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1.
Nanoscale ; 11(46): 22440-22445, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31746893

RESUMO

High-throughput growth of large size transition metal dichalcogenide (TMD) single crystals is an important challenge for their applications in the next generation electronic and optoelectronic integration devices. Here we report the high-throughput growth of submillimeter monolayer TMD single crystals by two-stage space confined chemical vapor deposition, where the nucleation density of TMD crystals is significantly decreased for the growth of large size monolayer crystals by the space confinement effect. Moreover, high-throughput growth of submillimeter TMD crystals is also achieved by stacking the substrates along the perpendicular direction to the flow of the reaction gases. The mobilities of the TMD materials produced in this way are up to 1.2, 17.0 and 25.0 cm2 (V s)-1 for monolayer WS2, WSe2 and MoS2 single crystals, respectively. The results demonstrate that two-stage space confined growth is a highly promising method for high-throughput fabrication of high-quality submillimeter monolayer TMD single crystals, which will pave a new pathway to large-scale production of TMD-based electronic and optoelectronic devices.

2.
Heart Lung ; 48(3): 261-265, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30497796

RESUMO

OBJECTIVE: Growing evidence indicates that both obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) may be closely associated with the prevalence of pulmonary embolism (PE). However, the relationship of overlap syndrome (OS) (coexistence of OSA and COPD) with PE is unclear. The purpose of this study was to investigate whether OS were associated with increased PE prevalence. METHODS: We performed a retrospective chart review of patients who underwent sleep study at Beijing An Zhen Hospital from 2011 to 2014. The association of OS with PE prevalence was estimated by using logistic regression models. RESULTS: In contrast to control patients (neither OSA nor COPD), those subjects with OS had higher odds of PE (OR9.61; 95%CI 4.02-21.31, p < 0.001) with significance persisting after adjusting for covariates (OR 5.66; 95%CI 1.80-16.18, p = 0.004). Meanwhile, patients with OS compared with those with isolated OSA also had significantly higher odds of PE in univariate (OR 4.79; 95%CI 2.04-10.33, p = 0.0007) and adjusted models (OR 3.89; 95%CI 1.27-10.68, p = 0.019). In subgroup analysis, patients with OS had higher odds of PE than control group among male subjects (OR 8.12, 95%CI1.86-31.87, p = 0.007) and patients ≥ 58years (OR 5.50, 95%CI 1.51-18.14, p = 0.012) in multivariable models. Percentage of total sleep time with saturation lower than 90% (T90) ≥ 2.6% was significantly associated with prevalence of PE (OR 4.72, 95%CI1.34-19.83, p = 0.015) in subgroup of patients older than 58. CONCLUSIONS: OS is independently associated with PE prevalence. Longitudinal studies are needed to better understand the relationship with incident PE.

3.
Gut Pathog ; 10: 37, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30214488

RESUMO

Background: Culture-based diagnostic methods cannot achieve rapid and precise diagnoses for the identification of multiple diarrhoeal pathogens (DPs). A high-throughput multiplex genetic detection system (HMGS) was adapted and evaluated for the simultaneous identification and differentiation of infectious DPs and a broad analysis of DP infection aetiology. Results: DP-HMGS was highly sensitive and specific for DP detection compared with culture-based techniques and was similar to singleplex real-time PCR. The uniform level of sensitivity of DP-HMGS for all DPs allowed us to remap the aetiology of acute diarrhoeal infections in Shanghai, correcting incidences of massively underdiagnosed DP species with accuracy approaching that of sequencing-based methods. The most frequent DPs were enteropathogenic Escherichia coli, rotavirus and Campylobacter jejuni. DP-HMGS detected two additional causes of infectious diarrhoea that were previously missed by routine culture-based methods: enterohemorrhagic E. coli and Yersinia enterocolitica. We demonstrated the age dependence of specific DP distributions, especially the distributions of rotavirus, intestinal adenovirus and Clostridium difficile in paediatric patients as well as those of dominant bacterial infections in adults, with a distinct "top 3" pattern for each age group. Finally, the multiplexing capability and high sensitivity of DP-HMGS allowed the detection of infections co-induced by multiple pathogens (approximately 1/3 of the cases), with some DPs preferentially co-occurring as infectious agents. Conclusions: DP-HMGS has been shown to be a rapid, specific, sensitive and appropriate method for the simultaneous screening/detection of polymicrobial DP infections in faecal specimens. Widespread use of DP-HMGS is likely to advance routine diagnostic and clinical studies on the aetiology of acute diarrhoea.

