Comparison of the Physical Characteristics and Behavior in ABC Transporter A1, A7 or Apolipoprotein E Knockout Mice with Lipid Transport Dysfunction.

The physical characteristics and behavior of the ATP-binding cassette (ABC) A1, A7, and apolipoprotein (apo) E knockout (KO) mice with lipid transport dysfunction were investigated. These KO mice exhibited adequate growth, and their body masses increased steadily. No remarkable changes were observed in their blood pressure and heart rate. However, there was a slight increase in the heart rate of the ABCA7 KO mice compared with that of the wild-type (WT) mice. ABCA1 and apoE KO mice showed hypo- and hyper-cholesterol concentrations in the plasma, respectively. With regard to the cerebrum, however, the weight of the ABCA1 KO mice was lighter than those of the other genotypes. Furthermore, the cholesterol, triglyceride and phospholipid concentrations, and fatty acid composition were generally similar. Compared with the WT mice, ABCA1 KO mice stayed for a shorter time in the closed arm of the elevated plus maze, and performed worse in the initial stage of the Morris water maze. To thermal stimuli, the ABCA1 and apoE KO mice showed hyper- and hypo-sensitivities, respectively. Only the response of the ABCA1 KO mice was significantly inhibited by pretreatment with indomethacin. A low concentration of the prostaglandin E metabolites was detected in the plasma of the ABCA1 KO mice. Thus, ABCA1 is thought to play a specific role in the neural function.

Effect of Acupuncture on Simple Obesity and Serum Levels of Prostaglandin E and Leptin in Sprague-Dawley Rats.

AIM: The study is aimed at investigating the curative effect of acupuncture on simple obesity and its influence on serum levels of prostaglandin E and leptin in Sprague-Dawley (SD) rats. METHODS: In the study, there are 50 male SD rats. We took 10 as healthy controls and fed 40 with a diet of high fat for 8 weeks. After the 40 rat model was established successfully, we fed 10 rats in the model group with a normal diet and treated 10 rats in the acupuncture group by acupuncture. During the experiment, the body fat and body length of rats were measured weekly, and Lee's index was calculated. After the treatment, the levels of leptin, prostaglandin E, C-reactive protein (CRP), triacylglycerol (TG), cholesterol (CHO), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were detected, and the liver fat morphology was observed by electron microscope. RESULTS: Acupuncture significantly downregulated the serum levels of CRP, TG, CHO, LDL, leptin, and prostaglandin E and upregulated the serum levels of HDL in rats with simple obesity. CONCLUSION: On basis of these results, it was found that acupuncture could boost fat metabolism and weight loss by inhibiting the production of leptin and prostaglandin E.

Altered plasma prostaglandin E2 levels in epilepsy and in response to antiepileptic drug monotherapy.

Prostaglandin E2 (PGE2), a physiologically active lipid compound, is increased in several diseases characterized by chronic inflammation. To determine its significance in epilepsy-associated inflammation and response to antiepileptic drug (AED), we evaluated the plasma PGE2 (median, pg/ml) levels in drug-free patients with epilepsy (N = 34) and patients receiving AED monotherapy (N = 55) in addition to that in healthy controls (N = 34). When compared to controls, plasma PGE2 levels were significantly elevated in all drug-free patients independent of the type of epilepsy (137.2 versus 475.7 pg/ml, p < 0.0001). Among the patients receiving AED monotherapy, only valproate responders showed a significant decrease compared to both drug-free patients (232.1 versus 475.7 pg/ml, p < 0.01) as well as valproate non-responders (232.1 versus 611.9 pg/ml, p < 0.0001). Both responders and non-responders on phenytoin or carbamazepine monotherapy had elevated PGE2 levels similar to drug-free patients. In addition, no difference was observed in plasma profiles of PGE2 precursor, arachidonic acid among the groups. Our work presents the clinical evidence of the association between plasma PGE2 levels and valproate efficacy in patients with epilepsy.

Traditional versus Percutaneous Transforaminal Endoforaminal Discectomy Effect on the Nervous System Function and Serum LEK, GFAP and PGE-2 in Patients with Senile Lumbar Spinal Stenosis.

