Effects of cepharanthine on experimental nasal allergy

The anti-allergic actions of cepharanthine were examined using experimental nasal allergy rats (rhinitis models). In the actively sensitized rhinitis models, leaks of pontamine sky blue (PSB) dye in the perfusate of the nasal cavity were suppressed by cepharanthine treatment. Leaks of PSB dye in the perfusate were also suppressed by ketotifen treatment. beta-Glucuronidase activity in the perfusate was lower in the cepharanthine group and in the ketotifen group. In the passively sensitized rhinitis models, leaks of PSB dye in the perfusate were suppressed by cepharanthine treatment. Leaks of PSB dye in the perfusate in the ketotifen group were also suppressed. However, beta-glucuronidase activity was not different among the three groups. Cepharanthine (0.025-25 mg/kg body weight) and ketotifen (0.1-10 mg/kg body weight) inhibited leaks of PSB into the perfusate in a dose-dependent manner. These results suggest that cepharanthine may be clinically effective for treating patients with nasal allergy, and its anti-allergic mechanism may be the same as that of ketotifen.     

Changes of lysosomal enzyme activities in experimental type I and type IV allergic models

Experimental allergy was induced in animals: asthma, a Type I allergy, was induced in guinea pigs by sensitizing them with alpha-amylase (inhalation), and experimental allergic encephalomyelitis (EAE), a Type IV allergy, was induced in rats. Pulmonary, brain and serum lysosomal enzyme activities were measured in normal and allergic conditions. beta-Glucuronidase (beta-G) and arylsulfatase (AS) activities were determined by the fluorescent technique. During the asthmatic attack, pulmonary lysosomal enzyme activities were not different from that in the normal state in guinea pigs. However, brain lysosomal enzyme activities were elevated markedly on the 1 st day of EAE induction. Brain beta-G activity was elevated on the 2nd day, and AS activity had a tendency to be increased. On the other hand, serum lysosomal enzyme activity was not altered significantly. In the experimental allergy, lysosomal enzyme activity was altered in Type IV, but not in Type I.     

Effects of an amphoteric antiallergic agent, HSR-609, on antigen-induced late phase nasal eosinophilia in brown Norway rats

The effect of a newly synthesized compound, HSR-609, on rat experimental rhinitis was investigated. In the first part of the study, a new experimental nasal allergic late phase eosinophilia model in Brown Norway (BN) rats was investigated. The increase in the number of antigen inhalations resulted in the proportional increase in the number of inflammatory cells such as macrophages, eosinophils and neutrophils in the nasal cavity lavage fluid (NCLF) at 5 h after each inhalation. The number of inflammatory cells reached a maximum 8 h after the antigen perfusion. Submaximum response was observed at 5 h after the antigen provocation. In this system, the serum IgG and IgE antibody titers measured by homologous passive cutaneous anaphylaxis were 160 and 640, respectively. In the second part of the study, the effects of prednisolone, cetirizine and a newly synthesized amphoteric antiallergic agent, HSR-609, on this allergic late nasal eosinophilia and neutrophilia in BN rats were investigated. Prednisolone and HSR-609 significantly inhibited the increase in the number of eosinophils in the NCLF but not cetirizine. Furthermore, prednisolone showed the inhibition of the increase in the number of macrophages and neutrophils in NCLF. These results suggest that this late phase eosinophilia model in the nose of BN rats may be useful for investigating the therapeutic drugs for nasal allergy and a newly synthesized amphoteric antiallergic agent, HSR-609, may be useful for the treatment of allergic rhinitis with eosinophilia.     

Reduction of reactivity to allergic rhinitis with intravenous administration of calcium. Clinical-experimental study on the effect of changes of local airway resistance after nasal allergen provocation

The antiallergic activity of calcium was investigated in 25 patients with allergic rhinitis by nasal provocation with increasing doses of phleum pratense during a symptom free interval. Prior to that provocation, the patients received 9 mmol calcium (Calcium-Sandoz) i.v. or placebo respectively (double blind cross-over design). The concentration of serum calcium increased after calcium injection by 0.45 +/- 0.055 mmol/l. Calcium exerted a significant protective effect as compared to placebo: higher allergen doses, (p = 0.021) i.e. 20433 biological units/ml vs. 7494 biological units/ml, were required in order to induce a defined allergic reaction (50% decrease of nasal air flow). The data thus furnish evidence that intravenous calcium reduces the allergic response in type I allergy.     

