Surfactant protein B detection and gene expression in chronic rhinosinusitis

INTRODUCTION: Surfactant protein (SP)-B is a hydrophobic protein secreted within pulmonary surfactant that facilitates the adsorption of surface-active lipids to the air-liquid interface of the alveoli and increases alveolar stability. SP-B may also have anti-inflammatory properties. It is implicated in decreasing the pulmonary inflammatory response to bacterial lipopolysaccharide. However, the expression and function of SP-B in the sinonasal cavities has not been elucidated. Our objective was to detect the presence of SP-B, measure alterations in several forms of chronic rhinosinusitis (CRS), and localize cellular protein expression. MATERIALS/METHODS: Sinus mucosal biopsies were performed in patients with allergic fungal rhinosinusitis (AFRS), nonatopic CRS with nasal polyposis (NP), and cystic fibrosis (CF) and in healthy controls. SP-B mRNA was measured in CRS and control patients using quantitative polymerase chain reaction. Immunoblot analysis and immunolocalization of SP-B were also performed. RESULTS: CF (n = 4) showed significantly increased levels of SP-B (169-fold) mRNA (P = .004) when compared with controls (n = 5). CRS with NP (n = 5) and AFRS (n = 7) also demonstrated elevated levels of SP- B (14-fold and 4-fold, respectively) when compared with the control group, although these were not statistically significant. Immunoblot analysis confirmed the presence of the translated product, and immunolocalization revealed expression in the epithelium and submucosal glandular elements. CONCLUSION: This is the first study to detect and characterize SP-B in human sinus mucosa. Furthermore, SP-B is significantly up-regulated in CF CRS.     

Innate and adaptive mediators in cystic fibrosis and allergic fungal rhinosinusitis

BACKGROUND: Surfactant-associated proteins (SP) A and D are both innate immunity mediators and produced in normal and diseased sinus mucosa. Cystic fibrosis (CF) is associated with Th1 adaptive inflammation whereas allergic fungal rhinosinusitis (AFRS) is associated with Th2 adaptive inflammation. The purpose of this study is to show and quantify the presence of SP A, SP D, tumor necrosis factor (TNF) alpha, (a Th1 marker), and eotaxin (a Th2 marker) in normal and diseased sinus mucosa. METHODS: Intraoperative sinus mucosal biopsy specimens from human volunteers were obtained during endoscopic sinus surgery for CF (n = 4), AFRS (n = 10), and normal controls (CTLs; n = 4). Specimens were evaluated for presence and quantity of SP A, SP D, and TNF-alpha using Western blot with semiquantitative immunoblot analysis. Eotaxin was quantified using ELISA immunoassay. Results were standardized and reported as picograms of mediator per microgram of total protein. RESULTS: SP A, SP D, and TNF-alpha levels in CF tissue extracts were 2-10 times higher than levels in AFRS tissue (with SP D and TNF-alpha reaching statistical significance) but CF tissue was not significantly higher than CTL tissue. SP A, SP D, and TNF-alpha were not significantly elevated in AFRS. Eotaxin showed elevated levels in CF and AFRS when compared with CTLs (p = 0.03 and 0.003, respectively). CONCLUSION: SP D and TNF-alpha are significantly increased in CF compared with AFRS, suggesting activation of both innate immunity and Th1-mediated inflammation and potential correlation between SPs and downstream adaptive immune responses.     

Effect of food on oral availability of apresoline and controlled release hydralazine in hypertensive patients.

Hydralazine is a vasodilator antihypertensive drug that has been in use for many years. Efficacy after oral administration correlates well with the levels of the drug in blood. Factors such as food ingestion that affect blood levels of hydralazine may therefore be of importance. There is dispute regarding the effect of food intake on blood levels of hydralazine and on the antihypertensive response. This randomized cross-over study examined the effect of food (642 K calories, 25 g protein, 43 g fat, 40 g carbohydrates, 32 mEq sodium, 17 mEq potassium) ingested immediately before hydralazine (taken as Apresoline, Ciba Geigy, or as slow-release hydralazine, SRH, Pennwalt Corporation) on the blood levels of hydralazine in 16 essential hypertensive patients who were slow acetylators currently taking at least 100 mg Apresoline daily. Peak blood hydralazine levels were reduced by food after both Apresoline and SRH, by 69 and 66%, respectively. Time to peak blood hydralazine concentration was delayed significantly with SRH. We could detect a statistically significant food-related reduction of area under blood hydralazine concentration versus time curves (AUC) only with Apresoline (by 44%). The AUC for SRH was decreased only 29% by food. Hydralazine should be taken at a consistent time with respect to meals.     

Growth hormone therapy in pre-pubertal children with Noonan syndrome: first year growth response and comparison with Turner syndrome

We studied the growth-promoting effect of treatment with recombinant human growth hormone in 23 prepubertal children with Noonan syndrome, aged between 5. 4 and 14. 3 y, and all with a height < 1. 4 SD for Tanner standards. The growth response and skeletal maturation after 1 y of recombinant human growth hormone treatment (0. 15 U/kg/day given by daily injection) in the Noonan syndrome patients was compared with the auxological changes observed in a group of 17 girls with Turner syndrome with a comparable age and height deficit who were treated with recombinant human growth hormone in a similar way. During 1 y of treatment, the mean ± SD height velocity increased by 4. 0 ± 1. 6 cm/y in the Noonan syndrome group and by 3. 6 ± 1. 3 cm/y in the Turner syndrome group. Height SDS for chronological age in the Noonan syndrome group increased by 0. 53 ± 0. 46 ( p < 0. 001). In the Noonan syndrome patients the changes in height velocity were positively related to birthweight ( r = 0. 48, p < 0. 05). The changes in height velocity or height SDS were not related to the age, height deficit or a delay in bone age maturation at start of treatment. In neither the patients with Noonan syndrome nor Turner syndrome was an acceleration of bone maturation found. We conclude that treatment with recombinant human growth hormone in pre-pubertal NS patients induces an increase in height velocity and height SDS comparable to that observed in Turner syndrome girls.     

Glucocorticoid receptors in cord blood lymphocytes of healthy neonates and of preterms suffering from respiratory distress syndrome

We measured the number of glucocorticoid receptors (GR) in cord blood lymphocytes and the binding affinity (K_d) in 15 term and in 20 preterm babies. Thirteen preterms of the latter group received prenatal steroid treatment. Seven preterms developed neonatal respiratory distress syndrome (NRDS). The number of GR and the K_d were similar in the term and preterm (with and without NRDS) babies. The maximum thymidine incorporation into DNA of cord blood lymphocytes from all preterms, with or without NRDS was suppressed when compared to that from term babies or adults. This could partly be explained by the antenatal steroid treatment. Sensitivity (ID₅₀) of the lymphocytes for the inhibitory effect of dexamefhasone was the same in all groups. In this study on the number and function of GR in lymphocytes, we were unable to find a relation between the functionality of the GR and the development of NRDS.