4.
Pain ; 159(2): 273-283, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29112008

RESUMO

Pain sensitization after partial infraorbital nerve transection (p-IONX) in mice not only presents in orofacial region, but also spreads to distant body parts. The roles of toll-like receptor 4 (TLR4) in orofacial pain and the spreading process are still unclear. Here, we found that mice with deficient TLR4 because of Tr4 gene point mutation (C3H/HeJ) or spontaneous deletion (C57BL/10ScNJ) developed tactile allodynia and thermal hyperalgesia in the vibrissal pad in a parallel way to their respective wild types (C3HeB/FeJ or C57BL/6J) after p-IONX. However, allodynia in the hind paw was absent in mice with TLR4 deficiency. Pharmacological antagonism of TLR4 with LPS-RS, administered either intracisternally or intrathecally, abrogated allodynia in the hind paw without affecting the hypersensitivity in the vibrissal pad and hyperalgesia in the hind paw. Although TNF-α expression was upregulated in both the medulla and lumbar cord, the expression of TLR4 downstream molecule MyD88 increased only in the lumbar cord after p-IONX in wild types. By contrast, hind paw hypersensitivity after partial sciatic nerve ligation was significantly attenuated by TLR4 deletion. The hypersensitivity, which did not spread to the vibrissal pad, was accompanied with upregulation of MyD88 in the lumbar cord rather than in the medulla. These results suggest that TLR4 participates in the spread of allodynia component of orofacial pain to distant body sites, but not trigeminal neuropathic pain or the spread of its hyperalgesia component. This study suggests that TLR4 may serve as a potential target for the management of widespread allodynia associated with orofacial pain.


Assuntos
Hiperalgesia/etiologia , Limiar da Dor/fisiologia , Receptor 4 Toll-Like/deficiência , Neuralgia do Trigêmeo/complicações , Análise de Variância , Animais , Feminino , Hiperalgesia/tratamento farmacológico , Ligadura/efeitos adversos , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fator 88 de Diferenciação Mieloide/metabolismo , Medição da Dor , Mutação Puntual/genética , Nervo Isquiático/lesões , Neuropatia Ciática/fisiopatologia , Fatores de Tempo , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/genética , Neuralgia do Trigêmeo/etiologia
5.
Exp Neurol ; 283(Pt A): 29-38, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27240522

RESUMO

Febrile seizures (FSs), the most common type of convulsive events in infants, are closely associated with temporal lobe epilepsy (TLE) in adulthood. It is urgent to investigate how FSs promote epileptogenesis and find the potential therapeutic targets. In the present study, we showed that the phosphorylation of GluN2B Tyr1472 gradually reached peak level at 24h after prolonged FSs and remained elevated during 7days thereafter. IL-1ß treatment alone, which in previous study mimicked the effect of prolonged FSs on adult seizure susceptibility, increased GluN2B Tyr1472 phosphorylation. Both IL-1 receptor antagonist (IL-1Ra) and IL-1R1 deletion were sufficient to reverse the prolonged FSs induced hyper-phosphorylation of GluN2B Tyr1472. GluN2B antagonist ifenprodil showed a wide therapeutic time-window (3days) to reverse the enhanced seizure susceptibility after prolonged FSs or IL-1ß treatment. Our study demonstrated that GluN2B phosphorylation at Tyr1472 site mediated by the transient increase of IL-1ß was involved in the enhanced adult seizure susceptibility after prolonged FSs, implicating GluN2B-containing NMDAR is a new potential drug target with a wide therapeutic time window to prevent epileptogenesis in patients with infantile FSs.


Assuntos
Suscetibilidade a Doenças/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Convulsões Febris/terapia , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Eletrochoque/efeitos adversos , Agonistas de Aminoácidos Excitatórios/toxicidade , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Comportamento Exploratório/efeitos dos fármacos , Humanos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Interleucina-1beta/uso terapêutico , Ácido Caínico/toxicidade , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Piperidinas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Receptores Tipo I de Interleucina-1/genética , Convulsões Febris/etiologia , Convulsões Febris/metabolismo
6.
Arch Oral Biol ; 70: 47-54, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27328150

RESUMO

Previous studies have demonstrated that low-magnitude, high-frequency (LMHF) mechanical vibrations (LM<1g; HF<20-90Hz) can benefit bone formation. However, the underlying mechanism is unclear. In this study, MC3T3-E1 cells were exposed to LMHF vibrations of different magnitudes to assess the effect of vibrations on ß-catenin expression, which regulates osteogenic differentiation. LMHF vibrations (0.14-0.49g)increased cell viability, alkaline phosphatase activity and calcification in a dose (magnitude)-dependent manner. The level of ß-catenin expression increased 1.6-fold using 0.49g LMHF vibrations compared to the control. Similarly, the use of LMHF vibrations increased Runx2 protein expression with the greatest effect at 0.32g exposure. The levels of BMP2, Osterix and Cyclin D1 protein expression were also elevated and were expressed highest in cells exposed to 0.49g. mRNA expression levels of these proteins were similarly affected by exposure to LMHF vibrations. These results suggest that LMHF vibrations promote cell viability and osteogenic differentiation of osteoblasts by up-regulating related proteins and genes. The activation of ß-catenin plays an important role in the effect of microvibration exposure in osteoblasts.


