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.     

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.     

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.     

Discrimination of normal and abnormal prothrombin and protein C in plasma using a calcium ion-inhibited monoclonal antibody to a common epitope on several vitamin K-dependent proteins

Vitamin K deficiency or administration of vitamin K antagonists results in the biosynthesis of abnormal des-gamma-carboxy forms of the vitamin K-dependent proteins. Monoclonal antibody H-11 binds several vitamin K- dependent proteins at a determinant that includes the first two residues of gamma-carboxyglutamic acid. Antibody H-11 binds fully carboxylated prothrombin and protein C in the presence of EDTA but binding is inhibited by the divalent metal ions, calcium, magnesium, and manganese. By contrast, des-gamma-carboxy prothrombin and protein C bind antibody H-11 the same in the presence of EDTA or calcium ion. Antibody H-11 thus appears to bind a conserved antigenic site containing gamma-carboxyglutamic acid that in the presence of divalent metal ion undergoes a conformational transition. This ability of antibody H-11 to bind des-gamma-carboxy prothrombin and protein C in the presence of calcium ion allowed the development of an immunoassay for these proteins in plasma. Prothrombin and protein C from stably anticoagulated individuals receiving warfarin were characterized by their ability to bind antibody H-11 in the presence of calcium ion. Binding of prothrombin and protein C to antibody H-11 in the presence of calcium correlated temporally with warfarin administration. The inability of calcium ion to inhibit binding of antibody H-11 to abnormal prothrombin and protein C in plasma suggests that the circulating forms of both proteins following warfarin administration cannot undergo the metal ion-dependent conformational transition that includes sequence residues 1 through 12.     

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.     

Zinc in CSF of patients with febrile convulsion

Objective : This prospective study was carried out from July-December 1999 to see the status of zinc in CSF of children with febrile convulsion and to compare this to that of control.Methods : Forty-two cases of febrile convulsion and 30 controls (fever without convulsion) were enrolled into the study. CSF zinc was estimated by atomic absorption spectrophotometry (AAS) in Atomic Energy Center, Dhaka and compared between the two groups.Results : The mean zinc level in CSF in the study sample was 40.19mgm/L and that in control was 74.98mgm/L This difference was statistically significant (p<0.001).Conclusion : The study concludes that a significantly lower of zinc exists in CSF of children with febrile. However no relationship was found between CSF zinc status with age, sex, degree & duration of fever and time of lumbar puncture after convulsion.     

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：     

Stroke in the young: relationship with iron deficiency anemia and thrombocytosis

The recognition and treatment of stroke in children is challenging as there are fundamental developmental differences in children compared to adults. A young boy presented with sudden weakness of right side of body followed by unconsciousness and convulsion that was not preceded by any history of fever or trauma. Neurological examination revealed upper motor neuron lesion in the right extremities. CT scan showed diffuse hypodense area in fronto-parietal regions. Complete blood count and iron profile evaluated iron deficiency anemia with thrombocytosis. Thrombosis resulting from thrombocytosis secondary to iron deficiency anemia was considered as etiological explanation of stroke in this young child.