Reinforcing efficacy of fat, as assessed by progressive ratio responding, depends upon availability not amount consumed

Intermittent limited access to an optional source of dietary fat can induce binge-type behavior in rats. However, the ability of such access to alter the reinforcing efficacy of fat has not been clearly demonstrated. In this study, performance under progressive ratio one (PR1) and three (PR3) schedules of shortening (fat) reinforcement was assessed in non-food deprived rats (n = 15/group). One group of rats had intermittent access to a dietary fat option (INT, 1-hour shortening access in the home cage each Monday, Wednesday, and Friday), whereas the other group had daily access to the fat option (D, 1-hour shortening access daily). Chow and water were continuously available. After five weeks, the INT group consumed more shortening during the 1-hour access period than did the D group. Rats were then trained to lever press for a solid shortening reinforcer (0.1 gm). INT rats earned significantly more reinforcers than did D rats under PR1, but not under PR3. Subgroups of INT and D rats (n = 7 each) were matched on the amount of shortening consumed in the home cage during week five of the protocol and the PR data were reanalyzed. The INT subgroup earned significantly more reinforcers than the D subgroup did under PR1, but not PR3. These results demonstrate that: (1) intermittent access to shortening in the home cage, but not the amount consumed during the access period (i.e. bingeing), increases the reinforcing efficacy of solid shortening; and (2) the type of PR schedule is critical in delineating differences between the groups.     

自身免疫性肝炎大鼠模型外周血淋巴细胞体外培养与褪黑素的影响

目的:观察褪黑素对体外培养淋巴细胞增殖及促进细胞因子分泌的作用。方法:实验于2004-10/2006-10在解放军第一二三医院南京军区肝病中心实验室完成。①实验材料:Wistar大鼠,雄性,3月龄,体质量(230±20)g,购自上海斯莱克实验动物有限责任公司。褪黑素:美国Sigma公司产品。②实验方法:采用弗氏完全佐剂加肝细胞特异性脂蛋白法建立自身免疫性肝炎大鼠模型。分别抽取正常大鼠及模型大鼠的外周血,实验室常规培养,并将其分为3组:褪黑素组培养基中加褪黑素使终浓度为2mg/L;促肝细胞生长素组培养基中加促肝细胞生长素使终浓度为2mg/L;空白对照组培养基中不加任何细胞分裂刺激剂。③实验评估:培养48h后,对外周血淋巴细胞进行常规计数并采用液体闪烁计数仪记录1min计数结果值。用于观察褪黑素与促肝细胞生长素促进外周血淋巴细胞增殖的效果。并检测培养上清液中的各细胞因子浓度,用于观察褪黑素与促肝细胞生长素促进外周血淋巴细胞分泌细胞因子的作用。结果:①褪黑素对正常大鼠外周血淋巴细胞有促进增殖作用,细胞数与1min计数值较空白对照组明显升高(P<0.05),促肝细胞生长素无促进外周血淋巴细胞增殖作用。②褪黑素对模型大鼠外周血淋巴细胞有促进增殖作用,细胞数与1min计数值较空白对照组明显升高(P<0.05),促肝细胞生长素无促进外周血淋巴细胞增殖作用。③在褪黑素作用下,正常大鼠Th1细胞因子IL-2和IFN-γ水平明显高于空白对照组和促肝细胞生长素组(P<0.01),Th2细胞因子IL-6明显升高(P<0.05),IL-4水平与空白对照组比较,差异不显著(P>0.05),促肝细胞生长素组Th1和Th2细胞因子与空白对照组无明显差异(P>0.05)。④在褪黑素作用下,模型大鼠Th1细胞因子IL-2和IFN-γ水平较空白对照和促肝细胞生长素组明显升高(P<0.05),Th2细胞因子IL-4和IL-6水平与空白对照和促肝细胞生长素组无明显差异(P>0.05)。结论:褪黑素对自身免疫性肝炎大鼠外周血淋巴细胞有较强的刺激分裂作用。     

Dw/LD-related molecular polymorphism of DR4 β-chains

The results of this study demonstrate the existence of molecular heterogeneity (polymorphism) within DR β-chains isolated from a single serologically defined DR phenotype, DR4. The data are consistent with the possibility that this polymorphism is related to the Dw/LD phenotype as defined with the cellular reagents, homozygous typing cells.     

Leukocyte depletion of random single-donor platelet transfusions does not prevent secondary human leukocyte antigen-alloimmunization and refractoriness: a randomized prospective study

We studied the value of leukocyte depletion of platelet transfusions for the prevention of secondary human leukocyte antigen (HLA)- alloimmunization in patients with a high-risk of prior immunization induced by pregnancies. Seventy-five female patients with hematologic malignancies (mostly acute leukemia) and a history of pregnancy were randomized to receive either standard random single-donor platelet transfusions (mean leukocytes, 430 x 10(6) per transfusion) or leukocyte-depleted random single-donor platelet transfusions. Leukocyte depletion to less than 5 x 10(6) leukocytes per platelet transfusion (mean leukocytes, 2 x 10(6) per transfusion) was achieved by filtration. Of the 62 evaluable patients, refractoriness to random donor platelets occurred in 41% (14 of 34) of the patients in the standard group and in 29% (8 of 28) of the patients in the filtered group (P = .52); anti-HLA antibodies developed in 43% (9 of 21) of individuals in the standard group and 44% (11 of 25) of cases in the filtered group. The time toward refractoriness and development of anti- HLA antibodies was similar for both groups. We conclude that leukocyte depletion of random single-donor platelet products to less than 5 x 10(6) per transfusion does not reduce the incidence of refractoriness to random donor platelet transfusion because of boostering of anti-HLA antibodies.     

