Hyaluronan synthases and hyaluronidases in nasal polyps.

Nasal polyps (NPs) are benign lesions of nasal and paranasal sinuses mucosa affecting 1-4 % of all adults. Nasal polyposis affects the quality of patient's life as it causes nasal obstruction, postnasal drainage, purulent nasal discharge, hyposmia or anosmia, chronic sinusitis, facial pain and snoring. Without treatment, the disease can alter the craniofacial skeleton in cases of extended growth of polyps. The development of NPs is caused by the hyperplasia of nasal or paranasal sinuses mucosa, and edema of extracellular matrix. This is usually the result of high concentration of high molecular mass hyaluronan (HA) which is either overproduced or accumulated from blood supply. The size of HA presents high diversity and, especially in pathologic conditions, chains of low molecular mass can be observed. In NPs, chains of about 200 kDa have been identified and considered to be responsible for the inflammation. The purpose of the present study was the investigation, in NPs and normal nasal mucosa (NM), of the expression of the wild-type and alternatively spliced forms of hyaluronidases, their immunolocalization, and the expression of HA synthases to examine the isoform(s) responsible for the increased amounts of HA in NPs. Hyaluronidases' presence was examined on mRNA (RT-PCR analysis) and protein (immunohistochemistry) levels. Hyaluronan synthases' presence was examined on mRNA levels. Hyaluronidases were localized in the cytoplasm of epithelial and inflammatory cells, as well as in the matrix. On mRNA level, it was found that hyal-1-wt was decreased in NPs compared to NM and hyal-1-v3, -v4 and -v5 were substantially increased. Moreover, HAS2 and HAS3 were the only hyaluronan synthases detected, the expression of which was almost similar in NPs and NM. Overall, the results of the present study support that hyaluronidases are the main enzymes responsible for the decreased size of hyaluronan observed in NPs; thus they behave as inflammatory agents. Therefore, they could be a potential target for the design of a more advanced treatment for nasal polyposis.

Determination of matrix metalloproteinase 9 (MMP-9) protein expression in laryngeal squamous cell carcinomas based on digital image analysis.

PURPOSE: Matrix metalloproteinases (MMPs) is a superfamily of proteins involved in angiogenesis and metastatic tissue invasion in many cancers. Overexpression of MMP- 9 has been detected in significant proportions of laryngeal squamous cell carcinomas (LSCCs), but its prognostic impact remains unclear. In this study we performed a digital image analysis for analyzing MMP-9 protein expression in a series of LSCCs correlating them with clinicopathological factors. METHODS: MMP-9 protein expression level was determined immunohistochemically in 30 tissue sections surgically derived from patients (21 male and 9 female) with LSCC. Using digital image analysis, we measured their corresponding protein expression levels (staining intensity/S.I. range values 0-255). RESULTS: Moderate and high MMP-9 protein expression levels (grouping as 2+/3+ overexpression) were detected in 19/30 (63.3%) cases. Statistical significance was observed correlating stage with SI (p=0.02), whereas a borderline association with differentiation grade of the examined tumors was also registered (p=0.05). Interestingly, high levels of MMP-9 expression were observed in cases that demonstrated a significant level of inflammatory (predominantly lymphocytic) infiltration. CONCLUSION: MMP-9 protein overactivation is a frequent and significant genetic event in LSCC, correlating with its biological behavior (increased TNM stage). MMP-9 seems to mediate an epithelial-stromal intra-reaction correlating also with induction of specific inflammation pathways.

Presence of hyaluronidase isoforms in nasal polyps.

BACKGROUND: Nasal polyps are benign lesions originating from the nasal mucosa or paranasal sinuses. The most important etiological factor seems to be increased hydration of epithelium and hyperplasia of the extracellular matrix, which may involve hyaluronan, a high molecular mass extracellular glycosaminoglycan. Degradation of hyaluronan proceeds through the action of specific hyaluronidases. OBJECTIVE: The aim of the present study was to investigate the hydrodynamic size of hyaluronan and the presence of the various hyaluronidase isoforms in nasal polyps. METHODS: Samples of polypoid mucosal tissue and normal nasal mucosa were obtained from twenty patients suffering from nasal polyposis. Zymographic analysis and western blotting were used to detect hyaluronidase activity. RESULTS: The results indicated the presence of hyaluronan of small molecular mass in all samples examined. About one third of it has a mean molecular mass of 240 kDa, exactly that required for the expression of inflammatory response. Laboratory analysis suggested that degradation of hyaluronan occurred through the action of three hyaluronidase isoforms: Hyal-1, Hyal-2 and PH-20. CONCLUSIONS: Since hyaluronan fragments of 200-250 kDa induce the expression of inflammatory cytokines, a specific role of hyaluronidases in the development or progression of nasal polyps may be concluded. Therefore, new treatment protocols may be proposed.

