Prostaglandin F2 Alpha Levels Research Articles

Histone deacetylase inhibitor givinostat has ameliorative effect in the colitis model.

ABSTRACTPurpose:To investigate the effect of givinostat treatment in acetic acid-induced ulcerative colitis model in rats.Methods:Thirty male Wistar albino rats were used. Rats were randomly divided into three equal groups, and colitis was induced on 20 rats by rectal administration of %4 solutions of acetic acid. Twenty rats with colitis were randomly divided into two groups. %0.9 NaCl (saline) solution was administered intraperitoneally to the first group of rats (saline group, n=10) at the dose of 1 mL/kg/day. Givinostat was administered intraperitoneally to the second group rats (Givinostat group, n=10) at the dose of 5 mg/kg/day. Samples were collected for biochemical analysis. Colon was removed for histopathological and biochemical examinations.Results:Plasma tumor necrosis factor-α (TNF-α), pentraxin-3 (PTX-3), and malondialdehyde levels were significantly decreased in the givinostat group compared to the saline group (p<0.05, p<0.001, and p<0.001 respectively; p<0.001, p<0.001, and p<0.001, respectively). Colon TNF-α and prostaglandin F2 alpha (PGF-2) levels were significantly decreased (p<0.05, and p<0.001, respectively). The givinostat group had a significantly lower histologic score than saline group (p<0.001, and p<0.001, respectively).Conclusions:Givinostat, a good protector and regenerator of tissue and an anti-inflammatory agent, may be involved in the treatment of colitis in the future.

NLRP3 inflammasome inhibitor MCC950 attenuates primary dysmenorrhea in mice via the NF-\u03baB/COX-2/PG pathway

BackgroundPrimary dysmenorrhea (PD) constitutes a common gynecological disease among young women. The NLRP3 inflammasome may be activated and expressed in PD, but the mechanistic link between NLRP3 inflammasome activation and PD is still unclear.MethodsTo investigate the potential role of NLRP3 inflammasome activation in the pathogenesis of PD, 30 female Kunming mice without pregnancy were used for experiments. The PD mouse model was constructed by 11 days of successive co-treatment with estradiol and oxytocin. MCC950, a potent and specific small-molecule inhibitor of the NLRP3 inflammasome, was used to treat PD mice. The disease level was assessed by the writhing response and hot water tail-flick test. The levels of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2α) in the uterine tissues of mice were detected by ELISA. The expression levels of protein and cytokines, including NLRP3, cysteine aspartic acid-specific protease 1 (caspase-1), interleukin (IL)-1β, IL-18, nuclear factor kappa B (NF-κB) p65, phospho-NF-κB p65, and cyclooxygenase-2 (COX-2) were revealed by western blot analysis.ResultsMCC950 greatly ameliorated the writhing response induced by the combination of oxytocin and estradiol, with an increasing length of tail-flick latency. MCC950 also significantly decreased the levels of PGF2α and PGE2, and the expressions of NLRP3, caspase-1, IL-1β, IL-18, phospho-NF-κB p65, NF-κB p65, and COX-2 in the uterus.ConclusionsMCC950 markedly alleviated the pain and pathological damage in PD mice by inhibiting NLRP3 activation. The underlying mechanism may be related to hypoactive uterine inflammation via suppression of NLRP3 activation and the NF-κB/COX-2/PG pathway in uteruses of PD mice.

Maternal azithromycin therapy for Ureaplasma parvum intraamniotic infection improves fetal hemodynamics in a nonhuman primate model

