Quasi-static and harmonic indentation of osteonal bone.

UNLABELLED: The purpose of the study was to compare Quasi-Static (QS) and harmonic (CSM) methods of indentation testing. Bone sections were obtained from mid-femoral diaphyses of dogs which received a pair of calcein labels. Labeled (n = 35) and unlabeled (n = 112) osteons were identified. Indentation modulus (IM) and hardness (H) for the CSM method were collected during the entire loading cycle to peak depth, while IM and H for QS method were calculated at a peak depth of 500 nm. RESULTS: The mean (SD) of the IM and H for labeled osteons were as follows: QS IM = 15.3 GPa (3.85) versus CSM IM = 14.7 GPa (3.58); P = .52 and QS H = .39 GPa (.171) versus CSM H = .42 GPa (.146); P = .32. The mean (SD) of the IM and H for unlabeled osteons were as follows: QS IM = 21.5 GPa (2.80) versus CSM IM = 20.6 GPa (2.53); P = .054 and QS H = .64 GPa (.117) versus CSM H = .70 GPa (.120); P = .017. There was no difference in IM and H for the two methods, except for H of the unlabeled osteons. In addition, for the CSM method, IM at 100 nm, 200 nm, 300 nm, 400 nm and 500 nm were not statistically significant different (P = .06). Bone is viscoelastic at an organ level. However, this component of its behavior was not detected at the length scale examined.

Comparison of hand-traced and computer-based cephalometric superimpositions.

OBJECTIVE: To determine the ability to produce comparable superimpositions using hand tracing and digital methods (Dolphin v10). In addition, if the two methods were comparable, we wanted to determine if a difference existed between the best-fit cranial base superimposition and S-N superimpositions using the digital method. METHODS AND MATERIALS: Sixty-four initial (T(1)) and final (T(2)) cephalometric film radiographs were obtained. Cranial base and regional superimpositions were completed independently for each pair of radiographs by either hand tracing and digital methods. To quantitatively evaluate the differences between the two methods, the hand and digital superimpositions were digitized to obtain x-y coordinates of routine cephalometric landmarks at T(2). Linear distance between multiple corresponding (hand and digital) T(2) cephalometric landmark locations (e.g., A point) were measured and defined as the T(2) landmark distance (T(2) LD). Additionally, 61 patient records were used to compare the digital method for best-fit cranial base superimpositions versus S-N superimpositions. A Friedman test was applied to examine for differences. RESULTS: The upper 95% confidence limit for the mean of the T(2) LD for hand and digital superimposition methods was <1 mm for all landmarks except maxillary incisor tip and apex. The upper 95% confidence interval for best-fit vs S-N was >1 mm for most landmarks. CONCLUSION: This study validates the use of superimpositions produced by Dolphin Imaging version 10 and is a necessary step forward toward widespread acceptance of digital superimpositions.

The acceptability of variations in smile arc and buccal corridor space.

OBJECTIVES: To evaluate the esthetic acceptability range of computer-generated variations in smile arc and buccal corridor. DESIGN: Web-based descriptive study using available subjects. SETTING AND SAMPLE POPULATION: The World Wide Web. Subjects for the main study included 115 lay and 131 orthodontist raters. EXPERIMENTAL VARIABLES: Buccal corridors and smile arcs, each presented for a female and a male image. Buccal corridors were presented as none, ideal and excessive. The smile arc was presented as flat, ideal and excessive. The nine male and female variations, as combinations of the above variables, were each presented twice to evaluate reliability. OUTCOME MEASURE: Acceptability of buccal corridors and smile arcs using the web-based instrument. An arbitrary super majority threshold of acceptability was set at 67% approval. RESULTS: Both laypersons and orthodontists showed good reliability (k >or= 0.70). There was a broad range of acceptability, but laypersons and orthodontists showed no significant differences on the two variables tested. While orthodontists and laypersons both found smiles with excessive buccal corridors to be significantly less acceptable than those with ideal or absent buccal corridors, they were still acceptable over 70% of the time. Flat smile arcs were only acceptable 50-60% of the time, while smiles with ideal and excessive smile arcs were significantly more acceptable 84-95% of the time. When examining buccal corridors and smile arcs together, excessive buccal corridors were significantly less acceptable than ideal or absent buccal corridors regardless of the smile arc. A flat smile arc significantly reduced the acceptability of any buccal corridor to below the threshold of acceptability. CONCLUSIONS: Laypersons and orthodontists have similar preferences when acceptability of buccal corridors and smile arcs are considered. Flat smile arcs are more detrimental to smile esthetics than variations in buccal corridors. Clinicians must realize that although attractiveness may be reduced by variations in buccal corridors and smile arcs, the result may still be acceptable to a majority of people.

