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1.
BMJ Open ; 11(8): e051127, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446499

RESUMO

INTRODUCTION: Ventriculoperitoneal shunt (VPS) remains the most widely used methods to treat communicating hydrocephalus. More recently, lumboperitoneal shunt (LPS) has been suggested as a reasonable option in some studies. However, there is lack of high-quality studies comparing these two techniques in order to certain the benefits and harms to use one of these two methods. The purpose of the current study is to determine the effectiveness and safety of the LPS versus the VPS in patients with communicating hydrocephalus. METHODS AND ANALYSIS: All eligible patients aged 18-90 years with communicating hydrocephalus will be recruited and then randomly allocated into LPS or VPS group in a ratio of 1:1. All patients will be analysed before shunt insertion, at the time of discharge, 1 month, 6 months, 12 months and 24 months postoperatively. The primary outcome measure is the rate of shunt failure at a 2-year follow-up term. The secondary outcomes include Keifer's Hydrocephalus Scale, National Institute of Health Stroke Scale, Glasgow Outcome Scale Extended, Evans index, safety endpoints and cost-effectiveness of hospital stay. ETHICS AND DISSEMINATION: The study will be performed in compliance with the Declaration of Helsinki (2002) of the World Medical Association. The study was approved by Institutional Review Board of West China Hospital. All patients will be fully informed the potential benefits, potential risks and responsibilities, those who will sign the informed consents once they are included. Preliminary and final results will be published in peer-reviewed journals and presented at national and international congresses. TRIAL REGISTRATION NUMBER: ChiCTR2100043839.


Assuntos
Hidrocefalia , Análise Custo-Benefício , Humanos , Hidrocefalia/cirurgia , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares , Derivação Ventriculoperitoneal/efeitos adversos
2.
Medicine (Baltimore) ; 100(31): e26691, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397802

RESUMO

BACKGROUND: Ventriculoperitoneal shunt (VPS) and lumboperitoneal shunt (LPS) remain the mainstay of idiopathic normal pressure hydrocephalus (INPH). There are no randomized controlled trials completed to compare the efficacy of these 2 shunt techniques. METHODS/DESIGN: We will conduct a monocentric, assessor-blinded, and randomized controlled trial titled "Comparison of Ventriculoperitoneal Shunt to Lumboperitoneal Shunt for the treatment of Idiopathic Normal Pressure Hydrocephalus: Phase I (COVLINPH-1)" trial and recruit patients at West China Hospital of Sichuan University since June 2021. And this trial is expected to end in December 2030. Eligible participants will be randomly assigned into LPS group and VPS group at ratio of 1:1 followed by evaluation before surgery, 1 month, 12 months, and 5 years after surgery. The primary outcome is the rate of shunt failure within 5 years. The secondary outcomes include modified Rankin Scale (mRS), INPH grading scale (INPHGS), mini-mental state examination (MMSE), and Evans index. We will calculate the rate of favorable outcome, which is defined as shunt success and an improvement of more than 1 point in the mRS at evaluation point. We will also analyze the complications throughout the study within 5 years after shunt insertion. DISCUSSION: The results of this trial will provide state-of-the-art evidence on the treatment option for patients with INPH, and will also generate the discussion regarding this subject. TRIAL REGISTRATION NUMBER: ChiCTR2000031555; Pre-results.


Assuntos
Hidrocefalia de Pressão Normal/cirurgia , Peritônio/cirurgia , Espaço Subaracnóideo/cirurgia , Derivação Ventriculoperitoneal , Drenagem/efeitos adversos , Drenagem/métodos , Humanos , Vértebras Lombares , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego , Derivação Ventriculoperitoneal/efeitos adversos
4.
Cell Prolif ; 54(9): e13108, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34374150

