To assess the effect of human atrial natriuretic peptide (HANP) on the pulmonary and systemic circulations during infrarenal abdominal aortic aneurysmectomy. DESIGN: A prospective, randomized study. SETTING: A university hospital. PARTICIPANTS: Forty-five patients undergoing infrarenal abdominal aortic aneurysmectomy. INTERVENTIONS: Abdominal aortic aneurysmectomy patients were randomly assigned to 1 of 3 groups (n = 15 for each group). They were infused with normal saline solution (SA), 0.02 microg/kg/min of HANP (LH), or 0.05 microg/kg/min of HANP (HH), starting 5 minutes after clamping. Hemodynamic variables were measured before/after clamping and unclamping. MEASUREMENTS AND MAIN RESULTS: Both mean pulmonary arterial pressure (MPAP) and the pulmonary vascular resistance index (PVRI) increased (v baseline) in the SA group. HANP attenuated the rises in MPAP and PVRI dose dependently (LH and HH groups v SA). Mean arterial pressure and systemic vascular resistance index were not significantly different among the 3 groups. CONCLUSION: HANP, infused during aortic clamping and abdominal aortic aneurysmectomy, attenuates the rises in pulmonary artery pressure and vascular resistance without severe systemic hypotension. This may result from direct and/or indirect pulmonary vascular effects of HANP because no HANP-induced changes in endothelin-1, angiotensin-II, and thromboxane B(2) were detected.
Assuntos
Aorta Abdominal/fisiologia , Aneurisma da Aorta Abdominal/tratamento farmacológico , Fator Natriurético Atrial/uso terapêutico , Artéria Pulmonar/fisiologia , Procedimentos Cirúrgicos Vasculares/métodos , Idoso , Idoso de 80 Anos ou mais , Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/fisiopatologia , Aneurisma da Aorta Abdominal/cirurgia , Pressão Sanguínea/fisiologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/prevenção & controle , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/uso terapêutico , Estudos Prospectivos , Resistência Vascular/fisiologia , Procedimentos Cirúrgicos Vasculares/efeitos adversosRESUMO
Transmembrane protein 168 (TMEM168) comprises 697 amino acid residues, including some putative transmembrane domains. It is reported that TMEM168 controls methamphetamine (METH) dependence in the nucleus accumbens (NAc) of mice. Moreover, a strong link between METH dependence-induced adaptive changes in the brain and mood disorders has been evaluated. In the present study, we investigated the effects of accumbal TMEM168 in a battery of behavioral paradigms. The adeno-associated virus (AAV) Tmem168 vector was injected into the NAc of C57BL/6J mice (NAc-TMEM mice). Subsequently, the accumbal TMEM168 mRNA was increased approximately by seven-fold when compared with the NAc-Mock mice (controls). The NAc-TMEM mice reported no change in the locomotor activity, cognitive ability, social interaction, and depression-like behaviors; however, TMEM168 overexpression enhanced anxiety in the elevated-plus maze and light/dark box test. The increased anxiety was reversed by pretreatment with the antianxiety drug diazepam (0.3 mg/kg i.p.). Moreover, the NAc-TMEM mice exhibited decreased prepulse inhibition (PPI) in the startle response test, and the induced schizophrenia-like behavior was reversed by pretreatment with the antipsychotic drug risperidone (0.01 mg/kg i.p.). Furthermore, accumbal TMEM168 overexpression decreased the basal levels of extracellular GABA in the NAc and the high K+ (100 mM)-stimulated GABA elevation; however, the total contents of GABA in the NAc remained unaffected. These results suggest that the TMEM168-regulated GABAergic neuronal system in the NAc might become a novel target while studying the etiology of anxiety and sensorimotor gating deficits.
Assuntos
Proteínas de Membrana/metabolismo , Núcleo Accumbens/metabolismo , Filtro Sensorial , Animais , Comportamento Animal , Diazepam/farmacologia , Dopamina/metabolismo , Ácido Glutâmico/metabolismo , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Risperidona/farmacologia , Filtro Sensorial/efeitos dos fármacos , Serotonina/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
Chronic exposure to methamphetamine causes adaptive changes in brain, which underlie dependence symptoms. We have found that the transmembrane protein 168 (TMEM168) is overexpressed in the nucleus accumbens of mice upon repeated methamphetamine administration. Here, we firstly demonstrate the inhibitory effect of TMEM168 on methamphetamine-induced behavioral changes in mice, and attempt to elucidate the mechanism of this inhibition. We overexpressed TMEM168 in the nucleus accumbens of mice by using an adeno-associated virus vector (NAc-TMEM mice). Methamphetamine-induced hyperlocomotion and conditioned place preference were attenuated in NAc-TMEM mice. Additionally, methamphetamine-induced extracellular dopamine elevation was suppressed in the nucleus accumbens of NAc-TMEM mice. Next, we identified extracellular matrix protein osteopontin as an interacting partner of TMEM168, by conducting immunoprecipitation in cultured COS-7 cells. TMEM168 overexpression in COS-7 cells induced the enhancement of extracellular and intracellular osteopontin. Similarly, osteopontin enhancement was also observed in the nucleus accumbens of NAc-TMEM mice, in in vivo studies. Furthermore, the infusion of osteopontin proteins into the nucleus accumbens of mice was found to inhibit methamphetamine-induced hyperlocomotion and conditioned place preference. Our studies suggest that the TMEM168-regulated osteopontin system is a novel target pathway for the therapy of methamphetamine dependence, via regulating the dopaminergic function in the nucleus accumbens.