Indentation properties of young and old osteons.

The purpose of this study was to quantify differences in indentation modulus and microhardness between labeled osteons identified by epifluorescent microscopy and neighboring unlabeled osteons. In microradiographs and backscattered images, newly formed osteons appear more radiolucent (darker) than older osteons. This is ascribed to incomplete mineralization of the osteon. However, the mechanical properties of these young osteons are unknown. Nine femoral cross-sectional specimens were obtained from five skeletally mature dogs. Prior to death, the dogs received a pair of calcein bone labels. Labeled osteons were identified under an epiflourescent microscope. Bone specimens were transferred to a nanoindenter specimen holder, and the previous identified labeled osteons were located. Labeled (n = 102) and unlabeled (n = 101) osteons were examined by instrumented indentation testing. Indents were made to a depth of 500 nm at a loading rate of 10 nm/second. There were significant differences in the indentation modulus (P < 0.001) of labeled (10.02 +/- 3.61 gigapascal (GPa), mean +/- standard deviation) and unlabeled (15.11 +/- 3.72 GPa) osteons. Similar differences existed in microhardness measurements. Newly formed osteons had lower modulus (34%) and hardness (41%) than older osteons found in femoral cross sections. These data provide information on the indentation moduli of osteons during an early phase of mineralization compared to osteons that have completed mineralization.

Biomechanical and histomorphometric analyses of monocortical screws at placement and 6 weeks postinsertion.

Maxillofacial screws are increasingly being used in orthodontics to provide anchorage for tooth movement. The objective of this study was to determine the biomechanical stability as well as the bone tissue response of screws at 6 weeks postinsertion in a canine model. Seven skeletally mature male dogs received 102 screws (2 x 6 mm or 2 x 8 mm) at predetermined sites. Twenty screws became loose or were lost during the 6-week undisturbed healing period. Forty-eight screws were randomized for mechanical testing and 34 for histology. Peak pullout strength was recorded and approximately 80-microm sections were examined for histomorphometric parameters. Statistical analyses were conducted by analysis of variance and Tukey-Kramer method. Mean +/- SE peak pullout strengths for the various sites ranged from 153.5 +/- 37.6 N to 389.3 +/- 32.5 N with no significant (P < .05) differences at immediate placement and 6 weeks postinsertion. Bone contact ranged from 79% to 95%. Histomorphometric analyses indicated higher bone formation rate in the mandible than in the maxilla and a gradient of decreasing turnover with increasing distance from the screw interface. These results provide the clinical orthodontist with an estimate of the holding power of these screws and an understanding of early biological healing response associated with self-drilling screws.

A comparison of the reliability and validity of 3 occlusal indexes of orthodontic treatment need.

Several occlusal indexes are currently used to ascertain eligibility for orthodontic treatment. A comparison of 3 indexes of orthodontic treatment need was made with the consensus opinion of a panel of 15 experienced orthodontists. Sets of study casts (170) representing the full spectrum of malocclusions were selected. An examiner, calibrated in the Dental Aesthetic Index, the Handicapping Labiolingual Deviation with the California Modification, and the Index of Orthodontic Treatment Need, scored the casts. The panel of orthodontists individually rated the same casts for their degree of orthodontic treatment need. The mean rating of the panel on the need for treatment was used as the gold standard for evaluating the validity of the indexes. Intrarater and interrater reliability was high (kappa > 0.8). Overall accuracy of the indexes, as reflected in area under receiver-operating characteristic curves, was also high: Dental Aesthetic Index, 95%; Handicapping Labiolingual Deviation with the California Modification, 94%; and Index of Orthodontic Treatment Need, 98%. Cutoff points for the indexes that resulted in the closest agreement with the gold standard differed from the published cutoff points for the indexes. The indexes appear to be valid measures of treatment need as perceived by orthodontists. The published cutoff points for the indexes were more conservative in assigning patients for treatment than a panel of orthodontists. However, adjusting the cutoff points moved all 3 indexes into close agreement with the experts.

