Fetal responses to maternal and intra-amniotic lipopolysaccharide administration in sheep

A link between intrauterine infection and premature labor is widely accepted, yet the fetal inflammatory responses to such infections are not well understood. Our aim was to use a sheep model in which an inflammatory state was induced by lipopolysaccharide (LPS) administration during pregnancy to the maternal systemic, intra-amniotic or extra-amniotic compartments. Fetal and maternal blood gases and uterine electromyographic activity along with fetal and maternal circulating concentrations of prostaglandins PGE2 and PGFM, cortisol, and interleukin-6 were determined. Maternal systemic LPS treatment resulted in mild maternal hypoxemia, a rise in temperature, greater fetal hypoxemia, and a marked rise in fetal cortisol and PGE2 concentrations that persisted for 48 h. Intra-amniotic administration of LPS at doses higher than those used systemically caused an increase in fetal cortisol and PGE2 concentrations as well as a rise in uterine activity, but these were lesser in magnitude. Extra-amniotic LPS administration caused no overt fetal or maternal inflammatory responses. We conclude that maternal LPS treatment markedly elevated fetal cortisol and PGE2 concentrations. This may be a potential protective mechanism that aids the fetus in the event of premature delivery. The attenuated fetal response to intra-amniotic LPS treatment, despite the much higher dose used, may support a role for the amniotic fluid in protecting the fetus from endotoxin exposure during pregnancy.     

Facilitation of suction termination using extra-amniotic prostaglandins in gel

Extra-amniotic prostaglandin E₂ (PGE₂) suspended in a slow release gel (Tylose) was instilled in 35 patients prior to a planned surgical termination in an attempt to dilate the cervix, minimize cervical trauma, and reduce the possible risk of cervical incompetence and its sequelae. Dilatation occurred in all patients to a minimum of 8 mm and 74% aborted before surgical evacuation performed 6 to 24 hours after injection. No serious side effects occurred. Extra-amniotic PGE₂ in gel should be considered as a primary procedure when the cervix is obviously immature on examination. If the cervix is found to be tight and unyielding at surgical dilatation, the latter procedure should be discontinued and PGE₂ in gel injected.     

Intra-amniotic urea and prostaglandin E2 for abortion. A clinical study to determine the efficacy of using a variable prostaglandin dosage

Intra-amniotic urea 80 g combined with either prostaglandin E₂ 5 mg or 10 mg was injected in two groups of patients to induce mid-trimester abortion. Abortion invariably resulted within 24 hours with both schedules used. The mean injection-abortion interval was not significantly shorter in those receiving the higher dose of prostaglandins. There were fewer gastrointestinal side effects in those receiving the lower dosage. This combined technique has some advantages over other methods used for a single initiating procedure only is required and nursing involvement is minimal.     

Pharmacotherapeutics of prostaglandin E2 and 15 (S) 15-methyl prostaglandin F2α in chronic schistosomal bladder ulcer: A clinico-endoscopic study

The pharmacotherapeutic effects of prostaglandin E₂ (PGE₂) and 15 (S) 15-methyl PGF_2α given by different routes of administration, were studied in 20 normal persons and 100 patients with chronic schistosomal bladder ulcer in comparison to normal saline and antimony dimercaptosuccinate drug. Prostaglandins produced a rapid significant amelioration in the ulcer symptom complex with a good percentage of ulcer disappearance on cystoscopy, while the antimony dimercaptosuccinate treated group showed a less early response which improved with follow up. This was in contrast to prostaglandins which showed relapse in the symptom-complex in some cases after a follow up period of 2 months. The combined use of schistosomicidal drugs together with, or followed by, prostaglandins might give better results.     

Therapeutic Abortion by Intra-amniotic Injection of Prostaglandins

Intra-amniotic injection of either prostaglandin F₂α or prostaglandin E₂ was used in an attempt to induce therapeutic abortion in mid-pregnancy in 27 patients. Termination of pregnancy was successful in 11 out of 13 cases when prostaglandin E₂ alone was used, but in only 6 out of 14 cases when prostaglandin F₂α was used. A further eight patients aborted after additional intravenous oxytocin stimulation, but the combined procedures failed altogether in two patients who were initially given prostaglandin F₂α. The technique was simple, free from serious side effects, and reasonably effective when prostaglandin E₂ was used.     

