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1.
BMC Musculoskelet Disord ; 20(1): 423, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31510985

RESUMO

BACKGROUND: Percutaneous kyphoplasty (PKP) can effectively treat osteoporotic vertebral compression fractures (OVCFs). Although satisfactory clinical outcomes can be achieved, bone cement leakage remains a primary complication of PKP. Previous studies have found many high risk factors for bone cement leakage into the spinal canal; however, less attention to the posterior wall morphologies of different vertebral bodies may be one reason for the leakage. Here, we investigated the effect of posterior vertebral wall morphology in OVCF patients on bone cement leakage into the spinal canal during PKP. METHODS: Ninety-eight OVCF patients with plain computed tomography (CT) scans and three-dimensional (3D) reconstruction images from T6 to L5 were enrolled. 3D-CT and multiplanar reconstructions (MPR) were used to measure the concave posterior vertebral wall depth (PVWCD) and the corresponding midsagittal diameter of the nonfractured vertebral body (VBSD), and the PVWCD/VBSD ratio was calculated. All subjects were divided into the thoracic or lumbar groups based on the location of the measured vertebrae to observe the value and differences in the PVWCD between both groups. The differences in PVWCD and PVWCD/VBSD between the thoracic and lumbar groups were compared. Three hundred fifty-seven patients (548 vertebrae) who underwent PKP within the same period were also divided into the thoracic and lumbar groups. The maximal sagittal diameter (BCSD), the area of the bone cement intrusion into the spinal canal (BCA), and the spinal canal encroachment rate (BCA/SCA × 100%) were measured to investigate the effect of the thoracic and lumbar posterior vertebral wall morphologies on bone cement leakage into the spinal canal through the Batson vein during PKP. RESULTS: The PVWCDs gradually deepened from T6 to T12 (mean, 4.6 mm); however, the values gradually became shallower from L1 to L5 (mean, 0.6 mm). The PVWCD/VBSD ratio was approximately 16% from T6 to T12 and significantly less at 3% from L1 to L5 (P < 0.05). The rate of bone cement leakage into the spinal canal through the Batson vein was 10.1% in the thoracic group and 3.7% in the lumbar group during PKP. In the thoracic group, the BCSD was 3.1 ± 0.5 mm, the BCA was 30.2 ± 3.8 mm2, and the BCA/SCA ratio was 17.2 ± 2.0%. In the lumbar group, the BCSD was 1.4 ± 0.3 mm, the BCA was 14.8 ± 2.2 mm2, and the BCA/SCA ratio was 7.4 ± 1.0%. The BCSD, BCA and BCA/SCA ratio were significantly higher in the thoracic group than in the lumbar group (P < 0.05). CONCLUSIONS: The PVWCD in the middle and lower thoracic vertebrae can help reduce bone cement leakage into the spinal canal by enabling avoiding bone cement distribution over the posterior 1/6 of the vertebral body during PKP. The effect of the difference between the thoracic and lumbar posterior vertebral wall morphology on bone cement leakage into the spinal canal through the Batson vein in OVCF patients during PKP is one reason that the rate of bone cement leakage into the thoracic spinal canal is significantly higher than that into the lumbar spinal canal.


Assuntos
Cimentos Ósseos/efeitos adversos , Corpos Estranhos/epidemiologia , Cifoplastia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Canal Medular/lesões , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/etiologia , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Humanos , Imageamento Tridimensional , Cifoplastia/métodos , Vértebras Lombares/anatomia & histologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Canal Medular/irrigação sanguínea , Canal Medular/diagnóstico por imagem , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/anatomia & histologia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Veias
2.
J Pharmacol Exp Ther ; 367(3): 473-482, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30228113

RESUMO

Hepatofibrosis can progress to cirrhosis and hepatocellular carcinoma (HCC). Prevention, stabilization, and reversal of disease progression are vital for patients with hepatofibrosis, and identifying the risk factors for hepatofibrosis is urgently needed. In this study, we examined the activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the fibrotic livers of HCC patients (n = 88) and comparied these results with activities in patients with normal livers (n = 74). A fibrosis-carcinoma rat model was used to study the activity of ADH in fibrosis and HCC and the relationship between innate ADH activity and the extent of hepatofibrosis or HCC. Substantial interindividual variations were found in the activities of ADH and ALDH in normal livers. The activity levels of total ADH, ADHI, and ADHII in fibrotic livers were significantly higher than those in normal livers (P < 0.001), whereas the activity of ALDH was slightly greater. The positive rates of ADHI and ADHII were 84.1% and 77.3%, respectively; the areas under the receiver operator characteristics (ROC) curve were 0.943 and 0.912, respectively. For the rat model compared with controls, ADH activity in liver was significantly increased at the fibrotic and HCC stages, and no significant difference was noted between ADH activity in the liver at these two stages. The innate activity of ADH in serum was well correlated with the extent of hepatofibrosis as indicated by Masson area%, Ki67+%, proliferating cell nuclear antigen +%, and GST-p average density at fibrotic stage but not at HCC stage. A higher level of activity of ADH is a risk factor for hepatofibrogenesis and might be a prevention target for hepatofibrosis.


