OBJECTIVETo investigate the role of TIM4 (T cell immunoglobulin and mucin domain molecule 4) in the pathogenesis of allergic rhinitis (AR) in mice, and to identify a novel therapeutic target for the treatment of AR.

METHODSTwenty-one male BALB/C mice of clean grade were divided into three groups randomly (n = 7 per group) including control, AR and anti-TIM4 antibody treatment groups. In order to induce upper airway allergic inflammation, the mice from AR and anti-TIM4 antibody treatment groups were sensitized by intraperitoneal injection followed by intranasal challenge with ovalbumin. Before the ovalbumin challenge, a group of mice was treated with anti-TIM4 antibody. To assess the AR model, behavioral observation with immunological assessments and HE staining of nasal tissues were performed. The TIM4 expression in nasal tissues in different groups of mice were assessed by immunofluorescence and RT-PCR.SPSS18.0 software was used to analyze the data.

RESULTSThe AR model in mice was successfully established as shown by behavioral observation and immunological evaluation. RT-PCR assays showed the relative expression of TIM4 mRNA in nasal mucosa of AR, control and anti-TIM4 antibody treatment mice was 16.29 ± 3.80, 0.51 ± 0.60, 1.64 ± 0.98, respectively. There was statistically significant differences mong three group (F = 46.56, P < 0.05). The expression of TIM4 in AR group was significantly higher than those in control group (t = 8.650, P < 0.05) and anti-TIM4 group (t = 8.027, P < 0.05). The expression of TIM4 was significantly reduced in the anti-TIM4 antibody group, as well as control group (t = -0.623, P > 0.05). More expression of TIM4 was detected in local nasal tissues of AR mice, mainly located below the pseudostratified ciliated columnar epithelium.

CONCLUSIONSTIM4 plays a crucial role in the pathogenesis of AR. Effective inhibition of TIM4 expression can partially reverse the pathological changes of AR.

Animals ; Disease Models, Animal ; Male ; Membrane Proteins ; metabolism ; Mice ; Mice, Inbred BALB C ; Rhinitis, Allergic ; metabolism ; pathology

OBJECTIVETo investigate the effect of the non adrenergic non cholinergic nerve (NANC) and substance P (SP) in allergic rhinoconjunctivitis by observing histamine nasal provocation induced conjunctivitis in guinea pigs.

METHODSForty male guinea pigs were randomly divided into five groups with each group consisting of eight guinea pigs. All anesthetized guinea pigs were exposed either to histamine (0.2%, 5 µl) (group B~E) or saline (5 µl, group A) via unilateral nostril. No pretreatment was done in group A and B while pretreatment was done in groups C~E through injection into the unilateral common carotid artery with cholinergic nerve inhibitor (atropine, 1 mg/kg, group C), cholinergic nerve inhibitor plus adrenergic nerve inhibitors (atropine, 1 mg/kg, phentolamine, 1 mg/kg plus Esmolol, 1 mg/kg, group D) and cholinergic nerve inhibitor, adrenergic nerve inhibitors plus SP receptor antagonist (the same treatment with group D plus D-SP 10(-6) mol/L, 1 µl/g, group E), respectively. To assess the ipsilateral conjunctival inflammatory reaction, conjunctiva leakage with Evans blue dye assessments and HE staining of conjunctival tissues were performed. The SP expression in ipsilateral conjunctival tissue in different groups of guinea pigs were assessed by immunofluorescence and RT-PCR. The activity of eosinophils was assessed by eosinophil major basic protein 1 (MBP1) with RT-PCR, meanwhile, the activity of mast cells was assessed by tryptase with RT-PCR. SPSS 17.0 software was used to analyze the data.

RESULTSAt 30 min after nasal application of histamine, ipsilateral conjunctivitis was successfully induced as shown by the change of conjunctiva leakage and histology. The content of Evans blue in ipsilateral conjunctival tissue of group A~E was (13.78 ± 2.48), (29.62 ± 3.31), (19.03 ± 1.47), (18.42 ± 2.52), (14.83 ± 2.14) µg/ml, respectively. There was statistically significant difference between group A and B (t = -10.66, P < 0.05), group B and C (t = 7.97, P < 0.05), group C and E (t = 4.51, P < 0.05). PT-PCR assays showed the relative expression of SP mRNA in ipsilateral conjunctival tissues of group A~E was (1.00 ± 0.04), (1.61 ± 0.09), (1.26 ± 0.03), (1.27 ± 0.06), (1.08 ± 0.05), respectively. There was statistically significant difference between group A and B (t = -22.04, P < 0.05), group B and C (t = 12.93, P < 0.05), group C and E (t = 11.85, P < 0.05). The expression of tryptase of ipsilateral conjunctiva was (1.00 ± 0.01), (1.01 ± 0.05), (1.02 ± 0.17), (1.00 ± 0.14), (1.01 ± 0.20), and the expression of MBP1 was (1.00 ± 0.03), (1.02 ± 0.15), (0.94 ± 0.08), (1.01 ± 0.07), (0.98 ± 0.13) in A~E groups. There was not statistically significant difference among five groups (F value was 1.93, 0.57, both P > 0.05).

