一氧化氮和一氧化氮合酶与肿瘤放疗敏感性的关系

一氧化氮(nitricoxide,NO)的生物学作用具有复杂性和多样性,在基础条件下诱导型一氧化氮合酶(induciblenitricoxidesynthase,iNOS)活性很低,当机体遭受微生物内外毒素、炎症介质等刺激时iNOS可诱导合成大量的NO.肿瘤生物学上一般认为高水平的NO对肿瘤细胞具有直接的细胞毒作用,而较低水平的NO具有生长刺激作用.多种试验显示NO的供体能增加肿瘤的放疗敏感性.研究认为,NO的生物学作用可能是通过p53依赖途径介导的.调节NO杀灭肿瘤或促进肿瘤生长,p53起到关键性的作用.已有多种药品作为放射敏化剂,NO供体药物在体内给药可能导致系统低血压,增加肿瘤血液灌注和氧合作用,具有潜在的促进肿瘤生长的作用,限制了其临床使用.直接将iNOS基因转染入肿瘤细胞内,肿瘤内的乏氧环境,可降低iNOS的活性而影响NO的产量.携带iNOS基因的腺病毒(adenoviralvectorcarryingtheiNOScDNA,AdiNOS)转染靶细胞导致iNOS过表达,产生大量NO,有望成为一种增加肿瘤放疗敏感性有效可行的方法.     

Tumor necrosis factor alpha-induced endothelial tissue factor is located on the cell surface rather than in the subendothelial matrix

Because there is no consensus regarding the precise distribution of induced endothelial tissue factor (TF), we studied TF activity in and on tumor necrosis factor alpha-stimulated cultured human umbilical vein endothelial cells (ECs) and their underlying matrix. TF was mainly expressed on the cell surface. Only small traces were found on the apical surface suggesting that TF is predominantly located on the basolateral side of the cell membrane. The presence of TF on the cell surface was confirmed by flow cytometry. Subendothelial TF activity appeared to be dependent upon the procedure used to remove the stimulated EC monolayer. Whereas ammonium hydroxide or hypotonic lysis resulted in relatively high levels of matrix-associated TF, virtually no TF was found on the matrix after mild enzymatic detachment of stimulated ECs. Cell removal with EDTA resulted in intermediate levels of matrix-associated TF. Neither the enzymatic treatment nor EDTA degraded or removed this TF activity. Similar patterns were observed for matrix-associated TF antigen and EC surface markers. Electron microscopic analysis showed cell fragments on the matrix after monolayer lysis. The findings strongly suggest that induced endothelial TF associated with the subendothelial matrix actually represents TF on EC remnants.     

Suicide with two shots to the head inflicted by a captive-bolt gun

An exceptional case of suicide with two shots to the head inflicted by a captive-bolt gun is reported here. The pathophysiology observed, and related literature, indicate that the capacity of the victim to fire a second shot depended on the depth of skull penetration by the first shot and the extent of damage to nerve structures. In this case, an ante mortem multi-detector computed tomography was possible. From discussion with the radiologist and a 3D reconstruction, the two-shot suicide scenario could be confirmed.     

N-(1-乙氧羰基-3-苯氨甲酰基丙基)甘氨酰甘氨酸衍生物的合成

报道4个N-(1-[1-乙氧羰基-3-(对甲)苯氨甲酰基]丙基甘氨酰｝-N-取代甘氨酸(XI_1～4)和5个1-[1-乙(或甲)氧羰基-3-(对甲)苯氨甲酰基]丙基-4-取代-1,4-哌嗪-2,5-二酮(XII_1～5)共9个估计有血管紧张素转化酶抑制活性化合物的合成和鉴定。所有这些化合物及9个相应的酯(X_1～9)均未见文献报道。药理初试结果,化合物XII₂,XII₅,XI₄和XII₁均有较强降压活性。     

Fatal wounds to the thorax caused by gunshots from blank cartridges

Lethal injuries of the thorax due to shots fired from blank cartridges calibre 8 mm are reported in three cases. The muzzle of the weapon was in contact with the left side of the breast (contact discharge) and injuries to bones were absent in all three cases. In two of the cases the pericardium was not involved but the anterior wall of the right heart ventricle was ruptured and death was due to cardiac tamponade. In the third case the pericardial sac and the left ventricle were both ruptured and the victim died due to rapid exsanguination. The cases demonstrate that the gas pressure from the exploding propellent of blank ammunition can be powerful enough to penetrate the thoracic wall. Received: 26 May 1997 / Received in revised form: 9 September 1997     