Ramatroban (Baynas): a review of its pharmacological and clinical profile]

Bayer has been interested in the observations that metabolites of arachidonic acid are involved in allergy and inflammation. Ramatroban was thus developed as a therapeutic agent for allergic and inflammatory diseases. Ramatroban showed an antagonistic action on the thromboxane A2 (TXA2) receptor in in vitro experiments using platelets or arteries. It inhibited the permeability of capillary and also the infiltration of eosinophils in nasal mucosa. Ramatroban had an inhibitory effect on the nasal resistance stimulated by either U-46619 or antigen challenge in in vivo experiments. The concentration of nasal TXA2 was increased when the antigen was challenged to allergic patients. Clinical trials demonstrated that ramatroban decreased sneezing, rhinorrhea, and rhinostenosis in patients enrolled in the study. No serious adverse reaction of ramatroban was observed in patients throughout the trials. The treatment with ramatroban is safe and improves nasal symptoms.     

Preseasonal prophylactic treatment with antihistamines suppresses nasal symptoms and expression of histamine H₁ receptor mRNA in the nasal mucosa of patients with pollinosis

Administration of antihistamines 2-4 weeks before the pollen season showed a greater inhibitory effect on nasal allergy symptoms in patients with seasonal allergic rhinitis. However, the mechanism of slow-onset effects of preseasonal treatment with antihistamines remains unclear. Here, we investigated the effect of preseasonal prophylactic treatment with antihistamines on nasal symptoms and the expression of histamine H? receptor (H1R) mRNA of the nasal mucosa in patients with cedar pollen pollinosis. During the peak pollen period, the expression of H1R mRNA in the nasal mucosa and the scores of sneezing and watery rhinorrhea in patients receiving preseasonal prophylactic treatment with antihistamines were significantly suppressed in comparison with those in the patients without treatment. Moreover, there was a significant correlation between the nasal symptoms and the expression of H1R mRNA in both patients with or without preseasonal prophylactic treatment. These findings suggest that preseasonal prophylactic treatment with antihistamines is more effective than on-seasonal administration to patients with pollinosis in reducing nasal symptoms during the peak pollen period by suppressing H1R gene expression in the nasal mucosa.     

Effect of olopatadine hydrochloride, an anti-histamine drug, on rhinitis induced by intranasal instillation of toluene-2,4-diisocyanate in rats

The main symptoms of allergic rhinitis (AR) are sneezing, rhinorrhea and nasal obstruction. In patients with AR, levels of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) increase. Olopatadine hydrochloride (olopatadine) is an anti-allergic agent with histamine H1 receptor antagonistic action. To investigate whether olopatadine has an effect on inflammatory reactions, toluene-2,4-diisocyanate (TDI)-sensitized rats were used as an animal model of nasal allergy. Nasal allergy signs (sneezing, rhinorrhea and inflammation) were induced after TDI challenge. Amounts of NGF and VEGF in the nasal lavage fluid increased. Olopatadine reduced nasal allergy signs and inhibited increases in NGF and VEGF. These findings suggest that the increases in NGF and VEGF production are involved in the mechanism responsible for nasal allergy signs in TDI-challenged rats. Other histamine H1 receptor antagonists did not inhibit and instillation of histamine did not increase TDI-induced NGF and VEGF production. Therefore, olopatadine appears to exert additional biological effects other than its blockade of the histamine H(1) receptor. These results suggest that suppression of neurogenic inflammatory reactions might be partially involved in the improvement of allergy signs after treatment with olopatadine.     

Effect of Terfenadine on Substance P and Vasoactive Intestinal Polypeptide Concentrations in Nasal Secretions from Patients with Nasal Allergy

Abstract— Before terfenadine treatment, the mean substance P and vasoactive intestinal polypeptide (VIP) concentrations in nasal secretions from nasal allergy patients tended to be higher than the values of healthy subjects. During terfenadine treatment, the mean substance P concentrations in nasal secretions from patients allergic to house dust or pollen were significantly decreased to 62 and 39% of the initial values, respectively. The mean VIP concentrations in nasal secretions from the house dust allergy patients and the pollen allergy patients were significantly decreased to 52 and 18% of the initial values, respectively. Plasma substance P and VIP concentrations were not affected by nasal allergic symptom and terfenadine treatment.     

