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.

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.

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.

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.

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.

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.

Mechanisms and mediators of psychological stress-induced rise in core temperature.

OBJECTIVE: Despite numerous case reports on "psychogenic fever," it remains uncertain how psychological stress raises core temperature and whether the rise in core temperature is a real fever or a hyperthermia. This article reviews studies on the psychological stress-induced rise in core temperature (PSRCT) in animals with the aim to facilitate studies on the mechanisms of so-called psychogenic fever in humans. METHODS: To address this question, we reviewed the mechanisms and mediators of the PSRCT and classic conditioning of the fever response in animals. RESULTS: The PSRCT is not due to the increased locomotor activity during stress, and the magnitude of the PSRCT is the same in warm and cold environments, indicating that it is a centrally regulated rise in temperature due to an elevated thermoregulatory "set point." The PSRCT caused by conventional psychological stress models, such as open-field stress, is attenuated by cyclooxygenase inhibitors, which block prostaglandin synthesis. On the other hand, the PSRCT elicited by an "anticipatory anxiety stress" is not inhibited by cyclooxygenase inhibitors but by benzodiazepines and serotonin Type 1A receptor agonists. The febrile response can be conditioned to neutral stimuli after paired presentation with unconditioned stimuli such as injection of lipopolysaccharide, a typical pyrogen. CONCLUSIONS: Most findings indicate that the PSRCT is a fever, a rise in the thermoregulatory set point. The PSRCT may occur through prostaglandin E2-dependent mechanisms and prostaglandin E2-independent, 5-HT-mediated mechanisms. The febrile response can be conditioned. Thus, these mechanisms might be involved in psychogenic fever in humans.

[Clinical significance of plasma PGE2 levels in pre- and post-operative patients with laryngeal carcinoma].

OBJECTIVE: To study the clinical significance of PGE2 Levels in patients with laryngeal carcinoma. METHOD: Radioimmunoassay was used to evaluate plasma PGE2 levels in 35 patients with laryngeal carcinoma. RESULT: The plasma PGE2 levels in patients with laryngeal carcinoma were significant higher than that of normal subjects (P < 0.05), but there was no correlation with the stage of laryngeal carcinoma (P > 0.05). The plasma PGE2 levels of postoperative patients with laryngeal carcinoma were significant lower than that of preoperative patients (P < 0.05). After operation, the plasma PGE2 levels of recurrent patients were significant higher than that in patients with no recurrence (P < 0.01). CONCLUSION: The determination of PGE2 levels in patient plasma may help the diagnosis and prognostic judgment of laryngeal carcinoma.

Secretion of progesterone, estradiol-17beta, PGE, PGF2alpha, and pregnancy-specific protein B by 90-day intact and ovariectomized pregnant ewes.

Ninety-day pregnant ewes were either laparotomized, ovaries left in situ or bilaterally ovariectomized, and a jugular venous catheter and an inferior vena cava catheter via the saphenous vein were installed. Seven days later, placenta slices were collected and incubated in vitro for 4 h. Secretions of progesterone, PGE, estradiol-17beta and pregnancy-specific protein B (PSPB) in vitro by placenta from ovariectomized ewes were increased (P < or = 0.05) by 2.7-, 3.6-, 2.2-, and 2.4-fold, respectively, when compared to placenta slices from intact 90-day pregnant ewes. Secretion of PGF2alpha in vitro was unchanged (P > or = 0.05). Ovariectomy decreased (P < or = 0.05) jugular venous progesterone for 78 h followed by a quadratic increase (P < or = 0.05), whereas progesterone remained unchanged (P > or = 0.05) in intact ewes over the 162-h sampling period. Ovariectomy increased (P < or = 0.05) PGE in inferior vena cava plasma over the last half of the 162-h sampling period, whereas concentration of PGF2alpha did not change (P > or = 0.05). Increases in PGE occurred before the increase in progesterone. Concentrations of PSPB in inferior vena cava plasma of ovariectomized pregnant ewes increased (P < or = 0.05) during the last half of the 162-h sampling period, but not in intact ewes (P > or = 0.05). PSPB increased before PGE and progesterone. Concentrations of estradiol-17beta in jugular venous plasma of ovariectomized pregnant ewes increased (P < or = 0.05) during the last half of the sampling period, but not in intact ewes (P > or = 0.05). Increases in estradiol-17beta occurred before increases in PSPB. It is concluded that these data support the hypothesis that estradiol-17beta may control placental secretion of PSPB; PSPB may regulate placental secretion of PGE; and PGE may regulate placental secretion of progesterone.

