Drotrecogin alfa (activated) prevents smoke-induced increases in pulmonary microvascular permeability and proinflammatory cytokine IL-1beta in rats.

In an established rat model of smoke inhalation injury, we conducted a dose-response study to examine the protective effects of Xigris [drotrecogin alfa (activated) (DrotAA)], a recombinant form of human activated protein C (APC). DrotAA is a serine protease (approximately 55 kD molecular weight) with the same amino acid sequence and the glycosylation site as human plasma-derived APC. A total of 120 F344/NH rats (half each gender, approximately 175 g body weight) were randomly divided into five groups and exposed nose-only to air or diesel fuel smoke for 20 min. These rats were then i.v. administered with DrotAA in 0, 5, 10, and 20 mg/kg body weight, respectively, immediately following smoke exposure. Treatment with DrotAA significantly attenuated smoke inhalation injury in a dose-dependent manner at 2 hours after insult, as indicated by preserving microvascular permeability and proinflammatory cytokine IL-1beta (but not TNF-alpha and neuropeptide substance P) in bronchoalveolar lavage fluid (BALF). Moreover, the rats treated with 20 mg/ kg of DrotAA had an improvement of the expiration phase of pulmonary dynamic compliance. At all dosages, however, DrotAA also significantly increased all phases of pulmonary resistance compared with either the controls or to smoke inhalation alone. Generally, these data suggest that DrotAA may exert an anti-inflammatory effect by inhibiting cytokine-mediated inflammatory amplification. However, additional studies following a clinical course are needed to confirm the maximum efficiency and possible side effects of this recombined human activated protein C.

Effects of a tartar control whitening dentifrice on tooth shade in a population with long-standing natural stain.

Changing and whitening tooth color in people with long-standing tooth stain without excessive hard tissue abrasion may represent one of the more difficult challenges for whitening dentifrices. An eight-week clinical trial was conducted to evaluate change in tooth color by a silica-based, enamel-safe tartar control whitening dentifrice compared to a marketed baking soda dentifrice control. First, a screening exercise was conducted to identify individuals with long-standing extrinsic dental stain. This exercise targeted adults who reported "stained teeth" and coffee/tea drinking or smoking, but who had no recent history of dental prophylaxis. Targeted subjects were examined for stain (Lobene Index) and tooth shade/color (Vita). A total of 291 adults having extrinsic stain and discolored teeth were enrolled in the study. Subjects were randomized to one of the two treatment groups, and all dentifrice use was unsupervised. Tooth color was measured at 4 and 8 weeks from shade values collected from the 8 incisors, and averages were determined from a linear ordering of the shade guide. A total of 278 evaluable subjects completed the 8-week study. Overall, the tartar control whitening dentifrice group experienced an improvement in color, differing statistically from baseline (p < 0.001) and from the marketed control (p < 0.05). Safety profiles for the two dentifrices were generally similar. Among patients with long-standing extrinsic stain, use of the tartar control whitening dentifrice resulted in superior overall tooth shade and reduced maximum or worst color compared to the marketed baking soda dentifrice control.

Breath effects of three marketed dentifrices: a comparative study evaluating single and cumulative use.

This randomized and controlled, examiner blind, parallel group study was undertaken to evaluate the efficacy of three commercial dentifrices on breath malodor. A total of 384 healthy adult subjects with oral malodor were randomized to one of four brushing groups, using either an antimicrobial dentifrice containing 0.45% stannous fluoride, an antitartar dentifrice containing 0.243% sodium fluoride and 5% pyrophosphate, an antimicrobial dentifrice containing 0.24% sodium fluoride and 0.30% triclosan/copolymer, or bottled distilled water which served as the negative experimental control. Breath quality was evaluated over a five-day period by second-person organoleptic grading and measurement of volatile sulfur levels. Following treatment, adjusted mean organoleptic scores and volatile sulfur levels were lowest for the stannous fluoride dentifrice group, with this group exhibiting superior breath quality compared to the negative control at three hours after a single brushing, and again at all cumulative use time points. While all test dentifrices showed some activity, only stannous fluoride had a second-person breath benefit. Breath effects for the other two dentifrices were limited to reductions in volatile sulfur levels at hours 99 and 104 for the antitartar sodium fluoride pyrophosphate dentifrice, and at hour 99 only for the antimicrobial sodium fluoride triclosan/copolymer dentifrice. This research establishes the comparative breath efficacy of three commercial dentifrices in a study model that may prove relevant for other dentifrice clinical trials.