A hyaluronic acid-based compound inhibits fibroblast senescence induced by oxidative stress in vitro and prevents oral mucositis in vivo.

Virtually all patients receiving radio- and chemotherapy for cancer develop oral mucositis, a severe and highly debilitating condition. The onset of mucositis is thought to involve the production of reactive oxygen species (ROS) in the submucosa. Here we investigated a possible protective effect of a commercial formulation of hyaluronic acid (HA) enriched with amino acids (Mucosamin(®)) against the damage induced by oxidative stress both in vitro and in vivo. Transient exposure of normal human oral fibroblasts to hydrogen peroxide (H(2)O(2)) led to irreversible senescence, as demonstrated by sustained increase in the levels of p16(INK4A) and SA-ßGal. Conditioned media from senescent fibroblasts induced detrimental effects on keratinocytes, as shown by reduced metabolic activity and migration capability. Pre-treatment with Mucosamin(®) prevented H(2)O(2) -induced, but not TGF-ß-induced, fibroblast senescence with a concomitant reduction of fibroblast-induced loss of keratinocyte vitality and functional activity. Finally, data from a case-series of patients undergoing radio/chemotherapy strongly suggested that prophylactic use of the hyaluronic acid-based compound in the form of a spray may be effective in preventing the onset of oral mucositis.

Lethality rescue and long-term amelioration of a citrullinemia type I mouse model by neonatal gene-targeting combined to SaCRISPR-Cas9.

Citrullinemia type I is a rare autosomal-recessive disorder caused by deficiency of argininosuccinate synthetase (ASS1). The clinical presentation includes the acute neonatal form, characterized by ammonia and citrulline accumulation in blood, which may lead to encephalopathy, coma, and death, and the milder late-onset form. Current treatments are unsatisfactory, and the only curative treatment is liver transplantation. We permanently modified the hepatocyte genome in lethal citrullinemia mice (Ass1fold/fold) by inserting the ASS1 cDNA into the albumin locus through the delivery of two AAV8 vectors carrying the donor DNA and the CRISPR-Cas9 platform. The neonatal treatment completely rescued mortality ensuring survival up to 5 months of age, with plasma citrulline levels significantly decreased, while plasma ammonia levels remained unchanged. In contrast, neonatal treatment with a liver-directed non-integrative AAV8-AAT-hASS1 vector failed to improve disease parameters. To model late-onset citrullinemia, we dosed postnatal day (P) 30 juvenile animals using the integrative approach, resulting in lifespan improvement and a minor reduction in disease markers. Conversely, treatment with the non-integrative vector completely rescued mortality, reducing plasma ammonia and citrulline to wild-type values. In summary, the integrative approach in neonates is effective, although further improvements are required to fully correct the phenotype. Non-integrative gene therapy application to juvenile mice ensures a stable and very efficient therapeutic effect.

Salivary gland biopsy: a comprehensive review of techniques and related complications.

OBJECTIVE: This study proposes a revision of the literature on the current techniques employed in salivary gland biopsy. METHODS: A systematic review of the literature between January 1990 and January 2010 was conducted using MEDLINE, Embase and the Cochrane Central Register of Controlled Trials. The search terms were: 'biopsy AND parotid AND Sjögren'; 'biopsy AND sublingual salivary gland AND Sjögren'; 'biopsy AND minor salivary gland AND Sjögren'; 'biopsy AND labial salivary gland AND Sjögren' and 'biopsy AND salivary glands AND connective disorders'. RESULTS: No study reporting submandibular salivary gland biopsy was found; 3 studies reported sublingual salivary gland biopsy; 1 study reported palate biopsy; 4 studies reported parotid gland biopsy and 21 studies reported minor salivary gland biopsy. CONCLUSION: Biopsy of salivary glands must be performed as last investigation and only when the other items are not complete enough to satisfy the diagnosis. The knowledge of complications and sequelae may be useful in order to minimize the risk.

Usefulness of the LigaSure vessel sealing system during superficial lobectomy of the parotid gland.