Assuntos
Osteoblastos/metabolismo , beta Catenina/biossíntese , Fosfatase Alcalina/metabolismo , Animais , Western Blotting , Calcificação Fisiológica , Linhagem Celular , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Camundongos , Osteoblastos/citologia , Osteogênese/fisiologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Regulação para Cima , Vibração , beta Catenina/genética
7.
J Neuroinflammation ; 13(1): 163, 2016 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-27342775

RESUMO

BACKGROUND: It is known that histamine participates in pain modulation. However, the effect of central histamine on neuropathic pain is not fully understood. Here, we report a critical time window for the analgesic effect of central histamine in the partial sciatic nerve ligation model of neuropathic pain. METHODS: Neuropathic pain was induced by partial sciatic nerve ligation (PSL) in rats, wild-type (C57BL/6J) mice and HDC(-/-) (histidine decarboxylase gene knockout) and IL-1R(-/-) (interleukin-1 receptor gene knockout) mice. Histidine, a precursor of histamine that can increase the central histamine levels, was administered intraperitoneally (i.p.). Histidine decarboxylase (HDC) enzyme inhibitor α-fluoromethylhistidine was administered intracerebroventricularly (i.c.v.). Histamine H1 receptor antagonist mepyramine and H2 receptor antagonist cimetidine were given intrathecally (i.t.) and intracisternally (i.c.). Withdrawal thresholds to tactile and heat stimuli were measured with a set of von Frey hairs and infrared laser, respectively. Immunohistochemistry and Western blot were carried out to evaluate the morphology of microglia and IL-1ß production, respectively. RESULTS: Histidine (100 mg/kg, i.p.) administered throughout days 0-3, 0-7, or 0-14 postoperatively (PO) alleviated mechanical allodynia and thermal hyperalgesia in the hindpaw following PSL in rats. Intrathecal histamine reversed PSL-induced thermal hyperalgesia in a dose-dependent manner and intracisternal histamine alleviated both mechanical allodynia and thermal hyperalgesia. Moreover, α-fluoromethylhistidine (i.c.v.) abrogated the analgesic effect of histidine. However, histidine treatment initiated later than the first postoperative day (treatment periods included days 2-3, 4-7, and 8-14 PO) did not show an analgesic effect. In addition, histidine treatment initiated immediately, but not 3 days after PSL, inhibited microglial activation and IL-1ß upregulation in the lumbar spinal cord, in parallel with its effects on behavioral hypersensitivity. Moreover, the inhibitory effects on pain hypersensitivity and spinal microglial activation were absent in HDC(-/-) mice and IL-1R(-/-) mice. H1 receptor antagonist mepyramine (200 ng/rat i.t. or i.c.), but not H2 receptor antagonist cimetidine (200, 500 ng/rat i.t. or 500 ng/rat i.c.), blocked the effects of histidine on pain behavior and spinal microglia. CONCLUSIONS: These results demonstrate that central histamine is analgesic within a critical time window in the PSL model of neuropathic pain via histamine H1 receptors. This effect may partly relate to the inhibition of microglial activation and IL-1ß production in the spinal cord following nerve injury.


Assuntos
Analgésicos/uso terapêutico , Sistema Nervoso Central/metabolismo , Histidina/uso terapêutico , Neuropatia Ciática , Analgésicos/farmacologia , Animais , Sistema Nervoso Central/efeitos dos fármacos , Cimetidina/farmacologia , Modelos Animais de Doenças , Vias de Administração de Medicamentos , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores Histamínicos H2/farmacologia , Histidina/farmacologia , Histidina Descarboxilase/deficiência , Histidina Descarboxilase/genética , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Limiar da Dor/efeitos dos fármacos , Pirilamina/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Interleucina-1/deficiência , Receptores de Interleucina-1/genética , Neuropatia Ciática/tratamento farmacológico , Neuropatia Ciática/metabolismo , Neuropatia Ciática/patologia
8.
Neurochem Res ; 41(10): 2719-2727, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27350579

