3.Protective effects of resveratrol on lipopolysaccharide-induced inflammatory toxicity in primary cortical astrocyte cultures.
Ben LIU ; Qing CHEN ; Jiang GUO ; Hao ZHOU ; Bin WANG ; Jin LI ; Shou-yi YU
Journal of Southern Medical University 2011;31(12):2052-2056
OBJECTIVETo study the anti-inflammatory effect of resveratrol in primary cortical astrocyte cultures stimulated by lipopolysaccharide (LPS) and explore the underlying mechanism of this protective effect.
METHODSThe astrocytes were cultured in the presence of resveratrol at different concentrations for 12 h followed by stimulation with lipopolysaccharide (LPS) for another 24 h. Lactate dehydrogenas (LDH) leakage volumes were detected, the cytotoxicity of resveratrol was examined using cell counting kit-8 (CCK-8), the release of NO was measured by Griess reaction, and the expression levels of TNF-α and iNOS were measured using ELISA and Western blotting respectively.
RESULTSThe purity of the astrocytes cultured in vitro was (95.49∓1.86)%. LPS treatment increased LDH leakage and reduced the survival rate of the astrocytes, resulting also in significantly increased NO and TNF-α release and iNOS protein expressions. Within the concentration range of 5-50 µmol/L, resveratrol effectively improved the survival rate of the astrocytes and decreased LDH leakage with a dose-response relationship. Only 25 and 50 µmol/L resveratrol produced obvious inhibitory effect on NO and TNF-α release and iNOS expression, while 5 µmol/L resveratrol had no such effects.
CONCLUSIONHigh concentration of resveratrol can inhibit the release of inflammatory mediators and improve the inflammation injury induced by LPS in astrocytes, the mechanism of which may involve the inhibition of iNOS/NO expression pathway.
Animals ; Animals, Newborn ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Astrocytes ; cytology ; Cerebral Cortex ; cytology ; Inflammation ; chemically induced ; Lipopolysaccharides ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Primary Cell Culture ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism
4.Progress on pharmacokinetic study of antibody-drug conjugates.
Jian-jun GUO ; Ran GAO ; Teng-fei QUAN ; Ling-yu ZHU ; Ben SHI ; Yong-yue ZHAO ; Jing ZHU ; Meng-sha LI ; Hai-zhi BU
Acta Pharmaceutica Sinica 2015;50(10):1203-1209
Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.
Antibodies, Monoclonal
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pharmacokinetics
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Cytotoxins
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pharmacokinetics
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Humans
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Immunoconjugates
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pharmacokinetics
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Neoplasms
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drug therapy
5.Treatment of osteonecrosis of the femoral head by using greater trochanteric bone flap pedicled with double blood vessels
De-Wei ZHAO ; Wei-Ming WANG ; Ben-Fie WANG ; Yao ZHANG ; Tie-Nan WANG ; Lin GUO ; Qiang SUN ; Jian-Min LU ; Xiao-Guang YU ;
Chinese Journal of Microsurgery 2000;0(03):-
Objective To evaluated the clinical results of treatment of osteonecrosis of the femoral head(ONFH)by using bone flap pedicled with gluteal muscle branch of ascending branch of the lateral femo- ral circumflex artery and transversal branch of the lateral femoral cireumflex artery.Methods Bone flap pedicled with double blood vessels was applied in 32 hips with stageⅡandⅢONFH according to the Fieat staging system.Fifteen hips were in stageⅡand 17 were in stageⅢ.All patients were followed up for a mean of 25 months(range,15-38 months)and were assessed clinically and radiologically according to Harris sco- ring.Selective digital subtraction angiography was performed in 9 cases to confirm the blood reconstruction of femoral head.Results Two cases underwent total hip replacement postoperatively.Preoperative and postop- erative Harris score were 55 and 88.6.Clinical success rate was 90.6% and radiological success rate was 87.5%.DSA demonstrated blood supply was found reconstruction in the necrotic femoral head.Conclusion Transplantation of bone flap pedicled with gluteal muscle branch of ascending branch of the lateral femoral circumflex artery and transversal branch of the lateral femoral circumflex artery appears to be a effective treat- ment for osteonecrosis of the femoral head,blood supply of bone flap and blood reconstruction of femoral head was confirmed.Early clinical results were satisfied.
6.Transcatheter aortic valve implantation assisted with microcatheter: a new method to avoid coronary artery obstruction.
Xiang CHEN ; Guo-Jun CHU ; Fei-Yu WANG ; Yu-Feng ZHU ; Ben ZHANG ; Xian-Xian ZHAO ; Yong-Wen QIN ; Jun-Bo GE
Chinese Medical Journal 2015;128(6):740-744
BACKGROUNDLack of fluoroscopic landmarks can make valve deployment more difficult in patients with absent aortic valve (AV) calcification. The goal of this article was to evaluate the feasibility and effectiveness of transcatheter implantation of a valved stent into the AV position of a goat, assisted with a microcatheter which provides accurate positioning of coronary artery ostia to help valved stent deployment.
