[Drug-induced rhinitis--significant adverse effect].
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Humans↗
Biomedical subjects
S K Steinsvåg
Publications and source records attributed to S K Steinsvåg.
Effects of benzalkonium chloride on innate immunity physiology of the human nasal mucosa in vivo.
OBJECTIVE: Benzalkonium chloride (BC) is a preservative commonly used in nasal decongestant sprays. It has been suggested that BC may be harmful to the nasal mucosa. The present study, involving healthy volunteers, examines effects of BC on nasal mucosal end-organ functions. METHODS: Isotonic saline and BC (0.1 mg/mL) were administered acutely to the nasal mucosa using a nasal pool device. Nasal symptoms were determined. Nasal lavage fluid levels of alpha2-macroglobulin and fucose were measured as indices of plasma exudation and glandular secretion, respectively. In addition, BC (0.1 mg/mL) was given as single actuations of 100 microL per nasal cavity three times daily for 10 days. The ability of histamine (0.4 mg/mL) to evoke nasal symptoms and plasma exudation responses was determined before and after the repeated BC administration series. RESULTS: BC produced immediate nasal smart or pain (P < .05), but tolerance to this response developed by repeated administrations. BC increased nasal mucosal output of fucose (P < .05), whereas nasal lavage fluid levels of alpha2-macroglobulin were unaffected. Histamine produced significant symptoms and mucosal exudation of alpha2-macroglobulin (P values < .01), equally before and after the 10 days of BC exposure. CONCLUSIONS: BC in dosages commonly used as preservative in nasal decongestant sprays produced short-term glandular secretion and nasal smart or pain. However, 10 days' frequent exposure to BC was not associated with untoward symptomatic effects, nor was a sensitive mucosal variable such as histamine-induced exudative responsiveness affected by this repeated exposure 1 BC.
Administration, Topical↗
Benzalkonium chloride interferes with energy production, secretion and morphology in human blood platelets.
Benzalkonium chloride (BC) is a bactericidal compound used as a topical antiseptic and as a preservative in various products for local treatment, e.g., eye and nose drops. BC is toxic to human cells, including those of the respiratory mucosa. Few studies have, however, focused on what cellular functions BC interferes with. The effects of BC were studied on washed human blood platelets in vitro . Cellular energy production as well as secretion were studied. Incubation of platelets with BC resulted in rapid swelling and toxic morphological changes. After incubation with BC oxidation of [1-14C] palmitate was inhibited, and both lactate dehydrogenase and endogenous serotonin were spontaneously released. Thrombin-induced secretion of serotonin was strongly reduced after BC exposure. Histological changes with increased size, spherical form, decreased numbers of pseudopodia, loss of an intact continuous tubulus system and reduced number of granules were found by scanning and transmission electron microscopy. It is concluded that the toxic effects of BC are because of interference with membrane function and energy production.
Journal Article↗
[Allergic rhinitis. Epidemiology, pathogenesis, investigation and treatment].
The incidence of allergic rhinitis is increasing, as is our knowledge of its pathogenesis, epidemiologic factors and optimal therapeutic principles. This paper discusses various allergy promoting factors and gives a brief update on current immunological concepts of allergy. Recent achievements in the pathogenesis of allergic rhinitis are discussed, as well as pharmacological and non-pharmacological treatment.
Global Health↗
The effects of topical nasal steroids on rat respiratory mucosa in vivo, with special reference to benzalkonium chloride.
Fifty rats were treated with topical nasal steroids with and without the preservative benzalkonium chloride in their right nostril twice daily for 21 days, while the left nostrils were exposed to 0.9% NaCl. By cutting the noses serially in frontal sections, the structure of the mucosal lining of all parts of the nose could be investigated. Areas with squamous cell metaplasia were observed in all nostrils exposed to topical steroids containing benzalkonium chloride. Such alterations were not observed in any nasal cavities exposed to the topical nasal steroid without the preservative or to 0.9% NaCl. In conclusion, benzalkonium chloride appears to be potentially toxic to the mucosa in vivo.
Administration, Topical↗
[Chronic non-allergic rhinitis. Etiology, diagnosis and treatment].
Chronic rhinitis can be defined as an inflammation of the nasal mucosa lasting for more than three months. The condition may be due to allergy or infection, or to a number of non-allergic and non-infectious causes, such as trauma, hormonal imbalance, toxic influence or locally applied drugs. The etiology, diagnostic procedures and treatment of non-allergic chronic rhinitis are discussed.
Chronic Disease↗
Nonadhesive stationary organ culture of human bronchial mucosa.