Allergen specific nasal challenge to latex in children with latex allergy: clinical and immunological evaluation

There are no data concerning the significance of allergen specific nasal challenge to latex (ASNCL) in the pediatric population and the effect of mometasone furoate nasal spray (MFNS), topic corticosteroid exerting a potent anti-inflammatory activity in children with latex allergic rhinitis. The aims of this study are: to investigate the clinical and immune pathological effects of ASNCL in children with latex allergy; to study the effects of MFNS pre-medication on the clinical and immune pathological effects of ASNCL in children with latex allergy. Thirteen children: 6 male and 7 female, mean (SD) age 9.6 (2.9) years, with latex allergy and seven children: 3 male and 4 female, mean (SD) age 9.9 (3.8) years, without latex allergy underwent ASNCL. Nasal symptoms were recorded, nasal lavage fluid was collected to measure tryptase, eosinophil cationic protein (ECP), interleukin-5, interferon-gamma levels, and spirometric test was performed for each patient without or with premedication with MFNS. ASNCL induced a clinical allergic response and increased tryptase levels only in children with latex allergy. No serious adverse events occurred after ASNCL. MFNS premedication reduced both tryptase and ECP levels only in children with latex allergy. ASNCL is a simple, reliable and useful tool to make or confirm the diagnosis of nasal symptoms due to latex; it allows us to study both clinical symptoms and local immunological changes. MFNS premedication before an ASNCL may prevent some immunological responses induced by ASNCL without clinical allergic modifications.     

曲安奈德喷雾剂对变应性鼻炎的作用

目的研究曲安奈德鼻腔局部给药对实验性变应性鼻炎动物模型的治疗作用及对组胺致大鼠鼻气道阻力增加的缓解作用。方法以实验性变应性鼻炎模型豚鼠和组胺致鼻气道阻力增加模型大鼠为试验对象 ,以豚鼠鼻腔分泌物量、喷嚏次数、搔鼻次数、鼻组织学及大鼠鼻气道阻力为指标 ,全面考察曲安奈德喷雾剂对变应性鼻炎的作用。结果曲安奈德鼻喷雾剂 (5 0、10 0、2 0 0 μg·kg-1,对卵蛋白致敏实验性变态反应性鼻炎豚鼠模型的各种变应性鼻炎的症状和体症均有明显改善作用 ;与模型对照组比较 ,各给药组动物鼻腔分泌物量、喷嚏次数、抓鼻次数明显减少 ,并可对抗组胺所致大鼠鼻气道阻力的增加。结论曲安奈德鼻喷雾剂鼻腔局部给药对实验性变应性鼻炎有显著改善作用     

复方苍耳子滴鼻剂对豚鼠变应性鼻炎的影响

目的观察复方苍耳子滴鼻剂对变应性鼻炎模型豚鼠症状的变化和血清组胺含量的影响。方法以甲苯-2,4-二异氰酸甲苯酯(TDI)作为致敏因子建立豚鼠鼻黏膜变态反应模型,以模型组、阳性药物组与空白组为对照,测定各组豚鼠鼻黏膜内组胺的含量及形态组织学的改变。结果 ①鼻部症状的改善情况:复方苍耳子滴鼻剂高、低剂量组药前总评分与药后总评分比较差异有统计学意义(P<0.05),能显著性改善慢性鼻炎模型动物的整体症状;②对血清组胺含量的影响:复方苍耳子滴鼻剂高、低剂量组血清组胺含量均显著低于模型组(P<0.05或0.01),能显著降低慢性鼻炎模型动物的血清组胺含量;③形态组织学的改变:复方苍耳子滴鼻剂高、低剂量对鼻黏膜上皮化生、腺体增生、血管增生或扩张及炎性细胞等方面均能显著改善慢性鼻炎模型动物的形态组织学。结论复方苍耳子滴鼻剂对豚鼠实验性变态反应性鼻炎有显著的改善作用。     

Histamine H1 receptors are involved in mouse nasal allergic responses: a demonstration with H1 receptor-deficient mice

The role of histamine H1 receptors in nasal allergic symptoms (sneezing and nasal rubbing) were studied using histamine H1 receptor-deficient mice. Intranasal instillation of histamine solution resulted in significant increases in sneezing and nasal rubbing in wild-type mice, whereas no increases were observed in histamine H1 receptor-deficient mice. The histamine H1 receptor agonist 2-pyridylethylamine induced sneezing and nasal rubbing in a dose-dependent-manner in wild-type mice, but no such increase was found in histamine H1 receptor-deficient mice. On the other hand, the histamine H2 receptor agonist dimaprit did not increase sneezing and nasal rubbing in wild-type mice. Histamine H1 receptor antagonists such as chlorpheniramine and epinastine significantly inhibited nasal allergic symptoms caused by histamine, but the histamine H2 receptor antagonists cimetidine and famotidine showed no effect. No additional effects were observed by combined use of chlorpheniramine and cimetidine or famotidine compared with cimetidine or famotidine alone. These results suggested that histamine H1 receptors play an important role in nasal allergy symptoms induced by histamine.     

