不同剂量外源性白介素17A干预对变应性鼻炎小鼠气道炎症的影响

目的 探讨不同剂量的外源性白细胞介素17A(IL-17A)干预对变应性鼻炎小鼠气道炎症的影响。 方法 将48只小鼠采用随机数字表法分为A、B、C、D、E、F组,每组8只。分别于第0、7、14天将溶于50 μL生理盐水的20 μg卵清蛋白(OVA)加2 mg铝佐剂腹腔注射处理D、E及F组小鼠,间隔7 d,于第22天开始鼻腔激发,每天每侧鼻孔各滴入OVA 10 μL,连续7 d。D、E及F组小鼠于每次OVA鼻腔激发前1 h分别给予生理盐水、IL-17A蛋白100 ng、IL-17A蛋白500 ng滴鼻,A、B及C组小鼠于相同时点予等量生理盐水腹腔注射并滴鼻,B、C组小鼠于每次生理盐水鼻腔激发前1 h分别给予IL-17A蛋白100 ng、IL-17A蛋白500 ng滴鼻。所有小鼠于最后一次激发后评估鼻部症状学变化,Diff-Quik染色观察鼻腔灌洗液(NLF)中嗜酸性粒细胞浸润情况,ELISA法检测血清及NLF中IL-6、IL-10水平,鼻黏膜组织行甲苯胺蓝染色观察肥大细胞数。 结果 4周末D组所有小鼠症状学评分均>5分,造模成功。A、B、C、D、E及F组症状学评分分别为1.5(1.0~2.8)、2.0(1.0~3.0)、2.5(2.0~3.0)、7.0(6.3~8.0)、3.0(2.3~3.8)及8.0(7.0~8.8)分。E组小鼠挠鼻及喷嚏次数少于D组(H=21.375, P=0.033; H=20.250, P=0.049)。D组小鼠血清及NLF中IL-6水平高于A组(H=25.750, P=0.004; H=20.688, P=0.047),IL-10水平低于A组(H=22.875, P=0.016; H=20.625, P=0.048)。E组小鼠血清及NLF中IL-6水平与A组相比差异无统计学意义(H=19.875, P=0.068; H=8.125, P>0.999)。E组小鼠血清中IL-10水平高于D组(H=27.062, P=0.002)。F组小鼠血清及NLF中IL-6水平高于A组(H=22.250, P=0.008; H=28.688, P=0.001)。F组小鼠血清及NLF中IL-10水平与D组相比差异无统计学意义(H=13.062, P=0.930; H=0.500, P>0.999)。C组小鼠NLF中嗜酸性粒细胞数高于A组(H=20.688, P=0.047)。E组小鼠NLF中嗜酸性粒细胞数低于D组(H=21.188, P=0.037)。F组小鼠NLF中嗜酸性粒细胞数与D组相比差异无统计学意义(H=2.875, P>0.999)。D组小鼠鼻黏膜组织中肥大细胞数与A组相比增多(H=27.188, P=0.002)。E组小鼠鼻黏膜组织中肥大细胞数少于D组(H=20.938, P=0.042)。F组小鼠鼻黏膜组织中肥大细胞数与D相比差异无统计学意义(H=1.188, P>0.999)。 结论 500 ng的外源性IL-17A能促使小鼠鼻腔嗜酸性粒细胞募集,100 ng的外源性IL-17A对变应性鼻炎小鼠模型气道炎症有保护作用。     

Bisphosphonate‐related osteonecrosis of the jaw and its associated risk factors: A belgian case series

Objectives:

Bisphosphonate‐related osteonecrosis of the jaw (BROJ) is a serious oral complication of bisphosphonate (BP) treatment involving the exposure of necrotic maxillary or mandibular bone. Our purpose is to describe the clinical presentation of 34 cases of BROJ and to identify potential risk factors.

Study Design:

A retrospective study was performed in four Belgian institutions.

Methods:

Complete medical histories were recorded and analyzed. These data include age, gender, initial disease requiring BP, type and duration of BP treatment, symptomatology and location of BROJ, prior dental procedures, treatment of the BROJ and treatment outcome, and radiographic, histological, and microbiological data.

Results:

Bisphosphonates (BP) were used in the management of disseminated cancers in 30 patients (88.5% of total studied), while four patients received BP due to osteoporosis (11.5%). The most frequently used BP was zoledronic acid in 29 patients (83%). Microbiological data obtained in 25 patients demonstrated that 72% of these patients were infected or colonized by an actinomyces. Eight of the 14 patients (57%) who received only medical treatment were cured. Of the 20 patients who underwent surgical treatments, only four were completely cured (20%). BROJ lesions smaller than 1 cm are associated with better prognosis in terms of treatment outcomes (P = .0009). Local treatments combined with long‐term antibiotics are also correlated with better prognosis (P = .02).

Conclusions:

Lesions smaller than 1 cm and lesions that were subject to medical treatments are associated with a better outcome. Surgical treatments appear to be non‐beneficial for BROJ. Laryngoscope, 119:323–329, 2009     

A randomized double‐blind study to compare the effects of nasal fluticasone and betamethasone on the hypothalamo–pituitary–adrenal axis and bone turnover in patients with nasal polyposis

Treatment of nasal polyposis with topical betamethasone is associated with suppression of the hypothalamo–pituitary–adrenal (HPA) axis and, potentially, has adverse effects on bone turnover. Fluticasone propionate is a potent corticosteroid with negligible absorption across the nasal mucosa and extensive first‐pass hepatic metabolism. We performed a randomized double‐blind study, in patients with nasal polyposis, comparing the effects of 8 weeks' treatment with betamethasone drops or fluticasone nasules on the HPA axis using the 1 µg tetracosactide test, and on bone turnover using two serum markers. Nine patients were allocated to each treatment. Betamethasone resulted in significant suppression in the tetracosactide test (P = 0.006), but fluticasone did not (P = 0.113). There were no differences in bone turnover or treatment efficacy between treatments. Treatment of nasal polyposis with topical betamethasone drops, but not with fluticasone nasules, suppresses the HPA axis and, given comparable efficacy, fluticasone administered via nasule should be the preferred agent.     

Identification of two novel mutations, c.232T>C and c.2006A>T, in SLC26A4 in a Chinese family associated with enlarged vestibular aqueduct

It is known that enlarged vestibular aqueduct syndrome is closely related to the SLC26A4 mutation. Up to date, more than 200 of SLC26A4 mutations have been described, and novel mutations are being continually identified in different countries and ethnic groups. In this study, two novel variations were identified in a Chinese family associated with enlarged vestibular aqueduct. The two novel substitutions, c.232T>C and c.2006A>T, were detected in exon 3 and exon 17 of the pendrin encoding gene, respectively. The T/C transversion at 232 nucleotide caused p.Y78H mutation while the A/T transversion at 2006 nucleotide caused p.D669V mutation.