Studies of the mechanism of passive anaphylaxis in human airway smooth muscle.

PubMed

Davis, C; Jones, T R; Daniel, E E

1983-07-01

This investigation was carried out to study allergic contraction of passively sensitized human airway smooth muscle in response to specific antigen challenge. We attempted to determine the role played by histamine, slow reaction substances (SRSs), and cyclooxygenase products in the mediation of this response in tracheal smooth muscle. Tissues were passively sensitized with serum from ragweed-sensitive patients (15 h, 4 degrees C). Subsequent challenge with ragweed antigen produced a slowly developing contraction. The peak contraction to a dose producing a maximal response was 37 +/- 6% of the carbachol maximum. Mepyramine (5 X 10(-6) M) did not alter the contraction. Methylprednisolone (2 X 10(-5) M) attenuated the response to antigen but had no significant effect on the contractile response to arachidonic acid. Indomethacin (5.6-28 X 10(-6) M) enhanced the peak antigen-induced contractions by 25 +/- 11% whereas 5,8,11,14-eicosatetraynoic acid (6.4 X 10(-5) M) selectively attenuated the antigen-induced contraction by 86 +/- 12%. Nordihydroguarietic acid (6-12 X 10(-6) M) attenuated both the antigen plus arachidonate induced responses. FPL-55712 (1-2 X 10(-6) M) antagonized the contractions to antigen. Compound 48/80 and goat antihuman immunoglobulin E produced similar slowly developing contractions in sensitized and in some nonsensitized tissues. These responses, except for an early component of the response to 48/80, were independent of histamine and were reversed by FPL-55712. These findings suggest that arachidonic acid metabolites mediate (slow reacting substances) and modulate (prostaglandins) allergic contraction of human airway smooth muscle while any histamine released contributes little or nothing to the contraction in the larger airways.

Interleukin(IL)-1 Regulates Ozone-enhanced Tracheal Smooth Muscle Responsiveness by Increasing Substance P (SP) Production in Intrinsic Airway Neurons of Ferret

PubMed Central

Wu, Z.-X.; Barker, J. S.; Batchelor, T. P.; Dey, R.D.

2008-01-01

Exposure to ozone induces airway hyperresponsiveness (AHR) mediated partly by SP released from nerve terminals of intrinsic airway neurons. Our recent studies showed that IL-1, an important multifunctional proinflammatory cytokine, increases synthesis and release of SP from intrinsic airway neurons. The purpose of this study is to investigate the possible involvement of endogenous IL-1 in modulating neural responses associated with ozone-enhanced airway responsiveness. Ferrets were exposed to 2 ppm ozone or filtered air for 3 hrs. IL-1 in the bronchoalveolar lavage (BAL) fluid was significantly increased in ozone-exposed animals and responses of tracheal smooth muscle to methacholine (MCh) and electrical field stimulation (EFS) were elevated significantly. Both the SP nerve fiber density in tracheal smooth muscle and the number of SP-containing neurons in airway ganglia were significantly increased following ozone exposure. Pretreatment with IL-1 receptor antagonist (IL-1 Ra) significantly diminished ozone-enhanced airway responses to EFS as well as ozone-increased SP in the airway. To selectively investigate intrinsic airway neurons, segments of ferret trachea were maintained in culture conditions for 24 hrs to eliminate extrinsic contributions from sensory nerves. The segments were then exposed to 2 ppm ozone in vitro for 3 hrs. The changes of ozone-induced airway responses to MCh and EFS, and the SP levels in airway neurons paralleled those observed with in vivo ozone exposure. The ozone-enhanced airway responses and neuronal SP levels were inhibited by pretreatment with IL-1 Ra. These findings show that IL-1 is released during ozone exposure enhances airway responsiveness by modulating SP expression in airway neurons. PMID:18718561

21 CFR 878.3720 - Tracheal prosthesis.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Tracheal prosthesis. 878.3720 Section 878.3720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3720 Tracheal prosthesis. (a...

Lipopolysaccharide induces VCAM-1 expression and neutrophil adhesion to human tracheal smooth muscle cells: Involvement of Src/EGFR/PI3-K/Akt pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, W.-N.; Luo, S.-F.; Wu, C.-B.

2008-04-15

In our previous study, LPS has been shown to induce vascular cell adhesion molecule-1(VCAM-1) expression through MAPKs and NF-{kappa}B in human tracheal smooth muscle cells (HTSMCs). In addition to these pathways, the non-receptor tyrosine kinases (Src), EGF receptor (EGFR), and phosphatidylinositol 3-kinase (PI3K) have been shown to be implicated in the expression of several inflammatory target proteins. Here, we reported that LPS-induced up-regulation of VCAM-1 enhanced the adhesion of neutrophils onto HTSMC monolayer, which was inhibited by LY294002 and wortmannin. LPS stimulated phosphorylation of protein tyrosine kinases including Src, PYK2, and EGFR, which were further confirmed using specific anti-phospho-Src, PYK2,more » or EGFR Ab, respectively, revealed by Western blotting. LPS-stimulated Src, PYK2, EGFR, and Akt phosphorylation and VCAM-1 expression were attenuated by the inhibitors of Src (PP1), EGFR (AG1478), PI3-K (LY294002 and wortmannin), and Akt (SH-5), respectively, or transfection with siRNAs of Src or Akt and shRNA of p110. LPS-induced VCAM-1 expression was also blocked by pretreatment with curcumin (a p300 inhibitor) or transfection with p300 siRNA. LPS-stimulated Akt activation translocated into nucleus and associated with p300 and VCAM-1 promoter region was further confirmed by immunofluorescence, immunoprecipitation, and chromatin immunoprecipitation assays. This association of Akt and p300 to VCAM-1 promoter was inhibited by pretreatment with PP1, AG1478, wortmannin, and SH-5. LPS-induced p300 activation enhanced VCAM-1 promoter activity and VCAM-1 mRNA expression. These results suggested that in HTSMCs, Akt phosphorylation mediated through transactivation of Src/PYK2/EGFR promoted the transcriptional p300 activity and eventually led to VCAM-1 expression induced by LPS.« less

Length oscillation induces force potentiation in infant guinea pig airway smooth muscle.

PubMed

Wang, Lu; Chitano, Pasquale; Murphy, Thomas M

2005-12-01

Deep inspiration counteracts bronchospasm in normal subjects but triggers further bronchoconstriction in hyperresponsive airways. Although the exact mechanisms for this contrary response by normal and hyperresponsive airways are unclear, it has been suggested that the phenomenon is related to changes in force-generating ability of airway smooth muscle after mechanical oscillation. It is known that healthy immature airways of both humans and animals exhibit hyperresponsiveness. We hypothesize that the profile of active force generation after mechanical oscillation changes with maturation and that this change contributes to the expression of airway hyperresponsiveness in juveniles. We examined the effect of an acute sinusoidal length oscillation on the force-generating ability of tracheal smooth muscle from 1 wk, 3 wk, and 2- to 3-mo-old guinea pigs. We found that the length oscillation produced 15-20% initial reduction in active force equally in all age groups. This was followed by a force recovery profile that displayed striking maturation-specific features. Unique to tracheal strips from 1-wk-old animals, active force potentiated beyond the maximal force generated before oscillation. We also found that actin polymerization was required in force recovery and that prostanoids contributed to the maturation-specific force potentiation in immature airway smooth muscle. Our results suggest a potentiated mechanosensitive contractile property of hyperresponsive airway smooth muscle. This can account for further bronchoconstriction triggered by deep inspiration in hyperresponsive airways.

Effects of neuropeptides and capsaicin on the canine tracheal vasculature in vivo.

PubMed

Salonen, R O; Webber, S E; Widdicombe, J G

1988-12-01

1. The nonadrenergic, noncholinergic nervous system may control the airway vasculature via various neuropeptides. We have perfused the cranial tracheal arteries of the anaesthetized dog and investigated the effects of neuropeptides and capsaicin (which is supposed to release neuropeptides from sensory nerve endings) on the tracheal vasculature by injecting them locally into the perfusion system. 2. Neurokinin A (NKA, 0.02-20 pmol), calcitonin gene-related peptide (CGRP, 2-200 pmol) and peptide histidine isoleucine (PHI, 0.02-2 nmol) dose-dependently decreased tracheal vascular resistance (Rtv). NKA was 10 and 100 times more potent than CGRP and PHI, respectively. The duration of the response to CGRP was greatly prolonged with larger doses. Galanin (0.2-2 nmol) had no appreciable effect on Rtv. 3. Neuropeptide Y (NPY 0.02-2 nmol) and bombesin (0.02-10 nmol) dose-dependently increased Rtv. However, the dose-response curve for bombesin was bell-shaped suggesting the development of tachyphylaxis with larger doses. In smaller doses, bombesin was twice as potent as NPY. The duration of the response to NPY was prolonged with larger doses. 4. With the exception of PHI no neuropeptide altered tracheal smooth muscle tone; PHI (1 and 2 nmol) caused small dilatations of the trachea. 5. The effects of capsaicin (2-100 nmol) were complex. Usually, the vascular response had two dose-dependent phases: a rapid vasoconstriction followed by a small, longer-lasting vasodilatation. The tracheal smooth muscle response was usually biphasic, a contraction followed by a relaxation. 6. According to previous and present data, the order of potency of the neuropeptides on the canine tracheal vasculature is for the vasodilators : NKA > vasoactive intestinal peptide (VIP) > CGRP > substance P > PHI, and for the vasoconstrictors: bombesin > NPY. The longer-acting neuropeptides (VIP, CGRP and NPY) may be more important than the shorter-acting neuropeptides (substance P, NKA, PHI and bombesin) as

Beta2-adrenoceptor-mediated tracheal relaxation induced by higenamine from Nandina domestica Thunberg.

PubMed

Tsukiyama, Muneo; Ueki, Takuro; Yasuda, Yoichi; Kikuchi, Hiroko; Akaishi, Tatsuhiro; Okumura, Hidenobu; Abe, Kazuho

2009-10-01

The fruit of Nandina domestica Thunberg (ND, Berberidaceae) has been used to improve cough and breathing difficulties in Japan for many years, but very little is known about the constituent of ND responsible for this effect. We have recently reported that the crude extract from ND (NDE) inhibits histamine- and serotonin-induced contraction of isolated guinea pig trachea, and the inhibitory activity was not explained by nantenine, a well-known alkaloid isolated from ND. To explore other constituent(s) of NDE with tracheal smooth muscle relaxant activity, we fractionated NDE and assessed the pharmacological effects of the fractions using isolated guinea pig tracheal ring preparations. NDE was introduced into a polyaromatic absorbent resin column and stepwise eluted to yield five fractions, among which only the 40 % methanol fraction was active in relaxing tracheal smooth muscle precontracted with histamine. Further separation of the 40 % methanol fraction with high-performance liquid chromatography yielded multiple subfractions, one of which was remarkably active in relaxing histamine-precontracted trachea. Chemical analysis with a time-of-flight mass spectrometer and nuclear magnetic resonance spectrometer identified the constituent of the most active subfraction as higenamine, a benzyltetrahydroisoquinoline alkaloid. The potency and efficacy of the active constituent from NDE in relaxing trachea were almost equivalent to synthetic higenamine. In addition, the effect of the active constituent from NDE was competitively inhibited by the selective beta (2)-adrenoceptor antagonist ICI 118,551. These results indicate that the major constituent responsible for the effect of NDE is higenamine, which probably causes the tracheal relaxation through stimulation of beta (2) adrenoceptors. Georg Thieme Verlag KG Stuttgart-New York.

Functional coupling between the Na+/Ca2+ exchanger and nonselective cation channels during histamine stimulation in guinea pig tracheal smooth muscle.

PubMed

Algara-Suárez, Paola; Romero-Méndez, Catalina; Chrones, Tom; Sánchez-Armass, Sergio; Meza, Ulises; Sims, Stephen M; Espinosa-Tanguma, Ricardo

2007-07-01

Airway smooth muscle (ASM) contracts partly due to an increase in cytosolic Ca(2+). In this work, we found that the contraction caused by histamine depends on external Na(+), possibly involving nonselective cationic channels (NSCC) and the Na(+)/Ca(2+) exchanger (NCX). We performed various protocols using isometric force measurement of guinea pig tracheal rings stimulated by histamine. We observed that force reached 53 +/- 1% of control during external Na(+) substitution by N-methyl-D-glucamine(+), whereas substitution by Li(+) led to no significant change (91 +/- 1%). Preincubation with KB-R7943 decreased the maximal force developed (52.3 +/- 5.6%), whereas preincubation with nifedipine did not (89.7 +/- 1.8%). Also, application of the nonspecific NCX blocker KB-R7943 and nifedipine on histamine-precontracted tracheal rings reduced force to 1 +/- 3%, significantly different from nifedipine alone (49 +/- 6%). Moreover, nonspecific NSCC inhibitors SKF-96365 and 2-aminoethyldiphenyl borate reduced force to 1 +/- 1% and 19 +/- 7%, respectively. Intracellular Ca(2+) measurements in isolated ASM cells showed that KB-R7943 and SKF-96365 reduced the peak and sustained response to histamine (0.20 +/- 0.1 and 0.19 +/- 0.09 for KB-R, 0.43 +/- 0.16 and 0.47 +/- 0.18 for SKF, expressed as mean of differences). Moreover, Na(+)-free solution only inhibited the sustained response (0.54 +/- 0.25). These data support an important role for NSCC and NCX during histamine stimulation. We speculate that histamine induces Na(+) influx through NSCC that promotes the Ca(2+) entry mode of NCX and Ca(V)1.2 channel activation, thereby causing contraction.

Difficulty in tracheal extubation followed by tracheal collapse after balloon dilatation for tracheal stenosis therapy: A case report.

PubMed

Li, Nana; Zhu, Linjia; Sun, Jie; Pan, Yinbing; Gao, Mei

2018-06-01

Tracheobronchomalacia (TBM) refers to the weakening trachea or the trachea loss of structural integrity of airway cartilaginous structures. It causes tracheal stenosis, resulting in significantly high rates of mortality. Bronchoplasty by high-pressure balloon dilation under general anesthesia is a simple but effective and safe method to treat tracheobronchial stenosis. However, recurrent postoperative dyspnea after extubation due to tracheal collapse is still a challenge for anesthetists. A 52-year-old man weighing 72 kg was scheduled for balloon dilatation surgery under general anesthesia because of breathing difficulties caused by tracheal stenosis. His previous medical history included rheumatoid arthritis, obstructive sleep apnea syndrome (OSAS), chronic bronchitis and a history of tracheal intubation. Laryngeal computerized tomography confirmed the stenosis at the level of thyroid gland. The tracheal collapse after balloon dilatation for tracheal stenosis therapy. Postoperatively, the patient presented with more serious and repetitive symptoms of dyspnea after extubation when compared to that before treatment. So, we had to re-insert the laryngeal mask airway (LMA), and exclude some anesthesia-associated factors, such as laryngospasm, bronchospasm and so on. After a series of treatments, we ultimately found the cause in time (the airway collapsed), and succeeded in tracheal extubation after the stent was inserted. The patient recovered well and reported high satisfaction with anesthesia management. In such an emergency even, the anesthesiologist should take valuable treatments to ensure the patient's effective ventilation. If the anesthesia-related factors can be eliminated, tracheomalacia or airway collapse should be considered whenever dyspnea occurs in the patients who unexpectedly fail to be extubated.

8-Bromo-cAMP decreases the Ca2+ sensitivity of airway smooth muscle contraction through a mechanism distinct from inhibition of Rho-kinase.

PubMed

Endou, Katsuaki; Iizuka, Kunihiko; Yoshii, Akihiro; Tsukagoshi, Hideo; Ishizuka, Tamotsu; Dobashi, Kunio; Nakazawa, Tsugio; Mori, Masatomo

2004-10-01

To clarify whether cyclic AMP (cAMP)/cAMP-dependent protein kinase (PKA) activation and Rho-kinase inhibition share a common mechanism to decrease the Ca2+ sensitivity of airway smooth muscle contraction, we examined the effects of 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP), a stable cAMP analog, and (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexane carboxamide dihydrochloride, monohydrate (Y-27632), a Rho-kinase inhibitor, on carbachol (CCh)-, guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS)-, 4beta-phorbol 12,13-dibutyrate (PDBu)-, and leukotriene D4 (LTD4)-induced Ca2+ sensitization in alpha-toxin-permeabilized rabbit tracheal and human bronchial smooth muscle. In rabbit trachea, CCh-induced smooth muscle contraction was inhibited by 8-BrcAMP and Y-27632 to a similar extent. However, GTPgammaS-induced smooth muscle contraction was resistant to 8-BrcAMP. In the presence of a saturating concentration of Y-27632, PDBu-induced smooth muscle contraction was completely reversed by 8-BrcAMP. Conversely, PDBu-induced smooth muscle contraction was resistant to Y-27632. In the presence of a saturating concentration of 8-BrcAMP, GTPgammaS-induced Ca2+ sensitization was also reversed by Y-27632. The 8-BrcAMP had no effect on the ATP-triggered contraction of tracheal smooth muscle that had been treated with calyculin A in rigor solutions. The 8-BrcAMP and Y-27632 additively accelerated the relaxation rate of PDBu- and GTPgammaS-treated smooth muscle under myosin light chain kinase-inhibited conditions. In human bronchus, LTD4-induced smooth muscle contraction was inhibited by both 8-BrcAMP and Y-27632. We conclude that cAMP/PKA-induced Ca2+ desensitization contains at least two mechanisms: 1) inhibition of the muscarinic receptor signaling upstream from Rho activation and 2) cAMP/PKA's preferential reversal of PKC-mediated Ca2+ sensitization in airway smooth muscle.

[Cervical tracheal resection with primary anastomosis for benign tracheal stricture in adult].

PubMed

Ye, Jin; Hu, Yan-Ming; Liu, Hui; Li, Jing-Jia; Wang, Zhi-Yuan; Li, Yuan

2013-07-01

To introduce the outcomes of tracheal resection with primary end to end anastomosis for benign cervical tracheal stenosis, and to discuss the strategy for prevention of surgical complications. A retrospective analysis was performed in 12 patients diagnosed as benign cervical tracheal stenosis from October 2009 to June 2012. Laryngo-tracheal endoscopic examination and computed tomography (CT) were used to assess the degree of stenosis, the grade of inflammation and edema of the subglottis and trachea, and the extent of stenosis and the remaining linear amount of normal airway. The Meyer and Cotton grading system was used to categorise the clinical severity of the stenoses. All patients underwent tracheal resection with primary end to end anastomosis. The length of cervical tracheal stenosis ranged from 2.3 to 4.1 cm. Grade II stenosis was present in three patients, Grade III stenosis was present in seven patients and grade IV stenosis in two patients. Successful extubation was achieved in all 12 cases. After surgery, temporary hoarseness occurred in 1 patient (8.3%); unilateral pulmonary atelectasis with pleural effusion occurred in 1 patient (8.3%); subcutaneous emphysema with infection occurred in 1 patient (8.3%); mild dysphagia occurred in 3 patients (25.0%); a slight deepening of the tone of voice occurred in 5 patients (41.7%), granulation tissue growth near the suture occurred in 3 patients (25.0%), and suture dehiscence did not occur in any patient. The follow-up period ranged from 6 months to 38 months, no patient developed restenosis. It presents a high success rate and good functional result of tracheal resection with primary end-to-end anastomosis. Therefore, it is an effective and reliable approach for the management of benign cervical tracheal stenosis. To avoid complications, the preoperative assessment, patients selection and postoperative management should be emphasized.

Pseudomonas aeruginosa lipopolysaccharide induces CF-like alteration of protein secretion by human tracheal gland cells.

PubMed

Kammouni, W; Figarella, C; Baeza, N; Marchand, S; Merten, M D

1997-12-18

Human tracheal gland (HTG) serous cells are now believed to play a major role in the physiopathology of cystic fibrosis. Because of the persistent inflammation and the specific infection by Pseudomonas aeruginosa in the lung, we looked for the action of the lipopolysaccharide (LPS) of this bacteria on human tracheal gland cells in culture by studying the secretion of the secretory leukocyte proteinase inhibitor (SLPI) which is a specific serous secretory marker of these cells. Treatment with Pseudomonas aeruginosa LPS resulted in a significant dose-dependent increase in the basal production of SLPI (+ 250 +/- 25%) whilst the SLPI transcript mRNA levels remained unchanged. This LPS-induced increase in secretion was inhibited by glucocorticoides. Furthermore, LPS treatment of HTG cells induces a loss of responsiveness to carbachol and isoproterenol but not to adenosine triphosphate. These findings indicate that HTG cells treated by Pseudomonas aeruginosa LPS have the same behavior as those previously observed with CF-HTG cells. Exploration by using reverse transcriptase polymerase chain reaction amplification showed that LPS downregulated cystic fibrosis transmembrane conductance regulator (CFTR) mRNA expression in HTG cells indicative of a link between CFTR function and consequent CF-like alteration in protein secretory process.

Idiopathic tracheal stenosis: a clinicopathologic study of 63 cases and comparison of the pathology with chondromalacia.

PubMed

Mark, Eugene J; Meng, Fanqing; Kradin, Richard L; Mathisen, Douglas J; Matsubara, Osamu

2008-08-01

Tracheal stenosis in adults usually is the result of mechanical injuries either from direct trauma or intubation. Rarely do cases develop in patients without such a precedent history, and there are few reports of the pathology of idiopathic tracheal stenosis (ITS). We reviewed clinicopathologically, 63 tracheal resections for tracheal stenosis in patients who had no antecedent explanation for their stenosis. We contrasted these 63 cases with 34 cases of tracheal stenosis owing to chondromalacia (CM) after mechanical injury. All 63 cases occurred in females, with a mean age of 49 years. The most common symptom was dyspnea on exertion. The average duration of symptoms was greater than 2 years. One-third of the patients gave a history of gastroesophageal reflux. All but one of the cases occurred in the subglottic region and/or upper one-third of the trachea. Pathologically, most cases showed extensive keloidal fibrosis and dilation of mucus glands, a finding that was not obvious in most cases of CM. ITS has relatively normal cartilage with smooth inner and outer perichondrium, whereas CM has extensive degeneration of cartilage with irregular border of inner perichondrium observable at shirt sleeve magnification. Immunohistochemical staining for estrogen receptor and progesterone receptor was positive in fibroblasts cells in most cases. ITS is a rare disease and restricted to females. It may represent some form of fibromatosis. ITS can be distinguished histologically from CM in tracheal resection specimens in most cases.

Characterization of a diadenosine tetraphosphate-receptor distinct from the ATP-purinoceptor in human tracheal gland cells.

PubMed

Saleh, A; Picher, M; Kammouni, W; Figarella, C; Merten, M D

1999-11-12

Human submucosal tracheal glands are now believed to play a major role in the physiopathology of cystic fibrosis, a genetic disease in which ATP is used as a therapeutic agent. However, actions of ATP on tracheal gland cells are not well known. ATP binds to P2 receptors and induced secretory leucocyte protease inhibitor (SLPI) secretion through formation of cyclic adenosine monophosphate and mobilization of intracellular [Ca(2+)]. Since diadenosine polyphosphates (ApnA) are also endogenous effectors of P2 receptors, we investigated their effects in a cell line (MM39) of human tracheal gland cells. Diadenosine tetraphosphates (Ap4A) induced significant stimulation (+50+/-12%) of SLPI secretion and to a similar extent to that of ATP (+65+/-10%). No significant effects were observed with diadenosine triphosphate (Ap3A), diadenosine pentaphosphate (Ap5A), ADP and 2-methylthio-adenosine triphosphate (2-MeS-ATP). Since Ap4A was weakly hydrolyzed (<2% of total), and the hydrolysis product was only inosine which is ineffective on cells, this Ap4A effect was not due to Ap4A hydrolysis in ATP and adenosine monophosphate (AMP). A mixture of Ap4A and ATP elicited only partial additive effects on SLPI secretion. ADP was shown to be a potent antagonist of ATP and Ap4A receptors, with IC(50)s of 0.8 and 2 microM, respectively. 2-MeS-ATP also showed antagonistic properties with IC(50)s of 20 and 30 microM for ATP- and Ap4A-receptors, respectively. Single cell intracellular calcium ([Ca(2+)](i)) measurements showed similar transient increases of [Ca(2+)](i) after ATP or Ap4A challenges. ATP desensitized the cell [Ca(2+)](i) responses to ATP and Ap4A, and Ap4A also desensitized the cell response to Ap4A. Nevertheless, Ap4A did not desensitize the cell [Ca(2+)](i) responses to ATP. In conclusion, both P2Y2-ATP-receptors and Ap4A-P2D-receptors seem to be present in tracheal gland cells. Ap4A may only bind to P2D-receptors whilst ATP may bind to both Ap4A- and ATP-receptors.

Massive aspiration past the tracheal tube cuff caused by closed tracheal suction system.

PubMed

Dave, Mital H; Frotzler, Angela; Madjdpour, Caveh; Koepfer, Nelly; Weiss, Markus

2011-01-01

Aspiration past the tracheal tube cuff has been recognized to be a risk factor for the development of ventilator-associated pneumonia (VAP). This study investigated the effect of closed tracheal suctioning on aspiration of fluid past the tracheal tube cuff in an in vitro benchtop model. High-volume low pressure tube cuffs of 7.5 mm internal diameter (ID) were placed in a 22 mm ID artificial trachea connected to a test lung. Positive pressure ventilation (PPV) with 15 cm H₂O peak inspiratory pressure and 5 cm H₂O positive end-expiratory pressure (PEEP) was used. A closed tracheal suction system (CTSS) catheter (size 14Fr) was attached to the tracheal tube and suction was performed for 5, 10, 15, or 20 seconds under 200 or 300 cm H₂O suction pressures. Amount of fluid (mL) aspirated along the tube cuff and the airway pressure changes were recorded for each suction procedure. Fluid aspiration during different suction conditions was compared using Kruskal-Wallis and Mann-Whitney test (Bonferroni correction [α = .01]). During 10, 15, and 20 seconds suction, airway pressure consistently dropped down to -8 to -13 cm H₂O (P < .001) from the preset level. Fluid aspiration was never observed under PPV + PEEP but occurred always during suctioning. Aspiration along the tube cuff was higher with -300 cm H₂O than with -200 cm H₂O suction pressure (P < .001) and was much more during 15 and 20 seconds suction time as compared to 5 seconds (P < .001). Massive aspiration of fluid occurs along the tracheal tube cuff during suction with the closed tracheal suction system. © SAGE Publications 2011.

Gas Exchange Models for a Flexible Insect Tracheal System.

PubMed

Simelane, S M; Abelman, S; Duncan, F D

2016-06-01

In this paper two models for movement of respiratory gases in the insect trachea are presented. One model considers the tracheal system as a single flexible compartment while the other model considers the trachea as a single flexible compartment with gas exchange. This work represents an extension of Ben-Tal's work on compartmental gas exchange in human lungs and is applied to the insect tracheal system. The purpose of the work is to study nonlinear phenomena seen in the insect respiratory system. It is assumed that the flow inside the trachea is laminar, and that the air inside the chamber behaves as an ideal gas. Further, with the isothermal assumption, the expressions for the tracheal partial pressures of oxygen and carbon dioxide, rate of volume change, and the rates of change of oxygen concentration and carbon dioxide concentration are derived. The effects of some flow parameters such as diffusion capacities, reaction rates and air concentrations on net flow are studied. Numerical simulations of the tracheal flow characteristics are performed. The models developed provide a mathematical framework to further investigate gas exchange in insects.

Effects of sodium metabisulphite on guinea pig contractile airway smooth muscle responses in vitro.

PubMed

Sun, J; Sakamoto, T; Chung, K F

1995-08-01

Sodium metabisulphite (MBS) is known to induce bronchoconstriction in asthmatic patients. The effects of MBS on guinea pig airway smooth muscle and on neurally mediated contraction in vitro have been examined. Tracheal and bronchial airway segments were placed in oxygenated buffer solution and electrical field stimulation was performed in the presence of indomethacin (10(-5) M) and propranolol (10(-6) M) for the measurement of isometric tension. Atropine (10(-6) M) was added to bronchial tissues. Concentrations of MBS up to 10(-3) M had no direct effect on airway smooth muscle contraction and did not alter either tracheal smooth muscle contraction induced by electrical field stimulation at all frequencies or acetylcholine-induced tracheal smooth muscle contraction. There was a similar response in the absence of epithelium, except for potentiation of the response induced by electrical field stimulation at 0.5 Hz (24 (10)% increase). However, MBS (10(-5), 10(-6) and 10(-7) M) augmented neurally-mediated non-adrenergic non-cholinergic contractile responses in the bronchi (13.3 (3.2)%, 23.8 (9.6)%, and 6.4 (1.6)%, respectively). MBS had no effect on the contractile response induced by substance P, but at higher concentrations (10(-3) M and 10(-4) M) it caused a time-dependent attenuation of responses induced by either electrical field stimulation or exogenously applied acetylcholine or substance P. MBS had no direct contractile responses but enhanced bronchoconstriction induced by activation of non-cholinergic neural pathways in the bronchus, probably through increased release of neuropeptides. At high concentrations MBS inhibited contractile responses initiated by receptor or neural stimulation.

Effects of sodium metabisulphite on guinea pig contractile airway smooth muscle responses in vitro.

PubMed Central

Sun, J.; Sakamoto, T.; Chung, K. F.

1995-01-01

BACKGROUND--Sodium metabisulphite (MBS) is known to induce bronchoconstriction in asthmatic patients. The effects of MBS on guinea pig airway smooth muscle and on neurally mediated contraction in vitro have been examined. METHODS--Tracheal and bronchial airway segments were placed in oxygenated buffer solution and electrical field stimulation was performed in the presence of indomethacin (10(-5) M) and propranolol (10(-6) M) for the measurement of isometric tension. Atropine (10(-6) M) was added to bronchial tissues. RESULTS--Concentrations of MBS up to 10(-3) M had no direct effect on airway smooth muscle contraction and did not alter either tracheal smooth muscle contraction induced by electrical field stimulation at all frequencies or acetylcholine-induced tracheal smooth muscle contraction. There was a similar response in the absence of epithelium, except for potentiation of the response induced by electrical field stimulation at 0.5 Hz (24 (10)% increase). However, MBS (10(-5), 10(-6) and 10(-7) M) augmented neurally-mediated non-adrenergic non-cholinergic contractile responses in the bronchi (13.3 (3.2)%, 23.8 (9.6)%, and 6.4 (1.6)%, respectively). MBS had no effect on the contractile response induced by substance P, but at higher concentrations (10(-3) M and 10(-4) M) it caused a time-dependent attenuation of responses induced by either electrical field stimulation or exogenously applied acetylcholine or substance P. CONCLUSIONS--MBS had no direct contractile responses but enhanced bronchoconstriction induced by activation of non-cholinergic neural pathways in the bronchus, probably through increased release of neuropeptides. At high concentrations MBS inhibited contractile responses initiated by receptor or neural stimulation. Images PMID:7570440

Stimulation of the BKCa channel in cultured smooth muscle cells of human trachea by magnolol

PubMed Central

Wu, S; Chen, C; Li, H; Lo, Y; Chen, S; Chiang, H

2002-01-01

Background: Magnolol, a compound isolated from the cortex of Magnolia officinalis, has been found to possess anti-allergic and anti-asthmatic activity. Methods: The effect of magnolol on ionic currents was studied in cultured smooth muscle cells of human trachea with the aid of the patch clamp technique. Results: In whole cell current recordings magnolol reversibly increased the amplitude of K+ outward currents. The increase in outward current caused by magnolol was sensitive to inhibition by iberiotoxin (200 nM) or paxilline (1 µM) but not by glibenclamide (10 µM). In inside out patches, magnolol added to the bath did not modify single channel conductance but effectively enhanced the activity of large conductance Ca2+ activated K+ (BKCa) channels. Magnolol increased the probability of these channel openings in a concentration dependent manner with an EC50 value of 1.5 µM. The magnolol stimulated increase in the probability of channels opening was independent of internal Ca2+. The application of magnolol also shifted the activation curve of BKCa channels to less positive membrane potentials. The change in the kinetic behaviour of BKCa channels caused by magnolol in these cells is the result of an increase in dissociation and gating constants. Conclusions: These results provide evidence that, in addition to the presence of antioxidative activity, magnolol is potent in stimulating BKCa channel activity in tracheal smooth muscle cells. The direct stimulation of these BKCa channels by magnolol may contribute to the underlying mechanism by which it acts as an anti-asthmatic compound. PMID:11809993

Receptors mediating the effects of substance P and neurokinin A on mucus secretion and smooth muscle tone of the ferret trachea: potentiation by an enkephalinase inhibitor.

PubMed Central

Webber, S. E.

1989-01-01

1. The effects of substance P (SP) and neurokinin A (NKA) were examined on tracheal smooth muscle tone, mucus volume output, lysozyme output and albumin transport across the ferret in vitro whole trachea in the presence and absence of the enkephalinase inhibitor, thiorphan. 2. SP (0.001-3 microM) and NKA (0.01-10 microM) contracted the tracheal smooth muscle and increased mucus volume, lysozyme and albumin outputs into the tracheal lumen. The EC50 values for SP and NKA for all of the variables measured were significantly reduced, and all of the maximum responses were significantly enhanced by thiorphan (10 microM). 3. In the presence of thiorphan, SP (1 microM) and NKA (10 microM) produced albumin concentrations in the secreted mucus (8.9 and 7.2 micrograms microliters-1) which were greater than those in the submucosal buffer (4.2 micrograms microliters-1). 4. In the presence of thiorphan, NKA was approximately 5 times more potent than SP at contracting the tracheal smooth muscle. Conversely SP was 23, 15 and 22 times more potent than NKA at stimulating mucus volume, lysozyme and albumin outputs respectively. 5. Thus, there is neutral endopeptidase in the ferret trachea in vitro which cleaves exogenously applied SP and NKA, thereby reducing the magnitude and potency of their actions. SP and NKA contract the ferret tracheal muscle probably by an action at NK2 (or NK3)-receptors but stimulate mucus volume output, lysozyme output and albumin transport across the tracheal wall probably by an action on NK1 receptors. PMID:2482101

Receptors mediating the effects of substance P and neurokinin A on mucus secretion and smooth muscle tone of the ferret trachea: potentiation by an enkephalinase inhibitor.

PubMed

Webber, S E

1989-12-01

1. The effects of substance P (SP) and neurokinin A (NKA) were examined on tracheal smooth muscle tone, mucus volume output, lysozyme output and albumin transport across the ferret in vitro whole trachea in the presence and absence of the enkephalinase inhibitor, thiorphan. 2. SP (0.001-3 microM) and NKA (0.01-10 microM) contracted the tracheal smooth muscle and increased mucus volume, lysozyme and albumin outputs into the tracheal lumen. The EC50 values for SP and NKA for all of the variables measured were significantly reduced, and all of the maximum responses were significantly enhanced by thiorphan (10 microM). 3. In the presence of thiorphan, SP (1 microM) and NKA (10 microM) produced albumin concentrations in the secreted mucus (8.9 and 7.2 micrograms microliters-1) which were greater than those in the submucosal buffer (4.2 micrograms microliters-1). 4. In the presence of thiorphan, NKA was approximately 5 times more potent than SP at contracting the tracheal smooth muscle. Conversely SP was 23, 15 and 22 times more potent than NKA at stimulating mucus volume, lysozyme and albumin outputs respectively. 5. Thus, there is neutral endopeptidase in the ferret trachea in vitro which cleaves exogenously applied SP and NKA, thereby reducing the magnitude and potency of their actions. SP and NKA contract the ferret tracheal muscle probably by an action at NK2 (or NK3)-receptors but stimulate mucus volume output, lysozyme output and albumin transport across the tracheal wall probably by an action on NK1 receptors.

Tracheal reconstruction with autogenous jejunal microsurgical transfer.

PubMed

Jones, R E; Morgan, R F; Marcella, K L; Mills, S E; Kron, I L

1986-06-01

Tracheal defects due to stricture formation, tracheomalacia, and neoplasms can present difficult reconstructive problems. Tracheal defects were surgically created in 6 dogs and primarily reconstructed with microsurgical free tissue transfer of autogenous jejunal segments. Primary healing was accomplished in all dogs without severe air leakage or infection. Bronchoscopy demonstrated no substantial secretions or tracheal narrowing. Gross pathological examination of the trachea revealed no evidence of tracheal disruption or infection. Direct measurements revealed no major tracheal narrowing. Microscopic examination demonstrated normal jejunal mucosa with a minimal amount of inflammatory change at the margins of the reconstruction at 6 weeks. Microvascular free tissue transfer of jejunal segments to correct cervical tracheal defects can readily be accomplished with excellent healing and maintenance of the tracheal lumen in dogs.

Tracheal invasion by Thyroid nodule in Thyroidectomy

DTIC Science & Technology

2017-10-20

through the first tracheal ring. The tracheal defect was fixed with a strap muscle flap and surgery concluded uneventfully. Following deep extubation, an...air leak at the surgical site was noted. The patient was reintubated, the incision was re-opened and the tracheal flap was revised to prevent tracheal leaking.

Extended resection of the trachea in a patient with cicatricial tracheal stenosis after tracheostomy complicated with esophageal-tracheal fistula and extensive defect of the frontal tracheal wall.

PubMed

Khudaybergenov, Shukhrat; Eshonkhodjaev, Otabek; Abdusalomov, Sodiqjon; Amanov, Bakhrom

2017-03-01

We present a case of one-stage radical surgical treatment of a 24-year-old female patient with cicatricial granulating tracheal stenosis after tracheostomy complicated by esophageal-tracheal fistula and an extensive defect of the anterior wall of the trachea after numerous unsuccessful attempts to correct the narrowing of the trachea and eliminate the fistula by endoscopic and open surgical techniques. The patient underwent extended tracheal resection with end-to-end anastomosis with liquidation of the esophageal-tracheal fistula and elimination of the defect of the anterior wall of the trachea by cervical access.

Tracheal reconstruction with a pleuroperiosteal flap.

PubMed

Krespi, Y P; Biller, H F; Baek, S M

1983-12-01

Reconstruction of extensive tracheal defects remains a difficult surgical problem. In many experiments restoration of tracheal mucosa by autogenous or homologous soft tissue grafts has usually failed because of rejection or tracheal obstruction. This experimental work employed a two-stage surgical procedure that allowed reconstruction of extensive circumferential full-thickness defects of the trachea. Stage I involved the creation of a vascularized pleuroperiosteal flap that was formed into a rigid tube around a Silastic stent. Stage II consisted of creation of a full-thickness circumferential tracheal defect and repair with the flap in those animals in which a suitable rigid tube had been formed. The results of these experiments argue strongly that a vascularized composite pleuroperiosteal flap can produce an adequate tracheal replacement.

Swine confinement buildings: effects of airborne particles and settled dust on airway smooth muscles.

PubMed

Demanche, Annick; Bonlokke, Jakob; Beaulieu, Marie-Josee; Assayag, Evelyne; Cormier, Yvon

2009-01-01

Swine confinement workers are exposed to various contaminants. These agents can cause airway inflammation and bronchoconstriction. This study was undertaken to evaluate if the bronchoconstrictive effects of swine barn air and settled dust are mediated by endotoxin, and if these effects are directly mediated on airway smooth muscles. Mouse tracheas where isolated and mounted isometrically in organ baths. Tracheas, with or without epithelium, were attached to a force transducer and tension was recorded. Concentrated swine building air at 68 EU/ml or settled dust extract at 0.01 g/ml were added for 20 minutes and tracheal smooth muscle contraction was measured. Direct role of LPS was assessed by removing it from air concentrates with an endotoxin affinity resin. Swine barn air and settled dust extract caused contraction of tracheal smooth muscle by 26 and 20%, respectively, of the maximal induced by methacholine. Removal of epithelium did not affect the contractile effects. LPS alone and LPS with peptidoglycans did not induce contraction. However, when endotoxin was removed from swine barn air concentrates, it lost 24% of its contractile effect. Concentrated swine barn air and settled dust have direct effects on airway smooth muscles. This effect is partially due to LPS but a synergy with other components of the environment of swine confinement buildings is required.

Peripheral Airway Smooth Muscle, but Not the Trachealis, Is Hypercontractile in an Equine Model of Asthma.

PubMed

Matusovsky, Oleg S; Kachmar, Linda; Ijpma, Gijs; Bates, Genevieve; Zitouni, Nedjma; Benedetti, Andrea; Lavoie, Jean-Pierre; Lauzon, Anne-Marie

2016-05-01

Heaves is a naturally occurring equine disease that shares many similarities with human asthma, including reversible antigen-induced bronchoconstriction, airway inflammation, and remodeling. The purpose of this study was to determine whether the trachealis muscle is mechanically representative of the peripheral airway smooth muscle (ASM) in an equine model of asthma. Tracheal and peripheral ASM of heaves-affected horses under exacerbation, or under clinical remission of the disease, and control horses were dissected and freed of epithelium to measure unloaded shortening velocity (Vmax), stress (force/cross-sectional area), methacholine effective concentration at which 50% of the maximum response is obtained, and stiffness. Myofibrillar Mg(2+)-ATPase activity, actomyosin in vitro motility, and contractile protein expression were also measured. Horses with heaves had significantly greater Vmax and Mg(2+)-ATPase activity in peripheral airway but not in tracheal smooth muscle. In addition, a significant correlation was found between Vmax and the time elapsed since the end of the corticosteroid treatment for the peripheral airways in horses with heaves. Maximal stress and stiffness were greater in the peripheral airways of the horses under remission compared with controls and the horses under exacerbation, potentially due to remodeling. Actomyosin in vitro motility was not different between controls and horses with heaves. These data demonstrate that peripheral ASM is mechanically and biochemically altered in heaves, whereas the trachealis behaves as in control horses. It is therefore conceivable that the trachealis muscle may not be representative of the peripheral ASM in human asthma either, but this will require further investigation.

A comparison of adenine and some derivatives on pig isolated tracheal muscle.

PubMed Central

Bach-Dieterle, Y.; Holden, W. E.; Junod, A. F.

1983-01-01

We studied the muscle relaxation induced by adenine and several adenine derivatives in strips of tracheal smooth muscle from pigs; in addition their metabolism by the tissue was examined. Adenine relaxed tissue which was contracted by carbachol, histamine, or KCl. Adenine's potency was similar to that of adenosine and ATP (threshold about 4 X 10(-5)M). In tissues with carbachol-induced tone, the adenine effect differed from adenosine and ATP by being slower in onset and in 'washout' time. Furthermore, neither dipyridamole nor theophylline modified the response to adenine. The relationship was examined between pharmacological effects and the metabolism of [3H]-adenosine and [3H]-adenine. Both substrates were taken up by the tissue and converted to nucleotides, but relaxation correlated with nucleotide accumulation only in the case of [3H]-adenine. We conclude that the site and mechanism of adenine-induced relaxation is different from that of adenosine and ATP in porcine tracheal muscle. PMID:6571222

Mounier-Kuhn syndrome: a case of tracheal smooth muscle remodeling.

PubMed

Cook, Daniel P; Adam, Ryan J; Abou Alaiwa, Mahmoud H; Eberlein, Michael; Klesney-Tait, Julia A; Parekh, Kalpaj R; Meyerholz, David K; Stoltz, David A

2017-02-01

Mounier-Kuhn syndrome is a rare clinical disorder characterized by tracheobronchial dilation and recurrent lower respiratory tract infections. While the etiology of the disease remains unknown, histopathological analysis of Mounier-Kuhn airways demonstrates that the disease is, in part, characterized by cellular changes in airway smooth muscle.

Extended resection of the trachea in a patient with cicatricial tracheal stenosis after tracheostomy complicated with esophageal-tracheal fistula and extensive defect of the frontal tracheal wall

PubMed Central

Khudaybergenov, Shukhrat; Abdusalomov, Sodiqjon; Amanov, Bakhrom

2017-01-01

We present a case of one-stage radical surgical treatment of a 24-year-old female patient with cicatricial granulating tracheal stenosis after tracheostomy complicated by esophageal-tracheal fistula and an extensive defect of the anterior wall of the trachea after numerous unsuccessful attempts to correct the narrowing of the trachea and eliminate the fistula by endoscopic and open surgical techniques. The patient underwent extended tracheal resection with end-to-end anastomosis with liquidation of the esophageal-tracheal fistula and elimination of the defect of the anterior wall of the trachea by cervical access. PMID:28515752

Fiber optic tracheal detection device

NASA Astrophysics Data System (ADS)

Souhan, Brian E.; Nawn, Corinne D.; Shmel, Richard; Watts, Krista L.; Ingold, Kirk A.

2017-02-01

Poorly performed airway management procedures can lead to a wide variety of adverse events, such as laryngeal trauma, stenosis, cardiac arrest, hypoxemia, or death as in the case of failed airway management or intubation of the esophagus. Current methods for confirming tracheal placement, such as auscultation, direct visualization or capnography, may be subjective, compromised due to clinical presentation or require additional specialized equipment that is not always readily available during the procedure. Consequently, there exists a need for a non-visual detection mechanism for confirming successful airway placement that can give the provider rapid feedback during the procedure. Based upon our previously presented work characterizing the reflectance spectra of tracheal and esophageal tissue, we developed a fiber-optic prototype to detect the unique spectral characteristics of tracheal tissue. Device performance was tested by its ability to differentiate ex vivo samples of tracheal and esophageal tissue. Pig tissue samples were tested with the larynx, trachea and esophagus intact as well as excised and mounted on cork. The device positively detected tracheal tissue 18 out of 19 trials and 1 false positive out of 19 esophageal trials. Our proof of concept device shows great promise as a potential mechanism for rapid user feedback during airway management procedures to confirm tracheal placement. Ongoing studies will investigate device optimizations of the probe for more refined sensing and in vivo testing.

Effects of ozone on the cholinergic secretory responsiveness of ferret tracheal glands

DOE Office of Scientific and Technical Information (OSTI.GOV)

McBride, R.K.; Oberdoerster, G.; Marin, M.G.

1991-06-01

Oxidant air pollutants exacerbate several pulmonary diseases. Inhalation of ozone has been shown to induce airway smooth muscle hyperresponsiveness. Oxidant injury could also affect airway secretory mechanisms. The authors postulated that oxidant exposure would alter the glycoconjugate secretory function of airway submucosal glands. To test this hypothesis they examined the effects of in vivo ozone exposure on the in vitro secretory responsiveness of ferret tracheal glands. Ferrets were exposed to 1 ppm ozone, 24 hr/day for 3 or 7 days. Following exposure, glandular explants, denuded of surface epithelial cells, were prepared and incubated in medium containing 3H-glucosamine for 18 hr.more » Basal secretion of labeled glycoconjugates was significantly increased 31% following 3 days of ozone exposure (P less than or equal to 0.05) and remained elevated 11% after 7 days of exposure compared to the air-exposed group. After 3 or 7 days of exposure to ozone, tracheal gland responsiveness to carbachol was increased as indicated by significantly lower EC50 values (log molar concentration) of -6.43 {plus minus} 0.04 (n = 6) and -6.50 {plus minus} 0.11 (n = 5), respectively; compared to -6.20 {plus minus} 0.08 (n = 6) for the air-exposed group. There was no difference in carbachol EC50 values for air and 7-day ozone-exposed animals treated with dexamethasone. Dexamethasone did not attenuate the ozone-induced increase in basal secretion. Tracheal gland responsiveness to {alpha}- or {beta}-adrenergic agonists was not changed by oxidant exposure. These experiments suggest that oxidant injury not only increases basal secretion of respiratory glycoconjugates but also increases tracheal gland sensitivity to a cholinergic agonist.« less

Surgical management of benign tracheal stenosis in Basrah

PubMed Central

Almudhafer, Muayyad M.; AI-Hassani, Fouzi A.A.; Benyan, Abdul-Khalik Z.

2013-01-01

Background: Tracheal stenosis is more frequent as a result of wide-spread use of endotracheal intubation and tracheostomy. Resection and tracheal reconstruction remain the treatment of choice in benign tracheal stenosis. Objectives: To report our experience in Basra and to identify the result of anastomosis after tracheal resection and management of those patients preoperatively and postoperatively. Methodology: A descriptive study of sixteen patients (aged 11–28 years, 10 male and 6 female) with tracheal stenosis who underwent tracheal resection and reconstruction in Basrah thoracic unit (Basra teaching hospital) from January 2008 to January 2011. Results: The result was excellent in 62.5%, good in 25%, and satisfactory in 12.5%. Postoperative complication occurred in 25% and treated successfully with no mortality. Follow-up was every 3 months for an average of 3.6 years. Conclusion: Resection and tracheal reconstruction is the treatment of choice in benign tracheal stenosis and achieved excellent results in management of the patients. PMID:25003058

Tracheal wall thickening is associated with the granulation tissue formation around silicone stents in patients with post-tuberculosis tracheal stenosis.

PubMed

Eom, Jung Seop; Kim, Hojoong; Jeon, Kyeongman; Um, Sang-Won; Koh, Won-Jung; Suh, Gee Young; Chung, Man Pyo; Kwon, O Jung

2013-07-01

Tracheal restenosis due to excessive granulation tissue around a silicone stent requires repeated bronchoscopic interventions in patients with post-tuberculosis tracheal stenosis (PTTS). The current study was conducted to identify the risk factors for granulation tissue formation after silicone stenting in PTTS patients. A retrospective study was conducted between January 1998 and December 2010. Forty-two PTTS patients with silicone stenting were selected. Clinical and radiological variables were retrospectively collected and analyzed. Tracheal restenosis due to granulation tissue formation were found in 20 patients (47.6%), and repeated bronchoscopic interventions were conducted. In multivariate analysis, tracheal wall thickness, measured on axial computed tomography scan, was independently associated with granulation tissue formation after silicone stenting. Furthermore, the degree of tracheal wall thickness was well correlated with the degree of granulation tissue formation. Tracheal wall thickening was associated with granulation tissue formation around silicone stents in patients with post-tuberculosis tracheal stenosis.

Decreased airway narrowing and smooth muscle contraction in hyperresponsive pigs.

PubMed

Turner, Debra J; Noble, Peter B; Lucas, Matthew P; Mitchell, Howard W

2002-10-01

Increased smooth muscle contractility or reduced smooth muscle mechanical loads could account for the excessive airway narrowing and hyperresponsiveness seen in asthma. These mechanisms were investigated by using an allergen-induced porcine model of airway hyperresponsiveness. Airway narrowing to electric field stimulation was measured in isolated bronchial segments, over a range of transmural pressures (0-20 cmH(2)O). Contractile responses to ACh were measured in bronchial segments and in isolated tracheal smooth muscle strips isolated from control and test (ovalbumin sensitized and challenged) pigs. Test airways narrowed less than controls (P < 0.0001). Test pigs showed reduced contractility to ACh, both in isolated bronchi (P < 0.01) and smooth muscle strips (P < 0.01). Thus isolated airways from pigs exhibiting airway hyperresponsiveness in vivo are hyporesponsive in vitro. The decreased narrowing in bronchi from hyperresponsive pigs may be related to decreased smooth muscle contractility. These data suggest that mechanisms external to the airway wall may be important to the hyperresponsive nature of sensitized lungs.

Tracheal Wall Thickening Is Associated with the Granulation Tissue Formation Around Silicone Stents in Patients with Post-Tuberculosis Tracheal Stenosis

PubMed Central

Eom, Jung Seop; Jeon, Kyeongman; Um, Sang-Won; Koh, Won-Jung; Suh, Gee Young; Chung, Man Pyo; Kwon, O Jung

2013-01-01

Purpose Tracheal restenosis due to excessive granulation tissue around a silicone stent requires repeated bronchoscopic interventions in patients with post-tuberculosis tracheal stenosis (PTTS). The current study was conducted to identify the risk factors for granulation tissue formation after silicone stenting in PTTS patients. Materials and Methods A retrospective study was conducted between January 1998 and December 2010. Forty-two PTTS patients with silicone stenting were selected. Clinical and radiological variables were retrospectively collected and analyzed. Results Tracheal restenosis due to granulation tissue formation were found in 20 patients (47.6%), and repeated bronchoscopic interventions were conducted. In multivariate analysis, tracheal wall thickness, measured on axial computed tomography scan, was independently associated with granulation tissue formation after silicone stenting. Furthermore, the degree of tracheal wall thickness was well correlated with the degree of granulation tissue formation. Conclusion Tracheal wall thickening was associated with granulation tissue formation around silicone stents in patients with post-tuberculosis tracheal stenosis. PMID:23709431

Engineered cartilaginous tubes for tracheal tissue replacement via self-assembly and fusion of human mesenchymal stem cell constructs.

PubMed

Dikina, Anna D; Strobel, Hannah A; Lai, Bradley P; Rolle, Marsha W; Alsberg, Eben

2015-06-01

There is a critical need to engineer a neotrachea because currently there are no long-term treatments for tracheal stenoses affecting large portions of the airway. In this work, a modular tracheal tissue replacement strategy was developed. High-cell density, scaffold-free human mesenchymal stem cell-derived cartilaginous rings and tubes were successfully generated through employment of custom designed culture wells and a ring-to-tube assembly system. Furthermore, incorporation of transforming growth factor-β1-delivering gelatin microspheres into the engineered tissues enhanced chondrogenesis with regard to tissue size and matrix production and distribution in the ring- and tube-shaped constructs, as well as luminal rigidity of the tubes. Importantly, all engineered tissues had similar or improved biomechanical properties compared to rat tracheas, which suggests they could be transplanted into a small animal model for airway defects. The modular, bottom up approach used to grow stem cell-based cartilaginous tubes in this report is a promising platform to engineer complex organs (e.g., trachea), with control over tissue size and geometry, and has the potential to be used to generate autologous tissue implants for human clinical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tachykinin receptor expression and function in human esophageal smooth muscle.

PubMed

Kovac, Jason R; Chrones, Tom; Preiksaitis, Harold G; Sims, Stephen M

2006-08-01

Tachykinins are present in enteric nerves of the gastrointestinal tract and cause contraction of esophageal smooth muscle; however, the mechanisms involved are not understood. Our aim was to characterize tachykinin signaling in human esophageal smooth muscle. We investigated functional effects of tachykinins on human esophageal smooth muscle using tension recordings and isolated cells, receptor expression with reverse transcription (RT)-polymerase chain reaction (PCR) and immunoblotting, intracellular Ca2+ responses using fluorescent indicator dyes, and membrane currents with patch-clamp electrophysiology. The mammalian tachykinins [substance P and neurokinin (NK) A and NKB] elicited concentration-dependent contractions of human esophageal smooth muscle. These responses were not affected by muscarinic receptor or neuronal blockade indicating a direct effect on smooth muscle cells (SMCs). Immunofluorescence and RT-PCR identified tachykinin receptors (NK1, NK2, and NK3) on SMCs. Contraction was mediated through a combination of Ca2+ release from intracellular stores and influx through L-type Ca2+ channels. NK2 receptor blockade inhibited the largest proportion of tachykinin-evoked responses. NKA evoked a nonselective cation current (I(NSC)) with properties similar to that elicited by muscarinic stimulation. The following paradigm is suggested: tachykinin receptor binding to SMCs releases Ca2+ from stores along with activation of I(NSC), which in turn results in membrane depolarization, L-type Ca2+ channel opening, rise of Ca2+ concentration, and contraction. These studies reveal new aspects of tachykinin signaling in human esophageal SMCs. Excitatory tachykinin pathways may represent targets for pharmacological intervention in disorders of esophageal dysmotility.

The inhibitory actions of prostaglandins on respiratory smooth muscle

PubMed Central

Main, I. H. M.

1964-01-01

Prostaglandin E1, in concentrations as low as 1 ng/ml., relaxed isolated tracheal muscle from cat, monkey, rabbit, guinea-pig and ferret. Tracheal muscle from the cat, monkey and rabbit did not exhibit inherent tone and the effect of prostaglandin E1 on these preparations was seen only after a sustained contraction had been produced by a previous dose of acetylcholine or of another agonist. Prostaglandins E2, E3 and F1α also relaxed isolated cat tracheal muscle which had been stimulated by acetylcholine: their activities relative to that of prostaglandin E1 were, respectively, 1.0, 0.2 and 0.002. In the anaesthetized cat prostaglandin E1 increased lung “resistance to inflation” (presumably comparable to bronchial resistance) and the heart rate. In the anaesthetized rabbit and guinea-pig, prostaglandin E1 antagonized the rise in resistance to inflation of the lungs obtained after vagal stimulation or after the intravenous injection of histamine; it sometimes lowered the resistance to inflation in these species. The possibility that prostaglandin may have a local physiological role in the control of bronchial smooth muscle tone is discussed. ImagesFig. 5Fig. 7 PMID:14211681

THE INHIBITORY ACTIONS OF PROSTAGLANDINS ON RESPIRATORY SMOOTH MUSCLE.

PubMed

MAIN, I H

1964-06-01

Prostaglandin E(1), in concentrations as low as 1 ng/ml., relaxed isolated tracheal muscle from cat, monkey, rabbit, guinea-pig and ferret. Tracheal muscle from the cat, monkey and rabbit did not exhibit inherent tone and the effect of prostaglandin E(1) on these preparations was seen only after a sustained contraction had been produced by a previous dose of acetylcholine or of another agonist. Prostaglandins E(2), E(3) and F(1alpha) also relaxed isolated cat tracheal muscle which had been stimulated by acetylcholine: their activities relative to that of prostaglandin E(1) were, respectively, 1.0, 0.2 and 0.002. In the anaesthetized cat prostaglandin E(1) increased lung "resistance to inflation" (presumably comparable to bronchial resistance) and the heart rate. In the anaesthetized rabbit and guinea-pig, prostaglandin E(1) antagonized the rise in resistance to inflation of the lungs obtained after vagal stimulation or after the intravenous injection of histamine; it sometimes lowered the resistance to inflation in these species. The possibility that prostaglandin may have a local physiological role in the control of bronchial smooth muscle tone is discussed.

[The cause and efficacy of benign tracheal stenosis].

PubMed

Su, Zhu-quan; Wei, Xiao-qun; Zhong, Chang-hao; Chen, Xiao-bo; Luo, Wei-zhan; Guo, Wen-liang; Wang, Ying-zhi; Li, Shi-yue

2013-09-01

To analysis the causes of benign tracheal stenosis and evaluate the curative effect of intraluminal bronchoscopic treatment. 158 patients with benign tracheal stenosis in our hospital from September 2005 to September 2012 were collected to retrospectively analysis the causes and clinic features of tracheal stenosis. Interventional treatments through bronchoscopy were used to treat the benign tracheal stenosis and the curative effects were evaluated. 158 cases of benign tracheal stenosis were recruited to our study, 69.6% of them were young and middle-aged. The main causes of benign tracheal stenosis were as follows: secondary to postintubation or tracheotomy in 61.4% (97/158), tuberculosis in 16% (26/158), benign tumor in 5.1% (8/158) and other 27 cases. 94.3% patients improved in symptoms with alleviation immediately after bronchoscopic treatment, the average tracheal diameter increased form (4.22 ± 2.06) mm to (10.16 ± 2.99) mm (t = 21.48, P < 0.01), dyspnea index decreased from 2.29 ± 0.75 to 0.63 ± 0.67 (t = 19.85, P < 0.01). The recurrence rate in 1 and 3 month after interventional treatment were 38.3% and 26.8%, respectively. The cases of benign tracheal stenosis were increasing year by year. The most common cause of benign tracheal stenosis was postintubation and tracheotomy. Interventional treatments through bronchoscopy is effective in treating benign tracheal stenosis, but repeated interventional procedures may be required to maintain the favorable long-term effects.

Ultrasonographic evaluation of tracheal collapse in dogs

PubMed Central

Eom, Kidong; Moon, Kumjung; Seong, Yunsang; Oh, Taeho; Yi, Sungjoon; Lee, Keunwoo

2008-01-01

Tracheal ultrasonography was performed to measure the width of the tracheal ring shadow and to assess the clinical relevance of these measurements for identifying tracheal collapse. The first tracheal ring width (FTRW) and thoracic inlet tracheal ring width (TITRW) were measured on both expiration and inspiration. The mean of the FTRW width (129 dogs) was greater in expiration (10.97 ± 1.02 mm, p = 0.001) than that in inspiration (9.86 ± 1.03 mm). For 51 normal dogs, the mean of the TITRW width was greater in expiration (9.05 ± 1.52 mm, p = 0.001) than in inspiration (8.02 ± 1.43 mm). For 78 tracheal collapse dogs, the mean of the TITRW width was greater in expiration (15.89 ± 1.01 mm, p = 0.001) than in inspiration (14.85 ± 1.17 mm). The TITRW/FTRW ratio of the normal dogs was higher (p = 0.001) in expiration (0.81 ± 0.09) than that in inspiration (0.79 ± 0.10). When compared between the normal and tracheal collapse dogs, the TITRW/FTRW ratio was also increased (p = 0.001) both in expiration (1.54 ± 0.09) and inspiration (1.47 ± 0.08), respectively. Based on these results, the cutoff level of the TITRW/FTRW ratio was statistically analyzed according to the receiver operating characteristic curve and it could be set at 1.16 in expiration and at 1.13 in inspiration. We have demonstrated that tracheal ultrasonography is a useful technique for the evaluation of tracheal collapse and it can be a supportive tool together with the radiographic findings for making the correct diagnosis. PMID:19043316

[Microcuff pediatric tracheal tube. A new tracheal tube with a high volume-low pressure cuff for children].

PubMed

Weiss, M; Dullenkopf, A; Gerber, A C

2004-01-01

Principles and characteristics of the recently introduced Microcuff paediatric tracheal tube (Microcuff, GmbH, Weinheim, Germany) with anatomically based depth markings, cuff-free subglottic tube shaft and short high volume-low pressure cuff with ultrathin cuff membrane are presented. First available tubes (ID 4.0 mm) were evaluated regarding cuff pressures required to seal the trachea and regarding the distance from the tube tip to the carina. After obtaining approval of the local ethical committee, 20 children aged 2-4 years, receiving tracheal intubation under general anaesthesia with muscle paralysis, were included. The tubes were placed during direct laryngoscopy and the glottic depth marking placed between the vocal cords. Cuff pressure to prevent audible air leakage at standardised ventilator settings (PIP 20 cm H(2)O/PEEP 5 cm H(2)O/RR20 x min(-1)) was assessed by means of a cuff pressure manometer within 5 min after intubation. Subsequently, the distance from the tube tip to the tracheal carina was measured by means of fibre bronchoscopy. Data are presented as the median (range). Patient age was 3.0 years (2.0-3.9 years), weight 13.5 kg (9.1-19.2 kg) and body length 95 cm (79-105 cm). The lowest cuff pressure required to seal the trachea ranged from 4-14 cmH(2)O (median 10 cm H(2)O), the distance from tube tip to tracheal carina was to 2.9 cm (2.0-4.5 cm). The new Microcuff paediatric tracheal tube with ultrathin high volume-low pressure cuff required tracheal sealing pressures below tracheal wall pressures usually required with uncuffed tracheal tubes for efficient sealing and ventilation at 20 cm H(2)O peak inspiratory pressure. The distance from the tube tip to carina was in the safe range in all patients.

Myosin Light Chain Kinase Is Necessary for Tonic Airway Smooth Muscle Contraction*

PubMed Central

Zhang, Wen-Cheng; Peng, Ya-Jing; Zhang, Gen-Sheng; He, Wei-Qi; Qiao, Yan-Ning; Dong, Ying-Ying; Gao, Yun-Qian; Chen, Chen; Zhang, Cheng-Hai; Li, Wen; Shen, Hua-Hao; Ning, Wen; Kamm, Kristine E.; Stull, James T.; Gao, Xiang; Zhu, Min-Sheng

2010-01-01

Different interacting signaling modules involving Ca2+/calmodulin-dependent myosin light chain kinase, Ca2+-independent regulatory light chain phosphorylation, myosin phosphatase inhibition, and actin filament-based proteins are proposed as specific cellular mechanisms involved in the regulation of smooth muscle contraction. However, the relative importance of specific modules is not well defined. By using tamoxifen-activated and smooth muscle-specific knock-out of myosin light chain kinase in mice, we analyzed its role in tonic airway smooth muscle contraction. Knock-out of the kinase in both tracheal and bronchial smooth muscle significantly reduced contraction and myosin phosphorylation responses to K+-depolarization and acetylcholine. Kinase-deficient mice lacked bronchial constrictions in normal and asthmatic airways, whereas the asthmatic inflammation response was not affected. These results indicate that myosin light chain kinase acts as a central participant in the contractile signaling module of tonic smooth muscle. Importantly, contractile airway smooth muscles are necessary for physiological and asthmatic airway resistance. PMID:20018858

Respiratory viral infection in obliterative airway disease after orthotopic tracheal transplantation.

PubMed

Kuo, Elbert; Bharat, Ankit; Goers, Trudie; Chapman, Will; Yan, Le; Street, Tyler; Lu, Wei; Walter, Michael; Patterson, Alexander; Mohanakumar, Thalachallour

2006-09-01

The long-term survival after human lung transplantation is limited by bronchiolitis obliterans syndrome (BOS). Clinically, community-acquired respiratory viral infections have been correlated with an increased incidence of BOS. The goal of this study was to investigate the role of respiratory viral infections in chronic lung allograft rejection using the murine orthotopic tracheal transplantation model. Eighty orthotopic tracheal transplants were performed using BALB/c and C57BL/6 mice. Recipient mice were infected intranasally with Sendai virus (SdV), a murine parainfluenza type I virus. Experiments altering the infectious dose, infection time, harvest time, allogeneic response, and viral response were performed. Tracheal allograft rejection was monitored using percent fibrosis and lamina propria to cartilage ratio measurements. Interferon-gamma ELISPOT analysis against irradiated donor (BALB/c) splenocytes was used as immunologic indicator of alloreactivity after transplantation. Sendai virus infection revealed a dose-dependent transient suppression of alloreactivity with a decrease in tracheal allograft fibrosis and frequency of alloreactive T cells at 30 days. This immunosuppression was reversed by day 60, leading to increased tracheal allograft fibrosis with a concomitant increase in the frequency of interferon-gamma producing alloreactive T cells. Pretransplant sensitization with donor antigens prevented the initial suppression of alloreactivity due to SdV infection. Furthermore, pretransplant immunization against SdV infection resulted in rapid clearing of the infection and reduced the immunopathology of rejection. Respiratory viral infections can cause enhanced tracheal allograft rejection despite the initial phase of transient immunosuppression. Early treatment or vaccination against the respiratory infections may represent a viable intervention to reduce the risk of chronic rejection.

Optical metabolic imaging for monitoring tracheal health

NASA Astrophysics Data System (ADS)

Sharick, Joe T.; Gil, Daniel A.; Choma, Michael A.; Skala, Melissa C.

2016-04-01

The health of the tracheal mucosa and submucosa is a vital yet poorly understood component of critical care medicine, and a minimally-invasive method is needed to monitor tracheal health in patients. Of particular interest are the ciliated cells of the tracheal epithelium that move mucus away from the lungs and prevent respiratory infection. Optical metabolic imaging (OMI) allows cellular-level measurement of metabolism, and is a compelling method for assessing tracheal health because ciliary motor proteins require ATP to function. In this pilot study, we apply multiphoton imaging of the fluorescence intensities and lifetimes of metabolic co-enzymes NAD(P)H and FAD to the mucosa and submucosa of ex vivo mouse trachea. We demonstrate the feasibility and potential diagnostic utility of these measurements for assessing tracheal health and pathophysiology at the single-cell level.

Indications and interventional options for non-resectable tracheal stenosis

PubMed Central

Bacon, Jenny Louise; Patterson, Caroline Marie

2014-01-01

Non-specific presentation and normal examination findings in early disease often result in tracheal obstruction being overlooked as a diagnosis until patients present acutely. Once diagnosed, surgical options should be considered, but often patient co-morbidity necessitates other interventional options. Non-resectable tracheal stenosis can be successfully managed by interventional bronchoscopy, with therapeutic options including airway dilatation, local tissue destruction and airway stenting. There are common aspects to the management of tracheal obstruction, tracheomalacia and tracheal fistulae. This paper reviews the pathogenesis, presentation, investigation and management of tracheal disease, with a focus on tracheal obstruction and the role of endotracheal intervention in management. PMID:24624290

21 CFR 868.5730 - Tracheal tube.

Code of Federal Regulations, 2010 CFR

2010-04-01

... ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5730 Tracheal tube. (a) Identification. A tracheal tube is a device inserted into a patient's trachea via the nose or mouth and used to maintain an open airway. (b...

Endoscopically placed nitinol stents for pediatric tracheal obstruction.

PubMed

Prasad, Mukesh; Bent, John P; Ward, Robert F; April, Max M

2002-11-11

To provide preliminary clinical data regarding endoscopically placed nitinol stents for children with tracheal obstruction as a temporizing measure to allow for trach tube decannulation while awaiting growth to allow for tracheal resection. This case series describes the experiences of two children (ages 5 and 15) who were dependent upon tracheotomy because of acquired tracheal obstruction. Both patients had combined tracheomalacia and tracheal stenosis. After failing tracheoplasty with rib graft augmentation both patients suffered from extensive tracheal disease, which was too long to allow for immediate tracheal resection. Endoscopic placement of nitinol stents in the obstructed tracheal segment using fluoroscopic guidance. All tracheotomy tubes were removed immediately after successful stent deployment with the patient still under general anesthesia. Four stents were placed in total. The first patient's initial stent was too narrow and was, therefore, removed and replaced at a later date with a larger diameter stent. The second patient experienced distal migration of his initial stent requiring stent removal and replacement at a later date. Both patients remain successfully decannulated (follow-up, 25 and 26 months) and are currently living more normal lives as they grow and await tracheal resection. Preliminary use of nitinol stents for pediatric tracheal obstruction has enabled successful decannulation in two children with complicated airways. Our results with this series of patients suggest that nitinol stents can be safely used in children as a temporizing measure until tracheal resection can be safely performed. With this approach children can live free from the hassles of trach care, social isolation and peer ridicule. Limited pediatric experience exists in the literature about nitinol stents. Thus, our experience with stent selection and placement will help others avoid problems encountered in this initial series. Copyright 2002 Elsevier Science Ireland

Effect of fenoterol-induced constitutive beta(2)-adrenoceptor activity on contractile receptor function in airway smooth muscle.

PubMed

de Vries, B; Roffel, A F; Zaagsma, J; Meurs, H

2001-11-23

In the present study, we investigated the effect of fenoterol-induced constitutive beta(2)-adrenoceptor activity on muscarinic receptor agonist- and histamine-induced bovine tracheal smooth muscle contractions. Bovine tracheal smooth muscle strips were incubated with 10 microM fenoterol or vehicle for various periods of time (5, 30 min, 18 h) at 37 degrees C. After extensive washout (3 h, 37 degrees C), isometric contractions were measured to the full muscarinic receptor agonist methacholine, the partial muscarinic receptor agonist 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium (McN-A-343) and histamine. Fenoterol treatment significantly reduced the sensitivity (pEC(50)) to methacholine in a time-dependent manner, without affecting maximal contraction (E(max)). Fenoterol treatment similarly reduced the pEC(50) of McN-A-343 and histamine; however, E(max) values were also reduced, to approximately 70% of control after 18-h treatment. The inverse agonist timolol, having no effect on control preparations, consistently restored the reduced pEC(50) and E(max) values of the contractile agonists. Remarkably, in the presence of timolol the pEC(50) values of McN-A-343 and histamine in fenoterol-treated airways were significantly enhanced compared to controls. In conclusion, fenoterol-induced constitutive beta(2)-adrenoceptor activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist timolol. Moreover, after beta(2)-adrenoceptor agonist treatment, inverse agonism by beta-adrenoceptor antagonists may cause enhanced airway reactivity to contractile mediators.

Implantation of Induced Pluripotent Stem Cell-Derived Tracheal Epithelial Cells.

PubMed

Ikeda, Masakazu; Imaizumi, Mitsuyoshi; Yoshie, Susumu; Nakamura, Ryosuke; Otsuki, Koshi; Murono, Shigeyuki; Omori, Koichi

2017-07-01

Compared with using autologous tissue, the use of artificial materials in the regeneration of tracheal defects is minimally invasive. However, this technique requires early epithelialization on the inner side of the artificial trachea. After differentiation from induced pluripotent stem cells (iPSCs), tracheal epithelial tissues may be used to produce artificial tracheas. Herein, we aimed to demonstrate that after differentiation from fluorescent protein-labeled iPSCs, tracheal epithelial tissues survived in nude rats with tracheal defects. Red fluorescent tdTomato protein was electroporated into mouse iPSCs to produce tdTomato-labeled iPSCs. Embryoid bodies derived from these iPSCs were then cultured in differentiation medium supplemented with growth factors, followed by culture on air-liquid interfaces for further differentiation into tracheal epithelium. The cells were implanted with artificial tracheas into nude rats with tracheal defects on day 26 of cultivation. On day 7 after implantation, the tracheas were exposed and examined histologically. Tracheal epithelial tissue derived from tdTomato-labeled iPSCs survived in the tracheal defects. Moreover, immunochemical analyses showed that differentiated tissues had epithelial structures similar to those of proximal tracheal tissues. After differentiation from iPSCs, tracheal epithelial tissues survived in rat bodies, warranting the use of iPSCs for epithelial regeneration in tracheal defects.

Tracheal Tube Design and Ventilator-Associated Pneumonia.

PubMed

Rouzé, Anahita; Jaillette, Emmanuelle; Poissy, Julien; Préau, Sébastien; Nseir, Saad

2017-10-01

Microaspiration of contaminated oropharyngeal and gastric secretions is the main mechanism for ventilator-associated pneumonia (VAP) in critically ill patients. Improving the performance of tracheal tubes in reducing microaspiration is one potential means to prevent VAP. The aim of this narrative review is to discuss recent findings on the impact of tracheal tube design on VAP prevention. Several randomized controlled studies have reported that subglottic secretion drainage (SSD) is efficient in VAP prevention. Meta-analyses have reported conflicting results regarding the impact of SSD on duration of mechanical ventilation, and one animal study raised concern about SSD-related tracheal lesions. However, this measure appears to be cost-effective. Therefore, SSD should probably be used in all patients with expected duration of mechanical ventilation > 48 h. Three randomized controlled trials have shown that tapered-cuff tracheal tubes are not useful to prevent VAP and should probably not be used in critically ill patients. Further studies are required to confirm the promising effects of continuous control of cuff pressure, polyurethane-cuffed, silver-coated, and low-volume low-pressure tracheal tubes. There is moderate evidence for the use of SSD and strong evidence against the use of tapered-cuff tracheal tubes in critically ill patients for VAP prevention. However, more data on the safety and cost-effectiveness of these measures are needed. Other tracheal tube-related preventive measures require further investigation. Copyright © 2017 by Daedalus Enterprises.

Nuclear fusion-independent smooth muscle differentiation of human adipose-derived stem cells induced by a smooth muscle environment.

PubMed

Zhang, Rong; Jack, Gregory S; Rao, Nagesh; Zuk, Patricia; Ignarro, Louis J; Wu, Benjamin; Rodríguez, Larissa V

2012-03-01

Human adipose-derived stem cells hASC have been isolated and were shown to have multilineage differentiation capacity. Although both plasticity and cell fusion have been suggested as mechanisms for cell differentiation in vivo, the effect of the local in vivo environment on the differentiation of adipose-derived stem cells has not been evaluated. We previously reported the in vitro capacity of smooth muscle differentiation of these cells. In this study, we evaluate the effect of an in vivo smooth muscle environment in the differentiation of hASC. We studied this by two experimental designs: (a) in vivo evaluation of smooth muscle differentiation of hASC injected into a smooth muscle environment and (b) in vitro evaluation of smooth muscle differentiation capacity of hASC exposed to bladder smooth muscle cells. Our results indicate a time-dependent differentiation of hASC into mature smooth muscle cells when these cells are injected into the smooth musculature of the urinary bladder. Similar findings were seen when the cells were cocultured in vitro with primary bladder smooth muscle cells. Chromosomal analysis demonstrated that microenvironment cues rather than nuclear fusion are responsible for this differentiation. We conclude that cell plasticity is present in hASCs, and their differentiation is accomplished in the absence of nuclear fusion. Copyright © 2011 AlphaMed Press.

Chloride channel blockade relaxes airway smooth muscle and potentiates relaxation by β-agonists

PubMed Central

Yim, Peter; Rinderspacher, Alison; Fu, Xiao Wen; Zhang, Yi; Landry, Donald W.; Emala, Charles W.

2014-01-01

Severe bronchospasm refractory to β-agonists continues to cause significant morbidity and mortality in asthmatic patients. We questioned whether chloride channels/transporters are novel targets for the relaxation of airway smooth muscle (ASM). We have screened a library of compounds, derivatives of anthranilic and indanyloxyacetic acid, that were originally developed to antagonize chloride channels in the kidney. We hypothesized that members of this library would be novel calcium-activated chloride channel blockers for the airway. The initial screen of this compound library identified 4 of 20 compounds that relaxed a tetraethylammonium chloride-induced contraction in guinea pig tracheal rings. The two most effective compounds, compounds 1 and 13, were further studied for their potential to either prevent the initiation of or relax the maintenance phase of an acetylcholine (ACh)-induced contraction or to potentiate β-agonist-mediated relaxation. Both relaxed an established ACh-induced contraction in human and guinea pig ex vivo ASM. In contrast, the prevention of an ACh-induced contraction required copretreatment with the sodium-potassium-chloride cotransporter blocker bumetanide. The combination of compound 13 and bumetanide also potentiated relaxation by the β-agonist isoproterenol in guinea pig tracheal rings. Compounds 1 and 13 hyperpolarized the plasma cell membrane of human ASM cells and blocked spontaneous transient inward currents, a measure of chloride currents in these cells. These functional and electrophysiological data suggest that modulating ASM chloride flux is a novel therapeutic target in asthma and other bronchoconstrictive diseases. PMID:24879056

Immediate, short‐, and long‐term changes in tracheal stent diameter, length, and positioning after placement in dogs with tracheal collapse syndrome

PubMed Central

Raske, Matthew; Berent, Allyson C.; McDougall, Renee; Lamb, Kenneth

2018-01-01

Background Intraluminal tracheal stenting is a minimally invasive procedure shown to have variable degrees of success in managing clinical signs associated with tracheal collapse syndrome (CTCS) in dogs. Objectives Identify immediate post‐stent changes in tracheal diameter, determine the extent of stent migration, and stent shortening after stent placement in the immediate‐, short‐, and long‐term periods, and evaluate inter‐observer reliability of radiographic measurements. Animals Fifty client‐owned dogs. Methods Retrospective study in which medical records were reviewed in dogs with CTCS treated with an intraluminal tracheal stent. Data collected included signalment, location, and type of collapse, stent diameter and length, and post‐stent placement radiographic follow‐up times. Radiographs were used to obtain pre‐stent tracheal measurements and post‐stent placement measurements. Results Immediate mean percentage change was 5.14%, 5.49%, and 21.64% for cervical, thoracic inlet, and intra‐thoracic tracheal diameters, respectively. Ultimate mean follow‐up time was 446 days, with mean percentage change of 2.55%, 15.09%, and 8.65% for cervical, thoracic inlet, and intra‐thoracic tracheal diameters, respectively. Initial mean stent length was 26.72% higher than nominal length and ultimate long‐term tracheal mean stent shortening was only 9.90%. No significant stent migration was identified in the immediate, short‐, or long‐term periods. Good inter‐observer agreement of radiographic measurements was found among observers of variable experience level. Conclusions and Clinical Importance Use of an intraluminal tracheal stent for CTCS is associated with minimal stent shortening with no clinically relevant stent migration after fluoroscopic placement. Precise stent sizing and placement techniques likely play important roles in avoiding these reported complications. PMID:29460368

The fate of homograft tracheal transplants in sheep.

PubMed

Behrend, Matthias; Kluge, Eva

2008-08-01

An established method of tracheal substitution is not yet available, but homograft tracheal transplantation might provide a realistic tracheal replacement. With the objective of sequentially examining the healing of tracheal homografts, we have established a suitable large-animal model. Five sheep received orthotopic tracheal transplantation of a 4-cm cervical tracheal homograft. The trachea was supported for 6 weeks with a self-expanding polyester stent. The plan was to euthanize the animals after 2, 4, 8, 12 and 16 weeks, or whenever complications occurred. The implantation itself was performed without complications. After 2 weeks the homograft was firmly encapsulated by connective tissue, without signs of necrosis or abscess. The original mucous membrane no longer existed; the cartilage rings were exposed. In all animals that were euthanized at the later dates, the homografts were completely absorbed and replaced by inflammatory scar tissue. This, in turn, was covered with a shiny cellular surface layer. The results from this animal experiment reveal-contrary to data published to date-that tracheal homografts are not incorporated but absorbed. They are replaced by scar/granulation tissue that cannot secure the stability of the trachea. Therefore, further experiments with respect to the biocompatability of homografts appear to be necessary.

Neurogenic vasoreactive response of human internal thoracic artery smooth muscle.

PubMed

Canver, C C; Cooler, S D; Saban, R

1997-09-01

The interaction between primary afferent neurons containing neuropeptides and the vascular smooth muscle is incompletely understood. To explore the function of perivascular afferent neurons and to determine whether they produce local effects on vascular smooth muscle cells, we investigated the effects of acute capsaicin and substance P administration in vitro on human internal thoracic arteries (ITA). Vessels were obtained from patients undergoing coronary bypass or from multiorgan transplant donors. Fourteen ITA segments (5 mm wide) were suspended as rings between two stainless-steel stirrups in water-jacketed (37 degrees C) tissue baths under 2.5 to 3 g of basal tension. The tissue baths contained 10 mL physiological salt solution (PSS) of the following composition (mM): NaCl, 119; KCl, 4.7; NaH2PO4, 1.0; MgCl2, 0.5; CaCl2, 2.5; NaHCO3, 25; and glucose, 11; aerated continuously with 95% O2 and 5% CO2. Peptidase inhibitors (phosphoramidon and captopril) were added to PSS to decrease peptide degradation. Mechanical responses were measured isometrically and recorded on a polygraph via isotonic force transducers. Vessels were preconstricted with submaximal concentrations of norepinephrine. After the tension had stabilized, substance P or capsaicin was added cumulatively to the tissue bath. At the end of the experiments, the viability of ITA was verified by its responses to endothelial-dependent (acetylcholine) and endothelial-independent (sodium nitroprusside) vasodilators. In the endothelium-intact ITA segments, substance P produced relaxation of ITA smooth muscle while it induced slight contraction when the ITA was devoid of its endothelium (P = 0.0585). The addition of capsaicin to human ITA primarily produced contractile effects on the developed smooth muscle force. The capsaicin-induced contraction of the ITA smooth muscle was independent of endothelial cell integrity, although contraction was greater in the endothelium-intact ITA segments (P = 0.0165). The

Synchrotron imaging of the grasshopper tracheal system : morphological and physiological components of tracheal hypermetry.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greenlee, K. J.; Henry, J. R.; Kirkton, S. D.

