硬膜外麻醉下子宫肌瘤切除术患者血浆ANP和RAAS′的调控

研究了１５例子宫肌瘤切除患者应用０．７５％布比卡因硬膜外麻醉血浆心钠素（ＡＮＰ）和肾素活性（ＰＲＡ），血管紧张素Ⅱ（ＡⅡ）－醛固酮（ＡＬ）系统（ＲＡＡＳ）的变化及相互调控。结果表明，血浆ＡＮＰ水平在麻醉１０ｍｉｎ后各时点明显低于麻醉前（Ｐ〈０．０５），ＰＲＡ在麻醉１０ｍｉｎ后亦明显低于麻醉前（Ｐ〈０．０１），而ＡⅡ和ＡＬ无显著改变（Ｐ〉０．０５）。提示０．７５％布比卡因硬膜外麻醉行子宫切除术ＡＮＰ     

颈内与肘静脉血中抗利尿激素和β—内啡肽含量的比较

目的：比较颈内静脉血和外周静脉血中抗利尿激素（ＡＤＨ）和β－内啡肽（β－ＥＰ）含量的差异。方法：应用放免法测定１７例患者麻醉前、气管插管后、手术中和手术后３０ｍｉｎ颈内静脉血与肘部静脉血的ＡＤＨ和β－ＥＰ水平。结果：颈内静脉血的血浆中ＡＤＨ平均含量（ｐｇ／ｍｌ）分别为１４２、１７３、３６７和１９２，β－ＥＰ平均含量（ｐｇ／ｍｌ）分别为３３２、４２７、８７６和４６３；肘静脉血的血浆中ＡＤＨ平均含量（ｐｇ／ｍｌ）分别为２８、３５、７８和３９，β－ＥＰ平均含量（ｐｇ／ｍｌ）分别为６８、８７、１８２和９６。肘静脉血中两种神经肽都显著低于颈内静脉血（Ｐ＜０．０１），但与颈内静脉血中ＡＤＨ和β－ＥＰ含量变化呈正相关（ｒ＝０．９１，Ｐ＜０．０１；ｒ＝０．８９，Ｐ＜０．０１）。结论：测定颈内静脉血中ＡＤＨ和β－ＥＰ含量更易反映出其动态的变化。     

小儿心脏手术前口服咪唑安定和氯胺酮混合液的临床观察

选择先天性心脏病小儿３５例，随机分为观察组（２０例）和吗啡组（１５例），观察组术前口服咪唑安定（０．５ｍｇ／ｋｇ）和氯胺酮（１２ｍｇ／ｋｇ）混合液，吗啡组肌肉注射吗啡（０．２ｍｇ／ｋｇ）。结果显示：观察组９０％的小儿易于与父母分离，与吗啡组（６６．７％）无明显差异（Ｐ＞０．０５）。达Ａ、Ｂ两级镇静者，观察组为８０％，吗啡组为４６．７％，两组差异非常显著（Ｐ＜０．０１）。观察组有８５％小儿静脉穿刺时合作或无反应，吗啡组仅４０％，两组差异显著（Ｐ＜０．０５）。两组麻醉诱导前和诱导时脉搏氧饱和度均正常，也未发生喉痉挛、缺氧、恶心和呕吐等井发症。术中血流动力学稳定，心脏自动复跳率、术后清醒时间、气管拔管时间和术后麻醉有关并发症，两组也无明显差异（Ｐ＞０．０５）。表明小儿心脏手术前口服咪唑安定和氯胺酮混合液，镇痛和镇静效果良好，血流动力学稳定，不增加围术期并发症，证明了术前口服咪唑安定和氯胺酮混合液在先天性心脏病小儿的安全性和可靠性。     

硬膜外麻醉下子宫肌瘤切除术患者血浆ANP和RAAS的调控

研究了１５例子宫肌瘤切除术患者应用０．７５％布比卡因硬膜外麻醉血浆心钠素（ＡＮＰ）和肾素活性（ＰＲＡ）、血管紧张素Ⅱ（ＡⅡ）－醛固酮（ＡＬ）系统（ＲＡＡＳ）的变化及相互调控。结果表明，血浆ＡＮＰ水平在麻醉１０ｍｉｎ后各时点明显低于麻醉前（Ｐ＜０．０５），ＰＲＡ在麻醉１０ｍｉｎ后亦明显低于麻醉前（Ｐ＜０．０１），而ＡⅡ和ＡＬ无显著改变（Ｐ＞０．０５）。提示０．７５％布比卡因硬膜外麻醉行子宫切除术ＡＮＰ和ＲＡＡＳ的变化，在维持和调节有效循环血量及外周血管阻力中发挥着重要的作用。     

