Endothelin-1 induced sustained contractions of tracheal smooth muscle involve an activation of protein kinase C

Endothelin-1, a potent vasoconstrictor peptide produces concentration dependent contractions in lamb tracheal smooth muscle. These contractions are not inhibited by low doses (up to 20 μM) of trifluoroperazine and W-7, the calmodulin/myosin light chain kinase (MLCK) inhibitors. At higher concentrations (200 μM), a delayed and poor reversal of isometric tensions results. These relaxations are coupled with a partial dephosphorylation of regulatory myosin light chain (MLC). Preincubation of fiber strips in MLCK inhibitors (200 μM) results in a delayed and attenuated contractile response but without a dephosphorylation of MLC. H-7, a putative protein kinase C antagonist (25–100 μM) abolishes endothelin-1 induced contractile effects rapidly (50% relaxation within 1–3 min). Moreover, such relaxations are accompanied by complete dephosphorylation of MLC. Phorbol 12, 13-dibutyrate, an exogenous activator of protein kinase C potentiates the endothelin induced contractions. Inactive phorbol ester, 4α-phorbol ester does not elicit any contractile response in the muscle. The down regulation of protein kinase C, on the other hand suppresses such potentiated contractile responses. These results suggest that endothelin-1 induced contractile tensions in tracheal smooth muscle are mediated by a mechanism that involves an activation of enzyme protein kinase C.     

Muscarinic agonists acting through M2 acetylcholine receptors stimulate the migration of an NO-sensitive guanylyl cyclase to the plasma membrane of bovine tracheal smooth muscle

Muscarinic agonists acting on bovine tracheal smooth muscle (BTSM) induce two separate cGMP signals, one at 20?sec associated with NO-sensitive-soluble-guanylyl-cyclase (NO-sGC) and another at 60?sec, linked to natriuretic-peptide-GC. The 20-sec-cGMP novel cascade starts with mAChRs, via unknown components, activates an NO-sGC. To unravel this cascade, in crude membranes isolated from intact BTSM strips exposed to muscarinic agonists, we detected GC activities increments at 20?sec and 60?sec. The 20-sec-GC is a NO-sensitive-GC, identified as α₁β₁-heterodimer. In reconstitution experiments with purified plasma membranes and cytosol, muscarinic agonists induced an NO-sGC migration in a dose-dependent manner, being inhibited by muscarinic antagonists displaying an M₂AChR profile and blocked by PTX, suggesting the involvement of G_o/G_i proteins. The NO-sGC related to migration was isolated and identified as an α₁β₁-heterodimer. This work shows that muscarinic agonists in BTSM induce a massive and selective α₁β₁-NO-sGC migration from cytoplasm to plasma membranes being responsible for the 20-sec-cGMP signal.     

改良微创肺泡表面活性物质技术对极早早产儿呼吸窘迫综合征患儿Th1/Th2细胞因子含量及心肌损伤指标的影响

摘要 目的：观察应用改良微创肺泡表面活性物质技术对极早早产儿呼吸窘迫综合征患儿Th1/Th2细胞因子含量及心肌损伤指标的影响。方法：以自2018年1月-2020年3月于本院院收治的104例极早早产儿呼吸窘迫综合征患儿为研究对象,按随机数字表法分为研究组（52例,给予改良微创肺泡表面活性物质技术治疗）和对照组（52例,给予气管插管-肺表面活性物质-拔管（INSURE）技术）。观察两组患儿治疗前、治疗7 d后的Th1/Th2细胞因子含量及心肌损伤指标,统计治疗后不良反应及并发症的发生率。结果：（1）干预前,两组患儿干扰素-γ（IFN-γ）、白介素-4（IL-4）及IFN-γ/IL-4含量比较,差异不显著（P＞0.05）;治疗后,两组IFN-γ及IFN-γ/IL-4含量均较治疗前降低,而IL-4含量明显上升;其中研究组IFN-γ及IFN-γ/IL-4含量均低于对照组,IL-4含量高于对照组,差异显著（P<0.05）。（2）干预前,两组患儿肌酸激酶同工酶（CK-MB）、肌酐蛋白（cTnI）及乳酸脱氢酶（LDH）含量比较,差异不显著（P＞0.05）;治疗后,两组CK-MB、cTnI及LDH含量均较治疗前降低,其中研究组CK-MB、cTnI及LDH含量均明显低于对照组（P<0.05）。（3）在治疗过程中,两组不良反应中心动过缓、经皮血氧饱和度（SpO2）下降、72 h内机械通气率及再次使用肺泡表面活性物质率比较,差异不显著（P＞0.05）。（4）在治疗过程中,两组并发症中早产儿视网膜病、坏死性小肠结肠炎、支气管肺发育不良、气胸、脑室内出血及死亡率比较,差异不显著（P＞0.05）。结论：应用改良微创肺泡表面活性物质技术可有效调节极早早产儿呼吸窘迫综合征患儿免疫功能,保护心肌细胞,且安全性高,值得临床推广使用。     

A qualitative model of mortality in honey bee (<Emphasis Type="Italic">Apis mellifera</Emphasis>) colonies infested with tracheal mites (<Emphasis Type="Italic">Acarapis woodi</Emphasis>)

The tracheal mite has been associated with colony deaths worldwide since the mite was first discovered in 1919. Yet controversy about its role in honey bee colony mortality has existed since that time. Other pathogens such as bacteria and viruses have been suggested as the cause of colony deaths as well as degenerative changes in individual honey bees. Using data from published work we developed a qualitative mortality model to explain colony mortality due to tracheal mite infestation in the field. Our model suggests that colonies of tracheal-mite infested honey bees, with no other pathogens present, can die out in the late winter/early spring period due to their inability to thermoregulate. An accumulation of factors conspire to cause colony death including reduced brood/bee population, loose winter clusters, reduced flight muscle function and increasing mite infestation. In essence a cascade effect results in the colony losing its cohesion and leading to its ultimate collapse.     