New therapeutic approaches to the treatment of nasal allergy: Antiinflammatory effects of H(1) receptor antagonists

Histamine is recognized as an important mediator of allergic rhinitis. In addition to the role it plays in the immediate-phase reaction of nasal allergy, histamine may play an important role in the late-phase reaction and protracted allergic inflammation. Histamine induces the synthesis or secretion of proinflammatory cytokines and the expression of adhesion molecules. Besides their traditional effects via H(1) receptor antagonism, antihistamines have been reported to possess multiple antiinflammatory effects. Continuous use of antihistamines may reduce the level of minimal persistent inflammation of nasal mucosa in allergy. Treatment of allergic rhinitis using antihistamines could contribute to the improvement in coexisting allergic inflammation of the lower airways. (c) 2001 Prous Science. All rights reserved.     

Effect of mucosal TRPV1 inhibition in allergic rhinitis

Abstract: Transient receptor potential vanilloid‐1 (TRPV1) has been implicated as a mediator of itch in allergic rhinitis. To address this possibility, we synthesized a TRPV1 blocker (SB‐705498) for nasal administration in patients with seasonal allergic rhinitis. The pharmacological activity of SB‐705498 was confirmed on human TRPV1‐expressing HEK293 cells, using fluorometric calcium imaging, and in patients with allergic rhinitis subjected to nasal capsaicin challenges. The effect of SB‐705498 was studied in patients with seasonal allergic rhinitis subjected to daily allergen challenges for 7 days, using a double‐blind, placebo‐controlled, randomized and cross‐over design. SB‐705498 was delivered by nasal lavage 2 min. before each allergen challenge. Primary end‐point was total nasal symptom score on days 5–7. Nasal peak inspiratory flow (nPIF) and eosinophil cationic protein (ECP) content in nasal lavages were also monitored. Daily topical applications of SB‐705498 at a concentration that inhibited capsaicin‐induced nasal symptoms had no effect on total symptom score, nPIF and ECP levels in allergen‐challenged patients with seasonal allergic rhinitis. The individual symptoms, nasal itch or sneezes, were also not affected. These findings may indicate that TRPV1 is not a key mediator of the symptoms in allergic rhinitis. However, additional studies, using drug formulations with a prolonged duration of action, should be conducted before TRPV1 is ruled out as a drug target in allergic rhinitis.     

Histamine H₁ receptor gene as an allergic diseases-sensitive gene and its impact on therapeutics for allergic diseases

Therapeutics targeting disease-sensitive genes are required for the therapy of multifactorial diseases. There is no clinical report on therapeutics for allergic disease-sensitive genes. We are focusing on the histamine H? receptor (H1R) as a sensitive gene. H1R mediates allergy histamine signals. H1R is a rate-limiting molecule of the H1R signal because the signal is increased with elevated receptor expression level. We discovered that the stimulation of H1R induced H1R gene expression through PKCδ activation, resulting in receptor upregulation. The mechanism of H1R gene expression was revealed to play a key role in the receptor expression level in studies using cultured HeLa cells and allergic rhinitis model rats. Preseasonal prophylactic treatment with antihistamines is recommended for the therapy of pollinosis. However, the mechanism of the therapy remains to be elucidated. We demonstrated that repeated pretreatment treatment with antihistamines in the allergic rhinitis model rats resulted not only in improvement of symptoms but also in suppressed elevation of H1R mRNA levels in the nasal mucosa. A clinical trial was then initiated. When symptoms and H1R mRNA levels in the nasal mucosa of pollinosis patients with or without preseasonal prophylactic treatment with antihistamines were examined, both symptoms and high levels of H1R mRNA were significantly improved in treated compared with untreated patients. These results strongly suggest that H1R is an allergic disease-sensitive gene.     

Suppression of histamine signaling by probiotic Lac-B: a possible mechanism of its anti-allergic effect

It has been shown that probiotic bacteria are effective for the treatment of allergic diseases. As histamine plays a central role in allergic diseases, it is possible that probiotic bacteria affect the allergy-related histamine signaling. Here, we investigated the effect of Lac-B, a mixture of freeze-dried Bifidobacterium infantis and Bifidobacterium longum, on the allergy-related histamine signaling. In the nasal allergy model rats made by sensitization and provocation with toluene 2,4-diisocyanate (TDI) for 3 weeks, TDI provocation caused acute allergy-like behaviors along with significant up-regulation of histamine H(1) receptor (H1R) and histidine decarboxylase (HDC) mRNA expression, increased HDC activity, histamine content, and [(3)H]mepyramine binding activity in nasal mucosa. Prolonged treatment with Lac-B (40 mg/rat, p.o.) significantly suppressed both the allergy-like behaviors and all of the above mentioned factors involved in histamine signaling. Our findings indicate that oral administration of Lac-B showed significant anti-allergic effect through suppression of both H1R and HDC gene expression followed by decrease in H1R, HDC protein level, and histamine content. Suppression of histamine signaling may be a novel target of probiotics in preventing allergic diseases.     

