Biomedical subjects

A Luts

Publications and source records attributed to A Luts.

At least 37 records · Page 2Linked to original sources

PubMed1993

Appearance of airway absorption and exudation tracers in guinea pig tracheobronchial lymph nodes.

This study examines the fate of extravasated plasma in inflammatory stimulus-challenged large tracheobronchial airways of ketamine-xylazine-anesthetized guinea pigs. Entry of plasma tracers into the airway lumen was determined by a validated noninjurious airway lavage technique. Removal by airway lymphatics was assessed by tracheobronchial lymph node levels of plasma tracers. Mucosal challenges with histamine (5 nmol), bradykinin (5 nmol), capsaicin (0.4 nmol), or allergen (ovalbumin, 3 pmol) increased the appearance of a plasma tracer (131I-labeled albumin previously injected intravenously) in the airway lumen within 10 min (10-20 times control; P < 0.001), whereas the contractile agent carbachol (8 nmol) was without exudative effect. The mediators were without effect, and capsaicin and allergen only slightly increased the lymph node level of plasma exudation tracer (1.5 times control; P < 0.05). Hence, removal via the lymphatic route of plasma macromolecules may be negligible in the acute and postacute phases of an airway exudation response. Experiments were also carried out with luminally applied macromolecular tracers. These were absorbed from the mucosal surface into the circulation, but a small portion was also transported to the lymph nodes, demonstrating the interconnections between the mucosa and the sampled nodes. Only capsaicin produced an increased node level of absorption tracer. Immunohistochemistry showed that the tracheobronchial tissue and lymph nodes are endowed with nerve fibers containing substance P, the release of which may have mediated lymph transport, vascular, and exudative effects of capsaicin in the present studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1993

Peptide-containing nerve fibers in human airways: distribution and coexistence pattern.

The occurrence, distribution and coexistence pattern of an array of neuropeptides and tyrosine hydroxylase in the human larynx, trachea, bronchi and lungs were studied by immunocytochemistry. A rich supply of nerve fibers containing vasoactive intestinal peptide (VIP) was seen close to blood vessels, glands and nonvascular smooth muscle. Pituitary adenylate cyclase-activating peptide (PACAP)-containing fibers were numerous among bundles of smooth muscle. Moderate numbers of helospectin-containing nerve fibers were seen in the nonvascular smooth muscle. The majority of neuropeptide Y (NPY)-containing fibers were located in the nonvascular smooth muscle; some fibers also occurred around blood vessels and glands. Substance P (SP) and calcitonin gene-related peptide (CGRP)-containing fibers were generally few and distributed beneath the epithelium, among bundles of smooth muscle, around blood vessels and glands. A conspicuous finding was the lack of SP- and CGRP-containing fibers within the respiratory epithelium. Galanin-containing nerve fibers were moderate in number among bundles of smooth muscle. Tyrosine hydroxylase-containing fibers were numerous around blood vessels and glands. The majority of the VIP-containing nerve fibers present in nonvascular smooth muscle also stored PACAP and helospectin. A subpopulation of VIP-containing fibers in both vascular and nonvascular smooth muscle and around glands stored NPY. Additionally, galanin was found to occur in many VIP-containing fibers located among bundles of smooth muscle.

Adrenergic Fibers↗

PubMed1993

Regional small-intestinal permeability in vitro to different-sized dextrans and proteins in the rat.

Molecular weight-dependent passage over different regions of the rat small intestine, using different-sized proteins/peptides and fluorescein isothiocyanate-dextrans in the 1- to 70-kDa range, was studied in vitro in modified Ussing chambers. The mucosal to serosal passage was inversely related to the molecular weight. After 120 min the passage in the proximal region usually dominated, but the nonapeptide (mercaptopropionic acid1, D-arginine8)-vasopressin differed by showing a consistently higher passage in the distal region. The similar apparent permeation coefficients obtained for the two macromolecular categories of corresponding molecular weight implied that the non-degradable dextrans could be used as permeability markers reflecting the passage per se of intact proteins. Furthermore, the results indicated two different transmucosal pathways, one of low permeability for molecules > 30 kDa, in which the molecular weight was of minor importance for the passage, and another more permeable one in the 1- to 30-kDa range, in which the passage was highly influenced by the molecular weight.

