Neuropeptide-mediated regulation of hapten-specific IgE responses in mice II. Mechanisms of substance P-mediated isotype-specific suppression of BPO-specific IgE antibody-forming cell responses induced in vitro

Previous studies in our laboratory have shown that substance P (SP), injected into benzylpenicilloyl-keyhole limpet hemocyanin (BPO-KLH) sensitized mice at the peak of the benzylpenicilloyl (BPO)-specific IgE response, suppressed these responses in isotype-specific fashion within 48 h. These studies also showed that SP, but not neurotensin (NT), serotonin (5-HT), somatostatin (SOM) or gastrin, suppressed BPO-specific memory IgE antibody-forming cell (AFC) responses induced in vitro, also in isotype-specific fashion. To investigate the mechanisms by which SP suppressed BPO-specific IgE AFC responses were induced in vitro, these responses were induced by culturing spleen cells from BPO-KLH sensitized mice for 5 days with BPO-KLH with or without whole SP, amino terminal SP (SP 1–4: Arg-Lys-Pro-Lys), or carboxy terminal SP (SP 8–11: Phe-Gly-Leu-Met). In some experiments, the SP receptor antagonist (d-Pro², d-Phe⁷, d-Trp⁹)-SP (d-SP) was included in culture. In other experiments anti-interferon monoclonal antibody (anti-IFNγ mAb) was included in culture. Whole SP and SP 8–11, but not SP 1–4, suppressed BPO-specific IgE AFC responses induced in vitro. The suppression obtained was IgE isotype-specific and dose-dependent. Inclusion of SP receptor antagonist (d-Pro², d-Phe⁷, d-Trp⁹)-SP inhibited suppression of BPO-specific memory IgE AFC responses by SP or SP 8–11. The SP-mediated suppression of BPO-specific memory IgE responses appeared to involve interferon gamma (IFNγ).     

动态观察脑出血患者血浆神经肽Y、神经降压素和胃动素的临床意义

动态观察脑出血患者血浆神经肽Y(NPY)、神经降压素(NT)和胃动素(MTL)的水平 变化,探讨其临床意义。方法采用放射免疫方法测定了46例脑出血患者及28例健康成人血浆NPY、NT及MTL的含量。结果脑出血患者血浆NPY、NT及MTL水平均明显高于对照组(P<0.001,P<0.01,P<0.01)。发病24h内即显著升高,NPY在4～7d、NT和MTL在1～3d达高峰,8～15d三者均开始下降,15d后仍在较高水平。重症患者NPY水平显著高于轻型和中型,中、重型患者NT水平显著高于轻型。大面积出血NPY、NT及MTL水平均高于小面积出血。伴发病积分≥6分者高于积分<6分者。伴上消化道出血者显著高于不伴上消化道出血者。结论NPY、NT及MTL参与了脑出血的发生及病理生理过程     

Multifactorial control of pituitary hormone secretion: the "wheels" of the brain

An attempt is made to deal with the complexity of the nerve fibers in the median eminence. Visual aids are presented in the shape of "wheels" that depict a dynamic interplay of neurochemicals which result in the release of hormones from the anterior pituitary gland. The multiplicity of neurochemicals in the median eminence is perceived to be responsible for the integrated control of pituitary hormone releasing factors.     

Brain-gut neuropeptides and the limitation of ethanol consumption

Recent studies have clearly shown powerful control of ingestive behavior by certain peptides known to be present in both brain and gut tissues. These "brain-gut neuropeptides" are thought to constitute endogenous factors responsible for the normal regulation of food intake. This review explores the potential for a role of these peptides in the limitation of ethanol intake, which shares several features with the control of food intake. The putative satiety role of the neuropeptides cholecystokinin and bombesin, and other brain-gut peptides is briefly described. The conclusion that voluntary ethanol intake is partially controlled as a function of the energy ethanol provides, and the rate of its utilization, is illustrated with data from recent studies of rat and hamster ethanol consumption. The possibility of neuropeptide influence on ethanol intake is presented in light of new findings that cholecystokinin and bombesin inhibit ethanol consumption in the rat. If neuropeptides are demonstrated to modulate ethanol intake by eliciting satiety, this information may be useful in the identification and understanding of the endogenous factors which regulate human alcohol intake, and will suggest possible peptide-based therapeutic interventions for control of alcohol abuse and alcoholism.     