Ureaplasma parvum infection is a prevalent cause of intrauterine infection associated with preterm birth, preterm premature rupture of membranes, fetal inflammatory response syndrome, and adverse postnatal sequelae. Elucidation of diagnostic and treatment strategies for infection-associated preterm labor may improve perinatal and long-term outcomes for these cases. This study assessed the effect of intraamniotic Ureaplasma infection on fetal hemodynamic and cardiac function and the effect of maternal antibiotic treatment on these outcomes. Chronically catheterized pregnant rhesus monkeys were assigned to control (n=6), intraamniotic inoculation with Ureaplasma parvum (107 colony-forming units/mL, n=15), and intraamniotic infection plus azithromycin treatment (12.5 mg/kg twice a day intravenously, n=8) groups. At approximately 135 days' gestation (term=165 days), pulsed and color Doppler ultrasonography was used to obtain measurements of fetal hemodynamics (pulsatility index of umbilical artery, ductus venosus, descending aorta, ductus arteriosus, aortic isthmus, right pulmonary artery, middle cerebral artery and cerebroplacental ratio, and left and right ventricular cardiac outputs) and cardiac function (ratio of peak early vs late transmitral flow velocity [marker of ventricular function], Tei index [myocardial performance index]). These indices were stratified by amniotic fluid proinflammatory mediator levels and cardiac histology. Umbilical and fetal pulmonary artery vascular impedances were significantly increased in animals from the intraamniotic inoculation with Ureaplasma parvum group (P<.05). Azithromycin treatment restored values to control levels. Amniotic fluid prostaglandin F2 alpha levels were significantly higher in animals with abnormal umbilical artery pulsatility index (>1.1) than in those with normal blood flow (P<.05; Spearman ρ=0.6, P<.05). In the intraamniotic inoculation with Ureaplasma parvum group, left ventricular cardiac output was significantly decreased (P<.001), and more animals had abnormal right-to-left ventricular cardiac output ratios (defined as >1.6, P<.05). Amniotic fluid interleukin-6 concentrations were elevated in cases of abnormal right-to-left ventricular cardiac output ratios compared with those in normal cases (P<.05). Fetal hemodynamic alterations were associated with intraamniotic Ureaplasma infection and ameliorated after maternal antibiotic treatment. Doppler ultrasonographic measurements merit continuing investigation as a diagnostic method to identify fetal cardiovascular and hemodynamic compromise associated with intrauterine infection or inflammation and in the evaluation of therapeutic interventions or clinical management of preterm labor.

The oxidative/anti-oxidative effects of sevoflurane on reproductive system of females: An experimental study.

Objective:A permanent balance exists between the production and elimination of reactive oxygen species in all living organisms. The aim of this study was to evaluate the effects of sevoflurane possibly causing an imbalance in the equation of reactive oxygen species on the female rat reproductive system.Materials and Methods:A total of 30 adult female Wistar-albino rats were placed into an anesthesia chamber to administer sevoflurane. Rats were randomly divided into six groups, each group consisting of five rats: the control group received 2 L/min O2 18 min/day for seven days; the first group received 1 minimum alveolar concentration (MAC) of sevoflurane and 2 L/min O2 18 min/day for seven days; the second group received 1 MAC of sevoflurane and 2 L/min O2 18 min/day for seven days with no treatment for the next seven days; the third group received 1 MAC of sevoflurane and 2 L/min O2 18 min/day for 14 days; the fourth group received 1 MAC of sevoflurane and 2 L/min O2 18 min/day for 14 days with no treatment for the next seven days; and the fifth group received 1 MAC of sevoflurane and 2 L/min O2 18 min/day for 14 days with no treatment for the next 14 days. Bilateral ovaries were subsequently removed for biochemical analysis of tissue anti-oxidative enzyme levels.Results:Slight fluctuations were detected in mean nitric oxide, prostaglandin E2, prostaglandin F2-alpha, superoxide dismutase, glutathione peroxidase, malondialdehyde, alginate dialdehyde, and xanthine oxidase levels between the groups; however, the differences were not significant (p>0.05).Conclusion:Sevoflurane has no effect on the activity of anti-oxidant systems in the rat ovary.

Exposure to di(2-ethylhexyl) phthalate inhibits luteal function via dysregulation of CD31 and prostaglandin F2alpha in pregnant mice.