Animals↗

PubMed1993

Turnover and distribution of cathepsin G in the rat.

The turnover of 125I labelled rat polymorphonuclear leukocyte (PMN) cathepsin G with retained enzymatic activity was followed 180 min after an intravenous injection. The plasma half-life of injected radioactivity was approximately 4.5 min. In the plasma sample 15 min after injection the main part of the radioactivity in a gel filtration eluted at the same volume as 3-iodo-tyrosine (3-IT). After 15 min the liver contained about one third of the injected radioactivity. Radioactivity in all organs declined in the course of time. In the pancreas autoradiography showed labelling at the localization of enzyme granules as soon as 15 min after the intravenous injection of radiolabelled substance. All these results suggest a rapid uptake and degradation of cathepsin G in the liver. The distribution of cathepsin G in tissues analysed in the normal rat were localized to the spleen, lymph nodes, and lung. PMNs were immunohistochemically stained, while in the lung indefinable epithelial cells were stained. When rat PMN cathepsin G was added to normal rat plasma, we could identify 36% bound to alpha 1-macroglobulin (alpha 1M) and 19% bound to alpha 1-inhibitor 3 (alpha 1I3) as judged from analysis of gel filtration chromatography and electroimmunoassay (EIA) with autoradiography.

Animals↗

PubMed1991

Pituitary adenylate cyclase activating peptide (PACAP) in guinea-pig lung: distribution and dilatory effects.

The lower airways of guinea-pigs were analyzed for pituitary adenylate cyclase activating peptide (PACAP) using immunocytochemistry. In the trachea a moderate supply of PACAP-immunoreactive nerve fibers occurred around smooth muscle bundles, glands and small blood vessels. In the lung, PACAP-immunoreactive nerve fibers were distributed around small glands and bronchi. A rich supply of PACAP immunoreactive nerve fibers was found around blood vessels in the lungs. PACAP-suppressed smooth muscle responses were analysed using isolated circular segments of trachea, pulmonary arteries and aorta of guinea-pigs. In both airways and arteries PACAP caused a concentration-dependent relaxation of precontracted segments. The maximal relaxation effects were more pronounced in the airways than in the arteries while the order of potency was aorta greater than pulmonary artery greater than trachea. The effect of PACAP was compared to those of acetylcholine (ACh) and vasoactive intestinal peptide (VIP). In the pulmonary artery the vasomotor responses expressed as maximal dilatation had the order: ACh greater than VIP = PACAP while the order of potency was PACAP = VIP greater than ACh. In the trachea, PACAP was slightly more potent than VIP. The relaxatory responses to PACAP in the trachea and the intrapulmonary arteries were unaffected by pretreatment with atropine, prazosin, yohimbine, propranolol, mepyramine, cimetidine and Spantide. Removal of the endothelium abolished PACAP-induced vascular relaxation. Conceivably, PACAP-containing nerve fibers play a role in the regulation of airway resistance and local blood flow.

Analysis of Variance↗

PubMed1991

PACAP, a VIP-like peptide, in neurons of the esophagus.

The lower esophagus of guinea-pig, cat, sheep and man was analyzed for pituitary adenylate cyclase activating peptide (PACAP), a novel vasoactive intestinal peptide (VIP)-like peptide, using immunocytochemistry and radioimmunoassay. PACAP-immunoreactive nerve fibers were numerous in the longitudinal and circular muscle layers of sheep and man, moderate in numbers in cat, while being few in the esophagus of guinea-pig. A few PACAP-immunoreactive nerve cell bodies and numerous nerve fibers were seen in the myenteric ganglia of the esophagus of cat, sheep and man. In the lower esophagus of cat, sheep and man all PACAP-containing nerve cell bodies and nerve fibers stored VIP. The results of radioimmunoassay of PACAP in extracts of specimens from man were in good agreement with the immunocytochemical findings. High performance liquid chromatography revealed one major peak of PACAP-like immunoreactivity in extracts of human esophagus. We suggest that neuronal PACAP may serve to modulate motor activity and secretion in the lower esophageal sphincter region.

