慢性内脏痛觉超敏大鼠及热板法疼痛小鼠模型对痛泻要方的镇痛反应

目的:观察痛泻要方对慢性内脏痛觉超敏大鼠模型及热板法疼痛小鼠模型疼痛阈值的影响。方法:实验于2005-10/12在广东药学院中药药理教研室实验室完成。选用SD大鼠60只及雌性NIH小鼠40只,由广东省实验动物中心提供。①慢性内脏痛觉超敏实验:取50只SD大鼠制作三硝基苯磺酸模型,其余10只作为正常对照组。灌注三硝基苯磺酸后第7天测腹壁收缩反射阈值,模型组与正常对照组比较腹壁收缩反射阈值显著降低,则证明造模成功。50只大鼠均造模成功,按随机数字表法分为5组,分别为蒸馏水组、罗痛定组(2.3mg/kg)、痛泻要方9.18g/kg组、痛泻要方4.59g/kg组及痛泻要方2.30g/kg组,每组各10只。给予各组大鼠灌胃相应剂量药物(10mL/kg),1次/d,给药7d。于第7天给药后用直结肠气囊扩张法检测腹壁收缩反射阈值。②热板法疼痛实验:取NIH小鼠40只,置于(55±0.5)℃的水浴烧杯上,以舔后足时间为正常痛阈。按随机数字表法分为5组,蒸馏水组、罗痛定组(4.5mg/kg)、痛泻要方18.75g/kg组、痛泻要方9.35g/kg组及痛泻要方4.67g/kg组,每组8只。分别灌胃给药,给药体积为10mL/kg,1次/d,连续3d,于第3天给药后分别测定其60min,90min,120min的痛阈值。结果:①各组大鼠经三硝基苯磺酸诱导的腹壁收缩反射阈值比较:痛泻要方9.18g/kg,4.59g/kg组及罗痛定组大鼠腹壁收缩反射阈值显著高于蒸馏水组(52.5±3.2)mmHg,(48.3±2.5)mmHg,(57.6±2.9)mmHg,(37.5±2.3)mmHg(P<0.05)。②各组小鼠热板法致痛的痛阈值比较:痛泻要方18.75g/kg,9.35g/kg,4.67g/kg组及罗痛定组小鼠的痛阈值在给药后60min,90min,120min时相点均显著高于蒸馏水组(P<0.05)。结论:中药痛泻要方能提高慢性内脏痛觉超敏大鼠模型及热板法疼痛小鼠模型的疼痛阈值,对慢性内脏痛有明显的治疗作用,可为临床治疗肠易激综合征腹痛提供实验依据。     

Renal outcome in adults with renal insufficiency and irregular asymmetric kidneys

Background  

The commonest cause of end-stage renal failure (ESRF) in children and young adults is congenital malformation of the kidney and urinary tract. In this retrospective review, we examine whether progression to ESRF can be predicted and whether treatment with angiotensin converting enzyme inhibitors (ACEI) can delay or prevent this.     

Views of hospice and palliative care among younger and older sexually diverse women

The aim of the present study was to explore end-of-life health care attitudes among younger and older sexually diverse women. Self-identified lesbian and heterosexual older women as well as lesbian and heterosexual middle-aged women were recruited. Results indicated that lesbian women held significantly more positive beliefs about hospice services and the role of alternative medicines in health care. No differences among sexual orientation were found for comfort discussing pain management but heterosexual women reported a significantly greater desire for life-sustaining treatments in the event of an incurable disease and severe life-limiting conditions (eg, feeding tube, life support, no brain response). Additionally, as expected, older women in this study held more positive beliefs about hospice and more comfort discussing pain management than middle-aged women.     

CYP1B1基因敲除对成年小鼠肝脏脂肪代谢的影响及可能机制

目的探讨CYP1B1对高脂膳食诱导的成年小鼠脂肪代谢的作用。方法 CYP1B1基因敲除(KO)和野生型(WT)雄性成年C57/BL小鼠(6 w龄)各16只,给予低脂(LFD,30%)、高脂肪(HFD,60%)饲料共6 w。小鼠处死后取血清、附睾脂肪和肝脏组织检测相应的生化和分子生物学指标。结果 6 w高脂膳食后,KO小鼠能量摄入总量稍高于WT小鼠,但其体重增量和附睾脂肪组织重量均显著低于WT小鼠;WT小鼠脂肪细胞直径明显大于KO小鼠,且血糖、血清及肝脏组织中甘油三酯(TG)水平亦明显高于KO小鼠;肝脏组织RT-PCR结果显示,CYP1B1基因敲除后,启动脂肪形成的核因子及脂肪合成相关基因如CD36、SREBP1c、SCD1等表达下降,而调控脂肪氧化分解的基因如CPT-1α,UCP-2表达显著上升;蛋白印迹结果显示,CYP1B1基因敲除增强腺苷-磷酸激酶(AMPK)的磷酸化。结论 CYP1B1基因敲除对成年小鼠营养性肥胖的保护作用可能与AMPK磷酸化增强并调控肝脏中脂肪代谢相关基因的表达有关。     

