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Biomedical subjects

A Laitinen

Publications and source records attributed to A Laitinen.

51 records · Page 3Linked to original sources
PubMed1987

Vascular actions of airway neuropeptides.

We have studied effects of several neuropeptides perfusing the cranial tracheal arteries bilaterally in anesthetized dogs. All the neuropeptides tested produced dose-related changes in vascular resistance. Substance P and VIP had similar potencies in decreasing tracheal vascular resistance. Neurokinin A (NKA) was the most potent dilator. Calcitonin gene-related peptide (CGRP) and peptide histidine isoleucine (PHI) were about 10 and 100 times less potent than NKA, respectively. Neuropeptide tyrosine (NPY) was one of the few constrictors of tracheal vessels at doses above 10(-11) mol. There seemed to be major differences between the neuropeptides with regard to the onset and duration of their vascular effects. NKA and PHI usually caused maximal vasodilatation within 15 to 30 s after the injection into the tracheal artery, and their vascular responses subsided within 1 to 2 min. With CGRP, the maximal dilatation of tracheal vessels came somewhat later, and more than half of the vascular response was still present 10 min after the injection of this neuropeptide. The maximal vasoconstrictor response to NPY came slowly, and the constriction showed only a little tendency to subside within 10 min after the injection. These results indicate that the long-acting neuropeptides VIP, CGRP, and NPY may be more important than the short-acting NKA and PHI in the physiologic regulation of airway blood flow. All the neuropeptides studied had effects on the contralateral tracheal vascular resistance. They were much more powerful than the classic mediators histamine and methacholine.

Animals↗
PubMed1987

Effects of inflammatory and other mediators on airway vascular beds.

The bronchial arteries extend to all lung structures in man with the exception only of the alveolar wall. In addition to providing nutrition to the lungs, the bronchial vessels can also function as a hemodynamic and gas-exchange system due to anastomoses with the pulmonary arteries; they also play a significant role in controlling the clearance of chemical mediators, regulating the development of airway wall edema, and controlling heat exchange in the tracheobronchial tree. We have measured the effects of inflammatory and other mediators on tracheal mucosal thickness and the changes in tracheal vascular resistance in dogs. Bradykinin, histamine, and methacholine had large "vasodilator" effects, decreasing vascular resistance, and they also clearly increased the thickness of the mucosa. Substance P, VIP, PGF2 alpha, and PGE1 had as large a response on vascular resistance as the drugs mentioned above, but only had small effects in increasing tracheal mucosal thickness. Salbutamol fell between these 2 groups with regard to the pattern of response. Phenylephrine had an opposite action, causing an increase in vascular resistance and a decrease in mucosal thickness. Despite the vasodilatation and the increase in vascular permeability due to vasoactive drugs, the changes in mucosal thickness were rather small and could not be correlated with the decreases in vascular resistance due to the different drugs. Such changes are unlikely to have an appreciable effect on tracheal airway resistance. The change in mucosal thickness may be more significant in those parts of the airways where the ratio of change in mucosal thickness to the radius of adjacent lumen is large, such as the nose and small conducting airways.

Animals↗
PubMed1986

Relationship between tracheal mucosal thickness and vascular resistance in dogs.

We have measured changes in tracheal mucosal thickness and tracheal vascular resistance in the dog. A probe was used to detect changes in height with time of the tracheal epithelium relative to an underlying cartilage. Tracheal vascular resistance was determined by perfusing a cranial tracheal artery at constant flow and measuring inflow pressure. Various drugs injected close-arterially were tested in 20 greyhounds anesthetized with pentobarbital sodium. Bradykinin, histamine, and methacholine significantly (P less than 0.01) decreased vascular resistance (-39.3 +/- 3.7, -47.3 +/- 4.2, and -22.5 +/- 5.2%, respectively) and increased the thickness of the mucosa (119.0 +/- 25.0, 61.9 +/- 25.0, and 46.3 +/- 6.4 micron). Substance P, vasoactive intestinal peptide, prostaglandin F2 alpha, and prostaglandin E, had large vasodilator actions (-31.4 +/- 5.0, -34.3 +/- 2.2, -21.9 +/- 2.8, and -31.5 +/- 2.4%) but only small effects on mucosal thickness (12.3 +/- 3.9, 13.0 +/- 3.4, 16.7 +/- 6.5, and 8.7 +/- 2.9 micron, respectively). Phenylephrine hydrochloride increased vascular resistance (19.8 +/- 1.7%) and decreased mucosal thickness (-23.9 +/- 3.1 micron). Thus airway vascular resistance and mucosal thickness always change in opposite directions, but drugs have different relative actions on the two variables. Even with large vasodilatations, the absolute changes in mucosal thickness were small and were unlikely to have an appreciable effect on tracheal airway resistance.