RESUMO

Long-term metformin treatment reduces the risk of stroke. However, the effective administration pattern and indications of metformin on acute cerebral ischemia are unclear. To investigate the neuroprotective treatment duration and dosage of metformin on focal ischemia mice and the association of neuroprotection with 5'-adenosine monophosphate-activated protein kinase (AMPK) regulations, male C57BL/6 mice were subjected to permanent or transient middle cerebral artery occlusion (MCAO) and metformin of 3, 10 and 30 mg/kg was intraperitoneally injected 1, 3 or 7 days prior to MCAO, or at the onset, or 1, 3 or 6 h after reperfusion, respectively. Infarct volumes, neurological deficit score, cell apoptosis, both total and phosphorylated AMPK expressions were assessed. Results showed that prolonged pretreatment to 7 days of metformin (10 mg/kg) significantly ameliorated brain infarct, neurological scores and cell apoptosis in permanent MCAO mice. Shorter (3 days or 1 day) or without pretreatment of metformin was not effective, suggesting a pretreatment time window. In transient MCAO mice, metformin showed no neuroprotection even with pretreatment. The expressions of total and phosphorylated AMPK were sharply decreased with effective metformin pretreatments in ischemic brains. Our data provided the first evidence that in acute ischemic injury, a 7-days pretreatment duration of 10 mg/kg metformin is necessary for its neuroprotection, and metformin may not be beneficial in the cases of blood reperfusion.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Metformina/farmacologia , Fármacos Neuroprotetores/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Apoptose/fisiologia , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/tratamento farmacológico , Masculino , Camundongos Endogâmicos C57BL , Neuroproteção/efeitos dos fármacos
9.
Pharmacology ; 97(5-6): 251-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26901681

RESUMO

BACKGROUND AND METHODS: Pregabalin alleviates stimulus-evoked neuropathic pain (NeuP) in some pain patients and rodents in models of painful neuropathies. But it is not known if pregabalin can also alleviate spontaneous NeuP. Sciatic and saphenous neurectomy in rats elicits spontaneous self-mutilation of the denervated hindpaw, a behavior that models spontaneous NeuP. We tested if pregabalin (20 or 30 mg/kg/day; twice daily, per os) for 7 days before denervation, or 42 days thereafter, can suppress this behavior. RESULTS: Compared with the vehicle, pregabalin administered in both treatment regimens markedly and significantly delayed autotomy onset and suppressed its levels for weeks after treatment cessation. CONCLUSIONS: At doses known to effectively suppress stimulus-evoked pain in rats, pregabalin can prevent development of spontaneous NeuP and suppress it postoperatively.


Assuntos
Analgésicos/administração & dosagem , Analgésicos/uso terapêutico , Neuralgia/tratamento farmacológico , Neuralgia/prevenção & controle , Pregabalina/administração & dosagem , Pregabalina/uso terapêutico , Administração Oral , Animais , Comportamento Animal/efeitos dos fármacos , Masculino , Ratos Sprague-Dawley , Nervo Isquiático/lesões
10.
Amino Acids ; 48(2): 365-74, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26374642

RESUMO

The potential role of protein O-GlcNAcylation in cancer has been studied extensively, and the spread of cancer cells to regional lymph nodes is the first step in the dissemination of breast cancer. However, the correlation between O-GlcNAcylation and lymphatic metastasis in breast cancer remains elusive. In this study, we demonstrated that the overall O-GlcNAcylation as well as O-GlcNAc transferase (OGT) tends to decrease in response to the augmentation of lymph node metastasis (LNM) in invasive ductal breast carcinomas (IDCs). Although accumulating evidence indicates that individual O-GlcNAcylation may be important in the pathogenesis of breast cancer, O-GlcNAcylated proteins in IDCs are still largely unexplored. Herein, O-GlcNAcylated proteins of IDCs were chemo-enzymatically enriched and identified via liquid chromatography combined with tandem mass spectrometry. In total, 155 O-GlcNAcylated proteins were determined, of which 41 were only observed in LNM tissues, while 40 were unique in non-LNM samples. Gene ontology analysis showed that O-GlcNAc is primarily a nucleocytoplasmic post-translational modification, and most enriched functional terms were related to cancer development in both metastatic and non-metastatic IDCs. Moreover, several O-GlcNAcylated proteins involved in glycolysis and its accessory pathway were identified from LNM and non-LNM groups, respectively. These results indicate that the O-GlcNAcylation statuses of individual proteins were independent of the overall O-GlcNAcylation levels of metastatic and non-metastatic IDCs. Aberrant O-GlcNAc modification of these proteins might be associated with LNM progression.


