Role of hematopoietic prostaglandin D synthase in biphasic nasal obstruction in guinea pig model of experimental allergic rhinitis.

We investigated the role of hematopoietic prostaglandin D synthase (H-PGDS) in biphasic nasal obstruction in allergic rhinitis using a new specific inhibitor, (N-methoxy-N-methyl)-4-(5-benzoylbenzimidazole-2-yl)-3,5-dimethylpyrrole-2-carboxamide hydrochloride (TAS-204). First, we developed a novel guinea pig model of allergic rhinitis. Guinea pigs sensitized to ovalbumin without adjuvant were challenged with intranasal exposure to ovalbumin once a week. After the 3rd antigen challenge, they exhibited biphasic nasal obstruction. Additionally, analysis of nasal lavage fluid revealed an increase in the level of prostaglandin D(2) in both early and late phases. Treatment with oral TAS-204 for 15 days during the period of antigen challenges suppressed increases in nasal airway resistance in both phases. It is noteworthy that the late phase nasal obstruction was almost completely abrogated by inhibiting H-PGDS alone. Eosinophil infiltration in nasal lavage fluid and nasal hyperresponsiveness to histamine was also reduced by TAS-204 administration. These findings suggest that H-PGDS plays a critical role in the development of allergic rhinitis, especially in the induction of late phase nasal obstruction.

Enzymatic study of tonsil tissue alkaline and acid phosphatase in children with recurrent tonsillitis and tonsil hypertrophy.

OBJECTIVE: Indications for tonsillectomy in recurrent tonsillitis are defined according to the number of episodes of acute bacterial infections in a year. However, little is known about the tonsil immune competence status in patients presenting with recurrent tonsillitis with either hypertrophied or atrophied tonsils, or in patients presenting with obstructive sleep apnoea. In this study we examined the tonsil immune status in children with 3-5 acute recurrent infections a year and in children with obstructive sleep apnoea by comparing the activity of tonsil and adenoid tissue nonspecific alkaline and acid phosphatase. METHODS: Specific activity of tonsil and adenoid tissue nonspecific alkaline and acid phosphatase was investigated in children who underwent tonsillectomy and adenoidectomy for recurrent infection (72 children) and for obstructive sleep apnoea (10 children). Tissue enzyme activities were measured using p-nitrophenylphosphate as a substrate. Tissue samples were examined by the haematoxylin-eosin histological technique. Statistical analyses were performed using SPSS v. 16 software. RESULTS: The tissue nonspecific alkaline phosphatase activity was similar in hypertrophied tonsils in the recurrent infection group and in the obstructive sleep apnoea group (3.437+/-1.226 and 3.978+/-0.762 U/mg of protein, respectively). The enzyme activity in both hypertrophied tonsil groups was significantly higher as compared to atrophied tonsils in the recurrent tonsillitis group, p=0.021 and p=0.006, respectively. The enzyme activity was significantly higher in the adenoids compared to the tonsils from all three groups. Contrary to this, no significant differences were noticed for tonsil and adenoid acid phosphatase activities among the groups. CONCLUSION: Similar acid phosphatase activity in all three groups implies that all three groups have preserved antigen presenting cell activity. In patients with hypertrophied tonsils similar tissue nonspecific alkaline phosphatase activity suggests preserved B cell tonsil immune activity, regardless of the pathology. Patients with atrophied tonsils had significantly lower alkaline phosphatase activity, indicating relative tonsil B cell immune deficiency. Thus, different immunological status in patients presenting with hypertrophied vs. atrophied tonsils could point to a different underlying pathophysiologic mechanism of the disease.

beta-Secretase expression in normal and functionally deprived rat olfactory bulbs: inverse correlation with oxidative metabolic activity.

Cerebral hypometabolism, mitochondrial dysfunction, and beta-amyloid peptide (Abeta) accumulation are well-characterized manifestations of Alzheimer's disease (AD). beta-Secretase (BACE) is a prerequisite for amyloidogenesis, and it is up-regulated in sporadic AD. To explore a potential in vivo mechanism by which Abeta production is modulated by neuronal activity and/or oxidative metabolism, we compared BACE expression with cytochrome c oxidase (CO) or succinic dehydrogenase (SDH) activity in normal and functionally deprived adult rat olfactory bulb. In normal bulb, BACE was expressed predominantly in the glomerular layer, but labeling intensity within individual glomeruli varied substantially. A strong negative correlation existed between BACE labeling intensity and CO or SDH activity among individual glomeruli. Unilateral naris occlusion resulted in elevated glomerular BACE labeling in the deprived bulbs relative to the nondeprived counterparts, which was correlated with decreased CO activity in the same anatomic location. Enhanced BACE labeling was confirmed by measurements of elevated protein levels, enzymatic activity, and beta-site cleavage products of amyloid precursor protein in bulb extracts. Our findings reveal a negative regulation of BACE expression by physiological neuronal activity and an intrinsic inverse correlation between BACE expression and oxidative metabolism at the first synapse on the olfactory pathway. The results point to a biological role of BACE in synapse function and plasticity as well as a potential mechanism whereby reduced neuronal activity or metabolism could lead to amyloid overproduction in synaptic terminals.