Facilitation of suction termination using extra-amniotic prostaglandins in gel

Extra-amniotic prostaglandin E2 (PGE2) suspended in a slow release gel (Tylose) was instilled in 35 patients prior to a planned surgical termination in an attempt to dilate the cervix, minimize cervical trauma, and reduce the possible risk of cervical trauma, and reduce the possible risk of cervical incompetence and its sequelae. Dilatation occurred in all patients to a minimum of 8 mm and 74% aborted before surgical evacuation performed 6 to 24 hours after injection. No serious side effects occurred. Extra-amniotic PGE2 in gel should be considered as a primary procedure when the cervix is obviously immature on examination. If the cervix is found to be tight and unyielding at surgical dilatation, the latter procedure should be dicontinued and PGE2 in gel injected.     

Proteomic analysis using protein chips to detect biomarkers in cervical and amniotic fluid in women with intra-amniotic inflammation

Intra-amniotic inflammation (IAI) may cause preterm birth with poor neonatal out-come. To identify novel biomarkers for IAI, we analyzed amniotic and cervical fluid samples from 27 patients with signs of threatening preterm birth with or without IAI by surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Seventeen proteins were significantly overexpressed in amniotic fluid from IAI cases and more often in women with preterm labor than those with rupture of membranes. Five of these were identified as human neutrophil protein 1-3, calgranulin A and B.     

Effect of Intra-amniotic Oestriol Sulphate on Uterine Contractions

The effects of oestriol sulphate on myometrial activity in a group of young primigravidae, who were at 41 or more weeks'' gestation, are compared with those of a placebo in a double-blind trial. Both compounds were administered over a period of six hours directly into the uterine cavity following artificial rupture of membranes. Intra-amniotic pressure recordings demonstrated a peak in the mean intensity in uterine contractions in the oestriol-treated and placebo-treated groups at six and four hours, respectively. The length of labour tended to be shorter in those patients having greater uterine activity.     

Prostaglandins mediate the fetal pulmonary response to intrauterine inflammation

Intra-amniotic (IA) lipopolysaccharide (LPS) induces intrauterine and fetal lung inflammation and increases lung surfactant and compliance in preterm sheep; however, the mechanisms are unknown. Prostaglandins (PGs) are inflammatory mediators, and PGE(2) has established roles in fetal lung surfactant production. The aim of our first study was to determine PGE(2) concentrations in response to IA LPS and pulmonary gene expression for PG synthetic [prostaglandin H synthase-2 (PGHS-2) and PGE synthase (PGES)] and PG-metabolizing [prostaglandin dehydrogenase (PGDH)] enzymes and PGE(2) receptors. Our second study aimed to block LPS-induced increases in PGE(2) with a PGHS-2 inhibitor (nimesulide) and determine lung inflammation and surfactant protein mRNA expression. Pregnant ewes received an IA saline or LPS injection at 118 days of gestation. In study 1, fetal plasma and amniotic fluid were sampled before and at 2, 4, 6, 12, and 24 h after injection and then daily, and fetuses were delivered 2 or 7 days later. Amniotic fluid PGE(2) concentrations increased (P < 0.05) 12 h and 3-6 days after LPS. Fetal lung PGHS-2 mRNA and PGES mRNA increased 2 (P = 0.0084) and 7 (P = 0.014) days after LPS, respectively. In study 2, maternal intravenous nimesulide or vehicle infusion began immediately before LPS or saline injection and continued until delivery 2 days later. Nimesulide inhibited LPS-induced increases in PGE(2) and decreased fetal lung IL-1β and IL-8 mRNA (P ≤ 0.002) without altering lung inflammatory cell infiltration. Nimesulide decreased surfactant protein (SP)-A (P = 0.05), -B (P = 0.05), and -D (P = 0.0015) but increased SP-C mRNA (P = 0.023). Thus PGHS-2 mediates, at least in part, fetal pulmonary responses to inflammation.     

Effects of an antiserum for epithelial-reticular cells of the thymus on T-dependent immune response

Relations between thymic factors and Prostaglandins (PG) were studied. We investigated on the effects of different incubation times with Thymosin Fraction 5 and Indomethacin on the release by spleen cells from normal or adult thymectomized mice. Prostaglandins were measured by radioimmunoassay. Thymosin induces an increase in PGE2 release on spleen cells obtained from thymectomized mice; the same effect was not observed on spleen cells obtained from normal mice.     