Assuntos
Acetilglucosamina/metabolismo , Carcinoma Ductal de Mama/patologia , Metástase Linfática/patologia , N-Acetilglucosaminiltransferases/metabolismo , Cromatografia Líquida , Feminino , Glicosilação , Humanos , Linfonodos/patologia , Processamento de Proteína Pós-Traducional , Proteômica , Espectrometria de Massas em Tandem
11.
Pain ; 157(3): 740-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26588696

RESUMO

Clinical studies show that chronic pain can spread to adjacent or even distant body regions in some patients. However, little is known about how this happens. In this study, we found that partial infraorbital nerve transection (p-IONX) in MRL/MPJ mice induced not only marked and long-lasting orofacial thermal hyperalgesia but also thermal hyperalgesia from day 3 postoperatively (PO) and tactile allodynia from day 7 PO in bilateral hind paws. Pain sensitization in the hind paw was negatively correlated with facial thermal hyperalgesia at early but not late stage after p-IONX. After a rapid activation of c-Fos, excitability and excitatory synaptic neurotransmission in lumbar dorsal horn neurons were elevated from day 3 and day 7 PO, respectively. In addition, microglial activation after p-IONX transmitted caudally from the Vc in the medulla to lumber dorsal horn in a time-dependent manner. Inhibition of microglial activation by minocycline at early but not late stage after p-IONX postponed and attenuated pain sensitization in the hind paw. These results indicate that neuropathic pain after p-IONX in MRL/MPJ mice spreads from the orofacial region to distant somatic regions and that a rostral-caudal transmission of central sensitization in the spinal cord is involved in the spreading process of pain hypersensitivity.


Assuntos
Hiperalgesia/patologia , Nervo Maxilar/lesões , Neuralgia/patologia , Medição da Dor , Animais , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Masculino , Camundongos , Neuralgia/etiologia , Neuralgia/metabolismo , Técnicas de Cultura de Órgãos , Medição da Dor/métodos , Limiar da Dor/fisiologia
12.
J Nanosci Nanotechnol ; 15(3): 2088-93, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26413624

RESUMO

In present study, we aimed at investigating the expression level of microRNA and the related gene which might be involved in retinopathy of prematurity. Neonatal SD rats were randomly divided into 2 groups, the first one having rats with NH4CI induced acidosis, as experimental group. We observed retinal vascular morphology and hyperplasia using microscope, for both experimental and control groups, in days 3, 5, 8, 10, 13 and 20 after birth. Total RNA from the retinal samples was obtained at each time point. MiR-126 and VEGF mRNA were measured by quantitative RT-PCR, while immunohistochemistry was applied to analyze the protein expression level of VEGF. Results showed significant differential expression of miR-126 in the acidosis-induced neonatal rats at day 8 when compared with control rats. The VEGF mRNA and protein quantitative results also demonstrated corresponding differential expression among the experimental and control groups. Results from this study revealed that VEGF mRNA and protein expression levels increased in day 10, while the expression of miR-126 was remarkably down-regulated. It is thus suggested that the miR-126 plays an important role in the development of acidosis-induced retinopathy.


Assuntos
Acidose/patologia , Regulação da Expressão Gênica , MicroRNAs/genética , Retina/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Animais Recém-Nascidos , Proliferação de Células , Feminino , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Neovascularização Patológica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Retina/fisiopatologia , Vasos Retinianos/patologia , Vasos Retinianos/fisiopatologia , Retinopatia da Prematuridade/genética , Retinopatia da Prematuridade/metabolismo , Retinopatia da Prematuridade/patologia , Retinopatia da Prematuridade/fisiopatologia
13.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 44(3): 315-22, 2015 May.
Artigo em Chinês | MEDLINE | ID: mdl-26350013

RESUMO

OBJECTIVE: To investigate whether the waveform of electrical stimulus affects the antiepileptic effect of focal low-frequency stimulation (LFS). METHODS: The antiepileptic effects of the LFS in sine, monophase square and biphase square waves were investigated in hippocampal kindled mice, respectively. RESULTS: Compared to the control group, sine wave focal LFS (30 s) inhibited seizure stages (2.85 ± 0.27 vs 4.75 ± 0.12, P<0.05), lowered incidence of generalized seizures (53.6% vs 96.5%, P<0.01) and reduced afterdischarge durations [(16.2 2 ± 1.69)s vs (30.29 ± 1.12)s, P<0.01] in hippocampal kindled mice, while monophase or biphase square wave LFS (30 s) showed no antiepileptic effect. Monophase square LFS (15 min) inhibited seizure stages (3.58 ± 0.16, P<0.05) and incidence of generalized seizures (66.7%,P<0.01), but had weaker inhibitory effect on hippocampal afterdischarge durations than sine wave LFS. In addition, pre-treatment and 3 s but not 10 s post-treatment with sine wave LFS resulted in suppression of evoked seizures (P<0.05 or P<0.01). CONCLUSION: The antiepileptic effect of LFS is dependent on its waveform. Sine wave may be optimal for closed-loop LFS treatment of epilepsy.