Assuntos
Locomoção/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Metanfetamina/farmacologia , Osteopontina/metabolismo , Animais , Células COS , Chlorocebus aethiops , Hibridização In Situ , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
We have identified SHATI/NAT8L in the brain of mice treated with methamphetamine. Recently, it has been reported that SHATI is N-acetyltransferase 8-like protein (NAT8L) that produces N-acetylaspatate (NAA) from aspartate and acetyl-CoA. We have generated SHATI/NAT8L knockout (Shati -/-) mouse which demonstrates behavioral deficits that are not rescued by single NAA supplementation, although the reason for which is still not clarified. It is possible that the developmental impairment results from deletion of SHATI/NAT8L in the mouse brain, because NAA is involved in myelination through lipid synthesis in oligodendrocytes. However, it remains unclear whether SHATI/NAT8L is involved in brain development. In this study, we found that the expression of Shati/Nat8l mRNA was increased with brain development in mice, while there was a reduction in the myelin basic protein (MBP) level in the prefrontal cortex of juvenile, but not adult, Shati -/- mice. Next, we found that deletion of SHATI/NAT8L induces several behavioral deficits in mice, and that glyceryltriacetate (GTA) treatment ameliorates the behavioral impairments and normalizes the reduced protein level of MBP in juvenile Shati -/- mice. These findings suggest that SHATI/NAT8L is involved in myelination in the juvenile mouse brain via supplementation of acetate derived from NAA. Thus, reduction of SHATI/NAT8L induces developmental neuronal dysfunction.
Assuntos
Encéfalo/metabolismo , Proteína Básica da Mielina/metabolismo , Acetiltransferases/deficiência , Acetiltransferases/genética , Acetiltransferases/metabolismo , Animais , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análise , Ácido Aspártico/farmacologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Cromatografia Líquida de Alta Pressão , Regulação para Baixo/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Espectrometria de Massas , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Knockout , Proteína Básica da Mielina/genética , Oligodendroglia/citologia , Oligodendroglia/metabolismo , Córtex Pré-Frontal/metabolismo , RNA Mensageiro/metabolismo , Comportamento SocialAssuntos
Dor/cirurgia , Radiocirurgia , Gânglio Estrelado , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestésicos Locais/uso terapêutico , Braço , Doença Crônica , Eletrocoagulação , Dor Facial/cirurgia , Feminino , Bloqueadores Ganglionares/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Medição da Dor , Resultado do TratamentoRESUMO
Periorbital pain is unusual in patients with blepharospasms. We report a patient with hemifacial spasms who presented with severe ipsilateral periorbital aching pain. After treatment with botulinum toxin type A, the left hemifacial spasms and left periorbital pain improved temporarily. Microvascular decompression surgery was then performed for the facial spasms. The patient's left hemifacial spasms disappeared immediately after the operation, and his left periorbital pain was also totally resolved.
Assuntos
Toxinas Botulínicas/uso terapêutico , Descompressão Cirúrgica , Dor Facial/terapia , Espasmo Hemifacial/fisiopatologia , Idoso , Humanos , MasculinoRESUMO
A novel N-acetyltransferase, Shati/Nat8l, was identified in the nucleus accumbens of mice repeatedly treated with methamphetamine (METH). Shati/Nat8l has been reported to inhibit the pharmacological action induced by METH. Shati/Nat8l produces N-acetylaspartate from aspartate and acetyl-CoA. Previously, we reported that overexpression of Shati/Nat8l in nucleus accumbens attenuates the response to METH by N-acetylaspartylglutamate (which is derived from N-acetylaspartate)-mGluR3 signaling in the mice brain. In the present study, to clarify the type of cells that produce Shati/Nat8l, we carried out in-situ hybridization for the detection of Shati/Nat8l mRNA along with immunohistochemical studies using serial sections of mice brain. Shati/Nat8l mRNA was detected in neuronal cells, but not in astrocytes or microglia cells. Next, we investigated the function of Shati/Nat8l in the neuronal cells in mice brain; then, we used an adeno-associated virus vector containing Shati/Nat8l for transfection and overexpression of Shati/Nat8l protein into the primary cultured neurons to investigate the contribution toward the neuronal activity of Shati/Nat8l. Overexpression of Shati/Nat8l in the mice primary cultured neurons induced axonal growth, but not dendrite elongation at day 1.5 (DIV). This finding indicated that Shati/Nat8l contributes toward neuronal development. LY341495, a selective group II mGluRs antagonist, did not abolish this axonal growth, and N-acetylaspartylglutamate itself did not abolish axon outgrowth in the same cultured system. The cultured neurons overexpressing Shati/Nat8l contained high ATP, suggesting that axon outgrowth is dependent on energy metabolism. This study shows that Shati/Nat8l in the neuron may induce axon outgrowth by ATP synthesis and not through mGluR3 signaling.
