Effect of Acetamınophen on Ovulation and Implantation in Female Mice

Acetaminophen is known to inhibit prostaglandin synthesis and activate the endocannabinoid system, thereby has been linked to the regulation of mammalian reproductive processes through the same. Growing evidence tends to link acetaminophen reproductive effects in the regulation of ovulation and/or implantation. To provide further evidence, this study was designed to determine the effect of acetaminophen on ovulation and/or implantation. Female Swiss white mice were randomly divided into two experiments, one testing effects on ovulation and the other testing effects on implantation. The two groups were further sub-divided into treatment and control groups, each having N=5 mice. The mice in the treatment groups (TG1 and TG2) received 200mg/kg of acetaminophen while those in the control groups (CG1 and CG2) received the same quantities of normal saline. Mice in experiment group one (TG1, CG1) received acetaminophen/placebo before mating. Those in experiment group two (TG2, CG2) received acetaminophen/placebo for seven days post-mating. The presence of a vaginal plug confirmed mating success. The mice were sacrificed on the 7th day of pregnancy, the uterus harvested and all observed implantation sites counted and recorded. In both treatment groups (TG1 and TG2), a significant reduction in the number of implantation sites (P≤0.05) was observed when compared with the respective control group (CG1 and CG2). The observation points towards a role of acetaminophen in the regulation of ovulation and implantation in female mice reproduction.

Treatment: NSAIDs

Non-steroidal anti-inflammatory drugs (NSAIDs) constitute a diverse group of medications that inhibit prostaglandin synthesis. NSAIDs form the first-line pharmacological therapy in ankylosing spondylitis (AS). A number of randomized controlled trials (RCTs) support the efficacy of NSAIDs in reducing pain and improving patient function. Head-to-head comparisons have demonstrated equivalent effect of different NSAIDs in symptom control. The proposed disease-modifying potential of regular NSAID therapy is debatable and recent literature provides evidence to the contrary. Several safety concerns have been raised regarding long-term use of NSAIDs, especially an increase in cardiovascular risk. This chapter discusses the pharmacology, efficacy in treatment of AS, disease-modifying potential, and safety concerns of NSAIDs.

The use of ibuprofen in the treatment of postoperative pain in dentistry

Postoperative pain is common complication after daily dental care. Non-steroidal anti-inflammatory drugs are among most widely prescribed analgesics for management of postoperative pain. The analgesic effect of a non-steroidal antiinflammatory drug (NSAID) is related to its ability to inhibit prostaglandin synthesis. Ibuprofen (2-proprionic acid derivate) was discovered in the 1960s as a representative of NSAIDs. It is a peripherally acting analgesic with a potent anti-inflammatory action. An extensive retrospective analysis of randomized clinical trials conducted over the last 40 years demonstrated that ibuprofen is effective in moderate to severe postoperative pain for different indications in dentistry. In comparison to other NSAIDs, ibuprofen is characterized by its efficiency, safety and good tolerance. The aim of this article was to present the most important pharmacological and therapeutic characteristics and side effects of ibuprofen used for postoperative pain treatment in dentistry.

Cryptococcus neoformans Produces Authentic Prostaglandin E2 without a Cyclooxygenase

ABSTRACT Many single-celled eukaryotes produce prostaglandin-like molecules, but these have not been absolutely verified by mass spectrometry. We have isolated, and identified by liquid chromatography-tandem mass spectrometry, authentic prostaglandin E2 from Cryptococcus neoformans. Cyclooxygenase inhibitors did not inhibit prostaglandin synthesis, and the cryptococcal genome lacks a cyclooxygenase homolog. Thus, novel enzymes must exist.