METHODSThe subjects were 10 healthy goats in this study. A microcatheter was introduced into the distal site of right coronary artery (RCA) through femoral artery sheath. A minimal thoracic surgery approach was used to access the apex of the heart. The apex of the left ventricle was punctured; a delivery catheter equipped with the valved stent was introduced over a stiff guidewire into the aorta arch. We could accurately locate the RCA ostia through the microcatheter placed in the RCA under fluoroscopy. After correct valve position was confirmed, the valved stent was implanted after rapid inflation of the balloon. The immediate outcome of the function of the valved stents was evaluated after implantation.
RESULTSAll ten devices were successfully implanted into the AV position of the goats. Immediate observation after the procedure showed that the valved stents were in the desired position after implantation by angiography, echocardiogram. No obstruction of coronary artery ostia occurred, and no moderate to severe aortic regurgitation was observed.
CONCLUSIONSWhen the procedure of transcatheter implantation of a balloon-expandable valved stent into the AV position of goats is assisted with microcatheter positioning coronary artery ostia, the success rate of operation can be increased in those with noncalcified AV.
Animals ; Aortic Valve ; surgery ; Female ; Goats ; Heart Valve Prosthesis Implantation ; methods ; Male ; Transcatheter Aortic Valve Replacement ; methods
7.Effect of superior retinacular artery damage on osteonecrosis of the femoral head.
Bao-yi LIU ; De-wei ZHAO ; Xiao-bing YU ; Lei YANG ; Lin GUO ; Ben-jie WANG
Chinese Medical Journal 2013;126(20):3845-3850
BACKGROUNDOsteonecrosis of the femoral head (ONFH) is the result of dysfunctional blood supply, but associations between specific damaged arteries, imaging changes and clinical sign require more understanding. We investigated characteristics of ONFH that pertain to blood supply, imaging appearance, and clinical feature to judge the prognosis of ONFH.
METHODSClinical data were collected for 92 patients (118 hips) with ONFH, including gender, age, duration of pain (from initial clinical presentation to arthroplasty), cause, stage, and classification. Magmatic resonance imaging and X-rays were obtained of all patients to diagnose ONFH. The sizes of lesions were classified by necrotic index. The location of necrosis was classified as Type A, B, or C using the grading system by magmatic resonance imaging and X-rays. All hips were imaged with digital subtraction angiography to visualize their blood-supply characteristics. Hips were divided into groups based on the source artery for femoral head damage: superior retinacular artery (S), inferior retinacular artery (I), and combined superior and inferior retinacular arteries (S+I). Via digital subtraction angiography, imaging appearances and clinical data in three groups were compared.
RESULTSONFH was caused by damage in either the superior or inferior retinacular artery, or both, in all of 118 hips. The group with only inferior retinacular artery damage reported longer hip pain duration than the other groups. The probability of the lesion extending laterally to the acetabular edge in group S was much more than it in group I. Necrosis indices of the patients in S and S+I were higher than those in group I.
CONCLUSIONSONFH associated with interruption of the superior and inferior retinacular arteries in this study. When the former alone was damaged, the necrosis of the volume was larger, the risk of femoral head collapse was higher and the time from initial clinical presentation to arthroplasty was shorter.
Adult ; Aged ; Angiography, Digital Subtraction ; Female ; Femur Head ; diagnostic imaging ; Femur Head Necrosis ; diagnostic imaging ; Humans ; Male ; Middle Aged ; Young Adult
8.Cyclosporine, prednisone, and high-dose immunoglobulin treatment of angioimmunoblastic T-cell lymphoma refractory to prior CHOP or CHOP-like regimen.
Xing-Gui CHEN ; He HUANG ; Ying TIAN ; Cheng-Cheng GUO ; Chao-Yong LIANG ; Yao-Ling GONG ; Ben-Yan ZOU ; Rui-Qing CAI ; Tong-Yu LIN
Chinese Journal of Cancer 2011;30(10):731-738
Angioimmunoblastic T-cell lymphoma (AITL) is a rare, distinct subtype of peripheral T-cell lymphoma, possessing an aggressive course and poor prognosis with no standard therapy. Twelve patients who have failed at least two initial CHOP or CHOP-like regimens were enrolled in this study and treated with individualized cyclosporine (CsA), prednisone (PDN), and monthly, high-dose intravenous immunoglobulin (HDIVIG). The dose of CsA was adjusted individually based on the blood trough concentration of CsA and renal function. All patients were examined for response, toxicity and survival. The most significant toxicities (≥ grade 2) were infection (16.7%), renal insufficiency (8.3%), hypertension (8.3%), diabetes (8.3%) and insomnia (16.7%). Discontinuation of treatment occurred in one patient (8.3%) due to grade 3 renal toxicity and subsequent grade 4 pulmonary infection. Treatment-related death was not observed. The overall response rate was 75.0% (complete response, 33.3%; partial response, 41.7%). With a median follow-up of 25.5 months, the median duration of response was 20 months (range, 12 to 49 months) and the median progression-free survival (PFS) was 25.5 months (range, 10 to 56 months). The 2-year PFS rate was 81.5%. Our findings indicate the combination of CsA, PDN and HDIVIG is an effective salvage regimen for refractory or relapsed AITL with predictable and manageable toxicity.
