No abstract

Possible genotoxic effects exerted by three widely used pesticides, permethrin, N,N-diethyl-m-toluamide (DEET) and diazinon, in primary human nasal mucosal cells were investigated. Primary nasal mucosa cells were prepared from tissue biopsies taken from 21 patients who underwent nasal surgery. Cells were exposed to 0.5-1.0 mM concentrations of permethrin, DEET and diazinon for 60 min. Genotoxic effects were detected by the alkaline microgel electrophoresis assay ("comet assay"). Within the concentration range, no significant cytotoxic effects were observed, but all three tested pesticides showed a significant genotoxic response that was concentration dependent. More pronounced genotoxic effects were observed in mucosal cells from the middle turbinate than in the inferior turbinate. The results provide some evidence for the potential carcinogenicity of these agents to human nasal mucosal cells. This should be further investigated.

Activation of the immune system increases systemic adrenal-derived glucocorticoid (GC) levels which downregulate the immune response as part of a negative feedback loop. While CD4+ T cells are essential target cells affected by GC, it is not known whether these hormones exert their major effects on CD4+ helper T cells, CD4+Foxp3+ regulatory T cells (Treg cells), or both. Here, we generated mice with a specific deletion of the glucocorticoid receptor (GR) in Foxp3+ Treg cells. Remarkably, while basal Treg cell characteristics and in vitro suppression capacity were unchanged, Treg cells lacking the GR did not prevent the induction of inflammatory bowel disease in an in vivo mouse model. Under inflammatory conditions, GR-deficient Treg cells acquired Th1-like characteristics and expressed IFN-gamma, but not IL-17, and failed to inhibit pro-inflammatory CD4+ T cell expansion in situ. These findings reveal that the GR is critical for Foxp3+ Treg cell function and suggest that endogenous GC prevent Treg cell plasticity toward a Th1-like Treg cell phenotype in experimental colitis. When equally active in humans, a rationale is provided to develop GC-mimicking therapeutic strategies which specifically target Foxp3+ Treg cells for the treatment of inflammatory bowel disease.

1) Measurement of CS of DPOAE using an extensive measurement paradigm revealed good test-retest repeatability, confirming the reliability of this audiologic tool. 2) CS of DPOAE does not predict individual susceptibility to mild TTS induced by impulse noise in humans. Possible explanations for the missing association are discussed. Future perspectives include longitudinal studies to further elucidate the association between medial olivocochlear bundle-activity and permanent threshold shift in humans. The goal is to develop a diagnostic tool for the prediction of individual noise vulnerability in humans, thereby preventing noise-induced hearing loss.

Our study strongly suggests that exposure to PCP, lindane, transfluthrin, cyfluthrin, and natural pyrethrum has a genotoxic effect on the epithelial cells of human nasal mucosa. In addition, we have shown that nasal structures differ in susceptibility to the various pesticides used in the tests. Thus, the study provides new evidence supporting the biological plausibility of PCP- and lindane-induced effects, thereby helping evaluate potential PCP- and lindane-induced mucous membrane carcinomas of these parts of the nose. In addition, our study shows that other substances that today are widely used for controlling pests have a considerable genotoxic effect on human target cells. The results obtained indicate the need for additional studies on the genotoxicity of these substances and their adverse effects on human health.

La dilatazione tubarica con balloon è stata recentemente annoverata com nuovo metodo minimamente invasive per il trattmento della disfunzione cronica ostruttiva della tuba di Eustachio. Per la prima volta nel mondo, abbiamo definito il ruolo della suddetta tecnica nel trattamento della disfunzione tubarica cronica non rispondente ad altri trattamenti. Sono stati analizzati i dati clinici di 60 bambini (età media: 6,3 anni; range: da 28 mesi a 12 anni) sottoposti a dilatazione della Tuba di Eustachio con il balloon di Bielefeld. In aggiunta, sono stati reclutati i genitori di altri 66 bambini sottoposti a dilatazione con balloon, ed è stato chiesto loro di compilare un questionario standardizzato, e di rispondere ad alcune domande riguardo il decorso postoperatorio dei loro bambini. Non ci sono state complicanze durante gli interventi chirurgici. I sintomi clinici sono migliorati in più dell’80% dei casi. Nessun paziente ha riferito un peggioramento sintomatologico. L’83% dei partecipanti è rimasto notevolmente soddisfatto dei risultati derivanti dal trattamento. La dilatazione con balloon è una tecnica semplice, rapida e sicura per il trattamento della disfunzione tubarica non rispondente ad altri trattamenti sia negli adulti, sia nei bambini. Ulteriori studi, preferibilmente multicentrici, sarebbero utili per definire al meglio le indicazioni già esistenti e potenziali nuovi indicazioni per questa tipologia di trattamento, e per stabilire definitivamente il ruolo di questa tecnica nella gestione della disfunzione tubarica cronica refrattaria.

The effects of locoregional postoperative radiation therapy (60 Gy on average) on cellular immunity were investigated in 11 patients with squamocellular carcinomas of the oral cavity, pharynx, or larynx. During radiation treatment, the total lymphocyte counts, CD8+ T-lymphocyte count, and especially CD4+ T-lymphocyte count decreased significantly. The mean CD4+ T-lymphocyte counts dropped from an average of 739/microl to 183/microl (p <0.001), and the CD4+/CD8+ quotient also decreased significantly. Not only the lymphocyte counts but also the in vitro lymphocyte stimulation responses to several mitogens decreased, with reductions averaging 10% to 50% of normal responses by the end of radiation therapy. Within 3 to 4 weeks after radiation therapy, the CD4+ T-lymphocyte counts and the in vitro lymphocyte stimulation responses showed a tendency toward normalization. This study shows that postoperative locoregional radiation therapy in patients with head and neck cancer induces a severe generalized impairment of cellular immunity.

Follicular dendriti c cell tumors are extremely rare. Only 17 cases have been previously described in the literature, and only three ofthem involved prima ry tumors ofthe oral cavity. We describe a new case of the latter, which occurred in a 51-year-old man who sought evaluationfo r a painl ess enlargement of his lef t palatine tonsil. The tonsil was excised, and histologic examination revealed that the tumor was a prima ry sarcoma that had arisen fr om the dendritic reticulum cells of the palatin e tonsil. Postoperatively, the tumor site was treated with percutaneous irradiation (total dose: 70 Gy). Af ter more than 5 years of f ollow-up, the patient showed no evidence of recurrence. We also discuss the salient f eatures of the immunohistochemical examination.