Regulation of Drosophila matrix metalloprotease Mmp2 is essential for wing imaginal disc:trachea association and air sac tubulogenesis

The Drosophila Dorsal Air Sac Primordium (ASP) is a tracheal tube that grows toward Branchless FGF-expressing cells in the wing imaginal disc. We show that the ASP arises from a tracheal branch that invades the basal lamina of the disc to juxtapose directly with disc cells. We examined the role of matrix metalloproteases (Mmps), and found that reducing Mmp2 activity perturbed disc-trachea association, altered peritracheal distributions of collagen IV and Perlecan, misregulated ASP growth, and abrogated development of the dorsal air sacs. Whereas the function of the membrane-tethered Mmp2 in the ASP is non-cell autonomous we find that it may have distinct tissue-specific roles in the ASP and disc. These findings demonstrate a critical role for Mmp2 in tubulogenesis post-induction, and implicate Mmp2 in regulating dynamic and essential changes to the extracellular matrix.     

The cancer cell secretome: A good source for discovering biomarkers?

Cancer is a leading cause of death. Early detection is usually associated with better clinical outcomes. Recent advances in genomics and proteomics raised hopes that new biomarkers for diagnosis, prognosis or monitoring therapeutic response will soon be discovered. Proteins secreted by cancer cells, referred also as “the cancer cell secretome”, is a promising source for biomarker discovery. In this review we will summarize recent advances in cancer cell secretome analysis, focusing on the five most fatal cancers (lung, breast, prostate, colorectal, and pancreatic). For each cancer type we will describe the proteomic approaches utilized for the identification of novel biomarkers. Despite progress, identification of markers that are superior to those currently used has proven to be a difficult task and very few, if any, newly discovered biomarker has entered the clinic the last 10 years.     

大鼠气管上皮细胞发生过程中Ca~(2+)-ATPase活性变化的形态学观察

本文应用光镜和电镜组化方法,对胚胎晚期至生后早期的 Wistar 大鼠气管上皮细胞Ca~(2+)-ATPase 的动态变化进行了观察。结果证实在胚胎期气管上皮细胞侧面膜和表面膜及纤毛细胞的纤毛干处有 Ca~(2+)-ATPase 活性反应产物,提示胚胎期气管上皮细胞之间可能已存在与气管上皮细胞分化、发育密切相关的钙;在生后早期,纤毛细胞的基粒和纤毛小根处出现活性 Ca~(2+)-ATPase,表明生后早期已出现纤毛运动,其对廓清气道具有重要意义。     

可视喉镜气管插管对心跳骤停抢救患者血流动力学及心肺复苏质量的影响

摘要 目的：探讨可视喉镜气管插管对心跳骤停抢救患者血流动力学及心肺复苏质量的影响。方法：选取联勤保障部队第九四〇医院于2020年4月~2022年5月期间收治的98例心跳骤停抢救患者为研究对象,根据插管方式将患者分为B组（可视喉镜气管插管,n=50）、A组（传统直接喉镜气管插管,n=48）。对比两组插管次数、声门暴露时间、插管时间、气道与牙齿损伤、心肺复苏质量及血流动力学指标变化情况,观察两组不良反应发生情况。结果：B组的插管次数少于A组,声门暴露时间、插管时间短于A组,气道与牙齿损伤比例少于A组（P<0.05）。B组的插管成功率、心肺复苏（CPR）成功率、存活率均高于A组（P<0.05）。B组插管后15 min的收缩压（SBP）、舒张压（DBP）、平均动脉压（MAP）及心率（HR）均低于A组同期（P<0.05）。B组的不良反应发生率低于A组（P<0.05）。结论：相比于传统直接喉镜气管插管用于心跳骤停抢救患者,可视喉镜气管插管可维持血流动力学稳定,提高插管成功率和心肺复苏质量,安全性较好。     

熊蜂气管内寄生螨布赫纳蝗螨的生物学特性观察

对新疆与河北地区野生明亮熊蜂及小峰熊蜂蜂王内寄生螨布赫纳蝗螨Locustacarus buchneri的生物学特性进行了初步观察。结果表明： 该螨对两种熊蜂的寄生率分别为10.43%和8.3%,寄生部位为气管与气囊。室内饲养至30天的蜂王体内寄生螨量明显高于饲养至60天的蜂王。未被螨寄生的蜂王与被寄生者比较,前者体重显著高于后者,但二者间产卵始期、产卵率、食卵率和存活率差异不显著。     

Tracheal agenesis with broncho-esophageal fistula in VACTERL / TACRD association

Tracheal agenesis (TA) is an extremely rare malformation. We report here autopsy findings in a case of TA with bronchoesophageal fistula of Floyd type III. The other malformations present included laryngeal atresia, Right lung hypolobulation, ventricular septal defect in membranous portion, bilateral cystic renal dysplasia, spleninculus, Meckel''s diverticulum, and imperforate anus. The constellations of malformations present in our case have overlapping features with Vertebral anomalies, Anal atresia, Cardiovascular anomalies, Tracheo-esophageal fistula, Esophageal atresia, Renal anomalies, Limb anomalies and Tracheal atresia or laryngo tracheal atresia, Cardiac anomalies, Renal anomalies, Duodenal atresia association described previously in the literature.