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Mechanisms involved in the relaxant action of the ethanolic extract of propolis in the guinea-pig trachea in-vitro.

This study examines the mechanisms by which the standardised ethanolic extract of propolis induces relaxation of the guinea-pig trachea in-vitro. In guinea-pig trachea with or without epithelium and contracted by histamine, the propolis extract caused reproducible and graded relaxation, with a mean EC50 value of 3.8 or 10.5 microg mL(-1) and Emax of 100%, respectively. The propolis extract-induced relaxation was markedly reduced (26+/-9 and 96+/-3%) when guinea-pig tracheas were exposed to Krebs solution containing elevated K+ in the medium (40 or 80 mM). Pre-incubation of guinea-pig tracheas with tetraethylamonium (100 mM) or with 4-aminopyridine (10mM) reduced the propolis extract-induced relaxation by 31+/-10% and 28+/-2%. Likewise, apamin (0.1 microM), charybdotoxin (0.1 microM) or iberiotoxin (0.1 microM) caused marked inhibition of propolis extract-mediated relaxation in guinea-pig trachea (percentage of inhibition: 65+/-3%, 60+/-5% and 65+/-9%, respectively). Also, glibenclamide (1 microM) inhibited the relaxant response caused by the propolis extract by 57+/-4%. Omega-conotoxin GIVA (0.1 microM) or capsaicin (1 microM) produced small but significant inhibition (30+/-5% or 47+/-7%, respectively) of the propolis extract-induced relaxation. The vasoactive intestinal peptide (VIP) antagonist D-p-Cl-Phe6,Leu17[VIP] porcine (0.1 microM) inhibited relaxation by 55+/-5%, while propranolol (1 microM) induced a parallel rightward displacement (about 20 fold) of the propolis extract concentration-response curve. Finally, the propolis extract-induced relaxation was inhibited by the nitric oxide synthase inhibitor L-N(G)-nitroarginine (L-NOArg, 100 microM) (48+/-6%), and by the soluble guanylatecyclase inhibitormethylene blue (10 microM) (37+/-6%), whilethe moreselectivesoluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolol[4,3-alquinoxalin-1-one (ODQ, 1 microM) produced only a parallel (about 3 fold) rightward displacement of the propolis extract concentration-response curve. Collectively, these results support the notion that the propolis extract-mediated relaxation in the guinea-pig trachea involves the release of nitric oxide, probably from sensory neurons, besides the activation of soluble guanylate cyclase and activation of Ca2+- and ATP-sensitive K+ channels. Furthermore, the stimulation of beta2-adrenergic and VIP receptors also seems to account for its relaxant action.

Adrenergic beta-Antagonists↗

A comparative study on the contraction induced by high K/Na deficient solution in the trachea, gall bladder and urinary bladder in guinea-pig.

In the present paper, a comparative study of high K solution was carried out on the mechanical response, wet and dry weights of tissue, and extracellular space of 14C-sorbitol in the trachea, gall bladder, and urinary bladder of guinea-pig. Hyperosmotic addition of KCl to the physiological solution produced a sustained contraction, while isosmotic substitution of K for Na in the physiological solution induced a contraction followed by a small sustained one in the trachea, gall bladder or urinary bladder. At 120 min after application of the substituted KCl, Na deficient solution, it increased cell water content in the smooth muscle cells of the trachea or gall bladder, but did not change that in the urinary bladder. Both the inhibition of contraction and the swelling in the trachea or gall bladder were prevented by the hyperosmotic application of sucrose or NaCl. The substitution for NaCl with the K salts with more permeable anions (I- greater than NO3- greater than Cl-) produced a greater inhibition of contraction in the trachea and gall bladder. Although the impermeable anion C2H5CO2- did not inhibit the contraction in the trachea, this anion partially inhibited it in the gall bladder. On the other hand, the inhibition of contraction in the urinary bladder was prevented by addition of pyruvate, oxalacetate or NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of aging on the response of guinea pig trachea to isoprenaline.

