Mechanism of uptake and retention of F-18 BMS-747 158-02 in cardiomyocytes: a novel PET myocardial imaging agent

Background BMS-747158-02 is a novel fluorine 18-labeled pyridazinone derivative designed for cardiac imaging. The uptake and retention mechanisms of F-18 BMS-747158-02 in cardiac myocytes were studied in vitro, and the biodistribution of F-18 BMS-747158-02 was studied in vivo in mice. Methods and Results Fluorine 19 BMS-747158-01 inhibited mitochondrial complex I (MC-I) in bovine heart submitochondrial particles with an IC₅₀ of 16.6±3 nmol/L that was comparable to the reference inhibitors of MC-1, rotenone, pyridaben, and deguelin (IC₅₀ of 18.2±6.7 nmol/L, 19.8±2.6 nmol/L, and 23.1±1.5 nmol/L, respectively). F-18 BMS-747158-02 had high uptake in monolayers of neonatal rat cardiomyocytes (10.3%±0.7% of incubated drug at 60 minutes) that was inhibited by 200 nmol/L of rotenone (91%±2%) and deguelin (89%±3%). In contrast, an inactive pyridaben analog, P-0 (IC₅₀ value>4 μmol/L in MC-1 assay), did not inhibit the binding of F-18 BMS-747158-02 in cardiomyocytes. Uptake and washout kinetics for F-18 BMS-747158-02 in rat cardiomyocytes indicated that the time to half-maximal (t_1/2) uptake was very rapid (approximately 35 seconds), and washout t_1/2 for efflux of F-18 BMS-747158-02 was greater than 120 minutes. In vivo biodistribution studies in mice showed that F-18 BMS-747158-02 had substatial myocardial uptake (9.5%±0.5% of injected dose per gram) at 60 minutes and heart-to-lung and heart-to-liver ratios of 14.1±2.5 and 8.3±0.5, respectively. Positron emission tomography imaging in the mouse allowed clear cardiac visualization and demonstrated sustained myocardial uptake through 55 minutes. Conclusions F-18 BMS-747158-02 is a novel positron emission tomography cardiac tracer targeting MC-I in cardiomyocytes with rapid uptake and slow washout. These characteristics allow fast and sustained accumulation in the heart.     

网状减张小切口缝合法提高大鼠背部张力皮瓣存活机制

Foropenseverewoundandthewoundafterdebridement,mostscholarsthinkthewoundshouldbeclosedindelayedfirst-phase.Meshrelaxingshortincision(MRSI)methodcanclosemoreskindeficiencyandhightensionopenwound,andavoidsubcutaneoushematomaandskinflapdrift.Intheexperiment,theexperimentalmodelonrattensionskinflaphasbeeninvolved,andthecontentofendothelin(ET)inratskinflaptissuehasbeenmeasuredinvariousperiodofwoundhealingaftermeshedrelaxingshortincisionsuturewithimmunohistochemistry,inordertodiscussprobablemechani…     

HLA-A*02 allele frequencies and haplotypic associations in Koreans

We have investigated the frequencies of HLA-A*02 alleles and their haplotypic associations with HLA-B and -DRB1 loci in 439 healthy unrelated Koreans, including 214 parents from 107 families. All of the 227 samples (51.7%) typed as A2 by serology were analyzed for A*02 alleles using polymerase chain reaction (PCR)-low ionic strength-single-strand conformation polymorphism (LIS-SSCP) method. A total of six different A*02 alleles were detected (A*02 allele frequency 29.6%): A*0201/9 (16.6%), *0203 (0.5%), *0206 (9.3%), *0207 (3.0%), and one each case of *0210 and *02 undetermined type. Two characteristic haplotypes showing the strongest linkage disequilibrium were A*0203-B38-DRB]*1502 and A*0207-B46-DRB1*0803. Besides these strong associations, significant two-locus associations (P<0.001) were observed for A*0201 with B61, DRB1*0901 and DRB1*1401, and for A*0206 with B48 and B61. HLA haplotypes carrying HLA-A2 showed a variable distribution of A*02 alleles, and all of the eight most common A2-B-DR haplotypes occurring at frequencies of > or =1% were variably associated with two different A*02 alleles. These results demonstrate that substantial heterogeneity is present in the distribution of HLA-A*02 alleles and related haplotypes in Koreans.     

Astrocytes and intracerebral immune responses

The astrocyte is the most abundant cell within the central nervous system (CNS). This cell subserves a multiplicity of important functions that contribute to the process of neural development as well as to the integrity of normal brain function. Adding to the already exhaustive list of capabilities, the astrocyte has now been demonstrated to function as an intracerebral antigen presenting cell. These findings are serving to revise our view of the brain as an immunoprivileged site and perhaps will shed some light on the pathogenetic mechanisms involved in a number of CNS disorders of immune dysregulation. In this review we provide some perspective on the regulatory mechanisms that influence astrocyte immune functions. Specifically, we address the role played by the major histocompatibility complex (MHC) antigens as well as adhesion molecules in the initiation of brain immune responses.     