Assuntos
Anticonvulsivantes , Estimulação Elétrica , Hipocampo/fisiopatologia , Excitação Neurológica , Convulsões/fisiopatologia , Animais , Epilepsia , Camundongos
14.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 40(4): 392-7, 2015 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-25931218

RESUMO

OBJECTIVE: To analyze the features of MRI and pathology for phyllodes tumor of the breast and to improve the diagnosis level. METHODS: The MRI data of 11 patients with phyllodes tumor of the breast were analyzed. The MRI features included morphology, signal intensity on pre-enhanced T1WI, appearance of dynamic contrast enhancement (DCE-MRI) and the type of time-signal intensity curve (TIC). RESULTS: The pathologic diagnosis for the 11 phyllodes tumor included 6 benign, 2 borderline and 3 malignant. All of the 11 tumors showed well-defined margins and lobulated lump. The signal intensity of tumor was lower (4 cases) than or equal (7 cases) to that of normal breast tissue on T1-weighted images. On T2-weighted images, 5 cases presented variegated appearance, 6 cases displayed high signal. Four cases showed patchy high signal on T1WI and T2WI. All patients underwent DCE-MRI and showed uneven enhancement. There were 7 cases in type I of TIC and 4 cases in type II. CONCLUSION: The imaging findings of phyllodes tumor on MR is characteristic but not specific, the final diagnosis still depends on the histopathologic examination.


Assuntos
Neoplasias da Mama/diagnóstico , Imagem por Ressonância Magnética , Tumor Filoide/diagnóstico , Meios de Contraste , Feminino , Humanos
15.
Neurosci Lett ; 588: 95-100, 2015 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-25562630

RESUMO

Febrile seizures (FSs) are the most common type of convulsions in childhood and complex FSs represent an increased risk for development of temporal lobe epilepsy. The aim of this study was to analyze the anticonvulsant effects of carnosine, an endogenous dipeptide composed of alanine and histidine, on hyperthermia induced seizure in immature mice. Injection of carnosine significantly increased the latency and decreased the duration of FSs in a dose-dependent manner. In addition, histidine had similar effects on FSs as carnosine. The protective effect of carnosine or histidine was completely abolished by α-fluoromethylhistidine (α-FMH), a selective and irreversible histidine decarboxylase inhibitor, or in histidine decarboxylase deficient (HDC-KO) mice. Peripheral carnosine administration increased the level of carnosine, histidine and histamine in the cortex and hippocampus of mice pups, but decreased glutamate contents in the cortex and hippocampus. These results indicate that carnosine can protect against FSs in mice pups through its conversion to histamine, suggesting that it may serve as an efficient anti-FSs drug in the future.


Assuntos
Anticonvulsivantes/uso terapêutico , Carnosina/uso terapêutico , Convulsões Febris/prevenção & controle , Animais , Anticonvulsivantes/metabolismo , Carnosina/metabolismo , Córtex Cerebral/metabolismo , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Histamina/metabolismo , Histidina/metabolismo , Histidina/uso terapêutico , Histidina Descarboxilase/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Convulsões Febris/metabolismo , Ácido gama-Aminobutírico/metabolismo
16.
Zhonghua Nei Ke Za Zhi ; 54(12): 1037-40, 2015 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-26887371

RESUMO

OBJECTIVE: To investigate the clinical characteristics of pulmonary hypertension(PH) in patients with chronic obstructive pulmonary disease(COPD) and study the related risk factors. METHODS: Patients with stable COPD enrolled in this study, undergoing examinations including full pulmonary function tests (PFT), 6-minute walk distance (6MWD), Exercise Oxyhemoglobin, Saint. George's respiratory questionnaire (SGRQ) and transthoracic echocardiography. Pulmonary artery systolic pressure(sPAP) ≥36 mmHg (1 mmHg=0.133 kPa) was defined as PH. RESULTS: A total of 251 patients were finally evaluable in this study. The frequency of PH was 55.4% (139/251) in patients with stable COPD. Significant differences were seen between patients with PH and without PH respectively in the following factors (mean P<0.05): proportion of age ≥ 60 years (69.8% vs 57.1%), forced expiratory volume in one second (FEV(1)) (% predicted) [(47.5±8.2)% vs (61.2±10.2)% and (49.8±7.9)% vs (66.4±11.3)%], sPAP [(41.9±9.1) mmHg vs (28.2±3.2) mmHg], exercise oxyhemoglobin desaturation [(-5.5±3.2)% vs (-2.2±1.2)%], 6MWD [(316.0±55.2)m vs (390.0±75.2)m]. The following variables were negatively correlated with sPAP : 6MWD (r=-0.330, P=0.003), FEV(1)(% predicted) (r=-0.210, P=0.024 and r=-0.130, P=0.012, respectively). The following variables were positively correlated with sPAP: age (r= 0.560, P= 0.031), exercise oxyhemoglobin desaturation> 3% (r= 0.540, P= 0.001). Logistic regression test has showed that age ≥ 60 years, exercise oxygen desaturation>3%, FEV(1) (% predicted) <50%, 6MWD <350 m were risk factors for PH in COPD. CONCLUSION: The incidence of PH in COPD increases with age, yet the performance of lung function and the activity of endurance decrease in elder patients. Sixty years or older, exercise oxygen desaturation> 3%, FEV(1) (% predicted) <50%, 6MWD <350 m are risk factors of PH in COPD. Echocardiography or right heart catheterization when needed should be considered to confirm the diagnosis.