2009-11-01

As grasshoppers increase in size during ontogeny, they have mass specifically greater whole body tracheal and tidal volumes and ventilation than predicted by an isometric relationship with body mass and body volume. However, the morphological and physiological bases to this respiratory hypermetry are unknown. In this study, we use synchrotron imaging to demonstrate that tracheal hypermetry in developing grasshoppers (Schistocerca americana) is due to increases in air sacs and tracheae and occurs in all three body segments, providing evidence against the hypothesis that hypermetry is due to gaining flight ability. We also assessed the scaling of air sac structure andmore » function by assessing volume changes of focal abdominal air sacs. Ventilatory frequencies increased in larger animals during hypoxia (5% O{sub 2}) but did not scale in normoxia. For grasshoppers in normoxia, inflated and deflated air sac volumes and ventilation scaled hypermetrically. During hypoxia (5% O{sub 2}), many grasshoppers compressed air sacs nearly completely regardless of body size, and air sac volumes scaled isometrically. Together, these results demonstrate that whole body tracheal hypermetry and enhanced ventilation in larger/older grasshoppers are primarily due to proportionally larger air sacs and higher ventilation frequencies in larger animals during hypoxia. Prior studies showed reduced whole body tracheal volumes and tidal volume in late-stage grasshoppers, suggesting that tissue growth compresses air sacs. In contrast, we found that inflated volumes, percent volume changes, and ventilation were identical in abdominal air sacs of late-stage fifth instar and early-stage animals, suggesting that decreasing volume of the tracheal system later in the instar occurs in other body regions that have harder exoskeleton.« less

Immediate, short-, and long-term changes in tracheal stent diameter, length, and positioning after placement in dogs with tracheal collapse syndrome.

PubMed

Raske, Matthew; Weisse, Chick; Berent, Allyson C; McDougall, Renee; Lamb, Kenneth

2018-03-01

Intraluminal tracheal stenting is a minimally invasive procedure shown to have variable degrees of success in managing clinical signs associated with tracheal collapse syndrome (CTCS) in dogs. Identify immediate post-stent changes in tracheal diameter, determine the extent of stent migration, and stent shortening after stent placement in the immediate-, short-, and long-term periods, and evaluate inter-observer reliability of radiographic measurements. Fifty client-owned dogs. Retrospective study in which medical records were reviewed in dogs with CTCS treated with an intraluminal tracheal stent. Data collected included signalment, location, and type of collapse, stent diameter and length, and post-stent placement radiographic follow-up times. Radiographs were used to obtain pre-stent tracheal measurements and post-stent placement measurements. Immediate mean percentage change was 5.14%, 5.49%, and 21.64% for cervical, thoracic inlet, and intra-thoracic tracheal diameters, respectively. Ultimate mean follow-up time was 446 days, with mean percentage change of 2.55%, 15.09%, and 8.65% for cervical, thoracic inlet, and intra-thoracic tracheal diameters, respectively. Initial mean stent length was 26.72% higher than nominal length and ultimate long-term tracheal mean stent shortening was only 9.90%. No significant stent migration was identified in the immediate, short-, or long-term periods. Good inter-observer agreement of radiographic measurements was found among observers of variable experience level. Use of an intraluminal tracheal stent for CTCS is associated with minimal stent shortening with no clinically relevant stent migration after fluoroscopic placement. Precise stent sizing and placement techniques likely play important roles in avoiding these reported complications. Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Tissue-engineered tracheal reconstruction using three-dimensionally printed artificial tracheal graft: preliminary report.

PubMed

Chang, Jae Won; Park, Su A; Park, Ju-Kyeong; Choi, Jae Won; Kim, Yoo-Suk; Shin, Yoo Seob; Kim, Chul-Ho

2014-06-01

Three-dimensional printing has come into the spotlight in the realm of tissue engineering. We intended to evaluate the plausibility of 3D-printed (3DP) scaffold coated with mesenchymal stem cells (MSCs) seeded in fibrin for the repair of partial tracheal defects. MSCs from rabbit bone marrow were expanded and cultured. A half-pipe-shaped 3DP polycaprolactone scaffold was coated with the MSCs seeded in fibrin. The half-pipe tracheal graft was implanted on a 10 × 10-mm artificial tracheal defect in four rabbits. Four and eight weeks after the operation, the reconstructed sites were evaluated bronchoscopically, radiologically, histologically, and functionally. None of the four rabbits showed any sign of respiratory distress. Endoscopic examination and computed tomography showed successful reconstruction of trachea without any collapse or blockage. The replaced tracheas were completely covered with regenerated respiratory mucosa. Histologic analysis showed that the implanted 3DP tracheal grafts were successfully integrated with the adjacent trachea without disruption or granulation tissue formation. Neo-cartilage formation inside the implanted graft was sufficient to maintain the patency of the reconstructed trachea. Scanning electron microscope examination confirmed the regeneration of the cilia, and beating frequency of regenerated cilia was not different from those of the normal adjacent mucosa. The shape and function of reconstructed trachea using 3DP scaffold coated with MSCs seeded in fibrin were restored successfully without any graft rejection. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

A simple in vitro culture system for tracheal cartilage development.

PubMed

Park, Jinhyung; Zhang, Jennifer J R; Choi, Ruth; Trinh, Irene; Kim, Peter C W

2010-02-01

Semi-circular tracheal cartilage is a critical determinant of maintaining architectural integrity of the respiratory airway. The current effort to understand the morphogenesis of tracheal cartilage is challenged by the lack of appropriate model systems. Here we report an in vitro tracheal cartilage system using embryonic tracheal–lung explants to recapitulate in vivo tracheal cartilage developmental processes. With modifications of a current lung culture protocol, we report a consistent in vitro technique of culturing tracheal cartilage from primitive mouse embryonic foregut for the first time. This tracheal culture system not only induces the formation of tracheal cartilage from the mouse embryonic foregut but also allows for the proper patterning of the developed tracheal cartilage. Furthermore, we show that this culture technique can be applied to culturing other types of cartilage in vertebrae, limbs, and ribs. We believe that this novel application of our in vitro culture system will facilitate the manipulation of cartilage development under various conditions and thus enabling us to advance our current limited knowledge on cartilage biology and development.

Effects of premedication with oral gabapentin on intraocular pressure changes following tracheal intubation in clinically normal dogs.

PubMed

Trbolova, Alexandra; Ghaffari, Masoud Selk; Capik, Igor

2017-09-19

Gabapentin is an antiepileptic drug widely approved as an add-on therapy for epilepsy treatment in human and dogs. There is a clinical impression that gabapentin is a suitable drug which attenuates the IOP elevation associated with tracheal intubation in humans. The present study performed to determine the effects of oral gabapentin on intraocular pressure (IOP) changes following tracheal intubation in dogs. Twenty adult healthy dogs were randomly assigned to treatment (n = 10) and control (n = 10) groups. Dogs in the treatment group received oral gabapentin (50 mg/kg) 2 h before induction of anesthesia and dogs in the control group received oral gelatin capsule placebo at the same time. The dogs were anesthetized with propofol 6 mg/kg, and anesthesia was maintained with a constant infusion of 0.2 mg/kg/min of propofol for 20 min. IOP were measured immediately before induction and then repeated immediately after induction, as well as 5 min, 10 min and 15 min following tracheal intubation in both groups. IOP was significantly higher immediately after induction, and 5 min after tracheal intubation when compared with IOP reading before induction in the control group. There was no statistically significant change in IOPs immediately after induction, and 5 min after tracheal intubation in comparison to the values before induction in the treatment group. Based on the findings of this study, preanesthetic oral administration of gabapentin significantly prevents an increase in the IOP associated with tracheal intubation in dogs anesthetized with propofol.

Visualisation of insect tracheal systems by lactic acid immersion.

PubMed

Ruan, Y; Li, Y; Zhang, M; Chen, X; Liu, Z; Wang, S; Jiang, S

2018-05-15

The endeavours to reveal the tracheal system of insects and some arachnids has a long history. The traditional way to observe a tracheal system in an insect body is by utilising the glycerin immersion method. In this study, we developed the lactic acid immersion method, which reveals a more complete tracheal system. By mounting various types of live specimens or body parts directly into lactic acid, multiple intact and complex tracheal systems were clearly visualised. The lactic acid immersion contributed to revealing tracheal systems by penetrating body tissue while reserving enough time for observation before the penetration of the tracheae. Preliminary comparisons were conducted between lactic acid and other mediae, including glycerin. It turned out that lactic acid immersion provides better details and more distinct structures. In our test, the optimal time for observing the tracheal system was 10-25 min after the organism was immersed in lactic acid. © 2018 The Authors Journal of Microscopy © 2018 Royal Microscopical Society.

A canine model of tracheal stenosis induced by cuffed endotracheal intubation

PubMed Central

Su, Zhuquan; Li, Shiyue; Zhou, Ziqing; Chen, Xiaobo; Gu, Yingying; Chen, Yu; Zhong, Changhao; Zhong, Minglu; Zhong, Nanshan

2017-01-01

Postintubation tracheal stenosis is a complication of endotracheal intubation. The pathological mechanism and risk factors for endotracheal intubation-induced tracheal stenosis remain not fully understood. We aimed to establish an animal model and to investigate risk factors for postintubation tracheal stenosis. Beagles were intubated with 4 sized tubes (internal diameter 6.5 to 8.0 mm) and cuff pressures of 100 to 200 mmHg for 24 hr. The status of tracheal wall was evaluated by bronchoscopic and histological examinations. The model was successfully established by cuffed endotracheal intubation using an 8.0 mm tube and an intra-cuff pressure of 200 mmHg for 24 hr. When the intra-cuff pressures were kept constant, a larger sized tube would induce a larger tracheal wall pressure and more severe injury to the tracheal wall. The degree of tracheal stenosis ranged from 78% to 91% at 2 weeks postextubation. Histological examination demonstrated submucosal infiltration of inflammatory cells, hyperplasia of granulation tissue and collapse of tracheal cartilage. In summary, a novel animal model of tracheal stenosis was established by cuffed endotracheal intubation, whose histopathological feathers are similar to those of clinical cases of postintubation tracheal stenosis. Excessive cuff pressure and over-sized tube are the risk factors for postintubation tracheal stenosis. PMID:28349955

Endogenous gamma-aminobutyric acid modulates tonic guinea pig airway tone and propofol-induced airway smooth muscle relaxation.

PubMed

Gallos, George; Gleason, Neil R; Virag, Laszlo; Zhang, Yi; Mizuta, Kentaro; Whittington, Robert A; Emala, Charles W

2009-04-01

Emerging evidence indicates that an endogenous autocrine/paracrine system involving gamma-aminobutyric acid (GABA) is present in airways. GABAA channels, GABAB receptors, and the enzyme that synthesizes GABA have been identified in airway epithelium and smooth muscle. However, the endogenous ligand itself, GABA, has not been measured in airway tissues. The authors sought to demonstrate that GABA is released in response to contractile agonists and tonically contributes a prorelaxant component to contracted airway smooth muscle. The amount and cellular localization of GABA in upper guinea pig airways under resting and contracted tone was determined by high pressure liquid chromatography and immunohistochemistry, respectively. The contribution that endogenous GABA imparts on the maintenance of airway smooth muscle acetylcholine-induced contraction was assessed in intact guinea pig airway tracheal rings using selective GABAA antagonism (gabazine) under resting or acetylcholine-contracted conditions. The ability of an allosteric agent (propofol) to relax a substance P-induced relaxation in an endogenous GABA-dependent manner was assessed. GABA levels increased and localized to airway smooth muscle after contractile stimuli in guinea pig upper airways. Acetylcholine-contracted guinea pig tracheal rings exhibited an increase in contracted force upon addition of the GABAA antagonist gabazine that was subsequently reversed by the addition of the GABAA agonist muscimol. Propofol dose-dependently relaxed a substance P contraction that was blocked by gabazine. These studies demonstrate that GABA is endogenously present and increases after contractile stimuli in guinea pig upper airways and that endogenous GABA contributes a tonic prorelaxant component in the maintenance of airway smooth muscle tone.

Endogenous γ-aminobutyric Acid Modulates Tonic Guinea Pig Airway Tone and Propofol-induced Airway Smooth Muscle Relaxation

PubMed Central

Gallos, George; Gleason, Neil R.; Virag, Laszlo; Zhang, Yi; Mizuta, Kentauro; Whittington, Robert A.; Emala, Charles W.

2009-01-01

Background Emerging evidence indicates that an endogenous autocrine/paracrine system involving γ-aminobutyric acid (GABA) is present in airways. GABAA channels, GABAB receptors and the enzyme that synthesizes GABA have been identified in airway epithelium and smooth muscle. However, the endogenous ligand itself, GABA, has not been measured in airway tissues. We sought to demonstrate that GABA is released in response to contractile agonists and tonically contributes a pro-relaxant component to contracted airway smooth muscle. Methods The amount and cellular localization of GABA in upper guinea pig airways under resting and contracted tone was determined by high pressure liquid chromatography and immunohistochemistry, respectively. The contribution that endogenous GABA imparts on the maintenance of airway smooth muscle acetylcholine-induced contraction was assessed in intact guinea pig airway tracheal rings using selective GABAA antagonism (gabazine) under resting or acetylcholine-contracted conditions. The ability of an allosteric agent (propofol) to relax a substance P-induced relaxation in an endogenous GABA-dependent manner was assessed. Results GABA levels increased and localized to airway smooth muscle following contractile stimuli in guinea pig upper airways. Acetylcholine-contracted guinea pig tracheal rings exhibited an increase in contracted force upon addition of the GABAA antagonist gabazine which was subsequently reversed by the addition of the GABAA agonist muscimol. Propofol dose-dependently relaxed a substance P contraction that was blocked by gabazine. Conclusion These studies demonstrate that GABA is endogenously present and increases following contractile stimuli in guinea pig upper airways and that endogenous GABA contributes a tonic pro-relaxant component in the maintenance of airway smooth muscle tone. PMID:19322939

Successful silicon stent for life-threatening tracheal wall laceration.

PubMed

Yamamoto, Shinichi; Endo, Shunsuke; Endo, Tetsuya; Mitsuda, Sayaka

2013-01-01

We report an 86-year-old woman with a large tracheal laceration caused by tracheal intubation at cardiopulmonary arrest who underwent a successful stent procedure. Tracheal laceration developed in the membranous portion longitudinally 6 cm in length to 2 cm above the carina. Following 9 days' tracheal intubation, a Y-shaped silicon stent was inserted over the lacerated trachea. Four months after the stenting procedure, we removed the Y-shaped silicon stent from the healed membranous wall. The patient returned to daily life without requiring thoracotomy.

The dopamine D1 receptor is expressed and facilitates relaxation in airway smooth muscle.

PubMed

Mizuta, Kentaro; Zhang, Yi; Xu, Dingbang; Mizuta, Fumiko; D'Ovidio, Frank; Masaki, Eiji; Emala, Charles W

2013-09-02

Dopamine signaling is mediated by Gs protein-coupled "D1-like" receptors (D1 and D5) and Gi-coupled "D2-like" receptors (D2-4). In asthmatic patients, inhaled dopamine induces bronchodilation. Although the Gi-coupled dopamine D2 receptor is expressed and sensitizes adenylyl cyclase activity in airway smooth muscle (ASM) cells, the Gs-coupled dopamine D1-like receptor subtypes have never been identified on these cells. Activation of Gs-coupled receptors stimulates cyclic AMP (cAMP) production through the stimulation of adenylyl cyclase, which promotes ASM relaxation. We questioned whether the dopamine D1-like receptor is expressed on ASM, and modulates its function through Gs-coupling. The mRNA and protein expression of dopamine D1-like receptor subtypes in both native human and guinea pig ASM tissue and cultured human ASM (HASM) cells was measured. To characterize the stimulation of cAMP through the dopamine D1 receptor, HASM cells were treated with dopamine or the dopamine D1-like receptor agonists (A68930 or SKF38393) before cAMP measurements. To evaluate whether the activation of dopamine D1 receptor induces ASM relaxation, guinea pig tracheal rings suspended under isometric tension in organ baths were treated with cumulatively increasing concentrations of dopamine or A68930, following an acetylcholine-induced contraction with or without the cAMP-dependent protein kinase (PKA) inhibitor Rp-cAMPS, the large-conductance calcium-activated potassium (BKCa) channel blocker iberiotoxin, or the exchange proteins directly activated by cAMP (Epac) antagonist NSC45576. Messenger RNA encoding the dopamine D1 and D5 receptors were detected in native human ASM tissue and cultured HASM cells. Immunoblots confirmed the protein expression of the dopamine D1 receptor in both native human and guinea pig ASM tissue and cultured HASM cells. The dopamine D1 receptor was also immunohistochemically localized to both human and guinea pig ASM. The dopamine D1-like receptor agonists

Management of esophageal stenting-associated esophagotracheal fistula, tracheal stenosis and tracheal rupture: a case report and review of the literature.

PubMed

Ji, Fanceng; Nie, Peihe; Yi, Fuxia; Zhang, Limin

2015-01-01

Although the placement of esophageal self-expandable stents (SES) can effectively relieve dysphagia after radiotherapy in patients with esophageal cancer (EC), it may induce severe esophageal complications. This article reports a case of emergency endotracheal intubation in an EC patient who suddenly developed severe dyspnea two months after SES placement. Electronic bronchoscopy of the patient's airway confirmed the diagnosis of esophagotracheal fistula, tracheal stenosis and tracheal rupture. Endotracheal intubation was successfully performed under the guidance of electronic bronchoscopy. Dyspnea due to tracheal stenosis was relieved effectively by inserting the tracheal catheter to a proper place under the guidance of electronic bronchoscopy. Bronchoscopic examination is strongly recommended in EC patients who are highly suspected as having airway stenosis associated with esophageal stenting, for which endotracheal intubation under the guidance of bronchoscopy is suggested.

Corkscrew trachea: a novel type of congenital tracheal stenosis.

PubMed

Bryant, Roosevelt; Morales, David L S

2009-06-01

The classic definition of congenital tracheal stenosis includes the presence of complete tracheal rings with absence of the membranous portion of the trachea. The morphologic type, based on Cantrell's classification, dictates the surgical management. In this report, we describe the presentation and surgical management of a novel type of distal congenital tracheal stenosis referred to as "corkscrew" trachea.

Endothelin ETA receptor expression in human cerebrovascular smooth muscle cells.

PubMed

Yu, J C; Pickard, J D; Davenport, A P

1995-11-01

1. Endothelin (ET) has been implicated in cerebrovasospasm for example, following subarachnoid haemorrhage, and blocking the interaction of ET with its receptors on cerebral vessels, may be of therapeutic benefit. The aim of our study was to characterize endothelin receptor sub-types on medial smooth muscle cells of human cerebral vessels. Cultures of vascular smooth muscle cells were explanted from human cerebral resistance vessels and characterized as human brain smooth muscle cells (HBSMCs). 2. Over a 48 h incubation period, HBSMC cultures secreted comparable levels of immunoreactive (IR) big endothelin-1 (big ET-1) and IR endothelin (ET): 12.7 +/- 10.3 and 8.3 +/- 5.6 pmol/10(6) cells, respectively (mean +/- s.e. mean from three different individuals), into the culture medium. 3. Total RNA was extracted from cultures of human brain smooth muscle cells. Reverse-transcriptase polymerase chain reaction (RI-PCR) assays and subsequent product separation by agarose gel electrophoresis revealed single bands corresponding to the expected product sizes encoding cDNA for ETA (299 base pairs) and ETB (428 base pairs) (n = 3 different cultures). 4. Autoradiography demonstrated the presence of specific binding sites for [125I]-ET-1 which labels all ET receptors, and [125I]-PD151242, an ETA subtype-selective antagonist which exclusively labels ETA receptors, but no specific-binding was detected using ETB subtype-selective [125I]-BQ3020 (n = 3 different cultures, in duplicate). 5. In saturation binding assays, [123I]-ET-1 bound with high affinity: KD = 0.8 +/- 0.1 nM and Bmax = 690 +/- 108 fmol mg-1. A one-site fit was preferred and Hill slopes were close to unity over the concentration range (10(-12) to 10(-8) M). [125I]-PD151242 also bound with similar affinity: KD = 0.4 +/- 0.1 nM and Bmax = 388 +/- 68 fmol mg-1 (mean +/- s.e. mean, n = 3 different cultures). Again, a one-site fit was preferred and Hill slopes were close to unity over the concentration range. Unlabelled PD

21 CFR 868.5750 - Inflatable tracheal tube cuff.

Code of Federal Regulations, 2010 CFR

2010-04-01

... cuff. (a) Identification. An inflatable tracheal tube cuff is a device used to provide an airtight seal between a tracheal tube and a patient's trachea. (b) Classification. Class II (performance standards). ...

Bronchoscopic Treatment in the Management of Benign Tracheal Stenosis: Choices for Simple and Complex Tracheal Stenosis.

PubMed

Dalar, Levent; Karasulu, Levent; Abul, Yasin; Özdemir, Cengiz; Sökücü, Sinem Nedime; Tarhan, Merve; Altin, Sedat

2016-04-01

Bronchoscopic treatment is 1 of the treatment choices for both palliative and definitive treatment of benign tracheal stenosis. There is no consensus on the management of these patients, however, especially patients having complex stenoses. The aim of the present study was to assess, in the largest group of patients with complex stenoses yet reported, which types of tracheal stenosis are amenable to optimal management by bronchoscopic treatment. The present study was a retrospective cohort study including 132 consecutive patients with benign tracheal stenoses diagnosed between August 2005 and January 2013. The mean age of the study population was 52 ± 18 years; 62 (47%) were women and 70 (53%) were men. Their lesions were classified as simple and complex stenoses. Simple stenoses (n = 6) were treated with 12 rigid and flexible bronchoscopic procedures (mean of 2 per patient); 5 stents were placed. The total success rate was 100%. Among the 124 complex stenoses, 4 were treated directly with surgical intervention. In total, 481 rigid and 487 flexible bronchoscopic procedures were performed in these patients. In this group, the success rate was 69.8%. From the present study, we propose that after accurate classification, interventional bronchoscopic management may have an important role in the treatment of benign tracheal stenosis. Bronchoscopic treatment should be considered as first-line therapy for simple stenoses, whereas complex stenoses need a multidisciplinary approach and often require surgical intervention. However, bronchoscopic treatment may be a valid conservative approach in the management of patients with complex tracheal stenosis who are not eligible for operative treatment. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Tracheal agenesis in a new born: lessons learnt.

PubMed

Naina, P; John, Mary; Kathar, Mohamed Abdul; Kumar, Manish

2018-06-17

Tracheal agenesis is a rare but fatal congenital tracheal malformation. Lack of prenatal symptom and a typical clinical presentation lead to failure to arrive at a correct diagnosis and confusion during resuscitation. We report a case of a newborn male child with type 2 tracheal agenesis. Despite a typical presentation, diagnosis was delayed after unsuccessful intubation, examination under anaesthesia and emergency tracheostomy. The embryology, diagnostic criteria and potential treatment options are discussed. This case report is valuable in increasing awareness of this rare condition and will help us in being better prepared in managing these children. Future studies should aim to find the optimal replacement for the tracheal. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Ventilation rate in adults with a tracheal tube during cardiopulmonary resuscitation: A systematic review.

PubMed

Vissers, Gino; Soar, Jasmeet; Monsieurs, Koenraad G

2017-10-01

The optimal ventilation rate during cardiopulmonary resuscitation (CPR) with a tracheal tube is unknown. We evaluated whether in adults with cardiac arrest and a secure airway (tracheal tube), a ventilation rate of 10min -1 , compared to any other rate during CPR, improves outcomes. A systematic review up to 14 July 2016. We included both adult human and animal studies. A GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach was used to evaluate the quality of evidence for each outcome. We identified one human observational study with 67 patients and ten animal studies (234 pigs and 30 dogs). All studies carried a high risk of bias. All studies evaluated for return of spontaneous circulation (ROSC). Studies showed no improvement in ROSC with a ventilation rate of 10 min-1 compared to any other rate. The evidence for longer-term outcomes such as survival to discharge and survival with favourable neurological outcome was very limited. A ventilation rate recommendation of 10 min-1 during adult CPR with a tracheal tube and no pauses for chest compression is a very weak recommendation based on very low quality evidence. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of the tracheal and laryngeal afferent neurones mediating cough in anaesthetized guinea-pigs

PubMed Central

Canning, Brendan J; Mazzone, Stuart B; Meeker, Sonya N; Mori, Nanako; Reynolds, Sandra M; Undem, Bradley J

2004-01-01

We have identified the tracheal and laryngeal afferent nerves regulating cough in anaesthetized guinea-pigs. Cough was evoked by electrical or mechanical stimulation of the tracheal or laryngeal mucosa, or by citric acid applied topically to the trachea or larynx. By contrast, neither capsaicin nor bradykinin challenges to the trachea or larynx evoked cough. Bradykinin and histamine administered intravenously also failed to evoke cough. Electrophysiological studies revealed that the majority of capsaicin-sensitive afferent neurones (both Aδ- and C-fibres) innervating the rostral trachea and larynx have their cell bodies in the jugular ganglia and project to the airways via the superior laryngeal nerves. Capsaicin-insensitive afferent neurones with cell bodies in the nodose ganglia projected to the rostral trachea and larynx via the recurrent laryngeal nerves. Severing the recurrent nerves abolished coughing evoked from the trachea and larynx whereas severing the superior laryngeal nerves was without effect on coughing. The data indicate that the tracheal and laryngeal afferent neurones regulating cough are polymodal Aδ-fibres that arise from the nodose ganglia. These afferent neurones are activated by punctate mechanical stimulation and acid but are unresponsive to capsaicin, bradykinin, smooth muscle contraction, longitudinal or transverse stretching of the airways, or distension. Comparing these physiological properties with those of intrapulmonary mechanoreceptors indicates that the afferent neurones mediating cough are quite distinct from the well-defined rapidly and slowly adapting stretch receptors innervating the airways and lungs. We propose that these airway afferent neurones represent a distinct subtype and that their primary function is regulation of the cough reflex. PMID:15004208

Gi-Coupled γ-Aminobutyric Acid–B Receptors Cross-Regulate Phospholipase C and Calcium in Airway Smooth Muscle

PubMed Central

Mizuta, Kentaro; Mizuta, Fumiko; Xu, Dingbang; Masaki, Eiji; Panettieri, Reynold A.

2011-01-01

γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system, and exerts its actions via both ionotropic (GABAA) and metabotropic (GABAB) receptors. Although the functional expression of GABAB receptors coupled to the Gi protein was reported for airway smooth muscle, the role of GABAB receptors in airway responsiveness remains unclear. We investigated whether Gi-coupled GABAB receptors cross-regulate phospholipase C (PLC), an enzyme classically regulated by Gq-coupled receptors in human airway smooth muscle cells. Both the GABAB-selective agonist baclofen and the endogenous ligand GABA significantly increased the synthesis of inositol phosphate, whereas GABAA receptor agonists, muscimol, and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol exerted no effect. The baclofen-induced synthesis of inositol phosphate and transient increases in [Ca2+]i were blocked by CGP35348 and CGP55845 (selective GABAB antagonists), pertussis toxin (PTX, which inactivates the Gi protein), gallein (a Gβγ signaling inhibitor), U73122 (an inhibitor of PLC-β), and xestospongin C, an inositol 1,4,5-triphosphate receptor blocker. Baclofen also potentiated the bradykinin-induced synthesis of inositol phosphate and transient increases in [Ca2+]i, which were blocked by CGP35348 or PTX. Moreover, baclofen potentiated the substance P–induced contraction of airway smooth muscle in isolated guinea pig tracheal rings. In conclusion, the stimulation of GABAB receptors in human airway smooth muscle cells rapidly mobilizes intracellular Ca2+ stores by the synthesis of inositol phosphate via the activation of PLC-β, which is stimulated by Gβγ protein liberated from Gi proteins coupled to GABAB receptors. Furthermore, crosstalk between GABAB receptors and Gq-coupled receptors potentiates the synthesis of inositol phosphate, transient increases in [Ca2+]i, and smooth muscle contraction through Gi proteins. PMID:21719794

Differential Effect of Zoledronic Acid on Human Vascular Smooth Muscle Cells

PubMed Central

Albadawi, Hassan; Haurani, Mounir J.; Oklu, Rahmi; Trubiano, Jordan P.; Laub, Peter J.; Yoo, Hyung-Jin; Watkins, Michael T.

2012-01-01

Introduction The activation of human vascular smooth muscle cell proliferation, adhesion and migration is essential for intimal hyperplasia formation. These experiments were designed to test whether Zoledronic Acid (ZA) would modulate indices of human smooth muscle cell activation, exert differential effects on proliferating vs. quiescent cells and determine whether these effects were dependent on GTPase binding proteins prenylation. ZA was chosen for testing in these experiments because it is clinically used in humans with cancer, and has been shown to modulate rat smooth muscle cell proliferation and migration. Methods Human aortic smooth muscle cells (HASMC) were cultured under either proliferating or growth arrest (quiescent) conditions in the presence or absence of ZA for 48 hours, whereupon the effect of ZA on HASMC proliferation, cellular viability, metabolic activity and membrane integrity were compared. In addition, the effect of ZA on adhesion and migration were assessed in proliferating cells. The effect of increased concentration of ZA on the mevalonate pathway and genomic/cellular stress related poly ADP Ribose polymerase (PARP) enzyme activity were assessed using the relative prenylation of Rap-1A/B protein and the formation of poly ADP- ribosylated proteins (PAR) respectively. Results There was a dose dependent inhibition of cellular proliferation, adhesion and migration following ZA treatment. ZA treatment decreased indices of cellular viability and significantly increased membrane injury in proliferating vs. quiescent cells. This was correlated with the appearance of unprenylated Rap-1A protein and dose dependent down regulation of PARP activity. Conclusions These data suggest that ZA is effective in inhibiting HASMC proliferation, adhesion and migration which coincide with the appearance of unprenylated RAP-1A/B protein, thereby suggesting that the mevalonate pathway may play a role in the inhibition of HASMC activation. PMID:23164362

Conventional tracheal tubes for intubation through the intubating laryngeal mask airway.

PubMed

Kundra, Pankaj; Sujata, N; Ravishankar, M

2005-01-01

The laryngeal mask airway (LMA)-Fastrach silicone wire-reinforced tracheal tube (FTST) was specially designed for tracheal intubation through the intubating LMA (ILMA). However, conventional tracheal tubes have been successfully used to accomplish tracheal intubation. We designed this study to evaluate the success rate of blind tracheal intubation through the ILMA by using the FTST, the Rusch polyvinyl chloride tube (PVCT), and the Rusch latex armored tube (LAT). One-hundred-fifty healthy adults of ASA physical status I and II who were undergoing elective surgery under general anesthesia were randomly allocated into three groups. FTST (n=50), prewarmed PVCT (n=50), and LAT (n=50) were used for tracheal intubation. Ease of tracheal intubation was assessed by the time taken, the number of attempts, and the number of maneuvers required for success. In addition, numbers of failed intubation attempts and times taken for ILMA removal were also recorded. After surgery, the incidence of trauma, sore throat, and hoarseness was noted. Significantly more frequent success in tracheal intubation was achieved with the PVCT and FTST (96%) compared with the LAT (82%) (P <0.05). Tracheal intubation on the first attempt was similar with the PVCT and FTST (86%) and was significantly more frequent than with the LAT (52%) (P <0.05). Esophageal placement was significantly more frequent with the LAT (29.7%) when compared with the PVCT and FTST (1.8% and 7.4%, respectively) (P <0.05). The authors conclude that a prewarmed PVCT can be used as successfully as the FTST for blind tracheal intubation through the ILMA, whereas the LAT is associated with more frequent failure and esophageal intubation.

Endotracheal tube leak pressure and tracheal lumen size in swine.

PubMed

Finholt, D A; Audenaert, S M; Stirt, J A; Marcella, K L; Frierson, H F; Suddarth, L T; Raphaely, R C

1986-06-01

Endotracheal tube "leak" is often estimated in children to judge the fit of uncuffed endotracheal tubes within the trachea. Twenty-five swine were intubated with uncuffed tracheal tubes to determine whether a more sensitive measurement of leaks could be devised and whether leak pressure estimates fit between tracheal tube and trachea. We compared leak pressure measurement using a stethoscope and aneroid manometer with a technique using a microphone, pressure transducer, and recorder, and found no differences between the two methods. The tracheas were then removed and slides prepared of tracheal cross-sectional specimens. Regression analysis revealed a linear relationship between tracheal lumen size and tracheal tube size for both low leak pressure (y = -0.4 + 0.79x, r = 0.88, P less than 0.05) and high leak pressure (y = -2.9 + 0.71x, r = 0.92, P less than 0.05) groups. We conclude that leak testing with a stethoscope and aneroid manometer is sensitive and accurate, and that tracheal tube leak pressure accurately portrays fit between tube and trachea.

Nelumbo nucifera leaves extracts inhibit mouse airway smooth muscle contraction.

PubMed

Yang, Xiao; Xue, Lu; Zhao, Qingyang; Cai, Congli; Liu, Qing-Hua; Shen, Jinhua

2017-03-20

Alkaloids extracted from lotus leaves (AELL) can relax vascular smooth muscle. However, whether AELL has a similar relaxant role on airway smooth muscle (ASM) remains unknown. This study aimed to explore the relaxant property of AELL on ASM and the underlying mechanism. Alkaloids were extracted from dried lotus leaves using the high temperature rotary evaporation extraction method. The effects of AELL on mouse ASM tension were studied using force measuring and patch-clamp techniques. It was found that AELL inhibited the high K + or acetylcholine chloride (ACh)-induced precontraction of mouse tracheal rings by 64.8 ± 2.9%, or 48.8 ± 4.7%, respectively. The inhibition was statistically significant and performed in a dose-dependent manner. Furthermore, AELL-induced smooth muscle relaxation was partially mediated by blocking voltage-dependent Ca 2+ channels (VDCC) and non-selective cation channels (NSCC). AELL, which plays a relaxant role in ASM, might be a new complementary treatment to treat abnormal contractions of the trachea and asthma.

Mechanisms altering airway smooth muscle cell Ca+ homeostasis in two asthma models.

PubMed

Kellner, Julia; Tantzscher, Juliane; Oelmez, Hamza; Edelmann, Martin; Fischer, Rainald; Huber, Rudolf Maria; Bergner, Albrecht

2008-01-01

Asthma is characterized by airway remodeling, altered mucus production and airway smooth muscle cell (ASMC) contraction causing extensive airway narrowing. In particular, alterations of ASMC contractility seem to be of crucial importance. The elevation of the cytoplasmic Ca(2+) concentration is a key event leading to ASMC contraction and changes in the agonist-induced Ca(2+) increase in ASMC have been reported in asthma. The aim of this study was to investigate mechanisms underlying these changes. Murine tracheal smooth muscle cells (MTSMC) from T-bet KO mice and human bronchial smooth muscle cells (HBSMC) incubated with IL-13 and IL-4 served as asthma models. Acetylcholine-induced changes in the cytoplasmic Ca(2+) concentration were recorded using fluorescence microscopy and the expression of Ca(2+) homeostasis regulating proteins was investigated with Western blot analysis. Acetylcholine-induced Ca(2+) transients were elevated in both asthma models. This correlated with an increased Ca(2+) content of the sarcoplasmic reticulum (SR). In MTSMC from T-bet KO mice, the expression of the SR Ca(2+) buffers calreticulin and calsequestrin was higher compared to wild-type mice. In HBSMC incubated with IL-13 or IL-4, the expression of ryanodine receptors, inositol-3-phosphate receptors and sarcoplasmic/endoplasmic reticulum Ca(2+) ATPases 2 was increased compared to HBSMC without incubation with interleukins. The enlarged acetylcholine-induced Ca(2+) transients could be reversed by blocking inositol-3-phosphate receptors. We conclude that in the murine asthma model the SR Ca(2+) buffer capacity is increased, while in the human asthma model the expression of SR Ca(2+) channels is altered. The investigation of the Ca(2+) homeostasis of ASMC has the potential to provide new therapeutical options in asthma. Copyright 2008 S. Karger AG, Basel.

Smooth muscle neurokinin-2 receptors mediate contraction in human saphenous veins.

PubMed

Mechiche, Hakima; Grassin-Delyle, Stanislas; Pinto, Francisco M; Buenestado, Amparo; Candenas, Luz; Devillier, Philippe

2011-05-01

Substance P (SP) and neurokinin A (NKA) are members of the tachykinin peptides family. SP causes endothelial-dependant relaxation but the contractile response to tachykinins in human vessels remains unknown. The objective was to assess the expression and the contractile effects of tachykinins and their receptors in human saphenous veins (SV). Tachykinin expression was assessed with RT-PCR, tachykinin receptors expression with RT-PCR and immunohistochemistry, and functional studies were performed in organ bath. Transcripts of all tachykinin and tachykinin receptor genes were found in SV. NK(1)-receptors were localized in both endothelial and smooth muscle layers of undistended SV, whereas they were only found in smooth muscle layers of varicose SV. The expression of NK(2)- and NK(3)-receptors was limited to the smooth muscle in both preparations. NKA induced concentration-dependent contractions in about half the varicose SV. Maximum effect reached 27.6±5.5% of 90 mM KCl and the pD(2) value was 7.3±0.2. NKA also induced the contraction of undistended veins from bypass and did not cause the relaxation of these vessels after precontraction. The NK(2)-receptor antagonist SR48968 abolished the contraction induced by NKA, and a rapid desensitization of the NK(2)-receptor was observed. In varicose SV, the agonists specific to NK(1)- or NK(3)-receptors did not cause either contraction or relaxation. The stimulation of smooth muscle NK(2)-receptors can induce the contraction of human SV. As SV is richly innervated, tachykinins may participate in the regulation of the tone in this portion of the low pressure vascular system. Copyright © 2011 Elsevier Ltd. All rights reserved.

Role of airway epithelial injury in murine orthotopic tracheal allograft rejection.

PubMed

Kuo, Elbert; Bharat, Ankit; Shih, Jennifer; Street, Tyler; Norris, Jenyi; Liu, Wei; Parks, William; Walter, Michael; Patterson, G Alexander; Mohanakumar, T

2006-10-01

Murine tracheal transplantation is a model used to study bronchiolitis obliterans syndrome, a major cause of morbidity and mortality after lung transplantation. Unlike murine heterotopic tracheal transplants, orthotopic transplantation does not cause luminal obliteration despite major histocompatibility antigen mismatch. Repopulation of the tracheal allografts with recipient-derived epithelium confers protection against luminal obliteration. The purpose of this study was to determine whether (1) orthotopic tracheal transplantation showed signs of allograft rejection, and (2) airway epithelial cell injury promoted orthotopic tracheal allograft rejection. Forty isogeneic (C57BL/6 to C57BL/6) and 40 allogeneic (BALB/c to C57BL/6) orthotopic tracheal transplants were performed. Damage to airway epithelial cells was induced by Sendai viral (SdV) infection and tracheal transplantation into non-reepithelializing matrix metalloproteinase-7 knockout (MMP7-KO) recipient mice. Percent fibrosis and lamina propria to cartilage ratio were calculated with computer assistance on harvested allografts. Allografts showed significantly more intramural fibrosis compared with isografts at 30, 60, and 180 days after transplant without luminal occlusion. Tracheal allografts infected with SdV showed an increase in fibrosis and lamina propria to cartilage ratio compared with noninfected controls. Allografts retrieved from MMP7-KO recipients also showed a significant increase in fibrosis and lamina propria to cartilage ratio. Although orthotopic tracheal transplantation does not cause luminal obliteration, it results in increased fibrosis in allografts. Damage to the respiratory epithelium by viral infection or defective reepithelialization after transplant as seen in MMP7-KO recipient mice leads to changes consistent with chronic allograft rejection, suggesting a role for epithelial injury in bronchiolitis obliterans syndrome development.

The dopamine D1 receptor is expressed and facilitates relaxation in airway smooth muscle

PubMed Central

2013-01-01

Background Dopamine signaling is mediated by Gs protein-coupled “D1-like” receptors (D1 and D5) and Gi-coupled “D2-like” receptors (D2-4). In asthmatic patients, inhaled dopamine induces bronchodilation. Although the Gi-coupled dopamine D2 receptor is expressed and sensitizes adenylyl cyclase activity in airway smooth muscle (ASM) cells, the Gs-coupled dopamine D1-like receptor subtypes have never been identified on these cells. Activation of Gs-coupled receptors stimulates cyclic AMP (cAMP) production through the stimulation of adenylyl cyclase, which promotes ASM relaxation. We questioned whether the dopamine D1-like receptor is expressed on ASM, and modulates its function through Gs-coupling. Methods The mRNA and protein expression of dopamine D1-like receptor subtypes in both native human and guinea pig ASM tissue and cultured human ASM (HASM) cells was measured. To characterize the stimulation of cAMP through the dopamine D1 receptor, HASM cells were treated with dopamine or the dopamine D1-like receptor agonists (A68930 or SKF38393) before cAMP measurements. To evaluate whether the activation of dopamine D1 receptor induces ASM relaxation, guinea pig tracheal rings suspended under isometric tension in organ baths were treated with cumulatively increasing concentrations of dopamine or A68930, following an acetylcholine-induced contraction with or without the cAMP-dependent protein kinase (PKA) inhibitor Rp-cAMPS, the large-conductance calcium-activated potassium (BKCa) channel blocker iberiotoxin, or the exchange proteins directly activated by cAMP (Epac) antagonist NSC45576. Results Messenger RNA encoding the dopamine D1 and D5 receptors were detected in native human ASM tissue and cultured HASM cells. Immunoblots confirmed the protein expression of the dopamine D1 receptor in both native human and guinea pig ASM tissue and cultured HASM cells. The dopamine D1 receptor was also immunohistochemically localized to both human and guinea pig ASM. The

Tracheal decannulation protocol in patients affected by traumatic brain injury.

PubMed

Zanata, Isabel de Lima; Santos, Rosane Sampaio; Hirata, Gisela Carmona

2014-04-01

Introduction The frequency of tracheostomy in patients with traumatic brain injury (TBI) contrasts with the lack of objective criteria for its management. The study arose from the need for a protocol in the decision to remove the tracheal tube. Objective To evaluate the applicability of a protocol for tracheal decannulation. Methods A prospective study with 20 patients, ranging between 21 and 85 years of age (average 33.55), 4 of whom were women (20%) and 16 were men (80%). All patients had been diagnosed by a neurologist as having TBI, and the anatomical region of the lesion was known. Patients were evaluated following criteria for tracheal decannulation through a clinical evaluation protocol developed by the authors. Results Decannulation was performed in 12 (60%) patients. Fourteen (70%) had a score greater than 8 on the Glasgow Coma Scale and only 2 (14%) of these were not able to undergo decannulation. Twelve (60%) patients maintained the breathing pattern with occlusion of the tube and were successfully decannulated. Of the 20 patients evaluated, 11 (55%) showed no signs suggestive of tracheal aspiration, and of these, 9 (82%) began training on occlusion of the cannula. The protocol was relevant to establish the beginning of the decannulation process. The clinical assessment should focus on the patient's condition to achieve early tracheal decannulation. Conclusion This study allowed, with the protocol, to establish six criteria for tracheal decannulation: level of consciousness, respiration, tracheal secretion, phonation, swallowing, and coughing.

Tracheal Decannulation Protocol in Patients Affected by Traumatic Brain Injury

PubMed Central

Zanata, Isabel de Lima; Santos, Rosane Sampaio; Hirata, Gisela Carmona

2014-01-01

Introduction The frequency of tracheostomy in patients with traumatic brain injury (TBI) contrasts with the lack of objective criteria for its management. The study arose from the need for a protocol in the decision to remove the tracheal tube. Objective To evaluate the applicability of a protocol for tracheal decannulation. Methods A prospective study with 20 patients, ranging between 21 and 85 years of age (average 33.55), 4 of whom were women (20%) and 16 were men (80%). All patients had been diagnosed by a neurologist as having TBI, and the anatomical region of the lesion was known. Patients were evaluated following criteria for tracheal decannulation through a clinical evaluation protocol developed by the authors. Results Decannulation was performed in 12 (60%) patients. Fourteen (70%) had a score greater than 8 on the Glasgow Coma Scale and only 2 (14%) of these were not able to undergo decannulation. Twelve (60%) patients maintained the breathing pattern with occlusion of the tube and were successfully decannulated. Of the 20 patients evaluated, 11 (55%) showed no signs suggestive of tracheal aspiration, and of these, 9 (82%) began training on occlusion of the cannula. The protocol was relevant to establish the beginning of the decannulation process. The clinical assessment should focus on the patient's condition to achieve early tracheal decannulation. Conclusion This study allowed, with the protocol, to establish six criteria for tracheal decannulation: level of consciousness, respiration, tracheal secretion, phonation, swallowing, and coughing. PMID:25992074

Cooling-induced contraction in ovine airways smooth muscle.

PubMed

Mustafa, S M; Pilcher, C W; Williams, K I

1999-02-01

The mechanism of cold-induced bronchoconstriction is poorly understood. This prompted the present study whose aim was to determine the step-wise direct effect of cooling on smooth muscle of isolated ovine airways and analyse the role of calcium in the mechanisms involved. Isolated tracheal strips and bronchial segments were suspended in organ baths containing Krebs' solution for isometric tension recording. Tissue responses during stepwise cooling from 37 to 5 degrees C were examined. Cooling induced a rapid and reproducible contraction proportional to cooling temperature in ovine tracheal and bronchial preparations which was epithelium-independent. On readjustment to 37 degrees C the tone returned rapidly to basal level. Maximum contraction was achieved at a temperature of 5 degrees C for trachea and 15 degrees C for bronchiole. Cooling-induced contractions (CIC) was resistant to tetrodotoxin (1; 10 micrometer), and not affected by the muscarinic antagonist atropine (1 micrometer) or the alpha-adrenergic antagonist phentolamine (1 micrometer), or the histamine H1-antagonist mepyramine (1 micrometer) or indomethacin (1 micrometer). Ca2+ antagonists (nifedipine and verapamil) and Mn2+ raised tracheal but not bronchiolar tone and augmented CIC. Incubation in Ca2+-free, EGTA-containing Krebs' solution for 5 min had no effect on CIC, although it significantly reduced KCl-induced contraction by up to 75%. Cooling inhibited Ca2+ influx measured using 45Ca2+ uptake. Caffeine (100 micrometer) significantly inhibited CIC. The results show that cooling-induced contractions do not appear to involve activation of nerve endings, all surface reception systems or Ca2+ influx. However, CIC is mainly dependent on release of intracellular Ca2+. Copyright 1999 The Italian Pharmacological Society.

Management of tracheal chondrosarcoma almost completely obstructing the airway: a case report.

PubMed

Andolfi, Marco; Vaccarili, Maurizio; Crisci, Roberto; Puma, Francesco

2016-07-11

Primary malignant tracheal tumors account for only 0.2 % of all malignancies of the respiratory tract. Tracheal chondrosarcoma is a rare condition and only 17 cases have been described in the literature from 1965 to date. Herein we report the very unusual case of a patient with a tracheal chondrosarcoma, electively treated by curative surgery despite the virtually complete obstruction of the airway. We present the case of a 79-year old Caucasian man with long-lasting wheezing misdiagnosed as asthma and affected by a tracheal chondrosarcoma almost completely obstructing the airway. Videobronchoscopy and imaging investigations revealed a well-circumscribed mass arising from the cartilaginous rings of the cervical trachea with a posterior residual respiratory space of about 1 mm. Because of the mobility and flaccidity of the uninvolved pars membranacea, the tiny respiratory space slightly expanded during inspiration and expiration allowing the patient to be treated without an essential emergency procedure. Standard tracheal intubation was impossible. Rigid bronchoscopy enabled placement of a small tracheal tube distally to the tumor. Successful cervical tracheal resection and reconstruction was then performed, achieving complete tumor excision. Histologically, the mass was characterized as a low-grade tracheal chondrosarcoma. Videobronchoscopy performed 9 months after surgery showed a wide, well healed tracheal anastomosis. Ten months after surgery, the patient is alive and disease free. Complete surgical resection is the treatment of choice for tracheal chondrosarcoma. Rigid bronchoscopy is an essential tool for diagnostic and therapeutic purposes. It allows the palliative maneuvers for obstruction relief but also, in resectable patients, the intraoperative safe and straightforward management of the obstructed airway.

Enkephalinase inhibitor potentiates substance P- and capsaicin-induced bronchial smooth muscle contractions in humans.

PubMed

Honda, I; Kohrogi, H; Yamaguchi, T; Ando, M; Araki, S

1991-06-01

To determine the roles of endogenously released tachykinins (substance P, neurokinins A and B) in human bronchial tissues, and to determine the roles of enkephalinase (neutral endopeptidase, E.C. 3.4.24.11) in regulating the effects of the tachykinins, we studied the effects of substance P and capsaicin, which releases tachykinins, on human bronchial smooth muscle contraction in the presence or absence of enkephalinase inhibitor phosphoramidon in vitro. Substance P alone caused human bronchial smooth muscle contraction at 10(-6) M or more. Phosphoramidon (10(-7) to 10(-5) M) potentiated the substance P-induced contraction in a dose-dependent fashion, and phosphoramidon shifted the dose-response curve to lower concentrations. Capsaicin (10(-5) or 10(-4) M) alone caused bronchial smooth muscle contraction in four tissues from nine patients. After the contraction by capsaicin reached a plateau, phosphoramidon (10(-5) M) increased and prolonged the contraction significantly. Furthermore, pretreatment of bronchial tissues with phosphoramidon (10(-5) M) potentiated capsaicin-induced contraction in all tissues from five patients. Phosphoramidon (10(-5) M) shifted the dose-response curve to capsaicin to lower concentrations more than 1 log unit. Captopril did not alter the contractile response to substance P, suggesting that angiotensin-converting enzyme does not regulate the contractile response to substance P in human bronchial smooth muscle in vitro. These results suggest that enkephalinase regulates the contractile effects of exogenous substance P and endogenous substances, probably tachykinins, released by capsaicin in the human bronchus.

Tracheal climate in laryngectomees after use of a heat and moisture exchanger.

PubMed

Keck, Tilman; Dürr, Jochen; Leiacker, Richard; Rettinger, Gerhard; Rozsasi, Ajnacska

2005-03-01

Heat and moisture exchangers (HME) are frequently used in the treatment and prevention of tracheobronchial dryness and infections. In this study, the short-term influence of the HME Prim-Air System (Heimomed, Kerpen, Germany) in laryngectomized patients was tested. Prospective study. After adaptation to the laboratory environment, tracheal humidity and temperature were measured before HME application, 1 minute after HME application, 10 minutes after HME application, 1 minute after removal of the HME, and 10 minutes after removal of the HME. When the HME was placed on the tracheal stoma, the end-inspiratory humidity and temperature increased significantly. Ten minutes after commencement of use of the HME, tracheal humidity further increased significantly. Ten minutes after removal of the HME, tracheal humidity and temperature decreased to values as before start of use of HME. The results indicate that short-term use of the HME Prim-Air system rapidly changes the tracheal climate. The significant increase in tracheal temperature and humidity may have beneficial effects on tracheal dryness in laryngectomized patients.

Effect of endogenous tachykinins on neuro-effector transmission of vagal nerve in guinea-pig tracheal tissue.

PubMed

Aizawa, H; Miyazaki, N; Inoue, H; Ikeda, T; Shigematsu, N

1990-01-01

To elucidate the effect of endogenous tachykinins on neuro-effector transmission of vagal nerves, we performed in vitro experiments using guinea-pig tracheal smooth muscle. The subthreshold dose (the highest dose which did not induce any smooth muscle contraction) of capsaicin (10(-8) to 10(-7) M) increased the amplitudes of contractions evoked by electrical field stimulation (EFS) significantly, but not those by acetylcholine (ACh). The inhibitor of neutral endopeptidase, phosphoramidon (10(-7) to 10(-6) M), increased the contractions evoked by EFS significantly. The inhibitor of cholinesterase, physostigmine (10(-6) to 10(-5) M), induced smooth muscle contractions, but such contractions were inhibited by atropine, suggesting the spontaneous release of ACh from the vagal nerve terminals. The subthreshold dose of substance P or capsaicin increased the contractions evoked by physostigmine. These results indicated that endogenous tachykinins increase the spontaneous ACh release as well as the ACh release in response to vagal stimulation from the nerve terminals. Furthermore, it is suggested that the excitatory effects of the tachykinins on the vagal neuro-effector transmission may be modulated by neutral endopeptidase in the guinea pig.

Tracheal anastomosis with the diode laser and fibrin tissue adhesive: an in vitro and in vivo investigation.

PubMed

Gleich, L L; Wang, Z; Pankratov, M M; Aretz, H T; Shapshay, S M

1995-05-01

Absorbable sutures have been advocated for tracheal anastomosis to reduce fibrosis and foreign body reaction leading to recurrent stenosis. Fibrin tissue adhesive (FTA) and diode laser welding with indocyanine green-dyed fibrinogen were evaluated in tracheal anastomosis to reduce the number of sutures and to improve healing. In vitro studies demonstrated strong anastomoses with a combination of laser welding and FTA with minimal tissue damage. In a controlled in vivo study, circumferential resections of canine tracheas were repaired with laser welding and FTA augmented with a few stay sutures. These anastomoses had less fibrosis and tissue damage than anastomoses in control animals repaired with sutures alone. This study supports investigation of laser welding and FTA in human beings for tracheal anastomosis and other procedures in which suturing may be difficult.

Optimisation of isolation of richly pure and homogeneous primary human colonic smooth muscle cells.

PubMed

Tattoli, I; Corleto, V D; Taffuri, M; Campanini, N; Rindi, G; Caprilli, R; Delle Fave, G; Severi, C

2004-11-01

Inherent properties of gastrointestinal smooth muscle can be assessed using isolated cell suspensions. Currently available isolation techniques, based on short 2-h enzymatic digestion, however, present the disadvantage of low cellular yield with brief viability. These features are an important limiting factor especially in studies in humans in which tissue may not be available daily and mixing of samples is not recommended. To optimise the isolation procedure of cells from human colon to obtain a richly pure primary smooth muscle cell preparation. Slices of circular muscle layer, obtained from surgical specimens of human colon, were incubated overnight in Dulbecco's modified eagle's medium supplemented with antibiotics, foetal bovine serum, an ATP-regenerating system and collagenase. On the following day, digested muscle strips were suspended in HEPES buffer, and spontaneously dissociated smooth muscle cells were harvested and used either immediately or maintained in suspension for up to 72 h. Cell yield, purity, viability, contractile responses, associated intracellular calcium signals and RNA and protein extraction were evaluated and compared to cell suspensions obtained with the current short digestion protocol. The overnight isolation protocol offers the advantage of obtaining a pure, homogeneous, long-life viable cell suspension that maintains a fully differentiated smooth muscle phenotype unchanged for at least 72 h and that allows multiple functional/biochemical studies and efficient RNA extraction from a single human specimen.

Effects of lipopolysaccharide from Pseudomonas aeruginosa on airway smooth muscle functions in guinea pigs.

PubMed

Yamawaki, I; Tamaoki, J; Kanemura, T; Horii, S; Takizawa, T

1990-01-01

To elucidate the mechanisms of airway hyperreactivity induced by lipopolysaccharide (LPS), we studied isolated tracheal segments from guinea pigs under isometric conditions in vitro. Guinea pigs were injected intraperitoneally with endotoxin (1 mg/kg; LPS from Pseudomonas aeruginosa, serotype 10) for 4 days, and animals treated with sterile nonpyrogenic saline served as controls. Histological examination of trachea revealed moderate structural damage of epithelial layer in the LPS-treated group. Treatment with LPS potentiated the contractile responses of tracheal smooth muscle to acetylcholine, causing a leftward displacement of dose-response curves so that the EC50 values decreased from 1.1 +/- 3.7 x 10(-5) to 4.4 +/- 3.7 x 10(-7) M (mean +/- SE, p less than 0.01). Likewise, LPS shifted the dose-response curves for histamine and substance P to lower concentrations by approximately 0.5-1.0 log U. Each of these potentiations was not affected by pretreatment of tissues with indomethacin or propranolol. Addition of isoproterenol to tracheal segments precontracted with acetylcholine caused concentration-dependent relaxation, an effect that was significantly greater in controls than in the LPS-treated group. These results suggest that airway hyperreactivity induced by LPS in guinea pigs may be attributed to a decreased ability of respiratory epithelial cells to generate a relaxing factor.

Rho Kinase (ROCK) collaborates with Pak to Regulate Actin Polymerization and Contraction in Airway Smooth Muscle.

PubMed

Zhang, Wenwu; Bhetwal, Bhupal P; Gunst, Susan J

2018-05-10

The mechanisms by which Rho kinase (ROCK) regulates airway smooth muscle contraction were determined in tracheal smooth muscle tissues. ROCK may mediate smooth muscle contraction by inhibiting myosin regulatory light chain (RLC) phosphatase. ROCK can also regulate F-actin dynamics during cell migration, and actin polymerization is critical for airway smooth muscle contraction. Our results show that ROCK does not regulate airway smooth muscle contraction by inhibiting myosin RLC phosphatase or by stimulating myosin RLC phosphorylation. We find that ROCK regulates airway smooth muscle contraction by activating the serine-threonine kinase Pak, which mediates the activation of Cdc42 and Neuronal-Wiskott-Aldrich Syndrome protein (N-WASp). N-WASP transmits signals from cdc42 to the Arp2/3 complex for the nucleation of actin filaments. These results demonstrate a novel molecular function for ROCK in the regulation of Pak and cdc42 activation that is critical for the processes of actin polymerization and contractility in airway smooth muscle. Rho kinase (ROCK), a RhoA GTPase effector, can regulate the contraction of airway and other smooth muscle tissues. In some tissues, ROCK can inhibit myosin regulatory light chain (RLC) phosphatase, which increases the phosphorylation of myosin RLC and promotes smooth muscle contraction. ROCK can also regulate cell motility and migration by affecting F-actin dynamics. Actin polymerization is stimulated by contractile agonists in airway smooth muscle tissues and is required for contractile tension development in addition to myosin RLC phosphorylation. We investigated the mechanisms by which ROCK regulates the contractility of tracheal smooth muscle tissues by expressing a kinase inactive mutant of ROCK, ROCK-K121G, in the tissues or by treating them with the ROCK inhibitor, H-1152P. Our results show no role for ROCK in the regulation of non-muscle or smooth muscle myosin RLC phosphorylation during contractile stimulation in this tissue

Bidirectional regulation of human colonic smooth muscle contractility by tachykinin NK(2) receptors.

PubMed

Nakamura, Akihiro; Tanaka, Takahiro; Imanishi, Akio; Kawamoto, Makiko; Toyoda, Masao; Mizojiri, Gaku; Tsukimi, Yasuhiro

2011-01-01

In this study, we attempted to clarify the mechanism of tachykinin-induced motor response in isolated smooth muscle preparations of the human colon. Fresh specimens of normal colon were obtained from patients suffering from colonic cancer. Using mucosa-free smooth muscle strips, smooth muscle tension with circular direction was monitored isometrically. Substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) produced marked contraction. All of these contractions were inhibited by saredutant, a selective NK(2)-R antagonist, but not by CP122721, a selective NK(1)-R antagonist or talnetant, a selective NK(3)-R antagonist. βAla(8)-NKA(4-10) induced concentration-dependent contraction similar to NKA, but Sar(9)-Met(11)-SP and Met-Phe(7)-NKB did not cause marked contraction. Colonic contraction induced by βAla(8)-NKA(4-10) was completely blocked by saredutant, but not by atropine. Tetrodotoxin or N(G)-nitro-L-arginine methyl ester pretreatment significantly enhanced βAla(8)-NKA(4-10)-induced contraction. Immunohistochemical analysis showed that the NK(2)-R was expressed on the smooth muscle layers and myenteric plexus where it was also co-expressed with neuronal nitric oxide synthase in the myenteric plexus. These results suggest that the NK(2)-R is a major contributor to tachykinin-induced smooth muscle contraction in human colon and that the NK(2)-R-mediated response consists of an excitatory component via direct action on the smooth muscle and an inhibitory component possibly via nitric oxide neurons.

Successful immunosuppressant-free heterotopic transplantation of tracheal allografts in the pig.

PubMed

De Wolf, Julien; Brieu, Mathias; Zawadzki, Christophe; Ung, Alexandre; Kipnis, Eric; Jashari, Ramadan; Hubert, Thomas; Fayoux, Pierre; Mariette, Christophe; Copin, Marie-Christine; Wurtz, Alain

2017-08-01

It has been demonstrated that both heterotopic and orthotopic transplants of epithelium-denuded cryopreserved tracheal allografts are feasible in immunosuppressant-free rabbits. Validation of these results in large animals is required before considering clinical applications. We evaluated the viability, immune tolerance and strain properties of such tracheal allografts heterotopically transplanted in a pig model. Ten tracheal segments, 5 short (5 rings) and 5 long (10 rings), were obtained from male Landrace pigs. The tracheal segments were surgically denuded of their epithelium, then cryopreserved and stored in a tissue bank for 33 to 232 days. After thawing, tracheal segments stented with a silicone tube were wrapped in the omentum in 2 groups of 5 female recipients. The animals did not receive any immunosuppressive drugs. The animals were euthanized from Day 6 to Day 90 in both groups. An effective revascularization of allografts regardless of length was observed. Lymphocyte infiltrate was shown in the early postoperative period and became non-significant after 30 days. Allografts displayed high levels of neoangiogenesis and viable cartilage rings with islets of calcification. Biomechanical measurements demonstrated strain properties similar to those of a fresh tracheal segment from Day 58. Our results demonstrate the acceptability and satisfactory stiffness of epithelium-denuded cryopreserved tracheal allografts implanted in the omentum, despite the absence of immunosuppressive drugs. Since the omentum has the capability to reach the tracheal region, this approach should be investigated in the setting of orthotopic transplants in a pig model before considering clinical applications. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Effects of lubiprostone on human uterine smooth muscle cells.

PubMed

Cuppoletti, John; Malinowska, Danuta H; Chakrabarti, Jayati; Ueno, Ryuji

2008-06-01

Lubiprostone, a bicyclic fatty acid derivative and member of a new class of compounds called prostones, locally activates ClC-2 Cl(-) channels without activation of prostaglandin receptors. The present study was specifically designed to test and compare lubiprostone and prostaglandin effects at the cellular level using human uterine smooth muscle cells. Effects on [Ca(2+)](i), membrane potential and [cAMP](i) in human uterine smooth muscle cells were measured. 10 nM lubiprostone significantly decreased [Ca(2+)](i) from 188 to 27 nM, which was unaffected by 100 nM SC-51322, a prostaglandin EP receptor antagonist. In contrast 10nM PGE(2) and PGE(1) both increased [Ca(2+)](i) 3-5-fold which was blocked by SC-51322. Similarly, lubiprostone and prostaglandins had opposite/different effects on membrane potential and [cAMP](i). Lubiprostone caused SC-51322-insensitive membrane hyperpolarization and no effect on [cAMP](i). PGE(2) and PGE(1) both caused SC-51322-sensitive membrane depolarization and increased [cAMP](i). Lubiprostone has fundamentally different cellular effects from prostaglandins that are not mediated by EP receptors.

Assays for in vitro monitoring of human airway smooth muscle (ASM) and human pulmonary arterial vascular smooth muscle (VSM) cell migration.

PubMed

Goncharova, Elena A; Goncharov, Dmitry A; Krymskaya, Vera P

2006-01-01

Migration of human pulmonary vascular smooth muscle (VSM) cells contributes to vascular remodeling in pulmonary arterial hypertension and atherosclerosis. Evidence also indicates that, in part, migration of airway smooth muscle (ASM) cells may contribute to airway remodeling associated with asthma. Here we describe migration of VSM and ASM cells in vitro using Transwell or Boyden chamber assays. Because dissecting signaling mechanisms regulating cell migration requires molecular approaches, our protocol also describes how to assess migration of transfected VSM and ASM cells. Transwell or Boyden chamber assays can be completed in approximately 8 h and include plating of serum-deprived VSM or ASM cell suspension on membrane precoated with collagen, migration of cells toward chemotactic gradient and visual (Transwell) or digital (Boyden chamber) analysis of membrane. Although the Transwell assay is easy, the Boyden chamber assay requires hands-on experience; however, both assays are reliable cell-based approaches providing valuable information on how chemotactic and inflammatory factors modulate VSM and ASM migration.

{beta}-Catenin regulates airway smooth muscle contraction.

PubMed

Jansen, Sepp R; Van Ziel, Anna M; Baarsma, Hoeke A; Gosens, Reinoud

2010-08-01

beta-Catenin is an 88-kDa member of the armadillo family of proteins that is associated with the cadherin-catenin complex in the plasma membrane. This complex interacts dynamically with the actin cytoskeleton to stabilize adherens junctions, which play a central role in force transmission by smooth muscle cells. Therefore, in the present study, we hypothesized a role for beta-catenin in the regulation of smooth muscle force production. beta-Catenin colocalized with smooth muscle alpha-actin (sm-alpha-actin) and N-cadherin in plasma membrane fractions and coimmunoprecipitated with sm-alpha-actin and N-cadherin in lysates of bovine tracheal smooth muscle (BTSM) strips. Moreover, immunocytochemistry of cultured BTSM cells revealed clear and specific colocalization of sm-alpha-actin and beta-catenin at the sites of cell-cell contact. Treatment of BTSM strips with the pharmacological beta-catenin/T cell factor-4 (TCF4) inhibitor PKF115-584 (100 nM) reduced beta-catenin expression in BTSM whole tissue lysates and in plasma membrane fractions and reduced maximal KCl- and methacholine-induced force production. These changes in force production were not accompanied by changes in the expression of sm-alpha-actin or sm-myosin heavy chain (MHC). Likewise, small interfering RNA (siRNA) knockdown of beta-catenin in BTSM strips reduced beta-catenin expression and attenuated maximal KCl- and methacholine-induced contractions without affecting sm-alpha-actin or sm-MHC expression. Conversely, pharmacological (SB-216763, LiCl) or insulin-induced inhibition of glycogen synthase kinase-3 (GSK-3) enhanced the expression of beta-catenin and augmented maximal KCl- and methacholine-induced contractions. We conclude that beta-catenin is a plasma membrane-associated protein in airway smooth muscle that regulates active tension development, presumably by stabilizing cell-cell contacts and thereby supporting force transmission between neighboring cells.

Directional asymmetries in human smooth pursuit eye movements.

PubMed

Ke, Sally R; Lam, Jessica; Pai, Dinesh K; Spering, Miriam

2013-06-27

Humans make smooth pursuit eye movements to bring the image of a moving object onto the fovea. Although pursuit accuracy is critical to prevent motion blur, the eye often falls behind the target. Previous studies suggest that pursuit accuracy differs between motion directions. Here, we systematically assess asymmetries in smooth pursuit. In experiment 1, binocular eye movements were recorded while observers (n = 20) tracked a small spot of light moving along one of four cardinal or diagonal axes across a featureless background. We analyzed pursuit latency, acceleration, peak velocity, gain, and catch-up saccade latency, number, and amplitude. In experiment 2 (n = 22), we examined the effects of spatial location and constrained stimulus motion within the upper or lower visual field. Pursuit was significantly faster (higher acceleration, peak velocity, and gain) and smoother (fewer and later catch-up saccades) in response to downward versus upward motion in both the upper and the lower visual fields. Pursuit was also more accurate and smoother in response to horizontal versus vertical motion. CONCLUSIONS. Our study is the first to report a consistent up-down asymmetry in human adults, regardless of visual field. Our findings suggest that pursuit asymmetries are adaptive responses to the requirements of the visual context: preferred motion directions (horizontal and downward) are more critical to our survival than nonpreferred ones.

Ketamine relaxes airway smooth muscle contracted by endothelin.

PubMed

Sato, T; Matsuki, A; Zsigmond, E K; Rabito, S F

1997-04-01

Endothelins (ETs) are synthesized not only in vascular endothelial cells but also in airway epithelial cells. Increased ET-1 has been demonstrated in bronchial epithelium of asthmatic patients, and, in severe asthma attacks, ET-1 increases in plasma and bronchoalveolar lavage fluid. In this study, we investigated whether ketamine (KET) relaxes ET-induced tracheal contractions. Female guinea pigs were killed with an overdose of pentobarbital. The trachea was removed and cut spirally into two strips that were mounted in an organ bath filled with Krebs-bicarbonate buffer. The response of each strip to 10(-7) M carbachol was taken as 100% contraction to which the response to ET was referred. The contribution of the epithelium to the relaxant effect of KET was studied in denuded tracheae or in the presence of 5 x 10(-5) M indomethacin. ET-1 (3 x 10(-8) M) induced contractions that were 76 +/- 3% of those induced by carbachol. KET reversed the response to ET-1 in a dose-dependent fashion. Similarly, ET-2 (3 x 10(-8) M) induced contractions that were 74 +/- 5% of those induced by carbachol, and KET also reversed this response in a dose-dependent manner. In epithelium-denuded strips, ET-1 induced contractions that were 104 +/- 3% of those induced by carbachol, and KET still reversed this response. The tonic phase of the response to ET-1 was equal (100 +/- 6%) to the response to carbachol, and KET did not affect it significantly. In the presence of ryanodine, KET reduced the ET-1-induced contraction from 67 +/- 2% to 36 +/- 3.%, P < 0.01. In the presence of nicardipine, KET also inhibited the ET-1-induced contraction. We conclude that KET relaxes the tracheal smooth muscle contracted by ETs via a mechanism that is independent of the tracheal epithelium. The relaxant effect of KET on the ET-induced contraction of the trachealis muscle is not dependent upon blockade of 1) sarcolemma influx of Ca2+ through the dihydropyridine Ca2+ channel or 2) the release of intracellular Ca2

Markers for human brain pericytes and smooth muscle cells.

PubMed

Smyth, Leon C D; Rustenhoven, Justin; Scotter, Emma L; Schweder, Patrick; Faull, Richard L M; Park, Thomas I H; Dragunow, Mike

2018-06-07

Brain pericytes and vascular smooth muscle cells (vSMCs) are a critical component of the neurovascular unit and are important in regulating cerebral blood flow and blood-brain barrier integrity. Identification of subtypes of mural cells in tissue and in vitro is important to any study of their function, therefore we identified distinct mural cell morphologies in neurologically normal post-mortem human brain. Further, the distribution of mural cell markers platelet-derived growth factor receptor-β (PDGFRβ), α-smooth muscle actin (αSMA), CD13, neural/glial antigen-2 (NG2), CD146 and desmin was examined. We determined that PDGFRβ, NG2, CD13, and CD146 were expressed in capillary-associated pericytes. NG2, and CD13 were also present on vSMCs in large vessels, however abundant CD146 and desmin staining was also detected in vSMCs on large vessels, co-labelling with αSMA. To determine whether cultures recapitulated observations from tissue, primary human brain pericytes derived from neurologically normal autopsies were analysed for the presence of pericyte markers by immunocytochemistry, western blotting and qPCR. The proteins observed in brain pericytes in tissue (PDGFRβ, αSMA, desmin, CD146, CD13, and NG2) were present in vitro, validating a panel of proteins that can be used to label brain pericytes and vSMCs in tissue and in vitro. Finally, we showed that the proteins CD146 and desmin that are expressed on large vessels in situ, are also selective markers of a smooth muscle cell phenotype in vitro. Copyright © 2018 Elsevier B.V. All rights reserved.

Polyflex stenting of tracheomalacia after surgery for congenital tracheal stenosis.

PubMed

Tibballs, James; Fasulakis, Stephen; Robertson, Colin F; Berkowitz, Robert G; Massie, John; Brizard, Christian; Rose, Elizabeth; Bekhit, Elhamy; Eyres, Robert; Ragg, Philip

2007-01-01

Polyflex self-expanding stents (Rüsch, Germany) were used in three young children who had presented with life-threatening long-segment tracheal stenosis with bronchial stenosis in two cases. Two children had slide tracheoplasties and subsequently aortic homografts and another tracheal resection and autotracheoplasty. However, in all cases persistent lower tracheal malacia necessitated stenting. Complications of granuloma, stent migration or dislodgement occurred in all cases. A fatal tracheo-aortic fistula occurred in one child. Granuloma in one was treated successfully with steroids. One child survives.

Gi-coupled γ-aminobutyric acid-B receptors cross-regulate phospholipase C and calcium in airway smooth muscle.

PubMed

Mizuta, Kentaro; Mizuta, Fumiko; Xu, Dingbang; Masaki, Eiji; Panettieri, Reynold A; Emala, Charles W

2011-12-01

γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system, and exerts its actions via both ionotropic (GABA(A)) and metabotropic (GABA(B)) receptors. Although the functional expression of GABA(B) receptors coupled to the G(i) protein was reported for airway smooth muscle, the role of GABA(B) receptors in airway responsiveness remains unclear. We investigated whether G(i)-coupled GABA(B) receptors cross-regulate phospholipase C (PLC), an enzyme classically regulated by G(q)-coupled receptors in human airway smooth muscle cells. Both the GABA(B)-selective agonist baclofen and the endogenous ligand GABA significantly increased the synthesis of inositol phosphate, whereas GABA(A) receptor agonists, muscimol, and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol exerted no effect. The baclofen-induced synthesis of inositol phosphate and transient increases in [Ca(2+)](i) were blocked by CGP35348 and CGP55845 (selective GABA(B) antagonists), pertussis toxin (PTX, which inactivates the G(i) protein), gallein (a G(βγ) signaling inhibitor), U73122 (an inhibitor of PLC-β), and xestospongin C, an inositol 1,4,5-triphosphate receptor blocker. Baclofen also potentiated the bradykinin-induced synthesis of inositol phosphate and transient increases in [Ca(2+)](i), which were blocked by CGP35348 or PTX. Moreover, baclofen potentiated the substance P-induced contraction of airway smooth muscle in isolated guinea pig tracheal rings. In conclusion, the stimulation of GABA(B) receptors in human airway smooth muscle cells rapidly mobilizes intracellular Ca(2+) stores by the synthesis of inositol phosphate via the activation of PLC-β, which is stimulated by G(βγ) protein liberated from G(i) proteins coupled to GABA(B) receptors. Furthermore, crosstalk between GABA(B) receptors and G(q)-coupled receptors potentiates the synthesis of inositol phosphate, transient increases in [Ca(2+)](i), and smooth muscle contraction through G

[Tracheal Intubation by Paramedics in a Local Community: Current Situation and Future Challenges].

PubMed

Takinami, Yoshikazu

2016-03-01

As of April 2013, 164 paramedics are certified to perform tracheal intubation in Fukui Prefecture. This study investigated the current situation surrounding tracheal intubation performed by paramedics in prehospital care. Subjects were 58 paramedics who completed practical training at our hospital. Post-training duration, number of tracheal intubation cases, number of attempts before successful tracheal intubation, disease involved, rate of return of spontaneous circulation, and prognosis were examined. Tracheal intubation was successful on the first attempt in 92% of cases. Rate of return of spontaneous circulation was high in paramedics whose post-training duration was short. No return of spontaneous circulation occurred after a second attempt. Four patients survived asphyxia or aspiration. It is important to perform successful tracheal intubation on the first attempt, to recognize the probability of successful resuscitation in patients with exogenous disease, and to strengthen the medical control system.

Reflex tracheal contraction during pulmonary venous congestion in the dog.

PubMed Central

Kappagoda, C T; Man, G C; Ravi, K; Teo, K K

1988-01-01

1. The effect of pulmonary venous congestion on tracheal tone was studied in dogs anaesthetized with alpha-chloralose. Pulmonary venous congestion was produced by partial obstruction of the mitral valve to increase left atrial pressure by 10 mmHg. Tracheal tone was measured in vivo by an isometric force displacement method. 2. Tracheal tone increased by 6.3 +/- 0.3 g from a control level of 91.6 +/- 2.8 g when left atrial pressure was increased by 10.5 +/- 0.3 mmHg. This response was abolished by cooling the cervical vagi to 8 degrees C at a point caudal to the origin of the superior laryngeal nerves. Also, sectioning the superior laryngeal nerves abolished this increase in tracheal tone. 3. Afferent activity recorded from rapidly adapting receptors of the airways increased significantly during pulmonary venous congestion. This increase in activity was abolished by cooling the vagi caudal to the recording site to 8-9 degrees C. 4. Administration of propranolol (0.5 mg/kg) failed to abolish this increase in tracheal tone while atropine (3 mg/kg) did so. 5. Stimulation of left atrial receptors without an increase in left atrial pressure and stimulation of right atrial receptors with and without increases in right atrial pressure did not cause any change in tracheal tone. 6. It is suggested that pulmonary venous congestion is associated with a reflex increase in tracheal tone, the afferent limb of which is formed by pulmonary receptors discharging into myelinated fibres in the cervical vagi and the efferent limb by parasympathetic cholinergic fibres in the superior laryngeal nerves. The afferent receptors are likely to be the rapidly adapting receptors. This reflex may be of importance in the development of the respiratory symptoms associated with left ventricular failure. PMID:3236242

Identification of FGF-dependent genes in the Drosophila tracheal system.

PubMed

Stahl, Markus; Schuh, Reinhard; Adryan, Boris

2007-01-01

The embryonic development of the tracheal system of the fruit fly Drosophila provides a paradigm for genetic studies of branching morphogenesis. Efforts of many laboratories have identified Branchless (Bnl, a fibroblast growth factor homologue) and Breathless (Btl, the receptor homologue) as crucial factors at many stages of tracheal system development. The downstream targets of the Bnl/Btl signalling cascade, however, remain mostly unknown. Misexpression of the bnl gene results in specific tracheal phenotypes that lead to larval death. We characterised the transcriptional profiles of targeted over-expression of bnl in the embryonic trachea and of loss-of-function bnl(P1) mutant embryos. Gene expression data was mapped to high-throughput in situ hybridisation based ImaGO-annotation. Thus, we identified and confirmed by quantitative PCR 13 Bnl-dependent genes that are expressed in cells within and outside of the tracheal system.

Fabrication of Chitosan Silk-based Tracheal Scaffold Using Freeze-Casting Method

PubMed Central

Nematollahi, Zeinab; Tafazzoli-Shadpour, Mohammad; Zamanian, Ali; Seyedsalehi, Amir; Mohammad-Behgam, Shadmehr; Ghorbani, Fariba; Mirahmadi, Fereshte

2017-01-01

Background: Since the treatments of long tracheal lesions are associated with some limitations, tissue engineered trachea is considered as an alternative option. This study aimed at preparing a composite scaffold, based on natural and synthetic materials for tracheal tissue engineering. Methods: Nine chitosan silk-based scaffolds were fabricated using three freezing rates (0.5, 1, and 2°C/min) and glutaraldehyde (GA) concentrations (0, 0.4, and 0.8 wt%). Samples were characterized, and scaffolds having mechanical properties compatible with those of human trachea and proper biodegradability were selected for chondrocyte cell seeding and subsequent biological assessments. Results: The pore sizes were highly influenced by the freezing rate and varied from 135.3×372.1 to 37.8×83.4 µm. Swelling and biodegradability behaviors were more affected by GA rather than freezing rate. Tensile strength raised from 120 kPa to 350 kPa by an increment of freezing rate and GA concentration. In addition, marked stiffening was demonstrated by increasing elastic modulus from 1.5 MPa to 12.2 MPa. Samples having 1 and 2°C/min of freezing rate and 0.8 wt% GA concentration made a non-toxic, porous structure with tensile strength and elastic modulus in the range of human trachea, facilitating the chondrocyte proliferation. The results of 21-day cell culture indicated that glycosaminoglycans content was significantly higher for the rate of 2°C/min (12.04 µg/min) rather than the other (9.6 µg/min). Conclusion: A homogenous porous structure was created by freeze drying. This allows the fabrication of a chitosan silk scaffold cross-linked by GA for cartilage tissue regeneration with application in tracheal regeneration. PMID:28131109

Effect of endothelin-1 on the serotonin-induced contraction of smooth muscle in the guinea pig trachea.

PubMed

Yoshida, M; Aizawa, H; Hara, N

1999-01-01

Endothelin (ET), a potent constrictor of smooth muscle including that of the airways, may contribute to the development of airway hyperresponsiveness. To investigate the role of ET-1 on the airway smooth muscle, we examined the effects of ET-1 on the serotonin-induced contraction of guinea pig tracheal smooth muscle. The changes in isometric tension evoked by serotonin were measured before and after the application of a subthreshold dose (a dose which did not induce smooth muscle contraction by itself) of ET-1. Serotonin caused smooth muscle contraction in a dose-dependent manner. The subthreshold doses of ET-1 (1 pM) and sarafotoxin 6c (1 pM), a selective ETB receptor agonist, were found to potentiate significantly the contraction induced by serotonin. A potentiating effect of ET-1 was not altered by indomethacin or calphostin C, a protein kinase C inhibitor. These results suggest that a subthreshold concentration of ET-1 can potentiate serotonin-induced contraction of smooth muscle through the activation of ETB receptor, while in contrast cyclooxygenase and protein kinase C were found not to be involved in this mechanism.

Primary tracheal papilloma disguised as asthma: A case report.

PubMed

Chen, Yan-Bin; Jiang, Jun-Hong; Guo, Ling-Chuan; Huang, Jian-An

2016-12-01

Tracheal papilloma presenting as asthma is a rare occurrence. We report a case of a 32-year-old male patient who presented with features of asthma. Flexible bronchoscopy demonstrated a large growth arising from the lower end of the trachea. Successful treatment using snare loop and argon plasma coagulation (APC) of the polyploidal growth was performed via flexible bronchoscope. The patient had immediate relief of airway obstruction and histopathological examination of the neoplasm demonstrated features of papilloma. Primary tracheal papilloma is mimicker of asthma, CT scan should be considered in patients with persistent chronic cough, or stridor. Endoscopic papillectomy is a safe and effective treatment and should be considered as first-line therapy for tracheal papilloma.