内毒素、降钙素原在鉴别急性胆管炎及急性胆囊炎中的意义

目的探讨内毒素(ET)、降钙素原(PCT)在鉴别急性胆管炎及急性胆囊炎中的价值。方法检测61例患者血清ET及PCT浓度,其中急性胆管炎组20例,急性胆囊炎组21例,慢性胆管炎组10例,慢性胆囊炎组10例,比较各组间ET及PCT的血清学浓度差异。结果急性胆管炎患者血清中ET、PCT水平较急性胆囊炎组明显升高(t=4.130,P0.05)。急性胆道感染较慢性胆道感染患者ET、PCT血清学水平明显升高(t=9.629,t=5.365,均P0.05)。结论联合检测患者血清ET、PCT浓度可提高急性胆道感染早期确诊率,且ET、PCT与胆道感染炎症程度密切相关。     

多发伤后β-内腓肽和细胞粘附分子表达变化及临床意义

目的：探讨多发伤病人血清β－ｅｎｄ及外周血多形核粒细胞（ＰＭＮｓ）ＣＤ１８、ＣＤ５４表达变化。方法：使用放免分析技术和流式细胞术分别检测６５例多发伤伤员入院时、伤后１、３、７天血清皮质醇、β－ｅｎｄ浓度和ＰＭＮｓ上ＣＤ１８、ＣＤ５４的平均荧光通道（ＭＦＣ）变化，１３例健康志愿者为对照组。结果：创伤病人血清皮质醇浓度在伤后２４小时内较对照组高（Ｐ＜０．００１），但创伤组间无差异；β－ｅｎｄ浓度入院时     

Vasoactive intestinal peptide regulates osteoclast activity via specific binding sites on both osteoclasts and osteoblasts

Clinical and experimental observations, together with immunohistochemical findings, suggest that neuro-osteogenic interactions may occur in the skeleton. In this study, we have examined the effect of vasoactive intestinal peptide (VIP), one of the neuropeptides present in bone, on the activity of the bone-resorbing osteoclast. Effects on bone resorption were assessed by counting the number of pits formed by rat osteoclasts incubated on devitalized slices of bovine cortical bone. Under conditions with an initially sparse density of stromal cells/osteoblasts, VIP caused a rapid cytoplasmic contraction and decreased motility of osteoclasts. This was coupled with a decrease in the number of resorption lacunae and a decrease in the total area resorbed by the osteoclasts in 48-h cultures. Time-course experiments revealed that the inhibitory effects on contraction and motility were transient and that the cells gradually regained their activity, such that, when culture time was prolonged to 120 h, a stimulatory effect by VIP on bone resorption was observed. When osteoclasts were incubated on bone slices, in the presence of an initially large number of stromal cells/osteoblasts, VIP treatment increased the number of resorption pits and total bone area resorbed in 48-h cultures. Using atomic force microscopy, we provide direct evidence that both osteoclasts and stromal cells/osteoblasts bind VIP. Also, VIP was shown to cause a rapid rise of intracellular calcium in osteoclasts and in a proportion (20%) of stromal cells/osteoblasts. Taken together, these data suggest that differentiated osteoclasts are equipped with receptors for VIP that are linked to a transient inhibition of osteoclast activity and, in addition, that stromal cells/osteoblasts have VIP receptors coupled to a delayed stimulation of osteoclastic resorption.     