Social stress induces glucocorticoid resistance in macrophages.

Stress-induced levels of plasma glucocorticoid hormones are known to modulate leukocyte function. These experiments examined the effects of a social stressor on the responsiveness of peripheral immune cells. Male mice experienced six evening cycles of social disruption (SDR), in which an aggressive male intruder was placed into their home cage for 2 h. Although circulating corticosterone was elevated in SDR mice, they had enlarged spleens and increased numbers of splenic leukocytes. Splenocytes from SDR and control mice were cultured with lipopolysaccharide and corticosterone. Cells from SDR mice exhibited decreased sensitivity to the antiproliferative effects of corticosterone, suggesting that the peripheral immune cells were resistant to glucocorticoids. In addition, SDR cells produced more interleukin (IL)-6. To determine which cell population was affected, we used antibody-labeled magnetic beads to deplete splenocyte suspensions of B cells or macrophages. Depletion of macrophages from SDR cultures, but not depletion of B cells, abolished both the corticosterone resistance and enhanced IL-6 secretion. These findings demonstrate that a psychosocial stressor induced glucocorticoid resistance in mouse splenic macrophages.

A comparison of cranial base growth in Class I and Class II skeletal patterns.

The purpose of this retrospective longitudinal study was to compare 7 cephalometric measurements of the cranial base in subjects with Class I and Class II skeletal patterns at ages 1 month, 2 years, and 14 years. A sample of 22 Class I and 21 Class II subjects was selected; the inclusion criteria were overjet, ANB, and Harvold unit difference. Analyses of head circumference, crown-rump length, and weight revealed no significant (P >.15) differences between the Class I and Class II infant subjects at the initial age (1 month). One angular and 6 linear measurements were first compared with a multivariate analysis of variance, which revealed significant effects for age (P <.0001) and the age by skeletal pattern interaction (P =.0266) but not for skeletal pattern (P =.3705). Analyses of variance showed significant (P <.0001) age effects for each of the cephalometric variables but no significant skeletal pattern effects (P >.10). The anterior cranial base measurement of nasion to sphenoethmoidal suture was the only variable found to have a significant age by skeletal pattern interaction (P <.006), which revealed a difference in the timing of its growth spurt that occurred between 1 month and 2 years in the Class I subjects and between 2 years and 14 years in the Class II subjects. There were no significant differences between the skeletal classes at any of the 3 ages evaluated. Conclusions from this study indicate that cranial base growth patterns are similar for Class I and Class II subjects and that the premise of a more obtuse "saddle angle" or cranial base angle in Class II skeletal patterns was not supported.

Cephalometric variables as predictors of Class II treatment outcome.

Cephalometric analysis of skeletodental features is accepted as an integral part of orthodontic diagnosis and treatment planning. This assumes that diagnostic cephalometric variables affect prognosis and thus help reduce malocclusion severity, which is the aim of orthodontic treatment. The aim of this study was to assess the predictive value of 41 commonly used cephalometric parameters with regard to pretreatment severity and treatment outcomes. Pretreatment severity was assessed by using the Peer Assessment Rating (PAR) occlusal index, an instrument that has been shown to be valid and reliable. Treatment outcomes consisted of (1) posttreatment malocclusion severity (post-PAR), (2) relative improvement (percent PAR reduction), and (3) treatment duration. Complete records, including cephalograms, of 223 treated Class II cases were analyzed by means of separate multiple linear regression models. Each of the outcome variables and the pretreatment severity served as the respective dependent variables, and the cephalometric parameters served as the independent or predictor variables. The cephalometric parameters explained 39.2% of the pretreatment severity variance, 17. 9% of posttreatment severity variance, 15.7% of relative treatment improvement variance, and 20.0% of treatment duration variance.

Gingival fluid ciprofloxacin levels at healthy and inflamed human periodontal sites.

