Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults.

VRC-HIVMAB060-00-AB (VRC01) is a broadly neutralizing HIV-1 monoclonal antibody (mAb) isolated from the B cells of an HIV-infected patient. It is directed against the HIV-1 CD4 binding site and is capable of potently neutralizing the majority of diverse HIV-1 strains. This Phase I dose-escalation study in healthy adults was conducted at the National Institutes of Health (NIH) Clinical Center (Bethesda, MD, USA). Primary objectives were the safety, tolerability and pharmacokinetics (PK) of VRC01 intravenous (i.v.) infusion at 5, 20 or 40 mg/kg, given either once (20 mg/kg) or twice 28 days apart (all doses), and of subcutaneous (s.c.) delivery at 5 mg/kg compared to s.c. placebo given twice, 28 days apart. Cumulatively, 28 subjects received 43 VRC01 and nine received placebo administrations. There were no serious adverse events or dose-limiting toxicities. Mean 28-day serum trough concentrations after the first infusion were 35 and 57 µg/ml for groups infused with 20 mg/kg (n = 8) and 40 mg/kg (n = 5) doses, respectively. Mean 28-day trough concentrations after the second infusion were 56 and 89 µg/ml for the same two doses. Over the 5-40 mg/kg i.v. dose range (n = 18), the clearance was 0.016 l/h and terminal half-life was 15 days. After infusion VRC01 retained expected neutralizing activity in serum, and anti-VRC01 antibody responses were not detected. The human monoclonal antibody (mAb) VRC01 was well tolerated when delivered i.v. or s.c. The mAb demonstrated expected half-life and pharmacokinetics for a human immunoglobulin G. The safety and PK results support and inform VRC01 dosing schedules for planning HIV-1 prevention efficacy studies.

The ability of 1.23% acidulated phosphate fluoride gel to inhibit simulated endogenous erosion in tooth roots.

BACKGROUND: Endogenous dental erosion is that produced by contact of gastric acids with tooth structure. It may affect exposed root cementum/dentine as well as coronal enamel, causing marked loss of mineral. The aim of this study was to determine whether 1.23 per cent acidulated phosphate fluoride gel, if applied to the surface cementum at certain intervals during an erosive acid challenge, could provide any protection against demineralization. MATERIALS AND METHODS: Roots of preserved extracted human teeth were painted with a water and acid resistant varnish, leaving two windows (3x1mm) of exposed dentine. These were placed in a solution containing 0.06MHCl and 2.2mMCaHPO4, which has been shown to simulate gastric acid when it meets the tooth surface. The roots were placed in the erosive solution unprotected (controls), or subject to APF application for four minutes prior to and every 10, 30 or 120 minutes during the erosive challenge. Roots were removed at either 6 or 12 hours, washed thoroughly and cut into 120microm thick sections. Depths of demineralization were measured using an optical graticule under polarized light microscopy. RESULTS: A high level of protection was provided when the roots were coated with APF gel every 10 or 30 minutes. CONCLUSIONS: APF gel will partially inhibit endogenous erosion of roots for up to 30 minutes if applied, for example, the night before a morning reflux episode. This should be considered along with other erosion control or reduction procedures for patients suffering from the effects of endogenous erosion.

Langerhans cell histiocytosis presenting as bilateral eosinophilic granulomata in the molar region of the mandible. A case report.

Eosinophilic granuloma represents one of a triad of lesions encompassing a disease under the generic name, histiocytosis X or Langerhans cell histiocytosis. Localised eosinophilic granuloma, multifocal eosinophilic granuloma, Hand-Schüller-Christian disease, and the most malignant form of histiocytosis, Letterer-Siwe disease, can all present as destructive bony lesions of the jaws. The present case was a 30-year-old man who presented with almost total destruction of the periodontal support to the left and right mandibular, 1st and 2nd molars. Whereas the radiographic features were typical of eosinophilic granuloma, the clinical appearance and mirror image presentation were unusual.