腹腔镜胆囊切除术中二氧化碳气腹对脑血流的影响

目的 观察腹腔镜期间二氧化碳气腹对患者脑血流的影响。方法 选择行腹腔镜胆囊切除术患者３０例,ＡＳＡⅠ～Ⅱ级、于气腹前、气腹后１０、３０ｍｉｎ分别采取桡动脉血管颈内静脉血,测定ＰａＯ２、ＰａＣＯ２、ＳａＯ３、颈内静脉血氧分压（ＰｉｖＯ２）和血氧和度（ＳｕｖＯ２）等值。结果与气腹前比较,气腹后１０ｍｉｎ、３０ｍｉｎ的ＳｕｖＯ２、颈内静脉血氧含量（ＣｕｖＯ２）和ＰａＣＯ２无显著性增加（Ｐ〈０．０１）,脑     

静吸复合麻醉中不同小剂量芬太尼对脑电边缘频率和双波谱指数的影响

目的 研究静吸复合麻醉中不同小剂量芬太尼对脑电边缘频率（ＳＥＦ）和双小的指数（ＢＩＳ的影响。方法 随机将ＡＳＡⅠ～Ⅱ级病人３０例分为Ⅰ、Ⅱ、Ⅲ组地全麻诱导吸入安氟醚达０．８ＭＡＣ后三组分别静注芬太尼３μｇ．ｋｇ＾０－１、５μｇ．ｋｇ＾－１,于给药后６ｍｉｎ记录每组病人的ＭＡＰ、ＨＲ、ＳＥＦ及ＢＩＳ。结果 三组 内、组间ＭＡＰ、ＨＲ相比均无显著差异（Ｐ〈０．０５）,ＢＩＳ无显著性差异（Ｐ〉０．０５）     

心肺转流时间对P（a—ET）CO2和肺泡死腔量的影响

观察９４例心内直视手术病人，探讨不同的心肺转流时间对Ｐ（ａ－ＥＴ）ＣＯ２和肺泡死腔量的影响。结果：停心肺转流后３０ｍｉｎ、６０ｍｉｎ时较心肺转流前Ｐ（ａ－ＥＴ）ＣＯ２和肺泡死腔量增加显著（Ｐ〈０．０５）或增加非常显著（Ｐ〈０．０１）。左向右分流两组不同心肺转流时间从Ｐ（ａ－ＥＴ）ＣＯ２和肺泡死腔量比较无显著差异（Ｐ〉０．０５）；风心病两组不同心肺转流时间的病人在停心肺转流后６０ｍｉｎ时，Ｐ（ａ－Ｅ     

高血压患者血小板聚集功能变化初步观察

为探讨高血压患者务小板聚集功能（ＰＡＧ）变化与血栓性疾病间的关系，观察了５３例高血压患者的ＰＡＧ。高血压组１分钟聚集类（１ｍｉｎＡＲ）５分钟聚集率（５ｍｉｎＡＲ）、最大聚集率（ＭＡＲ）明显高于对照组，而解聚率（Ｉ）明显低于对照组（Ｐ〈０．０５）。高血压合并脑梗塞组１ｍｉｎＡＲ、５ｍｉｎＡＲ、ＭＡＲ及Ｉ较对照组有高度统计学差异（Ｐ〈０．００５）。单纯高血压组１ｍｉｎＡＲ、５ｍｉｎＡＲ、ＭＡＲ与对照组     

地塞米松对肺癌切除术病人血清过氧化脂质胰岛素皮质醇的影响

４０例肺癌切除术病人，随机分为对照（Ｓ）组和地塞米松（Ｓ－Ｄ）组，采用氯胺酮－安氟醚静吸复合麻醉，对血清中过氧化脂质、胰岛素和皮质醇进行了初步观察。结果表明，血清过氧化脂质Ｓ－Ｄ组于手术毕显著低于Ｓ组（Ｐ〈０．０５）；血清胰岛素两组间没有统计学差异；血清皮质醇Ｓ－Ｄ组于气管插管后显著高于Ｓ组（Ｐ〈０．０５）。作者认为肺癌切除术病人术前给地塞米松可有效地降低血清中过氧化脂质含量，利于维护脏器功能。     