Characterization of primary cilia in human airway smooth muscle cells.

PubMed

Wu, Jun; Du, Hui; Wang, Xiangling; Mei, Changlin; Sieck, Gary C; Qian, Qi

2009-08-01

Considerable evidence indicates a key role for primary cilia of mammalian cells in mechanochemical sensing. Dysfunctions of primary cilia have been linked to the pathogenesis of several human diseases. However, cilia-related research has been limited to a few cell and tissue types; to our knowledge, no literature exists on primary cilia in airway smooth muscle (ASM). The aim of this study was to characterize primary cilia in human ASM. Primary cilia of human bronchial smooth muscle cells (HBSMCs) were examined using immunofluorescence confocal microscopy, and scanning and transmission electron microscopy. HBSMC migration and injury repair were examined by scratch-wound and epidermal growth factor (EGF)-induced migration assays. Cross-sectional images of normal human bronchi revealed that primary cilia of HBSMCs within each ASM bundle aggregated at the same horizontal level, forming a "cilium layer." Individual cilia of HBSMCs projected into extracellular matrix and exhibited varying degrees of deflection. Mechanochemical sensing molecules, polycystins, and alpha2-, alpha5-, and beta1-integrins were enriched in cilia, as was EGF receptor, known to activate jointly with integrins during cell migration. Migration assays demonstrated a ciliary contribution to HBSMC migration and wound repair. The primary cilia of ASM cells exert a role in sensing and transducing extracellular mechanochemical signals and in ASM injury repair. Defects in ASM ciliary function could potentially affect airway wall maintenance and/or remodeling, possibly relating to the genesis of bronchiectasis in autosomal dominant polycystic kidney disease, a disease of ciliopathy.

Enhanced elastin synthesis and maturation in human vascular smooth muscle tissue derived from induced-pluripotent stem cells.

PubMed

Eoh, Joon H; Shen, Nian; Burke, Jacqueline A; Hinderer, Svenja; Xia, Zhiyong; Schenke-Layland, Katja; Gerecht, Sharon

2017-04-01

Obtaining vascular smooth muscle tissue with mature, functional elastic fibers is a key obstacle in tissue-engineered blood vessels. Poor elastin secretion and organization leads to a loss of specialization in contractile smooth muscle cells, resulting in over proliferation and graft failure. In this study, human induced-pluripotent stem cells (hiPSCs) were differentiated into early smooth muscle cells, seeded onto a hybrid poly(ethylene glycol) dimethacrylate/poly (l-lactide) (PEGdma-PLA) scaffold and cultured in a bioreactor while exposed to pulsatile flow, towards maturation into contractile smooth muscle tissue. We evaluated the effects of pulsatile flow on cellular organization as well as elastin expression and assembly in the engineered tissue compared to a static control through immunohistochemistry, gene expression and functionality assays. We show that culturing under pulsatile flow resulted in organized and functional hiPSC derived smooth muscle tissue. Immunohistochemistry analysis revealed hiPSC-smooth muscle tissue with robust, well-organized cells and elastic fibers and the supporting microfibril proteins necessary for elastic fiber assembly. Through qRT-PCR analysis, we found significantly increased expression of elastin, fibronectin, and collagen I, indicating the synthesis of necessary extracellular matrix components. Functionality assays revealed that hiPSC-smooth muscle tissue cultured in the bioreactor had an increased calcium signaling and contraction in response to a cholinergic agonist, significantly higher mature elastin content and improved mechanical properties in comparison to the static control. The findings presented here detail an effective approach to engineering elastic human vascular smooth muscle tissue with the functionality necessary for tissue engineering and regenerative medicine applications. Obtaining robust, mature elastic fibers is a key obstacle in tissue-engineered blood vessels. Human induced-pluripotent stem cells have

Temporal and spatial dynamics underlying capacitative calcium entry in human colonic smooth muscle.

PubMed

Kovac, Jason R; Chrones, Tom; Sims, Stephen M

2008-01-01

Following smooth muscle excitation and contraction, depletion of intracellular Ca(2+) stores activates capacitative Ca(2+) entry (CCE) to replenish stores and sustain cytoplasmic Ca(2+) (Ca(2+)(i)) elevations. The objectives of the present study were to characterize CCE and the Ca(2+)(i) dynamics underlying human colonic smooth muscle contraction by using tension recordings, fluorescent Ca(2+)-indicator dyes, and patch-clamp electrophysiology. The neurotransmitter acetylcholine (ACh) contracted tissue strips and, in freshly isolated colonic smooth muscle cells (SMCs), caused elevation of Ca(2+)(i) as well as activation of nonselective cation currents. To deplete Ca(2+)(i) stores, the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitors thapsigargin and cyclopiazonic acid were added to a Ca(2+)-free bathing solution. Under these conditions, addition of extracellular Ca(2+) (3 mM) elicited increased tension that was inhibited by the cation channel blockers SKF-96365 (10 microM) and lanthanum (100 microM), suggestive of CCE. In a separate series of experiments on isolated SMCs, SERCA inhibition generated a gradual and sustained inward current. When combined with high-speed Ca(2+)-imaging techniques, the CCE-evoked rise of Ca(2+)(i) was associated with inward currents carrying Ca(2+) that were inhibited by SKF-96365. Regional specializations in Ca(2+) influx and handling during CCE were observed. Distinct "hotspot" regions of Ca(2+) rise and plateau were evident in 70% of cells, a feature not previously recognized in smooth muscle. We propose that store-operated Ca(2+) entry occurs in hotspots contributing to localized Ca(2+) elevations in human colonic smooth muscle.

A pre-operative planning for endoprosthetic human tracheal implantation: a decision support system based on robust design of experiments.

PubMed

Trabelsi, O; Villalobos, J L López; Ginel, A; Cortes, E Barrot; Doblaré, M

2014-05-01

Swallowing depends on physiological variables that have a decisive influence on the swallowing capacity and on the tracheal stress distribution. Prosthetic implantation modifies these values and the overall performance of the trachea. The objective of this work was to develop a decision support system based on experimental, numerical and statistical approaches, with clinical verification, to help the thoracic surgeon in deciding the position and appropriate dimensions of a Dumon prosthesis for a specific patient in an optimal time and with sufficient robustness. A code for mesh adaptation to any tracheal geometry was implemented and used to develop a robust experimental design, based on the Taguchi's method and the analysis of variance. This design was able to establish the main swallowing influencing factors. The equations to fit the stress and the vertical displacement distributions were obtained. The resulting fitted values were compared to those calculated directly by the finite element method (FEM). Finally, a checking and clinical validation of the statistical study were made, by studying two cases of real patients. The vertical displacements and principal stress distribution obtained for the specific tracheal model were in agreement with those calculated by FE simulations with a maximum absolute error of 1.2 mm and 0.17 MPa, respectively. It was concluded that the resulting decision support tool provides a fast, accurate and simple tool for the thoracic surgeon to predict the stress state of the trachea and the reduction in the ability to swallow after implantation. Thus, it will help them in taking decisions during pre-operative planning of tracheal interventions.

Tubeless tracheal resection and reconstruction for management of benign stenosis.

PubMed

Caronia, Francesco Paolo; Loizzi, Domenico; Nicolosi, Tommaso; Castorina, Sergio; Fiorelli, Alfonso

2017-12-01

We reported a tubeless tracheal resection and reconstruction for the management of benign posttracheostomy tracheal stenosis. A 34-year-old man with stridor, severe respiratory distress, and recurrent pneumonia was referred to our attention for treatment of benign posttracheostomy tracheal stenosis. As he refused general anesthesia, the procedure was performed while he was under local anesthesia and spontaneous ventilation. Sedation was started with infusion of dexmedetomidine 0.7 mg/kg/min and of remifentanil 0.5 mg/kg/h; also, 40%-50% oxygen was delivered using a laryngeal mask at a rate of 3.5 mL/min. An additional dose of 2% lidocaine was injected into the surgical site during the operation to achieve an adequate level of anesthesia. A standard resection and reconstruction of trachea was carried out and no recurrence was found in the follow-up of 41 months. Tubeless tracheal surgery seems to be a feasible and safe procedure. Larger prospective series should validate our results. © 2017 Wiley Periodicals, Inc.

External tracheal stabilization technique for acquired tracheomalacia using a tailored silicone tube.

PubMed

Cho, Jong Ho; Kim, HoJoong; Kim, Jhingook

2012-10-01

Here, we describe an external tracheal stabilization technique used in a patient with tracheomalacia. A 56-year-old man presented with tracheomalacia due to prolonged mechanical ventilation. The malacic tracheal segment was approximately 2 cm in length. The malacic segment was covered with a silicone tube sutured in place using Prolene sutures (Ethicon, Somerville, NJ). Several anchoring sutures were placed between the tracheal mucosa and the silicone tube without violating the mucosal continuity. The patient was discharged on postoperative day 5 without complication. This method of external tracheal stabilization is a less invasive alternative for the management of this particular patient. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Tracheal Injuries Complicating Prolonged Intubation and Tracheostomy.

PubMed

Cooper, Joel D

2018-05-01

Respiratory care advances such as the introduction of ventilatory assistance have been associated with postintubation airway stenosis resulting from tracheal injury at the site of the inflatable cuff on endotracheal or tracheostomy tubes. Low-pressure cuffs have significantly reduced this occurrence. Loss of airway stability at the site of a tracheostomy stoma may result in tracheal stenosis. Subglottic stenosis may result from a high tracheostomy site at, or just inferior to, the cricoid arch, or to malposition of an endotracheal tube cuff. Awareness of these complications and their causes is essential to prevent their occurrence. Copyright © 2018 Elsevier Inc. All rights reserved.

Cellular distribution and function of ion channels involved in transport processes in rat tracheal epithelium.

PubMed

Hahn, Anne; Faulhaber, Johannes; Srisawang, Lalita; Stortz, Andreas; Salomon, Johanna J; Mall, Marcus A; Frings, Stephan; Möhrlen, Frank

2017-06-01

Transport of water and electrolytes in airway epithelia involves chloride-selective ion channels, which are controlled either by cytosolic Ca 2+ or by cAMP The contributions of the two pathways to chloride transport differ among vertebrate species. Because rats are becoming more important as animal model for cystic fibrosis, we have examined how Ca 2+ - dependent and cAMP- dependent Cl - secretion is organized in the rat tracheal epithelium. We examined the expression of the Ca 2+ -gated Cl - channel anoctamin 1 (ANO1), the cystic fibrosis transmembrane conductance regulator (CFTR) Cl - channel, the epithelial Na + channel ENaC, and the water channel aquaporin 5 (AQP5) in rat tracheal epithelium. The contribution of ANO1 channels to nucleotide-stimulated Cl - secretion was determined using the channel blocker Ani9 in short-circuit current recordings obtained from primary cultures of rat tracheal epithelial cells in Ussing chambers. We found that ANO1, CFTR and AQP5 proteins were expressed in nonciliated cells of the tracheal epithelium, whereas ENaC was expressed in ciliated cells. Among nonciliated cells, ANO1 occurred together with CFTR and Muc5b and, in addition, in a different cell type without CFTR and Muc5b. Bioelectrical studies with the ANO1-blocker Ani9 indicated that ANO1 mediated the secretory response to the nucleotide uridine-5'-triphosphate. Our data demonstrate that, in rat tracheal epithelium, Cl - secretion and Na + absorption are routed through different cell types, and that ANO1 channels form the molecular basis of Ca 2+ -dependent Cl - secretion in this tissue. These characteristic features of Cl - -dependent secretion reveal similarities and distinct differences to secretory processes in human airways. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Ex vivo tracheomalacia model with 3D-printed external tracheal splint.

PubMed

Kaye, Rachel; Goldstein, Todd; Aronowitz, Danielle; Grande, Daniel A; Zeltsman, David; Smith, Lee P

2017-04-01

To design and evaluate an ex vivo model of tracheomalacia with and without a three-dimensional (3D)-printed external tracheal splint. Prospective, ex vivo animal trial. Three groups of ex vivo porcine tracheas were used: 1) control (unmanipulated trachea), 2) tracheomalacia (tracheal rings partially incised and crushed), and 3) splinted tracheomalacia (external custom tracheal splint fitted onto group 2 trachea). Each end of an ex vivo trachea was sealed with a custom-designed and 3D-printed cap; a transducer was placed through one end to measure the pressure inside the trachea. Although the negative pressure was applied to the tracheal lumen, the tracheal wall collapse was measured externally and internally using a bronchoscope. Each group had at least three recorded trials. Tracheal diameter was evaluated using ImageJ software (National Institutes of Health, Bethesda, MD) and was averaged between two raters. Average tracheal occlusion percentage was compared using Student t test. The average occlusion was 31% for group 1, 87.4% for group 2, and 20% for group 3. Significant differences were found between the control and tracheomalacia groups (P < 0.01) and the tracheomalacia and splinted tracheomalacia groups (P < 0.01). There was no significant difference between the control and splinted tracheomalacia groups (P = 0.13). Applied pressure was plotted against occlusion and regression line slope differed between the tracheomalacia (0.91) and control (0.12) or splinted tracheomalacia (0.39) groups. We demonstrate the potential for an ex vivo tracheomalacia model to reproduce airway collapse and show that this collapse can be treated successfully with a 3D-printed external splint. These results are promising and justify further studies. N/A. Laryngoscope, 127:950-955, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Liver resection for metastases of tracheal adenoid cystic carcinoma: Report of two cases.

PubMed

Hashimoto, Shintaro; Sumida, Yorihisa; Tobinaga, Shuichi; Wada, Hideo; Wakata, Kouki; Nonaka, Takashi; Kunizaki, Masaki; Hidaka, Shigekazu; Kinoshita, Naoe; Sawai, Terumitsu; Nagayasu, Takeshi

2018-05-16

Tracheal adenoid cystic carcinoma (ACC) is rare and accounts for <1% of all lung cancers. Although ACC is classified as a low-grade tumor, metastases are frequently identified in the late period. Extrapulmonary metastases are rare, and their resection has rarely been reported. Case 1: A 77-year-old man underwent tracheal resection for ACC with postoperative radiation (60 Gy) 14 years before　(at the age of 63). He underwent two subsequent pulmonary resections for metastases. Fourteen years after the first operation, he underwent extended right posterior segmentectomy with resection of segment IV and radiofrequency ablation for metastases of ACC to the liver. He was diagnosed with metastases to the kidney with peritoneal dissemination 4 years after the liver resection and died of pneumonia 2 years later. Case 2: A 53-year-old woman underwent a two-stage operation involving tracheal resection for ACC and partial resection of liver segments II and V for metastases of ACC to the liver. The tracheal margin was histopathologically positive. Postoperative radiation was performed, and she was tumor-free for 10 months after the liver resection. Complete resection of tracheal ACC provides better survival. Radiotherapy is also recommended. However, the optimal treatment for metastases of ACC is unclear, especially because liver resection for metastases of tracheal ACC is rarely reported. Our two cases of metastases of tracheal ACC were surgically managed with good outcomes. Liver resection for metastases of tracheal ACC may contribute to long survival. Copyright © 2018. Published by Elsevier Ltd.

Nitric oxide and vasoactive intestinal peptide as co-transmitters of airway smooth-muscle relaxation: analysis in neuronal nitric oxide synthase knockout mice.

PubMed

Hasaneen, Nadia A; Foda, Hussein D; Said, Sami I

2003-09-01

Both vasoactive intestinal peptide (VIP) and nitric oxide (NO) relax airway smooth muscle and are potential co-transmitters of neurogenic airway relaxation. The availability of neuronal NO synthase (nNOS) knockout mice (nNOS-/-) provides a unique opportunity for evaluating NO. To evaluate the relative importance of NO, especially that generated by nNOS, and VIP as transmitters of the inhibitory nonadrenergic, noncholinergic (NANC) system. In this study, we compared the neurogenic (tetrodotoxin-sensitive) NANC relaxation of tracheal segments from nNOS-/- mice and control wild-type mice (nNOS(+/+)), induced by electrical field stimulation (EFS). We also examined the tracheal contractile response to methacholine and its relaxant response to VIP. EFS (at 60 V for 2 ms, at 10, 15, or 20 Hz) dose-dependently reduced tracheal tension, and the relaxations were consistently smaller (approximately 40%) in trachea from nNOS-/- mice than from control wild-type mice (p < 0.001). VIP (10(- 8) to 10(-6) mol/L) induced concentration-dependent relaxations that were approximately 50% smaller in nNOS-/- tracheas than in control tracheas. Methacholine induced concentration-dependent contractions that were consistently higher in the nNOS-/- tracheas relative to wild-type mice tracheas (p > 0.05). Our data suggest that, in mouse trachea, NO is probably responsible for mediating a large (approximately 60%) component of neurogenic NANC relaxation, and a similar (approximately 50%) component of the relaxant effect of VIP. The results imply that NO contributes significantly to neurogenic relaxation of mouse airway smooth muscle, whether due to neurogenic stimulation or to the neuropeptide VIP.

Neurophysiology and Neuroanatomy of Smooth Pursuit in Humans

ERIC Educational Resources Information Center

Lencer, Rebekka; Trillenberg, Peter

2008-01-01

Smooth pursuit eye movements enable us to focus our eyes on moving objects by utilizing well-established mechanisms of visual motion processing, sensorimotor transformation and cognition. Novel smooth pursuit tasks and quantitative measurement techniques can help unravel the different smooth pursuit components and complex neural systems involved…

Inhibition by TNF-alpha and IL-4 of cationic lipid mediated gene transfer in cystic fibrosis tracheal gland cells.

PubMed

Bastonero, Sonia; Gargouri, Myriem; Ortiou, Sandrine; Guéant, Jean-Louis; Merten, Marc D

2005-11-01

In vivo, tracheal gland serous cells highly express the cystic fibrosis transmembrane conductance regulator (cftr) gene. This gene is mutated in the lethal monogenic disease cystic fibrosis (CF). Clinical trials in which the human CFTR cDNA was delivered to the respiratory epithelia of CF patients have resulted in weak and transient gene expression. As CF is characterized by mucus inspissation, airway infection, and severe inflammation, we tested the hypothesis that inflammation and especially two cytokines involved in the Th1/Th2 inflammatory response, interleukin 4 (IL-4) and TNFalpha, could inhibit gene transfer efficiency using a model of human CF tracheal gland cells (CF-KM4) and Lipofectamine reagent as a transfection reagent. The specific secretory defects of CF-KM4 cells were corrected by Lipofectamine-mediated human CFTR gene transfer. However, this was altered when cells were pre-treated with IL-4 and TNFalpha. Inhibition of luciferase reporter gene expression by IL-4 and TNFalpha pre-treated CF-KM4 cells was measured by activity and real-time RT-PCR. Both cytokines induced similar and synergistic inhibition of transgene expression and activity. This cytokine-mediated inhibition could be prevented by anti-inflammatory agents such as glucocorticoids but not by non-steroidal (NSAI) agents. This data suggests that an inflammatory context generated by IL-4 and TNFalpha can inhibit human CFTR gene transfer in CF tracheal gland cells and that glucocorticoids may have a protecting action. Copyright (c) 2005 John Wiley & Sons, Ltd.

Development and Function of the Drosophila Tracheal System.

PubMed

Hayashi, Shigeo; Kondo, Takefumi

2018-06-01

The tracheal system of insects is a network of epithelial tubules that functions as a respiratory organ to supply oxygen to various target organs. Target-derived signaling inputs regulate stereotyped modes of cell specification, branching morphogenesis, and collective cell migration in the embryonic stage. In the postembryonic stages, the same set of signaling pathways controls highly plastic regulation of size increase and pattern elaboration during larval stages, and cell proliferation and reprograming during metamorphosis. Tracheal tube morphogenesis is also regulated by physicochemical interaction of the cell and apical extracellular matrix to regulate optimal geometry suitable for air flow. The trachea system senses both the external oxygen level and the metabolic activity of internal organs, and helps organismal adaptation to changes in environmental oxygen level. Cellular and molecular mechanisms underlying the high plasticity of tracheal development and physiology uncovered through research on Drosophila are discussed. Copyright © 2018 by the Genetics Society of America.

Tracheal Papilloma Treated with Cryotherapy and Interferon-α: A Case Report and Review of the Literature

PubMed Central

Yıldırım, Fatma; Türk, Murat; Demircan, Sedat; Akyürek, Nalan; Yurdakul, Ahmet Selim

2015-01-01

Tracheal papilloma (TP) is characterized by papillomatous growth of the bronchial epithelium that involves the trachea as a response to Human Papilloma Virus (HPV) infection. A 40-year-old male, with 3-month history of progressive dyspnea was admitted to our hospital, and there were no any other respiratory symptoms. Physical examination was unremarkable. Chest computed tomography (CT) showed that there was a papillomatous mass at the distal trachea. The lesion occupied 80% of tracheal lumen. This patient received cryotherapy and mechanical debridement under general anesthesia and postoperative pathology showed endotracheal papillomatosis. Patient was treated with interferon-α (IFN-α) and he showed no recurrence at the 8th month of his therapy. PMID:25789192

Polo-like Kinase 1 Regulates Vimentin Phosphorylation at Ser-56 and Contraction in Smooth Muscle*

PubMed Central

Li, Jia; Wang, Ruping; Gannon, Olivia J.; Rezey, Alyssa C.; Jiang, Sixin; Gerlach, Brennan D.; Liao, Guoning

2016-01-01

Polo-like kinase 1 (Plk1) is a serine/threonine-protein kinase that has been implicated in mitosis, cytokinesis, and smooth muscle cell proliferation. The role of Plk1 in smooth muscle contraction has not been investigated. Here, stimulation with acetylcholine induced Plk1 phosphorylation at Thr-210 (an indication of Plk1 activation) in smooth muscle. Contractile stimulation also activated Plk1 in live smooth muscle cells as evidenced by changes in fluorescence resonance energy transfer signal of a Plk1 sensor. Moreover, knockdown of Plk1 in smooth muscle attenuated force development. Smooth muscle conditional knock-out of Plk1 also diminished contraction of mouse tracheal rings. Plk1 knockdown inhibited acetylcholine-induced vimentin phosphorylation at Ser-56 without affecting myosin light chain phosphorylation. Expression of T210A Plk1 inhibited the agonist-induced vimentin phosphorylation at Ser-56 and contraction in smooth muscle. However, myosin light chain phosphorylation was not affected by T210A Plk1. Ste20-like kinase (SLK) is a serine/threonine-protein kinase that has been implicated in spindle orientation and microtubule organization during mitosis. In this study knockdown of SLK inhibited Plk1 phosphorylation at Thr-210 and activation. Finally, asthma is characterized by airway hyperresponsiveness, which largely stems from airway smooth muscle hyperreactivity. Here, smooth muscle conditional knock-out of Plk1 attenuated airway resistance and airway smooth muscle hyperreactivity in a murine model of asthma. Taken together, these findings suggest that Plk1 regulates smooth muscle contraction by modulating vimentin phosphorylation at Ser-56. Plk1 activation is regulated by SLK during contractile activation. Plk1 contributes to the pathogenesis of asthma. PMID:27662907

21 CFR 878.3720 - Tracheal prosthesis.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) Identification. The tracheal prosthesis is a rigid, flexible, or expandable tubular device made of a silicone... of the trachea or trachealbronchial tree. It may be unbranched or contain one or two branches. The...

Fluoroscopic and radiographic evaluation of tracheal collapse in dogs: 62 cases (2001-2006).

PubMed

Macready, Dawn M; Johnson, Lynelle R; Pollard, Rachel E

2007-06-15

To compare the use of radiography and fluoroscopy for detection and grading of tracheal collapse in dogs. Retrospective case series. Animals-62 dogs with tracheal collapse. For each dog, tracheal collapse was confirmed fluoroscopically and lateral cervical and thoracic radiographic views were reviewed. A board-certified radiologist (who was unaware of the dogs' clinical history) evaluated the cervical, thoracic inlet, thoracic, carinal, and main stem bronchial regions in all fluoroscopic videos and radiographic images for evidence of collapse. Cervical, thoracic inlet, thoracic, and carinal regions in both radio-graphic and fluoroscopic studies were graded for collapse (0%, 25%, 50%, 75%, or 100% decrease in diameter). Lateral cervical and thoracic radiographic images were available for 54 dogs, and inspiratory and expiratory lateral cervical and thoracic radiographic images were available for 8 dogs. For detection of tracheal collapse, assessment of radiographic views was sensitive and had the best negative predictive value in the cervical and thoracic inlet regions. Assessment of radiographic views was most specific and had the best positive predictive value in the thoracic inlet, thoracic, carina, and main stem bronchial regions. Radiography underestimated the degree of collapse in all areas. Review of inspiratory and expiratory views improved the accuracy of radiography for tracheal collapse diagnosis only slightly. Compared with fluoroscopy, radiography underestimated the frequency and degree of tracheal collapse. However, radiography appears to be useful for screening dogs with potential tracheal collapse.

Functional expression of the TMEM16 family of calcium-activated chloride channels in airway smooth muscle

PubMed Central

Remy, Kenneth E.; Danielsson, Jennifer; Funayama, Hiromi; Fu, Xiao Wen; Chang, Herng-Yu Sucie; Yim, Peter; Xu, Dingbang; Emala, Charles W.

2013-01-01

Airway smooth muscle hyperresponsiveness is a key component in the pathophysiology of asthma. Although calcium-activated chloride channel (CaCC) flux has been described in many cell types, including human airway smooth muscle (HASM), the true molecular identity of the channels responsible for this chloride conductance remains controversial. Recently, a new family of proteins thought to represent the true CaCCs was identified as the TMEM16 family. This led us to question whether members of this family are functionally expressed in native and cultured HASM. We further questioned whether expression of these channels contributes to the contractile function of HASM. We identified the mRNA expression of eight members of the TMEM16 family in HASM cells and show immunohistochemical evidence of TMEM16A in both cultured and native HASM. Functionally, we demonstrate that the classic chloride channel inhibitor, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), inhibited halide flux in cultured HASM cells. Moreover, HASM cells displayed classical electrophysiological properties of CaCCs during whole cell electrophysiological recordings, which were blocked by using an antibody selective for TMEM16A. Furthermore, two distinct TMEM16A antagonists (tannic acid and benzbromarone) impaired a substance P-induced contraction in isolated guinea pig tracheal rings. These findings demonstrate that multiple members of this recently described family of CaCCs are expressed in HASM cells, they display classic electrophysiological properties of CaCCs, and they modulate contractile tone in airway smooth muscle. The TMEM16 family may provide a novel therapeutic target for limiting airway constriction in asthma. PMID:23997176

Functional expression of the TMEM16 family of calcium-activated chloride channels in airway smooth muscle.

PubMed

Gallos, George; Remy, Kenneth E; Danielsson, Jennifer; Funayama, Hiromi; Fu, Xiao Wen; Chang, Herng-Yu Sucie; Yim, Peter; Xu, Dingbang; Emala, Charles W

2013-11-01

Airway smooth muscle hyperresponsiveness is a key component in the pathophysiology of asthma. Although calcium-activated chloride channel (CaCC) flux has been described in many cell types, including human airway smooth muscle (HASM), the true molecular identity of the channels responsible for this chloride conductance remains controversial. Recently, a new family of proteins thought to represent the true CaCCs was identified as the TMEM16 family. This led us to question whether members of this family are functionally expressed in native and cultured HASM. We further questioned whether expression of these channels contributes to the contractile function of HASM. We identified the mRNA expression of eight members of the TMEM16 family in HASM cells and show immunohistochemical evidence of TMEM16A in both cultured and native HASM. Functionally, we demonstrate that the classic chloride channel inhibitor, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), inhibited halide flux in cultured HASM cells. Moreover, HASM cells displayed classical electrophysiological properties of CaCCs during whole cell electrophysiological recordings, which were blocked by using an antibody selective for TMEM16A. Furthermore, two distinct TMEM16A antagonists (tannic acid and benzbromarone) impaired a substance P-induced contraction in isolated guinea pig tracheal rings. These findings demonstrate that multiple members of this recently described family of CaCCs are expressed in HASM cells, they display classic electrophysiological properties of CaCCs, and they modulate contractile tone in airway smooth muscle. The TMEM16 family may provide a novel therapeutic target for limiting airway constriction in asthma.

Air-Q laryngeal airway for rescue and tracheal intubation.

PubMed

Ads, Ayman; Auerbach, Frederic; Ryan, Kelly; El-Ganzouri, Abdel R

2016-08-01

We report the successful use of the Air-Q laryngeal airway (Air-Q LA) as a ventilatory device and a conduit for tracheal intubation to rescue the airway in a patient with difficult airway and tracheal stenosis. This is the first case report of the device to secure the airway after two episodes of hypoxemia in the operating room and intensive care unit. Consent for submission of this case report was obtained from our institution's human studies institutional review board given that the patient died a few months after his discharge from the hospital before his personal consent could be obtained and before preparation of this report. All personal identifiers that could lead to his identification have been removed from this report. A 59-year-old man was scheduled for a flexible and rigid bronchoscopy with possible laser excision of tracheal stenosis. He had a history of hypertension, atrial fibrillation, and diabetes. Assessment of airway revealed a thyromental distance of 6.5 cm, Mallampati class II, and body weight of 110 kg. He had hoarseness and audible inspiratory/expiratory stridor with Spo2 90% breathing room air. After induction and muscle relaxation, tracheal intubation and flexible bronchoscopy were achieved without incident. The patient was then extubated and a rigid bronchoscopy was attempted but failed with Spo2 dropping to 92%; rocuronium 60 mg was given, and reintubation was accomplished with a 7.5-mm endotracheal tube. A second rigid bronchoscopy attempt failed, with Spo2 dropping to 63%. Subsequent direct laryngoscopy revealed a bloody hypopharynx. A size 4.5 Air-Q LA was placed successfully and confirmed with capnography, and Spo2 returned to 100%. The airway was suctioned through the Air-Q LA device, and the airway was secured using a fiberoptic bronchoscope to place an endotracheal tube of 7.5-mm internal diameter. The case was canceled because of edema of the upper airway from multiple attempts with rigid bronchoscopy. The patient was transported

Subcellular trafficking of FGF controls tracheal invasion of Drosophila flight muscle

PubMed Central

Peterson, Soren J.; Krasnow, Mark A.

2015-01-01

SUMMARY To meet the extreme oxygen demand of insect flight muscle, tracheal (respiratory) tubes ramify not only on its surface, as in other tissues, but also within T-tubules and ultimately surrounding every mitochondrion. Although this remarkable physiological specialization has long been recognized, its cellular and molecular basis is unknown. Here we show that Drosophila tracheoles invade flight muscle T-tubules through transient surface openings. Like other tracheal branching events, invasion requires the Branchless FGF pathway. However, localization of the FGF chemoattractant changes from all muscle membranes to T-tubules as invasion begins. Core regulators of epithelial basolateral membrane identity localize to T-tubules, and knockdown of AP-1γ, required for basolateral trafficking, redirects FGF from T-tubules to surface, increasing tracheal surface ramification and preventing invasion. We propose that tracheal invasion is controlled by an AP-1-dependent switch in FGF trafficking. Thus, subcellular targeting of a chemoattractant can direct outgrowth to specific domains including inside the cell. PMID:25557078

Welded tracheal stent removal in a child under cardiopulmonary bypass.

PubMed

Kao, S C; Chang, W K; Pong, M W; Cheng, K W; Chan, K H; Tsai, S K

2003-08-01

Metallic tracheal stents have been used in the treatment of paediatric tracheomalacia for more than a decade. We describe a case in which critical airway obstruction occurred during removal of a welded tracheal stent using a rigid bronchoscope under general anaesthesia. Life-saving cardiopulmonary bypass was instituted urgently, and the welded stent was then removed successfully by directly opening the trachea.

Preliminary study for a newly designed silicone stent and delivery system for canine obstructive tracheal disease.

PubMed

Kim, Dae-Hyun; Choi, Chi-Bong; Chung, Wook-Hun; Lee, Sung-Ho; Lee, A-Jin; Jeong, Jae-Seung; Kim, Ho-Joong; Kim, Hwi-Yool

2012-10-01

The goal of this study was to prove the possibility of using silicone stents broadly used for human medicine in canine obstructive tracheal disease. A silicone stent anatomically designed for canine trachea was tested on 5 beagle dogs for 8 weeks. The stent was carefully inserted using a newly developed delivery device under fluoroscopic guidance. There were no technical difficulties in placing the stent during the procedure. Previously reported complications of airway stenting such as stent migration or granulation tissue formation did not occur in any of the cases. In addition, removal of the stent was as simple as inserting it, and complications were absent. The stent introduced in this study could possibly be applied to various canine obstructive tracheal diseases.

Prediction of the mid-tracheal level using surface anatomical landmarks in adults

PubMed Central

Jang, Young-Eun; Kim, Eun-Hee; Song, In-Kyung; Lee, Ji-Hyun; Ryu, Ho-Geoul; Kim, Hee-Soo; Kim, Jin-Tae

2017-01-01

Abstract Endotracheal tube (ETT) should be placed at the optimal level to avoid single lung ventilation or accidental extubation. This study was performed to estimate the mid-tracheal level by using surface anatomical landmarks in adult patients. Neck computed tomography images of 329 adult patients between the ages of 16 and 79 years were reviewed. In the midline sagittal plane, the levels corresponding to the vocal cords, cricoid cartilage, suprasternal notch, manubriosternal junction, and carina were identified. The surface distances from the cricoid cartilage to the suprasternal notch (extCC-SSN) and that from the suprasternal notch to the manubriosternal junction (extSSN-MSJ) were measured. The relationship between mid-tracheal level and the surface distances was analyzed using Bland–Altman plot. The difference between the extCC-SSN and the mid-tracheal level was −6.6 (12.5) mm, and the difference between the extSSN-MSJ and the mid-tracheal level was −19.2 (6.1) mm. The difference between the extCC-SSN and the mid-tracheal level was smaller in females compared with males [−1.7 (11.7) mm vs −12.8 (10.7) mm; P < 0.001]. The mid-tracheal level, which is helpful in planning the insertion depth of an ETT, can be predicted by the surface distance between the cricoid cartilage and suprasternal notch in adults, especially in females. PMID:28328810

Clinical evaluation of stethoscope-guided inflation of tracheal tube cuffs.

PubMed

Kumar, R D C; Hirsch, N P

2011-11-01

Tracheal tube cuffs are commonly inflated to pressures exceeding the recommended upper limit of 30 cmH(2)O. We evaluated whether a stethoscope-guided method of cuff inflation results in pressures within the recommended range. Patients were randomly assigned to receive one of two methods of cuff inflation. In the standard 'just seal' group, air was introduced into the tracheal cuff until the audible leak at the mouth disappeared. In the stethoscope-guided group, air was introduced into the cuff until a change from harsh to soft breath sounds occurred, whilst listening with a stethoscope bell placed over the thyroid cartilage. Twenty-five patients were recruited to each group. The median (IQR [range]) cuff pressure in the 'just seal' group was 34 (28-40 [18-49]) cmH(2)O, and in the stethoscope-guided group was 20 (20-26 [16-28]) cmH(2)O, p < 0.0001. The stethoscope-guided method of tracheal tube cuff inflation is a novel, simple technique that reliably results in acceptable tracheal cuff pressures. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

The Sophora flavescens flavonoid compound trifolirhizin inhibits acetylcholine induced airway smooth muscle contraction.

PubMed

Yang, Nan; Liang, Banghao; Srivastava, Kamal; Zeng, Jia; Zhan, Jixun; Brown, LaVerne; Sampson, Hugh; Goldfarb, Joseph; Emala, Charles; Li, Xiu-Min

2013-11-01

Asthma is a serious health problem worldwide, particularly in industrialized countries. Despite a better understanding of the pathophysiology of asthma, there are still considerable gaps in knowledge as well as a need for classes of drugs. ASHMI™ (Anti-asthma Herbal Medicine Intervention) is an aqueous extract of Ganoderma lucidum (Fr.) P. Karst (Ling Zhi), Sophora flavescens Aiton (Ku Shen) and Glycyrrhiza uralensis Fisch. ex DC (Gan Cao). It prevents allergic asthma airway hyper-reactivity in mice and inhibits acetylcholine (ACh) induced airway smooth muscle (ASM) contraction in tracheal rings from allergic asthmatic mice. The purpose of this research was to identify individual herb(s) and their active compound(s) that inhibit ASM contraction. It was found that S. flavescens, but not G. lucidum or G. uralensis aqueous extracts, inhibited ASM contraction in tracheal rings from asthmatic mice. Bioassay-guided isolation and identification of flavonoid fractions/compound(s) via methylene chloride extraction, preparative HPLC fractionation, and LC-MS and NMR spectroscopic analyses showed that trifolirhizin is an active constituent that inhibits acetylcholine mediated ASM contraction or directly relaxes pre-contracted ASM independent of β2-adrenoceptors. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Sophora Flavescens flavonoid compound trifolirhizin inhibits acetylcholine induced airway smooth muscle contraction

PubMed Central

Zeng, Jia; Zhan, Jixun; Brown, LaVerne; Sampson, Hugh; Goldfarb, Joseph; Emala, Charles; Li, Xiu-Min

2014-01-01

Asthma is a serious health problem worldwide, particularly in industrialized countries. Despite a better understanding of the pathophysiology of asthma, there are still considerable gaps in knowledge as well as a need for new classes of drugs. ASHMI™ (Anti-asthma Herbal Medicine Intervention) is an aqueous extract of Ganoderma lucidum (Fr.) P. Karst (Ling Zhi), Sophora flavescens Aiton (Ku Shen) and Glycyrrhiza uralensis Fisch. ex DC (Gan Cao). It prevents allergic asthma airway hyper-reactivity in mice and inhibits acetylcholine (ACh) induced airway smooth muscle (ASM) contraction in tracheal rings from allergic asthmatic mice. The purpose of this research was to identify individual herb(s) and their active compound(s) that inhibit ASM contraction. It was found that Sophora flavescens (S. flavescens), but not Ganoderma lucidum (G. lucidum) or Glycyrrhiza uralensis (G. uralensis) aqueous extracts, inhibited ASM contraction in tracheal rings from asthmatic mice. Bioassay-guided isolation and identification of flavonoid fractions/compound(s) via methylene chloride extraction, preparative HPLC fractionation, and LC-MS and NMR spectroscopic analyses showed that trifolirhizin is an active constituent that inhibits acetylcholine mediated ASM contraction or directly relaxes pre-contracted ASM independent of β2-adrenoceptors. PMID:23993294

Tracheal palpation to assess endotracheal tube depth: an exploratory study.

PubMed

McKay, William P; Klonarakis, Jim; Pelivanov, Vladko; O'Brien, Jennifer M; Plewes, Chris

2014-03-01

Correct placement of the endotracheal tube (ETT) occurs when the distal tip is in mid-trachea. This study compares two techniques used to place the ETT at the correct depth during intubation: tracheal palpation vs placement at a fixed depth at the patient's teeth. With approval of the Research Ethics Board, we recruited American Society of Anesthesiologists physical status I-II patients scheduled for elective surgery with tracheal intubation. Clinicians performing the tracheal intubations were asked to "advance the tube slowly once the tip is through the cords". An investigator palpated the patient's trachea with three fingers spread over the trachea from the larynx to the sternal notch. When the ETT tip was felt in the sternal notch, the ETT was immobilized and its position was determined by fibreoptic bronchoscopy. The position of the ETT tip was compared with our hospital standard, which is a depth at the incisors or gums of 23 cm for men and 21 cm for women. The primary outcome was the incidence of correct placement. Correct placement of the ETT was defined as a tip > 2.5 cm from the carina and > 3.5 cm below the vocal cords. Movement of the ETT tip was readily palpable in 77 of 92 patients studied, and bronchoscopy was performed in 85 patients. Placement by tracheal palpation resulted in more correct placements (71 [77%]; 95% confidence interval [CI] 74 to 81) than hospital standard depth at the incisors or gums (57 [61%]; 95% CI 58 to 66) (P = 0.037). The mean (SD) placement of the ETT tip in palpable subjects was 4.1 (1.7) cm above the carina, 1.9 cm (1.5-2.3 cm) below the ideal mid-tracheal position. Tracheal palpation requires no special equipment, takes only a few seconds to perform, and may improve ETT placement at the correct depth. Further studies are warranted.

Fatal complication from a balloon-expandable tracheal stent in a child: a case report.

PubMed

Stotz, William H; Berkowitz, Ivor D; Hoehner, Jeff C; Tunkel, David E

2003-01-01

The use of airway stents in the pediatric population is uncommon, reflected in the few patient series reported in the literature. We describe a fatal complication of tracheal stent placement in an 18-month-old child with spondylothoracic dysplasia. Case report. Intensive care unit of a tertiary academic pediatric center. An 18-month-old child with spondylothoracic dysplasia who underwent tracheal stent placement for tracheomalacia. Management of an acute upper-airway hemorrhage. The patient died, despite aggressive interventions. Use of tracheal stents in pediatric patients with tracheomalacia is not without risks; tracheal erosion with severe hemoptysis is an infrequent but devastating complication of this intervention.

Subcellular trafficking of FGF controls tracheal invasion of Drosophila flight muscle.

PubMed

Peterson, Soren J; Krasnow, Mark A

2015-01-15

To meet the extreme oxygen demand of insect flight muscle, tracheal (respiratory) tubes ramify not only on its surface, as in other tissues, but also within T-tubules and ultimately surrounding every mitochondrion. Although this remarkable physiological specialization has long been recognized, its cellular and molecular basis is unknown. Here, we show that Drosophila tracheoles invade flight muscle T-tubules through transient surface openings. Like other tracheal branching events, invasion requires the Branchless FGF pathway. However, localization of the FGF chemoattractant changes from all muscle membranes to T-tubules as invasion begins. Core regulators of epithelial basolateral membrane identity localize to T-tubules, and knockdown of AP-1γ, required for basolateral trafficking, redirects FGF from T-tubules to surface, increasing tracheal surface ramification and preventing invasion. We propose that tracheal invasion is controlled by an AP-1-dependent switch in FGF trafficking. Thus, subcellular targeting of a chemoattractant can direct outgrowth to specific domains, including inside the cell. Copyright © 2015 Elsevier Inc. All rights reserved.

In-vivo characterization of a 3D hybrid scaffold based on PCL/decellularized aorta for tracheal tissue engineering.

PubMed

Ghorbani, Fariba; Moradi, Lida; Shadmehr, Mohammad Behgam; Bonakdar, Shahin; Droodinia, Atosa; Safshekan, Farzaneh

2017-12-01

As common treatments for long tracheal stenosis are associated with several limitations, tracheal tissue engineering is considered as an alternative treatment. This study aimed at preparing a hybrid scaffold, based on biologic and synthetic materials for tracheal tissue engineering. Three electrospun polycaprolactone (PCL) scaffolds, namely E1 (pure PCL), E2 (collagen-coated PCL) and E3 (PCL blended with collagen) were prepared. Allogeneic aorta was harvested and decellularized. A biodegradable PCL stent was fabricated and inserted into the aorta to prevent its collapse. Scaffold characterization results revealed that the 2-h swelling ratio of E2 was significantly higher than those of E1 and E3. In the first 3months, E2 and E3 exhibited almost equal degradabilities (significantly higher than that of E1). Moreover, tensile strengths of all samples were comparable with those of human trachea. Using rabbit's adipose-derived mesenchymal stem cells (AMSCs) and primary chondrocytes, E3 exhibited the highest levels of GAG release within 21days as well as collagen II and aggrecan expression. Fot the next step, AMSC-chondrocyte co-culture seeded scaffold was sutured to the acellular aorta, implanted into rabbits' muscle, and finally harvested after 4weeks of follow up. Harvested structures were totally viable due to the angiogenesis created by the muscle. H&E and alcian blue staining results revealed the presence of chondrocytes in the structure and GAG in the produced extracellular matrix. Since tracheal replacement using biologic and synthetic scaffolds usually results in tracheal collapse or granulation formation, a hybrid construct may provide the required rigidity and biocompatibility for the substitute. Copyright © 2017. Published by Elsevier B.V.

Association of tracheal mucus or blood and airway neutrophilia with racing performance in Thoroughbred horses in an Australian racing yard.

PubMed

Salz, R O; Ahern, B J; Boston, R; Begg, L M

2016-04-01

To determine the variation of tracheal mucus scores, tracheal blood scores and transendoscopic tracheal wash (TW) cytology in a population of Thoroughbred (TB) racehorses and assess their association with racing performance. A total of 220 endoscopic examinations were performed and TWs obtained from 155 TB racehorses. Samples were collected 60-120 min following gallop work. Tracheal mucus score, tracheal blood score and TW cytology were analysed and their association with racing performance assessed. Of the total examinations and samples, 194 from 135 horses fitted the criteria for inclusion. The overall prevalence of visible tracheal mucus was 2.5% (5/194) and of increased tracheal mucus was 0%. The prevalence of visible tracheal blood was 8.8% (17/194) and of increased tracheal blood was 4.6% (9/194). A total of 36% (70/194) of TWs contained elevated percentages of neutrophils and of these, 96% (67/70) occurred in the absence of any visible tracheal mucus. There was no significant association between tracheal mucus score or TW cytology and subsequent racing performance. There was a statistically significant association (P = 0.004) between increased tracheal blood scores and poor racing performance. Visible tracheal blood seen after strenuous exercise in clinically normal TB racehorses was a risk factor for poor racing performance, but the presence of airway neutrophilia was not. No horses in this study were found to have increased tracheal mucus, so the association of increased tracheal mucus with racing performance could not be assessed. © 2016 Australian Veterinary Association.

Actions of cAMP on calcium sensitization in human detrusor smooth muscle contraction.

PubMed

Hayashi, Maya; Kajioka, Shunichi; Itsumi, Momoe; Takahashi, Ryosuke; Shahab, Nouval; Ishigami, Takao; Takeda, Masahiro; Masuda, Noriyuki; Yamaguchi, Akito; Naito, Seiji

2016-01-01

To clarify the effect of cAMP on the Ca(2+) -sensitized smooth muscle contraction in human detrusor, as well as the role of novel exchange protein directly activated by cAMP (Epac) in cAMP-mediated relaxation. All experimental protocols to record isometric tension force were performed using α-toxin-permeabilized human detrusor smooth muscle strips. The mechanisms of cAMP-mediated suppression of Ca(2+) sensitization activated by 10 μm carbachol (CCh) and 100 μm GTP were studied using a selective rho kinase (ROK) inhibitor, Y-27632, and a selective protein kinase C (PKC) inhibitor, GF-109203X. The relaxation mechanisms were further probed using a selective protein kinase A (PKA) activator, 6-Bnz-cAMP and a selective Epac activator, 8-pCPT-2'-O-Me-cAMP. We observed that CCh-induced Ca(2+) sensitization was inhibited by cAMP in a concentration-dependent manner. GF-109203X (10 μm) but not Y-27632 (10 μm) significantly enhanced the relaxation effect induced by cAMP (100 μm). 6-Bnz-cAMP (100 μm) predominantly decreased the tension force in comparison with 8-pCPT-2'-O-Me-cAMP (100 μm). We showed that cAMP predominantly inhibited the ROK pathway but not the PKC pathway. The PKA-dependent pathway is dominant, while Epac plays a minor role in human detrusor smooth muscle Ca(2+) sensitization. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

RANTES release by human airway smooth muscle: effects of prostaglandin E(2) and fenoterol.

PubMed

Lazzeri, N; Belvisi, M G; Patel, H J; Chung, K F; Yacoub, M H; Mitchell, J A

2001-12-21

In human airway smooth muscle cells, the levels of RANTES were increased upon stimulation with interleukin-1beta together with tumour necrosis factor-alpha (TNF-alpha) (10 ng ml(-1) for each). In this study, we have assessed the effects of prostaglandin E(2) and the beta(2)-adrenoceptor agonist, fenoterol on RANTES (regulated upon activation, normal T cell expressed and secreted) release by these cells. The levels of RANTES released by human airway smooth muscle cells were measured after 24 h of treatment. Prostaglandin E(2) and fenoterol, only in presence of a cyclo-oxygenase inhibitor indomethacin (10(-6) M), provoked a concentration-dependent reduction in RANTES release. These data suggest that, in settings where cyclo-oxygenase activity is low, both drugs may relieve the symptoms of airway diseases by reducing RANTES production.

Unregulated smooth-muscle myosin in human intestinal neoplasia.

PubMed

Alhopuro, Pia; Phichith, Denis; Tuupanen, Sari; Sammalkorpi, Heli; Nybondas, Miranda; Saharinen, Juha; Robinson, James P; Yang, Zhaohui; Chen, Li-Qiong; Orntoft, Torben; Mecklin, Jukka-Pekka; Järvinen, Heikki; Eng, Charis; Moeslein, Gabriela; Shibata, Darryl; Houlston, Richard S; Lucassen, Anneke; Tomlinson, Ian P M; Launonen, Virpi; Ristimäki, Ari; Arango, Diego; Karhu, Auli; Sweeney, H Lee; Aaltonen, Lauri A

2008-04-08

A recent study described a recessive ATPase activating germ-line mutation in smooth-muscle myosin (smmhc/myh11) underlying the zebrafish meltdown (mlt) phenotype. The mlt zebrafish develops intestinal abnormalities reminiscent of human Peutz-Jeghers syndrome (PJS) and juvenile polyposis (JP). To examine the role of MYH11 in human intestinal neoplasia, we searched for MYH11 mutations in patients with colorectal cancer (CRC), PJS and JP. We found somatic protein-elongating frameshift mutations in 55% of CRCs displaying microsatellite instability and in the germ-line of one individual with PJS. Additionally, two somatic missense mutations were found in one microsatellite stable CRC. These two missense mutations, R501L and K1044N, and the frameshift mutations were functionally evaluated. All mutations resulted in unregulated molecules displaying constitutive motor activity, similar to the mutant myosin underlying mlt. Thus, MYH11 mutations appear to contribute also to human intestinal neoplasia. Unregulated MYH11 may affect the cellular energy balance or disturb cell lineage decisions in tumor progenitor cells. These data challenge our view on MYH11 as a passive differentiation marker functioning in muscle contraction and add to our understanding of intestinal neoplasia.

Paclitaxel Drug-eluting Tracheal Stent Could Reduce Granulation Tissue Formation in a Canine Model

PubMed Central

Wang, Ting; Zhang, Jie; Wang, Juan; Pei, Ying-Hua; Qiu, Xiao-Jian; Wang, Yu-Ling

2016-01-01

Background: Currently available silicone and metallic stents for tracheal stenosis are associated with many problems. Granulation proliferation is one of the main complications. The present study aimed to evaluate the efficacy of paclitaxel drug-eluting tracheal stent in reducing granulation tissue formation in a canine model, as well as the pharmacokinetic features and safety profiles of the coated drug. Methods: Eight beagles were randomly divided into a control group (bare-metal stent group, n = 4) and an experimental group (paclitaxel-eluting stent group, n = 4). The observation period was 5 months. One beagle in both groups was sacrificed at the end of the 1st and 3rd months, respectively. The last two beagles in both groups were sacrificed at the end of 5th month. The proliferation of granulation tissue and changes in tracheal mucosa were compared between the two groups. Blood routine and liver and kidney function were monitored to evaluate the safety of the paclitaxel-eluting stent. The elution method and high-performance liquid chromatography were used to characterize the rate of in vivo release of paclitaxel from the stent. Results: Compared with the control group, the proliferation of granulation tissue in the experimental group was significantly reduced. The drug release of paclitaxel-eluting stent was the fastest in the 1st month after implantation (up to 70.9%). Then, the release slowed down gradually. By the 5th month, the release reached up to 98.5%. During the observation period, a high concentration of the drug in the trachea (in the stented and adjacent unstented areas) and lung tissue was not noted, and the blood test showed no side effect. Conclusions: The paclitaxel-eluting stent could safely reduce the granulation tissue formation after stent implantation in vivo, suggesting that the paclitaxel-eluting tracheal stent might be considered for potential use in humans in the future. PMID:27824004

A visual stethoscope to detect the position of the tracheal tube.

PubMed

Kato, Hiromi; Suzuki, Akira; Nakajima, Yoshiki; Makino, Hiroshi; Sanjo, Yoshimitsu; Nakai, Takayoshi; Shiraishi, Yoshito; Katoh, Takasumi; Sato, Shigehito

2009-12-01

Advancing a tracheal tube into the bronchus produces unilateral breath sounds. We created a Visual Stethoscope that allows real-time fast Fourier transformation of the sound signal and 3-dimensional (frequency-amplitude-time) color rendering of the results on a personal computer with simultaneous processing of 2 individual sound signals. The aim of this study was to evaluate whether the Visual Stethoscope can detect bronchial intubation in comparison with auscultation. After induction of general anesthesia, the trachea was intubated with a tracheal tube. The distance from the incisors to the carina was measured using a fiberoptic bronchoscope. While the anesthesiologist advanced the tracheal tube from the trachea to the bronchus, another anesthesiologist auscultated breath sounds to detect changes of the breath sounds and/or disappearance of bilateral breath sounds for every 1 cm that the tracheal tube was advanced. Two precordial stethoscopes placed at the left and right sides of the chest were used to record breath sounds simultaneously. Subsequently, at a later date, we randomly entered the recorded breath sounds into the Visual Stethoscope. The same anesthesiologist observed the visualized breath sounds on the personal computer screen processed by the Visual Stethoscope to examine changes of breath sounds and/or disappearance of bilateral breath sound. We compared the decision made based on auscultation with that made based on the results of the visualized breath sounds using the Visual Stethoscope. Thirty patients were enrolled in the study. When irregular breath sounds were auscultated, the tip of the tracheal tube was located at 0.6 +/- 1.2 cm on the bronchial side of the carina. Using the Visual Stethoscope, when there were any changes of the shape of the visualized breath sound, the tube was located at 0.4 +/- 0.8 cm on the tracheal side of the carina (P < 0.01). When unilateral breath sounds were auscultated, the tube was located at 2.6 +/- 1.2 cm on the

Functional optical imaging of tracheal health (Conference Presentation)

NASA Astrophysics Data System (ADS)

Gil, Daniel A.; Sharick, Joe T.; Gamm, Ute A.; Choma, Michael A.; Skala, Melissa C.

2017-04-01

The health of the tracheal mucosa is an important, but poorly understood, aspect of critical care medicine. Many critical care patients are mechanically ventilated through an endotracheal tube that can cause local inflammation and blunt damage to the ciliated epithelial cells lining the trachea. These cilia clear mucus and infectious agents from the respiratory tract, so impaired ciliary function may lead to increased susceptibility to respiratory infection. Therefore, a minimally-invasive method to monitor mucosal health and ciliary function in intubated patients would be valuable to critical care medicine. Optical metabolic imaging (OMI) can quantitatively assess the metabolic state of cells by measuring the fluorescence intensities of endogenous metabolic co-enzymes NAD(P)H and FAD. OMI is especially attractive for assessing tracheal health because OMI is label-free, and ciliary function is tightly linked to the levels of NAD(P)H and FAD. In this study, we apply widefield OMI to ex vivo mouse tracheae (n=6), and demonstrate that the optical redox ratio (fluorescence intensity of NAD(P)H divided by the intensity of FAD) is sensitive to changes in the cellular metabolism of the tracheal mucosa. We observed a 46% increase in the redox ratio 20 minutes after treatment with 10mM of sodium cyanide (p<0.001, 95% CI [40%, 52%]), an inhibitor of oxidative cellular respiration. In addition to being a proof-of-concept demonstration, Pseudomonas aeruginosa, an important cause of morbidity and mortality in CF patients and in the ICU, produces hydrogen cyanide. Our results support the development of minimally-invasive fiber-optic probes for in vivo monitoring of tracheal health.

Acute tracheal oedema and haemorrhage with fibrinonecrotic tracheitis in pigs--a porcine counterpart of bovine honker syndrome?

PubMed

Szeredi, L; Dán, Á; Makrai, L; Takács, N; Biksi, I

2015-01-01

Cases of acute tracheal oedema and haemorrhage with fibrinonecrotic tracheitis have been described in Hungarian pig herds. Clinical signs and gross and microscopical tracheal lesions bore resemblance to those of bovine 'honker syndrome'. Diagnostic examination of affected tracheas and corresponding lungs revealed the presence of a variety of agents; however, in some cases tracheal lesions developed without detectable pathogens or associated pulmonary pathology. In line with the bovine condition, this suggests the possibility of cough-induced tracheal damage as an initiating factor for this tracheal change in swine. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fetal Endoscopic Tracheal Intubation: A New Fetoscopic Procedure to Ensure Extrauterine Tracheal Permeability in a Case with Congenital Cervical Teratoma.

PubMed

Cruz-Martinez, Rogelio; Moreno-Alvarez, Oscar; Garcia, Maritza; Méndez, Antonio; Pineda, Hugo; Cruz-Martinez, Miriam Alejandra; Cruz, Miriam A; Martinez-Morales, Cecilia

2015-01-01

Congenital neck masses are associated with high perinatal mortality and morbidity secondary to airway obstruction due to a mass effect of the tumor with subsequent neonatal asphyxia and/or neonatal death. Currently, the only technique designed to establish a secure neonatal airway is the ex utero intrapartum treatment (EXIT) procedure, which involves neonatal tracheal intubation while fetal oxygenation is maintained by the uteroplacental circulation in a partial fetal delivery under maternal general anesthesia. We present a case with a giant cervical teratoma and huge displacement and compression of the fetal trachea that was treated successfully at 35 weeks of gestation with a novel fetoscopic procedure to ensure extrauterine tracheal permeability by means of a fetal endoscopic tracheal intubation (FETI) before delivery. The procedure consisted of a percutaneous fetal tracheoscopy under maternal epidural anesthesia using an 11-Fr exchange catheter covering the fetoscope that allowed a conduit to introduce a 3.0-mm intrauterine orotracheal cannula under ultrasound guidance. After FETI, a conventional cesarean section was performed uneventfully with no need for an EXIT procedure. This report is the first to illustrate that in cases with large neck tumors involving fetal airways, FETI is feasible and could potentially replace an EXIT procedure by allowing prenatal airway control.

Traumatic tracheal diverticulum corrected with resection and anastomosis during one-lung ventilation and total intravenous anesthesia in a cat.

PubMed

Sayre, Rebecca S; Lepiz, Mauricio; Wall, Corey; Thieman-Mankin, Kelley; Dobbin, Jennifer

2016-11-01

This report describes the clinical findings and diagnostic images of a traumatic intrathoracic tracheal avulsion with a tracheal diverticulum in a cat. Furthermore, a complete description of the tracheal resection and anastomosis using one-lung ventilation (OLV) with total and partial intravenous anesthesia is made. A 3-year-old neutered male domestic shorthair cat weighing 6.8 kg was presented to the University Teaching Hospital for evaluation of increased respiratory noise 3 months following unknown trauma. Approximately 12 weeks prior to presentation, the cat had been seen by the primary care veterinarian for respiratory distress. At that time, the cat had undergone a tracheal ballooning procedure for a distal tracheal stricture diagnosed by tracheoscopy. The tracheal ballooning had provided only temporary relief. At presentation to our institution, the cat had increased respiratory effort with harsh upper airway noise auscultated during thoracic examination. The remainder of the physical examination was normal. Diagnostics included a tracheoscopy and a thoracic computed tomographic examination. The cat was diagnosed with tracheal avulsion, pseudotrachea with a tracheal diverticulum, and stenosis of the avulsed tracheal ends. Surgical correction of the tracheal stricture via a thoracotomy was performed using OLV with total and partial intravenous anesthesia. The cat recovered uneventfully and at last follow-up was active and doing well. This case report describes OLV using standard anesthesia equipment that is available at most private practices. Furthermore, this case describes the computed tomographic images of the intrathoracic tracheal avulsion and offers a positive outcome for tracheal resection and anastomosis. © Veterinary Emergency and Critical Care Society 2015.

Comparison of Fluoroscopy and Computed Tomography for Tracheal Lumen Diameter Measurement and Determination of Intraluminal Stent Size in Healthy Dogs

PubMed Central

Williams, Jackie M.; Krebs, Ingar A.; Riedesel, Elizabeth A.; Zhao, Qianqian

2015-01-01

Tracheal collapse is a progressive airway disease that can ultimately result in complete airway obstruction. Intraluminal tracheal stents are a minimally invasive and viable treatment for tracheal collapse once the disease becomes refractory to medical management. Intraluminal stent size is chosen based on the maximum measured tracheal diameter during maximum inflation. The purpose of this prospective, cross-sectional study was to compare tracheal lumen diameter measurements and subsequent selected stent size using both fluoroscopy and CT and to evaluate inter- and intraobserver variability of the measurements. Seventeen healthy Beagles were anesthetized and imaged with fluoroscopy and CT with positive pressure ventilation to 20 cm H2O. Fluoroscopic and CT maximum tracheal diameters were measured by 3 readers. Three individual measurements were made at 8 pre-determined tracheal sites for dorsoventral (height) and laterolateral (width) dimensions. Tracheal diameters and stent sizes (based on the maximum tracheal diameter + 10%) were analyzed using a linear mixed model. CT tracheal lumen diameters were larger compared to fluoroscopy at all locations. When comparing modalities, fluoroscopic and CT stent sizes were statistically different. Greater overall variation in tracheal diameter measurement (height or width) existed for fluoroscopy compared to CT, both within and among observers. The greater tracheal diameter and lower measurement variability supported the use of CT for appropriate stent selection to minimize complications in veterinary patients. PMID:26784924

Non-muscle (NM) myosin heavy chain phosphorylation regulates the formation of NM myosin filaments, adhesome assembly and smooth muscle contraction.

PubMed

Zhang, Wenwu; Gunst, Susan J

2017-07-01

Non-muscle (NM) and smooth muscle (SM) myosin II are both expressed in smooth muscle tissues, however the role of NM myosin in SM contraction is unknown. Contractile stimulation of tracheal smooth muscle tissues stimulates phosphorylation of the NM myosin heavy chain on Ser1943 and causes NM myosin filament assembly at the SM cell cortex. Expression of a non-phosphorylatable NM myosin mutant, NM myosin S1943A, in SM tissues inhibits ACh-induced NM myosin filament assembly and SM contraction, and also inhibits the assembly of membrane adhesome complexes during contractile stimulation. NM myosin regulatory light chain (RLC) phosphorylation but not SM myosin RLC phosphorylation is regulated by RhoA GTPase during ACh stimulation, and NM RLC phosphorylation is required for NM myosin filament assembly and SM contraction. NM myosin II plays a critical role in airway SM contraction that is independent and distinct from the function of SM myosin. The molecular function of non-muscle (NM) isoforms of myosin II in smooth muscle (SM) tissues and their possible role in contraction are largely unknown. We evaluated the function of NM myosin during contractile stimulation of canine tracheal SM tissues. Stimulation with ACh caused NM myosin filament assembly, as assessed by a Triton solubility assay and a proximity ligation assay aiming to measure interactions between NM myosin monomers. ACh stimulated the phosphorylation of NM myosin heavy chain on Ser1943 in tracheal SM tissues, which can regulate NM myosin IIA filament assembly in vitro. Expression of the non-phosphorylatable mutant NM myosin S1943A in SM tissues inhibited ACh-induced endogenous NM myosin Ser1943 phosphorylation, NM myosin filament formation, the assembly of membrane adhesome complexes and tension development. The NM myosin cross-bridge cycling inhibitor blebbistatin suppressed adhesome complex assembly and SM contraction without inhibiting NM myosin Ser1943 phosphorylation or NM myosin filament assembly. Rho

Standard methods for tracheal mite research

USDA-ARS?s Scientific Manuscript database

This chapter, for the COLOSS Beebook from the Bee Research Center in Switzerland, summarizes all the current information about the tracheal mite (Acarapis woodi) infesting honey bees (Apis mellifera). The chapter covers the effects on bees, its life history, and its range, as well as the identifica...

Treatment of congenital tracheal stenosis by balloon-expandable metallic stents in paediatric intensive care unit

PubMed Central

Xu, Xuan; Li, Dandan; Zhao, Shuyu; Liu, Xicheng; Feng, Zhichun; Ding, Hui

2012-01-01

The aim of this study was to evaluate the use of balloon-expandable metallic stents in the treatment of children with congenital tracheal stenosis in whom conventional therapy has failed. From 2010 to 2011, balloon-expandable metallic stents were implanted into the trachea of eight infants aged 2–20 months in the paediatric intensive care unit. The infants had severe airway obstruction caused by congenital tracheal stenosis. Tracheal stents were placed after intraluminal balloon dilatation of the tracheal stenosis, inserted with balloon catheters and implanted into the desired position bronchoscopically. The stents were 12 to 29 mm long and 4 mm in diameter. Seven children were relieved of airway obstruction after this procedure. However, a child died due to severe sepsis after the placement of bronchial stents. No granulation tissue developed over the stents in any of the children. Stents have been in place for 1–6 months after insertion without any other complication. Balloon-expandable metallic stents are effective in relieving airway obstruction by congenital tracheal stenosis in children. This technique may provide an important remedy for congenital tracheal stenosis in children. PMID:22361127

Interleukin-1beta-induced airway hyperresponsiveness enhances substance P in intrinsic neurons of ferret airway.

PubMed

Wu, Z-X; Satterfield, B E; Fedan, J S; Dey, R D

2002-11-01

Interleukin (IL)-1beta causes airway inflammation, enhances airway smooth muscle responsiveness, and alters neurotransmitter expression in sensory, sympathetic, and myenteric neurons. This study examines the role of intrinsic airway neurons in airway hyperresponsiveness (AHR) induced by IL-1beta. Ferrets were instilled intratracheally with IL-1beta (0.3 microg/0.3 ml) or saline (0.3 ml) once daily for 5 days. Tracheal smooth muscle contractility in vitro and substance P (SP) expression in tracheal neurons were assessed. Tracheal smooth muscle reactivity to acetylcholine (ACh) and methacholine (MCh) and smooth muscle contractions to electric field stimulation (EFS) both increased after IL-1beta. The IL-1beta-induced AHR was maintained in tracheal segments cultured for 24 h, a procedure that depletes SP from sensory nerves while maintaining viability of intrinsic airway neurons. Pretreatment with CP-99994, an antagonist of neurokinin 1 receptor, attenuated the IL-1beta-induced hyperreactivity to ACh and MCh and to EFS in cultured tracheal segments. SP-containing neurons in longitudinal trunk, SP innervation of superficial muscular plexus neurons, and SP nerve fiber density in tracheal smooth muscle all increased after treatment with IL-1beta. These results show that IL-1beta-enhanced cholinergic airway smooth muscle contractile responses are mediated by the actions of SP released from intrinsic airway neurons.

Pharmacological and molecular characterization of muscarinic receptor subtypes in human esophageal smooth muscle.

PubMed

Preiksaitis, H G; Krysiak, P S; Chrones, T; Rajgopal, V; Laurier, L G

2000-12-01

Esophageal peristalsis is dependent on activation of muscarinic receptors, but little is known about the roles of specific receptor subtypes in the human esophagus. We examined muscarinic receptor expression and function in human esophageal smooth muscle obtained from patients undergoing resection for cancer. [(3)H]Quinuclidinyl benzylate (QNB)-specific binding was similar in longitudinal muscle (B(max) = 106 +/- 22 fmol/mg of protein, K(d) = 68 +/- 9 pM) and circular muscle (B(max) = 81 +/- 16 fmol/mg of protein, K(d) = 79 +/- 15 pM). Subtype-selective antagonists inhibited [(3)H]QNB similarly in muscle from both layers. Further analysis of antagonist inhibition of [(3)H]QNB binding showed a major site (60-70%) with antagonist affinity profile consistent with the M2 subtype and a second site that could not be classified. Reverse transcription-polymerase chain reaction and immunoblotting demonstrated the presence of all five known muscarinic receptor subtypes, and immunocytochemistry on acutely isolated smooth muscle cells confirmed the expression of each subtype on the muscle cells. Subtype-selective antagonists had similar inhibitory effects on carbachol-evoked contractions in longitudinal muscle and circular muscle strips with pA(2) values of 9.5 +/- 0.1 and 9.6 +/- 0.2 for 4-diphenylacetoxy-N-methylpiperidine methiodide, 7.1 +/- 0.1 and 7.0 +/- 0.2 for pirenzepine, and 6.2 +/- 0.2 and 6.4 +/- 0.2 for methoctramine, respectively. We conclude that human esophageal smooth muscle expresses muscarinic receptor subtypes M1 through M5. The antagonist sensitivity profile for muscle contraction is consistent with activation of the M3 subtype.

Fluid flow releases fibroblast growth factor-2 from human aortic smooth muscle cells

NASA Technical Reports Server (NTRS)

Rhoads, D. N.; Eskin, S. G.; McIntire, L. V.

2000-01-01

This study tested the hypothesis that fluid shear stress regulates the release of fibroblast growth factor (FGF)-2 from human aortic smooth muscle cells. FGF-2 is a potent mitogen that is involved in the response to vascular injury and is expressed in a wide variety of cell types. FGF-2 is found in the cytoplasm of cells and outside cells, where it associates with extracellular proteoglycans. To test the hypothesis that shear stress regulates FGF-2 release, cells were exposed to flow, and FGF-2 amounts were measured from the conditioned medium, pericellular fraction (extracted by heparin treatment), and cell lysate. Results from the present study show that after 15 minutes of shear stress at 25 dyne/cm(2) in a parallel-plate flow system, a small but significant fraction (17%) of the total FGF-2 was released from human aortic smooth muscle cells. FGF-2 levels in the circulating medium increased 10-fold over medium from static controls (P<0.01). A 50% increase in FGF-2 content versus control (P<0.01) was found in the pericellular fraction (extracted by heparin treatment). Furthermore, a significant decrease in FGF-2 was detected in the cell lysate, indicating that FGF-2 was released from inside the cell. Cell permeability studies with fluorescent dextran were performed to examine whether transient membrane disruption caused FGF-2 release. Flow cytometry detected a 50% increase in mean fluorescence of cells exposed to 25 dyne/cm(2) versus control cells. This indicates that the observed FGF-2 release from human aortic smooth muscle cells is likely due to transient membrane disruption on initiation of flow.

Management of a traumatic tracheal tear: a case report.

PubMed

Barrett, Eric

2011-12-01

This case report describes a posterior tracheal tear in a healthy 8-year-old girl. The child sustained the injury while riding her scooter, when the handlebars of the scooter dislodged after running into the curb, causing the shaft to strike her in the manubrium of the sternum. The child presented with subcutaneous emphysema of the neck and the supraclavicular region bilaterally. Before the patient's arrival, the surgical and anesthesia team had extensive discussion regarding the child's perioperative management, which included the need to maintain spontaneous ventilation to avoid opening the tracheal tear and producing a further increase in the size of the pneumomediastinum. The anesthesia machine was prepared for a general anesthetic along with a wide array of appropriately sized endotracheal tubes. In addition to appropriately sized laryngoscope blades, a fiberoptic scope and video laryngoscope were immediately available. Spontaneous respirations were maintained throughout the procedure, and the case proceeded uneventfully. This case represents the need for proper preparation and communication between providers to manage all possible scenarios of a traumatic tracheal tear.

Human small bowel as a useful tool to investigate smooth muscle effects of potential therapeutics in organophosphate poisoning.

PubMed

Marquart, Katharina; Prokopchuk, Olga; Worek, Franz; Thiermann, Horst; Martignoni, Marc E; Wille, Timo

2018-09-01

Isolated organs proofed to be a robust tool to study effects of (potential) therapeutics in organophosphate poisoning. Small bowel samples have been successfully used to reveal smooth muscle relaxing effects. In the present study, the effects of obidoxime, TMB-4, HI-6 and MB 327 were investigated on human small bowel tissue and compared with rat data. Hereby, the substances were tested in at least seven different concentrations in the jejunum or ileum both pre-contracted with carbamoylcholine. Additionally, the cholinesterase activity of native tissue was determined. Human small intestine specimens showed classical dose response-curves, similar to rat tissue, with MB 327 exerting the most potent smooth muscle relaxant effect in both species (human EC 50 =0.7×10 -5 M and rat EC 50 =0.7×10 -5 M). The AChE activity for human and rat samples did not differ significantly (rat jejunum=1351±166 mU/mg wet weight; rat ileum=1078±123 mU/mg wet weight; human jejunum=1030±258 mU/mg wet weight; human ileum=1293±243 mU/mg wet weight). Summarizing, our isolated small bowel setup seems to be a solid tool to investigate the effects of (potential) therapeutics on pre-contracted smooth muscle, with data being transferable between rat and humans. Copyright © 2017 Elsevier B.V. All rights reserved.

Management of benign dynamic "A-shape" tracheal stenosis: a retrospective study of 60 patients.

PubMed

Plojoux, Jérôme; Laroumagne, Sophie; Vandemoortele, Thomas; Astoul, Philippe J; Thomas, Pascal A; Dutau, Hervé

2015-02-01

Benign tracheal stenosis complicates tracheal intubation or tracheostomy in 0.6% to 65% of cases. Surgical resection is the standard treatment. Endoscopic management is used for inoperable patients with 17% to 69% success. Dynamic "A-shape" tracheal stenosis (DATS) results in a dynamic stenosis with anterior fracture of tracheal cartilage and frequently associated posterior malacia. We report the results of our multidisciplinary management. Sixty patients with DATS were included. Management decision was made during initial bronchoscopy. When suitable, patients were referred to thoracic surgery for tracheal resection. Posterior localized tracheomalacia was treated with laser photocoagulation of the posterior tracheal wall. Tracheal stents were placed if the stenosis persisted after laser treatment. The choice of stent (straight silicone, hour-glass shaped silicone, T-tube, or fully-covered self-expandable metallic stent) was based on operator's judgment. After 12 to 18 months, stents were removed. If the stenosis persisted after stent removal, surgery was reconsidered. If surgery was not possible, a stent was replaced. In case of satisfactory result, a stent was replaced only after recurrence. Stable patients after treatment were considered as success, requirement of long-term tracheostomy or T tube as failure, and long-term stent as partial success. All patients developed DATS after tracheostomy. Thirty-three patients had posterior tracheomalacia. In 13 patients, mild stenosis required only endoscopic surveillance. Two patients were referred to thoracic surgery for tracheal resection surgery. Endoscopic management was the initial therapy in 45 patients (75%) and was considered successful in 23 patients (51%), partially successful in 10 (22%), and failed in 12 (27%). Five patients with successful outcomes required only laser therapy. Overall 70 stents were placed in 35 patients, with a migration rate of 31%. The DATS management was successful in 63%. Stent migration

Non-vascular smooth muscle cells in the human choroid: distribution, development and further characterization

PubMed Central

May, Christian Albrecht

2005-01-01

To characterize further non-vascular smooth muscle cells (NVSMC) in the choroid of the human eye, extensive morphological studies were performed including a three-dimensional distribution of NVSMC in the adult human eye and their appearance during development. Whole mounts and sections through the choroid and sclera of eyes of 42 human donors (between the 13th week of gestation and 89 years of age) were stained with antibodies against smooth muscle actin and other markers for smooth muscle cells. On the basis of their morphological localization, three groups of NVSMC could be distinguished in the adult eyes: (a) a semicircular arrangement of NVSMC in the suprachoroid and inner sclera, around the entry of posterior ciliary arteries and nerves; (b) NVSMC parallel to the vessels in the posterior eye segment between the point of entry of the posterior ciliary arteries and the point of exit of the vortex veins; and (c) a dense plaque-like arrangement of NVSMC in the suprachoroid, overlying the foveal region. The last of these groups showed most pronounced interindividual differences. During development, the first NVSMC to be observed at the 20th week of gestation belonged to group b. A complete NVSMC network was first observed in a 6-year-old donor eye. All three groups stained positive for smoothelin, caldesmon and calponin in all localizations. The NVSMC show a distinct distribution that might reflect different aspects of their function in the choroid and suprachoroid. All cells could be histochemically characterized as truly contractile. PMID:16191166

Effects of magnesium sulfate on airway smooth muscle contraction in rats.

PubMed

Betul Altinisik, Hatice; Kirdemir, Pakize; Altinisik, Ugur; Gokalp, Osman

2016-08-01

Aim To investigate the effect of magnesium sulfate (MgSO4) at different doses on isolated tracheal smooth muscle contraction in rats induced by different mechanisms. Methods Twelve rats' tracheas were placed into organ bath. Consecutively, acetylcholine (10-6,10-5,10-4 M), histamine(10-8,10-5,10-3 M) and KCl (30,60 mM) solutions was administered for contractions. MgSO4 from 10-4 to 10-1 M concentrations were subsequently administered after each constrictive agent and relaxation degrees were recorded. Results In the acetylcholine and KCl groups, dose dependent strong contractions were observed, but not in the histamine group and that group was excluded. Significant relaxation occurred with gradually increasing doses of MgSO4. In the high dose KCl group, a slight increase in contractions after the administration of 10-4 and 10-3 M MgSO4 was recorded. Conclusion We suggest that MgSO4 is effective in relaxing airway smooth muscle contractions caused by different factors; however, it must be considered that low doses of MgSO4 may only lead to a slight increase in contractions. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

Use of the silicone tracheal T-tube for tracheostenosis or tracheomalacia.

PubMed

Liu, H C; Wang, L S; Fahn, H J; Lee, Y C; Lu, C C; Chan, K H; Huang, M H

1996-09-01

Tracheobtenosib and tracheomalacia are trivial diseases. The conventional choice of managements with tracheostomy, either temporary or long-term usage, can only partially resolve the problems of airway obstruction. Silicone tracheal T-tube presents a substitute for it. We present 5 patients with tracheostenosis or tracheomalacia managed with nine procedures of long silicone Montgomery T-tube prothesis between 1984 and 1994 in VGH-Taipei. The primary diagnosis included tracheal injury (2), postintubation tracheal stenosis (2), and stenosis due to endotracheal tuberculosis (1). Three patients received a long segmental T-tube for permanent endotracheal stenting and the other two patients used T-tube insertion for temporary stenting of the trachea for 7 and 11 months, respectively, with satisfactory results. All patients got immediate benefit from the prothesis in respiration with simple postoperative care. Two patients with temporary T-tube placement had it successfully removed in 7 and 11 months, respectively. Placement of the T-tube for subglottic stenosis also protected the function of phonation. The tracheal T-tube restored airway patency reliably with good long-term results and could be the preferred management of chronic upper airway obstructive disease not amenable to surgical repair. The most common complication was airway obstruction caused by either granulations or sticky mucoid substance. Three patients and six tubes (60%) developed granulation obstruction and the average duration of granuloma formation was 7.7 months. Laser phototherapy or surgical intervention, such as tracheoplasty, with change of the T-tube was carried out for granuloma obstruction. T-tube is a good endoprothesis for tracheostenosis and tracheomalacia with minimal complication for cases of long tracheostenosis or complex tracheal injury.

BMI as a Predictor for Potential Difficult Tracheal Intubation in Males.

PubMed

Uribe, Alberto A; Zvara, David A; Puente, Erika G; Otey, Andrew J; Zhang, Jianying; Bergese, Sergio D

2015-01-01

Difficult tracheal intubation is a common source of mortality and morbidity in surgical and critical care settings. The incidence reported of difficult tracheal intubation is 0.1%-13% and reaches 14% in the obese population. The objective of our retrospective study was to investigate and compare the utility of body mass index (BMI) as indicator of difficult tracheal intubation in males and females. We performed a retrospective chart review of patients who underwent abdominal surgeries with American Society of Anesthesiologists I to V under general anesthesia requiring endotracheal intubation. The following information was obtained from medical records for analysis: gender, age, height, weight, BMI, length of patient stay in the Post Anesthesia Care Unit, past medical history of sleep apnea, Mallampati score, and the American Society of Anesthesiologists classification assigned by the anesthesia care provider performing the endotracheal intubation. Of 4303 adult patients, 1970 (45.8%) men and 2333 (54.2%) women were enrolled in the study. Within this group, a total of 1673 (38.9%) patients were morbidly obese. The average age of the study group was 51.4 ± 15.8 and the average BMI was 29.7 ± 8.2 kg/m(2). The overall incidence of the encountered difficult intubations was 5.23% or 225 subjects. Thus, our results indicate that BMI is a reliable predictor of difficult tracheal intubation predominantly in the male population; another strong predictor, with a positive linear correlation, being the Mallampati score. In conclusion, our data shows that BMI is a reliable indicator of potential difficult tracheal intubation only in male surgical patients.

Mechanistic insights of sulfur mustard-induced acute tracheal injury in rats.

PubMed

Zhu, Xiao-Ji; Xu, Rui; Meng, Xiao; Chu, Hai-Bo; Zhao, Chao; Lian, Cheng-Jin; Wang, Tao; Guo, Wen-Jun; Zhang, Sheng-Ming

2014-01-01

Sulfur mustard (SM) is believed to be a major threat to civilian populations because of the persistent asymmetric threat by nonstate actors, such as terrorist groups, the ease of synthesis and handling, and the risk of theft from stockpiles. The purpose of this study was to establish mechanisms of acute tracheal injury in rats induced by SM using histopathologic, immunohistochemical, and biochemical parameters. Male rats (Sprague-Dawley) were anesthetized, intratracheally intubated, and exposed to 2 mg/kg of SM. Animals were euthanized 6-, 24-, 48-, and 72-hour postexposure, and intracavitary blood samples from the heart and tracheal tissues were collected. Exposure of rats to SM resulted in rapid tracheal injury, including tracheal epithelial cell shedding, focal ulceration, and abundant lymphocyte invasion of the submucosa. There was also evidence of a large number of apoptotic cells in the epithelium and submucosa, the serum levels of tumor necrosis factor α, interleukin 1β (IL) 1β, IL-6, and γ-glutamyl transferase peaked at 24 hours, and the serum levels of lactate dehydrogenase, glutathione peroxidase, and thiobarbituric acid reactive substance peaked at 6 hours. The SM exposure also resulted in a loss of the cellular membrane, leakage of cytoplasm, fuzzy mitochondrial cristae, medullary changes in ciliated and goblet cells, and the nuclear chromatin appeared marginated in basal cells and fibroblasts. The results in the propylene glycol group were the same as the control group. These data demonstrated the histologic changes, inflammatory reactions, apoptosis, oxidative stress, and DNA damage following SM (2 mg/kg)-induced acute tracheal injury; the severity of changes was time dependent. © The Author(s) 2014.

Tracheal tube biofilm removal through a novel closed-suctioning system: an experimental study.

