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Glumetz (Depomed, Inc., Menlo Park, CA, USA) is a recently approved gastric retentive extended-release formulation of metformin (M-ER) that provides effective, sustained and well-tolerated glycemic control with once daily administration. Pharmacokinetic studies have demonstrated a similar bioavailability of M-ER administered once daily to immediate-release metformin given twice daily. In addition, M-ER has demonstrated a nearly linear dose proportionality with a relative bioavailability of highest dose to lowest dose of 80%, whereas with immediate-release metformin the relative bioavailability of the highest dose to the lowest dose is only 58%. M-ER demonstrated a positive food effect and should be administered with a meal, preferably the evening meal. Because metformin is only eliminated through renal mechanisms, the use of M-ER, as is the case with other formulations, is contraindicated in patients with renal impairment. Administration of M-ER with sulfonylureas (SUs) had no effect on the pharmacokinetics of metformin. In controlled clinical trials M-ER demonstrated efficacy for 24 weeks as a monotherapy or in combination with SU. Additionally, glycemic control was maintained for an extra 24 weeks in an open-label monotherapy extension study of M-ER. M-ER was well tolerated in all studies.

First and second maxillary molar tooth germs with their surrounding bone were removed from 9-day-old mice, freed of the reduced enamel epithelium, re-inserted crown downwards in their bony crypts and then transplanted in the subcutaneous tissue of hosts of the same age and litter. Grafts were removed 14 days later and prepared for light and electron microscopy. In the areas where the reduced enamel epithelium was missing, a layer of cementum-like tissue was present on the enamel surface, always associated with cells showing the typical features of cementoblasts. A thin electron-lucent layer of fine fibrillar material separated the enamel surface from the new hard tissue which was composed of densely-packed collagen mixed with a ground substance. Where the cementum-like tissue was thick, cells were trapped in a collagenous matrix. The cementogenesis on enamel was strictly dependent on the absence of the reduced enamel epithelium. Thus, when exposed to follicular tissue, the surface of immature enamel appears to exert an influence on follicular cells and stimulate cementogenesis. This hypothesis could explain the presence of overgrowths of cementum in the cervical region of tooth crowns where the reduced enamel epithelium may be particularly vulnerable.

THE PRESENT STUDY was undertaken to verify whether acid conditioning of the root surface can promote new connective tissue attachment in man. A flap was raised over two maxillary central incisors, with 6-mm pockets, which had to be extracted in a 72-year-old woman. Following root planning, a rectangular area was delineated by a groove on the buccal surface of the teeth. Inside these limits, cementum was removed and the denuded dentin was etched with a 50% gelified phosphoric acid solution (pH, 1.3) for 1 minute and the flap was repositioned. Forty-two days later, the experimental teeth were extracted, and undecalcified specimens were prepared routinely for transmission electron microscopy. Results showed that new connective tissue attachment had occurred between healing connective tissues and acid-treated dentin surface, with functionally oriented Sharpey's fibers. The mechanism of new connective tissue attachment could be observed as a typical cementum crystallites deposition on a denuded dentin matrix coupled with an active collagen fibrils synthesis. This process resulted in the incorporation of fibers into the new superficial layer of cementoïd tissue.

After injection of vinblastine sulfate (VLB) cells of the epithelial root sheath (ERS) showed accumulation of phagosomes lysosomes and, in particular, of exocytosis vesicles facing the basal lamina. An unusual frequency of cell contacts was also noted between pulp mesenchyme and ERS. In the periradicular zone the cells showed accentuated signs of a squamous-like evolution. In addition, numerous mitotic figures were seen arrested at prometaphase all along the tissue: the mitotic arrest index was higher at the tip of the sheath and decreased more coronally. These findings strongly suggest that ERS participates actively to the formation of the basal lamina. They show that heterogenous cell relations frequently occur during root morphogenesis; however they put into question the role of ERS in cementogenesis. The existence of a high mitotic potential in ERS can explain its consistent morphology and might reflect a process of differential mitotic sequences involved in odontoblast differentiation.