Maternal serum and amniotic fluid levels of human placental lactogen in gestational diabetes

Abstract. Human placental lactogen (hPL) levels were measured radioimmunologically in maternal serum and in amniotic fluid between the 37th and 39th weeks of gestation in sixteen gestational diabetic and thirty normal pregnant women. There was no significant difference in maternal serum hPL levels between diabetic (6.1 μ g/ml) and normal pregnant women (6.4 μ g/ml). In contrast, the diabetic group was found to have significantly ( P< 0.001) higher concentrations of amniotic fluid hPL (1.2 μ g/ml) than normal pregnant women (0.8 μ g/ml).     

游离雌三醇和人胎盘催乳素测定在子痫前期的意义

目的：探讨血清游离雌三醇(uE3)和人胎盘催乳素(hPL)与子痫前期的关系。方法选取2013年6月至2014年6月诊断为子痫前期的孕妇123例纳入观察组,同期健康孕妇150例纳入对照组,两组孕妇均分别在妊娠28~<32周和妊娠32~36周各采血一次,检测血清 uE3和 hPL 水平并进行比较。结果对照组妊娠结局优于观察组。随着孕周增加两组孕妇血清 uE3和 hPL 水平有升高趋势,在相同孕期中对照组血清 uE3和 hPL 水平均较观察组高,差异均有统计学意义(P <0.05)。结论子痫前期孕妇血清 uE3和 hPL 水平下降,与妊娠结局相关。     

Maternal serums and amniotic fluid levels of human placental lactogen in gestational diabetes.

Human placental lactogen (hPL) levels were measured radioimmunologically in maternal serum and in amniotic fluid between the 37th and 39th weeks of gestation in sixteen gestational diabetic and thirty normal pregnant women. There was no significant difference in maternal serum hPL levels between diabetic (6.1 microgram/ml) and normal pregnant women (6.4 microgram/ml). In contrast, the diabetic group was found to have significantly (P less than 0.001) higher concentrations of amniotic fluid hPL (1.2 microgram/ml) than normal pregnant women (0.8 microgram/ml).     

Effects of trkB and trkC neurotrophin receptor agonists on thermal nociception: a behavioral and electrophysiological study

Nerve-growth factor (NGF), a member of the neurotrophin family, plays an important role in nociceptor function. Prompted by a previous unexpected finding that NT-4/5, as well as NGF sensitizes single nociceptors to noxious heat, we have explored the relative potency of all neurotrophins in eliciting thermal hyperalgesia. NGF, brain-derived neurotrophic factor (BDNF), NT-4/5 and NT-3 were injected locally into the hind paw of rats, and the behavioral response to noxious heat was compared with that from the other paw that received an identical injection of vehicle. Like NGF, agonists of tyrosine kinaseB (trkB) receptors (NT-4/5 and BDN F) induced thermal hyperalgesia in the first 5 h after treatment (NT-4/5>BDNF) but the effect had worn off by 24 h. In contrast, the trkC agonist NT-3 had no effect on the response to noxious heat. Electrophysiological recordings from single C-fibres in the in vitro skin-saphenous nerve preparation revealed sensitization to noxious heat stimuli after direct application of BDNF to the receptive field, as previously noted for NT-4/5, and in parallel with the behavioral findings. NT-3 was ineffective as in the behavioral studies. These results suggest that trkB agonists BDNF and NT-4/5 as well as the trkA agonist NGF can regulate nociceptive responses to noxious heat.     