OBJECTIVE: To compare the influence of percutaneous transforaminal endoscopic discectomy (PTED) and traditional operation on the nervous system function and the serum leu-enkephalin (LEK), glial fibrillary acidic protein (GFAP) and prostaglandin E-2 (PGE-2) in patients with senile lumbar spinal stenosis. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Department of Orthopedics Two, Xinjiang Changji Hui Autonomous Prefecture People's Hospital, Xinjiang, China, from March 2017 to March 2018. METHODOLOGY: A total of 146 patients with senile lumbar spinal stenosis were randomly divided into control group and observation group, 73 in each group. Control group underwent traditional operation, while the observation group underwent PTED. General situation of operation, serum LEK, GFAP, PGE-2, American Spinal Injury Association (ASIA) score and Japanese Orthopaedic Association (JOA) score were compared. RESULTS: Intraoperative blood loss in observation group was less than that in control group (p<0.001). Both operation time and length of hospital stay in observation group were shorter than those in control group (both p<0.001). At 24 hours later after operation, both levels of serum LEK and ASIA score in observation group were higher than those in control group (p=0.006 and p<0.001, respectively), and levels of serum GFAP and PGE-2 and JOA score in observation group were all lower than those in control group (all p<0.001). CONCLUSION: Compared with traditional operation, PTED has the advantages of less intraoperative blood loss, shorter operation time and length of hospital stay, etc. Besides, PTED can effectively reduce serum LEK, BFGF and PGE-2 expression in patients; and dramatically improve their nervous system function and lumbar function.

Lipid derivatives of arachidonic acid used as markers of atherosclerotic plaque instability: a pilot study.

BACKGROUND: To compare the results of computer estimation of atherosclerotic plaque with biochemical data and ascertain any relationship with the occurrence of stroke. METHODS: The study involved 20 atherosclerotic plaques causing 70-99% stenosis of internal carotid arteries (ICA). Ultrasonographic examination (USG) images of plaques were analyzed using a computer program. A histogram was obtained for each plaque and a gray scale median (GSM) was determined for each histogram in order to measure the echogenicity of an examined plaque. Then the plaques, collected during endarterectomy, were examined with regard to the concentration of prostaglandins E2 (PGE2), thromboxane A2 (TXA2), and 8 - epi-prostaglandin F2α. This data was compared with GSM and the occurrence of stroke. RESULTS: The statistical analysis showed significant correlations between low GSM and the occurrence of strokes. Out of 10 plaques with GSM<35, 6 (60.0%) were associated with a stroke. In contrast, out of 10 plaques with GSM>35, only 1 (10.0%) had a stroke. In addition, there were significant differences in the plaque content of PGE 2, (P<0.05) and (TXA2, P<0.011) between groups. CONCLUSIONS: High levels of PGE2 and TXA2, correlated with the low GSM values, may be the features of unstable plaques and that may be associated with a risk for stroke.

Polyphenol supplementation inhibits physiological increase of prostaglandin E2 during reproductive period - A randomized clinical trial.

Anti-inflammatory property of polyphenols and their effect on the metabolism of prostaglandins is not established in healthy humans. This study aimed to evaluate the effect of polyphenol supplementation in plasma levels of prostaglandin E2 and other markers of inflammation and oxidative stress in women using contraceptives. In this randomized double-blind clinical trial, women aged 25-35 years were selected. Participants received capsules containing polyphenols or placebo, to be consumed for fifteen days. From 40 women randomized, 28 completed the study. Control group showed a significant increase in the levels of PGE2 (p=0.01) while the polyphenols group showed no change in these levels (p=0.79). There was an increase in hs-CRP (p<0.01) and F2-isoprostane (p=0.04) in the control group. The GSSG to GSH ratio significantly reduced in the polyphenols group (p=0.02). Supplementation with polyphenol capsules inhibited the increase in markers of inflammation and oxidative stress in women of childbearing age using combined hormonal contraceptives.

The effect of metritis on luteal function in dairy cows.