RESUMO

OBJECTIVES: Necroptosis is widespread in neurodegenerative diseases. Here, we examined necroptosis in the hippocampus and cortex after hydrocephalus and found that a necroptosis pathway inhibitor alleviates necroptosis and provides neuroprotective effects. MATERIALS AND METHODS: Hydrocephalus was induced in C57BL/6 mice by kaolin. Haematoxylin and eosin (HE), Nissl, PI and Fluoro-Jade B (FJB) staining were used for general observations. Phosphorylated receptor-interacting protein kinase 3 (p-RIP3) and phosphorylated mixed lineage kinase domain-like (p-MLKL) were measured by Western blotting and immunohistochemistry. Scanning electron microscopy (SEM) was used to observe ependymal cilia. Magnetic resonance imaging (MRI) and the Morris water maze (MWM) test were used to assess neurobehavioral changes. Immunofluorescence was used to detect microglial and astrocyte activation. Inflammatory cytokines were measured by Western blotting and RT-PCR. RESULTS: Obvious pathological changes appeared in the hippocampus and cortex after hydrocephalus, and expression of the necroptosis markers p-RIP3, p-MLKL and inflammatory cytokines increased. Necrostatin-1 (Nec-1) and GSK872 reduced necrotic cell death, attenuated p-RIP3 and p-MLKL levels, slightly improved neurobehaviours and inhibited microglial and astrocyte activation and inflammation. CONCLUSIONS: RIP1/RIP3/MLKL mediates necroptosis in the cortex and hippocampus in a hydrocephalus mouse model, and Nec-1 and GSK872 have some neuroprotective effects.


Assuntos
Proteínas Ativadoras de GTPase/metabolismo , Hidrocefalia/metabolismo , Necroptose/fisiologia , Fármacos Neuroprotetores/metabolismo , Proteínas Quinases/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Hidrocefalia/induzido quimicamente , Imidazóis/metabolismo , Indóis/metabolismo , Inflamação/metabolismo , Caulim/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Necroptose/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
5.
Brain Res Bull ; 175: 26-36, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34280481

RESUMO

Low-grade gliomas (LGGs) are slow-growing brain cancer in central nervous system neoplasms. EMILIN2 is an extracellular matrix (ECM) protein which could influence the progress of some tumour which is unclear in LGG. In our study, the methylation, expression, prognosis and immune value of EMILIN2 in LGG were analysed through bioinformatics analysis. We analysed the LGG data from The Cancer Genome Atlas (TCGA) and discovered that the EMILIN2 expression, negatively correlated to the EMILIN2 methylation, could predict a poor prognosis and was associated with different clinical parameters. Moreover, univariate and multivariate Cox regression were performed in CGGA, which showed that the EMILIN2 could be an independent prognostic biomarker in LGG. Moreover, EMILIN2 expression showed a correlation with gene makers in some immune cells, which identified the significance of EMILIN2 in immune infiltration. Finally, we used RT-PCR to verify the EMILIN2 expression level in different grades which showed there were significantly different (P < 0.05). Similarly, high expression of EMILIN2 could predict a poor prognosis (P = 0.0078). In conclusion, EMILIN2 could act as an independent prognostic biomarker which might be associated with the malignancy and development of gliomas and play a crucial role in glioma in immune infiltration.

6.
Sci Rep ; 11(1): 1815, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33469041

RESUMO

Goldfish is an ornamental fish with diverse phenotypes. However, the limited genomic resources of goldfish hamper our understanding of the genetic basis for its phenotypic diversity. To provide enriched genomic resources and infer possible mechanisms underlying skin pigmentation, we performed a large-scale transcriptomic sequencing on 13 adult goldfish tissues, larvae at one- and three-days post hatch, and skin tissues with four different color pigmentation. A total of 25.52 Gb and 149.80 Gb clean data were obtained using the PacBio and Illumina platforms, respectively. Onto the goldfish reference genome, we mapped 137,674 non-redundant transcripts, of which 5.54% was known isoforms and 78.53% was novel isoforms of the reference genes, and the remaining 21,926 isoforms are novel isoforms of additional new genes. Both skin-specific and color-specific transcriptomic analyses showed that several significantly enriched genes were known to be involved in melanogenesis, tyrosine metabolism, PPAR signaling pathway, folate biosynthesis metabolism and so on. Thirteen differentially expressed genes across different color skins were associated with melanogenesis and pteridine synthesis including mitf, ednrb, mc1r, tyr, mlph and gch1, and xanthophore differentiation such as pax7, slc2a11 and slc2a15. These transcriptomic data revealed pathways involved in goldfish pigmentation and improved the gene annotation of the reference genome.