Die Bedeutung der Qualität von Vollblut und Erythrozytenkonzentraten für die Eigenbluttransfusion Eine Literaturübersicht und Metaanalyse der Erythrozytenüberlebensraten in vivo

The separation of whole blood into components is the state-of-the-art in transfusion of allogeneic blood. The main reasons are the negative effects of the buffy coat and the need for FFP. Nevertheless, especially in Germany whole blood is being rejected more and more even as autologous blood. However, most of the negative effects of the buffy coat do not apply to autologous blood. Additionally, these patients usually do not develop coagulation disorders and therefore do not need plasma as a hemostatic component. On the other hand, separation into components of autologous blood leads to an increase of costs and to logistic problems that restrict autologous blood predeposit to a few institutions. Therefore, we have reviewed the literature in order to find a scientific basis for this. Methods. We analysed all articles listed by MEDLINE during the last 12 years that dealt with the quality of whole blood or red cell concentrates. In addition, all references were included that contributed relevant information to the topic. A total of 135 original articles, abstracts, reviews, letters or editorials were analysed that referred to standard preparations and storage media. In 48 papers the in vivo red cell survival was studied. 28 of which fulfilled the prerequisites to be included into a meta-analysis. The following in vitro parameters were also evaluated: pH, potassium load of the units, ATP and DPG concentration of the red cells. Results and discussion. Whole blood (resuspended in CPDA-1) and red cell units (stabilized in CPDA-1 or additive solutions) with a different buffy coat or leucocyte content have comparable pH values and red cell 2,3-DPG and ATP concentrations at the end of the approved storage time. The potassium load of a whole blood unit appears to be higher than red cell concentrates, but this is to some extent caused by the higher plasma content of whole blood and is not thought to be a clinically relevant problem for patients receiving only a few units. A number of studies demonstrate that dependent upon the leucocyte content of a red cell unit, leucocyte metabolites and enzymes are released and accumulate during storage. A detrimental influence on the integrity of the red cell membrane was found in several in vitro studies. Nevertheless, a significant improvement in red cell survival by leucocyte reduction was detected by only one group. Undoubtedly, non-hemolytic febrile transfusion reactions (NHFTR) are generally caused by an antibody-antigen interaction due to the transfusion of allogeneic buffy coat. On the other hand, there is some evidence that non-specific immunological mechanisms such as the release of histamine or cytokines are also capable of causing NHFTR. Thus, these reactions are expected to occur in autologous blood transfusion. However, so far, there are no data about the frequency and severity of these reactions and whether they are more likely to emerge after transfusion of blood units with a particular preparation. Blood transfusions can cause septic complications due to bacterial contamination of the transfused units. These fatal but rare complications may be reduced by pre-storage filtration of blood, but there is no indication that buffy coat reduction is effective. Three cases with septic complications have been reported after autologous transfusion, in two of which red cell concentrates (at least one was free of buffy coat) had been used. Thus, there is no justification for the conclusion that the risk of septic complications is increased by transfusion of whole blood. After all, whole blood and red cell concentrates exhibit only minor differences in relevant in vitro parameters. Hence, a higher incidence of adverse effects following the transfusion of autologous whole blood compared to autologous red cell concentrations is unlikely. Therefore, the 24?h in vivo recovery is considered to be the most valid criterion to assess the quality of red cell preparations. We summarized the results of eligible studies in a meta-analysis and concluded from these data that there is no statistical difference in the in vivo recovery of the transfused red cells between whole blood and filtered red cell concentrates suspended in additive solution. Red cell concentrates suspended in CPDA-1, particularly with a high hematocrit, show significantly worse red cell survival rates than whole blood and should not be in clinical use any more. Conclusion. Whole blood and buffy-coat-free red cell concentrates in an additive solution have an equal therapeutic efficacy. When restricted to a few units (i.e., 2–3), the transfusion of autologous whole blood does not show more frequent or more serious side effects than autologous red cell concentrates. Thus, whole blood can be regarded as the red cell preparation of choice for the majority of clinical settings in autologous transfusion.     

Efficacy of smoking prevention program 'Smoke-free Kids': study protocol of a randomized controlled trial

Background  

A strong increase in smoking is noted especially among adolescents. In the Netherlands, about 5% of all 10-year olds, 25% of all 13-year olds and 62% of all 17-year olds report ever smoking. In the U.S., an intervention program called 'Smoke-free Kids' was developed to prevent children from smoking. The present study aims to assess the effects of this home-based smoking prevention program in the Netherlands.