PubMed

Aguilera Xiol, E; Li Bassi, G; Wyncoll, D; Ntoumenopoulos, G; Fernandez-Barat, L; Marti, J D; Comaru, T; De Rosa, F; Rigol, M; Rinaudo, M; Ferrer, M; Torres, A

2015-11-01

Tracheal tube biofilm develops during mechanical ventilation. We compared a novel closed-suctioning system vs standard closed-suctioning system in the prevention of tracheal tube biofilm. Eighteen pigs, on mechanical ventilation for 76 h, with P. aeruginosa pneumonia were randomized to be tracheally suctioned via the KIMVENT* closed-suctioning system (control group) or a novel closed-suctioning system (treatment group), designed to remove tracheal tube biofilm through saline jets and an inflatable balloon. Upon autopsy, two tracheal tube hemi-sections were dissected for confocal and scanning electron microscopy. Biofilm area, maximal and minimal thickness were computed. Biofilm stage was assessed. Sixteen animals were included in the final analysis. In the treatment and control group, the mean (sd) pulmonary burden was 3.34 (1.28) and 4.17 (1.09) log cfu gr(-1), respectively (P=0.18). Tracheal tube P. aeruginosa colonization was 5.6 (4.9-6.3) and 6.2 (5.6-6.9) cfu ml(-1) (median and interquartile range) in the treatment and control group, respectively (P=0.23). In the treatment group, median biofilm area was 3.65 (3.22-4.21) log10 μm2 compared with 4.49 (4.27-4.52) log10 μm2 in the control group (P=0.031). In the treatment and control groups, the maximal biofilm thickness was 48.3 (26.7-71.2) µm (median and interquartile range) and 88.8 (43.8-125.7) µm, respectively. The minimal thickness in the treatment and control group was 0.6 (0-4.0) µm and 23.7 (5.3-27.8) µm (P=0.040) (P=0.017). Earlier stages of biofilm development were found in the treatment group (P<0.001). The novel CSS reduces biofilm accumulation within the tracheal tube. A clinical trial is required to confirm these findings and the impact on major outcomes. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Acute lung injury after tracheal instillation of acidified soya-based or Enfalac formula or human breast milk in rabbits.

PubMed

Chin, C; Lerman, J; Endo, J

1999-03-01

The aim of this study was to compare the severity of the acute lung injury after tracheal instillation of acidified soya-based or Enfalac infant formula, or human breast milk (HBM) in anesthetized rabbits. Alveolar-arterial oxygen tension gradient (A-aDO2) and dynamic compliance were measured before (baseline) and hourly for four hours after tracheal instillation of 0.8 ml x kg(-1) soya-based or Enfalac infant formula or HBM (all acidified to pH 1.8 with hydrochloric acid) or no fluid (control) in 24 anesthetized and tracheotomized adult rabbits. The A-aDO2, the difference between alveolar and arterial oxygen tensions, was corrected for barometric pressure and carbon dioxide tension. Dynamic compliance was the ratio of the expired tidal volume to the peak inspiratory airway pressure, normalized to body weight. Baseline A-aDO2 and dynamic compliance were similar among the four groups. In the control rabbits, A-aDO2 remained unchanged throughout the four hours, whereas mean A-aDO2 increased 180 mm Hg in the soya-based group (P < 0.0025) and 350 and 275 mm Hg in the Enfalac and HBM groups respectively (P < 0.0002). The order of the A-aDO2 post-instillation was Enfalac approximately/= HBM > soya > control (P < 0.0002). Dynamic compliance decreased 10-12% in the control rabbits during the four post-instillation measurements compared with baseline (P < 0.033), decreased 20% in the soya-based group (P < 0.0002) and 40-50% in the Enfalac and HBM groups (P < 0.0002). The severity of the acute lung injury after intratracheal instillation of infant feeds in a volume of 0.8 ml x kg(-1) and at pH 1.8 in rabbits depends in part, on the type of feed: Enfalac approximately/= HBM > soya > control.

Use of a Nitinol Wire Stent for Management of Severe Tracheal Stenosis in an Eclectus Parrot (Eclectus roratus).

PubMed

Mejia-Fava, Johanna; Holmes, Shannon P; Radlinsky, MaryAnn; Johnson, Dan; Ellis, Angela E; Mayer, Jörg; Schnellbacher, Rodney; Divers, Stephen J

2015-09-01

A 25-year-old, female eclectus parrot (Eclectus roratus) presented for dyspnea 3 weeks after anesthesia and surgery for egg yolk coelomitis. Radiography, computed tomography, and tracheoscopy revealed multiple tracheal strictures spanning a length of 2.6 cm in the mid to distal trachea. Histopathologic examination revealed mild fibrosis, inflammation, and hyperplasia consistent with acquired tracheal strictures. Tracheal resection was not considered possible because of the length of the affected trachea. The strictures were resected endoscopically, and repeated balloon dilation under fluoroscopic guidance over the course of 10 months resulted in immediate but unsustained improvement. Computed tomography was used to measure the stenotic area. A 4 × 36-mm, custom-made, nitinol wire stent was inserted into the trachea under fluoroscopic guidance. After stent placement, intermittent episodes of mild to moderate dyspnea continued, and these responded to nebulization with a combination of saline, acetylcysteine, and dexamethasone. Multiple attempts to wean the patient off nebulization therapy and to switch to a corticosteroid-free combination were unsuccessful. The parrot eventually developed complications, was euthanatized, and necropsy was performed. Histologically, the tracheal mucosa had widespread erosion to ulceration, with accumulation of intraluminal exudate and bacteria, severe degeneration of skeletal muscle and tracheal rings, prominent fibrosis, and mild to moderate, submucosal inflammation. Clinicopathologic findings in this case suggested tracheomalacia, which has not been previously described in birds. Custom-made tracheal stents can be used for severe tracheal stenosis in birds when tracheal resection and anastomosis is not possible. Complications of tracheal stent placement in birds may include tracheitis and tracheomalacia. To our knowledge, this is the first report of tracheal stent placement in an avian species.

Head-Elevated Patient Positioning Decreases Complications of Emergent Tracheal Intubation in the Ward and Intensive Care Unit.

PubMed

Khandelwal, Nita; Khorsand, Sarah; Mitchell, Steven H; Joffe, Aaron M

2016-04-01

Based on the data from elective surgical patients, positioning patients in a back-up head-elevated position for preoxygenation and tracheal intubation can improve patient safety. However, data specific to the emergent setting are lacking. We hypothesized that back-up head-elevated positioning would be associated with a decrease in complications related to tracheal intubation in the emergency room environment. This retrospective study was approved by the University of Washington Human Subjects Division (Seattle, WA). Eligible patients included all adults undergoing emergent tracheal intubation outside of the operating room by the anesthesiology-based airway service at 2 university-affiliated teaching hospitals. All intubations were through direct laryngoscopy for an indication other than full cardiopulmonary arrest. Patient characteristics and details of the intubation procedure were derived from the medical record. The primary study endpoint was the occurrence of a composite of any intubation-related complication: difficult intubation, hypoxemia, esophageal intubation, or pulmonary aspiration. Multivariable logistic regression was used to estimate the odds of the primary endpoint in the supine versus back-up head-elevated positions with adjustment for a priori-defined potential confounders (body mass index and a difficult intubation prediction score [Mallampati, obstructive sleep Apnea, Cervical mobility, mouth Opening, Coma, severe Hypoxemia, and intubation by a non-Anesthesiologist score]). Five hundred twenty-eight patients were analyzed. Overall, at least 1 intubation-related complication occurred in 76 of 336 (22.6%) patients managed in the supine position compared with 18 of 192 (9.3%) patients managed in the back-up head-elevated position. After adjusting for body mass index and the Mallampati, obstructive sleep Apnea, Cervical mobility, mouth Opening, Coma, severe Hypoxemia, and intubation by a non-Anesthesiologist score, the odds of encountering the

Real-time tracheal ultrasonography for confirmation of endotracheal tube placement during cardiopulmonary resuscitation.

PubMed

Chou, Hao-Chang; Chong, Kah-Meng; Sim, Shyh-Shyong; Ma, Matthew Huei-Ming; Liu, Shih-Hung; Chen, Nai-Chuan; Wu, Meng-Che; Fu, Chia-Ming; Wang, Chih-Hung; Lee, Chien-Chang; Lien, Wan-Ching; Chen, Shyr-Chyr

2013-12-01

This study aimed to evaluate the accuracy of tracheal ultrasonography for assessing endotracheal tube position during cardiopulmonary resuscitation (CPR). We performed a prospective observational study of patients undergoing emergency intubation during CPR. Real-time tracheal ultrasonography was performed during the intubation with the transducer placed transversely just above the suprasternal notch, to assess for endotracheal tube positioning and exclude esophageal intubation. The position of trachea was identified by a hyperechoic air-mucosa (A-M) interface with posterior reverberation artifact (comet-tail artifact). The endotracheal tube position was defined as endotracheal if single A-M interface with comet-tail artifact was observed. Endotracheal tube position was defined as intraesophageal if a second A-M interface appeared, suggesting a false second airway (double tract sign). The gold standard of correct endotracheal intubation was the combination of clinical auscultation and quantitative waveform capnography. The main outcome was the accuracy of tracheal ultrasonography in assessing endotracheal tube position during CPR. Among the 89 patients enrolled, 7 (7.8%) had esophageal intubations. The sensitivity, specificity, positive predictive value, and negative predictive value of tracheal ultrasonography were 100% (95% confidence interval [CI]: 94.4-100%), 85.7% (95% CI: 42.0-99.2%), 98.8% (95% CI: 92.5-99.0%) and 100% (95% CI: 54.7-100%), respectively. Positive and negative likelihood ratios were 7.0 (95% CI: 1.1-43.0) and 0.0, respectively. Real-time tracheal ultrasonography is an accurate method for identifying endotracheal tube position during CPR without the need for interruption of chest compression. Tracheal ultrasonography in resuscitation management may serve as a powerful adjunct in trained hands. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Altered Expression of Human Smooth Muscle Myosin Phosphatase Targeting (MYPT) Isovariants with Pregnancy and Labor.

PubMed

Lartey, Jon; Taggart, Julie; Robson, Stephen; Taggart, Michael

2016-01-01

Myosin light-chain phosphatase is a trimeric protein that hydrolyses phosphorylated myosin II light chains (MYLII) to cause relaxation in smooth muscle cells including those of the uterus. A major component of the phosphatase is the myosin targeting subunit (MYPT), which directs a catalytic subunit to dephosphorylate MYLII. There are 5 main MYPT family members (MYPT1 (PPP1R12A), MYPT2 (PPP1R12B), MYPT3 (PPP1R16A), myosin binding subunit 85 MBS85 (PPP1R12C) and TIMAP (TGF-beta-inhibited membrane-associated protein (PPP1R16B)). Nitric oxide (NO)-mediated smooth muscle relaxation has in part been attributed to activation of the phosphatase by PKG binding to a leucine zipper (LZ) dimerization domain located at the carboxyl-terminus of PPP1R12A. In animal studies, alternative splicing of PPP1R12A can lead to the inclusion of a 31-nucleotide exonic segment that generates a LZ negative (LZ-) isovariant rendering the phosphatase less sensitive to NO vasodilators and alterations in PPP1R12ALZ- and LZ+ expression have been linked to phenotypic changes in smooth muscle function. Moreover, PPP1R12B and PPP1R12C, but not PPP1R16A or PPP1R16B, have the potential for LZ+/LZ- alternative splicing. Yet, by comparison to animal studies, the information on human MYPT genomic sequences/mRNA expressions is scant. As uterine smooth muscle undergoes substantial remodeling during pregnancy we were interested in establishing the patterns of expression of human MYPT isovariants during this process and also following labor onset as this could have important implications for determining successful pregnancy outcome. We used cross-species genome alignment, to infer putative human sequences not available in the public domain, and isovariant-specific quantitative PCR, to analyse the expression of mRNA encoding putative LZ+ and LZ- forms of PPP1R12A, PPP1R12B and PPP1R12C as well as canonical PPP1R16A and PPP1R16B genes in human uterine smooth muscle from non-pregnant, pregnant and in

A critical role of nicotinamide phosphoribosyltransferase in human telomerase reverse transcriptase induction by resveratrol in aortic smooth muscle cells

PubMed Central

Huang, Peixin; Riordan, Sean M.; Heruth, Daniel P.; Grigoryev, Dmitry N.; Zhang, Li Qin; Ye, Shui Qing

2015-01-01

Aging is the predominant risk factor for cardiovascular diseases and contributes to a considerably more severe outcome in patients with acute myocardial infarction. Resveratrol, a polyphenol found in red wine, is a caloric restriction mimetic with potential anti-aging properties which has emerged as a beneficial nutraceutical for patients with cardiovascular disease. Although resveratrol is widely consumed as a nutritional supplement, its mechanism of action remains to be elucidated fully. Here, we report that resveratrol activates human nicotinamide phosphoribosyltransferase (NAMPT), SIRT4 and telomerase reverse transcriptase (hTERT) in human aortic smooth muscle cells. Similar observations were obtained in resveratrol treated C57BL/6J mouse heart and liver tissues. Resverotrol can also augment telomerase activity in both human pulmonary microvascular endothelial cells and A549 cells. Blocking NAMPT and SIRT4 expression prevents induction of hTERT in human aortic smooth muscle cells while overexpression of NAMPT elevates the telomerase activity induced by resveratrol in A549 cells. Together, these results identify a NAMPT-SIRT4-hTERT axis as a novel mechanism by which resveratrol may affect the anti-aging process in human aortic smooth muscle cells, mouse hearts and other cells. These findings enrich our understanding of the positive effects of resveratrol in human cardiovascular diseases. PMID:25926556

Tracheal Atresia with Segmental Esophageal Duplication: An Unusual Anatomic Arrangement.

PubMed

Gaerty, Kirsten; Thomas, Joseph T; Petersen, Scott; Tan, Edwin; Kumar, Sailesh; Gardener, Glenn; Armes, Jane

2016-01-01

An unusual anatomic configuration of segmental tracheal agenesis/atresia with esophageal duplication on autopsy in a fetus that demised in utero at 29 weeks is reported. The mother was scanned initially for a cardiac anomaly at 20 weeks and on follow-up scan at 27 weeks had polyhydramnios and underwent amnioreduction. The final autopsy diagnosis was vertebral, ano-rectal, cardiac, tracheoesophageal, renal, and limb malformations (VACTERL). We discuss the autopsy findings along with the embryological mechanisms and compare the configuration with Floyd's classification for tracheal agenesis. The difficulties in prenatal diagnosis are discussed.

Pediatric Patients with High Pulmonary Arterial Pressure in Congenital Heart Disease Have Increased Tracheal Diameters Measured by Computed Tomography.

PubMed

Ohashi, Nobuko; Imai, Hidekazu; Seino, Yutaka; Baba, Hiroshi

2017-12-06

Determination of the appropriate tracheal tube size using formulas based on age or height often is inaccurate in pediatric patients with congenital heart disease (CHD), particularly in those with high pulmonary arterial pressure (PAP). Here, the authors compared tracheal diameters between pediatric patients with CHD with high PAP and low PAP. Retrospective clinical study. Hospital. Pediatric patients, from birth to 6 months of age, requiring general anesthesia and tracheal intubation who underwent computed tomography were included. Patients with mean pulmonary artery pressure >25 mmHg were allocated to the high PAP group, and the remaining patients were allocated to the low PAP group. The primary outcome was the tracheal diameter at the cricoid cartilage level, and the secondary goal was to observe whether the size of the tracheal tube was appropriate compared with that obtained using predictable formulas based on age or height. The mean tracheal diameter was significantly larger in the high PAP group than in the low PAP group (p < 0.01). Pediatric patients with high PAP required a larger tracheal tube size than predicted by formulas based on age or height (p = 0.04 for age and height). Pediatric patients with high PAP had larger tracheal diameters than those with low PAP and required larger tracheal tubes compared with the size predicted using formulas based on age or height. Copyright © 2017 Elsevier Inc. All rights reserved.

Oxygen dose responsiveness of human fetal airway smooth muscle cells.

PubMed

Hartman, William R; Smelter, Dan F; Sathish, Venkatachalem; Karass, Michael; Kim, Sunchin; Aravamudan, Bharathi; Thompson, Michael A; Amrani, Yassine; Pandya, Hitesh C; Martin, Richard J; Prakash, Y S; Pabelick, Christina M

2012-10-15

Maintenance of blood oxygen saturation dictates supplemental oxygen administration to premature infants, but hyperoxia predisposes survivors to respiratory diseases such as asthma. Although much research has focused on oxygen effects on alveoli in the setting of bronchopulmonary dysplasia, the mechanisms by which oxygen affects airway structure or function relevant to asthma are still under investigation. We used isolated human fetal airway smooth muscle (fASM) cells from 18-20 postconceptual age lungs (canalicular stage) to examine oxygen effects on intracellular Ca(2+) ([Ca(2+)](i)) and cellular proliferation. fASM cells expressed substantial smooth muscle actin and myosin and several Ca(2+) regulatory proteins but not fibroblast or epithelial markers, profiles qualitatively comparable to adult human ASM. Fluorescence Ca(2+) imaging showed robust [Ca(2+)](i) responses to 1 μM acetylcholine (ACh) and 10 μM histamine (albeit smaller and slower than adult ASM), partly sensitive to zero extracellular Ca(2+). Compared with adult, fASM showed greater baseline proliferation. Based on this validation, we assessed fASM responses to 10% hypoxia through 90% hyperoxia and found enhanced proliferation at <60% oxygen but increased apoptosis at >60%, effects accompanied by appropriate changes in proliferative vs. apoptotic markers and enhanced mitochondrial fission at >60% oxygen. [Ca(2+)](i) responses to ACh were enhanced for <60% but blunted at >60% oxygen. These results suggest that hyperoxia has dose-dependent effects on structure and function of developing ASM, which could have consequences for airway diseases of childhood. Thus detrimental effects on ASM should be an additional consideration in assessing risks of supplemental oxygen in prematurity.

Secure closure of the tracheal incision after natural orifice transluminal endoscopic surgery with a surgical sealant (CoSeal).

PubMed

Liu, Yun-Hen; Wu, Yi-Cheng; Chen, Tzu-Ping; Ko, Po-Jen

2011-09-01

To evaluate the effectiveness of surgical sealant (CoSeal) in sealing the tracheal assess sites after transtracheal thoracoscopy. Two dogs underwent transtracheal thoracic exploration and pericardial window creation. The thoracic cavity was approached with flexible bronchoscope through a 9-mm tracheal incision. The pericardial window was performed with a needle knife via the working channel of the bronchoscope, and the tracheal assess site was closed with CoSeal using a rubber catheter. The integrity of tracheal healing was evaluated under positive pressure ventilation. Transtracheal creation of pericardial window and closure of tracheal incision with CoSeal was successfully performed in both dogs. There was no evidence of air leaks from the chest tube during positive pressure ventilation. Autopsy revealed no injury to the mediastinum and intrathoracic structure. Endoscopic closure of tracheal access site of NOTES with CoSeal appears to be a feasible technique.

Effects of tracheal occlusion with retinoic acid administration on normal lung development.

PubMed

Delabaere, Amélie; Marceau, Geoffroy; Coste, Karen; Blanchon, Loïc; Déchelotte, Pierre-Jean; Blanc, Pierre; Sapin, Vincent; Gallot, Denis

2017-05-01

Tracheal occlusion (TO) is an investigational therapy for severe congenital diaphragmatic hernia that decreases pulmonary hypoplasia, but sustained TO also induces deficient surfactant synthesis. Intramuscular maternal administration of retinoic acid (RA) in a surgical rabbit model of congenital diaphragmatic hernia showed a beneficial effect on lung maturation. We evaluated the potential of RA delivery into the trachea and studied the combined effects of TO and RA on normal lung development. Experiments were performed on normal rabbit fetuses. Liposomes and capric triglyceride (Miglyol ® ), alone and with RA, were administered in the trachea just before TO (d26). Lung morphology and surfactant production were studied at term (d30). Tracheal occlusion increased lung weight and enhanced alveolar development but increased apoptotic activity and decreased surfactant expression. Tracheal injection of RA improved surfactant production to levels of normal controls. We established the potential of liposome and Miglyol as RA vehicle for delivering this bioactive molecule in the fetal airways. Tracheal RA injection seems to oppose the effects of TO in fetuses with normal lungs. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

Management of complex benign post-tracheostomy tracheal stenosis with bronchoscopic insertion of silicon tracheal stents, in patients with failed or contraindicated surgical reconstruction of trachea.

PubMed

Tsakiridis, Kosmas; Darwiche, Kaid; Visouli, Aikaterini N; Zarogoulidis, Paul; Machairiotis, Nikolaos; Christofis, Christos; Stylianaki, Aikaterini; Katsikogiannis, Nikolaos; Mpakas, Andreas; Courcoutsakis, Nicolaos; Zarogoulidis, Konstantinos

2012-11-01

Tracheal stenosis is a potentially life-threatening condition. Tracheostomy and endotracheal intubation remain the commonest causes of benign stenosis, despite improvements in design and management of tubes. Post-tracheostomy stenosis is more frequently encountered due to earlier performance of tracheostomy in the intensive care units, while the incidence of post-intubation stenosis has decreased with application of high-volume, low-pressure cuffs. In symptomatic benign tracheal stenosis the gold standard is surgical reconstruction (often after interventional bronchoscopy). Stenting is reserved for symptomatic tracheal narrowing deemed inoperable, due to local or general reasons: long strictures, inflammation, poor respiratory, cardiac or neurological status. When stenting is decided, silicone stent insertion is considered the treatment of choice in the presence of inflammation and/or when removal is desirable. We inserted tracheal silicone stents (Dumon) under general anaesthesia through rigid bronchoscopy in two patients with benign post-tracheostomy stenosis: a 39-year old woman with failed initial operation, and continuous relapses with proliferation after multiple bronchscopic interventions, and a 20-year old man in a poor neurological status, with a long tracheal stricture involving the subglottic larynx (lower posterior part), and inflamed tracheostomy site tissues (positive for methicillin resistant staphylococcus aureus). The airway was immediately re-establish, without complications. At 15- and 10-month follow-up (respectively) there was no stent migration, luminal patency was maintained without: adjacent structure erosion, secretion adherence inside the stents, granulation at the ends. Tracheostomy tissue inflammation was resolved (2(nd) patient), new infection was not noted. The patients maintain good respiratory function and will be evaluated for scheduled stent removal. Silicone stents are removable, resistant to microbial colonization and are

Management of complex benign post-tracheostomy tracheal stenosis with bronchoscopic insertion of silicon tracheal stents, in patients with failed or contraindicated surgical reconstruction of trachea

PubMed Central

Tsakiridis, Kosmas; Darwiche, Kaid; Visouli, Aikaterini N.; Machairiotis, Nikolaos; Christofis, Christos; Stylianaki, Aikaterini; Katsikogiannis, Nikolaos; Mpakas, Andreas; Courcoutsakis, Nicolaos; Zarogoulidis, Konstantinos

2012-01-01

Tracheal stenosis is a potentially life-threatening condition. Tracheostomy and endotracheal intubation remain the commonest causes of benign stenosis, despite improvements in design and management of tubes. Post-tracheostomy stenosis is more frequently encountered due to earlier performance of tracheostomy in the intensive care units, while the incidence of post-intubation stenosis has decreased with application of high-volume, low-pressure cuffs. In symptomatic benign tracheal stenosis the gold standard is surgical reconstruction (often after interventional bronchoscopy). Stenting is reserved for symptomatic tracheal narrowing deemed inoperable, due to local or general reasons: long strictures, inflammation, poor respiratory, cardiac or neurological status. When stenting is decided, silicone stent insertion is considered the treatment of choice in the presence of inflammation and/or when removal is desirable. We inserted tracheal silicone stents (Dumon) under general anaesthesia through rigid bronchoscopy in two patients with benign post-tracheostomy stenosis: a 39-year old woman with failed initial operation, and continuous relapses with proliferation after multiple bronchscopic interventions, and a 20-year old man in a poor neurological status, with a long tracheal stricture involving the subglottic larynx (lower posterior part), and inflamed tracheostomy site tissues (positive for methicillin resistant staphylococcus aureus). The airway was immediately re-establish, without complications. At 15- and 10-month follow-up (respectively) there was no stent migration, luminal patency was maintained without: adjacent structure erosion, secretion adherence inside the stents, granulation at the ends. Tracheostomy tissue inflammation was resolved (2nd patient), new infection was not noted. The patients maintain good respiratory function and will be evaluated for scheduled stent removal. Silicone stents are removable, resistant to microbial colonization and are

Resected Tracheal Adenoid Cystic Carcinoma: Improvements in Outcome at a Single Institution.

PubMed

Yang, Haitang; Yao, Feng; Tantai, Jicheng; Zhao, Yang; Tan, Qiang; Zhao, Heng

2016-01-01

Primary tracheal cancer comprises a heterogeneous and rare group of neoplasms. Management of patients with primary tracheal carcinoma at our institution has improved in recent years. This retrospective review included patients with localized primary tracheal adenoid cystic carcinoma treated surgically at our institution between January 1995 and December 2014. Patients were classified according to the timing of first operation: "early years" operation was performed between January 1995 and December 2002, and subsequent "recent years" operation was associated with improved management and a focus on early diagnosis. The proportion of patients with tracheal malignancy who underwent operation for adenoid cystic carcinoma increased with time. Patients in the recent group were significantly younger than those in the early group at diagnosis (49.3 ± 7.8 years versus 45.7 ± 9.4 years; p = 0.042), and the resected tumor size and tracheal lengths tended to be smaller (28.2 ± 7.6 mm versus 30.3 ± 7.0 mm; p = 0.161) and shorter (32.1 ± 7.7 mm versus 34.4 ± 6.7 mm; p = 0.123). The use of postoperative radiotherapy in patients with R1 resection was also managed more effectively in the recent group compared with the early group (90.6% versus 65.0%; p = 0.009). Five- and 10-year overall survival rates in the early and recent groups were 86.4% and 90.8%, and 31.8% and 61.2%, respectively (p = 0.084), and the corresponding 5- and 10-year disease-free survival rates were 39.7% and 75.3%, and 9.9% and 21.2%, respectively (p = 0.025). There have been improved outcomes of adenoid cystic carcinomas. Early diagnosis, experienced surgical treatments, and postoperative adjuvant radiotherapy for patients with positive margins may contribute to the improved survival of patients with primary tracheal adenoid cystic carcinoma. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Differential gene expression profiling of human adipose stem cells differentiating into smooth muscle-like cells by TGFβ1/BMP4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elçin, Ayşe Eser; Parmaksiz, Mahmut; Dogan, Arin

Regenerative repair of the vascular system is challenging from the perspectives of translational medicine and tissue engineering. There are fundamental hurdles in front of creating bioartificial arteries, which involve recaputilation of the three-layered structure under laboratory settings. Obtaining and maintaining smooth muscle characteristics is an important limitation, as the transdifferentiated cells fail to display mature phenotype. This study aims to shed light on the smooth muscle differentiation of human adipose stem cells (hASCs). To this end, we first acquired hASCs from lipoaspirate samples. Upon characterization, the cells were induced to differentiate into smooth muscle (SM)-like cells using a variety ofmore » inducer combinations. Among all, TGFβ1/BMP4 combination had the highest differentiation efficiency, based on immunohistochemical analyses. hSM-like cell samples were compared to hASCs and to the positive control, human coronary artery-smooth muscle cells (hCA-SMCs) through gene transcription profiling. Microarray findings revealed the activation of gene groups that function in smooth muscle differentiation, signaling pathways, extracellular modeling and cell proliferation. Our results underline the effectiveness of the growth factors and suggest some potential variables for detecting the SM-like cell characteristics. Evidence in transcriptome level was used to evaluate the TGFβ1/BMP4 combination as a previously unexplored effector for the smooth muscle differentiation of adipose stem cells. - Highlights: • Human adipose stem cells (hASCs) were isolated, characterized and cultured. • Growth factor combinations were evaluated for their effectiveness in differentiation using IHC. • hASCs were differentiated into smooth muscle (SM)-like cells using TGF-β1 and BMP4 combination. • Microarray analysis was performed for hASCs, SM-like cells and coronary artery-SMCs. • Microarray data was used to perform hierarchical clustering and

Age-dependent contribution of Rho kinase in carbachol-induced contraction of human detrusor smooth muscle in vitro

PubMed Central

Kirschstein, Timo; Protzel, Chris; Porath, Katrin; Sellmann, Tina; Köhling, Rüdiger; Hakenberg, Oliver W

2014-01-01

Aim: Activation of muscarinic receptors on the detrusor smooth muscle is followed by contraction, which involves both myosin light chain kinase (MLCK) and Rho kinase (ROCK). The aim of this study was to determine the relative contributions of MLCK and ROCK to carbachol-induced contraction of human detrusor smooth muscle in vitro. Methods: Detrusor smooth muscle strips were prepared from the macroscopically unaffected bladder wall of patients underwent cystectomy. The strips were fixed in an organ bath, and carbachol or KCl-induced isometric contractions were measured by force transducers. Results: Addition of carbachol (0.4-4 μmol/L) into the bath induced concentration-dependent contractions of detrusor specimens, which was completely abolished by atropine (1 μmol/L). Pre-incubation of detrusor specimens with either the MLCK inhibitor ML-9 or the ROCK inhibitors HA1100 and Y-27632 (each at 10 μmol/L) significantly blocked carbachol-induced contractions as compared to the time-control experiments. Moreover, MLCK and ROCK inhibition were equally effective in reducing carbachol-induced contractions. The residual carbachol-induced contractions in the presence of both MLCK and ROCK inhibitors were significantly smaller than the contractions obtained when only one enzyme (either MLCK or ROCK) was inhibited, suggesting an additive effect of the two kinases. Interestingly, ROCK-mediated carbachol-induced contractions were positively correlated to the age of patients (r=o.52, P<0.05). Conclusion: Both MLCK and ROCK contribute to carbachol-induced contractions of human detrusor smooth muscle. ROCK inhibitors may be a new pharmacological approach to modulate human bladder hyperactivity. PMID:24122009

Age-dependent contribution of Rho kinase in carbachol-induced contraction of human detrusor smooth muscle in vitro.

PubMed

Kirschstein, Timo; Protzel, Chris; Porath, Katrin; Sellmann, Tina; Köhling, Rüdiger; Hakenberg, Oliver W

2014-01-01

Activation of muscarinic receptors on the detrusor smooth muscle is followed by contraction, which involves both myosin light chain kinase (MLCK) and Rho kinase (ROCK). The aim of this study was to determine the relative contributions of MLCK and ROCK to carbachol-induced contraction of human detrusor smooth muscle in vitro. Detrusor smooth muscle strips were prepared from the macroscopically unaffected bladder wall of patients underwent cystectomy. The strips were fixed in an organ bath, and carbachol or KCl-induced isometric contractions were measured by force transducers. Addition of carbachol (0.4-4 μmol/L) into the bath induced concentration-dependent contractions of detrusor specimens, which was completely abolished by atropine (1 μmol/L). Pre-incubation of detrusor specimens with either the MLCK inhibitor ML-9 or the ROCK inhibitors HA1100 and Y-27632 (each at 10 μmol/L) significantly blocked carbachol-induced contractions as compared to the time-control experiments. Moreover, MLCK and ROCK inhibition were equally effective in reducing carbachol-induced contractions. The residual carbachol-induced contractions in the presence of both MLCK and ROCK inhibitors were significantly smaller than the contractions obtained when only one enzyme (either MLCK or ROCK) was inhibited, suggesting an additive effect of the two kinases. Interestingly, ROCK-mediated carbachol-induced contractions were positively correlated to the age of patients (r=o.52, P<0.05). Both MLCK and ROCK contribute to carbachol-induced contractions of human detrusor smooth muscle. ROCK inhibitors may be a new pharmacological approach to modulate human bladder hyperactivity.

Association between pathogens from tracheal aspirate and oral biofilm of patients on mechanical ventilation.

PubMed

Souza, Luana Carneiro Diniz; Mota, Vanise Barros Rodrigues da; Carvalho, Alícia Valéria Dos Santos Zaranza de; Corrêa, Rita da Graça Carvalhal Frazão; Libério, Silvana Amado; Lopes, Fernanda Ferreira

2017-06-05

The aim of this study was to detect possible associations between respiratory pathogens from tracheal aspirate and oral biofilm samples in intubated patients in an intensive care unit (ICU), and to identify the most common respiratory pathogens in oral biofilm, particularly in patients that developed ventilator-associated pneumonia (VAP). Two oral biofilm samples were collected from the tongue of intubated patients (at admission and after 48 hours) and analyzed by culture with the Antibiotic Sensitivity Test. The results from the tongue biofilm samples were compared with the tracheal secretions samples. A total of 59.37% of patients exhibited the same species of pathogens in their tracheal aspirate and oral biofilm, of which 8 (42.1%) developed VAP, 10 (52.63%) did not develop pneumonia and one (5.26%) had aspiration pneumonia. There was a statistically significant association between presence of microorganisms in the tracheal and mouth samples for the following pathogens: Klebsiella pneumoniae, Candida albicans, Pseudomonas aeruginosa, Enterobacter gergoviae, Streptococcus spp and Serratia marcescens (p < 0.05). Pathogens that are present in tracheal aspirates of intubated patients can be detected in their oral cavity, especially in those who developed VAP or aspiration pneumonia. Thus, the results indicate that an improved oral care in these patients could decrease ICU pneumonia rates.

Tracheal worms

USGS Publications Warehouse

Cole, Rebecca A.

1999-01-01

Infection by tracheal worms often results in respiratory distress due to their location in the trachea or bronchi and their obstruction of the air passage. Infections by these parasitic nematodes or roundworms in waterbirds, primarily ducks, geese, and swans, are usually due to Cyathostoma bronchialis and infection of land birds are usually due to Syngamus trachea. However, both genera infect a variety of species, including both land and waterbirds. Infections with S. trachea have been more extensively studied than infections with Cyathostoma sp. because of its previous importance as a disease-causing parasite of poultry in many parts of the world. Changes in husbandry practices to modern intensive methods for poultry production have essentially eliminated S. trachea as an agent of disease in chickens, but it is an occasional cause of disease in turkeys raised on range.

Iatrogenic tracheal laceration in the setting of chronic steroids.

PubMed

Singh, Punit; Wojnar, Margaret; Malhotra, Anita

2017-02-01

We report the case of a 71-year-old woman with end-stage chronic obstructive pulmonary disease who presented with a 10-cm tracheal laceration from a presumed traumatic intubation in the setting of respiratory distress and chronic obstructive pulmonary disease exacerbation and subsequently developed significant subcutaneous emphysema along her neck and mediastinum in addition to her peritoneum and mesentery. We were successfully able to treat this patient conservatively up until the time that tracheostomy was warranted. We discuss and review tracheobronchial injuries with respect to etiology, risk factors, and management and hope to benefit health care providers managing airways in patients at risk for tracheal injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Middle finger length-based tracheal intubation depth improves the rate of appropriate tube placement in children.

PubMed

Zhou, Qing-he; Xiao, Wang-pin; Zhou, Hong-mei

2015-11-01

It is challenging for anesthetists to determine the optimal tracheal intubation depth in children. We hypothesize that a measure three times the length of the middle finger can be used for predicting tracheal tube depth in children. Eighty-six children (4-14 years of age) were included in this study. After the children were anesthetized, a fiberoptic bronchoscope (FOB) was inserted into the trachea, the lengths from the upper incisor teeth to carina and vocal cords were measured, and a suitably sized cuffed tracheal tube was inserted into the trachea. Age-based and middle finger length-based formulas were used to determine the tracheal intubation depth. All 86 children enrolled were included in this study. Compared with the age-based intubation, the rate of appropriate tube placement was higher for middle finger length-based intubation (88.37% vs 66.28%, P = 0.001). The proximal intubation rate was lower in middle finger length-based intubation (4.65% vs 32.56%, P < 0.001). There was only weak evidence for a difference in the distal intubation rate between the two methods (6.97% vs 1.16%, P = 0.054). The correlation coefficient between middle finger length and optimal tracheal tube depth was larger than that between age and optimal tracheal tube depth (0.883 vs 0.845). Our data indicate that the appropriate tube placement rate can be improved by using three times the middle finger length as the tracheal intubation depth in children. © 2015 John Wiley & Sons Ltd.

Use of silicone tracheal stoma stents for temporary tracheostomy in dogs with upper airway obstruction.

PubMed

Trinterud, T; Nelissen, P; White, R A S

2014-11-01

To report the use of silicone tracheal stoma stents for temporary tracheostomy in dogs with upper airway obstruction. Retrospective review of medical records for dogs in which silicone tracheal stoma stents were placed. Eighteen dogs had a silicone tracheal stoma stent placed for maintenance of a tracheostomy stoma for periods ranging from three hours to eight months. No intra-operative or immediate postoperative complications were recorded. In 11 dogs the stent was removed by simple traction after a period ranging from 36 hours to 6 weeks, and the tracheal stoma was left to heal by second intention. Five of the 18 dogs were determined as being tracheostomy dependent and underwent conversion to permanent tracheostomy after a period ranging from five days to eight months following stent placement. One dog was euthanased after three months, with the stent still in place, because of poor respiratory function, and one dog died of unrelated reasons. In 6 of 10 dogs (60%) where the stent was in place for five days or more, granulation tissue formation caused dislodgement of the stent. Silicone tracheal stoma stents may be used as an alternative to conventional tracheostomy tubes in selected dogs with upper airway obstruction. Long-term use of the stent beyond five days is not recommended because of granulation tissue formation. The long-term consequences of partial tracheal ring resection are unknown. © 2014 British Small Animal Veterinary Association.

A novel simple external fixation for securing silicone stent in patients with upper tracheal stenosis

PubMed Central

Lin, Xiaoxiao; Ye, Min; Li, Yuping

2018-01-01

Upper tracheal stenosis is considered as a potentially life-threatening condition. Silicone stenting is an attractive treatment option for patients with upper tracheal stenosis. However, its use has been compromised by a major complication, stent migration. In the report, we introduced a novel external fixation of silicone stent which only needed one puncture site and involved a silicon chip as an anchoring device. All equipment and materials including the silicon chip were available in routine bronchoscopy suite. The method had been successfully performed in three patients with upper tracheal stenosis at our institution. And the patients were monitored for over 20 months after the intervention, and no spontaneous stent migration occurred. Therefore, we believe this is a simple and reliable approach for improving the outcome of silicone stenting in patients with upper tracheal stenosis and should be introduced in clinical practice.

Tracheal obstruction caused by an expandable metallic stent: a case of successful removal of the stent.

PubMed

Okuyama, Hiroomi; Kubota, Akio; Kawahara, Hisayoshi; Oue, Takaharu; Nose, Satoko; Ihara, Toshiyuki

2005-07-01

We report a case of tracheal obstruction caused by an expandable metallic stent. A 3-month-old girl with severe tracheomalacia had a placement of a Palmaz stent. At 3 years of age, she developed progressive dyspnea. The CT scan showed tracheal obstruction caused by granulation tissue over the stent. At operation, the stent was found to have penetrated the posterior tracheal wall. Under partial cardiopulmonary bypass, the stent was removed along with the membranous wall of the trachea, and the trachea was reconstructed using slide tracheoplasty. Tracheal obstruction is one of the serious complications caused by an expandable metallic stent. Direct open approach to the trachea under cardiopulmonary bypass is thought to be a safe way to manage this problem.

Tracheal epithelial-myoepithelial carcinoma associated with sarcoid-like reaction: A case report

PubMed Central

Dong, Huawei; Tatsuno, Brent K.; Betancourt, Jaime; Oh, Scott S.

2014-01-01

Epithelial-myoepithelial carcinomas are rare tumors that primarily originate in the salivary glands but have also been found in the tracheobronchial tree. We report the first case of epithelial-myoepithelial carcinoma associated with sarcoidosis. A 61 year old Hispanic man presented with altered mental status and hypercalcemia. Imaging revealed diffuse intra-thoracic and intra-abdominal lymphadenopathy. A diagnostic bronchoscopy was performed where an incidental tracheal nodule was discovered and biopsied. Pathology was consistent with epithelial-myoepithelial carcinoma. Lymph node biopsy demonstrated non-caseating granulomas consistent with sarcoidosis. Patient underwent tracheal resection of the primary tumor with primary tracheal reconstruction. Hypercalcemia subsequently normalized with clinical improvement. Repeat CT imaging demonstrated complete resolution of lymphadenopathy. Our findings are suggestive of a possible paraneoplastic sarcoid-like reaction to the epithelial-myoepithelial carcinoma with associated lymphadenopathy and symptomatic hypercalcemia. PMID:26029574

Oxygen dose responsiveness of human fetal airway smooth muscle cells

PubMed Central

Hartman, William R.; Smelter, Dan F.; Sathish, Venkatachalem; Karass, Michael; Kim, Sunchin; Aravamudan, Bharathi; Thompson, Michael A.; Amrani, Yassine; Pandya, Hitesh C.; Martin, Richard J.; Prakash, Y. S.

2012-01-01

Maintenance of blood oxygen saturation dictates supplemental oxygen administration to premature infants, but hyperoxia predisposes survivors to respiratory diseases such as asthma. Although much research has focused on oxygen effects on alveoli in the setting of bronchopulmonary dysplasia, the mechanisms by which oxygen affects airway structure or function relevant to asthma are still under investigation. We used isolated human fetal airway smooth muscle (fASM) cells from 18–20 postconceptual age lungs (canalicular stage) to examine oxygen effects on intracellular Ca2+ ([Ca2+]i) and cellular proliferation. fASM cells expressed substantial smooth muscle actin and myosin and several Ca2+ regulatory proteins but not fibroblast or epithelial markers, profiles qualitatively comparable to adult human ASM. Fluorescence Ca2+ imaging showed robust [Ca2+]i responses to 1 μM acetylcholine (ACh) and 10 μM histamine (albeit smaller and slower than adult ASM), partly sensitive to zero extracellular Ca2+. Compared with adult, fASM showed greater baseline proliferation. Based on this validation, we assessed fASM responses to 10% hypoxia through 90% hyperoxia and found enhanced proliferation at <60% oxygen but increased apoptosis at >60%, effects accompanied by appropriate changes in proliferative vs. apoptotic markers and enhanced mitochondrial fission at >60% oxygen. [Ca2+]i responses to ACh were enhanced for <60% but blunted at >60% oxygen. These results suggest that hyperoxia has dose-dependent effects on structure and function of developing ASM, which could have consequences for airway diseases of childhood. Thus detrimental effects on ASM should be an additional consideration in assessing risks of supplemental oxygen in prematurity. PMID:22923637

Endobronchial angiofibroma in the aberrant tracheal bronchus presenting as spontaneous pneumomediastinum.

PubMed

Kim, Kyung Soo; Moon, Young Kyu; Jeon, Hyun Woo; Park, Chan Beom; Ahn, Myeong Im; Lee, Kyo Young; Park, Jae Kil

2015-07-22

Spontaneous pneumomediastinum is a self-limiting benign disease but abnormal bronchial lesions can be rarely found incidentally, and in selected cases will require surgical resection. A 38-year-old man presented with a spontaneous pneumomediastinum. Chest computed tomography revealed an incidental linear endobronchial tumour in the aberrant tracheal bronchus. The tumour was removed surgically and diagnosed with a rare benign tumour of endobronchial angiofibroma. We report a rare case of endobronchial angiofibroma in the aberrant tracheal bronchus which was detected during the evaluation of a spontaneous pneumomediastinum.

Novel technique for relieving anastomotic tension using halo-vest immobilization after tracheal sleeve resection.

PubMed

Imai, Kazuhiro; Minamiya, Yoshihiro; Saito, Hajime; Miyakoshi, Naohisa; Hongo, Michio; Kasukawa, Yuji; Ishikawa, Yoshinori; Motoyama, Satoru; Sato, Yusuke; Shimada, Yoichi; Ogawa, Jun-ichi

2013-07-01

We describe a novel technique of using halo-vest-enforced immobilization to relieve anastomotic tension after tracheal sleeve resection. Immediately after the tracheal sleeve resection, four halo titanium pins were inserted in the skulls of the patients to secure the halo-vest. All patients fitted with halo-vests were able to eat and drink and their clinical course was good. Bronchoscopy confirmed the absence of anastomotic leaks and stenoses, and there were no complications associated with the halo-vest. We believe that ensuring neck flexion using a halo-vest after tracheal sleeve resection is an excellent way of relieving anastomotic tension that would predispose the wound to dehiscence.

Treatment of Tracheal Mucoepidermoid Carcinoma by Argon Plasma Coagulation During Pregnancy

PubMed Central

Kesrouani, Assaad; Dabar, Georges; Rahal, Samir; Ghorra, Claude

2015-01-01

Mucoepidermoid carcinoma of the tracheobronchial tree is a rare airway tumor (<1% of all lung tumors). In adults, the majority of primary tracheal tumors are malignant. Management during pregnancy is complex and requires weighing maternal and fetal prognosis. Reported cases describe surgical resection following cesarean section. We report the first case to be treated by Argon-Plasma Coagulation (APC) in pregnancy. A 35-year-old Caucasian woman G1P0, at 27 weeks of gestation was admitted to the emergency department because of hemoptysis and severe dyspnea. Bronchoscopy and biopsies diagnosed primary tracheal mucoepidermoid carcinoma. Following an episode of tracheal bleeding, she was intubated. After thorough explanations to the family and obtaining informed consent, therapeutic bronchoscopy, under general anesthesia using a rigid bronchoscope, was performed. The tumor was cored out with the tip of the bronchoscope and removed with an alligator forceps. The tumor bed was coagulated with APC. The obstetrical team was ready to intervene in case of maternal emergency. Immediate follow-up was good, and she left the hospital 4 days later. She delivered at 39 weeks of gestation by cesarean section because of dystocia. Five years later, the patient is doing well without any signs or symptoms of recurrence. Pediatric follow-up is normal. Argon Plasma Coagulation for treatment of mucoepidermoid tracheal carcinoma is feasible during pregnancy. Reporting this case could lead to less aggressive management of mucoepidermoid carcinoma in pregnant patients. PMID:26011218

Treatment of tracheal mucoepidermoid carcinoma by argon plasma coagulation during pregnancy.

PubMed

Kesrouani, Assaad; Dabar, Georges; Rahal, Samir; Ghorra, Claude

2015-05-01

Mucoepidermoid carcinoma of the tracheobronchial tree is a rare airway tumor (<1% of all lung tumors). In adults, the majority of primary tracheal tumors are malignant. Management during pregnancy is complex and requires weighing maternal and fetal prognosis. Reported cases describe surgical resection following cesarean section. We report the first case to be treated by Argon-Plasma Coagulation (APC) in pregnancy. A 35-year-old Caucasian woman G1P0, at 27 weeks of gestation was admitted to the emergency department because of hemoptysis and severe dyspnea. Bronchoscopy and biopsies diagnosed primary tracheal mucoepidermoid carcinoma. Following an episode of tracheal bleeding, she was intubated. After thorough explanations to the family and obtaining informed consent, therapeutic bronchoscopy, under general anesthesia using a rigid bronchoscope, was performed. The tumor was cored out with the tip of the bronchoscope and removed with an alligator forceps. The tumor bed was coagulated with APC. The obstetrical team was ready to intervene in case of maternal emergency. Immediate follow-up was good, and she left the hospital 4 days later. She delivered at 39 weeks of gestation by cesarean section because of dystocia. Five years later, the patient is doing well without any signs or symptoms of recurrence. Pediatric follow-up is normal. Argon Plasma Coagulation for treatment of mucoepidermoid tracheal carcinoma is feasible during pregnancy. Reporting this case could lead to less aggressive management of mucoepidermoid carcinoma in pregnant patients.

Colorimetric carbon dioxide detector to determine accidental tracheal feeding tube placement.

PubMed

Howes, Daniel W; Shelley, Eric S; Pickett, William

2005-04-01

To determine the accuracy of colorimetric CO2 detection compared to the reference standard two-step radiological confirmation of feeding tube position. A prospective study was conducted with patients presenting to a 21-bed medical-surgical intensive care unit. An adapter was developed using an endotracheal tube adapter to connect a colorimetric CO2 detector to a feeding tube in an airtight manner. In part I of the study a feeding tube connected to the colorimeter was inserted into the endotracheal tubes of ten ventilated patients to test the device's ability to detect tracheal placement. In part II patients undergoing feeding tube insertion had tube position confirmed with the colorimeter as well as the reference standard two-step x-ray. In phase I the colorimeter correctly identified tracheal placement in all ten patients. In phase II 93/100 procedures ultimately were eligible; the colorimeter had a sensitivity of 0.88 (95% confidence interval: 0.65-1.00) and specificity of 0.99 (0.97-1.00). The device missed one of the eight tracheal placements. Agreement between the colorimeter and two-step x-ray interpretations was excellent (Kappa 0.86; standard error 0.10). We describe a novel, convenient method to confirm esophageal feeding tube placement. The device is easily assembled and inexpensive, but should not be reused. Colorimetric determination of tracheal feeding tube placement with this device has excellent agreement with the reference standard two-step radiological technique.

Differentiation of Human Adipose Derived Stem Cells into Smooth Muscle Cells Is Modulated by CaMKIIγ

PubMed Central

Aji, Kaisaier; Maimaijiang, Munila; Aimaiti, Abudusaimi; Rexiati, Mulati; Azhati, Baihetiya; Tusong, Hamulati

2016-01-01

The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is known to participate in maintenance and switches of smooth muscle cell (SMC) phenotypes. However, which isoform of CaMKII is involved in differentiation of adult mesenchymal stem cells into contractile SMCs remains unclear. In the present study, we detected γ isoform of CaMKII in differentiation of human adipose derived stem cells (hASCs) into SMCs that resulted from treatment with TGF-β1 and BMP4 in combination for 7 days. The results showed that CaMKIIγ increased gradually during differentiation of hASCs as determined by real-time PCR and western blot analysis. The siRNA-mediated knockdown of CaMKIIγ decreased the protein levels and transcriptional levels of smooth muscle contractile markers (a-SMA, SM22a, calponin, and SM-MHC), while CaMKIIγ overexpression increases the transcriptional and protein levels of smooth muscle contractile markers. These results suggested that γ isoform of CaMKII plays a significant role in smooth muscle differentiation of hASCs. PMID:27493668

Regeneration of tracheal epithelium using mouse induced pluripotent stem cells.

PubMed

Ikeda, Masakazu; Imaizumi, Mitsuyoshi; Yoshie, Susumu; Otsuki, Koshi; Miyake, Masao; Hazama, Akihiro; Wada, Ikuo; Omori, Koichi

2016-01-01

Conclusion The findings demonstrated the potential use of induced pluripotent stem cells for regeneration of tracheal epithelium. Objective Autologous tissue implantation techniques using skin or cartilage are often applied in cases of tracheal defects with laryngeal inflammatory lesions and malignant tumor invasion. However, these techniques are invasive with an unstable clinical outcome. The purpose of this study was to investigate regeneration in a tracheal defect site of nude rats after implantation of ciliated epithelium that was differentiated from induced pluripotent stem cells. Method Embryoid bodies were formed from mouse induced pluripotent stem cells. They were cultured with growth factors for 5 days, and then cultured at the air-liquid interface. The degree of differentiation achieved prior to implantation was determined by histological findings and the results of real-time polymerase chain reaction. Embryoid bodies including ciliated epithelium were embedded into collagen gel that served as an artificial scaffold, and then implanted into nude rats, creating an 'air-liquid interface model'. Histological evaluation was performed 7 days after implantation. Results The ciliated epithelial structure survived on the lumen side of regenerated tissue. It was demonstrated histologically that the structure was composed of ciliated epithelial cells.

Tracheal T-Tube Stent for Laryngotracheal Stenosis: Ten Year Experience

PubMed Central

Dass, Arjun; M Nagarkar, Nitin; K Singhal, Surinder; Verma, Hitesh

2014-01-01

Introduction: The purpose of this retrospective study was to evaluate the outcome following stenting over a period of 10 years in patients with chronic laryngotracheal stenosis. Materials and Methods: Between 2000–2010, out of 111 patients with laryngotracheal trauma, 71 underwent tracheal T-stenting for laryngotracheal stenosis in the Department of Otorhinolaryngology at the Government Medical College and Hospital, Chandigarh, India. All 71 patients underwent stenting by tracheal T-stent through an external approach. The follow-up period ranged from 3–10 years (mean, 3.2 years). The tracheal T-stent was removed after a minimum period of 6–12 months. Results: The majority of patients in this study were aged less than 10 years or between the ages of 20–30 years. A pre-operative tracheostomy (emergency or elective) was performed in all patients. of 71 patients, decannulation was not possible in six (8%). Conclusion: Management of laryngotracheal stenosis is a challenging problem that demands a multidisciplinary approach from surgical teams well trained in this field. The ideal treatment option should be individualized according to patient characteristics. The use of silastic stents has both advantages and disadvantages. PMID:24505573

Resection and anastomosis for benign tracheal stenosis: Single institution experience of 18 cases.

PubMed

Kumar, Arvind; Asaf, Belal Bin; Puri, Harsh Vardhan; Abdellateef, Amr

2017-01-01

Tracheal stenosis is a complex condition caused by altered inflammatory response to injury and subsequent excessive circumferential scar formation. Surgical resection, wherever possible, offers the best long-term results. Nonsurgical methods provide immediate relief to all can be curative in few but mostly serve as an excellent bridge to surgery in majority. The purpose of this study is to retrospectively evaluate the outcome following surgery for benign tracheal stenosis at our center. This retrospective analysis was conducted on 18 patients who underwent resection and anastomosis for tracheal stenosis at our center between March 2012 and December 2015. Their records were analyzed for demography, history, clinical presentation, computed tomography, bronchoscopy details, preoperative interventions, indications for and details of surgery, the procedure performed, postoperative complications, and course during 6 months follow-up. The patients had a varied list of pathologies for which they were either intubated or tracheostomized. The length of stenosis ranged between 1 cm and 4 cm. The diameter of stenotic segment ranged between 0 mm and 10 mm. Average length of resected segment was 3 cm, and number of tracheal rings resected ranged from 2 to 9. Postoperative complications occurred in four patients (22.22%). All our patients were in the "excellent outcome" category at discharge as well as at 3 months follow-up. Surgical management of tracheal stenosis is challenging and requires multidisciplinary team approach. Thorough preoperative preparation and multidisciplinary planning regarding need for and timing of surgery, meticulous intraoperative technique, and aggressive postoperative care is key to successful surgery, which can provide long-lasting cure to these patients.

Case report of apatinib mesylate treatment in rare advanced tracheal adenoid cystic carcinoma

PubMed Central

2017-01-01

A 57‐year‐old man was admitted to our department 10 years ago, diagnosed with tracheal adenoid cystic carcinoma. After discontinuing chemotherapy and radiotherapy, the disease recurred in December 2016. Apatinib mesylate (500 mg/day) was administered and computed tomography revealed that his symptoms were significantly relieved. Treatment with apatinib mesylate represents a novel method of treatment for tracheal adenoid cystic carcinoma. PMID:28892250

Non-invasive methods to maintain cervical spine position after pediatric tracheal resections.

PubMed

Aydinyan, Kahren K; Day, Jonathan D; Troiano, Gina M; Digoy, G Paul

2017-07-01

To present our experience with two methods of neck stabilization after pediatric tracheal resection with primary anastomosis as possible alternatives to the traditional chest-chin suture. Children undergoing tracheal resection and/or cricotracheal resection with anastomosis under tension were placed in cervical spine flexion postoperatively with either a chest-chin (Grillo) suture, an Aspen cervical collar or Trulife Johnson cervical-thoracic orthosis (CTO). A retrospective chart review of tracheal resections performed between 2005 and 2016 was completed to evaluate the positive and negative factors associated with each neck flexion technique. Of the 20 patients, there were 13 patients with the Grillo suture, 4 with the Aspen collar and 3 patients with the Johnson CTO. There were 13 tracheal resection procedures and 7 cricotracheal resections, all of which had anastomosis under tension. One major anastomosis dehiscence was noted with the Grillo suture technique which required reoperation. Two patients with the Grillo suture experienced skin breakdown at the suture site. The Aspen cervical collar, which fixed the cervical spine and prevented lateral and rotational motion, was limited in several cases in that it placed the spine in slight hyperextension. The Johnson CTO provided the most support in a flexed position and prevented cervical spine motion in all directions. No anastomosis complications were noted with the Aspen collar or the Johnson CTO, however, several patients sustained minor cutaneous wounds. In this series the Aspen cervical collar and Johnson CTO were used successfully as non-Grillo alternatives to postoperative neck stabilization in pediatric tracheal resections. Modifications to both devices are proposed to minimize cutaneous injuries and increase immobilization of the cervical spine in the desired flexed position. Although these devices appear to be safe and may be better tolerated, further innovation is needed to improve the design and fit of

The tracheal system in post-embryonic development of holometabolous insects: a case study using the mealworm beetle.

PubMed

Raś, Marcin; Iwan, Dariusz; Kamiński, Marcin Jan

2018-06-01

The tracheal (respiratory) system is regarded as one of the key elements which enabled insects to conquer terrestrial habitats and, as a result, achieve extreme species diversity. Despite this fact, anatomical data concerning this biological system is relatively scarce, especially in an ontogenetic context. The purpose of this study is to provide novel and reliable information on the post-embryonic development of the tracheal system of holometabolous insects using micro-computed tomography methods. Data concerning the structure of the respiratory system acquired from different developmental stages (larvae, pupae and adults) of a single insect species (Tenebrio molitor) are co-analysed in detail. Anatomy of the tracheal system is presented. Sample sizes used (29 individuals) enabled statistical analysis of the results obtained. The following aspects have been investigated (among others): the spiracle arrangement, the number of tracheal ramifications originating from particular spiracles, the diameter of longitudinal trunks, tracheal system volumes, tracheae diameter distribution and fractal dimension analysis. Based on the data acquired, the modularity of the tracheal system is postulated. Using anatomical and functional factors, the following respiratory module types have been distinguished: cephalo-prothoracic, metathoracic and abdominal. These modules can be unambiguously identified in all of the studied developmental stages. A cephalo-prothoracic module aerates organs located in the head capsule, prothorax and additionally prolegs. It is characterised by relatively thick longitudinal trunks and originates in the first thoracic spiracle pair. Thoracic modules support the flight muscles, wings, elytra, meso- and metalegs. The unique feature of this module is the presence of additional longitudinal connections between the neighbouring spiracles. These modules are concentrated around the second prothoracic and the first abdominal spiracle pairs. An abdominal module

Basally activated nonselective cation currents regulate the resting membrane potential in human and monkey colonic smooth muscle

PubMed Central

Dwyer, Laura; Rhee, Poong-Lyul; Lowe, Vanessa; Zheng, Haifeng; Peri, Lauren; Ro, Seungil; Sanders, Kenton M.

2011-01-01

Resting membrane potential (RMP) plays an important role in determining the basal excitability of gastrointestinal smooth muscle. The RMP in colonic muscles is significantly less negative than the equilibrium potential of K+, suggesting that it is regulated not only by K+ conductances but by inward conductances such as Na+ and/or Ca2+. We investigated the contribution of nonselective cation channels (NSCC) to the RMP in human and monkey colonic smooth muscle cells (SMC) using voltage- and current-clamp techniques. Qualitative reverse transcriptase-polymerase chain reaction was performed to examine potential molecular candidates for these channels among the transient receptor potential (TRP) channel superfamily. Spontaneous transient inward currents and holding currents were recorded in human and monkey SMC. Replacement of extracellular Na+ with equimolar tetraethylammonium or Ca2+ with Mn2+ inhibited basally activated nonselective cation currents. Trivalent cations inhibited these channels. Under current clamp, replacement of extracellular Na+ with N-methyl-d-glucamine or addition of trivalent cations caused hyperpolarization. Three unitary conductances of NSCC were observed in human and monkey colonic SMC. Molecular candidates for basally active NSCC were TRPC1, C3, C4, C7, M2, M4, M6, M7, V1, and V2 in human and monkey SMC. Comparison of the biophysical properties of these TRP channels with basally active NSCC (bINSCC) suggests that TRPM4 and specific TRPC heteromultimer combinations may underlie the three single-channel conductances of bINSCC. In conclusion, these findings suggest that basally activated NSCC contribute to the RMP in human and monkey colonic SMC and therefore may play an important role in determining basal excitability of colonic smooth muscle. PMID:21566016

Mangiferin Prevents Guinea Pig Tracheal Contraction via Activation of the Nitric Oxide-Cyclic GMP Pathway

PubMed Central

Vieira, Aline B.; Coelho, Luciana P.; Insuela, Daniella B. R.; Carvalho, Vinicius F.; dos Santos, Marcelo H.; Silva, Patricia MR.; Martins, Marco A.

2013-01-01

Previous studies have described the antispasmodic effect of mangiferin, a natural glucoside xanthone (2-C-β-Dgluco-pyranosyl-1,3,6,7-tetrahydroxyxanthone) that is present in mango trees and other plants, but its mechanism of action remains unknown. The aim of this study was to examine the potential contribution of the nitric oxide-cyclic GMP pathway to the antispasmodic effect of mangiferin on isolated tracheal rings preparations. The functional effect of mangiferin on allergic and non-allergic contraction of guinea pig tracheal rings was assessed in conventional organ baths. Cultured tracheal rings were exposed to mangiferin or vehicle, and nitric oxide synthase (NOS) 3 and cyclic GMP (cGMP) levels were quantified using western blotting and enzyme immunoassays, respectively. Mangiferin (0.1–10 µM) inhibited tracheal contractions induced by distinct stimuli, such as allergen, histamine, 5-hydroxytryptamine or carbachol, in a concentration-dependent manner. Mangiferin also caused marked relaxation of tracheal rings that were precontracted by carbachol, suggesting that it has both anti-contraction and relaxant properties that are prevented by removing the epithelium. The effect of mangiferin was inhibited by the nitric oxide synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME) (100 µM), and the soluble guanylate cyclase inhibitor, 1H-[1], [2], [4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 µM), but not the adenylate cyclase inhibitor, 9-(tetrahydro-2-furyl)adenine (SQ22536) (100 µM). The antispasmodic effect of mangiferin was also sensitive to K+ channel blockers, such as tetraethylammonium (TEA), glibenclamide and apamin. Furthermore, mangiferin inhibited Ca2+-induced contractions in K+ (60 mM)-depolarised tracheal rings preparations. In addition, mangiferin increased NOS3 protein levels and cGMP intracellular levels in cultured tracheal rings. Finally, mangiferin-induced increase in cGMP levels was abrogated by co-incubation with either ODQ or L

Treatment of Benign Tracheal Stenosis Using Endoluminal Spray Cryotherapy.

PubMed

Bhora, Faiz Y; Ayub, Adil; Forleiter, Craig M; Huang, Chyun-Yin; Alshehri, Khalid; Rehmani, Sadiq; Al-Ayoubi, Adnan M; Raad, Wissam; Lebovics, Robert S

2016-11-01

Tracheal stenosis is a debilitating disorder with heterogeneity in terms of disease characteristics and management. Repeated recurrences substantially alter patients' quality of life. There is limited evidence for the use of spray cryotherapy (SCT) in the management of benign airway disease. To report our early results for the use of SCT in patients with benign tracheal stenosis. Data were extracted from the medical records of a consecutive series of patients with benign airway stenosis secondary to granulomatosis with polyangiitis (GPA) (n = 13), prior tracheotomy or tracheal intubation (n = 8), and idiopathic strictures (n = 5) treated from September 1, 2013, to September 30, 2015, at a tertiary care hospital. Airway narrowing was quantified on a standard quartile grading scale. Response to treatment was assessed by improvement in airway caliber and the time interval for reintervention. Delivery of 4 5-second SCT cycles and 2 balloon dilatations. Twenty-six patients (median [range] age, 53 [16-83] years; 20 [77%] female) underwent 48 SCT sessions. Spray cryotherapy was successfully used without any substantial intraoperative or postoperative complications in all patients. In a median (range) follow-up of 11 (1-26) months, all patients had improvement in symptoms. Before the institution of SCT, 23 patients (88%) had grade III or IV stenosis. At the last evaluation after induction of SCT, 4 (15%) had grade III or IV stenosis, with a mean (SD) change of 1.39 (0.51) (P < .001). Patients with GPA required significantly fewer SCT procedures (mean [SD], 1.38 [0.96] vs 2.31 [1.18]; P = .03) during the study period. Spray cryotherapy was a safe adjunct modality to accomplish airway patency in patients with benign tracheal stenosis. Although efficacy evidence is limited for SCT, it may be useful for patients who have experienced treatment failure with conventional modalities. Further analysis of this cohort will determine the physiologic durability of

Sivelestat relaxes vascular smooth muscle contraction in human gastric arteries.

PubMed

Amemori, Hiroko; Maeda, Yoshinori; Torikai, Arisu; Nakashima, Mikio

2011-12-01

Sivelestat sodium hydrate (sivelestat) is a novel synthetic drug and specific inhibitor of neutrophil elastase that has been approved in Japan as a treatment for acute lung injury associated with systemic inflammatory response syndrome. It is important to determine how sivelestat affects hemodynamics and the regulatory mechanisms of vascular smooth muscle (VSM). We recently found that sivelestat relaxes porcine coronary artery VSM via selective inhibition of Ca(2+) sensitization induced by a receptor agonist without affecting the normal Ca(2+)-induced contraction. Although sivelestat relaxes porcine artery, its effects on human artery are unknown; therefore, the purpose of the present study was to assess the effects of sivelestat on human artery. In the present study, sivelestat induced concentration-dependent (1 × 10(-6) to 3 × 10(-4) M) vasorelaxation in U46619 (1 nM) and sphingosylphosphorylcholine (SPC) (30 mM)-precontracted human gastric artery with or without endothelium, but sivelestat did not induce vasorelaxation in conditions of high K(+) (40 mM) depolarization. Sivelestat inhibited VSM contraction by an agonist and SPC, and it did not affect Ca(2+)-induced normal physiologic contraction.

Predictive value of α-amylase in tracheal aspirates for ventilator-associated pneumonia in elderly patients.

PubMed

Qu, Ge-Ping; Fang, Xiang-Qun; Xu, Ya-Ping; Shi, Min; Wang, Yang; Gong, Mei-Liang; Fang, Hao-Ming

2018-04-01

This study aims to investigate the correlation between α-amylase in tracheal aspirates and risk factors of aspiration, as well as ventilator-associated pneumonia (VAP), in elderly patients undergoing mechanical ventilation and explore the clinical value of α-amylase for predicting VAP. Tracheal aspirates were collected from elderly patients within 2 weeks after tracheal intubation in mechanical ventilation, and α-amylase was detected. Patients were grouped according to the presence of VAP. The correlation between α-amylase and risk factors of aspiration before intubation, as well as VAP, were analyzed. The sample of this study comprised 147 patients. The average age of these patients was 86.9 years. The incidence of VAP was 21% during the study period. Tracheal aspirate α-amylase level increased with the increase in the number of risk factors for aspiration before intubation, α-amylase level was significantly higher in the VAP group than in the non-VAP group, the area under the receiver operating characteristic curve (ROC) of the diagnostic value of α-amylase for VAP was 0.813 (95% CI: 0.721-0.896), threshold value was 4,681.5 U/L, sensitivity was 0.801 and specificity was 0.793. Logistic multivariate analysis revealed the following risk factors for VAP: a number of risk factors before intubation of ≥3, a Glasgow score of <8 points, the absence of continuous aspiration of subglottic secretion and a tracheal aspirate α-amylase level of >4681.5 U/L. Tracheal aspirate α-amylase can serve as a biomarker for predicting VAP in elderly patients undergoing mechanical ventilation. © 2017 John Wiley & Sons Ltd.

Metabolism of native and naturally occurring multiple modified low density lipoprotein in smooth muscle cells of human aortic intima.

PubMed

Tertov, V V; Orekhov, A N

1997-01-01

The subfraction of low density lipoprotein (LDL) with low sialic acid content that caused accumulation of cholesterol esters in human aortic smooth muscle cells has been found in the blood of coronary atherosclerosis patients. It was demonstrated that this subfraction consists of LDL with small size, high electronegative charge, reduced lipid content, altered tertiary structure of apolipoprotein B, etc. LDL of this subfraction is naturally occurring multiple-modified LDL (nomLDL). In this study we compared the binding, uptake and proteolytic degradation of native LDL and nomLDL by smooth muscle cells cultured from human grossly normal intima, fatty streaks, and atherosclerotic plaques. Uptake of nomLDL by normal and atherosclerotic cells was 3.5- and 6-fold, respectively, higher than uptake of native LDL. Increased uptake of nomLDL was due to increased binding of this LDL by intimal smooth muscle cells. The enhanced binding is explained by the interaction of nomLDL with cellular receptors other than LDL-receptor. Modified LDL interacted with the scavenger receptor, asialoglycoprotein receptor, and also with cell surface proteoglycans. Rates of degradation of nomLDL were 1.5- and 5-fold lower than degradation of native LDL by normal and atherosclerotic cells, respectively. A low rate of nomLDL degradation was also demonstrated in homogenates of intimal cells. Activities of lysosomal proteinases of atherosclerotic cells were decreased compared with normal cells. Pepstatin A, a cathepsin D inhibitor, completely inhibited lipoprotein degradation, while serine, thiol, or metallo-proteinase inhibitors had partial effect. This fact reveals that cathepsin D is involved in initial stages of apoB degradation by intimal smooth muscle cells. Obtained data show that increased uptake and decreased lysosomal degradation of nomLDL may be the main cause of LDL accumulation in human aortic smooth muscle cells, leading to foam cell formation.

Smooth Muscle-Like Cells Generated from Human Mesenchymal Stromal Cells Display Marker Gene Expression and Electrophysiological Competence Comparable to Bladder Smooth Muscle Cells.

PubMed

Brun, Juliane; Lutz, Katrin A; Neumayer, Katharina M H; Klein, Gerd; Seeger, Tanja; Uynuk-Ool, Tatiana; Wörgötter, Katharina; Schmid, Sandra; Kraushaar, Udo; Guenther, Elke; Rolauffs, Bernd; Aicher, Wilhelm K; Hart, Melanie L

2015-01-01

The use of mesenchymal stromal cells (MSCs) differentiated toward a smooth muscle cell (SMC) phenotype may provide an alternative for investigators interested in regenerating urinary tract organs such as the bladder where autologous smooth muscle cells cannot be used or are unavailable. In this study we measured the effects of good manufacturing practice (GMP)-compliant expansion followed by myogenic differentiation of human MSCs on the expression of a range of contractile (from early to late) myogenic markers in relation to the electrophysiological parameters to assess the functional role of the differentiated MSCs and found that differentiation of MSCs associated with electrophysiological competence comparable to bladder SMCs. Within 1-2 weeks of myogenic differentiation, differentiating MSCs significantly expressed alpha smooth muscle actin (αSMA; ACTA2), transgelin (TAGLN), calponin (CNN1), and smooth muscle myosin heavy chain (SM-MHC; MYH11) according to qRT-PCR and/or immunofluorescence and Western blot. Voltage-gated Na+ current levels also increased within the same time period following myogenic differentiation. In contrast to undifferentiated MSCs, differentiated MSCs and bladder SMCs exhibited elevated cytosolic Ca2+ transients in response to K+-induced depolarization and contracted in response to K+ indicating functional maturation of differentiated MSCs. Depolarization was suppressed by Cd2+, an inhibitor of voltage-gated Ca2+-channels. The expression of Na+-channels was pharmacologically identified as the Nav1.4 subtype, while the K+ and Ca2+ ion channels were identified by gene expression of KCNMA1, CACNA1C and CACNA1H which encode for the large conductance Ca2+-activated K+ channel BKCa channels, Cav1.2 L-type Ca2+ channels and Cav3.2 T-type Ca2+ channels, respectively. This protocol may be used to differentiate adult MSCs into smooth muscle-like cells with an intermediate-to-late SMC contractile phenotype exhibiting voltage-gated ion channel

Cultured smooth muscle cells of the human vesical sphincter are more sensitive to histamine than are detrusor smooth muscle cells.

PubMed

Neuhaus, Jochen; Oberbach, Andreas; Schwalenberg, Thilo; Stolzenburg, Jens-Uwe

2006-05-01

To compare histamine receptor expression in cultured smooth muscle cells from the human detrusor and internal sphincter using receptor-specific agonists. Smooth muscle cells from the bladder dome and internal sphincter were cultured from 5 male patients undergoing cystectomy for bladder cancer therapy. Calcium transients in cells stimulated with carbachol, histamine, histamine receptor 1 (H1R)-specific heptanecarboxamide (HTMT), dimaprit (H2R), and R-(alpha)-methylhistamine (H3R) were measured by calcium imaging. Histamine receptor proteins were detected by Western blot analysis and immunocytochemistry. H1R, H2R, and H3R expression was found in tissue and cultured cells. Carbachol stimulated equal numbers of detrusor and sphincter cells (60% and 51%, respectively). Histamine stimulated significantly more cells than carbachol in detrusor (100%) and sphincter (99.34%) cells. Calcium responses to carbachol in detrusor and sphincter cells were comparable and did not differ from those to histamine in detrusor cells. However, histamine and specific agonists stimulated more sphincter cells than did carbachol (P <0.001), and the calcium increase was greater in sphincter cells than in detrusor cells. Single cell analysis revealed comparable H2R responses in detrusor and sphincter cells, but H1R and H3R-mediated calcium reactions were significantly greater in sphincter cells. Histamine very effectively induces calcium release in smooth muscle cells. In sphincter cells, histamine is even more effective than carbachol regarding the number of reacting cells and the intracellular calcium increase. Some of the variability in the outcome of antihistaminic interstitial cystitis therapies might be caused by the ineffectiveness of the chosen antihistaminic or unintentional weakening of sphincteric function.

Repeated partial endoscopic resections as treatment for two patients with inoperable tracheal tumours

PubMed Central

Nakratzas, G.; Wagenaar, J. P. M.; Reintjes, M.; Scheffer, E.; Swierenga, J.

1974-01-01

Nakratzas, G., Wagenaar, J. P. M., Reintjes, M., Scheffer, E., and Swierenga, J. (1974).Thorax, 29, 125-131. Repeated partial endoscopic resections as treatment for two patients with inoperable tracheal tumours. Two cases of tracheal tumour are described, one a carcinoid and the other an adenoid cystic carcinoma (cylindroma). Both patients were treated by repeated partial bronchoscopic resections. The patients are in good health nine and three years respectively after treatment. Images PMID:4363463

Endoscopic treatment with fibrin glue of post-intubation tracheal laceration

PubMed Central

Cascone, Roberto; Di Natale, Davide; Pierdiluca, Matteo; Mastromarino, Rossella; Natale, Giovanni; De Ruberto, Emanuele; Messina, Gaetana; Vicidomini, Giovanni; Santini, Mario

2017-01-01

Post-intubation tracheal laceration (PITL) is a rare and potential life-threatening condition requiring prompt diagnosis and treatment. A conservative treatment is indicated in patients with laceration <2 cm in length while surgery is the treatment of choice for laceration >4 cm. For laceration between 2–4 cm, the best treatment is debate; some authors recommend surgery while others do not definitely exclude endoscopic treatment. Herein, we reported the endoscopic treatment with fibrin glue of PITL. The procedure is performed using a standard video-bronchoscopy in operating room; the patient is in spontaneous breathing and deep sedation. After identification of tracheal laceration, the fibrin glue is injected through a dedicated double lumen catheter into the lesion. After mixing both components of fibrin glue, polymerization of fibrin occurs resulting in an elastic and opaque clot that closes the lesion. The key success of the procedure is based on accurate patient selection. Patients are eligible if (I) they are clinically stable and in spontaneous respiration; (II) with a small and superficial tracheal laceration (≤4 cm in length and without oesophageal injury); (III) localized at level of the upper or middle trachea; and (IV) without clinical and/or radiological signs of mediastinal collection, of emphysema or pneumomediastinum progression, and of infection. PMID:29078663

The Safety and efficacy of a new self-expandable intratracheal nitinol stent for the tracheal collapse in dogs

PubMed Central

Kim, Joon-young; Han, Hyun-jung; Yun, Hun-young; Lee, Bora; Jang, Ha-young; Eom, Ki-dong; Park, Hee-myung

2008-01-01

To evaluate the potential utility of a self-expandable intratracheal nitinol stent with flared ends for the treatment of tracheal collapse in dogs, endotracheal stenting therapy was performed under fluoroscopic guidance in four dogs with severe tracheal collapse. During the 4 to 7 month follow-up, after stent implantation, clinical signs, including dyspnea and respiratory distress, dramatically improved in all dogs. The radiographs showed that the implanted stents improved the tracheal collapse, and there were no side effects such as collapse, shortening or migration of the stents. In conclusion, the self-expandable intratracheal nitinol stents provided adequate stability to the trachea and were effective for attenuating the clinical signs associated with severe tracheal collapse. PMID:18296893

A case of tracheal leiomyoma misdiagnosed as asthma.

PubMed

Öztürk, Ayperi; Aktaş, Zafer; Yılmaz, Aydın; Yeşildağlı, Havva; Memiş, Leyla

2016-12-01

Primary benign tumors of trachea are rare. Of them, tracheal leiomyoma, constitutes only 1% of all benign lower respiratory tract tumors. Here, we present a case of tracheal leiomyoma who has been receiving high doses of inhaled corticosteroids and bronchodilators for a year with a misdiagnosis of asthma. As the symptoms did not resolve with an overtreatment, she has been undergone radiologic study to find a possible alternative diagnosis. The chest roentgenogram revealed an opacity in the upper mediastinum. In computed tomography, a lesion has been detected in proximal trachea, arising from the posterior wall and protruding through the lumen and almost obliterating the air column. Rigid bronchoscopy has been performed under general anesthesia due to a high risk of bleeding and the endobronchial lesion, freely moving with respiration, has been removed and cryotherapy was applied to the base of the lesion. Receiving the histopathological diagnosis of leiomyoma, the patient is now on 12th month of the follow-up without any recurrence.

Tracheoesophageal fistula--a complication of prolonged tracheal intubation.

PubMed

Paraschiv, M

2014-01-01

Tracheoesophageal fistula most commonly occurs as a complication of prolonged tracheal intubation. The incidence decreased after the use of low pressure and high volume endotracheal cuffs, but the intensive care units continue to provide such cases. The abnormal tracheoesophageal communication causes pulmonary contamination (with severe suppuration) and impossibility to feed the patient. The prognosis is reserved, because most patients are debilitated and ventilator dependent, with severe neurological and cardiovascular diseases. The therapeutic options are elected based on respiratory, neurological and nutritional status. The aim of conservative treatment is to stop the contamination (drainage gastrostomy, feeding jejunostomy) and to treat the pulmonary infection and biological deficits. Endoscopic therapies can be tried in cases with surgical contraindication. Operation is addressed to selected cases and consists in the dissolution of the fistula, esophageal suture with or without segmental tracheal resection associated. Esophageal diversion is rarely required. The correct indication and timing of surgery, proper surgical technique and postoperative care are prerequisites for adequate results.

Tracheoesophageal fistula - a complication of prolonged tracheal intubation

PubMed Central

Paraschiv, M

2014-01-01

Tracheoesophageal fistula most commonly occurs as a complication of prolonged tracheal intubation. The incidence decreased after the use of low pressure and high volume endotracheal cuffs, but the intensive care units continue to provide such cases. The abnormal tracheoesophageal communication causes pulmonary contamination (with severe suppuration) and impossibility to feed the patient. The prognosis is reserved, because most patients are debilitated and ventilator dependent, with severe neurological and cardiovascular diseases. The therapeutic options are elected based on respiratory, neurological and nutritional status. The aim of conservative treatment is to stop the contamination (drainage gastrostomy, feeding jejunostomy) and to treat the pulmonary infection and biological deficits. Endoscopic therapies can be tried in cases with surgical contraindication. Operation is addressed to selected cases and consists in the dissolution of the fistula, esophageal suture with or without segmental tracheal resection associated. Esophageal diversion is rarely required. The correct indication and timing of surgery, proper surgical technique and postoperative care are prerequisites for adequate results. PMID:25713612

Metabolism of substance P and neurokinin A by human vascular endothelium and smooth muscle.

PubMed

Wang, L; Sadoun, E; Stephens, R E; Ward, P E

1994-01-01

Analysis of SP and NKA metabolism by human vascular endothelium, relative to that in human plasma, identified integrative, multiple pathways for the processing of circulating SP (but not NKA) by angiotensin-converting enzyme (ACE; EC 3.4.15.1), dipeptidyl(amino)peptidase IV (DAP IV; EC 3.4.14.5), and aminopeptidase M (AmM; EC 3.4.11.2). In contrast, SP and NKA, which may diffuse into or be neurally released within the vessel wall, were both metabolized by smooth muscle neutral endopeptidase-24.11 (NEP-24.11; EC 3.4.24.11). Collectively, these studies indicate peptide-specific and site-specific differential processing of SP and NKA by human plasma and vasculature.

Tracheal Suctioning Improves Gas Exchange but not Hemodynamics in Asphyxiated Lambs with Meconium Aspiration

PubMed Central

Lakshminrusimha, Satyan; Mathew, Bobby; Nair, Jayasree; Gugino, Sylvia F.; Koenigsknecht, Carmon; Rawat, Munmun; Nielsen, Lori; Swartz, Daniel D.

2014-01-01

Background Current neonatal resuscitation guidelines recommend tracheal suctioning of non-vigorous neonates born through meconium stained amniotic fluid. Methods We evaluated the effect of tracheal suctioning at birth in 29 lambs with asphyxia induced by cord occlusion and meconium aspiration during gasping. Results Tracheal suctioning at birth (n=15) decreased amount of meconium in distal airways (53±29 particles/mm2 lung area) compared to no-suction (499±109 particles/mm2, n=14, p<0.001). Three lambs in the suction group had cardiac arrest during suctioning requiring chest compressions and epinephrine. Onset of ventilation was delayed in the suction group (146±11 vs. 47±3 sec in no-suction group, p=0.005). There was no difference in pulmonary blood flow, carotid blood flow, pulmonary or systemic blood pressure between the two groups. Left atrial pressure was significantly higher in the suction group. Tracheal suctioning resulted in higher PaO2/FiO2 levels (122±21 vs. 78±10 mmHg) and ventilator efficiency index (0.3±0.05 vs.0.16±0.03). Two lambs in the no-suction group required inhaled NO. Lung 3-nitrotyrosine levels were higher in the suction group (0.65±0.03 ng/μg protein) compared to the no-suction group (0.47 ± 0.06). Conclusion Tracheal suctioning improves oxygenation and ventilation. Suctioning does not improve pulmonary/systemic hemodynamics or oxidative stress in an ovine model of acute meconium aspiration with asphyxia. PMID:25406897

Heat shock protein 70 secretion by neonatal tracheal tissue during mechanical ventilation: association with indices of tissue function and modeling.

