Heimia salicifolia Link and Otto (family Lythraceae), alternatively named Heimis salicifolia (H.B.K.) Link, is a relatively small shrub found In tropical and subtropical regions of South America, Mexico and Texas (1-2). The plant is known under many common names such as "abre-o-sol" (sun-opener) in the Rio Grande del Sur, "quiebra arado" (plow-breaker) in Argentina and "herva de la vida" (herb of 11fe) in Brazil (1). There is much folklore associated with Heimia salicifolia. In Mexico the name sinicuiche (twisted foot) is used for the plant as well as for an intoxicating beverage produced from its leaves. Inbibiting the beverage is said to cause a feeling of giddiness, lassitude, deafness, forgetfulness, withdrawal from society and a sensation of che's surroundings becoming darker. Overindulgence is said to cause a peculiar yellow vision and memory loss with no "hangover the next day (3).

No description available.

Although prostaglandins (PG) and oxytocin are crucial mediators of uterine contractility, their receptor-mediated effects during the menstrual cycle, pregnancy and labour are not fully understood. The aim of this thesis was to elucidate the functional expression of EP, FP, TP and oxytocin receptors in isolated human myometrium relative to myocyte mRNA and signal transduction pathways. Myometrial samples were obtained from consenting non-pregnant and pregnant donors. Functional techniques were used to determine isometric muscle contractions. Primary uterine myocytes and fibroblasts were cultured at term to identify stimulated changes in calcium (Ca2+), cyclic adenosine monophosphate (cAMP) and mRNA. Myometrial strips exhibited spontaneous contractions, which were most active midcycle under oestrogenic conditions. At this time intrinsic contractility and responsiveness to uterotonins decreased towards the fundus. PGE2 produced bellshaped responses with predominant utero-relaxant effects mediated via the EP2 subtype. Although activity was partially restored by PGE2 through EP3/1 receptors, tissue excitation was more pronounced at FP, TP and oxytocin receptors. Despite high FP mRNA expression, the lower segment uterus was particularly responsive to U46619 and oxytocin at term pregnancy. Even so, Ca2+ mobilisation by oxytocin was greater via principal release from intracellular stores. Incubations with atosiban, progesterone and a rho-kinase inhibitor reduced oxytocin-stimulated Ca2+ transients. EP2 also attenuated oxytocic effects but this appeared to be mediated through cAMP rather than Ca2+ signalling pathways. With advancing labour, intrinsic myogenic activity declined in parallel with oxytocin desensitisation. However, TP-induced contractions were continued in the lower parturient uterus. These findings demonstrate that PG and oxytocin receptor expression are regulated in a hormone-dependent temporal and spatial manner. EP2-mediated cAMP formation appears to promote uterine quiescence, whilst TP receptors may control muscle tonus during parturition. These receptors and their messenger systems represent effective tocolytic targets for uterine hypercontractile disorders, such as dysmenorrhoea and preterm labour. / Allergan Inc.

Kurdistan Regional Government/Ministry of Higher Education and Scientific Research

Prostaglandins are integral mediators in reproductive processes but their exact role in uterine function is still not clear. In addition, ethical restraints have limited the availability of human tissue to investigate uterine prostanoid receptor populations. The aim of this thesis was to characterise the prostanoid receptors on the human and rat myometrium in order to evaluate the potential of the rat as an animal model of human uterine function and disease. For functional analysis of myometrial prostanoid receptors the immersion technique was utilised. LC-ESI-MS/MS was also used to measure the ex vivo myometrial release of prostanoid metabolites. The results show that both the rat and human uterus displays cyclical changes in uterine motility, with myogenicity greatest in the follicular and oestrus stages. The data also indicate that whilst the human uterus is responsive to EP3, EP2, TP, FP and IP receptor agonists, a functional population of only EP3, EP2 and FP receptors is present on the rat uterus, although the TP receptor appears to be upregulated at gestation and post-partum. The results also show that myometrial prostanoid release in the human uterus is cyclically regulated, with the greatest amount of prostaglandins being released during the late follicular stage. In conclusion, although similarities do exist with regard to the ovarian regulation of uterine motility in both the rat and human uterus, the differences in the apparent functional prostaglandin receptor populations between the two species suggest further work is required before the rat can be used as a model of human uterine function. / Allergan Inc

