Investigation of the prevalence and severity of foot pad dermatitis at the slaughterhouse in fattening turkeys reared in organic production systems in Germany.

The present study shows the prevalence and severity of foot pad dermatitis (FPD) in turkeys reared in organic production systems assessed at slaughterhouses in Germany. The investigations of altogether 1,860 turkeys of the strains Kelly Broad Breasted Bronze (Kelly BBB; 540 toms, 540 hens) and British United Turkeys (B.U.T.) 6 and the Test Product 7 (TP 7; 780 hens) showed that 97.7% of the examined turkeys were diagnosed with different degrees of FPD. Only 4.6% of the toms and 1.3% of the hens had feet without lesions. Most frequent were necrotic lesions measuring up to 2 cm in diameter (64.3% of all turkeys). Extensive necrotic lesions of the foot pads (toms: 29.8%; hens: 12.4%) and necrosis of superficial scales (toms: 11.3%; hens: 7.6%) were less frequent. Plantar abscesses were rare findings (1.9%). In general, the feet of the Kelly BBB hens were more affected by foot pad lesions than those of the Kelly BBB toms. There were significant differences between the investigated flocks concerning the occurrence of foot pad lesions. The aim in rearing turkeys must be the reduction of FPD.

Chronic exposure to a GSM-like signal (mobile phone) does not stimulate the development of DMBA-induced mammary tumors in rats: results of three consecutive studies.

Certain epidemiological and experimental studies raised concerns about the safety of radiofrequency (RF) electromagnetic fields because of a possible increased risk of leukemia and lymphoma. In this study, an RF field used in mobile telecommunication was tested using 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in female Sprague-Dawley rats as a model for human breast cancer. Three experiments were carried out under strictly standardized conditions and were started on the same day of three consecutive years. The field consisted of a GSM-like signal (900 MHz pulsed at 217 Hz, pulse width 577 micros) of relatively low power flux density (100 microW/cm(2) +/- 3 dB) and was applied continuously throughout each experiment to freely moving animals. The specific absorption rates averaged over the whole body were 17.5-70 mW/kg. The highest values in young animals were at or around the exposure limit permissible for the general public (i.e. 80 mW/kg). The animals were palpated weekly for the presence of mammary tumors and were killed humanely when tumors reached a diameter of 1-2 cm to allow a reliable histopathological classification and a distinction between malignant and benign subtypes. The overall results of the three studies are that there was no statistically significant effect of RF-field exposure on tumor latency and that the cumulative tumor incidence at the end of the experiment was unaffected as well. The risk ratios were 1.08 (95% CI: 0.91-1.29) and 0.96 (95% CI: 0.85-1.07) for benign and malignant tumors, respectively. These observations are in agreement with other published findings. In the first experiment, however, the median latency for the development of the first malignant tumor in each animal was statistically significantly extended for RF-field-exposed animals compared to controls (278 days compared to 145 days, P = 0.009). No such differences were detected in the two subsequent experiments. These results show that low-level RF radiation does not appear to possess carcinogenic or cancer-promoting effects on DMBA-induced mammary tumors. To explain the mechanisms underlying the different results obtained in the three experiments, a hypothesis is presented which is based upon the neuroendocrine control mechanisms involved in the promotion of DMBA-induced mammary tumors. Despite the apparent absence of stimulatory effects of low-level RF-field exposure on the development and growth of solid tumors, it will be necessary to verify these results for leukemias and lymphomas, which may have completely different biological control mechanisms.

Seasonal rhythms of 6-sulphatoxymelatonin (aMT6s) excretion in female rats are abolished by growth of malignant tumors.

The effect of development and growth of malignant tumors on pineal melatonin production was studied in two different hormone-dependent tumor systems in female rats. Urinary excretion of 6-sulphatoxymelatonin (aMT6s), the metabolic end product of melatonin, which parallels its production, was determined by radioimmunoassay at fortnightly or monthly intervals over the period of 1 year in female F344 Fischer rats bearing chemically-induced mammary carcinomas and in BDII/Han rats with spontaneous endometrial carcinomas. Untreated Fischer rats and BDII/Han rats in which tumor growth was suppressed by treatment with a progestin served as controls. Based on the cosinor analysis, animals without tumors showed significant seasonal rhythms of aMT6s excretion, with peaks in August (Fischer rats) and in May (BDII/Han rats). In contrast, such rhythms were absent in animals with developing and manifest tumors. It is concluded that animals kept under constant environmental conditions still show seasonal rhythms of pineal activity. Tumor development and growth affect pineal activity leading to disturbance of these rhythms.