PubMed

Chong, Euming; Dysart, Kevin C; Chidekel, Aaron; Locke, Robert; Shaffer, Thomas H; Miller, Thomas L

2009-04-01

Mechanical ventilation (MV) of the neonatal airway alters mechanical properties and activates tissue-modeling pathways. Heat shock protein (HSP70) is a marker of tissue injury and modulates inflammation, which may influence subsequent pulmonary tissue modeling by matrix metalloproteinases (MMPs). HSP70 secretion is up-regulated in MV airway tissues and associated with changes in airway elasticity and secretion of MMPs. Proximal tracheal segments were isolated in 13 newborn lambs and were either MV for 4 h or SHAM. At baseline and hourly, tracheal segments were flushed and tracheal elasticity was determined. Tracheal wash fluid was assayed for HSP70 by ELISA and for MMPs by substrate zymography. HSP70 secretion increased from baseline to a peak at 1 h in both groups (p < 0.01), greater in the MV group (p < 0.05), and returned to baseline values by 2 h. This response was in contrast to the progressive decrease in tracheal elasticity (p < 0.05). The HSP70 elevation pattern was noted in MMP-2, but beyond 1 h, MMP-2 returned to baseline values in MV group but remained elevated in SHAM (p < 0.05). HSP70 secretion is associated with the degree of biophysical tracheal injury as well as the time course of MMP-2 secretion by tracheal tissues.

Rescue patient from tracheal obstruction by dislocated bronchial stent during tracheostomy surgery with readily available tools: A case report.

PubMed

Chang, Hung-Yu; Man, Kee-Ming; Liao, Kate Hsiurong; Chiang, Yi-Ying; Chen, Kuen-Bao

2017-09-01

Airway stenting is a well-established method that relieves symptoms and maintains airway patency in patients with airway obstruction. Serious complications caused by airway stents such as stent dislocation and airway obstruction during surgery are life-threatening. An 80-year-old man was treated with bronchial stent for left bronchus obstruction caused by metastatic esophageal cancer. During tracheostomy surgery, he suffered from acute tracheal obstruction caused by dislocated bronchial stent. Esophageal cancer, left bronchus obstruction, respiratory failure, tracheal obstruction. Threading a 5.0-sized endotracheal tube combined with an Eschmann tracheal tube introducer to prop up the collapsed stent. The bronchial stent was re-expanded and threaded into right main bronchus and ventilation restored. Patient with airway stent undergoing surgery with airway involved should be performed under the support of a backup physician and equipment that are capable of handling potentially life-threatening complications of airway stent. If not, in the emergent situation of tracheal obstruction due to tracheal/bronchial stent, protruding through the stent with a suitable, small-sized endotracheal tube with Eschmann tracheal tube introducer may be an alternative skill for saving life weighted with possible complications.

Triple-layered polyurethane prosthesis with wrinkles for repairing partial tracheal defects.

PubMed

Lee, Ja H; Park, Hae S; Oh, Se H; Lee, Jin H; Kim, Jin R; Kim, Hyun J; Jung, Soo Y; Chung, Sung M; Choi, Hong S; Kim, Han S

2014-12-01

The purpose of this study was to develop a triple-layered artificial polyurethane (PU) scaffold with a wrinkled layer for reconstruction of partial tracheal defects. Animal experiment. PU/Pluronic F127 solution was transformed into an asymmetrically porous PU membrane by an immersion precipitation method. The nonporous wrinkled film was prepared by a simple casting of the PU solution on a grooved mold. The triple-layered wrinkled PU scaffolds were fabricated by simple inosculating between the wrinkled film and the porous membranes as in a sandwich (porous/wrinkled/porous structure). Scaffolds were transplanted into 10 New Zealand rabbits after creating tracheal windows. Endoscopic and histological examinations and mechanical tests were performed. The thickness and outer pore size of the prepared triple-layered PU scaffold were ∼1.95 mm and ∼200 μm, respectively. The wrinkled PU scaffold showed better maximum flexural strength compared to the nonwrinkled scaffold (1.03 ± 0.19 vs. 0.56 ± 0.09 MPa). Eight of 10 rabbits survived through all of the examinations and procedures. Endoscopic findings revealed that respiratory mucosa was observed over the scaffold at 3 weeks, and it was an entirely covered scaffold at 6 weeks. The circular framework of the tracheal lumen was maintained in seven of 10 rabbits. Histologic findings showed that ciliated respiratory mucosa covered the surface of the scaffolds. The tensile strength of the scaffold-implanted trachea was lower than that of the normal control. A wrinkled, triple-layered PU scaffold can be used as a ready-made scaffold for reconstruction of partial tracheal defects. NA. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

In-depth evaluation of commercially available human vascular smooth muscle cells phenotype: Implications for vascular tissue engineering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Timraz, Sara B.H., E-mail: sara.timraz@kustar.ac.ae; Farhat, Ilyas A.H., E-mail: ilyas.farhat@outlook.com; Alhussein, Ghada, E-mail: ghada.alhussein@kustar.ac.ae

In vitro research on vascular tissue engineering has extensively used isolated primary human or animal smooth muscle cells (SMC). Research programs that lack such facilities tend towards commercially available primary cells sources. Here, we aim to evaluate the capacity of commercially available human SMC to maintain their contractile phenotype, and determine if dedifferentiation towards the synthetic phenotype occurs in response to conventional cell culture and passaging without any external biochemical or mechanical stimuli. Lower passage SMC adopted a contractile phenotype marked by a relatively slower proliferation rate, higher expression of proteins of the contractile apparatus and smoothelin, elongated morphology, andmore » reduced deposition of collagen types I and III. As the passage number increased, migratory capacity was enhanced, average cell speed, total distance and net distance travelled increased up to passage 8. Through the various assays, corroborative evidence pinpoints SMC at passage 7 as the transition point between the contractile and synthetic phenotypes, while passage 8 distinctly and consistently exhibited characteristics of synthetic phenotype. This knowledge is particularly useful in selecting SMC of appropriate passage number for the target vascular tissue engineering application, for example, a homeostatic vascular graft for blood vessel replacement versus recreating atherosclerotic blood vessel model in vitro. - Highlights: • Ability of human smooth muscle cells to alter phenotype in culture is evaluated. • Examined the effect of passaging human smooth muscle cells on phenotype. • Phenotype is assessed based on morphology, proliferation, markers, and migration. • Multi-resolution assessment methodology, single-cell and cell-population. • Lower and higher passages than P7 adopted a contractile and synthetic phenotype respectively.« less

Stem-cell-based, tissue engineered tracheal replacement in a child: a 2-year follow-up study

PubMed Central

Elliott, Martin J; De Coppi, Paolo; Speggiorin, Simone; Roebuck, Derek; Butler, Colin R; Samuel, Edward; Crowley, Claire; McLaren, Clare; Fierens, Anja; Vondrys, David; Cochrane, Lesley; Jephson, Christopher; Janes, Samuel; Beaumont, Nicholas J; Cogan, Tristan; Bader, Augustinus; Seifalian, Alexander M; Hsuan, J Justin; Lowdell, Mark W; Birchall, Martin A

2015-01-01

Summary Background Stem-cell-based, tissue engineered transplants might offer new therapeutic options for patients, including children, with failing organs. The reported replacement of an adult airway using stem cells on a biological scaffold with good results at 6 months supports this view. We describe the case of a child who received a stem-cell-based tracheal replacement and report findings after 2 years of follow-up. Methods A 12-year-old boy was born with long-segment congenital tracheal stenosis and pulmonary sling. His airway had been maintained by metal stents, but, after failure, a cadaveric donor tracheal scaffold was decellularised. After a short course of granulocyte colony stimulating factor, bone marrow mesenchymal stem cells were retrieved preoperatively and seeded onto the scaffold, with patches of autologous epithelium. Topical human recombinant erythropoietin was applied to encourage angiogenesis, and transforming growth factor β to support chondrogenesis. Intravenous human recombinant erythropoietin was continued postoperatively. Outcomes were survival, morbidity, endoscopic appearance, cytology and proteomics of brushings, and peripheral blood counts. Findings The graft revascularised within 1 week after surgery. A strong neutrophil response was noted locally for the first 8 weeks after surgery, which generated luminal DNA neutrophil extracellular traps. Cytological evidence of restoration of the epithelium was not evident until 1 year. The graft did not have biomechanical strength focally until 18 months, but the patient has not needed any medical intervention since then. 18 months after surgery, he had a normal chest CT scan and ventilation-perfusion scan and had grown 11 cm in height since the operation. At 2 years follow-up, he had a functional airway and had returned to school. Interpretation Follow-up of the first paediatric, stem-cell-based, tissue-engineered transplant shows potential for this technology but also highlights the need for

Transoral tracheal intubation of rodents using a fiberoptic laryngoscope.

PubMed

Costa, D L; Lehmann, J R; Harold, W M; Drew, R T

1986-06-01

A fiberoptic laryngoscope which allows direct visualization of the deep pharynx and epiglottis has been developed for transoral tracheal intubation of small laboratory mammals. The device has been employed in the intubation and instillation of a variety of substances into the lungs of rats, and with minor modification, has had similar application in mice, hamsters, and guinea pigs. The simplicity and ease of handling of the laryngoscope permits one person to intubate large numbers of enflurane anesthetized animals either on an open counter top or in a glove-box, as may be required for administration of carcinogenic materials. Instillation of 7Be-labeled carbon particles into the lungs of mice, hamsters, rats, and guinea pigs resulted in reasonably consistent interlobal distribution of particles for each test animal species with minimal tracheal deposition. However, actual lung tissue doses of carbon exhibited some species dependence.

Attenuation of airway smooth muscle contractility via flavonol-mediated inhibition of phospholipase-Cβ

PubMed Central

Brown, Amy; Danielsson, Jennifer; Townsend, Elizabeth A.; Zhang, Yi; Perez-Zoghbi, Jose F.; Emala, Charles W.

2016-01-01

Enhanced contractility of airway smooth muscle (ASM) is a major pathophysiological characteristic of asthma. Expanding the therapeutic armamentarium beyond β-agonists that target ASM hypercontractility would substantially improve treatment options. Recent studies have identified naturally occurring phytochemicals as candidates for acute ASM relaxation. Several flavonoids were evaluated for their ability to acutely relax human and murine ASM ex vivo and murine airways in vivo and were evaluated for their ability to inhibit procontractile signaling pathways in human ASM (hASM) cells. Two members of the flavonol subfamily, galangin and fisetin, significantly relaxed acetylcholine-precontracted murine tracheal rings ex vivo (n = 4 and n = 5, respectively, P < 0.001). Galangin and fisetin also relaxed acetylcholine-precontracted hASM strips ex vivo (n = 6–8, P < 0.001). Functional respiratory in vivo murine studies demonstrated that inhaled galangin attenuated the increase in lung resistance induced by inhaled methacholine (n = 6, P < 0.01). Both flavonols, galangin and fisetin, significantly inhibited purified phosphodiesterase-4 (PDE4) (n = 7, P < 0.05; n = 7, P < 0.05, respectively), and PLCβ enzymes (n = 6, P < 0.001 and n = 6, P < 0.001, respectively) attenuated procontractile Gq agonists' increase in intracellular calcium (n = 11, P < 0.001), acetylcholine-induced increases in inositol phosphates, and CPI-17 phosphorylation (n = 9, P < 0.01) in hASM cells. The prorelaxant effect retained in these structurally similar flavonols provides a novel pharmacological method for dual inhibition of PLCβ and PDE4 and therefore may serve as a potential treatment option for acute ASM constriction. PMID:26773068

Attenuation of airway smooth muscle contractility via flavonol-mediated inhibition of phospholipase-Cβ.

PubMed

Brown, Amy; Danielsson, Jennifer; Townsend, Elizabeth A; Zhang, Yi; Perez-Zoghbi, Jose F; Emala, Charles W; Gallos, George

2016-04-15

Enhanced contractility of airway smooth muscle (ASM) is a major pathophysiological characteristic of asthma. Expanding the therapeutic armamentarium beyond β-agonists that target ASM hypercontractility would substantially improve treatment options. Recent studies have identified naturally occurring phytochemicals as candidates for acute ASM relaxation. Several flavonoids were evaluated for their ability to acutely relax human and murine ASM ex vivo and murine airways in vivo and were evaluated for their ability to inhibit procontractile signaling pathways in human ASM (hASM) cells. Two members of the flavonol subfamily, galangin and fisetin, significantly relaxed acetylcholine-precontracted murine tracheal rings ex vivo (n = 4 and n = 5, respectively, P < 0.001). Galangin and fisetin also relaxed acetylcholine-precontracted hASM strips ex vivo (n = 6-8, P < 0.001). Functional respiratory in vivo murine studies demonstrated that inhaled galangin attenuated the increase in lung resistance induced by inhaled methacholine (n = 6, P < 0.01). Both flavonols, galangin and fisetin, significantly inhibited purified phosphodiesterase-4 (PDE4) (n = 7, P < 0.05; n = 7, P < 0.05, respectively), and PLCβ enzymes (n = 6, P < 0.001 and n = 6, P < 0.001, respectively) attenuated procontractile Gq agonists' increase in intracellular calcium (n = 11, P < 0.001), acetylcholine-induced increases in inositol phosphates, and CPI-17 phosphorylation (n = 9, P < 0.01) in hASM cells. The prorelaxant effect retained in these structurally similar flavonols provides a novel pharmacological method for dual inhibition of PLCβ and PDE4 and therefore may serve as a potential treatment option for acute ASM constriction. Copyright © 2016 the American Physiological Society.

Tracheal reconstruction with a composite graft: fascial flap-wrapped allogenic aorta with external cartilage-ring support

PubMed Central

Wurtz, Alain; Hysi, Ilir; Kipnis, Eric; Zawadzki, Christophe; Hubert, Thomas; Jashari, Ramadan; Copin, Marie-Christine; Jude, Brigitte

2013-01-01

OBJECTIVES Animal and clinical studies have demonstrated the feasibility of tracheal replacement by silicone-stented allogenic aortas. In clinical trials, however, this graft did not show mature cartilage regeneration into the grafts as was observed in animal models. To solve this issue, we investigated tracheal replacement with a composite graft based on a fascial flap-wrapped allogenic aorta with external cartilage-ring support in a rabbit model. METHODS Seven male 'Géant des Flandres' and 'New Zealand' rabbits served as donors of aortas and cartilage rings, respectively. Nineteen female 'New Zealand' rabbits were used as recipients. First, in nine animals, neoangiogenesis of the composite graft following a wrap using a pedicled lateral thoracic fascial flap and implantation under the skin of the chest wall was investigated. Animal sacrifice was scheduled at regular intervals up to 38 days. Second, 10 animals underwent tracheal replacement with the composite graft after a 7-to-9 day revascularization period, and were followed-up to death. Macroscopic and microscopic examinations were used to study the morphology, stiffness and viability of the construct. RESULTS There was one operative death after tracheal replacement. The first group of animals was found to have a satisfactory tubular morphology and stiffness of their construct associated with preserved histological structure of cartilages and moderate to severe aortic ischaemic lesions. In the group of rabbits having undergone tracheal replacement, the anatomical results were characterized by a discrepancy between the severity of ischaemic lesions involving both allogenic aorta and cartilage rings and the satisfactory biomechanical characteristics of the graft in 7 of 10 animals, probably due to cartilage calcification deposits associated with inflammatory scar tissue ensuring the stiffness of the construct. CONCLUSIONS Our investigations demonstrate the feasibility of the replacement of circumferential

Effects of supramaximal balloon dilatation pressures on adult cricoid and tracheal cartilage: A cadaveric study.

PubMed

Durvasula, Venkata S P B; Shalin, Sara C; Tulunay-Ugur, Ozlem E; Suen, James Y; Richter, Gresham T

2018-06-01

Cricoid fracture is a serious concern for balloon dilatation in airway stenosis. Furthermore, there are no studies examining tracheal rupture in balloon dilatation of stenotic segments. The aim of this study was to evaluate the effect of supramaximal pressures of balloons on the cricoid and tracheal rings. Prospective cadaveric study. Seven cadaveric laryngotracheal complexes of normal adults with intact cricothyroid membranes were acquired. Noncompliant vascular angioplasty balloons (BARD-VIDA) were used for dilatation. The subglottis and trachea were subjected to supramaximal dilatation pressures graduated to nominal burst pressure (NBP) and, if necessary, rated burst pressure (RBP). Larger-diameter balloons, starting from 18 mm size to 24 mm, were used. Dilatations were maintained for 3 minutes. The cricoid ring was disrupted by larger-diameter balloons (22 mm and 24 mm) even at lower pressures (less than NBP) in six cases. Tracheal cartilages were very distensible, and external examination after supramaximal dilatation (24 mm close to RBP) revealed no obvious cartilage fractures or trachealis tears. Histopathological examination revealed sloughing of mucosa in the areas corresponding to balloon placement, but no microfractures or disruption of the perichondrium of tracheal ring cartilages. These results indicate that the cricoid is vulnerable to injury from larger balloons even at lower dilatation pressures. The tracheal cartilages and the membranous wall of the trachea remained resilient to supramaximal dilatation and larger balloons. NA. Laryngoscope, 128:1304-1309, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

The Role of Presepsin Obtained from Tracheal Aspirates in the Diagnosis of Early Onset Pneumonia in Intubated Newborns.

PubMed

Savić, Dragana; Simović, Aleksandra; Marković, Slavica; Kostić, Gordana; Vuletić, Biljana; Radivojević, Snezana; Lišanin, Marina; Igrutinović, Zoran; Pavlović, Radisa

2018-04-14

To investigate the role of presepsin obtained from tracheal aspirate of intubated newborns in the diagnosis of early neonatal pneumonia. A cross-sectional observational study was performed on 60 intubated newborns during the two-year period. Tracheal aspirate for examination was taken in aseptic conditions in usual toilets, by lavage with 2 ml of 0.9% NaCl in Mucus suction set. On the same day, presepsin (blood) was measured. There were 34 newborns in the examined group (with pneumonia) and 26 in the control group. Patient groups were similar regarding demographic characteristics related to gender and Apgar score. The coefficients of simple linear correlation revealed the statistically significant connection between presepsin (from tracheal aspirate) and birth body weight, presepsin (plasma), maternal infection and pneumonia. Significant differences in the values of presepsin (from tracheal aspirate) (p < 0.001) and birth body weight (p = 0.036) were found. In intubated newborns, measurements of presepsin obtained from tracheal aspirate suggested that it can be used as a complementary marker in diagnosing early onset neonatal pneumonia.

Laryngeal and tracheal afferent nerve stimulation evokes swallowing in anaesthetized guinea pigs

PubMed Central

Tsujimura, Takanori; Udemgba, Chioma; Inoue, Makoto; Canning, Brendan J

2013-01-01

We describe swallowing reflexes evoked by laryngeal and tracheal vagal afferent nerve stimulation in anaesthetized guinea pigs. The swallowing reflexes evoked by laryngeal citric acid challenges were abolished by recurrent laryngeal nerve (RLN) transection and mimicked by electrical stimulation of the central cut ends of an RLN. By contrast, the number of swallows evoked by upper airway/pharyngeal distensions was not significantly reduced by RLN transection but they were virtually abolished by superior laryngeal nerve transection. Laryngeal citric acid-evoked swallowing was mimicked by laryngeal capsaicin challenges, implicating transient receptor potential vanilloid 1 (TRPV1)-expressing laryngeal afferent nerves arising from the jugular ganglia. The swallowing evoked by citric acid and capsaicin and evoked by electrical stimulation of either the tracheal or the laryngeal mucosa occurred at stimulation intensities that were typically subthreshold for evoking cough in these animals. Swallowing evoked by airway afferent nerve stimulation also desensitized at a much slower rate than cough. We speculate that swallowing is an essential component of airway protection from aspiration associated with laryngeal and tracheal afferent nerve activation. PMID:23858010

Case report of apatinib mesylate treatment in rare advanced tracheal adenoid cystic carcinoma.

PubMed

Wang, Hongmei

2017-11-01

A 57-year-old man was admitted to our department 10 years ago, diagnosed with tracheal adenoid cystic carcinoma. After discontinuing chemotherapy and radiotherapy, the disease recurred in December 2016. Apatinib mesylate (500 mg/day) was administered and computed tomography revealed that his symptoms were significantly relieved. Treatment with apatinib mesylate represents a novel method of treatment for tracheal adenoid cystic carcinoma. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Effect of clenbuterol on tracheal mucociliary transport in horses undergoing simulated long-distance transportation.

PubMed

Norton, J L; Jackson, K; Chen, J W; Boston, R; Nolen-Walston, R D

2013-01-01

Pneumonia is observed in horses after long-distance transportation in association with confinement of head position leading to reduction in tracheal mucociliary clearance rate (TMCR). Clenbuterol, a beta-2 agonist shown to increase TMCR in the horse, will ameliorate the effects of a fixed elevated head position on large airway contamination and inflammation in a model of long-distance transportation model. Six adult horses. A cross-over designed prospective study. Horses were maintained with a fixed elevated head position for 48 hours to simulate long-distance transport, and treated with clenbuterol (0.8 μg/kg PO q12h) or a placebo starting 12 hours before simulated transportation. TMCR was measured using a charcoal clearance technique. Data were collected at baseline and 48 hours, and included TMCR, tracheal wash cytology and quantitative culture, rectal temperature, CBC, fibrinogen, and serum TNFα, IL-10, and IL-2 levels. There was a 18-21 day washout between study arms, and data were analyzed using regression analysis and Wilcoxon rank-sum tests. Tracheal mucociliary clearance rate was significantly decreased after transportation in both treatment (P = .002) and placebo (P = .03) groups. There was a significant effect of treatment on TMCR, with the treatment group showing half the reduction in TMCR compared with the placebo group (P = .002). Other significant differences between before- and after-transportation samples occurred for serum fibrinogen, peripheral eosinophil count, quantitative culture, tracheal bacteria, and degenerate neutrophils, though no treatment effect was found. Treatment with clenbuterol modestly attenuates the deleterious effects of this long-distance transportation model on tracheal mucociliary clearance. Copyright © 2013 by the American College of Veterinary Internal Medicine.

Learning From Experience: Improving Early Tracheal Extubation Success After Congenital Cardiac Surgery.

PubMed

Winch, Peter D; Staudt, Anna M; Sebastian, Roby; Corridore, Marco; Tumin, Dmitry; Simsic, Janet; Galantowicz, Mark; Naguib, Aymen; Tobias, Joseph D

2016-07-01

The many advantages of early tracheal extubation following congenital cardiac surgery in young infants and children are now widely recognized. Benefits include avoiding the morbidity associated with prolonged intubation and the consequences of sedation and positive pressure ventilation in the setting of altered cardiopulmonary physiology. Our practice of tracheal extubation of young infants in the operating room following cardiac surgery has evolved and new challenges in the arena of postoperative sedation and pain management have appeared. Review our institutional outcomes associated with early tracheal extubation following congenital cardiac surgery. Inclusion criteria included all children less than 1 year old who underwent congenital cardiac surgery between October 1, 2010, and October 24, 2013. A total of 416 patients less than 1 year old were included. Of the 416 patients, 234 underwent tracheal extubation in the operating room (56%) with 25 requiring reintubation (10.7%), either immediately or following admission to the cardiothoracic ICU. Of the 25 patients extubated in the operating room who required reintubation, 22 failed within 24 hours of cardiothoracic ICU admission; 10 failures were directly related to narcotic doses that resulted in respiratory depression. As a result of this review, we have instituted changes in our cardiothoracic ICU postoperative care plans. We have developed a neonatal delirium score, and have adopted the "Kangaroo Care" approach that was first popularized in neonatal ICUs. This provision allows for the early parental holding of infants following admission to the cardiothoracic ICU and allows for appropriately selected parents to sleep in the same beds alongside their postoperative children.

Intermittent subglottic secretion drainage may cause tracheal damage in patients with few oropharyngeal secretions.

PubMed

Suys, E; Nieboer, K; Stiers, W; De Regt, J; Huyghens, L; Spapen, H

2013-12-01

Injurious prolapse of tracheal mucosa into the suction port has been reported in up to 50% of intubated patients receiving continuous aspiration of subglottic secretions. We investigated whether similar injury could be inflicted by automated intermittent aspiration. Six consecutive patients, intubated with the Mallinckrodt TaperGuard Evac™ endotracheal tube, were studied. A flow sensor was placed between the vacuum regulating system and the mucus collector. Intermittent suctioning was performed at a pressure of -125 mmHg with a 25s interval and duration of 15s. After 24h, a CT scan of the tracheal region was performed. Excessive negative suction pressure, a fast drop in aspiration flow to zero, and important "swinging" movements of secretions in the evacuation line were observed in all patients. Oral instillation of antiseptic mouthwash restored normal aspiration flow and secretion mobility. CT imaging showed marked entrapment of tracheal mucosa into the suction port in all patients. In patients with few oropharyngeal secretions, automated intermittent subglottic aspiration may result in significant and potential harmful invagination of tracheal mucosa into the suction lumen. A critical amount of fluid must be present in the oropharynx to assure adequate and safe aspiration. Copyright © 2013 Elsevier Ltd. All rights reserved.

Radiotherapy for Tracheal-Bronchial Cystic Adenoid Carcinomas.

PubMed

Levy, A; Omeiri, A; Fadel, E; Le Péchoux, C

2018-01-01

Primary tracheal-bronchial adenoid cystic carcinoma (thoracic adenoid cystic carcinoma; TACC) is a rare and aggressive malignant tumour. Radiotherapy results have not been previously individualised in this setting. Records of 31 patients with TACC (74% tracheal and 26% bronchial) who received radiotherapy between February 1984 and September 2014 were retrospectively analysed. Surgical removal of the primary tumour was carried out for most (71%) patients, and 13/22 (59%) had R1 or R2 (1/22) margins. The mean tumour size was 4.1 cm, 10 (32%) had associated lymph node involvement and 13 (41%) had perineural invasion (PNI). Adjuvant and definitive radiotherapy were delivered for 22 (71%) and nine patients, respectively. The mean delivered dose was 62 Gy (40-70 Gy) and eight patients had a radiotherapy boost (mean 19 Gy, range 9-30 Gy, two with endobronchial brachytherapy). At a median follow-up of 5.7 years, the 5 year overall survival and progression-free survival (PFS) rates were 88% and 61%, respectively. There were three local relapses and 10 metastatic relapses (mean delay 3.2 years), resulting in 5 year local and metastatic relapse rates of 10% and 26%, respectively. The prognostic factors in the univariate analysis for both decreased overall survival and PFS were: age ≥50 years (hazard ratio 6.2 and 3.8) and the presence of PNI (hazard ratio 10.3 and 4.1); and for PFS only: a radiotherapy dose ≤ 60 Gy (hazard ratio 3.1). Late toxicities were: tracheotomy due to symptomatic tracheal stenosis (n = 5), G3 dyspnoea (n = 4), hypothyroidism (n = 5) and pericarditis (n = 4). Radiotherapy dose may affect local control and the presence of PNI should be considered as an adverse prognostic factor. TACC irradiation conferred good local control rates, when comparing these results with historical series. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Distal Tracheal Resection and Reconstruction: State of the Art and Lessons Learned.

PubMed

Mathisen, Douglas

2018-05-01

Tracheal disease is an infrequent problem requiring surgery. A high index of suspicion is necessary to correctly diagnose the problems. Primary concerns are safe control and assessment of the airway, familiarity with the principles of airway surgery, preserving tracheal blood supply, and avoiding anastomotic tension. A precise reproducible anastomotic technique must be mastered. Operation requires close cooperation with a knowledgeable anesthesia team. The surgeon must understand how to achieve the least tension on the anastomosis to avoid. It is advisable to examine the airway before discharge to check for normal healing and airway patency. Copyright © 2018 Elsevier Inc. All rights reserved.

Mechanism for substance P-induced relaxation of precontracted airway smooth muscle during development.

PubMed

Mhanna, M J; Dreshaj, I A; Haxhiu, M A; Martin, R J

1999-01-01

Release of substance P (SP) from sensory nerve endings of the tracheobronchial system modulates airway smooth muscle contraction and may cause relaxation of precontracted airways. We sought to elucidate the effect of postnatal maturation on SP-induced relaxation of precontracted airways and determine the roles of endogenously generated nitric oxide (NO) and prostaglandins (PGs). Cylindrical airway segments were isolated from the midtrachea of rats at four different ages, 1, 2, and 4 wk and 3 mo, and contracted to 50-75% of the maximum response induced by bethanechol. SP was then administered in the absence and presence of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the PG inhibitor indomethacin, or both. Relaxation of airways with SP decreased significantly with advancing postnatal age. SP-induced tracheal relaxation was consistently attenuated by pretreatment with L-NAME, indomethacin, or both. In a different group of animals, L-NAME significantly attenuated the relaxant response of airways to PGE2 exposure, but indomethacin had no significant effect on the relaxant response to exogenous NO. We conclude that SP induces a relaxant effect on precontracted airway smooth muscle, which decreases with advancing age and is mediated via SP-induced release of NO and/or PG.

Cysteinyl leukotrienes promote human airway smooth muscle migration.

PubMed

Parameswaran, Krishnan; Cox, Gerard; Radford, Katherine; Janssen, Luke J; Sehmi, Roma; O'Byrne, Paul M

2002-09-01

Cysteinyl leukotrienes promote airway smooth muscle (ASM) contraction and proliferation. Little is known about their role in ASM migration. We investigated this using cultured human ASMs (between the second and fifth passages) obtained from the large airways of resected nonasthmatic lung. Platelet-derived growth factor-BB (1 ng/ml) promoted significant (3.5-fold) ASM migration of myocytes across collagen-coated 8- micro m polycarbonate membranes in Transwell culture plates. Leukotriene E(4) (10(-7), 10(-8), 10(-9) M) did not demonstrate a chemotactic effect; it did promote chemokinesis. Priming by leukotriene E(4) (10(-7) M) significantly augmented the directional migratory response to platelet-derived growth factor (1.5-fold, p < 0.05). This was blocked by montelukast (10(-6) M), demonstrating the effect to be mediated by the cysteinyl leukotriene receptor. The "priming effect" was also partially attenuated by prostaglandin E(2) (10(-7) M). Whereas both the chemokinetic and the chemotactic "primed" responses were equally attenuated by a p38 mitogen-activated protein kinase inhibitor (SB203580, 25 micro M) and by a Rho-kinase inhibitor (Y27632, 10 micro M), the chemotactic response showed greater inhibition than chemokinesis by a phosphatidylinositol-3 kinase inhibitor (LY294002, 50 micro M). These experiments suggest that cysteinyl leukotrienes play an augmentary role in human ASM migration. The phosphatidylinositol-3 kinase pathway is a key signaling mechanism in the chemotactic migration of ASM cells in response to cysteinyl leukotrienes.

Essential role for calcium waves in migration of human vascular smooth muscle cells.

PubMed

Espinosa-Tanguma, Ricardo; O'Neil, Caroline; Chrones, Tom; Pickering, J Geoffrey; Sims, Stephen M

2011-08-01

Vascular smooth muscle cell (SMC) migration is characterized by extension of the lamellipodia at the leading edge, lamellipodial attachment to substrate, and release of the rear (uropod) of the cell, all of which enable forward movement. However, little is known regarding the role of intracellular cytosolic Ca(2+) concentration ([Ca(2+)](i)) in coordinating these distinct activities of migrating SMCs. The objective of our study was to determine whether regional changes of Ca(2+) orchestrate the migratory cycle in human vascular SMCs. We carried out Ca(2+) imaging using digital fluorescence microscopy of fura-2 loaded human smooth muscle cells. We found that motile SMCs exhibited Ca(2+) waves that characteristically swept from the rear of polarized cells toward the leading edge. Ca(2+) waves were less evident in nonpolarized, stationary cells, although acute stimulation of these SMCs with the agonists platelet-derived growth factor-BB or histamine could elicit transient rise of [Ca(2+)](i). To investigate a role for Ca(2+) waves in the migratory cycle, we loaded cells with the Ca(2+) chelator BAPTA, which abolished Ca(2+) waves and significantly reduced retraction, supporting a causal role for Ca(2+) in initiation of retraction. However, lamellipod motility was still evident in BAPTA-loaded cells. The incidence of Ca(2+) oscillations was reduced when Ca(2+) release from intracellular stores was disrupted with the sarcoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin or by treatment with the inositol 1,4,5-trisphosphate receptor blocker 2-aminoethoxy-diphenyl borate or xestospongin C, implicating Ca(2+) stores in generation of waves. We conclude that Ca(2+) waves are essential for migration of human vascular SMCs and can encode cell polarity.

Iptakalim inhibits PDGF-BB-induced human airway smooth muscle cells proliferation and migration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Wenrui; Kong, Hui; Zeng, Xiaoning

Chronic airway diseases are characterized by airway remodeling which is attributed partly to the proliferation and migration of airway smooth muscle cells (ASMCs). ATP-sensitive potassium (K{sub ATP}) channels have been identified in ASMCs. Mount evidence has suggested that K{sub ATP} channel openers can reduce airway hyperresponsiveness and alleviate airway remodeling. Opening K{sup +} channels triggers K{sup +} efflux, which leading to membrane hyperpolarization, preventing Ca{sup 2+}entry through closing voltage-operated Ca{sup 2+} channels. Intracellular Ca{sup 2+} is the most important regulator of muscle contraction, cell proliferation and migration. K{sup +} efflux decreases Ca{sup 2+} influx, which consequently influences ASMCs proliferation andmore » migration. As a K{sub ATP} channel opener, iptakalim (Ipt) has been reported to restrain the proliferation of pulmonary arterial smooth muscle cells (PASMCs) involved in vascular remodeling, while little is known about its impact on ASMCs. The present study was designed to investigate the effects of Ipt on human ASMCs and the mechanisms underlying. Results obtained from cell counting kit-8 (CCK-8), flow cytometry and 5-ethynyl-2′-deoxyuridine (EdU) incorporation showed that Ipt significantly inhibited platelet-derived growth factor (PDGF)-BB-induced ASMCs proliferation. ASMCs migration induced by PDGF-BB was also suppressed by Ipt in transwell migration and scratch assay. Besides, the phosphorylation of Ca{sup 2+}/calmodulin-dependent kinase II (CaMKII), extracellular regulated protein kinases 1/2 (ERK1/2), protein kinase B (Akt), and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) were as well alleviated by Ipt administration. Furthermore, we found that the inhibition of Ipt on the PDGF-BB-induced proliferation and migration in human ASMCs was blocked by glibenclamide (Gli), a selective K{sub ATP} channel antagonist. These findings provide a strong evidence to support that

Peripheral neurolymphomatosis with tracheal asphyxia: a case report and literature review.

PubMed

Liu, Zuofeng; Jiang, Tao; Hou, Ni; Jia, Yongqian

2015-08-23

Neurolymphomatosis (NL) is an extremely rare disease and tracheal asphyxia due to NL has not been previously reported. A 54-year-old Chinese woman with a history of diffuse large B-cell lymphoma in her first complete remission developed peripheral neuropathy and tracheal asphyxia. Neurolymphomatosis involving the right brachial plexus and the right vagus nerve was demonstrated by PET/CT, but not by MRI. She underwent urgent tracheotomy and impact chemotherapy using rituximab combined with high dose methotrexate and involved field radiotherapy. She achieved a second complete remission. PET/CT plays valuable role in differentiating NL from other neuropathies in patients with lymphoma. Complete remission can be achieved in NL due to large B-cell lymphoma.

Functional Constituents of a Local Serotonergic System, Intrinsic to the Human Coronary Artery Smooth Muscle Cells

PubMed Central

Baskar, Kannan; Sur, Swastika; Selvaraj, Vithyalakashmi; Agrawal, Devendra K.

2015-01-01

Human coronary artery smooth muscle cells (HCASMCs) play an important role in the pathogenesis of coronary atherosclerosis and coronary artery diseases (CAD). Serotonin is a mediator known to produce vascular smooth muscle cell (VSMC) mitogenesis and contribute to coronary atherosclerosis. We hypothesize that the human coronary artery smooth muscle cell possesses certain functional constituents of the serotonergic system such as: tryptophan hydroxylase and serotonin transporter. Our aim was to examine the presence of functional tryptophan hydroxylase-1 (TPH1) and serotonin transporter (SERT) in HCASMCs. The mRNA transcripts by qPCR and protein expression by Western blot of TPH1 and SERT were examined. The specificity and accuracy of the primers were verified using DNA gel electrophoresis and sequencing of qPCR products. The functionality of SERT was examined using a fluorescence dye-based serotonin transporter assay. The enzymatic activity of TPH was evaluated using UPLC. The HCASMCs expressed both mRNA transcripts and protein of SERT and TPH. The qPCR showed a single melt curve peak for both transcripts and in sequence analysis the amplicons were aligned with the respective genes. SERT and TPH enzymatic activity was present in the HCASMCs. Taken together, both TPH and SERT are functionally expressed in HCASMCs. These findings are novel and represent an initial step in examining the clinical relevance of the serotonergic system in HCASMCs and its role in the pathogenesis of coronary atherosclerosis and CAD. PMID:25861735

Increase in tracheal investment with beetle size supports hypothesis of oxygen limitation on insect gigantism.

PubMed

Kaiser, Alexander; Klok, C Jaco; Socha, John J; Lee, Wah-Keat; Quinlan, Michael C; Harrison, Jon F

2007-08-07

Recent studies have suggested that Paleozoic hyperoxia enabled animal gigantism, and the subsequent hypoxia drove a reduction in animal size. This evolutionary hypothesis depends on the argument that gas exchange in many invertebrates and skin-breathing vertebrates becomes compromised at large sizes because of distance effects on diffusion. In contrast to vertebrates, which use respiratory and circulatory systems in series, gas exchange in insects is almost exclusively determined by the tracheal system, providing a particularly suitable model to investigate possible limitations of oxygen delivery on size. In this study, we used synchrotron x-ray phase-contrast imaging to visualize the tracheal system and quantify its dimensions in four species of darkling beetles varying in mass by 3 orders of magnitude. We document that, in striking contrast to the pattern observed in vertebrates, larger insects devote a greater fraction of their body to the respiratory system, as tracheal volume scaled with mass1.29. The trend is greatest in the legs; the cross-sectional area of the trachea penetrating the leg orifice scaled with mass1.02, whereas the cross-sectional area of the leg orifice scaled with mass0.77. These trends suggest the space available for tracheae within the leg may ultimately limit the maximum size of extant beetles. Because the size of the tracheal system can be reduced when oxygen supply is increased, hyperoxia, as occurred during late Carboniferous and early Permian, may have facilitated the evolution of giant insects by allowing limbs to reach larger sizes before the tracheal system became limited by spatial constraints.

Increase in tracheal investment with beetle size supports hypothesis of oxygen limitation on insect gigantism

PubMed Central

Kaiser, Alexander; Klok, C. Jaco; Socha, John J.; Lee, Wah-Keat; Quinlan, Michael C.; Harrison, Jon F.

2007-01-01

Recent studies have suggested that Paleozoic hyperoxia enabled animal gigantism, and the subsequent hypoxia drove a reduction in animal size. This evolutionary hypothesis depends on the argument that gas exchange in many invertebrates and skin-breathing vertebrates becomes compromised at large sizes because of distance effects on diffusion. In contrast to vertebrates, which use respiratory and circulatory systems in series, gas exchange in insects is almost exclusively determined by the tracheal system, providing a particularly suitable model to investigate possible limitations of oxygen delivery on size. In this study, we used synchrotron x-ray phase–contrast imaging to visualize the tracheal system and quantify its dimensions in four species of darkling beetles varying in mass by 3 orders of magnitude. We document that, in striking contrast to the pattern observed in vertebrates, larger insects devote a greater fraction of their body to the respiratory system, as tracheal volume scaled with mass1.29. The trend is greatest in the legs; the cross-sectional area of the trachea penetrating the leg orifice scaled with mass1.02, whereas the cross-sectional area of the leg orifice scaled with mass0.77. These trends suggest the space available for tracheae within the leg may ultimately limit the maximum size of extant beetles. Because the size of the tracheal system can be reduced when oxygen supply is increased, hyperoxia, as occurred during late Carboniferous and early Permian, may have facilitated the evolution of giant insects by allowing limbs to reach larger sizes before the tracheal system became limited by spatial constraints. PMID:17666530

Developmental plasticity and stability in the tracheal networks supplying Drosophila flight muscle in response to rearing oxygen level.

PubMed

Harrison, Jon F; Waters, James S; Biddulph, Taylor A; Kovacevic, Aleksandra; Klok, C Jaco; Socha, John J

2018-04-01

While it is clear that the insect tracheal system can respond in a compensatory manner to both hypoxia and hyperoxia, there is substantial variation in how different parts of the system respond. However, the response of tracheal structures, from the tracheoles to the largest tracheal trunks, have not been studied within one species. In this study, we examined the effect of larval/pupal rearing in hypoxia, normoxia, and hyperoxia (10, 21 or 40kPa oxygen) on body size and the tracheal supply to the flight muscles of Drosophila melanogaster, using synchrotron radiation micro-computed tomography (SR-µCT) to assess flight muscle volumes and the major tracheal trunks, and confocal microscopy to assess the tracheoles. Hypoxic rearing decreased thorax length whereas hyperoxic-rearing decreased flight muscle volumes, suggestive of negative effects of both extremes. Tomography at the broad organismal scale revealed no evidence for enlargement of the major tracheae in response to lower rearing oxygen levels, although tracheal size scaled with muscle volume. However, using confocal imaging, we found a strong inverse relationship between tracheole density within the flight muscles and rearing oxygen level, and shorter tracheolar branch lengths in hypoxic-reared animals. Although prior studies of larger tracheae in other insects indicate that axial diffusing capacity should be constant with sequential generations of branching, this pattern was not found in the fine tracheolar networks, perhaps due to the increasing importance of radial diffusion in this regime. Overall, D. melanogaster responded to rearing oxygen level with compensatory morphological changes in the small tracheae and tracheoles, but retained stability in most of the other structural components of the tracheal supply to the flight muscles. Copyright © 2017 Elsevier Ltd. All rights reserved.

Induction of apoptosis by pyrrolidinedithiocarbamate and N-acetylcysteine in vascular smooth muscle cells.

PubMed

Tsai, J C; Jain, M; Hsieh, C M; Lee, W S; Yoshizumi, M; Patterson, C; Perrella, M A; Cooke, C; Wang, H; Haber, E; Schlegel, R; Lee, M E

1996-02-16

Pyrrolidinedithiocarbamate (PDTC) and N-acetylcysteine (NAC) have been used as antioxidants to prevent apoptosis in lymphocytes, neurons, and vascular endothelial cells. We report here that PDTC and NAC induce apoptosis in rat and human smooth muscle cells. In rat aortic smooth muscle cells, PDTC induced cell shrinkage, chromatin condensation, and DNA strand breaks consistent with apoptosis. In addition, overexpression of Bcl-2 suppressed vascular smooth muscle cell death caused by PDTC and NAC. The viability of rat aortic smooth muscle cells decreased within 3 h of treatment with PDTC and was reduced to 30% at 12 h. The effect of PDTC and NAC on smooth muscle cells was not species specific because PDTC and NAC both caused dose-dependent reductions in viability in rat and human aortic smooth muscle cells. In contrast, neither PDTC nor NAC reduced viability in human aortic endothelial cells. The use of antioxidants to induce apoptosis in vascular smooth muscle cells may help prevent their proliferation in arteriosclerotic lesions.

Design of a muscle cell-specific expression vector utilising human vascular smooth muscle alpha-actin regulatory elements.

PubMed

Keogh, M C; Chen, D; Schmitt, J F; Dennehy, U; Kakkar, V V; Lemoine, N R

1999-04-01

The facility to direct tissue-specific expression of therapeutic gene constructs is desirable for many gene therapy applications. We describe the creation of a muscle-selective expression vector which supports transcription in vascular smooth muscle, cardiac muscle and skeletal muscle, while it is essentially silent in other cell types such as endothelial cells, hepatocytes and fibroblasts. Specific transcriptional regulatory elements have been identified in the human vascular smooth muscle cell (VSMC) alpha-actin gene, and used to create an expression vector which directs the expression of genes in cis to muscle cells. The vector contains an enhancer element we have identified in the 5' flanking region of the human VSMC alpha-actin gene involved in mediating VSMC expression. Heterologous pairing experiments have shown that the enhancer does not interact with the basal transcription complex recruited at the minimal SV40 early promoter. Such a vector has direct application in the modulation of VSMC proliferation associated with intimal hyperplasia/restenosis.

Effect of rocuronium on the bispectral index under anesthesia and tracheal intubation.

PubMed

Yue, Hui; Han, Jinyu; Liu, Ling; Wang, Kaiyuan; Li, Jincheng

2016-12-01

The aim of the present study was to investigate the effect of various doses of rocuronium on bispectral index (BIS) responses to propofol induction and tracheal intubation, as well as the role of the non-depolarization muscle relaxant rocuronium on the depth of sedation. A total of 72 patients (American Society of Anesthesiologists physical status I-II) were anaesthetized with propofol using a target-controlled infusion, and randomly divided into two sedation level groups (n=36). The patients were divided into 2 groups according to the BIS value: A normal sedation group (group 1), with a stable BIS value at 40-60, and a deep sedation group (group 2), with a BIS value <20 or with burst suppression. Each group was randomly divided into 4 subgroups A-D (n=9) according to the various doses of rocuronium (0.3, 0.6, 0.9 and 1.2 mg/kg). Tracheal intubation was performed after 2 min of rocuronium administration. BIS, electromyography (EMG), heart rate (HR) and mean arterial pressure (MAP) were recorded continuously and averaged over 1 min during baseline (T1), steady state (T2), 2 min after rocuronium infusion (T3), and 0, 2 and 5 min after tracheal intubation. The results demonstrated that HR and MAP decreased significantly at T2 and T3 compared with T1. Following tracheal intubation (L0), HR and MAP significantly increased compared with T2 and T3, and returned to levels similar to those prior to intubation after 5 min. In group 1C and 1D, BIS was significantly decreased at T3 compared with T2; BIS was significantly increased at L0 compared with T3 in group 1A and 1B. EMG at earlier stages of anesthesia was significantly higher compared with other points, and was significantly increased at L0 compared with T3 in group 1A and 1B. These results demonstrated that BIS response may be associated with the dosage of rocuronium in the normal sedation group, although no association was observed with the deep sedation group. Tracheal intubation resulted in marked hemodynamic

An Overview of Tracheal Stenosis Research Trends and Hot Topics.

PubMed

Farzanegan, Roya; Feizabadi, Mansoureh; Ghorbani, Fariba; Movassaghi, Masoud; Vaziri, Esmaeil; Zangi, Mahdi; Lajevardi, Seyedamirmohammad; Shadmehr, Mohammad Behgam

2017-09-01

Tracheal stenosis remains a challenge in the thoracic surgery field. Recognizing the hot topics and major concepts in this area would help the health policy makers to determine their own priorities and design the effective research plans. The present study analyzed and mapped the topics and trends of tracheal stenosis studies over time as well as authors' and countries' contributions. Search results were obtained employing Bibexcel. To determine cold and hot topics, co-occurrence analysis was applied using three international databases 'Web of Science', 'PubMed' and 'Scopus'. Appropriately, different categories in the articles such as keywords, authors, and countries were explored via VOSviewer and NetDraw. Afterward, the trends of research topics were depicted in four time-intervals from 1945 to 2015 by ten co-occurrence terms. The majority of articles were limited to case series and retrospective studies. The studies had been conducted less frequently on prevention, risk factors and incidence determination but extensively on treatment and procedures. Based on the articles indexed in WOS, 45 countries and 8,260 authors have contributed to scientific progress in this field. The highest degree of cooperation occurred between the USA and England with 15 common papers. Most of the published literature in tracheal stenosis research field was about surgical and non-surgical treatments. Conducting the screening and prevention studies would diminish the burden of this disease on the health system as well as the patients and their families' well-being.

Efficacy of transoral intraluminal Wallstents for tracheal stenosis or tracheomalacia.

PubMed

Casiano, R R; Numa, W A; Nurko, Y J

2000-10-01

The efficacy and safety of intraluminal Wallstent Endoprosthesis (Boston Scientific/ Medi-Tech, Quincy, MA) placement to restore airway patency in patients with tracheal stenosis or tracheomalacia are unknown. Retrospective review in setting of tertiary, referral, and academic center. A retrospective review of 13 consecutive patients over a 2-year period who underwent transoral resection of tracheal stenosis and immediate transoral Wallstent placement. One patient had tracheomalacia. All of the patients were considered at high risk for transcervical surgery or had failed prior traditional open procedures. The average patient age was 54.2 years, with nine male and four female patients. All had Cotton/Myer stenoses (grades II to IV) with moderate to severe degrees of inspiratory stridor. Four patients were tracheotomy dependent. The length of stenosis varied from 1 to 4 cm. One patient had a 10-cm segment of tracheomalacia. At the time of writing, none of the patients has had a problem with significant migration or extrusion and most of the patients have incorporated the stent well without any short-term obstructive granulation tissue. After a mean follow-up of 15 months (range, 4-24 mo). 10 of the 12 patients with stenosis (83%) have remained free of any inspiratory noise during breathing. The one patient with tracheomalacia also has remained free of symptoms. Transoral Wallstents appear to be safe and may be a reasonable alternative in the restoration of airway patency in select patients with tracheal stenosis or tracheomalacia.

A microprocessor-controlled tracheal insufflation-assisted total liquid ventilation system.

PubMed

Parker, James Courtney; Sakla, Adel; Donovan, Francis M; Beam, David; Chekuri, Annu; Al-Khatib, Mohammad; Hamm, Charles R; Eyal, Fabien G

2009-09-01

A prototype time cycled, constant volume, closed circuit perfluorocarbon (PFC) total liquid ventilator system is described. The system utilizes microcontroller-driven display and master control boards, gear motor pumps, and three-way solenoid valves to direct flow. A constant tidal volume and functional residual capacity (FRC) are maintained with feedback control using end-expiratory and end-inspiratory stop-flow pressures. The system can also provide a unique continuous perfusion (bias flow, tracheal insufflation) through one lumen of a double-lumen endotracheal catheter to increase washout of dead space liquid. FRC and arterial blood gases were maintained during ventilation with Rimar 101 PFC over 2-3 h in normal piglets and piglets with simulated pulmonary edema induced by instillation of albumin solution. Addition of tracheal insufflation flow significantly improved the blood gases and enhanced clearance of instilled albumin solution during simulated edema.

[Simulated uterus microenvironment induced human placental mesenchymal stem cells differentiation to uterus smooth muscle cells in vitro].

PubMed

Li, Chang-dong; Zhang, Wei-yuan; Yuan, Chun-li; Han, Li-ying

2008-12-09

To develop a new method to promote the differentiation of mesenchymal stem cells derived from human placenta (pMSC) to uterus smooth muscle cells (uSMC) in simulated uterus microenvironment. MSCs were isolated from human placenta, cultivated, and analyzed for their phenotype by flow cytometry. The multipotential differentiation of the pMSC was examined by chondrogenic, adipogenic, and osteogenetic induction. uSMC were isolated from uteri resected during operation and co-cultivated with the pMSC in a Transwell chamber simulating Two, 4, and 8 days later RT-PCR and Western blotting were used to detect the mRNA and protein expression of alpha-actin, calmodulin, and myosin heavy chains (MHC), the markers of smooth muscle differentiation at the early, middle, and late stages. On day 8 RT-PCR was used to detect the expression of estrogen receptor in these 2 groups of cells, then estrogen was used to stimulate these cells and the protein kinase C (PKC) activity was examined. The pMSC could be induced into adipocytes, osteocytes, and chondrocytes respectively. After co-culture with uSMC, the morphology of the pMSC changed closely into that of the uSMC, and MHC was expressed in the pMSC. Estrogen receptor was positive in both groups of cells. The PKC activity increased, especially in the cell membrane, after stimulation of estrogen. The postpartum human placenta can be used as an important and novel source of multipotent stem cells for tissue engineering and genetic engineering. Placental MSC have the potential to differentiate into smooth muscle cells under the simulated uterus microenvironment in vitro.

MicroRNA-124 controls human vascular smooth muscle cell phenotypic switch via Sp1.

PubMed

Tang, Yangfeng; Yu, Shangyi; Liu, Yang; Zhang, Jiajun; Han, Lin; Xu, Zhiyun

2017-09-01

Phenotypic switch of vascular smooth muscle cells (VSMCs) plays an important role in the pathogenesis of atherosclerosis and aortic dissection. However, the mechanisms of phenotypic modulation are still unclear. MicroRNAs have emerged as important regulators of VSMC function. We recently found that microRNA-124 (miR-124) was downregulated in proliferative vascular diseases that were characterized by a VSMC phenotypic switch. Therefore, we speculated that the aberrant expression of miR-124 might play a critical role in human aortic VSMC phenotypic switch. Using quantitative RT-PCR, we found that miR-124 was dramatically downregulated in the aortic media of clinical specimens of the dissected aorta and correlated with molecular markers of the contractile VSMC phenotype. Overexpression of miR-124 by mimicking transfection significantly attenuated platelet-derived growth factor-BB-induced human aortic VSMC proliferation and phenotypic switch. Furthermore, we identified specificity protein 1 (Sp1) as the downstream target of miR-124. A luciferase reporter assay was used to confirm direct miR-124 targeting of the 3'-untranslated region of the Sp1 gene and repression of Sp1 expression in human aortic VSMCs. Furthermore, constitutively active Sp1 in miR-124-overexpressing VSMCs reversed the antiproliferative effects of miR-124. These results demonstrated a novel mechanism of miR-124 modulation of VSMC phenotypic switch by targeting Sp1 expression. NEW & NOTEWORTHY Previous studies have demonstrated that miR-124 is involved in the proliferation of a variety of cell types. However, miRNAs are expressed in a tissue-specific manner. We first identified miR-124 as a critical regulator in human aortic vascular smooth muscle cell differentiation, proliferation, and phenotype switch by targeting the 3'-untranslated region of specificity protein 1. Copyright © 2017 the American Physiological Society.

Impact of tracheal cuff shape on microaspiration of gastric contents in intubated critically ill patients: study protocol for a randomized controlled trial.

PubMed

Jaillette, Emmanuelle; Brunin, Guillaume; Girault, Christophe; Zerimech, Farid; Chiche, Arnaud; Broucqsault-Dedrie, Céline; Fayolle, Cyril; Minacori, Franck; Alves, Isabelle; Barrailler, Stephanie; Robriquet, Laurent; Tamion, Fabienne; Delaporte, Emmanuel; Thellier, Damien; Delcourte, Claire; Duhamel, Alain; Nseir, Saad

2015-09-25

Ventilator-associated pneumonia (VAP) is the most common infection in intubated critically ill patients. Microaspiration of the contaminated gastric and oropharyngeal secretions is the main mechanism involved in the pathophysiology of VAP. Tracheal cuff plays an important role in stopping the progression of contaminated secretions into the lower respiratory tract. Previous in vitro studies suggested that conical cuff shape might be helpful in improving tracheal sealing. However, clinical studies found conflicting results. The aim of this study is to determine the impact of conical tracheal cuff shape on the microaspiration of gastric contents in critically ill patients. This prospective cluster randomized controlled crossover open-label trial is currently being conducted in ten French intensive care units (ICUs). Patients are allocated to intubation with a polyvinyl chloride (PVC) standard (barrel)-shaped or a PVC conical-shaped tracheal tube. The primary objective is to determine the impact of the conical shaped tracheal cuff on abundant microaspiration of gastric contents. Secondary outcomes include the incidence of microaspiration of oropharyngeal secretions, tracheobronchial colonization, VAP and ventilator-associated events. Abundant microaspiration is defined as the presence of pepsin at significant level (>200 ng/ml) in at least 30 % of the tracheal aspirates. Pepsin and amylase are quantitatively measured in all tracheal aspirates during the 48 h following inclusion. Quantitative tracheal aspirate culture is performed at inclusion and twice weekly. We plan to recruit 312 patients in the participating ICUs. BEST Cuff is the first randomized controlled study evaluating the impact of PVC tracheal-cuff shape on gastric microaspirations in patients receiving invasive mechanical ventilation. Enrollment began in June 2014 and is expected to end in October 2015. ClinicalTrials.gov Identifier: NCT01948635 (registered 31 August 2013).

A brief history of tracheostomy and tracheal intubation, from the Bronze Age to the Space Age.

PubMed

Szmuk, Peter; Ezri, Tiberiu; Evron, Shmuel; Roth, Yehudah; Katz, Jeffrey

2008-02-01

To present a concise history of tracheostomy and tracheal intubation for the approximately forty centuries from their earliest description around 2000 BC until the middle of the twentieth century, at which time a proliferation of advances marked the beginning of the modern era of anesthesiology. Review of the literature. The colorful and checkered past of tracheostomy and tracheal intubation informs contemporary understanding of these procedures. Often, the decision whether to perform a life-saving tracheostomy or tracheal intubation has been as important as the technical ability to perform it. The dawn of modern airway management owes its existence to the historical development of increasingly effective airway devices and to regular contributions of research into the pathophysiology of the upper airway.

A Clonal Genetic Screen for Mutants Causing Defects in Larval Tracheal Morphogenesis in Drosophila

PubMed Central

Baer, Magdalena M.; Bilstein, Andreas; Leptin, Maria

2007-01-01

The initial establishment of the tracheal network in the Drosophila embryo is beginning to be understood in great detail, both in its genetic control cascades and in its cell biological events. By contrast, the vast expansion of the system during larval growth, with its extensive ramification of preexisting tracheal branches, has been analyzed less well. The mutant phenotypes of many genes involved in this process are probably not easy to reveal, as these genes may be required for other functions at earlier developmental stages. We therefore conducted a screen for defects in individual clonal homozygous mutant cells in the tracheal network of heterozygous larvae using the mosaic analysis with a repressible cell marker (MARCM) system to generate marked, recombinant mitotic clones. We describe the identification of a set of mutants with distinct phenotypic effects. In particular we found a range of defects in terminal cells, including failure in lumen formation and reduced or extensive branching. Other mutations affect cell growth, cell shape, and cell migration. PMID:17603107

Alkaline phosphatase activity in airway fluid obtained by tracheal wash from adult horses.

PubMed

Viscardi, Vanessa; Jorge, Maria Luisa L A; Silva, Katia M; Sad, Eliene P; Fonseca, Ana Beatriz M; Alencar, Nayro X; Lessa, Daniel Augusto B

2016-06-01

Collection of fluid from the lower respiratory tract (LRT) plays an important role in both the pathophysiological investigation and diagnosis of respiratory tract disease. Enzymes such as ALP are, among others, indicators of cell damage or death, type II pneumocyte proliferation, and neutrophil invasion, and have been useful as biomarkers of respiratory disease in other species. The purpose of this study was to determine and compare tracheal wash (TW) ALP activity in healthy horses and horses with LRT inflammation (LRTI) determined by TW cytology profile. Tracheal washes were collected from asymptomatic adult geldings to measure ALP activity. The horses were allocated to the healthy group or the group with LRT inflammation based on differential leukocyte counts of TW preparations. Horses with > 20% neutrophils and > 1% eosinophils were allocated to the LRTI group, the horses with < 20% neutrophils and < 1% eosinophils were the controls. Tracheal wash ALP activity, measured using a semiautomatic chemistry analyzer, was statistically significantly higher in 18 horses with LRTI (18.9 ± 11.2 × 10(3) U/L) than in healthy horses (10.3 ± 5.9 × 10(3) U/L) (P = .021). Determining tracheal wash ALP activity is a simple, inexpensive and safe technique that can be used to facilitate the early diagnosis of equine respiratory disease, since it is higher in asymptomatic adult horses with a TW cytology profile consistent with LRT inflammation than in healthy adult horses with a normal TW cytology profile. © 2016 American Society for Veterinary Clinical Pathology.

Pharmacology and Immunological Mechanisms of an Herbal Medicine, ASHMI™ on Allergic Asthma

PubMed Central

Zhang, Tengfei; Srivastava, Kamal; Wen, Ming-Chun; Yang, Nan; Cao, Jing; Busse, Paula; Birmingham, Neil; Goldfarb, Joseph; Li, Xiu-Min

2015-01-01

Allergic asthma is a chronic and progressive inflammatory disease for which there is no satisfactory treatment. Studies reported tolerability and efficacy of an anti-asthma herbal medicine intervention (ASHMI) for asthma patients, developed from traditional Chinese medicine. To investigate the pharmacological actions of ASHMI on early- and late-phase airway responses (EAR and LAR), Ovalbumin (OVA)-sensitized mice received 6 weeks of ASHMI treatment beginning 24 h following the first intra tracheal OVA challenge. EAR were determined 30 min following the fourth challenge and LAR 48 h following the last challenge. ASHMI effects on cytokine secretion, murine tracheal ring contraction and human bronchial smooth muscle cell prostaglandin (PG) production were also determined. ASHMI abolished EAR, which was associated with significantly reduced histamine, leukotriene C4, and OVA-specific IgE levels, as well as LAR, which was associated with significantly reduced bronchoalveolar lavage fluid (BALF) eosinophils, decreased airway remodeling, and lower Th2 cytokine levels in BALF and splenocyte cultures. Furthermore, ASHMI inhibited contraction of murine tracheal rings and increased production of the potent smooth muscle relaxer PGI2. ASHMI abrogation of allergic airway responses is associated with broad effects on asthma pathological mechanisms. PMID:19998324

In vitro characterization of design and compressive properties of 3D-biofabricated/decellularized hybrid grafts for tracheal tissue engineering.

PubMed

Johnson, Christopher; Sheshadri, Priyanka; Ketchum, Jessica M; Narayanan, Lokesh K; Weinberger, Paul M; Shirwaiker, Rohan A

2016-06-01

Infection or damage to the trachea, a thin walled and cartilage reinforced conduit that connects the pharynx and larynx to the lungs, leads to serious respiratory medical conditions which can often prove fatal. Current clinical strategies for complex tracheal reconstruction are of limited availability and efficacy, but tissue engineering and regenerative medicine approaches may provide viable alternatives. In this study, we have developed a new "hybrid graft" approach that utilizes decellularized tracheal tissue along with a resorbable polymer scaffold, and holds promise for potential clinical applications. First, we evaluated the effect of our decellularization process on the compression properties of porcine tracheal segments, and noted approximately 63% decrease in resistance to compression following decellularization. Next we developed four C-shape scaffold designs by varying the base geometry and thickness, and fabricated polycaprolactone scaffolds using a combination of 3D-Bioplotting and thermally-assisted forming. All scaffolds designs were evaluated in vitro under three different environmental testing conditions to determine the design that offered the best resistance to compression. These were further studied to determine the effect of gamma radiation sterilization and cyclic compression loading. Finally, hybrid grafts were developed by securing these optimal design scaffolds to decellularized tracheal segments and evaluated in vitro under physiological testing conditions. Results show that the resistance to compression offered by the hybrid grafts created using gamma radiation sterilized scaffolds was comparable to that of fresh tracheal segments. Given that current clinical attempts at tracheal transplantation using decellularized tissue have been fraught with luminal collapse and complications, our data support the possibility that future embodiments using a hybrid graft approach may reduce the need for intraluminal stenting in tracheal transplant

Severe tracheal stenosis with tracheopathia osteoplastica-like changes due to traumatic blunt injury.

PubMed

Kakinuma, Kazutaka; Morikawa, Kei; Miyamoto, Yasuhiro; Saji, Hisashi; Mineshita, Masamichi; Miyazawa, Teruomi

2014-12-01

A 17-year-old man was injured in a motorcycle accident, leading to a complex cerebral contusion and hepatic injury. Approximately one month after being discharged from the hospital, the patient experienced gradually progressive dyspnea on exertion. Chest computed tomography revealed severe upper tracheal stenosis; thus, emergency tracheotomy and subsequent tracheoplasty were performed. Microscopically, the deformation of tracheal cartilage and extensive interstitial ossification/fibro-elastic changes were observed. To our knowledge, this is the first report documenting the ossification of the trachea that rapidly progressed after injury, which was confirmed by surgical resection of the upper trachea.

Inhibition of agonist-induced smooth muscle contraction by picotamide in the male human lower urinary tract outflow region.

PubMed

Hennenberg, Martin; Tamalunas, Alexander; Wang, Yiming; Keller, Patrick; Schott, Melanie; Strittmatter, Frank; Herlemann, Annika; Yu, Qingfeng; Rutz, Beata; Ciotkowska, Anna; Stief, Christian G; Gratzke, Christian

2017-05-15

Male lower urinary tract symptoms (LUTS) due to bladder outlet obstruction are characterized by abnormal smooth muscle contractions in the lower urinary tract. Alpha 1 -adrenoceptor antagonists may induce smooth muscle relaxation in the outflow region and represent the current gold standard of medical treatment. However, results may be unsatisfactory or inadequate. Apart from α 1 -adrenoceptor agonists, smooth muscle contraction in the outflow region may be induced by thromboxane A 2 (TXA 2 ), endothelins, or muscarinic receptor agonists. Here, we studied effects of the thromboxane A 2 receptor (TP receptor) antagonist picotamide on contraction in the human male bladder trigone and prostate. Carbachol, the α 1 -adrenoceptor agonist phenylephrine, the thromboxane A 2 analog U46619, and electric field stimulation (EFS) induced concentration- or frequency-dependent contractions of trigone tissues in an organ bath. Picotamide (300µM) inhibited carbachol-, phenylephrine-, U46619-, and EFS-induced contractions. Endothelins 1-3 induced concentration-dependent contractions of prostate tissues, which were inhibited by picotamide. Analyses using real time polymerase chain reaction and antibodies suggested expression of thromboxane A 2 receptors and synthase in trigone smooth muscle cells. Thromboxane B 2 (the stable metabolite of thromboxane A 2 ) was detectable by enzyme immune assay in trigone samples, with most values ranging between 50 and 150pg/mg trigone protein. Picotamide inhibits contractions induced by different stimuli in the human lower urinary tract, including cholinergic, adrenergic, thromboxane A 2 - and endothelin-induced, and neurogenic contractions in different locations of the outflow region. This distinguishes picotamide from current medical treatments for LUTS, and suggests that picotamide may induce urodynamic effects in vivo. Copyright © 2017. Published by Elsevier B.V.

Oxytocin receptors expressed and coupled to Ca2+ signalling in a human vascular smooth muscle cell line.

PubMed

Yazawa, H; Hirasawa, A; Horie, K; Saita, Y; Iida, E; Honda, K; Tsujimoto, G

1996-03-01

1. In a human vascular smooth muscle cell line (HVSMC), binding experiments with [3H]-arginine8-vasopressin (AVP) have shown the existence of a homogeneous population of binding sites with affinity (Kd value) of 0.65 nM and a maximum number of binding sites (Bmax) of 122 fmol mg-1 protein. 2. Nonlabelled compounds compete for [3H]-AVP binding in the HVSMC membrane with an order of potency of oxytocin > lyspressin > or = AVP > Thr4, Gly7-oxytocin > (beta-mercapto-beta-beta-cyclopentamethylenepropionyl-O-Me Tyr2, Arg8) vasopressin > desmopressin > OPC21268 > OPC31260. This order was markedly different from that observed in rat vascular smooth muscle cells (A10), a well-established V1A receptor system. 3. In HVSMC both oxytocin and AVP increased inositol 1,4,5-trisphosphate (IP3) production and [Ca2+]i response, but the efficacy of the responses was greater for oxytocin than AVP. 4. Reverse transcription-polymerase chain reaction (RT-PCR) assay detected only oxytocin receptor but not V1A or V2 receptors in HVSMC, whereas only V1A receptors were found in A10 cells. 5. In conclusion, in HVSMC only oxytocin receptors are expressed among the vasopressin receptor family, and they coupled to phosphatidyl inositol (PI) turnover/Ca2+ signalling. This unexpected observation should provide new insight into the functional role of the oxytocin receptor in a human vascular smooth muscle cell line.

Characterization of the EP receptor types that mediate longitudinal smooth muscle contraction of human colon, mouse colon and mouse ileum.

PubMed

Fairbrother, S E; Smith, J E; Borman, R A; Cox, H M

2011-08-01

Prostaglandin E(2) (PGE(2) ) is an inflammatory mediator implicated in several gastrointestinal pathologies that affect normal intestinal transit. The aim was to establish the contribution of the four EP receptor types (EP(1-4) ), in human colon, that mediate PGE(2) -induced longitudinal smooth muscle contraction. Changes in isometric muscle tension of human colon, mouse colon and mouse ileum were measured in organ baths in response to receptor-specific agonists and antagonists. In addition, lidocaine was used to block neurogenic activity to investigate whether EP receptors were pre- or post-junctional. PGE(2) contracted longitudinal muscle from human and mouse colon and mouse ileum. These contractions were inhibited by the EP(1) receptor antagonist, EP(1) A in human colon, whereas a combination of EP(1) A and the EP(3) antagonist, L798106 inhibited agonist responses in both mouse preparations. The EP(3) agonist, sulprostone also increased muscle tension in both mouse tissues, and these responses were inhibited by lidocaine in the colon but not in the ileum. Although PGE(2) consistently contracted all three muscle preparations, butaprost decreased tension by activating smooth muscle EP(2) receptors in both colonic tissues. Alternatively, in mouse ileum, butaprost responses were lidocaine-sensitive, suggesting that it was activating prejunctional EP(2) receptors on inhibitory motor neurons. Conversely, EP(4) receptors were not functional in all the intestinal muscle preparations tested. PGE(2) -induced contraction of longitudinal smooth muscle is mediated by EP(1) receptors in human colon and by a combination of EP(1) and EP(3) receptors in mouse intestine, whereas EP(2) receptors modulate relaxation in all three preparations. © 2011 Blackwell Publishing Ltd.

Receptor-based differences in human aortic smooth muscle cell membrane stiffness

NASA Technical Reports Server (NTRS)

Huang, H.; Kamm, R. D.; So, P. T.; Lee, R. T.

2001-01-01

Cells respond to mechanical stimuli with diverse molecular responses. The nature of the sensory mechanism involved in mechanotransduction is not known, but integrins may play an important role. The integrins are linked to both the cytoskeleton and extracellular matrix, suggesting that probing cells via integrins should yield different mechanical properties than probing cells via non-cytoskeleton-associated receptors. To test the hypothesis that the mechanical properties of a cell are dependent on the receptor on which the stress is applied, human aortic smooth muscle cells were plated, and magnetic beads, targeted either to the integrins via fibronectin or to the transferrin receptor by use of an IgG antibody, were attached to the cell surface. The resistance of the cell to deformation ("stiffness") was estimated by oscillating the magnetic beads at 1 Hz by use of single-pole magnetic tweezers at 2 different magnitudes. The ratio of bead displacements at different magnitudes was used to explore the mechanical properties of the cells. Cells stressed via the integrins required approximately 10-fold more force to obtain the same bead displacements as the cells stressed via the transferrin receptors. Cells stressed via integrins showed stiffening behavior as the force was increased, whereas this stiffening was significantly less for cells stressed via the transferrin receptor (P<0.001). Mechanical characteristics of vascular smooth muscle cells depend on the receptor by which the stress is applied, with integrin-based linkages demonstrating cell-stiffening behavior.

Recurrent airway obstructions in a patient with benign tracheal stenosis and a silicone airway stent: a case report

PubMed Central

Sriram, KB; Robinson, PC

2008-01-01

Airway stents (silicone and metal stents) are used to treat patients with benign tracheal stenosis, who are symptomatic and in whom tracheal surgical reconstruction has failed or is not appropriate. However airway stents are often associated with complications such as migration, granuloma formation and mucous hypersecretion, which cause significant morbidity, especially in patients with benign tracheal stenosis and relatively normal life expectancy. We report a patient who had frequent critical airway obstructions over 8 years due to granuloma and mucus hypersecretion in a silicone airway stent. The problem was resolved when the silicone stent was removed and replaced with a covered self expanding metal stent. PMID:18840299

Effects of the dual TP receptor antagonist and thromboxane synthase inhibitor EV-077 on human endothelial and vascular smooth muscle cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petri, Marcelo H.; Tellier, Céline; Michiels, Carine

2013-11-15

Highlights: •EV-077 reduced TNF-α induced inflammation in endothelial cells. •The thromboxane mimetic U69915 enhanced vascular smooth muscle cell proliferation. •EV-077 inhibited smooth muscle cell proliferation. -- Abstract: The prothrombotic mediator thromboxane A{sub 2} is derived from arachidonic acid metabolism through the cyclooxygenase and thromboxane synthase pathways, and transduces its effect through the thromboxane prostanoid (TP) receptor. The aim of this study was to determine the effect of the TP receptor antagonist and thromboxane synthase inhibitor EV-077 on inflammatory markers in human umbilical vein endothelial cells and on human coronary artery smooth muscle cell proliferation. To this end, mRNA levels ofmore » different proinflammatory mediators were studied by real time quantitative PCR, supernatants were analyzed by enzyme immune assay, and cell proliferation was assessed using WST-1. EV-077 significantly decreased mRNA levels of ICAM-1 and PTX3 after TNFα incubation, whereas concentrations of 6-keto PGF1α in supernatants of endothelial cells incubated with TNFα were significantly increased after EV-077 treatment. Although U46619 did not alter coronary artery smooth muscle cell proliferation, this thromboxane mimetic enhanced the proliferation induced by serum, insulin and growth factors, which was significantly inhibited by EV-077. In conclusion, EV-077 inhibited TNFα-induced endothelial inflammation and reduced the enhancement of smooth muscle cell proliferation induced by a thromboxane mimetic, supporting that the thromboxane pathway may be associated with early atherosclerosis in terms of endothelial dysfunction and vascular hypertrophy.« less

Correlation Between Endotracheal Tube Cuff Pressure and Tracheal Wall Pressure Using Air and Saline Filled Cuffs

DTIC Science & Technology

2017-01-31

AFRL-SA-WP-SR-2017-0004 Correlation Between Endotracheal Tube Cuff Pressure and Tracheal Wall Pressure Using Air- and Saline -Filled...Correlation Between Endotracheal Tube Cuff Pressure and Tracheal Wall Pressure Using Air- and Saline -Filled Cuffs 5a. CONTRACT NUMBER FA8650-14...descending from altitude. When using saline in the ETT cuff, TW pressure differences with the 7.5 high-volume, low-pressure cuff and 8.0 TaperGuard

Three-Dimensional Human Bronchial-Tracheal Epithelial Tissue-Like Assemblies (TLAs) as Hosts for Severe Acute Respiratory Syndrome (SARS)-CoV Infection

NASA Technical Reports Server (NTRS)

Suderman, M. T.; McCarthy, M.; Mossell, E.; Watts, D. M.; Peters, C. J.; Shope, R.; Goodwin, T. J.

2006-01-01

A three-dimensional (3-D) tissue-like assembly (TLA) of human bronchial-tracheal mesenchymal (HBTC) cells with an overlay of human bronchial epithelial (BEAS-2B) cells was constructed using a NASA Bioreactor to survey the infectivity of SARS-CoV. This TLA was inoculated with a low passage number Urbani strain of SARS-CoV. At selected intervals over a 10-day period, media and cell aliquots of the 3-D TLA were harvested for viral titer assay and for light and electron microscopy examination. All viral titer assays were negative in both BEAS-2B two-dimensional monolayer and TLA. Light microscopy immunohistochemistry demonstrated antigen-antibody reactivity with anti-SARS-CoV polyclonal antibody to spike and nuclear proteins on cell membranes and cytoplasm. Coronavirus Group 2 cross-reactivity was demonstrated by positive reaction to anti-FIPV 1 and anti-FIPV 1 and 2 antibodies. TLA examination by transmission electron microscopy indicated increasing cytoplasmic vacuolation with numerous electron-dense bodies measuring 45 to 270 nm from days 4 through 10. There was no evidence of membrane blebbing, membrane duplication, or fragmentation of organelles in the TLAs. However, progressive disruption of endoplasmic reticulum was observed throughout the cells. Antibody response to SARS-CoV specific spike and nucleocapsid glycoproteins, cross-reactivity with FIPV antibodies, and the cytoplasmic pathology suggests this HBTE TLA model is permissive to SARS-CoV infection.

Strategies to prevent ventilation-associated pneumonia: the effect of cuff pressure monitoring techniques and tracheal tube type on aspiration of subglottic secretions: an in-vitro study.

PubMed

Carter, Eleanor L; Duguid, Alasdair; Ercole, Ari; Matta, Basil; Burnstein, Rowan M; Veenith, Tonny

2014-03-01

Ventilation-associated pneumonia (VAP) is the commonest nosocomial infection in intensive care. Implementation of a VAP prevention care bundle is a proven method to reduce its incidence. The UK care bundle recommends maintenance of the tracheal tube cuff pressure at 20 to 30  cmH₂O with 4-hourly pressure checks and use of tracheal tubes with subglottic aspiration ports in patients admitted for more than 72  h. To evaluate the effects of tracheal tube type and cuff pressure monitoring technique on leakage of subglottic secretions past the tracheal tube cuff. Bench-top study. Laboratory. A model adult trachea with simulated subglottic secretions was intubated with a tracheal tube with the cuff inflated to 25  cmH₂O. Experiments were conducted using a Portex Profile Soft Seal tracheal tube with three cuff pressure monitoring strategies and using a Portex SACETT tracheal tube with intermittent cuff pressure checks. Rate of simulated secretion leakage past the tracheal tube cuff. Mean ± SD leakage of fluid past the Profile Soft Seal tracheal tube cuff was 2.25 ± 1.49  ml  min⁻¹ with no monitoring of cuff pressure, 2.98 ± 1.63  ml  min⁻¹ with intermittent cuff pressure monitoring and 3.83 ± 2.17  ml  min⁻¹ with continuous cuff pressure monitoring (P <0.001). Using a SACETT tracheal tube with a subglottic aspiration port and aspirating the simulated secretions prior to intermittent cuff pressure checks reduced the leakage rate to 0.50 ± 0.48  ml  min⁻¹ (P <0.001). Subglottic secretions leaked past the tracheal tube cuff with all tube types and cuff pressure monitoring strategies in this model. Significantly higher rates were observed with continuous cuff pressure monitoring and significantly lower rates were observed when using a tracheal tube with a subglottic aspiration port. Further evaluation of medical device performance is needed in order to design more effective VAP prevention strategies.

The "Hitch Stitch": An Effective Method of Preventing Migration in High Tracheal Stenosis.

PubMed

Mehta, Ravindra M; Singla, Abhinav; Shah, Aashish; Loknath, Chakravarthi

2017-01-01

The incidence of caudal stent migration in high tracheal stenting is 13-21% and is common with silicone stents. This can lead to major problems, including emergency repeat procedures. Several antimigration methods are described, but have limitations in terms of their success rate, availability, cost or ease of the procedure. We describe an innovative method of stent migration prevention using a simple percutaneous anchoring "hitch stitch", validated in a large series. After tracheal stent placement, an Ethilon suture was passed into the stent lumen through an 18-G needle. To take this suture back to the exterior to complete the stitch, a retrieval loop was passed through another 14-G percutaneous cannula inserted into the stent lumen. Bronchoscopically, using a forceps the first suture was pulled inside the loop, the loop was retracted, the suture was exteriorized, and the knot was completed and embedded subcutaneously. While removing the stent, an endoscopic scissor was used to cut the stitch to free the stent. A total of 42 "hitch stitches" were done in 29 patients over 5 years, predominantly for silicone stents. Indications for stenting included postintubation tracheal stenosis (83.3%), malignancy (11.9%) and tracheoesophageal fistula (4.8%, metal stents). The procedure was successful in 41/42 (97.6%) patients. Stitch removal was uncomplicated. This is the largest series of an external stent anchoring procedure as a migration prevention strategy in high tracheal stenting, applicable to both silicone and metal stents. Stent migration prevention using this "hitch stitch" is simple, safe and successful, without any complications during stent removal. © 2016 S. Karger AG, Basel.

Effect of tracheal tube cuff shape on fluid leakage across the cuff: an in vitro study.

PubMed

Dave, M H; Frotzler, A; Spielmann, N; Madjdpour, C; Weiss, M

2010-10-01

This study compared the fluid leakage in the new 'tapered' shaped against the classic 'cylindrical' shaped tracheal tube cuffs when placed in different sized tracheas. The 7.5 mm internal diameter (ID) tracheal tube cuffs-Tapered Seal Guard (TSG), Standard Seal Guard (SSG), Hi-Lo, Microcuff, Ruesch, and Portex Profile-were compared in an in vitro apparatus. Vertical artificial tracheas with 16, 20, and 22 mm ID were intubated, 5 ml clear water was applied above the unlubricated tube cuffs, and fluid leakage was measured up to 60 min. Data of tapered vs non-tapered tube cuffs (16 observations) were compared for each tracheal diameter using the Mann-Whitney test. Median (range) fluid leakage (ml) at 60 min was 2.14 (0.05-4.88), 1.14 (0.00-4.84), and 0.13 (0.00-1.32), respectively, for 16, 20, and 22 mm tracheas in the TSG tube studies when compared with 4.58 (0.44-4.88), 2.21 (0.00-4.81), and 0.00 (0.00-4.81) in the SSG tube and 4.54 (1.54-4.82), 0.90 (0.00-4.49), and 4.85 (4.40-4.99) in the Microcuff tube studies. Leakage in all polyvinylchloride (PVC) tube cuffs was almost complete (5 ml) within 5 min (P<0.001). The tapered PU tube cuff was as effective as the cylindrical PU cuffs in smaller tracheal diameters and was more efficient than the cylindrical Microcuff PU tube cuff in larger tracheal diameter in preventing subglottic fluid leakage across the tube cuff tested in this in vitro study. PVC tube cuffs leaked much more and faster than PU cuffs.

Possible role of bioactive peptides in the regulation of human detrusor smooth muscle - functional effects in vitro and immunohistochemical presence.