Effect of trilostane on PGE, PGF2alpha, estradiol-17beta, and progesterone secretion and pregnancy of 90-day ovariectomized pregnant ewes.

Ninety-day pregnant sheep were ovariectomized and received vehicle or trilostane every 12 h through 132 h, starting at 72 h postovariectomy. All trilostane-treated ewes aborted (P < or = 0.05) between 36 and 50 h after initiation of treatment. Profiles of progesterone in jugular venous blood differed (P < or = 0.05) and was lower (P < or = 0.05) in trilostane-treated ewes. Profiles of estradiol-17beta in jugular venous plasma of trilostane-treated ewes differed (P < or = 0.05) from controls. Estradiol-17beta increased after the first two treatments, followed by a return 2 h later to pretreatment levels (P > or = 0.05), which was followed by a sustained increase (P < or = 0.05) in estradiol-17beta. Profiles of PGF2alpha in inferior vena cava plasma of trilostane-treated ewes differed and were greater (P < or = 0.05) and occurred with the sustained increase in estradiol-17beta and the onset of most of the abortions. Profiles of PGE in inferior vena cava plasma between control and trilostane-treated 90-day pregnant ewes did not differ (P > or = 0.05). It is concluded that abortions occur at midpregnancy in sheep when the estradiol-17beta : progesterone ratio changes sufficiently to cause a sustained increase in estradiol-17beta and PGF2alpha but without changing placental secretion of PGE.

Effect of prostaglandin F2alpha (PGF2alpha), indomethacin, tamoxifen or estradiol-17beta on prostaglandin E (PGE), PGF2alpha and estradiol-17beta secretion in 88 to 90-day pregnant sheep.

Treatment with PGF2alpha plus estradiol-17beta aborts 90-day pregnant ewes, whereas PGF2alpha or estradiol-17beta alone does not abort ewes. The objective of this experiment was to evaluate whether tamoxifen, an estrogen receptor antagonist, estradiol-17beta, prostaglandin F2alpha (PGF2alpha), indomethacin, or some of their interactions affected ovine uterine/placental secretion of PGF2alpha, estradiol-17beta or prostaglandins E (PGE), because a single treatment with PGF2alpha and estradiol-17beta given every 6 h aborts 90-day pregnant ewes. Concentrations of PGF2alpha in uterine venous blood were increased (P < or = 0.05) by estradiol-17beta, PGF2alpha + estradiol-17beta, and PGF2alpha + tamoxifen, and decreased (P < or = 0.05) by indomethacin or PGF2alpha + indomethacin at 72 h when compared to the 0 h samples. Concentrations of PGE in uterine venous blood were decreased (P < or = 0.05) by indomethacin and PGF2alpha + indomethacin and increased (P < or = 0.05) by PGF2alpha + estradiol-17beta at 72 h when compared to the 0 h samples. Concentrations of PGF2alpha in inferior vena cava blood at 6 h were increased (P < or = 0.05) by PGF2alpha either alone or in combination with indomethacin, tamoxifen, or estradiol-17beta, which is due to the PGF2alpha injected. Concentrations of PGF2alpha in inferior vena cava blood in PGF2alpha + estradiol-17beta-treated 88- to 90-day pregnant ewes increased (P < or = 0.05) linearly over the 72-h sampling period and averaged 4.0 + 0.4 ng/ml. Concentrations of PGF2alpha in inferior vena cava blood of control, PGF2alpha, tamoxifen, PGF2alpha + indomethacin, PGF2alpha + tamoxifen, and estradiol-17beta-treated ewes did not differ (P > or = 0.05) and averaged 0.4 + 0.04 ng/ml. Profiles of PGE in inferior vena cava blood of 88- to 90-day pregnant ewes treated with vehicle, PGF2alpha, estradiol-17beta, tamoxifen, tamoxifen + PGF2alpha, or estradiol-17beta + PGF2alpha did not differ (P > or = 0.05). Concentrations of PGE in inferior vena cava blood of 88- to 90-day pregnant ewes treated with indomethacin or PGF2alpha + indomethacin were lower (P < or = 0.05) than in control ewes. Concentrations of estradiol-17beta in jugular venous plasma of PGF2alpha + estradiol-17beta-treated 88- to 90-day pregnant ewes increased linearly and differed (P < or = 0.05) from controls. Profiles of estradiol-17beta in jugular venous plasma of PGF2alpha, indomethacin, tamoxifen, and PGF2alpha + tamoxifen and PGF2alpha + indomethacin, estradiol-17beta, and controls did not differ (P > or = 0.05). It is concluded that treatment with a single injection of PGF2alpha and estradiol-17beta given every 6 h causes a linear increase in PGF2alpha and estradiol-17beta.