BACKGROUND: Disturbed uterine involution impairs ovarian function in the first weeks after calving. This study analyzed the long-term effect of metritis on luteal function of 47 lactating Holstein-Friesian cows during the first four postpartum estrous cycles. Cows with abnormal uterine enlargement and malodorous lochia were classified as having metritis (group M, n = 18), and all others were considered healthy (group H, n = 29). Luteal size was measured once between days 9 and 13 of the first (group H, n = 11; group M, n = 12), second (group H, n = 23; group M, n = 18) and fourth (group H, n = 11; group M, n = 7) postpartum luteal phases. Serum progesterone concentration was measured at the same time. Sixteen cows (group H, n = 9; group M, n = 7) underwent transvaginal luteal biopsy for gene expression analysis of steroidogenic regulatory proteins during the second and fourth cycles. Cows with persistence of the corpus luteum (CL) underwent determination of luteal size, luteal biopsy and serum progesterone measurement once between days 29 and 33, followed by prostaglandin treatment to induce luteolysis. The same procedures were repeated once between days 9 and 13 of the induced cycle. RESULTS: The cows in group M had smaller first-cycle CLs than the cows in group H (p = 0.04), but progesterone concentrations did not differ between groups. Luteal size, progesterone concentration and gene expression did not differ between the two groups during the second and fourth cycles. Compared with healthy cows (10%), there was a trend (p = 0.07) toward a higher prevalence of persistent CLs in cows with metritis (33%). Persistent CLs were limited to the first cycle. Persistent CLs and the induced cyclic CLs did not differ with regard to the variables investigated. CONCLUSIONS: An effect of metritis on luteal activity was apparent in the first postpartum estrous cycle. However, after the first postpartum cycle, no differences occurred in analyzed parameters between metritis and control cows. Therefore, a metritis is able to impair luteal activity transiently, but does not seem to have a long-term effect on luteal function.

[Study on analgesic and accompanying toxic and side effects of euodiae fructus based on clinical efficacy dose].

OBJECTIVE: To observe and study the toxic and side effects of water extracts from Euodiae Fructus accompanied with its efficacy analgesic dose and its mechanism, in order to provide experimental basis for the correlation between its "efficacy-toxicity". METHOD: Mice were randomly divided into 5 groups according to weight, namely the normal group, the voltaren group, and Euodiae Fructus water extracts high, middle and low dose groups. Mice were administered with drugs for consecutively seven days, abdominally injected with acetic acid at 90 min and treated with hot plates after the last administration to establish the pain model, in order to the toxic and side effects accompanied with the efficacy. Besides toxic symptoms in mice, activities of ALT and AST, and content of BUN and Cr in serum were detected to calculate indexes in livers and kidneys. The other part of serum was collected to detect the content and activities of PGE2, MDA, SOD, NO, NOS, GSH and GSH-PX in serum. RESULT: Continuous oral administration of water extracts from Euodiae Fructus of efficacy dose could significantly decrease the frequency of writhe in mice and increase the hot plate pain threshold, with good dose-efficacy relationship. During the administration, mice showed such toxic symptoms as diarrhoea, idle move, dysphoria and slow growth of weight. The activities of both ALT and AST in serum and hepatic tissues were remarkably increased and the liver size remarkably increased, without notable chance in content of BUN and CR in serum. Kidney size increased in only the high dose group. The content and activities of PGE2, SOD, GSH, GSH-PX in serum notably decreased, where the content and activities of MDA, NO, NOS in serum increased. The above-mentioned changes gradually aggravated with the rise in dose. There was significant difference compared with the model group, showing 'dose-toxicity' relationship to certain extent. CONCLUSION: Continuous oral administration of certain dose of water extracts from Euodiae Fructus to mice can generate the toxic and side effects in liver accompanying with the analgesic effect, and show dose-dependence relationship to some extent. Its analgesic mechanism is related to the reduction of PGE, content in blood, while its toxic mechanism is related to oxidative injury to some extent.

Influence of stressor duration on leukocyte and hormonal responses in male Southeastern five-lined skinks (Plestiodon inexpectatus).