头孢菌素类药物皮肤过敏的试验及皮试方法的研究

目的观察和分析头孢菌素类药物皮肤过敏的实验以及皮试方法。方法选择我院2010年1月至2011年1月接收的治疗过程中使用头孢菌素类药物的500例住院患者,随机平均分成皮试组与非皮试组,分别观察患者用药后的情况。结果有青霉素过敏史的患者占19.80%,皮试阳性占有率中,其他物质过敏史的占12.02%,无过敏史的占0.55%;皮试阴性组用药后发生的不良用药反应以及过敏反应明显低于非皮试组患者,两组数据差异显著,具有统计学意义。结论影响头孢菌素类药物出现不良药物反应以及皮试阳性发生率的主要因素是患者的过敏史,因此,对具有过敏史患者用药前应该对患者进行采取拟用药皮试。     

The effect of levocabastine nasal spray in nasal provocation tests

The effect of levocabastine, a new specific H1 antagonist, has been investigated against a placebo in nasal provocation tests on 42 allergic patients divided into two parallel groups. The results obtained show that it significantly inhibited the nasal reaction to the allergen and seems to have a long-lasting effect in allergic patients.     

Studies on the experimental allergic rhinitis induced by Japanese cedar pollen--role of cysteinyl leukotrienes in nasal allergic symptoms

Cysteinyl leukotrienes (CysLTs: LTC4, LTD4, and LTE4) are a family of potent inflammatory mediators that appear to contribute to the pathophysiologic features of allergic rhinitis. Because treatment with a CysLT1 receptor antagonist and a 5-lipoxygenase inhibitor modified allergen-induced nasal blockage in patients with allergic rhinitis, and CysLTs were detected in nasal cavity lavage fluid, it has been suggested that CysLTs act as significant inflammatory mediators in allergic rhinitis. The role of CysLTs was evaluated in our experimental allergic rhinitis model in sensitized guinea pigs which shows biphasic nasal blockage, sneezing and nasal hyperresponsiveness to LTD4 induced by repetitive inhalation challenge with Japanese cedar pollen. In this model, the CysLT1 receptor antagonist pranlukast suppressed the late-phase nasal blockage but not early blockage and sneezing. Nasal hyperresponsiveness (nasal blockage) to LTD4 was largely blocked by pranlukast, naphazoline, and N omega-nitro-L-arginine-methyl ester. The results demonstrate that nasal blockage induced by CysLTs is mainly due to dilatation of nasal blood vessels, which can be induced by the nitric oxide produced through CysLT1 receptor activation. On the other hand, when pollen inhalation challenge was performed in the presence of nasal hyperresponsiveness, antigen-induced biphasic nasal blockage and sneezing were considerably enhanced and CysLTs contributed to both symptoms, suggesting that nasal hyperresponsiveness induces aggravation of antigen-induced nasal symptoms. The results presented in this study further suggest that our model is a good representative of human allergic rhinitis and offer evidence that CysLTs are chemical mediators mainly responsible for allergic nasal symptoms.     

薄荷脑鼻腔原位凝胶剂的制备及安全性研究

目的 制备薄荷脑鼻用原位凝胶剂,并对其进行安全性考察。方法 采用去乙酰结冷胶为材料制备离子敏感性原位凝胶。考察鼻腔原位凝胶对蟾蜍鼻黏膜纤毛的毒性及大鼠鼻黏膜的影响;并进行家兔皮肤刺激实验和豚鼠皮肤过敏实验,观察皮肤反应并评分。结果 薄荷脑鼻用原位凝胶剂对蟾蜍鼻黏膜纤毛无显著毒性,对大鼠鼻黏膜形态及细胞分化无显著影响;对家兔完整皮肤无刺激作用,豚鼠皮肤无过敏反应。结论 薄荷脑鼻用原位凝胶剂具有制备工艺简便、纤毛毒性低、生理相容性好的优点,开发为经鼻给药系统可行性良好。