Animals↗

PubMed1991

Peptide-containing nerve fibers in the fungiform papillae of pigs and rats.

The occurrence and distribution of an array of neuropeptides and dopamine-beta-hydroxylase in the fungiform papillae of pigs and rats were studied by immunocytochemistry. Structural differences between the fungiform papillae of the two species were correlated to differences in the occurrence and distribution of neuropeptides. Calcitonin gene-related peptide-, substance P- and neurokinin A-containing fibers were numerous in the fungiform papillae of both species, although their distribution within the papilla differed. In the pig, the majority of these fibers ended within the taste buds, while in the rat numerous fibers also penetrated the adjacent epithelium. Galanin- and bombesin-immunoreactive nerve fibers could not be detected in the rat fungiform papillae, while in the pig many, but not all, of the fungiform papillae contained bombesin- and galanin-positive nerve fibers. Vasoactive intestinal peptide- and peptide histidine isoleucine-immunoreactive fibers occurred in the fungiform papillae of both species. A few neuropeptide Y-containing fibers and dopamine-beta-hydroxylase-positive (presumably adrenergic) fibers could be observed in the porcine papillae only.

Animals↗

PubMed1991

Pituitary adenylate cyclase-activating peptide (PACAP), a new vasoactive intestinal peptide (VIP)-like peptide in the respiratory tract.

Pituitary adenylate cyclase-activating peptide (PACAP) is a vasoactive intestinal peptide (VIP)-like peptide recently isolated from ovine hypothalami. Nerve fibers displaying PACAP immunoreactivity were found in the respiratory tract of rats, guinea pigs, ferrets, pigs, sheep and squirrel monkeys. A moderate supply of PACAP-immunoreactive fibers was seen in the nasal mucosa of guinea pigs. Few to moderate numbers of PACAP-containing fibers occurred in the tracheo-bronchial wall of rats, guinea pigs, ferrets, pigs, sheep and squirrel monkeys. The fibers were distributed beneath the epithelium, around blood vessels and seromucous glands, and among bundles of smooth muscle. In the lungs, the immunoreactive fibers were observed close to small bronchioli. A few PACAP-immunoreactive nerve cell bodies were seen in the sphenopalatine and otic ganglia of guinea pigs. Simultaneous double immunostaining of the respiratory tract of sheep and ferrets revealed that all PACAP-containing nerve fibers stored VIP. We suggest that neuronal PACAP may take part in the regulation of smooth muscle tone and glandular secretion.

Animals↗

PubMed1991

Chemical coding of endocrine cells of the airways: presence of helodermin-like peptides.

The epithelium of the airways is rich in endocrine cells containing serotonin and/or a wide variety of regulatory peptides. These cells usually occur in clusters in the lungs but are also found scattered in the larynx and trachea. In the present study, endocrine cells in the airways of mouse, rat, hamster, guinea pig, pig, sheep and squirrel monkey were examined for the presence of serotonin, helodermin-like peptides and other regulatory peptides using immunocytochemistry and radioimmunoassay. In addition, we looked for the protein gene product 9.5 (PGP), which occurs in many peptide hormone-producing endocrine cells in the body. Both clustered and scattered endocrine cells in the airways were found to display coexistence of serotonin and peptides, such as a helodermin-like peptide, calcitonin and calcitonin gene-related peptide (CGRP). The PGP-immunoreactive cells were numerous and included elements containing serotonin and/or regulatory peptides. An additional PGP-immunoreactive endocrine cell population lacked serotonin and regulatory peptides. Helodermin-immunoreactive material was demonstrated in endocrine cells of the airways in the mouse and hamster but not in any of the other species studied. Serotonin was an endocrine cell constituent in all the species studied. Calcitonin and CGRP could be demonstrated by immunocytochemistry in the mouse, rat, and hamster, but not in the guinea pig, sheep, pig and monkey.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Acute and late radiation damage in mouse bladder: a comparison of urination frequency and cystometry.