Simultaneous determination of prostaglandin E1, prostaglandin E0 and 15-keto-prostaglandin E0 in human plasma by gas chromatography/negative-ion chemical-ionization tandem mass spectrometry.

A sensitive and selective routine method for the simultaneous determination of prostaglandin E1 (PGE1), prostaglandin E0 (PGE0) and 15-keto-prostaglandin E0 (15-keto-PGE0) in human plasma is described using deuterated internal standards. The analytes were isolated from acidified human plasma by solid-phase extraction by means of Bond Elut C18 cartridges and derivatized to the pentafluorobenzyl (PFB) ester methoxime. The analytes were purified on Bond Elut Si cartridges and converted to the trimethylsilyl (TMS) ether. Quantitation was achieved by gas chromatography-negative-ion chemical-ionization tandem mass spectrometry. The precursor ion [M-PFB]- = [P]- carried more than 80% of the total ion current. Collision activated decomposition (CAD) of [P]- resulted in characteristic product ions of which the [P-2(CH3)3SiOH]- ion (PGE1) and the [P-(CH3)3SiOH]- ion (PGE0 and 15-keto-PGE0) were used for quantitation. The lower limit of quantitation (LLQ) was 2 pg/ml (PGE1 and PGE0) and 10 pg/ml (15-keto-PGE0) extracted from 2 ml of human plasma. Linear calibration curves were obtained over the concentration range 2-100 pg/ml (PGE1 and PGE0) and 10-500 pg/ml (15-keto-PGE0). In all cases, the precision and accuracy were < 17%. The present method has been applied successfully to pharmacokinetic and clinical studies in humans.

[Prognostic importance of preclinically evaluated biochemical mediators in polytrauma]. / Prognostische Bedeutung präklinisch erfasster biochemischer Mediatoren beim Polytrauma.

UNLABELLED: There is compelling data from several clinical studies on the impact of various anti- and proinflammatory mediators on traumatized patients. Immediate trauma-related results, however, are only available from animal experiments so far. Therefore, in this prospective clinical study the following questions were addressed: (I) Is there any marker in the preclinical phase that give information independent of and better than conventional studies conducted so far, (II) does this possible factor prove to be a (significant) predictor of late complications and/or poor overall outcome, and (III) does this mediator provide information that can alter treatment decisions? METHODS: Upon approval of the local IRB/IEC, 85 patients (pts) were enrolled who suffered from multiple injuries. The pts were rescued by the helicopter-based service of the German Army Hospital in Ulm. The first blood samples were drawn at the site of accident and at admission, then in hourly to daily intervals. The plasma concentrations of following mediators were analyzed: Prostanoids, products of O2-radicals, soluble adhesion molecules, various cytokines, C-reactive protein, creatinine kinase, and neopterin. All values were calculated in relation to the actual plasma protein content to eliminate fluid-induced dilution effects. Subsets of patients were performed according to the severity of trauma (ISS < 9; 9-17; 18-31; > 32), based on the different injury pattern, and survivors versus nonsurvivors as well. RESULTS: As early as at the scene of accident, all patients revealed a severity-dependent increase in most mediators' plasma levels. There was, however, also a pattern-related inflammatory response that was most pronounced in pts who had suffered from thoracic trauma irrespective of whether it was associated with multiple trauma. In a total, 15 pts died within 72 h after the accident. In those casualties, the plasma concentrations of prostaglandin E2 (P < 0.03), glutathione (P < 0.01) as well as creatinine kinase (P < 0.05) were more markedly elevated when compared with survivors. CONCLUSION: Although there were severity-dependent as well as pattern-related releases of various mediators, which in part were more apparent in nonsurviving patients, we failed in proving any predictive marker to specifically discriminate outcome.

Is the attenuation of beta-adrenergic agonist efficacy during labor caused by elevated prostaglandin E levels?

