[The results of preclinical trials of the Soviet recombinant preparation of human interferon alpha-2 (reaferon)].
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Biomedical subjects
Publications and source records attributed to V I Marchenko.
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The authors relate the results of a clinical study of the Soviet recombination alpha-interferon (reaferon) in 46 patients with chronic myeloleukemia at different stages of the disease. Reaferon is shown to be tolerated well, to have a low percentage of side effects in particular high temperature and allergic reactions, to possess no hepato-, nephro- and cardiotoxicity. It has been proved that in patients with chronic myeloleukemia reaferon produces an independent antiproliferative effect and is capable of controlling the leukemic process without chemotherapeutic drug (in the stable chronic phase of the disease). Doses and administration of reaferon for a long time are suggested in order to prolong the disease course.
The results of the clinical trials of human recombinant interferon alpha-2 (reaferon) make it possible to come to the conclusion that the preparation is well-tolerated and produces a pronounced therapeutic effect in a number of viral and oncological diseases. The Pharmacological Committee of the USSR has recommended reaferon for use in acute hepatitis B, hairy cell leukemia, renal cancer at stage IV, disseminated sclerosis, ocular herpes. The use of reaferon has been found to be promising in the treatment of papillomatosis of the larynx, Kaposi's sarcoma, mycosis fungoides, chronic myeloleukemia.
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An analysis of 534 patients has shown that laparoscopy is a method of high diagnostic informative value. The correct diagnosis was made in 515 patients (96.4%). Diagnostic errors were noted in 19 patients (3.6%). The greatest problems appeared in diagnosing thrombosis of mesenterial vessels and acute appendicitis in cases with the retrocecal disposition of the vermiform process. Surgical operations under control of a laparoscope were fulfilled by strict indications. Good immediate results were obtained in 81.9% of the patients.
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The ointment containing pig leukocytic interferon had a pronounced therapeutic effect in herpetic affections of the face skin and genitalia. It prevented eruption, shortened the period of its healing and eliminated subjective sensations. The therapeutic effect was observed in 265 (87.7 per cent) out of 302 patients with recurring Herpes simplex treated with ointment.
An ointment containing porcine leucocytic interferon (PLI) with the use of lanolin as the base and addition of human serum albumin for stabilization of the antiviral activity and Tris-or Hepes-buffer solutions for stabilization of the medium pH value was studied. The trials on volunteers with herpetic affections of the face and genitalia showed absolute safety of the drug, its areactivity and sufficiently high therapeutic efficacy as compared to an ointment containing human leucocytic interferon. The positive effect was observed in 52 out of 78 patients. On the basis of these data the PLI may be recommended for further clinical trials.
Tonsils excised from human beings for chronic tonsillitis have been shown to be an accessible and sufficiently rich source of human lymphocytes. Tonsil cells produced interferon as intensively as blood leukocytes and the properties of this interferon were similar to those of leukocyte interferon. The optimal conditions for interferon production by tonsil cells were established.
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When Krebs-2 ascitic carcinoma is transplanted to mice, administration of interferon may produce either a stimulating or an inhibiting effect on replication of carcinoma cells in the peritoneal cavity depending on the responsiveness of mice (intact or vaccinated with Newcastle disease virus) and the state of the transplanted cells ("common" or "tolerant"). Parallelism was observed in changes of the intensity of cell multiplications and indices of their enzymatic activity under the influence of exogenic interferon.
The fact of non-simultaneous thawing of protein and water was used for concentration of interferon from pre-frozen preparations. As thawing proceeded, 5 sequential fractions equal in a volume were removed from preparations of human leucocyte, mouse macrophage and tissue chick interferons; the titers of their antiveral activity in the first fraction were 4--8-fold higher than the initial titer, and this activity decreased gradually to a titer which was 2-fold lower than the initial in the fifth fraction. The total amount of interferon units in all the fractions was 1.8--3.8-fold higher than in the initial preparation taken in a volume corresponding to the total volume of all the fractions. As addition of the Vth fraction to the Ist fraction reduced the titer of interferon in it to the initial level, it is suggested that in interferon preparations there is an inhibitor of its effect, "anti-interferon".
Comparisons of native preparation of mouse interferons, "macrophage" and "Krebs" revealed some differences, Thus, the minimal time necessary for the development of resistance to vesicular stomatitis virus (VSV) in L cells treated with "macrophage" and "Krebs" interferon was 5 and 2 hours, respectively. The activity of the lysosomal enzyme of acid phosphatase was considerably higher in the cells treated with "Krebs" interferon and infected with VSV than with "macrophage" interferon. Differences in the antiviral and antioncogenic properties of fractions No. 1 and No. 5 of these interferons obtained in fractionation of native interferon preparations by the cryomethod were demonstrated. In particular, fraction No. 5 of "Krebs" interferon, in contrast to that of "macrophage" interferon, had no antioncogenic properties but did have antiviral properties. It is suggested that these differences are due to the presence in native preparations of different substances capable of exerting an effect on interferon.
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