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1.
Sci Rep ; 10(1): 6332, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286436

RESUMO

To investigate and establish a reference interval (RI) of neuron-specific enolase (NSE) in southwest China's healthy population by using the laboratory information system database. A total of 86957 periodic health examination individuals of the medical examination center in West China Hospital from 2016 to 2018 were included in the study. We used the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate the outliers, and the normal distribution method and the nonparametric method to estimate the 95% distribution RI. The NSE 95% distribution RI we established in healthy populations in southwest China through normal distribution and nonparametric method were 0-19.64 ng/ml and 0-20.46 ng/ml, respectively. The obtained RIs verification conformed to the standard and was significantly different from the reagent instruction(P < 0.05). The RI established by the nonparametric method was superior to the RI of the normal distribution method and reagent instruction(P < 0.05). We initially established an NSE RI that was suitable for the healthy southwest China population. The Box-Cox conversion combined with the Tukey method and nonparametric method is a reliable and straightforward indirect method for reference interval acquisition, which is suitable for the promotion and application of clinical laboratory.

2.
Metab Brain Dis ; 35(5): 793-807, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32215835

RESUMO

Inflammatory demyelination in the central nervous system (CNS) is a hallmark of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Besides MS disease-modifying therapy, targeting myelin sheath protection/regeneration is currently a hot spot in the treatment of MS. Here, we attempt to explore the therapeutic potential of Bilobalide (BB) for the myelin protection/regeneration in EAE model. The results showed that BB treatment effectively prevented worsening and demyelination of EAE, accompanied by the inhibition of neuroinflammation that should be closely related to T cell tolerance and M2 macrophages/microglia polarization. BB treatment substantially inhibited the infiltration of T cells and macrophages, thereby alleviating the enlargement of neuroinflammation and the apoptosis of oligodendrocytes in CNS. The accurate mechanism of BB action and the feasibility of clinical application in the prevention and treatment of demyelination remain to be further explored.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32088665

RESUMO

Context: Cervical spondylosis (CS) is a very common, age-related, chronic, disc-degeneration condition. Alternative medicine has been widely used to treat neck pain in CS. However, no randomized controlled trials have focused on the effects and safety of percutaneous neuromuscular electrical stimulation (PNMES) for neck-pain relief in patients with CS. Objective: The study aimed to evaluate the effects and safety of PNMES for treating neck pain in patients with cervical spondylosis (CS). Design: The research team designed a two-arm, double-blinded, randomized, sham-controlled trial. Setting: The study was conducted at the People's Hospital of Yan'an in Yan'an, China. Participants: Participants were 124 patients with neck pain from CS at the hospital. Intervention: Participants were randomly divided into an intervention group and a control group in a ratio of 1:1. The intervention group received PNMES (PNMES group), and the control group received sham PNMES for 30 minutes daily 3 times weekly, for 12 weeks. Outcome Measures: The outcome measures included: (1) a visual analog scale (VAS), (2) a test of cervical range of motion (ROM), and (3) the neck disability index (NDI) score. All outcome measurements were measured immediately postintervention and in a follow-up at 4 weeks postintervention. In addition, AEs were also recorded duration the period of treatment. Results: Immediately postintervention and at the follow-up, the PNMES group exhibited decreases in the mean VAS (P < .01) and NDI score (P < .01) that were significantly greater than those of the control group. Additionally, the increase in the mean ROM was significantly higher in the PNMES group than that in the control group, both immediately postintervention and at the follow-up (P < .01). No AEs were found in either group. Conclusions: The results of this study have demonstrated that PNMES is more effective than sham PNMES for neck-pain relief in patients with CS.

