In this study, we have found that dipeptidylpeptidase IV (DPPIV) plays in vivo an active role in the modulation of the inflammatory response of chronic rhinosinusitis. Human nasal mucosa expresses DPPIV-like immunoreactivity in submucosal seromucus glands, leukocytes, and endothelial cells of blood vessels. DPPIV enzymatic activity in nasal tissue biopsies taken from patients suffering from chronic rhinosinusitis was correlated inversely with the density of inflammatory cells in the nasal mucosa, and the DPPIV activity rose when chronic rhinosinusitis was treated. By using a pig animal model, we have shown that the intranasal administration of recombinant DPPIV decreased the vasodilatation induced by exogenous substance P (SP), a proinflammatory peptide released by sensory nerves. In contrast, an inhibitor of DPPIV enhanced the vasodilatatory effect at low doses of SP. SP5-11 was 100- to 1000-fold less potent than SP as a vasodilator of the nasal mucosa. The vasodilatatory effect of SP was abolished by a NK1 receptor antagonist. In conclusion, these results suggest a new pathophysiological pathway for rhinitis based on clinical observations in humans, indicating the involvement of an enzyme to modulate non-adrenergic and non-cholinergic substrate that occurred during nasal dysfunctions.

Objective: To evaluate the feasibility and efficacy of endoscopic neck dissection (END) in human cadavers. Study Design: Experimental self-controlled study. Methods: END on five human cadavers through three openings: one for the camera, one for the dissecting instrument, and one for a grasping one. The tissue specimens removed were divided into traditional neck groups (I to V). After the completion of END, open neck dissection was performed using standard surgical techniques and the remaining tissue within each neck group was retrieved. The important neck structures (carotid artery, internal jugular vein, cranial nerves X, XI, and XII, phrenic nerve) were evaluated for lesions. A pathologist evaluated each specimen, without knowing its exact origin in terms of neck group or side, and type of surgical technique used. For each specimen, the number of retrieved lymph nodes and their anatomic integrity was analyzed. Results: Ten neck dissections were performed on 5 cadavers, without any major difficulty. An injury of the internal jugular vein occurred twice and once the phrenic nerve was cut. Little tissue was usually left for open surgical dissection. The average number of retrieved lymph nodes by endoscopy was 4.9 ؎ 2.7 (mean ؎ standard deviation). Completion open neck dissection retrieved an additional 0.5 ؎ 0.5 lymph nodes. Efficacy of END was 92 ؎ 10%. The majority of retrieved lymph nodes were intact but exhibited important postmortem autolysis artifacts. Conclusions: Endoscopic neck dissection is possible in human cadavers and is free of lesions to major structures. The majority of neck lymph nodes can be removed endoscopically.

Interleukin-1 receptor antagonist (IL-1Ra) is a natural IL-1 inhibitor, which competitively inhibits binding of IL-1 to its receptors. IL-1Ra is produced as four different isoforms, one secreted (sIL-1Ra) and three intracellular (icIL-1Ra1, 2, 3), derived from the same gene. We previously observed increased production of icIL-1Ra1 in the joints of mice with collageninduced arthritis (CIA). However, due to its intracellular localization, the biological role of icIL1Ra1 remains unknown. The aim of the present study was to examine the effect of the icIL1Ra1 isoform, as compared to that of sIL-1Ra, in the CIA model by comparing transgenic (tg) mice overexpressing icIL-1Ra1 or sIL-1Ra to their wild-type littermates. Serum levels of tg human IL-1Ra were elevated in sIL-1Ra and, to a lesser extent, also in icIL-1Ra1 mice. Clinical scoring indicated that none of the icIL-1Ra1 or sIL-1Ra tg mice developed CIA, whereas arthritis was present in, respectively, 60% and 100% of their wild-type littermates. Histological and radiological analyses confirmed the absence of arthritis in icIL-1Ra1 and sIL-1Ra tg mice. Accordingly, circulating levels of the acute-phase protein serum amyloid A tended to be lower in icIL-1Ra1 tg mice than in their wild-type littermates and were significantly lower in sIL-1Ra tg mice than in controls. In contrast, no difference was observed between the groups regarding serum levels of anti-type II collagen antibodies and ex vivo spleen cell proliferative response to collagen. In conclusion, icIL-1Ra1, which is released into the extracellular space when produced in high amounts, has a similar anti-arthritic effect as sIL-1Ra.

The severity of antigen-induced arthritis (AIA) is decreased in leptin-deficient ob/ob mice. However, joint inflammation in AIA depends on the immune response, which is impaired in ob/ob mice. In the present study we investigated the effects of leptin deficiency on zymosan-induced arthritis (ZIA), which is independent of adaptive immunity. Arthritis was induced by injection of zymosan into the knee joint. Joint swelling was similar after 6 and 24 hours in ob/ob and control mice. However, it remained elevated in ob/ob animals on day 3 whereas values normalized in controls. Histology revealed similar articular lesions in all animals on day 3, but on days 14 and 21 arthritis tended to be more severe in ob/ob mice. The acute phase response, reflected by circulating levels of IL-6 and serum amyloid A, was also more pronounced in ob/ob mice, although corticosterone was significantly elevated in these animals. Similar results were obtained in leptin receptor-deficient db/db mice. Thus, in contrast to AIA, ZIA is not impaired in leptindeficient animals. On the contrary, resolution of acute inflammation appears to be delayed in the absence of leptin or leptin signalling, suggesting that chronic leptin deficiency interferes with adequate control of the inflammatory response in ZIA.

Psammomatous melanotic schwannoma (PMS) is a rare pigmented tumor that can be part of the Carney complex. Here, we describe the case of a 35-year-old female patient presenting an isolated subcutaneous PMS. Histopathological analysis could not formally exclude the malignant nature of the tumor. The challenging histological diagnosis and consequently the management of the patient are described.