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Biomedical subjects

P Stierna

Publications and source records attributed to P Stierna.

At least 55 records · Page 3Linked to original sources

Effect of glucocorticosteroid treatment on glucocorticoid receptor expression in human adipocytes.

The influence of glucocorticoid excess on expression of the glucocorticoid receptor (GR) and beta-adrenoceptor subtype was studied in isolated adipocytes obtained by sc fat biopsies from 17 healthy individuals. The biopsies were taken before and after 7 days of treatment with 25 mg prednisolone, given orally. GR and beta 1- and beta 2-adrenoceptor messenger ribonucleic acid (mRNA) levels were measured with a solution hybridization assay, and the number of beta 1- and beta 2-adrenoceptor binding sites was determined in radioligand binding experiments. GR protein levels were determined by Western blot analysis using an anti-GR antibody. Both GR protein and GR mRNA levels decreased significantly (P < 0.05) by about 50% after treatment, whereas no significant changes were demonstrated in either beta 1- or beta 2-adrenoceptor mRNA levels. The number of beta 2-adrenoceptor-binding sites, however, increased by 70% after treatment (P < 0.05), whereas the number of beta 1-adrenoceptor binding sites was not affected. The affinity of each receptor subtype was not significantly altered by steroid treatment. In conclusion, an in vivo glucocorticoid excess decreases GR mRNA as well as GR protein levels and selectively increases beta 2-adrenoceptor density in sc fat cells of healthy individuals. This indicates that glucocorticoids modulate human adipose metabolism by altering the expression of regulatory proteins at various mRNA and post-mRNA levels.

Adipocytes↗

Effects of intranasal glucocorticoids on endogenous glucocorticoid peripheral and central function.

Glucocorticoids are among the most potent antiinflammatory agents that can be used in the treatment of rhinitis. Their mechanisms of action are multiple and complex and a number of reports describe significant systemic effects of locally administered glucocorticoids. In order to evaluate the short-term systemic effects of intranasally administered glucocorticoids, 14 normal healthy subjects were treated with two doses of either budesonide (BUD) or fluticasone propionate (FP) for 2 weeks. Before treatment, at regular intervals during the treatment, 1 week and finally 6 weeks after termination of treatment, the effects on glucocorticoid receptor (GR) and methallothionein (MTIIa) mRNA expression levels were examined in peripheral lymphocytes using a solution hybridization assay. Serum cortisol, osteocalcin and urinary cortisol levels were also determined. An insulin tolerance test (ITT) was performed at the end of the second week of treatment and at the end of the 6-week washout period with no statistically significant change in cortisol response. In peripheral lymphocytes, GR mRNA levels were significantly down-regulated. MTIIa mRNA levels increased significantly. Serum osteocalcin decreased significantly during treatment with both BUD and FP. Serum cortisol decreased after 1 week of treatment whereas urinary cortisol was not affected until the second week of treatment. In conclusion, intranasal glucocorticoids at clinically recommended doses have not only significant systemic effects on adrenal function, but also have an effect on specific gene expression in peripheral lymphocytes. These effects are receptor-dependent, reversible, and according to serum and urinary cortisol levels and ITT, leave the hypothalamic-pituitary-adrenal function intact. Finally, these short-term systemic effects were not associated with any of the noticeable side-effects usually observed during long-term treatment with glucocorticoids.

Administration, Intranasal↗

Basic experimental studies of ostial patency and local metabolic environment of the maxillary sinus.

Experimental studies of human maxillary sinus gas exchange show that there is a balance between inflow of air through the maxillary ostium and local consumption as long as the functional size of the ostium is at least 5 mm2. Maxillary sinus mucosal blood flow is 30-40 ml/100 g tissue per minute, as measured in plethysmographic studies. This blood flow can bind and transport only half of the absorbed oxygen, the rest is consumed. Experimental histo- and biochemical studies of sinusitis show anaerobic mucosal metabolism with shortage of energy supply due to inadequate oxygen supply. There is no decrease in oxidative enzyme capacity of the mucosal epithelium. Analysis of organic acids in purulent secretion indicates that the high lactate and CO2 concentration found is mainly the result of leucocyte glycolysis with local lactic acidosis. Both ostial occlusion and the initiation of bacterial growth in serous sinusitis may be secondary to an initial inflammatory response, resulting in local tissue pathology and swelling of the ostiomeatal complex, as well as creating the appropriate redox potential for further bacterial growth in the secretions.

Humans↗

Microorganisms and leukocytes in purulent sinusitis: a symbiotic relationship in metabolism.