Assuntos
Hipertensão Pulmonar/complicações , Doença Pulmonar Obstrutiva Crônica/complicações , Fatores Etários , Ecocardiografia , Feminino , Volume Expiratório Forçado , Humanos , Hipertensão Pulmonar/fisiopatologia , Incidência , Masculino , Oxigênio , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função Respiratória , Fatores de Risco , Inquéritos e Questionários
17.
Autophagy ; 10(10): 1801-13, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25126734

RESUMO

Transient cerebral ischemia leads to endoplasmic reticulum (ER) stress. However, the contributions of ER stress to cerebral ischemia are not clear. To address this issue, the ER stress activators tunicamycin (TM) and thapsigargin (TG) were administered to transient middle cerebral artery occluded (tMCAO) mice and oxygen-glucose deprivation-reperfusion (OGD-Rep.)-treated neurons. Both TM and TG showed significant protection against ischemia-induced brain injury, as revealed by reduced brain infarct volume and increased glucose uptake rate in ischemic tissue. In OGD-Rep.-treated neurons, 4-PBA, the ER stress releasing mechanism, counteracted the neuronal protection of TM and TG, which also supports a protective role of ER stress in transient brain ischemia. Knocking down the ER stress sensor Eif2s1, which is further activated by TM and TG, reduced the OGD-Rep.-induced neuronal cell death. In addition, both TM and TG prevented PARK2 loss, promoted its recruitment to mitochondria, and activated mitophagy during reperfusion after ischemia. The neuroprotection of TM and TG was reversed by autophagy inhibition (3-methyladenine and Atg7 knockdown) as well as Park2 silencing. The neuroprotection was also diminished in Park2(+/-) mice. Moreover, Eif2s1 and downstream Atf4 silencing reduced PARK2 expression, impaired mitophagy induction, and counteracted the neuroprotection. Taken together, the present investigation demonstrates that the ER stress induced by TM and TG protects against the transient ischemic brain injury. The PARK2-mediated mitophagy may be underlying the protection of ER stress. These findings may provide a new strategy to rescue ischemic brains by inducing mitophagy through ER stress activation.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Estresse do Retículo Endoplasmático , Fármacos Neuroprotetores/uso terapêutico , Tapsigargina/uso terapêutico , Tunicamicina/uso terapêutico , Ubiquitina-Proteína Ligases/metabolismo , Animais , Apoptose/efeitos dos fármacos , Isquemia Encefálica/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Glucose/deficiência , Camundongos , Fármacos Neuroprotetores/farmacologia , Oxigênio/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Tapsigargina/farmacologia , Tunicamicina/farmacologia
18.
CNS Neurosci Ther ; 20(10): 883-92, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24990156

RESUMO

INTRODUCTION: The upregulation of Nav1.8 in primary afferents plays a critical role in the development and persistence of neuropathic pain. The mechanisms underlying the upregulation are not fully understood. AIMS: The present study aims to investigate the regulatory effect of histamine on the expression of Nav1.8 in primary afferent neurons and its involvement in neuropathic pain. RESULTS: Histamine at 10(-8) M increased the expression of Nav1.8 in cultured DRG neurons. This effect could be blocked by H2 receptor antagonist cimetidine or famotidine, but not by H1 receptor antagonist pyrilamine or dual H3 /H4 antagonist thioperamide. Peri-sciatic administration of histamine increased Nav1.8 expression in the sciatic nerve and L4/L5 DRG neurons in a dose-dependent manner, accompanied with remarkable mechanical allodynia and heat hyperalgesia in the ipsilateral hindpaw. Famotidine but not pyrilamine or thioperamide inhibited Nav1.8 upregulation and pain hypersensitivity. In addition, famotidine (40 mg/kg, i.p.) not only suppressed autotomy behavior in the rat neuroma model of neuropathic pain but also attenuated mechanical allodynia and thermal hyperalgesia following partial sciatic nerve ligation. Moreover, famotidine inhibited Nav1.8 upregulation in the neuroma and ligated sciatic nerve. CONCLUSIONS: Our findings indicate that histamine increases Nav1.8 expression in primary afferent neurons via H2 receptor-mediated pathway and thereby contributes to neuropathic pain. H2 receptor antagonists may potentially be used as analgesics for patients with neuropathic pain.