CONCLUSIONSHistamine nasal provocation induced allergic inflammatory response of ipsilateral conjunctiva in guinea pigs. Neural factors including NANC nerves and its medium SP participated this nose-ocular reflex process. These data help to develop a more scientific clinical treatment strategy.

Animals ; Conjunctiva ; physiopathology ; Conjunctivitis, Allergic ; chemically induced ; metabolism ; Eosinophils ; cytology ; Guinea Pigs ; Histamine ; adverse effects ; Male ; Mast Cells ; cytology ; Neurons ; cytology ; Substance P ; metabolism ; Tryptases

OBJECTIVETo evaluate the dynamic change of salivary gland function in patients with nasopharyngeal carcinoma (NPC) before and after intensity modulated radiotherapy (IMRT) by DWMRI.

METHODSTwenty-three NPC patients confirmed by pathology were enrolled. Male/Female: 19/4. The age was from 37 to 69 years. All cases underwent salivary glands examination by DWMRI before IMRT, at the end of IMRT, 6 months and 12 months after IMRT, at the same time the ADC value of salivary glands were calculated. The patients were divided into two groups: G1, Dmean < 26 Gy, G2, Dmean ≥ 26 Gy. SPSS 13.0 and SAS 8.2 software was used to analyze the date.

RESULTSThe ADC values of parotid in two group patients at rest were not significantly different between 6 months after and at the end of IMRT (t value was 0.732, 1.405, all P > 0.05). The ADC values of parotid in two group patients at rest were significantly lower in the 12 months after IMRT than at the end of IMRT (t value 2.621, 3.417, all P < 0.05). During the period of acid stimulation, A significant change of ADC in parotid was found in G1 (all P < 0.05) and no significant change of ADC in parotid was found in G2 at the various follow-up time after IMRT (all P > 0.05). At the various follow-up time after IMRT, the average ADC values of parotid were significantly higher in G2 than G1 in the same time points of acid stimulation (all P < 0.05). The ADC values of submandibular glands at rest were significantly higher at the various follow-up time after IMRT than before IMRT (t value was -9.782, -8.963, -7.722, all P < 0.05). During the period of acid stimulation no significant change of ADC in submandibular glands was found after IMRT (F = 1.124, P = -0.348).

CONCLUSIONSThe changes of salivary function can be well reflected by ADC values. There is a good clinical application value of DWMRI for evaluating radiation-induced salivary glands functional changes and observing salivary function recovery during the follow-up period after IMRT.

Adult ; Aged ; Carcinoma ; Diffusion Magnetic Resonance Imaging ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; radiotherapy ; Parotid Gland ; radiation effects ; Radiotherapy Dosage ; Radiotherapy, Intensity-Modulated ; Recovery of Function ; Salivary Glands ; radiation effects ; Submandibular Gland ; radiation effects

OBJECTIVETo dynamically analyze the change of xerostomia in patients with nasopharyngeal carcinoma after radiotherapy by DW MRI.

METHODSTwenty-three nasopharyngeal carcinoma patients confirmed by pathology were enrolled. Male/Female: 19/4. The age was from 37 to 69 years. The patients were divided into two groups: G1, Dmean<26 Gy, G2, Dmean ≥ 26 Gy. All patients underwent salivary glands examination by DW MRI before IMRT, at the end of IMRT, 6 months and 12 months after IMRT, at the same time the ADC value of salivary glands were calculated. According to the RTOG/EORTC salivary gland injury grading standard and referring the subjective index, the degree of xerostomia was assessed. SPSS 13.0 and SAS 8.2 software were used to analyze the data.

RESULTSAt the end of IMRT, the change tendency of ADC in parotid and submandibular glands value was different in patients with different degree of xerostomia (F = 11.52, P < 0.01). At the end of IMRT, a significant difference for degree of xerostomia could be found in patients within different irradiation dose groups (Z = -3.622, P < 0.01). Clinical stage, treatment mode and age had no significant effect on the degree of xerostomia for patients at the end of IMRT (Z value was -0.791, -0.949, 2.488, all P > 0.05). A significant difference of xerostomia degree in patients was found at the various follow-up time after IMRT (χ(2) = 19.59, P < 0.01).

CONCLUSIONSThere is good correlation between the function of salivary gland and subjective rating of xerostomia in patients with nasopharyngeal carcinoma after radiotherapy. The degrees of salivary gland function and dry mouth in patients with nasopharyngeal carcinoma damage evaluate with illuminated dose increases. The function of salivary gland gradually restored and the degree of dry mouth gradually reduce with the extension of time after radiotherapy.

Carcinoma ; Humans ; Nasopharyngeal Neoplasms ; complications ; radiotherapy ; Parotid Gland ; Radiotherapy Dosage ; Radiotherapy, Intensity-Modulated ; Salivary Glands ; Submandibular Gland ; Xerostomia ; etiology