Identification of HLA-A*0224: implications for PCR-SSP HLA typing

We describe a novel HLA-A*02 allele, A*0224, that was identified after a comparison of DNA and serological typing revealed a discrepancy in the HLA-A types: HLA-A2 was defined by serology but was not detected by the polymerase chain reaction using sequence-specific primers (PCR-SSP). DNA sequencing indicated the presence of a variant HLA-A*02 allele that differed from A*0201 by a single base (C/A) at position 453. This base substitution corresponded to the annealing site of a primer common to the two A*02-amplifying PCR-SSP mixtures used in the method. This provides an explanation for the results and highlights a limitation of PCR-SSP methods even where two PCR mixtures are used to detect alleles. Serological titration studies suggested that A*0201, A*0205 and A*0224 are unlikely to be differentiated during routine serological typing.     

不同烧结温度对双相钙磷陶瓷颗粒材料介孔结构及其成骨性能的影响

目的通过体内外实验检测不同烧结温度下制备的不同介孔直径双相钙磷陶瓷（biphasic calcium phosphate，BCP）颗粒材料成骨能力差_02;，为筛选具备更好临床应用参数的 BCP 材料提供依据002;方法将羟基磷灰石（hydroxyapatite，HA）及 β-磷酸三钙（β-tricalcium phosphate，β-TCP）以 8&#x02236;2 比例混合后，分别在 1 050、1 150 及 1 250&#x02103; 下烧制 3 h 制备 3 种 BCP 材料（分别设为材料1、2、3），比表面积测试法（Brunauer-Emmett-Teller test，BET）测量材料的颗粒内部孔隙率及介孔直径、体积、面积，X 线衍射（X-ray diffraction，XRD）评估材料组成成份，扫描电镜观察材料微观表面形态002;体外将第 3 代 SD 大鼠 BMSCs 与各材料共培养 7 d（分别设为 A、B、C 组），扫描电镜观察细胞黏附情况，鬼笔环肽染色观察 BMSCs 贴附于材料表面后的形态，细胞计数试剂盒 8 法检测细胞增殖活027;002;体内建立比格犬_02;位成骨模型：取 9 只比格犬，于每只犬双侧竖脊肌内制作 9 个肌袋，将肌袋随机分为 3 组（每组 3 个/只），A、B、C 组分别置入材料 1、2、3002;术后 1、2、3 个月分别麻醉 3 只比格犬取材行 HE、Masson 及番红固绿染色，计算 BCP 间隙中的成骨面积比；行实时荧光定量 PCR（real-time fluorescence quantitative PCR，qRT-PCR）检测成骨相关基因 ALP、骨桥蛋白（osteopontin，OPN）、骨钙素（osteocalcin，OC）的表达002;结果BET 检测示随烧结温度增加，颗粒内部孔隙率无明显变化，但介孔直径、体积及面积逐渐减小；XRD 检测示 3 种材料均可见 HA 及 β-TCP 两种 X 线衍射波；扫描电镜观察示 3 种材料表面有广泛分布的微孔，孔间有空隙相连002;体外实验示 BMSCs 在 3 种材料表面黏附、增殖，B、C 组材料的细胞生物相容027;优于 A 组002;体内实验结果示，术后 2 个月开始 3 种材料颗粒孔隙内即可见明显的骨样组织沉积002;各组成骨面积比随时间延长均增加，术后 2、3 个月 A 组成骨面积比显著高于 B、C 组，1 个月时显著高于 B 组（P<0.05）002;qRT-PCR 检测示，A 组成骨相关基因表达在 2 个月时出现峰值，B、C 组各成骨相关基因表达随时间延长逐渐增加002;术后 1 个月 A 组 ALP 和 OPN mRNA 相对表达量显著高于 B、C 组，术后 2 个月 A 组 OC mRNA 相对表达量显著高于 B、C 组，术后 3 个月 B、C 组 ALP mRNA 相对表达量及 B 组 OPN mRNA 相对表达量显著高于 A 组（P<0.05）；其余各时间点各组间比较各基因 mRNA 相对表达量差_02;均无统计学意义（P>0.05）002; 结论不同烧结温度下制备的 BCP 材料，其介孔直径随温度增加而减小002;不同介孔直径的 BCP 材料_02;位成骨能力存在差_02;，其中直径为 12.57 nm 的 BCP 材料能更早激活成骨基因，具备更强的成骨能力002;介孔直径可作为一个优化 BCP 材料成骨能力的指标002;     

消炎痛对中晚期原发性肝癌病人NK细胞及T淋巴细胞亚群的影响

观察中晚期原发性肝癌病人在口服呋喃氟尿嘧啶的基础上加用消炎痛 (吲哚美辛 ) (治疗组 )和不加用消炎痛 (对照组 )外周血自然杀伤 (NK)细胞及T淋巴细胞亚群的变化。结果发现 :治疗组治疗后NK细胞活性较治疗前及较对照组治疗后显著提高 (P <0 .0 5 ,P <0 .0 1) ,而T淋巴细胞亚群的变化差异无显著性。提示消炎痛能增强中晚期原发性肝癌NK细胞的活性     

Pediatric intestinal transplantation

Advancements in donor management, organ preservation and operative techniques, as well as immunosuppressive therapies, have provided children with intestinal failure and its complications a chance not only for enteral autonomy but also long-term survival through intestinal transplantation (ITx). First described in the 1960’s, experience has grown in managing these complex patients both pre- and post-transplant. The goals of this review are to provide a brief history of intestinal transplantation and intestinal rehabilitation in pediatric patients, followed by focused discussions of the indications for ITx, induction and maintenance immunosuppression therapies, common post-operative complications, and outcomes/quality of life post-transplant.