Groups of 30 Wistar rats of each sex were treated with 2,2'-methylenebis(4-ethyl-6-tert-butylphenol) (MBEBP) in the diet at levels of 0, 0.03, 0.1 and 0.3% for up to 18 months. In both sexes, survival rates of treated groups were similar to those of the controls. Body weight gain was depressed (0.3% group in males, 0.1 and 0.3% groups in females). Slight anaemia (0.3% groups in both sexes) and increase of blood urea nitrogen (0.3% groups in both sexes) were observed. Histopathologically, vacuolization of the parathyroid gland cells (0.3% group in males and all treated groups in females) and degenerative changes of the kidney (0.1 and 0.3% groups in males) were observed. No neoplastic responses following MBEBP administration were noted. From these results, the no-observed-adverse-effect level (NOAEL) for MBEBP toxicity was estimated as 12 mg kg-1 body wt. day-1 in male rats. In female rats, the lowest-observed-adverse-effect level (LOAEL) was estimated as 15 mg kg-1 body wt. day-1.

Animals↗

PubMedDate not supplied

Spontaneous diabetes-like syndrome in WBN/KOB rats.

Spontaneous hyperglycemia, glycosuria, hypoinsulinemia, and glucose intolerance were observed in some WBN/Kob rats, at about 9 months of age, and in all at the age of 17 months. Females did not present this pathology. Histopathologic examination of the pancreas revealed severe changes in male rats at the age of 3 months. Between 3 and 6 months of age a distinct infiltration of inflammatory cells was found around islets and among adjacent acinar cells. At the same time, marked fibrosis was seen around the pancreatic ducts and blood vessels. With advancing age the fibrous tissue gradually invaded extensive areas of the pancreas where also the islets became involved in fibrotic degeneration. At 17 months of age and later, an obvious decrease in islet number and size (less than 50 mu in diameter) was observed, even in relatively unaffected areas of the organ. Frequent bilateral cataracts began to appear at about 15 months of age. Opacities were first observed in the periphery of the lens, then increased rapidly in intensity and extended centripetally. Nineteen-month-old male rats were hypersensitive to exogenous insulin, but showed no significant decrease in blood glucose level when treated with oral tolbutamide. These results suggest that these rats suffered from a decreased insulinogenic response.

Aging↗

PubMedDate not supplied

Six-month toxicity study of butylated hydroxyanisole in beagle dogs.

Groups of three or four male and female beagle dogs were maintained for 6 months on diets containing BHA at concentrations of 0 (control group), 0.25, 0.5 and 1.0% (w/w). The average daily intake of BHA was about 60 mg/kg body weight in the 0.25% group, 110 mg/kg in the 0.5% group and 220 mg/kg in the 1.0% group. All animals survived the entire experimental period without showing signs of toxicity other than a dose-related retardation of growth. Serum biochemical examinations conducted at 1, 3 and 6 months revealed a slight decrease in albumin concentration and an elevation of alkaline phosphatase and leucine aminopeptidase activity in the higher dose groups. Histopathological and histometrical examination showed no evidence of mucosal alteration in the stomach, oesophagus or duodenum attributable to the administration of BHA. The mitotic index in the squamous epithelium of the distal oesophagus was comparable in the control and BHA-treated groups. Liver weights were increased in BHA-treated groups, but there were no related histopathological changes. From these data it is concluded that feeding of BHA-supplemented diets at palatable concentrations for 6 months has no pathological effects on the stomach, oesophagus, duodenum or liver of beagle dogs.

Administration, Oral↗

PubMedDate not supplied

Rapid neointima formation with elastic laminae similar to the natural arterial wall on an adipose tissue fragmented vascular prosthesis.

A vascular prosthesis that can induce a neointima similar to a natural arterial wall is reported. The authors have developed a sealing method using autologous tissue fragments. The sealed graft showed many advantages, with characteristic neointima formation in an animal study. The grafts were implanted in the thoracic descending aortae of 40 dogs and were removed from 1 hour to 608 days after implantation. Another 40 dogs, used as controls, had a fabric graft implanted using the preclotting method. The luminal surface of the sealed graft was completely endothelialized and the original adipose tissue fragments were absorbed within 1 month. Smooth muscle cells infiltrated and proliferated at the same time as endothelialization took place. Most of the smooth muscle cells were arranged in parallel rows and oriented circumferentially within the graft. At 1 month, elastic fibers appeared around the smooth muscle cells near the anastomotic sites. In the long-term specimens, these elastic fibers constituted a fine lamina in the neointima. Intimal hyperplasia and degenerative changes in the neointima were not observed. These results indicated that the sealing method could induce a very stable neointima with a smooth muscle cell layer and elastic laminae similar to a natural arterial wall within a short period of time throughout the graft wall, with maintenance of the neointima for a long period of time after implantation.

Adipose Tissue↗

PubMedDate not supplied

A functional neointima with regularly arranged smooth muscle cells in a fabric vascular prosthesis transplanted with autologous venous tissue fragments.

Regular arrangement of smooth muscle cells underneath an endothelial cell layer was observed in the neointima of a fabric vascular prosthesis treated with new technology to accelerate endothelialization, i.e., transplantation of autologous venous tissue fragments in the graft wall. This finding indicated that the neointima has a vital function as the intima of the blood vessel. A canine left jugular vein was minced and stirred into 20 ml of saline containing 1,000 IU heparin. It was injected with pressure into a fabric prosthesis (4 mm inner diameter [ID], 3.5 cm in length, Water porosity: 4,000 ml) to create the tissue fragmented, heparinized graft. The graft was implanted into the same animal from which the jugular vein was taken. Forty tissue fragmented heparinized (TFH) grafts were implanted in both carotid arteries of 20 dogs and explanted from 1 hr to 400 days after implantation. In this study, the neointimae of the grafts implanted for more than 1 month are analyzed, with a focus on the arrangement of smooth muscle cells in the neointima. A circumferential arrangement of smooth muscle cells with a thin layer of longitudinally arranged cells underneath was seen in the neointimae, which resemble the arrangement of smooth muscle cells in the natural arterial wall. Some areas had a thin smooth muscle cell layer in the longitudinal direction just under the endothelial cell layer. At anastomotic sites, they ran in parallel rows in the longitudinal direction. The authors previously clarified that the smooth muscle cells arrange in parallel rows in the direction of strain caused by tensile stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