To study the effect of aging on the beta-adrenergic receptor potency of isoprenaline, tracheas from 3-, 6-, 10-, 40- and 100-week-old guinea pigs were used as test tissues. The pD2 values (potency) of isoprenaline increased with age in tracheas treated with corticosterone, but decreased in untreated tracheas. The pA2 value of propranolol against isoprenaline estimated in the treated tracheas did not change with age. Specific binding of [3H]-dihydroalprenolol to the microsomal fractions from the tracheal muscles from 6-, 10- and 40-week-old guinea pigs was analyzed with Scatchard plots. The capacity of maximum binding sites of [3H]-dihydroalprenolol increased with increasing age, while its dissociation constant did not change. Age-related increase in the potency of isoprenaline in the tracheas treated with corticosterone is considered to be due to the increase in the total amount (density) of beta-adrenoceptors. However, the potency of the drug in untreated tracheas decreased with age. These results suggest that extraneuronal uptake plays an important role in the beta-adrenergic action of isoprenaline in older (40 and 100 weeks) guinea pigs.

Aging↗

Different effects of imidapril and enalapril on aminopeptidase P activity in the mouse trachea.

It has been reported that the incidence of angiotensin-converting enzyme (ACE) inhibitor-related dry cough is significantly less with the ACE inhibitor imidapril than with the ACE inhibitor enalapril in hypertensive patients. Bradykinin (BK) in the trachea is believed to play some role in this adverse effect. The present study was undertaken to evaluate the effects of imidapril and enalapril on the activity of aminopeptidase P (APP), one of the BK-metabolizing enzymes, in the mouse trachea. Imidapril (0.5 mg/kg) or enalapril (0.5 mg/ kg) was given orally to mice once daily for 7 days. Drug concentrations and APP activity in the trachea were determined at the end of the experiment. Active metabolites (imidaprilat and enalaprilat), but not parent drugs (imidapril and enalapril) were detected in the trachea after a repeated dose for 7 days. Tissue concentrations of imidaprilat and enalaprilat did not significantly differ. The APP activity in the trachea did not significantly change after the 7th dose of imidapril. However, the enzyme activity was significantly inhibited after the final dose of enalapril. Thus, the present study showed that enalapril, but not imidapril inhibited the airway APP activity during repeated dosing. This finding is compatible with previous reports that the incidence of dry cough is lower with imidapril than with enalapril, and with the hypothesis that the dry cough induced by ACE inhibitors may be related to accumulation of BK in the trachea.

Aminopeptidases↗

Age-dependent changes of elements in human trachea.

To elucidate compositional changes of human trachea by aging, element contents in tracheae were determined by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of seven men and seven women, ranging in age from 61 to 97 yr. The sulfur content of the tracheae decreased gradually with aging. In regard to calcium and phosphorus, both the contents increased to about threefold amounts in their seventies compared with those in their sixties, and decreased thereafter. The contents of calcium and phosphorus were the highest in their seventies. Therefore, it is likely that surplus calcium released from bones is deposited temporally in the trachea, and the deposits are released from the trachea at older age. Based on our results of human cartilages, there are two types in regard to calcium accumulation: The first type is that calcium accumulation occurs progressively with aging; the second one is that calcium accumulation becomes the highest in the seventies or eighties, and decreases thereafter. Therefore, the trachea belongs to the second type. Furthermore, the magnesium content remained constant through the age range.

Aged↗

Transport across rat trachea in vitro after exposure to cytoskeleton-active drugs in vitro or to ozone in vivo.