In the human uterus prostaglandins (PG) PGE2, PGD2, PGI2, PGF2¿ and Thromboxane A2 (TXA2), also termed prostanoids, are synthesised and deactivated to 15-keto PGE2, J2 metabolites, 6-keto-PGF1¿, 15-keto PGF2¿ and TXB2 respectively. However, not all metabolites have been analysed simultaneously within the same tissue. The primary objective of this thesis was to determine full uterine prostanoid profiles in human non-pregnancy, pregnancy and parturition, to better understand these processes and find suitable tocolytic targets. In addition, ten cytokines in human cervico-vaginal fluid (CVF) were measured according to interval to labour to test their suitability as labour onset predictors, with a view to developing a test to determine women at risk of preterm labour. Prostanoid analysis was carried out in endometrium (n=9) and myometrium (n=15- 16) donated by non-pregnant women and lower segment myometrium obtained from pregnant women (before (n=14) and after labour onset (n=7)) by liquid chromatography coupled with electrospray ionisation mass spectrometry (LC/ESIMS/ MS). Cytokines produced by CVF collected from pregnant donors (20-41 weeks gestation, n=2-10) were investigated using Enzyme-Linked Immunosorbent Assay (ELISA) or Luminex®. Human endometrium produced greater concentrations of TXB2, PGE2 and PGF2¿ than myometrium in vitro (p<0.05). Fifteen prostanoids were detected in human myometrium. Production of 6-keto-PGF1¿, PGE1 and PGF1¿ increased whilst 15- keto PGE2 and PGJ2 decreased at term pregnancy (37-41 weeks gestation) versus non-pregnancy (p<0.05). Myometrium from parturient donors synthesised TXB2 and PGE2 more abundantly than the non-labouring equivalent. Cytokine concentration was greatest in CVF sampled the week before labour, in particular Interleukin-6 (IL-6), Macrophage Inflammatory Protein-1¿ (MIP-1¿) and Monocyte Chemotactic Protein-1 (MCP-1) (p<0.05). Endometrial TXB2, PGE2 and PGF2¿ could aid in proliferation of glandular epithelium prior to ovulation. Prostacyclin may facilitate prolongation of pregnancy to term and thromboxane could contribute to uterine stimulation during labour. Cervical dilation may be influenced by PGE2 in lower segment myometrium. MCP- 1, MIP-1¿ and IL-6 could mark a short interval to labour onset. / Allergan Inc.

The purpose of this study was to determine the effect of prostaglandin (PG) inhibition on the sympathetic and pressor responses to isometric handgrip (HG) at 40% of maximal voluntary contraction (MVC) to exhaustion and postcontraction muscle ischemia (PC). To accomplish this heart rate (HR), arterial pressure (n=10) and plasma norepinephrine (NE) levels (n=8) were measured in 10 healthy male subjects during HG at 40% of MVC to exhaustion and during PC. The subjects were given a double-blind administration of either placebo (PLAC) or a single 100 mg dose of indomethacin (IND). The order of administration was counterbalanced and a one week drug washout period was provided between conditions. Mean arterial pressure increased 25±5 vs. 22±4 mmHg during the second minute of HG and 26±2 vs. 21±5 during the last minute of PC in PLAC vs. IND (P>.05), respectively. Heart rate was increased 21±4 vs. 17±3 bpm during the second minute of HG in PLAC vs. IND (P>.05), respectively and returned to control values during PC in both trials. Plasma NE increased 343189 vs. 289±89 pg/ml after HG and 67514132 vs. 6324132 pg/ml after PC (P>.05) in PLAC vs. IND, respectively. Therefore, PG inhibition does not alter sympathetic or arterial pressure responses during sustained isometric exercise in humans. This may suggest that 1) PGs not important in metaboreceptor stimulation of sympathetic or pressor responses to sustained isometric contractions in humans or 2) PGs may play only a small role in the regulation of these variables which may be masked by the effects of other stimuli. Index terms: prostaglandins, pressor reflex, muscle sympathetic nerve activity, static exercise / Ph. D.

