[Hepatotoxicological studies of pyrazolone derivatives on rats. Part 2: The study of propyphenazone and phenazone (author's transl)]. / Lebertoxikologische Untersuchungen von Pyrazolonderivaten an Ratten. 2. Mitteilung: Untersuchung von Propyphenazon und Phenazon.

In female rats the administration of 1,5 mmol/kg of, respectively, propyphenazone and phenazone over a period of 12 weeks produces a histologically detectable fatty degeneration and reactive-inflammatory changes of the liver, presumably caused by reactive metabolites. These slight morphological alterations do not lead to an increase in plasma enzyme activities. Only in case of phenazone administration, reduced increases in body weight are indicative of a toxic effect. The acceleration of hexobarbital degradation and N-demethylation and the increase in liver weight testify to the inductive activity of both these compounds.

[Hepatotoxicological studies of pyrazolone derivatives on rats. Part 1: The study of aminophenazone (author's transl)]. / Lebertoxikologische Untersuchunen von Pyrazolonderivaten an Ratten. 1. Mitteilung: Untersuchung von Aminophenazon.

After oral application of aminophenazone to animals (170 and 340 mg/kg daily, over up to 17 weeks), the authors investigated the effect of this drug on some liver functions and performed also a morphological study. They found that aminophenazone produces an increase of the smooth ER, peripheral fatty degradation and reactive-inflammatory responses of the liver, the intensity of these phenomena being dependent upon the dose and time of application. The increase of the smooth ER is the expression of the inductive effect which persists throughout the whole experimental period and manifests itself by accelerated degradation of hexobarbital, increased N-demethylation, increased ascorbic acid synthesis and increased liver weight. The increase in body weight is reduced in the animals treated. The enzyme activities in the plasma lie within the range observed with control animals; they are no indicator of the slight live changes stated. Reactive metabolites and/or the impairment of other metabolic reactions may be considered to be the cause of the hepatotoxic effect of aminophenazone.

[Ligament repair with PDS (polydioxanone) in chronic insufficiency of the fibular ligament of the upper ankle joint: experimental and clinical experiences]. / Die Bandplastik mit PDS (Polydioxanon) bei der chronischen fibularen Bandinsuffizienz am oberen Sprunggelenk: Experimentelle und klinische Erfahrungen.

From September 1988 till February 1989, 14 patients with chronic ligamentous rupture of the ankle had been operated on using PDS-plasty. Of 12 patients checked in follow-up examination (mean postoperative period 45 weeks), only two showed good or very good results. Most patients had the same signs of chronic instability as preoperatively. Two patients had been reoperated on. Intraoperatively we did not find a biological substitute along the PDS guide line. In an experiment on the rat we examined histological changes and tensile strength at appointed times. Histological data showed no biological substitute of PDS. We also found residues of PDS even after 300 days. After a short time loss of tensile strength occurred. In view of an aseptical necrosis that occurred in our experiments, we must point out the risk of foreign body granulomas.

[Ultrastructural characteristics of fibroblasts, myofibroblasts, and fibroclasts in the process of wound healing (author's transl)]. / Ultrastrukturelle Charakterisierung von Fibroblasten, Myofibroblasten und Fibroklasten im Wundheilungsprozess.

5 types of fibroblasts were characterized by histomorphometrical and ultrastructural examinations of the wound healing of rats, 3, 7, 14 and 21 days p. op. These cells were undifferentiated mesenchymal cells, immature fibroblasts, mature fibroblasts, myofibroblasts and fibroclasts. The functions of these cells were discussed with respect to cell proliferation, synthesis, and degradation of collagen.

[Experimental chronic stomach ulcer]. / Das experimentelle chronische Ulcus ventriculi.

A survey of different methods for the production of experimental gastric ulcer in rats is given. 20 male Wistarrats got a chronic gastric ulcer after the injection of 0.05 ml acetic acid (30%) under the serosa. We documented the developing of the ulcer in phases by means of histology. In contrast to other models the Acetic Acid Injection Ulcer (by Takagi et al. 1969) shows similar histology and chronicity to human histology and chronicity.

[Macroscopic and microscopic study of local compatibility of silicone rubber in short- and long-term experiments]. / Makroskopische und mikroskopische Untersuchung der lokalen Verträglichkeit von Silikonkautschuken im Kurz- und Langzeitversuch.

