Biomedical subjects
P Goldie
Publications and source records attributed to P Goldie.
Arachidonic acid metabolites in experimental otitis media and effects of anti-inflammatory drugs.
Previous studies have shown that arachidonic acid (AA) metabolites are important in the pathogenesis of otitis media with effusion. The AA metabolites in 4 different experimental models for otitis media were analyzed, and the effect of anti-inflammatory drugs was studied. Purulent otitis media was induced in rats by inoculation of Streptococcus pneumoniae in the tympanic bulla, serous otitis media by blocking the tympanal orifice of the eustachian tube, and mucoid otitis media by combining the two procedures. Middle ear effusion was also induced by stimulating the external auditory canal with cold air. Indomethacin and hydrocortisone were used to inhibit AA metabolism in the latter model. Lipoxygenase products dominated in the purulent and cold air otitis media models. Cyclooxygenase products dominated in the mucoid and serous models. Indomethacin inhibited accumulation of middle ear effusion in the cold air otitis media model, whereas hydrocortisone did not. Apart from AA metabolites, other mechanisms and mediators appear to be responsible for the increased vessel permeability observed in the cold air otitis media model, such as interactions between mast cells and nerves in the middle ear mucosa.
Mechanisms of otitis media development. Involvement of neurogenic inflammation.
The mucosal lining of the middle ear cavity, in particular that of the tympanic membrane and its pars flaccida, exhibits a number of sensory nerves containing the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP). The mucosa is not only rich in nerves and blood vessels but also contains numerous mast cells. It is possible that interactions between histamine-containing mast cells and SP-containing and CGRP-containing nerves--neurogenic inflammation--is one of the mechanisms involved in vessel permeability changes in otitis media with effusion.
Vascular events in experimental otitis media models: a comparative study.
The vascular leakage and components of middle ear effusion (MEE) were determined and compared in various experimental otitis media models in the rat: purulent otitis media (POM); serous otitis media (SOM); mucoid-like otitis media (MOM); stimulating the external auditory canal with a 14 degrees C airstream and vagotomy. When the Evans blue technique was used, all otitis media models exhibited a significant increase in middle ear vessel permeability. The MEEs contained numerous PMNLs, except for animals stimulated with a 14 degrees C airstream, in which the MEE was free of cells. The IgG/SIgA ratio in MEEs indicated that the MEE components are derived from serum in the early phases of fluid accumulation, in these otitis media models. In POM, MEE components appeared to be derived from local synthesis by the middle ear mucosa as well.
Identification and characterization of middle ear vascular leakage sites in experimental otitis media.
The site of leakage in middle ear vessels was determined and characterized in experimental otitis media in rats. Middle ear effusion was induced by intravenous administration or local application in the tympanic bulla of substance P (SP), acetylcholine, and histamine. In another experiment, a 14 degrees C airstream was blown into the external auditory canal. Colloidal carbon was used to trace leakage sites at the light and electron microscopic levels. All mediators tested and the 14 degrees C airstream resulted in an increased number of leaking vessels in the pars flaccida and the middle ear mucosa. The leakage sites were restricted to capillaries and postcapillary venules. Increased numbers of degranulated pars flaccida mast cells were observed for SP only. Interendothelial gaps formed in leakage vessels after administration of mediators and stimulation of the external auditory canal with a 14 degrees C airstream. Also, cytoplasmic vesicle-like structures within the endothelial cells increased in number following SP and histamine treatment, suggesting that an increased permeability in experimental otitis media does not occur exclusively through interendothelial gaps.
Biochemical characterization of Plasmodium falciparum hemozoin.
Hemozoin, the pigment granule which develops within the blood stage food vacuole of the malaria parasite Plasmodium falciparum, was biochemically characterized. Hemozoin was found to be composed of 65% protein, 16% ferriprotoporphyrin-IX (hematin), 6% carbohydrate, and trace amounts of lipid and nucleic acids. The overwhelming majority of the protein component is a mixture of native and denatured human globin non-covalently associated with the metalloporphyrin. Immunoelectron microscopy, employing anti-human hemoglobin as a probe, identified in situ association of hemoglobin with hemozoin. Hemozoin produced within diabetic blood had a higher proportion of carbohydrate, suggesting that the carbohydrate component comes from non-enzymatic glycosylation of hemoglobin.
Neuropeptides in intact and denervated tympanic membranes. An immunohistofluorescence study in the rat.