4.
CNS Neurosci Ther ; 26(1): 76-89, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31124292

RESUMO

BACKGROUND: Multiple sclerosis is characterized by demyelination/remyelination, neuroinflammation, and neurodegeneration. Cuprizone (CPZ)-induced toxic demyelination is an experimental animal model commonly used to study demyelination and remyelination in the central nervous system. Fasudil is one of the most thoroughly studied Rho kinase inhibitors. METHODS: Following CPZ exposure, the degree of demyelination in the brain of male C57BL/6 mice was assessed by Luxol fast blue, Black Gold II, myelin basic protein immunofluorescent staining, and Western blot. The effect of Fasudil on behavioral change was determined using elevated plus maze test and pole test. The possible mechanisms of Fasudil action were examined by immunohistochemistry, flow cytometry, ELISA, and dot blot. RESULTS: Fasudil improved behavioral abnormalities, inhibited microglia-mediated neuroinflammation, and promoted astrocyte-derived nerve growth factor and ciliary neurotrophic factor, which should contribute to protection and regeneration of oligodendrocytes. In addition, Fasudil inhibited the production of myelin oligodendrocyte glycoprotein antibody and the infiltration of peripheral CD4+ T cells and CD68+ macrophages, which appears to be related to the integrity of the blood-brain barrier. CONCLUSION: These results provide evidence for the therapeutic potential of Fasudil in CPZ-induced demyelination. However, how Fasudil acts on microglia, astrocytes, and immune cells remains to be further explored.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31809961

RESUMO

Individualized therapy involves genetic test of drug metabolism, which provides information about the initial dose and therapeutic drug monitoring for adjusting the subsequent dose. Consequently, toxic side effects are expected to be minimized and therapeutic effects to be maximized. In this study, an ultra-performance liquid chromatography tandem mass spectrometry method that was specific, accurate and sensitive was developed to simultaneously determine azathioprine two metabolites, 6-thioguanine nucleotides (6-TGN) and 6-methyl-mercaptopurine riboside (6-MMPr) in the whole blood lysate. We precipitated the sample by trifluoroacetic acid under the protection of dithiothreitol, with 6-MMPr and 6-TGN being hydrolyzed to produce 6-methymercaptopurine and 6-thioguanine. In the chromatographic separation, Waters ACQUITY BEH C18 (2.1 × 100 mm, 1.7 µm) chromatographic column was applied and gradient elution was conducted with 0.02 mol/L ammonium acetate buffer (which contains 0.3% formic acid) and acetonitrile at a flow rate of 0.4 ml/min. Tandem mass spectrometry in multiple reaction monitoring mode was applied for detection via electrospray ionization source in positive ionization mode. The analyzing process lasted for no more than 2 min. The calibration curve for each metabolite fitted a least squares model (weighed 1/X) from 1.25 to 5000 ng/ml (r2 > 0.99). The ion pairs were detected as 6-MMP m/z 167.07 â†’ 152.15, 6-TG m/z 168.06 â†’ 134.13, and internal standard m/z 171.07 â†’ 137.14. Under the guidance of FDA guidelines for bioanalytical method validation, we carried out validation and obtained satisfactory results. The method was successfully utilized for monitoring the concentrations of each metabolite from 65 affected patients who had received azathioprine maintenance therapy and achieved optimal results.

6.
Trop Med Int Health ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31802572

RESUMO

OBJECTIVE: Tuberculosis (TB) treatment success rates are high in China, but there are still a considerable number of cases who have unfavourable treatment outcomes (UTO). We aimed to determine the proportion of TB patients with UTO and to assess whether baseline characteristics that included glycaemic status [normal fasting blood glucose (FBG), transient hyperglycaemia and diabetes mellitus (DM)] and vitamin D status were associated with UTO. METHOD: Prospective cohort study conducted between November 2015 and July 2016 at six clinics within routine TB services in Jilin province, where persons with TB were consecutively recruited. Data analysis was performed using the chi-squared test and multivariate logistic regression. RESULTS: Of the 306 recruited TB patients, 96 (31.4%) had smear-positive pulmonary TB, 187 (61.1%) had smear-negative pulmonary TB and 23 (7.5%) had extrapulmonary TB (EPTB). Of these, 95 (31.1%) had normal blood glucose, 83 (27.1%) had transient hyperglycaemia and 128 (41.8%) had DM. 227 (74.2%) patients had vitamin D deficiency/severe deficiency. There were 125 (40.8%) patients with UTO of whom the majority were lost to follow-up (57.6%) or not evaluated (28.8%). UTO was significantly associated with smear-negative pulmonary TB (P = 0.009), EPTB (P < 0.001) and DM (P = 0.007). CONCLUSION: The proportion of TB patients with UTO increased with smear-negative pulmonary TB, EPTB and DM. TB programmes need to pay more attention to these issues and ensure intensive patient support to those at risk and early detection of DM.