Assuntos
Acetiltransferases/metabolismo , Axônios/metabolismo , Encéfalo/metabolismo , Trifosfato de Adenosina , Animais , Axônios/fisiologia , Células Cultivadas , Dendritos/metabolismo , Metabolismo Energético , Hipocampo/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Neurônios/metabolismoAssuntos
Dor Pós-Operatória/etiologia , Dor de Ombro/etiologia , Espondilose/complicações , Cirurgia Torácica Vídeoassistida/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/terapia , Radiografia , Dor de Ombro/terapia , Espondilose/diagnóstico por imagem , Resultado do TratamentoRESUMO
We previously reported that unclamping of an abdominal aortic cross-clamp causes initial dilation of pial arteries followed by sustained constriction. Both milrinone and colforsin daropate have a vasodilator action, and both have been used in such critical conditions as abdominal aortic aneurysmectomy. We measured cerebral pial arteriolar diameters using a rabbit closed cranial window preparation before (baseline) and 15 min after the start of an IV infusion of 0.9% saline (control group), milrinone, or colforsin daropate (0.05 and 0.5 microg . /kg(-1) . min(-1)) (pre-clamp), just after aortic clamping, 20 min after clamping, and at 0 to 60 min after unclamping. In the control group, a significant decrease in diameter persisted for at least 60 min after unclamping (maximum, -15% for large and -26% for small arterioles versus baseline). These values were significantly smaller after both doses of milrinone and the larger dose of colforsin daropate (-5% and -8%, 10% and 12%, and -2% and -5%, respectively vs baseline, at 60 min). In a second experiment, changes in regional cerebral blood flow and tissue oxygen tension reflected changes in vascular variables. Thus, sustained cerebral pial arteriolar constriction induced by aortic unclamping can be attenuated by IV milrinone or colforsin daropate.
Assuntos
Aorta Abdominal/fisiologia , Colforsina/análogos & derivados , Colforsina/uso terapêutico , Milrinona/uso terapêutico , Vasoconstrição/efeitos dos fármacos , Vasodilatadores/uso terapêutico , Animais , Arteríolas/efeitos dos fármacos , Arteríolas/fisiologia , Gasometria , Dióxido de Carbono/sangue , Circulação Cerebrovascular/efeitos dos fármacos , Constrição , Concentração de Íons de Hidrogênio , Oxigênio/sangue , CoelhosRESUMO
We previously demonstrated that lumbar intrathecal alpha(2) agonists attenuate hypercapnia-induced cerebral vasodilation. The combination of intrathecal clonidine and neostigmine is being investigated as pain therapy. The effects of their combination on cerebrovascular reactivity are unknown. We allocated rabbits anesthetized with pentobarbital to two groups: (a) clonidine (normal saline followed 30 min later by clonidine 2 microg/kg, both into the lumbar intrathecal space; n = 6), and (b) neostigmine-pretreatment (neostigmine 2 microg/kg followed 30 min later by clonidine 2 microg/kg, both into the lumbar intrathecal space; n = 6). We then evaluated the hypercapnia-induced changes in pial arteriolar diameter in these two groups using the closed cranial window preparation. The pial arteriolar dilator response to hypercapnia was significantly attenuated in the clonidine group (14% +/- 4%, 4% +/- 4%, 6% +/- 6%, and 5% +/- 7% for before and 30, 60, and 90 min, respectively). Neither normal saline nor neostigmine alone induced any change in the cerebral reactivity to hypercapnia. Pretreatment with neostigmine completely prevented the clonidine-induced attenuation of the hypercapnic cerebral vasodilation attenuated by intrathecal clonidine (16% +/- 7%, 15% +/- 6%, 12% +/- 6%, and 16% +/- 8%, respectively).