Diacerein inhibits Estradiol-benzoate induced cervical hyperkeratosis in female rats.

Cervical hyperkeratosis is a common gynecological lesion and usually caused by inflammation or trauma. We investigated the effect of Diacerein on Estradiol benzoate-induced cervical hyperkeratosis. Diacerein (50mg/kg/day) was given orally to rats for 4 weeks in the presence or absence of cervical hyperkeratosis induced by intramuscular injection of Estradiol benzoate (60µg/100g) 3 times per week for 4 weeks. We measured the serum levels of total cholesterol, uterine weights, uterine tissue malondialdehyde, total nitrites, superoxide dismutase activity, caspase-3, interleukin-1b immunoexpression and histopathology. Our results showed that Estradiol benzoate succeeded to induce cervical hyperkeratosis which was detected by typical histopathological changes. In addition; there was significant reduction in superoxide dismutase levels and caspase-3 immunoexpression but significant increase in serum total cholesterol, malondialdehyde, total nitrites and interleukin-1b immunoexpression. Diacerein could improve all measured parameters to normal levels. It markedly prevented cervical hyperkeratosis through its anti-inflammatory (IL-1b receptor inhibitor), antioxidant and anti-apoptotic effects.

Lupron depot prevention of antispermatogenic/antifertility activity of the indenopyridine, CDB-4022, in the rat.

The goals of this study were to determine the CDB-4022 dose-response relationship for induction of acute decreases in testicular weight and germ cell depopulation in rats; establish the threshold dose of CDB-4022 required to induce infertility; and investigate whether CDB-4022-induced testicular damage could be prevented by a GnRH agonist (Lupron Depot). Reduction of testis weight and germ cell depopulation were observed 7 days after a single oral dose of 1 mg CDB-4022/kg, whereas 0.5 mg/kg had no observable effect. These effects were maximal at 12.5 or 25 mg CDB-4022/kg. After a single oral dose of either 2.5 or 5 mg/kg, CDB-4022 induced infertility in five of five treated rats by Week 5, whereas only one of five males was rendered infertile at a dose of 1 mg/kg. Proven fertile male rats (6/group) were treated with vehicle, CDB-4022 alone (2.5 mg/kg on Day 0), CDB-4022 plus Lupron Depot (on Weeks -1, 2, 5, and 8), or Lupron Depot alone. Control males demonstrated normal fertility throughout a 32-wk cohabitation period. Five of six rats were rendered transiently infertile with Lupron Depot alone, but all recovered fertility. CDB-4022 treatment resulted in infertility in all six rats, and only one of six regained fertility. Combined treatment also caused infertility in all six rats, but four of six recovered fertility (P = 0.08 compared to CDB-4022 alone). Testicular weight was decreased in the three treatment groups compared to vehicle controls; testicular weights were ranked from highest to lowest as follows: vehicle > Lupron Depot > Lupron Depot + CDB-4022 > CDB-4022. The tubule differentiation index of Lupron Depot-treated rats (96 +/- 4%) was not different from vehicle-treated rats (100%). CDB-4022 treatment decreased the number of differentiating tubules (15 +/- 8%). Lupron Depot plus CDB-4022 treatment resulted in a greater number of differentiating tubules (53 +/- 12%) than CDB-4022 alone, but this was still lower than vehicle- or Lupron Depot-treated rats. These data indicate that 2.5 mg/kg of CDB-4022 was the oral threshold dose that caused testicular damage rendering the majority of adult male rats permanently infertile within the study interval; 12.5 mg/kg of CDB-4022 induced maximal testicular damage. Suppression of gonadotropins and/or testosterone production by treatment with Lupron Depot before and after CDB-4022 prevented the CDB-4022-induced irreversible testicular damage.

[Therapy of secondary effects produced by anovulatory agents]. / Terapéutica de los efectos secundarios producidos por anovulatorios

PIP: The most common side effects produced by anovulatory contraceptives are similar to those experienced in the 1st months of pregnancy, e.g., weight gain, nausea, and fatigue. In an effort to determine to what extent such side effects were attributable to the medication and to what extent they were psychological, KN-1055 was administered to 43 women taking anovulatory contraceptives. 10 began taking both substances simultaneously; none of them had any side effects. The remaining 33 were selected from a group of 140 already taking anovulatories because they were experiencing side effects. Experience of side effects was not found to be related to either age or parity. Side effects were eliminated within 14 days of administration of 2 tablets daily of KN-10055 in 15 cases, which was thought to be a very good result; within 28 days in 13 cases, a good result; and in more than 28 days in 3 cases. In 2 cases KN-10055 did not eliminate side effects; such effects were therefore thought to be of psychological origin. Treatment during 2 cycles was sufficient, though KN-10055 can be taken for as many cycles as necessary.^ieng

Studies on the antifertility effect and metabolism of a new, postcoital oral contraceptive, 2-methyl-3-ethyl-4-phenyl-delta-4-cyclohexene carboxylic acid, sodium salt (ORF-4463).

PIP: Studies on the antifertility effect and metabolism of a new postcoital oral contraceptive, 2-methyl-3-ethyl-4-phenyl-delta 4-cyclohexene carboxylic, sodium salt (ORF-4563) are presented. 25 mcg/kg of ORF-4563 administered orally to female rats on the morning of sperm deposition prevented pregnancy. This effect was blocked by the ad ministration of beta-diethylaminoethyldephenylpropylacetate (SKF-525A) and SKF-525A did not block the antifertility activity of cartain para-substituted derivatives of ORF-4563. In the rabbit much higher doses (higher than 60 mg/kg in 1 rabbit) were required to prevent pregnancy when the compound was given orally 24 hours after mating. This compound is excreted via the kidney much more rapidly in the rabbit than the rat with less than 1% appearing in the urine as unchanged material. The conversion of the effective dose (ED) 50 in rabbits to the ED100 was accomplished by the conjunct administration of probenecid. Labeled drug-distribution studies in the rabbit revealed that the highest amounts at 4 hours were found in bladder urine, then in serum, kidney and bile. The oviductal fluid showed peak levels of the drug at 48 hours and a persistence for several days.^ieng