Ex Vivo Application of Carbon Monoxide in University of Wisconsin Solution to Prevent Intestinal Cold Ischemia/Reperfusion Injury

Carbon monoxide (CO), a byproduct of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. In vivo recipient CO inhalation at low concentrations prevented ischemia/reperfusion (I/R) injury associated with small intestinal transplantation (SITx). This study examined whether ex vivo delivery of CO in University of Wisconsin (UW) solution could ameliorate intestinal I/R injury. Orthotopic syngenic SITx was performed in Lewis rats after 6 h cold preservation in control UW or UW that was bubbled with CO gas (0.1-5%) (CO-UW). Recipient survival with intestinal grafts preserved in 5%, but not 0.1%, CO-UW improved to 86.7% (13/15) from 53% (9/17) with control UW. At 3 h after SITx, grafts stored in 5% CO-UW showed improved intestinal barrier function, less mucosal denudation and reduced inflammatory mediator upregulation compared to those in control UW. Preservation in CO-UW associated with reduced vascular resistance (end preservation), increased graft cyclic guanosine monophosphate levels (1 h), and improved graft blood flow (1 h). Protective effects of CO-UW were reversed by ODQ, an inhibitor of soluble guanylyl cyclase. In vitro culture experiment also showed better preservation of vascular endothelial cells with CO-UW. The study suggests that ex vivo CO delivery into UW solution would be a simple and innovative therapeutic strategy to prevent transplant-induced I/R injury.     

对芸香科芦荟不会发生接触性过敏

芦荟自古就被用作化妆品和药物添加剂，近来更受喜爱。虽应用广泛，但过敏反应罕有报道。作者用芦荟叶的油性提取物、来自整个植株的芦荟粉及浓缩的芦荟凝胶，对相继就诊的702例患者做斑贴试验。设计专门的问卷调查芦荟的使用、使用原因、使用部位、不良反应、患者职业、个人爱好及是否为遗传性过敏体质。患者均未对任一制剂发生任何反应。需对芦荟所含的两种成分加以鉴别：即芦荟叶皮含有的具有促进肠蠕动、潜在抗菌及抗癌特性的蒽醌类物质。     

Statins are associated with a reduced infrarenal abdominal aortic aneurysm growth.

OBJECTIVE: To evaluate the effect of statins on aneurysm growth in a group of consecutive patients under surveillance for infrarenal aortic aneurysms (AAA). MATERIALS AND METHODS: All patients (59 statin users, 91 non-users) under surveillance between January 2002 and August 2005 with a follow-up for aneurysm growth of at least 12 months and a minimum of three diameter evaluations were retrospectively included in the analysis. Multiple regression analysis, weighted with the number of observations, was performed to test the influence of statins on AAA growth rate. RESULTS: During a median period of 3.1 (1.1-13.1) years the overall mean aneurysm growth rate was 2.95+/-2.8 mm/year. Statin users had a 1.16 mm/year lower AAA growth rate compared to non-users (95% CI 0.33-1.99 mm/year). Increased age was associated with a slower growth (-0.09 mm/year per year, p = 0.003). Female gender (+1.82 mm/year, p = 0.008) and aneurysm diameter (+0.06 mm/year per mm, p = 0.049) were associated with increased AAA growth. The use of non-steroidal anti-inflammatory drugs, chronic lung disease, or other cardiovascular risk factors were not independently associated with AAA growth. CONCLUSIONS: Statins appear to be associated with attenuation of AAA growth, irrespective of other known factors influencing aneurysm growth.     

The vagal nerve as a link between the nervous and immune system in the instance of polymicrobial sepsis

Background The role of the vagal nerve in the autonomic nervous system is widely well known. Recently, an additional function was revealed serving as a connector between the nervous and immune system. This connection is called the “cholinergic inflammatory pathway.” Through stimulation of the acetylcholine receptors located upon the macrophages, the “unspecific” immune system can be directly influenced. Methods The vagal nerve was completely transected directly posterior to its passage through the diaphragm. The effect of complete vagotomy was analyzed using a murine model of polymicrobial peritonitis (colon ascendens stent peritonitis, CASP). Survival and clinical course of vagotomized or sham-operated mice were analyzed in the CASP model. Results After CASP surgery, vagotomy led to a significantly increased mortality (64.7%) in comparison to sham-vagotomized animals (34%). No difference in the bacterial load of various tissues (lung, liver, spleen, blood, lavage fluid, and kidney) from septic animals with or without vagotomy was observed. Vagotomized animals reveal elevated serum cytokine levels (TNF, IL-6, IL-10, and MCP-1) 20 h after the induction of polymicrobial peritonitis. Conclusion The vagal nerve is therefore an important modulator of the immune system. W. Kessler and T. Traeger contributed equally to this work Best of Forum Papers presented at the Annual Meeting of the German Society of Surgery, 2–5 May 2006, Berlin, Germany     

Modern wound dressings: Making and properties. II. Wound dressings containing immobilized proteolytic enzymes (a review)

Published data devoted to making and characterization of the properties of polymeric wound dressings with proteolytic action are reviewed. These data are indicative of individual dependence of the physicochemical properties, activity, and stability of each particular enzyme on the type of polymer matrix and the method of immobilization. In order to obtain wound dressings, which are active in physiological medium and retain their activity upon sterilization, it is necessary to optimize the composition and characteristics of a polymer matrix and the enzyme included into its structure. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 8, pp. 24–28, August, 2006.     

Induktionschemotherapie zur Evaluation einer definitiven Radiochemotherapie bei Patienten mit Larynxkarzinomen

Ohne Zusammenfassung     

BCR-ABL activity and its response to drugs can be determined in CD34+ CML stem cells by CrkL phosphorylation status using flow cytometry.

In chronic myeloid leukaemia, CD34(+) stem/progenitor cells appear resistant to imatinib mesylate (IM) in vitro and in vivo. To investigate the underlying mechanism(s) of IM resistance, it is essential to quantify Bcr-Abl kinase status at the stem cell level. We developed a flow cytometry method to measure CrkL phosphorylation (P-CrkL) in samples with <10(4) cells. The method was first validated in wild-type (K562) and mutant (BAF3) BCR-ABL(+) as well as BCR-ABL(-) (HL60) cell lines. In response to increasing IM concentration, there was a linear reduction in P-CrkL, which was Bcr-Abl specific and correlated with known resistance. The results were comparable to those from Western blotting. The method also proved to be reproducible with small samples of normal and Ph(+) CD34(+) cells and was able to discriminate between Ph(-), sensitive and resistant Ph(+) cells. This assay should now enable investigators to unravel the mechanism(s) of IM resistance in stem cells.