Binding chemistry and molecular heterogeneity of neurotensin binding protein(s)/receptor in adult chicken tissues.

The study focuses on the importance of Tyr11 amino acid (AA) and subsequent stereochemistry involved in the binding process of neurotensin (NT) with its receptor (NTR)/binding protein(s) as well as the size heterogeneity. Using the binding of 125I-NT with several chicken tissues, it is identified that one of the crucial factors behind all high affinity (Kd ~10 pM) interactions is due to phenolic-OH (Φ-OH) at the para (p) position of Tyr11 within RRPYIL-CO2H (NT8-13) sequence. Replacing the p-OH only in Tyr11 by substituting with p-Cl, p-F and p-NH2 results in significant change of the binding affinity (Kd); p-OH ≈ p-NH2 (~10 pM), p-Cl (~100 pM), p-F (~120 pM). Interestingly, p-NH2 equals to p-OH displaying the highest affinity. Experiments conducted by binding several of the 125I-azido–NT analogs having azido group attached at different positions within the NT molecule have further confirmed the necessity of RRPYIL sequence for high affinity ligand-receptor interaction. The role of Tryp11 in place of Tyr11 in addition to the results above establishes a significant possibility of H–bonding occurring between p-OH of NT and NTR inside the docking space. Photo labeling of the liver tissue by substituted 125I-Y3-azido-NT analogs shows several specifically labeled bands with considerable range of molecular weight (Mr ~90-30 kDa) variations. These results indicate the existence of molecular heterogeneity concerning the sizes of NTR or else any NT binding proteins in the avian tissues. Further, the study has revealed that besides liver, several other chicken tissues also express similar specific high affinity binding (Kd ~20 pM) with varying capacities (Bmax). The order for Bmax is: liver (1.2 pMol/mg) gall bladder (1.03 pMol/mg) > spleen (0.43 pMol/mg) > brain (0.3 pMol/mg) > colon lung (0.15 pMol/mg). In all cases, the binding was reduced by GTPgS (ED50 ~ 0.05 nM), NEM (ED50 ~ 0.50 mM) and NaCl (ED50 ~30 mM), indicating the existence of NTR identical to the mammalian type-1.

Effect of intra nasally applied fluticasone propionate and levocabastine on the expression of aquaporin 5 in nasal mucosa of rat with experimental allergic rhinitis / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the expression and distribution of aquaporin 5(AQP5) in allergic rhinitis(AR)treated by fluticasone propionate and levocabastine.Method:Forty Wister rats were divided randomly into AR(n=30) and control groups(n=10). After AR models were established, the AR rats were divided evenly into F group, L group and AR control group.Three groups were treated respectively for 28 days, then the expression of AQP5 in nasal mucous membrane were detected by immumohistochemistry assay.Result:The distribution of AQP5 was consistent in all groups. The expression of AQP5 in F group was significantly different from L group and AR group (P 0.05). The expression of AQP5 in L group was significantly different from that in control group(P<0.05).Conclusion:High expressions of AQP5 in rat with AR indicated the positive correlation between AQP5 and AR. AQP5 might be one of pathological factors of AR concered with gland's excessive secretion and tissue edema. Glucocorticoid can down-regulate the expression of AQP5,but H1-receptor antagonist can not reduce the expression of AQP5.

Clinical Effect of Levocabastine Eye Drops on Allergic Conjunctivitis

Levocabastine, a selective H1-receptor antagonist, has been evaluated in the management of allergic conjunctivitis and its efficacy was compared between the skin test positive and negative groups. A total of 20 patients who was clinically diagnosed as allergic conjunctivitis were processed for the skin test. According to the results of skin test, patients were divided into two groups; skin test positive (15) and negative (5). Livostin(levocabastine 0.5mg/ml) eye drops were topically instilled 2 times per day for 1 week. Both subjective and objective findings were assessed by a 4-point scase (0=none, 1=mild, 2=moderate, 3=severe). The parameters used for the examination of drug effectiveness were itching, tearing, chemosis, lid swelling and injection. 85.5% (17 put of 20) of the patients showed effects on the management of their symptoms and signs. No significant difference was observed in its effectiveness between skin test positive and negative groups. The results of present clinical trials suggest that Livostin eye drops may be an attractive therapeutic option for the management of allergic conjunctivitis.

The Therapeutic Effect of Levocabastine Eye Drops on Allergic Conjunctivitis: A Multicenter Study

The efficacy nd tolerance of topical administration of levocabastine(0.5mg/ml)were evaluated in patients with allergic conjunctivitis. A total of 166 patients who had a typical history of atopy and a positive skin test were recruited in this study. Five clinicl symptoms(itch, tearing, chemosis, lid edema and conjunctival injection) were assessed according to a four point scale before the treatment and at 1 and 2 weeks post-therapy. Total symptom severity score before the therapy, 6.68, was remarkably decreased to 2.86 at 1 week and 2.08 at 2 weeks after the treatment. The investigators rated the treatment as globally good or excellent in 68.1% of patients checked at 1 week and 72.5% at 2 weejs after treatment. And the patients evaluated that the therapy ws good to excellent in 66.9% at 1 week and 73.1% at 2 weeks after treatment. Levocabastine eye drops has a fast onet of action with 55.4% of the patients feeling symptom relief within 15 minutes after the first administration. The adverse effect was experienced in 44 patients. Ocular irritation sign, such as foreign body sensation or soreness, was the most frequently reported complaint. These results suggest that levocabastine eye drops is an effective and safe topical alternative for treatment of allergic conjunctivitis.