7.
Neurotox Res ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31721051

RESUMO

The cuprizone (CPZ)-induced demyelination is a relatively reproducible animal model and has been extremely useful for identifying the specific cellular and molecular signals that regulate oligodendrocyte survival and efficiency of oligodendrogenesis and remyelination. Here, we reported the temporal and spatial dynamics of astroglial reaction and immune response in CPZ-induced demyelinating model. CPZ did not induce significant microglia and astrocyte reaction after 2 weeks of feeding. After 4-6 weeks of CPZ feeding, microglia and astrocytes were markedly migrated and accumulated in myelin sheath. Simultaneously, the expression of tight junction protein ZO-1 was declined and the infiltration of CD4+IFNγ+ and CD4+IL-17+ T cells was increased in the brain, accompanied by increased production of IFN-γ and IL-17 in the extract of brain. However, the levels of IFN-γ and IL-17 were reduced, while IL-6 and TNF-α were elevated in the supernatant of splenocytes. At the 4th and 6th weeks of feeding, CPZ caused astrocyte activation and upregulated the expression of BDNF, CNTF, and IGF-II, providing a neurotrophic microenvironment in the brain. At this stage, NG2+ and PDGF-Rα+ oligodendroglia progenitor cells were enhanced in the corpus callosum, but the myelin sheath is still severely lost. Therefore, targeting microglia to improve the inflammatory microenvironment should contribute to the remyelination.

8.
Int Immunopharmacol ; 77: 105929, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31677497

RESUMO

Ethyl pyruvate (EP), a simple derivative of the endogenous energy substrate pyruvate, provides strong anti-inflammatory and anti-oxidative properties. but its role in remyelination has not been explored. In this study, EP efficiently improved the behavioural performance and histological demyelination in cuprizone (CPZ)-induced mouse model. In terms of action, EP treatment enhanced microglia migration, increased the phagocytosis of myelin debris by BV2 microglia and primary microglia, induced cell proliferation and subsequent cell death. At the same time, EP induced microglia to exhibit M2 phenotype, representing decreased iNOS/TNF-α and increased Arg-1/IL-10. In addition, EP decreased microglia enrichment in myelin sheath, and declined TLR4/p-NF-kb/p65 and IL-1ß and IL-6, inhibiting microglia-mediated neuroinflammation. As a result, EP treatment promoted the generation of oligodendrocyte progenitor cells (OPCs) and the differentiation from maturation to mature oligodendrocytes, which may be related to the up-regulation of Sox2. Given these data, we provided the proof-of-experiment that EP should be beneficial in multiple sclerosis or demyelinating lesions. However, further studies on the possibility to use EP as therapeutic application are warranted.