No / Previous studies in this laboratory have suggested that the isolated uterus from non-pregnant mice has a prostaglandin F and a thromboxane receptor population similar to that found in human myometrium. The aim of this study was to investigate any regional variation in myogenic activity ) and the and responsiveness to prostaglandin F(2alpha) (PGF(2alpha) thromboxane mimetic U46619 in the mouse uterus taken during different stages of the oestrous cycle and during pregnancy. Uterine samples from BKW mice were taken from different anatomical segments along the length of each uterine horn and set up for superfusion at 2 ml/min with Krebs solution (containing 1 microM indometacin) at 37 degrees C, and gassed with 95%O(2)/5%CO(2). Responses (area under the curve) are expressed as a percentage of the final contraction induced by hypotonic shock. Data are expressed as the means +/- s.e.m. of n=5-12 and were analysed using Student's paired t-test or two-way ANOVA with a Bonferroni post hoc test. Regional variation in myogenic activity was observed in all tissues studied except those taken during labour. These tissues displayed significantly greater myogenic activity than tissues taken at late gestation and at all stages of the oestrous cycle. Tissues from pregnant animals were generally more responsive to U46619 and PGF(2alpha) than tissues taken from non-pregnant animals. Tissues taken from the upper segment of the uterine horn were more responsive to both agonists during the oestrous cycle. The findings demonstrated that the hormonal milieu and site of excision are important for myogenic activity and responsiveness.

Yes / Sunburn is a commonly occurring acute inflammatory process, with dermal vasodilatation and leukocyte infiltration as central features. Ultraviolet (UV) B-induced hydrolysis of membrane phospholipids releases polyunsaturated fatty acids and their subsequent metabolism by cyclooxygenases (COX) and lipoxygenases (LOX) may produce potent eicosanoid mediators modulating different stages of the inflammation. Our objective was to identify candidate eicosanoids formed during the sunburn reaction in relation to its clinical and histological course. We exposed skin of healthy humans (n=32) to UVB and for 72h examined (i) expression of pro- and anti-inflammatory eicosanoids using LC/ESI-MS/MS and (ii) immunohistochemical expression of COX-2, 12-LOX, 15-LOX and leucocyte markers, while (iii) quantifying clinical erythema. We show that vasodilatory prostaglandins (PG)E2, PGF2¿ and PGE3 accompany the erythema in the first 24-48h, associated with increased COX-2 expression at 24h. Novel, potent leukocyte chemoattractants 11-, 12- and 8-monohydroxy-eicosatetraenoic acid (-HETE) are elevated from 4-72h, in association with peak dermal neutrophil influx at 24h, and increased dermal CD3+ lymphocytes and 12- and 15-LOX expression from 24-72h. Anti-inflammatory metabolite 15-HETE shows later expression, peaking at 72h. Sunburn is characterized by overlapping phases of increases in COX products followed by LOX products that may regulate subsequent events and ultimately its resolution. / The Wellcome Trust

Gliomas são tumores do sistema nervoso central e o glioblastoma multiforme (GBM) é sua forma mais comum e de pior prognóstico. A proliferação desordenada, migração estão entre os processos biológicos que conferem ao GBM um comportamento altamente agressivo. O objetivo deste estudo foi analisar in vitro o papel de PGE2 na proliferação, migração e apoptose da linhagem de glioma humano T98G através de tratamento com ácido gama-linolênico (GLA), Ibuprofeno (IBU) e adição de prostaglandina E1 (PGE1) e prostaglandina E2 (PGE2) exógeno. Nossos resultados demonstraram através uma diminuição nas taxas de proliferação e de migração e uma indução de apoptose nas células T98G tratadas com GLA ou IBU. Por outro lado, a adição exógeno de PGE1 ou PGE2 resultou num aumentou da proliferação e da migração e numa inibição da apoptose. Esses resultados demonstram a influência de PGE2 na linhagem T98G. / Gliomas are tumors of the central nervous system and glioblastoma multiforme (GBM) is the most common form with the worst prognosis. Uncontrolled cell proliferation, migration are among the biological processes that give GBM a highly aggressive behavior. The aim of this study was to analyze in vitro the role of PGE2 the proliferation, migration and apoptosis of the T98G human glioma cell line through treatment with gamma-linolenic acid (GLA), ibuprofen (IBU) and the addition of exogenous prostaglandin E1 (PGE1) and prostaglandin E2 (PGE2). Our results demonstrated through various tests a decrease in the rates of proliferation and migration and an induction of apoptosis in T98G cells treated with GLA or IBU. On the other hand, the addition of exogenous PGE1 or PGE2 resulted in increased proliferation and migration and inhibition of apoptosis. These results demonstrate the influence of PGE2 in the T98G cell line.