Assuntos
Álcool Desidrogenase/metabolismo , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Fígado/metabolismo , Fígado/patologia , Adulto , Idoso , Aldeído Desidrogenase/metabolismo , Aldeído Oxirredutases/metabolismo , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Isoenzimas/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Ratos , Ratos Sprague-Dawley
3.
J Pharmacol Exp Ther ; 365(2): 398-407, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29467309

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common types of primary liver cancer and the third most frequent cause of cancer death worldwide. Diethylnitrosamine (DEN) is one of the recognized risk factors for hepatocarcinogenesis likely due to CYP2E1-mediated metabolic activation. However, CYP2E1-mediated DEN metabolic activity in non-neoplastic liver tissue from HCC patients has not been determined; the role of CYP2E1 activity, in particular CYP2E1 constitutive activity and CYP2E1 inhibited activity, with respect to the hepatocarcinogenesis induced by DEN is not yet clear. Herein, we determined CYP2E1-mediated DEN metabolic activity in non-neoplastic liver tissue from HCC patients and found that CYP2E1-mediated DEN metabolic activity was significantly elevated with a 43.3% positive rate, and clinicopathologic parameters did not affect the activity. Then, using a Sprague-Dawley rat liver tumor model induced by DEN, the relationship between CYP2E1 constitutive/inhibited activity and hepatocarcinogenesis was explored. The results showed that the CYP2E1 constitutive activity was strongly correlated with tumor incidence and severity of liver tumorigenesis (nodule numbers and size), whereas inhibition of CYP2E1 activity decreased hepatocyte proliferation, liver injury, and liver carcinogenesis in the presence of DEN. In conclusion, the higher CYP2E1 activity would lead to an increased incidence of HCC as a result of CYP2E1-mediated DEN activation. Therefore, higher CYP2E1 activity might be a risk factor for HCC induced by DEN.


Assuntos
Carcinogênese/induzido quimicamente , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/patologia , Citocromo P-450 CYP2E1/metabolismo , Dietilnitrosamina/farmacologia , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia , Animais , Carcinogênese/efeitos dos fármacos , Inibidores do Citocromo P-450 CYP2E1/farmacologia , Feminino , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Ratos , Ratos Sprague-Dawley
4.
Mol Carcinog ; 57(10): 1371-1382, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29917271

RESUMO

Hepatofibrosis is an important susceptibility factor for hepatocarcinogenesis. However, only a handful of cases of hepatofibrosis will develop into hepatocellular carcinoma (HCC). As cytochrome P450 2E1 (CYP2E1) is involved in the metabolism and activation of many known environmental toxicants and procarcinogens, this enzyme may play a role in the development of hepatocarcinogenesis subsequent to hepatofibrosis. Herein, we evaluated whether higher CYP2E1 activity is a risk factor for the development of hepatocarcinogenesis from hepatofibrosis. CYP2E1 activity in fibrotic tissues from 72 HCC patients and in normal liver tissues from 59 control subjects was determined along with the severity of hepatofibrosis in hepatocarcinogenesis patients. Similarly, using a rat diethylnitrosamine-induced hepatocarcinogenesis model, CYP2E1 activity at the hepatofibrosis and hepatocarcinogenesis stages was determined, the correlation between CYP2E1 activity at the hepatofibrosis stage and hepatocarcinogenesis was explored, and the impact of inhibition of CYP2E1 activity on hepatocarcinogenesis was studied. The results showed that while CYP2E1 activity in HCC patients with underlying hepatofibrosis was increased, the severity of hepatofibrosis did not correlate with CYP2E1 activity. In the rat hepatocarcinogenesis model, unexpectedly, CYP2E1 activity was found to decrease from hepatofibrosis to hepatocarcinogenesis. Importantly, however, hepatofibrotic rats with higher CYP2E1 activity developed a more severe form of HCC. Moreover, inhibition of CYP2E1 activity could decrease the occurrence and development of HCC in rats. In conclusion, higher CYP2E1 activity may be a risk factor for hepatocarcinogenesis from hepatofibrosis, which raises the possibility of screening patients with hepatofibrosis for CYP2E1 activity to better estimate their risk for hepatocarcinogenesis.


