Biomechanische Untersuchungen zur Axialkraftübertragung bei verschiedenen Plattenosteosynthesen

The anchorage of various internal fixation plates on bones was tested. The results showed significant differences depending on the type of plates and the number of screws. Normal round hole plates slipped at higher forces more often than dynamic-compression plates (DCP). DC-plates with a rough surface revealed a higher strength than the same plates with a smooth surface. The anchorage strength of the plate-bone connection does not increase proportionally to the number of screws.     

The effect of N-nitroso-2-methoxy-2,6-dimethylmorpholine on endocrine and exocrine pancreas of Syrian hamsters

N-Nitroso-2-methoxy-2,6-dimethylmorpholine (MeNDMM), a cyclic derivative of the proposed proximate pancreatic carcinogen N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine (HPOP), is shown to have an almost selective cytotoxic effect on pancreatic beta-cells when a single high dose is given to Syrian hamsters. Hence in this aspect its effect is comparable to that of streptozotocin, which has a glucose moiety similar to the MeNDMM structure. However, contrary to the effect of streptozotocin, low single (subdiabetogenic) doses of MeNDMM led to the development of pancreatic ductular and mixed ductular-insular neoplasms; only 1 animal also had islet cell adenoma. It therefore seems that MeNDMM possesses an affinity for both endocrine and exocrine pancreatic tissue. Other target tissues of MeNDMM were the forestomach, intra- and extrahepatic bile ducts, liver, kidneys and vagina. The tumors of these organs appeared in various incidences, partially in relation to dose and/or survival time. The possible mechanisms of the MeNDMM effect upon the endocrine and the exocrine pancreas is discussed.     

Histogenesis of tumors from the nasal cavities induced by diethylnitrosamine.

Chronic subcutaneous (s.c.) or single intravenous (i.v.) injections of diethylnitrosamine (DEN) to gerbils (Meriones unguiculatus) led to the induction of carcinomas of the nasal cavities in a high incidence. These neoplasms were multifocal in origin, frequently showing mixed cellular patterns of the following cell types: large cuboidal cells, nonciliated columnar cells, ciliated columnar cells, small cells, and squamous epithelial cells. No sensory cells of the olfactory mucosa or neurofibrillar differentiations were found in these neoplasms, although several showed rosette- and pseudorosette-like formations. Dose and route of administration seemed to influence the site of origin and the patterns of cellularity of these tumors. Whereas chronic s.c. injections resulted in carcinomas of the olfactory region, being mostly composed of large cuboidal cells, single i.v. injections led to the development of carcinomas mainly originating from the respiratory-olfactory mucosal junction and composed preferentially of nonciliated and ciliated columnar cells.     

Sex differences in the effects of retinoids on carcinogenesis by N-nitrosobis(2-oxopropyl)amine in Syrian hamsters

Syrian hamsters were given in a single dose of N-nitrosobis(2-oxopropyl)-amine (BOP) (40 mg/kg, s.c.) and 1 week later were fed 1 of 4 retinoid types (13-cis-retinoic acid (13-cis-RA), N-ethylretinamide (ERA), 2-hydroxyethylretinamide (OH-ERA), or 4-hydroxyphenylretinamide (PRA)) each at 3 levels (0.05, 0.1, 0.2 mM/kg diet). The pancreatic carcinoma incidence was not influenced significantly by feeding retinoids. The pancreatic adenoma incidence, however, was reduced by feeding each of the retinoids to female hamsters, with the reduction varying with the retinoid fed (13-cis-RA greater than ERA and OH-ERA greater than PRA). In male hamsters increased numbers of pancreatic adenomas were observed after feeding OH-ERA and PRA. Tumors induced in other tissues were reduced by retinoids in females, but not in males. Females fed 13-cis-RA and ERA had a lower incidence of gall bladder polyps, and feeding OH-ERA reduced the liver tumor incidence. Food consumption and serum alkaline phosphatase ans aspartate amino transferase activities were not influenced by BOP or retinoid type or level. Body and pancreas weight were influenced by retinoid level, but the effects were not consistently dose-related.     

