缺血缺氧性脑病新生儿血浆孤啡肽含量变化的意义及护理

目的 研究血浆孤啡肽含量变化在新生儿缺血缺氧性脑病中的作用.方法 用RIA方法测定新生儿缺血缺氧性脑病患儿血浆孤啡肽含量.结果 缺血缺氧性脑病组血浆孤啡肽含量明显高于对照组(P＜0.01).结论 孤啡肽含量变化在新生儿缺血缺氧性脑病发病过程中起重要作用.     

新生儿缺血缺氧性脑病的护理

新生儿缺血缺氧性脑病(HIE)是新生儿期最常见的中枢神经系统疾病，是围产期脑损伤最常见的原因，是新生儿致残和死亡的主要原因之一。目前，由于HIE发病机制尚未完全阐明，还没有一种肯定的特效疗法，仍是以支持治疗为主的综合治疗方法。护理是综合治疗的关键性环节。因此采用科学的方     

新生儿缺血缺氧性脑病的护理

新生儿缺血缺氧性脑病(简称HIE)主要是指在围产期宫内发生和二氧化碳的交换障碍而导致新生儿脑的缺血缺氧损害。临床上出现的一系列脑病的表现。     

新生儿缺血缺氧性脑病的多元护理

目的：探讨新生儿缺血缺氧性脑病（HIE）患儿的多元护理干预效果以及对神经系统的影响.方法：对我院2013年1月～2013年5月新生儿科39例诊断为HIE的新生儿,采取回顾性分析的方法,观察多元护理干预对新生儿缺血缺氧性脑病的影响.结果：经过多元护理干预,治愈34例,占87.18％;好转4例,占10.26％;自动出院1例,占2.56％.结论：多元护理干预对患儿的预后特别是神经系统发育有积极意义.     

80例新生儿缺血缺氧性脑病的护理

对80例新生儿缺血缺氧性脑病(HIE)给予积极治疗与护理,即保持呼吸道通畅、减轻脑水肿、控制惊厥、降低颅内压、纠正缺氧、营养脑细胞、加强基础护理、防止并发症、注意保暖等,结果治愈70例,好转5例,放弃治疗5例。     

新生儿缺血缺氧性脑病62例临床护理

目的:探讨新生儿缺血缺氧性脑病(HIE)的有效护理方法.方法:对62例HIE患儿严密观察病情变化,及时了解血糖、血压、体温等变化并积极正确处理.根据惠儿病情轻重程度,给予纠正缺氧、脱水、适量输液,加强呼吸道护理,控制惊厥,维持内环境稳定等措施.结果:本组治愈47例,自动出院4例,死亡2例,病程4～30 d,平均15.3 d.结论:对HIE患儿保持体温、血压、血氧饱和度、血糖、酸碱平衡、电解质正常,维持内环境稳定,保证足够的能量供给,降低颅内压,控制惊厥对减少其后遗症的发生具有重要意义.     

8O例新生儿缺血缺氧性脑病的护理

对80例新生儿缺血缺氧性脑病（HIE）给予积极治疗与护理，即保持呼吸道通畅、减轻脑水肿、控制惊厥、降低颅内压、纠正缺氧、营养脑细胞、加强基础护理、防止并发症、注意保暖等，结果治愈70例，好转5例，放弃治疗5例。     

新生儿缺血缺氧性脑病护理体会

新生儿缺血缺氧性脑病(Hypoxic-ischemic encphalopathy，HIE)是新生儿常见的严重疾病，合理治疗与护理可降低死亡率，减少神经系统后遗症。结合本院1998年以来收治的HIE患儿16例，现就其临床观察与护理总结报告如下：     

Hypoxic-ischemic encephalopathy and plasma beta-endorphin

In an attempt to determine whether hypoxic-ischemic encephalopathy in and of itself or its associated pathologic conditions lead to increased concentrations of plasma beta-endorphin (beta-ED), measurements were made in three groups of term infants. Group 1 (control) consisted of 8 infants with a mean gestation of 38.6 +/- (SE) 0.4 weeks, a mean birth weight of 3,420 +/- 150 g, and a mean postnatal age of 1.4 +/- 0.7 days. Group 2 consisted of 10 infants with a mean gestational age, birth weight and postnatal age of 40.1 +/- 0.5 weeks, 3,310 +/- 80 g and 3,9 +/- 1.1 days, and group 3 included 6 infants with a mean gestational age, birth weight and postnatal age of 40.4 +/- 1 weeks, 3,650 +/- 310 g, and 2.8 +/- 1 days, respectively. The group 2 and 3 infants suffered clinical and neurological evidence of hypoxic-ischemic brain injury from perinatal asphyxia; however, the infants in group 2 suffered additional problems such as meconium aspiration, persistent fetal circulation with ongoing hypoxemia as measured by transcutaneous or umbilical arterial oxygen monitoring. The group 3 infants were normoxemic after resuscitation. The mean plasma beta-ED concentrations were 19 +/- (SE) 2.7, 103 +/- 35.7 and 25 +/- 4.5 pg/ml in groups 1, 2 and 3, respectively. A significant elevation of plasma beta-ED concentration was observed in group 2 when compared to groups 1 and 3. The association of increased plasma beta-ED concentration in infants with hypoxic-ischemic encephalopathy associated with ongoing hypoxemia suggests that hypoxemia may act as a strong stimulus for plasma beta-ED release in term infants.     