Environmental stressors elicit elevations of plasma glucocorticoid hormones. Stressors also result in increases in the circulating heterophil to lymphocyte ratio (H:L ratio), which has been linked to increased glucocorticoids. Recently, there has been debate about the extent to which stress-induced elevations of corticosterone are tied to increases in the H:L ratio and about whether one measure of physiological stress might be used in lieu of the other. Few studies have examined the responses of both variables to standardized stressors in free-living animals, especially reptiles. Stressors may also affect levels of other hormones, such as prostaglandins or testosterone, that may influence leukocytes. Therefore, the H:L ratio, corticosterone, prostaglandin E(2) (PGE(2) ), and testosterone were monitored in free-living male southeastern five-lined skinks, Plestiodon inexpectatus, in response to various durations of confinement stress. Skinks confined for 1 hr had elevated H:L ratios and elevated corticosterone concentrations. In addition, corticosterone was positively correlated with the H:L ratio. In contrast, there were no effects of 2 hr of confinement on the H:L ratio, in spite of maximal corticosterone. Plasma PGE(2) was not affected by 15, 30, or 60 min of confinement but was positively correlated with monocytes and negatively correlated with lymphocytes in the 1 hr of confinement experiment. Consistent with many other studies of reptiles, confinement stress did not result in suppressed testosterone. Overall, the results indicate that, in reptiles at least, the H:L ratio and plasma corticosterone do not covary consistently and one measure of stress cannot be used in lieu of the other.

Mechanistic links between oxidative/nitrosative stress and tumor necrosis factor alpha in letrozole-induced murine polycystic ovary: biochemical and pathological evidences for beneficial effect of pioglitazone.

This study aimed to investigate the possible relationship between ovarian functionality and the oxidative response during cystogenesis induced by hyperandrogenization with letrozole and examine protective effect of the peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, pioglitazone (PIO), in polycystic ovary (PCO). Ovarian cysts were induced by oral administration of letrozol (1 mg/kg/day) for 21 consecutive days in the female rats. Effective dose of PIO (20 mg/kg/day) was administrated orally for 21 days. Serum estradiol (E), progesterone (P), testosterone (T), and the ovarian immunomodulator prostaglandin E (PGE) were analyzed as biomarkers of ovarian function. To determine the role of oxidative stress in PCO, the level of cellular lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and peroxynitrite (ONOO), and tumor necrosis factor alpha (TNF-α) as a marker of inflammation and apoptosis were measured in serum and the ovaries. Letrozole-induced PCO in rats exhibited a significant increase in LPO and ONOO in serum and ovary while significantly decreased serum and ovarian SOD, CAT, and GPx. Serum T and TNF-α, and ovarian PGE were increased in animals with cysts compared with healthy controls, while E and P diminished. When compared to control group, letrozole-treated group showed irregular sexual cycles, polycystic ovaries characterized by high incidence of sub-capsular ovarian cyst with diminished or scant granulosa cell layer, increased number of atretic pre-antral and antral follicles and absence of corpus luteum. There were almost no primary, secondary, and tertiary follicles observed in PCO rats. All measured parameters were improved by PIO and reached close to normal levels. The present study further supports the role of oxidative/nitrosative stress and infiammatory responses in the pathogenesis of letrozole-induced hyperandrogenic PCO rats. Results indicate that PIO is able to exert direct antioxidative and anti-inflammatory effects on the endocrine, biochemical, and pathological alterations independent of its possible effects mediated via increased insulin sensitivity in hyperandrogenized PCO.

Anti-tumor effects of proteoglycan from Phellinus linteus by immunomodulating and inhibiting Reg IV/EGFR/Akt signaling pathway in colorectal carcinoma.

Proteoglycan (P1) purified from Phellinus linteus has been reported to have anti-disease activities. The objectives of our research were to determine the anti-tumor effect and possible mechanisms of P1 on human cancer cells. Cell inhibition assay showed that P1 has an antiproliferative effect on HepG2, HT-29, NCI-H 460 and MCF-7 human colon cancer cells, especially it was very effective in inhibiting HT-29 cells. When HT-29-bearing mice were treated with P1(100mg/kg), there was relative increase in spleen and thymus weights, the plasmatic pIgR and IgA levels were significantly increased, also there was a notable decrease in plasmatic PGE2, Reg IV, EGFR and Akt concentrations measured by ELISA. RT-PCR analysis suggested that P1-induced HT-29 apoptosis appeared to be associated with a decrease in the levels of expression of Reg IV and EGFR. These results suggest that P1 might have two potential roles in treating cancer; it acts as an immunopotentiator partly through protecting T cells from escaping PGE2 attack and enhancing the mucosal IgA response, and as a direct inhibitor by disrupting the Reg IV/EGFR/Akt signaling pathway.