PubMed

Uckert, Stefan; Stief, Christian G; Lietz, Burckhard; Burmester, Martin; Jonas, Udo; Machtens, Stefan A

2002-09-01

Results from basic research implicate a role for bioactive peptides in controlling the mammalian lower urinary tract. Although various peptides are assumed to be involved in the potentiaton or inhibition of cholinergic or purinergic activity in the urinary bladder, there is still much controversy regarding the mode of action and functional significance of such peptides in detrusor smooth muscle. Thus, we evaluated the functional effects of atrial natriuretic peptide (ANP), calcitonin gene related peptide (CGRP), endothelin 1 (ET-1), substance P (SP) and vasoactive intestinal polypeptide (VIP) on isolated strip preparations of human detrusor smooth muscle and determined the presence of those peptides in the human detrusor by means of immunohistochemistry. The effects of peptides on isometric tension of isolated detrusor strip preparations and on tissue levels of cyclic nucleotides cAMP and cGMP were compared to those of adenylyl cyclase activator forskolin (F), nitric oxide donor Na(+)-nitroprusside (SNP) and non-specific phosphodiesterase (PDE) inhibitor papaverine (P). The effects of the compounds on isometric tension of isolated human detrusor smooth muscle were examined using the organ bath technique. To determine time- and dose-dependent effects on cyclic nucleotide levels, bladder strips were exposed to increasing doses of F, SNP, P, ANP, CGRP and VIP, then rapidly frozen in liquid nitrogen and homogenised in the frozen state. cAMP and cGMP were extracted and assayed using specific radioimmunoassays. The presence of peptides was investigated by light microscopy using the Avidin-Biotin-Complex (ABC) method. F, P and VIP most effectively reversed the carbachol-induced tension of isolated human detrusor strips. Relaxing effects of ANP, CGRP and SNP were negligible. In contrast, ET-1 and SP elicited dose-dependent contractions of the tissue. The relaxing effects of F, P and VIP were accompanied by an increase in cAMP and cGMP levels, respectively. Light microscopy

The effects of water lubrication of tracheal tubes on post-intubation airway complications: study protocol for a randomized controlled trial.

PubMed

Kim, Eugene; Yang, Seong Mi; Yoon, So Jeong; Bahk, Jae-Hyon; Seo, Jeong-Hwa

2016-11-25

Water is known to have lubricating properties, thus it is used for lubrication of tracheal tubes to reduce airway injuries caused by intubation. However, there is no definite evidence to substantiate the beneficial effects of lubricating tracheal tubes using water for attenuating airway injuries. Moreover, the lubrication pretreatment may cause contamination of the tube, leading to respiratory infections. Therefore, this trial aims to assess whether no pretreatment of tracheal tubes does not increase post-intubation airway complications as compared with water lubrication of tubes. This is a prospective, double-blind, single-center, parallel-arm, noninferiority, randomized controlled trial to be conducted in participants aged 20-80 years who are undergoing elective surgery under general anesthesia with orotracheal intubation. Participants are randomly assigned into one of two groups depending on whether intubation is performed using a tracheal tube lubricated with water (n = 150) or without any pretreatment (n = 150). The primary outcome is the incidence of sore throat at 0, 2, 4, and 24 h after surgery, which is analyzed with a noninferiority test. The secondary outcomes are the incidence and severity of postoperative hoarseness, oropharyngeal injuries, and respiratory infections. Because we hypothesized that lubricating tracheal tubes using water has no advantage in reducing airway injuries associated with intubation, we will compare the incidence of sore throat, which is the most common complaint after intubation, in a noninferiority manner. This is the first randomized controlled trial to investigate the possibly beneficial or harmful effects of lubricating tracheal tubes using water before intubation. We expect that this trial will provide useful evidence to formulate a protocol for preparing tracheal tubes before intubation. This trial is registered at ClinicalTrials.gov on 1 July 2015 ( NCT02492646 ).

adrift, a novel bnl-induced Drosophila gene, required for tracheal pathfinding into the CNS.

PubMed

Englund, C; Uv, A E; Cantera, R; Mathies, L D; Krasnow, M A; Samakovlis, C

1999-04-01

Neurons and glial cells provide guidance cues for migrating neurons. We show here that migrating epithelial cells also contact specific neurons and glia during their pathfinding, and we describe the first gene required in the process. In wild-type Drosophila embryos, the ganglionic tracheal branch navigates a remarkably complex path along specific neural and glial substrata, switching substrata five times before reaching its ultimate target in the CNS. In adrift mutants, ganglionic branches migrate normally along the intersegmental nerve, but sporadically fail to switch to the segmental nerve and enter the CNS; they wind up meandering along the ventral epidermis instead. adrift encodes a novel nuclear protein with an evolutionarily conserved motif. The gene is required in the trachea and is expressed in the leading cells of migrating ganglionic branches where it is induced by the branchless FGF pathway. We propose that Adrift regulates expression of tracheal genes required for pathfinding on the segmental nerve, and FGF induction of adrift expression in migrating tracheal cells promotes the switch from the intersegmental to the segmental nerve.

Functional Reconstruction of Tracheal Defects by Protein-Loaded, Cell-Seeded, Fibrous Constructs in Rabbits

PubMed Central

Ott, Lindsey M.; Vu, Cindy H.; Farris, Ashley L.; Fox, Katrina D.; Galbraith, Richard A.; Weiss, Mark L.; Weatherly, Robert A.

2015-01-01

Tracheal stenosis is a life-threatening disease and current treatments include surgical reconstruction with autologous rib cartilage and the highly complex slide tracheoplasty surgical technique. We propose using a sustainable implant, composed of a tunable, fibrous scaffold with encapsulated chondrogenic growth factor (transforming growth factor-beta3 [TGF-β3]) or seeded allogeneic rabbit bone marrow mesenchymal stromal cells (BMSCs). In vivo functionality of these constructs was determined by implanting them in induced tracheal defects in rabbits for 6 or 12 weeks. The scaffolds maintained functional airways in a majority of the cases, with the BMSC-seeded group having an improved survival rate and the Scaffold-only group having a higher occurrence of more patent airways as determined by microcomputed tomography. The BMSC group had a greater accumulation of inflammatory cells over the graft, while also exhibiting normal epithelium, subepithelium, and cartilage formation. Overall, it was concluded that a simple, acellular scaffold is a viable option for tracheal tissue engineering, with the intraoperative addition of cells being an optional variation to the scaffolds. PMID:26094554

Functional relevance of acoustic tracheal design in directional hearing in crickets.

PubMed

Schmidt, Arne K D; Römer, Heiner

2016-10-15

Internally coupled ears (ICEs) allow small animals to reliably determine the direction of a sound source. ICEs are found in a variety of taxa, but crickets have evolved the most complex arrangement of coupled ears: an acoustic tracheal system composed of a large cross-body trachea that connects two entry points for sound in the thorax with the leg trachea of both ears. The key structure that allows for the tuned directionality of the ear is a tracheal inflation (acoustic vesicle) in the midline of the cross-body trachea holding a thin membrane (septum). Crickets are known to display a wide variety of acoustic tracheal morphologies, most importantly with respect to the presence of a single or double acoustic vesicle. However, the functional relevance of this variation is still not known. In this study, we investigated the peripheral directionality of three co-occurring, closely related cricket species of the subfamily Gryllinae. No support could be found for the hypothesis that a double vesicle should be regarded as an evolutionary innovation to (1) increase interaural directional cues, (2) increase the selectivity of the directional filter or (3) provide a better match between directional and sensitivity tuning. Nonetheless, by manipulating the double acoustic vesicle in the rainforest cricket Paroecanthus podagrosus, selectively eliminating the sound-transmitting pathways, we revealed that these pathways contribute almost equally to the total amount of interaural intensity differences, emphasizing their functional relevance in the system. © 2016. Published by The Company of Biologists Ltd.

Efficiency of a pneumatic device in controlling cuff pressure of polyurethane-cuffed tracheal tubes: a randomized controlled study

PubMed Central

2013-01-01

Background The primary objective of this study was to determine the efficiency of a pneumatic device in controlling cuff pressure (Pcuff) in patients intubated with polyurethane-cuffed tracheal tubes. Secondary objectives were to determine the impact of continuous control of Pcuff, and cuff shape on microaspiration of gastric contents. Methods Prospective randomized controlled study. All patients requiring intubation and mechanical ventilation ≥48 h were eligible. The first 32 patients were intubated with tapered polyurethane-cuffed, and the 32 following patients were intubated with cylindrical polyurethane-cuffed tracheal tubes. Patients randomly received 24 h of continuous control of Pcuff using a pneumatic device (Nosten®), and 24 h of routine care of Pcuff using a manometer. Target Pcuff was 25 cmH2O. Pcuff was continuously recorded, and pepsin was quantitatively measured in all tracheal aspirates during these periods. Results The pneumatic device was efficient in controlling Pcuff (med [IQ] 26 [24, 28] vs 22 [20, 28] cmH2O, during continuous control of Pcuff and routine care, respectively; p = 0.017). In addition, percentage of patients with underinflation (31% vs 68%) or overinflation (53% vs 100%) of tracheal cuff, and percentage of time spent with underinflation (0.9 [0, 17] vs 14% [4, 30]) or overinflation (0 [0, 2] vs 32% [9, 54]) were significantly (p < 0.001) reduced during continuous control of Pcuff compared with routine care. No significant difference was found in microaspiration of gastric content between continuous control of Pcuff compared with routine care, or between patients intubated with tapered compared with cylindrical polyurethane-cuffed tracheal tubes. Conclusion The pneumatic device was efficient in controlling Pcuff in critically ill patients intubated with polyurethane-cuffed tracheal tubes. Trial registration The Australian New Zealand Clinical Trials Registry (NCT01351259) PMID:24369057

Direct modulation of tracheal Cl--channel activity by 5,6- and 11,12-EET.

PubMed

Salvail, D; Dumoulin, M; Rousseau, E

1998-09-01

Using microelectrode potential measurements, we tested the involvement of Cl- conductances in the hyperpolarization induced by 5,6- and 11,12-epoxyeicosatrienoic acid (EET) in airway smooth muscle (ASM) cells. 5,6-EET and 11,12-EET (0.75 microM) caused -5.4 +/- 1.1- and -3.34 +/- 0.95-mV hyperpolarizations, respectively, of rabbit tracheal cells (from a resting membrane potential of -53.25 +/- 0.44 mV), with significant residual repolarizations remaining after the Ca2+-activated K+ channels had been blocked by 10 nM iberiotoxin. In bilayer reconstitution experiments, we demonstrated that the EETs directly inhibit a Ca2+-insensitive Cl- channel from bovine ASM; 1 microM 5,6-EET and 1.5 microM 11,12-EET lowered the unitary current amplitude by 40 (n = 6 experiments) and 44.7% (n = 4 experiments), respectively. Concentration-dependent decreases in channel open probability were observed, with estimated IC50 values of 0.26 microM for 5,6- and 1.15 microM for 11,12-EET. Furthermore, pharmacomechanical tension measurements showed that both regioisomers induced significant bronchorelaxations in epithelium-denuded ASM strips. These results suggest that 5,6- and 11,12-EET can act in ASM as epithelium-derived hyperpolarizing factors.

Tracheal gas insufflation combined with high-frequency oscillatory ventilation.

PubMed

Dolan, S; Derdak, S; Solomon, D; Farmer, C; Johanningman, J; Gelineau, J; Smith, R B

1996-03-01

To determine the efficacy of tracheal insufflation delivered by two different catheter designs on CO2 elimination when used in conjunction with high-frequency oscillatory ventilation. A nonrandomized before and after trial. Each animal served as his own control. Ten mongrel dogs weighing 20.9 +/- 1.9 kg. Four animals were assigned to a normal lung group and six animals underwent lung injury by large volume saline lavage. Permissive hypercapnia was allowed to occur by selecting oscillator settings that would lead to alveolar hypoventilation. Proximal mean airway pressure was kept constant. Tracheal gas was insufflated at 1 cm above the carina for 30 min periods at gas flows of 5 to 15 L/min. Carinal pressure, hemodynamic parameters (cardiac output, mean arterial pressure, pulmonary artery occlusion pressure), and gas exchange parameters (PaCO2, PaO2, PaO2/FIO2, shunt fraction, D O2) were measured. For the normal dogs, at catheter flow of 15 L/min; the forward thrust catheter increased carinal pressure and Pao2/FIO2 BY 30% (p<.003) and 105% (p<.005), respectively. The forward thrust catheter reduced Paco2 by 40% (p<.04). The reverse thrust catheter increased PaO2/FIO2 by 102% (p<.001) and decreased pressure and PaCO2 by 44% (p<.001) and 34% (p<.003), respectively. For the injured dogs, at catheter flow rate of 15 L/min, the forward thrust catheter increased carinal pressure, PaO2, and PaO2/FIO2 by 6% (p<.001), 23% (p<.001), and 24% (p<.02), respectively. The forward thrust catheter reduced PaCO2 by 29% (p<.002). The reverse thrust catheter increased PaO2 and PaO2/FIO2 both by 11% (p<.02) and reduced carinal pressure and PaCO2 by 23% (p<.001) and 18% (p<.002), respectively. Tracheal gas insufflation is capable of improving oxygenation and ventilation in acute lung injury when combined with high-frequency oscillatory ventilation. The addition of this second gas flow at the level of the carina raises or lowers distal airway pressure, the magnitude of which is dependent

Tracheal intubation in the ice-pick position with video laryngoscopes: a randomised controlled trial in a manikin.

PubMed

Wetsch, Wolfgang A; Hellmich, Martin; Spelten, Oliver; Schier, Robert; Böttiger, Bernd W; Hinkelbein, Jochen

2013-09-01

Tracheal intubation in nonstandardised positions is associated with a higher risk of tube misplacement and may have deleterious consequences for patients. Video laryngoscopes for tracheal intubation facilitate both glottic view and success rates. However, their use in the ice-pick position has not been evaluated. To evaluate the role of video laryngoscopes for tracheal intubation in the ice-pick position. A randomised, controlled manikin trial. A standardised airway manikin was placed in the corner of a room. Tracheal intubation was only possible from the lower right side of the manikin. In randomised order, participants used a standard Macintosh laryngoscope and GlideScope Ranger, Storz C-MAC, Pentax AWS, Airtraq and McGrath Series5 video laryngoscopes. Statistical analysis was performed using the Wilcoxon signed-rank and McNemar's tests; A P value of less than 0.05 was deemed statistically significant. Twenty anaesthesiologists, all emergency medicine board-certified. Time to first ventilation (primary); time to glottic view and confirmation of tube position (secondary). Successful ventilation was achieved most rapidly with the Macintosh laryngoscope (36.1 ± 13.4 s; reference method), followed by the Airtraq (38.4 ± 36.3 s; P = n.s.), Pentax AWS (51.6 ± 43.3 s; P = n.s.) and Storz C-Mac (62.7 ± 49.7 s; P = n.s.). The use of the GlideScope Ranger (79.8 ± 61.9 s, P = 0.01) and McGrath series5 (79.8 ± 58.5 s, P = 0.023) resulted in significantly longer times. When comparing overall intubation success, the rate of successful tracheal intubation was higher with the Airtraq than with the McGrath Series5 (P = 0.031; all others n.s.). The use of video laryngoscopes did not result in higher success rates or faster tracheal intubation in the ice-pick position when compared with conventional laryngoscopy in this manikin study. www.clinicaltrials.gov, NCT01210105.

Low serum IGF-1 and increased cytokine levels in tracheal aspirate samples are associated with bronchopulmonary dysplasia.

PubMed

Yılmaz, Cansu; Köksal, Nilgün; Özkan, Hilal; Dorum, Bayram Ali; Bağcı, Onur

2017-01-01

Yılmaz C, Köksal N, Özkan H, Dorum BA, Bağcı O. Low serum IGF-1 and increased cytokine levels in tracheal aspirate samples are associated with bronchopulmonary dysplasia. Turk J Pediatr 2017; 59: 122-129. Despite developments in the perinatal and neonatal care, bronchopulmonary dysplasia (BPD) is still the most frequently seen long-term complication in preterm infants. The aim of this prospective study is to investigate the association between the development of BPD and serial measurements of IGF-1 levels and their relationship with levels of IGF-1 and cytokine in tracheal aspirate fluids. A total of 40 premature infants, born at a gestational age of ≤ 32 weeks, were enrolled in the study. On postnatal day-1, 3, 7, 21 and 28 serum IGF-1 levels and IGF-1 levels, IL-6, IL-8, IL-10 and TNF-alpha levels in tracheal aspirate fluid samples of intubated cases were examined. Mean gestational age of 40 patients included in the study was 29.41 ± 2.23 weeks, and their mean birth weight was 1,256.85 ± 311.48 g. BPD was detected in 35% of cases. Mean gestational week and birth weight of the cases that developed BPD were 30 ± 3 weeks and 1,150 ± 295 g, respectively. Serum IGF-1 levels on postnatal day-1, 3, 7, 21 and 28 in cases who developed BPD were significantly lower when compared with those without BPD (p < 0.01). Levels of IL-6, IL-8, IL-10, and TNF-alpha in tracheal aspirate samples were significantly higher in cases with BPD compared to those without BPD (p < 0.05). IGF-1 levels in tracheal aspirate fluid samples did not differ significantly based on the presence of BPD (p > 0.05). Severity of BPD was associated with decreased serum IGF-1 levels and increased cytokine levels in tracheal aspirate samples.

On the Visual Input Driving Human Smooth-Pursuit Eye Movements

NASA Technical Reports Server (NTRS)

Stone, Leland S.; Beutter, Brent R.; Lorenceau, Jean

1996-01-01

Current computational models of smooth-pursuit eye movements assume that the primary visual input is local retinal-image motion (often referred to as retinal slip). However, we show that humans can pursue object motion with considerable accuracy, even in the presence of conflicting local image motion. This finding indicates that the visual cortical area(s) controlling pursuit must be able to perform a spatio-temporal integration of local image motion into a signal related to object motion. We also provide evidence that the object-motion signal that drives pursuit is related to the signal that supports perception. We conclude that current models of pursuit should be modified to include a visual input that encodes perceived object motion and not merely retinal image motion. Finally, our findings suggest that the measurement of eye movements can be used to monitor visual perception, with particular value in applied settings as this non-intrusive approach would not require interrupting ongoing work or training.

Neuropeptides degranulate serous cells of ferret tracheal glands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gashi, A.A.; Borson, D.B.; Finkbeiner, W.E.

1986-08-01

To determine whether serous or mucous cells in tracheal submucosal glands respond to the neuropeptides substance P (SP) and vasoactive intestinal peptide (VIP). The authors studied the peptide-induced changes in gland cell morphology accompanying release of TVSO4-labeled macromolecules from tracheal explants of ferrets. Explants were labeled for 1 h in medium containing TVSO4 and washed for 3.5 additional hours. Base-line secretion in the absence of drugs declined between 1.5 and 3.5 h after the pulse. Between 2.5 and 3.5 h, the average percent change in counts per minute recovered per sample period was not significantly different from zero. Substance Pmore » and VIP added 4 h after labeling each increased greatly the release of TVSO4-labeled macromolecules above base line. Bethanechol, a muscarinic-cholinergic agonist, increased secretion by an average of 142% above base line. Light and electron microscopy of the control tissues showed glands with narrow lumens and numerous secretory granules. Glands treated with SP or VIP had enlarged lumens and the serous cells were markedly degranulated. These phenomena were documented by morphometry and suggest that SP and VIP cause secretion from glands at least partially by stimulating exocytosis from serous cells.« less

COMPOSITION OF GLYCOPROTEINS SECRETED BY TRACHEAL EXPLANTS FROM VARIOUS ANIMAL SPECIES

EPA Science Inventory

The acidic and neutral glycoproteins secreted by cultured tracheal explants from pigs, sheep, rats, mice, monkeys, guinea pigs, dogs, and chickens were purified and fractionated by column chromatography on DEAE-cellulose and by electrophoresis on cellulose acetate. The ratios of ...

Pilot Study Comparing Closed Versus Open Tracheal Suctioning in Postoperative Neonates and Infants With Complex Congenital Heart Disease.

PubMed

Tume, Lyvonne N; Baines, Paul B; Guerrero, Rafael; Hurley, Margaret A; Johnson, Robert; Kalantre, Atul; Ramaraj, Ram; Ritson, Paul C; Walsh, Laura; Arnold, Philip D

2017-07-01

To determine the hemodynamic effect of tracheal suction method in the first 36 hours after high-risk infant heart surgery on the PICU and to compare open and closed suctioning techniques. Pilot randomized crossover study. Single PICU in United Kingdom. Infants undergoing surgical palliation with Norwood Sano, modified Blalock-Taussig shunt, or pulmonary artery banding in the first 36 hours postoperatively. Infants were randomized to receive open or closed (in-line) tracheal suctioning either for their first or second study tracheal suction in the first 36 hours postoperatively. Twenty-four infants were enrolled over 18 months, 11 after modified Blalock-Taussig shunt, seven after Norwood Sano, and six after pulmonary artery banding. Thirteen patients received the open suction method first followed by the closed suction method second, and 11 patients received the closed suction method first followed by the open suction method second in the first 36 hours after their surgery. There were statistically significant larger changes in heart rate (p = 0.002), systolic blood pressure (p = 0.022), diastolic blood pressure (p = 0.009), mean blood pressure (p = 0.007), and arterial saturation (p = 0.040) using the open suction method, compared with closed suctioning, although none were clinically significant (defined as requiring any intervention). There were no clinically significant differences between closed and open tracheal suction methods; however, there were statistically significant greater changes in some hemodynamic variables with open tracheal suctioning, suggesting that closed technique may be safer in children with more precarious physiology.

Retrograde light-guided laryngoscopy for tracheal intubation: clinical practice and comparison with conventional direct laryngoscopy.

PubMed

Yang, Tao; Hou, Jiong; Li, Jinbao; Zhang, Xu; Zhu, Xiaoyan; Ni, Wen; Mao, Yanfei; Deng, Xiaoming

2013-05-01

Tracheal intubation with conventional laryngoscopy requires many trials until beginners are sufficiently skilled in intubating patients safely. To facilitate intubation, the authors used retrograde light-guided laryngoscopy (RLGL) and compared its feasibility with conventional direct laryngoscopy (DL). Twenty operators participated in a prospective, randomized, open-label, parallel-arm study. These operators intubated 205 patients randomly according to a computer-generated procedure by using either DL or RLGL (five intubations with each technique). The primary outcome was the success rate of tracheal intubation. The authors evaluated the success rate of tracheal intubation, the time to glottic exposure and tracheal intubation, and the Cormack and Lehane grades. Compared with DL, the success rate was greater in the RLGL group for all five intubations (72% vs. 47%; rate difference, 25%; 95% CI [11.84-38.16%], P < 0.001). This was associated with a shorter time to glottic exposure (median [25th and 75th percentile]; 27 [15; 42] vs. 45 [30; 73] s, P < 0.001), shorter intubation time (66 [44; 120] vs. 120 [69; 120] s, P < 0.001), and decreased throat soreness (mean ± SD; visual analog scale, 2.1 ± 0.9 vs. 3.7 ± 1.0 cm, P = 0.001) in the RLGL group compared to the DL group. RLGL is an alternative intubation technique. In our study, it enables beginners to intubate patients more successfully and quickly than conventional DL.

Repair of tracheal epithelium by basal cells after chlorine-induced injury

PubMed Central

2012-01-01

Background Chlorine is a widely used toxic compound that is considered a chemical threat agent. Chlorine inhalation injures airway epithelial cells, leading to pulmonary abnormalities. Efficient repair of injured epithelium is necessary to restore normal lung structure and function. The objective of the current study was to characterize repair of the tracheal epithelium after acute chlorine injury. Methods C57BL/6 mice were exposed to chlorine and injected with 5-ethynyl-2′-deoxyuridine (EdU) to label proliferating cells prior to sacrifice and collection of tracheas on days 2, 4, 7, and 10 after exposure. Airway repair and restoration of a differentiated epithelium were examined by co-localization of EdU labeling with markers for the three major tracheal epithelial cell types [keratin 5 (K5) and keratin 14 (K14) for basal cells, Clara cell secretory protein (CCSP) for Clara cells, and acetylated tubulin (AcTub) for ciliated cells]. Morphometric analysis was used to measure proliferation and restoration of a pseudostratified epithelium. Results Epithelial repair was fastest and most extensive in proximal trachea compared with middle and distal trachea. In unexposed mice, cell proliferation was minimal, all basal cells expressed K5, and K14-expressing basal cells were absent from most sections. Chlorine exposure resulted in the sloughing of Clara and ciliated cells from the tracheal epithelium. Two to four days after chlorine exposure, cell proliferation occurred in K5- and K14-expressing basal cells, and the number of K14 cells was dramatically increased. In the period of peak cell proliferation, few if any ciliated or Clara cells were detected in repairing trachea. Expression of ciliated and Clara cell markers was detected at later times (days 7–10), but cell proliferation was not detected in areas in which these differentiated markers were re-expressed. Fibrotic lesions were observed at days 7–10 primarily in distal trachea. Conclusion The data are

[POSTRESUSCITATION CICATRICIAL TRACHEAL STENOSIS. CURRENT STATE OF THE PROBLEM - THE SUCCESSES, THE HOPES AND DISAPPOINTMENTS.

PubMed

Parshin, V D; Vyzhigina, M A; Rusakov, M A; Parshin, V V; Titov, V A; Starostin, A V

2016-09-01

Currently, the trend continues to increase the number ofpatients with cicatricial tracheal stenosis (CTS). Therefore, prevention and treatment ofthis disease remains topical. The main cause ofcicatricial tracheal stenosis is damaging the trachea during mechanical ventilation. The scheme ofprevention of this disease in Russia hasn't brought the desired results. to clarify the modern etiology of cicatricial tracheal stenosis, to identify the trend in incidence rates, to determine whether there is an optimal safe alternative to tracheostomy including the use of minimally invasive techniques, to improve diagnostic and therapeutic algorithm at various stages of assistance, and also to study the results of innovative operations and new ways of maintaining gas exchange. 1128 patients with cicatricial tracheal stenosis was treated from 1963 to 2015 in Petrovsky National Research Centre of Surgery and IMSechenov First Moscow State Medical University. Over time methods of di- agnosis, methods of anesthesia and operations have been varied. In this regard all patients were divided into two groups depending on the period of time from 1963 to 2000 (297 patients) andfrom 2001 to 2015 (831 patients). In recent decades there is a steady increase in the number of treated patients. So, if in the first group during the year operational treatment about the CTS 8,0 patients were underwent, in the second - to 55.4. Cicatricial tracheal stenosis appeared after lung mechanical ventilation at 1025 (for 90.9%) patients. They have undergone both radical one-stage treatment and multi-stage and sequential intraluminal procedures. In general there is a clear trend towards more aggressive surgical tactics. So, if in thefirst group, the tracheal resection with anastomosis was performedin 59 patients only, the second-330. Thefrequency ofpostoperative complications and mortality in the second group ofpatients was 12.9 and 0.7 %, respectively. Only a reasonable combination of all treatment methods

Smooth muscle contraction and growth of stromal cells in the human prostate are both inhibited by the Src family kinase inhibitors, AZM475271 and PP2.

PubMed

Wang, Yiming; Gratzke, Christian; Tamalunas, Alexander; Rutz, Beata; Ciotkowska, Anna; Strittmatter, Frank; Herlemann, Annika; Janich, Sophie; Waidelich, Raphaela; Liu, Chunxiao; Stief, Christian G; Hennenberg, Martin

2016-12-01

In benign prostatic hyperplasia, increased prostate smooth muscle tone and prostate volume may contribute alone or together to urethral obstruction and voiding symptoms. Consequently, it is assumed there is a connection between smooth muscle tone and growth in the prostate, but any molecular basis for this is poorly understood. Here, we examined effects of Src family kinase (SFK) inhibitors on prostate contraction and growth of stromal cells. SFK inhibitors, AZM475271 and PP2, were applied to human prostate tissues to assess effects on smooth muscle contraction, and to cultured stromal (WPMY-1) and c-Src-deficient cells to examine effects on proliferation, actin organization and viability. SFKs were detected by real time PCR, western blot and immunofluorescence in human prostate tissues, some being located to smooth muscle cells. AZM475271 (10 μM) and PP2 (10 μM) inhibited SFK in prostate tissues and WPMY-1 cells. Both inhibitors reduced α 1 -adrenoceptor-mediated and neurogenic contraction of prostate strips. This may result from cytoskeletal deorganization, which was observed in response to AZM475271 and PP2 in WPMY-1 cells by staining of actin filaments with phalloidin. This was paralleled by reduced proliferation of wildtype but not of c-Src-deficient cells; cytotoxicity was mainly observed at higher concentrations (>50 μM). In human prostate, smooth muscle tone and growth are both controlled by an SFK-dependent process, which may explain their common role in bladder outlet obstruction. Targeting prostate smooth muscle tone and prostate growth simultaneously by a single compound may, in principal, be possible. © 2016 The British Pharmacological Society.

Smooth muscle contraction and growth of stromal cells in the human prostate are both inhibited by the Src family kinase inhibitors, AZM475271 and PP2

PubMed Central

Wang, Yiming; Tamalunas, Alexander; Rutz, Beata; Ciotkowska, Anna; Strittmatter, Frank; Herlemann, Annika; Janich, Sophie; Waidelich, Raphaela; Liu, Chunxiao; Stief, Christian G; Hennenberg, Martin

2016-01-01

Background and Purpose In benign prostatic hyperplasia, increased prostate smooth muscle tone and prostate volume may contribute alone or together to urethral obstruction and voiding symptoms. Consequently, it is assumed there is a connection between smooth muscle tone and growth in the prostate, but any molecular basis for this is poorly understood. Here, we examined effects of Src family kinase (SFK) inhibitors on prostate contraction and growth of stromal cells. Experimental Approach SFK inhibitors, AZM475271 and PP2, were applied to human prostate tissues to assess effects on smooth muscle contraction, and to cultured stromal (WPMY‐1) and c‐Src‐deficient cells to examine effects on proliferation, actin organization and viability. Key Results SFKs were detected by real time PCR, western blot and immunofluorescence in human prostate tissues, some being located to smooth muscle cells. AZM475271 (10 μM) and PP2 (10 μM) inhibited SFK in prostate tissues and WPMY‐1 cells. Both inhibitors reduced α1‐adrenoceptor‐mediated and neurogenic contraction of prostate strips. This may result from cytoskeletal deorganization, which was observed in response to AZM475271 and PP2 in WPMY‐1 cells by staining of actin filaments with phalloidin. This was paralleled by reduced proliferation of wildtype but not of c‐Src‐deficient cells; cytotoxicity was mainly observed at higher concentrations (>50 μM). Conclusions and Implications In human prostate, smooth muscle tone and growth are both controlled by an SFK‐dependent process, which may explain their common role in bladder outlet obstruction. Targeting prostate smooth muscle tone and prostate growth simultaneously by a single compound may, in principal, be possible. PMID:27638545

Tracheal cuff pressure monitoring in the ICU: a literature review and survey of current practice in Queensland.

PubMed

Talekar, C R; Udy, A A; Boots, R J; Lipman, J; Cook, D

2014-11-01

The application of tracheal cuff pressure monitoring is likely to vary between institutions. The aim of this study was therefore to review current evidence concerning this intervention in the intensive care unit (ICU) and to appraise regional practice by performing a state-wide survey. Publications for review were identified through searches of PubMed, EMBASE and Cochrane (1977 to 2014). All studies in English relevant to critical care and with complete data were included. Survey questions were developed by small-group consensus. Public and private ICUs across Queensland were contacted, with responses obtained from a representative member of the medical or nursing staff. Existing literature suggests significant variability in tracheal cuff pressure monitoring in the ICU, particularly in the applied technique, frequency of assessment and optimal intra-cuff pressures. Twenty-nine respondents completed the survey, representing 80.5% (29/36) of ICUs in Queensland. Twenty-eight out of twenty-nine respondents reported routinely monitoring tracheal cuff function, primarily employing cuff pressure measurement (26/28). Target cuff pressures varied, with 3/26 respondents aiming for 10 to 20 cmH2O, 10/26 for 21 to 25 cmH2O, and 13/26 for 26 to 30 cmH2O. Fifteen out of twenty-nine reported they had no current guideline or protocol for tracheal cuff management and only 16/29 indicated there was a dedicated area in the clinical record for reporting cuff intervention. Our results indicate that many ICUs across Queensland routinely measure tracheal cuff function, with most utilising pressure monitoring devices. Consistent with existing literature, the optimum cuff pressure remains uncertain. Most, however, considered that this should be a routine part of ICU care.

Human mast cell and airway smooth muscle cell interactions: implications for asthma.

PubMed

Page, S; Ammit, A J; Black, J L; Armour, C L

2001-12-01

Asthma is characterized by inflammation, hyperresponsiveness, and remodeling of the airway. Human mast cells (HMCs) play a central role in all of these changes by releasing mediators that cause exaggerated bronchoconstriction, induce human airway smooth muscle (HASM) cell proliferation, and recruit and activate inflammatory cells. Moreover, the number of HMCs present on asthmatic HASM is increased compared with that on nonasthmatic HASM. HASM cells also have the potential to actively participate in the inflammatory process by synthesizing cytokines and chemokines and expressing surface molecules, which have the capacity to perpetuate the inflammatory mechanisms present in asthma. This review specifically examines how the mediators of HMCs have the capacity to modulate many functions of HASM; how the synthetic function of HASM, particularly through the release and expression of stem cell factor, has the potential to influence HMC number and activation in an extraordinarily potent and proinflammatory manner; and how these interactions between HMCs and HASM have potential consequences for airway structure and inflammation relevant to the disease process of asthma.

Interventional bronchoscopy for treatment of tracheal obstruction secondary to benign or malignant thyroid disease.

PubMed

Noppen, Marc; Poppe, Kris; D'Haese, Jan; Meysman, Marc; Velkeniers, Brigitte; Vincken, Walter

2004-02-01

Surgery is the treatment of choice for symptomatic tracheal obstruction due to benign or malignant thyroid disease. In case of inoperability, or when surgery is refused, few therapeutic alternatives are available. Interventional bronchoscopic procedures have only been reported anecdotally. The objective of this study is to evaluate the results of interventional bronchoscopic procedures in the treatment of severe tracheal obstruction due to thyroid disease. Retrospective cohort analysis. University hospital, tertiary referral center. Thirty consecutive patients referred for bronchoscopic treatment of benign (n = 17) or malignant (n = 13) thyroid-related upper airway obstruction due to tracheomalacia, extrinsic compression, and/or tracheal ingrowth. Indications for bronchoscopic treatment were medical or surgical inoperability, prevention or treatment of tracheomalacia, and refusal of surgery. There were no procedure-related complications. Rigid bronchoscopy with dilatation, stenting and/or Nd-YAG laser treatment, and clinical follow-up. Subjective improvement, pulmonary function tests, early and late complications, and survival. In the benign group, immediate (100% relief of dyspnea) and long-term (88% relief of dyspnea) results were excellent after airway stenting (21 stents used in 17 patients). There was one unrelated death 1 week after stenting in a 98-year-old patient. There were 6% and 30% short-term and long-term complications, respectively, that could be managed endoscopically. In the malignant group, Nd-YAG laser treatment (n = 3) and stenting (n = 13) yielded immediate and long-term success in 92% of patients. There were 15% short-term and 8% long-term complications. Median survival time was 540 days. Interventional bronchoscopic procedures including Nd-YAG laser treatment and stenting are valuable alternatives to surgery in inoperable thyroid-induced tracheal obstruction, or when surgery is refused.

Tracheal lacerations after endotracheal intubation: a proposed morphological classification to guide non-surgical treatment.

PubMed

Cardillo, Giuseppe; Carbone, Luigi; Carleo, Francesco; Batzella, Sandro; Jacono, Raffaelle Dello; Lucantoni, Gabriele; Galluccio, Giovanni

2010-03-01

Postintubation tracheobronchial lacerations (PITLs) are traditionally managed surgically. We sought to evaluate the rationale for non-surgical management of PITL. From January 2003 to November 2008, 30 patients with PITL were observed in our institution. PITL were graded as follows: Level I - mucosal or submucosal tracheal involvement without mediastinal emphysema and without oesophageal injury; Level II - tracheal lesion up to the muscular wall with subcutaneous or mediastinal emphysema without oesophageal injury or mediastinitis; Level IIIA - complete laceration of the tracheal wall with oesophageal or mediastinal soft-tissue hernia without oesophageal injury or mediastinitis; Level IIIB - any laceration of the tracheal wall with oesophageal injury or mediastinitis. All patients with Level I, II and IIIA PITL were treated conservatively with endoscopic instillation of fibrin glue (Tissucol, Baxter Healthcare, Deerfield, MA, USA). All patients with Level I (n=3), II (n=24) and IIIA (n=2) PITL were successfully treated conservatively. The patient with a Level IIIB injury underwent posterolateral thoracotomy repair of the trachea. No mortality was reported. Mean hospital stay was 12.9 days. Flexible bronchoscopy at 7, 28, 90 and 180 days showed no abnormalities. Complete healing was attained in all patients by day 28. Level I or II PITL should be managed non-surgically. When adequate respiratory status is present, Level IIIA PITL can be managed conservatively in selected institutions only, because these injuries are high-risk injuries. Any PITL associated with injury involving the oesophagus or with mediastinitis (Level IIIB) must be treated as soon as possible by surgery. Copyright (c) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Neuron-derived orphan receptor 1 promoted human pulmonary artery smooth muscle cells proliferation.

PubMed

Wang, Chang-Guo; Lei, Wei; Li, Chang; Zeng, Da-Xiong; Huang, Jian-An

2015-05-01

As a transcription factor of the nuclear receptor superfamily, neuron-derived orphan receptor 1 (NOR1) is induced rapidly in response to various extracellular stimuli. But, it is still unclear its role in pulmonary artery smooth muscle cells proliferation. Human PASMCs were cultured in vitro and stimulated by serum. The special antisense oligodeoxynucleotides (AS-ODNs) were used to knockdown human NOR1 gene expression. Real-time PCR and Western-blot were used to evaluate the gene expression and protein levels. Fetal bovine serum (FBS) induced human PASMCs proliferation in a dose dependent manner. Furthermore, FBS promoted NOR1 gene expression in a dose dependent manner and a time dependent manner. 10% FBS induced a maximal NOR1 mRNA levels at 2 h. FBS also induced a significant higher NOR1 protein levels as compared with control. The NOR1 over-expressed plasmid significantly promoted DNA synthesis and cells proliferation. Moreover, the special AS-ODNs against human NOR1 not only prevented NOR1 expression but also inhibited DNA synthesis and cells proliferation significantly. The NOR1 over-expression plasmid could up-regulate cyclin D1 expression markedly, but the AS-ODNs inhibited cyclin D1 expression significantly. So, we concluded that NOR1 could promote human PASMCs proliferation. Cyclin D1 might be involved in this process.

Involvement of MAPKs, NF-{kappa}B and p300 co-activator in IL-1{beta}-induced cytosolic phospholipase A{sub 2} expression in canine tracheal smooth muscle cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, S.-F.; Lin, C.-C.; Chen, H.-C.

2008-11-01

Cytosolic phospholipase A{sub 2} (cPLA{sub 2}) plays a pivotal role in mediating agonist-induced arachidonic acid release for prostaglandin (PG) synthesis during stimulation with interleukin-1{beta} (IL-1{beta}). However, the mechanisms underlying IL-1{beta}-induced cPLA{sub 2} expression and PGE{sub 2} synthesis by canine tracheal smooth muscle cells (CTSMCs) have not been defined. IL-1{beta} induced cPLA{sub 2} protein and mRNA expression, PGE{sub 2} production, and phosphorylation of p42/p44 MAPK, p38 MAPK (ATF{sub 2}), and JNK (c-Jun) in a time- and concentration-dependent manner, determined by Western blotting, RT-PCR, and ELISA, which was attenuated by the inhibitors of MEK1/2 (U0126), p38 MAPK (SB202190), and JNK (SP600125), ormore » transfection with dominant negative mutants of MEK1/2, p38, and JNK, respectively. Furthermore, IL-1{beta}-induced cPLA{sub 2} expression and PGE{sub 2} synthesis was inhibited by a selective NF-{kappa}B inhibitor (helenalin) or transfection with dominant negative mutants of NF-{kappa}B inducing kinase (NIK), I{kappa}B kinase (IKK)-{alpha}, and IKK-{beta}. Consistently, IL-1{beta} stimulated both I{kappa}B-{alpha} degradation and NF-{kappa}B translocation into nucleus in these cells. NF-{kappa}B translocation was blocked by helenalin, but not by U0126, SB202190, and SP600125. MAPKs together with NF-{kappa}B-activated p300 recruited to cPLA{sub 2} promoter thus facilitating the binding of NF-{kappa}B to cPLA{sub 2} promoter region and expression of cPLA{sub 2} mRNA. IL-1{beta}-induced cPLA{sub 2} expression and PGE{sub 2} production was inhibited by actinomycin D and cycloheximide, indicating the involvement of transcriptional and translational events in these responses. These results suggest that in CTSMCs, IL-1{beta}-induced cPLA{sub 2} expression and PGE{sub 2} synthesis was independently mediated through activation of MAPKs and NF-{kappa}B pathways and was connected to p300 recruitment and activation.« less

Tracheal ceramic rings for tracheomalacia: a review after 17 years.

PubMed

Göbel, Gyula; Karaiskaki, Niki; Gerlinger, Imre; Mann, Wolf J

2007-10-01

Despite different support techniques, the surgical management of tracheomalacia is still a challenging problem. Satisfactory results after internal stenting are above 80%, whereas, when performing external stenting using biocompatible ceramic rings, results are reported at over 90%. The purpose of this study was to examine the efficiency of surgical treatment in patients with segmentary tracheomalacia using external ceramic ring grafts. In this retrospective study, we collected data from 12 patients who underwent surgery during the last 17 years for symptomatic segmentary tracheomalacia by use of biocompatible aluminum-oxide ceramic rings. All except one patient had undergone previous tracheostomy, six had a history of long-term intubation, two had previous trauma, and two patients had previous cancer treatment including radiotherapy. One of the patients still had an existing tracheostoma, which was closed when a ceramic ring was implanted. Tracheal wall collapse with pseudoglottis formation or flattened anterior-posterior tracheal diameter was documented with fiberoscopy at rest, and both pre- and postoperative airway resistance measurements were performed in all 12 patients using a spirometer. After malacic segments were found to be expandable using rigid tracheoscopy while the patient was under general anesthesia, preparation of the trachea was performed using a midline vertical incision in the neck. Subsequently, the malacic trachea was expanded by placing and suturing proper-sized ceramic ring(s) around it. In all patients, surgical expansion of the malacic segment using ceramic rings was successfully carried out without major complications while inspiratory stridor was resolved. Airway resistance decreased significantly from an average of 0.62 to 0.385 kPascal. Although the results of applying internal tracheal stents are encouraging, complications such as stent migration, granulation tissue and fistula formation, and mucociliary transport arrest are possible

ASM-024, a Piperazinium Compound, Promotes the In Vitro Relaxation of β2-Adrenoreceptor Desensitized Tracheas

PubMed Central

Israël-Assayag, Evelyne; Beaulieu, Marie-Josée; Cormier, Yvon

2015-01-01

Inhaled β2-adrenoreceptor agonists are widely used in asthma and chronic obstructive pulmonary disease (COPD) for bronchoconstriction relief. β2-adrenoreceptor agonists relax airway smooth muscle cells via cyclic adenosine monophosphate (cAMP) mediated pathways. However, prolonged stimulation induces functional desensitization of the β2-adrenoreceptors (β2-AR), potentially leading to reduced clinical efficacy with chronic or prolonged administration. ASM-024, a small synthetic molecule in clinical stage development, has shown activity at the level of nicotinic receptors and possibly at the muscarinic level and presents anti-inflammatory and bronchodilator properties. Aerosolized ASM-024 reduces airway resistance in mice and promotes in-vitro relaxation of tracheal and bronchial preparations from animal and human tissues. ASM-024 increased in vitro relaxation response to maximally effective concentration of short—acting beta-2 agonists in dog and human bronchi. Although the precise mechanisms by which ASM-024 promotes airway smooth muscle (ASM) relaxation remain unclear, we hypothesized that ASM-024 will attenuate and/or abrogate agonist-induced contraction and remain effective despite β2-AR tachyphylaxis. β2-AR tachyphylaxis was induced with salbutamol, salmeterol and formoterol on guinea pig tracheas. The addition of ASM-024 relaxed concentration-dependently intact or β2-AR desensitized tracheal rings precontracted with methacholine. ASM-024 did not induce any elevation of intracellular cAMP in isolated smooth muscle cells; moreover, blockade of the cAMP pathway with an adenylate cyclase inhibitor had no significant effect on ASM-024-induced guinea pig trachea relaxation. Collectively, these findings show that ASM-024 elicits relaxation of β2-AR desensitized tracheal preparations and suggest that ASM-024 mediates smooth muscle relaxation through a different target and signaling pathway than β2-adrenergic receptor agonists. These findings suggest ASM-024

ASM-024, a piperazinium compound, promotes the in vitro relaxation of β2-adrenoreceptor desensitized tracheas.

PubMed

Israël-Assayag, Evelyne; Beaulieu, Marie-Josée; Cormier, Yvon

2015-01-01

Inhaled β2-adrenoreceptor agonists are widely used in asthma and chronic obstructive pulmonary disease (COPD) for bronchoconstriction relief. β2-Adrenoreceptor agonists relax airway smooth muscle cells via cyclic adenosine monophosphate (cAMP) mediated pathways. However, prolonged stimulation induces functional desensitization of the β2-adrenoreceptors (β2-AR), potentially leading to reduced clinical efficacy with chronic or prolonged administration. ASM-024, a small synthetic molecule in clinical stage development, has shown activity at the level of nicotinic receptors and possibly at the muscarinic level and presents anti-inflammatory and bronchodilator properties. Aerosolized ASM-024 reduces airway resistance in mice and promotes in-vitro relaxation of tracheal and bronchial preparations from animal and human tissues. ASM-024 increased in vitro relaxation response to maximally effective concentration of short-acting beta-2 agonists in dog and human bronchi. Although the precise mechanisms by which ASM-024 promotes airway smooth muscle (ASM) relaxation remain unclear, we hypothesized that ASM-024 will attenuate and/or abrogate agonist-induced contraction and remain effective despite β2-AR tachyphylaxis. β2-AR tachyphylaxis was induced with salbutamol, salmeterol and formoterol on guinea pig tracheas. The addition of ASM-024 relaxed concentration-dependently intact or β2-AR desensitized tracheal rings precontracted with methacholine. ASM-024 did not induce any elevation of intracellular cAMP in isolated smooth muscle cells; moreover, blockade of the cAMP pathway with an adenylate cyclase inhibitor had no significant effect on ASM-024-induced guinea pig trachea relaxation. Collectively, these findings show that ASM-024 elicits relaxation of β2-AR desensitized tracheal preparations and suggest that ASM-024 mediates smooth muscle relaxation through a different target and signaling pathway than β2-adrenergic receptor agonists. These findings suggest ASM-024

Family Presence During Pediatric Tracheal Intubations.

PubMed

Sanders, Ronald C; Nett, Sholeen T; Davis, Katherine Finn; Parker, Margaret M; Bysani, G Kris; Adu-Darko, Michelle; Bird, Geoffrey L; Cheifetz, Ira M; Derbyshire, Ashley T; Emeriaud, Guillaume; Giuliano, John S; Graciano, Ana Lia; Hagiwara, Yusuke; Hefley, Glenda; Ikeyama, Takanari; Jarvis, J Dean; Kamat, Pradip; Krishna, Ashwin S; Lee, Anthony; Lee, Jan Hau; Li, Simon; Meyer, Keith; Montgomery, Vicki L; Nagai, Yuki; Pinto, Matthew; Rehder, Kyle J; Saito, Osamu; Shenoi, Asha N; Taekema, Hester Christianne; Tarquinio, Keiko M; Thompson, Ann E; Turner, David A; Nadkarni, Vinay M; Nishisaki, Akira

2016-03-01

Family-centered care, which supports family presence (FP) during procedures, is now a widely accepted standard at health care facilities that care for children. However, there is a paucity of data regarding the practice of FP during tracheal intubation (TI) in pediatric intensive care units (PICUs). Family presence during procedures in PICUs has been advocated. To describe the current practice of FP during TI and evaluate the association with procedural and clinician (including physician, respiratory therapist, and nurse practitioner) outcomes across multiple PICUs. Prospective cohort study in which all TIs from July 2010 to March 2014 in the multicenter TI database (National Emergency Airway Registry for Children [NEAR4KIDS]) were analyzed. Family presence was defined as a family member present during TI. This study included all TIs in patients younger than 18 years in 22 international PICUs. Family presence and no FP during TI in the PICU. The percentage of FP during TIs. First attempt success rate, adverse TI-associated events, multiple attempts (≥ 3), oxygen desaturation (oxygen saturation as measured by pulse oximetry <80%), and self-reported team stress level. A total of 4969 TI encounters were reported. Among those, 81% (n = 4030) of TIs had documented FP status (with/without). The median age of participants with FP was 2 years and 1 year for those without FP. The average percentage of TIs with FP was 19% and varied widely across sites (0%-43%; P < .001). Tracheal intubations with FP (vs without FP) were associated with older patients (median, 2 years vs 1 year; P = .04), lower Paediatric Index of Mortality 2 score, and pediatric resident as the first airway clinician (23%, n = 179 vs 18%, n = 584; odds ratio [OR], 1.4; 95% CI, 1.2-1.7). Tracheal intubations with FP and without FP were no different in the first attempt success rate (OR, 1.00; 95% CI, 0.85-1.18), adverse TI-associated events (any events: OR, 1.06; 95% CI, 0.85-1.30 and severe events: OR

Effects of heat and moisture exchangers on tracheal mucociliary clearance in laryngectomized patients: a multi-center case-control study.

PubMed

van den Boer, C; Muller, S H; van der Noort, V; Olmos, R A Valdés; Minni, A; Parrilla, C; Hilgers, F J M; van den Brekel, M W M; van der Baan, S

2015-11-01

After total laryngectomy, inspired air is no longer optimally conditioned by the upper airways. Impaired mucociliary clearance and histological changes of respiratory epithelium, such as loss of ciliated cells, have been described in laryngectomized patients. Heat and moisture exchangers (HMEs) are passive humidifiers that re-condition the inspired air. Aim of this study was to assess the effect of HMEs on tracheal epithelium and tracheal mucus transport velocity (TMV). Tracheal brush biopsies were collected in three groups of TLE patients: 21 long-term HME users, 10 non-HME users, and 16 non-HME users before and after 4-9 months HME use. Tracheal epithelium biopsies were assessed using a digital high-speed camera mounted onto a light microscope. TMV was determined by scintigraphy in the first two patient groups. Significantly more ciliated cells were found in HME users compared to non-HME users (p = 0.05). TMV was higher in HME users (median 2 mm/min; 0-7.9) compared to non-HME users (median 0.8 mm/min; 0-12.3), but this difference was not significant (p = 0.37). One-hour breathing without HME in long-term HME users did not measurably decrease TMV (p = 0.13). The long-term use of an HME restores/prevents the loss of tracheal ciliated cells. A significant improvement in TMV was not found. Short-term (one hour) detachment of an HME has no measurable effect on TMV.

Comparison between the Trachway video intubating stylet and Macintosh laryngoscope in four simulated difficult tracheal intubations: A manikin study

PubMed Central

Ong, Jimmy; Lee, Chia-Ling; Huang, Shen-Jer; Shyr, Ming-Hwang

2016-01-01

Objectives: It remains to be determined whether the TVI-4000 Trachway video intubating (TVI) stylet (Markstein Sichtec Medical Corp, Taichung, Taiwan), an airway device for novices, improves airway management practice by experienced anesthesiologists. The aim of this study was to evaluate the feasibility of using the TVI stylet in difficult tracheal intubation situations compared with that of using the Macintosh laryngoscope on an airway manikin. Materials and Methods: Ten anesthesiologists (with 3–21 years’ experience), including three senior residents, participated. We compared tracheal intubation in four airway scenarios: normal airway, tongue edema, cervical spine immobilization, and tongue edema combined with cervical spine immobilization. The time of tracheal intubation (TTI), success rate, and perceived difficulty of intubation for each scenario were compared and analyzed. Results: The TTI was significantly shorter in both the tongue edema and combined scenarios with the TVI stylet compared with the Macintosh laryngoscope (21.60 ± 1.45 seconds vs. 24.07 ± 1.58 seconds and 23.73 ± 2.05 seconds vs. 26.6 ± 2.77 seconds, respectively). Success rates for both devices were 100%. Concomitantly, participants rated using the TVI stylet in these two scenarios as being less difficult. Conclusion: The learning time for tracheal intubation using the TVI stylet in difficult airway scenarios was short. Use of the TVI stylet was easier and required a shorter TTI for tracheal intubation in the tongue edema and combined scenarios. PMID:28757736

Tracheal reaction to three different intraluminal stents in an animal model of tracheomalacia.

PubMed

Weinberg, Mark; Sandbank, Judith; Flumenblit, Yoseph; Klin, Baruch; Vinograd, Itzhak

2005-06-01

Three different internal airway stents were studied in an animal model of tracheomalacia: the Palmaz stent (Johnson & Johnson, Warren, New Jersey) and the NIR stent (Medinol Ltd., Tel Aviv, Israel)--both made of stainless steel in the form of tubular mesh--and the Nitinol stent, made of nickel-titanium formed into a spiral shape. All three stents could be adequately stabilized in the malacic tracheal segment. The Nitinol stent (Medinol Ltd., Tel Aviv, Israel) proved to be less reactive to the tracheal mucosa, demonstrated higher biocompatibility with significantly less granulation tissue formation, and showed superior radial resistance. Extraction of the Nitinol stent also proved to be much smoother. This stent may be the stent of choice in the treatment of tracheo- and bronchomalacia.

Surgical removal of a tracheal foreign body from a whooping crane (Grus americana)

USGS Publications Warehouse

Howard, P.E.; Dein, F.J.; Langenberg, J.A.; Frischmeyer, K.J.; Brunson, D.

1991-01-01

The left wing of a whooping crane (Grus americana) was amputated for treatment of severe nonunion and malunion fractures of the radius and ulna. During the postoperative convalescent period, the bird aspirated a corn kernel and subsequently suffered episodic bouts of dyspnea. The bird was anesthetized with tiletamine-zolazepam. Attempts to deliver the kernel through the glottis with endoscopic instruments were unsuccessful. The corn kernel was retrieved via a tracheotomy incision. Endoscopy of the trachea 2 mo postoperatively showed complete healing of the tracheal incision. Mucosal integrity had been reestablished, and tracheal lumen diameter was not compromised. The bird continues in good health 2.5 yr after surgery, shows no sign of respiratory disease, and currently is in a captive breeding program.

Composite cervical skin and cartilage flap provides a novel large airway substitute after long-segment tracheal resection.

PubMed

Fabre, Dominique; Singhal, Sunil; De Montpreville, Vincent; Decante, Benoit; Mussot, Sacha; Chataigner, Olivier; Mercier, Olaf; Kolb, Frederic; Dartevelle, Philippe G; Fadel, Elie

2009-07-01

Airway replacement after long-segment tracheal resection for benign and malignant disease remains a challenging problem because of the lack of a substitute conduit. Ideally, an airway substitute should be well vascularized, rigid, and autologous to avoid infections, airway stenosis, and the need for immunosuppression. We report the development of an autologous tracheal substitute for long-segment tracheal resection that satisfies these criteria and demonstrates excellent short-term functional results in a large-animal study. Twelve adult pigs underwent long-segment (6 cm, 60% of total length) tracheal resection. Autologous costal cartilage strips measuring 6 cm x 2 mm were harvested from the chest wall and inserted at regular 0.5-cm intervals between dermal layers of a cervical skin flap. The neotrachea was then scaffolded by rotating the composite cartilage skin flap around a silicone stent measuring 6 cm in length and 1.4 cm in diameter. The neotrachea replaced the long segment of tracheal resection, and the donor flap site was closed with a double-Z plasty. Animals were killed at 1 week (group I, n = 4), 2 weeks (group II, n = 4), and 5 weeks (group III, n = 4). In group III the stent was removed 1 week before death. Viability of the neotrachea was monitored by means of daily flexible bronchoscopy and histologic examination at autopsy. Long-term morbidity and mortality were determined by monitoring weight gain, respiratory distress, and survival. There was no mortality during the study period. Weight gain was appropriate in all animals. Daily bronchoscopy and postmortem histologic evaluation confirmed excellent viability of the neotrachea. There was no evidence of suture-line dehiscence. Five animals had distal granulomas that were removed by using rigid bronchoscopy. In group III 1 animal had tracheomalacia, which was successfully managed by means of insertion of a silicon stent. Airway reconstruction with autologous cervical skin flaps scaffolded with costal

Neuronal Control of Metabolism through Nutrient-Dependent Modulation of Tracheal Branching

PubMed Central

Linneweber, Gerit A.; Jacobson, Jake; Busch, Karl Emanuel; Hudry, Bruno; Christov, Christo P.; Dormann, Dirk; Yuan, Michaela; Otani, Tomoki; Knust, Elisabeth; de Bono, Mario; Miguel-Aliaga, Irene

2014-01-01

Summary During adaptive angiogenesis, a key process in the etiology and treatment of cancer and obesity, the vasculature changes to meet the metabolic needs of its target tissues. Although the cues governing vascular remodeling are not fully understood, target-derived signals are generally believed to underlie this process. Here, we identify an alternative mechanism by characterizing the previously unrecognized nutrient-dependent plasticity of the Drosophila tracheal system: a network of oxygen-delivering tubules developmentally akin to mammalian blood vessels. We find that this plasticity, particularly prominent in the intestine, drives—rather than responds to—metabolic change. Mechanistically, it is regulated by distinct populations of nutrient- and oxygen-responsive neurons that, through delivery of both local and systemic insulin- and VIP-like neuropeptides, sculpt the growth of specific tracheal subsets. Thus, we describe a novel mechanism by which nutritional cues modulate neuronal activity to give rise to organ-specific, long-lasting changes in vascular architecture. PMID:24439370

Inhibition of adrenergic human prostate smooth muscle contraction by the inhibitors of c-Jun N-terminal kinase, SP600125 and BI-78D3.

PubMed

Strittmatter, F; Walther, S; Gratzke, C; Göttinger, J; Beckmann, C; Roosen, A; Schlenker, B; Hedlund, P; Andersson, K E; Stief, C G; Hennenberg, M

2012-07-01

BACKGROUND AND PURPOSE α(1) -Adrenoceptor-induced contraction of prostate smooth muscle is mediated by calcium- and Rho kinase-dependent mechanisms. In addition, other mechanisms, such as activation of c-jun N-terminal kinase (JNK) may be involved. Here, we investigated whether JNK participates in α(1)-adrenoceptor-induced contraction of human prostate smooth muscle. EXPERIMENTAL APPROACH Prostate tissue was obtained from patients undergoing radical prostatectomy. Effects of the JNK inhibitors SP600125 (50 µM) and BI-78D3 (30 µM) on contractions induced by phenylephrine, noradrenaline and electric field stimulation (EFS) were studied in myographic measurements. JNK activation by noradrenaline (30 µM) and phenylephrine (10 µM), and the effects of JNK inhibitors of c-Jun phosphorylation were assessed by Western blot analyses with phospho-specific antibodies. Expression of JNK was studied by immunohistochemistry and fluorescence double staining. KEY RESULTS The JNK inhibitors SP600125 and BI-78D3 reduced phenylephrine- and noradrenaline-induced contractions of human prostate strips. In addition, SP600125 reduced EFS-induced contraction of prostate strips. Stimulation of prostate tissue with noradrenaline or phenylephrine in vitro resulted in activation of JNK. Incubation of prostate tissue with SP600125 or BI-78D3 reduced the phosphorylation state of c-Jun. Immunohistochemical staining demonstrated the expression of JNK in smooth muscle cells of human prostate tissue. Fluorescence staining showed that α(1A)-adrenoceptors and JNK are expressed in the same cells. CONCLUSIONS AND IMPLICATIONS Activation of JNK is involved in α(1)-adrenoceptor-induced prostate smooth muscle contraction. Models of α(1)-adrenoceptor-mediated prostate smooth muscle contraction should include this JNK-dependent mechanism. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Formalin produces depolarizations in human airway smooth muscle in vitro.

PubMed

Richards, Ira S; DeHate, Robin B

2006-03-01

Respiratory irritants may result in airway smooth muscle (ASM) depolarization and bronchoconstriction. We examined the effect of formalin on membrane potentials in human ASM in two types of in vitro preparations: strip preparations, which contain functional sensory and motor nerve endings and cultured cells, which lack these nerve endings due to the tissue dissociation process. Depolarizations occurred in atropine-treated strip preparations in response to formalin exposures, but not in similarly-treated cultured cells, suggesting a role for non-cholinergic mediators in formalin-induced depolarization. It is suggested that formalin may act as an irritant to produce bronchoconstriction that is mediated by the release of endogenous substance P (SP) from peripheral sensory nerve endings. This is supported by our observation that exogenous SP produced depolarizations of a magnitude similar to those produced by formalin in both strip preparations and cultured cells. In addition, capsaicin, which releases endogenous SP from nerve endings, produced depolarizations of a magnitude similar to formalin in strip preparations, but was without effect in cultured cells.

Gene Expression Programs of Human Smooth Muscle Cells: Tissue-Specific Differentiation and Prognostic Significance in Breast Cancers

PubMed Central

Chi, Jen-Tsan; Rodriguez, Edwin H; Wang, Zhen; Nuyten, Dimitry S. A; Mukherjee, Sayan; van de Rijn, Matt; van de Vijver, Marc J.; Hastie, Trevor; Brown, Patrick O

2007-01-01

Smooth muscle is present in a wide variety of anatomical locations, such as blood vessels, various visceral organs, and hair follicles. Contraction of smooth muscle is central to functions as diverse as peristalsis, urination, respiration, and the maintenance of vascular tone. Despite the varied physiological roles of smooth muscle cells (SMCs), we possess only a limited knowledge of the heterogeneity underlying their functional and anatomic specializations. As a step toward understanding the intrinsic differences between SMCs from different anatomical locations, we used DNA microarrays to profile global gene expression patterns in 36 SMC samples from various tissues after propagation under defined conditions in cell culture. Significant variations were found between the cells isolated from blood vessels, bronchi, and visceral organs. Furthermore, pervasive differences were noted within the visceral organ subgroups that appear to reflect the distinct molecular pathways essential for organogenesis as well as those involved in organ-specific contractile and physiological properties. Finally, we sought to understand how this diversity may contribute to SMC-involving pathology. We found that a gene expression signature of the responses of vascular SMCs to serum exposure is associated with a significantly poorer prognosis in human cancers, potentially linking vascular injury response to tumor progression. PMID:17907811

Gene expression programs of human smooth muscle cells: tissue-specific differentiation and prognostic significance in breast cancers.

PubMed

Chi, Jen-Tsan; Rodriguez, Edwin H; Wang, Zhen; Nuyten, Dimitry S A; Mukherjee, Sayan; van de Rijn, Matt; van de Vijver, Marc J; Hastie, Trevor; Brown, Patrick O

2007-09-01

Smooth muscle is present in a wide variety of anatomical locations, such as blood vessels, various visceral organs, and hair follicles. Contraction of smooth muscle is central to functions as diverse as peristalsis, urination, respiration, and the maintenance of vascular tone. Despite the varied physiological roles of smooth muscle cells (SMCs), we possess only a limited knowledge of the heterogeneity underlying their functional and anatomic specializations. As a step toward understanding the intrinsic differences between SMCs from different anatomical locations, we used DNA microarrays to profile global gene expression patterns in 36 SMC samples from various tissues after propagation under defined conditions in cell culture. Significant variations were found between the cells isolated from blood vessels, bronchi, and visceral organs. Furthermore, pervasive differences were noted within the visceral organ subgroups that appear to reflect the distinct molecular pathways essential for organogenesis as well as those involved in organ-specific contractile and physiological properties. Finally, we sought to understand how this diversity may contribute to SMC-involving pathology. We found that a gene expression signature of the responses of vascular SMCs to serum exposure is associated with a significantly poorer prognosis in human cancers, potentially linking vascular injury response to tumor progression.

Palliation of Postintubation Tracheal Stenosis Using Insulation-Tipped Diathermic Knife 2: A Case Report

PubMed Central

Yoon, Seon Bin; Park, Yong Won; Cheon, Mi Ju; Koh, Young Min; Park, Sanghoon; Kim, Se Joong; Lee, Seung Hyeun

2015-01-01

Objective To report the first case of using the insulation-tipped diathermic knife 2 (IT knife-2) for the treatment of postintubation tracheal stenosis. Clinical Presentation and Intervention A 71-year-old female patient with a history of endotracheal intubation 3 years earlier presented with throat discomfort, gross wheezing and dyspnea. Chest imaging and bronchoscopy demonstrated a strand-like tracheal stenosis in the upper trachea. The IT knife-2 was used to treat the patient and the lesion was palliated without complication. Conclusion This case was successfully treated with the IT knife-2 and thus implies a potential usefulness of the IT knife-2 as a new modality for bronchoscopic intervention. PMID:26390388

[Vocal cord paralysis associated with tracheal intubation: incidence, risk analysis, and classification of severity].

PubMed

Kikura, Mutsuhito; Suzuki, Yuji; Itagaki, Taiga; Sato, Tsunehisa; Nishino, Junko

2015-01-01

Vocal cord paralysis after tracheal intubation is rare. It causes severe hoarseness and aspiration, and delays recovery and discharge. Arytenoid cartilage dislocation and recurrent nerve paralysis are main causes of vocal cord paralysis. Physical stimulation of the tracheal tube as well as patient and surgical characteristics also contribute. Vocal cord paralysis occurs in 1 (0.07%) of 1,500 general surgery patients and on the left side in 70% of cases. It is associated with surgery/anesthesia time (two-fold, 3-6 hours; 15-fold, over 6 hours), age (three-fold, over 50 years), and diabetes mellitus or hypertension (two-fold). Symptoms resolve in 2-3 months. In adult cardiovascular surgery, vocal cord paralysis occurs in 1 (0.7-2%) of 50-100 cardiac surgery patients and 1 (8.6-32%) of 3-10 thoracic aortic surgery patients. In pediatric cardiac surgery, vocal cord paralysis occurs in 1 (0.1-0.5%) of 200-1,000 patients. We classified the severity of vocal cord paralysis as I, severe hoarseness; II, aspiration or dysphagia; and III, bilateral vocal cord paralysis, aspiration pneumonia, or the need for tracheal re-intubation or tracheotomy. We discuss the importance of informed consent for the patient and family.

Interleukin-4 activates large-conductance, calciumactivated potassium (BKCa) channels in human airway smooth muscle cells

PubMed Central

Martin, Gilles; O’Connell, Robert J.; Pietrzykowski, Andrzej Z.; Treistman, Steven N.; Ethier, Michael F.; Madison, J. Mark

2014-01-01

Large-conductance, calcium-activated potassium (BKCa) channels are regulated by voltage and near-membrane calcium concentrations and are determinants of membrane potential and excitability in airway smooth muscle cells. Since the T helper–2 (Th2) cytokine, interleukin (IL)-4, is an important mediator of airway inflammation, we investigated whether IL-4 rapidly regulated BKCa activity in normal airway smooth muscle cells. On-cell voltage clamp recordings were made on subconfluent, cultured human bronchial smooth muscle cells (HBSMC). Interleukin-4 (50 ng ml−1), IL-13 (50 ng ml−1) or histamine (10 μm) was added to the bath during the recordings. Immunofluorescence studies with selective antibodies against the α and β1 subunits of BKCa were also performed. Both approaches demonstrated that HBSMC membranes contained large-conductance channels (>200 pS) with both calcium and voltage sensitivity, all of which is characteristic of the BKCa channel. Histamine caused a rapid increase in channel activity, as expected. A new finding was that perfusion with IL-4 stimulated rapid, large increases in BKCa channel activity (77.2 ± 63.3-fold increase, P < 0.05, n = 18). This large potentiation depended on the presence of external calcium. In contrast, IL-13 (50 ng ml−1) had little effect on BKCa channel activity, but inhibited the effect of IL-4. Thus, HBSMC contain functional BKCa channels whose activity is rapidly potentiated by the cytokine, IL-4, but not by IL-13.These findings are consistent with a model in which IL-4 rapidly increases near-membrane calcium concentrations to regulate BKCa activity. PMID:18403443

A Prospective Observational Study of Technical Difficulty With GlideScope-Guided Tracheal Intubation in Children.

PubMed

Zhang, Bin; Gurnaney, Harshad G; Stricker, Paul A; Galvez, Jorge A; Isserman, Rebecca S; Fiadjoe, John E

2018-05-09

The GlideScope Cobalt is one of the most commonly used videolaryngoscopes in pediatric anesthesia. Although visualization of the airway may be superior to direct laryngoscopy, users need to learn a new indirect way to insert the tracheal tube. Learning this indirect approach requires focused practice and instruction. Identifying the specific points during tube placement, during which clinicians struggle, would help with targeted education. We conducted this prospective observational study to determine the incidence and location of technical difficulties using the GlideScope, the success rates of various corrective maneuvers used, and the impact of technical difficulty on success rate. We conducted this observational study at our quaternary pediatric hospital between February 2014 and August 2014. We observed 200 GlideScope-guided intubations and documented key intubation-related outcomes. Inclusion criteria for patients were <6 years of age and elective surgery requiring endotracheal intubation. We documented the number of advancement maneuvers required to intubate the trachea, the location where technical difficulty occurred, the types of maneuvers used to address difficulties, and the tracheal intubation success rate. We used a bias-corrected bootstrapping method with 300 replicates to determine the 95% confidence interval (CI) around the rate of difficulty with an intubation attempt. After excluding attempts by inexperienced clinicians, there were 225 attempts in 187 patients, 58% (131 of 225; bootstrap CI, 51.6%-64.6%]) of the attempts had technical difficulties. Technical difficulty was most likely to occur when inserting the tracheal tube between the plane of the arytenoid cartilages to just beyond the vocal cords: "zone 3." Clockwise rotation of the tube was the most common successful corrective maneuver in zone 3. The overall tracheal intubation success rate was 98% (CI, 95%-99%); however, the first attempt success rate was only 80% (CI, 74%-86%). Patients

Cell surface marker profiling of human tracheal basal cells reveals distinct subpopulations, identifies MST1/MSP as a mitogenic signal, and identifies new biomarkers for lung squamous cell carcinomas.

PubMed

Van de Laar, Emily; Clifford, Monica; Hasenoeder, Stefan; Kim, Bo Ram; Wang, Dennis; Lee, Sharon; Paterson, Josh; Vu, Nancy M; Waddell, Thomas K; Keshavjee, Shaf; Tsao, Ming-Sound; Ailles, Laurie; Moghal, Nadeem

2014-12-31

The large airways of the lungs (trachea and bronchi) are lined with a pseudostratified mucociliary epithelium, which is maintained by stem cells/progenitors within the basal cell compartment. Alterations in basal cell behavior can contribute to large airway diseases including squamous cell carcinomas (SQCCs). Basal cells have traditionally been thought of as a uniform population defined by basolateral position, cuboidal cell shape, and expression of pan-basal cell lineage markers like KRT5 and TP63. While some evidence suggests that basal cells are not all functionally equivalent, few heterogeneously expressed markers have been identified to purify and study subpopulations. In addition, few signaling pathways have been identified that regulate their cell behavior. The goals of this work were to investigate tracheal basal cell diversity and to identify new signaling pathways that regulate basal cell behavior. We used flow cytometry (FACS) to profile cell surface marker expression at a single cell level in primary human tracheal basal cell cultures that maintain stem cell/progenitor activity. FACS results were validated with tissue staining, in silico comparisons with normal basal cell and lung cancer datasets, and an in vitro proliferation assay. We identified 105 surface markers, with 47 markers identifying potential subpopulations. These subpopulations generally fell into more (~ > 13%) or less abundant (~ < 6%) groups. Microarray gene expression profiling supported the heterogeneous expression of these markers in the total population, and immunostaining of large airway tissue suggested that some of these markers are relevant in vivo. 24 markers were enriched in lung SQCCs relative to adenocarcinomas, with four markers having prognostic significance in SQCCs. We also identified 33 signaling receptors, including the MST1R/RON growth factor receptor, whose ligand MST1/MSP was mitogenic for basal cells. This work provides the largest description to date of

Cuff depth and continuous chest auscultation method for determination of tracheal tube insertion depth in nasal intubation: observational study.

PubMed

Ouchi, Kentaro; Sugiyama, Kazuna

2016-04-01

Incorrect endobronchial placement of the tracheal tube can lead to serious complications. Hence, it is necessary to determine the accuracy of tracheal tube positioning. Markers are included on tracheal tubes, in the process of their manufacture, as indicators of approximate intubation depth. In addition, continuous chest auscultation has been used for determining the proper position of the tube. We examined insertion depth using the cuff depth and continuous chest auscultation method (CC method), compared with insertion depth determined by the marker method, to assess the accuracy of these methods. After induction of anesthesia, tracheal intubation was performed in each patient. In the CC method, the depth of tube insertion was measured when the cuff had passed through the glottis, and again when breath sounds changed in quality; the depth of tube insertion was determined from these values. In the marker method, the depth of tube insertion was measured and determined when the marker of the tube had reached the glottis, using insertion depth according to the marker as an index. Insertion depth by the marker method was 26.6 ± 1.2 cm and by the CC method was 28.0 ± 1.2 cm (P < 0.0001). The CC method indicated a significantly greater depth than the marker method. This study determined the safe range of tracheal tube placement. Tube positions determined by the CC method were about 1 cm deeper than those determined by the marker. This information is important to prevent accidental one-lung ventilation and accidental extubation. UMIN No. UMIN000011375.

Prophylactic dexamethasone decreases the incidence of sore throat and hoarseness after tracheal extubation with a double-lumen endobronchial tube.

PubMed

Park, Sang-Hyun; Han, Sung-Hee; Do, Sang-Hwan; Kim, Jung-Won; Rhee, Ka-young; Kim, Jin-Hee

2008-12-01

Postoperative sore throat and hoarseness are common complications after tracheal intubation, particularly after using a double-lumen endobronchial tube (DLT). We conducted a prospective, randomized, double-blind, placebo-controlled study to evaluate the efficacy of dexamethasone for reducing the incidence and severity of postoperative sore throat and hoarseness. One hundred sixty-six patients (aged 18-75 yr) scheduled for thoracic surgery with a DLT were enrolled. Before induction of general anesthesia, 0.1 mg/kg dexamethasone (Group D1), 0.2 mg/kg dexamethasone (Group D2), or a placebo (Group P) were infused i.v. in a double-blind and prospectively randomized manner. Glottic exposure as defined by Cormack and Lehane score, resistance to DLT insertion, number of intubation attempts, time to achieve intubation, and the duration of tracheal intubation were recorded. At 1 h and 24 h after tracheal extubation, the patients were evaluated for sore throat and hoarseness using a visual analog scale (VAS; where 0 = no pain and 100 = worst pain imaginable). One hour after tracheal extubation, the incidence of postoperative sore throat and hoarseness, along with the severity of sore throat were lower in Group D1 (31%, P = 0.021; 11%, P = 0.003; and VAS 12.4, P < 0.001, respectively) and D2 (11%, P = 0.001; 4%, P = 0.001; and VAS 6.6, P < 0.001, respectively) compared with Group P (53%, 36% and VAS 30.9, respectively). Twenty-four hours after tracheal extubation, the incidence of postoperative sore throat, hoarseness, and the severity of sore throat were significantly lower in Group D2 (27%, P = 0.002; 15%, P = 0.001; and VAS 29.9, P < 0.002, respectively) compared with Group D1 (47%, 31%, and VAS = 43.9, respectively) and Group P (57%, 45%, and VAS = 51.3, respectively). There was no complication associated with the dexamethasone administration. The prophylactic use of 0.2 mg/kg of dexamethasone significantly decreases the incidence and severity of sore throat and hoarseness

Anatomical study of the left superior mediastinal lymphatics for tracheal branches of left recurrent laryngeal nerve-preserving mediastinoscope-assisted surgery in esophageal cancer.

PubMed

Nakajima, Yutaka; Tokairin, Yutaka; Nakajima, Yasuaki; Kawada, Kenro; Nagai, Kagami; Yamaguchi, Kumiko; Akita, Keiichi; Kawano, Tatsuyuki

2018-03-01

Curative treatment of esophageal cancer requires meticulous superior mediastinal lymphadenectomy, in addition to esophagectomy, because superior mediastinal lymph node metastases are common in esophageal cancer. When preserving the tracheal branches of the left recurrent laryngeal nerve (RLN), good anatomical understanding is required for confirmation of the positional relationships between the courses of lymphatic vessels, lymph node distribution, and the left RLN and its tracheal branches. We performed a detailed anatomical examination of these relationships. Macroscopic anatomical observation and histological examination was performed on cadavers. In addition to hematoxylin and eosin staining, immunostaining using antipodoplanin antibody D2-40 (podoplanin) was performed to identify the lymphatic vessels. The tracheal branches of the left RLN were clearly observed, but no lymphatic vessels crossing the ventral or dorsal side of the branches were identified either macro-anatomically or histologically. No complex lymphatic network structure straddling the plane composed of tracheal branches of the left RLN was found in the left superior mediastinum. This suggests that dissection of the lymph nodes around the left RLN via the pneumomediastinum method using the left cervical approach may allow preservation of the tracheal branches of the left RLN by maintaining dissection accuracy.

Airflow in Tracheobronchial Tree of Subjects with Tracheal Bronchus Simulated Using CT Image Based Models and CFD Method.

PubMed

Qi, Shouliang; Zhang, Baihua; Yue, Yong; Shen, Jing; Teng, Yueyang; Qian, Wei; Wu, Jianlin

2018-03-01

Tracheal Bronchus (TB) is a rare congenital anomaly characterized by the presence of an abnormal bronchus originating from the trachea or main bronchi and directed toward the upper lobe. The airflow pattern in tracheobronchial trees of TB subjects is critical, but has not been systemically studied. This study proposes to simulate the airflow using CT image based models and the computational fluid dynamics (CFD) method. Six TB subjects and three health controls (HC) are included. After the geometric model of tracheobronchial tree is extracted from CT images, the spatial distribution of velocity, wall pressure, wall shear stress (WSS) is obtained through CFD simulation, and the lobar distribution of air, flow pattern and global pressure drop are investigated. Compared with HC subjects, the main bronchus angle of TB subjects and the variation of volume are large, while the cross-sectional growth rate is small. High airflow velocity, wall pressure, and WSS are observed locally at the tracheal bronchus, but the global patterns of these measures are still similar to those of HC. The ratio of airflow into the tracheal bronchus accounts for 6.6-15.6% of the inhaled airflow, decreasing the ratio to the right upper lobe from 15.7-21.4% (HC) to 4.9-13.6%. The air into tracheal bronchus originates from the right dorsal near-wall region of the trachea. Tracheal bronchus does not change the global pressure drop which is dependent on multiple variables. Though the tracheobronchial trees of TB subjects present individualized features, several commonalities on the structural and airflow characteristics can be revealed. The observed local alternations might provide new insight into the reason of recurrent local infections, cough and acute respiratory distress related to TB.

Marital status is an independent prognostic factor for tracheal cancer patients: an analysis of the SEER database.

PubMed

Li, Mu; Dai, Chen-Yang; Wang, Yu-Ning; Chen, Tao; Wang, Long; Yang, Ping; Xie, Dong; Mao, Rui; Chen, Chang

2016-11-22

Although marital status is an independent prognostic factor in many cancers, its prognostic impact on tracheal cancer has not yet been determined. The goal of this study was to examine the relationship between marital status and survival in patients with tracheal cancer. Compared with unmarried patients (42.67%), married patients (57.33%) had better 5-year OS (25.64% vs. 35.89%, p = 0.009) and 5-year TCSS (44.58% vs. 58.75%, p = 0.004). Results of multivariate analysis indicated that marital status is an independent prognostic factor, with married patients showing better OS (hazard ratio [HR] = 0.78, 95% confidence interval [CI] 0.64-0.95, p = 0.015) and TCSS (HR = 0.70, 95% CI 0.54-0.91, p = 0.008). In addition, subgroup analysis suggested that marital status plays a more important role in the TCSS of patients with non-low-grade malignant tumors (HR = 0.71, 95% CI 0.53-0.93, p = 0.015). We extracted 600 cases from the Surveillance, Epidemiology, and End Results (SEER) database. Variables were compared by Pearson chi-squared test, t-test, log-rank test, and multivariate Cox regression analysis. Overall survival (OS) and tracheal cancer-specific survival (TCSS) were compared between subgroups with different pathologic features and tumor stages. Marital status is an independent prognostic factor for survival in patients with tracheal cancer. For that reason, additional social support may be needed for unmarried patients, especially those with non-low-grade malignant tumors.

Histone deacetylase 8 regulates cortactin deacetylation and contraction in smooth muscle tissues

PubMed Central

Li, Jia; Chen, Shu; Cleary, Rachel A.; Wang, Ruping; Gannon, Olivia J.; Seto, Edward

2014-01-01

Histone deacetylases (HDACs) are a family of enzymes that mediate nucleosomal histone deacetylation and gene expression. Some members of the HDAC family have also been implicated in nonhistone protein deacetylation, which modulates cell-cycle control, differentiation, and cell migration. However, the role of HDACs in smooth muscle contraction is largely unknown. Here, HDAC8 was localized both in the cytoplasm and the nucleus of mouse and human smooth muscle cells. Knockdown of HDAC8 by lentivirus-encoding HDAC8 shRNA inhibited force development in response to acetylcholine. Treatment of smooth muscle tissues with HDAC8 inhibitor XXIV (OSU-HDAC-44) induced relaxation of precontracted smooth muscle tissues. In addition, cortactin is an actin-regulatory protein that undergoes deacetylation during migration of NIH 3T3 cells. In this study, acetylcholine stimulation induced cortactin deacetylation in mouse and human smooth muscle tissues, as evidenced by immunoblot analysis using antibody against acetylated lysine. Knockdown of HDAC8 by RNAi or treatment with the inhibitor attenuated cortactin deacetylation and actin polymerization without affecting myosin activation. Furthermore, expression of a charge-neutralizing cortactin mutant inhibited contraction and actin dynamics during contractile activation. These results suggest a novel mechanism for the regulation of smooth muscle contraction. In response to contractile stimulation, HDAC8 may mediate cortactin deacetylation, which subsequently promotes actin filament polymerization and smooth muscle contraction. PMID:24920679

Chloride channel blockers promote relaxation of TEA-induced contraction in airway smooth muscle

PubMed Central

Yim, Peter D.; Gallos, George; Perez-zoghbi, Jose F.; Trice, Jacquelyn; Zhang, Yi; Siviski, Matthew; Sonett, Joshua; Emala, Charles W.