Animals↗
PubMed1985

VIP like immunoreactive nerves in human respiratory tract. Light and electron microscopic study.

The present study provides light and electron microscopical evidence of Vasoactive Intestinal Peptide - (VIP) like immunoreactive nerves in human lower respiratory tract. Peroxidase antiperoxidase (PAP) technique was used to localize VIP-like immunoreactivity light microscopically and ultrastructurally. Under light microscopy, VIP-like immunoreactive nerves were observed in the smooth muscle layer of secondary bronchi to small bronchioli, and in bronchial glands. In addition, positive immunoreactive nervous network to VIP was found around nerve cell bodies in small microganglia. The bronchial epithelium of airway tract did not receive any VIP positive nerve fibers. Ultrastructurally VIP-like positive immunoreaction was localized in large granular vesicles ranging from 90 to 210 nm. Usually VIP-like positive immunoreactive nerve profiles contained several immunoreactive large vesicles (100-210). However, nerve profiles containing only a few positive large vesicles (80-150) were also observed. Under electron microscopy VIP-positive nerve profiles corresponded ultrastructurally to nerve profiles containing large granular vesicles observed in conventional electronmicroscopy. The present study provides new information about the innervation of human lower airway tract and widens the concept of their functional regulation on the anatomical basis reported here.

Bronchi↗
PubMed1985

Ultrastructural organisation of intraepithelial nerves in the human airway tract.

Intraepithelial nerves of human airway tract were studied by electron microscopy after conventional glutaraldehyde fixation. Specimens were obtained from five patients at three different airway levels--the trachea, the right upper lobe bronchus, and segmental bronchus. Intraepithelial axon profiles were located either near the basement membrane or close to the lumen but were rare in the intermediate area of the epithelium. Axon profiles close to the lumen were seen only in the central airways (levels 1 and 2), while profiles close to the basement membrane were seen in all three levels.

Adult↗
PubMed1985

Damage of the airway epithelium and bronchial reactivity in patients with asthma.

We measured bronchial reactivity to inhaled histamine and prepared electron micrographs from bronchial biopsies from 8 asthmatic patients who never smoked (2 females, 6 males, 18 to 62 yr of age). Judging from their clinical histories and the need for medication and long-term follow-up of PEF values, 2 of them had mild asthma, 3 moderately severe, and 3 severe asthma. They had not experienced respiratory infections for at least 2 months prior to the study. The result, obtained from the cumulative dose-response curve, was expressed as the provocative dose (PD20) of histamine producing a 20% fall in forced expiratory volume in one second (FEV1). In 5 patients, the PD20 varied from 0.049 mg to 2.234 mg. In the sixth patient, only PD15 could be measured (5.187 mg). In 2 patients, the low initial FEV1 values, because of severe, partly irreversible obstruction, prevented the measurement of bronchial reactivity. Bronchial biopsies were taken with rigid tube bronchoscopy from 3 levels: (1) at the carina of the right upper lobe, (2) at the opening of the right middle or lower lobe, and (3) inside the right lower lobe. The specimens were prepared for both light and electron microscopy. Fresh biopsies showed that asthma patients can have epithelial destruction at all levels of the airways. The ciliated cells appeared to be the most destroyed cell type in the epithelium. Intraepithelial nerves and mast cells were seen. Epithelial destruction in the respiratory tract of the asthma patients with mild to severe bronchial hyperresponsiveness was prominent enough to expose the epithelial nerves for specific or nonspecific stimuli.

Adolescent↗
PubMed1985

Autonomic innervation of the human respiratory tract as revealed by histochemical and ultrastructural methods.

