Zhenghua Zhu

Peroxisome Proliferator-Activated Receptor–γ Agonist Induces Regulatory T Cells in a Murine Model of Allergic Rhinitis

Objective. To evaluate the effects of peroxisome proliferator-activated receptor (PPAR)–γ agonist on the induction of regulatory T cells (Tregs) in a murine model of allergic rhinitis. Study Design. Randomized controlled trial. Setting. Animal study. Subjects and Methods. BALB/c mice that received ovalbumin sensitization and challenge served as the ovalbumin group (n = 6). Two separate groups of 6 mice received intragastric administration with PPAR-γ agonist pioglitazone (30 mg/kg/d) or pioglitazone plus PPAR-γ antagonist GW9662 (0.5 mg/d) before each ovalbumin challenge. The control group (n = 6) was treated with drug vehicle alone. Various allergic responses were assessed. Real-time polymerase chain reaction was performed to investigate the mRNA expression of forkhead box P3 (Foxp3), T-bet, and GATA-3. Flow cytometry was used to determine the percentage of Tregs. Results. Mice developed typical pathophysiological allergic rhinitis features after the ovalbumin challenge. The frequencies of sneezing and scratching were significantly decreased by pioglitazone treatment (P < .0001). Eosinophils infiltration and the levels of interleukin-5 and interferon-γ in nasal cavity lavage fluid and sera immunoglobulin E were also markedly decreased by pioglitazone (P < .001). The expression of Foxp3 mRNA and the population of Tregs were significantly increased by pioglitazone (P < .05). Cotreatment with GW9662 reversed the anti-inflammatory effects of pioglitazone. The effects of PPAR-γ agonist on Foxp3 mRNA expression and Tregs induction were abrogated by administration of GW9662. Conclusion. PPAR-γ agonist attenuates upper airway allergic inflammation in a PPAR-γ-dependent fashion, and the beneficial effects of pioglitazone in airway allergic inflammation may be mediated by induction of Tregs.

Pioglitazone attenuates allergic inflammation and induces production of regulatory T lymphocytes.

Background Peroxisome proliferator–activated receptor gamma (PPAR-gamma) agonists have been shown to be involved in the regulation of allergic inflammatory responses. The molecular mechanisms by which PPAR-gamma activation inhibits the inflammatory process have not been well understood. Methods BALB/c mice received ovalbumin (OVA) sensitization followed by OVA intranasal challenge. Mice in the treatment group received intragastric administration with pioglitazone (PIO; 30 mg/kg) before each OVA challenge. Various allergic responses were then assessed. Results The frequencies of sneezing and nose-scratching and eosinophil infiltration decreased significantly in the PIO treatment group compared with the OVA group (p < 0.05). The PIO treatment also showed that the levels of nasal cavity lavage fluid interleukin (IL)-5 and sera OVA-specific immunoglobulin E (IgE) were markedly reduced (p < 0.05). PIO significantly increased the expression of Foxp3 mRNA (p < 0.05) and induced production of regulatory T lymphocyte (p < 0.01) compared with the OVA group. Conclusion Given the potent effectiveness shown by PIO, we conclude that PPAR-gamma agonists deserve investigation as potential therapies for human allergic upper airway inflammation.

Exome sequencing identifies a mutation in TMC1 as a novel cause of autosomal recessive nonsyndromic hearing loss

BackgroundAutosomal recessive non-syndromic hearing loss (ARNSHL) is highly heterogeneous, and mutations in the gene encoding transmembrane channel-like 1 (TMC1) have been implicated in its development. To date, 35 homozygous mutations in TMC1, identified in over 60 families worldwide, have been shown to be associated with ARNSHL. However, few of these mutations were detected in the Chinese population. In this study, we describe a pathogenic missense mutation located in the T5–T6 domain of TMC1 in a three-generation Chinese family with 14 members.MethodsWhole exome sequencing was performed using samples from one unaffected individual and two affected individuals to systematically search for deafness susceptibility genes. Candidate mutations and cosegregation of the phenotype were verified by polymerase chain reaction and Sanger sequencing in all of the family members.ResultsWe identified a novel TMC1 mutation in exon 20, c.1979C>T, p.P660L, which segregated with prelingual autosomal recessive sensorineural hearing loss.ConclusionsWe found a new missense mutation in the T5–T6 domain of TMC1, which is highly conserved in many species. These data support the potential conserved role of p.P660L in human TMC1 function.

