The effect of intravesical Bacillus Calmette-Guerin instillations on the expression of inducible nitric oxide synthase in humans.

The activation of the inducible isoform of nitric oxide synthase (NOS) is associated with the production of large quantities of nitric oxide in response to cytokine stimulation. Bacillus Calmette-Guerin (BCG) mode of action against bladder carcinoma remains unclear, although a plethora of local and systemic events may follow its intravesical instillation. The present study was designed to investigate the expression of inducible NOS in normal and neoplastic urothelium and its alteration following tumor resection and subsequent intravesical immunotherapy. Bladder carcinoma and autologous normal bladder tissue specimens were procured from 36 patients undergoing transurethral resection. Tissue specimens were obtained from the same patients at first cystoscopy following six weekly intravesical instillations. Inducible NOS protein expression was assessed by immunohistochemistry in all tissue specimens. Immunostaining of normal urothelium for iNOS before treatment was negative in all but four cases. BCG treatment induced iNOS expression in tumor-free bladder tissue in 24 cases (66.6%). There were only four early tumor recurrences; interestingly, they corresponded to the cases with tumor cells expressing iNOS before BCG treatment, while novel tumors were also iNOS immunoreactive. BCG upregulated iNOS expression in normal human urothelial cells in vivo suggesting a role for nitric oxide in BCG mediated antitumor activity. Inducible NOS was detected in certain tumor specimens before and after BCG treatment implying a possible involvement in pro-tumor action.     

麻黄碱复合利多卡因对顺式阿曲库铵肌松效应的影响

目的比较麻黄碱预处理、利多卡因预处理和麻黄碱复合利多卡因预处理对顺式阿曲库铵起效时间、插管条件及其血流动力学的影响。方法选择全麻下行择期手术的患者120例随机分为4组,Ⅰ组生理盐水0.5ml,Ⅱ组麻黄碱70μg/kg,Ⅲ组利多卡因1.5mg/kg,Ⅳ组麻黄碱复合利多卡因70μg/kg+1.5mg/kg,预处理3min后4组患者均静脉注射顺式阿曲库铵0.15mg/kg,在5s内注射完成。患者入睡后行肌松监测,使用4个成串刺激(TOF),待T1达最大抑制程度时行气管插管,记录肌松起效时间,评估气管插管条件,同时观察HR、BP的变化。结果Ⅱ、Ⅲ、Ⅳ组肌松起效时间明显短于Ⅰ组(P0.05),而且Ⅳ组起效时间较Ⅱ、Ⅲ组短(P0.05);Ⅱ、Ⅲ、Ⅳ组气管插管优良率高于Ⅰ组(P0.05),但Ⅱ、Ⅲ组气管插管优良率比较无统计学意义;各组麻醉诱导期间均无明显心血管不良反应。结论麻黄碱复合利多卡因70μg/kg+1.5mg/kg预处理为较好的选择。     

The effect of oncotic pressure on heart muscle mitochondria

The role of oncotic pressure (i.e. pressure created by non-penetrants of high molecular weight) in structural responses of mitochondria has been studied.

It has been found that treatment of beef of rabbit heart mitochondria by a synthetic non-penetrant of high molecular weight, polyvinyl pyrrolidone, induces a decrease in the intermembrane (intracristal) space and an increase in the matrix space of mitochondria. As a result, the appearance of the in vitro mitochondria proves to be similar to that of the in situ ones. If a Waring blender is used to homogenize the tissue, only a portion of the mitochondria respond to polyvinyl pyrrolidone. If a glass-Teflon homogenizer is used instead all the mitochondria prove responsive. The addition of 0.5 mM polyvinyl pyrrolidone is found to be sufficient for the effect to be observable.

In the presence of polyvinyl pyrrolidone, energy-dependent changes in mitochondrial structure can be demonstrated. The increase in matrix space by polyvinyl pyrrolidone treatment enlarges even more when an energy source, a penetrating weak acid and a penetrating cation are added. The size of the matrix increases in the following order: (1) de-energized mitochondria without polyvinyl pyrrolidone, (2) de-energized + polyvinyl pyrrolidone, (3) energized + polyvinyl pyrrolidone, (4) as (3) + phosphate (“twisted” configuration of cristae), (5) as (3) + phosphate + Ca²⁺. Structural changes resembling those indicated in points (2)–(5) are shown for mitochondria in the tissue, when pieces of rat diaphragm muscle treated with an uncoupler, phosphate, and Ca²⁺ were studied in conditions excluding anaerobiosis.

The effect of polyvinyl pyrrolidone is suggested to be due to it balancing the oncotic pressure created by high molecular weight compounds dissolved in the intermembrane water, which are incapable of penetrating the outer mitochondrial membrane. A concept is discussed considering mitochondrial structure changes as a function of the osmotic gradient across the inner membrane and the oncotic gradient across the outer membrane of mitochondria.     

The effect of hydrostatic pressure on S-layer-supported lipid membranes

We report on the behavior of unsupported and surface layer (S-layer)-supported lipid membranes at the application of a uniform hydrostatic pressure. At a hydrostatic pressure gradient higher than 6 N/m(2), unsupported lipid membranes, independent from which side pressurized and S-layer-supported lipid membranes pressurized from the lipid-faced side revealed a pronounced increase in capacitance. A maximal hydrostatic pressure gradient of 11.0 N/m(2) resulted in an almost doubling of the capacitance of the (composite) membranes. S-layer-supported lipid membranes showed a hysteresis in the capacitance versus pressure plot, indicating that this composite structure required a certain time to reorient when the pressure gradient acting from the lipid-faced side was balanced. By contrast, the S-layer-supported lipid membrane pressurized from the protein-faced side revealed only a minute increase in capacitance (C/C(0,max)=1.17+/-0.05), reflecting only minor pressure-induced area expansion. In addition, no hysteresis could be observed, indicating that no rearrangement of the composite membrane occurred. The maximal induced tension was with 4.3+/-0.2 mN/m, significantly higher than that of unsupported (2.5+/-0.3 mN/m) and S-layer-supported lipid membranes pressurized from the lipid-faced side (2.6+/-0.1 mN/m).