Biomedical subjects

S Hellström

Publications and source records attributed to S Hellström.

At least 91 records · Page 5Linked to original sources

PubMed1991

A comparison of hyaluronan and fibronectin in the healing of tympanic membrane perforations.

Fibronectin and 1% hyaluronan, two extracellular matrix components, were applied to tympanic membrane (TM) perforations, using the laboratory rat as an animal model. The perforations occupied the upper, posterior quadrant of the TM. Saline-treated and untreated perforations of equal size served as controls. Fifty percent of the perforations treated daily with hyaluronan healed prior to the first closures of the other groups. The use of fibronectin did not enhance the healing rate. The hyaluronan-treated perforations were covered initially by a sheet of keratin and hyaluronan containing abundant inflammatory cells. Within this keratin-hyaluronan cover, hyperplastic stratified keratinizing epithelium advanced and bridged the gap of the perforation ahead of the approaching connective tissue. These findings indicate that exogenously applied hyaluronan could be valuable in the clinical situation and should be tried to improve the healing of TM perforations.

Animals↗

PubMed1991

Localization of hyaluronan in various muscular tissues. A morphological study in the rat.

The histochemical distribution of hyaluronan (hyaluronic acid, HYA) was analysed in various types of muscles in the rat by use of a hyaluronan-binding protein (HABP) and the avidin-biotin/peroxidase complex staining procedure. Microwave-aided fixation was used to retain the extracellular location of the glycosaminoglycan. In skeletal muscles, HYA was detected in the connective tissue sheath surrounding the muscles (epimysium), in the septa subdividing the muscle fibre bundles (perimysium) and in the connective tissue surrounding each muscle fibre (endomysium). HYA was heterogeneously distributed in all striated muscles. In skeletal muscles with small fibre dimensions (e.g., the lateral rectus muscle of the eye and the middle ear muscles), HYA was predominantly accumulated around the individual muscle fibres. Perivascular and perineural connective tissue formations were distinctly HYA-positive. In cardiac muscles, HYA was randomly distributed around the branching and interconnecting muscle fibres. In comparison, smooth muscle tissue was devoid of HYA.

Animals↗

PubMed1991

Transection of carotid sinus nerve inhibits the turnover of dopamine and norepinephrine in long-term hypoxic carotid bodies: a biochemical and morphometric study.

To assess the efferent influence of the carotid sinus nerve on the catecholamine function and the vascularity in long-term hypoxic carotid bodies, rats were exposed to hypoxia (10% O2 in nitrogen for 1 and 3 weeks) after unilateral transection of the sinus nerve. In the intact carotid bodies, long-term hypoxia elicited several biochemical and morphological alterations: increased turnover of dopamine and norepinephrine, increased volume density of blood vessels, decreased volume density of glomic tissue. Transection of the sinus nerve reduced but did not abolish the increase in turnover of dopamine and norepinephrine evoked by hypoxia without preventing the structural alterations. Immunocytochemical studies revealed the presence of nerve fibres exhibiting neuropeptide Y-like immunoreactivity which persisted after the excision of the carotid sinus nerve. Nerve fibres showing substance P-like immunoreactivity were found in the intact carotid bodies but not in the carotid bodies deprived of sinus nerve. It is concluded that the sinus nerve exerts a stimulatory efferent control on the synthesis and release of dopamine and norepinephrine in rat carotid body during long-term hypoxia, but no appreciable vasodilatory influence on the glomic vasculature. A possible role of substance P contained in the endings of the carotid sinus nerve is discussed.

Animals↗

PubMed1991

Hyaluronan in human skeletal muscle of lower extremity: concentration, distribution, and effect of exercise.

The concentration and localization of hyaluronan (HYA) were determined in biopsy specimens from resting human quadriceps femoris and anterior tibial muscles. The influence of physical exercise on HYA concentrations in the quadriceps femoris muscle and in blood was also evaluated. A sensitive radioassay was used for the quantification of HYA. The distribution of the glycosaminoglycan was demonstrated using a histochemical method that involved microwave-aided fixation and an HYA-binding protein. At rest, the muscle HYA concentration was 34.9 +/- 23.6 (SD) micrograms/g muscle wet wt with a large interindividual variation. Exercise had no significant effect on the muscle HYA concentration. The serum HYA concentration increased from 35.9 +/- 22.7 to 53.4 +/- 57.1 micrograms/l during exercise, but 30 min after the exercise the HYA concentration was significantly lower (19.1 +/- 6.3 micrograms/l) than the initial preexercise value. In resting skeletal muscles of the lower extremity, HYA was heterogeneously distributed in the perimysium and endomysium. Perivascular and perineural connective tissues were distinctly HYA positive.