The supply of fresh bronchial tissue from human donors for in vitro culture is limited. Routine fiberoptic bronchoscopy offers a safe and easy procedure for obtaining minor biopsies and we wanted to see if the material provided could be used for organ culture by using a simple liquid overlay technique. Bronchial biopsies were cut into fragments 400-500 microns and kept immersed in a standard serum-supplemented medium for 40 days. An agar base prevented adhesion of the tissue. By light and electron microscopy it was shown that the tissue fragments had a differentiated epithelium at their surface throughout the culture period. An outgrowth of epithelial cells on the scaffold of the exposed stroma, covering the surface of the whole fragment, occurred within the first 5 days of culture. This epithelium was partly ciliated, 2-4 cell layers thick with squamous and cuboidal cells and expressed epithelial markers (cytokeratin and Ber-Ep4). The amount of cilia increased during the first 15 days of culture. The epithelium rested on a neosynthesized basement membrane as visualized by electron microscopy and immunohistochemistry with antibodies directed against collagen IV, laminin, and fibronectin. The central stroma consisted of loose connective tissue with fibroblasts. This simple tissue culture model combines maintenance and neoformation of bronchial epithelium on top of a living natural substrate, thus enabling direct biological studies on clinical biopsy material under perfectly viable conditions.
Adult↗
Effects of topical nasal steroids on human respiratory mucosa and human granulocytes in vitro.
Human respiratory mucosa and human granulocytes were exposed to topical nasal steroids in vitro. The preparations containing benzalkonium chloride and benzalkonium chloride alone destroyed the mucosa within 10 days. The same preparations also inhibited human neutrophil actin polymerization, degranulation and oxidative burst in vitro in a time and concentration dependent manner. Preparations without benzalkonium chloride, as well as the steroid compounds themselves, did not have these effects. It is concluded that benzalkonium chloride has toxic effects on human respiratory mucosa and human neutrophils in vitro.
Adenoids↗
The effect of a benzalkonium chloride-containing nasal spray on human respiratory mucosa in vitro as a function of concentration and time of action.
Human respiratory mucosa was exposed to oxymetazoline nasal spray in varying concentrations and for varying periods of time in vitro. The drug destroyed the tissue in a concentration- and time-dependent manner. In the experiments with various concentrations of the spray, some tissue fragments retained their viability throughout the experiment. This number increased parallel to a decrease in concentrations of the test substance. All the tissue fragments exposed to undiluted nose spray underwent severe destructive alterations during the exposure period. These alterations appeared first and were most extensive in those exposed for the longest periods of time. It has previously been demonstrated that the toxic effect of oxymetazoline nasal spray in vitro is probably due to the preservative benzalkonium chloride. The apparent lack of consistency between the toxic effects of benzalkonium chloride in vitro and in vivo is discussed, with special reference to protective systems absent in vitro but present in vivo.
Adenoids↗
The effect of decongestive nosedrops on human respiratory mucosa in vitro.
The aim of this study was to investigate the morphological effects of decongestive drops and sprays on human respiratory mucosa in vitro. Precultured fragments of adenoid tissue in a specially designed tissue culture system were exposed to decongestive preparations for 10 minutes once a day for 10 days. Tissue exposed to preparations preserved with benzalkonium chloride and tissue exposed to benzalkonium chloride alone underwent severe morphological alterations. Unpreserved decongestive substances did not have this effect. Benzalkonium chloride is a well-documented toxic substance in several respects. Supported by previous studies, it may seem unfortunate to use it as an additive in decongestive preparations.
Adenoids↗
Inhibition of human neutrophil actin polymerization, phagocytosis and oxidative burst by components of decongestive nosedrops.
Human neutrophil functions have been examined after exposure of leukocytes to components of decongestive nosedrops in vitro. Both the vasoactive components oxymethazoline chloride and xylomethazoline chloride, as well as the preservative benzalkonium chloride, showed a concentration- and time-dependent deleterious effect on neutrophil actin polymerization, phagocytosis and oxidative burst. The most toxic of the drug components was benzalkonium chloride, which in the commercial nosedrops tested was present in concentrations about 20 times higher than that compatible with intact neutrophil functions. These findings suggest possible inhibition of mucosal neutrophil activity following exposure to nosedrops in vivo, and support earlier reports that have questioned the use of preservatives in decongestive nosedrops.
Actins↗
Human respiratory mucosa in a nonadhesive stationary organ culture system.