Characterization of human skeletal stem and bone cell populations using dielectrophoresis

Dielectrophoresis (DEP) is a non‐invasive cell analysis method that uses differences in electrical properties between particles and surrounding medium to determine a unique set of cellular properties that can be used as a basis for cell separation. Cell‐based therapies using skeletal stem cells are currently one of the most promising areas for treating a variety of skeletal and muscular disorders. However, identifying and sorting these cells remains a challenge in the absence of unique skeletal stem cell markers. DEP provides an ideal method for identifying subsets of cells without the need for markers by using their dielectric properties. This study used a 3D dielectrophoretic well chip device to determine the dielectric characteristics of two osteosarcoma cell lines (MG‐63 and SAOS‐2) and an immunoselected enriched skeletal stem cell fraction (STRO‐1 positive cell) of human bone marrow. Skeletal cells were exposed to a series of different frequencies to induce dielectrophoretic cell movement, and a model was developed to generate the membrane and cytoplasmic properties of the cell populations. Differences were observed in the dielectric properties of MG‐63, SAOS‐2 and STRO‐1 enriched skeletal populations, which could potentially be used to sort cells in mixed populations. This study provide evidence of the ability to characterize different human skeletal stem and mature cell populations, and acts as a proof‐of‐concept that dielectrophoresis can be exploited to detect, isolate and separate skeletal cell populations from heterogeneous bone marrow cell populations. Copyright © 2012 John Wiley & Sons, Ltd.     

Occurrence of allogeneic HLA and non-HLA antibodies after transfusion of prestorage filtered platelets and red blood cells: a prospective study [see comments]

The incidence and consequences of HLA and non-HLA immunization were evaluated in 229 patients with aplastic thrombocytopenia. All patients were transfused with prestorage filtered red blood cells and platelets. On admission, 29 patients presented with HLA antibodies due to prior immunization by pregnancy and/or blood transfusions. Of the 200 patients showing no detectable HLA antibodies on admission, 164 could be evaluated. HLA antibodies developed in 2.7% (3 of 112) of the patients with a negative risk history of prior immunization. The occurrence of HLA antibodies in patients with a history of previous pregnancies or prior non-leukocyte-depleted blood transfusions (risk history positive) was 31% (16 of 52). Of the total of 48 patients who were or became alloimmunized, 92% (44 of 48) had a positive risk history. Ten patients with broad multispecific HLA antibodies with a panel reactivity (PRA) of greater than 70% required transfusions with HLA-matched platelets. Patients with HLA antibodies with lower PRA could be supported by random donor platelets. Two patients developed platelet-specific antibodies, causing transfusion refractoriness that necessitated selecting platelets by the absence of a platelet-specific antigen. Using prestorage leukocyte depletion of red cells and platelets with less than 5 x 10(6) residual leukocytes, 95% of the patients, including patients with a previous risk history or with HLA antibodies with low PRA, can be supported with random donor transfusions for the entire duration of their thrombocytopenic periods.     

阻塞性睡眠呼吸暂停低通气综合征患者的内皮细胞凋亡与内皮功能异常有关

背景与目的：阻塞性睡眠呼吸暂停低通气综合征（OSAHS）患者罹患心血管疾病的危险性增加。内皮细胞损伤被认为是动脉硬化的始动机制之一。本研究观察了OSAHS患者循环中凋亡的内皮细胞与血管收缩功能异常的关系。方法：研究对象包括14例确诊OSAHS患者和10例健康对照。在基线以及持续气道内正压（CPAP）治疗8周后测定臂动脉血流介导扩张（反映内皮依赖臂动脉扩张的指标）。采用流式细胞术测量循环中凋亡的内皮细胞。结果：     

Endothelin-1 and blood pressure after inhibition of nitric oxide synthesis in human septic shock

BACKGROUND: The systemic hypotension during human sepsis has been ascribed to increased production of nitric oxide (NO). Therefore, inhibitors of NO synthesis have been used in the treatment of hypotension in patients with septic shock. In addition, NO production may inhibit the synthesis and vasoconstrictor effects of endothelin-1 (ET-1). In this study, we tested whether ET-1 contributed to the vasopressor action of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in patients with severe septic shock. METHODS AND RESULTS: Compared with healthy volunteers, patients with septic shock had increased plasma levels of nitrite/nitrate (37+/-5 [SEM] versus 12+/-5 mmol/L, P<0.01), the stable end products of NO metabolism, and ET-1 (45+/-7 versus 3+/-2 pg/mL, P<0.001). Plasma ET-1 concentration was not related to plasma nitrite/nitrate concentration or blood pressure. Continuous infusion of L-NAME (1 mg. kg-1. h-1 IV) for 12 hours increased mean arterial pressure by 43+/-5% and systemic vascular resistance by 64+/-10% (both P<0.01). The increase in blood pressure and systemic vascular resistance correlated positively with the level of ET-1 (both P<0. 005) but not with plasma nitrite/nitrate level. L-NAME infusion did not result in significant changes in the plasma concentrations of ET-1 or nitrite/nitrate. CONCLUSIONS: NO and ET-1 may both play a role in the cardiovascular derangements of human sepsis. Although L-NAME does not increase ET-1 concentration in patients with septic shock, the vasopressor response induced by L-NAME depends on the plasma level of ET-1. These findings may indicate that inhibitors of NO synthesis unmask a tonic pressor response of ET-1 in human septic shock.