9.
Int Immunopharmacol ; 75: 105819, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31421546

RESUMO

Although several therapies are approved, none promote re-myelination in multiple sclerosis (MS) patients, limiting their ability for sustained recovery. Thus, treatment development in MS has the opportunity to tackle the challenges, including experimental therapies targeting neuroprotection and re-myelination. Here, we provide a novel therapeutic target for Ginkgolide K (GK) that is now becoming a very critical natural compound to treat demyelination and neurodegeneration. GK improves behavioral dysfunction and demyelination in cuprizone (CPZ) model, followed by the migration and enrichment of astrocytes in the corpus callosum. Both in vitro and in vivo experiments demonstrates that GK triggers the upregulation of Nrf2/HO-1 in astrocytes and inhibition of p-NF-kB/p65, which is associated with the outcome of anti-inflammation and anti-oxidation by suppressing the production of IL-6 and TNFα as well as nitric oxide and iNOS in astrocytes. Further findings suggest that IGF/PI3K, but not BDNF, was induced in the corpus callosum after GK treatment, revealing that Nrf2 activation inhibited caspase-3 and apoptosis in O4+ oligodendrocytes possibly through IGF/PI3K signaling molecules. Since the current immunomodulatory therapies for MS have failed to prevent patients from entering the progressive phase of the disease, thus targeting Nrf2 in astrocytes with GK would be an ideal strategy for myelin protection and regeneration.


Assuntos
Astrócitos/efeitos dos fármacos , Ginkgolídeos/farmacologia , Lactonas/farmacologia , Bainha de Mielina/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Somatomedinas/metabolismo , Animais , Astrócitos/metabolismo , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Células Cultivadas , Cuprizona , Citocinas/metabolismo , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/metabolismo , Ginkgolídeos/uso terapêutico , Lactonas/uso terapêutico , Masculino , Camundongos Endogâmicos C57BL
10.
Front Pharmacol ; 10: 766, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354482

RESUMO

Vascular calcification is an important pathogenic process in atherosclerosis (AS); however, its immediate cause is unknown. Our previous study demonstrated that carbonic anhydrase 1 (CA1) stimulates ossification and calcification in ankylosing spondylitis and breast cancer. The current study investigated whether CA1 plays an important role in AS calcification and whether the CA inhibitor methazolamide (MTZ) has a therapeutic effect on AS. We successfully established an AS model by administration of a high-fat diet to apolipoprotein E (ApoE-/-) mice. The treated animals had significantly increased serum levels of high-density lipoprotein cholesterol (HDL-c) and nitric oxide (NO) and decreased serum concentrations of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), interleukin (IL-6), interferon (IFN)-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α), chemokine (C-X-C motif) ligand 1/keratinocyte-derived chemokine (CXCL1/KC), and C-C motif chemokine ligand 2 (CCL2)/monocyte chemoattractant protein 1 (MCP-1). The treated mice also had reduced AS plaque areas and fat accumulation, with no clear calcium deposition in the intima of the blood vessels. CA1 expression was significantly increased in the aortic lesions, particularly in calcified regions, but the expression was dramatically lower in the mice that received MTZ treatment or MTZ preventive treatment. CA1 was also highly expressed in human AS tissues and in rat vascular smooth muscle cells (VSMCs) with ß-glycerophosphate (㒐ß-GP)-induced calcification. Acetazolamide (AZ), a CA inhibitor with a chemical structure similar to MTZ, markedly suppressed calcification and reduced CA1, IL-6, IFN-γ, GM-CSF, and TNF-α expression in cultured VSMCs. Anti-CA1 small interfering ribonucleic acid (siRNA) significantly suppressed calcification, cell proliferation, and migration, promoted apoptosis, and reduced IL-6, IFN-γ, GM-CSF, and TNF-α secretion in cultured VSMCs. These results demonstrated that CA1 expression and CA1-mediated calcification are significantly associated with AS progression. MTZ significantly alleviated AS and suppressed CA1 expression and proinflammatory cytokine secretion, indicating the potential use of this drug for AS treatment.