纳洛酮用于新生儿窒息复苏的临床观察

观察纳洛酮（ＮＡＬ）用于新生儿窒息复苏的效果，并与碳酸氢钠（ＳＢ）进行比较，４０例产后重度窒息新生儿随机分为两组，每组２０例，分别限出生后立即静脉注射ＮＡＬ或ＳＢ，同时通畅呼吸道，地行有效通气，距首次注药后１０ｍｉｎ两组均经静脉重复注药一次，结果：ＮＡＬ组新生儿３ｍｉｎ，５ｍｉｎＡｐｇａｒ评分显著高于ＳＢ组（Ｐ〈０．０１，Ｐ〈０．０５），自主呼吸建立时间亦明显早ＳＢ组（Ｐ〈０．０１），呼吸频率及心     

SIRT2 Regulates LPS-Induced Renal Tubular CXCL2 and CCL2 Expression

Sirtuin 2 (SIRT2), a NAD⁺-dependent histone deacetylase, is involved in carcinogenesis and genomic instability and modulates proinflammatory immune responses. However, its role in renal inflammatory injury has not been demonstrated. In this study, we explored the expression patterns of CXCL2 and CCL2 in kidney tissue from Sirt2^−/− and Sirt2^+/+ mice and in mouse proximal tubular epithelial (MPT) cells. CXCL2 and CCL2 were significantly downregulated at both the mRNA and the protein levels in kidneys of LPS-treated Sirt2^−/− mice compared with those of LPS-treated Sirt2^+/+ mice. Furthermore, SIRT2 deficiency ameliorated LPS-induced infiltration of neutrophils and macrophages, acute tubular injury, and decrease of renal function. Supporting these observations, CXCL2 and CCL2 expression levels were lower in MPT cells treated with SIRT2-siRNA than in cells treated with control-siRNA, and adenovirus-mediated overexpression of SIRT2 in MPT cells significantly increased the LPS-induced expression of CXCL2 and CCL2 at the mRNA and protein levels. In addition, SIRT2 interacted with mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), and SIRT2-knockdown increased the acetylation of MKP-1 and suppressed the phosphorylation of p38 MAPK and c-Jun N-terminal kinase in LPS-treated MPT cells. SIRT2 also regulated p65 binding to the promoters of CXCL2 and CCL2. Taken together, these findings indicate that SIRT2 is associated with expression of renal CXCL2 and CCL2 and that regulation of SIRT2 might be an important therapeutic target for renal inflammatory injury.     

Multidomain synthetic peptide B2A2 synergistically enhances BMP-2 in vitro.

A multidomain, synthetic peptide designated B2A2 synergizes the activity of BMP-2. B2A2 interacts with BMP receptor isoforms, potentiating the action of BMP-2 in activating alkaline phosphatase and triggering Smad and MAPK signaling. B2A2's design permits its delivery as a local surface coating as well as a soluble co-factor, thus broadening potential bioengineering applications. INTRODUCTION: BMP-2 induces osteogenic differentiation and accelerates bone repair. Although BMP-2 inhibitors have been discovered, no BMP-2 mimetics or enhancers that function in the physiological range have yet been found. Here we report that a synthetic peptide designated B2A2, consisting of (1) a BMP receptor-targeting sequence, (2) a hydrophobic spacer, and (3) a heparin-binding sequence, is a positive modulator of recombinant BMP-2. MATERIALS AND METHODS: Cultures of mesenchymal cell lines C2C12 and C3H10T1/2 were given B2A2, recombinant BMP-2, or both. Alkaline phosphatase (ALP) activity was assayed by conversion of paranitrophenol phosphate (PNPP). Signaling through Smad and MAP kinase pathways was monitored by Western blot. Receptor binding was assessed by incubating immobilized B2A2 with soluble recombinant receptor-Fc chimeras and detecting bound receptor by anti-Fc antibody ELISA. Surface coating of medical device materials was done by first dip-coating with silyl-heparin, followed by B2A2. RESULTS AND CONCLUSIONS: Treatment of cells with B2A2 alone marginally increased ALP activity. However, B2A2 plus BMP-2 resulted in 5- to 40-fold augmentation of ALP compared with BMP-2 alone in C3H10T1/2 or C2C12 cells, respectively. This synergistic enhancement was observed over a broad concentration range (4-1000 ng/ml BMP-2). B2A2 interacted directly with BMP receptor isoforms (preferentially to BMPR-Ib and ActivinR-II). In cells, B2A2 + BMP-2 led to a repression of MAP kinase and an increase of Smad activation, consistent with known activation pathways of BMP-2. B2A2 was ineffective when paired with other cytokine/growth factors (basic fibroblast growth factor [FGF-2], TGF-beta1, vascular endothelial growth factor [VEGF]). Simultaneous co-administration was not strictly required. Pulse-chase experiments revealed that temporal separations up to 1 h were still effective. B2A2 was also effective when delivered in a polystyrene- or stainless steel-coated surface through a heparin platform (silyl-heparin) while BMP-2 was added exogenously in solution. These results suggest that B2A2 might promote aggregation of receptor subunits, enabling BMP-2 to activate signaling pathways at effectively lower concentrations. Synthetic multidomain constructs like B2A2 may be useful to accelerate bone repair/deposition through augmentation of endogenous levels of BMP-2 or through local BMP-2 contained in artificial or engineered matrices.     