Full-length tracheas from Sprague-Dawley rats were exposed to cytoskeleton-active drugs in short-term organ culture, and the permeability of the tracheal epithelium was measured by instilling radiotracers into the lumen and assay of the radioactivity appearing in the external bathing medium. In vitro treatment with cytochalasin D (cyto D, 2-10 x 10(-6) M) increased the rate of movement of [14C]mannitol across the epithelium. Exposure to vinblastine (VB, 10(-4) M) alone had no significant effect. However, VB in combination with cyto D increased the permeability in a dose-dependent manner. In vivo exposure to ozone (O3, 0.8 or 2.0 ppm, 2 h) had only a slight effect on the rate of movement of the tracer as measured in vitro immediately after exposure. At 24 h postexposure there was no significant difference in permeability between ozone- and air-exposed tracheas. Prior in vivo O3 exposure sensitized the tracheas to the in vitro effects of cyto D; treatment of O3-exposed tracheas with cyto D immediately after O3 exposure produced a greater than additive effect on permeability measured in vitro. VB at concentrations up to 10(-4) M had no enhancing effect on permeability in O3-exposed tracheas. Sham exposure to clean air did not affect permeability compared to untreated (shelf) controls. Electron microscopic studies demonstrated penetration of horseradish peroxidase into intercellular spaces in the tracheas treated in vitro with cyto D or cyto D plus VB. Cyto D is known to affect intracellular microfilaments that have attachments at or near the cell surface, while VB affects microtubules associated with internal cellular structures. Therefore, the synergistic effect on tracheal permeability observed with O3 and cyto D, but not with O3 and VB, suggests that O3 may change cell surface structures associated with the microfilamentous cytoskeleton.

Animals↗

[The effect of epithelium on inhibition of histamine-induced contraction of guinea-pig isolated trachea by potassium channel opener Rp 52891].

To evaluate whether the relaxant effect of Rp 52891 on isolated normal or sensitized guinea-pigs trachea is influenced by the removal of airway epithelium, twenty-four normal and sensitized guinea-pigs were randomly divided into two groups: epithelium-intact trachea and epithelium-denuded trachea. The effect of Rp 52891 on contraction elicited by histamine in epithelium-intact and epithelium-denuded trachea was investigated, and it was compared with that of aminophylline or isoprenaline. The results revealed that there was no significant difference in histamine-induced contractile response between normal and sensitized isolated trachea. The inhibitory effect of Rp 52891 on the contractile response of histamine was significantly reduced by removing the epithelium but that of aminophylline or isoprenaline was not changed. These results suggested that Rp 52891 may directly relax the airway smooth muscle of guinea-pigs in vitro, the epithelium of guinea-pigs trachea may modulate the relaxant effect of Rp 52891.

Aminophylline↗

[Resection of the trachea in acquired cicatricial stenosis].

The objective of the submitted paper is to draw attention to the possible occurrence of post-cannulation ciccatrial stenoses of the trachea after long-term artificial pulmonary ventilation and possibilities of a surgical solution. The optimal therapeutic method is resection of the stenotic portion of the trachea. The authors present an account on 22 patients where during the period from 1996-1998 a resection of the trachea was performed. Of basic importance for indication for resection of the trachea is bronchoscopic, X-ray (tomograms) and CT examination which assesses the diameter, site and length of the stenosis. The limiting factor is assessment of the length of the stenotic portion. In stenoses longer than 5-6 cm it is useful to consider insertion of a stent. The authors made resections of the trachea of a maximum length of 55 mm. As to postoperative complications restenoses were most frequent and were resolved by implantation of a Montgomery T-tube. Indications of patients for surgery on account of stenosis of the trachea calls for close interdisciplinary collaboration of the bronchologist, radiologist and thoracic surgeon. Due to the small number of patients operated with this complication it is useful to concentrate these patients in specialized departments.

Adult↗

[The autotransplanted tracheas wrapped in united muscle flap of the neck: an experiment].

OBJECTIVE: To investigate the way of revascularization of donator's trachea wrapped in united muscle flap. METHODS: Using fiberoptic bronchoscopy, histopathology and microangiography, we evaluated the tracheal mucosal blood flow, the survival rate, the percentage of patency, and the graft viability of autograft tracheas with varying lengths wrapped in one-sided sternocephalic muscle flap and two-sided sternohyoid-sternothyroid muscle flap and autograft tracheas with the length of 5 rings without wrapped in muscle flap in 32 dogs. RESULTS: In the tracheal autograft wrapped in the united muscle flap group with a length less than 4 centimeters, the submucosal blood flow of graft could be detected by laser blood flowmetry one week after transplantation, and it reached 60% of the normal, which had no significant difference between the place near the site of anastomosis and the middle part of the graft. Dense vessels could be found to grow from the wrapped muscles into the autografted trachea by microangiography. Histopathological examination demonstrated that the structure of the autograft was the same as what it originally was. the inner surface of the autograft was covered with pseudostratified columnar ciliary epithelia, and no necrotic tracheal cartilages were found. Every autograft could survive over long time. However, at 1 week, most mucous membrane in the middle part of the graft with length over 4 cm was in gray or in pale; hyperemia, edema, and haemorrhage were found near the site of anastomosis. Mucosal blood flow measured by laser blood flowmetry in the middle part of the graft was significantly less than that near the site of anastomosis. Malacia, dissolution or granulation hyperplasia occurred in midportion of the major grafts shortly after transplanatation. As for those autografted trachea without wrapping in muscles flap, mucous membranes turned black one week after the transplantation and all dogs died of graft necrosis later. CONCLUSION: One-sided sternocephalic muscle flap and two-sided sternohyoid-sternothyroid muscle flap can provide blood for the graft and the grafted trachea can survive for a long time.