The major findings and conclusions of this study are the following: Indirect evidence for the presence of the bronchoconstrictive transmitter acetylcholine in the human bronchial smooth muscle was obtained by demonstration of acetylcholinesterase-positive nerve fibers and nerve profiles of cholinergic type. Acetylcholinesterase-positive nerve fibers and nerve profiles of cholinergic type were found in human bronchial glands. A sparse adrenergic innervation of the human bronchial smooth muscle and glands was found by using catecholamine histofluorescence. This observation was supported by finding ultrastructurally adrenergic-like nerve profiles close to smooth muscle cells. Direct evidence for the presence of a new possible bronchodilating transmitter VIP (vasoactive intestinal peptide) in the human bronchial smooth muscle was obtained both by light microscopical demonstration of VIP immunoreactive nerve fibers and by localization of VIP like immunoreactivity in granules in nerve profiles. Nerve fibers containing VIP-immunoreactivity were found in the human bronchial glands by light microscopy. Substance P-immunoreactive nerves were found in the lower respiratory tract of the rabbit but not of man by light microscopy. Intraepithelial nerves were demonstrated in man from trachea to segmental bronchi and their concentration was established. The intraepithelial nerves seem to have two predominant locations: either close to the airway lumen or near the basement membrane. Nerves near the lumen were found only in larger airways e.g. trachea and lobar bronchi.

Acetylcholinesterase↗
PubMed1985

Electron microscopic study on the innervation of the human lower respiratory tract: evidence of adrenergic nerves.

Samples of human lung were studied electron microscopically after fixation with glutaraldehyde and osmium tetroxide. Three different types of nerve profiles were found in the human lower respiratory tract. Type I nerve profiles contained small agranular vesicles 30-50 nm and large granular vesicles ranging from 60 nm to 210 nm. Type II nerve profiles contained small granular vesicles 30-50 nm and a few large granular vesicles ranging from 60 to 120 nm. Type III nerve profiles contained predominantly large irregular vesicles ranging from 60 to 210 nm, and only a few small agranular vesicles. The present electron microscopic results indicate that the smooth muscle layer of human bronchial tree receives adrenergic nerves.

Adrenergic Fibers↗
PubMed1983

Immunohistochemical demonstration of substance P in the lower respiratory tract of the rabbit and not of man.

Substance P (SP)-immunoreactive nerve fibres were searched for at all levels of both fetal and adult human lower respiratory tract. Because the demonstrability of substance P immunoreactivity varies between different animal species, rabbit pulmonary tissue was also subjected to SP immunohistochemistry. Human irises and corneas served as positive human controls. The specimens were taken from 10 human lungs during pulmonary operations. Tracheal tissue was obtained from three patients during bronchoscopy. Five fetal human lungs were examined. Human specimens examined included the trachea, main bronchi, segmental bronchi, and peripheral pulmonary tissue. In addition, the tracheobronchial tissues of four rabbits were studied. SP immunoreaction was demonstrated in formaldehyde-fixed cryostat sections by either the indirect immunofluorescence technique or the peroxidase-antiperoxidase procedure. Both monoclonal and conventional antibodies to SP were tested. In the rabbit SP-immunoreactive nerves were found in both the submucosa and the smooth muscle layer of the main bronchi and trachea. Specimens from human trachea, bronchi, and bronchioli were all negative. Since the SP immunoreaction was easily demonstrated in both human cornea and human iris, it was concluded that there are no SP-immunoreactive nerves in the human pulmonary tissues or that their SP content is very low and below the sensitivity of all the techniques used.

Animals↗
PubMed1983

Non-specific bronchial reactivity and ultrastructure of the airway epithelium in patients with sarcoidosis and allergic alveolitis.

There are subgroups of subjects showing increased bronchial responsiveness to histamine among patients with sarcoidosis and with allergic alveolitis (farmer's lung). In these subjects the airway reactivity is comparable with that usually encountered in patients with asthma and in many cases of bronchitis. In many of our patients with hyperreactive sarcoidosis and alveolitis, the increased reactivity was transient, lasting for one to two months during the acute stage of the disease. By electron microscopy we have shown that some of these patients have extensive epithelial damage which could increase epithelial permeability and uncover superficial afferent nerve endings. Indeed, superficial epithelial afferent nerves were found, and it is possible that irritation of these nerve endings causes enhanced bronchoconstriction via the vagal reflex. The transient nature of the hyperreactivity observed in patients with sarcoidosis and alveolitis may indicate that the epithelial changes are readily reversible. The recovery of the epithelium could perhaps be demonstrated by taking serial bronchial biopsies during the course of the disease. Because the electron microscopic specimens represented only a small area of bronchial epithelium, it is difficult to draw any conclusions as to a quantitative relationship between the amount of total epithelial damage and the degree of bronchial reactivity.