妊娠期高血压患者血清脂联素与胎盘基质金属蛋白酶-9的相关性研究

目的探讨妊娠期高血压患者血清脂联素水平与胎盘基质金属蛋白酶-9(MMP-9)的关系。方法根据疾病严重程度,将145例妊娠期高血压孕妇分为轻度妊高征组72例和重度妊高征组73例,以同期正常分娩的孕妇60例为对照组,比较各组血清脂联素水平与MMP-9的表达情况。结果妊高征各组与对照组血清脂联素比较均下降(P0.05)。妊高征各组与对照组MMP-9阳性率比较,差异有统计学意义(P0.05或P0.01);重度妊高征组MMP-9阳性率显著低于轻度妊高征组及对照组(P0.01)。妊高征患者血清脂联素水平与胎盘MMP-9阳性表达率呈正相关(r=0.71,P0.05)。结论血清脂联素水平降低及胎盘组织MMP-9表达率下降可能促进了妊娠高血压疾病的发生与发展。     

Interaction between tramadol and two anti-emetics on nociception and gastrointestinal transit in mice.

BACKGROUND: Clinical studies suggest that tramadol-induced analgesia is partially antagonized by ondansetron. AIMS: To investigate the type of interaction between tramadol and two anti-emetics on antinociception and gastrointestinal transit in mice. METHODS: We assessed the antinociceptive (acetic acid writhing test, plantar test) and antitransit (charcoal meal) effects of tramadol individually, and combined with ondansetron or droperidol in female Swiss CD-1 mice. Isobolograms and analysis of variance were used to determine the type of interaction. RESULTS: In the writhing test, tramadol, ondansetron and droperidol, each induced dose-related inhibition of nociception. The ED(50)'s were: tramadol 4.2+/-0.33 mg kg(-1); ondansetron 1.03+/-0.05 mg kg(-1), and droperidol 1.00+/-0.14 mg kg(-1). Dose-response curves were also obtained with tramadol combined with ondansetron or droperidol at 1:1 fixed ratios. The isobolographic analysis demonstrated antagonism for both combinations. In the plantar test, the ED(50) for tramadol was 51.4+/-2.3 mg kg(-1), but no dose-response curves could be obtained with ondansetron or droperidol individually. The interaction was assessed from dose-response curves to tramadol in the presence of a fixed dose of ondansetron (0.1 mg kg(-1)) or droperidol (0.05 mg kg(-1)). The results show antagonism between tramadol-ondansetron (p<0.05) and no interaction for the tramadol-droperidol combination. Both anti-emetics antagonized the antitransit effects of tramadol. CONCLUSIONS: The interaction of tramadol with ondansetron or droperidol on antinociception can be antagonistic or additive, depending on the type of stimuli. Both anti-emetics antagonize the anti-transit effects of tramadol. The results demonstrate antagonism between tramadol and the two anti-emetics for analgesia and inhibition of gastrointestinal transit, supporting previous clinical studies.     

How placental growth factor detection might improve diagnosis and management of pre-eclampsia

Pre-eclampsia complicates around 5% of pregnancies and hypertensive disorders of pregnancy are responsible for over 60,000 maternal deaths worldwide annually. Identifying women with pre-eclampsia is a major goal of antenatal care in order to target increased surveillance, allow stabilizing therapies to be implemented and to enable timely delivery. Current risk assessment is based on clinical history, imperfect assessment of clinical signs (e.g., hypertension and proteinuria) and nonspecific biochemical markers, all of which are subject to considerable error. This is further confounded by underlying maternal disease such as chronic hypertension or renal pathology. Angiogenic factors reflect the underlying pathophysiology of pre-eclampsia and there is emerging evidence that they can now be used for more accurate risk assessment. The most promising of these factors include placental growth factor and soluble fms-like tyrosine kinase-1. Used at point of care, these can accurately discriminate true disease in suspected cases and subsequent need for delivery.     