BackgroundDi(2-ethylhexyl) phthalate (DEHP) exposure reduces embryo implantations, increases embryonic loss, and decreases fetal body weights. However, whether it is associated with the alteration of luteal function remains unknown. Thus, our aim in this study was to explore the effect and mechanism of DEHP on luteal function in pregnant mice in vivo.MethodsMice were administered DEHP by gavage at 125, 250, 500 mg/kg/day from gestational days (GD) 1 to 9 or 13. Levels of serum progesterone and estradiol were measured by radioimmunoassay. The numbers and sizes of corpora lutea were calculated by ovarian histomorphology. Steroidogenic enzymes were assessed by qRT-PCR. CD31 protein was detected by immunocytochemistry, and prostaglandin F2alpha (PGF2alpha) levels were evaluated by enzyme immunoassay.ResultsTreatment with DEHP significantly inhibited progesterone secretion in pregnant mice in a dose-dependent manner but did not inhibit estradiol production on GD 9 and 13. Treatment also showed concomitant decreases in transcript levels for key steroidogenic enzymes (CYP11A, 3β-HSD, and StAR) on GD 13. Furthermore, DEHP administration significantly reduced the numbers and sizes of corpora lutea on GD 13. No significant changes in the ratio of ovary weight vs. body weight were observed between the control group and treated animals on GD 9 and 13. In addition, treatment with DEHP significantly inhibited CD31 expression of corpora lutea, whereas plasma PGF2alpha levels in DEHP treatment groups were significantly higher compared with the control groups on GD 9 and 13.ConclusionsThe results show DEHP significantly inhibits luteal function of pregnant mice in vivo, with a mechanism that seems to involve the down-regulation of progesterone and steroidogenic enzymes message RNA, the decrease in CD31 expression, and the increase in PGF2alpha secretion.Electronic supplementary materialThe online version of this article (doi:10.1186/s12958-015-0013-4) contains supplementary material, which is available to authorized users.

Fluorofenidone inhibits nicotinamide adeninedinucleotide phosphate oxidase via PI3K/Akt pathway in the pathogenesis of renal interstitial fibrosis

Oxidative stress plays an important role in the progression of renal interstitial fibrosis. The nicotinamide adeninedinucleotide phosphate (NADPH) oxidase (Nox) family is considered one of the major sources of reactive oxygen species (ROS). In the present study, we investigated the inhibitory effects of a novel anti-fibrotic agent, Fluorofenidone (AKF-PD), upon Nox-mediated oxidative stress and deposition of extracellular matrix (ECM) in the development of renalinterstitial fibrosis. AKF-PD was used to treat renal fibrosis in unilateral ureteral obstruction (UUO) obstructive nephropathy in rats. The expression of Nox homologues, p-Akt, collagen I and III were detected by immunoblotting or immunohistochemistry. Levels of 8-iso prostaglandin F2alpha (8-Iso PGF2a) was measured by enzyme linked immunosorbent assay. In addition, ROS and the expression of collagen I (1a), Nox subunits and p-Akt was measured in angiotensin (Ang) II-stimulated rat proximal tubular epithelial (NRK-52E) cells in culture. AKF-PD treatment significantly attenuated tubulo-interstitial injury, ECM deposition and oxidative stress in fibrotic rat kidneys. In addition, AKF-PD inhibited the expression of ROS, Collagen I (1a), Nox2, p-Akt in Ang II-stimulated NRK-52E cells. AKF-PD attenuates the progression of renal interstitial fibrosis partly by suppressing NADPH oxidase and ECM deposition via the PI3K/Akt signalling pathway, suggesting AKF-PD is a potential novel therapeutic agent against renal fibrosis.

The influence of intravenous laser therapy on prostaglandin E2 and F2-alpha dynamics and the state of microcirculation in the patients presenting with gastroesophageal reflux disease

The objective of the present work was to study the influence of low-frequency laser radiation on the levels of prostaglandins E2 and F2-alpha and characteristics of microcirculation in the patients suffering from gastroesophageal reflux disease (GERD). A total of 112 patients at the age from 19 to 79 years presenting with GERD were examined. 78 of them were given the complete 10-day course of intravenous laser therapy based on a Matriks-VLOK ("Matriks", Russia) therapeutic laser set emitting in the continuous mode at a wavelength of 0.405 mcm with the radiation power 1-11.5 mW at the output of the main lightguide. The characteristics of interest were determined before and after the treatment. It was shown that laser irradiation resulted in the elevation of pro-inflammatory prostaglandin levels and the improvement of parameters of microcirculation.

