The effect of kavinton on bronchial tonus in bronchial asthma patients

Intravenous cavinton given in a dose of 10 mg for 3 days was studied for its effects on bronchial tone in 40 patients with bronchial asthma. Respiratory parameters were pneumotaxometrically determined and cerebral circulatory parameters were rheographically measured prior to and following the drug injection. The findings have demonstrated that cavinton significantly decreased bronchial tone improved cerebral circulation, particularly in patients with bronchial asthma and chronic cerebral circulatory disorders.     

Chronic bronchitis--alterations of the bronchial mucosa

The mucociliary transport system is usually an important defense system which protects the body against a variety of noxious agents. Reactions of the bronchial mucosa to chronic infections are seen in the ciliated cells, the amount of globlet cells, in modifications of the basement membrane underlying the bronchial epithelium and an altered percentage of inflammatory cells. In ciliated cells the following atypia can be seen: thickening of the ciliar membrane, swollen cilia, formation of compound cilia, disarrangement of microtubules. Common alterations of the basement membrane are: increased diameter of the basement membrane zone, inhomogeneous staining pattern of the basement membrane zone, formation of cytoplasmatic protrusions, formation of double layers of the basement membrane and increased number of cytoplasmatic bound vesicles. Structural abnormalities of the basement membrane will lead to disturbances of the zone of transition and have to be interpreted as a sign of disregulation in the process of diffusion and resorption. The inflammatory response of the epithelium during chronic bronchitis and asthma shows many similarities. The bronchial epithelium has a specific reaction pattern which supports the response against different noxious agents. So all findings have to be interpreted as unspecific pathological changes. All alterations may show different degrees of severity and are dependent on individual pattern and the severity of chronic process. Electronmicroscopical examinations in combination with lightmicroscopical findings and immuno-histochemistry and seen in context with clinical data help to understand the mechanism of the inflammatory process.     

Experimental studies on acute and chronic action of azelastine on nasal mucosa in guinea pigs, rats and dogs

Azelastine (CAS 37932-96-0) nasal spray (Allergodil, Rhinolast, Astelin) was investigated in acute experiments in guinea pigs and after a 26-week local application period with daily repeated administration for effects on ciliary beat activity (acute experiments) and morphology of nasal mucosa. The commercially available spray did not inhibit ciliary beat activity in guinea pigs nor did it cause any inflammatory or atrophic changes after 26-week daily local application on nasal mucosa in rats and dogs.     

Lack of effect of azelastine and ketoconazole coadministration on electrocardiographic parameters in healthy volunteers

Azelastine, an antihistamine with additional pharmacologic properties, was evaluated for a possible influence on pharmacokinetic and electrocardiographic parameters due to its coadministration with CYP3A4 inhibitor ketoconazole (200 mg every 12 hrs). Twelve volunteers entered this three-period, open-label study. Electrocardiographic parameters (PR, QRS and QTc intervals and U-wave morphology) were monitored after 14 days of azelastine HCl (4.4 mg every 12 hrs), after 7 days of either azelastine/ketoconazole or azelastine/placebo, and after a 21-day washout period, which was then followed by a 7-day administration of ketoconazole alone. None of the treatments resulted in meaningful alterations of electrocardiographic variables. Pharmacokinetic parameters could not be estimated because ketoconazole metabolites interfered with azelastine assay procedures. In vitro tests with human liver microsomes were used to characterize azelastine's inhibition spectrum. Azelastine did not inhibit CYP3A4 activity but it did inhibit CYP2D6 and CYP2C19 activity with Ki values exceeding maximum plasma concentration by 120 to 800-fold. Therefore, in vitro tests and the absence of electrocardiographic effects suggests azelastine can be safely administered with CYP3A4 inhibitors.     

Effects of ketotifen on symptoms and on bronchial mucosa in patients with atopic asthma

Ketotifen is marketed throughout the world as an antiallergy drug, but whether it affects infiltration of inflammatory cells into airway mucosa is not known. We studied the effects of ketotifen on symptoms, pulmonary function, and airway inflammation in 25 patients with atopic asthma. Patients took ketotifen (1 mg twice daily) or a matching placebo for 8 weeks in a double-blind, parallel-group study. Data recorded on diary cards were used for 2 weeks before treatment began, and they were used for the last 2 weeks of treatment to study asthma symptoms, use of beta 2-agonists, and peak expiratory flow (PEF). Pulmonary function tests, bronchial responsiveness to methacholine, and fiberoptic bronchoscopy were performed before and after treatment. Biopsy specimens were obtained by bronchoscopy. Specimens were stained immunohistochemically with monoclonal antibodies against stored eosinophil cationic protein (EG1), the secreted form of eosinophil cationic protein (EG2), mast-cell tryptase (AA1), neutrophil elastase (NP57), CD3, CD4, CD8, and CD25. The numbers of positively stained cells in the lamina propria were counted. Compared with the placebo, the ketotifen-treated group exhibited significant improvement of asthma symptoms (P < 0.05) and bronchial responsiveness (P < 0.05). This was accompanied by a reduction of EG2+ eosinophils (P < 0.05), CD3+ T cells (P < 0.001), CD4+ T cells (P < 0.01), and CD25+ activated T cells (P < 0.01) in the bronchial mucosa. These results suggested that the beneficial effects of ketotifen in bronchial asthma may result from consequent inhibition of activated eosinophils and T-cell recruitment into the airway. Moreover, ketotifen may relieve allergic inflammation in bronchial asthma.     