Functional damage in the mouse bladder was measured sequentially from 1 to 53 weeks after irradiation with a range of X ray doses (10 to 30 Gy). Damage was assessed from the independent assays of urination frequency and cystometric measurement of bladder volume at a constant intravesical pressure. There was an early, transient wave of damage from 1 to 3 weeks after bladder irradiation. During this period the urination frequency was increased to greater than or equal to 2 times control levels in 20 to 70% of the mice (depending on dose) after 15 to 30 Gy. Bladder volume was reduced to less than or equal to 50% of control values in 20 to 40% of the mice after doses of 20 to 30 Gy. This early damage usually lasted for less than 1 week and occurred at times ranging from 5 to 21 days, independent of dose. There was no significant correlation between response as measured by the two assays on an individual animal basis during the early period. The incidence of reduced bladder volume, measured cystometrically in anesthetized mice, tended to be less than the incidence of increased urination frequency, measured in non-anesthetized animals. Late bladder damage developed from 16 to 40 weeks after doses of greater than or equal to 20 Gy, and the time of onset was inversely related to dose. Less than 20% of mice treated with 10 to 15 Gy developed late bladder damage as assessed by increased urination frequency or reduced bladder volume. Late bladder damage was irreversible and there was a good correlation between response of individual animals as measured by the two assays. We conclude that changes in both urination frequency and bladder volume can be used as quantitative measures of early and late functional damage after bladder irradiation. The early, transient damage was not associated with changes in the urothelium or muscle layers of the bladder, whereas the late, persistent damage was accompanied by epithelial denudation and focal hyperplasia, with fibrosis and ulceration after higher doses.

Animals↗

PubMed1991

Hydrogen peroxide-induced epithelial damage increases terbutaline transport in guinea-pig tracheal wall: implications for drug delivery.

An isolated vagus nerve-tracheal tube preparation from guinea-pig was treated intraluminally with hydrogen peroxide (H2O2) at various concentrations. Exposure to, 100 mmol/L H2O2 for 20 min was chosen for further experiments since it appeared to cause selective damage to the epithelium. Thus the subepithelial layers of the tracheal wall appeared intact as judged by light microscopic examination. The response to nerve stimulation (increase in intratracheal pressure) was attenuated by only about 20%. Terbutaline administration into the tracheal lumen caused a concentration-dependent inhibition of the response to nerve stimulation. In tracheal preparations pretreated with 100 mmol/L H2O2 there was a 20-fold decrease in the EC50 for terbutaline. The EC50 for terbutaline added to the external medium was not changed by the H2O2 pretreatment. The efflux of 3H-terbutaline from the tracheal lumen into the external medium was three times higher in H2O2-treated than in control preparations. It is concluded that in the H2O2-damaged epithelium the absorption of terbutaline is enhanced resulting in a better availability of the drug in the smooth muscle layer after intraluminal administration.

Animals↗

PubMed1991

Plasma exudation as a first line respiratory mucosal defence.

A great variety of provocations of the airway mucosa produce extravasation of plasma from the abundant subepithelial microvessels. A plasma exudate has important actions through its volume, its specific and unspecific binding proteins, its enzyme systems, and its potent peptides (of kinin, complement, coagulation, fibrinolysis and other systems). If allowed to operate on the surface of an intact mucosa the plasma exudate would have important roles in normal airway defence. Recent observations in guinea-pig tracheobronchial airways and in human nasal airways suggest that the mucosal exudation of plasma into the airway lumen is a non-injurious fully reversible process. Threshold exudative responses thus resulted in the appearance of an 'unfiltered' plasma exudate not only in the lamina propria but also on the surface of an undisrupted mucosa. Even after extensive luminal entry of exudate the epithelial lining was intact, as judged by light, fluorescence and electron microscopy. Hence, the epithelial barrier was reversibly permeable when approached from beneath by the plasma exudate. This was a distinct increase in outward permeability, because even during the exudation of plasma the mucosa remained a barrier to luminal solutes. It is possible that the exudate itself, by a slight compressive action on the basolateral aspect of epithelial cells, creates intercellular pathways for its entry into the lumen. Contrary to current beliefs, we propose that plasma exudation should be considered a first line respiratory defence mechanism operating together with other systems of the mucosal surface.

