Further investigation on meloxicam contraceptivity in female rabbits: luteinizing unruptured follicles, a microscopic evidence.

Meloxicam, a selective cyclooxygenase-2 inhibitor, was administered orally or intravaginally, to sperm-positive female rabbits to assess its effect on ovulation. A single oral dose (20 mg/kg), administered 5 h postcoitus resulted in 100% contraceptive rate. On the other hand, for females receiving meloxicam suppositories (14.9 mg/kg), 5 h postcoitus, the contraceptive rate was 62.5% compared to placebo. The decrease in the contraceptive effect of meloxicam suppository may be due to the rejection of the dose by some females. Corpora lutea, maternal plasma progesterone, ovary fresh weight and maternal body weight gain were not affected by meloxicam treatment compared to placebo. Histopathologically, the surface of the ovary of meloxicam-treated females appears irregular and dilated due to the presence of different-sized cysts. Some of the cystic follicles were retained ova. Further, immunohistochemical stains for estrogen and progesterone receptors showed positive staining in granulosa cells and the wall of the unruptured follicle. It is concluded that contraceptive effect of meloxicam in female rabbits resulted in a failure of follicular rupturing.

Meloxicam inhibits rabbit ovulation.

The nonsteroidal antiinflammatory, selective cyclo-oxygenase-2 (COX-2) inhibitor, meloxicam, was tested to assess its effect on rabbit ovulation. Meloxicam in different doses was administered intraperitoneally (ip) to adult female Californian rabbits at 2, 5, 8, and 24 h postcoitus with sperm-positive rabbits. Rabbits were killed on Day 10 of gestation. Meloxicam produced significant inhibition of ovulation in rabbits. This inhibition of ovulation by meloxicam was dose- and time-dependent. Ovulation in rabbits was completely inhibited by a single ip administration of meloxicam (20 mg/kg) when the drug was administered at 2 and 5 h postcoitus, whereas neither ovulation nor implantation were inhibited (pregnancy rate 75%) by the same dose administered 24 h postcoitus (approximately 14 h post ovulation). Further, ovulation was completely inhibited by 10 mg/kg of meloxicam when the drug was administered at 5 or 8 h postcoitus, but there was less inhibition of ovulation when 10 mg/kg of the drug was administered at 2 or 24 h postcoitus (pregnancy rate 25 and 80%, respectively). Corpora lutea, maternal plasma progesterone, ovary fresh weight, and maternal body weight gain were affected by meloxicam treatment. Histopathological findings observed in the ovaries of treated rabbits included microscopic dilatation of graffian follicles, particularly mature follicles. Some of the follicles were cystically dilated in addition to severe hemorrhage within the follicles which lost ova. These results show that ovulation can be inhibited in rabbits by meloxicam. Further studies are needed to assess the value of selective COX-2 inhibitors as potential nonhormonal contraceptive agents.

Aluminum phosphide fatalities, new local experience.

Aluminum phosphide (AlP) pesticide is a highly toxic, low cost, and easily accessible rodenticidal agent. Its toxicity results from the liberation of phosphine gas upon exposure to moisture, which leads to multisystem involvement, resulting in serious consequences. The highly toxic parathion insecticide was a common cause of mortality in pesticide fatalities, prior to its banning. Its toxicity was familiar to the public as well as to physicians. Recently, ten fatalities due to AlP were encountered within a three-month period during spring, when it was used as a rodenticide in the vicinity of grain stores. The victims' ages ranged from 1-34 years. The circumstances of death were accidental in six cases, suicidal in two and possibly homicidal in two cases. Retrospectively, the clinical manifestations, scene investigation, autopsy, histological and toxicological findings supported the diagnosis of AlP intoxication. Immediate recognition was difficult due to unfamiliarity of the agent to the physicians. The occurrence of these fatalities might suggest changes of pattern in pesticide poisoning. This should raise the attention of the physician to the problem of AlP poisoning and also necessitates the awareness of the public to the hazards of this poison. Education, proper handling, strict observation and abiding by the regulations controlling this material are good protective measures against AlP poisoning.

Effects of castor bean extract and ricin A-chain on ovulation and implantation in rabbits.

The anti-implantation and antiovulation effects of castor bean extract (CBE) and ricin A-chain (RAC) were evaluated in rabbits. Both CBE and RAC, administered intraperitoneally on days 5-9 of pregnancy, exhibited a pronounced decrease in maternal body weight gain and in death of all fetuses. A significant (p < 0.01) decrease of implantation sites resulted after rabbits were treated with RAC on the first 6 consecutive days of pregnancy. When female rabbits were treated with RAC for 10 consecutive days followed by human chorionic gonadotropin (hCG) (50 IU/kg intravenously), there was a 30% reduction in the number of corpora lutae. These data clearly indicate that CBE and RAC possess potent effects on implantation and ovulation in rabbits. The protein contents of castor bean extract, separated by polyacrylamide gel electrophoresis, revealed the presence of several protein bands, ricin toxin being a major constituent of the extract.