Adult↗

PubMed1991

Tympanic-membrane structure--new views. A comparative study.

In recent years, the rat has attracted increasing interest as an experimental animal in otological research. In the present study, the structure of the rat tympanic membrane (TM) is compared with that of a traditional experimental animal, the guinea pig, and with the human TM. The normal guinea pig TM consists mainly of a single layer of coarse fiber bundles, in contrast to the more solid layers of radial and circular fibers in man and rat. The investigation reveals similar architectural features in the rat and human TM, whereas the guinea pig TM differs structurally.

Aged↗

PubMed1991

Hyaluronan applied to lesioned round window membrane is free from cochlear ototoxicity.

Hyaluronan (HYA) in 1% solution was instilled into the round window (RW) niche of rats (n = 6) prior to perforating the round window membrane (RWM). Cochlear functioning and structure were then monitored by recording auditory brainstem responses (ABRs) at 2-31.5 kHz and by scanning electron microscopy. Perforation of the RWM alone (n = 6) resulted in immediate loss of ABR thresholds between 6 and 31.5 kHz in 2 of 6 animals. Similar results were obtained after instilling HYA into the RW niche and subsequent RWM perforation (n = 6). After 2 months, ABR thresholds were recorded at all frequencies in the HYA-treated animals, whereas in 2 of the controls no ABR thresholds could be elicited at 20 and 31.5 kHz. However, in both treatment groups the mean ABR thresholds and mean latencies for wave II at the ABR threshold returned to the pre-surgical (normal) range after 2 months. With respect to the cochlear morphology the results in both treatment groups were also alike including minor structural changes in hair cell stereociliae but no loss of hair cells. It is concluded that HYA, when instilled into the middle ear with the inner ear opened, is free from cochlear otoxicity.

Animals↗

PubMed1991

Decalcification by perfusion. A new method for rapid softening of temporal bones.

We describe a new technique, decalcification by perfusion, for the softening of bony tissue. The blood circulatory system was perfused in 16 rats via a cannula through the left heart ventricle with a fixative followed by New Decalc (an acidic demineralizer) for 30-240 minutes. Perfusion decalcification for 120 minutes softened all heads and middle ear specimens could be easily sampled and prepared for studies by both light and electron microscope. For comparison, a conventional immersion technique required 72 hours of decalcification to accomplish softening. The perfusion technique considerably reduced the time needed to decalcify the tissue and preserved the morphology better than did the immersion procedure.

Animals↗

PubMed1991

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.

Humans↗

PubMed1990

Sequential analysis of serum proteins in middle ear effusions. A study in rats with experimentally induced serous and purulent otitis media.

Two otomicroscopically well-defined types of otitis media (OM)--one culture-negative serous (SOM) and the other purulent (POM)--were induced in rats by mechanically obstructing the eustachian tube or by splitting the soft palate. Samples of middle ear effusions (MEE) produced and sera were characterized electrophoretically and immunochemically at 1, 2, 3, 4 and 6 weeks after inducing middle ear fluid. The levels of albumin, transferrin, IgG, IgG1, IgG2, IgM, IgA, and secretory IgA (S-IgA) were determined. All proteins increased 3- to 10-fold in the MEE of the SOM group, whereas the concentrations in the POM group were low. Concentrations of some of the MEE proteins were seen to increase during the course of SOM, while concentrations in the POM group appeared to diminish. The protein content of the MEE in SOM and POM changed dynamically during the observation period. These alterations differed between the two types of OM, reflecting the differing mechanisms that produce the MEE content. These findings indicate that sequential characterization of effusion material in animal OM models may elicit information which might allow staging of this complex disease clinically.

Albumins↗

PubMed1990

Electrophysiological effects of the clinically used local anesthetics lidocaine, lidocaine-prilocaine and phenol on the rat's inner ear.

Local anesthetics, even if applied to the outer ear canal, may still enter the middle ear, running the risk of penetrating the round window. To elucidate the effect of certain topical anesthetics on the inner ear, the round window niche in the laboratory rat's middle ear was exposed separately to lidocaine, lidocaine-prilocaine and phenol. Auditory brain-stem responses (ABR) were recorded at 2, 4, 6, 8, 12, 16, 20, and 31.5 kHz before the application, and 24 h, 3 weeks, 2 months and 6 months after exposure. After terminating the 6-month ABR measurements, the animal were sacrificed and the temporal bones fixed and decalcified for light microscopic analysis. All three drugs affected the ABR thresholds and the cochlear morphology with a pattern characteristic for each drug. At 24 h, all three substances caused severe impairment of ABR thresholds, followed by a period of restitution lasting up to 2 months. Even 6 months after exposure, the ABR thresholds at and above 12 kHz were impaired, as compared with the pretreatment level, for all substances tested. In the lower frequencies the original ABR threshold was reached in the order: (1) lidocaine, (2) lidocaine-prilocaine, (3) phenol. The cochlear structures were unaffected by lidocaine, whereas lidocaine-prilocaine and phenol caused morphological damage which was most pronounced after exposure to phenol. The heterogeneity of the changes in the ABR thresholds suggests differences in the mechanism of action of each type of local anesthetic investigated. The effects following lidocaine were transient. However, clinicians must be aware of the ototoxic potential of both lidocaine and phenol.