宫内暴露于高雄激素对小鼠胎盘营养转运体表达的影响

目的探讨宫内暴露于高雄激素对小鼠胎盘营养转运体表达的影响。方法选择2018年1-3月购置的6~8周龄ICR雌性小鼠,自然受精后6.5 d开始每天给予颈部皮下注射脱氢表雄酮(60 mg·kg^-1·d^-1)构建实验组,单纯玉米油注射构建对照组,第18.5天采用颈椎脱臼法处死小鼠后,收集胎鼠及胎盘标本,比较两组小鼠存活率、胎鼠体质量、胎盘质量、胎盘转运效率及目的基因mRNA表达水平。结果实验组与对照组胚胎总着床数、存活数差异均无统计学意义(P>0.05);实验组平均窝仔数、存活率低于对照组(P<0.05);实验组与对照组胎盘转运效率差异无统计学意义(P>0.05);实验组胎鼠体质量、胎盘质量均低于对照组(P<0.05);实时荧光定量PCR法检测两组胎盘的葡萄糖转运体mRNA表达水平,结果表明,与对照组相比,实验组胎盘Slc2a1、Slc2a2、Slc2a3、Slc2a9、Slc2a12 mRNA表达水平均出现不同程度下调(P<0.05);实验组Slc38a1、Slc38a2、Slc38a4、Slc43a2、Slc7a5、Slc7a8 mRNA表达水平下调(P<0.05)。结论宫内暴露于高雄激素中能降低胎盘质量与胎鼠体质量,能降低胎盘氨基酸转运体和葡萄糖转运体mRNA表达水平,提示宫内暴露于高雄激素会影响妊娠末期胎盘营养转运能力。     

Time course of UVA- and UVB-induced inflammation and hyperalgesia in human skin

Dose-dependency and time course of hyperalgesia and erythema following UVA (16.8 and 36 J/cm²) and UVB (one and three times the minimum erythema threshold) irradiation was investigated in 10 healthy human subjects. Skin patches (1.5 cm in diameter) on the ventral side of the upper leg were irradiated with UVA or UVB light. Hyperaemia (Laser Doppler flowmetry, infrared thermography), thermal hyperalgesia to radiant heat stimuli, and mechanical hyperalgesia to controlled impact stimuli were tested at 1, 6, 12, 24, 48 and 96 h after irradiation. Dose-dependent delayed hyperaemia and hyperalgesia was induced only by UVB irradiation. UVB-induced increase in blood flow peaked at 12 h after irradiation and normalized by 96 h. Although superficial blood flow, as measured by Laser Doppler flowmetry, increased up to eight-fold, no significant increase of skin temperature was detected using infrared thermography. Development of mechanical and thermal hyperalgesia was delayed and reached a plateau between 24 and 48 h. In contrast to UVB, UVA irradiation of up to 36 J/cm², sufficient to produce intense tanning of the skin, did not induce significant hyperalgesia or delayed hyperaemia. It is concluded that UVB- but not UVA-irradiation is a suitable experimental model of subacute thermal and mechanical hyperalgesia. The different time courses of erythema and hyperalgesia indicate that inflammatory mediators responsible for vasodilatation are not identical with those inducing hyperalgesia.     

妊娠母体血清hPL、uE3水平与子痫前期的关系

目的 分析妊娠母体血清人胎盘生乳素(hPL)和游离雌三醇(uE3)水平对子痫前期的预测价值.方法 采用放射免疫(RIA)法检测80例子痫前期孕妇和80例健康孕妇28孕周时母体血清hPL、uE3水平.结果 子痫前期组孕妇血清hPL、uE3水平分别为(6.20±1.34)μg/mL、(81.35±27.09)ng/mL,健康孕妇组hPL、uE3水平分别为(8.96±1.57)μg/mL、(89.77±35.50)ng/mL.相比健康孕妇组,子痫前期组hPL水平显著降低(P<0.05),血清uE3水平差异无统计学意义(P>0.05).血清hPL和uE3水平的ROC曲线下面积分别为0.90(95%可信区间:0.83～0.97)、0.55(95%可信区间:0.42～0.68).结论 孕中期妊娠母体血清hPL的水平可作为子痫前期临床预测指标.     