Since the exchange of gases, as well as metabolites, is greatly impeded in a paranasal sinus empyema, it is not unlikely that certain organic substances be retained and accumulated in purulent secretion. In this study, secretions aspirated from experimentally infected maxillary sinuses of 26 rabbits were analysed biochemically. Quantitatively, by far the most important acid accumulated in secretions was lactic acid. Lactate induces metabolic acidosis and exerts an inhibitory effect on mammalian defense mechanisms. Lactate may also be used as an energy source by certain microorganisms. In spite of its leukocytic origin lactic acid thus promotes the continuation of a bacterial infection. In addition, certain other organic acids of bacterial origin were found, which, in different ways, contribute to the impediment of antimicrobial defense functions.

Animals↗

The inflammatory response of the sinus and nasal mucosa during sinusitis: implications for research and therapy.

Since it is difficult to evaluate the state of an infected sinus mucosa by histopathology, much of the present knowledge of the morphology in sinusitis is based on animal experiments. When experimental sinusitis is induced in the rabbit, the inflammatory response in the nose appears to be more pronounced than that in the maxillary sinus. In the animal model, histological findings include epithelial desquamation, edema, goblet cell hyperplasia and, in severe cases, fibrosis, bone reaction and formation of polyps in the nose and in the antrum. These local pathological findings may persist in the nasal middle meatus and the paranasal sinuses for a considerable time and predispose the mucosa to recurrences of infection. By investigation with recently introduced advanced techniques such as magnetic resonance imaging (MRI), a protracted pathological state in the sinus mucosa can be recorded also in humans for months after an episode of acute sinusitis. Future human and experimental studies of the local inflammatory response and of the cellular pathology over time will yield further guidelines for improved therapy and prevention of acute sinusitis.

Animals↗

The efficacy of oxymetazoline administered with a nasal bellows container and combined with oral phenoxymethyl-penicillin in the treatment of acute maxillary sinusitis.

The efficacy of a new administration form of oxymetazoline, a nasal bellows container, was investigated in two separate studies by means of a combined treatment with phenoxymethyl-penicillin for acute maxillary sinusitis. In the first study (study 1), oxymetazoline administered with a bellows (OXBE) was compared both with a placebo belows (PLBE) as well as with oxymetazoline and placebo administered with a conventional nasal spray (OXSP respective PLSP) in 73 patients. In the second study (study 2), OXBE was compared only with PLBE in 48 patients. Objective evaluation was made by comparing the radiographical improvement in conventional plain sinus X-ray images. A scoring system corresponding to the outcome of antral irrigation was used for evaluating the X-ray pictures. Subjective symptoms; nasal stuffiness and pain, were assessed by registrations on visual analogue scales. Neither with regard to radiographical improvement nor to decrease in subjective symptoms could any significant differences be found between the different treatment modes. Oxymetazoline administered with a nasal bellows thus did not accelerate the rate of healing of acute maxillary sinusitis in these two studies. It is inferred from these results that decongestion of the sinus ostia is not of primary importance for the course of healing of a manifest acute sinusitis.

Acute Disease↗

Lysozyme and lactoferrin in human maxillary sinus mucosa during chronic sinusitis. An immunohistochemical study.

Immunohistochemistry was used to study the localization of lysozyme (LZ) and lactoferrin (LF) in the human sinus mucosa during recurrent and chronic sinusitis. Serous cells of submucosal mixed glands and polymorphonuclear leukocytes both displayed a strongly positive staining reaction to both LZ and LF in the normal mucosa. A positive though weak staining for LZ and LF could also be found occasionally within goblet cells. In the mucosa from patients with recurrent or chronic sinusitis, the staining reaction to LZ appeared to intensify in goblet cells. Furthermore, an increased immunoreactivity of glands vis-à-vis LZ and LF was also noted occasionally. Atypical glands were frequently found in mucosa from patients with chronic sinusitis. The epithelium of these latter glands often showed an intense staining reaction to LF, but a rather weak reaction to LZ. The results of the present study suggest that the observed increase in LZ and LF secreting activity of goblet cells, epithelial cells and newly formed atypical glands may play a part in the defense mechanism of the sinus mucosa during the course of chronic sinusitis.

Adult↗

Airway obstruction. New modalities in treatment.

The key to successful therapy of airway obstruction is always to first secure the airway. The primary care physician needs to understand the airway anatomy and the causes of airway obstruction. As a team, the primary care physician and the otolaryngologist can evaluate and treat these disorders.

Airway Obstruction↗

Regeneration of maxillary sinus mucosa following surgical removal. Experimental study in rabbits.