Anesthetics, Local↗

PubMed1990

An improved technique for hyaluronan histochemistry using microwave irradiation.

A hyaluronan binding protein (HABP), extracted from cartilage, was biotin-labelled and used for histochemical localization of hyaluronan (HA) in tissue sections. Various tissues were fixed for a mixture of formaldehyde and glutaraldehyde during microwave irradiation. The microwave oven when set at 700 W and 45 degrees C yielded an intense and specific staining of HA. Under these conditions the relative proportion of the two aldehydes did not influence the staining intensity. Aldehyde fixation during microwave irradiation for HA histochemistry, (1) save time, (2) eliminates the use of cetylpyridinium chloride (CPC), and (3) improves the reproducibility.

Adrenal Glands↗

PubMed1990

Hyaluronan reflects the pre-fibrotic inflammation in irradiated rat lung: concomitant analysis of parenchymal tissues and bronchoalveolar lavage.

The pathogenesis of pulmonary fibrosis is a complicated chain of interactions between cells and molecules. During recent years bronchoalveolar lavage (BAL) in patients with various interstitial lung disorders has increased our knowledge of the fibrosis process and focused on new interesting interactions. Here we present an animal model which makes it possible to apply both morphological and immunohistochemical tissue staining to perform bronchoalveolar lavage in the same animal. Irradiation is an established method for experimentally evoking lung fibrosis in animals. Rats received irradiation (30 Gy) to the lower parts of both lungs. Bronchoalveolar lavage was performed in the right lung. The biochemical determination of lavage concentration of hyaluronan (HA) and cellular differential counts were compared with interstitial morphology. Animals were sacrificed and analysed 2, 4, 6, 8 and 10 weeks after irradiation. After 6 weeks a massive increase in connective tissue mast cells was seen in the peribronchial and alveolar-interstitial tissue. This mastocytosis was closely related to a marked increase in HA. It became obvious that, in this model, cellular analysis of BAL fluid did not correctly reflect the cellular changes in the lung interstitium. While BAL revealed a pronounced increase of neutrophils with no--or only very few--mast cells, a concomitant increase in mononuclear cells and mast cells was seen in the lung interstitium. In contrast an increase in HA in BAL correlated well with an increase in HA-deposition in the lung interstitium, indicating that measurement of a non-cellular component, such as HA, may better reflect the tissue inflammation.

Animals↗

PubMed1990

Secretory effects of 5-hydroxytryptamine following neonatal sympathectomy in rat parotid gland.

Unilateral sympathetic denervation of rat parotid glands was performed within 4 h after birth. Nine weeks later the glands were used for in-vitro studies of amylase secretion, and 86Rb+ was used as a marker for potassium efflux. The non-denervated contralateral glands served as controls. The tissue concentrations of 5-hydroxytryptamine and its metabolite 5-hydroxyindole acetic acid were also measured. 5-Hydroxytryptamine caused a significant dose-dependent increase in amylase secretion, which was inhibited by methysergide. There was no difference between controls and denervated glands. 5-Hydroxytryptamine was without effect on potassium efflux from either denervated or control glands. The sympathectomy caused increased levels of 5-hydroxytryptamine and 5-hydroxyindole acetic acid as compared with contralateral controls. The results suggest that 5-hydroxytryptamine influences the two main secretory processes in rat parotid gland differently. A significant amylase discharge was seen following 5-hydroxytryptamine stimulation, whereas no effect was seen on 86Rb+ efflux. Although it is also proposed that there are no 5-hydroxytryptamine-associated nerves in the superior cervical ganglion innervating parotid tissue, it seems that there is a complex connection between the sympathetic pathway and the serotoninergic system.

Amylases↗

PubMed1990

Development of the arterial chemoreflex and turnover of carotid body catecholamines in the newborn rat.