Animals↗

[Complete disruption of cervical trachea, whose distal airways were migrated into the mediastinum].

The first case was a 55-year-old man, who suffered by a rope while driving his motor bicycle. On 7th day after injury, tracheotomy was scheduled due to progressive dyspnea. Following intubation of a endotracheal tube, his trachea was ruptured. The second case was a 16-year-old man, who was stabbed his trachea with a sword by his mother. His trachea completely separated following coughing during the examination of bronchoscopy. For 2 cases, we immediately excised their necks for tracheotomy but couldn't find their distal portion of trachea, because they were migrated into the mediastinum. We inserted our finger into the mediastinum for exploration and could draw it back. Both case's postoperative course was uneventful. Whenever cervical trachea is completely separated, tracheal distal end may be pulled down into the mediastinum. We invited new technique of exploration for migrated trachea using our finger.

Adolescent↗

Characterization of the contractile serotonergic receptor in guinea pig trachea with agonists and antagonists.

5-Hydroxytryptamine (5-HT)2 receptors can be partially characterized by their sensitivity to ketanserin blockade and increase in phosphoinositide turnover upon stimulation. Previously, the contraction of guinea pig trachea to 5-HT was shown to be antagonized by the 5-HT2 receptor antagonists ketanserin and LY53857. However, 5-HT did not dramatically increase phosphoinositide turnover in guinea pig trachea, suggesting that the contractile receptor may be different from the classically defined 5-HT2 receptor. The present in vitro studies better characterize this receptor, using diverse serotonergic agonists and antagonists to profile in more detail the contractile serotonergic receptor in guinea pig trachea. With regard to agonists, the 5-HT2 receptor agonists DOI and alpha-methyl-5-HT contracted guinea pig trachea with greater potency than quipazine, 5-methoxytryptamine, 5-carboxamidotryptamine, 8-hydroxy-2-(di-N-propylamino)tetralin and 2-methyl-5-HT. Sumatriptan and 1-(3-chlorophenyl)-piperazine (10 nM-100 microM) were inactive as agonists. A strong correlation between agonist potency (EC50) and reported 5-HT receptor binding affinities was found for both the 5-HT1C (r = 0.890) and 5-HT2 (r = 0.831) receptor. Ketanserin, spiperone, ritanserin, LY53857, 1-napthylpiperazine, 1-(3-chlorophenyl)-piperazine, rauwolscine, ICS 205-930, cyanopindolol and sumatriptan all blocked 5-HT-induced contractions in guinea pig trachea. As occurred with agonist potencies, strong correlations were found between reported 5-HT1C (r = 0.814) and 5-HT2 (r = 0.912) receptor binding affinities in brain membranes and apparent dissociation constants (KB) for the 10 antagonists of 5-HT induced contraction in guinea pig trachea.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamines↗

[Biomechanical characteristics of the trachea and its reconstruction].