Pyrogenic cytokines did not mediate a stress interview-induced hyperthermic response in a patient with psychogenic fever: a case report.

OBJECTIVE: To investigate if pyrogenic cytokines mediated psychological stress-induced hyperthermic response in a patient with psychogenic fever. Despite many case reports on psychogenic fever, the mechanism responsible for how psychological stress increases core body temperature (Tc) in humans is not yet known. CASE PRESENTATION: A 13-year-old girl with fever (>38 degrees C) of unknown causes was referred to our department because psychogenic fever was suspected. To determine if the fever was actually induced by psychological stress, we conducted a 60-minute stress interview. Her baseline oral temperature was 36.60 degrees C and it began to increase immediately after commencement of the interview, reaching a maximum of 37.42 degrees C 20 minutes after the end of the interview. The plasma level of prostaglandin E(2) and the serum interleukin-6 level were increased 90 minutes after the interview. Serum levels of interleukin-1alpha, interleukin-1beta, and macrophage inflammatory protein-1alpha were all less than their minimum detectable level throughout the observation period. We also measured the patient's thermal preference by immersing her hands in warm (40 degrees C) and cold (20 degrees C) water. Her preference changed from cold to warm only during the increasing phase of oral temperature. CONCLUSIONS: This case report shows that a stress interview actually increased Tc in a patient with psychogenic fever. This study suggests that, although pyrogenic cytokines are not involved, the stress interview-induced increase in Tc was an active hyperthermia under the control of the brain, as is infection-induced fever.

Is endothelin-1 luteolytic or antiluteolytic in ewes?

Endothelin-1 (ET-1) has been reported to mediate prostaglandin (PG) F(2)alpha (PGF(2)alpha)-induced luteolysis. Prostaglandins E (PGE; PGE(1)+PGE(2)) are associated with implantation, maternal recognition of pregnancy, and are antiluteolytic and luteotropic in vitro and in vivo. ET-1 increased PGE secretion by bovine luteal tissue in vitro from cows where estrus was not synchronized or when estrus was synchronized with lutalyse and did not affect luteal PGF(2)alpha or progesterone secretion, which does not support the concept that ET-1 is luteolytic or mediates PGF(2)alpha luteolysis. Therefore, the objective of this experiment was to determine whether ET-1 infused every 6h from 2400 h on day 10-1800 h on day 18 of the ovine estrous cycle either into the interstitial tissue of the ovarian vascular pedicle (IP) or intrauterine (IU) adjacent to the luteal-containing ovary was luteolytic in ewes. Treatments were: Vehicle-IP; Vehicle-IU; ET-1-IP; or ET-1-IU. Weights of corpora lutea differed (P< or = 0.05) among treatment groups. Weights of corpora lutea at 1800 h on day 18 were: VEH-IP-247+/-38 mg; VEH-IU-195+/-31 mg; ET-1-IP-626+/-74 mg; and ET-1-IU-542+/-69 mg. Luteal weights on day 18 in ET-1-IP or ET-1-IU-treated ewes did not differ (P> or =0.05), but were heavier (P< or =0.05) than in the Vehicle-IP or Vehicle-IU treatment groups which did not differ (P> or =0.05). Profiles of progesterone in jugular venous plasma of both control groups treated with Vehicle-IP or Vehicle-IU were lower (P< or =0.05) than in ewes treated with ET-1-IP or ET-1-IU, which did not differ (P> or =0.05) between ET-1-IP or ET-1-IU treatment groups. Treatment with ET-1-IP or ET-1-IU increased (P< or =0.05) the PGE:PGF(2)alpha ratio when compared to the Vehicle-IP or Vehicle-IU treatment groups, which did not differ (P> or =0.05) between each other. In summary, ET-1 prevented the decrease in luteal weights and the decline in progesterone, but increased the PGE:PGF(2)alpha ratio when compared to controls. Therefore, it is concluded that ET-1 is not luteolytic in ewes, but instead may be luteotropic or antiluteolytic by altering uterine secretion of the PGE:PGF(2)alpha ratio, since PGE(1) or PGE(2) are luteotropic in vitro and in vivo, PGE(1) or PGE(2) prevent PGF(2)alpha-induced luteolysis in vitro and in vivo, and PGE(1) and PGE(2) increase two-fold in ewe endometrium to prevent luteolysis during early pregnancy.