1. The peripheral, arterial chemoreceptors in the carotid body are active and responsive in the fetus. At birth, when oxygenation increases, the chemoreceptors are silenced. Over the next few days the sensitivity is reset toward the adult level and the chemoreceptors influence breathing during normal conditions. In order to investigate the underlying mechanisms of this resetting we examined the strength of the chemoreflex in newborn rats and correlated this to the contents of dopamine and noradrenaline in the carotid bodies of the newborn pups and near-term fetuses. Furthermore, turnover rates of dopamine and noradrenaline were determined in newborn rats up to 1 week of age by analysis of catecholamine decreases after inhibition of synthesis with alpha-methyl-p-tyrosine. 2. Chemoreceptor influence was assessed by the method of 'physiological chemodenervation' with hyperoxia of 15-20 s duration in unanaesthetized rat pups. Relative changes in ventilation elicited by hyperoxia were determined by body plethysmography. We found no change in ventilation on the day of birth either in vaginally born rats or in near-term pups delivered by Caesarean section. After 1 day there was a significant decrease in ventilation of -19.4 +/- 2.3% (mean +/- S.E.M.) and at 7 days of age the decrease was -28.8 +/- 2.2%, suggesting an increasing influence from the peripheral chemoreceptors. 3. The contents of dopamine and noradrenaline were measured by high-performance liquid chromatography. Dopamine increased from 3.7 +/- 0.4 pmol (pair of carotid bodies)-1 in the fetus to a peak of 15.9 +/- 2.6, 6-12 h after birth followed by a decline to 7.1 +/- 0.7 at 7 days of age. Noradrenaline levels increased from 1.3 +/- 0.3 in the fetus to 9.6 +/- 1.1 pmol (pair of carotid bodies)-1 after 4 days. The turnover rate of dopamine decreased from 4.4 pmol (pair of carotid bodies)-1 h-1 0-6 h after birth to 1.0 at 6-12 h of age. The turnover rate of noradrenaline also decreased over the first hours following delivery. 4. Since dopamine is an inhibitory neuromodulator in this system, we suggest that the increase in sensitivity seen after the first day of life is, at least in part, due to a decrease in the release of dopamine and thus a removal of an inhibitory mechanism.

Animals↗

PubMed1990

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.

Animals↗

PubMed1990

A mast cell secretagogue, compound 48/80, prevents the accumulation of hyaluronan in lung tissue injured by ionizing irradiation.

Irradiation with a single dose of 30 Grey on the basal regions of the lungs of Sprague-Dawley rats induced a peribronchial and alveolar inflammation. Infiltration of mast cells in the edematous alveolar interstitial tissue and also in the peribronchial tissue were characteristic features of the lesion. The appearance of mast cells was already seen 4 wk after irradiation and by weeks 6 to 8 there was a heavy infiltration. The staining properties suggested that they were connective tissue-type mast cells. The infiltration of mast cells was paralleled by an accumulation of hyaluronan (hyaluronic acid) in the alveolar interstitial tissue 6 and 8 wk after irradiation. The recovery of hyaluronan (HA) during bronchoalveolar lavage (BAL) of the lungs also increased at this time. Treatment with a mast cell secretagogue, compound 48/80, induced a distinct reduction of granulated mast cells in the alveolar tissue. Regular treatment with compound 48/80 from the time of irradiation considerably reduced the HA recovery during BAL and the HA accumulation in the interstitial tissue but did not affect the interstitial infiltration of mononuclear cells and polymorphonuclear leukocytes. By contrast, an accumulation of HA in the alveolar interstitial space was induced when compound 48/80 was given not until mast cell infiltration of the lung had started. The effects of compound 48/80 indicate that the connective tissue response after lung irradiation is dependent on whether or not mast cell degranulation is induced before or after the mast cell infiltration of the alveolar tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Hydrocortisone delay of tissue repair of experimental tympanic membrane perforations.

The effects of topically applied hydrocortisone on experimental tympanic membrane (TM) perforations in rats were evaluated by otomicroscopy and light microscopy. Standardized TM perforations, occupying the whole upper rear quadrant, were performed, and a 2% hydrocortisone suspension (CORT) was applied once daily for 10 consecutive days. Application of CORT caused a delayed healing pattern, and even at 1 month only 2 of 12 perforations had healed. The keratinizing squamous epithelial cells of the TM appeared hypertrophic, whereas hyperplasia, characterizing a nontreated healing TM perforation, was less prominent. The connective tissue layer of the CORT-treated TM was invaded by abundant inflammatory cells, mainly polymorphonuclear leukocytes. Also, when applied to an intact TM, CORT caused hypertrophy of the epidermal cells and an inflammatory reaction within the TM.

Animals↗

PubMed1990

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.

Acetylcholine↗