A rapid regeneration of the epithelium takes place in the maxillary sinus in rabbits after experimental operative removal of the mucosa. Two weeks postoperatively the previously denuded areas have reepithelialized. The subepithelial glands, however, do not seem to regenerate. The normal sinus mucosa contains numerous serous glands in the lamina propria, but in the regenerated mucosa these glands are replaced by dense connective tissue. Atypical glands and polyp formations are sometimes encountered, but goblet cells are sparse. Furthermore, the sinus cavity on the operated side is reduced in size compared with the nonoperated side because of fibrosis and periosteal reactions including bone degradation and neogenesis. This study indicates that although the mucosa is reepithelialized within 2 weeks, the regeneration of the lamina propria is incomplete, and reactive cellular processes such as bone remodeling, fibroblast proliferation, and formation of polyps and "atypical glands" are characteristic of regenerating mucosa.

Animals↗

Mucosal fine structure in experimental sinusitis.

Rabbit maxillary sinuses were inoculated with Streptococcus pneumoniae and Bacteroides fragilis, and the histologic response in the sinus mucosa was observed over a 12-week period. An increased height of the cylindric cells and hyperplasia of the basal cells were frequent findings irrespective of the pathogen inoculated. The disease was found to influence the character of the secretory product from epithelial secretory cells and to degranulate the subepithelial glands. Ciliary loss was a transitional finding. A reduction in the number of mitochondria, the occurrence of deformed short microvilli, and cytoplasmic blebbing were seen in the cells devoid of normal cilia. It is inferred from this study that pneumococcal sinusitis in rabbits is a self-limiting process, and the mucosal sequelae of the acute infection are persisting goblet cells, slight focal fibrosis, and edema. Inoculation with B fragilis produces a chronic inflammatory process, with infiltration of mononuclear cells, luminal dilatation of the glands exhibiting zymogen granule depletion, and an increased thickness of the whole mucosal layer.

Animals↗

Formation of mucosal polyps in the nasal and maxillary sinus cavities by infection.

Unilateral maxillary sinusitis was experimentally induced in New Zealand White rabbits with Streptococcus pneumoniae serotype 3, Bacteroides fragilis NCTC 9343, and Staphylococcus aureus V8. In another group of rabbits, sinusitis was induced by blocking of the sinus ostium only. Bacteriologic and light microscopic analysis was performed after 5 days to 1 month. Granulation-like polyps developed after deep mucosal inflammatory trauma initiating fibroblast proliferation, angiogenesis, and epithelial migration to cover the polyp. In regions of a more superficial trauma-characterized by epithelial desquamation and fibroblast growth-proliferation and differentiation of basal cells resulted in the formation of microcavities dissecting off edematous polyps. Polyps could be found in all sinusitis groups, irrespective of inducing agent. The cellular events of polyp formation appear to be the result of a continuous inflammatory reaction and are not directly related to the presence of a certain microorganism. Instead, the potential of any microorganism to induce a deep mucosal trauma or epithelial desquamation seems essential for its ability to initiate polyp formation.

Animals↗

Pneumococcal antigens and serum antibody responses in experimentally induced sinusitis.

Maxillary sinusitis was induced in New Zealand White rabbits with Streptococcus pneumoniae serotype 3 and the serum antibody response was recorded by enzyme immunoassay. Activity of the three major immunoglobulin classes, viz. IgG, IgA and IgM, against the type-specific capsular polysaccharide, the cell wall C-polysaccharide as well as its subunit phosphorylcholine was analyzed. A pronounced increase in immunoglobulins reactive to the specific capsular antigen was observed throughout the study period, with the rise being particularly noticeable during the first 2 weeks. An increase in anti-C-polysaccharide antibodies was also evident, but no reaction to phosphorylcholine could be detected. Although the histological findings at 3 and 4 weeks varied in spite of similar serum antibody responses, a correlation appeared to exist between a more rapidly increasing anti-capsular IgG production and the prevalence of a purulent sinus secretion.

Animals↗

Experimental maxillary sinusitis induced by Bacteroides fragilis. A bacteriological and histological study in rabbits.

Experimental anaerobic maxillary sinusitis was induced in New Zealand White rabbits by blocking the ostium and inoculating Bacteroides fragilis, strain NCTC 9343. The animals were examined histologically and bacteriologically after 5 days, and 2, 3 and 4 weeks. All the infected sinuses displayed signs of moderate or severe inflammation throughout the study period. Ciliary damage and desquamation, hyperplasia and metaplasia of the epithelium were characteristic features. Furthermore, heavy leukocyte- and, particularly, round cell-infiltration, fibrosis, periosteal hyperplasia and bone degradation and -formation were also frequently encountered. The secretory cell count in the epithelium increased, including the regeneration of goblet cells. After 4 weeks no obvious recovery could be seen, and the inducing microorganism was re-isolated in the majority of cases. In comparison with experimental pneumococcal sinusitis, the B. fragilis infection exerts a more prolonged and severe inflammation.