BACKGROUND: Polymorphonuclear leukocytes (PMNs) take up and accumulate ciprofloxacin. This may allow them to enhance the delivery of this agent to the inflamed periodontium. METHODS: Cross-sectional and longitudinal approaches were used to test the hypothesis. In the cross-sectional study, 7 periodontally healthy adults and 8 adults with untreated periodontitis were administered three doses of ciprofloxacin (500 mg bid). Gingival fluid (GF) and serum samples were obtained after 28 hours and analyzed by high-performance liquid chromatography (HPLC). In the longitudinal study, 8 adult periodontitis subjects were administered 500 mg ciprofloxacin bid for 8 days. After 28 hours, GF from 4 sites with 5 to 8 mm probing depths was sampled in each subject, serum samples were obtained, and 2 of the 4 sites were root planed. GF and serum were sampled again 7 days later (196 hours after the initial dose). RESULTS: The mean ciprofloxacin levels in the GF and serum of periodontally healthy subjects were 2.52 +/- 0.22 microg/ml and 0.47 +/- 0.05 microg/ml, respectively. In subjects with periodontitis, these levels were 2.69 +/- 0.44 microg/ml and 0.61 +/- 0.13 microg/ml, respectively. GF ciprofloxacin levels were significantly higher than corresponding serum levels in healthy and diseased subjects (P<0.01), but there were no significant differences in GF or serum levels between the 2 subject groups. Since GF flow was significantly higher at diseased sites, however, more ciprofloxacin was distributed to these sites than to healthy sites. In the longitudinal study, GF flow at 196 hours was 16% lower at root planed sites than at untreated control sites (P = 0.412). The minor decrease in this index of inflammation was accompanied by a small (9%), but statistically significant (P= 0.007), decrease in GF ciprofloxacin levels. CONCLUSIONS: GF ciprofloxacin levels decreased slightly at inflamed periodontal sites after root planing, but were significantly higher than serum levels even at healthy periodontal sites. Inflammation may enhance the distribution of ciprofloxacin to diseased sites, but it is not a major determinant of GF ciprofloxacin levels.

Use of sevoflurane inhalation sedation for outpatient third molar surgery.

This study attempted to determine if sevoflurane in oxygen inhaled via a nasal hood as a sole sedative agent would provide an appropriate level of deep sedation for outpatient third molar surgery. Twenty-four patients scheduled for third molar removal were randomly assigned to receive either nasal hood inhalation sevoflurane or an intravenous deep sedation using midazolam and fentanyl followed by a propofol infusion. In addition to measuring patient, surgeon, and dentist anesthesiologist subjective satisfaction with the technique, physiological parameters, amnesia, and psychomotor recovery were also assessed. No statistically significant difference was found between the sevoflurane and midazolam-fentanyl-propofol sedative groups in physiological parameters, degree of amnesia, reported quality of sedation, or patient willingness to again undergo a similar deep sedation. A trend toward earlier recovery in the sevoflurane group was identified. Sevoflurane can be successfully employed as a deep sedative rather than a general anesthetic for extraction of third molars in healthy subjects.

Dentofacial morphology and upper respiratory function in 8-10-year-old children.

OBJECTIVES: The aim of this preliminary study was to assess the nature of associations between selected dentofacial morphological variables and respiratory mode as measured by percent nasality (%N) as part of an ongoing longitudinal study. DESIGN: Cross-sectional cohort study. SETTING AND SAMPLE POPULATION: The Pediatric Clinical Study Center, Children's Hospital, Columbus, OH. Ninety-eight normal children were tested. EXPERIMENTAL VARIABLE: Normal variation in %N. OUTCOME MEASURE: Selected dentofacial morphological variables including total and lower anterior face heights, face width, and palatal arch width and %N were estimated. RESULTS: Small associations between morphologic features and respiratory mode were found, but none were statistically significant. CONCLUSION: No evidence exists for the classic association between 'mouth breathing' and the stereotype of the 'adenoid facies'.

Referral patterns, lesion prevalence, and patient care parameters in a clinical oral pathology practice.

