Relationship between crevicular aspartate aminotransferase levels and periodontal disease progression.

BACKGROUND: Aspartate aminotransferase (AST), an enzyme released from necrotic cells, has been identified in gingival crevicular fluid (GCF), and elevated levels are associated with periodontal tissue destruction. The aim of this study was to examine the relationship between elevated GCF levels of AST and periodontal disease progression. METHODS: Over a 12-month period, 8 to 10 interproximal sites in 41 periodontitis subjects (PS) and 15 healthy subjects (HS) were monitored. Clinical measurements included relative attachment level (RAL), probing depth, and bleeding on probing (BOP). Semiquantitative levels of GCF AST (< 800 microIU, > or = 800 microIU, and > or = 1,200 microIU) were determined using a chairside assay. At the 6- and 12-month visits, scaling and root planing and prophylaxis were performed in the PS and HS, respectively. Sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) were calculated for 2 diagnostic criteria (AST > or = 800 microIU, AST > or = 1,200 microIU) utilizing 4 thresholds of disease progression as determined by 2 methods (absolute change in relative attachment level and cumulative sum [CUSUM]). RESULTS: The percentage of sites exhibiting AST > or = 800 microIU, AST > or = 1,200 microIU, and BOP in the PS was significantly (P<0.02) lower at 6 and 12 months compared to baseline. The use of crevicular AST activity to monitor periodontal disease progression was associated with many false-positive results. Overall, low specificities, PPV, and odds ratios were demonstrated by the assay when using 2 diagnostic criteria and 4 thresholds of disease progression. The high NPV suggest that a negative AST test result was indicative of a periodontally stable site. CONCLUSIONS: These results demonstrate that elevated levels of AST were present at sites that did not subsequently exhibit disease progression. The high prevalence of AST-positive sites due to gingival inflammation diminished the test's ability to discriminate between progressive and stable, but inflamed, sites.

The safety and efficacy of nebulized levalbuterol compared with racemic albuterol and placebo in the treatment of asthma in pediatric patients.

BACKGROUND: Limited dose-response information is available for nebulized beta2 -agonists, especially in young children. OBJECTIVE: The purpose of this study was to determine the safety and efficacy of increasing doses of nebulized levalbuterol (Xopenex; the pure R-isomer of racemic albuterol) and racemic albuterol compared with placebo in the treatment of asthma in pediatric patients. METHODS: In this randomized, double-blind, crossover study, children (aged 3 to 11 years) with asthma (resting FEV1 50% to 80% of predicted normal [Polgar's] values) were treated with either levalbuterol, racemic albuterol, or placebo. Eligible subjects underwent a screening visit followed by 4 treatment visits. At each treatment visit, serial pulmonary function tests were completed before and after the treatment; plasma was collected to determine enantiomer levels, and safety was evaluated. RESULTS: Five 3- to 5-year-old patients and twenty-eight 6- to 11-year-old patients completed the study, and a total of 87 doses of levalbuterol were administered. In the 6- to 11-year-old group, all doses of levalbuterol were significantly greater than placebo in peak change and percent peak change in FEV1 and area under the FEV1 versus time curve (P <.05). The FEV1 values over the 8-hour study period were similar for levalbuterol 0.31 and 0.63 mg and racemic albuterol 2.5 mg and were greatest after levalbuterol 1.25 mg. Median plasma levels of R-albuterol depended on dose and were 0.4, 0.7, 1.2, and 1.0 after levalbuterol 0.31 mg, 0.63 mg, and 1.25 mg and racemic albuterol 2.5 mg, respectively. All patients in the 2.5-mg racemic albuterol arm had measurable plasma levels of S-albuterol, although S-albuterol levels were undetectable in most patients in the levalbuterol arms. In a few patients who received levalbuterol, S-albuterol levels were detected, which was likely because of the use of racemic albuterol as a concomitant medication. All active treatments were well tolerated. beta-Mediated changes in heart rate, potassium, and glucose were dose dependent for all active treatment groups. CONCLUSION: Levalbuterol caused a significantly greater increase in FEV1 than placebo, and FEV1 values were comparable with or better than those observed with racemic albuterol. beta-Mediated side effects were lower for an equipotent dose of levalbuterol when compared with racemic albuterol. Treatment with levalbuterol resulted in plasma levels that were dose dependent and had an approximate correlation with pharmacodynamic parameters.

Improved bronchodilation with levalbuterol compared with racemic albuterol in patients with asthma.