The distribution and origin of peptide-containing and sympathetic nerve fibers were studied in the tympanic membrane of rats with intact innervation, and in rats following sympathectomy, vagotomy, or capsaicin treatment. Nerve fibers showing substance-P-like immunoreactivity (SP-LI), calcitonin gene-related peptide (CGRP)-LI, vasoactive intestinal polypeptide (VIP)-LI, enkephalin-LI, neuropeptide Y (NPY)-LI and tyrosine hydroxylase (TH)-LI were detected along blood vessels in the pars flaccida, the external auditory canal and in the fibrocartilaginous ring of the pars tensa. In the pars flaccida there were numerous fibers demonstrating SP-LI and CGRP-LI, while there were few such fibers in the pars tensa. In both portions of the tympanic membrane these fibers were present within and beneath the keratinized stratified squamous epithelium. In the pars flaccida, nerve fibers showing SP-LI and CGRP-LI were also seen near mast cells. Sympathectomy led to a loss of nerve fibers showing TH-LI and NPY-LI, whereas the other peptide-containing nerve fibers remained unaffected. Vagotomy did not reduce the immunoreactivity for any of the neuropeptides studied. Capsaicin treatment caused a reduction in nerve fibers displaying SP-LI and CGRP-LI. The abundance of nerve fibers showing SP-LI and CGRP-LI in the keratinized squamous epithelium indicates that the tympanic membrane is richly supplied with sensory nerves. The localization of nerve fibers exhibiting these latter substances in the vicinity of mast cells in the pars flaccida suggests that this part of the tympanic membrane is a site where neurogenic inflammation occurs.
Dextran density gradient purification of Plasmodium sporozoites.
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Pharmacological characterization of receptors on blood vessels in the tympanic membrane involved in otitis media.
Acetylcholine dropped onto the meatal surface of the tympanic membrane evoked vasodilatation and a vascular leakage to the middle ear cavity. The vasoreactions were atropine-resistant. Substance P and vasoactive intestinal polypeptide (VIP) injected intravenously caused a marked vascular leakage and VIP also vasodilatation. These blood vessel changes seem to be regulated by the parasympathetic nerves as they were inhibited by vagotomy. Constriction of the tympanic membrane vessels was mediated through alpha-receptors.
Mechanisms in middle ear effusion production caused by irritation of the external auditory canal.
In an animal model, a stream of chilled air blown into the external auditory canal evoked an edematous pars flaccida and accumulation of a serous effusion in the attic. The degree of inflammatory changes depended on the temperature of the stimuli. The nervous system appears to mediate the observed changes, as the vagus nerve, representing the parasympathetic system, potentiates vascular leakage, and the sympathetic nerves inhibit leakage.
Middle ear effusion induced by a stream of air in the external auditory canal. A temperature-related phenomenon.
The blowing of chilled (14 degrees C) air into the external auditory canal (EAC) resulted in a profuse middle ear fluid production. The stimulation caused marked changes in the pars flaccida of the tympanic membrane. A slight vasodilatation was noted in the oedematous loose connective tissue layer of the pars flaccida. The abundant mast cells showed no signs of degranulation. When stimulating animals with air at 22 degrees C, only minimal effusion production and tympanic membrane changes could be induced. At 34 degrees C, no changes occurred at all. Thus it was shown that temperature is an important factor when provoking middle ear effusion by stimulating the EAC. As fluid production is one of the major signs in OME, one may speculate whether temperature may be an overlooked etiologic agent in this disease.
Autonomic nerves and middle ear fluid production. An experimental study in the rat.
The production of middle ear effusion by mechanical stimulation was studied in sympathectomized and vagotomized animals. Mechanical stimulation was obtained by a 14 degree C airstream in the external auditory canal. In sympathectomized animals this procedure caused effusion production and vasoconstriction of pars flaccida vessels. Mechanical stimulation in the vagotomized animals did not cause any production of effusion material. Degranulated mast cells were observed in all animals, including controls. The study indicates that the vagal nerve, in contrast to the sympathetic nerves, is involved in the mechanisms causing the leakage of fluid into the middle ear cavity, when cold air is blown into the external auditory canal.
Middle ear effusion induced by various inflammatory mediators and neuropeptides. An experimental study in the rat.
Vascular leakage in the middle ear cavity was studied after i.v. administration of various substances in rats and determined by the Evans blue technique. Bradykinin, histamine, serotonin, acetylcholine, substance P (SP) and vasoactive intestinal polypeptide (VIP) resulted in extravasation of Evans blue. In the case of bradykinin and histamine, the leakage was dose dependent. Calcitonin gene-related peptide (CGRP) did not affect vessel permeability. In other experiments the effect of histamine antagonists was tested on production of middle ear effusion, caused by blowing air at 14 degrees C into the external auditory canal (EAC). The increase in vessel permeability in this otitis media model was inhibited by the H2-receptor antagonist cimetidine, at doses 0.1 and 1.0 mg/ml. Diphenhydramine, an H1-receptor antagonist, arrested only partly middle ear fluid accumulation. Our study demonstrated that various inflammatory mediators and neuropeptides are capable of inducing vascular leakage in the middle ear cavity. It was also concluded that H2-receptors are involved in the regulation of middle ear vascular permeability.