Prostaglandins

Resveratrol is a natural molecule with antioxidant action. Moreover, resveratrol is also considered to be a molecule with anti-inflammatory action, an effect attributed to suppression of prostaglandin (PG) biosynthesis. The aim of the present study was to investigate the effects of resveratrol, a polyphenol present in most red wines, on reactive oxygen species formation as well as on arachidonic acid (AA) release, cyclooxygenase expression, and PG synthesis in murine resident peritoneal macrophages. Results show that resveratrol exerted a strong inhibitory effect on superoxide radical (O2−) and hydrogen peroxide (H2O2) produced by macrophages stimulated by lipopolysaccharides (LPS) or phorbol esters (PMA). Resveratrol also significantly decreased [3H]AA release induced by LPS and PMA or by exposure to O2− or H2O2. Resveratrol treatment caused a significant impairment of cyclooxygenase-2 (COX-2) induction stimulated by LPS and PMA or by O2− or H2O2 exposure. These effects of resveratrol on [3H]AA release and COX-2 overexpression were correlated with a marked reduction of PG synthesis. Our results indicate that the antioxidant action of resveratrol affects AA mobilization and COX-2 induction.

Although dysmenorrhea is a leading cause of gynecologic complaints among adolescents, its pathogenesis is incompletely understood. The purpose of this study was to determine the role of prostaglandins and leukotrienes in the pathogenesis of dysmenorrhea. Twenty patients with dysmenorrhea aged 16.2+/-1.2 years and 20 healthy age-matched controls with eumenorrhea (absence of pain during menstruation) were included in the study. Serial measurements of serum PGF2alpha and urinary LTE4 levels during the menstrual cycle were obtained; serum progesterone was measured and ultrasonographic evaluations were made. LTE4 and PGF2alpha levels decreased on the third day and recovered on the 10th day of the menstrual cycle in both groups. Urinary LTE4 levels were higher in the control group than in the patient group on the 1st, 3rd and 10th days of the cycle (p<0.05 for each). This study suggests that there is a distinct pattern of leukotriene production during the menstrual cycle, but the chang...

An inherited deficiency of the mitochondrial protein frataxin causes Friedreich's ataxia (FRDA); the mechanism by which this deficiency triggers neuro- and cardio-degeneration is unclear. Microarrays of neural tissue of animal models of the disease showed decreases in antioxidant genes, and increases in inflammatory genes. Cyclooxygenase (COX)-derived oxylipins are important mediators of inflammation. We measured oxylipin levels using tandem mass spectrometry and ELISAs in multiple cell and animal models of FRDA. Mass spectrometry revealed increases in concentrations of prostaglandins, thromboxane B2, 15-HETE and 11-HETE in cerebellar samples of knockin knockout mice. One possible explanation for the elevated oxylipins is that frataxin deficiency results in increased COX activity. While constitutive COX1 was unchanged, inducible COX2 expression was elevated over 1.35-fold (P < 0.05) in two Friedreich's mouse models and Friedreich's lymphocytes. Consistent with higher ...

Prostanoids act leading roles in a myriad of physiologic and pathologic processes because these autacoids participate in the amplification of biological responses induced by innumerable stimuli. The formation of prostanoids is operated by two synthases named cyclooxygenase(COX)-1 and COX-2. Traditional nonsteroidal antiinflammatory drugs (tNSAIDs) and COX-2 inhibitors (coxibs) give rise to antipyretic, analgesic, and antiinflammatory actions, through their reversible clogging of the COX channel of COX-2 - apart from aspirin which modifies irreversibly the catalytic activity of COX-2. tNSAIDs and COX-2 inhibitors resulted clinically equivalent for the relief of acute pain and symptoms of arthropathies but they failed to modify disease progression. Clinical evidence of the possible contribution of COX-1 in inflammation and pain in some occasion - as suggested by experimental and pharmacology studies - is orphan because none efficacy trial with COX inhibitors was designed to establish ...

The administration of oxytocic drugs during caesarean section is an important intervention to prevent uterine atony or treat established postpartum haemorrhage. Considerable past and current research has shown that these agents have a narrow therapeutic range. A detailed knowledge by anaesthetists of optimal doses and side effects is therefore required. Oxytocin remains the first line agent. In view of receptor desensitisation, second line agents may be required, namely ergot alkaloids and prostaglandins. This review examines the adverse haemodynamic and side effects, and methods for their limitation. An approach to dosing and choices of agent for the limitation of postpartum haemorrhage is suggested.

The implantation process involves complex and synchronized molecular and cellular events between the uterus and the implanting embryo. These events are regulated by paracrine and autocrine factors. Trophoblast invasion and migration through the uterine wall is mediated by molecular and cellular interactions, controlled by the trophoblast and the maternal microenvironment. This review is focused on the molecular constituents of the human trophoblast, their actions and interactions, including interrelations with the uterine endometrium.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are nowadays widely used in ophthalmology to reduce eye inflammation, pain, and cystoid macular edema associated with cataract surgery. Recently, new topical NSAIDs have been approved for topical ophthalmic use, allowing for greater drug penetration into the vitreous. Hence, new therapeutic effects can be achieved, such as reduction of exudation secondary to age-related macular degeneration or diabetic maculopathy. We provide an updated review on the clinical use of NSAIDs for retinal diseases, with a focus on the potential future applications.

