Foregut cyst of the oesophageal wall in a cynomolgus monkey (Macaca fascicularis).

Congenital oesophageal cysts of foregut origin are rare in animals and human beings. This report describes a case in a 4-year-old cynomolgus monkey with no clinical symptoms. The cyst, which was located within the oesophageal submucosal tissue near the mid-point of the oesophagus, was lined with pseudostratified ciliated epithelium and had a thin layer of submucosal tissue. The cyst was surrounded by a smooth muscle layer which was partly intermingled with the circular muscle layer of the oesophagus. The muscularis mucosae of the oesophagus was not shared with the cyst wall. Simple tubular glands were present, opening into the cyst lumen. No communication between the cyst lumen and the oesophagus was observed. Cartilaginous tissue, which is a diagnostic feature of bronchogenic cysts, was not identified in the cyst wall. On the basis of the histopathological features, a foregut cyst of the oesophagus was diagnosed.

Therapeutic effects of water-soluble echinocandin compounds on Pneumocystis pneumonia in mice.

The therapeutic effectiveness of water-soluble echinocandin compounds obtained from Coleophoma empetri F-11899, which has a strong inhibitory effect on the growth of fungi, was examined in nude mice with experimental Pneumocystis pneumonia. The studies demonstrated the potential usefulness of the compounds.

Restoration of Leydig cells after repeated administration of ethane dimethanesulfonate in adult rats.

Adult male rats were repeatedly treated with ethane dimethanesulfonate (EDS), an agent known to destroy Leydig cells selectively. Following a second injection, changes in serum testosterone levels and histological and morphometric changes of Leydig cells showed the time course to be similar to those after the first treatment. The number and volume of Leydig cells markedly decreased at day 2, began to increase from day 7, and recovered to the values of the control rats at day 30, concomitant with the changes of serum testosterone levels. Cells in the interstitial tissue labeled with bromodeoxyuridine markedly increased in number at day 2, gradually decreased thereafter, and returned to the values of the controls at day 14. During this period, cells undergoing mitosis were seen, their type unable to be determined, but were presumed to be regenerating Leydig cells. Even 30 days following four treatments with intervals of 30 days each, serum testosterone levels were the same as those in the controls. Also the numerical and volume densities of Leydig cells and the volume of an average Leydig cell were the same as those of the controls. Mitosis was observed in mature Leydig cells at this period, if any. It appears that new Leydig cells began to proliferate by division earlier than 14 days after EDS, allowing that there were several stages of proliferation, and that the source of reappearing Leydig cells may not be a limited number of precursor cells, implying the presence of stem cells for Leydig cells.

Effect of Prograf (FK506) on spermatogenesis in rats.

Prograf (FK506) was given to male mature rats in a daily subcutaneous dose of 1 or 3 mg/kg/day for 2 weeks to investigate its effect on spermatogenesis. Prograf dose-dependently sperm counts and motility, but did not affect testosterone level in the serum of rats. Histopathologically, there were no abnormal changes in the testis, seminal vesicle or prostate in any rats dosed with Prograf, but intra-ductal eosinophilic globules, probably degeneration of the sperm cells, were observed in the epididymis of the 3 mg/kg/day group. Sperm counts and motility returned to the control levels after stopping of the drug. The results indicate that Prograf decreased sperm counts and motility through direct action on the sperm in the epididymis, but not the production of sperm in the testis. Cyclosporine A (CsA) was used as the reference drug in the present study. Thirty mg/kg/day of CsA also decreased sperm counts and motility, and stopping of the drug led to the recovery of these changes. The males dosed with Prograf for 2 weeks were mated with non-dosed females to investigate its effect on the fertility potential of the males. Prograf did not affect copulation or fertility index, but a decrease in the number of live fetuses associated with implantation loss was observed in the 3 mg/kg/day group. The changes were considered to be due to the decrease of sperm counts and motility, although 1 mg/kg/day of Prograf, 5-10 times the clinical dose, did not affect any fertility parameters including implantation index.

Tacrolimus (FK506)-induced nephrotoxicity in spontaneous hypertensive rats.