Total suppression of spontaneous endometrial carcinoma in BDII/Han rats by melengestrol acetate.

Female virgin BDII/Han rats develop spontaneous endometrial carcinoma (EC) in incidences up to 90%. Our objective was to determine whether lifelong administration of the progestin melengestrol acetate (MGA) would suppress those tumors. Four groups of 20 rats aged 24-28 days were employed Group I animals were untreated controls. Groups II, III, and IV were fed 0.1, 0.2, and 0.4 mg MGA/kg daily in their diet during their lifetimes. All treated groups were free from EC during their lifetimes with an increased lifespan up to 30%. The controls, in contrast, had an EC incidence of 85%. Histologically, with one exception all tumors were classified as adenocarcinoma. While most of the control rats died from EC, nearly all animals of groups II and III died from age-related diseases. Rats in group IV showed side effects due to the glucocorticoid properties of MGA. Besides alopecia and obesity an acceleration of chronic progressive nephrosis was observed. The study establishes the validity of the prophylactic approach to spontaneous hormone-dependent cancers in a rat tumor model.

Lewis rats of the inbred strain LEW/Han: life expectancy, spectrum and incidence of spontaneous neoplasms.

Although Lewis rats are frequently used in biomedical research, little is known about their life-data and spontaneous pathology. Therefore, it was the aim of this study to determine the life expectancy, spectrum and incidence of spontaneous neoplasms of the inbred rat strain LEW/Han. A total of 629 LEW/Han rats (305 females and 324 males) from a specified pathogen-free breeding colony were kept from weaning up to their natural death under defined environmental conditions. A complete histological examination was performed on all organs and macroscopically altered tissues of all animals which died during the first three years of the study. These were 296 female (98%) and 213 male (66%) rats. The mean lifespan of the females (27.7 +/- 5.1 months) was significantly shorter than that of the males (32.5 +/- 6.6 months). In both sexes, the lifespan was mainly determined by the occurrence of neoplasms. Of the large spectrum of 52 histologically different tumour types, the highest incidences were observed for adenomas of the pituitary gland and adenomas/adenocarcinomas of the adrenal cortex in both sexes, mammary gland tumours and endometrial carcinomas in females, and C-cell adenomas/adenocarcinomas of the thyroid gland and tumours of the haemopoietic system in males. Of these, the high incidences of tumours of the haemopoietic system in males (27.7%) and of endometrial carcinomas in females (45.2%) should be considered as characteristic features of the strain.

Progression of renal failure in the Han: SPRD polycystic kidney rat.

The Han: SPRD Pkd rat mutant is an autosomal dominant rat model with incomplete penetration of polycystic renal transformation. Progressive renal failure occurs in heterozygous male animals. The mechanisms of progression have not been elucidated. To identify some pathogenetic factors involved we subjected male SPRD Pkd rats (and their non-affected littermates as controls) to uninephrectomy (UNX), castration or enalapril treatment. To assess progression S-urea at age 150 days was chosen as endpoint. (i) In uninephrectomized male Han: SPRD Pkd (n = 12 animals per group) S-urea at age 150 days was consistently above 300 mg/dl, while it was 245 mg/dl (191-290) in control Han: SPRD Pkd. (ii) In castrated male Han: SPRD median S urea at 150 days was 100 mg/dl (69-211) compared to sham-operated male Han: SPRD controls (245; 191-290). Castration did not, however, prevent accelerated progression after uninephrectomy. (iii) Enalapril (50 mg/l) in the drinking fluid did not significantly lower median systolic blood pressure (by plethysmography) in animals on 0.2% sodium diet (at 185 days 160 mmHg; 140-170 versus 170; 140-195 in non-enalapril controls), although circulating ACE was significantly inhibited (17 U; 11-33 versus 89; 52-108 in controls). S-urea at age 185 days was not significantly different in the 2 groups. In conclusion, the Han: SPRD Pkd model differs from human ADPKD to some extent. Uninephrectomy accelerates renal failure in the rat, but not in humans. On the other hand, in contrast to human ADPKD the renin system is suppressed in the rat model and ACE inhibition does not affect the course of renal failure.

History and pathology of an enzootic Pneumocystis carinii pneumonia in athymic Han:RNU and Han:NZNU rats.