The effects of metformin on uterine tissue of hyperandrogenized BALB/c mice

The present study investigated the role of the N, N'-dimethylbiguanide metformin (50 mg/kg body weight in 0.05 ml water, given orally with a canulla) in preventing the adverse effects generated by hyperandrogenism on uterine function. Daily injection of dehydroepiandrosterone (DHEA: 6 mg/100 g body weight in 0.1 ml oil) for 20 consecutive days induces polycystic ovaries in BALB/c mice. In this model we found that DHEA produced alterations on uterine histology closely related to the development of pre-cancerous structures concomitantly with increased incidence of uterine apoptosis. The injection of DHEA induced a pro-inflammatory status since uterine prostaglandin (PG) F2 alpha levels and cyclooxygenase 2 were increased although PGE levels were decreased. Furthermore, DHEA promoted a pro-oxidant status since it increased nitric oxide synthase (NOS) activity and decreased superoxide dismutase and catalase activities and the antioxidant metabolite glutathione levels. DHEA also regulated the percentages of CD4+ and CD8+ T lymphocyte that infiltrate uterine tissue. When metformin was administered together with DHEA uterine histology and apoptosis did not differ when compared with controls. Therefore, metformin prevented the pro-inflammatory and pro-oxidative status generated by DHEA and restores the ratios of CD4+ and CD8+ T cells to those observed in controls. We conclude that metformin is able to restore either directly or indirectly uterine function by preventing some inflammatory and oxidative alterations produced by hyperandrogenism.

PROSTAGLANDINS IN HUMAN MILK

Levels of prostaglandin E2 and prostaglandin F2 alpha were measured by radioimmunoassay in aliquots of foremilk and hindmilk obtained at different stages of lactation (colostrum, transitional, and mature milk) from six healthy nursing mothers who delivered at term. Immunoreactive prostaglandin E2 and prostaglandin F2 alpha were detected in all fresh human milk samples, but not in cows' milk-based formulas. Further studies are necessary to investigate the role of these hormones in the physiologic function, the extrauterine adaptation, and the cytoprotective effect on the gastrointestinal tract in the breast-fed human infant.

LH, FSH, TSH, prolactin, HCG and prostaglandin F2 alpha in patients with treated testis tumors.

Various kinds of treatments of testicular cancer results in significant changes in peptide hormones, particularly LH and FSH. In some cases, compensated hypothyroidism as indicated by increased TSH with normal T3 are observed. Serum levels of prostaglandin F2 alpha are also elevated after therapy without relation to the stage of the disease. During followup, these patients are found to complain of impotence and infertility, and the evaluation of serum analysis of peptide hormones must consider both the normal hormonal findings of treated testicular cancer patients and recurrence of endocrine active tumor. The hormonal changes from hypophyseal origin are secondary to the primary testicular damages in patients complaining of impotence without tumor recurrence.

Family history of premature cardiovascular disease as a sole and independent risk factor for increased carotid intima–media thickness

The aim of this study was to evaluate carotid intima-media thickness (cIMT) in children with a positive family history of premature cardiovascular disease (PFHPCD) and the relationship between cIMT and other known risk factors (insulin resistance, oxidant status and lipid profile) involved in structural vascular changes. Anthropometric measurements and inflammatory markers [isoprostanes (prostaglandin F-2alpha)] were evaluated in 24 prepubertal children (10 boys, 14 girls, mean age 7.9 +/- 2.37 years) with PFHPCD and compared with 25 healthy prepubertal children (11 boys, 14 girls). Fasting insulin and glycemia levels were evaluated and homeostasis model assessment of insulin resistance and fasting glucose-insulin ratio were calculated in all children. High-resolution ultrasound technique was used to evaluate cIMT. Children with PFHPCD had an increased cIMT (P = 0.001) in comparison with healthy controls. No significant differences were found in terms of fasting insulin levels (P = 0.416), glucose-insulin ratio (P = 0.454) and homeostasis model assessment of insulin resistance (P = 0.317) between children with PFHPCD and controls. Prostaglandin F-2alpha levels were significantly higher in children with PFHPCD than in controls (P = 0.003). In order to evaluate the relationship between cIMT and other known risk factors, a multiple linear regression analysis was performed. A direct correlation was found between cIMT and prostaglandin F-2alpha (beta = 0.905; P = 0.002; r2, 0.63) even after adjusting for confounding factors (age, sex, BMI). Signs of precocious cardiovascular risk are detectable in children with PFHPCD already during prepuberty. Furthermore, impaired oxidant-antioxidant status would be implicated in the detected abnormalities of the vascular wall, suggesting a pivotal role of hereditary and genetic predisposition in the pathogenesis of increased cIMT.