PGD2-CRTH2 Pathway Promotes Tubulointerstitial Fibrosis

Urinary excretion of lipocalin-type PGD₂ synthase (L-PGDS), which converts PG H₂ to PGD₂, increases in early diabetic nephropathy. In addition, L-PGDS expression in the tubular epithelium increases in adriamycin-induced nephropathy, suggesting that locally produced L-PGDS may promote the development of CKD. In this study, we found that L-PGDS–derived PGD₂ contributes to the progression of renal fibrosis via CRTH2-mediated activation of Th2 lymphocytes. In a mouse model, the tubular epithelium synthesized L-PGDS de novo after unilateral ureteral obstruction (UUO). L-PGDS-knockout mice and CRTH2-knockout mice both exhibited less renal fibrosis, reduced infiltration of Th2 lymphocytes into the cortex, and decreased production of the Th2 cytokines IL-4 and IL-13. Furthermore, oral administration of a CRTH2 antagonist, beginning 3 days after UUO, suppressed the progression of renal fibrosis. Ablation of IL-4 and IL-13 also ameliorated renal fibrosis in the UUO kidney. Taken together, these data suggest that blocking the activation of CRTH2 by PGD₂ might be a strategy to slow the progression of renal fibrosis in CKD.Kidney failure is a public health problem worldwide, with increasing incidence and prevalence, high costs, and poor outcomes. CKD is generally progressive, incurable, and ultimately fatal, although some patients resolve with little or no sequelae. Because current treatment is basically limited to slowing the progression to ESRD using angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers, more efficient therapies with different or additional modes of action are clearly needed.Regardless of disease etiology, tubulointerstitial fibrosis is the common pathway leading to ESRD in many kidney diseases and is regarded as a prognostic factor for renal function.^1–3 It is noteworthy that some clinical trials are proving that antifibrotic therapies, such as pirfenidone against diabetic nephropathy,⁴ are also effective for CKD. Therefore, elucidating the etiological mechanism underlying renal fibrosis and developing novel therapeutic strategies remains a serious, unmet medical need.Lipocalin-type PGD₂ synthase (L-PGDS) is a secretary protein of the lipocalin superfamily that converts PG H₂, a common precursor of prostanoids, to PGD₂. Because the urinary excretion of L-PGDS increases in the early stage of diabetic nephropathy,^5,6 as well as in patients with essential hypertension without any apparent renal injury,⁷ urinary L-PGDS may be an early diagnostic marker of renal injury in these patients. There is evidence indicating that, in the monkey kidney, L-PGDS is synthesized de novo in the loop of Henle, podocytes, and Bowman’s capsule of the glomeruli.⁸ Furthermore, L-PGDS gene expression in the tubular epithelium was increased in adriamycin-induced nephropathy.⁹ These findings suggest that, under conditions of tubulointerstitial stress, locally produced L-PGDS may be involved in the development of CKD. However, the precise pathophysiological significance of L-PGDS in the kidney remains to be determined.PGD₂ interacts with two receptors, the prostanoid DP₁ receptor and the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). Activation of the DP₁ receptor by PGD₂ has been shown to produce vasodilation¹⁰ and bronchodilation.¹¹ Furthermore, the DP₁ receptor is expressed by certain leukocyte populations,^12,13 including dendritic cells, where it controls various functions, including cytokine production. CRTH2 was originally identified as an orphan receptor expressed by Th2 lymphocytes. CRTH2 is not structurally related to the DP₁ receptor and belongs to the family of chemokine receptors. Activation of CRTH2 by PGD₂ plays an important role in allergic inflammation via the recruitment of Th2 lymphocytes and other leukocytes¹⁴ and, perhaps more importantly, by driving the production of the Th2 cytokines IL-4, IL-5, and IL-13.¹⁵