Adult↗
PubMed1982

Catecholamine- and acetylcholinesterase-containing nerves in human lower respiratory tract.

The innervation of human lower respiratory tract was studied with special emphasis on airways with sodium-potassium glyoxylic acid (SPG) and acetylcholinesterase (AChE) methods to demonstrate catecholamine-containing and acetylcholinesterase-containing nerve fibers. AChE-method revealed a rich network of cholinesterase positive nerves both inside the bronchial glands where they run around and between the acini, and the airway smooth muscle from secondary bronchi to terminal bronchioli. No AChE-positive fibers were found in connection with the blood vessels or within the epithelium of bronchi or bonchioli. The AChE-positive nerve fibers in bronchial smooth muscle greatly outnumbered those containing catecholamine. The SPG-method revealed the presence of adrenergic nerves from the level of secondary bronchi to that of terminal bronchioli. These nerve fibers were most abundant in bronchial glands, where their amount was equal and distribution similar to those of AChE-containing nerve fibers. Outside the glands adrenergic fibers were constantly seen in connection with the bronchial blood vessels in connective tissues surrounding bronchi. A few nerve fibers were also present in airway smooth muscle from the secondary bronchi to terminal bronchioli.

Acetylcholinesterase↗
PubMedDate not supplied

Inhaled corticosteroid treatment and extracellular matrix in the airways in asthma.

Even mild asthmatics with a short duration of the disease show at the morphological level a picture of chronic inflammation with airway epithelial changes and influx of inflammatory cells into the airway mucosa. Several studies have shown that inhaled corticosteroid treatment can ameliorate this inflammation. In addition, even a morphologically normal epithelial structure may be restored. However, factors which may lead to more chronic disease have remained obscure. Recent studies are now focusing on the reversibility of collagen deposition in the airway epithelial basement membrane. Airway epithelial and stromal interactions may be important when a change at this level occurs.

Administration, Inhalation↗
PubMedDate not supplied

Pathology of asthma.

Appreciation of the early damage that occurs to the respiratory epithelium has been limited by the use of autopsy specimens from fatally stricken asthmatics as a source of representative specimens. The use of bronchoscopy to obtain specimens from patients early in the course of their asthma has allowed a new understanding of the evolution of pathological changes that occur in asthma. Newly diagnosed, mild asthmatics have been shown to have bronchial goblet cell hyperplasia in addition to increased numbers of mast cells and eosinophils in the respiratory epithelium, and increased eosinophil granule protein deposition within the lamina propria. Endothelial gaps in postcapillary venules are greater in asthmatic airways, suggesting that increased plasma transudation may contribute to the known epithelial cell shedding characteristic of asthma attacks. Asthmatic inflammation, even early in the course of the disease, includes vascular permeability changes, inflammatory cell infiltration, epithelial cell shedding, and goblet cell hyperplasia, replacing the normal ciliated epithelium. Current investigation evaluating the effects of asthmatic inflammation on epithelial cell attachment to each other and to the extracellular matrix molecules regulated by adhesion glycoproteins will likely enhance further the understanding of the pathological changes that occur within the asthmatic airway.

Asthma↗
PubMedDate not supplied

Inhaled corticosteroid treatment for asthma.

Increased numbers of goblet cells associated with decrease in the ciliated epithelium occur at an early stage in the patient with asthma. Recent bronchial biopsy studies have demonstrated that these changes may occur even in the mildest asthmatic patient. The protective function of the epithelium is thus compromised and secretion enhanced in early asthma. Anti-inflammatory therapy should be employed at an early stage in the asthmatic patient. Avoidance of allergen is also essential if the source of the inflammation is atopic disease. Inhaled corticosteroids not only reduce bronchial hyperresponsitivity, but also improve the diurnal variation that occurs in lung function in the asthmatic patient. Inhaled corticosteroid therapy is associated with the normalization of the ciliated to goblet cell ratio and a reduction in the inflammatory cell infiltrate, including most notably a reduction in eosinophil within the lamina propria and respiratory epithelium. These changes induced by inhaled corticosteroids are not noted when inhaled beta 2-agonists are employed alone as therapy for asthma. The use of inhaled corticosteroids may thus potentially reverse the pathologic changes that occur even in the early asthmatic patient, whereas utilization of inhaled beta 2-agonists failed to improve histologic abnormalities that occur in early asthma.

Administration, Inhalation↗