Role of color Doppler imaging in diagnosing and managing pregnancies complicated by placental chorioangioma

PURPOSE: The purpose of this study was to evaluate the role of color Doppler imaging in the diagnosis and management of placental chorioangioma. METHODS: The medical records, sonographic reports, and sonograms of all pregnant women who had placental masses diagnosed in our sonography unit during the years 1992 through 2000 and had been evaluated using both gray-scale and color Doppler sonography were included in this study. Subjective evaluation of the amount and distribution of intralesional vascularity by color Doppler imaging was made in all cases. Cases of chorioangioma of the placenta were compared with cases of placental hemorrhage or subchorionic hematoma. The outcomes of the pregnancies were also recorded. RESULTS: Fifteen cases of placental masses were evaluated; 8 of them were identified as placental hemorrhage or subchorionic hematoma on the basis of the sonographic findings. The other 7 cases were identified prenatally as placental chorioangioma, at a mean menstrual age of 23 weeks and a mean maternal age of 29 years. The mean size of the tumor was 6.5 cm (range, 4-13 cm). All cases of chorioangioma showed either substantial internal vascularity or a large feeding vessel within the tumor. Three infants were delivered at term with favorable outcome; 2 of them demonstrated reduction of the intratumoral blood flow during follow-up. The other 4 cases were delivered at or before 32 weeks' menstrual age (1 intrauterine fetal death, 2 terminated pregnancies, and 1 normal infant). No case of placental hematoma demonstrated blood flow within the lesion or was associated with complications of the pregnancy. CONCLUSIONS: Color Doppler imaging helps differentiate placental chorioangioma from other placental lesions and may be useful in the prenatal follow-up of chorioangioma.     

The role of preterm placental calcification in high-risk pregnancy as a predictor of poor uteroplacental blood flow and adverse pregnancy outcome

This prospective cohort study aims to clarify the role of preterm placental calcification in high-risk (i.e., hypertension, diabetes, placenta previa or severe anemia) pregnant women as a predictor of poor uteroplacental blood flow (absent or reverse end-diastolic velocity [AREDV]) and adverse pregnancy outcome. Monthly ultrasound was performed starting at 28 weeks' gestation to establish the diagnosis of Grade III placental calcification, with measurement of Doppler velocimetry in the umbilical vessels at 32 weeks' gestation. The participants were classified into three groups: Group A (n = 776), a low-risk group without antenatal complication; group B (n = 42), a high-risk group with preterm (28 to 36 weeks) placental calcification; and group C (n = 71), a high-risk control group without preterm (<36 weeks) placental calcification. Analyzed by logistic regression, the risks of AREDV (OR 4.32, 95%CI 1.25 to 14.94), adverse maternal outcome including postpartum hemorrhage (OR 3.98, 95% CI 1.20 to 13.20), placental abruption (OR 4.80, 95% CI 1.19 to 19.35), maternal transfer to intensive care unit (OR 3.83, 95% CI 1.10 to 13.33) and adverse fetal outcome including preterm birth (OR 3.86, 95% CI 1.32 to 11.29), low birth weight (OR 2.99, 95% CI 1.11 to 8.03), low Apgar score (OR 5.14, 95% CI 1.64 to 16.08) and neonatal death (OR 4.52, 95% CI 1.15 to 17.73) were greater in group B compared with group C. In contrast, the risks of AREDV and adverse pregnancy outcome were significantly lower in group A than those in group C, except postpartum hemorrhage (OR 0.53, 95% CI 0.19 to 1.46). We conclude that in high-risk pregnant women, the presence of preterm placental calcification is a predictor of poor uteroplacental flow and adverse pregnancy outcome, requiring closer surveillance for maternal and fetal well-being. This finding helps identify the most dangerous population among high-risk pregnant women.     