11.
Am J Transl Res ; 11(2): 1066-1072, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30899406

RESUMO

In spite of a variety of designs for the lumbar interbody fusion cage, there is no consensus on the optimal design so far. Different cage designs may cause different extent of X-ray exposure to visualize the cage positon intraoperatively. In this study, we retrospectively evaluated the X-ray exposure and clinical outcomes of the direction-changeable cage in transforaminal lumbar interbody fusion (TLIF). The patients were divided into the direction-changeable cage group (group A, n=79) and non-direction-changeable cage group (group B, n=84). Intraoperative implantation duration, cage position adjustment times, implantation fluoroscopy times, fluoroscopy exposure time of cage implantation, Oswestry Disability Index (ODI) and visual analogue scale (VAS) scores were recorded before and after operation at the last follow-up. CT scanning was performed to evaluate lumbar fusion. All the patients underwent single-level TLIF and were followed up for 12 to 18 months. In the group A, intraoperative implantation duration, cage position adjustment times, implantation fluoroscopy times, and fluoroscopy exposure time of cage implantation were 6.7 ± 3.6 min, 1.2 ± 0.4 times, 2.5 ± 0.6 times, 7.84 ± 1.83 s, retrospectively. In the group B, these parameters were 11.5 ± 5.9 min, 2.6 ± 1.3 times, 5.8 ± 1.7 times, and 15.31 ± 5.16 s retrospectively, which were higher than those in the non-direction-changeable cage group with statistical significance (P<0.05). In terms of ODI and VAS scores, there was no statistical difference between the two groups before or after operation at the last follow-up (P>0.05). Regarding to the complications, there were 4 cases (4.49%) in the group A, with 3 cases of non-union and 1 case of dural laceration. Eight cases (10.53%) showed complications in the group B, with 7 cases of non-union and 1 case of infection. There was a significant difference between the groups in terms of the complication rate (P<0.05). In conclusion, the direction-changeable cage has merits like lower radiation exposure and fewer complications compared to the non-direction-changeable cage in treating isthmic lumbar spondylolisthesis. Both cages could yield equal clinical outcomes.

12.
Exp Physiol ; 104(6): 876-886, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30811744

RESUMO

NEW FINDINGS: What is the central question of this study? Oligomeric proanthocyanidin has the capacity to alleviate abnormalities in neurological functioning. However, whether oligomeric proanthocyanidin can reduce the progression of demyelination or promote remyelination in demyelinating diseases remains unknown. What is the main finding and its importance? Oligomeric proanthocyanidin can improve cuprizone-induced demyelination by inhibiting immune cell infiltration, reversing overactivated microglia, decreasing the inflammatory cytokines secreted by inflammatory cells and decreasing the production of myelin oligodendrocyte glycoprotein35-55 -specific antibody in the brain. ABSTRACT: Demyelinating diseases of the CNS, including multiple sclerosis, neuromyelitis optica and acute disseminated encephalomylitis, are characterized by recurrent primary demyelination-remyelination and progressive neurodegeneration. In the present study, we investigated the therapeutic effect of oligomeric proanthocyanidin (OPC), the most effective component of grape seed extract, in cuprizone-fed C57BL/6 mice, a classic demyelination-remyelination model. Our results showed that OPC attenuated abnormal behaviour, reduced demyelination and increased expression of myelin basic protein and expression of O4+ oligodendrocytes in the corpus callosum. Oligomeric proanthocyanidin also reduced the numbers of B and T cells, activated microglia in the corpus callosum and inhibited secretion of inflammatory factors. Furthermore, concentrations of myelin oligodendrocyte glycoprotein-specific antibodies were significantly reduced in serum and brain homogenates after OPC treatment. Together, these results demonstrate a potent therapeutic effect for OPC in cuprizone-mediated demyelination and clearly highlight multiple effects of this natural product in attenuating myelin-specific autoantibodies and the inflammatory microenvironment in the brain.