A report is given on the history and pathology of an enzootic outbreak of spontaneous Pneumocystis carinii pneumonia (PCP) that occurred in a colony of male and female athymic Han:RNU rnu/rnu and Han:NZNU rnuN/rnuN rats maintained in a longevity study from weaning up to their natural death. The rats were obtained from specified pathogen free (SPF) breeding colonies and were kept in a barrier type animal quarter with standardized housing conditions. Groups of heterozygous, euthymic littermates in the same room remained unaffected. First cases of PCP were observed simultaneously in both stocks and both sexes when the rats were 15 to 18 months old. During the following 18 months, most of the animals developed pneumonia. Shortly prior to death the animals showed dyspnea and cachexia. Gross examination revealed focal or diffuse pulmonary consolidation. Histologically, characteristic lung lesions consisted of an interstitial pneumonia with perivascular and peribronchiolar infiltrations and with clusters of foamy macrophages within single or groups of alveoli. Most prominent in moderate and severe infections was an amorphous, honey-combed eosinophilic material within enlarged alveolar spaces. The diagnosis was based on the histological identification of Pneumocystis carinii (Pc) cysts in lung sections stained with Grocott's methenamine silver and was confirmed immunohistochemically. The evaluation of all evidence leads to the conclusion that Pc was introduced into the experimental colony by care-takers. The high incidence of PCP and its resemblance to human PCP indicate the suitability of athymic Han:RNU and Han:NZNU rats as natural models for this disease.

Nude rats as a model of natural Pneumocystis carinii pneumonia: sequential morphological study of lung lesions.

A spontaneous infection with Pneumocystis carinii (P.c.) caused enzootic fatal pneumonia in a long-term experiment with athymic Rowett Nude (Han:RNU rnu/rnu) and New Zealand Nude (Han:NZNU rnuN/rnuN) rats. In order to reproduce the infection and to characterize the early pathogenesis of lung lesions, 13 young athymic Han:RNU and Han:NZNU rats from P.c.-free breeding colonies were housed together in one room with chronically P.c.-infected rats. They were killed after 8, 12, 16, 20 or 24 weeks, and their lungs were examined for P.c. infection by means of light microscopy, immunohistochemistry and transmission electron microscopy. Lung lesions progressed from a mild interstitial pneumonia with scattered alveolar macrophages (8 weeks) to a severe diffuse interstitial pneumonia with widespread areas of distended alveoli, filled with foamy material. In all lungs, P.c. antigen was detected immunohistochemically, developing from small intra-alveolar aggregations of organisms into large multifocal clusters. Ultrastructurally, P.c. trophozoites and cysts were seen attached to type I pneumocytes and lying free in the alveolar lumen. Chronic severe P.c. pneumonia (20 and 24 weeks) was characterized by masses of P.c. trophozoites in the alveoli and alveolar walls, extensive proliferation of type II pneumocytes and interstitial fibrosis. The easy and consistent horizontal transmission of spontaneous P.c. pneumonia to previously non-infected athymic Han:RNU and Han:NZNU rats and the similarity of the disease to human infection demonstrate both rat strains to be excellent models for studying pulmonary pneumocystosis of immunodeficient human patients.

The EnDA endometrial adenocarcinoma: an oestrogen-sensitive, metastasizing, in vivo tumour model of the rat.

A high percentage of endometrial carcinomas contain oestrogen and progesterone receptors. For endocrine therapy of recurrent endometrial carcinoma, only high-dose progestins are in clinical use. As, therefore, the development of new endocrine treatment strategies is of great interest, suitable animal models for this tumour are essential. Up to now, only human tumour xenografts transplanted in immune-deficient nude mice, but no syngeneic in vivo tumour models, have been available. In the present article we describe the hormone sensitivity of the EnDA endometrial adenocarcinoma of the DA/Han rat growing as s.c. implants in DA/Han rats and athymic nude mice in serial passage. In both species, the tumour expresses oestrogen, but no progesterone receptors. Transplanted in DA/Han rats or nude mice, ovariectomy reduced tumour weight by 64% and 46% respectively. In both species substitution of ovariectomized animals with oestradiol restored tumour weights to intact control levels. Oestradiol substitution of intact animals did not further enhance tumour growth. The growth of the primary tumour was inhibited by medroxyprogesterone acetate (MPA) at a dose of 100 mg/kg by 67% and by tamoxifen at a dose of 20 mg/kg by 38%. Lung metastases were regularly seen in both species, although to a lesser extent in nude mice than in DA/Han rats. Tamoxifen treatment did not alter the number of lung metastases, whereas MPA or ovariectomy produced a significant reduction in the number of lung metastases. The EnDA endometrial carcinoma of the DA/Han rat with respect to its oestrogen sensitivity, oestrogen receptor expression, morphology and metastatic growth, grossly resembles a typical endometrial adenocarcinoma and can therefore be regarded as a useful in vivo experimental model for the evaluation of new endocrine treatment strategies.