Assuntos
Genoma , Carpa Dourada/genética , Anotação de Sequência Molecular , Pigmentação da Pele/genética , Transcriptoma , Processamento Alternativo , Animais , Fenótipo
7.
J Oral Facial Pain Headache ; 32(2): e22­e27, 2018 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-29561918

RESUMO

AIMS: To investigate whether nasopharyngeal airway (NPA) intubation could reduce the risk of complications caused by radiofrequency thermocoagulation (RFT) of the trigeminal ganglion. METHODS: From November 1, 2014 to May 1, 2015, 200 patients treated with sedation (combination of sufentanil and propofol) were randomly divided into two groups, one in which NPA intubation was used (intervention group) and one in which it was not used (control group). The primary outcome was the frequency of hypoxemia, and secondary outcomes were the frequency of hypotension, nasal mucosa damage, corneal numbness, masticatory weakness, palsies of other cranial nerves, and intracranial hemorrhage. Statistical analyses were performed by using the Statistical Package for Social Sciences version 19.0. A P value < .05 was considered to reflect statistical significance. Differences in the frequencies of adverse events between the two groups were assessed by using Fisher exact test. RESULTS: Five patients in the intervention group showed minor nasal mucosa injury (P = .027). Hypoxemia (19 vs 3, P < .001), corneal numbness (12 vs 4), and masticatory weakness (11 vs 3) occurred more frequently in the control group than in the intervention group (P < .05). No significant differences in the incidence of hypotension or palsies of other cranial nerves were observed between the two groups (P > .05). CONCLUSION: NPA intubation can reduce the frequency of hypoxemia and complications related to the thermocoagulation of the trigeminal ganglion with minor risks for nasopharyngeal injury.

8.
Pain Physician ; 20(5): E633-E645, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28727708

RESUMO

BACKGROUND: Postherpetic neuralgia (PHN) is a refractory condition that impairs the patient's quality of life (QoL), it develops secondary to herpes zoster infection. Therefore, it's important to prevent the transition of acute/subacute zoster-related pain to PHN. Despite of numerous studies, the optimal intervention that reduces PHN incidence is still unknown. OBJECTIVE: We evaluate the efficacy of short-term spinal cord stimulation (stSCS) in patients with refractory acute/subacute zoster-related pain. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center/teaching hospital. METHODS: A total of 46 patients who presented with acute/subacute zoster-related pain, and had previously failed conventional therapies, underwent stSCS treatment. Visual analog scale (VAS), Short Form Health Survey 12 items (SF-12), and analgesic consumptions were recorded before stSCS, post-stSCS, 2 weeks, and 1, 3, 6, 9, and 12 months after stimulation. RESULTS: The VAS scores at post-stSCS, 2 weeks, and 1, 3, 6, 9, and 12 months after stSCS treatment were significantly decreased compared with the baseline score (P < 0.001). Thirty-two patients (69.6%, 32/46) achieved the minimal clinically important difference (MCID), including 18 patients (39.1%, 18/46) who achieved complete pain relief (VASless than orequal to2). During the follow-up period, the efficacy of stSCS didn't decrease and VAS scores were declining. Similarly, SF-12 scores and analgesic consumptions improved after stSCS treatment. The efficacy of stSCS did not differ significantly among patients with different durations of acute/subacute zoster-related pain starting from the onset of rash. No serious adverse effects were observed in the entire follow-up period. LIMITATIONS: This study was not a randomized prospective controlled study. We did not compare the outcomes with patients presenting with mild or moderate pain, and did not compare the efficacy of stSCS treatment with conventional therapies. CONCLUSIONS: stSCS is a safe, effective, and less invasive analgesic method for patients with refractory acute/subacute zoster-related pain. KEY WORDS: Herpes zoster, zoster-related pain, postherpetic neuralgia, spinal cord stimulation, VAS.


