In vivo chronic and in vitro acute effects of di(2-ethylhexyl) phthalate on pseudopregnant rabbit corpora lutea: possible involvement of peroxisome proliferator-activated receptor gamma.

The in vivo chronic and in vitro acute effects of di(2-ethylhexyl) phthalate (DEHP) on the reproductive function of peroxisome proliferator-activated receptor gamma (PPARG) were studied in rabbit corpora lutea (CL) at early stage (Day 4), midstage (Day 9), and late stage (Day 13) of pseudopregnancy. The rabbits were in vivo treated with DEHP for 15 days before induction of pseudopregnancy. Immunohistochemistry provided evidence for the presence of PPARG, prostaglandin endoperoxide synthase 1 (PTGS1), PTGS2, prostaglandin E2-9-ketoreductase (PGE2-9-K), and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in all the luteal cells during pseudopregnancy. DEHP decreased progesterone plasma levels and CL production in all the luteal stages and PPARG protein and gene expressions in early and mid-CL. DEHP in vivo treatment reduced PTGS2 protein expression at the late stage and that of PGE2-9-K at all the stages, whereas PTGS1 and 3beta-HSD were not affected. In in vitro cultured CL, DEHP alone, the PPARG antagonist T0070907 alone, or DEHP plus T0070907 diminished progesterone production and 3beta-HSD activity and increased PGF2alpha and PTGS2 in early and mid-CL, whereas DEHP plus the PPARG agonist 15d-PGJ2 did not affect these hormones and enzymes. All the in vitro treatments did not affect PGE2 secretion as well as PTGS1 and PGE2-9-K enzymatic activities in all the luteal stages. These results provided evidence that DEHP favors functional luteolysis of pseudopregnant rabbit CL, with a mechanism that seems to involve PPARG expression down-regulation, an increase of PTGS2 activity and prostaglandin F2alpha secretion, 3beta-HSD down-regulation, and decrease in progesterone.

Long-term effects of moderate protein diet on renal function and low-grade inflammation in older adults with type 2 diabetes and chronic kidney disease.

OBJECTIVES: The aim of this study was to determine the long-term effects of a moderate protein diet (MPD) on renal function, low-grade inflammation, and oxidative stress in older adults with type 2 diabetes, which to date are unclear. METHODS: Seventy-four older adults with type 2 diabetes and chronic kidney disease (stage G3b-G4) were enrolled in the study. During the 4-wk baseline period (T0), all patients were asked to follow a normal protein diet regimen, providing 1.1 g/kg daily. Successively, all patients were asked to follow an MPD, for 36 mo, providing 0.7 g/kg daily, for only 6 d/wk. Patients who refused to follow an MPD treatment were included in the control (NPD [normal protein diet] group). During the 36 mo of the study, creatinine clearance, blood urea nitrogen, proteinuria, blood pressure, glycated hemoglobin (Hb)A1c, fat-free mass, low-grade inflammation (interleukin-6 and C-reactive protein) were evaluated monthly and oxidative stress (urinary 8-epiprostaglandin [Epi-PG]F2α) was evaluated every 3 mo. RESULTS: During T0, mean creatinine clearance, proteinuria, blood urea nitrogen, blood pressure, HbA1c, fat free mass, low-grade inflammation, and oxidative stress were similar in both groups. After 36 mo, a significant reduction in decline of renal function was observed in the MPD group but not in controls (2.4 ± 0.2 versus 5.7 ± 0.5 mL·min·y, respectively; P < 0.05 versus control). Similarly, a significant reduction in proteinuria, serum interleukin-6, serum C-reactive protein, and urinary 8-Epi-PGF2α excretion, was observed in the MPD group (P < 0.05 versus NPD). CONCLUSION: In older adults with type 2 diabetes, long-term effects of an MPD regimen are associated with a significant decline of renal function, proteinuria, low-grade inflammation, and oxidative stress without a change in fat-free mass.

To explore the correlation analysis between the changes of cognitive function and the expression levels of serum ICAM-1 and 8-iso-PGF2α in patients with acute ischemic stroke / 中风与神经疾病杂志