Under uniaxial loading, the mechanical properties of fifteen canine tracheas were tested by CSS-2100 electronic universal testing machine, (produced by Changchun Institute of Testing Machines), which was equipped with X-Y recorder, deformation testing gauge and Super Computer, etc. Tracheas of 22 healthy adult dogs were divided into 3 groups. The 1st group contained normal tracheas, the 2nd group contained tracheas medially cut and the tension test. These features from one-dimension tensile anastomosed end-to-end with 0.2 mm silk sutures. The 3rd group contained those anastomosed with 0.3 mm silk sutures. The results showed that in the 1st group although there was a nonlinear stress-strain relationship, the linear segment was not clear. The stress produced by the suture formed the incisive force because of small section area and stress concentration. The thickness of the membrane paries of the canine trachea was greater than that of the annular ligament, but smaller than that of the cartilage ring. The length of the membrane paries was smaller than that of the cartilage ring. Consequently, an uneven stress distribution was seen. The results of this experiment might serve as a basis for further research on the biomechanical implications of human trachea reconstruction.

Anastomosis, Surgical↗

Passive serum antibody causes temporary recovery from influenza virus infection of the nose, trachea and lung of nude mice.

BALB/c normal and nude mice were infected with a non-lethal mouse-passaged A/PC/1/73 (H3N2) influenza virus in order to assess the role of T cells on the course of disease of the nose, trachea and lung. The tracheal epithelium of both mouse strains was desquamated by 3 days after infection. Although normal regeneration began, nude mice never completed that regeneration whereas normal mice had fully regenerated tracheas by Day 14. This failure to complete the recovery was also evident from the continued virus shedding by the nude mouse. In order to assess the role of serum antibody on recovery from infection, ferret, goat or mouse antibody to H3N2 influenza virus was passively administered to nude mice after infection. It resulted in a transient decrease in virus shedding from the nose, trachea and lung, and complete but temporary regeneration of the tracheal epithelium. However, later in the course of the infection, when serum antibody levels were no longer detectable, the tracheal epithelium of these animals redesquamated and large amounts of virus were again shed from nose, trachea and lungs. We conclude that: (i) desquamation of the ciliated epithelium of the trachea is not T-cell dependent; and (ii) serum antibody can contribute to temporary recovery from infection, but by itself is insufficient for permanent recovery of the nose, trachea or lung.

Animals↗

[Anatomical analysis of small bronchial arteries in front of the trachea by 3D-CT and digital subtraction angiography: implications for esophageal cancer surgery].

To preserve blood supply to the trachea and bronchus in the surgical procedure for esophageal cancer, anatomical characteristics of small bronchial arteries which course in front of the trachea were analysed by three-dimensional computed tomography (3D-CT) and digital subtraction angiography (DSA). In the 3D-CT study using five mediastina, three dimensional images of the bronchial arteries were reconstructed after the injection of contrast medium into the intercostobronchial arteries. Thus the detailed vascular network of the course of the small bronchial arteries in front of the trachea could be delineated. In the DSA study using seven mediastina, through this network of bronchial arteries, the branches originating from the aorta and the arteries supplying the cranial portion of the trachea could be viewed. These results indicate that the bronchial arteries are connected by a vascular network in front of the trachea. Based on these detailed findings, it is considered critical to avoid damage to the intercostobronchial artery and also the network of bronchial arteries in order to preserve blood supply to the trachea and bronchus.

Angiography, Digital Subtraction↗

Selectivity profile of some recent muscarinic antagonists in bovine and guinea-pig trachea and heart.

The functional affinities of some recently developed subtype-selective muscarinic antagonists towards bovine tracheal smooth muscle muscarinic M3 receptors were established and compared to binding affinities for bovine cardiac M2 and functional affinities for guinea-pig tracheal smooth muscle M3 receptors; functional affinities towards bovine or guinea-pig cardiac M2 receptors were determined when the M2/M3 selectivity in bovine tissues deviated from reported guinea-pig data. It was found that the M2-selective antagonist AQ-RA 741 showed similar high affinities in bovine and guinea-pig heart (8.27-8.41); the affinity in bovine trachea, however, was almost 10-fold higher than in guinea-pig trachea (7.51-6.63). The M3-selective antagonist DAC 5945 displayed functional affinities that were similarly high in bovine and guinea-pig trachea (8.16-8.24) and approximately a 100-fold lower in bovine and guinea-pig heart (6.15-6.36); with this compound, the binding affinity in bovine cardiac membranes (6.92) was clearly higher than the functional affinity, as has meanwhile also been reported for the guinea-pig. With the M3-selective muscarinic antagonists p-fluorohexahydrosiladifenidol and UH-AH 371, affinities towards bovine tracheal muscarinic M3 receptors were 0.3 log units higher than in guinea-pig trachea (7.36-7.09 and 8.43-8.13, respectively), and, in case of p-fluorohexahydrosiladifenidol, both were lower than previously reported for the guinea-pig ileum (typically 7.8). In some instances, especially AQ-RA 741 in bovine trachea and p-fluorohexahydrosiladifenidol in bovine and guinea-pig trachea, the M3 receptor affinities found here correlated better to the reported M1 than to the M3 receptor affinities. It is concluded that small, but occasionally clear species and tissue differences exist with regard to the affinities of muscarinic receptor antagonists for smooth muscle M3 receptors, and it is suggested that this may be due to small, but potentially important differences in their amino acid sequences.

