Effects of periplocoside X on midgut cells and digestive enzymes activity of the soldiers of red imported fire ant.

The pathological effects of ingested periplocoside X, an insecticidal component isolated from the root of Periploca sepium Bunge, on the midgut epithelial cells of the soldiers of red imported fire ant were studied and the symptom was described. The results showed that periplocoside X could induce a severe, time-dependent cytotoxicity in the midgut epithelial cells. An optical microscopy showed that epithelial cells swelled firstly and then lysed. Transmission electron microscopy (TEM) showed that numerous swollen lysosomes were appeared, microvilli were disrupted and sloughed off, and the numbers of the rough endoplasmic reticulum and the mitochondria decreased sharply in earlier stage. Numerous vacuoles were observed in the later stage. Finally, periplocoside X resulted in cell death by cytolysis. Assay of main three digestive enzymes activity indicated that amylase activity was significantly inhibited, but no significant changes were seen for lipase activity and total protease activity. So it is suggested that periplocoside X induced mainly to organic damage of midgut epithelium cells of insect. In all, insect midgut is one of targets for periplocoside X.

Polypodoside A, an intensely sweet constituent of the rhizomes of Polypodium glycyrrhiza.

Polypodoside A, a novel intensely sweet constituent of the rhizomes of Polypodium glycyrrhiza, was established by spectral and chemical methods as 26-O-alpha-L-rhamnopyranosyl-polypodogenin-3-O-alpha-L-rhamnopyran osyl- (1----2)-beta-D-glucopyranoside [1]. At the doses tested, this isolate was not acutely toxic for mice and was nonmutagenic with Salmonella typhimurium strain TM677. This compound was rated by a human taste panel as exhibiting 600 times the sweetness intensity of a 6% w/v aqueous sucrose solution.

The morphologic effects of synthetic reproductive steroids on the mammary gland of rhesus monkeys. Mestranol, ethynerone, mestranol-ethynerone, chloroethynyl norgestrel-mestranol, and anagestone acetate-mestranol combinations.

A total of 213 treated and 16 control monkeys comprising 12 experimental groups was evaluated for determination of the long-term (10 years) effects of various dosages of a variety of synthetic oral contraceptive steroids on the mammary glands of rhesus monkeys. The steroid hormones included mestranol, ethynerone, a combination of mestranol and ethynerone, chlorethynyl norgestrel plus mestranol, and anagestone acetate plus mestranol. Various degrees of physiologic lobular hyperplasia and lactational changes were observed in association with all of these steroid hormones; these changes appeared dose-dependent. Mestranol caused a proliferative atypia ranging from a minimal to a moderate degree in 8 of 34 (23%) animals, but it was not dose-related. Eleven of 15 monkeys (73%) administered ethynerone developed proliferative atypia, ranging in degree from minimal to severe, including one invasive carcinoma and 2 lesions resembling intraductal carcinoma in the human. The mestranol and ethynerone combination produced a proliferative atypia in 22 of 52 animals (42%), including five identical to intraductal carcinoma in the human and one identical to lobular neoplasia. Of the 40 monkeys administered anagestone acetate and mestranol, 20 (50%) developed proliferative atypias; the atypias ranged from mild to severe and included five resembling intraductal carcinoma in human breast. The chloroethynyl norgestrel and mestranol combination induced proliferative atypia in 25 of 52 monkeys (49%); six of these atypias were severe and indistinguishable from intraductal carcinoma of the human breast; and one, if in the human breast, would reflect a solid variant of an invasive carcinoma. Only 2 of the 16 control monkeys (12%) developed proliferative atypias, and these were of minimal to mild degree. The occurrence of severe degrees of atypia identical to intraductal carcinoma in the human breast and invasive carcinoma associated with hormone administration suggests a carcinogenic effect.

Malignant mammary tumors in beagle dogs dosed with investigational oral contraceptive steroids.