Importance of cyclooxygenase 2-mediated low-grade inflammation in the development of fructose-induced insulin resistance in rats.

This study was designed to examine the role of cyclooxygenase (COX) 2-mediated low-grade inflammation in the development of fructose-induced whole body and muscular insulin resistance in rats. The rats were on regular or fructose-enriched diets for 8 weeks. Fructose-fed rats were further divided into 3 groups (n = 8 per group). There were fructose-fed rats, fructose-fed rats with nimesulide (a selective COX2 inhibitor, 30 mg/kg/day, gavage) and fructose-fed rats with celecoxib (a selective COX2 inhibitor, 30 mg/kg/day, gavage). The present result showed that fructose-induced time-dependent increases in systolic blood pressure and fasting plasma insulin and triglyceride levels were significantly suppressed in rats treated with nimesulide or cerecoxib. The ratio of area under glucose curve divided by area under insulin curve obtained during the oral glucose tolerance test was significantly decreased in fructose-fed rats, which were markedly reversed in those co-treated with nimesulide or celecoxib. Accordingly, fructose-induced decrease in insulin-stimulated glucose uptake in soleus muscle was significantly reversed in those combined with nimesulide or celecoxib. Fructose-induced time-dependent increases in plasma 8-isoprostane and PGE metabolites were concomitantly suppressed by nimesulide or celecoxib co-treatment. The present study demonstrates that the COX2-mediated low-grade inflammation, especially mediated by increase in oxidative stress was important in the development of insulin resistance in fructose-fed rats.

Inhibition of caspase-dependent spontaneous apoptosis via a cAMP-protein kinase A dependent pathway in neutrophils from sickle cell disease patients.

Sickle cell disease (SCD) is a chronic inflammatory condition characterized by high leucocyte counts, altered cytokine levels and endothelial cell injury. As the removal of inflammatory cells by apoptosis is fundamental for the resolution of inflammation, we aimed to determine whether the leucocyte apoptotic process is altered in SCD. Neutrophils from SCD individuals showed an inhibition of spontaneous apoptosis when cultured in vitro, in the presence of autologous serum for 20 h. Intracellular cyclic adenosine monophosphate (cAMP) levels were approximately twofold increased in SCD neutrophils; possible cAMP-upregulating factors present in SCD serum include interleukin-8, granulocyte-macrophage colony-stimulating factor and prostaglandin. Accordingly, co-incubation of SCD neutrophils with KT5720, a cAMP-dependent protein kinase (PKA) inhibitor, abrogated increased SCD neutrophil survival. Caspase-3 activity was also significantly diminished in SCD neutrophils cultured for 16 h and this activity was restored when cells were co-incubated with KT5720. BIRC2 (encoding cellular inhibitor of apoptosis protein 1, cIAP(1)), MCL1 and BAX expression were unaltered in SCD neutrophils; however, BIRC3 (encoding the caspase inhibitor, cIAP(2)), was expressed at significantly higher levels. Thus, we report an inhibition of spontaneous SCD neutrophil apoptosis that appears to be mediated by upregulated cAMP-PKA signalling and decreased caspase activity. Increased neutrophil survival may have significant consequences in SCD; contributing to leucocytosis, tissue damage and exacerbation of the chronic inflammatory state.

Ibuprofen use during extreme exercise: effects on oxidative stress and PGE2.

PURPOSE: Oxidative stress was examined with use (N = 29) or nonuse (N = 25) of ibuprofen in ultramarathoners after the Western States Endurance Run. METHODS: Oxidative stress was assessed by measuring plasma and urinary F2-isoprostanes, plasma nitrite, and plasma urate. A urinary prostaglandin E2 metabolite (PGE-M) was used as an end point to assess ibuprofen use. Ibuprofen users consumed 600 and 1200 mg of ibuprofen the day before and on race day, respectively, and nonusers avoided all antiinflammatory medications. Blood and urine were collected in the morning before the race and immediately after the race. RESULTS: Use compared with nonuse of ibuprofen significantly increased plasma (P

Full automation of solid-phase microextraction/on-fiber derivatization for simultaneous determination of endocrine-disrupting chemicals and steroid hormones by gas chromatography-mass spectrometry.