Assuntos
Dor Aguda/terapia , Herpes Zoster/complicações , Neuralgia Pós-Herpética/terapia , Avaliação de Processos e Resultados em Cuidados de Saúde , Estimulação da Medula Espinal/métodos , Dor Aguda/etiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia Pós-Herpética/etiologia , Estudos Retrospectivos
9.
Pain Physician ; 19(5): E721-8, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27389115

RESUMO

BACKGROUND: Postherpetic neuralgia (PHN) is often refractory to existing treatments. Treatment of the dorsal root ganglion (DRG) using monopolar pulsed radiofrequency (PRF), which is a non- or minimally neurodestructive technique, is not efficacious in all patients. OBJECTIVES: This study aimed to determine the safety and clinical efficacy of bipolar high-voltage, long-duration PRF on the DRG in PHN patients. STUDY DESIGN: Self before-after controlled clinical trial. SETTING: Department of Pain Medicine, the First Affiliated Hospital of China Medical University. METHODS: Ninety patients diagnosed with PHN for > 3months were included. Bipolar high-voltage, long-duration PRF at 42°C for 900 seconds was applied after the induction of paresthesias covered the regions of hyperalgesic skin. The therapeutic effects were evaluated using a visual analog scale (VAS) and the 36-item Short Form health survey (SF-36) before treatment and one, 4, 8, and 12 weeks after PRF. RESULTS: The VAS scores at one, 4, 8, and 12 weeks after PRF treatment were significantly lower than before treatment (P < 0.001). The SF-36 scores, which included physical functioning, physical role, bodily pain, general health perceptions, vitality, social function, emotional role, and the mental health index, were significantly improved up to 12 weeks after PRF treatment (P < 0.001). No serious adverse effects were identified following treatment. The main adverse reactions included pain, tachycardia, and high blood pressure (especially when the field strength was enhanced). LIMITATIONS: Single center study, relatively small number of patients, lack of a control group. CONCLUSION: Bipolar high-voltage, long-duration PRF on the DRG is an effective and safe therapeutic alternative for PHN patients. This treatment could improve the quality of life of PHN patients. CLINICAL TRIAL REGISTRATION: NO ChiCTR-OCS-14005461.


Assuntos
Neuralgia Pós-Herpética/terapia , Avaliação de Resultados em Cuidados de Saúde , Tratamento por Radiofrequência Pulsada/métodos , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tratamento por Radiofrequência Pulsada/efeitos adversos
10.
Int J Nurs Stud ; 59: 156-62, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27222460

RESUMO

OBJECTIVE: To compare the efficacy of several antiseptics in decreasing the blood culture contamination rate. DESIGN: Network meta-analysis. DATA SOURCE: Electronic searches of PubMed and Embase were conducted up to November 2015. Only randomized controlled trials or quasi-randomized controlled trials were eligible. We applied no language restriction. A comprehensive review of articles in the reference lists was also accomplished for possible relevant studies. REVIEW METHODS: Relevant studies evaluating efficacy of different antiseptics in venous puncture site for decreasing the blood culture contamination rate were included. The data were extracted from the included randomized controlled trials by two authors independently. The risk of bias was evaluated using Detsky scale by two authors independently. We used WinBUGS1.43 software and statistic model described by Chaimani to perform this network meta-analysis. Then graphs of statistical results of WinBUGS1.43 software were generated using 'networkplot', 'ifplot', 'netfunnel' and 'sucra' procedure by STATA13.0. Odds ratio and 95% confidence intervals were assessed for dichotomous data. A probability of p less than 0.05 was considered to be statistically significant. Compared with ordinary meta-analyses, this network meta-analysis offered hierarchies for the efficacy of different antiseptics in decreasing the blood culture contamination rate. RESULTS: Seven randomized controlled trials involving 34,408 blood samples were eligible for the meta-analysis. No significant difference was found in blood culture contamination rate among different antiseptics. No significant difference was found between non-alcoholic antiseptics and alcoholic antiseptics, alcoholic chlorhexidine and povidone iodine, chlorhexidine and iodine compounds, povidone iodine and iodine tincture in this aspect, respectively. CONCLUSIONS: Different antiseptics may not affect the blood culture contamination rate. Different intervals between the skin disinfection and the venous puncture, the different settings (emergency room, medical wards, and intensive care units) and the performance of the phlebotomy may affect the blood culture contamination rate.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Hemocultura , Desinfecção , Ensaios Clínicos Controlados Aleatórios como Assunto , Pele/efeitos dos fármacos , Teorema de Bayes , Humanos
11.
Cell Biochem Biophys ; 72(1): 137-40, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25572054

