Biodistribution of a carborane-containing porphyrin as a targeting agent for Boron Neutron Capture Therapy of oral cancer in the hamster cheek pouch

Boron Neutron Capture Therapy (BNCT) is a bimodal cancer treatment based on the selective accumulation of 10B in tumors and concurrent irradiation with thermalized neutrons. The short-range, high-LET radiation produced by the capture of neutrons by 10B could potentially control tumor while sparing normal tissue if the boron compound targets tumor selectively within the treatment volume. In previous studies, we proposed and validated the hamster cheek pouch model of oral cancer for BNCT studies, proved that absolute and relative uptake of the clinically employed boron compound boronophenylalanine (BPA) would be potentially therapeutic in this model and provided evidence of the efficacy of in vivo BPA-mediated BNCT to control hamster oral mucosa tumors with virtually no damage to normal tissue. We herein present the biodistribution and pharmacokinetics of a lipophilic, carborane-containing tetraphenylporphyrin (CuTCPH) in the hamster oral cancer model. CuTCPH is a novel, non-toxic compound that may be advantageous in terms of selective and absolute delivery of boron to tumor tissues. For potentially effective BNCT, tumor boron concentrations from a new agent should be greater than 30 ppm and tumor/blood and tumor/normal tissue boron concentration ratios should be greater than 5/1 without causing significant toxicity. We administered CuTCPH intraperitoneally (i.p.) as a single dose of 32 microg/g body weight (b.w.) (10 microg B/g b.w.) or as four doses of 32 microg/g b.w. over 2 days. Blood (Bl) and tissues were sampled at 3, 6, 12, 24, 48, and 72 h in the single-dose protocol and at 1-4 days after the last injection in the multidose protocol. The tissues sampled were tumor (T), precancerous tissue surrounding tumor, normal pouch (N), skin, tongue, cheek and palate mucosa, liver, spleen, parotid gland and brain. The maximum mean B ratios for the single-dose protocol were T/N: 9.2/1 (12h) and T/Bl: 18.1/1 (72 h). The B value peaked to 20.7+/-18.5 ppm in tumor at 24h. The multidose protocol maximum mean ratios were T/N: 11.9/1 (3 days) and T/Bl: 235/1 (4 days). Absolute boron concentration in tumor reached a maximum value of 116 ppm and a mean value of 71.5+/-48.3 ppm at 3 days. The fact that absolute and relative B values markedly exceeded the BNCT therapeutic threshold with no apparent toxicity may confer on this compound a therapeutic advantage. CuTCPH-mediated BNCT would be potentially useful for the treatment of oral cancer in an experimental model.     

Langerin+ versus CD1a+ Langerhans cells in human gingival tissue: a comparative and quantitative immunohistochemical study

Langerhans cells (LC) are dendritic cells of the immune system able to capture intraepithelial pathogens and migrate to regional lymph nodes to present them to naive T cells. Up to now immunohistological studies on human gingival LC have been carried out using antibodies against HLA-DR or CD1a molecules. A new marker of LC called Langerin (CD207) and described, among other subcellular localisations, in the Birbeck granules is now available in immunohistochemistry. The purpose of this in situ study was to quantify and to compare Langerin+ versus CD1a+ LC number in order to show differences in the expression of these molecules, if any, and to determine which marker is the most specific. The present study was conducted using nine frozen healthy gingival samples. Double immunofluorescence procedures were performed with an anti-Langerin antibody revealed by FITC and with an anti-CD1a-PE antibody. Mounted slides were analysed by fluorescence microscopy and quantifications were performed on projected slides associated with a grid of 0.015 mm(2). Our results have shown that 1/ the number of CD1a+ LC was significantly increased (P=0.01) when compared with Langerin+ LC 2/ 92% of Langerin+ LC co-expressed CD1a 3/ only 82% of CD1a+ cells co-expressed Langerin 4/ a positive correlation was noted between CD1a+ and Langerin+ LC numbers. The present study has revealed the heterogeneity in the phenotype of gingival LC population and shown that Langerin seems the most specific marker for the study of LC.     

The effectiveness of bonded composite restorations in the treatment of painful,cracked teeth: six-month clinical evaluation

This study investigated the clinical efficacy of a bonded resin composite restoration with and without cuspal coverage for the treatment of painful, cracked teeth. Patients in a private dental practice who presented with complaints were selected. Inclusion criteria were sensitivity to cold, biting and a clinically-visible crack after removal of the existing restoration. All 40 teeth were restored with a three-step total etch system (Phosphoric acid/Clearfil SA primer/PhotoBond), 20 with cuspal coverage and 20 without. Patients were interviewed at one week, five weeks and six months regarding the presence of pain. In addition, the teeth were clinically examined after six months to reveal any sensitivity. At one week, patients reported that 12 teeth (30%) were free of pain and 28 teeth (70%) still had symptoms. At five weeks, patients reported that 25 teeth (62.5%) were free of pain and 13 teeth (32.5%) still had symptoms. Two teeth (5%) needed endodontic treatment after two and five weeks. At six months, patients reported that 30 teeth (75%) were functioning without any complaints. Upon clinical examination, only 20 teeth (50%) were free of symptoms. No statistically significant difference between the results of the teeth treated with and without cuspal coverage could be shown (Fischer's exact test at p<0.05).     

Prospective evaluation of the referral pattern to restorative dentistry consultation clinics in Ireland

The objective of this study was to analyse pattern of referral to Restorative Dentistry Consultation Clinics in a Dental Teaching Hospital. Patient demographic details and referral information were collected on new patient clinics. The majority of patients were female (62.1%). The greatest proportion of patients, 41.6%, was referred from the adjacent urban area. The highest percentage of referrals was from general practitioners, (37.6%). The main referral reasons were periodontal (24.7%), fixed prosthodontics (18.6%), endodontics (10.7%) and removable prosthodontics (8.3%). The study clearly showed that the majority of patients referred were female and from close proximity to the Hospital. Patients were referred for a broad range of restorative reasons.     

Nervus intermedius neuralgia: a case report

Nervus intermedius neuralgia (NIN) is an uncommon disorder that affects a sensory branch of the facial nerve. This condition usually provokes a very intense and stabbing pain localized in the depth of the ear canal. Due to the close anatomical proximity, temporomandibular joint (TMJ) pathologies should be included in the differential diagnosis. The treatment of NIN has not been established, although it seems reasonable that the therapeutic approaches used in other more common craniofacial neuralgias, such as trigeminal neuralgia, should be effective. In this paper, the authors present a case report of a female patient diagnosed with NIN who was successfully managed with pharmacological treatment.     

Surgical approaches to cavernous haemangiomas of the orbit

Cavernous haemangiomas are the most common orbital masses and the second most common cause of unilateral proptosis after thyroid ophthalmopathy. We retrospectively analysed 19 patients with retrobulbar cavernous haemangiomas, 9 of whom had lateral orbitotomy to remove retrobulbar cavernous haemangiomas located superior (n=4), inferior (n=2) or lateral (n=3) to the optic nerve. Seven patients had lateral orbitotomy together with an anterior medial approach to gain access to retrobulbar cavernous haemangiomas located medially to the optic nerve in the posterior half of the orbit. An anterior approach was used in 3 patient with an anteriorly located cavernous haemangioma. We describe here the planning of surgical treatment based on the site of the lesion.