Correlation between the amplitude of glucose excursion and plasma 8-iso prostaglandin F2alpha level in subjects with different types of glucose regulation

To investigate the effect of glucose excursion on oxidative stress that is expressed by plasma 8-iso prostaglandin F2alpha (8-iso) level. Continuous glucose monitor system (CGMS) was used to calculate the mean amplitude of glycemic excursion (MAGE), mean blood glucose (MBG) and its standard deviation (SDBG), mean 1 h preprandial glucose value (1 h-prePG) and 3 h post-prandial glucose value (3 h PPG) over 24 h period, area under the ROC curve when the blood glucose within 24 h > 5.6 mmol/L (AUC 5.6), mean of daily differences (MODD), and mean postprandial glucose excursion (MPPGE) on 33 individuals with normal glucose regulation (NGR), 25 subjects with impaired glucose regulation (IGR), and 25 patients with newly diagnosed type 2 diabetes mellitus (T2DM) for 3 days. Plasma 8-iso level was determined by EIA. The plasma 8-iso level of the T2DM patients was 230 ng/L, significantly higher than that of the subjects with IGR (199 ng/L, P < 0.05) and that of the NGR subjects (156 ng/L, P < 0.01). Patients with T2DM also had higher levels of glycated hemoglobin (HbA1c), MBG, SDBG, 1 h pre-PG and 3 h PPG, MAGE, and MODD than those of the NGR and IGR subjects (P < 0.05 or 0.01). The plasma 8-iso level and parameters of glucose excursion of the IGR subjects were all significantly higher than those of the NGR individuals (P < 0.05 or 0.01). Plasma 8-iso level was positively correlated with MAGE, MBG, SDBG, 1 h pre-PG, 3 h PPG, MODD, and HbA1c in all groups. Further analysis showed that the relationship between plasma 8-iso level and MAGE remained significant after adjustment for the other parameters of glucose excursion in multiple linear regression analysis (multiple R(2) = 0.55 for the model including MAGE). Standardized regression coefficients were 0.694 (P = 0.000) for MAGE. Glucose excursion exhibits a stronger triggering effect on oxidative stress than chronic sustained hyperglycemia in the subjects with IGR and T2DM.

Clinical study on the treatment of premature ejaculation by Uighur medicine Gu-jing-mai-si-ha Tablet (固精麦斯哈片)

To observe the effect of Uighur medicine gu-jing-mai-si-ha tablet (GJMSHT) for treatment of premature ejaculation (PE) and to explore part of its mechanism. The condition of patients was scored by related questionnaire, and the intravaginal ejaculation latency time (IELT) was observed before and after GJMSHT treatment, with the blood levels of nitric oxide (NO) and prostaglandin F2alpha (PGF2alpha) detected in PE patients as well. The results were compared with those in the control group. After treatment, the scores of PE and IELT, as well as the levels of NO and PGF2alpha, all increased significantly compared to those before treatment in the treated group (P<0.01), while in the control group, all the parameters were insignificantly changed (P>0.05). Therefore, the difference of these parameters between the two groups after treatment all showed statistical significance (P<0.01). GJMSHT could treat PE effectively, its mechanism is possibly by strengthening the coordination of the related smooth muscles through increasing the blood levels of NO and PGF2alpha, and the endurance of patients to the cavitary effect of prostatico-urethral pressure, thus postponing the arrival of urgent ejaculatory feeling.