体感诱发电位指标观察孤啡肽对大鼠脑缺血的作用

目的探讨孤啡肽在脑缺血中的作用。方法在大鼠大脑中动脉栓塞动物模型上,侧脑室注射(icv)不同剂量孤啡肽,以体感诱发电位(SEP)和脑梗死体积为指标观察孤啡肽对脑缺血的作用。结果大鼠脑缺血后SEP波幅降低,侧脑室分别注射10、1μg孤啡肽SEP进一步抑制;同时增大脑梗死灶的体积,而相同条件icv0.1μg孤啡肽SEP的波幅和脑梗死灶的体积与对照组比较无统计学差异。结论icv孤啡肽加重大鼠脑缺血。     

Changes in nociceptin/orphanin FQ levels in rat brain regions after acute and chronic cannabinoid treatment in conjunction with the development of antinociceptive tolerance

It has been indicated that acute and chronic morphine administrations enhance nociceptin/orphanin FQ (N/OFQ) levels in the brain, which might play role in the development of tolerance to the antinociceptive effect of morphine. Accordingly, N/OFQ receptor (NOP) antagonists have been shown to prevent the development of antinociceptive tolerance to morphine. Our aim is to observe whether cannabinoids, similarly to opioids, enhance N/OFQ levels in pain‐related brain regions and whether antagonism of NOP receptors attenuates the development of tolerance to the antinociceptive effect of cannabinoids. Hot plate and Tail flick tests are used to assess the antinociceptive response in Sprague‐Dawley rats. N/OFQ levels are measured in cortex, amygdala, hypothalamus, periaqueductal gray, nucleus raphe magnus and locus coeruleus of rat brains using Western blotting and immunohistochemistry. Within 9 days, animals became completely tolerant to the antinociceptive effect of the cannabinoid agonist WIN 55,212‐2 (2, 4, 6 mg/kg, i.p.). Chronic administration of JTC‐801, a NOP receptor antagonist, at a dose that exerted no effect on its own (1 mg/kg, i.p.), attenuated development of tolerance to the antinociceptive effect of WIN 55,212‐2 (4 mg/kg, i.p.). Western blotting and immunohistochemistry results showed that N/OFQ levels significantly increased in amygdala, periaqueductal gray, nucleus raphe magnus and locus coeruleus of rat brains when WIN 55,212‐2 was combined with JTC‐801. We hypothesize that, similar to opioids, chronic cannabinoid + NOP antagonist administration may enhance N/OFQ levels and NOP receptor antagonism prevents development of tolerance to cannabinoid antinociception.     

新生儿缺氧缺血性脑病的螺旋CT评价

目的评价螺旋CT对新生儿缺氧缺血性脑病(简称HIE)的诊断价值。方法对112例HIE有明确围产期窒息史,且有临床症状的病例进行螺旋CT检查,分析CT表现。结果本组112例HIE中,轻度46例,中度57例,重度9例,38例合并颅内出血,死亡1例。结论螺旋CT有助于明确HIE的脑损伤情况,对预后的评估有价值。     

Endogenous orphanin FQ/nociceptin is involved in the development of morphine tolerance

The neuropeptide orphanin FQ/nociceptin (OFQ/N) has been shown to counteract several effects of endogenous and exogenous opioids, and it has been proposed as an opioid-modulating agent involved in the development of morphine tolerance and dependence. However, conflicting results have been obtained from animal models using different protocols to induce morphine tolerance. Here, we report that both genetic and pharmacological blockade of OFQ/N signaling can effectively prevent development of morphine tolerance. OFQ/N knockout mice injected daily with low doses of morphine (10 mg/kg) fail to develop tolerance even after 3 weeks of treatment, whereas their wild-type litter mates show profound tolerance starting after 10 days. Likewise, coadministration of morphine together with the synthetic N/OFQ peptide antagonist, J-113397 (1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one), is able to block tolerance development in normal mice. These data indicate that release of endogenous OFQ/N after morphine administration might produce a gradual decline of analgesic potency, i.e., tolerance. Interestingly, tolerant and nontolerant groups of mice receiving repeated daily low morphine doses did not differ in their withdrawal behavior after naloxone injection. In contrast, mice receiving escalating doses of morphine developed analgesic tolerance independent of their OFQ/N genotype, whereas withdrawal symptoms were attenuated in OFQ/N-deficient animals. These results indicate that the endogenous OFQ/N system is differentially involved in morphine tolerance development and establishment of opiate dependence, depending on the specific morphine dosage regimen. Furthermore, it suggests that OFQ/N antagonists could provide a novel therapeutic strategy to attenuate morphine tolerance development.     