Skeletal muscle injuries are a common problem in trauma and orthopaedic surgery. Muscle injuries undergo the healing phases of degeneration, inflammation, regeneration, and fibrosis. Current and experimental therapies to improve muscle regeneration and limit muscle fibrosis include conservative and surgical principles with the adjuvant use of non-steroidal anti-inflammatory drugs (NSAIDs) and growth factor manipulation. NSAIDs appear to have a paradoxical effect on the healing of muscle injuries with early signs of improvement and subsequent late impairment in functional capacity and histology. In vitro and in vivo studies have explored the role of the cyclooxygenases and prostaglandins in the biological processes of healing muscle, including precursor cell activation, myoblast proliferation, myoblast fusion, and muscle protein synthesis. Through use of more specific cyclooxygenase inhibitors, we may be able to better understand the role of inflammation in muscle healing.

Summary. The existing data on the hormonal factors involved in human parturition indicate that the steroid hormones, progesterone and the oestrogens, play only a facilitatory role in the initiation of labour. A definite role for fetal adrenal steroids in this process has yet to be established, and they too may serve only a facilitating function. The stimulation of the uterine muscle during labour results from an interaction of oxytocin and prostaglandin (PG) F2α. Recent evidence suggests that oxytocin is most important for the initial phase of labour, whereas increased synthesis of PGF2α is essential for the progression of labour. The role of PGE2 remains unclear, but this PG may play an important role in the ripening of the cervix which in turn is essential for successful parturition. The finding of maximal oxytocin receptor concentrations in the myometrium in labour adds strong support to the notion that oxytocin is the trigger for uterine contractions. The factors which control oxytocin receptor formation are therefore important; this may be one of the processes where the steroids play a crucial role. Oxytocin is also one of the stimuli that increase uterine PG synthesis; the coupling of oxytocin receptor occupancy and PG synthetase activity in uterine tissues may be another crucial factor in the mechanism of labour. The formation of gap junctions between the myometrial cells also seems essential for the synchronization and progression of myometrial activity. We propose, therefore, that the co-ordinating of oxytocin receptor formation, PG synthesis and gap junction formation is a key to the initiation and maintenance of human labour. The fetus may fulfil such a co-ordinating role through its influence on placental oestrogen production, through mechanical distention of the uterus, and through its secretion of neurohypophysial hormones and other stimulators of PG synthesis.

The female gender reduces the risk, but succumbs more to cardiovascular disease. The hypothesis that shortterm
(8 weeks) Streptozotocin-induced diabetes could produce greater female thanmale vascular tissue reactivity
and themechanistic basiswere explored. Aortic ring responses to Phenylephrine were examined in age- and
sex-matched normoglycaemic/diabetic rats. The normoglycaemic male tissue contracted significantly more than
the normoglycaemic female and the male/female diabetic tissues. Endothelial-denudation, L-NAME or MB
reversed these differences suggesting an EDNO-cGMP dependence. 17β-oestradiol exerted relaxant effect
on all endothelium-denuded (and normoglycaemic endothelium-intact male) tissues, but not endotheliumintact
normoglycaemic female. The greater male tissue contraction is attributable to absent 17β-oestradiolmodulated
relaxation. Indomethacin blockade of COX attenuatedmale normoglycaemic and female diabetic
tissue contraction (both reversed by L-NAME), but augmented diabetic male tissue contraction. These data
are consistent with the raised contractile TXA2 and PGE2 in normoglycaemic male and diabetic female tissues,
and the relaxant PGI2 in diabetic male (and female). The higher levels of PGI2 in the normoglycaemic
and diabetic female perhaps explain their greater relaxant response to Acetylcholine compared to the respective
male. In conclusion, there is an endothelium-dependent gender difference in the effect of short
term diabetes on vascular tissue reactivity which is COX mediated.

Four multiparous Holstein cows were used in a 4 x 4 Latin square experiment to study the effects of fat sources rich in omega-3 fatty acids on milk production and composition, follicular development, and prostaglandin secretion. All cows were fed a total mixed diet containing 60% grass silage and 40% concentrate. The four treatments were concentrates based either on Megalac, formaldehyde-treated whole linseed, a mixture (50:50, oil basis) of fish oil and formaldehyde-treated whole linseed, or no fat source in the concentrate but with 500 g per day of linseed oil being infused into the duodenum. Feed intakes and milk yield were similar among treatments. In general, the lowest digestibility was observed for the formaldehyde-treated whole linseed treatment. Feeding fish oil decreased milk fat and protein percentages. Alpha-linolenic acid increased from 1.0 to 13.9% of milk fatty acids with linseed oil infusion. This confirms the high potential to incorporate alpha-linolenic acid into m...