Assuntos
Carcinogênese/patologia , Carcinoma Hepatocelular/patologia , Citocromo P-450 CYP2E1/metabolismo , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Adulto , Animais , Carcinogênese/induzido quimicamente , Carcinogênese/metabolismo , Carcinoma Hepatocelular/enzimologia , Dietilnitrosamina , Feminino , Humanos , Cirrose Hepática/enzimologia , Neoplasias Hepáticas/enzimologia , Masculino , Pessoa de Meia-Idade , Ratos Sprague-Dawley , Fatores de Risco
5.
Neural Regen Res ; 17(8): 1703-1710, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35017417

RESUMO

The currently recommended management for acute traumatic spinal cord injury aims to reduce the incidence of secondary injury and promote functional recovery. Elevated intraspinal pressure (ISP) likely plays an important role in the processes involved in secondary spinal cord injury, and should not be overlooked. However, the factors and detailed time course contributing to elevated ISP and its impact on pathophysiology after traumatic spinal cord injury have not been reviewed in the literature. Here, we review the etiology and progression of elevated ISP, as well as potential therapeutic measures that target elevated ISP. Elevated ISP is a time-dependent process that is mainly caused by hemorrhage, edema, and blood-spinal cord barrier destruction and peaks at 3 days after traumatic spinal cord injury. Duraplasty and hypertonic saline may be promising treatments for reducing ISP within this time window. Other potential treatments such as decompression, spinal cord incision, hemostasis, and methylprednisolone treatment require further validation.

6.
Oncotarget ; 8(68): 112199-112210, 2017 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-29348818

RESUMO

Hepatofibrosis, which leads to cirrhosis and eventual hepatocellular carcinoma, is a common response to chronic toxin-mediated liver injury. Nitrosamines are potent hepatotoxic agents that cause necrosis and subsequent fibrosis in the liver as a result of cytochrome P450 2E1 (CYP2E1)-dependent metabolism, which generates toxic metabolites that form adducts with nucleic acids, leading to hepatotoxicity and mutagenesis. Herein, CYP2E1 activity and content were determined in fibrotic liver tissue from patients with hepatocellular carcinoma. The relationship between CYP2E1 innate activity and hepatofibrogenesis was evaluated, the effect of inhibition of CYP2E1 activity on hepatofibrosis was determined in a Sprague-Dawley rat model of diethylnitrosamine-induced hepatofibrosis. The results demonstrated that the CYP2E1 activities in human fibrotic tissues are significantly higher than that in normal liver tissues. In rats treated with diethylnitrosamine, the livers demonstrated various degree of fibrotic changes and collagen deposition in individual rats. The Ishak score, which determines the stage of fibrosis, correlated with CYP2E1 innate activity, with greater fibrosis in rat livers with higher CYP2E1 innate activity. Inhibition of CYP2E1 during diethylnitrosamine treatment decreased hepatofibrosis and there was an inverse correlation between the degree of inhibition and the extent of hepatofibrosis. Therefore, high CYP2E1 activity is a risk factor for hepatofibrogenesis induced by nitrosamines.

7.
Front Pharmacol ; 7: 255, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27588003

RESUMO

Sodium (±)-5-bromo-2-(α-hydroxypentyl) benzoate (BZP) is a potential cardiovascular drug and exerts potent neuroprotective effect against transient and long-term ischemic stroke in rats. BZP could convert into 3-butyl-6-bromo-1(3H)-isobenzofuranone (Br-NBP) in vitro and in vivo. However, the pharmacokinetic profiles of BZP and Br-NBP still have not been evaluated. For the purpose of investigating the pharmacokinetic profiles, tissue distribution, and plasma protein binding of BZP and Br-NBP, a rapid, sensitive, and specific method based on liquid chromatography coupled to mass spectrometry (LC-MS/MS) has been developed for determination of BZP and Br-NBP in biological samples. The results indicated that BZP and Br-NBP showed a short elimination half-life, and pharmacokinetic profile in rats (3, 6, and 12 mg/kg; i.v.) and beagle dogs (1, 2, and 4 mg/kg; i.v.gtt) were obtained after single dosing of BZP. After multiple dosing of BZP, there was no significant accumulation of BZP and Br-NBP in the plasma of rats and beagle dogs. Following i.v. single dose (6 mg/kg) of BZP to rats, BZP and Br-NBP were distributed rapidly into all tissues examined, with the highest concentrations of BZP and Br-NBP in lung and kidney, respectively. The brain distribution of Br-NBP in middle cerebral artery occlusion (MCAO) rats was more than in normal rats (P < 0.05). The plasma protein binding degree of BZP at three concentrations (8000, 20,000, and 80,000 ng/mL) from rat, beagle dog, and human plasma were 98.1-98.7, 88.9-92.7, and 74.8-83.7% respectively. In conclusion, both BZP and Br-NBP showed short half-life, good dose-linear pharmacokinetic profile, wide tissue distribution, and different degree protein binding to various species plasma. This was the first preclinical pharmacokinetic investigation of BZP and Br-NBP in both rats and beagle dogs, which provided vital guidance for further preclinical research and the subsequent clinical trials.

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