Alteration of adenoid tissue alkaline and acid phosphatase in children with secretory otitis media.

OBJECTIVE: The role of pharyngeal lymphoid tissue in etiopathogenesis of secretory otitis is not yet defined. The influence of tonsillar and adenoid mass, weight, obstruction of naspharyngeal orrifitium, bacterial reservoire or some immunological events are of scientific interest. Tissue nonspecific alkaline phosphatase (TNAP) and acid phosphatase (ACP) are enzymes detected in lymphoid tissue, TNAP as characteristic of B cells, ACP as a characteristic of macrophages and folucullardentritic cells. These enzymes interfere in cell metabolism by removing 5' phosphate group from nucleotides and proteins. Specific activity and kinetic properties were studied in palatinal tonsils and adenoids of children with secretory otitis (OME) and compared with children with recurrent tonsillitis without ear involvement. METHOD: Adenoid and tonsillar tissue of l7 children with OME and 30 children with recurrent tonsillitis were subjected to biochemical investigation using method of releasing of p-nitrophenol from p-nitrophenylphosphate (pNPP). Kinetic parameters as Michaelis-Menten constant were calculated by non-linear regression estimation method. RESULTS: Specific activity of adenoid alkaline phosphatase was lower in children with OME in relation to children with recurrent tonsillitis (t=5.733507, p<0.01). Specific activity of adenoid acid phosphatase was also lower in children with OME (t=3.655456, p<0.01). pH optimum for both enzymes was the same in these two groups of children. Michaelis-Menten constant for both enzymes was significantly higher in adenoid of children with OME than in children with recurrent tonsillitis suggesting lower enzyme affinity for the substrate. CONCLUSION: Differences in specific activities and kinetic properties of adenoid alkaline and acid phosphatases between children with OME and children with recurrent tonsillitis without OME were verified in this study. The results of the study are not able to explain the alteration of alkaline and acid phosphatase characteristics but could point to some possible and specific role of nasopharyngeal lymphoid tissue in pathogenesis of secretary otitis.

[Endogenously formed nitric oxide in nasal mucosa of the human: detection by nicotinamide-adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry]. / Endogen gebildetes Stickstoffmonoxyd in der Nasenschleimhaut des Menschen: Nachweis mittels Nikotinamid Adenin Dinukleotid Phosphat-Diaphorase (NADPH-d) Histochemie.

BACKGROUND: Nitric oxide (NO) is an intercellular transmitter, both in the central and in the peripheral nervous system. In addition to nerve cells, NO is also produced in epithelial cells of various tissues and in the endothelium. NO is formed by the action of nitric oxide synthase (NOS). There is evidence that NOS can be marked by NADPH-diaphorase (NADPH-d) activity in many cell types. The aim of this study was to identify NOS-positive structures in human nasal mucosa by using NADPH-d-histochemistry. METHODS: Frozen sections from inferior turbinates were fixed with buffered formalin and then treated according to the description of Vincent and Kimura. Additionally, the same sections underwent a double staining procedure for acetylcholinesterase (Karnovski-Roots) to show a correlation with cholinergic nerve structures. RESULTS: Strong reactions were found in the epithelium and in nerve fibres, compared to less NADPH-d activity in seromucous glands and the endothelium of the different vessel types. Singular NADPH-d positive nerves were found within nerve bundles, periarterially, in the subepithelial layer and surrounding glands and their ducts. A frequent localisation of NADPH-d could be detected in parasympathetic nerve fibres. CONCLUSIONS: The occurrence of NADPH-d in epithelial, glandular and nerval structures suggests that NOS takes part in physiological functions and possible pathophysiological processes of the nose. Similar to findings in various other organs this investigation demonstrated that the neurotransmitter NO can also be associated with the parasympathetic nervous system in the human nasal mucosa.

Adult naris closure profoundly reduces tyrosine hydroxylase expression in mouse olfactory bulb.

Peripheral afferent innervation appears to be required for the expression of the dopamine phenotype in the rodent main olfactory bulb. Experiments utilizing neonatal naris closure as a means of sensory deprivation also suggest that odor-induced afferent activity is required for the expression of the phenotype. These experiments are confounded, however, by the significant postnatal maturation of the dopamine system. The current experiments utilized adult unilateral naris closure to address this issue. As with neonatal closure, adult deprivation produces a profound reduction in the expression of tyrosine hydroxylase (TH), the first enzyme in the dopamine biosynthetic pathway. By 4 days a small decrease is observed in TH activity and immunoreactivity. Activity reaches a nadir of 12% of control levels at about 1 month. TH mRNA is reduced similarly when analyzed at about 2 months post-closure. Glutamic acid decarboxylase protein and mRNA expression, which are co-localized with TH, remain at close to control levels indicating the continued presence of the dopamine neurons. The time-course of the loss of TH is identical to that for zinc sulphate-induced denervation of the olfactory bulb. These data support the hypothesis that odor modulated afferent activity is required for expression of the dopamine phenotype and that, if a trophic factor is involved, its release is also activity dependent.