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Eun-Joo Shin Yunsung Nam Thu-Hien Thi Tu Yong Kwang Lim Myung-Bok Wie Dae-Joong Kim Ji Hoon Jeong Hyoung-Chun Kim 《Archives of toxicology》2016,90(4):937-953
We investigated whether protein kinase C (PKC) is involved in trimethyltin (TMT)-induced neurotoxicity. TMT treatment (2.8 mg/kg, i.p.) significantly increased PKCδ expression out of PKC isozymes (i.e., α, βI, βII, δ, and ?) in the hippocampus of wild-type (WT) mice. Consistently, treatment with TMT resulted in significant increases in cleaved PKCδ expression. Genetic or pharmacological inhibition (PKCδ knockout or rottlerin) was less susceptible to TMT-induced seizures than WT mice. TMT treatment increased glutathione oxidation, lipid peroxidation, protein oxidation, and levels of reactive oxygen species. These effects were more pronounced in the WT mice than in PKCδ knockout mice. In addition, the ability of TMT to induce nuclear translocation of Nrf2, Nrf2 DNA-binding activity, and upregulation of γ-glutamylcysteine ligase was significantly increased in the PKCδ knockout mice and rottlerin (10 or 20 mg/kg, p.o. × 6)-treated WT mice. Furthermore, neuronal degeneration (as shown by nuclear chromatin clumping and TUNEL staining) in WT mice was most pronounced 2 days after TMT. At the same time, TMT-induced inhibition of phosphoinositol 3-kinase (PI3K)/Akt signaling was evident, thereby decreasing phospho-Bad, expression of Bcl-xL and Bcl-2, and the interaction between phospho-Bad and 14-3-3 protein, and increasing Bax expression and caspase-3 cleavage were observed. Rottlerin or PKCδ knockout significantly protected these changes in anti- and pro-apoptotic factors. Importantly, treatment of the PI3K inhibitor LY294002 (0.8 or 1.6 µg, i.c.v.) 4 h before TMT counteracted protective effects (i.e., Nrf-2-dependent glutathione induction and pro-survival phenomenon) of rottlerin. Therefore, our results suggest that down-regulation of PKCδ and up-regulations of Nrf2-dependent glutathione defense mechanism and PI3K/Akt signaling are critical for attenuating TMT neurotoxicity. 相似文献
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四川龙胆系龙胆科龙胆属植物 ,生于山野坡林下及水湿地带主要分布于云南、四川、贵州等地 ,一年生草本植物 ,高 2 .5 8m;茎直立 ,黄绿色 ;叶稍带肉质 ,稍尖 ,两面有光泽 ;根部有很多分枝[1,2 ] 。龙胆科植物在《神农本草经》中作为中品收载[3 ] ,具有泻胆肝火 ,清热燥湿的功效。用于骨间寒热 ,湿热黄疸 ,寒湿脚气 ,咽喉痛 ,目赤 ,口苦 ,阴部湿痒等证 [4]。在临床上广泛应用 ,自 1 91 3年 Ashahina等从该属植物的根部分离得到苦味成分龙胆苦碱( gentiopicrin)以来[5] ,对该属植物的化学成分已有大量研究报道 ,主要含生物碱 ,黄酮类 ,酚类 ,… 相似文献
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Ki-Won Kim Kee-Yong Ha Jun-Seok Lee Suk-Woo Nam Young-Kyun Woo Tae-Hong Lim Howard S. An 《The spine journal》2009,9(4):323-329
Background contextIt was recently demonstrated that the postnatal transition from a notochordal to a fibrocartilaginous nucleus pulposus (NP) is accomplished exogenously by chondrocytes migrating from hyaline cartilage end plates (CEs) into the ectopic notochordal NP region. Although our previous in vivo studies showed evidences for the migration of CE chondrocyte from hyaline CEs into the notochordal NP, it is unknown whether CE chondrocytes of the intervertebral disc (IVD) really have a motile property. In addition, the effect of notochordal cells on this property has not been elucidated.PurposeThe purpose of this in vitro study was to demonstrate whether CE chondrocytes of the IVD are capable of migration, and whether there is any biological link between notochordal cells and CE chondrocytes that may regulate the CE chondrocyte migration.Study design/settingIn vitro cell migration assays were performed using rat IVDs.MethodsNotochordal cells and chondrocytes were obtained from the NP and CE tissues, respectively, and were cultured separately. The different numbers of notochordal cells and the supernatant (conditioned medium) that contained soluble factors produced by notochordal cells were used to demonstrate their effects on the migration of CE chondrocytes. Bovine serum albumin (BSA) and lysophosphatidic acid (LPA) were used as negative and positive controls, respectively.ResultsCompared with BSA, LPA, notochordal cells (N=4×, 2×, 1×, and 0.5×105), and its conditioned media (unconcentrated