Functions of estrogens and anti-estrogens in the rat endometrial adenocarcinoma cell lines RUCA-I and RUCA-II.

Inbred rats of the DA/Han and BDII/Han strains have been proposed as suitable model systems for studying hormonal carcinogenesis, because they die mainly from hormone-dependent endometrial adenocarcinoma. Here we characterize the RUCA-I cell line derived from an endometrial adenocarcinoma of an inbred DA/Han rat and the RUCA-II cell line derived from an endometrial adenocarcinoma of an inbred BDII/Han rat. The RUCA-I cell line, if transplanted to the neck of female DA/Han rats, gives rise to endometrial adenocarcinomas at the ectopic site. The morphology of these ectopically grown tumors is predominantly of the moderately differentiated sub-class. In contrast, ectopic tumor growth of the RUCA-II cell line can be observed only if cells are transplanted to athymic nude mice. Biochemically, both cell lines are characterized by the stable expression of estrogen receptors. However, no statistically significant mitotic response of RUCA-I and RUCA-II cells to estradiol was measurable, and no induction of expression of the progesterone receptor by estradiol was detectable, although estradiol transformed the estrogen receptor into its stable DNA-binding state. In contrast, the rate of proliferation of RUCA-I but not of RUCA-II cells was reduced in the presence of 10(-6) M tamoxifen. From these results we conclude that (i) both cell lines, RUCA-I and RUCA-II, represent a new and promising endometrial tumor model; (ii) the mechanism of the hormone-dependent growth regulation of RUCA-I and RUCA-II cells is obviously impaired; (iii) the RUCA-I cell line appears to be a suitable model system for the study of molecular aspects of estrogen- and tamoxifen-dependent gene expression.

Age-associated versus husbandry-related pathology of aging rats.

Longevity studies in four rat strains, Han:WIST, Han:SPRD, DA/Han, and BDII/Han are surveyed. These animals were kept under specified pathogen free conditions in the same animal house under the same maintenance conditions from weaning to natural death. Genetic and pathologic influences on longevity of these four strains are summarized.

Altered tenascin expression during spontaneous endometrial carcinogenesis in the BDII/Han rat.

The BDII/Han rat develops spontaneous endometrial adenocarcinoma, which appears virtually identical histologically to human endometrial adenocarcinoma. The incidence rate of cancer formation in the rat is 90% and the mean lifetime of the animals is 22 months. This animal model therefore, is useful in the study of molecular aspects of spontaneous transformation as well as mammalian neoplastic progression. In this study we address the in-situ expression of tenascin, an extracellular matrix glycoprotein, during normal cyclic growth, during development of proliferative states, and during malignant transformation of the endometrium. Trace amounts of immunocytochemically detectable tenascin were found in 10% of young BDII/Han rats with a normal estrus cycle. In these inbred animals no tenascin was detectable in uteri without neoplastic progressive alterations of the endometrium. Tenascin immunoreactivity first appeared during proliferation in one of three uteri with cystic glandular hyperplasia. Prominent tenascin expression was detectable in all adenomatous hyperplasia, but restricted to the stromal mesenchyme, that surrounded the glands. In all endometrial adenocarcinomas tested, essentially the entire extracellular space of the stromal mesenchyme was immunoreactive with anti-tenascin antibodies while the epithelial glands themselves were negative. This staining pattern was observed independent of the degree of tumor differentiation or extent of myometrial invasion. The tenascin staining pattern was not significantly altered in tumors transplanted into the soft tissues of the neck of female BDII/Han rats. From our studies we conclude that tenascin may be a marker for the early detection of proliferative endometrial states.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence and morphology of spontaneous thyroid tumours in different strains of rats.