Extended trials were carried out on the purpose of finding optimal silicone rubber materials for endotheses, among others macroscopical and microscopical examinations of local compatibility after implantation in rats and dogs. Short-term experiments on 7 kinds of silicone rubber (VEB Chemiewerk Nünchritz) showed that subcutaneous and intramuscular implantation was well tolerated by rats. Optimal terms for removal were the 7th and the 28th day. Long-term trials of 4 kinds of silicone rubber in rats and dogs up to 1 year yielded no significantly different results compared with control materials from the Dow Corning Corporation. After comparing trials for biostability, 2 silicone rubbers were recommended for clinical use. Optimal terms for removing in long-term experiments were the 3rd, 6th, and 12th month. In the rat experiments after 6 months the thickness of the capsule remained constant, as morphometrically determined. This might be crucial in the assessment of long-term compatibility.

[Morphometric and histologic studies after transplantation of avital xenogenic tissues]. / Morphometrische und histologische Untersuchungen nach Transplantation avitaler xenogener Gewebe.

The reaction of subcutaneous soft tissue on xenogenic grafts was studied by means of morphometric and histological methods. Xenogenic grafts of human dura and bovine vessels were prepared with fibrin tissue adhesives and with a Lys-Pro-derivative which is an angiogenic factor in other animal models. The best results could be demonstrated in the animal group in which the Lys-Pro-derivative was used, 7, 28, and 87 d after operation.

[Histological, electron microscopical and X-ray microanalytical findings in malakoplakia of the kidney (author's transl)]. / Histologische, elektronenmikroskpische und röntgenmikroanalytische Befunde bei der Malakoplakie der Niere.

Malakoplakia which was found in the kidney if a man aged 55 years is described. This rare granulomatous lesion was extirpated together with a renal cyst. So-called Hansemann-cells with inclusion bodies and ring structures were found by light and electronmicroscopic examinations. These concentrically arranged ring like structures were not typical Michaelis-Gutmann-bodies, and they consisted of microfibrils and small granula. Using X-ray microprobe analysis could be detected calcium. These findings were considered to be an early stage of malakoplakia.

[Comparative animal experiments of different tissue adhesives. I. Tensile strength studies. II. Histologic and morphometric studies]. / Vergleichende tierexperimentelle Untersuchungen verschiedener Gewebeklebstoffe. Teil I: Zerreissfestigkeitsuntersuchungen. Teil II: Histologische und morphometrische Untersuchungen.

This paper for the first time presents the results of extensive histological and histomorphometric studies investigating the tensile strength of tissue adhesives in model experiments on animals. The material used in comparative studies were TISSEEL, a human adhesive based on fibrinogen, HISTOACRYL-blue, a cyanoacrylate, and KL-3, a type of urethane adhesive. All the materials used in these studies were shown to be principally suitable as tissue adhesives. TISSEEL, the biological adhesive, was obviously superior to all the other adhesives whereas the two synthetic adhesives HISTOACRYL-blue and KL-3 were found to be roughly equal in their properties. The animal model described in the present paper is recommended for use as a standard technique for testing the suitability of new tissue adhesives.

Evaluation of liver function tests after administration of aminophenazone.

Known liver function tests (activities of ASAT = L-Aspartate: 2-oxoglutarate aminotransferase, ALAT = L-Alanine: 2-oxoglutarate aminotransferase, GLDH = Glutamate-dehydrogenase, LDH = Lactate-dehydrogenase in serum) are not qualified for detecting minimal histopathological liver alterations induced by aminophenazon.

Histological studies into rat liver following long-term application of aminophenazone, phenazone, and propyphenazone.

Morphological studies by means of light microscopy are important for toxicological drug testing. More complete information on potential damage can be obtained only by combination of pharmacological, biochemical, hepatofunctional, and morphological tests and studies. No systematic tests had been applied to rats, in the past. Therefore, aminophenazone, phenazone, and propyphenazone were tested for periods up to 16 weeks. Long-term application of the three pyrazolone derivatives resulted in the following dose-dependent and time-dependent alterations: hepatocyte enlargement, fatty degeneration and reactive-inflammatory changes along with single-cell necrosis, round cellular infiltration of periportal fields, and Kupffer cell activation. The alterations differed in intensity by the following order: aminophenazone greater than phenazone greater than propyphenazone.

[Preparation and experimental studies with an allogenic tissue adhesive during the addition of a dipeptide which promotes wound healing]. / Präparation und experimentelle Untersuchungen mit einem allogenen Gewebekleber unter Zusatz eines wundheilungsfördernden Dipeptides.

The indication for application of tissue sealants in operative medicine was extended in the last years. With an allogenic fibrin adhesive system produced from coagulation plasma-fractions COHN I and cryoprecipitate an effective tissue glue system is introduced which is comparable to international known preparations. By addition of a wound healing compound to this tissue glue the revascularisation and connective tissue organisation of the wound area can be accelerated. Experimental data with this combined sealant prove the excellent sealing of the wound surfaces and an increased tension strength of the sealed wound.