and fivefold concentrated) significantly increased migration of CE chondrocytes (p<.05 in all comparisons). Particularly, notochordal cells and its conditioned media increased migration in a number- and concentration-dependent manner, respectively.ConclusionsThis study demonstrates that CE chondrocytes of the IVD are capable of migration and that soluble factors produced by notochordal cells stimulate the migration. These results provide a plausible explanation to the question of why CE chondrocytes of the IVD migrate into the ectopic NP region during the natural transition from the notochordal to fibrocartilaginous NP. 相似文献
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Namita Wagle Nha Nam Do Jack Yu James L. Borke 《American journal of orthodontics and dentofacial orthopedics》2005,127(6):655-661
BACKGROUND: The periodontal ligament (PDL) is a soft tissue interposed between the tooth and the alveolar bone. It is responsible for transmission of forces in vivo; this promotes bone remodeling. The purpose our study was to use fractal analysis to quantify the complex morphology of the PDL-bone interface. METHODS: We used Scion Image (Scion Corp, Frederick, Md) and Benoit fractal analysis (Tru Soft International, St. Petersburg, Fla) programs to calculate the fractal dimension of the PDL-bone interface in rats via the box-counting method. Rats in the experimental groups received an initial force of 0.1N or 0.5N with customized springs for 6 hours. RESULTS: Our studies showed an increase in normal fractal dimension at the root apices of the rats' maxillary molars. We also found evidence that the fractal dimension varies along the entire root length from the apex to the cementoenamel junction. CONCLUSIONS: Mechanical loading might lead to an increase in fractal dimension at the PDL-bone interface apart from mechanisms of bone cell directed remodeling. These changes in fractal dimension are proportional to loading and could provide a new parameter for force determination in orthodontic tooth movement. 相似文献
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CM Reid M. Nelson P. Beckinsale P. Ryan LMH Wing LJ Beilin MA Brown GLR Jennings CI Johnston J. Marley JJ McNeil TO Morgan J. Shaw ID Steven MJ West 《Clinical and experimental pharmacology & physiology》1997,24(5):370-373
1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial. 相似文献
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Ischemic necrosis of the entire femoral head and rapidly destructive hip disease: potential causative relationship 总被引:6,自引:0,他引:6
Kyung Nam Ryu Eui Jong Kim Myung Chul Yoo Yong Koo Park David J. Sartoris Donald Resnick 《Skeletal radiology》1997,26(3):143-149
Objective. Rapidly destructive hip disease (RDHD) is an uncommon disorder of the hip that has been considered a disease of unknown cause
and distinct from ischemic necrosis of the femoral head. The objective of this study was to investigate ischemic necrosis
of the femoral head as one potential cause of RDHD. Design and patients. In 600 patients who underwent MR imaging of the hip, 20 cases of ischemic necrosis involving the entire femoral head in 18
patients (3%) were retrospectively studied with routine radiography and MR imaging. All patients had surgically confirmed
ischemic necrosis of the femoral head. Results and conclusions. All patients showed rapid destruction of the femoral head on routine radiography and MR imaging as compared with the gradual
onset of clinical symptoms. Plain radiographs showed several bone fragments at the inferomedial aspect of the femoral head
(75%), acetabular erosions (55%), eccentric depression at the lateral articular surface of the femoral head conforming to
the adjacent acetabulum (35%), and mild osteoarthritis (15%). Bone sclerosis was often present at sites of impaction between
the femoral head and the acetabulum. MR imaging showed marked distention of the joint capsule in all cases. In 14 of 20 cases,
the contents of the joint space showed predominantly low or intermediate signal intensity on T1- and T2-weighted images. Ischemic
necrosis involving the entire femoral head may represent one of the causes of RDHD. 相似文献