OBJECTIVE: To evaluate the usefulness of the LigaSure Precise instrument in superficial lobectomy of the parotid gland. DESIGN: Prospective study of the surgical procedures in the LigaSure Vessel Sealing System and comparison with a conventionally treated control group. SETTING: Secondary care academic referral center. Patients Thirty-five patients with a parotid gland benign tumor were randomly allocated to 2 superficial lobe parotidectomy groups: 17 using the LigaSure procedure (group A) and 18 using the conventional method (group B). MAIN OUTCOME MEASURES: During the past few years, different methods of achieving hemostasis in parotid gland surgery have been tested as means of decreasing operative time and facial nerve injuries by controlling bleeding. With the whole LigaSure Vessel Sealing System, we experienced the usefulness of the LigaSure Precise instrument in superficial lobectomy of the parotid gland. RESULTS: No statistically significant differences were noted between the 2 groups in mean age, tumor diameter, length of hospital stay, time to return to work, or number of adverse events during or after surgery. Operative time was significantly shorter in group A than in group B (P < .001). Total operative time for conservative partial parotidectomy with traditional excision ranged from 115 to 235 minutes (mean, 155.8 minutes). Using the LigaSure system, the mean operative time was 136.4 minutes. Salivary fistulas were more common in group A (3 of 17 patients), with no cases in group B. CONCLUSIONS: The LigaSure method is comparable with but not superior to the conventional method. The main advantages of the LigaSure system are its "sutureless technique" and operative time savings; however, the cost is considerably higher.

Endoscopic management of salivary gland obstructive diseases in patients with Sjögren's syndrome.

PURPOSE: To evaluate, on the basis of our clinical experience, the reliability of an endoscopic approach to the management of obstructive salivary diseases related to Sjögren's syndrome. MATERIAL AND METHODS: A retrospective review of all patients affected by Sjögren's syndrome who were followed up at the Maxillo-Facial Unit of the Second University of Naples Hospital and referred from the Reumatology Unit of the same hospital from September 2007 to July 2012 for chronic obstructive sialadenitis unresponsive to medical therapy. A total of 34 patients (29 women and 5 men) were recruited for this study. After the detection of the impaired gland, under local anesthesia with lidocaine 2% to the orifice region and a gradual dilation of the duct orifice, the diagnostic unit was introduced into the duct and was advanced forward until reaching the ductal system, with continuous lavage with isotonic saline solution. The plaques were washed out, and any strictures were dilated. Mucus plugs and debris were removed with irrigation or with a forceps if necessary. RESULTS: Our cohort included 34 patients with a mean age of 51.76 years. A total of 60 parotid glands and 25 submandibular glands were explored and treated. Strictures were found in 38 glands (38 of 85; 45%), mucus plugs in 47 glands (47 of 85; 55%), mucus plugs and strictures together in three glands (3 of 85; 4%), and kinks in two glands (2 of 85; 2%). In 32 parotid glands (32 of 60; 53%) the Stensen duct was affected, in two (2 of 60; 3%) only secondary ducts, and in 18 (18 of 60; 30%) both. In submandibular glands explored, strictures and mucus plugs were mainly observed in Wharton ducts. Symptomatic improvement was achieved in 29 patients (29 of 34; 85%), in a follow-up period ranging from 5 months to 3 years. CONCLUSIONS: Interventional sialoendoscopy is a viable technique to treat acute symptomatology in patients with obstructive salivary gland diseases related to Sjögren's syndrome and refractory to conventional management.

Neurosensory disturbance of the inferior alveolar nerve after bilateral sagittal split osteotomy: a systematic review.

PURPOSE: The evaluation of neurosensory disturbance of the inferior alveolar nerve (IAN) can be performed by purely subjective, relatively objective, or purely objective methods. The aim of this study was to provide a systematic review of the incidence of inferior alveolar nerve sensory disturbance after bilateral sagittal split osteotomy, as well as the frequency of recovery of sensory function using objective methods of evaluation only. MATERIALS AND METHODS: Searches were conducted employing MEDLINE, Scirus, and the Cochrane Central Register of Controlled Trials (CENTRAL). Seven studies were included in this review. RESULTS: This systematic review has shown that the frequency of nerve impairment evaluated by subjective methods was higher than that indicated by studies adopting objective methods at each time of follow-up considered. In particular at the seventh postoperative day the frequency obtained using the objective methods was 63.3% while that obtained with subjective methods was 83%. At 1 year follow-up a frequency of sensory impairment of 12.8% was obtained using objective methods and a frequency of 18.4% when subjective methods were used. The data were analysed using the index of inter-rater reliability (Cohen's Kappa) with the degree of nerve damage evaluated by objective methods considered the "gold standard." The value of Cohen's Kappa at 1 week follow-up is 0.53; at 1 year follow-up it increased to 0.90. CONCLUSIONS: On the basis of these results, objective methods provide the most sensitive diagnostic tests at early controls-within 3 months of the operation. At later control points the sensitivity increases and the inter-rater reliability is satisfactory.