Extracranial projections of meningeal afferents and their impact on meningeal nociception and headache

Headaches can be evoked by activation of meningeal nociceptors, but an involvement of pericranial tissues is debated. We aimed to examine a possible extracranial innervation by meningeal afferents in the rat. For in vivo neuronal tracing, dextran amines were applied to the periosteum underlying the temporal muscle. Labeling was observed 2 days later in the parietal dura mater, trigeminal ganglion, and spinal trigeminal nucleus with confocal and electron microscopy. In the hemisected rat head, extracellular recordings were made from meningeal nerve fibers. Release of calcitonin gene-related peptide (CGRP) from the cranial dura mater during noxious stimulation of pericranial muscles was quantified. In vivo capsaicin was injected into the temporal muscle while meningeal blood flow was recorded. In the parietal dura mater, labeled C- and Aδ fibers ramified extensively, accompanied the middle meningeal artery, and passed through the spinosus nerve into the maxillary and mandibular, but not the ophthalmic division of the trigeminal ganglion. Some fibers could be traced into the ipsilateral spinal trigeminal nucleus. Electrophysiological recordings revealed afferent fibers with mechanosensitive receptive fields both in the dura mater and in the parietal periosteum. Noxious stimulation of the temporal muscle caused CGRP release from the dura mater and elevated meningeal blood flow. Collaterals of meningeal nerve fibers project through the skull, forming functional connections between extra- and intracranial tissues. This finding offers a new explanation of how noxious stimulation of pericranial tissues can directly influence meningeal nociception associated with headache generation and why manual therapies of pericranial muscles may be useful in headaches.     

Effects of ibogaine on naloxone-precipitated withdrawal in morphine-dependent mice

In naive mice, ibogaine at a tremorigenic dose (30 mg/kg, ip), did not produce antinociception but did potentiate the antinociceptive potency of morphine in the tail-flick test. In morphine-dependent mice, ibogaine did not eliminate withdrawal symptoms but significantly increased the number of repetitive vertical jumps induced by naloxone, whatever the duration of the chronic morphine treatment. By comparison, repetitive jumping induced by alpha-napthoxyacetic acid (alpha-NOAA), a non-convulsant drug which induced jumping without affecting other morphine-withdrawal signs, was not significantly modified by ibogaine. These results indicate that while acute antinociceptive effects of morphine are modulated by ibogaine, this drug, shown to alleviate opiate dependence in man, does not attenuate in mice opioid withdrawal manifestations.     

Memantine elicits spinal blockades of motor function,proprioception, and nociception in rats

Although memantine blocks sodium currents and produces local skin anesthesia, spinal anesthesia with memantine is unknown. The purpose of the study was to evaluate the local anesthetic effect of memantine in spinal anesthesia and its comparison with a widely used local anesthetic lidocaine. After intrathecally injecting the rats with five doses of each drug, the dose—response curves of memantine and lidocaine were constructed. The potencies of the drugs and durations of spinal anesthetic effects on motor function, proprioception, and nociception were compared with those of lidocaine. We showed that memantine produced dose‐dependent spinal blockades in motor function, proprioception, and nociception. On a 50% effective dose (ED₅₀) basis, the rank of potency was lidocaine greater than memantine (P < 0.05 for the differences). At the equipotent doses (ED₂₅, ED₅₀, ED₇₅), the block duration produced by memantine was longer than that produced by lidocaine (P < 0.05 for the differences). Memantine, but not lidocaine, displayed more sensory/nociceptive block than motor block. The preclinical data demonstrated that memantine is less potent than lidocaine, whereas memantine produces longer duration of spinal anesthesia than lidocaine. Memantine shows a more sensory‐selective action over motor blockade.     

High-Intensity Extended Swimming Exercise Reduces Pain-Related Behavior in Mice: Involvement of Endogenous Opioids and the Serotonergic System

The present study examined the hyponociceptive effect of swimming exercise in a chemical behavioral model of nociception and the mechanisms involved in this effect. Male mice were submitted to swimming sessions (30 min/d for 5 days). Twenty-four hours after the last session, we noticed that swimming exercise decreased the number of abdominal constriction responses caused by acetic acid compared with the nonexercised group. The hyponociception caused by exercise in the acetic acid test was significantly attenuated by intraperitoneal (i.p.) pretreatment of mice with naloxone (a nonselective opioid receptor antagonist, 1 mg/kg), ρ-chlorophenylalanine methyl ester (PCPA, an inhibitor of serotonin synthesis, 100 mg/kg once a day for 4 consecutive days), and by bilateral adrenalectomy. Collectively, the present results provide experimental evidences indicating for the first time that high-intensity extended swimming exercise reduces pain-related behavior in mice. The mechanisms involve an interaction with opioid and serotonin systems. Furthermore, endogenous opioids released by adrenal glands probably are involved in this effect.     

