Approach to juxtarenal inflammatory aneurysms

The incidence of inflammatory abdominal aortic aneurysm (IAAA) in a late review of the literature is estimated about 2-15% overall aortic aneurysms. In our data this type of aneurysm is 3.6 overall aortic aneurysms treated. In the majority of the cases, IAAA is juxtarenal or infrarenal. Ethiopathogenesis of IAAA till today is not certain. Recent hypothesis on IAAA attribute the same ethiopathogenesis in both atherosclerotic and inflammatory aneurysm. The interaction of genetic, environmental and infective factors should be able to determine an autoimmune inflammatory reaction of variable severity. 80% of the patients suffering from IAAA present abdominal or lumbar pain, loss of weight and increase of the RC sedimentation velocity. The IAAA's natural history goes to rupture. Entrapment of nearstanding organs totally involved in the fibrotic process is the most frequent complication. Usually there is a compression of the ureter and the duodenum with consequenced hydroureteronephrosis and bowel obstruction. Preoperative diagnosis is possible; CT scan and MRI guarantee and accuracy about 90%. Intraoperatively the external wall of IAAA appears whitish and translucent and always there are tenacious adhesion given by the avventital wounds inflammation. Confirm is given by the histological examination of the aneurysmatic wall and peravventitial tissues. Our experience and a late review of the literature concorde that surgical indication for the treatment of IAAA is the same for the atherosclerotic one. This conviction is supported by the fact that the diagnostic methodical evolution and the improvement in mininvasive surgical technique lowered perioperating morbility and mortaliy. We prefer, according with many authors, retroperitoneal approach to juxtarenal IAAA, instead of standardized transperitoneal access with xifo-pubical or transversal under costal incision. This approach offers some advantages as easier exposition of aorta, whose postero-lateral wall is hardly ever involved in inflammatory process, little duodenum's and left renal veins manipulation and low incidence of paralytic ileum and respiratory disease. Endovascular surgery hasn't in this moment any role in juxtarenal IAAA treatment because this type of aneurysm has inadequate proximal neck. In the future, probably, endovascular repair will be possible using a new type of endograft with renal legs. Often surgical treatment is inadequate to control retroperitorenal fibrosis and so surgeon has to use perioperating pharmacolocical therapy.     

Ammodytase, a metalloprotease from Vipera ammodytes ammodytes venom, possesses strong fibrinolytic activity

Ammodytase, a high molecular mass metalloproteinase with fibrinogenolytic and fibrinolytic activities, was purified from long-nosed viper (Vipera ammodytes ammodytes) venom by gel filtration, affinity and ion-exchange chromatographies. The enzyme is a single-chain glycoprotein with apparent molecular mass of 70 kDa and isoelectric point of 6.6. Ammodytase shows very weak hemorrhagic activity, and only at doses higher than 20 μg. Consistent with this, it partially degrades some components of the extracellular matrix in vitro. It cleaves the Aα-chain of fibrinogen preferentially at peptide bonds Glu⁴⁴¹-Leu⁴⁴² and Glu⁵³⁹-Phe⁵⁴⁰. Its preference for bulky and hydrophobic amino acids at the P1′ position in substrates is demonstrated by its hydrolysis of only the Gln⁴-His⁵ and Tyr¹⁶-Leu¹⁷ bonds in the B-chain of insulin. Ammodytase is able to dissolve fibrin clots. It neither activates nor degrades plasminogen and prothrombin, and has no effect on collagen- or ADP-induced platelet aggregation in vitro. LC/MS and MS/MS analyses of its tryptic fragments demonstrated that ammodytase is a P-III class snake venom metalloproteinase composed of metalloproteinase, disintegrin-like and cysteine-rich domains. Its similarity to hemorrhagins from V. a. ammodytes venom, accompanied by very low toxicity, makes ammodytase a promising candidate as an antigen to prepare antisera against these most dangerous components of the viper's venom. Moreover, its ability to degrade fibrin clots suggests its clinical use as an antithrombotic agent.     

5-En-androstene-3 beta,17 beta-diol inhibits the growth of MCF-7 breast cancer cells when oestrogen receptors are blocked by oestradiol.

Adrenal androgens show a dual and apparently opposite effect on the growth of oestrogen-responsive breast cancer: they stimulate growth on their own, but counteract the growth-stimulatory effect of oestrogens. Focusing on the inhibitory action we have studied the effects of 5-en-androstene-3 beta,17 beta-diol (ADIOL) on the growth of oestrogen-responsive MCF-7 breast cancer cells in the presence of oestrogens (oestradiol and diethylstilboestrol), antiestrogens (tamoxifen) and antiandrogens (hydroxyflutamide). The inhibition of oestrogen-stimulated growth, attained with nanomolar concentrations of ADIOL, was not modified by increasing concentrations of diethylstilboestrol up to 100 nM. This inhibition was counteracted by antiandrogens, which were unable to block the ADIOL stimulatory effect in steroid-free medium. On the other hand, in the presence of tamoxifen ADIOL showed an additive antiproliferative activity also in steroid-free medium, rather than the usual stimulatory effect. These results suggest that ADIOL stimulates breast cancer cell growth via oestrogen receptors, but inhibits oestrogen-stimulated growth via androgen receptors.     

Intradermal hepatitis B vaccination in thalassaemia.

Fifty six children with thalassaemia, and 118 healthy subjects, who had all been immunised with an intramuscular injection of hepatitis B vaccine (HB-VAX) into the deltoid area three years previously, were given booster doses intradermally. All responders (good = hepatitis B surface (HBs) antibody titre greater than or equal to 10 U/l; poor = HBs antibody titre less than 10 U/l) showed pronounced increase in anti-HBs titre, in many cases above 1000 U/l. We also found positive HBs antibody response after further doses (two to four) at intervals of 15 days in non-responders (those patients who formerly had shown no HBs antibody titre after the conventional schedule of vaccination). The humoral response was always preceded by a delayed tissue hypersensitivity reaction. In conclusion, vaccine against hepatitis B virus given in low doses intradermally produces an effective immune response; it is a useful method of enhancing the antibody response in exposed patients, and of vaccinating those who do not respond initially.