OBJECTIVE: The purpose of this study was to determine the following parameters in a referral-based private practice oral and maxillofacial pathology clinic: (1) sources of clinical referrals; (2) types of problems referred; and (3) clinical effectiveness of treatment. STUDY DESIGN: Clinical charts were reviewed for a cohort of 362 patients seen over a 2 1/2-year period (1993-1995). From these charts, we determined the source of referral and the final diagnosis for each patient. In addition, 50 patients were randomly selected and surveyed by telephone; each was asked a series of questions to determine the following: (1) the number of health care practitioners previously seen with regard to the patient's condition; (2) the length of time that the condition had been present before the patient came to the oral and maxillofacial pathology clinic; (3) the costs associated with medications and office visits that had been incurred before the patient came to the oral and maxillofacial pathology clinic; (4) the costs associated with medications and office visits that were incurred at the oral and maxillofacial pathology clinic; and (5) the patient's level of satisfaction with the oral and maxillofacial pathology clinic. RESULTS: Fifty-five percent of the referrals came from dentists, and 45% came from physicians. The 3 problems most commonly seen were candidiasis (12%), burning mouth syndrome (10%), and lichen planus (8%). For the 50 patients who were interviewed, the mean number of health care practitioners seen previously was 2.2 (range, 1-9). The mean time from initial symptoms to evaluation by an oral pathologist was 15 months. The mean approximate cost of medications and office visits before evaluation by an oral pathologist was $350 (range, $30-$4,000; median, $100); this compared with a cost of $94 (range, $50-$300; median, $70) for the patient visit and medications associated with the oral pathology appointment. The difference was statistically significant (P < or = .001). CONCLUSIONS: This preliminary study suggests that the clinical evaluation of oral lesions by an oral pathologist appears to be cost-effective and should be an integral part of a comprehensive health management system. These results should be corroborated by similar multicenter studies.

Distortion of three-unit implant frameworks during casting, soldering, and simulated porcelain firings.

PURPOSE: The aim of this study was to assess distortion inherent in casting, soldering, and simulated porcelain firings of screw-retained, implant-supported three-unit fixed partial dentures (FPDs). MATERIALS AND METHODS: Ten wax patterns were fabricated on a die-stone cast containing two implants, 20 mm apart from center to center. Five specimens were cast in a high-palladium alloy, exposed to simulated porcelain firings, sectioned, and then soldered with low-fusing solder. Five specimens were cast, sectioned, soldered with high-fusing solder, and then exposed to simulated porcelain firings. For each specimen, two horizontal and six vertical distances between appropriately scribed reference points were measured with a traveling microscope. Comparisons were made among the various measurements taken after wax-pattern fabrication, casting, high- and low-fusing soldering, and each porcelain firing. Data were analyzed using a repeated-measures factorial ANOVA (alpha = 0.05). RESULTS: Significant difference was detected in the amount of horizontal distortion during casting (53 +/- 24 microns) and high-fusing soldering (-49 +/- 50 microns), as well as in the amount of horizontal distortion during high-fusing soldering (-49 +/- 50 microns) and low-fusing soldering (17 +/- 26 microns). However, no clinically significant difference was found in the amount of horizontal distortion during casting, low-fusing, and high-fusing soldering. The greatest amount of distortion during the simulated porcelain firings took place during the oxidizing cycle. CONCLUSIONS: Soldering did not improve the casting misfit of a three-unit implant-retained FPD model. Metal-ceramic implant frameworks should be oxidized before intraoral fit evaluation.

Lateral cephalometric analysis of asymptomatic volunteers and symptomatic patients with and without bilateral temporomandibular joint disk displacement.

Few studies of dentofacial and orthodontic structural relationships relative to temporomandibular joint (TMJ) dysfunction have been reported. We undertook this investigation to determine any correlation of orthodontic and dentofacial characteristics with TMJ bilateral disc displacement. The population of patients was selected from a TMJ clinic where a control group of asymptomatic volunteers had been previously established and standardized. Differences in skeletal structural features were determined among three study groups: (1) asymptomatic volunteers with no TMJ disk displacement, (2) symptomatic patients with no TMJ disc displacement, and (3) symptomatic patients with bilateral TMJ disk displacement. Thirty-two asymptomatic volunteers without disk displacement (25 female, 7 male) were compared with the same number each of symptomatic patients without TMJ disk displacement and symptomatic patients with bilateral TMJ disk displacement. All subjects had undergone a standardized clinical examination, bilateral TMJ magnetic resonance imaging, and lateral cephalometric radiographic analysis. The groups were matched according to sex, TMJ status, age, and Angle classification of malocclusion. Seventeen lateral cephalometric radiographic cranial base, maxillomandibular, and vertical dimension variables were evaluated and compared among the study groups. The mean angle of SNB, or the intersection of the sella-nasion plane and the nasion-point B line (indicating mandibular retrognathism relative to cranial base), of the symptomatic patients-with-displacement group was significantly smaller than that in the asymptomatic volunteers and symptomatic patients without bilateral disk displacement (p < 0.05). Female subjects showed smaller linear measurements of mandibular length, lower facial height, and total anterior facial height than male subjects in all three groups (p < 0.05). The mean angle of ANB, or the intersection of the nasion-point A and nasion-point B planes (indicating retrognathism of mandible relative to maxilla), was significantly greater in female than in male subjects, in all groups (p < 0.05). Symptomatic patients with bilateral disk displacement had a retropositioned mandible, indicated by a smaller mean SNB angle compared with that in asymptomatic volunteers and symptomatic patients with no disk displacement on either side. Lateral cephalometric radiographic assessment may improve predictability of TMJ disk displacement in orthodontic patients but is not diagnostic; nor does the assessment explain any cause-and-effect relationship.