Nociceptin/orphanin FQ exacerbates excitotoxic white-matter lesions in the murine neonatal brain

Intracerebral administration of the excitotoxin ibotenate to newborn mice induces white-matter lesions, mimicking brain lesions that occur in human preterm infants. Nociceptin (NC), also called orphanin FQ, is the endogenous ligand of the opioid receptor-like 1 (ORL1) receptor and does not bind classical high-affinity opioid receptors. In the present study, administration of NC exacerbated ibotenate-induced white-matter lesions while coadministration of ibotenate with either of two NC antagonists reduced excitotoxic white-matter lesions by up to 64%. Neither ibotenate plus endomorphin I (a selective mu receptor agonist), nor ibotenate plus naloxone (a classical opioid receptor antagonist) modulated the excitotoxic lesion. Pretreatment with antisense oligonucleotides targeting the NC precursor peptide mRNA significantly reduced ibotenate-induced white-matter damage. Finally, high doses of fentanyl, which stimulates both classical mu-opioid receptors and ORL1, exacerbated excitotoxic white-matter lesion. This toxic effect was blocked by inhibiting ORL1 but not classical opioid receptors. Together, these findings show that endogenous or exogenous stimulation of the ORL1 receptor can be neurotoxic and that blocking NC signaling protects the white matter against excitotoxic challenge. These data point to potential new avenues for neuroprotection in human preterm infants at high risk of brain lesions.     

In vivo pain-inhibitory role of nociceptin/orphanin FQ in spinal cord

Because nociceptin/orphanin FQ (N/OFQ) has both pronociceptive (hyperalgesia) and antinociceptive actions in pharmacological experiments, and there is no significant difference in the nociceptive responses between NOP(-/-) mice and their wild-type (NOP(+/+)) littermates, the physiological role of N/OFQ in pain regulation remains to be determined. Under the hypothesis that the use of molecularly distinct nociception test may reveal the pain modality-specific role of N/OFQ, we attempted to examine the physiological role of N/OFQ in pain transmission by using newly developed algogenic-induced nociceptive flexion test in NOP(-/-) and NOP(+/+) mice or NOP antagonist-treated mice. The nociceptive flexor responses upon intraplantar injection of bradykinin or substance P, which stimulates polymodal substance P-ergic fibers, were markedly potentiated in NOP(-/-) mice, compared with those in its NOP(+/+) mice. However, there were no significant changes in NOP(-/-) mice with adenosine triphosphate or prostaglandin I(2) agonist, which stimulates glutamatergic but not substance P-ergic fibers. The nocifensive responses induced by substance P (i.t.) were also potentiated in NOP(-/-) mice. On the other hand, there were no significant differences in NK1-like immunoreactivity, [(3)H]substance P binding, or NK1 gene expression in the dorsal horn of the spinal cord between NOP(-/-) and NOP(+/+) mice. In addition, NOP antagonists decreased the threshold in nociception tests driving spinal substance P neurotransmission. All these findings suggest that the N/OFQ-ergic neuron may play an in vivo inhibitory role on the second-order neurons for primary polymodal substance P-ergic fibers in the spinal cord.     

Determinants of ligand selectivity at the kappa-receptor based on the structure of the orphanin FQ receptor

It is unclear how opioid selectivity and activation are regulated within the receptor core. In previous studies, the OFQ receptor was converted into a functional opioid receptor by mutating five amino acids at three sites to the corresponding residues conserved across the mu-, kappa-, and delta-opioid receptors, suggesting that these sites comprise an opioid binding pocket. To examine this hypothesis, the present study examines whether these conserved residues represent an opioid binding pocket in the context of the opioid receptors, i.e., does their removal from opioid receptors destroy opioid ligand binding? The reciprocal mutations K227A (transmembrane [TM]5), IHI290-292VQV (TM6), and I316T (TM7) were evaluated in the kappa-opioid receptor. In terms of alkaloid binding, there were no changes in affinity for mutants K227A and IHI290-292VQV. At mutant I316T, antagonist binding was unaltered, but there was a trend toward slightly decreased agonist affinity. In contrast, the binding of peptides had a more complex pattern. Again, K227A and IHI290-292VQV did not decrease the binding affinity of dynorphin-related peptides. Mutant I316T had 10- to 20-fold decreased affinity for dynorphin-related peptides, suggesting that I316 is part of a critical dynorphin recognition site. In response to alkaloid stimulation, I316T activated more G-protein(s) than wild type, and similar levels were observed in response to dynorphin stimulation. Overall, these results suggest that ligands are capable of achieving high-affinity binding through interaction with multiple sites/conformations of the receptor. These different modes of interaction have different down-stream results in terms of receptor activation and signal transduction.