Fragments of human adenoid tissue were transferred to a nonadhesive, stationary organ culture system. The culture period was 40 days. In culture, beating cilia could be observed at the surface of the fragments. Light microscopy, scanning electron microscopy, and transmission electron microscopy showed that the tissue fragments were covered by a multilayered, pseudostratified, ciliated epithelium. Beneath the epithelium was a basement membrane. At the start of the culture period, the central parts of the fragments were dominated by lymphocytes. These lymphocytes gradually disappeared and were replaced by a collagen-containing stroma with scattered fibroblasts. The tissue fragments can be used as an organ culture model for normal respiratory mucosa.
Adenoids↗
[Biofeedback. Theory and clinical value].
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Biofeedback, Psychology↗
Ultrastructural investigation of fetal rat brain hemisphere tissue in nonadherent stationary organ culture.
Fetal rat brain fragments grown in nonadherent stationary organ culture for 50 days have been investigated ultrastructurally. Synaptogenesis and myelin formation occurred at the same time as the corresponding time-dependent events in the developing brain in vivo. Intermediate junctions were observed between cellular processes lining a central cavity in the fragments and later associated with astrocytes at the surface. Gap junctions and tight junctions were also present. In some fragments cilia were observed in the central cavity. Subependymal basement membrane labyrinths were observed in all fragments after 10 days in culture. The ultrastructural characteristics and the tissue-like structure in general were preserved for at least 50 days in this tissue culture system. The brain fragments may therefore be a valuable supplement to existing culture methods for nervous tissue.
Animals↗
Reaggregation of fetal rat brain cells in a stationary culture system. I: Methodology and cell identification.
A stationary tissue culture system for reaggregation cultures of rat brain cells is described. Aggregates were formed by placing cells at high concentration in liquid overlay cultures on a nonadherent nutrient agar surface. No physical stress in the form of rotation or shaking was applied to the aggregating cell population. Transmission electron microscopy and immunohistochemistry showed that the cells developed from homogeneously dispersed, immature cells in Day 4 aggregates, to mature astrocytes, oligodendrocytes, and neurons in Day 20 aggregates. Twenty days older aggregates had a tightly packed neuropil which was most prominent in a cell-sparse outer layer of the aggregates. When the aggregates were allowed to adhere to a substrate, both glial fibrillary acidic protein (GFAP) positive and negative cells were observed migrating out from the aggregates. Cells giving a positive reaction for neuron specific enolase (NSE) were also present. This reaggregation procedure, with transfer of selected brain cell aggregates into agar-coated multiwells is an alternative three-dimensional culture system which can be potentially useful in the study of morphogenesis and cell interactions in the nervous system.
Animals↗
Fetal rat brain hemisphere tissue in nonadherent stationary organ culture.
A simple organ culture system for brain tissue is described. Fragments of fetal rat brain hemisphere tissue are explanted to multiwell dishes base-coated with semisolid agar. In this system nonadherent organ culture can be performed for at least 50 days. Cell migration, biochemical and morphological differentiation and the formation of a layered architecture seem to mimic some of the phenomena occurring in the developing rat brain in vivo. The fragments may therefore be a useful organ culture model for nervous tissue.
Animals↗
Interaction between rat glioma cells and normal rat brain tissue in organ culture.
A system for coculture between normal rat brain fragments and multicellular spheroids of rat glioma cells is described. The tumor cells were derived from fetal BD IX rats treated transplacentally with the carcinogen N-ethyl-N-nitrosourea (CAS: 759-73-9). Brain fragments were obtained from fetal BD IX rats and precultured for 20 days before confrontation with multicellular tumor spheroids. The cocultures were grown in nonadherent stationary organ culture for 30 days. Due to morphologic similarities between normal brain cells and tumor cells, the tumor cells were labeled with tritiated thymidine, which made them easily recognizable in autoradiographs. The two structures adhered to each other, and glioma cells progressively invaded and replaced the normal brain tissue. Invasion and replacement are characteristic features of brain tumors in vivo. Therefore, this organotypic and syngeneic model may be useful for investigation of these phenomena outside the body.
Animals↗
Interaction between glioma cells and normal brain tissue in organ culture studied by scanning electron microscopy.
Scanning electron microscopy was employed to investigate cocultures between normal rat brain fragments and spheroids consisting of rat glioma cells. Lamellipodia were seen to arise from tumor cells at the border between the two structures and touch the surface of the fragment. Cytoplasmic extensions from malignant cells appeared to penetrate into the brain fragment. Leading lamellae were extended from the tumor cells as they migrated along the normal surface and gradually covered the fragment. Tumor cells formed broad foot-plates against the normal surface. No alterations of the brain fragment were observed ahead of the tumor cells. Thus there were specific changes of the surface microarchitecture of the malignant cells, but not of the normal brain tissue.
Animals↗