Of 172 beagle dogs administered investigational oral contraceptive steroids for 2.4-5.2 years, 9 developed malignant mammary tumors. At necropsy their ages varied from 41 to 70 months, with a mean age of 4.9 years. The malignant tumors were observed in 1 dog that received ethynerone plus mestranol at 1.05 mg/kg/day and in 4 dogs that received chlorethynyl norgestrel plus mestranol at 1.05 mg/kg/day. Also, 4 dogs that received anagestone acetate plus mestranol at either 0.44 or 1.10 mg/kg/day developed malignant mammary tumors. Malignant tumors were not seen in 33 dogs administered mestranol at 0.02 and 0.05 mg/kg/day for 7 years or in 18 dogs given ethynerone without mestranol at 1.00 mg/kg/day for 5 years. No malignant tumors were observed in 18 control dogs maintained for 7 years without treatment. Three dogs had single malignant mammary nodules, 3 dogs had 2 malignant nodules, 2 dogs had 4-6 malignant nodules, and 1 dog in the treatment group given high dosages of ethynerone plus mestranol had 14 mammary nodules composed of fibrosarcoma. The malignant tumors were histologically classified as 5 anaplastic carcinomas, 2 solid carcinomas, 1 tubular adenocarcinoma, 1 squamous cell carcinoma, and 1 fibrosarcoma. Most dogs had only 1 histologic type of cancer (8/9 dogs); however, 1 dog had carcinomas of both solid and anaplastic types involving different glands. Metastases were present in 5 dogs and most often involved regional lymph nodes and lung.

[Ultrastructural study of rat liver after administration of an aminated steroid (author's transl)]. / Etude ultrastructurale du tissu hépatique chez le rat, après administration d'un stéroïde aminé.

The administration of amino-3 beta hydroxy-20 beta pregnene-5, to the male Wistar rat, per os, at doses of 100 and 200 mg/kg/24 h, induce the development of a chronic active hepatitis. The ultrastructural observation shows slight changes only in perilobular hepatocytes at the beginning of treatment; then hepatocellular alterations progressively increase and may be observed in the whole lobule after 40 and 80 days of treatment; the progression of hepatocellular damage is associated with collagen increase and bile duct proliferation. The interest of this experimental hepatitis, as a model analogous to human chronic active hepatitis, is discussed.

Mammary nodules in beagle dogs administered investigational oral contraceptive steroids.

Of 172 beagle dogs administered oral contraceptive steroids for 5-7 years, 114 developed 1,156 nodules in the mammary gland region. Most of these nodules arose 2.5-3.5 years after initiation of treatment. Approximately 16% of the nodules were transient and disappeared spontaneously from the mammary gland during the study. A total of 925 nodules were present in 99 dogs at the time of death or necropsy. These nodules were classified as benign mammary dysplasias (7.0%), lobular or intraductal hyperplasias (31.4%), simple adenomas (20.8%), complex adenomas (25.4%), benign mixed tumors (5.3%), malignant tumors (3.6%), or nonmammary lesions (6.5%). Histologically, the mammary nodules were representative primarily of the hyperplasias and tumors that occur spontaneously in the mammary glands of the dog. The only major exception was the presence of 82 simple adenomas that had basaloid features. Most of the contraceptive-related mammary nodules developed in dogs receiving the combination of progestion and mestranol at 10 or 25 times the proposed human dosage. Control dogs and dogs receiving mestrenol alone had few mammary nodules. Combinations of anagestone acetate and mestranol and chloroethynyl norgestrel (WY-4355) and mestranol produced large numbers of nodules at 10 and 25 times the proposed human dosage, whereas ethynerone plus mestranol produced large numbers of nodules only at 25 times the proposed human dosage. Ethynerone, when given alone at 25 times the proposed human dosage, was associated with fewer mammary nodules. Malignant neoplasms were seen in dogs given 10 and 25 times the proposed human dosage of anagestone acetate plus mestranol and 25 times the proposed human dosage of WY-4355 plus mestranol and ethynerone plus mestranol. This study strongly associates certain combinations of progestin and mestranol with mammary neoplasia in dogs.