Inducing labour with vaginally administered prostaglandin E2.

In 50 consecutive pregnant women at a 125-bed community hospital with 1000 deliveries annually, labour was induced with prostaglandin E2 administered intravaginally. There were no stillbirths or neonatal deaths, and complications in the mothers were few. In nine women (18%) oxytocin was subsequently administered because of a failure of labour to progress; in spite of this, cesarean section was required in two (4%) of the patients. The overall cesarean section rate was 6%. Prostaglandins have been used routinely to induce labour in the United Kingdom for several years. This noninvasive method is safe, effective and well received by women in a community hospital setting, including those wanting "natural childbirth".     

The mode of action of Aescin and the release of prostaglandins

The horse-chestnut saponin Aescin, an anti-exudative compound, induces contraction of isolated portal vein of rat and rabbit. This effect appears to be mediated by Prostaglandins of F_α type.The ability of Aescin to stimulate generation and release of Prostaglandins has been demonstrated in isolated lung of the rat. Mass-fragmentographic analysis of the lung effluent indicate that when Aescin is perfused through this organ the release of PGF_2α is increased. The capability of Aescin to generate Prostaglandins is discussed in connection with its anti-exudative activity.     

Spinal injuries due to front-end bale loaders.

Of 22 patients admitted to Plains Health Centre, Regina, from January 1979 to April 1986 with spinal injuries due to farming accidents, 7 had injuries related to tractor-mounted front-end bale loaders. In contrast, none of the 12 patients admitted with farm-related spinal injuries from 1974 through 1978 had injuries related to bale loaders. All seven injuries occurred when a front-end loader was used to move a large, round hay bale. In each case when the loader arms were raised past the horizontal plane the bale rolled back onto the unprotected tractor operator. There were five thoracic injuries, one cervical injury and one lumbar injury. All seven bony injuries healed. Four of the patients had permanent neurologic sequelae; two of the four had paraplegia. All seven patients suffered disability that impaired work performance; all five farmers suffered some loss of income. None of these injuries would have occurred if available safety equipment had been in place.     

ISS与APACHEⅡ评分对急诊多发伤患者伤情评估的价值分析

目的:探讨损伤严重程度计分法(Injuryseverityscore,ISS)和慢性健康评分(Acute physiology and chronic health evaluation scoreⅡ,APACHEⅡ)评分对急诊多发伤患者伤情评估的应用价值。方法:将我院自2016年6月至2019年6月急诊收治的多发伤患者85例作为研究对象,分别使用ISS和APACHEⅡ评分,追踪患者住院期间的伤情严重程度和预后情况。结果:急诊多发伤患者入院时ISS评分和APACHEⅡ评分越高,患者ICU收住率和死亡率越高,患者预后越差(P0.05);死亡的急诊多发伤患者ISS评分和APACHE-Ⅱ评分均明显高于存活组(P0.05)。ISS评分预测急诊多发伤患者死亡的灵敏度为87.06%,特异性为85.88%,APACHE-Ⅱ评分预测急诊多发伤患者死亡的灵敏度和特异性分别为88.24%和87.06%,差异无统计学意义(P0.05),两者联合预测急诊多发伤患者死亡的灵敏度为95.29%,特异性为94.12%,均优于单独预测(P0.05)。结论:ISS评分和APACHE-Ⅱ评分能够较为准确的评估急诊多发伤患者的病情严重程度,对患者预后具有较好的预测价值,两者结合使用的应用价值更高。     

Surgical management of traumatic disruption of the descending aorta.

During an 11 1/2-year period, 20 consecutive patients presenting with a traumatic disruption of the proximal descending aorta underwent an emergency operative repair. The mean age was 26 years (range 15 to 62), and 13 (65%) were male. Associated injuries were frequent and required additional major operative procedures in half of the cases. Two patients died as a result of associated intracranial injuries, for a hospital survival of 90%. The operative repair was accomplished by graft replacement of the involved segment of the aorta in all but one patient who underwent a primary repair. Simple aortic crossclamping was used in 8 patients (40%) and heparinless femoral-femoral venoarterial bypass in 12 patients (60%). Neither renal failure nor paraplegia in any of the patients. Four patients required thoracic reoperations. These results indicate that an aggressive multidisciplinary surgical approach can produce favorable results in patients with traumatic descending aortic injuries.     