Aged
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Antineoplastic Combined Chemotherapy Protocols
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therapeutic use
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Combined Modality Therapy
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Cyclophosphamide
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therapeutic use
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Disease-Free Survival
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Doxorubicin
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therapeutic use
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Female
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Follow-Up Studies
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Humans
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Immunoglobulins
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administration & dosage
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therapeutic use
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Infusions, Intravenous
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Lymphoma, T-Cell, Peripheral
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drug therapy
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therapy
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Male
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Middle Aged
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Neoplasm Recurrence, Local
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Prednisolone
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therapeutic use
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Remission Induction
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Salvage Therapy
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Vincristine
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therapeutic use
9.Conservative methods for osteonecrosis of the femoral head: the review of 1005 cases.
De-wei ZHAO ; Wei-ming WANG ; Ben-jie WANG ; Tie-nan WANG ; Jian-min LU ; Lin GUO ; Xu CUI ; Xiao-guang YU
Chinese Journal of Surgery 2005;43(16):1054-1057
OBJECTIVETo research on the conservative methods used to preserve the femoral head of patients with osteonecrosis of the femoral head.
METHODSIn these series surgical procedures the osteonecrotic lesion was removed and various vascularized bone blocks or periosteal flaps with its nutrient vessels were transferred to regain sphericity of the femoral head and reinforce the sequestrum. The current study assessed 1005 patients (1226 hips) operated on from 1989 to 2002 with an average follow-up of 5.1 years (range, 1.5-15 years). The mean age of the patients was 37.4 years (range, 17-65 years).
RESULTSSixty-one hips (57 patients) had conversion surgery to a total hip arthroplasty because of progressive collapse or severe pain, or both. In the patients without failure, postoperative Harris hip score improved significantly. Of the 1174 reconstructions that were in situ, 1041 (89.4%) were clinically successful, and 878 (75.4%) were radiologically successful. In relation to the stage of necrosis according to the classification system of Ficat and Alert, good results were achieved in 95.3% of the patients with stages II disease, 87.9% with stages III and 60.8% with stages IV.
CONCLUSIONSConservative methods of vascularized bone block or periosteal flap transfer should be considered in active symptomatic patients to preserve the femoral head. In addition, the earlier the stages of the disease the better outcome could be obtained.
Adolescent ; Adult ; Aged ; Bone Transplantation ; methods ; Female ; Femur ; surgery ; Femur Head Necrosis ; surgery ; Follow-Up Studies ; Humans ; Male ; Microsurgery ; Middle Aged ; Retrospective Studies
10.Simple Pemberton's ilium osteotomy and combined unter-trochanter derotation-varisation osteotomy for developmental dysplasia of the hip.
Hai-yang ZHAO ; Chang-sheng LI ; Wei FENG ; Chen YANG ; Ben-feng YU ; Jian-guo LIU
China Journal of Orthopaedics and Traumatology 2012;25(4):287-290
OBJECTIVETo retrospectively compare the therapeutic effects of simple Pemberton's ilium osteotomy and combined unter-trochanter derotation-varisation osteotomy for developmental dysplasia of the hip (DDH).
METHODSClinical data of 141 DDH patients who received either simple Pemberton's ilium osteotomy (n=57; 12 male and 45 female; age range 3-8 years) or combined unter-trochanter derotation-varisation osteotomy (n=84; 15 male and 69 female; age range 4-9 years) from January 2004 to January 2009 were collected. Postoperative complications, Severin's radiological outcomes and therapeutic outcomes as evaluated by Mcay criteria were compared between the two groups 2 years after operation.
RESULTSThe patients in simple Pemberton group were followed-up for 30-52 months (mean 38 months) and the patients in the combination group were followed-up for 32-51 months (mean 37 months). There were 7 cases of dislocation, 4 cases of avescular necrosis of femoral head and 5 cases of joint stiffness in simple Pemberton group vs 0 case of dislocation, contraction of the limb and ANFH,2 cases of joint stiffness in the combination group. Two years after surgery, the result as evaluated by McKay criteria was excellent in 27 cases, good in 18 cases and fair in 12 cases in simple Pemberton group vs. 52, 25 and 7 cases in the combination group. The overall clinical outcome in the combination group was better than that in simple Pemberton group. Severin X-ray evaluation showed excellent in 27 cases, good in 15 cases and fair in 15 cases in simple Pemberton group vs. 53, 22 and 9 cases in the combination group,indicating that the overall result in the combination group was better than that in simple Pemberton group.
CONCLUSIONThe overall clinical outcome of the combination group is better than that of simple Pemberton group in the treatment of pediatric DDH, especially in reducing postoperative complications and functional recovery. The patients in the combination group reported a higher postoperative satisfaction as compared with those in simple Pemberton group.
Bone Diseases, Developmental ; etiology ; surgery ; Child ; Child, Preschool ; Female ; Femur ; surgery ; Hip Dislocation, Congenital ; complications ; surgery ; Humans ; Ilium ; surgery ; Male ; Osteotomy ; methods