13.
Clin Immunol ; 201: 35-47, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30660624

RESUMO

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system characterized by oligodendrocyte loss and progressive neurodegeneration. The cuprizone (CPZ)-induced demyelination is widely used to investigate the demyelination/remyelination. Here, we explored the therapeutic effects of Hydroxyfasudil (HF), an active metabolite of Fasudil, in CPZ model. HF improved behavioral abnormality and reduced myelin damage in the corpus callosum. Splenic atrophy and myelin oligodendrocyte glycoprotein (MOG) antibody were observed in CPZ model, which were partially restored and obviously inhibited by HF, therefore reducing pathogenic binding of MOG antibody to oligodendrocytes. HF inhibited the percentages of CD4+IL-17+ T cells from splenocytes and infiltration of CD4+ T cells and CD68+ macrophages in the brain. HF also declined microglia-mediated neuroinflammation, and promoted the production of astrocyte-derived brain derived neurotrophic factor (BDNF) and regeneration of NG2+ oligodendrocyte precursor cells. These results provide potent evidence for the therapeutic effects of HF in CPZ-induced demyelination.


Assuntos
1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Doenças Desmielinizantes/tratamento farmacológico , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/uso terapêutico , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Cuprizona , Citocinas/imunologia , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/imunologia , Doenças Desmielinizantes/patologia , Modelos Animais de Doenças , Macrófagos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/patologia
14.
Medicine (Baltimore) ; 98(3): e14137, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30653146

RESUMO

The aim of this study was to investigate the correlation between CYP2C19 genotype and dose-adjusted voriconazole (VCZ) trough concentrations (C0/dose).We analyzed the correlation between CYP2C192(681G>A), CYP2C193(636G>A), and CYP2C1917(-806C>T) genetic polymorphisms and the dose-corrected pre-dose concentration (C0/dose) in 106 South-western Chinese Han patients.The frequencies of variant alleles of CYP2C192, 3, and 17 were 29.7%, 4.25%, and 0.92%. For 49.3% of the VCZ samples, the therapeutic window between 1.5 and 5.5 µg/ml was reached. Following the first dose VCZ measurement, in subsequent samples the proportion of VCZ C0 within the therapeutic window increased, suggesting effective therapeutic drug monitoring (TDM) (P = .001). The VCZ C0 was significantly different (P = .010) between patients with normal metabolism (NMs), intermediate metabolism (IMs), and poor metabolism (PMs). The VZC C0/dose was 12.2 (interquartile range (IQR), 8.33-18.2 µg·ml/kg·day), and 7.68 (IQR, 4.07-16.3 µg·ml/kg·day) in PMs and IMs patients, respectively, which was significantly higher than in NMs phenotype patients (4.68; IQR, 2.51-8.87 µg·ml/kg·day, P = .008 and P = .014).This study demonstrated that the VCZ C0/dose was significantly influenced by the CYP2C19 genotype in South-western Chinese Han patients. In this patient population, more over-exposure was observed in patients with a CYP2C19 genotype associated with poor or intermediate metabolism. CYP2C19 genotype-based dosing combined with TDM will support individualization of VCZ dosing, and potentially will minimize toxicity and maximize therapeutic efficacy.


Assuntos
Antifúngicos/administração & dosagem , Citocromo P-450 CYP2C19/genética , Monitoramento de Medicamentos/métodos , Infecções Fúngicas Invasivas/tratamento farmacológico , Voriconazol/administração & dosagem , Adulto , Alelos , Antifúngicos/sangue , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Coortes , Feminino , Genótipo , Humanos , Infecções Fúngicas Invasivas/genética , Masculino , Pessoa de Meia-Idade , Testes Farmacogenômicos , Fenótipo , Polimorfismo Genético , Estudos Retrospectivos , Voriconazol/sangue
15.
Int Immunopharmacol ; 66: 69-81, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30445309

