Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1997-06-03
2000-05-23
Housel, James C.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
424 945, 435 74, 436 16, 436501, 514 2, G01N 3353, G01N 335661, A61K 3851, A01N 3718
Patent
active
060664657
DESCRIPTION:
BRIEF SUMMARY
The subject of the present invention is a new process for the diagnostic assessment and monitoring, as well as a medicament for the therapy, of states of shock in humans.
BACKGROUND OF THE INVENTION
In the western industrial nations, every year thousands die directly from various forms of shock or the immediate results of the shock. As shock, one understands an acutely occurring, faulty regulation of the blood supply of vital organs due to blood pressure decrease. From this acutely occurring faulty regulation, there frequently develop diffuse or selective organ damages and protracted organ failure which, in about 10 to 30% of the cases, leads to death (cf., e.g., Pschyrembel, Klin. Worterbuch, de Gruyter Berlin, 1992). Such shock reactions can occur on the basis of acute and chronic infections, in the case of pre-damaged patients (post-operative), treatment with cytostatics, etc. or also without recognizable cause, mostly as a result of otherwise harmless bacterial infections. One differentiates between anaphylactic, bacterial, septic, post-traumatic, cardiogenic, haemorrhagic, hypovolaemic, neurogenic and toxic forms of shock. A common factor appears to exist in the coexistence of an altered defense behavior of the body with regard to frequently harmless microbes on the basis of simultaneous and shortly previously occurring traumatic, surgical, immunological, medicamentous or toxic previous damaging of the organism (cf., e.g., Bochner, B. S. et al., N. Engl. J. Med., 1991, 3241 1785). Hitherto, a uniform and safe therapy process, especially of the post-traumatic, post-operative, toxic or septic shock has not existed (Barron, R. L., Clin. Pharm. 1993, 12, 829). Dependable criteria for the assessment of the prognosis and of the therapy success in the case of shock illnesses do not exist. Therefore, specific, recognized and rationally based therapy concepts have not been developed, presumably because of the absence of prognostic parameters.
Therefore, the task exists to find a new process for the diagnostic assessment and monitoring, as well as a medicament for the therapy, of states of shock in humans.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows the concentration of cyclophilins in the blood of shock patients. Letters A-E designate individual patients.
DETAILED DESCRIPTION OF THE INVENTION
Surprisingly, in the case of the analysis of the blood of shock patients, it was found that some of them, shortly after beginning or in the further course of the shock illness, showed to a considerable extent cyclophilins in the serum of their blood. Patients who, at any point in time during the shock illness (between the first and fifteenth day), show cyclophilins in the serum to a clearly measurable extent died with great regularity in spite of intensive therapeutic efforts of the treating physician. Patients who survived showed, up to healing, at no point of time in measurable extent cyclophilins in the cell-free parts of their blood (serum, plasma, plasma fractions, etc.).
According to today's state of knowledge, all cells of the human and animal organism, as well as many bacteria, plant cells, etc., contain a special group of cytoplasmic proteins, the cyclophilins (Galat, A., Eur. J. Biochem. 1993, 216, 689). They serve to regulate protein folding, protein stability, protein liberation and also protein formation in connection with the regulation of the function of cells in the normal state or stress, such as, e.g., infections, transplant rejections etc. (Galat v. supra). Cyclophilins have been ascertained not only in the cytoplasm but also in the nucleus of eukaryotic cells (Galat v., supra). However, they do not normally occur in the extracellular medium and no important extracellular effects have been ascribed to them.
The here-reported observation contradicts the state of knowledge insofar as it is here reported for the first time that in connection with the shock illness, in the case of patients in which the shock occurrence finally led to death, already long before their death (days to weeks), consid
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Bochner et al., "Anaphylaxis" The New England Journal of Medicine, vol. 342(25):1785-1790, (1991).
Barron, Pathophysiology of Septic Shock And Implications for Therapy, Clinical Pharmacy, vol. 12:829-845, (1993).
Galat, "Peptidylproline cis-trans-isomerases: Immunophilins", Eur. J. Biochem., vol. 216:689-707, (1993).
De Boer et al., "Interplay Of Complement And Cytokines In The Pathogenesis Of Septic Shock", Immunopharmacology, vol. 24:135-148, (1992).
Bang et al., "Interleukin-8 Is A Cyclosporin A Binding Protein", Experientia, vol. 49:533-538, (1993).
Bang Holger
Brune Kay
Tiegs Gesa
Wendel Albrecht
Housel James C.
Paz Arzneimittel-Entwicklungsgesellschaft mbH
Swartz Rodney P.
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