Dexamethasone suppresses allergic rhinitis and amplifies CD4(+) Foxp3(+) regulatory T cells in vitro.

Glucocorticosteroids (GCs) are highly effective in mitigating allergic inflammation. In this study, we investigate the effects of dexamethasone (DEX) on regulatory T cells (Tregs) in a murine model of allergic rhinitis (AR).

The predictive role of dual source CT for esophageal foreign bodies

INTRODUCTION Esophageal foreign bodies can be a danger to a patients life. Flexible or rigid endoscopy is a commonly used type of invasive investigation for these, and radiological examinations are also useful. STUDY DESIGN Series of reports. METHODS AND RESULTS Multi-slice spiral CT (MSCT) can confirm and locate most foreign bodies. Dual source CT (DSCT) is a more advanced technique with double speed, 20% of the radiation dosage and higher resolution, so it is more suitable for possible esophageal foreign bodies, especially in children, with no need for sedation. We provide a preliminary experiment of a DSCT scan of two fish, and we present a series of 11 cases with DSCT scans of which 5 were positive. CONCLUSIONS Timely diagnosis and accurate localization are paramount for endoscopy. DSCT is very useful for diagnosis and evaluation of esophageal foreign bodies.

Peroxisome proliferator-activated receptor γ agonist suppresses mast cell maturation and induces apoptosis

Peroxisome proliferator-activated receptor gamma (PPAR γ), is important in the immunoregulation of the allergic response. Mast cells are the most important inflammatory cells in immediate hypersensitivity and allergic diseases. However, there is limited information regarding the effects of PPAR γ on mast cell maturation. In the present study, mouse bone marrow-derived mast cells (BMMCs) were cultured in interleukin (IL)-3 and stem cell factor (SCF), in the presence or absence of the PPAR γ agonist, pioglitazone (PIO). The expression levels of the tyrosine kinase receptor CD117 and the high affinity IgE receptor FcεRI α, were assessed by flow cytometry, cell viability was assessed by Alamar-Blue assay and histamine release was determined by measuring the activity of β-hexosaminidase. IL-3 and SCF are required for the development of mast cells in vitro. PIO dose-dependently inhibited the expression of CD117 and FcεRI α, and the maturation of BMMCs. Treatment with PIO additionally inhibited the formation of granules and reduced the expression of β-hexosaminidase. In addition, reverse transcription-polymerase chain reaction analysis revealed that BMMCs treated with PIO expressed a lower level of mast cell protease (MCP)-6 mRNA and PIO treatment enhanced the level of PPAR γ mRNA. Furthermore, PIO induced mast cell progenitor apoptosis. PPAR γ agonists may maintain mast cell homeostasis by inhibiting maturation of their precursors. The inhibitory effects of PPAR γ agonists include suppression of the activation of mast cells and a decrease in mast cell function in the inflammatory response. Therefore, PPAR γ agonists may serve as effective anti-inflammatory reagents in the treatment of allergic reactions.

Complete earlobe keloid resection with fistulectomy.

BACKGROUND The earlobe is a location with a high risk of keloid scar formation. Keloid scars pose a surgical challenge from recidivation. The objective of this study was to investigate a new surgical approach for the treatment of auricular keloids. METHODS AND RESULTS In the past 4 years, 11 earlobe keloids of 9 patients have been excised by fistulectomy (perforation operation). All of the patients were followed up for at least 12 months without recurrence. CONCLUSIONS As a new surgical approach, a perforation operation together with fistulectomy is suitable for lobular keloids.

Cross-over study of topical anaesthesia with tetracaine solution for transoral rigid laryngoscopy.