RESUMO

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system characterized by recurrent and progressive demyelination, neuroinflammation and oligodendrocyte loss. The cuprizone (CPZ) model is characterized by primary and reversible demyelination, accompanied by oligodendrocyte loss and neuroinflammation. In the current study, we explored the efficiency of Bilobalide in the demyelination and remyelination. The results demonstrate that Bilobalide improved behavioral abnormality and promoted remyelination in the corpus callosum by using Luxol Fast Blue, Black Gold II and myelin basic protein (MBP) staining. We for the first time found that CPZ caused the splenic atrophy and induced the formation of myelin oligodendrocyte glycoprotein (MOG) antibody, which was attenuated by Bilobalide. Thus, Bilobalide decreased the loss of O4+ oligodendrocytes possibly through MOG antibody-dependent cell cytotoxicity. Bilobalide also prevented the infiltration of CD4+ T cells, CD68+ macrophages and B220+ B cells within the brain, and reduced the inflammatory microenvironment mediated with Iba1+iNOS+ and Iba1+NF-kB+ microglia after CPZ challenge, accompanied by the inhibition of IL-1ß and IL-6 in the brain. These results identify a potent therapeutic efficiency for Bilobalide and highlight clear pleiotropic effects of the compound beyond specific autoantibody and inflammatory microenvironment in CPZ-mediated demyelination.


Assuntos
Corpo Caloso/efeitos dos fármacos , Ciclopentanos/uso terapêutico , Doenças Desmielinizantes/tratamento farmacológico , Furanos/uso terapêutico , Ginkgolídeos/uso terapêutico , Inflamação/tratamento farmacológico , Esclerose Múltipla/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Oligodendroglia/efeitos dos fármacos , Animais , Autoanticorpos/sangue , Comportamento Animal , Corpo Caloso/fisiologia , Cuprizona , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Imunidade Humoral/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Glicoproteína Mielina-Oligodendrócito/imunologia , Oligodendroglia/fisiologia
16.
Medicine (Baltimore) ; 97(26): e11080, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29952946

RESUMO

BACKGROUND: This study aimed to evaluate the effectiveness and safety of percutaneous neuromuscular electrical stimulation (PNMES) for treating neck pain in patients with cervical spondylosis (CS). METHODS: One hundred and twenty four patients with neck pain of CS were included, and then they were randomly divided into a PNMES group and a control group in a ratio of 1:1. All patients received PNMES or sham PNMES 30 minutes daily, 3 times weekly for 12 weeks. The primary outcome was assessed by the visual analog scale (VAS). The secondary outcomes were evaluated by the cervical range of motion (ROM), neck disability index (NDI) score, as well as the adverse events (AEs). All outcome measurements were measured at the end of 12-week treatment, and 4-week follow-up after treatment. RESULTS: At the end of the 12-week treatment, and 4-week follow-up, the patients receiving PNMES exhibited more decrease in the mean VAS (P < .01), and NDI (P < .01) respectively, compared with the patients receiving sham PNMES. Additionally, the increase in the mean ROM was also significantly higher in the PNMES group than that in the sham PNMES group at the end of the 12-week treatment, and 4-week follow-up, respectively (P < .01). No AEs were found in either group. CONCLUSIONS: The results of this study demonstrated that PNMES is more effective than Sham PNMES for neck pain relief in patients with CS.


Assuntos
Vértebras Cervicais/patologia , Estimulação Elétrica/instrumentação , Cervicalgia/fisiopatologia , Pescoço/fisiopatologia , Espondilose/fisiopatologia , Estimulação Elétrica Nervosa Transcutânea/instrumentação , Adulto , Método Duplo-Cego , Estimulação Elétrica/efeitos adversos , Estimulação Elétrica/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cervicalgia/terapia , Manejo da Dor/métodos , Amplitude de Movimento Articular/fisiologia , Espondilose/terapia , Estimulação Elétrica Nervosa Transcutânea/efeitos adversos , Estimulação Elétrica Nervosa Transcutânea/métodos , Resultado do Tratamento , Escala Visual Analógica
17.
ISA Trans ; 71(Pt 2): 206-214, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28823415