Animals↗

The trachea: normal anatomic features, imaging and causes of displacement.

Radiologists have long regarded the trachea as one of their "blind spots," even though this structure can be visualized as well as, if not better than, any other intrathoracic component because of the excellent intrinsic contrast provided by air within the trachea and by the tracheal interfaces with the mediastinum and the lung. Despite this ease of visualization, radiologists may overlook tracheal abnormalities in their diligence in examining the pulmonary parenchyma and the heart. The trachea can be imaged by a variety of techniques, including plain radiography, computed tomography (CT) and magnetic resonance imaging. Important tracheal interfaces include the right and left paratracheal stripes and the tracheoesophageal stripe. The right posterolateral tracheal band is best seen with CT. The trachea is generally a midline structure displaced slightly to the right by the aortic arch. Various conditions, including mediastinal masses and vascular anomalies, may bow, displace or indent the trachea. Such appearances are most commonly seen in patients with thyroid masses or a right-sided aortic arch. Enlarged nodes do not usually narrow the trachea unless they are much harder than the cartilaginous rings, as occurs in nodular sclerosing Hodgkin's disease, or the rings are soft, as is the case in children.

Humans↗

[Prevention of ventilation hypoxia in surgical interventions on the open trachea].

Presents an analysis of artificial ventilation of the lungs (AVL) during interventions on the open trachea in 32 patients. Before crossing the trachea common AVL through an orotracheal tube was used. At the stage of resection of a portion of the trachea ventilation of one or both lungs was carried out through a tube inserted from the outside as shunting respiration using a method which ruled out additional dissection of the membranous wall of the trachea or main bronchus. At the stage of formation of intertracheal and tracheobronchial anastomosis AVL was resumed through a thin orotracheal tube moved further into the distal stump of the trachea or the main bronchus. High-frequency AVL through a thin orotracheal catheter at a frequency of 150/min provides adequate oxygenation of the blood and creates favorable conditions for the intervention on the open trachea during creating a tracheal anastomosis.

Adult↗

[Postintubation stenosis of the trachea--case reviews].

Stenoses of the respiratory tract are life threatening conditions of various origins. The authors give referrence on 21 patients operated for postintubation stenoses of their trachea at the IInd Surgical Clinic of the UPJS Medical Faculty, the Faculty Hospital of L. Pasteur in Kosice, from 01. 01. 1999 to 30. 06. 2005. All patients had a tracheobronchoscopic examination and a CT examination completed prior to the procedure. Within 24 hours of their admission, 9 patients were operated, 7 underwent resection procedures and 2 patients had Montgomery's T-cannula introduced. 12 patients had their procedures planned, and were operated later than 24 hours after their admission. 10 patients underwent resections of the trachea, 2 had Montgomery's T-cannula implanted. The postoperative course following the resection of the trachea was without complications in 14 patients, 1 patient experienced transitional oedema in the anastomosis and 2 patients suffered restenoses. In this patient group, no fatal case was recorded. The authors stress up multidisciplinary approach in the diagnostics and treatment of the postintubation stenoses of trachea. In cases of postintubation stenoses of trachea, resection of the trachea with primary anastomosis represents the most advantageous treatment approach for the patient.

Adult↗