Influence of Natural Honey on Biochemical and Hematological Variables in AIDS: A case study

Honey lowers prostaglandins and elevates nitric oxide (NO) in various biological fluids in normal persons. NO and prostaglandin play a role in pathogenesis of AIDS. The study was designed to assess the effect of natural honey on prostaglandins and NO levels, blood indices and biochemical tests in a 40 year-old woman with AIDS. This presentation is a case story of a 40 year-old women with a long history of AIDS treated with 80g of natural honey. Plasma and urinary prostaglandin F2 alpha and thromboxane B2 levels, plasma, urine and saliva content of NO-end product (total nitrite) and hematological tests were estimated before and 3 hours after oral consumption of 80g of natural honey. These variables, in addition to biochemical tests, were re-estimated after 21 days of daily consumption of 80g of natural honey. Results showed that prostaglandins level compared with normal subjects were elevated in patient with AIDS. Natural honey decreased prostaglandins levels, and elevated NO-end product, percentage of lymphocytes, platelet count, and serum protein, albumin and copper levels. It might be concluded that natural honey decreased prostaglandins level, elevated NO production and improved hematological and biochemical tests in a patient with a long history of AIDS.

Individual and Combined Effects of Selective Cyclooxygenase‐2 Inhibitor and Omega‐3 Fatty Acid on Endotoxin‐Induced Periodontitis in Rats

The present study was planned to evaluate the individual and combined effects of selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, and omega-3 fatty acid on the gingival tissue levels of prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha), leukotriene B4 (LTB4), and platelet activating factor (PAF) in endotoxin-induced periodontitis in rats. Experimental periodontitis was induced by repeated injection of Escherichia coli endotoxin (LPS). Forty-four adult male Sprague-Dawley rats were divided into five study groups: saline control, LPS, celecoxib, omega-3 fatty acid, and combination celecoxib and omega-3 fatty acid. Celecoxib and omega-3 fatty acid were given either as a single agent or as a combination therapy during 14 days of the study period. At the end of the 2-week protocol, the rats were sacrificed, the gingival tissues were dissected and extracted, and the extracts were analyzed for PGE2, PGF2alpha, and LTB4 levels by enzyme immunoassay and for PAF levels by radioimmunoassay. The defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by using parametric tests. LPS injection resulted in significantly more bone loss than the saline controls (P<0.05) and significant elevations in the gingival tissue levels of all the analyzed mediators except PGF2alpha. Individual administration of celecoxib revealed significant reductions in PGE2 and PAF levels (P <0.05), while omega-3 fatty acid provided significant reduction in PGE2, PGF2alpha, and LTB4 levels compared to the LPS group (P <0.05). Combined administration of celecoxib and omega-3 fatty acid exhibited significantly lower values than those of the LPS group in all the analyzed membrane phospholipid mediators (P <0.05), which approximated the levels in the saline control group (P>0.05). The results of the present study indicate that celecoxib and omega-3 fatty acid, when used individually, show a rather partial effect on the control of the analyzed mediators, but when combined they show a synergic effect and provide significant reductions in the gingival tissue levels of PGE2, PGF2alpha, LTB4, and PAF in LPS-induced experimental periodontitis. These findings may pioneer further clinical human studies investigating the possible place of celecoxib and omega-3 fatty acid in periodontal treatment.

Effects of Combined Systemic Administration of Low‐Dose Doxycycline and Alendronate on Endotoxin‐Induced Periodontitis in Rats