RESUMO

Stochastic resonance (SR) is widely used as an enhanced signal detection method in machinery fault diagnosis. However, the system parameters have significant effects on the output results, which makes it difficult for SR method to achieve satisfactory analysis results. To solve this problem and improve the performance of SR method, this paper proposes an adaptive SR method based on grey wolf optimizer (GWO) algorithm for machinery fault diagnosis. Firstly, the SR system parameters are optimized by the GWO algorithm using a redefined signal-to-noise ratio (SNR) as optimization objective function. Then, the optimal SR output matching the input signal can be adaptively obtained using the optimized parameters. The proposed method is validated on a simulated signal detection and a rolling element bearing test bench, and then applied to the gear fault diagnosis of electric locomotive. Compared with the conventional fixed-parameter SR method, the adaptive SR method based on genetic algorithm (GA-SR) as well as the well-known fast kurtogram method, the proposed method can achieve a greater accuracy. The results indicated that the proposed method has great practical values in engineering.

18.
Sci Rep ; 6: 32827, 2016 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-27601295

RESUMO

In this paper, we present a high quality single-photon source based on the two-level system undergoing rapid adiabatic passage (RAP). A trigger strategy (sweet region) is suggested to optimize the single-photon emission and explain a counter-intuitive phenomenon on the optimal parameters. The RAP strategy of single-photon source is robust against control error and environmental fluctuation.

19.
Sci Rep ; 6: 28959, 2016 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-27353375

RESUMO

In this paper, the nature of the multi-order resonance and coherent destruction of tunneling (CDT) for two-level system driven cross avoided crossing is investigated by employing the emitted photons 〈N〉 and the Mandel's Q parameter based on the photon counting statistics. An asymmetric feature of CDT is shown in the spectrum of Mandel's Q parameter. Also, the CDT can be employed to suppress the spontaneous decay and prolong waiting time noticeably. The photon emission pattern is of monotonicity in strong relaxation, and homogeneity in pure dephasing regime, respectively.

20.
Arch Pathol Lab Med ; 140(1): 75-80, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26717058

RESUMO

CONTEXT: Cardiac troponins have become the gold standard for diagnosing acute myocardial infarction (AMI) in the general population; however, their diagnostic accuracy for hemodialysis (HD) patients presenting with chest pain or dyspnea is uncertain. OBJECTIVE: To examine the diagnostic accuracy of high-sensitivity cardiac troponin T (hs-cTnT) assay for AMI in HD patients. DESIGN: In this prospective study, we enrolled 670 consecutive stable HD patients presenting with chest pain or dyspnea on routine predialysis therapy in the nephrology department. Receiver operating characteristic (ROC) curves were used to examine the diagnostic accuracy of hs-cTnT levels at enrollment in HD patients presenting with chest pain or dyspnea, and the dynamic change in these levels after 3 hours. RESULTS: Acute myocardial infarction was the adjudicated final diagnosis in 12% of HD patients. Among patients with a final diagnosis other than AMI, 97% had a plasma hs-cTnT concentration above the 99th percentile. At the time of enrollment, the area under the ROC curve of hs-cTnT levels for diagnosis of AMI was 0.68 (95% confidence interval [CI], 0.62-0.74; P < .001) with a cutoff value of 107.7 ng/L; the relative change after 3 hours was 0.90 (95% CI, 0.82-0.96, P < .001) with a cutoff value of 24%, and the absolute change was 0.88 (95% CI, 0.82-0.94, P < .001) with a cutoff value of 32.6 ng/L. The prognostic value for 40-day mortality varied with the magnitude of elevation in hs-cTnT levels. CONCLUSIONS: Tracking the dynamic change in hs-cTnT levels during the short term significantly increased this measure's diagnostic accuracy for AMI in HD patients.


Assuntos
Medições Luminescentes/métodos , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Diálise Renal/efeitos adversos , Troponina T/sangue , Adulto , Idoso , Área Sob a Curva , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade
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