BACKGROUND: Racemic albuterol is an equal mixture of (R)-albuterol (levalbuterol), which is responsible for the bronchodilator effect, and (S)-albuterol, which provides no benefit and may be detrimental. OBJECTIVE: We sought to compare 2 doses of a single enantiomer, levalbuterol (0.63 mg and 1.25 mg), and equivalent amounts of levalbuterol administered as racemic albuterol with placebo in patients with moderate-to-severe asthma. METHODS: This was a randomized, double-blind, parallel-group trial. Three hundred sixty-two patients 12 years of age or older were treated with study drug administered by means of nebulization 3 times daily for 28 days. The primary endpoint was peak change in FEV1 after 4 weeks. RESULTS: The change in peak FEV1 response to the first dose in the combined levalbuterol group was significantly greater compared with the combined racemic albuterol group (0.92 and 0.82 L, respectively; P =.03), with similar but nonsignificant results after 4 weeks (0.84 and 0.74 L, respectively). Improvement in FEV1 was similar for levalbuterol 0.63 mg and racemic albuterol 2.5 mg and greatest for levalbuterol 1.25 mg. Racemic albuterol 1.25 mg demonstrated the weakest bronchodilator effect, particularly after chronic dosing. The greatest increase in FEV1 was seen after levalbuterol 1.25 mg, especially in subjects with severe asthma. All active treatments were well tolerated, and beta-adrenergic side effects after administration of levalbuterol 0.63 mg were reduced relative to levalbuterol 1.25 mg or racemic albuterol 2.5 mg. At week 4, the predose FEV1 value was greatest in patients who received levalbuterol or placebo when compared with those who received racemic albuterol. The difference was more evident and was statistically significant in patients who were not receiving inhaled corticosteroids. CONCLUSION: Levalbuterol appears to provide a better therapeutic index than the standard dose of racemic albuterol. These results support the concept that (S)-albuterol may have detrimental effects on pulmonary function.

The effect of different diagnostic thresholds on incidence of disease progression.

Detection of periodontal disease progression occurs when a predetermined threshold of attachment loss is exceeded during longitudinal monitoring. The incidence of disease progression in a population may be dependent on the method and threshold utilized to identify significant changes in attachment level measurements. The aim of this study was to investigate the effect of utilizing different methods and thresholds on the incidence of disease progression in an untreated periodontitis population. The relationship between baseline clinical parameters and disease progression was also examined. A total of 411 interproximal sites in 46 individuals were monitored monthly over a 6-month period. Disease progression was determined by the cumulative sum (CUSUM) method and by the absolute change in relative attachment level between months 0 and 6 utilizing 3 different thresholds for attachment level change (0.58 mm, 1.16 mm, and 1.74 mm) based upon examiner repeatability using an automated probe. Utilizing the CUSUM method, 49 of 411 sites (11.9%) demonstrated attachment loss over the 6-month observation period. When attachment level changes > or = 0.58 mm, > or = 1.16 mm, and > or = 1.74 mm were used to identify disease progression, the percentage of sites exhibiting deterioration were 19.5%, 8.8%, and 2.9%, respectively. These results demonstrate that the apparent incidence of disease progression was dependent on the method and threshold utilized to detect progressive sites. When utilizing the CUSUM and 0.58 mm thresholds a significant (P < 0.05), but weak relationship (r = -0.26) was observed between baseline relative attachment level measurements and sites exhibiting disease progression. This finding suggests that sites with significant but relatively less attachment loss may be more likely to experience further breakdown compared to sites with a history of greater periodontal destruction.

Enantiospecific inhibition of ligature-induced periodontitis in beagles with topical (S)-ketoprofen.