BACKGROUND Transoral rigid laryngoscopy with videostroboscopy is the most practical method to visualise the vocal folds. The optimal topical anaesthesia regimen for transoral rigid laryngoscopy has not yet been established. OBJECTIVE To compare patient comfort and compliance with various topical anaesthetics for transoral rigid laryngoscopy. METHODS Each of 10 patients received a random topical administration of either 2 per cent lidocaine gel, 1 per cent tetracaine gel or 1 per cent tetracaine solution, 10 minutes before undergoing rigid laryngoscopy with videostroboscopy. During follow-up laryngoscopies, the agent with the lowest mean visual analogue scale score for discomfort was then used to study the timing of topical anaesthetic application: the agent was given to the patient 5, 10 or 15 minutes before laryngoscopy (with the timing randomly selected). RESULTS Compared with lidocaine gel or tetracaine gel, laryngoscopy with topical tetracaine solution was more comfortable. There was a statistically significant difference in discomfort score between the 5 and 10 minute application groups, but not between the 10 and 15 minute groups. CONCLUSION Tetracaine solution, applied topically 10 minutes before transoral rigid laryngoscopy, significantly decreases patient discomfort.

Evaluation of Neck Lymph Node Metastasis on Contrast-Enhanced Ultrasound: An Animal Study

Objectives To assess the performance of contrast-enhanced ultrasound (CEUS) intended to differentiate hyperplastic from malignant neck lymph nodes in an animal model. Methods Twenty-four New Zealand rabbits were randomly divided into two groups: neck lymph node metastasis group (12 rabbits) and reactive hyperplastic lymph node group (12 rabbits). Tongue VX2 carcinoma with cervical lymph node metastasis was induced in 12 rabbits by injecting VX2 carcinoma suspension into the left tongue submucosa. Hyperplastic neck lymph nodes were induced by injecting egg yolk in the submandibular region of the rabbits in hyperplastic group. CEUS were performed in both groups before and after intravenous administration of SonoVue. The site, number, echogenicity, longitudinal and transverse nodal dimensions, patterns of enhancement of the neck lymph nodes were observed and recorded. Results In both groups only one lymph node was found in the left (tumor) side of the neck. CEUS found 12 of 12 metastatic lymph nodes in metastasis group, and diagnosed 11 of 12 lymph nodes as metastatic. Histopathologic analysis revealed metastatic lesions in all 12 rabbits, each with one lymph node, and all 12 lymph nodes in hyperplastic group is inflammation lymph nodes. All 12 cases in the hyperplastic group showed centripetal homogeneous enhancement while in the metastasis group one case showed centripetal homogeneous enhancement, three cases showed centrifugal heterogeneous enhancement, and eight cases showed diffused heterogeneous enhancement. Only one lymph node was dissected on the left side of the neck in each rabbit in both groups. Conclusion CEUS can play a role in discriminating metastatic from hyperplastic lymph nodes in head and neck carcinoma.

Treatment for 15 Cases of Cervical Tuberculosis

After a detailed medical history had been taken along with clinical examination, excision biopsy of involved nodes was performed in patients with cervical lymphadenopathy. Biopsy of the deep cervical abscess was performed on the occasions when the cervical lymph nodes were either negative or uncertain and clinical suspicion was high for tuberculosis. Routine tests including complete blood count, erythrocyte sedimentation rate (ESR), Mantoux test (purified protein derivative skin test), chest radiography, transnasal fiberoptic laryngoscopy, cervical and abdominal ultrasound, and sputum examination for acid‐fast bacilli were also performed in all of the patients. After confirmation of diagnosis, all patients were transferred to the Department of Pulmonary Tuberculosis and treated with standard chemotherapy. All of the patients were followed up at monthly intervals for at least 6 months and progress was assessed by clinical examination as well as 3‐monthly ESR estimation. Tuberculosis was the most common cause of cervical lymphadenopathy or abscess, accounting for 15 out of 52 cases. Other causes included metastatic (11 patients), nonspecific inflammation (14 patients), lymphoma (4 patients), infectious branchial cleft cysts (2 patients), or other infectious cervical cysts (6 patients).