Assuntos
Agonistas dos Receptores Histamínicos/farmacologia , Histamina/farmacologia , Canal de Sódio Disparado por Voltagem NAV1.8/metabolismo , Receptores Histamínicos H2/metabolismo , Ciática/patologia , Células Receptoras Sensoriais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Animais , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Famotidina/farmacologia , Gânglios Espinais/citologia , Histamina/uso terapêutico , Agonistas dos Receptores Histamínicos/uso terapêutico , Antagonistas dos Receptores Histamínicos H2/farmacologia , Hiperalgesia/tratamento farmacológico , Hiperalgesia/fisiopatologia , Masculino , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
19.
Nat Commun ; 5: 3334, 2014 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-24566390

RESUMO

The role of the histamine H3 receptor (H3R) in cerebral ischaemia/reperfusion (I/R) injury remains unknown. Here we show that H3R expression is upregulated after I/R in two mouse models. H3R antagonists and H3R knockout attenuate I/R injury, which is reversed by an H3R-selective agonist. Interestingly, H1R and H2R antagonists, a histidine decarboxylase (HDC) inhibitor and HDC knockout all fail to compromise the protection by H3R blockade. H3R blockade inhibits mTOR phosphorylation and reinforces autophagy. The neuroprotection by H3R antagonism is reversed by 3-methyladenine and siRNA for Atg7, and is diminished in Atg5⁻/⁻ mouse embryonic fibroblasts. Furthermore, the peptide Tat-H3R(CT414-436), which blocks CLIC4 binding with H3Rs, or siRNA for CLIC4, further increases I/R-induced autophagy and protects against I/R injury. Therefore, H3R promotes I/R injury while its antagonism protects against ischaemic injury via histamine-independent mechanisms that involve suppressing H3R/CLIC4 binding-activated autophagy, suggesting that H3R inhibition is a therapeutic target for cerebral ischaemia.


Assuntos
Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Histamina/metabolismo , Receptores Histamínicos H3/metabolismo , Animais , Proteína 5 Relacionada à Autofagia , Canais de Cloreto/genética , Canais de Cloreto/metabolismo , Agonistas dos Receptores Histamínicos/farmacologia , Antagonistas dos Receptores Histamínicos H3/farmacologia , Histidina Descarboxilase/genética , Histidina Descarboxilase/metabolismo , Masculino , Camundongos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Receptores Histamínicos H3/genética
20.
J Cereb Blood Flow Metab ; 34(2): 275-83, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24192637

RESUMO

Acidosis is one of the key components in cerebral ischemic postconditioning that has emerged recently as an endogenous strategy for neuroprotection. We set out to test whether acidosis treatment at reperfusion can protect against cerebral ischemia/reperfusion injury. Adult male C57BL/6 J mice were subjected to 60-minute middle cerebral arterial occlusion followed by 24-hour reperfusion. Acidosis treatment by inhaling 10%, 20%, or 30% CO2 for 5 or 10 minutes at 5, 50, or 100 minutes after reperfusion was applied. Our results showed that inhaling 20% CO2 for 5 minutes at 5 minutes after reperfusion-induced optimal neuroprotection, as revealed by reduced infarct volume. Attenuating brain acidosis with NaHCO3 significantly compromised the acidosis or ischemic postconditioning-induced neuroprotection. Consistently, both acidosis-treated primary cultured cortical neurons and acute corticostriatal slices were more resistant to oxygen-glucose deprivation/reperfusion insult. In addition, acidosis inhibited ischemia/reperfusion-induced apoptosis, caspase-3 expression, cytochrome c release to cytoplasm, and mitochondrial permeability transition pore (mPTP) opening. The neuroprotection of acidosis was inhibited by the mPTP opener atractyloside both in vivo and in vitro. Taken together, these findings indicate that transient mild acidosis treatment at reperfusion protects against cerebral ischemia/reperfusion injury. This neuroprotection is likely achieved, at least partly, by inhibiting mPTP opening and mitochondria-dependent apoptosis.


Assuntos
Acidose , Dióxido de Carbono/farmacologia , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão , Bicarbonato de Sódio/sangue , Acidente Vascular Cerebral , Acidose/sangue , Acidose/induzido quimicamente , Acidose/tratamento farmacológico , Animais , Isquemia Encefálica/sangue , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/fisiopatologia , Masculino , Camundongos , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/fisiopatologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/fisiopatologia
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