2014-01-01

Enhanced airway smooth muscle (ASM) contraction is an important component in the pathophysiology of asthma. We have shown that ligand gated chloride channels modulate ASM contractile tone during the maintenance phase of an induced contraction, however the role of chloride flux in depolarization-induced contraction remains incompletely understood. To better understand the role of chloride flux under these conditions, muscle force (human ASM, guinea pig ASM), peripheral small airway luminal area (rat ASM) and airway smooth muscle plasma membrane electrical potentials (human cultured ASM) were measured. We found ex vivo guinea pig airway rings, human ASM strips and small peripheral airways in rat lungs slices relaxed in response to niflumic acid following depolarization-induced contraction induced by K+ channel blockade with tetraethylammonium chloride (TEA). In isolated human airway smooth muscle cells TEA induce depolarization as measured by a fluorescent indicator or whole cell patch clamp and this depolarization was reversed by niflumic acid. These findings demonstrate that ASM depolarization induced contraction is dependent on chloride channel activity. Targeting of chloride channels may be a novel approach to relax hypercontractile airway smooth muscle in bronchoconstrictive disorders. PMID:24662476

Chloride channel blockers promote relaxation of TEA-induced contraction in airway smooth muscle.

PubMed

Yim, Peter D; Gallos, George; Perez-Zoghbi, Jose F; Trice, Jacquelyn; Zhang, Yi; Siviski, Matthew; Sonett, Joshua; Emala, Charles W

2013-01-01

Enhanced airway smooth muscle (ASM) contraction is an important component in the pathophysiology of asthma. We have shown that ligand gated chloride channels modulate ASM contractile tone during the maintenance phase of an induced contraction, however the role of chloride flux in depolarization-induced contraction remains incompletely understood. To better understand the role of chloride flux under these conditions, muscle force (human ASM, guinea pig ASM), peripheral small airway luminal area (rat ASM) and airway smooth muscle plasma membrane electrical potentials (human cultured ASM) were measured. We found ex vivo guinea pig airway rings, human ASM strips and small peripheral airways in rat lungs slices relaxed in response to niflumic acid following depolarization-induced contraction induced by K(+) channel blockade with tetraethylammonium chloride (TEA). In isolated human airway smooth muscle cells TEA induce depolarization as measured by a fluorescent indicator or whole cell patch clamp and this depolarization was reversed by niflumic acid. These findings demonstrate that ASM depolarization induced contraction is dependent on chloride channel activity. Targeting of chloride channels may be a novel approach to relax hypercontractile airway smooth muscle in bronchoconstrictive disorders.

Hyperphosphatemia induces cellular senescence in human aorta smooth muscle cells through integrin linked kinase (ILK) up-regulation.

PubMed

Troyano, Nuria; Nogal, María Del; Mora, Inés; Diaz-Naves, Manuel; Lopez-Carrillo, Natalia; Sosa, Patricia; Rodriguez-Puyol, Diego; Olmos, Gemma; Ruiz-Torres, María P

2015-12-01

Aging is conditioned by genetic and environmental factors. Hyperphosphatemia is related to some pathologies, affecting to vascular cells behavior. This work analyze whether high concentration of extracellular phosphate induces vascular smooth muscle cells senescence, exploring the intracellular mechanisms and highlighting the in vivo relevance of this phenomenon. Human aortic smooth muscle cells treated with β-Glycerophosphate (BGP, 10mM) suffered cellular senescence by increasing p53, p21 and p16 expression and the senescence associated β-galactosidase activity. In parallel, BGP induced ILK overexpression, dependent on the IGF-1 receptor activation, and oxidative stress. Down-regulating ILK expression prevented BGP-induced senescence and oxidative stress. Aortic rings from young rats treated with 10mM BGP for 48h, showed increased p53, p16 and ILK expression and SA-β-gal activity. Seven/eight nephrectomized rats feeding a hyperphosphatemic diet and fifteenth- month old mice showed hyperphosphatemia and aortic ILK, p53 and p16 expression. In conclusion, we demonstrated that high extracellular concentration of phosphate induced senescence in cultured smooth muscle through the activation of IGF-1 receptor and ILK overexpression and provided solid evidences for the in vivo relevance of these results since aged animals showed high levels of serum phosphate linked to increased expression of ILK and senescence genes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Life-Saving Esophageal Intubation in Neonate With Undiagnosed Tracheal Agenesis: A Case Report.

PubMed

Sattler, Christopher; Chiao, Franklin; Stein, David; Murphy, Denise

2017-07-01

A 3-day-old, 2.2-kg former 34-week premature infant with imperforate anus required loop ileostomy surgery. At delivery, the child had respiratory distress. Endotracheal intubation was "confirmed" by detection of exhaled carbon dioxide with a Pedi-Cap (Covidien, Dublin, Ireland) and subsequent chest x-ray. On arrival to the operating room, the pulse oximeter reading was 100% despite a large leak around the endotracheal tube and high-airway pressures. Packing the throat reduced the leak and increased the tidal volume. Intraoperative bronchospasm occurred during the surgery. On postoperative day 1, fiberoptic examination by an otolaryngologist revealed esophageal intubation and the absence of laryngeal opening. Subsequent computed tomography scan revealed Floyd type II tracheal agenesis. To our knowledge, this is the only case of tracheal agenesis diagnosed after a non-airway related procedure. We discussed how the diagnosis was missed.

Nitinol stents in the treatment of benign proximal tracheal stenosis or tracheomalacia.

PubMed

Isa, A Y; Macandie, C; Irvine, B W

2006-01-01

Nitinol stents have been used in the treatment of benign tracheal stenosis. A retrospective review of five patients treated at Stobhill Hospital over the last six and a half years is presented. Age at presentation ranged from 17 to 76 years. The minimum follow-up period was 23 months and the maximum was 78 months. All our patients were successfully decannulated, with none requiring recannulation. Four patients developed granulation tissue related to the stent at intervals ranging from three weeks to 41 months post stenting. Topical mitomycin C application has been useful after resection of granulations using the carbon dioxide (CO2) laser. Stent migration occurred in one patient three weeks after insertion. Nitinol stents are easy to insert and effective in the treatment of tracheal stenosis, but can have associated morbidity. Their use should be considered carefully, as insertion should be regarded as permanent. Publications reporting experience and outcome with the use of Nitinol stents in the trachea are reviewed.

Effects of the dual TP receptor antagonist and thromboxane synthase inhibitor EV-077 on human endothelial and vascular smooth muscle cells.

PubMed

Petri, Marcelo H; Tellier, Céline; Michiels, Carine; Ellertsen, Ingvill; Dogné, Jean-Michel; Bäck, Magnus

2013-11-15

The prothrombotic mediator thromboxane A2 is derived from arachidonic acid metabolism through the cyclooxygenase and thromboxane synthase pathways, and transduces its effect through the thromboxane prostanoid (TP) receptor. The aim of this study was to determine the effect of the TP receptor antagonist and thromboxane synthase inhibitor EV-077 on inflammatory markers in human umbilical vein endothelial cells and on human coronary artery smooth muscle cell proliferation. To this end, mRNA levels of different proinflammatory mediators were studied by real time quantitative PCR, supernatants were analyzed by enzyme immune assay, and cell proliferation was assessed using WST-1. EV-077 significantly decreased mRNA levels of ICAM-1 and PTX3 after TNFα incubation, whereas concentrations of 6-keto PGF1α in supernatants of endothelial cells incubated with TNFα were significantly increased after EV-077 treatment. Although U46619 did not alter coronary artery smooth muscle cell proliferation, this thromboxane mimetic enhanced the proliferation induced by serum, insulin and growth factors, which was significantly inhibited by EV-077. In conclusion, EV-077 inhibited TNFα-induced endothelial inflammation and reduced the enhancement of smooth muscle cell proliferation induced by a thromboxane mimetic, supporting that the thromboxane pathway may be associated with early atherosclerosis in terms of endothelial dysfunction and vascular hypertrophy. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Secondary Metabolites in Allergic Plant Pollen Samples Modulate Afferent Neurons and Murine Tracheal Rings.

PubMed

Božičević, Alen; De Mieri, Maria; Nassenstein, Christina; Wiegand, Silke; Hamburger, Matthias

2017-11-22

Plant pollens are strong airborne elicitors of asthma. Their proteinaceous allergens have been studied intensively, but little is known about a possible contribution of pollen secondary metabolites to the nonallergic exacerbation of asthma. Pollen samples originating from 30 plant species were analyzed by HPLC coupled to PDA, ESIMS, and ELSD detectors and off-line NMR spectroscopy. Polyamine conjugates, flavonoids, and sesquiterpene lactones were identified. Polyamine conjugates were characteristic of all Asteraceae species. The presence of sesquiterpene lactones in Asteraceae pollen varied between species and pollen lots. All plant pollen, including those from non-Asteraceae species, contained to some extent electrophiles as determined by their reaction with N-acetyl-l-cysteine. Selected pollen extracts and pure compounds were tested in murine afferent neurons and in murine tracheal preparations. Tetrahydrofuran extracts of Ambrosia artemisiifolia and Ambrosia psilostachya pollen and a mixture of sesquiterpene lactones coronopilin/parthenin increased the intracellular Ca 2+ concentration in 15%, 32%, and 37% of cinnamaldehyde-responsive neurons, respectively. In organ bath experiments, only the sesquiterpene lactones tested induced a weak dilatation of naïve tracheas and strongly lowered the maximal methacholine-induced tracheal constriction. A tetrahydrofuran extract of A. psilostachya and coronopilin/parthenin led to a time-dependent relaxation of the methacholine-preconstricted trachea. These results provide the first evidence for a potential role of pollen secondary metabolites in the modulation of the tracheal tone.

Evaluation of a rat tracheal epithelial cell culture assay system to identify respiratory carcinogens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steele, V.E.; Arnold, J.T.; Arnold, J.V.

1989-01-01

To evaluate a short-term epithelial cell assay system to detect respiratory carcinogens, primary cultures of rat tracheal epithelial cells were exposed to a series of 17 compounds and scored for morphologically transformed cell colonies 28 days later. The test compounds included known carcinogens and noncarcinogens in volatile or liquid form. Tracheal epithelial cells were isolate from F344 rats, plated onto collagen-coated dishes, and exposed to the test compounds on day 1 for 24 hours. At day 30 the cultures were fixed, stained, and scored for colonies having a density greater than 1,300 cells/mm{sup 2}. With standardized protocols, such colonies aremore » very infrequent in media and solvent control cultures. Concentration levels for each chemical were chosen over a range from nontoxic to toxic levels. Highly positive compounds in this assay included benzo(a)pyrene, benzo(l)aceanthrylene, 3-methylcholanthrene, and formaldehyde. Compounds which were negative in this assay included pyrene, benzo(e)pyrene, and 4-nitroquinoline-N-oxide. Examining the concordance of in vitro results with whole animal carcinogenesis studies revealed an accuracy of 88% with one false-positive and one false-negative compound. The results of these studies indicate that the rat tracheal epithelial cell assay may be useful in identifying potential respiratory carcinogens in our environment.« less

Tracheal stricture and fistula: management with a barbed silicone-covered retrievable expandable nitinol stent.

PubMed

Kim, Yong Hee; Shin, Ji Hoon; Song, Ho-Young; Kim, Jin Hyoung

2010-02-01

The purpose of this study was to evaluate the safety and effectiveness of a barbed silicone-covered retrievable expandable nitinol stent in preventing stent migration in patients with tracheal strictures or fistulas. Under fluoroscopic guidance, barbed silicone-covered retrievable expandable nitinol stents were placed in 15 patients with tracheal strictures, two patients with fistulas, two patients with combined strictures and fistulas, and one patient with variable extrathoracic airway obstruction. The three pairs of barbs were attached to the external stent surface at the middle of the stent at equal intervals. Technical success, improvement in respiratory status, complications, and related interventions were evaluated. The technical success rate was 100%, and respiratory status improved or the fistula closed in all 20 patients. Complications included sputum retention (three patients), tumor overgrowth (three patients), pain (one patient), and granulation tissue formation (one patient). No stent migration occurred, even in the three patients without fixed strictures. Four stents subsequently were removed because of complications, and one stent was removed because the patient's condition improved. Stent removal was not difficult and was uneventful. The silicone membranes and barbs of the removed stents were intact. Use of a barbed silicone-covered retrievable expandable nitinol stent relieves dyspnea and facilitates fistula closure in patients with benign or malignant tracheal strictures or fistulas. The barbed design of the stent is important in preventing migration.

Robust Smoothing: Smoothing Parameter Selection and Applications to Fluorescence Spectroscopy∂

PubMed Central

Lee, Jong Soo; Cox, Dennis D.

2009-01-01

Fluorescence spectroscopy has emerged in recent years as an effective way to detect cervical cancer. Investigation of the data preprocessing stage uncovered a need for a robust smoothing to extract the signal from the noise. Various robust smoothing methods for estimating fluorescence emission spectra are compared and data driven methods for the selection of smoothing parameter are suggested. The methods currently implemented in R for smoothing parameter selection proved to be unsatisfactory, and a computationally efficient procedure that approximates robust leave-one-out cross validation is presented. PMID:20729976

[The current views of the problem of the plastic correction of the laryngo-tracheal defects in the patients presenting with combined laryngeal stenoses].

PubMed

Selezneva, L V

2017-01-01

The present review of the literature is designed to analyze the currently available methods for the plastic correction of the laryngo-tracheal defects in the patients presenting with combined laryngeal stenoses at the concluding stage of their medical rehabilitation. We looked through 56 literature sources including 28 publications of the foreign authors. The different approaches to the plastic correction of the laryngo-tracheal defects have been critically considered with special reference to their advantages and disadvantages. The importance of the problem under consideration arises from the necessity of the search for the new methods of plastic correction of the laryngo-tracheal defects.

The platelet-derived growth factor receptor/STAT3 signaling pathway regulates the phenotypic transition of corpus cavernosum smooth muscle in rats.

PubMed

Yan, Jun-Feng; Huang, Wen-Jie; Zhao, Jian-Feng; Fu, Hui-Ying; Zhang, Gao-Yue; Huang, Xiao-Jun; Lv, Bo-Dong

2017-01-01

Erectile dysfunction (ED) is a common clinical disease that is difficult to treat. We previously found that hypoxia modulates the phenotype of primary corpus cavernosum smooth muscle cells (CCSMCs) in rats, but the underlying molecular mechanism is still unknown. Platelet-derived growth factor receptor (PDGFR)-related signaling pathways are correlated with cell phenotypic transition, but research has been focused more on vascular smooth muscle and tracheal smooth muscle and less on CCSMCs. Here, we investigated the role of PDGFR-related signaling pathways in penile CCSMCs, which were successfully isolated from rats and cultured in vitro. PDGF-BB at 5, 10, or 20 ng/ml altered CCSMC morphology from the original elongated, spindle shape to a broader shape and promoted the synthetic phenotype and expression of the related proteins vimentin and collagen-I, while inhibiting the contractile phenotype and expression of the related proteins smooth muscle (SM) α-actin (α-SMA) and desmin. Inhibition of PDGFR activity via siRNA or the PDGFR inhibitor crenolanib inhibited vimentin and collagen-I expression, increased α-SMA and desmin expression, and considerably inhibited serine-threonine protein kinase (AKT) and signal transducer and activator of transcription 3 (STAT3) phosphorylation. STAT3 knockdown promoted the contractile phenotype, inhibited vimentin and collagen-I expression, and increased α-SMA and desmin expression, whereas AKT knockdown did not affect phenotype-associated proteins. STAT3 overexpression in CCSMC cells weakened the suppressive effect of PDGFR inhibition on the morphology and phenotypic transformation induced by PDGF-BB. Through activation of the PDGFR/STAT3 signaling pathway, PDGF promoted the synthetic phenotype transition; thus, regulation of this pathway might contribute to ED therapy.

Tidal Volume Estimation Using the Blanket Fractal Dimension of the Tracheal Sounds Acquired by Smartphone

PubMed Central

Reljin, Natasa; Reyes, Bersain A.; Chon, Ki H.

2015-01-01

In this paper, we propose the use of blanket fractal dimension (BFD) to estimate the tidal volume from smartphone-acquired tracheal sounds. We collected tracheal sounds with a Samsung Galaxy S4 smartphone, from five (N = 5) healthy volunteers. Each volunteer performed the experiment six times; first to obtain linear and exponential fitting models, and then to fit new data onto the existing models. Thus, the total number of recordings was 30. The estimated volumes were compared to the true values, obtained with a Respitrace system, which was considered as a reference. Since Shannon entropy (SE) is frequently used as a feature in tracheal sound analyses, we estimated the tidal volume from the same sounds by using SE as well. The evaluation of the performed estimation, using BFD and SE methods, was quantified by the normalized root-mean-squared error (NRMSE). The results show that the BFD outperformed the SE (at least twice smaller NRMSE was obtained). The smallest NRMSE error of 15.877% ± 9.246% (mean ± standard deviation) was obtained with the BFD and exponential model. In addition, it was shown that the fitting curves calculated during the first day of experiments could be successfully used for at least the five following days. PMID:25923929

Tidal volume estimation using the blanket fractal dimension of the tracheal sounds acquired by smartphone.

PubMed

Reljin, Natasa; Reyes, Bersain A; Chon, Ki H

2015-04-27

In this paper, we propose the use of blanket fractal dimension (BFD) to estimate the tidal volume from smartphone-acquired tracheal sounds. We collected tracheal sounds with a Samsung Galaxy S4 smartphone, from five (N = 5) healthy volunteers. Each volunteer performed the experiment six times; first to obtain linear and exponential fitting models, and then to fit new data onto the existing models. Thus, the total number of recordings was 30. The estimated volumes were compared to the true values, obtained with a Respitrace system, which was considered as a reference. Since Shannon entropy (SE) is frequently used as a feature in tracheal sound analyses, we estimated the tidal volume from the same sounds by using SE as well. The evaluation of the performed estimation, using BFD and SE methods, was quantified by the normalized root-mean-squared error (NRMSE). The results show that the BFD outperformed the SE (at least twice smaller NRMSE was obtained). The smallest NRMSE error of 15.877% ± 9.246% (mean ± standard deviation) was obtained with the BFD and exponential model. In addition, it was shown that the fitting curves calculated during the first day of experiments could be successfully used for at least the five following days.

Tropism and Infectivity of Influenza Virus, Including Highly Pathogenic Avian H5N1 Virus, in Ferret Tracheal Differentiated Primary Epithelial Cell Cultures

PubMed Central

Zeng, Hui; Goldsmith, Cynthia S.; Maines, Taronna R.; Belser, Jessica A.; Gustin, Kortney M.; Pekosz, Andrew; Zaki, Sherif R.; Katz, Jacqueline M.

2013-01-01

Tropism and adaptation of influenza viruses to new hosts is partly dependent on the distribution of the sialic acid (SA) receptors to which the viral hemagglutinin (HA) binds. Ferrets have been established as a valuable in vivo model of influenza virus pathogenesis and transmission because of similarities to humans in the distribution of HA receptors and in clinical signs of infection. In this study, we developed a ferret tracheal differentiated primary epithelial cell culture model that consisted of a layered epithelium structure with ciliated and nonciliated cells on its apical surface. We found that human-like (α2,6-linked) receptors predominated on ciliated cells, whereas avian-like (α2,3-linked) receptors, which were less abundant, were presented on nonciliated cells. When we compared the tropism and infectivity of three human (H1 and H3) and two avian (H1 and H5) influenza viruses, we observed that the human influenza viruses primarily infected ciliated cells and replicated efficiently, whereas a highly pathogenic avian H5N1 virus (A/Vietnam/1203/2004) replicated efficiently within nonciliated cells despite a low initial infection rate. Furthermore, compared to other influenza viruses tested, VN/1203 virus replicated more efficiently in cells isolated from the lower trachea and at a higher temperature (37°C) compared to a lower temperature (33°C). VN/1203 virus infection also induced higher levels of immune mediator genes and cell death, and virus was recovered from the basolateral side of the cell monolayer. This ferret tracheal differentiated primary epithelial cell culture system provides a valuable in vitro model for studying cellular tropism, infectivity, and the pathogenesis of influenza viruses. PMID:23255802

Tropism and infectivity of influenza virus, including highly pathogenic avian H5N1 virus, in ferret tracheal differentiated primary epithelial cell cultures.

PubMed

Zeng, Hui; Goldsmith, Cynthia S; Maines, Taronna R; Belser, Jessica A; Gustin, Kortney M; Pekosz, Andrew; Zaki, Sherif R; Katz, Jacqueline M; Tumpey, Terrence M

2013-03-01

Tropism and adaptation of influenza viruses to new hosts is partly dependent on the distribution of the sialic acid (SA) receptors to which the viral hemagglutinin (HA) binds. Ferrets have been established as a valuable in vivo model of influenza virus pathogenesis and transmission because of similarities to humans in the distribution of HA receptors and in clinical signs of infection. In this study, we developed a ferret tracheal differentiated primary epithelial cell culture model that consisted of a layered epithelium structure with ciliated and nonciliated cells on its apical surface. We found that human-like (α2,6-linked) receptors predominated on ciliated cells, whereas avian-like (α2,3-linked) receptors, which were less abundant, were presented on nonciliated cells. When we compared the tropism and infectivity of three human (H1 and H3) and two avian (H1 and H5) influenza viruses, we observed that the human influenza viruses primarily infected ciliated cells and replicated efficiently, whereas a highly pathogenic avian H5N1 virus (A/Vietnam/1203/2004) replicated efficiently within nonciliated cells despite a low initial infection rate. Furthermore, compared to other influenza viruses tested, VN/1203 virus replicated more efficiently in cells isolated from the lower trachea and at a higher temperature (37°C) compared to a lower temperature (33°C). VN/1203 virus infection also induced higher levels of immune mediator genes and cell death, and virus was recovered from the basolateral side of the cell monolayer. This ferret tracheal differentiated primary epithelial cell culture system provides a valuable in vitro model for studying cellular tropism, infectivity, and the pathogenesis of influenza viruses.

PKC-dependent regulation of Kv7.5 channels by the bronchoconstrictor histamine in human airway smooth muscle cells.

PubMed

Haick, Jennifer M; Brueggemann, Lioubov I; Cribbs, Leanne L; Denning, Mitchell F; Schwartz, Jeffrey; Byron, Kenneth L

2017-06-01

Kv7 potassium channels have recently been found to be expressed and functionally important for relaxation of airway smooth muscle. Previous research suggests that native Kv7 currents are inhibited following treatment of freshly isolated airway smooth muscle cells with bronchoconstrictor agonists, and in intact airways inhibition of Kv7 channels is sufficient to induce bronchiolar constriction. However, the mechanism by which Kv7 currents are inhibited by bronchoconstrictor agonists has yet to be elucidated. In the present study, native Kv7 currents in cultured human trachealis smooth muscle cells (HTSMCs) were observed to be inhibited upon treatment with histamine; inhibition of Kv7 currents was associated with membrane depolarization and an increase in cytosolic Ca 2+ ([Ca 2+ ] cyt ). The latter response was inhibited by verapamil, a blocker of L-type voltage-sensitive Ca 2+ channels (VSCCs). Protein kinase C (PKC) has been implicated as a mediator of bronchoconstrictor actions, although the targets of PKC are not clearly established. We found that histamine treatment significantly and dose-dependently suppressed currents through overexpressed wild-type human Kv7.5 (hKv7.5) channels in cultured HTSMCs, and this effect was inhibited by the PKC inhibitor Ro-31-8220 (3 µM). The PKC-dependent suppression of hKv7.5 currents corresponded with a PKC-dependent increase in hKv7.5 channel phosphorylation. Knocking down or inhibiting PKCα, or mutating hKv7.5 serine 441 to alanine, abolished the inhibitory effects of histamine on hKv7.5 currents. These findings provide the first evidence linking PKC activation to suppression of Kv7 currents, membrane depolarization, and Ca 2+ influx via L-type VSCCs as a mechanism for histamine-induced bronchoconstriction. Copyright © 2017 the American Physiological Society.

Diamond Smoothing Tools

NASA Technical Reports Server (NTRS)

Voronov, Oleg

2007-01-01

Diamond smoothing tools have been proposed for use in conjunction with diamond cutting tools that are used in many finish-machining operations. Diamond machining (including finishing) is often used, for example, in fabrication of precise metal mirrors. A diamond smoothing tool according to the proposal would have a smooth spherical surface. For a given finish machining operation, the smoothing tool would be mounted next to the cutting tool. The smoothing tool would slide on the machined surface left behind by the cutting tool, plastically deforming the surface material and thereby reducing the roughness of the surface, closing microcracks and otherwise generally reducing or eliminating microscopic surface and subsurface defects, and increasing the microhardness of the surface layer. It has been estimated that if smoothing tools of this type were used in conjunction with cutting tools on sufficiently precise lathes, it would be possible to reduce the roughness of machined surfaces to as little as 3 nm. A tool according to the proposal would consist of a smoothing insert in a metal holder. The smoothing insert would be made from a diamond/metal functionally graded composite rod preform, which, in turn, would be made by sintering together a bulk single-crystal or polycrystalline diamond, a diamond powder, and a metallic alloy at high pressure. To form the spherical smoothing tip, the diamond end of the preform would be subjected to flat grinding, conical grinding, spherical grinding using diamond wheels, and finally spherical polishing and/or buffing using diamond powders. If the diamond were a single crystal, then it would be crystallographically oriented, relative to the machining motion, to minimize its wear and maximize its hardness. Spherically polished diamonds could also be useful for purposes other than smoothing in finish machining: They would likely also be suitable for use as heat-resistant, wear-resistant, unlubricated sliding-fit bearing inserts.

Collagen-conjugated tracheal prosthesis tested in dogs without omental wrapping and silicone stenting.

PubMed

Liu, Yu; Lu, Tao; Zhang, Yongxing; Qiao, Yulei; Xi, Junjie; Wang, Qun

2016-11-01

Artificial tracheas fabricated from collagen-conjugated mesh appear to overcome fatal postoperative complications, namely anastomotic dehiscence and prosthesis dislocation. Such prostheses are incorporated by host tissue, provided they are wrapped in omentum (necessitating an additional abdominal procedure) and a silicone tube is used as a stent (to be extracted several weeks postoperatively). To mitigate related host impact (i.e. injury, pain and distress), we investigated the feasibility of implanting this type of tracheal prosthesis (∼5 cm in length) alone, without omental wrapping and use of a silicone stent. Porous-type tracheal prostheses that were reinforced with a continuous polypropylene spiral and sealed by collagen sponge from porcine skin replaced segments of cervical trachea (∼5 cm long) in 10 dogs through the method of telescopic anastomosis. Omental wrapping and silicone stent placement were omitted. Postoperatively, bronchoscopic examination was performed periodically. When dogs died or were sacrificed, tracheal prostheses were harvested for haematoxylin and eosin staining and electron microscopic scanning of luminal surface conditions. With the exception of one death from an anaesthesia-related incident during fibre-optic bronchoscopy (postsurgical week 1), nine dogs survived uneventfully (until sacrifice), without prosthesis dislocation or anastomotic dehiscence. The longest observation period was 2 years and 8 months. Bronchoscopic examination revealed that no stenosis or local infection was evident in the prostheses of five dogs. Moderate (n = 2) and slight (n = 2) stenoses were observed in the other four animals. All four animals survived for a long time, without dyspnoea or stridor. Histological examination showed that partial inner surface of the artificial trachea was covered with the pseudostratified ciliated epithelium. Regeneration of ciliated epithelium was also confirmed by scanning electron microscopy. This pilot study revealed

Pressure and volume changes of tracheal tube cuff following inflation with various inflating agents during nitrous oxide anesthesia.

PubMed

Bajaj, Pramila; Nanda, Rajan; Goyal, Pradeep KR

2004-10-01

The study was designed to investigate the changes in pressure and volume of a tracheal tube-cuff inflated with air, mixture of N2O + O2, saline and 4% lidocaine during nitrous oxide anesthesia. This study was conducted in 80 patients (33 male & 47 female). The pressure and volume of a tracheal tube cuff increased with air, decreased with mixture of N2O + O2 and almost remained the same with saline and 4% lidocaine. The complications were more in the air group.

Evidence Supports Tradition: The in Vitro Effects of Roman Chamomile on Smooth Muscles.

PubMed

Sándor, Zsolt; Mottaghipisheh, Javad; Veres, Katalin; Hohmann, Judit; Bencsik, Tímea; Horváth, Attila; Kelemen, Dezső; Papp, Róbert; Barthó, Loránd; Csupor, Dezső

2018-01-01

The dried flowers of Chamaemelum nobile (L.) All. have been used in traditional medicine for different conditions related to the spasm of the gastrointestinal system. However, there have been no experimental studies to support the smooth muscle relaxant effect of this plant. The aim of our research was to assess the effects of the hydroethanolic extract of Roman chamomile, its fractions, four of its flavonoids (apigenin, luteolin, hispidulin, and eupafolin), and its essential oil on smooth muscles. The phytochemical compositions of the extract and its fractions were characterized and quantified by HPLC-DAD, the essential oil was characterized by GC and GC-MS. Neuronally mediated and smooth muscle effects were tested in isolated organ bath experiments on guinea pig, rat, and human smooth muscle preparations. The crude herbal extract induced an immediate, moderate, and transient contraction of guinea pig ileum via the activation of cholinergic neurons of the gut wall. Purinoceptor and serotonin receptor antagonists did not influence this effect. The more sustained relaxant effect of the extract, measured after pre-contraction of the preparations, was remarkable and was not affected by an adrenergic beta receptor antagonist. The smooth muscle-relaxant activity was found to be associated with the flavonoid content of the fractions. The essential oil showed only the relaxant effect, but no contracting activity. The smooth muscle-relaxant effect was also detected on rat gastrointestinal tissues, as well as on strip preparations of human small intestine. These results suggest that Roman chamomile extract has a direct and prolonged smooth muscle-relaxant effect on guinea pig ileum which is related to its flavonoid content. In some preparations, a transient stimulation of enteric cholinergic motoneurons was also detected. The essential oil also had a remarkable smooth muscle relaxant effect in this setting. Similar relaxant effects were also detected on other visceral

New stent surface materials: the impact of polymer-dependent interactions of human endothelial cells, smooth muscle cells, and platelets.

PubMed

Busch, Raila; Strohbach, Anne; Rethfeldt, Stefanie; Walz, Simon; Busch, Mathias; Petersen, Svea; Felix, Stephan; Sternberg, Katrin

2014-02-01

Despite the development of new coronary stent technologies, in-stent restenosis and stent thrombosis are still clinically relevant. Interactions of blood and tissue cells with the implanted material may represent an important cause of these side effects. We hypothesize material-dependent interaction of blood and tissue cells. The aim of this study is accordingly to investigate the impact of vascular endothelial cells, smooth muscle cells and platelets with various biodegradable polymers to identify a stent coating or platform material that demonstrates excellent endothelial-cell-supportive and non-thrombogenic properties. Human umbilical venous endothelial cells, human coronary arterial endothelial cells and human coronary arterial smooth muscle cells were cultivated on the surfaces of two established biostable polymers used for drug-eluting stents, namely poly(ethylene-co-vinylacetate) (PEVA) and poly(butyl methacrylate) (PBMA). We compared these polymers to new biodegradable polyesters poly(l-lactide) (PLLA), poly(3-hydroxybutyrate) (P(3HB)), poly(4-hydroxybutyrate) (P(4HB)) and a polymeric blend of PLLA/P(4HB) in a ratio of 78/22% (w/w). Biocompatibility tests were performed under static and dynamic conditions. Measurement of cell proliferation, viability, glycocalix width, eNOS and PECAM-1 mRNA expression revealed strong material dependency among the six polymer samples investigated. Only the polymeric blend of PLLA/P(4HB) achieved excellent endothelial markers of biocompatibility. Data show that PLLA and P(4HB) tend to a more thrombotic response, whereas the polymer blend is characterized by a lower thrombotic potential. These data demonstrate material-dependent endothelialization, smooth muscle cell growth and thrombogenicity. Although polymers such as PEVA and PBMA are already commonly used for vascular implants, they did not sufficiently meet the criteria for biocompatibility. The investigated biodegradable polymeric blend PLLA/P(4HB) evidently represents a

Estrogen receptor beta signaling inhibits PDGF induced human airway smooth muscle proliferation.

PubMed

Ambhore, Nilesh Sudhakar; Katragadda, Rathnavali; Raju Kalidhindi, Rama Satyanarayana; Thompson, Michael A; Pabelick, Christina M; Prakash, Y S; Sathish, Venkatachalem

2018-04-20

Airway smooth muscle (ASM) cell hyperplasia driven by persistent inflammation is a hallmark feature of remodeling in asthma. Sex steroid signaling in the lungs is of considerable interest, given epidemiological data showing more asthma in pre-menopausal women and aging men. Our previous studies demonstrated that estrogen receptor (ER) expression increases in asthmatic human ASM; however, very limited data are available regarding differential roles of ERα vs. ERβ isoforms in human ASM cell proliferation. In this study, we evaluated the effect of selective ERα and ERβ modulators on platelet-derived growth factor (PDGF)-stimulated ASM proliferation and the mechanisms involved. Asthmatic and non-asthmatic primary human ASM cells were treated with PDGF, 17β-estradiol, ERα-agonist and/or ERβ-agonist and/or G-protein-coupled estrogen receptor 30 (GPR30/GPER) agonist and proliferation was measured using MTT and CyQuant assays followed by cell cycle analysis. Transfection of small interfering RNA (siRNA) ERα and ERβ significantly altered the human ASM proliferation. The specificity of siRNA transfection was confirmed by Western blot analysis. Gene and protein expression of cell cycle-related antigens (PCNA and Ki67) and C/EBP were measured by RT-PCR and Western analysis, along with cell signaling proteins. PDGF significantly increased ASM proliferation in non-asthmatic and asthmatic cells. Treatment with PPT showed no significant effect on PDGF-induced proliferation, whereas WAY interestingly suppressed proliferation via inhibition of ERK1/2, Akt, and p38 signaling. PDGF-induced gene expression of PCNA, Ki67 and C/EBP in human ASM was significantly lower in cells pre-treated with WAY. Furthermore, WAY also inhibited PDGF-activated PCNA, C/EBP, cyclin-D1, and cyclin-E. Overall, we demonstrate ER isoform-specific signaling in the context of ASM proliferation. Activation of ERβ can diminish remodeling in human ASM by inhibiting pro-proliferative signaling pathways

P2X1 receptor-mediated inhibition of the proliferation of human coronary smooth muscle cells involving the transcription factor NR4A1.

PubMed

Hinze, Annette Viktoria; Mayer, Peter; Harst, Anja; von Kügelgen, Ivar

2013-12-01

Adenine nucleotides acting at P2X1 receptors are potent vasoconstrictors. Recently, we demonstrated that activation of adenosine A2B receptors on human coronary smooth muscle cells inhibits cell proliferation by the induction of the nuclear receptor subfamily 4, group A, member 1 (NR4A1; alternative notation Nur77). In the present study, we searched for long-term effects mediated by P2X1 receptors by analyzing receptor-mediated changes in cell proliferation and in the expression of NR4A1. Cultured human coronary smooth muscle cells were treated with selective receptor ligands. Effects on proliferation were determined by counting cells and measuring changes in impedance. The induction of transcription factors was assessed by qPCR. The P2X receptor agonist α,β-methylene-ATP and its analog β,γ-methylene-ATP inhibited cell proliferation by about 50 % after 5 days in culture with half-maximal concentrations of 0.3 and 0.08 μM, respectively. The effects were abolished or markedly attenuated by the P2X1 receptor antagonist NF449 (carbonylbis-imino-benzene-triylbis-(carbonylimino)tetrakis-benzene-1,3-disulfonic acid; 100 nM and 1 μM). α,β-methylene-ATP and β,γ-methylene-ATP applied for 30 min to 4 h increased the expression of NR4A1; NF449 blocked or attenuated this effect. Small interfering RNA directed against NR4A1 diminished the antiproliferative effects of α,β-methylene-ATP and β,γ-methylene-ATP. α,β-methylene-ATP (0.1 to 30 μM) decreased migration of cultured human coronary smooth muscle cells in a chamber measuring changes in impedance; NF449 blocked the effect. In conclusion, our results demonstrate for the first time that adenine nucleotides acting at P2X1 receptors inhibit the proliferation of human coronary smooth muscle cells via the induction of the early gene NR4A1.

[Difficult fiberoptic tracheal intubation in 1 month-old infant with Treacher Collins Syndrome].

PubMed

Fuentes, Ricardo; De la Cuadra, Juan Carlos; Lacassie, Hector; González, Alejandro

Neonates and small infants with craniofacial malformation may be very difficult or impossible to mask ventilate or intubate. We would like to report the fiberoptic intubation of a small infant with Treacher Collins Syndrome using the technique described by Ellis et al. An one month-old infant with Treacher Collins Syndrome was scheduled for mandibular surgery under general endotracheal anesthesia. Direct laryngoscopy for oral intubation failed to reveal the glottis. Fiberoptic intubation using nasal approach and using oral approach through a 1.5 size laryngeal mask airway were performed; however, both approach failed because the fiberscope loaded with a one 3.5mm ID uncuffed tube was stuck inside the nasal cavity or inside the laryngeal mask airway respectively. Therefore, the laryngeal mask airway was keep in place and the fiberoptic intubation technique described by Ellis et al. was planned: the tracheal tube with the 15mm adapter removed was loaded proximally over the fiberscope; the fiberscope was advanced under video-screen visualization into the trachea; the laryngeal mask airway was removed, leaving the fiberscope in place; the tracheal tube was passed completely through the laryngeal mask airway and advanced down over the fiberscope into the trachea; the fiberscope was removed and the 15mm adapter was reattached to the tracheal tube. The fiberoptic intubation method through a laryngeal mask airway described by Ellis et al. can be successfully used in small infants with Treacher Collins Syndrome. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Improving smoothing efficiency of rigid conformal polishing tool using time-dependent smoothing evaluation model

NASA Astrophysics Data System (ADS)

Song, Chi; Zhang, Xuejun; Zhang, Xin; Hu, Haifei; Zeng, Xuefeng

2017-06-01

A rigid conformal (RC) lap can smooth mid-spatial-frequency (MSF) errors, which are naturally smaller than the tool size, while still removing large-scale errors in a short time. However, the RC-lap smoothing efficiency performance is poorer than expected, and existing smoothing models cannot explicitly specify the methods to improve this efficiency. We presented an explicit time-dependent smoothing evaluation model that contained specific smoothing parameters directly derived from the parametric smoothing model and the Preston equation. Based on the time-dependent model, we proposed a strategy to improve the RC-lap smoothing efficiency, which incorporated the theoretical model, tool optimization, and efficiency limit determination. Two sets of smoothing experiments were performed to demonstrate the smoothing efficiency achieved using the time-dependent smoothing model. A high, theory-like tool influence function and a limiting tool speed of 300 RPM were o

Evaluation of a smartphone camera system to enable visualization and image transmission to aid tracheal intubation with the Airtraq(®) laryngoscope.

PubMed

Lee, Delice Weishan; Thampi, Swapna; Yap, Eric Peng Huat; Liu, Eugene Hern Choon

2016-06-01

Using three-dimensional printing, we produced adaptors to attach a smartphone with camera to the eyepiece of the Airtraq(®) laryngoscope. This low-cost system enabled a team to simultaneously view the laryngoscopy process on the smartphone screen, and also enabled image transmission. We compared the Airtraq(®) with the smartphone Airtraq(®) system in a crossover study of trainee anesthesiologists performing tracheal intubation in a manikin. We also evaluated the smartphone Airtraq(®) system for laryngoscopy and tracheal intubation in 30 patients, including image transmission to and communication with a remote instructor. In the manikin study, the smartphone Airtraq(®) system enabled instruction where both trainee and instructor could view the larynx simultaneously, and did not substantially increase the time required for intubation. In the patient study, we were able to view the larynx in all 30 patients, and the remote instructor was able to receive the images and to respond on correctness of laryngoscopy and tracheal tube placement. Tracheal intubation was successful within 90s in 19 (63 %) patients. In conclusion, use of a smartphone with the Airtraq(®) may facilitate instruction and communication of laryngoscopy with the Airtraq(®), overcoming some of its limitations.

Application of Electrocautery Needle Knife Combined with Balloon Dilatation versus Balloon Dilatation in the Treatment of Tracheal Fibrotic Scar Stenosis.

PubMed

Bo, Liyan; Li, Congcong; Chen, Min; Mu, Deguang; Jin, Faguang

Electrocautery needle knives can largely reduce scar and granulation tissue hyperplasia and play an important role in treating patients with benign stricture. The aim of this retrospective study was to evaluate the efficacy and safety of electrocautery needle knife combined with balloon dilatation versus balloon dilatation alone in the treatment of tracheal stenosis caused by tracheal intubation or tracheotomy. We retrospectively analysed the clinical data of 43 patients with tracheal stenosis caused by tracheotomy or tracheal intubation in our department from January 2013 to January 2016. Among these 43 patients, 23 had simple web-like stenosis and 20 had complex steno sis. All patients were treated under general anaesthesia, and the treatment methods were (1) balloon dilatation alone, (2) needle knife excision of fibrotic tissue combined with balloon dilatation, and (3) needle knife radial incision of fibrotic tissue combined with balloon dilatation. After treatment the symptoms, such as shortness of breath, were markedly improved immediately in all cases. The stenosis degree of patients who were treated with the elec-trocautery needle knife combined with balloon dilatation had better improvement compared with that of those treated with balloon dilatation treatment alone after 3 months (0.45 ± 0.04 vs. 0.67 ± 0.05, p < 0.01), and the proportion of restenosis occurrence that required further treatment was decreased at 6 months (46.9 vs. 81.8%), especially for the web-like stenosis patients, as most of their stenoses dilated with no obvious restenosis and achieved clinical cure. Electrocautery needle knife combined with balloon dilatation is an effective and safe treatment for tracheal fibrotic stenosis compared with balloon dilatation alone. © 2017 S. Karger AG, Basel.

Nerve growth factor-enhanced airway responsiveness involves substance P in ferret intrinsic airway neurons.

PubMed

Wu, Z-X; Dey, R D

2006-07-01

Nerve growth factor (NGF), a member of the neurotrophin family, enhances synthesis of neuropeptides in sensory and sympathetic neurons. The aim of this study was to examine the effect of NGF on airway responsiveness and determine whether these effects are mediated through synthesis and release of substance P (SP) from the intrinsic airway neurons. Ferrets were instilled intratracheally with NGF or saline. Tracheal smooth muscle contractility to methacholine and electrical field stimulation (EFS) was assessed in vitro. Contractions of isolated tracheal smooth muscle to EFS at 10 and 30 Hz were significantly increased in the NGF treatment group (10 Hz: 33.57 +/- 2.44%; 30 Hz: 40.12 +/- 2.78%) compared with the control group (10 Hz: 27.24 +/- 2.14%; 30 Hz: 33.33 +/- 2.31%). However, constrictive response to cholinergic agonist was not significantly altered between the NGF treatment group and the control group. The NGF-induced modulation of airway smooth muscle to EFS was maintained in tracheal segments cultured for 24 h, a procedure that causes a significant anatomic and functional loss of SP-containing sensory fibers while maintaining viability of intrinsic airway neurons. The number of SP-containing neurons in longitudinal trunk and superficial muscular plexus and SP nerve fiber density in tracheal smooth muscle all increased significantly in cultured trachea treated with NGF. Pretreatment with CP-99994, an antagonist of neurokinin 1 receptor, attenuated the NGF-induced increased contraction to EFS in cultured segments but had no effect in saline controls. These results show that the NGF-enhanced airway smooth muscle contractile responses to EFS are mediated by the actions of SP released from intrinsic airway neurons.

Pharmacologic properties of brewery dust extracts in vitro.

PubMed

Schachter, E N; Zuskin, E; Rienzi, N; Goswami, S; Castranova, V; Whitmer, M; Siegel, P

2001-06-01

To study the effects of extracts of brewery dust on isolated guinea pig tracheal smooth muscle in vitro. Parallel pharmacologic intervention on guinea pig tracheal rings that were obtained from the same animal. Mount Sinai School of Medicine, Department of Pulmonary Medicine. The isolated guinea pig tracheal tissue of 18 guinea pigs. Pretreatment of guinea pig rings by mediator-modifying agents before challenge with the brewery dust extracts. The effect of brewery dust extracts on isolated guinea pig tracheal smooth muscle was studied using water-soluble extracts of dust obtained from brewery materials, including hops, barley, and brewery yeast. Dust extracts were prepared as a 1:10 (wt/vol) aqueous solution. Dose-related contractions of nonsensitized guinea pig tracheas were demonstrated using these extracts. The dust extracts contained significant quantities of bacterial components (eg, endotoxin and n-formyl-methionyl-leucyl-phenylalanine), but these agents were not thought to contribute directly to the constrictor effect of the dusts. Pharmacologic studies were performed by pretreating guinea pig tracheal tissue with the following drugs known to modulate smooth muscle contraction: atropine; indomethacin; pyrilamine; LY171883; nordihydroguaiaretic acid; captopril; thiorphan; verapamil; and TMB8. The constrictor effects of the dust extracts were inhibited by a wide variety of agents, the patterns of which depended on the dust extract. Atropine consistently and strikingly reduced the contractile effects of these extracts. These observations may suggest an interaction of the extracts with parasympathetic nerves or, more directly, with muscarinic receptors. The inhibition of contraction by the blocking of other mediators was less effective and varied with the dust extract. We suggest that brewery dust extracts cause a dose-related airway smooth muscle constriction by nonimmunologic mechanisms involving a variety of airway mediators and, possibly, cholinergic

Stimulation of aortic smooth muscle cell mitogenesis by serotonin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nemecek, G.M.; Coughlin, S.R.; Handley, D.A.

1986-02-01

Bovine aortic smooth muscle cells in vitro responded to 1 nM to 10 ..mu..M serotonin with increased incorporation of (/sup 3/H)thymidine into DNA. The mitogenic effect of serotonin was half-maximal at 80 nM and maximal above 1 ..mu..M. At a concentration of 1 ..mu..M, serotonin stimulated smooth muscle cell mitogenesis to the same extent as human platelet-derived growth factor (PDGF) at 12 ng/ml. Tryptamine was approx. = 1/10th as potent as serotonin as a mitogen for smooth muscle cells. Other indoles that are structurally related to serotonin (D- and L-tryptophan, 5-hydroxy-L-tryptophan, N-acetyl-5-hydroxytryptamine, melatonin, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol) and quipazine weremore » inactive. The stimulatory effect of serotonin on smooth muscle cell DNA synthesis required prolonged (20-24 hr) exposure to the agonist and was attenuated in the presence of serotonin D receptor antagonists. When smooth muscle cells were incubated with submaximal concentrations of serotonin and PDGF, synergistic rather than additive mitogenic responses were observed. These data indicate that serotonin has a significant mitogenic effect on smooth muscle cells in vitro, which appears to be mediated by specific plasma membrane receptors.« less

Smooth Tubercle Bacilli: Neglected Opportunistic Tropical Pathogens.

PubMed

Aboubaker Osman, Djaltou; Bouzid, Feriel; Canaan, Stéphane; Drancourt, Michel

2015-01-01

Smooth tubercle bacilli (STB) including "Mycobacterium canettii" are members of the Mycobacterium tuberculosis complex (MTBC), which cause non-contagious tuberculosis in human. This group comprises <100 isolates characterized by smooth colonies and cordless organisms. Most STB isolates have been obtained from patients exposed to the Republic of Djibouti but seven isolates, including the three seminal ones obtained by Georges Canetti between 1968 and 1970, were recovered from patients in France, Madagascar, Sub-Sahara East Africa, and French Polynesia. STB form a genetically heterogeneous group of MTBC organisms with large 4.48 ± 0.05 Mb genomes, which may link Mycobacterium kansasii to MTBC organisms. Lack of inter-human transmission suggested a yet unknown environmental reservoir. Clinical data indicate a respiratory tract route of contamination and the digestive tract as an alternative route of contamination. Further epidemiological and clinical studies are warranted to elucidate areas of uncertainty regarding these unusual mycobacteria and the tuberculosis they cause.

Smooth Tubercle Bacilli: Neglected Opportunistic Tropical Pathogens

PubMed Central

Aboubaker Osman, Djaltou; Bouzid, Feriel; Canaan, Stéphane; Drancourt, Michel

2016-01-01

Smooth tubercle bacilli (STB) including “Mycobacterium canettii” are members of the Mycobacterium tuberculosis complex (MTBC), which cause non-contagious tuberculosis in human. This group comprises <100 isolates characterized by smooth colonies and cordless organisms. Most STB isolates have been obtained from patients exposed to the Republic of Djibouti but seven isolates, including the three seminal ones obtained by Georges Canetti between 1968 and 1970, were recovered from patients in France, Madagascar, Sub-Sahara East Africa, and French Polynesia. STB form a genetically heterogeneous group of MTBC organisms with large 4.48 ± 0.05 Mb genomes, which may link Mycobacterium kansasii to MTBC organisms. Lack of inter-human transmission suggested a yet unknown environmental reservoir. Clinical data indicate a respiratory tract route of contamination and the digestive tract as an alternative route of contamination. Further epidemiological and clinical studies are warranted to elucidate areas of uncertainty regarding these unusual mycobacteria and the tuberculosis they cause. PMID:26793699

Comparison between traditional and small-diameter tube-assisted bronchoscopic balloon dilatation in the treatment of benign tracheal stenosis.

PubMed

Li, Li-Hua; Liang, Yi-Lin; Li, Yu; Xu, Ming-Peng; Li, Wen-Tao; Liu, Guang-Nan

2018-03-01

To compare the safety and efficacy between using a small-diameter tube-assisted bronchoscopic balloon dilatation (BBD) and the traditional BBD in the treatment of benign tracheal stenosis. A retrospective study included 58 patients with benign tracheal stenosis from August 2009 to December 2014 was made. The patients who underwent traditional BBD were divided into group A, and who underwent a small-diameter tube-assisted BBD were divided into group B. The tracheal diameter, dyspnea index and blood gas analysis results were detected before and after BBD. Efficacy and complications were evaluated after BBD. There were significant differences in oxygen saturation (PaO 2 ) during the operations comparing with before and after operations in group A (P = .005), while there was no significant difference in group B (P = .079). The tracheal diameter obviously increased (in group A, from 4.16 ± 1.43 mm to 12.47 ± 1.41 mm, P = .000; in group B: from 4.94 ± 1.59 mm to 12.61 ± 1.41 mm, P = .000). Dyspnea index obviously decreased (group A: from 3.21 ± 0.93 to 0.50 ± 0.59, P = .000; group B: from 3.24 ± 0.89 to 0.65 ± 0.69, P = .000). The immediately cure rate in both groups was 100%. Long-term effect was significantly better in group B than that in group A (85.3% vs 59.1%, P = .021), at the end of the follow-up period. Small-diameter tube-assisted BBD obtains better safety and long-term efficacy than the traditional BBD in the treatment of benign tracheal stenosis. However, close attention should be given to the risk of the adverse effects caused by carbon dioxide retention. © 2017 John Wiley & Sons Ltd.

A comparison of the I-gel supraglottic airway as a conduit for tracheal intubation with the intubating laryngeal mask airway: a manikin study.

PubMed

Michalek, P; Donaldson, W; Graham, C; Hinds, J D

2010-01-01

Insertion of a supraglottic airway and tracheal intubation through it may be indicated in resuscitation scenarios where conventional laryngoscopy fails. Various supraglottic devices have been used as conduits for tracheal intubation, including the intubating laryngeal mask airway (ILMA), the Ctrach laryngeal mask and the I-gel supraglottic airway. A prospective study with 25 participants evaluated the success rate of blind intubation (using a gum-elastic bougie, an Aintree intubating catheter (AIC) and designated tracheal tube) and fibrescope-guided tracheal intubation (through the intubating laryngeal mask airway and the I-gel supraglottic airway) on three different airway manikins. Twenty-five anaesthetists performed three intubations with each method on each of three manikins. The success rate of the fibrescope-guided technique was significantly higher than blind attempts (P<0.0001) with both devices. For fibreoptic techniques, there was no difference found between the ILMA and I-gel (P>0.05). All blind techniques were significantly more successful in the ILMA group compared to the I-gel (P<0.0001 for bougie, Aintree catheter and tracheal tube, respectively). The results of this study show that, in manikins, fibreoptic intubation through both ILMA and I-gel is a highly successful technique. Blind intubation through the I-gel showed a low success rate and should not be attempted. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Interleukin-4 upregulates RhoA protein via an activation of STAT6 in cultured human bronchial smooth muscle cells.

PubMed

Chiba, Yoshihiko; Todoroki, Michiko; Misawa, Miwa

2010-02-01

Interleukin-4 (IL-4) is believed to play a role in allergic bronchial asthma, and has been suggested to cause hyperresponsiveness of airway smooth muscle. In the present study, the effects of IL-4 on the expression of RhoA protein, a monomeric GTP-binding protein that contributes to the contraction of smooth muscle, were determined in cultured human bronchial smooth muscle cells (hBSMCs). Incubation of hBSMCs with IL-4 (100ng/mL) caused a distinct phosphorylation of signal transducer and activator of transcription 6 (STAT6), a major signal transducer activated by IL-4, indicating that IL-4 is capable of activating signal transduction in the hBSMCs directly. IL-4 also caused a significant increase in the expression level of RhoA protein: the peak of the upregulation of RhoA protein was observed at 12-24h after the IL-4 treatment. Both the phosphorylation of STAT6 and the upregulation of RhoA protein induced by IL-4 were inhibited by the co-incubation with AS1517499, a selective inhibitor of STAT6, in a concentration-dependent fashion. These findings suggest that IL-4 is capable of inducing an upregulation of RhoA via an activation of STAT6 in cultured hBSMCs. The RhoA upregulation induced by IL-4, one of the Th2 cytokines upregulated in the airways of allergic bronchial asthmatics, might result in an augmentation of bronchial smooth muscle contractility, that is one of the causes of airway hyperresponsiveness. Copyright 2009 Elsevier Ltd. All rights reserved.

Saline instillation before tracheal suctioning decreases the incidence of ventilator-associated pneumonia.

PubMed

Caruso, Pedro; Denari, Silvia; Ruiz, Soraia A L; Demarzo, Sergio E; Deheinzelin, Daniel

2009-01-01

To compare the incidence of ventilator-associated pneumonia (VAP) with or without isotonic saline instillation before tracheal suctioning. As a secondary objective, we compared the incidence of endotracheal tube occlusion and atelectasis. Randomized clinical trial. The study was conducted in a medical surgical intensive care unit of an oncologic hospital. We selected consecutive patients needing mechanical ventilation for >72 hrs. Patients were allocated into two groups: a saline group that received instillation of 8 mL of saline before tracheal suctioning and a control group which did not. VAP was diagnosed based on clinical suspicion and confirmed by bronchoalveolar lavage quantitative culture. The incidence of atelectasis on daily chest radiography and endotracheal tube occlusions were recorded. The sample size was calculated to a power of 80% and a type I error probability of 5%. One hundred thirty patients were assigned to the saline group and 132 to the control group. The baseline demographic variables were similar between groups. The rate of clinically suspected VAP was similar in both groups. The incidence of microbiological proven VAP was significantly lower in the saline group (23.5% x 10.8%; p = 0.008) (incidence density/1.000 days of ventilation 21.22 x 9.62; p < 0.01). Using the Kaplan-Meier curve analysis, the proportion of patients remaining without VAP was higher in the saline group (p = 0.02, log-rank test). The relative risk reduction of VAP in the saline instillation group was 54% (95% confidence interval, 18%-74%) and the number needed to treat was eight (95% confidence interval, 5-27). The incidence of atelectases and endotracheal tube occlusion were similar between groups. Instillation of isotonic saline before tracheal suctioning decreases the incidence of microbiological proven VAP.

Tracheal bioengineering: the next steps. Proceeds of an International Society of Cell Therapy Pulmonary Cellular Therapy Signature Series Workshop, Paris, France, April 22, 2014.

PubMed

Weiss, Daniel J; Elliott, Martin; Jang, Queenie; Poole, Brian; Birchall, Martin

2014-12-01

There has been significant and exciting recent progress in the development of bioengineering approaches for generating tracheal tissue that can be used for congenital and acquired tracheal diseases. This includes a growing clinical experience in both pediatric and adult patients with life-threatening tracheal diseases. However, not all of these attempts have been successful, and there is ongoing discussion and debate about the optimal approaches to be used. These include considerations of optimal materials, particularly use of synthetic versus biologic scaffolds, appropriate cellularization of the scaffolds, optimal surgical approaches and optimal measure of both clinical and biologic outcomes. To address these issues, the International Society of Cell Therapy convened a first-ever meeting of the leading clinicians and tracheal biologists, along with experts in regulatory and ethical affairs, to discuss and debate the issues. A series of recommendations are presented for how to best move the field ahead. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

The biophysics of asthmatic airway smooth muscle.

PubMed

Stephens, Newman L; Li, Weilong; Jiang, He; Unruh, H; Ma, Xuefei

2003-09-16

It is clear that significant advances have been made in the understanding of the physiology, biochemistry and molecular biology of airway smooth muscle (ASM) contraction and how the knowledge obtained from these approaches may be used to elucidate the pathogenesis of asthma. Not to belittle other theories of smooth muscle contraction extant in the field, perhaps the most outstanding development has been the formulation of plasticity theory. This may radically alter our understanding of smooth muscle contraction. Its message is that while shortening velocity and capacity are linear functions of length, active force is length independent. These changes are explained by the ability of thick filament protein to depolymerize at short lengths and to increase numbers of contractile units in series at lengths greater than optimal length or L(ref). Other advances are represented by the report that the major part of ASM shortening is complete within the initial first 20% of contraction time, that the nature and history of loading determine the extent of shortening and that these findings can be explained by the finding that the crossbridges are cycling four times faster than in the remaining time. Another unexpected finding is that late in the course of isotonic relaxation the muscle undergoes spontaneous activation which delays relaxation and smoothes it out; speculatively this could minimize turbulence of airflow. On the applied front evidence now shows the shortening ability of bronchial smooth muscle of human subjects of asthma is significantly increased. Measurements also indicate that increased smooth muscle myosin light chain kinase content, via increased actomyosin ATPase activity could be responsible for the changes in contractility.

Right upper lobe atelectasis after tracheal extubation in a morbidly obese patient

PubMed Central

Uzman, Sinan; Toptaş, Mehmet; Yanaral, Tumay Uludag

2012-01-01

Summary Background: Acute lobar collapse caused by a reflex bronchoconstriction was previously reported to occur during the induction of anesthesia, however there are no reports on its occurrence during the emergence period. Case Report: A 56-year-old morbidly obese woman was scheduled for surgery due to a gastric ulcer perforation. Anesthesia was induced with thiopental 500 mg, fentanyl and rocuronium, and maintained with sevoflurane in a N2O/O2 mixture. The operative procedure and anesthesia were uneventful; however, the patient developed a sudden decrease in SaO2 and blurring of consciousness after extubation. She was re-intubated and ventilated with 100% O2. Arterial blood gas analysis at that time showed respiratory acidosis and hypoxemia. Further work-up revealed a bronchospasm-induced right upper lobe atelectasis, which occurred immediately after tracheal extubation. The patient was successfully treated using mechanical ventilation and bronchodilators. Conclusions: Bronchospasm may cause acute lobar atelectasis immediately after tracheal extubation. Morbid obesity and the use of 100% oxygen may facilitate atelectasis formation during emergence from anesthesia. PMID:23569513

Tracheal volume in the pupa of the Saturniid moth Hyalophora cecropia determined with inert gases.

PubMed

Bridges, C R; Kestler, P; Scheid, P

1980-06-01

Tracheal volume (VTr) was measured in pupae of the Giant silkworm moth Hyalophora cecropia (Saturniidae, Lepidoptera, Insecta) using inert gas wash-out techniques. The animal was placed in a small vessel that was continuously ventilated (rate, V) by a gas mixture containing 20% O2 in N2; the inflowing (F1) and outflowing gas fractions (FE) of the vessel could be continuously measured by a respiratory mass spectrometer. At the onset of a spiracular constriction period, which was evidenced from the FECO2 trace, the mixture was rapidly replaced by pure Ar. At the subsequent burst, the amount of N2 emerging from the animal, MN2, was calculated from V and the difference (FE--F1)N2. VTr was calculated from MN2 and the N2 concentration in the tracheal system before constriction (assumed to equal that in the ventilating gas before replacement by Ar). Measurements were repeated with N2 and Ar replacing each other. VTr average 48 microliter . g-1 (range 39 to 59) for animals of 5.8 g average body weight (range 3.4 to 9.9), when inert gas solubility in body fluids was accounted for. Both size and stage in pupal development appear to affect VTr. These values show reasonable agreement with literature data, mostly obtained by emptying the tracheal gas space by mechanical compression.

Ion transport by primary cultures of canine tracheal epithelium: methodology, morphology, and electrophysiology.

PubMed

Welsh, M J

1985-01-01

Canine tracheal epithelial cells were isolated by enzymatic and mechanical dispersion and cultured on permeable supports. The cells formed confluent monolayers and retained most of the morphologic characteristics of the intact epithelium, including apical microvilli, apical tight junctions, and a moderately interdigitated lateral intercellular space. The cells also retained the functional properties of the epithelium. The monolayer responded to addition of isoproterenol with the characteristic changes in cellular electrical properties expected for stimulation of C1 secretion: isoproterenol increased transepithelial voltage, depolarized apical membrane voltage, and decreased both transepithelial resistance and the ratio of apical-to-basolateral membrane resistance. Examination of the cellular response to ion substitutions and inhibitors of C1 secretion indicate that the cultured monolayers retain the same cellular mechanisms of ion transport as the intact epithelium. Thus, primary cultures of tracheal epithelium may provide a useful preparation for future studies of the mechanism and regulation of C1 secretion by airway epithelia.

TGF-beta1 inhibits Cx43 expression and formation of functional syncytia in cultured smooth muscle cells from human detrusor.

PubMed

Neuhaus, Jochen; Heinrich, Marco; Schwalenberg, Thilo; Stolzenburg, Jens-Uwe

2009-02-01

Human detrusor smooth muscle cells (hBSMCs) are coupled by connexin 43 (Cx43)-positive gap junctions to form functional syncytia. Gap junctional communication likely is necessary for synchronised detrusor contractions and is supposed to be altered in voiding disturbances. Other authors have shown that the pleiotropic cytokine TGF-beta1 upregulates Cx43 expression in human aortic smooth muscle cells. In this study, we examined the TGF-beta1 effects on Cx43 expression in cultured hBSMCs. hBSMC cultures, established from patients undergoing cystectomy, were treated with recombinant human TGF-beta1. Cx43 expression was then examined by Western blotting, real-time PCR, and immunocytochemistry. Dye-injection experiments were used to study the size of functional syncytia. Dye-coupling experiments revealed stable formation of functional syncytia in passaged cell cultures (P1-P4). Stimulation with TGF-beta1 led to significant reduction of Cx43 immunoreactivity and coupling. Cx43 protein expression was significantly downregulated and Cx43 mRNA was only 30% of the control level. Interestingly, low phosphorylation species of Cx43 were particularly affected. Our experiments demonstrated a significant down regulation of connexin 43 by TGF-beta1 in cultured hBSMCs. These findings support the view that TGF-beta1 is involved in the pathophysiology of urinary bladder dysfunction.

Effect of prophylactic bronchodilator treatment with intravenous colforsin daropate, a water-soluble forskolin derivative, on airway resistance after tracheal intubation.

PubMed

Wajima, Zen'ichiro; Shiga, Toshiya; Yoshikawa, Tatsusuke; Ogura, Akira; Imanaga, Kazuyuki; Inoue, Tetsuo; Ogawa, Ryo

2003-07-01

After induction of anesthesia, lung resistance increases. The authors hypothesized that prophylactic bronchodilator treatment with intravenous colforsin daropate, a water-soluble forskolin derivative, before tracheal intubation would result in decreased lung resistance and increased lung compliance after tracheal intubation when compared with placebo medication. Forty-six adult patients were randomized to placebo or colforsin daropate treatment. Patients in the control group received normal saline; patients in the colforsin group received 0.75 microg. kg-1 x min-1 colforsin daropate intravenously until the study ended. Thirty minutes after the study began, the authors administered 5 mg/kg thiamylal and 5 microg/kg fentanyl for induction of general anesthesia and 0.3 mg/kg vecuronium for muscle relaxation. A 15-mg. kg-1. h-1 continuous infusion of thiamylal followed anesthetic induction. Four, 8, 12, and 16 min after tracheal intubation, mean airway resistance (R(awm)), expiratory airway resistance (R(awe)), and dynamic lung compliance (C(dyn)) were measured. Patients in the colforsin group had significantly lower R(awm) and R(awe) and higher C(dyn) after intubation than those in the control group. Differences in R(awm), R(awe), and C(dyn) between the two groups persisted through the final measurement at 16 min. At 4 min after intubation, smokers had a higher R(awm) and a lower C(dyn) than nonsmokers in the control group. After treatment by intravenous colforsin daropate, R(awm), R(awe), and C(dyn) values were similar for smokers and nonsmokers after tracheal intubation. Prophylactic treatment with colforsin daropate produced lower R(awm) and R(awe) and higher C(dyn) after tracheal intubation when compared with placebo medication. Pretreatment before intubation may be beneficial and advantageous for middle-aged smokers.

External fixation of proximal tracheal airway stents: a modified technique.

PubMed

Majid, Adnan; Fernandez-Bussy, Sebastian; Kent, Michael; Folch, Erik; Fernandez, Liliana; Cheng, George; Gangadharan, Sidhu P

2012-06-01

Treatment of subglottic and proximal tracheal stenosis for nonsurgical candidates includes tracheostomy, Montgomery T tubes, and silicone stents. When used in lesions with concomitant malacia, silicone stents have a high incidence of migration. We describe a simple and effective technique of securing endoluminal stents using an Endo Close suturing device (Coviden, Boston, MA) and an external silicone button in 9 consecutive patients. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Inhibition of Adrenergic and Non-Adrenergic Smooth Muscle Contraction in the Human Prostate by the Phosphodiesterase 10-Selective Inhibitor TC-E 5005.

PubMed

Hennenberg, Martin; Schott, Melanie; Kan, Aysenur; Keller, Patrick; Tamalunas, Alexander; Ciotkowska, Anna; Rutz, Beata; Wang, Yiming; Strittmatter, Frank; Herlemann, Annika; Yu, Qingfeng; Stief, Christian G; Gratzke, Christian

2016-11-01

The phosphodiesterase (PDE) 5 inhibitor tadalafil is available for treatment of male lower urinary tract symptoms (LUTS), while the role of other PDE isoforms for prostate smooth muscle tone is still unknown. Here, we examined effects of the PDE10-selective inhibitor TC-E 5005 on smooth muscle contraction in human prostate tissue. Prostate samples were obtained from patients undergoing radical prostatectomy. Expression of PDE10 was addressed by RT-PCR, Western blot, and fluorescence staining with different markers. Effects of TC-E 5005 and tadalafil on contraction, and relaxation of prostate strips were studied via organ bath. PDE10A was detectable by RT-PCR, Western blot, and fluorescence staining in prostate tissues. Colocalization with markers suggested expression of PDE10A in smooth muscle cells and catecholaminergic nerves. Norepinephrine, the α1 -adrenergic agonist phenylephrine, the thromboxane A2 analogue U46619, and endothelins 1-3 induced concentration-dependent contractions of prostate strips, while electric field stimulation (EFS) induced frequence-dependent contractions. Application of TC-E 5005 (500 nM) caused significant inhibition of norepinephrine-, phenylephrine-, and endothelin-3-induced contractions. Inhibition of EFS-induced contractions by TC-E 5005 ranged around 50%, resembling inhibition of EFS-induced contractions by tadalafil (10 μM). The prostacyclin analog treprostinil and the nitric oxide donor DEA NONOate induced relaxations of precontracted prostate strips, which were significantly amplified by TCE 5005. The PDE10-selective inhibitor TC-E 5005 inhibits adrenergic and neurogenic smooth muscle contractions in the human prostate. TC-E 5005 inhibits neurogenic contractions with similar efficacy than tadalafil, so that urodynamic effects in vivo appear possible. Prostate 76:1364-1374, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Ryanodine receptors decant internal Ca2+ store in human and bovine airway smooth muscle.

PubMed

Tazzeo, T; Zhang, Y; Keshavjee, S; Janssen, L J

2008-08-01

Several putative roles for ryanodine receptors (RyR) were investigated in human and bovine airway smooth muscle. Changes in intracellular Ca2+ concentration ([Ca2+]i) and membrane current were investigated in single cells by confocal fluorimetry and patch-clamp electrophysiology, respectively, whereas mechanical activity was monitored in intact strips with force transducers. RyR released Ca2+ from the sarcoplasmic reticulum in a ryanodine- and chloroethyl phenol (CEP)-sensitive fashion. Neither ryanodine nor CEP inhibited responses to KCl, cholinergic agonists or serotonin, indicating no direct role for RyR in contraction; in fact, there was some augmentation of these responses. In tissues pre-contracted with carbachol, the concentration-response relationships for isoproterenol and salmeterol were unaffected by ryanodine; relaxations due to a nitric oxide donor were also largely unaffected. Finally, it was examined whether RyR were involved in regulating [Ca2+]i within the subplasmalemmal space using patch-clamp electrophysiology as well as Ca2+ fluorimetry: isoproterenol increased [Ca2+]i- and Ca2+-dependent K+ current activity in a ryanodine-sensitive fashion. In conclusion, ryanodine receptors in airway smooth muscle are not important in directly mediating contraction or relaxation. The current authors speculate instead that these allow the sarcoplasmic reticulum to release Ca2+ towards the plasmalemma (to unload an overly full Ca2+ store and/or increase the Ca2+-buffering capacity of the sarcoplasmic reticulum) without affecting bronchomotor tone.

Tracheal aspirate Gram stain has limited sensitivity and specificity for detecting Staphylococcus aureus.

PubMed

Tetenta, Sodienye; Metersky, Mark L

2011-01-01

The increasing incidence of respiratory infections due to methicillin resistant Staphylococcus aureus has resulted in increased empirical use of antibiotics active against this pathogen. There are limited data available as to whether the Gram stain of respiratory tract secretions accurately predicts growth of S. aureus. We theorized that the distinctive morphology of S. aureus would allow rapid, accurate identification of the organism in respiratory secretions. The authors reviewed all available Gram stains of tracheal aspirates sent to our hospital's microbiology laboratory between 1 April 2008 and 31 October 2008, while blinded to the culture result, and recorded the presence or absence of organisms with a morphology consistent with S. aureus. These results were correlated with the semiquantitative culture result. Among 136 tracheal aspirates studied, 50 (37%) grew S. aureus. The Gram stain was read as positive for organisms consistent with S. aureus in 34 of these. Among 86 samples that did not grow S. aureus, the Gram stain was read as negative in 62. Therefore, the Gram stain had a sensitivity of 68%, a specificity of 72%, a negative predictive value of 80% and a positive predictive value of 59% for culture of S. aureus. False negative Gram stains were more likely when the culture revealed only rare or small growth of S. aureus (P = 0.01). In this study, the tracheal aspirate Gram stain read by an experienced clinician who was not a microbiologist, was not accurate enough to reliably predict the growth of S. aureus. © 2010 The Authors. Respirology © 2010 Asian Pacific Society of Respirology.

Endogenous Cardiac Troponin T Modulates Ca2+-Mediated Smooth Muscle Contraction

PubMed Central

Kajioka, Shunichi; Takahashi-Yanaga, Fumi; Shahab, Nouval; Onimaru, Mitsuho; Matsuda, Miho; Takahashi, Ryosuke; Asano, Haruhiko; Morita, Hiromitsu; Morimoto, Sachio; Yonemitsu, Yoshikazu; Hayashi, Maya; Seki, Narihito; Sasaguri, Toshiuyki; Hirata, Masato; Nakayama, Shinsuke; Naito, Seiji

2012-01-01

Mechanisms linked to actin filaments have long been thought to cooperate in smooth muscle contraction, although key molecules were unclear. We show evidence that cardiac troponin T (cTnT) substantially contributes to Ca2+-mediated contraction in a physiological range of cytosolic Ca2+ concentration ([Ca2+]i). cTnT was detected in various smooth muscles of the aorta, trachea, gut and urinary bladder, including in humans. Also, cTnT was distributed along with tropomyosin in smooth muscle cells, suggesting that these proteins are ready to cause smooth muscle contraction. In chemically permeabilised smooth muscle of cTnT+/− mice in which cTnT reduced to ~50%, the Ca2+-force relationship was shifted toward greater [Ca2+]i, indicating a sizeable contribution of cTnT to smooth muscle contraction at [Ca2+]i < 1 μM. Furthermore, addition of supplemental TnI and TnC reconstructed a troponin system to enhance contraction. The results indicated that a Tn/Tn-like system on actin-filaments cooperates together with the thick-filament pathway. PMID:23248744

Do Not Burn Your Airway Bridge: A Technique to Safely Exchange a Tracheostomy Tube for a Tracheal Tube.

PubMed

Patiño, Miguel Alejandro; Truong, Dam-Thuy; Truong, Angela; Cata, Juan Pablo

2016-10-01

Tracheostomy is one of the most ancient and commonly performed surgical procedures. When tracheostomized patients require a subsequent intervention, it is usually necessary to exchange the tracheostomy tube for a tracheal tube, which can be dangerous. These potential complications may be overlooked or underestimated by the anesthesia providers. An inability to ventilate the patient and replace the tube after removal of a fresh tracheostomy tube can escalate rapidly to a life-threatening crisis. We present a case in which an airway exchange catheter was used to safely replace a tracheostomy tube with a tracheal tube in a patient with a fresh tracheostomy.

Long-term outcome of conventional endotracheal tube balloon dilation of tracheal stenosis in a dog.

PubMed

Kahane, Nili; Segev, Gilad

2014-01-01

This report describes a successful dilation of tracheal stenosis in a 16-year-old dog using a conventional endotracheal tube balloon. This technique should be considered as palliative treatment when owners decline other therapeutic options.

Substance P released from intrinsic airway neurons contributes to ozone-enhanced airway hyperresponsiveness in ferret trachea.

PubMed

Wu, Zhong-Xin; Satterfield, Brian E; Dey, Richard D

2003-08-01

Exposure to ozone (O3) induces airway hyperresponsiveness mediated partly through the release of substance P (SP) from nerve terminals in the airway wall. Although substantial evidence suggests that SP is released by sensory nerves, SP is also present in neurons of airway ganglia. The purpose of this study was to investigate the role of intrinsic airway neurons in O3-enhanced airway responsiveness in ferret trachea. To remove the effects of sensory innervation, segments of ferret trachea were maintained in culture conditions for 24 h before in vitro exposure to 2 parts/million of O3 or air for 1 h. Sensory nerve depletion was confirmed by showing that capsaicin did not affect tracheal smooth muscle responsiveness to cholinergic agonist or contractility responses to electrical field stimulation (EFS). Contractions of isolated tracheal smooth muscle to EFS were significantly increased after in vitro O3 exposure, but the constrictor response to cholinergic agonist was not altered. Pretreatment with CP-99994, an antagonist of the neurokinin 1 receptor, attenuated the increased contraction to EFS after O3 exposure but had no effect in the air exposure group. The number of SP-positive neurons in longitudinal trunk ganglia, the extent of SP innervation to superficial muscular plexus nerve cell bodies, and SP nerve fiber density in tracheal smooth muscle all increased significantly after O3 exposure. The results show that release of SP from intrinsic airway neurons contributes to O3-enhanced tracheal smooth muscle responsiveness by facilitating acetylcholine release from cholinergic nerve terminals.

Morphology of the tracheal system of camel spiders (Chelicerata: Solifugae) based on micro-CT and 3D-reconstruction in exemplar species from three families.

PubMed

Franz-Guess, Sandra; Klußmann-Fricke, Bastian-Jesper; Wirkner, Christian S; Prendini, Lorenzo; Starck, J Matthias

2016-09-01

We studied the tracheal system of exemplar species representing three families of Solifugae Sundevall, 1833, i.e., Galeodes granti Pocock, 1903, Ammotrechula wasbaueri Muma, 1962 and Eremobates sp., using μCT-imaging and 3D-reconstruction. This is the first comparative study of the tracheal system of Solifugae in 85 years and the first using high-resolution nondestructive methods. The tracheal system was found to be structurally similar in all three species, with broad major tracheae predominantly in the prosoma as well as anastomoses (i.e., connections between tracheal branches from different stigmata) in the prosoma and opisthosoma. Differences among the three species were observed in the presence or absence of cheliceral air sacs, the number of tracheae supplying the heart, and the ramification of major tracheae in the opisthosoma. The structure of the tracheal system with its extensive branches and some anastomoses is assumed to aid rapid and efficient gas exchange in the respiratory tissues of these active predators. The large diameter of cheliceral tracheae (air sacs) of taxa with disproportionally heavier chelicerae suggests a role in weight reduction, enabling solifuges to reach greater speeds during predation. The air sacs may also permit more rapid and efficient gaseous exchange, necessary to operate the musculature of these structures, thereby improving their use for predation in an environment where prey is scarce. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Intrarenal smooth muscle: histology of a complex urodymamic machine].

PubMed

Arias, L F; Ortiz-Arango, N

2013-03-01

To know better the microscopic arrangement of the bundles of smooth muscle in the human renal parenchyma, their distribution and anatomical relationships, trying to make a reconstruction of this muscular system. Five adult human kidneys and one fetal kidney were processed "in toto" with cross sections every 300μm. In the histological sections we identify the smooth muscle fibers trying to determine its insertion, course and anatomical relationship with other structures of the kidney tissue. There are bundles of smooth muscle fibers of variable thickness parallel to the edges of the medullary pyramids, bundles that surrounding the medulla in a spiral course, and bundles that accompany arcuate vessels, the latter being the most abundant and easy to identify. These groups of muscle fibers do not have a precise or constant insertion site, their periodicity is not homogeneous and they are not a direct extension of the muscle of the renal pelvis, although some bundles are in contact with it. There are also unusual and inconstant small muscle fibers no associated to vessels in the interstitium of the cortex and, exceptionally, in the medulla. There is a complex microscopic system of smooth muscle fibers that partially surround the renal medulla and are related to renal pelvic muscles without a direct continuity with them. Although this small muscular system is under-recognized, could be very important in urodynamics. Copyright © 2012 AEU. Published by Elsevier Espana. All rights reserved.

Saccular lung cannulation in a ball python (Python regius) to treat a tracheal obstruction.

PubMed

Myers, Debbie A; Wellehan, James F X; Isaza, Ramiro

2009-03-01

An adult male ball python (Python regius) presented in a state of severe dyspnea characterized by open-mouth breathing and vertical positioning of the head and neck. The animal had copious discharge in the tracheal lumen acting as an obstruction. A tube was placed through the body wall into the caudal saccular aspect of the lung to allow the animal to breathe while treatment was initiated. The ball python's dyspnea immediately improved. Diagnostics confirmed a bacterial respiratory infection with predominantly Providencia rettgeri. The saccular lung (air sac) tube was removed after 13 days. Pulmonary endoscopy before closure showed minimal damage with a small amount of hemorrhage in the surrounding muscle tissue. Respiratory disease is a common occurrence in captive snakes and can be associated with significant morbidity and mortality. Saccular lung cannulation is a relatively simple procedure that can alleviate tracheal narrowing or obstruction, similar to air sac cannulation in birds.

Evaluation of magnesium-yttrium alloy as an extraluminal tracheal stent.

PubMed

Luffy, Sarah A; Chou, Da-Tren; Waterman, Jenora; Wearden, Peter D; Kumta, Prashant N; Gilbert, Thomas W

2014-03-01

Tracheomalacia is a relatively rare problem, but can be challenging to treat, particularly in pediatric patients. Due to the presence of mechanically deficient cartilage, the trachea is unable to resist collapse under physiologic pressures of respiration, which can lead to acute death if left untreated. However, if treated, the outcome for patients with congenital tracheomalacia is quite good because the cartilage tends to spontaneously mature over a period of 12 to 18 months. The present study investigated the potential for the use of degradable magnesium-3% yttrium alloy (W3) to serve as an extraluminal tracheal stent in a canine model. The host response to the scaffold included the formation of a thin, vascularized capsule consisting of collagenous tissue and primarily mononuclear cells. The adjacent cartilage structure was not adversely affected as observed by bronchoscopic, gross, histologic, and mechanical analysis. The W3 stents showed reproducible spatial and temporal fracture patterns, but otherwise tended to corrode quite slowly, with a mix of Ca and P rich corrosion product formed on the surface and observed focal regions of pitting. The study showed that the approach to use degradable magnesium alloys as an extraluminal tracheal stent is promising, although further development of the alloys is required to improve the resistance to stress corrosion cracking and improve the ductility. Copyright © 2013 Wiley Periodicals, Inc.

Human Motion Perception and Smooth Eye Movements Show Similar Directional Biases for Elongated Apertures

NASA Technical Reports Server (NTRS)

Beutter, Brent R.; Stone, Leland S.

1997-01-01

Although numerous studies have examined the relationship between smooth-pursuit eye movements and motion perception, it remains unresolved whether a common motion-processing system subserves both perception and pursuit. To address this question, we simultaneously recorded perceptual direction judgments and the concomitant smooth eye movement response to a plaid stimulus that we have previously shown generates systematic perceptual errors. We measured the perceptual direction biases psychophysically and the smooth eye-movement direction biases using two methods (standard averaging and oculometric analysis). We found that the perceptual and oculomotor biases were nearly identical suggesting that pursuit and perception share a critical motion processing stage, perhaps in area MT or MST of extrastriate visual cortex.