Expression of cytokine mRNA transcripts in renal cell carcinoma

The nm23 gene has been proposed as a candidate tumor metastasis suppressor in some human cancers. Sialyl Lewis X (sLex) has been demonstrated to play an important role in the adhesion of human cancer cells to human vascular endothelium, inducing metastasis. Little information has been reported about the correlation between the expression of nm23 and sialylated carbohydrate antigens. In the present study, 102 surgically resected primary breast cancer tissues were sectioned and stained with antibody against nm23-H1 and sLex. Of the 102 cases, 39 (38.2%) cases with a reduced expression of nm23-H1 were observed, and the numbers of sLex-positive cases were 61 (59.8%), respectively. The reduced expression of nm23-H1 and the positive expression of sLex were significantly associated with lymph node involvement. Among the 100 patients who underwent curative surgery, the disease-free survival rate was significantly correlated to both the nm23-H1 and sLex expressions. No interrelated expressions were found between nm23-H1 and sLex. In multivariate analysis using Cox regression model, combination assay of nm23-H1 and sLex expression emerged as independent significant prognostic factors. These results suggest that nm23-H 1 gene and sLex may be involved in different steps of the metastatic process in human breast cancer, and immunohistochemical detection of the combination of sLex and nm23-H1 may be a biologic marker of prognostic significance.     

The effect of chairside relining materials on rat palatal mucosa

OBJECTIVES: To investigate the effects of denture relining materials on oral mucosa in vivo in a rat model. METHODS: Denture-like appliances covering the palate in Wistar rats were relined with a resilient soft linting material and a hard 'chairside' relining material. The effects on the palatal epithelium were studied by quantitative analysis using computerized planimetry. RESULTS: The relining materials caused an increase in the thickness of the keratinized layer, while not increasing the total epithelial thickness. CONCLUSIONS: Relining materials are not totally without effect on oral mucosa. Further in vivo research is indicated.     

The effect of glucocorticoids on mineral metabolism in bronchial asthma patients]

Nuclear-absorption spectrophotometry (AAC-508, Hitachi, Japan) and selective ionometry (microlyte, Kone, Finland) were employed to measure magnesium and calcium concentrations in the serum, red cells, lymphocytes, 24-h urine and exhaled air moisture in 40 patients with hormone-dependent asthma (BA) and 15 BA patients given beclomet, becotid in inhalations and injections of hydrocortisone, prednisolone and dexason. Intravenous infusions and steroid inhalations in moderate doses for 10-14 days induce only insignificant changes in bivalent cation homeostasis. Complications associated with deranged mineral metabolism occurred more frequently in BA patients on long-term (at least 4 years) courses of oral glucocorticoids. Increased renal and bronchial excretion of magnesium and calcium in patients with hormone-dependent BA with complications of glucocorticoid therapy shows its significant contribution to development of steroid osteopathy and myopathy.     

Effect of macrolides on cytokine mRNA expression in human whole blood model

Recently, low dose and long term use of Macrolides (Mls) has been reported to be effective in treatment of chronic lower respiratory tract infections, however its mechanism is still obscure. We evaluated the effect of Mls (EM, AZM, RKM) on cytokine mRNA expressions. We preincubated the whole blood with several concentrations of Mls and removed the Mls and then stimulated human whole blood with LPS as an experimental vivo model. In order to examine cytokine mRNA expressions, we used the RT-PCR method. Cytokine mRNA expressions were suppressed significantly (p < 0.05) by pretreatment with EM, AZM; moreover, the suppression was peaked at low concentrations (0.04 approximately 0.2 microgram/ml). Although, Cytokine mRNA expressions were not suppressed by pretreatment with RKM. These results suggest that EM, AZM have suppression on Cytokine mRNA expressions, and consequently, this suppression has a reasonable effect for DPB patients.     