@#To explore the correlation analysis between the changes of cognitive function and the expression levels of serum ICAM-1 and 8-iso-PGF2α in patients with acute ischemic stroke. Method A total of 100 patients with Acute ischemic stroke admitted to our hospital from August 2017 to October 2019 were divided into group A （60 cases，MoCA score<26 points） and group B （40 cases，MoCA） according to the MoCA score Score ≥26 points）. Enzyme-linked immunosorbent assay was used to determine the expression levels of ICAM-1 and 8-iso-PGF2α in the two groups. Spearman was used to analyze the correlation between serum ICAM-1 and 8-iso-PGF2α and MoCA scores. Logistic regression was used to analyze Acute ischemic stroke. Influencing factors of patients’ cognitive function changes. ROC curve analysis of serum ICAM-1，8-iso-PGF2α expression for the diagnostic value of cognitive function in patients with Acute ischemic stroke. Results The expression of serum ICAM-1 and 8-iso-PGF2α in group A was significantly higher than that in group B （P<0.05）；Serum ICAM-1 and 8-iso-PGF2α expression levels were significantly correlated with the location of infarct，carotid atherosclerosis，carotid stenosis，NIHSS score，MoCA，and age （P<0.05），but not related to education level （P> 0.05）. The infarcts were located in the thalamus，temporal lobe and frontal lobe. NIHSS score，diabetes and hypertension were independent risk factors for cognitive dysfunction in patients with Acute ischemic stroke （P<0.05）. The sensitivity and specificity of ICAM-1 and 8-iso-PGF2α in diagnosing the changes of cognitive function in patients with Acute ischemic stroke were 93.00% and 90.00% （P<0.05）. Conclusion The expression of serum ICAM-1 and 8-iso-PGF2α is closely related to the changes of cognitive function in patients with Acute ischemic stroke.

Vías implicadas en la luteólisis bovina / Bovine luteolysis: intracellular signals

El cuerpo lúteo es una glándula endocrina transitoria que produce progesterona durante un tiempo determinado por la gestación. Cuando no hay preñez, el cuerpo lúteo sufre un proceso de regresión conocido como luteólisis, el cual divide en: funcional, por la pérdida de la capacidad de sintetizar progesterona; y estructural, por la pérdida de integridad celular. La luteólisis es inducida principalmente por la PGF2α, y de manera secundaria a través de otras rutas paralelas mediadas por calcio, citoquinas, especies reactivas de oxígeno y endotelinas. Todos estos factores conducen finalmente a la inhibición de la esteroidogénesis y/o en la inducción de la apoptosis. En este artículo tratamos de integrar la información disponible en la literatura y proponemos un mapa de los eventos celulares y moleculares que dan cuenta de este fenómeno fundamental en la reproducción de la especie bovina.

The corpus luteum is a transient gland that produces progesterone during a period of time that is determined by the length of gestation. When there is no gestation the corpus luteum undergoes regression, a process commonly known as luteolysis. This process has been divided in: functional, since there is a lost of the capacity to synthesize progesterone; and structural, because there is a disruption of the cellular structure. PGF2α, is the principal luteolytic factor, but there are other parallel pathway mediated by calcium, cytokines, reactive oxygen species and endothelins. All these routes end up in inhibition of steroidogenesis and/or apoptosis. In this article we try to integrate the information present in the literature and propose a map depicting the major cellular and molecular events taking place in this process that is fundamental en bovine reproduction.

Effect of Prostaglandin F2alpha on the Production of Nitric Oxide in Cultured Ciliary Muscle Cells

PURPOSE: To investigate whether prostaglandin F2alpha (PGF2alpha) affects on the production of nitric oxide (NO) in cultured ciliary muscle (CM) cells. METHODS: Following primary culture of CM cells from porcine eyes, the cells were exposed to PGF2alpha (PhXA85, latanoprost free acid) with and without pretreatments of NO synthase inhibitor (L-NAME, N omega- Nitro-L-arginine methyl ester) and cyclooxygenase inhibitors (indomethacin and dexamethasone) for 3 days. The cellular survivals were also evaluated in serum-deprived and hypoxic conditions induced by sodium cyanide. The cellular survival and nitrite production were assessed by MTT and Griess assay, respectively. RESULTS: PGF2alpha enhanced the production of NO significantly in cultured CM cells in a dose-dependent manner, while various inhibitors abolished this effect. PGF2alpha was not cytoprotective in serum-deprived and hypoxic conditions. CONCLUSIONS: The current results suggest that PGF2alpha potentiates NO production but is not cytoprotective in CM cells. This PGF2alpha-induced NO production in CM cells may be involved in the regulation of uveoscleral outflow.

Prostaglandin F2 alpha levels of ovarian follicular and peritoneal fluid during preovulatory phase in the women with and without endometriosis / 대한산부인과학회잡지