OBJECTIVE: Our purpose was to investigate whether attenuation of beta-adrenergic agonist efficacy during labor is due to elevated prostaglandin E levels. STUDY DESIGN: beta-Receptor function (response to beta-agonist or forskolin) was tested in mononuclear leukocytes collected from women at term before or during labor. beta-Receptor function was also tested in mononuclear leukocytes of nonlaboring patients after in vitro incubation with oxytocin (1 micromol/L), prostaglandin E2 (10 micromol/L), prostaglandin F2alpha (10 micromol/L), or buffer alone. RESULTS: Mononuclear leukocytes from women in active labor exhibited a significant attenuation of beta-adrenergic receptor function as a result of reduced adenylyl cyclase activity. This effect could be induced in mononuclear leukocytes from nonlaboring women by preincubation with prostaglandin E but not oxytocin or prostaglandin F. CONCLUSIONS: Prostaglandin E induces heterologous desensitization of the beta-adrenergic receptor system in mononuclear leukocytes, comparable to that seen during labor. We speculate that during labor the elevated levels of prostaglandin E may induce similar effects on the myometrium, thereby decreasing the efficacy of beta-agonists as tocolytics.

Fetal and maternal endocrine changes approaching parturition in the goat: lack of evidence for prostaglandins E2 and F2alpha as signals for luteolysis.

We investigated the temporal relationship of fetal cortisol secretion to circulating concentrations of fetal ACTH1-39 and its high-molecular weight precursors in goats. We also measured the concentrations of progesterone, estradiol-17beta estrone sulfate, prostaglandin (PG) E, PGF2alpha, and PGF2alpha metabolite (PGFM) in maternal arterial plasma over the last month of gestation. Prostaglandin concentrations were also measured in utero-ovarian venous plasma. There was a positive association between ACTH1-39 in fetal plasma and the prepartum surge in fetal cortisol that commenced 8 days before labor. The fetal cortisol surge was followed by a simultaneous decrease in maternal progesterone and an increase in plasma estrogens commencing 3-4 days before labor. No change in basal prostaglandin concentration occurred before this time. There was a positive veno-arterial difference of PGE and PGF2alpha across the uterine vascular bed, confirming the uteroplacental unit as a major source of these eicosanoids in the plasma of the pregnant doe. We conclude that the fetal signal for parturition precedes luteolysis by some 5 days and find no evidence of changes in the basal concentrations of PGE and PGF2alpha in maternal plasma at the time of luteolysis.

[State of prostanoid-regulating function of the lungs in patients subjected to thoracic surgery]. / Sostoianie prostanoidreguliruiushchei funktsii legkikh u bol'nykh pri torakal'nykh operatsiiakh.

Lung capacity to regulate the level of plasma prostanoids at the expense of their destruction or extra synthesis is one of their numerous non-gas-exchange functions. Prostaglandins A, E, and F, prostacyclin, and thromboxane were measured in the arterial and venous blood of 23 patients before and after surgery. The level of prostanoids was sharply increased in surgical patients. Substrates with the broncho- and vasoconstrictive action predominate in the blood of patients with obstructive and restrictive changes in the lungs, this eventually leading to complications in the postoperative period.

Eicosanoid and amino acid metabolism in transient acute psychoses with psychedelic symptoms.

It has been hypothesized that a disturbance of glutathione (GSH) metabolism might be a common factor in many psychiatric disorders. The aim of the present study was to test this hypothesis in transient acute psychotic patients with distorted perceptions. Since the metabolism of GSH is related to that of thromboxane B2 (TXB2), prostaglandin E (PGE) and some amino acids, we determined these substances in the plasma of 15 patients and 17 normal controls. Plasma concentrations of TXB2 were significantly higher and concentrations of serine and tryptophan were significantly lower in patients than in controls. Large variation was observed in plasma PGE levels in patients, although mean values did not differ significantly from controls. These results are consistent with the hypothesis that the metabolism of GSH is impaired in transient psychotic states.

[Comparative characterization of results of the immunoenzyme method of interleukin-1 determination in blast transformation reaction with indomethacin]. / Savnitel'naia kharakteristika rezul'tatov opredeleniia interleikina-1 immunofermentnym metodom i v reaktsii blasttransformatsii s indometatsinom.

Comparison of the results of blast transformation test and enzyme immunoassay of interleukin-1 in the blood serum and culture fluid demonstrated that assessment of phytohemagglutinin (PHA)-effected level of proliferative activity of lymphocytes is more informative for the diagnosis of manifest forms of HIV infection. Combined addition of PHA and indomethacin to cell culture by shifting the balance between prostaglandin E and interleukin-1 helps assess the contribution of macrophages to the development of HIV infection.