Role of endothelial factors in active hyperemic responses in contracting canine muscle

We investigated whether endothelium-derived relaxing factor (EDRF) and prostaglandins, which may be released under conditions of increased blood flow, contribute to the active hyperemia in contracting muscle of anesthetized dogs. The venous outflow from the left gastrocnemius muscle was isolated and measured. The tendon was cut and placed in a force transducer. One group served as a control (Con; n = 9); EDRF synthesis was inhibited using N omega-nitro-L-arginine methyl ester (L-NAME) in a second group (n = 9), and a third group (n = 7) received L-NAME and indomethacin (L-NAME+Indo) to inhibit prostaglandin synthesis. After resting measurements, the distal end of the cut sciatic nerve was stimulated to produce isometric contractions at 1, 2, 4, and 6 twitches/s for 6–8 min, separated by 25-min recovery periods. Blood flow and O2 uptake increased linearly from resting values of 11.8 +/- 2.4 and 0.3 +/- 0.05 ml.100 g-1.min-1, respectively, to maximal values of 84.2 +/- 5.1 and 11.1 +/- 0.7 ml.100 g-1.min-1 in the Con group; neither these values nor those for tension development were different from values observed at comparable contraction frequencies in the L-NAME and L-NAME+Indo groups. At rest, resistance was greater (P < 0.05) in both the L-NAME and L-NAME+Indo groups compared with Con, the highest value (P < 0.05) occurring in the L-NAME+Indo group. Muscle resistance decreased (P < 0.05) in all groups at all contraction frequencies; the values were not different among the three groups.

Role of endothelium-derived relaxing factor in parasympathetic coronary vasodilation

Vasodilation following the infusion of acetylcholine is due to the release of endothelium-derived relaxing factor (EDRF). However, the role of EDRF in neurogenic coronary vasodilation, when acetylcholine is released outside the vessel at the adventitial-medial junction, has not been established. The action of EDRF in parasympathetic coronary vasodilation was tested in the present study using a specific inhibitor of EDRF synthesis, nitro-L-arginine methyl ester (L-NAME). Experiments were conducted on closed-chest, alpha-chloralose-anesthetized dogs with the heart paced at a constant rate. Phentolamine and propranolol were administered to block alpha- and beta-adrenergic receptors, and ibuprofen was given to inhibit prostaglandin synthesis. Intracoronary infusion of L-NAME decreased the coronary vasodilation in response to intracoronary acetylcholine or vagal stimulation. The coronary response to the endothelium-independent vasodilator nitroglycerin was unaffected by L-NAME. These data demonstrate that L-NAME specifically inhibits coronary vasodilation caused by acetylcholine and vagal stimulation, indicating that parasympathetic coronary vasodilation is dependent on EDRF.

Gastric ulceration induced by nonsteroidal anti-inflammatory drugs is a neutrophil-dependent process

The hypothesis that neutrophils play an important role in the pathogenesis of gastric ulceration induced by nonsteroidal anti-inflammatory drugs (NSAIDs) was tested in rats. Rats made neutropenic by prior treatment with an antibody to rat neutrophils raised in goat were found to be significantly more resistant to the gastric-damaging actions of indomethacin or naproxen than were control rats or rats pretreated with normal goat serum. The reduction of damage in neutropenic rats was not due to effects of the antineutrophil serum on either gastric acid secretion or the ability of indomethacin or naproxen to inhibit prostaglandin synthesis. Gastric cyclooxygenase activity was inhibited by greater than 95% in both normal and neutropenic rats that received indomethacin or naproxen. Reduction of circulating neutrophil numbers by treating rats with methotrexate also resulted in a significant reduction in the susceptibility to gastric damage induced by indomethacin. Since activation of circulating neutrophils appeared to be important in the development of gastric erosions after administration of indomethacin, and in the significant changes in vascular endothelial integrity (Monastral Blue staining) observed within 15 min of indomethacin administration, we investigated the possibility that leukotrienes (LTs) and platelet-activating factor (PAF) might be involved in the pathogenesis of indomethacin-induced ulceration. Changes in gastric LTB4 synthesis were not observed after indomethacin administration. Pretreatment with either an LTD4 antagonist or a PAF antagonist was without significant effect on the extent of gastric damage induced by indomethacin. These results suggest an important role for neutrophils in the pathogenesis of NSAID-induced gastric ulceration. Neutrophils may be important in the vascular injury that occurs early after administration of these compounds.