OBJECTIVE: The aim was to evaluate whether the differences of PG concentration in follicular and peritoneal fluid during preovulatory phase exist between the women with and without endometriosis. MATERIAL AND METHODS: Twenty-three patients with endometriosis, 8 were stage I-II and 15 were stage III-IV, and another 23 patients without endometriosis were undergone laparotomy during late follicular phase. Peritoneal fluid from 46 patients and follicular fluid from 42 patients were obtained, and these samples were analyzed double times for PGF2alpha, PGE2 and estradiol. RESULTS: The mean level of PGF2alphain the peritoneal fluid was significantly higher in the group with endometriosis than in the control(P=0.0293), especially more significant in stage I-II endometriosis. Although there was no significant difference of PGF2alphaconcentration in the follicular fluid between the groups, the stage III-IV endometriosis group showed slightly higher PGF2alphalevel than both the stage I-II group and the control(P=0.0604). And also, there was significant positive correlation with the level of PGF2alphaand estradiol in the follicular fluid only in the endometriosis group(r=0.4988, P=0.0154), not in the control. However, there was no difference in the level of PGE2 and estradiol in the peritoneal or follicular fluid between the groups. CONCLUSION: Some alterations of PGF2alphalevel exist in the women with endometriosis. These are significantly higher PGF2alphalevel in peritoneal fluid with mild endometriosis and slightly higher PGF2alphalevels in follicular fluid with extensive endometriosis during preovulatory phase, which suggest that PGF2alphamay play some roles in subfertility associated with endometriosis.

Umbilical Cord Arterial Concentrations of Isoprostane(8-iso-PGF2alpha) in Newborn Infants

PURPOSE: We measured the umbilical cord arterial concentrations of isoprostane(8-iso-PGF2alpha) and intended to decide whether the umbilical cord arterial concentrations of isoprostane could be used as a useful parameter for lipid peroxidation in newborn infants. METHODS: The isoprostane and malondialdehyde(MDA) concentrations of the umbilical cord were measured by enzyme immunoassay and TBARS(thiobarbituric acid reactive substance) assay in 33 preterm and 28 term infants, respectively. The concentrations of isoprostane and MDA were compared between preterm infants and term infants, and were analysed for association with perinatal risk factors and neonatal complications. RESULTS: Umbilical cord arterial concentrations of isoprostane were 704.7+/-635.6 pg/mL and 421.9+/-306.5 pg/mL in preterm and term infants, respectively. Umbilical cord arterial concentrations of MDA were 44.0+/-22.9 micrometer/L and 26.2+/-10.7 micrometer/L in preterm and term infants, respectively. Umbilical cord arterial concentrations of isoprostane and MDA in preterm infants were significantly higher than those in term infants(P<0.05). The umbilical cord arterial concentrations of isoprostane were significantly associated with perinatal risk factors such as fetal distress, oligohydramnios, and breech delivery in preterm infants and pregnancy-induced hypertension in term infants(P<0.05). CONCLUSION: Umbilical cord arterial concentrations of isoprostane in preterm infants were higher than those in term infants, and those are significantly associated with some perinatal risk factors.

Changes in the Levels of Eicosanoids and Isoprostane (8-iso-PGF2alpha) in the Newborn Rat Brain after Hypoxic-Ischemic Injury

PURPOSE: The changes in the levels of eicosanoids and isoprostane (8-iso-PGF2alpha) were investigated in brain tissue of 7 day-old rats after hypoxic-ischemic (HI) injury. METHODS: The 7 day-old newborn rats underwent right unilateral common carotid artery ligation followed by exposure to hypoxia with 8% oxygen for 150 minutes. There after, the pups were decapitated during reoxygenation 21% period of 0, 1, 6, 24, and 72 hours and their cerebral hemisheres were dissected through sagittal plane. Ipsilateral and contralateral cerebral hemesheres to common carotid artery ligation were used to determine the water content for estimation of severity of brain edema (n=5) and to measure the levels of eicosanoid and isoprostane (n=7). The levels of 6-keto-PGF1alpha, TXB2, and PGE2 were measured by RP-HPLC (reversed-phase high-performance liquid chromatography) and the levels of isoprostane (8-iso-PGF2alpha) were measured by enzyme immunoassay. The changes of eicosanoid and isoprostane levels during reoxygenation period were observed and comparisons between ipsilateral and contralateral hemispheres were done. RESULTS: The edema of ipsilateral cerebral hemesheres to common carotid artery ligation was more severe than that of contralateral cerebral hemisheres (P<0.05). The levels of 6-keto-PGF1alpha, TXB2, and PGE2 were found to increase during the early period of reoxygenation after HI insult, peak at 1 hour, and then decrease to the control levels at 72 hour (P<0.05). But, the levels of 8-iso-PGF2alpha did not significantly increase during the period of reoxygenation. The levels of 6-keto-PGF1alpha, TXB2, and PGE2 of ipsilateral hemispheres had a tendency to be higher than those of contralateral hemispheres during the initial 6 hour reoxygenation period, but the levels of 8-iso-PGF2alpha of ipsilateral hemispheres were significantly higher than those of contralateral hemispheres during the relatively later reoxygenation period (P<0.05). CONCLUSION: Reoxygenation after hypoxic-ischemic injury increased the levels of 6-keto-PGF1alpha, TXB2, and PGE2 in 7 day-old rat brain during the early period of reoxygenation, but the levels of isoprostane (8-iso-PGF2alpha) were not significantly increased during the reoxygenation period after HI injury.