[Monoiodoacetic acid-induced arthropathy of the rabbit knee--a contribution to the pathogenesis of arthrosis]. / Die Monojodazetat-induzierte Arthropathie am Kaninchenknie--Ein Beitrag zur Pathogenese der Arthrose.

A chemically-induced joint degeneration was produced by an one-time intraarticular injection of the glycolysis inhibitor monoiodic acetate into the rabbit knee joint (32 joints of 16 rabbits + 4 control animals). The investigation is founded on Kalbhen's animal model of osteoarthrosis and on Salter's and Moskowitz' experiments. Histomorphological examinations were done in intervals of 1 day to 12 weeks. The results raise several open questions in experimental as well as clinical aspects. On that account these results were discussed pathogenetically in the view of the own pathophysiological and biocybernetical conception of osteoarthrosis development.

Stimulation of wound healing, using brain extract with fibroblast growth factor (FGF) activity. I. Quantitative and biochemical studies into formation of granulation tissue.

In rats with polyvinyl rings implanted under the dorsal skin, the formation of granulation tissue was found to be stimulated by application of brain extract with fibroblast growth factor (FGF) S3 activity which had been obtained from cattle. This stimulating effect on wound healing proved to depend on doses and was detectable in rats aged two and six months on the third and seventh postoperative days. The desired action could be induced only by repetitive administration of FGF S3 or by coupling of the latter to SYSpur-derm, a synthetic dermatoplastic material. More fractions with potential action upon formation of granulation tissue proved to be obtainable from further biochemical separation of FGF S3. One of such fractions was successfully concentrated to a potentiality by which one tenth of the normal dose yielded the same effect as the full dose. Hexosamine and hydroxyproline levels were measured, at the same time, and found to stimulate fibroblasts. The findings are discussed.

Stimulation of wound healing, using brain extract with fibroblast growth factor (FGF) activity. II. Histological and morphometric examination of cells and capillaries.

Reported in this paper are studies by which evidence was produced to increased formation of granulation tissue in rats, aged two and six months, seven days after repeated localised administration of brain extract from cattle with FGF activity (fibroblast growth factor). Such increased formation of granulation tissue was attributable to the formation in the same granulation tissue of larger amounts of capillaries, which actually provided conditions for better blood supply. The above increase was associated with stimulation of the synthetic function of fibroblasts and myofibroblasts in the granulation tissue. Comprehensive morphometric tests, including differential counting, appeared to show that additional effects had to be assumed, in particular on macrophages and lymphocytes. Such increase in angiogenesis seemed to suggest that in the in vivo model studied FGF proved to be, first of all, a factor of angiogenesis rather than a factor of fibroblast growth. The above results, as obtained from rats which differed in age, exhibited a certain variation in response to FGF. This seems to underline the importance of age-dependent examination also in the context of pharmacological studies.

Stimulation of wound healing, using brain extract with fibroblast growth factor (FGF) activity. III. Electron microscopy, autoradiography, and ultrastructural autoradiography of granulation tissue.

A bovine brain fraction with FGF activity (fibroblast growth factor) increased the formation of granulation tissue of rats in an experimental wound healing model. It was characterised by intensified formation of new capillaries, stimulation of the synthesis function of fibroblasts and myofibroblasts, and proliferation of freshly developed granulation tissue. The results obtained from light microscopy and autoradiographic electron microscopy with 3H-thymidine suggested significant increase in the labelling of activated, undifferentiated endothelial cells in vascular sprouts and of differentiated endothelial cells in developed capillaries. FGF S3 appeared to speed up the differentiation of freshly formed endothelial cells. Also labelled were pericytes and other fibroblastoid cells, undifferentiated mesenchymal cells, juvenile undifferentiated fibroblasts, mature fibroblasts, myofibroblasts, and macrophages. Pericytes are presumed to be preferential precursors of myofibroblasts, on account of their occurrence in time and similar ultrastructural parameters. Close neighbourhood of lymphocytes and labelled fibroblasts gave rise to the assumption of specific effects, such as stimulation by lymphokines.

[Animal experiment research on the application of a human bone collagen substance]. / Tierexperimentelle Untersuchungen zum Einsatz einer Human-Knochen-Kollagen-Substanz.

The possibility of the application demineralised human cortical substance with a particle size of 315 micron was investigated on the filling of artificial defects at the tibial diaphysis in rabbit. A clear induction of the bone healing was observed histologically on the transplant side already after 4 weeks and the absence of a periosseous callus formation radiologically.