To clarify the profile of the tacrolimus (FK506)-induced nephrotoxicity and its mechanism, 1, 2 and 4 mg/kg/day of tacrolimus was administered intramuscularly (i.m.) to spontaneous hypertensive rats (SHR) for 2 weeks, and biochemical and pathological parameters were studied in the animals. The acute nephrotoxicity of tacrolimus was characterized as increase of blood urea nitrogen (BUN) and plasma creatinine (P-Cr) levels in the groups of 1 mg/kg/day and more, decrease of creatinine clearance (CCr) value in the groups of 2 mg/kg/day and more, and histopathologically luminal narrowing of the arteriole adjacent the glomerulus in the groups of 1 mg/kg/day and more. These changes were associated with an increase of plasma renin activity (PRA) and urinary thromboxane B2 content and decrease of 6-keto-prostagrandinF1 alpha (6-keto-PGF1 alpha) content. Nilvadipine, which is one of the Ca2+ antagonist and is known to have renal vasodilating activity, prevented both biochemical and histopathological changes due to tacrolimus. The results indicated that the acute nephrotoxicity of tacrolimus was derived from impairment of glomerular function associated with the constriction of the renal arteriole brought about by the drug. All of these renal disorders induced by tacrolimus recovered completely or partially when the drug was withdrawn for 2 or 4 weeks. Consequently, the acute nephrotoxicity of tacrolimus in SHR was considered to be reversible.

Effects of hydrochloric acid on the development of enterochromaffin-like (ECL) cell hyperplasia in the rat stomach induced by omeprazole.

In the present study, gastric pH was lowered by hydrochloric acid to investigate whether the cause of enterochromaffin-like (ECL) cell hyperplasia was due to the inhibition of acid secretion by omeprazole or due to the direct action of the drug. Omeprazole was given to female Crj:CD (SD) rats in a daily oral dose of 2 or 8 mg/kg for 13 weeks, and 20 ml/kg of 0.12 N HCl was further given orally to the animals 3 and 6 hours after each dosing. The animals were killed at the end of the dosing period, and the stomach was removed and weighed. The thickness of the gastric wall was measured and ECL cell count and area rate of the cells were calculated with an image analyzer. There were no effects of the treatment with HCl on stomach weight or thickness of the gastric wall, but ECL cell count and area rate of the cells decreased markedly by the treatment with HCl. Therefore, the cause of gastric ECL cell hyperplasia induced by omeprazole was suggested to be sustained high gastric pH levels.

The high incidence of atrial thrombosis in mice given doxorubicin.

Doxorubicin (DX)-treated mice represent an animal model for studying new drugs for heart disease. Coincidentally, in the collection of damaged myocardial tissue, thrombosis was detected in the atrium. The incidence reached 75% in mice given 4 mg/kg DX iv 10 times. They were white thrombi consisting of the fibrin, platelets, and neutrophils. Cardiac muscle damage was more prominent in the atria than in the ventricles. Light microscopically, vacuolization and degeneration of atrial myocytes and interstitial inflammatory cell infiltration were observed. Electron microscopy revealed dilatation of the sarcoplasmic reticulum and an increase in number of normal and/or degenerate mitochondria. Inflammation extended from the cardiac muscle to the endocardium. The cause of atrial thrombosis in DX-treated mice is unknown but may relate to endocardial damage and changes of blood flow in the atrium secondary to cardiac muscle damage. DX-treated mice could serve as an experimental animal model for the evaluation of efficacy and toxicity of antithrombotic or antiplatelet drugs.

Morphological and functional changes of islets of Langerhans in FK506-treated rats.

FK506, a new immunosuppressant, caused glucose intolerance in rats given daily oral doses of 1, 5, or 10 mg/kg/day for 14 days, but did not induce hyperglycemia under normal feeding. Besides the glucose intolerance, insulin secretion was impaired and insulin levels in the pancreas were lowered. Histopathologically, there was vacuolation of the Langerhans islets in the animals given 10 mg/kg. After withdrawal of the drug, these changes in pancreatic function and morphology returned to normal within 2 weeks. The findings indicate that FK506 caused dose-dependent but reversible islet toxicity in rats.