A fully automated method using direct immersion solid-phase microextraction (DI-SPME) and headspace on-fiber silylation for simultaneous determinations of exogenous endocrine-disrupting chemicals (EDCs) and endogenous steroid hormones in environmental aqueous and biological samples by gas chromatography-mass spectrometry (GC-MS) was developed and compared to a previously reported manual method. Three EDCs and five endocrine steroid hormones were selected to evaluate this method. The extraction and derivatization time, ion strength, pH, incubation temperature, sample volume, and extraction solvent were optimized. Satisfactory results in pure water were obtained in terms of linearity of calibration curve (R2=0.9932-1.0000), dynamic range (3 orders of magnitude), precision (4-9% RSD), as well as LOD (0.001-0.124 microg L(-1)) and LOQ (0.004-0.413 microg L(-1)), respectively. These results were similar to those obtained using a manual method, and moreover, the precision was improved. This new automated method has been applied to the determinations of target compounds in real samples used in our previous study on a manual SPME method. Exogenous octylphenol (OP), technical grade nonylphenol (t-NP), and diethylstilbestrol (DES) were at 0.13, 5.03, and 0.02 microg L(-1) in river water and 3.76, 13.25, and 0.10 microg L(-1) in fish serum, respectively. Natural steroid hormones estrone (E1), 17beta-estradiol (E2), and testosterone (T) were at 0.19, 0.11, and 6.22 microg L(-1) in river water; and in female fish serum E1, E2, and pregnenolone (PREG) were at 1.37, 1.95, and 6.25 microg L(-1), respectively. These results were confirmed by the manual method. The developed fully automated SPME and on-fiber silylation procedures showed satisfactory applications in environmental analysis and the performances show improved precision and a reduced analysis time compared to the manual method.

Síndrome de exceso de prostaglandina E, en conejos / Hyperprostaglandin E syndrome in rabbits

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Contribution of interaction between nitric oxide and cyclooxygenases to the production of prostaglandins in carrageenan-induced inflammation.

BACKGROUND: Nitric oxide (NO) and prostaglandins (PGs) are crucial mediators contributing to generation of inflammatory responses and pain. This study was designed to investigate the effects of peripherally released NO on cyclooxygenase (COX) expression/activation and production of PGs in carrageenan-induced inflammation. METHODS: A microdialysis probe was implanted subcutaneously into the skin of hind paws of rats. The concentrations of NO metabolites, PGE2, and 6-keto-PGF1alpha (metabolite of PGI2) in the dialysate were measured. Carrageenan was injected into the plantar surface of the hind paw during perfusion of the dialysis catheter with modified Ringer's solution or N-monomethyl-L-arginine acetate. In addition, the effects of the selective COX-1 inhibitor SC-560 and the selective COX-2 inhibitor NS-398 on the production of NO, PGE2, and 6-keto-PGF1alpha were examined. Western blotting was performed to evaluate the expression of COX-1 and COX-2 in the skin at the site of the inflammation. RESULTS: Carrageenan injection resulted in increases in the concentrations of NO, PGE2, and PGI2, and these increases were completely suppressed by N-monomethyl-L-arginine acetate. SC-560 effectively inhibited the increase in PGE2 and PGI2 concentrations for the first 2 h, and NS-398 inhibited 3-6 h after carrageenan. Western blot analysis showed that the concentrations of both COX-1 and COX-2 in the skin increased after carrageenan. The up-regulation of COX-1 in the skin was observed 3 and 6 h after carrageenan and was not suppressed in the rats treated with N-monomethyl-L-arginine acetate. The up-regulation of COX-2 in the skin was also observed 3 and 6 h after carrageenan and was completely suppressed in the rats treated with N-monomethyl-L-arginine acetate. CONCLUSION: The results of the current study suggest that NO activates COX-1 in the early phase of carrageenan and up-regulates COX-2 expression in the late phase in the skin, resulting in production of PGE2 and PGI2 at the site of inflammation, which would contribute to exacerbation of the inflammatory process.