In this study, a cationic water-soluble ceramide analog L-threo-C 6 -pyridinium-ceramide-bromide (L-t-C 6 -Pyr-Cer), which exhibits high solubility and bioavailability, inhibited the growth of various human head and neck squamous cell carcinoma (HNSCC) cell lines at low IC 50 concentrations, independent of their p53 status. Consistent with its design to target negatively charged intracellular compartments, L-t-C 6 -Pyr-Cer accumulated mainly in mitochondria-, and nuclei-enriched fractions upon treatment of human UM-SCC-22A cells [human squamous cell carcinoma (SCC) of the hypopharynx] at 1 to 6 h. In addition to its growth-inhibitory function as a single agent, the supra-additive interaction of L-t-C 6 -Pyr-Cer with gemcitabine (GMZ), a chemotherapeutic agent used in HNSCC, was determined using isobologram studies. Then, the effects of this ceramide, alone or in combination with GMZ, on the growth of UM-SCC-22A xenografts in SCID mice was assessed following the determination of preclinical parameters, such as maximum tolerated dose, clearance from the blood, and bioaccumulation. Results demonstrated that treatment with L-t-C 6 -PyrCer in combination with GMZ significantly prevented the growth of HNSCC tumors in vivo. The therapeutic efficacy of L-t-C 6 -Pyr-Cer/ GMZ combination against HNSCC tumors was approximately 2.5-fold better than that of the combination of 5-fluorouracil/cisplatin. In addition, liquid chromatography/mass spectroscopy analysis showed that the levels of L-t-C 6 -Pyr-Cer in HNSCC tumors weresignificantly higher than its levels in the liver and intestines; interestingly, the combination with GMZ increased the sustained accumulation of this ceramide by approximately 40%. Moreover, treatment with L-t-C 6 -Pyr-Cer/GMZ combination resulted in a significant inhibition of telomerase activity and decrease in telomere length in vivo, which are among downstream targets of ceramide.Human head and neck squamous cell carcinomas (HNSCCs) are among the five most common cancers in the world. Global occurrence of HNSCC is high, and it is estimated that approximately 780,000 new patients are diagnosed with HNSCC each year in the adult population. There are approximately 41,000 new HNSCC cases diagnosed annually in the United States in 2004, and the overall 5-year survival of patients with stage III and IV disease remains less than 50% (Her, 2001;Jemal et al., 2004).Historically, chemotherapy did not play a curative role in the treatment of HNSCC but was reserved for palliative therapy. Surgery and radiation therapy remained the primary curative options; however, complications of these ther-

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Allergic rhinitis is the most common atopic disorder seen in ENT clinics. It is diagnosed by history, physical exam and objective testing. Patient education, environmental control measures, pharmacotherapy, and allergen-specific immunotherapy are the cornerstones of allergic rhinitis treatment and can significantly reduce the burden of disease. Current treatment guidelines include antihistamines, intranasal corticosteroids, oral and intranasal decongestants, intranasal anticholinergics, intranasal cromolyn, and leukotriene receptor antagonists. In the mechanism of allergic rhinitis, histamine is responsible for major allergic rhinitis symptoms such as rhinorrhea, nasal itching and sneezing. Its effect on nasal congestion is less evident. In contrast, leukotrienes result in increase in nasal airway resistance and vascular permeability. Antihistamines and leukotriene receptor antagonists are commonly used in the treatment of allergic rhinitis. The published literature about combined antihistamines and leukotriene antagonists in mono- or combination therapy is reviewed and presented.

Upper and lower airways can be considered as a unified morphofunctional unit. In this paper, nasobronchial interactions are evaluated based on literature.To discuss nasobronchial interactions, literature review from PubMed since 1982 is evaluated. Data base was including the terms "nasobronchial interaction, nasal and bronchial". Asthma and rhinosinusitis may be associated with environmental factors and immunological predisposition. Treatment of rhinosinusitis may decrease asthma exacerbations. It was concluded that "one airway, one disease"-concept may be accepted when considering naso-bronchial interaction. Asthma treatment should also mean treating the nose as good as treating patients with nasal symptoms. To reach the succesful results ıt should be associated with evaluation of lung functions.

In the present study, we investigated the outcomes of sublingual immunotherapy (SLIT) in house dust mite-induced allergic rhinitis (HDM-AR) patients. In this prospective, multicentric study, 186 patients with AR who had positive skin prick test results for HDMs were included. The patients were administered SLIT using Staloral 300 for 1 year. Evaluation of the patients regarding symptom scores, clinical findings and Rhinitis Quality of Life Questionnaire (RQLQ) scores was performed at baseline, and then at 6 and 12 months of therapy. Our results showed that, for all of the evaluated items (symptom scores, clinical findings and RQLQ scores), 12-month values were significantly lower than those at 6 months and baseline. Similarly, 6-month values were significantly lower than those at baseline. There were no complications in any of our patients. SLIT for HDM-AR is a treatment modality that can be used safely. We obtained better results than expected, and the treatment showed a positive psychological effect; the patients believed that SLIT was the final step of treatment and, which made them feel better.

Case presentationErythema multiforme like allergic contact dermatitis associated with laurel oil: a rare presentation

There was no statistically significant difference between groups. VEMP responses were found to be normal in NIDDM patients with or without PNP.

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