Absorption↗

PubMed1991

Toluene diisocyanate produces an increase in airway tone that outlasts the inflammatory exudation phase.

Toluene diisocyanate (TDI) is a causative agent in occupational asthma. Through an oral catheter TDI, 0.03 microliters, dissolved in 0.02 ml olive oil, was superfused on the tracheobronchial mucosa of anaesthetized guinea-pigs. TDI induced plasma exudation into both airway tissue and lumen (peak effect: 5 hr; duration approximately 17 hr). Light microscopy examinations demonstrated that the epithelium was not disrupted by this process (and that microvessels are abundant just beneath the epithelium). At days 6 and 21 after exposure to TDI PAS-positive cells were increased, but no other histological alterations were found. Also, the occurrence of peptide-containing nerve fibres was not altered by TDI. After TDI-exposure the airway smooth muscle tone was elevated as examined in vitro at base-line and at concentration-response to carbachol. The largest increases in tone were recorded 21 days after exposure to TDI. The abnormally large tone was not associated with an increased thickness of the smooth muscle layer nor was it associated with reduced effects of either beta 2-agonist (terbutaline) or xanthine- (theophylline) relaxants. It is concluded that TDI-induced plasma exudation into guinea-pig airways occurs for 17 hr without disrupting the epithelial lining and without causing major changes in the airway peptidergic innervation. Both the airway tone, and the number of mucous cells, are increased for at least 3 weeks after exposure to TDI.

Airway Resistance↗

PubMed1990

VIP-containing nerve fibres in the submandibular gland of the dog and protein secretion in vitro in response to VIP.

Previously, administration of VIP has been shown to elicit no flow of saliva from the submandibular gland of the dog. However, in the present study we found VIP to cause release of protein in vitro from canine submandibular gland tissue. Furthermore, VIP-containing nerve fibres were demonstrated in large numbers in association with acini. Thus, VIP may be involved in the nervous regulation of salivary protein secretion in the dog.

Animals↗

PubMed1990

Peptide-containing nerve fibers in the circumvallate papillae.

The occurrence and distribution of an array of neuropeptides and dopamine-beta-hydroxylase in the circumvallate papillae of monkey, pig, cow, ferret, cat, rat and mouse was studied by immunocytochemistry. The animals were chosen to represent species with different diets. Substance P/neurokinin A- and calcitonin gene-related peptide-containing fibers were numerous in the circumvallate papillae of all animals examined, with the highest frequency in monkey, pig, cow, rat and mouse; in ferret and cat moderate numbers were detected. Vasoactive intestinal peptide/peptide histidine isoleucine amide-containing fibers were numerous in the circumvallate papillae of pig, while they were moderate in number in monkey, ferret and mouse. Neuropeptide Y-containing fibers were few to moderate in number in the circumvallate papillae of all species. Galanin-containing fibers were numerous in the pig circumvallate papillae, while only a few fibers could be detected in monkey, cow, cat, rat and mouse. Somatostatin-containing fibers were seen only in the cat circumvallate papillae, gastrin-releasing peptide-containing fibers in the cow and cat, cholecystokinin/gastrin-containing fibers in the pig and cow. Dopamine-beta-hydroxylase-containing fibers were detected in all animals studied. They were few to moderate in number in the circumvallate papillae. There was no obvious link between the peptidergic innervation pattern and the food habits.

Animals↗

PubMed1990

Peptide-containing neurons projecting to the vocal cords of the rat: retrograde tracing and immunocytochemistry.