Human motion perception and smooth eye movements show similar directional biases for elongated apertures

NASA Technical Reports Server (NTRS)

Beutter, B. R.; Stone, L. S.

1998-01-01

Although numerous studies have examined the relationship between smooth-pursuit eye movements and motion perception, it remains unresolved whether a common motion-processing system subserves both perception and pursuit. To address this question, we simultaneously recorded perceptual direction judgments and the concomitant smooth eye-movement response to a plaid stimulus that we have previously shown generates systematic perceptual errors. We measured the perceptual direction biases psychophysically and the smooth eye-movement direction biases using two methods (standard averaging and oculometric analysis). We found that the perceptual and oculomotor biases were nearly identical, suggesting that pursuit and perception share a critical motion processing stage, perhaps in area MT or MST of extrastriate visual cortex.

Human Rhinovirus Infection of Epithelial Cells Modulates Airway Smooth Muscle Migration.

PubMed

Shariff, Sami; Shelfoon, Christopher; Holden, Neil S; Traves, Suzanne L; Wiehler, Shahina; Kooi, Cora; Proud, David; Leigh, Richard

2017-06-01

Airway remodeling, a characteristic feature of asthma, begins in early life. Recurrent human rhinovirus (HRV) infections are a potential inciting stimulus for remodeling. One component of airway remodeling is an increase in airway smooth muscle cell (ASMC) mass with a greater proximity of the ASMCs to the airway epithelium. We asked whether human bronchial epithelial cells infected with HRV produced mediators that are chemotactic for ASMCs. ASMC migration was investigated using the modified Boyden Chamber and the xCELLigence Real-Time Cell Analyzer (ACEA Biosciences Inc., San Diego, CA). Multiplex bead analysis was used to measure HRV-induced epithelial chemokine release. The chemotactic effects of CCL5, CXCL8, and CXCL10 were also examined. Supernatants from HRV-infected epithelial cells caused ASMC chemotaxis. Pretreatment of ASMCs with pertussis toxin abrogated chemotaxis, as did treatment with formoterol, forskolin, or 8-bromo-cAMP. CCL5, CXCL8, and CXCL10 were the most up-regulated chemokines produced by HRV-infected airway epithelial cells. When recombinant CCL5, CXCL8, and CXCL10 were used at levels found in epithelial supernatants, they induced ASMC chemotaxis similar to that seen with epithelial cell supernatants. When examined individually, CCL5 was the most effective chemokine in causing ASMC migration, and treatment of supernatant from HRV-infected epithelial cells with anti-CCL5 antibodies significantly attenuated ASMC migration. These findings suggest that HRV-induced CCL5 can induce ASMC chemotaxis and thus may contribute to the pathogenesis of airway remodeling in patients with asthma.

Smoking and Female Sex: Independent Predictors of Human Vascular Smooth Muscle Cells Stiffening

PubMed Central

Dinardo, Carla Luana; Santos, Hadassa Campos; Vaquero, André Ramos; Martelini, André Ricardo; Dallan, Luis Alberto Oliveira; Alencar, Adriano Mesquita; Krieger, José Eduardo; Pereira, Alexandre Costa

2015-01-01

Aims Recent evidence shows the rigidity of vascular smooth muscle cells (VSMC) contributes to vascular mechanics. Arterial rigidity is an independent cardiovascular risk factor whose associated modifications in VSMC viscoelasticity have never been investigated. This study’s objective was to evaluate if the arterial rigidity risk factors aging, African ancestry, female sex, smoking and diabetes mellitus are associated with VMSC stiffening in an experimental model using a human derived vascular smooth muscle primary cell line repository. Methods Eighty patients subjected to coronary artery bypass surgery were enrolled. VSMCs were extracted from internal thoracic artery fragments and mechanically evaluated using Optical Magnetic Twisting Cytometry assay. The obtained mechanical variables were correlated with the clinical variables: age, gender, African ancestry, smoking and diabetes mellitus. Results The mechanical variables Gr, G’r and G”r had a normal distribution, demonstrating an inter-individual variability of VSMC viscoelasticity, which has never been reported before. Female sex and smoking were independently associated with VSMC stiffening: Gr (apparent cell stiffness) p = 0.022 and p = 0.018, R2 0.164; G’r (elastic modulus) p = 0.019 and p = 0.009, R2 0.184 and G”r (dissipative modulus) p = 0.011 and p = 0.66, R2 0.141. Conclusion Female sex and smoking are independent predictors of VSMC stiffening. This pro-rigidity effect represents an important element for understanding the vascular rigidity observed in post-menopausal females and smokers, as well as a potential therapeutic target to be explored in the future. There is a significant inter-individual variation of VSMC viscoelasticity, which is slightly modulated by clinical variables and probably relies on molecular factors. PMID:26661469

The Drosophila homologue of SRF acts as a boosting mechanism to sustain FGF-induced terminal branching in the tracheal system.

PubMed

Gervais, Louis; Casanova, Jordi

2011-04-01

Recent data have demonstrated a crucial role for the transcription factor SRF (serum response factor) downstream of VEGF and FGF signalling during branching morphogenesis. This is the case for sprouting angiogenesis in vertebrates, axonal branching in mammals and terminal branching of the Drosophila tracheal system. However, the specific functions of SRF in these processes remain unclear. Here, we establish the relative contributions of the Drosophila homologues of FGF [Branchless (BNL)] and SRF [Blistered (BS)] in terminal tracheal branching. Conversely to an extended view, we show that BNL triggers terminal branching initiation in a DSRF-independent mechanism and that DSRF transcription induced by BNL signalling is required to maintain terminal branch elongation. Moreover, we report that increased and continuous FGF signalling can trigger tracheal cells to develop full-length terminal branches in the absence of DSRF transcription. Our results indicate that DSRF acts as an amplifying step to sustain the progression of terminal branch elongation even in the wild-type conditions of FGF signalling.

Novel treatment strategies for smooth muscle disorders: Targeting Kv7 potassium channels.

PubMed

Haick, Jennifer M; Byron, Kenneth L

2016-09-01

Smooth muscle cells provide crucial contractile functions in visceral, vascular, and lung tissues. The contractile state of smooth muscle is largely determined by their electrical excitability, which is in turn influenced by the activity of potassium channels. The activity of potassium channels sustains smooth muscle cell membrane hyperpolarization, reducing cellular excitability and thereby promoting smooth muscle relaxation. Research over the past decade has indicated an important role for Kv7 (KCNQ) voltage-gated potassium channels in the regulation of the excitability of smooth muscle cells. Expression of multiple Kv7 channel subtypes has been demonstrated in smooth muscle cells from viscera (gastrointestinal, bladder, myometrial), from the systemic and pulmonary vasculature, and from the airways of the lung, from multiple species, including humans. A number of clinically used drugs, some of which were developed to target Kv7 channels in other tissues, have been found to exert robust effects on smooth muscle Kv7 channels. Functional studies have indicated that Kv7 channel activators and inhibitors have the ability to relax and contact smooth muscle preparations, respectively, suggesting a wide range of novel applications for the pharmacological tool set. This review summarizes recent findings regarding the physiological functions of Kv7 channels in smooth muscle, and highlights potential therapeutic applications based on pharmacological targeting of smooth muscle Kv7 channels throughout the body. Published by Elsevier Inc.

Propofol preferentially relaxes neurokinin receptor-2-induced airway smooth muscle contraction in guinea pig trachea.

PubMed

Gleason, Neil R; Gallos, George; Zhang, Yi; Emala, Charles W

2010-06-01

Propofol is the anesthetic of choice for patients with reactive airway disease and is thought to reduce intubation- or irritant-induced bronchoconstriction by decreasing the cholinergic component of vagal nerve activation. However, additional neurotransmitters, including neurokinins, play a role in irritant-induced bronchoconstriction. We questioned the mechanistic assumption that the clinically recognized protective effect of propofol against irritant-induced bronchoconstriction during intubation was due to attenuation of airway cholinergic reflexes. Muscle force was continuously recorded from isolated guinea pig tracheal rings in organ baths. Rings were subjected to exogenous contractile agonists (acetylcholine, histamine, endothelin-1, substance P, acetyl-substance P, and neurokinin A) or to electrical field stimulation (EFS) to differentiate cholinergic or nonadrenergic, noncholinergic nerve-mediated contraction with or without cumulatively increasing concentrations of propofol, thiopental, etomidate, or ketamine. Propofol did not attenuate the cholinergic component of EFS-induced contraction at clinically relevant concentrations. In contrast, propofol relaxed nonadrenergic, noncholinergic-mediated EFS contraction at concentrations within the clinical range (20-100 mum, n = 9; P < 0.05), and propofol was more potent against an exogenous selective neurokinin-2 receptor versus neurokinin-1 receptor agonist contraction (n = 6, P < 0.001). Propofol, at clinically relevant concentrations, relaxes airway smooth muscle contracted by nonadrenergic, noncholinergic-mediated EFS and exogenous neurokinins but not contractions elicited by the cholinergic component of EFS. These findings suggest that the mechanism of protective effects of propofol against irritant-induced bronchoconstriction involves attenuation of tachykinins released from nonadrenergic, noncholinergic nerves acting at neurokinin-2 receptors on airway smooth muscle.

Effects of tachykinins on uterine smooth muscle.

PubMed

Patak, E N; Pennefather, J N; Story, M E

2000-11-01

1. Sensory nerves supplying the mammalian uterus have been shown to contain substance P (SP) and neurokinin (NK)A. This review presents some of the advances that have led to a greater understanding of the effects of tachykinins on uterine smooth muscle. 2. The cell-surface peptidase neprilysin (EC.3 24.11, endopeptidase 24.11, enkephalinase, CALLA, CD10) has been shown to play a major role in regulating the actions of tachykinins on both rat and human myometrium. Because this peptidase is known to be regulated by steroids and pregnancy, its effects may be of physiological relevance. 3. Tachykinins produce contractions of isolated myometrial preparations from non-pregnant rats and mice. The NK2 receptor mediates these effects in rat uterus, while the NK1 receptor may mediate these effects in the mouse uterus. 4. The effects of tachykinins have been examined on myometrial preparations obtained at Caesarean section from near-term pregnant women. In the presence of the peptidase inhibitors (thiorphan, captopril and bestatin), the mammalian tachykinins SP, NKA and NKB produced concentration-dependent uterine contractions. 5. The order of agonist potency NKA > SP = NKB suggested that NK2 receptors mediate uterine contractions in the human. This was confirmed using the stable analogues [Sar9,Met(O2)11]SP, [Lys5MeLeu9Nle10]NKA(4-10) and [N-MePhe7]NKB, which are NK1, NK2 and NK3 receptor selective, respectively. Only [Lys5MeLeu9Nle10]NKA(4-10) produced concentration-related contractions of human uterine smooth muscle. 6. The experimental findings described in the present review, taken together with results published previously in the literature, indicate that tachykinin peptides may play a physiological or pathophysiological role in regulating uterine smooth muscle activity. However, more extensive research will be required to confirm such a role for these peptides.

The influence of a heat and moisture exchanger on tracheal climate in a cold environment.

PubMed

Zuur, J Karel; Muller, Sara H; Vincent, Andrew; Sinaasappel, Michiel; de Jongh, Frans H C; Hilgers, Frans J M

2009-09-01

The incidence of pulmonary complaints, severe tracheitis and lung function deterioration is increased during wintertime in laryngectomized individuals. We analyzed how a heat and moisture exchanger (HME) performs in cold and dry ambient circumstances, and how its efficiency in this environmental climate might be improved. Randomized crossover. Intra-tracheal temperature and humidity were measured in 10 laryngectomized patients with and without HME, in a cold (mean, 4.7 degrees C) and dry (mean, 4.5 mgH2O/L) room. Presence of an HME causes the intra-tracheal mean humidity minima and maxima to increase with 4.2 mgH2O/L (95%CI: 3.3-5.0 mgH2O/L; p<0.001) and 2.4 mgH2O/L (95%CI: 1.7-3.1 mgH2O/L; p<0.001), respectively. The intra-tracheal mean temperature minima and maxima increased with 3.9 degrees C (95%CI: 2.7-5.1 degrees C; p<0.001) and 1.2 degrees C (95%CI: 0.8-1.2 degrees C; p<0.001), respectively. In the majority of patients, the calculated relative humidity values appear to reach well above 100% during inspiration. In a cold environment, presence of an HME significantly increases both inspiratory and expiratory temperature and humidity values. Relative humidity calculations suggest the formation of condense droplets during inspiration. To further increase its effectiveness, improvement of the HME's thermal capacity should be aimed for.

Snake Envenomation Causing Distant Tracheal Myonecrosis

PubMed Central

Khimani, Amina; Mcnierney, Afton; Surani, Sara; Surani, Salim

2013-01-01

Snakebites are often believed to be poisonous. However, this is not always the case. In fact, each bite differs from snake to snake, depending on if the snake is poisonous and if there is envenomation. Venom in pit viper snakebites is often associated with local necrosis. The abundant literature selections and research articles justify local myonecrosis due to envenomation, but there is not much in the literature regarding myonecrosis at a site distant from the snakebite. We hereby present a case of a 42-year-old man who was transferred to our emergency department after a rattlesnake bit him twice. The patient, besides developing local myonecrosis at the site of the snakebite, developed necrosis of the scrotum as well as tracheal pressure myonecrosis at the site of the endotracheal tube balloon. In this review, we will attempt to discuss the myonecrosis pathophysiology and management related to the rattle snakebite. PMID:24083047

PDK1/Akt/PDE4D axis identified as a target for asthma remedy synergistic with β2 AR agonists by a natural agent arctigenin.

PubMed

Fang, R; Cui, Q; Sun, J; Duan, X; Ma, X; Wang, W; Cheng, B; Liu, Y; Hou, Y; Bai, G

2015-12-01

Asthma is a heterogenetic disorder characterized by chronic inflammation with variable airflow obstruction and airway hyper-responsiveness. As the most potent and popular bronchodilators, β2 adrenergic receptor (β2 AR) agonists bind to the β2 ARs that are coupled via a stimulatory G protein to adenylyl cyclase, thereby improving cAMP accumulation and resulting in airway smooth muscle relaxation. We previously demonstrated arctigenin had a synergistic function with the β2 AR agonist, but the target for this remained elusive. Chemical proteomics capturing was used to enrich and uncover the target of arctigenin in human bronchial smooth muscle cells, and reverse docking and molecular dynamic stimulation were performed to evaluate the binding of arctigenin and its target. In vitro enzyme activities and protein levels were demonstrated with special kits and Western blotting. Finally, guinea pig tracheal muscle segregation and ex vivo function were analysed. Arctigenin bound to PDK1 with an ideal binding free energy -25.45 kcal/mol and inhibited PDK1 kinase activity without changing its protein level. Additionally, arctigenin reduced PKB/Akt-induced phosphorylation of PDE4D, which was first identified in this study. Attenuation of PDE4D resulted in cAMP accumulation in human bronchial smooth muscle. The inhibition of PDK1 showed a synergistic function with β2 AR agonists and relaxed the constriction of segregated guinea pig tracheal muscle. The PDK1/Akt/PDE4D axis serves as a novel asthma target, which may benefit airflow obstruction. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Influence of short distance transportation on tracheal bacterial content and lower airway cytology in horses.

PubMed

Allano, Marion; Labrecque, Olivia; Rodriguez Batista, Edisleidy; Beauchamp, Guy; Bédard, Christian; Lavoie, Jean-Pierre; Leclere, Mathilde

2016-08-01

The aim of this study was to determine the effects of short distance transportation on airway mucus, cytology and bacterial culture to identify potential biases in the diagnosis of airway diseases in referral centres. Eight healthy adult horses were studied using a prospective cross-over design. Mucus scores, tracheal wash (cytology, bacterial culture) and bronchoalveolar lavage fluid (BALF; cytology) were obtained while stabled and following 2.5 h transportation (with and without hay). Neutrophil counts, percentages and BALF neutrophilia frequency increased following transport without hay (P <0.05). No effect was observed on tracheal cytology and bacterial count (P > 0.05). BALF neutrophilia could develop solely as a result of transportation or due to interactions between repeated transports, ambient temperature, head position or other environmental factors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ethical issues in laryngology: tracheal stenting as palliative care.

PubMed

Kazi, Aasif A; Flowers, W Jeffrey; Barrett, Jeanna M; O'Rourke, Ashli K; Postma, Gregory N; Weinberger, Paul M

2014-07-01

To improve understanding of aspects of end-of-life care that may not be intuitive to the otolaryngology community. A comprehensive review of the literature was performed by searching Medline, Embase, and Google Scholar databases. Primary manuscripts' bibliographies were reviewed to identify any nonindexed references. Prospective consultation by means of one-on-one interviews was sought from nonotolaryngology key stakeholders in the areas of hospice nursing care and patient advocacy in order to identify pertinent issues. We identified over 1,000 articles published from 1965 to 2013 on the topic of tracheal stents, as well as over 40,000 on hospice/end-of-life care. Three articles focusing specifically on palliative care and airway stenting were identified, of which three were case reports and none were definitive reviews. There are a number of significant issues and concepts unique to hospice care. These are likely unfamiliar to all except for head and neck oncology-specialized otolaryngologists. An example is that hospice care focuses on quality of life rather than prolongation of life (such as curative surgery). Patients with nonoperable tracheal obstruction from malignancy face an unpleasant demise from suffocation. For those patients, stenting can relieve suffering by restoring airway patency. Airway stenting can be a valid palliative care option, even for terminal patients receiving hospice care, when performed to relieve airway obstruction and improve quality of life. End-of-life ethics is an underdeveloped area of otolaryngology that should be explored. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

S100A8 protein attenuates airway hyperresponsiveness by suppressing the contraction of airway smooth muscle.

PubMed

Xu, Yu-Dong; Wang, Yu; Yin, Lei-Miao; Park, Gyoung-Hee; Ulloa, Luis; Yang, Yong-Qing

2017-02-26

Airway hyperresponsiveness (AHR) is a major clinical problem in allergic asthma mainly caused by the hypercontractility of airway smooth muscles (ASM). S100A8 is an important member of the S100 calcium-binding protein family with a potential to regulate cell contractility. Here, we analyze the potential of S100A8 to regulate allergen-induced AHR and ASM contraction. Treatment with recombinant S100A8 (rS100A8) diminished airway hyperresponsiveness in OVA-sensitized rats. ASM contraction assays showed that rS100A8 reduced hypercontractility in both isolated tracheal rings and primary ASM cells treated by acetylcholine. rS100A8 markedly rescued the phosphorylation level of myosin light chain induced by acetylcholine in ASM cells. These results show that rS100A8 plays a protective role in regulating AHR in asthma by inhibiting ASM contraction. These results support S100A8 as a novel therapeutic target to control ASM contraction in asthma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

[An experimental study of successful tracheal replacement using pedicled latissimus dorsi muscle flap and soft Marlex mesh].

PubMed

Hayashi, A

1991-02-01

The present experimental study was undertaken to evaluate the efficacy of combined latissimus dorsi muscle flap and soft Marlex mesh in the reconstruction of the trachea. Thirty-one mongrel dogs underwent a two-stage operation. In the first stage operation, they were divided into four groups for implanting a different prosthesis. A silicone rod was used as the core and this was rolled with soft Marlex mesh to make a prosthesis (Group A and B: without reinforce, Group C: reinforced by wrapping stainless steel mesh, Group D: reinforced with helical stain steel wire). The latissimus dorsi muscle flap was rolled circumferentially around the prosthesis and it was left in place for a period of 4 to 6 weeks. In the second stage operation, the long pedicled muscle flap with the biologically organized prosthesis was mobilized to be guided into the cervix, and the tracheal reconstruction was done with them following circumferential tracheal resection. In result, five of six dogs of group D survived more than 6 months after the replacement without anastomotic leakage or stenosis causing inflammatory granulation. Organization with neo-vascularity of the prosthesis at the time of the tracheal reconstruction was important firstly to avoid incurring complications concerning anastomosis and secondly for long-term stability of the healing and epithelialization of the prosthesis.

Efficacy and tolerance of a new silicone stent for the treatment of benign tracheal stenosis: preliminary results.

PubMed

Vergnon, J M; Costes, F; Polio, J C

2000-08-01

In inoperable patients with tracheal stenosis who are treated using silicone stents, stent migration occurs in 18.6% of cases. To decrease the migration rate, we have designed a new silicone stent with narrow central and larger distal parts. This study analyzes the stability and tolerance of this new stent. Preliminary prospective study conducted in two French university hospitals. Thirteen inoperable patients with benign complex tracheal stenosis due to intubation or tracheotomy. Tracheal stent insertion was performed under general anesthesia with a rigid bronchoscope. The patients were followed up clinically up to stent removal, which was planned at 18 months. Stent insertion or removal was very simple and did not differ from other silicone stents. No migration occurred after a mean follow-up of 22.8 months. Minimal granuloma formation occurred in only one patient (7.7%). Sputum retention remained similar to that with other silicone stents and could be improved by a smoother internal wall. Stents have been removed in seven patients after a mean duration of 19.6 months, with a complete stenosis cure in four cases. This new stent combines the excellent stability of the metallic stents and the tolerance and easy removal of straight silicone stents. This allows a prolonged use in order to obtain curative action.

Ureter smooth muscle cell orientation in rat is predominantly longitudinal.

PubMed

Spronck, Bart; Merken, Jort J; Reesink, Koen D; Kroon, Wilco; Delhaas, Tammo

2014-01-01

In ureter peristalsis, the orientation of the contracting smooth muscle cells is essential, yet current descriptions of orientation and composition of the smooth muscle layer in human as well as in rat ureter are inconsistent. The present study aims to improve quantification of smooth muscle orientation in rat ureters as a basis for mechanistic understanding of peristalsis. A crucial step in our approach is to use two-photon laser scanning microscopy and image analysis providing objective, quantitative data on smooth muscle cell orientation in intact ureters, avoiding the usual sectioning artifacts. In 36 rat ureter segments, originating from a proximal, middle or distal site and from a left or right ureter, we found close to the adventitia a well-defined longitudinal smooth muscle orientation. Towards the lamina propria, the orientation gradually became slightly more disperse, yet the main orientation remained longitudinal. We conclude that smooth muscle cell orientation in rat ureter is predominantly longitudinal, though the orientation gradually becomes more disperse towards the proprial side. These findings do not support identification of separate layers. The observed longitudinal orientation suggests that smooth muscle contraction would rather cause local shortening of the ureter, than cause luminal constriction. However, the net-like connective tissue of the ureter wall may translate local longitudinal shortening into co-local luminal constriction, facilitating peristalsis. Our quantitative, minimally invasive approach is a crucial step towards more mechanistic insight into ureter peristalsis, and may also be used to study smooth muscle cell orientation in other tube-like structures like gut and blood vessels.

[Anesthetic management of a patient with Creutzfeldt-Jacob disease undergoing tracheal separation].

PubMed

Kanzaki, Rieko; Hamada, Hiroshi; Fukuda, Hideki; Kawamoto, Masashi

2012-10-01

We gave anesthesia for tracheal separation in a patient with Creutzfeldt-Jakob disease. The patient, a 33-year-old woman, was bedridden and unable to communicate, and was going to undergo a tracheal separation procedure for repeated bouts of aspiration pneumonia. After a tracheostomy with local anesthesia and sedation with propofol, general anesthesia was induced and maintained with propofol (1.5-3.0 microg x ml(-1), target controlled infusion) and remifentanil (0.05-0.15 microg x kg(-1) x min(-1)). We did not use an anesthetic apparatus from the standpoint of infection control, and provided manual ventilation with a disposable Jackson-Rees circuit. During the operation, an entropy monitor indicated alternating extremely low (0-10) and high (90-100) values without circulatory change, probably due to a previously existing electroencephalographic abnormality. The surgery was uneventful, and spontaneous breathing and eyelid opening occurred about 10 minutes after discontinuation of remifentanil and propofol. In such infected patients, abnormal prion proteins can exist outside of the central nervous system throughout the period of anesthetic management. Therefore, careful infection control must be undertaken, even if the surgical site is not directly related to the central nervous system.

Stimulated Raman and Brillouin scattering of polarization-smoothed and temporally smoothed laser beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berger, R.L.; Lefebvre, E.; Langdon, A.B.

1999-04-01

Control of filamentation and stimulated Raman and Brillouin scattering is shown to be possible by use of both spatial and temporal smoothing schemes. The spatial smoothing is accomplished by the use of phase plates [Y. Kato and K. Mima, Appl. Phys. {bold 329}, 186 (1982)] and polarization smoothing [Lefebvre {ital et al.}, Phys. Plasmas {bold 5}, 2701 (1998)] in which the plasma is irradiated with two orthogonally polarized, uncorrelated speckle patterns. The temporal smoothing considered here is smoothing by spectral dispersion [Skupsky {ital et al.}, J. Appl. Phys. {bold 66}, 3456 (1989)] in which the speckle pattern changes on themore » laser coherence time scale. At the high instability gains relevant to laser fusion experiments, the effect of smoothing must include the competition among all three instabilities. {copyright} {ital 1999 American Institute of Physics.}« less

Nitric oxide production by cultured human aortic smooth muscle cells: stimulation by fluid flow

NASA Technical Reports Server (NTRS)

Papadaki, M.; Tilton, R. G.; Eskin, S. G.; McIntire, L. V.

1998-01-01

This study demonstrated that exposure of cultured human aortic smooth muscle cells (SMC) to fluid flow resulted in nitric oxide (NO) production, monitored by nitrite and guanosine 3',5'-cyclic monophosphate production. A rapid burst in nitrite production rate was followed by a more gradual increase throughout the period of flow exposure. Neither the initial burst nor the prolonged nitrite production was dependent on the level of shear stress in the range of 1.1-25 dyn/cm2. Repeated exposure to shear stress after a 30-min static period restimulated nitrite production similar to the initial burst. Ca(2+)-calmodulin antagonists blocked the initial burst in nitrite release. An inhibitor of nitric oxide synthase (NOS) blocked nitrite production, indicating that changes in nitrite reflect NO production. Treatment with dexamethasone or cycloheximide had no effect on nitrite production. Monoclonal antibodies directed against the inducible and endothelial NOS isoforms showed no immunoreactivity on Western blots, whereas monoclonal antibodies directed against the neuronal NOS gave specific products. These findings suggest that human aortic SMC express a constitutive neuronal NOS isoform, the enzymatic activity of which is modulated by flow.

A decade of using intraluminal tracheal/bronchial stents in the management of tracheomalacia and/or bronchomalacia: is it better than aortopexy?

PubMed

Valerie, Evans P; Durrant, Audrey C; Forte, Vito; Wales, Paul; Chait, Peter; Kim, Peter C W

2005-06-01

We compared the efficacy and clinical outcomes of aortopexy versus tracheal stents in the management of tracheomalacia. A retrospective analysis of 25 consecutive patients undergoing aortopexy (n = 11; 8 boys, 3 girls) or tracheal stents (n = 14; 9 boys, 5 girls) between 1993 and 2003 was performed. Both treatment groups, aortopexy versus stents, were comparable in their mean age of diagnosis, timing of intervention, surgical indications ("dying spell" or failed extubation), and previous underlying conditions. The operative time (190 vs 72 minutes) and blood loss (26 vs 0 mL) were significantly greater in aortopexy group (P < .01). There were no perioperative deaths in either group. Interestingly, 4 of 11 patients in the aortopexy group developed pericardial effusion (P < .01). With stents in place for a mean of 15 (range 2-41) months, 3 of 8 patients with stent removal had significant granulation tissue requiring further dilatation. No death was observed in aortopexy group, whereas 1 stent-related death and 1 cardiac arrest requiring median sternotomy occurred during stent removal in 44 and 32 months' follow-up, respectively. Both aortopexy and tracheal stents are effective treatment modalities in the management of tracheomalacia. However, although aortopexy is associated with early perioperative complications, tracheal stents are associated with higher failure rate and more severe stent-related morbidity and mortality.

smoothG

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barker, Andrew T.; Gelever, Stephan A.; Lee, Chak S.

2017-12-12

smoothG is a collection of parallel C++ classes/functions that algebraically constructs reduced models of different resolutions from a given high-fidelity graph model. In addition, smoothG also provides efficient linear solvers for the reduced models. Other than pure graph problem, the software finds its application in subsurface flow and power grid simulations in which graph Laplacians are found

Effects of epithelium removal on relaxation of airway smooth muscle induced by vasoactive intestinal peptide and electrical field stimulation.

PubMed Central

Farmer, S. G.; Togo, J.

1990-01-01

1. We have studied the effect of epithelium removal on relaxation of guinea-pig isolated tracheal smooth muscle induced by vasoactive intestinal peptide (VIP) or stimulation of non-adrenergic, non-cholinergic (NANC) inhibitory nerves. Also examined were the effects of inhibitors of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE). 2. Epithelium removal produced a 3.6 +/- 0.4 fold leftward shift in the VIP concentration-response curve. The supersensitivity to VIP, following epithelium removal was abolished by phosphoramidon or thiorphan (NEP inhibitors), but unaffected by captopril (an ACE inhibitor). In intact trachea, the NEP inhibitors produced leftward shifts in the VIP curves similar to those produced by epithelium removal. 3. In contrast to responses to exogenous VIP, neurogenic NANC inhibitory responses to electrical field stimulation were affected neither by epithelial denudation nor by the peptidase inhibitors. 4. As in previous studies, epithelium removal increased tracheal sensitivity to isoprenaline. This was not altered by pretreatment with a cocktail of peptidase inhibitors. Thus, the effect of the NEP inhibitors on responses to VIP appears to be relatively specific. 5. These data indicate that exogenous VIP is a substrate for airway NEP, since inhibition of the enzyme potentiates the peptide. This is further evidence that the airway epithelium provides a source for the metabolism of mediators. 6. In guinea-pig trachea the NEP responsible for cleaving VIP may be located largely in the epithelial layer, since NEP inhibition was without effect on sensitivity to VIP in epithelium-denuded preparations. If VIP is a NANC inhibitory neurotransmitter in this tissue its degradation endogenously does not appear to involve epithelial NEP. PMID:2196967

Income Smoothing: Methodology and Models.

DTIC Science & Technology

1986-05-01

studies have all followed a similar research process (Figure 1). All were expost studies and included the following steps: 1. A smoothing technique(s) or...researcher methodological decisions used in past empirical studies of income smoothing (design type, smoothing device norm, and income target) are discussed...behavior. The identification of smoothing, and consequently the conclusions to be drawn from smoothing studies , is found to be sensitive to the three

An approach to tracheostomy in a patient with an expandable metallic tracheal stent.

PubMed

Madden, Brendan P; Sheth, Abhijat

2005-09-01

With increasing use of expandable metallic stents to manage patients with a variety of endobronchial pathologies, some will have a subsequent need for tracheostomy insertion. We describe a successful technique to insert a tracheostomy using rigid and fibre-optic bronchoscopy in a patient who had an 8 cm expandable metallic tracheal stent deployed previously on account of tracheomalacia.

The Neural Basis of Smooth Pursuit Eye Movements in the Rhesus Monkey Brain

ERIC Educational Resources Information Center

Ilg, Uwe J.; Thier, Peter

2008-01-01

Smooth pursuit eye movements are performed in order to prevent retinal image blur of a moving object. Rhesus monkeys are able to perform smooth pursuit eye movements quite similar as humans, even if the pursuit target does not consist in a simple moving dot. Therefore, the study of the neuronal responses as well as the consequences of…

Intracellular pH changes in human aortic smooth muscle cells in response to fluid shear stress

NASA Technical Reports Server (NTRS)

Stamatas, G. N.; Patrick, C. W. Jr; McIntire, L. V.

1997-01-01

The smooth muscle cell (SMC) layers of human arteries may be exposed to blood flow after endothelium denudation, for example, following balloon angioplasty treatment. These SMCs are also constantly subjected to pressure driven transmural fluid flow. Flow-induced shear stress can alter SMC growth and metabolism. Signal transduction mechanisms involved in these flow effects on SMCs are still poorly understood. In this work, the hypothesis that shear stress alters the intracellular pH (pHi) of SMC is examined. When exposed to venous and arterial levels of shear stress, human aortic smooth muscle cells (hASMC) undergo alkalinization. The alkalinization plateau persisted even after 20 min of cell exposure to flow. Addition of amiloride (10 micromoles) or its 5-(N-ethyl-N-isopropyl) analog (EIPA, 10 micromoles), both Na+/H+ exchanger inhibitors, attenuated intracellular alkalinization, suggesting the involvement of the Na+/H+ exchanger in this response. The same concentrations of these inhibitors did not show an effect on pHi of hASMCs in static culture. 4-Acetamido-4'-isothio-cyanatostilbene-2,2'-disulfonic acid (SITS, 1 mM), a Cl-/HCO3- exchange inhibitor, affected the pHi of hASMCs both in static and flow conditions. Our results suggest that flow may perturb the Na+/H+ exchanger leading to an alkalinization of hASMCs, a different response from the flow-induced acidification seen with endothelial cells at the same levels of shear stress. Understanding the flow-induced signal transduction pathways in the vascular cells is of great importance in the tissue engineering of vascular grafts. In the case of SMCs, the involvement of pHi changes in nitric oxide production and proliferation regulation highlights further the significance of such studies.

P21-Activated Kinase Inhibitors FRAX486 and IPA3: Inhibition of Prostate Stromal Cell Growth and Effects on Smooth Muscle Contraction in the Human Prostate

PubMed Central

Wang, Yiming; Gratzke, Christian; Tamalunas, Alexander; Wiemer, Nicolas; Ciotkowska, Anna; Rutz, Beata; Waidelich, Raphaela; Strittmatter, Frank; Liu, Chunxiao; Stief, Christian G.; Hennenberg, Martin

2016-01-01

Prostate smooth muscle tone and hyperplastic growth are involved in the pathophysiology and treatment of male lower urinary tract symptoms (LUTS). Available drugs are characterized by limited efficacy. Patients’ adherence is particularly low to combination therapies of 5α-reductase inhibitors and α1-adrenoceptor antagonists, which are supposed to target contraction and growth simultaneously. Consequently, molecular etiology of benign prostatic hyperplasia (BPH) and new compounds interfering with smooth muscle contraction or growth in the prostate are of high interest. Here, we studied effects of p21-activated kinase (PAK) inhibitors (FRAX486, IPA3) in hyperplastic human prostate tissues, and in stromal cells (WPMY-1). In hyperplastic prostate tissues, PAK1, -2, -4, and -6 may be constitutively expressed in catecholaminergic neurons, while PAK1 was detected in smooth muscle and WPMY-1 cells. Neurogenic contractions of prostate strips by electric field stimulation were significantly inhibited by high concentrations of FRAX486 (30 μM) or IPA3 (300 μM), while noradrenaline- and phenylephrine-induced contractions were not affected. FRAX486 (30 μM) inhibited endothelin-1- and -2-induced contractions. In WPMY-1 cells, FRAX486 or IPA3 (24 h) induced concentration-dependent (1–10 μM) degeneration of actin filaments. This was paralleled by attenuation of proliferation rate, being observed from 1 to 10 μM FRAX486 or IPA3. Cytotoxicity of FRAX486 and IPA3 in WPMY-1 cells was time- and concentration-dependent. Stimulation of WPMY-1 cells with endothelin-1 or dihydrotestosterone, but not noradrenaline induced PAK phosphorylation, indicating PAK activation by endothelin-1. Thus, PAK inhibitors may inhibit neurogenic and endothelin-induced smooth muscle contractions in the hyperplastic human prostate, and growth of stromal cells. Targeting prostate smooth muscle contraction and stromal growth at once by a single compound is principally possible, at least under

P21-Activated Kinase Inhibitors FRAX486 and IPA3: Inhibition of Prostate Stromal Cell Growth and Effects on Smooth Muscle Contraction in the Human Prostate.

PubMed

Wang, Yiming; Gratzke, Christian; Tamalunas, Alexander; Wiemer, Nicolas; Ciotkowska, Anna; Rutz, Beata; Waidelich, Raphaela; Strittmatter, Frank; Liu, Chunxiao; Stief, Christian G; Hennenberg, Martin

2016-01-01

Prostate smooth muscle tone and hyperplastic growth are involved in the pathophysiology and treatment of male lower urinary tract symptoms (LUTS). Available drugs are characterized by limited efficacy. Patients' adherence is particularly low to combination therapies of 5α-reductase inhibitors and α1-adrenoceptor antagonists, which are supposed to target contraction and growth simultaneously. Consequently, molecular etiology of benign prostatic hyperplasia (BPH) and new compounds interfering with smooth muscle contraction or growth in the prostate are of high interest. Here, we studied effects of p21-activated kinase (PAK) inhibitors (FRAX486, IPA3) in hyperplastic human prostate tissues, and in stromal cells (WPMY-1). In hyperplastic prostate tissues, PAK1, -2, -4, and -6 may be constitutively expressed in catecholaminergic neurons, while PAK1 was detected in smooth muscle and WPMY-1 cells. Neurogenic contractions of prostate strips by electric field stimulation were significantly inhibited by high concentrations of FRAX486 (30 μM) or IPA3 (300 μM), while noradrenaline- and phenylephrine-induced contractions were not affected. FRAX486 (30 μM) inhibited endothelin-1- and -2-induced contractions. In WPMY-1 cells, FRAX486 or IPA3 (24 h) induced concentration-dependent (1-10 μM) degeneration of actin filaments. This was paralleled by attenuation of proliferation rate, being observed from 1 to 10 μM FRAX486 or IPA3. Cytotoxicity of FRAX486 and IPA3 in WPMY-1 cells was time- and concentration-dependent. Stimulation of WPMY-1 cells with endothelin-1 or dihydrotestosterone, but not noradrenaline induced PAK phosphorylation, indicating PAK activation by endothelin-1. Thus, PAK inhibitors may inhibit neurogenic and endothelin-induced smooth muscle contractions in the hyperplastic human prostate, and growth of stromal cells. Targeting prostate smooth muscle contraction and stromal growth at once by a single compound is principally possible, at least under experimental

Vasoactive intestinal peptide stimulates tracheal submucosal gland secretion in ferret

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peatfield, A.C.; Barnes, P.J.; Bratcher, C.

1983-07-01

We studied the effect of vasoactive intestinal peptide (VIP) on the output of 35S-labeled macromolecules from ferret tracheal explants either placed in beakers or suspended in modified Ussing chambers. In Ussing chamber experiments, the radiolabel precursor, sodium (35S)sulfate, and all drugs were placed on the submucosal side of the tissue. Washings were collected at 30-min intervals from the luminal side and were dialyzed to remove unbound 35S, leaving radiolabeled macromolecules. Vasoactive intestinal peptide at 3 X 10(-7) M stimulated bound 35S output by a mean of + 252.6% (n . 14). The VIP response was dose-dependent with a near maximalmore » response and a half maximal response at approximately 10(-6) M and 10(-8), M, respectively. The VIP effect was not inhibited by a mixture of tetrodotoxin, atropine, I-propranolol, and phentolamine. Vasoactive intestinal peptide had no effect on the electrical properties of the of the tissues. We conclude that VIP stimulates output of sulfated-macromolecules from ferret tracheal submucosal glands without stimulating ion transport. Our studies also suggest that VIP acts on submucosal glands via specific VIP receptors. Vasoactive intestinal peptide has been shown to increase intracellular levels of cyclic AMP, and we suggest that this may be the mechanism for its effect on the output of macromolecules. This mechanism may be important in the neural regulation of submucosal gland secretion.« less

Effect of just-in-time simulation training on tracheal intubation procedure safety in the pediatric intensive care unit.

PubMed

Nishisaki, Akira; Donoghue, Aaron J; Colborn, Shawn; Watson, Christine; Meyer, Andrew; Brown, Calvin A; Helfaer, Mark A; Walls, Ron M; Nadkarni, Vinay M

2010-07-01

Tracheal intubation-associated events (TIAEs) are common (20%) and life threatening (4%) in pediatric intensive care units. Physician trainees are required to learn tracheal intubation during intensive care unit rotations. The authors hypothesized that "just-in-time" simulation-based intubation refresher training would improve resident participation, success, and decrease TIAEs. For 14 months, one of two on-call residents, nurses, and respiratory therapists received 20-min multidisciplinary simulation-based tracheal intubation training and 10-min resident skill refresher training at the beginning of their on-call period in addition to routine residency education. The rate of first attempt and overall success between refresher-trained and concurrent non-refresher-trained residents (controls) during the intervention phase was compared. The incidence of TIAEs between preintervention and intervention phase was also compared. Four hundred one consecutive primary orotracheal intubations were evaluated: 220 preintervention and 181 intervention. During intervention phase, neither first-attempt success nor overall success rate differed between refresher-trained residents versus concurrent non-refresher-trained residents: 20 of 40 (50%) versus 15 of 24 (62.5%), P = 0.44 and 23 of 40 (57.5%) versus 18 of 24 (75.0%), P = 0.19, respectively. The resident's first attempt and overall success rate did not differ between preintervention and intervention phases. The incidence of TIAE during preintervention and intervention phases was similar: 22.0% preintervention versus 19.9% intervention, P = 0.62, whereas resident participation increased from 20.9% preintervention to 35.4% intervention, P = 0.002. Resident participation continued to be associated with TIAE even after adjusting for the phase and difficult airway condition: odds ratio 2.22 (95% CI 1.28-3.87, P = 0.005). Brief just-in-time multidisciplinary simulation-based intubation refresher training did not improve the resident

[Complications and the management of fully covered retrievable metal stent placement in benign tracheal stenosis].

PubMed

Wang, Zheng-yu; Wang, Yong-li; Chen, Guang-li; Liang, Xi-hong; Wang, Zhen-chang; Ma, Jian-zhong; Wu, Guang-zhong; Zhang, Xiao-ping

2012-11-01

To study complications and the management of the use of covered retrievable expandable metallic stents in the treatment of benign tracheal stenosis. Fully covered retrievable metal stents were placed in 21 patients with benign tracheal stenosis. Stent-related complications and the management were reviewed and analysed. Twenty-eight fully covered retrievable metallic stents were successfully placed fluoroscopically in 21 patients. Stents were removed 4 - 12 months [mean (5.5 ± 2.2) mouths] after placement in all patients. Stent-related complications included granulation tissue (n = 18), stent migration (n = 4), stent expectoration (n = 2), halitosis (n = 8), mucous retention (n = 21) and mucus plugging (n = 1). Granulation tissue was removed with a carbon dioxide laser in 2 patients. Stents were replaced for 2 times and 3 times respectively in 2 patients after stent migration and stent expectoration. An additional stent was placed in 2 patients after stent migration. Symptom of halitosis was relieved after prolonged course of systemic antibiotics treatment in 8 patients. Symptom of mucous retention was relieved with nebulized saline and N-acetylcysteine saline inhalation. Mucous plug was expelled after severe coughing after suctioning using an aspirator in one patient. There were statistically significant differences in stricture diameter, rank of tachypnea and pulmonary function (FEV(1)) in all 21 patients before stent insertion and after stents removal. No patient has experienced recurrence during the follow-up period of 1 - 36 months [mean (23.2 ± 8.0) months]. Fully covered retrievable metallic stent may be a safe and effective in benign tracheal stenosis. Stent-related complications may be effectively managed.

On the Morphological Description of Tracheal and Esophageal Displacement and Its Phylogenetic Distribution in Avialae

PubMed Central

Klingler, Jeremy J.

2016-01-01

This research examines the evolution and phylogenetic distribution of a peculiar and often overlooked character seen in birds, herein called tracheal and esophageal displacement. Tracheal and esophageal displacement refers to an asymmetrically situated trachea and/or esophagus along the length of the neck. This contrasts with what would be perceived as the “normal” (midsagittal) placement of these organs, wherein the two organs are situated along the ventral midline of the neck with no deviation. A total of forty-two bird species were examined (thirty-six of which came from dissections whereas six came from comments from previous literature or personal observations), as well as turtles, lizards, crocodylians, and mammals. This study found that essentially all birds have a laterally displaced trachea and/or esophagus. Lizards and mammals were seen to have normal, midsagittally placed tracheae and esophagi. Crocodylians were interesting in that alligators were defined by a normally situated trachea and esophagus whereas some crocodiles were characterized by displacement. In birds, the displacement may occur gradually along the neck, or it may happen immediately upon exiting the oropharynx. Displacement of these organs in birds is the result of a heavily modified neck wherein muscles that restrict mobility of the trachea and esophagus in lizards, alligators, and mammals (e.g., m. episternocleidomastoideus, m. omohyoideus, and m. sternohyoideus) no longer substantially restrict positions of the trachea and esophagus in birds. Rather, these muscles are modified in ways which may assist with making tracheal movements. The implications of this study may provide interesting insights for future comparisons in extinct taxa. PMID:27648952

Accuracy of tracheal aspirate gram stain in predicting Staphylococcus aureus infection in ventilator-associated pneumonia.

PubMed

Seligman, Renato; Seligman, Beatriz Graeff Santos; Konkewicz, Loriane; Dos Santos, Rodrigo Pires

2015-01-01

The Gram stain can be used to direct initial empiric antimicrobial therapy when complete culture is not available. This rapid test could prevent the initiation of inappropriate therapy and adverse outcomes. However, several studies have attempted to determine the value of the Gram stain in the diagnosis and therapy of bacterial infection in different populations of patients with ventilator-associated pneumonia (VAP) with conflicting results. The objective of this study is to evaluate the accuracy of the Gram stain in predicting the existence of Staphylococcus aureus infections from cultures of patients suspected of having VAP. This prospective single-center open cohort study enrolled 399 patients from December 2005 to December 2010. Patients suspected of having VAP by ATS IDSA criteria were included. Respiratory secretion samples were collected by tracheal aspirate (TA) for standard bacterioscopic analysis by Gram stain and culture. Respiratory secretion samples collected by tracheal aspirates of 392 patients were analyzed by Gram stain and culture. When Gram-positive cocci were arranged in clusters, the sensitivity was 68.4%, specificity 97.8%, positive predictive value 88.1% and negative predictive value 92.8% for predicting the presence of Staphylococcus aureus in culture (p < 0.001). A tracheal aspirate Gram stain can be used to rule out the presence of Staphylococcus aureus in patients with a clinical diagnosis of VAP with a 92.8% Negative Predictive Value. Therefore, 7.2% of patients with Staphylococcus aureus would not be protected by an empiric treatment that limits antimicrobial coverage to Staphylococcus aureus only when Gram positive cocci in clusters are identified.

[Pain assessment of tracheal suctioning on brain injury patients by pain behavioral indicator scale (ESCID)].

PubMed

López-López, C; Murillo-Pérez, M A; Morales-Sánchez, C; Torrente-Vela, S; Orejana-Martín, M; García-Iglesias, M; Cuenca-Solanas, M; Alted-López, E

2014-01-01

To assess pain response on patients with moderate to severe head injury before a common nursing procedure: tracheal suctioning. An observational longitudinal pilot study with consecutive sampling performed from September to December of 2012. Pain was assessed by a pain behavioral indicator scale 5 minutes before, meanwhile and 15 minutes after tracheal suctioning the days 1, 3 and 6 of their intensive care unit (ICU) stay, as well as a non-painful procedure: rubbing with gauze the forearm of the patient. Pseudo-analgesia and hemodynamic variables were also recorded. Descriptive analysis of the variables, inferential statistics with t-student and Anova with SPSS 17.0; statistical tests were considered significant if the critical level observed was less than 5% (P<.05). Pain was assessed on 27 patients. 82% suffered from severe head trauma and 18% moderate. The average pain value during nursing procedure day 1 was 3, 18±2.6, day 3: 2, 59±2 and day 6: 3, 94±2.3. There was a significant increase in mean pain while performing suctioning during the three days of assessment (P<.05); however no significant differences between the average pain value on the three days of the assessment (P>.05) were shown. Data for the painless procedure were significantly different on day 6 (P<.05) CONCLUSION: During tracheal suctioning in patients with head injury in the first 6 days in the ICU, objective mild-moderate pain according to ESCID scale has been detected. Copyright © 2013 Elsevier España, S.L.U. y SEEIUC. All rights reserved.

Expression and function of K(V)2-containing channels in human urinary bladder smooth muscle.

PubMed

Hristov, Kiril L; Chen, Muyan; Afeli, Serge A Y; Cheng, Qiuping; Rovner, Eric S; Petkov, Georgi V

2012-06-01

The functional role of the voltage-gated K(+) (K(V)) channels in human detrusor smooth muscle (DSM) is largely unexplored. Here, we provide molecular, electrophysiological, and functional evidence for the expression of K(V)2.1, K(V)2.2, and the electrically silent K(V)9.3 subunits in human DSM. Stromatoxin-1 (ScTx1), a selective inhibitor of K(V)2.1, K(V)2.2, and K(V)4.2 homotetrameric channels and of K(V)2.1/9.3 heterotetrameric channels, was used to examine the role of these channels in human DSM function. Human DSM tissues were obtained during open bladder surgeries from patients without a history of overactive bladder. Freshly isolated human DSM cells were studied using RT-PCR, immunocytochemistry, live-cell Ca(2+) imaging, and the perforated whole cell patch-clamp technique. Isometric DSM tension recordings of human DSM isolated strips were conducted using tissue baths. RT-PCR experiments showed mRNA expression of K(V)2.1, K(V)2.2, and K(V)9.3 (but not K(V)4.2) channel subunits in human isolated DSM cells. K(V)2.1 and K(V)2.2 protein expression was confirmed by Western blot analysis and immunocytochemistry. Perforated whole cell patch-clamp experiments revealed that ScTx1 (100 nM) inhibited the amplitude of the voltage step-induced K(V) current in freshly isolated human DSM cells. ScTx1 (100 nM) significantly increased the intracellular Ca(2+) level in DSM cells. In human DSM isolated strips, ScTx1 (100 nM) increased the spontaneous phasic contraction amplitude and muscle force, and enhanced the amplitude of the electrical field stimulation-induced contractions within the range of 3.5-30 Hz stimulation frequencies. These findings reveal that ScTx1-sensitive K(V)2-containing channels are key regulators of human DSM excitability and contractility and may represent new targets for pharmacological or genetic intervention for bladder dysfunction.

[A case report of the laryngeal edema and peripheral cyanosis after extubation of the tracheal tube].

PubMed

Itatani, Keiichi; Nishiyama, Tomoki; Hanaoka, Kazuo

2003-08-01

A 65-year-old male in malnutrition due to advanced colon cancer underwent resection of transverse colon tumor and the invaded abdominal muscles with necrosis and abscess. After epidural catheter insertion between Th 10-11 for 9 cm cephalad, anesthesia was induced with thiopental 200 mg and fentanyl 50 micrograms. Tracheal intubation was done with vecuronium 5 mg, and anesthesia was maintained with sevoflurane with nitrous oxide in oxygen and epidural block. During surgery, systolic blood pressure often went up to 130 to 140 mmHg and down to 50 to 60 mmHg. Dopamine 3-5 micrograms.kg-1.min-1 was administered but occasional ephedrine bolus injection was still necessary. The intestine, including the intact part, was edematous. After the surgery, when systolic blood pressure was stable at about 130 mmHg and his consciousness was clear with regular spontaneous respiration, the tracheal tube was removed. However, soon after the extubation, expiratory stridor and cyanosis of the bilateral hands and feet were observed. Hydrocortisone 200 mg and nicardipine 0.5 mg were administered and room temperature was raised. About 30 minutes later, stridor and cyanosis subsided. In the ward after surgery, only hoarseness was observed. The stridor might have been due to the laryngeal edema, which could be attributed to stimulation by tracheal tube in the patient with malnutrition. The hemodynamic instability during surgery and cyanosis after extubation might have come from changes of the vascular resistance by sepsis.

Notch Signaling in Vascular Smooth Muscle Cells

PubMed Central

Baeten, J.T.; Lilly, B.

2018-01-01

The Notch signaling pathway is a highly conserved pathway involved in cell fate determination in embryonic development and also functions in the regulation of physiological processes in several systems. It plays an especially important role in vascular development and physiology by influencing angiogenesis, vessel patterning, arterial/venous specification, and vascular smooth muscle biology. Aberrant or dysregulated Notch signaling is the cause of or a contributing factor to many vascular disorders, including inherited vascular diseases, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, associated with degeneration of the smooth muscle layer in cerebral arteries. Like most signaling pathways, the Notch signaling axis is influenced by complex interactions with mediators of other signaling pathways. This complexity is also compounded by different members of the Notch family having both overlapping and unique functions. Thus, it is vital to fully understand the roles and interactions of each Notch family member in order to effectively and specifically target their exact contributions to vascular disease. In this chapter, we will review the Notch signaling pathway in vascular smooth muscle cells as it relates to vascular development and human disease. PMID:28212801

N-acetylcysteine does not improve the endothelial and smooth muscle function in the human saphenous vein.

PubMed

Sharif, Muhammad Anees; Bayraktutan, Ulvi; Young, Ian Stuart; Soong, Chee Voon

2007-01-01

Oxidative stress can lead to vein graft dysfunction in the saphenous vein. This ex vivo study is aimed to compare the effects of increasing concentrations of the antioxidant N-acetylcysteine (NAC) with heparinized saline (HS) on endothelial and smooth muscle function in the human saphenous vein. Long saphenous vein segment obtained during infrainguinal bypass surgery was divided into 7 rings; 1 immersed in HS and the remaining 6 in increasing NAC concentrations (0.0025%, 0.005%, 0.01%, 0.02%, 0.03%, and 0.04%). Rings were mounted in an organ bath, and relaxant responses to acetylcholine and sodium nitroprusside were assessed through isometric tension studies. Endothelium-dependent relaxations were observed in 77 vein segments from 11 patients. No significant difference was seen in veins treated with either lower NAC concentrations (0.0025%, 0.005%, 0.01%, 0.02%, and 0.03%) or HS. However, HS-treated veins showed significantly better relaxation compared to those treated with maximum (0.04%) NAC (P < .05). Endothelium-independent relaxations were observed in 91 segments from 13 patients. No difference in relaxation was observed between veins treated with HS or any of the NAC concentrations. In conclusion, lower NAC concentrations do not offer better endothelial protection than HS, whereas the highest NAC concentration has a detrimental effect on endothelium-dependent relaxation. Moreover, NAC did not show beneficial effect on direct smooth muscle relaxation.

Arachidonate-Regulated Ca2+ Influx in Human Airway Smooth Muscle

PubMed Central

Thompson, Michael A.; Prakash, Y. S.

2014-01-01

Plasma membrane Ca2+ influx, especially store-operated Ca2+ entry triggered by sarcoplasmic reticulum (SR) Ca2+ release, is a key component of intracellular calcium concentration ([Ca2+]i) regulation in airway smooth muscle (ASM). Agonist-induced Ca2+ oscillations in ASM that involve both influx and SR mechanisms have been previously demonstrated. In nonexcitable cells, [Ca2+]i oscillations involve Ca2+ influx via arachidonic acid (AA) –stimulated channels, which show similarities to store-operated Ca2+ entry, although their molecular identity remains undetermined. Little is known about AA-regulated Ca2+ channels or their regulation in ASM. In enzymatically dissociated human ASM cells loaded with the Ca2+ indicator, fura-2, AA (1–10 μM) triggered [Ca2+]i oscillations that were inhibited by removal of extracellular Ca2+. Other fatty acids, such as the diacylglycerol analog, 1-oleoyl-2-acetyl-SN-glycerol, oleic acid, and palmitic acid (10 μM each), failed to elicit similar [Ca2+]i responses. Preincubation with LaCl3 (1 μM or 1 mM) inhibited AA-induced oscillations. Inhibition of receptor-operated channels (SKF96,365 [10 μM]), lipoxygenase (zileuton [10 μM]), or cyclooxygenase (indomethacin [10 μM]) did not affect oscillation parameters. Inhibition of SR Ca2+ release (ryanodine [10 μM] or inositol 1,4,5-trisphosphate receptor inhibitor, xestospongin C [1 μM]) decreased [Ca2+]i oscillation frequency and amplitude. Small interfering RNA against caveolin-1, stromal interaction molecule 1, or Orai3 (20 nM each) reduced the frequency and amplitude of AA-induced [Ca2+]i oscillations. In ASM cells derived from individuals with asthma, AA increased oscillation amplitude, but not frequency. These results are highly suggestive of a novel AA-mediated Ca2+–regulatory mechanism in human ASM, reminiscent of agonist-induced oscillations. Given the role of AA in ASM intracellular signaling, especially with inflammation, AA-regulated Ca2+ channels could potentially

Use of nitinol self-expandable stents in 26 dogs with tracheal collapse.

PubMed

Beranek, J; Jaresova, H; Rytz, U

2014-02-01

A study was designed to describe a novel approach to the treatment of tracheal collapse (TC) in dogs using self-expandable nitinol stents. Medical records were reviewed retrospectively for 26 client owned dogs in which nitinol stents were deployed. The entire length of trachea was supported independently of the extent of TC. Two overlapping stents were used instead of one in cases where one stent was not spanning the entire trachea adequately. The diameter of the cranial radiolucent portion of trachea, just behind the cricoid cartilage, was measured as a specific landmark to select the appropriate size of the stent. Two self-expandable nitinol stents were inserted in 9 of 26 dogs; the trachea in the rest of the cases was supported with only one stent. A follow up tracheoscopy was performed in 10 of 26 cases with recurrent clinical signs. Secondary tracheal stenosis in these cases was caused by stent fracture, granuloma or excessive stent shortening. Additional stents were placed successfully to expand the stenotic lumen. A support of the entire trachea may decrease risk of nitinol fracture at the end of the implant. Long term clinical improvement (25 of 26 dogs, 96 %) is comparable with the results of other studies.

Distinguishing tracheal and esophageal tissues with hyperspectral imaging and fiber-optic sensing

NASA Astrophysics Data System (ADS)

Nawn, Corinne D.; Souhan, Brian E.; Carter, Robert, III; Kneapler, Caitlin; Fell, Nicholas; Ye, Jing Yong

2016-11-01

During emergency medical situations, where the patient has an obstructed airway or necessitates respiratory support, endotracheal intubation (ETI) is the medical technique of placing a tube into the trachea in order to facilitate adequate ventilation of the lungs. Complications during ETI, such as repeated attempts, failed intubation, or accidental intubation of the esophagus, can lead to severe consequences or ultimately death. Consequently, a need exists for a feedback mechanism to aid providers in performing successful ETI. Our study examined the spectral reflectance properties of the tracheal and esophageal tissue to determine whether a unique spectral profile exists for either tissue for the purpose of detection. The study began by using a hyperspectral camera to image excised pig tissue samples exposed to white and UV light in order to capture the spectral reflectance properties with high fidelity. After identifying a unique spectral characteristic of the trachea that significantly differed from esophageal tissue, a follow-up investigation used a fiber optic probe to confirm the detectability and consistency of the different reflectance characteristics in a pig model. Our results characterize the unique and consistent spectral reflectance characteristic of tracheal tissue, thereby providing foundational support for exploiting spectral properties to detect the trachea during medical procedures.

Application of State-Space Smoothing to fMRI Data for Calculation of Lagged Transinformation between Human Brain Activations

NASA Astrophysics Data System (ADS)

Watanabe, Jobu

2009-09-01

Mutual information can be given a directional sense by introducing a time lag in one of the variables. In an author's previous study, to investigate the network dynamics of human brain regions, lagged transinformation (LTI) was introduced using time delayed mutual information. The LTI makes it possible to quantify the time course of dynamic information transfer between regions in the temporal domain. The LTI was applied to functional magnetic resonance imaging (fMRI) data involved in neural processing of the transformation and comparison from three-dimensional (3D) visual information to a two-dimensional (2D) location to calculate directed information flows between the activated brain regions. In the present study, for more precise estimation of LTI, Kalman filter smoothing was applied to the same fMRI data. Because the smoothing method exploits the full length of the time series data for the estimation, its application increases the precision. Large information flows were found from the bilateral prefrontal cortices to the parietal cortices. The results suggest that information of the 3D images stored as working memory was retrieved and transferred from the prefrontal cortices to the parietal cortices for comparison with information of the 2D images.

Effects of fenoterol and ipratropium on respiratory resistance of asthmatics after tracheal intubation.

PubMed

Wu, R S; Wu, K C; Wong, T K; Tsai, Y H; Cheng, R K; Bishop, M J; Tan, P P

2000-03-01

We have studied the effects of a beta-agonist, fenoterol, and a cholinergic antagonist, ipratropium, on post-intubation total respiratory system resistance (Rrs) in asthmatics who developed increased Rrs after tracheal intubation. Sixteen stable asthmatics in whom Rrs increased after intubation were allocated randomly to receive either 10 puffs of fenoterol (group F) or 10 puffs of ipratropium (group IB) via a metered dose inhaler 5 min after intubation. Anaesthesia was induced and maintained with propofol i.v. Rrs was recorded before treatment and again 5, 15 and 30 min after treatment. Rrs decreased significantly from pretreatment values by mean 53 (SD 8)%, 53 (7)% and 58 (6)% at 5, 15 and 30 min, respectively, in group F, but declined by only 12 (6)%, 15 (4)% and 17 (5)% in group IB. At all times after treatment, patients in the fenoterol group had significantly lower Rrs values than those in the ipratropium group. We conclude that increased Rrs after tracheal intubation in asthmatics can be reduced effectively by treatment with fenoterol. A secondary finding of our study was that even after induction of anaesthesia with propofol, patients with a history of asthma may develop high Rrs.

Hedgehog Is a Positive Regulator of FGF Signalling during Embryonic Tracheal Cell Migration

PubMed Central

Butí, Elisenda; Mesquita, Duarte; Araújo, Sofia J.

2014-01-01

Cell migration is a widespread and complex process that is crucial for morphogenesis and for the underlying invasion and metastasis of human cancers. During migration, cells are steered toward target sites by guidance molecules that induce cell direction and movement through complex intracellular mechanisms. The spatio-temporal regulation of the expression of these guidance molecules is of extreme importance for both normal morphogenesis and human disease. One way to achieve this precise regulation is by combinatorial inputs of different transcription factors. Here we used Drosophila melanogaster mutants with migration defects in the ganglionic branches of the tracheal system to further clarify guidance regulation during cell migration. By studying the cellular consequences of overactivated Hh signalling, using ptc mutants, we found that Hh positively regulates Bnl/FGF levels during embryonic stages. Our results show that Hh modulates cell migration non-autonomously in the tissues surrounding the action of its activity. We further demonstrate that the Hh signalling pathway regulates bnl expression via Stripe (Sr), a zinc-finger transcription factor with homology to the Early Growth Response (EGR) family of vertebrate transcription factors. We propose that Hh modulates embryonic cell migration by participating in the spatio-temporal regulation of bnl expression in a permissive mode. By doing so, we provide a molecular link between the activation of Hh signalling and increased chemotactic responses during cell migration. PMID:24651658

Hedgehog is a positive regulator of FGF signalling during embryonic tracheal cell migration.

PubMed

Butí, Elisenda; Mesquita, Duarte; Araújo, Sofia J

2014-01-01

Cell migration is a widespread and complex process that is crucial for morphogenesis and for the underlying invasion and metastasis of human cancers. During migration, cells are steered toward target sites by guidance molecules that induce cell direction and movement through complex intracellular mechanisms. The spatio-temporal regulation of the expression of these guidance molecules is of extreme importance for both normal morphogenesis and human disease. One way to achieve this precise regulation is by combinatorial inputs of different transcription factors. Here we used Drosophila melanogaster mutants with migration defects in the ganglionic branches of the tracheal system to further clarify guidance regulation during cell migration. By studying the cellular consequences of overactivated Hh signalling, using ptc mutants, we found that Hh positively regulates Bnl/FGF levels during embryonic stages. Our results show that Hh modulates cell migration non-autonomously in the tissues surrounding the action of its activity. We further demonstrate that the Hh signalling pathway regulates bnl expression via Stripe (Sr), a zinc-finger transcription factor with homology to the Early Growth Response (EGR) family of vertebrate transcription factors. We propose that Hh modulates embryonic cell migration by participating in the spatio-temporal regulation of bnl expression in a permissive mode. By doing so, we provide a molecular link between the activation of Hh signalling and increased chemotactic responses during cell migration.

Diversity of acoustic tracheal system and its role for directional hearing in crickets

PubMed Central

2013-01-01

Background Sound localization in small insects can be a challenging task due to physical constraints in deriving sufficiently large interaural intensity differences (IIDs) between both ears. In crickets, sound source localization is achieved by a complex type of pressure difference receiver consisting of four potential sound inputs. Sound acts on the external side of two tympana but additionally reaches the internal tympanal surface via two external sound entrances. Conduction of internal sound is realized by the anatomical arrangement of connecting trachea. A key structure is a trachea coupling both ears which is characterized by an enlarged part in its midline (i.e., the acoustic vesicle) accompanied with a thin membrane (septum). This facilitates directional sensitivity despite an unfavorable relationship between wavelength of sound and body size. Here we studied the morphological differences of the acoustic tracheal system in 40 cricket species (Gryllidae, Mogoplistidae) and species of outgroup taxa (Gryllotalpidae, Rhaphidophoridae, Gryllacrididae) of the suborder Ensifera comprising hearing and non hearing species. Results We found a surprisingly high variation of acoustic tracheal systems and almost all investigated species using intraspecific acoustic communication were characterized by an acoustic vesicle associated with a medial septum. The relative size of the acoustic vesicle - a structure most crucial for deriving high IIDs - implies an important role for sound localization. Most remarkable in this respect was the size difference of the acoustic vesicle between species; those with a more unfavorable ratio of body size to sound wavelength tend to exhibit a larger acoustic vesicle. On the other hand, secondary loss of acoustic signaling was nearly exclusively associated with the absence of both acoustic vesicle and septum. Conclusion The high diversity of acoustic tracheal morphology observed between species might reflect different steps in the evolution

High concentrations of landiolol, a beta(1)-adrenoceptor antagonist, stimulate smooth muscle contraction of the rat trachea through the Rho-kinase pathway.

PubMed

Shibata, Osamu; Nishioka, Kenji; Yamaguchi, Masakazu; Makita, Tetsuji; Sumikawa, Koji

2008-01-01

Gradually progressing contraction of airway smooth muscle is suggested to be due to the Rho-kinase signaling pathway. In our preliminary study in rat tracheas, landiolol, a beta(1)-adrenoceptor antagonist, at high doses caused gradually progressing contraction, and this contraction reached a plateau after 20 min. Therefore, this study was carried out to clarify whether landiolol could stimulate the Rho-kinase pathway or the phosphatidylinositol (PI) response in the rat trachea. Seventy-eight male Wistar rats weighing 250-350 g were used for the experiments. Their tracheas were cut into 3-mm-wide ring segments or 1-mm-wide slices. Measurements of isometric tension and [(3)H] inositol monophosphate (IP(1)) production were conducted, using these tracheal rings or slices. Data values are expressed as means +/- SD, and statistical significance (P < 0.05) was determined using analysis of variance (ANOVA). Landiolol (700 microM)-induced contraction was completely inhibited by fasudil at 30 microM, while the landiolol-induced contraction was not inhibited by 4-diphenylacetoxy-N-methyl-piperidine methobromide (4-DAMP), ketanserin, or nicardipine. Landiolol did not stimulate IP(1) production. These results suggest that high concentrations of landiolol could cause airway smooth muscle contraction through the Rho-kinase pathway, but not through the PI response coupled with muscarinic M(3) receptors, 5-HT receptors or the activation of L-type Ca(2+) channels.

Smooth muscle myosin isoform expression and LC20 phosphorylation in innate rat airway hyperresponsiveness.

PubMed

Gil, Fulvio R; Zitouni, Nedjma B; Azoulay, Eric; Maghni, Karim; Lauzon, Anne-Marie

2006-11-01

Four smooth muscle myosin heavy chain (SMMHC) isoforms are generated by alternative mRNA splicing of a single gene. Two of these isoforms differ by the presence [(+)insert] or absence [(-)insert] of a 7-amino acid insert in the motor domain. The rate of actin filament propulsion of the (+)insert SMMHC isoform, as measured in the in vitro motility assay, is twofold greater than that of the (-)insert isoform. We hypothesized that a greater expression of the (+)insert SMMHC isoform and greater regulatory light chain (LC(20)) phosphorylation contribute to airway hyperresponsiveness. We measured airway responsiveness to methacholine in Fischer hyperresponsive and Lewis normoresponsive rats and determined SMMHC isoform mRNA and protein expression, as well as essential light chain (LC(17)) isoforms, h-caldesmon, and alpha-actin protein expression in their tracheae. We also measured tracheal muscle strip contractility in response to methacholine and corresponding LC(20) phosphorylation. We found Fischer rats have more (+)insert mRNA (69.4 +/- 2.0%) (mean +/- SE) than Lewis rats (53.0 +/- 2.4%; P < 0.05) and a 44% greater content of (+)insert isoform relative to total myosin protein. No difference was found for LC(17) isoform, h-caldesmon, and alpha-actin expression. The contractility experiments revealed a greater isometric force for Fischer trachealis segments (4.2 +/- 0.8 mN) than Lewis (1.9 +/- 0.4 mN; P < 0.05) and greater LC(20) phosphorylation level in Fischer (55.1 +/- 6.4) than in Lewis (41.4 +/- 6.1; P < 0.05) rats. These results further support the contention that innate airway hyperresponsiveness is a multifactorial disorder in which increased expression of the fast (+)insert SMMHC isoform and greater activation of LC(20) lead to smooth muscle hypercontractility.

Expression and coupling of neurokinin receptor subtypes to inositol phosphate and calcium signaling pathways in human airway smooth muscle cells.

PubMed

Mizuta, Kentaro; Gallos, George; Zhu, Defen; Mizuta, Fumiko; Goubaeva, Farida; Xu, Dingbang; Panettieri, Reynold A; Yang, Jay; Emala, Charles W

2008-03-01

Neuropeptide tachykinins (substance P, neurokinin A, and neurokinin B) are present in peripheral terminals of sensory nerve fibers within the respiratory tract and cause airway contractile responses and hyperresponsiveness in humans and most mammalian species. Three subtypes of neurokinin receptors (NK1R, NK2R, and NK3R) classically couple to Gq protein-mediated inositol 1,4,5-trisphosphate (IP3) synthesis and liberation of intracellular Ca2+, which initiates contraction, but their expression and calcium signaling mechanisms are incompletely understood in airway smooth muscle. All three subtypes were identified in native and cultured human airway smooth muscle (HASM) and were subsequently overexpressed in HASM cells using a human immunodeficiency virus-1-based lentivirus transduction system. Specific NKR agonists {NK1R, [Sar9,Met(O2)11]-substance P; NK2R, [beta-Ala8]-neurokinin A(4-10); NK3R, senktide} stimulated inositol phosphate synthesis and increased intracellular Ca2+ concentration ([Ca2+]i) in native HASM cells and in HASM cells transfected with each NKR subtype. These effects were blocked by NKR-selective antagonists (NK1R, L-732138; NK2R, GR-159897; NK3R, SB-222200). The initial transient and sustained phases of increased [Ca2+]i were predominantly inhibited by the IP3 receptor antagonist 2-aminoethoxydiphenyl borate (2-APB) or the store-operated Ca2+ channel antagonist SKF-96365, respectively. These results show that all three subtypes of NKRs are expressed in native HASM cells and that IP3 levels are the primary mediators of NKR-stimulated initial [Ca2+]i increases, whereas store-operated Ca2+ channels mediate the sustained phase of the [Ca2+]i increase.

Contrast and assimilation in motion perception and smooth pursuit eye movements.

PubMed

Spering, Miriam; Gegenfurtner, Karl R

2007-09-01

The analysis of visual motion serves many different functions ranging from object motion perception to the control of self-motion. The perception of visual motion and the oculomotor tracking of a moving object are known to be closely related and are assumed to be controlled by shared brain areas. We compared perceived velocity and the velocity of smooth pursuit eye movements in human observers in a paradigm that required the segmentation of target object motion from context motion. In each trial, a pursuit target and a visual context were independently perturbed simultaneously to briefly increase or decrease in speed. Observers had to accurately track the target and estimate target speed during the perturbation interval. Here we show that the same motion signals are processed in fundamentally different ways for perception and steady-state smooth pursuit eye movements. For the computation of perceived velocity, motion of the context was subtracted from target motion (motion contrast), whereas pursuit velocity was determined by the motion average (motion assimilation). We conclude that the human motion system uses these computations to optimally accomplish different functions: image segmentation for object motion perception and velocity estimation for the control of smooth pursuit eye movements.

Spatial and temporal traction response in human airway smooth muscle cells

NASA Technical Reports Server (NTRS)

Tolic-Norrelykke, Iva Marija; Butler, James P.; Chen, Jianxin; Wang, Ning

2002-01-01

Tractions that cells exert on their substrates are essential in cell spreading, migration, and contraction. These tractions can be determined by plating the cells on a flexible gel and measuring the deformation of the gel by using fluorescent beads embedded just below the surface of the gel. In this article we describe the image correlation method (ICM) optimized for determining the displacement field of the gel under a contracting cell. For the calculation of the traction field from the displacement field we use the recently developed method of Fourier transform traction cytometry (FTTC). The ICM and FTTC methods are applied to human airway smooth muscle cells during stimulation with the contractile agonist histamine or the relaxing agonist isoproterenol. The overall intensity of the cell contraction (the median traction magnitude, the energy transferred from the cell to the gel, and the net contractile moment) increased after activation with histamine, and decreased after treatment with isoproterenol. Cells exhibited regional differences in the time course of traction during the treatment. Both temporal evolution and magnitude of traction increase induced by histamine varied markedly among different cell protrusions, whereas the nuclear region showed the smallest response. These results suggest that intracellular mediators of cell adhesion and contraction respond to contractile stimuli with different rates and intensities in different regions of the cell.

Smooth muscle in human bronchi is disposed to resist airway distension.

PubMed

Gazzola, Morgan; Henry, Cyndi; Couture, Christian; Marsolais, David; King, Gregory G; Fredberg, Jeffrey J; Bossé, Ynuk

2016-07-15

Studying airway smooth muscle (ASM) in conditions that emulate the in vivo environment within which the bronchi normally operate may provide important clues regarding its elusive physiological function. The present study examines the effect of lengthening and shortening of ASM on tension development in human bronchial segments. ASM from each bronchial segment was set at a length approximating in situ length (Linsitu). Bronchial tension was then measured during a slow cyclical strain (0.004Hz, from 0.7Linsitu to 1.3Linsitu) in the relaxed state and at graded levels of activation by methacholine. In all cases, tension was greater at longer ASM lengths, and greater during lengthening than shortening. The threshold of methacholine concentration that was required for ASM to account for bronchial tension across the entire range of ASM lengths tested was on average smaller by 2.8 logs during lengthening than during shortening. The length-dependency of ASM tension, together with this lower threshold of methacholine concentration during lengthening versus shortening, suggest that ASM has a greater ability to resist airway dilation during lung inflation than to narrow the airways during lung deflation. More than serving to narrow the airway, as has long been thought, these data suggest that the main function of ASM contraction is to limit airway wall distension during lung inflation. Copyright © 2016 Elsevier B.V. All rights reserved.

Smooth muscle in the maintenance of increased airway resistance elicited by methacholine in humans.

PubMed

Chapman, David G; Pascoe, Chris D; Lee-Gosselin, Audrey; Couture, Christian; Seow, Chun Y; Paré, Peter D; Salome, Cheryl M; King, Gregory G; Bossé, Ynuk

2014-10-15

Airway narrowing is maintained for a prolonged period after acute bronchoconstriction in humans in the absence of deep inspirations (DIs). To determine whether maintenance of airway smooth muscle (ASM) shortening is responsible for the persistence of airway narrowing in healthy subjects following transient methacholine (MCh)-induced bronchoconstriction. On two separate visits, five healthy subjects underwent MCh challenges until respiratory system resistance (Rrs) had increased by approximately 1.5 cm H2O/L/s. Subjects took a DI either immediately after or 30 minutes after the last dose. The extent of renarrowing following the bronchodilator effect of DI was used to assess the continued action of MCh (calculated as percent change in Rrs from the pre-DI Rrs). We then used human bronchial rings to determine whether ASM can maintain shortening during a progressive decrease of carbachol concentration. The increased Rrs induced by MCh was maintained for 30 minutes despite waning of MCh concentration over that period, measured as attenuated renarrowing when the DI was taken 30 minutes after compared with immediately after the last dose (7 min post-DI, -36.2 ± 11.8 vs. 14.4 ± 13.2%; 12 min post-DI, -39.5 ± 9.8 vs. 15.2 ± 17.8%). Ex vivo, ASM shortening was largely maintained during a progressive decrease of carbachol concentration, even down to concentrations that would not be expected to induce shortening. The maintenance of airway narrowing despite MCh clearance in humans is attributed to an intrinsic ability of ASM to maintain shortening during a progressive decrease of contractile stimulation.

PM2.5 promotes human bronchial smooth muscle cell migration via the sonic hedgehog signaling pathway.

PubMed

Ye, Xiuqin; Hong, Wei; Hao, Binwei; Peng, Gongyong; Huang, Lingmei; Zhao, Zhuxiang; Zhou, Yumin; Zheng, Mengning; Li, Chenglong; Liang, Chunxiao; Yi, Erkang; Pu, Jinding; Li, Bing; Ran, Pixin

2018-03-02

The contribution of airway remodeling in chronic obstructive pulmonary disease (COPD) has been well documented, with airway smooth muscle cell proliferation and migration playing a role in the remodeling process. Here, we aimed to verify the effects of fine particulate matter (PM2.5) on human bronchial smooth muscle cell (HBSMC) migration and to explore the underlying signaling pathways. HBSMC apoptosis, proliferation and migration were measured using flow cytometry, cell counting and transwell migration assays, respectively. The role of the hedgehog pathway in cell migration was assessed by western blotting to measure the expression of Sonic hedgehog (Shh), Gli1 and Snail. Furthermore, siRNA was used to knock down Gli1 or Snail expression. PM2.5 induced HBSMC apoptosis in a dose-dependent manner, although certain concentrations of PM2.5 did not induce HBSMC proliferation or apoptosis. Interestingly, cell migration was stimulated by PM2.5 doses far below those that induced apoptosis. Additional experiments revealed that these PM2.5 doses enhanced the expression of Shh, Gli1 and Snail in HBSMCs. Furthermore, PM2.5-induced cell migration and protein expression were enhanced by recombinant Shh and attenuated by cyclopamine. Similar results were obtained by knocking down Gli1 or Snail. These findings suggest that PM2.5, which may exert its effects through the Shh signaling pathway, is necessary for the migration of HBSMCs. These data define a novel role for PM2.5 in airway remodeling in COPD.

Tungstate-Targeting of BKαβ1 Channels Tunes ERK Phosphorylation and Cell Proliferation in Human Vascular Smooth Muscle

PubMed Central

Fernández-Mariño, Ana Isabel; Cidad, Pilar; Zafra, Delia; Nocito, Laura; Domínguez, Jorge; Oliván-Viguera, Aida; Köhler, Ralf; López-López, José R.; Pérez-García, María Teresa; Valverde, Miguel Ángel; Guinovart, Joan J.; Fernández-Fernández, José M.

2015-01-01

Despite the substantial knowledge on the antidiabetic, antiobesity and antihypertensive actions of tungstate, information on its primary target/s is scarce. Tungstate activates both the ERK1/2 pathway and the vascular voltage- and Ca2+-dependent large-conductance BKαβ1 potassium channel, which modulates vascular smooth muscle cell (VSMC) proliferation and function, respectively. Here, we have assessed the possible involvement of BKαβ1 channels in the tungstate-induced ERK phosphorylation and its relevance for VSMC proliferation. Western blot analysis in HEK cell lines showed that expression of vascular BKαβ1 channels potentiates the tungstate-induced ERK1/2 phosphorylation in a Gi/o protein-dependent manner. Tungstate activated BKαβ1 channels upstream of G proteins as channel activation was not altered by the inhibition of G proteins with GDPβS or pertussis toxin. Moreover, analysis of Gi/o protein activation measuring the FRET among heterologously expressed Gi protein subunits suggested that tungstate-targeting of BKαβ1 channels promotes G protein activation. Single channel recordings on VSMCs from wild-type and β1-knockout mice indicated that the presence of the regulatory β1 subunit was essential for the tungstate-mediated activation of BK channels in VSMCs. Moreover, the specific BK channel blocker iberiotoxin lowered tungstate-induced ERK phosphorylation by 55% and partially reverted (by 51%) the tungstate-produced reduction of platelet-derived growth factor (PDGF)-induced proliferation in human VSMCs. Our observations indicate that tungstate-targeting of BKαβ1 channels promotes activation of PTX-sensitive Gi proteins to enhance the tungstate-induced phosphorylation of ERK, and inhibits PDGF-stimulated cell proliferation in human vascular smooth muscle. PMID:25659150

Cue-dependent memory-based smooth-pursuit in normal human subjects: importance of extra-retinal mechanisms for initial pursuit.

PubMed

Ito, Norie; Barnes, Graham R; Fukushima, Junko; Fukushima, Kikuro; Warabi, Tateo

2013-08-01

Using a cue-dependent memory-based smooth-pursuit task previously applied to monkeys, we examined the effects of visual motion-memory on smooth-pursuit eye movements in normal human subjects and compared the results with those of the trained monkeys. These results were also compared with those during simple ramp-pursuit that did not require visual motion-memory. During memory-based pursuit, all subjects exhibited virtually no errors in either pursuit-direction or go/no-go selection. Tracking eye movements of humans and monkeys were similar in the two tasks, but tracking eye movements were different between the two tasks; latencies of the pursuit and corrective saccades were prolonged, initial pursuit eye velocity and acceleration were lower, peak velocities were lower, and time to reach peak velocities lengthened during memory-based pursuit. These characteristics were similar to anticipatory pursuit initiated by extra-retinal components during the initial extinction task of Barnes and Collins (J Neurophysiol 100:1135-1146, 2008b). We suggest that the differences between the two tasks reflect differences between the contribution of extra-retinal and retinal components. This interpretation is supported by two further studies: (1) during popping out of the correct spot to enhance retinal image-motion inputs during memory-based pursuit, pursuit eye velocities approached those during simple ramp-pursuit, and (2) during initial blanking of spot motion during memory-based pursuit, pursuit components appeared in the correct direction. Our results showed the importance of extra-retinal mechanisms for initial pursuit during memory-based pursuit, which include priming effects and extra-retinal drive components. Comparison with monkey studies on neuronal responses and model analysis suggested possible pathways for the extra-retinal mechanisms.