Systemic and topical administration of non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce periodontal disease progression in both animal models and human subjects. Our present research focuses on single enantiomers of these agents to examine whether enantiospecific therapy will be efficacious in slowing periodontitis. The purpose of this study was to evaluate the inhibitory effects of (S)-ketoprofen on experimentally induced alveolar bone loss in beagle dogs. 16, 18-month-old, female beagles were brought to optimal periodontal health over a 2-week pretreatment period. Experimental periodontitis was then induced by placing silk ligatures around premolar and molar teeth and by instituting a soft, plaque-promoting diet. At baseline, animals were randomized to 1 of 4 groups, consisting of 2x daily administration of (1) placebo dentifrice, (2) 0.3% (S)-ketoprofen dentifrice, (3) 3.0% (S)-ketoprofen dentifrice, or (4) 10.0 mg (S)-ketoprofen capsules (p.o.) over a 60 day treatment period. Standardized, periapical radiographs exposed at days 1 and 60 were analyzed by computer-assisted digital radiography in order to assess the rate of alveolar bone loss. Secondary outcomes included technetium 99m-tin-diphosphonate (99mTc-Sn-MDP) uptake and the gingival index. At baseline, no differences were observed among the groups for linear bone height or 99mTc-Sn-MDP uptake ratios. From days 1 to 60, cohorts differed significantly in terms of bone loss rates (p < 0.001). In particular, beagles treated with systemic or topical (S)-ketoprofen (0.3% or 3.0% dentifrices) exhibited significantly lower mean rates of bone loss compared to placebo treated beagles (p < 0.05). Group differences in mean radiopharmaceutical uptake ratio changes approached significance (ANOVA, p = 0.07), where animals treated with topical 0.3% (S)-ketoprofen demonstrated a reduction and other groups demonstrated elevations over the 60-day dosing period. Treatment cohorts did differ significantly with respect to changes in mean gingival indices (p < 0.05). Animals treated with 0.3% or 3.0% (S)-ketoprofen dentifrice exhibited significantly reduced elevations in gingival index scores as compared to placebo treated animals. These data provide evidence that enantiospecific therapy with (S)-ketoprofen, topically or systemically delivered, may alter the progression of periodontal disease in the beagle dog model.

Alteration of the bed nucleus of the stria terminalis (BNST) in young female Djungarian hamsters (Phodopus campbelli) exposed to adult males.

Central components of the vomeronasal system appear to mediate extrahypothalamic control of gonadotropin release during male-induced acceleration of puberty onset in female rodents. In order to describe the bed nucleus of the stria terminalis (BNST) and to determine whether this component of the vomeronasal system is altered following early puberty onset, the anterior BNST of female Djungarian hamsters (Phodopus campbelli) was subdivided into three regions: medial, lateral, and ventral. The cross-sectional area, soma size, and neuronal density of each subdivision was compared among female hamsters in three groups: (1) young females showing accelerated reproductive development following a period of housing with an adult male, (2) young females matched by age with the accelerated females but housed alone during the same period, and (3) older females at the age of spontaneous puberty. Females housed with an adult male and undergoing accelerated puberty onset had significantly smaller lateral anterior BNST subdivisions than females housed alone for the same period (10 days following weaning) or housed alone until the age of spontaneous puberty onset (25 days following weaning). The size of the ventral and medial subdivisions was not different in the three groups. Furthermore, although soma size and neuronal density differed markedly among the anterior BNST subdivisions, these subdivision characteristics were similar in the accelerated, prepubertal, and older pubertal females. Our finding demonstrates that a central component of the vomeronasal system undergoes neuroanatomical alteration in response to environmental stimuli and recommends further examination of the BNST during this dynamic ontogenetic period.

Acceleration of reproductive development in female Djungarian hamsters by adult males.

Housing young female Djungarian hamsters (Phodopus campbelli) with an adult male accelerates uterine and ovarian development and there is a strong relationship between uterine weight and ovarian measures (e.g., follicular size). Uterine weights of females housed with an adult male for 10 days following weaning are comparable to values from females housed alone for 25 days. Removal of endogenous androgens by castration eliminated the capacity of adult males to accelerate reproductive development in young females and treatment of castrated males with exogenous androgens maintained the production of the acceleratory chemosignal. When adult male urine and ventral gland sebum were examined as possible sources for the acceleratory chemosignal, only male urine had an acceleratory effect on reproductive development. Thus, female Djungarian hamsters respond with accelerated reproductive development to androgen-dependent chemosignals in the urine of adult males. These mechanisms are similar to those found in several other rodents but contrast with the lack of such effects in the golden hamster (Mesocricetus auratus).

Scent marking by male dwarf hamsters (Phodopus sungorus campbelli) in response to conspecific odors.

Male hamsters (Phodopus sungorus campbelli) scent marked at greater frequencies in the presence of conspecific odor, either male or female, than in clean areas. Marking rates were not different between male and female odor conditions. In contrast, the pattern of investigation in response to conspecific odor did differ between the male and the female odor conditions. When male odors were used as stimuli, investigative sniffing increased at the scent marking sites but when female odors were used as stimuli investigative sniffing increased throughout the arena. Thus, male dwarf hamsters direct their scent marks at both male and female conspecifics, discriminate between male and female odor, and investigate in a different manner areas scent marked by males and females.