Cervical ripening and plasma prostaglandin levels. Comparison of endocervical and extra-amniotic PGE2

Two modes of cervical application of a gel containing PGE2 have been compared in a total of 30 patients with indication for induction of labor and unripe cervix. Fifteen patients had gel injected endocervically; in 10 patients the gel contained 400 micrograms PGE2, in 5 controls the gel was inactive. Fifteen subjects had a 15 ml Foley catheter passed through the cervix and placed extra-amniotically; in 10 of them 3 ml gel with 400 or 800 micrograms PGE2 was injected, while 5 controls received inactive gel. Plasma levels of 13,14-dihydro-15-keto-PGE2 alpha (PGFM) were measured in blood samples drawn before and 1/2, 1, 2, 4, 6, and 8 hours after gel application. Neither the Foley catheter nor the application of inactive gel caused significant changes in the cervical scores or the PGFM levels. PGE2 in the endocervix increased cervical scores without altering plasma PGFM levels. Extra-amniotic PGE2 caused a more rapid increase of the cervical scores and a progressive rise in PGFM levels. The plasma (PGFM) levels were found to be related to the degree and to the rate of cervical dilatation. The correlation with cervical dilatation was highly significant. Labor began spontaneously or after artificial rupture of the membranes in 80% of the extra-amniotic, and 50% of the endocervical PGE2-group, but in none of the controls. These data indicate that increased uterine PGF2 alpha production is not necessary for the early stages of cervical ripening, whereas dilatation beyond 4 cm does not proceed without such increase.     

神经酰胺(ceramide)信使途径

生物体内神经酰胺有多种生成途径。作为重要的第二信使,神经酰胺在多种信号转导过程中发挥广泛作用,从而影响细胞生长、增殖、分化、凋亡及损伤等多种生理、病理过程。此机制的发现被认为是近年来信号转导研究的重要进展之一。     

神经酰胺信使途径

生物体内神经酰胺有多种生成途径。作为重要的第二信使,神经酰胺在多种信号转导过程中发挥广泛作用,从而影响细胞生长、增殖、分化、凋亡及损伤等多种生理、病理过程。此机制的发现被认为是近年来信号转导研究的重要进展之一。     

A comparison of the contractile activity of PGD2 and PGF2 alpha on human isolated bronchus

Prostaglandins may be implicated in the bronchoconstriction which occurs in asthma. Prostaglandins F2 alpha (PGF2 alpha) and D2 (PGD2) have been reported to produce bronchoconstriction in asthmatic subjects in vivo and PGF2 alpha contracts human isolated airway smooth muscle. We examined the relative efficacy and potency of PGF2 alpha and PGD2 on human bronchial spiral strips taken from 6 patients at thoracotomy. PGF2 alpha had greater efficacy than PGD2. The mean % Tmax (percentage of maximal contractile response) +/- s.e. mean were 84 +/- 7 and 54 +/- 7 respectively (P less than 0.05). PGF2 alpha (mean pD2 +/- s.e. mean = 6.39 +/- 0.6) tended to be more potent than PGD2 (5.68 +/- 0.2). Since, in vivo, PGD2 has greater efficacy and potency than PGF2 alpha, our results suggest that the in vivo effect of these prostaglandins does not result solely from an action on airway muscle.     

Bioproduction of prostaglandins in a transgenic liverwort, Marchantia polymorpha

Prostaglandins are biologically active substances used in a wide range of medical treatments. Prostaglandins have been supplied mainly by chemical synthesis; nevertheless, the high cost of prostaglandin production remains a factor. To lower the cost of prostaglandin production, we attempted to produce prostaglandins using a liverwort, Marchantia polymorpha L., which accumulates arachidonic acid, which is known as a substrate of prostaglandins. Here we report the first bioproduction of prostaglandins in plant species by introducing a cyclooxygenase gene from a red alga, Gracilaria vermiculophylla into the liverwort. The transgenic liverworts accumulated prostaglandin F_2α, prostaglandin E₂ and prostaglandin D₂ which were not detected in the wild-type liverwort. Moreover, we succeeded in drastically increasing the bioproduction of prostaglandins using an in vitro reaction system with the extracts of transgenic liverworts.