Doxycycline has been widely used in periodontal treatment for its antimicrobial and anti-enzymatic effects. Recently, bisphosphonates have been shown to inhibit alveolar bone resorption. The aim of the present study was to evaluate the effects of doxycycline and the bisphosphonate alendronate on the gingival tissue levels of prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha), leukotriene B4 (LTB4), and platelet-activating factor (PAF) in endotoxin-induced periodontal breakdown in rats. Experimental periodontitis was induced by repeated injection of Escherichia coli endotoxin (LPS) and 44 adult male Sprague-Dawley rats were divided into five study groups as follows: LPS, doxycycline + LPS, alendronate + LPS, doxycycline + alendronate + LPS, and saline control. Doxycycline and alendronate were given either as a single agent or as a combination therapy during the 7-day study period. At the end of the 1-week protocol, the rats were sacrificed, the gingival tissues were dissected and extracted, and the extracts were analyzed for PGE2, PGF2alpha, LTB4, and PAF levels. The defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by using parametric tests. Alveolar bone loss measurements revealed significantly higher values in LPS, doxycycline + LPS, alendronate + LPS, and doxycycline + alendronate + LPS groups in comparison to the saline control group (P <0.05). Combined administration of doxycycline and alendronate exhibited the most prominent inhibition on gingival tissue levels of PGE2 and PGF2alpha (P<0.05). Doxycycline + alendronate + LPS group also significantly reduced LTB4 and PAF levels, although doxycycline provided the most reduction in the levels of these mediators (P <0.05). Alendronate and/or doxycycline may provide significant inhibition of the major inflammatory mediators of periodontal tissue destruction, and combined administration of these agents may provide beneficial effects in periodontal treatment. However, this hypothesis must be further verified by clinical human trials before introducing its use in dental practice.

Dietary Lutein/Zeaxanthin Decreases Ultraviolet B-Induced Epidermal Hyperproliferation and Acute Inflammation in Hairless Mice

Lutein and zeaxanthin are carotenoids found in green leafy vegetables with interesting antioxidant properties. They are present in high concentrations in the fovea centralis of the human retina and their role in the prevention of age-related macula degeneration has been reported. We have investigated the effect of orally administered lutein and zeaxanthin in the cutaneous response to ultraviolet B irradiation. Female hairless SKh-1 mice receiving 0.4% and 0.04% lutein plus zeaxanthin-enriched diet for 2 wk were exposed to single doses of ultraviolet B radiation. Skin biopsies were taken at 24 and 48 h after irradiation and analyzed for the presence of apoptotic cells, proliferating cells, and expression of proliferating cell nuclear antigen. Our results show a clear ultraviolet-induced dose-dependent inflammatory response. Orally administered 0.4% lutein and zeaxanthin decreased significantly the edematous cutaneous response (p<0.01) as determined by the reduction of the UVB-induced increase of ear bifold thickening. Additionally, dietary carotenoids were efficient in reducing the ultraviolet B-induced increases in the percentage of proliferating cell nuclear antigen (p<0.05), bromodeoxyuridine (p<0.05), and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling-positive cells (p<0.01). These data demonstrate that oral supplementation of lutein and zeaxanthin diminishes the effects of ultraviolet B irradiation by reducing acute inflammatory responses and ultraviolet-induced hyperproliferative rebound.

Prostaglandin levels in seminal plasma and sperm extracts of the domestic turkey, and the effects of cyclooxygenase inhibitors on sperm mobility

BackgroundTurkey reproduction is by artificial insemination using pooled semen so there is interest in storing semen. Fertilizing capacity declines after six hours storage, possibly due to poor sperm mobility. Prostaglandins (PG) affect mammalian sperm motility, but avian sperm has not been widely studied. For this study, levels of PG E1, E2, and F2 alpha in turkey seminal plasma and sperm extract, and effects of cyclooxygenase (COX) inhibitors on sperm mobility were determined.MethodsSeminal Plasma and sperm extract PG E1, E2, and F2 alpha, from 1.0 mL pooled semen, were measured by ELISA. In Trial 1, PG were determined from 122 wk old toms (n = 4). Trial 2 used 36 wk old toms (n = 7). For Trial 3, PGE2 only was measured from 48 wk (n = 6) and 154 wk old toms (n = 3). The effects of non-specific COX inhibitors indomethacin, diclofenac, tolmetin, or aspirin (n = 10), or specific COX-1 or COX-2 inhibitors (n = 3) on sperm mobility were measured (Accudenz swim-down test).ResultsSeminal plasma PG (pg/mL) in Trials 1 and 2, respectively, were 185.2 ± 88.4 and 187.2 ± 33.7 for PGE1; 141.4 ± 43.1 and 100.4 ± 14.6 for PGF2 alpha; and 431.0 ± 155.1 for PGE2 (Trial 1 only). Sperm extract PG (pg/10 billion cells) in Trials 1 and 2, respectively, were 215.1 ± 38.1 and 208.9 ± 41.5 for PGE1; 133.7 ± 51.7 and 49.8 ± 8.3 for PGF2 alpha; and 52.3 ± 8.6 for PGE2 (Trial 1 only). In Trial 3, seminal plasma PGE2 (pg/mL) in older versus younger males was 1097.9 ± 99.3 versus 853.2 ± 144.6 and sperm extract PGE2 (pg/10 billion cells) was 208.0 ± 56.1 versus 102.4 ± 14.8. Cyclooxygenase inhibitors (0.001 to 10 mM) decreased sperm mobility: indomethacin 15 to 100%; diclofenac 4 to 100%; tolmetin 27 to 74%; aspirin (tested at 0.01 to 15 mM) 22 to 42%; resveratrol (COX-1) and NS-398 (COX-2), both tested at 0.1 to 10 mM, 38 to 98% and 44 to 85%, respectively.ConclusionThese results indicate that PG are present in turkey seminal plasma and sperm, and COX inhibitors decrease turkey sperm mobility.