Alterations in expression of dopamine receptors and neuropeptides in the striatum of GTP cyclohydrolase-deficient mice

The hph-1 mice have defective tetrahydrobiopterin biosynthesis and share many neurochemical similarities with l-dopa-responsive dystonia (DRD) in humans. In both, there are deficiencies in GTP cyclohydrolase I and low brain levels of dopamine (DA). Striatal tyrosine hydroxylase (TH) levels are decreased while the number of DA neurones in substantia nigra (SN) appears normal. The hph-1 mouse is therefore a useful model in which to investigate the biochemical mechanisms underlying dystonia in DRD. In the present study, the density of striatal DA terminals and DA receptors and the expression of D-1, D-2, and D-3 receptors, preproenkephalin (PPE-A), preprotachykinin (PPT), and nitric oxide synthase (NOS) mRNAs in the striatum and nucleus accumbens and nigral TH mRNA expression were examined. Striatal DA terminal density as judged by specific [3H]mazindol binding was not altered while the levels of TH mRNA were elevated in the SN of hph-1 mice compared to control (C57BL) mice. Total and subregional analysis of the striatum and nucleus accumbens showed that D-2 receptor ([3H]spiperone) binding density was increased while D-1 receptor ([3H]SCH 23390) and D-3 receptor ([3H]7-OH-DPAT) binding density was not altered. In the striatum and nucleus accumbens, expression of PPT mRNA was elevated but PPE-A mRNA, D-1, D-2 receptor, and nNOS mRNA were not changed in hph-1 mice compared to controls. These findings suggest that an imbalance between the direct strionigral and indirect striopallidal output pathways may be relevant to the genesis of DRD. However, the pattern of changes observed is not that expected as a result of striatal dopamine deficiency and suggests that other effects of GTP cyclohydrolase I deficiency may be involved.     

Role of endogenous ghrelin in growth hormone secretion, appetite regulation and metabolism

Ghrelin, a 28-amino acid hormone that is acylated post-translation, is the endogenous ligand for the growth hormone (GH) secretagogue (GHS) receptor (GHS-R). The highest concentrations of ghrelin are found in the stomach; however ghrelin peptide is also present in hypothalamic nuclei known to be important in the control of GH and feeding behavior. Exogenous ghrelin potently stimulates pituitary GH release through a mechanism that is dependent, in part, on endogenous GH-releasing hormone. Whether endogenous ghrelin plays a role in the control of GH secretion and growth is not clear and ghrelin deficient animals appear to grow normally. In contrast, experimental animal and clinical data suggest that abnormalities in GHS-R signaling could impact growth. Ghrelin or other GHS are clinically useful for GH-testing and limited data suggest that they might be useful in the treatment of some patients with GH deficiency. Substantial data have implicated ghrelin as an important regulator of feeding behavior and energy equilibrium. Ghrelin has a potent orexigenic effect in both animals and humans and this effect is mediated through hypothalamic neuropeptide Y (NPY) and Agouti-related peptide (AgRP). Appetite simulation coupled with other metabolic effects promotes weight gain during chronic treatment with ghrelin. These metabolic effects are in part mediated through an increase in respiratory quotient (VQ). Presence of ghrelin appears to be necessary for the development of obesity in some animal models. Whether abnormalities in ghrelin signaling are involved in human obesity is not yet known.     

高血压病患者血浆中6种神经肽含量的变化

目的 了解高血压病患者血浆6种神经肽(6NP),即神经肽Y、降钙素基因相关肽、P物质、脑啡肽神经降压肽及血管活性肠肽的含量,探讨其在高血压病发病中的临床意义。方法 选择符合WHO诊断标准的高血压病(EH)30例,其中Ⅰ、Ⅱ、Ⅲ期各10例,应用放射免疫法(RIA)动态观察血浆6NP含量的变化,并以30例正常人作对照组。结果 EH组与对照组比较差异非常显著(P<0.01);EH组中的Ⅰ、Ⅱ、Ⅲ期组间差异亦非常显著(P<0.01)。结论 血浆6NP的含量与EH的严重程度密切相关;6NP均参与3EH的病理生理过程。