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Clinical symptoms of patients with mastocytosis may include skin reactions, but also gastrointestinal symptoms with hyperacidity and dysmotility (e.g. ulcer, diarrhea, pain). They are mostly caused by mediators derived from activated mast cells. In order to investigate the impact of leukotrienes on the clinical symptoms excretion of leukotriene B4 (LTB4) and leukotrienes C4-D4-E4 (cysteinyl-leukotrienes) into urine was studied in 9 patients with indolent systemic mastocytosis divided into a group with high and low intensity of symptoms and in 11 healthy volunteers. Leukotriene excretion was determined by ELISA and correlated with methylhistamine excretion. Patients with systemic mastocytosis with high and low intense symptoms showed significantly higher urinary excretion of cysteinyl-leukotrienes than controls. There was a positive correlation of cysteinyl-leukotriene excretion and urinary methylhistamine excretion. LTB4 excretion was also significantly increased in patients with systemic mastocytosis compared to healthy volunteers. No correlation of urinary LTB4 excretion with urinary methylhistamine was observed. The present study demonstrates that urinary excretion of LTB4 and cysteinyl-leukotrienes LTC4-D4-E4 is clearly enhanced in indolent systemic mastocytosis Hence, determination of leukotriene excretion into urine can be used as a tool in the diagnostic and in the therapeutic monitoring of systemic mastocytosis.

Salicylate intolerance is defined as a nonspecific antigen-induced pseudo-allergic hypersensitivity reaction which can occur upon contact of an organism with salicylic acid, its derivatives or other related organic or inorganic acids of similar chemical structure. Since the effects of nonsteroidal anti-inflammatory drugs (NSAID) intolerance are by no means always severe or life-endangering but may just as well present as oligosymptomatic or local disorders (e.g. abdominal pain, diarrhea, we decided to evaluate the characteristics of patients with salicylate intolerance on the basis of gastroenterological case material of Medical Department I of Erlangen University. On the basis of the findings from the Erlangen interdisciplinary data register of chronic inflammatory gastrointestinal disease, the signs and symptoms of NSAID intolerance were found to constitute a diagnosis of great practical import to clinical medicine (allergology, dermatology, immunology, other disorders etc.) including gastroenterology. For approx. 2-7% of all patients with inflammatory bowel syndrome and food allergies this poses a new diagnostic and therapeutic challenge which may concern physicians from any of the disciplines involved. When presented with patients with chronic active disease who are suffering from these symptoms one should, therefore, in future give greater thought to the possibility of salicylate intolerance, all the more as there are meaningful dietetic, diagnostic and therapeutic options available for these persons.

Antiviral therapy of human immunodeficiency virus (HIV) infection is currently based on inhibition of reverse transcriptase by dideoxynucleosides, such as azidothymidine. Because of widespread toxicity it is reasonable to selectively target these drugs to infected cells. This may be accomplished utilizing drug-LDL conjugates, which are internalized via cell specific receptor pathways. With respect to HIV infection, scavenger receptors of the macrophage system seems to offer a hopeful perspective. This pathway requires chemical modification of surface polarity of the LDL. Cell experiments were conducted in HepG2 hepatocytes, which express apolipoprotein B receptors, and in P388 macrophages, which express scavenger receptors. LDL particles to be conjugated were isolated from blood donor plasma and from LDL-apheresis waste material. Non-covalent LDL conjugation with amphiphilic nucleoside derivatives produced only an unspecific nucleoside transfer to cell membranes, due to instability of the LDL conjugates. An experimental method (coincubation test) was developed to identify those conjugates that are stable in the presence of other lipophilic compartments. Covalent coupling of nucleosides to the apolipoprotein B moiety of LDL particles resulted in stable conjugates. As a consequence, the surface charge became negative, and the LDL displayed scavenger receptor affinity rather than apolipoprotein B receptor affinity. Selective targeting of nucleosides to macrophages can be accomplished by covalent coupling to LDL.

Low density lipoproteins (LDL) have the potential to serve as cell specific drug carriers. The LDL may be derived in large quantities from LDL-apheresis procedures. Therefore, LDL particles isolated from the waste of three types of LDL-apheresis were investigated concerning their functional integrity in cell transport tests. LDL particles obtained from dextran sulfate-apheresis (DSA) and heparin extracorporeal lipoprotein precipitation (HELP)-LDL-apheresis are capable of specific internalization into HepG2 cells via the apoB receptor pathway. DSA-LDL-apoB appears to be split into two fragments as judged by SDS gel-polyacrylamide gel electrophoresis without changing transport behavior. Membrane differential filtration (MDF)- and HELP-derived LDL particles showed parallel transport behavior and electrophoretic mobility. Acetylated LDL particles obtained from MDF-LDL-apheresis and from blood donation plasma were transported into P388-macrophages via the scavenger receptor pathway. The results confirm the use of LDL particles from LDL-apheresis as substrates for transformation into drug carriers.