Acute Disease↗

Cellular regeneration and recovery of the maxillary sinus mucosa. An experimental study in rabbits.

Unilateral maxillary sinusitis was induced in 30 New Zealand White rabbits with Streptococcus pneumoniae or Bacteroides fragilis. In another group of 15 rabbits without infection, the sinus mucosa was surgically removed in defined areas. In both series, the sinuses were serially sectioned for histological analysis of the cellular regenerative capacity. In maxillary sinusitis induced by Bacteroides fragilis, an inflammatory and also reparative process involving all mucosal layers including the underlying periosteum was seen. The more superficial trauma as found in pneumococcal sinusitis eventually led to restitution ad integrum. Following surgical removal, the denuded sinus-lining was reepithelized by a flattened ciliated epithelium on a lamina propria displaying fibrosis and lacking serous glands. The restoration of the rabbit maxillary sinus mucosa after surgical trauma thus leads to structural abnormalities of the epithelium as well as the lamina propria, and these changes are likely to interfere with the normal function of the sinus mucosa.

Animals↗

Lactic acid isomers and fatty acids in sinus secretion: a longitudinal study of bacterial and leukocyte metabolism in experimental sinusitis.

Concentrations of the two optic isomers of lactate (D- and L-form) as well as glucose, succinate, acetate, butyrate, isovalerate and valerate were examined in purulent sinus secretions. The samples were obtained from rabbit maxillary sinuses, experimentally infected with Streptococcus pneumoniae or Bacteroides fragilis. More soluble acids such as acetate displayed relatively low levels in the secretion, despite a high microbial production. A substantial increase in D-lactate concentration was found in secretions only the first day after induction of pneumococcal sinusitis, and not in bacteroides sinusitis. L-lactate levels were particularly high in secretions of a marked purulent character, and this isomer can be considered as indicator of anaerobic glycolysis in the leukocytes. Less diffusible fatty acids such as butyrate and isovalerate accumulated in the secretion, in spite of a relatively lower production rate, and are thus more reliable indicators of bacterial metabolism.

Animals↗

Practical management of epistaxis.

Epistaxis is a very common presenting symptom of patients seen in the emergency room or the physician's office. An understanding of the nasal anatomy and physiology is important for proper treatment of these patients. New methods of treatment are discussed briefly.

Catheterization↗

Mucosubstance histochemistry of the maxillary sinus mucosa in experimental sinusitis: a model study on rabbits.

The histochemical properties of mucosubstances within the sinus mucosa were examined in rabbits affected with experimental sinusitis, induced either by blocking the maxillary sinus ostium (occlusion group) or in addition by an inoculation of Streptococcus pneumoniae (pneumococcal group). An increase in periodic acid-Schiff positive epithelial secretory cells was found, as well as regeneration of goblet cells in the epithelium from the 2nd week. The goblet cells proved to contain periodate-reactive acid mucins, particularly during the early stages, as well as periodate-unreactive, purely acid mucins which were prevalent throughout the study. Among the alcian blue positive goblet cells, 0-40% (usually 5-20%) contained acid sialomucins, while the rest stained positive for sulphomucins. The submucosal glands and the large lateral nasal and maxillary glands were not histochemically influenced by the induced inflammatory state. No obvious difference in the histochemical staining pattern was seen between the two groups. A comparative microbiological analysis of the groups was also included in the study.

Acute Disease↗

Chronic maxillary sinusitis. Energy metabolism in sinus mucosa and secretion.

The energy metabolism in maxillary sinus mucosa and secretion from 41 patients with, in most cases, recurrent or chronic sinusitis was studied and compared with that in mucosal samples from patients with no previous history of sinus abnormality or infection. In freeze-dried samples, glucose and lactate were measured by enzymatic assays and adenine nucleotides by HPLC. In chronic sinusitis the lactate concentration in the mucosa was increased, probably as a result of increased glycolysis or of impaired diffusion within the mucosa. The lactate concentrations in purulent and non-purulent secretions were 16.3 and 1.1 mmol x kg-1 w.w., respectively. The higher concentration in the purulent secretion was due mainly to leucocyte metabolism. The adenine nucleotide contents in the mucosa were similar in all groups studied. Anaerobic bacteria were isolated only in secretions with a high lactate concentration.

Adenine Nucleotides↗