Characterization of the IgG-Fc receptor on human platelets

To determine quantitatively the number and avidity of receptors for the Fc portion of IgG on human platelets, we have measured the binding to platelets of human monomeric monoclonal IgG, and of small covalently crosslinked polymers of IgG1 labeled with 125I. The binding of labeled IgG1 monomers to platelets is too weak to permit quantitation. The binding of dimers or larger polymers of IgG1 is much more avid (greater at 4 degrees C than 37 degrees C), is readily reversible, and is saturable. The number of receptor sites ranges from 400 to 2000 per platelet and the mean equilibrium association constant (Ka) for the binding of dimers at 4 degrees C is 2.2 x 10(7) M-1 +/- 0.9 x 10(7) M- 1. The binding is specific for the Fc portion of IgG, and IgG1 and IgG3 bind to the receptors much more avidly than IgG2 or IgG4. Unlabeled IgG1 dimers are about 7--8-fold more potent in inhibiting binding than are IgG1 monomers, and larger polymers are even more potent than dimers. Thus, the Fc receptors on platelets bind human IgG1 with the same specificity and similar avidity as Fc receptors on polymorphonuclear leukocytes (PMNs), but PMNs have about 300-fold more receptors per unit of surface area than platelets.     

Autologous and allogeneic bone marrow transplantation for poor prognosis patients with B-cell chronic lymphocytic leukemia

Twenty patients with poor prognosis B-cell chronic lymphocytic leukemia (B-CLL) underwent uniform high-dose chemoradiotherapy followed by rescue with multiple monoclonal antibody-purged autologous bone marrow (BM) (12 patients) or T-cell-depleted allogeneic BM from HLA-identical siblings (8 patients) in a pilot study to assess the feasibility of BM transplantation (BMT) in this disease. All had poor prognosis disease by either staging, BM pattern, tumor doubling time criteria, or cytogenetics. All patients achieved remission criteria (defined as < or = 2 adenopathy, absence of splenomegaly, < or = 20% of the intertrabecular space involved on BM biopsy) before BMT. Despite the use of fludarabine, a median of three treatment regimens were required to achieve BMT eligibility. After BMT, all patients achieved complete hematologic engraftment. Toxicities were not significantly different between autologous versus allogeneic BMT. Two toxic deaths were observed. Of 19 evaluable patients, 17 clinical complete clinical remissions (89%) were observed, with 2 patients (1 allogeneic and 1 autologous) exhibiting persistent BM disease. Complete clinical remissions were documented at the phenotypic and molecular level for the majority of patients in whom dual fluorescence for CD5 and CD20 (15 of 15; 100%) and Ig gene rearrangements (11 of 14; 79%) were performed. Although long-term follow-up is needed to assess any potential impact on the disease-free and overall survival of these patients, this study shows the feasibility of using high-dose chemoradiotherapy and BMT in patients with poor prognosis B-CLL.     

Positively selected autologous blood CD34+ cells and unseparated peripheral blood progenitor cells mediate identical hematopoietic engraftment after high-dose VP16, ifosfamide, carboplatin, and epirubicin

To investigate the feasibility of peripheral blood CD34+ cell selection and to analyze CD34+ cell-mediated engraftment after high-dose chemotherapy, we performed a phase I/II trial in 21 patients with advanced malignancies. The rationale for the selection of CD34+ cells from peripheral blood progenitor cell (PBPC) collections is based on the observation that contaminating tumor cells can be depleted approximately 3 logs using this procedure. CD34+ cells from chemotherapy+granulocyte colony-stimulating factor-mobilized PBPCs were positively selected with an avidin-biotin immunoadsorption column (CEPRATE SC system). One leukapheresis product with a median number of 2.8 x 10(6) CD34+ cells/kg was labeled with a biotinylated anti-CD34 monoclonal antibody and subsequently processed over the column. The yield of selected CD34+ cells was 73% +/- 24.6%. The purity of the CD34+ cell fraction was 61.4% +/- 19.7%. CD34+ cells were shown to represent predominantly committed progenitors coexpressing CD33, CD38, and HLA-DR molecules (lin+). They gave rise to myeloid as well as erythroid and multilineage colonies in vitro. In addition, positively selected CD34+ cells also comprised early hematopoietic progenitor cells, as shown by the presence of CD34+/lin- cells. Transfusion of positively selected CD34+ cells (2.5 x 10(6) CD34+/kg; range, 0.45 to 5.1) after high-dose VP16 (1,500 mg/m2), ifosfamide (12 g/m2), carboplatin (750 mg/m2), and epirubicin (150 mg/m2) (VIC-E) in 15 patients resulted in a rapid and stable engraftment of hematopoiesis without any adverse events. As compared with 13 historical control patients reconstituted with a comparable number of unseparated PBPCs, time to neutrophil and platelet recovery was identical in both groups (absolute neutrophil count > 500/microL, day + 12; platelet count > 50,000/microL, day + 15). These data indicate that autologous peripheral blood CD34+ cells and unseparated PBPCs mediate identical reconstitution of hematopoiesis after high-dose VIC-E chemotherapy. Because positive selection of CD34+ cells from mobilized blood results in a median 403-fold depletion of T cells, allogeneic CD34+ cells from mobilized blood should be investigated as an alternative to bone marrow cells for allotransplantation.