The distribution and origin of neuropeptide Y-, vasoactive intestinal peptide- and calcitonin gene-related peptide-containing nerve fibers and adrenergic (dopamine-beta-hydroxylase-containing) fibers in the rat larynx were studied by retrograde tracing and selective denervations in combination with immunocytochemistry. An injection of the retrograde tracer True Blue to the right vocal cord resulted in the appearance of labelled nerve cell bodies in the ipsi- and contralateral superior cervical and stellate ganglia, the thyroid ganglia, the jugular-nodose ganglionic complexes, in the ipsilateral trigeminal and dorsal root ganglia at levels C2 and C3 and in local tracheal ganglia. Judging from the number of labelled nerve cell bodies, the jugular-nodose ganglionic complexes, dorsal root ganglia and superior cervical ganglia provide the greater part of the vocal cord innervation. Most of the True Blue-labelled nerve cell bodies in the superior cervical and stellate ganglia contained neuropeptide Y. In the thyroid ganglia the majority of labelled nerve cell bodies contained vasoactive intestinal peptide. In the jugular-nodose ganglionic complex and the dorsal root ganglia the majority of the labelled nerve cell bodies stored calcitonin gene-related peptide. Retrograde tracing and denervation studies revealed that all noradrenaline- and the majority of neuropeptide Y-containing nerve fibers emanate from the superior cervical and stellate ganglia. A minor population of neuropeptide Y-containing nerve fibers originate in local tracheal ganglia. The vasoactive intestinal peptide-containing nerve fibers originate in the thyroid ganglion and local tracheal ganglia, whereas calcitonin gene-related peptide-containing nerve fibres emanate from the dorsal root ganglia (C2-C3), the trigeminal ganglia and the jugular-nodose ganglia.

Animals↗

PubMed1990

Long-term recovery and reirradiation tolerance of mouse bladder.

The aim of this study was to investigate the influence of overall treatment time on the development and repair of radiation injury in the bladder. The bladders of mice were irradiated with 2 equal doses of X rays separated by 1 day, 3 months or 9 months. Additional groups of mice were given 8 or 16 Gy (approximately 20% and 60%, respectively, of a full tolerance dose) and subsequently reirradiated with a range of test doses after 3 or 9 months. Functional bladder damage was assessed from measurements of urination frequency and bladder compliance (measured cystometrically). There was a very early onset of functional damage (within 2 weeks) when mice were reirradiated 9 months after a dose of 16 Gy. Lower initial doses of 8 Gy did not alter the time of expression of damage after reirradiation. The early damage was probably due to stimulated cellular proliferation, which occurred after 16 Gy but not after 8 Gy, causing rapid expression of retreatment injury. Reirradiation tolerance for late bladder damage was inversely related to the dose given in the first treatment but was independent of the interval between treatments. There was no evidence for increased tolerance as the interval between treatments increased from 1 day to 9 months, which suggests that protracting the overall treatment time will not lead to sparing of late radiation damage in the bladder.

Animals↗

PubMed1990

The airway epithelial lining in guinea pigs is intact promptly after the mucosal crossing of a large amount of plasma exudate.

In the present study of anaesthetized guinea pigs, we have confirmed by chemical analyses that 10 min after topical mucosal provocation with capsaicin 0.4 nmol of platelet-activating factor 8 nmol plasma macromolecular tracers (FITC-dextran, molecular weight 156 kD, previously injected intravenously) have been significantly exuded into airway tissue and lumen. We have also examined the airway mucosa and the mucosal surface material using fluorescence, light, and electron microscopy. Thus we have demonstrated by histological techniques that promptly after the induction of large exudative responses plasma macromolecules are abundant in the lumen as well as in the lamina propria. Furthermore, the exudate is seen on the surface of a mucosa that has an intact epithelial lining. These observations are evidence in favour of the possibility that plasma exudation into the lumen is a first-line defense mechanism of the normal airway mucosa.

Animals↗