RESUMO

Our objective is to analyze and observe the different administration routes of parecoxib sodium pretreatment on the behavioral improvement of rats with neuropathic pain to provide the preclinical data of parecoxib sodium on neuropathic pain treatment. 30 SD rats were randomly divided into five groups, including model group, sham operation group, intrathecal injection group (IT group), intraperitoneal injection group (IP group), and perineural infiltration group (PI group). The rats in model group and three parecoxib sodium pretreatment groups received spinal nerve ligation (SNL). Heat pain test and 50 % paw mechanical withdrawal threshold test (50 % PMWT) were use to assess the responses after parecoxib sodium pretreatment. 50 % PMWT results of right foot in five groups had no statistical difference (P > 0.05); 50 % PMWT results of left and right feet in three parecoxib sodium pretreatment groups were obviously higher than SNL group at different time points, which was statistically different (P < 0.05); in comparison with three pretreatment groups, the data of left foot in IT group were obviously higher than PI group and IP group, and the comparison among three groups had significant difference (P < 0.05). However, the data of right foot had no significant difference among three groups (P > 0.05). Paw thermal withdrawal latency (PTWL) results of left and right feet in five groups had no significant difference before surgery (P > 0.05); after the establishment of neuropathic model, PTWL results in five groups were significantly decreased; however, PTWL results of left and right feet at 3 days after surgery in IT group were significantly higher than the two other pretreatment groups (P < 0.05); PTWL results of left and right feet at 7 and 14 days after surgery had no significant difference. Parecoxib sodium pretreatment can effectively improve the behaviors caused by neuropathic pain, and intrathecal injection is the most effective route of administration.


Assuntos
Analgésicos/administração & dosagem , Isoxazóis/administração & dosagem , Neuralgia/tratamento farmacológico , Animais , Modelos Animais de Doenças , Esquema de Medicação , Temperatura Alta , Inflamação , Injeções Intraperitoneais , Injeções Espinhais , Masculino , Manejo da Dor , Medição da Dor , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Nervos Espinhais/cirurgia
12.
J Headache Pain ; 15: 42, 2014 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-24950698

RESUMO

BACKGROUND: To investigate the possible association between the serotonin transporter gene (5-HTTLPR) and rs 25531 polymorphism and the susceptibility and the pain severity in Trigeminal Neuralgia patients. METHODS: A total of 244 TN patients and 280 age and sex matched healthy volunteer were recruited. 5-HTTLPR and rs 25531 genotyping were performed. All patients received the carbamazepine treatment and the treatment response was evaluated at 6 months. RESULTS: The genotype distribution of 5-HTTLPR between TN patients and controls were significantly different. The TN Patients had a higher prevalence of short-short genotype than controls. The short-short genotype carriers are also significantly associated with higher pain severity and poorer carbamazepine treatment response compared to the long-long genotype carriers. In contrast, the rs 25531 polymorphism was not associated with the susceptibility to TN, neither with the pain severity and the treat response to carbamazepine. CONCLUSION: The 5-HTTLPR polymorphism is associated with the susceptibility to TN and pain severity of TN.