The incidence and morphology of thyroid neoplasms in different strains and stocks of rats are reported. The frequency of thyroid tumours varied to a great extent between different strains of rats. Low incidences were observed in DA/Han (0.85 per cent) and BDII/Han rats (1.25 per cent), while somewhat higher incidences occurred in Han:WIST rats (7.3 per cent). The highest number of thyroid tumour-bearing rats was found in the Han:SPRD stock (55.5 per cent). Thyroid neoplasms were classified histologically as polymorphofollicular adenomas, papillary adenomas, cystadenomas, polymorphofollicular carcinomas, papillary carcinomas, C-cell adenomas and C-cell carcinomas (medullary carcinomas). C-cell neoplasms were predominant in Han:SPRD rats (93.0 per cent), while the majority of tumour-bearing Han:WIST rats (61.4 per cent) had follicular tumours.

[Pathological changes in Streptobacillus moniliformis infection of C57bl/6J mice]. / Pathologische Veränderungen bei Streptobacillus moniliformis Infektion von C57BL/6J Müsen.

An epizootic disease caused by Streptobacillus moniliformis occurred in C57BL/6J mice. Pathological lesions included abscessation of lymph nodes and chronic polyarthritis and osteomyelitis. Histological features of the disease are described. The most important differential diagnosis, infectious ectromelia of mice, is discussed.

Mortality and tumour incidence of Han:SPRD rats.

In a longevity study a total of 394 Han:SPRD rats (200 males and 194 females) were kept in a barrier type animal quarter from weaning until their natural death. The mean life span of males was 29.6 +/- 5 months, that of females 27.6 +/- 6.2 months. The most frequent neoplasms in females were mammary gland tumours (63.4%). Neoplasms of endocrine organs were common in animals of both sexes. Thyroid neoplasms, predominantly of C-cell origin, occurred in 60% of the males and 51.5% of the females. Pituitary gland tumours were observed in 53% of male and 45.1% of female rats. Further frequent tumours of the endocrine system included phaeochromocytomas (23% in males, 15.5% in females), adrenal cortex neoplasms (6% in males, 13.5% in females) and tumours of islet cells of the pancreas (20.8% in males, 8.2% in females). An uncommonly high incidence of squamous cell neoplasms (16% in males; 9.3% in females) of the preputial and clitoral gland was observed in this stock. Further organs frequently affected by neoplasms were the skin/subcutis and brain.

The effect of food restriction by time-scheduled feeding on the development of body-weight, lifespan and incidence of spontaneous tumours and diseases in male Han:SPRD rats.

Food consumption, development of body weight, lifespan and incidence of spontaneous diseases and tumours were investigated in 3 groups of 96 male Han:SPRD rats each maintained in a longevity study from weaning up to their natural death. All rats were fed a commercial cereal-based diet. One group received food ad libitum and was used as control group. Access to the diet was controlled in the other two groups by means of an automatic timer. The rats of one of the latter groups were fed nocturnally (4 x 42 min daily during the dark period) and those of the other adiurnally (4 x 42 min daily, each two times during dark and light period). Time-scheduled feeding caused an evident food restriction compared with the food consumption of the rats fed ad libitum. This food restriction, however, was significantly more pronounced in the younger animals during the first weeks after weaning than in the older rats. The body weight development corresponded to the feed intake. In animals subjected to food restriction the weight remained below that of rats fed ad libitum during all age periods. Furthermore, time-scheduled feeding caused an important increase of the mean life expectancy and a reduction in the incidences of chronic nephropathy and purulent and chronic forms of prostatitis. Only a slight effect of controlled feeding was observed on the incidence of alveolar lipoproteinosis. Time-scheduled feeding did not cause a reduction in the incidence of tumours, but it delayed their occurrence. The risk to develop various types of tumours during the third year of life was significantly higher in the ad libitum group than in the rats fed by a controlled regime. The automaton Han:CHRONOFEEDER, used in this study, has proved to be an appropriate, relatively inexpensive and easily installable feeding system for automatic control of food accessibility. It is suitable to implement controlled feeding and food restriction of rodents in longterm experiments.

Renal hypertension in rats with hereditary polycystic kidney disease.

Hereditary polycystic kidney disease (PKD) was observed in a Han:SPRD rat mutant. Cysts were of tubular origin and occurrence was more pronounced in males than in females. In male rats polycystic kidney disease was associated with a marked elevation of systolic blood pressure. Therefore this rat mutant can be considered as a laboratory animal model for renal hypertension associated with adult polycystic kidney disease in man.