胎盘生长因子、血小板参数及子宫动脉血流参数预测子痫前期的临床意义

目的 探讨胎盘生长因子(PLGF)、血小板参数及子宫动脉血流参数预测子痫前期的临床意义.方法 回顾性选取2019年1月至2020年8月在东莞市长安医院和东莞市人民医院产检过程中确诊为子痫前期的60例孕妇为研究组,并选择同时期在两家医院分娩的60例正常孕妇为对照组.收集并分析两组孕妇妊娠早期的PLGF、血小板计数(PLT...     

Beneficial actions of neurotrophin treatment on diabetes-induced hypoalgesia in mice

Studies were carried out in streptozotocin-treated diabetic mice to evaluate their behavioral responses to different noxious stimuli. In opposition to rats, streptozotocin-injected diabetic mice display a persistent hypoalgesia to non-noxious mechanical stimulation (von Frey monofilament). Similarly, nocifensive responses of diabetic mice to formalin injection were significantly reduced in both acute and inflammatory phases. However, no overt differences were detected between nondiabetic and diabetic mice in their sensitivity to noxious heat (radiant heat), cold (acetone), or noxious mechanical (pinprick) stimuli applied to the hind paw. To evaluate whether neurotrophin treatment could normalize the sensory deficits, nerve growth factor (NGF) or glial cell line-derived neurotrophic factor (GDNF) was administered intrathecally to diabetic mice for 3 weeks. Neurotrophin-treated mice were also compared to mice that received insulin for 3 weeks. Both NGF and insulin treatment significantly restored mechanical and chemogenic behavioral responses of diabetic mice. In contrast, GDNF treatment only reversed behavioral responses to chemogenic stimuli during the acute phase of the formalin test. These results demonstrate that diabetic mice develop reduced sensitivity to mechanical and chemical stimuli. Furthermore, these studies show that dorsal root ganglion neurons in diabetic mice are responsive to treatment with either NGF or GDNF; however, these 2 neurotrophins differ in their ability to affect distinct somatosensations.     

Nociceptor activation and protein extravasation induced by inflammatory mediators in human skin.

Protein extravasation (PE) is known to play an important role in inflammatory conditions. In this study we used dermal microdialysis to apply inflammatory mediators (histamine, bradykinin, serotonin) to human skin. Locally induced PE was compared to pain ratings and axon reflex erythema measured simultaneously. Linear microdialysis capillaries (outer diameter 0.4 mm; cut-off 3000 kDa) were inserted intracutaneously at a length of 1.5 cm in the volar forearm of healthy volunteers. The capillaries were perfused with Ringer's solution at a constant flow rate of 4 microl/min. The perfusate was sampled at 15-min intervals and was analysed for total protein concentration. After a baseline of 60 min, the perfusion was switched to inflammatory mediators for 30 min and then back to vehicle again. Sensations evoked by the stimulation were assessed on a visual analogue scale and visible axon reflex erythema was measured planimetrically.Dose-dependent increases in PE could be assessed for all inflammatory mediators tested. Bradykinin (10(-7)M) induced a significant PE, whereas serotonin was effective only at a concentration of 10(-3)M. While serotonin in lower concentrations induced moderate burning pain and an axon reflex flare but no PE, bradykinin provoked PE without pain or axon reflex flare at a concentration of 10(-7)M. Application of histamine similarly evoked PE at lower concentrations as compared to the induction of itch sensation and axon reflex flare.It is concluded that there is no link between nociceptor activation and protein extravasation induced by inflammatory mediators in healthy human skin.