Assuntos
Dor/diagnóstico , Dor/genética , Polimorfismo Genético/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Índice de Gravidade de Doença , Neuralgia do Trigêmeo/diagnóstico , Neuralgia do Trigêmeo/genética , Adulto , Idoso , Suscetibilidade a Doenças/diagnóstico , Suscetibilidade a Doenças/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/epidemiologia , Neuralgia do Trigêmeo/epidemiologia
13.
PLoS One ; 9(3): e89149, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24598860

RESUMO

This study was designed to investigate the anti-inflammatory and anti-nociceptive activity of the methanol extract from the aerial part of Phlomis younghusbandii (MEAP) and to explore the possible related mechanisms. Anti-inflammatory effects of MEAP were evaluated by using the ear edema test induced by dimethylbenzene and vascular permeability test induced by acetic acid. Anti-nociceptive activities of MEAP were evaluated by the chemical nociception in models of acetic acid-induced writhing and formalin-induced hind paw licking, and by the thermal nociception in hot plate tests. Mechanisms of MEAP activities also were explored by evaluating expression levels of TNF-α, IL-6 and iNOS induced by LPS using real-time fluorogenic PCR and expression of COX-2 using Western blotting and an open-field test. The results indicated that the MEAP administered orally could significantly decrease ear edema induced by dimethylbenzene and increase vascular permeability induced by acetic acid. Additionally, the nociceptions induced by acetic acid and formalin were significantly inhibited. The anti-nociceptive effect could not be decreased by naloxone in the formalin test, and MEAP did not affect the normal autonomic activities of mice. Expression levels of pro-inflammatory cytokines (TNF-α, IL-6, iNOS) induced by LPS were decreased obviously by treatment with MEAP. Furthermore, COX-2 expression in the spinal dorsal horns of the pain model mice induced by formalin was significantly down-regulated by MEAP. In conclusion, MEAP has significant anti-inflammatory and antinociceptive activities, and the mechanisms may be related to the down-regulated expression of TNF-α, IL-6, iNOS and COX-2.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Phlomis/química , Componentes Aéreos da Planta/química , Extratos Vegetais/farmacologia , Analgésicos/isolamento & purificação , Animais , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Indometacina/farmacologia , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Metanol/química , Camundongos Endogâmicos ICR , Morfina/farmacologia , Nociceptividade/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Solventes/química , Corno Dorsal da Medula Espinal/efeitos dos fármacos , Corno Dorsal da Medula Espinal/enzimologia , Fator de Necrose Tumoral alfa/metabolismo
14.
Tumour Biol ; 35(6): 5213-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24510348

RESUMO

Propofol is one of the most commonly used intravenous anesthetic agents during cancer resection surgery. It can influence proliferation, motility, and invasiveness of cancer cells in vitro and in vivo. However, the role of the propofol in the lung cancer cells remains unclear. In this study, we demonstrated the effects of propofol on the proliferation and the apoptosis of lung cancer cell H460 by using colony formation assay and flow cytometry. Propofol also decreased tumor size and weight in established xenografted tumors. Furthermore, propofol-induced endoplasmic reticulum (ER) stress was determined by Western blot.


Assuntos
Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Propofol/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/patologia
15.
Exp Biol Med (Maywood) ; 236(12): 1427-36, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22075552