Uterine responses to exogenous oxytocin before and after pre-partum luteolysis in the cow.

The aim of this study was to test the functional status of uterine oxytocin receptors in cows in vivo around parturition. The animals received consecutive, intra-arterial injections of 800, 1,600 and 3,200 mU of oxytocin at three different stages: during late gestation (days 260-274), at 12 h and at 24 h after intramuscular injection of a prostaglandin F2alpha analogue at day 275 to induce parturition. Cows (n = 6) had been provided with myometrial electrodes and a catheter had been installed in the aorta and in a branch of the uterine vein (UV). Regular blood samples were obtained from the UV from 5 min before until 45 min after each oxytocin injection to measure plasma levels of prostaglandin F2alpha (PGF2alpha) and oxytocin. Uterine electromyographic (EMG) activity was registered continuously during each experiment. The increase of oxytocin levels in UV plasma after intra-arterial injections was dose dependent (p < 0.02). Pre- and post treatment oxytocin levels at 24 h after induction of parturition were significantly increased (p = 0.0313). Both during late pregnancy and at 12 h after induction of parturition, oxytocin caused a significant increase in EMG activity (p = 0.022). After the 3,200 mU dose the increase was significantly higher than with the other 2 doses (p = 0.004). After each dose, EMG activity returned to baseline levels within some 15 min. At 24 h after induction of parturition, the pre-treatment level of EMG activity had increased. Doses of 800 mU and 1,600 mU of oxytocin produced a significant (p = 0.022) increment of EMG activity, which was of the same magnitude as during the preceding stages; after 3,200 mU of oxytocin the response was significantly higher than before (p = 0.008). No significant increases of PGF2alpha levels in UV plasma could be measured after oxytocin injections at any of the three stages. It is concluded that the myometrium of the pregnant cow responds in vivo to physiological doses of oxytocin. At 24 h after induction of parturition, when luteolysis has occurred and a parturient pattern of parturient myometrial activity has already started to develop, the response is enhanced. Physiological doses of oxytocin did not evoke a spurt release of PGF2alpha in uterine venous blood during the peripartal period.

Plasma Concentrations of 13,14-dihydro-15-keto PGF2α and Progesterone During the Oviposition Cycle of the Domestic Goose (Anser anser domesticus)

Plasma 13,14-dihydro-15-keto prostaglandin F2alpha (PGFM) and progesterone levels were determined in actively ovulating, 1- to 2-yr-old female geese (Anser anser domesticus) at hourly intervals during the oviposition cycle, using the enzyme immunoassay (EIA) technique. The plasma PGFM concentration showed a peak at the time of oviposition and decreased to a basal level after oviposition. Progesterone levels began to surge approximately 12 to 13 h before ovulation and reached a peak 2 to 3 h before ovulation. The plasma progesterone concentrations returned to basal level at the time of ovulation. The present method of EIA was found to have practical application in analyses of progesterone and PGFM in plasma of birds.