Mechanisms of bronchial self-cleaning. Surface studies on the bronchial mucosa, bronchial basement membrane and subepithelial connective tissue. A scanning electronmicroscopic study

Bronchial mucosa and bronchial basement membranes of man and of healthy slaughter animals were examined with the scanning electron microscope. The surface relief of the normal human bronchus mucosa is composed of a system of bulge-like prominences and valleys. There are parallel recesses and narrow valleys which run parallel to the longitudinal axis of the bronchus. Man and pig have the same kind of surface relief in bronchus. A fundamental different type of surface area relief is exhibited by the cow and the sheep. The bronchial basement membrane is a homogeneous plate with dune-like prominences and trough-shaped depressions. Often one can see perforations of variable size. The structures of the basement membranes have a great variability and no species-specifity. There are the same types of dysplasias in the bronchus mucosa in man and in animals. The differences are based upon in the wideness of the expansion and in the grade of the dysplasias in man.     

mRNA differential display of colonic mucosa cells in ulcerative colitis

Vascular cells are an important target for gene transfer because of their potential to deliver gene products both locally and systemically. Direct retroviral gene transfer to vascular cells in vivo has been limited by inefficient rates of transduction. We hypothesized that vascular cell transduction efficiency (TE), during short retroviral incubation periods, is significantly improved in vitro and in vivo using centrifugation to increase viral titer. Furthermore, we hypothesized a linear relationship between concentration of viable viral particles (measured as colony-forming units (CFUs)/cell) and retroviral TE during short incubation periods. Cultured rat pulmonary artery endothelial cells (RPAECs), rat aortic smooth muscle cells (RSMCs), and human iliac artery endothelial cells (HIAECs) demonstrated a strong correlation between TE and high concentrations of virus (> 100 CFU/cell) during retroviral incubation periods of 10 to 60 minutes. High titers, and thereby high concentrations, were achieved by centrifugation and resuspension in a fraction of the original volume. Titers was consistently increased tenfold, for a twentyfold increase in concentration by volume. A 20-minute incubation with a Moloney murine leukemia-derived retroviral vector coding for human placental alkaline phosphatase, pLJhpAP, at a concentration of 1150 CFU/cell yielded TEs of 10.6% +/- 0.7%, 40.4% +/- 1.6%, and 15.1% +/- 2.0% for RPAECs, RSMCs, and HIAECs, respectively. A similar effect was shown using the Moloney murine leukemia-derived MFGlacZ retroviral vector, coding for Escherichia coli beta-galactosidase. Increased titer and concentration had no effect on target cell viability, as shown by trypan blue exclusion. Although RSMCs had the most cells transduced in a given incubation period (p < 0.05), RPAECs had the highest replication rate (p < 0.05), suggesting the importance of factors other than cell cycle on retroviral TEs during short, clinically relevant incubation periods. In subsequent in vivo experiments, gene transfer was achieved in the rat carotid artery during a 20-minute incubation period infusing the concentrated pLJhpAP retrovirus after carotid balloon injury. Rats infused with virus 2 days after balloon injury exhibited hpAP activity (0 to 10 cells/section/rat) in the neointima of five out of six rats. Rats infused 4 days after balloon injury exhibited hpAP activity (0 to 25 cells/section/rat) in the media and adventitia of five out of five rats. Control rats that received the balloon injury alone or the balloon injury and unconcentrated retrovirus exhibited zero hpAP activity. We conclude that the TE of retroviral-mediated gene transfer to vascular cells in vitro and in vivo can be improved during short, clinically relevant incubation periods using centrifugation to increase retroviral titer, and thereby concentration of viable viral particles.     

The effect of salben on the rheological properties of the bronchial secretion

We report a case of a 1.5 cm cystine staghorn calculus of the right lower pole in a 32 year female known cystinuric patient. With a 200 microns Holmium laser probe through a 9,5 F flexible ureteroscope the calculus was fragmented in small particles. An internal ureteral stent was inserted at the end of the procedure. All but one small residual fragments were evacuated spontaneously after removal of the stent. This case shows that flexible ureteroscopy combined with the Holmium laser is a safe and efficient procedure to treat medium size renal cystine calculi. It can be repeated in case of recurrence with minimal trauma to the urologic tract.     

Increased expression of interleukin-16 in bronchial mucosa of subjects with atopic asthma

We have made hinge variants of two human Fab's in order to investigate the factors involved in the formation of dimeric Fab's in the periplasm of E. coli. Hinges containing one or more copies of the IgG1 hinge with various numbers of spacing residues were tested. Fab's with hinges based on the gamma2, gamma3 and gamma4 isotypes were also tested. We find that the IgG1 hinge sequence can form approximately 35% F(ab')2 in vivo in shake flask experiments, but that only (approximately) 5% F(ab')2 can be produced during fermentation. IgM and IgA tail-pieces added to Fab's did not effect their multimerisation. The possible role of growth conditions upon F(ab')2 formation in vivo is discussed.