RESUMO

Obesity is a major risk factor for coronary artery disease, but its impact on anesthetic-induced cardioprotective actions is unexplored. We tested whether obesity inhibits anesthetic sevoflurane-induced preconditioning and whether this effect is mediated via the AMP-activated protein kinase (AMPK) signaling pathway. Sprague-Dawley rats were fed a high-fat (HF, 45% kcal as fat) or low-fat (LF, 10% kcal as fat) diet for 12 weeks. HF-fed rats developed metabolic disturbances including visceral obesity, hyperinsulinemia, hyperleptinemia and dyslipidemia. HF- or LF-fed rats subjected to 25 min of myocardial ischemia followed by 120 min of reperfusion were assigned to the following groups: control, sevoflurane preconditioning, sevoflurane plus AMPK inhibitor ara-A or AMPK activator A769662 alone. Infarct size was similar between the two control groups. Sevoflurane preconditioning significantly reduced infarct size in LF-fed rats but failed to induce cardioprotection in HF-fed rats. Phosphorylation of AMPK and endothelial nitric oxide synthase, as well as myocardial nitrite and nitrate, were also increased by sevoflurane preconditioning in LF-fed rats but not in HF-fed rats. Pretreatment with ara-A inhibited phosphorylation of AMPK and reversed sevoflurane preconditioning-induced cardioprotection in LF-fed rats, whereas it had no effects in HF-fed rats. In addition, sevoflurane preconditioning failed to enhance reactive oxygen species (ROS) generation in the myocardium of HF-fed rats compared with LF-fed rats. Direct activation of AMPK with A769662 equally increased phosphorylation of AMPK and reduced infarct size in both LF- and HF-fed rats. The results suggest that diet-induced obesity suppresses sevoflurane preconditioning-induced cardioprotective action, probably due to a diminished effect of sevoflurane preconditioning on activation of the ROS-mediated AMPK signaling pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/fisiologia , Anestésicos Inalatórios/farmacologia , Precondicionamento Isquêmico Miocárdico , Éteres Metílicos/farmacologia , Traumatismo por Reperfusão Miocárdica/enzimologia , Obesidade/complicações , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Dieta Hiperlipídica , Masculino , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/metabolismo , Nitratos/metabolismo , Óxido Nítrico Sintase/metabolismo , Nitritos/metabolismo , Obesidade/etiologia , Fosforilação , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Sevoflurano , Transdução de Sinais
16.
Clin Exp Pharmacol Physiol ; 38(11): 747-54, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21824173

RESUMO

1. Animal studies suggest that propofol protects against endotoxaemia-induced lung and kidney injury. Upregulation of aquaporin expression in lung tissue mediates these effects, but the mechanism of action in the kidney is unclear. The present study examined the protective effects of propofol on endotoxaemia-induced acute kidney injury in rats. 2. A rat model of endotoxaemia was established using lipopolysaccharide (LPS). We determined the effects of 10% propofol administration 1 h before, during and 1 h after LPS-induced endotoxaemia on expression of aquaporin (AQP)-2, tumour necrosis factor (TNF)-α, intercellular adhesion molecule (ICAM)-1, caspase 3, Bcl-2 and Bax using reverse transcription-polymerase chain reaction, western blotting and immunocytochemistry. Renal morphology, superstructure, apoptosis and function were also assessed. 3. Normal renal tubular structure was seen in the propofol pretreated group, but LPS treatment resulted in changes to renal tissue morphology. Propofol treatment improved renal function in LPS-treated rats. Pretreatment with propofol 1 h before LPS normalized urine and serum osmolality, serum creatinine and blood urea nitrogen to control levels. Lipopolysaccharide downregulated expression of AQP-2 and downregulated the expression of ICAM-1 and TNF-α. These effects were reversed by propofol treatment. Lipopolysaccharide reduced the Bcl2 : Bax ratio and induced renal cell apoptosis and these effects were reduced by propofol treatment. Overall, propofol pretreatment had greater effects than concurrent treatment or propofol administration after LPS induction of endotoxaemia. 4. In conclusion, propofol pretreatment protected renal function in a rat model of endotoxaemia. Further studies are necessary to confirm this effect in other experimental models and in humans.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Endotoxemia/tratamento farmacológico , Propofol/farmacologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Injúria Renal Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Aquaporinas/biossíntese , Aquaporinas/genética , Nitrogênio da Ureia Sanguínea , Caspase 3/biossíntese , Caspase 3/genética , Creatinina/sangue , Regulação para Baixo/genética , Endotoxemia/induzido quimicamente , Endotoxemia/genética , Endotoxemia/patologia , Molécula 1 de Adesão Intercelular/biossíntese , Molécula 1 de Adesão Intercelular/genética , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Lipopolissacarídeos , Masculino , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima , Proteína X Associada a bcl-2/biossíntese , Proteína X Associada a bcl-2/genética
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