Necrotizing fasciitis of the head and neck: report of 5 cases and review of the literature.

BACKGROUND: Necrotizing fasciitis (NF) is a severe, rapidly spreading soft tissue infection of polymicrobial origin. This condition most frequently affects thorax, abdominal wall, extremities, perineum and groin, but according to recent literature the head and neck area is also involved with increasing frequency. PATIENTS AND METHODS: Five cases of head and neck NF were detected among patients who were admitted at the Department of Otorhinolaryngology-Head and Neck Surgery of the University Hospital of Patras, Patras, Greece, over a 5-years period. Various parameters including patients' health status, co-morbidity, etiology, microbiology, affected area, antibiotic therapy, hospital stay, surgical treatment and complications were considered. CONCLUSIONS: The management of NF should comprise of hemodynamic and respiratory evaluation and monitoring, broad-spectrum i.v. antimicrobial therapy, surgical debridement and nutritional support. Close postoperative management of NF patients remains of paramount importance.

Rhinocerebral mucormycosis: an update.

BACKGROUND AND OBJECTIVES: Mucormycoses are a group of invasive infections caused by filamentous fungi of the Mucoraceae family, with the rhinocerebral form of the disease being the most common in large case series. In the present paper we review the characteristics of the rhinocerebral form of the disease. EVIDENCE AND INFORMATION SOURCES: The present review is based on the analysis of the current literature on rhinocerebral mucormycosis. STATE OF THE ART: Rhinocerebral mucormycosis is associated with immunocompromised patient state, haemochromatosis, desferrioxamine therapy and prolonged corticosteroid therapy. Uncontrolled diabetes and increased serum iron are regarded as the two leading predisposing factors for the development of the disease. Currently, treatment for the disease is based on three main principles; rapid reversal of underlying predisposing factors, antifungal therapy with amphotericin B and timely surgical intervention. PERSPECTIVES: Antifungal drugs of the azole group and new iron chelating agents--deferasirox, deferiprone--have been supported as alternative options to amphotericin B or as salvage therapy. CONCLUSIONS: Rhinocerebral mucormycosis requires a high level of awareness if early diagnosis and treatment is to be achieved. Large scale evaluation of arising treatment options is a mandatory course of action in the future research of the disease.

Lateral neck abscess caused by Streptococcus bovis in a patient with undiagnosed colon cancer.

Bacteraemia or endocarditis caused by Streptococcus bovis, a non-enterococcal group D streptococcus, is a very common finding in patients suffering from intestinal tumours or other colon diseases. A case of a patient with a laternal neck abscess caused by S. bovis is reported. During the treatment the patient was found to have colonic malignant lesions. The problems in the appropriate diagnosis and the possible correlation between these two clinical entities are presented and discussed.

Periapical abscesses: causal bacteria and antibiotic sensitivity.

The purpose of this study was to investigate the aerobic and anaerobic flora of periapical abscesses and evaluate their susceptibility to various antibiotics. In 52 patients, with a diagnosis of periapical abscesses, pus cultures were taken. Forty-two aerobes and 122 anaerobes were revealed, with 2 or more than 2 anaerobic strains isolated in 36 patients. Infections were purely aerobic in 6%, purely anaerobic in 17% and mixed in 75%, while in 2% of the specimens there was no growth of microorganisms. Among anaerobes, microorganisms from the Bacteroides group (38.5%), Peptostreptococcus spp. (24.6%), Peptococcus spp. (13.9%), and Fusobacterium spp. (4.1%), predominated in all cultures. Among aerobes the most prevalent bacteria were streptococci (47.6%) followed by staphylococci (35.6%) while Enterobacteriaceae were isolated in 4.8% of specimens. Selected susceptibility tests performed on several anaerobic species revealed that nitroimidazole derivatives, chloramphenicol and clindamycin retain their broad spectrum killing activity against anaerobes, followed by cefoxitin and moxalactam. Of the newer quinolones, ofloxacin was the most effective. It is evident that the high isolation rate of anaerobic bacteria should influence empiric therapeutic decisions.