Enhancement of experimental pancreatic cancer in Syrian golden hamsters by dietary fat

The effects of dietary fat on the induction and development of pancreatic ductular adenocarcinoma were studied in randombred Syrian golden hamsters. Diets containing low-fat (LF) or high-fat (HF) levels of corn oil [4.5 or 18.0 g/385 kilocalorie (kcal)], contributing 10 or 41% of the calories, respectively, were fed either before or after a single injection of N-nitrosobis(2-oxopropyl)amine (BOP) (10 mg/kg body wt). Control hamsters were fed corn oil at a medium-fat (MD) level (9 g/385 kcal) for life. The incidence of ductular adenocarcinomas increased in both males and females (LF diet, 16%; HF diet, 34%) when the HF diet was fed after BOP treatment. The average number of carcinomas per carcinoma-bearing animal also increased (LF diet, 1.3; HF diet, 3.0), but the carcinoma incidence was not influenced by these diets being fed before carcinogen treatment. The incidence of ductular adenomas was high with all treatments and was not influenced by diet. However, the number of adenomas was increased in animals fed HF diets. In addition, the incidence of acinar cell nodules was elevated in animals fed the MF and HF diets after BOP administration. These results showed that dietary fat modified the development of experimental ductular adenocarcinoma of the pancreas.     

Persistence of DNA single-strand breaks and other tests as indicators of the liver carcinogenicity of 1-nitroso-5,6-dihydrouracil and the noncarcinogenicity of 1-nitroso-5,6-dihydrothymine

The cyclic nitrosourea 1-nitroso-5,6-dihydrothymine [(NDHT) 1-nitrosodihydrothymine] was not significantly carcinogenic when it was administered for 1 year in drinking water (206 mg/liter) to MRC-Wistar rats. In acute toxicity tests, ip injection of saline solutions of 1-nitroso-5,6-dihydrouracil [(NDHU) CAS: 16813-36-8; 1-nitrosohydrouracil], a strong liver carcinogen in rats, produced only mild liver toxicity but marked focal degeneration of myocardial fibers. NDHU injected ip in water solution produced subcapsular liver damage. NDHU, but not NDHT, induced unscheduled DNA synthesis in hepatocyte primary cultures. NDHU, NDHT, and methylnitrosourea [(MNU) CAS: 684-93-5; N-methyl-N-nitrosourea], a liver carcinogen only under special conditions, were tested for their ability, when injected ip into rats, to produce liver DNA damage measured as strand breaks by alkaline sucrose gradient centrifugation. The three nitrosoureas produced similar maximum DNA damage of 2.2-3.2 strand breaks/10(8) daltons. Eighty percent of the damage due to NDHU persisted for 7 days, and the damage at that time was significantly greater than that produced by NDHT and MNU. The varying persistence of liver DNA damage may explain why NDHU, but not NDHT, is a liver carcinogen.     

Prevention of rectal cancer induced by N-nitrosobis(2-oxopropyl)-amine by exogenous testosterone in MRC rats

Rectal carcinogenicity of N-nitrosobis(2-oxopropyl)amine (BOP)in male MRC Wistar rats was shown to be inhibited by exogenoustestosterone (T) when the hormone was given during, but notafter, administration of the carcinogen. This effect was independentof the dose and frequency of BOP, which was given either weeklyfor 20 weeks orally or daily for 3 days subcutaneously. Since,except for prostatic cancer, the incidence and the patternsof other BOP-induced tumors were not altered by T, this hormoneseems to play a specific role in the rectal carcinogenesis ofBOP.     

Treatment of experimental ovarian carcinoma with monthly injection of the agonist D-Trp-6-LH-RH: a preliminary report

Hormones, particularly gonadotropins, have been implicated in the development of ovarian cancer. Chronic administration of agonistic analogs of luteinizing-hormone releasing-hormone (LH-RH) induces an inhibition of the pituitary-gonadal axis. The blockade of the release of luteinizing-hormone and follicle-stimulating hormone (FSH) may exert a possible therapeutic effect on ovarian cancer. We examined the results of prolonged administration of D-Trp-6-LH-RH, an agonistic analog of LH-RH in experimental ovarian cancer. We used the recently developed ovarian cancer model in rats, which is produced by treatment of pregnant rats with N-nitrosobis(2-oxopropyl)amine (BOP), following which a high incidence of ovarian tumors are induced in the offspring. In morphologic aspects the induced tumor resembles human ovarian neoplasms. Once a month administration of a delayed release preparation of microcapsules of D-Trp-6-LH-RH prolonged the survival and decreased tumor growth and the incidence of metastases. Additional experimental and clinical studies are needed to determine the efficacy of the treatment with LH-RH analogs in ovarian cancer.