Clinical comparison of bioabsorbable barriers with non-resorbable barriers in guided tissue regeneration in the treatment of human intrabony defects.

The purpose of the study was to compare the effects of guided tissue regeneration (GTR) with expanded polytetrafluoroethylene (ePTFE) non-resorbable barriers and polylactic acid bioabsorbable barriers in humans with intrabony defects due to periodontitis. Ten patients presented with 2 intrabony defects each. Mucoperiosteal flaps were performed. One of the defects was randomly assigned for placement of the ePTFE barrier over the roots and alveolar bone and the other defect with placement of the polylactic acid barrier. A minimum of 9 months after barrier placement, surgical reentry was performed. The data were evaluated by the Wilcoxon matched-pairs signed-ranks test and the Fisher exact test. Treatment with both types of barriers produced significant changes from baseline for all parameters, except in the ePTFE group for the amount of bony crest resorption (P = 0.055) and in the polylactic acid group for increased recession (P = 0.109). The results showed no significant differences between the barriers for any parameters: probing depth reduction (polylactic acid 2.60 +/- 1.90, ePTFE 2.80 +/- 1.40; P = 1.000); attachment gain (polylactic acid 1.40 +/- 1.43, ePTFE 1.90 +/- 1.29; P = 0.336); increased recession (polylactic acid 0.80 +/- 1.40, ePTFE 1.10 +/- 0.99; P = 0.531); amount of vertical bone fill (polylactic acid 1.60 +/- 1.84, ePTFE 2.00 +/- 2.49; P = 0.984); bony crest resorption (polylactic acid -1.30 +/- 1.06, ePTFE -1.30 +/- 1.63; P = 1.000); depth of bony defect reduction (polylactic acid 2.90 +/- 1.20, ePTFE 3.30 +/- 1.70; P = 0.750); width of bony defect reduction (polylactic acid 2.20 +/- 1.23, ePTFE 2.20 +/- 1.23; P = 0.875); or volumetric changes (polylactic acid 33.50 +/- 19.70 microl, ePTFE 34.00 +/- 18.40 microl; P = 0.750).

Comparison of resorbable and nonresorbable guided bone regeneration materials: a preliminary study.

The purpose of this study was to compare bone regeneration within a surgically created defect using three different resorbable membranes (polyglactin 910 knitted mesh/Vicryl, freeze-dried fascia lata, and crosslinked bovine type I collagen/BioMend) and two nonresorbable membranes (expanded polytetrafluoroethylene/Gore Tex, and polytetrafluoroethylene/Millipore). Each of three adult male dogs underwent surgical preparation of six bicortical defects of the calvarium, each 1.5 cm in diameter. The experimental barrier membranes were placed on both sides of the defects (inner and outer cranial tables). Five of the six defects were covered randomly by one of the five membrane materials, and one was left uncovered to serve as a negative control. The animals were sacrificed 10 weeks after membrane placement. Bone response was measured clinically, as well as radiographically, via densitometric examination. All surgical sites healed uneventfully. Variable degrees of new bone growth were present at all sites when evaluated by both clinical and radiographic examination. The general trend of observed osseous response indicates a greater, although not statistically significant, degree of bone growth using nonresorbable membranes. The animal model employed appears to be an efficient and reliable means of evaluating guided bone regeneration membranes.

Neuroendocrine regulation of cytokine production during experimental influenza viral infection: effects of restraint stress-induced elevation in endogenous corticosterone.

A murine model of influenza viral infection was used to examine the neuroendocrine regulation of cytokine production. Restraint stress (RST) was used to activate the hypothalamic-pituitary-adrenal axis and elevate corticosterone (CORT) levels in influenza A/Puerto Rico/8/34 (PR8) virus-infected C57BL/6 mice. The type II glucocorticoid receptor antagonist RU486 was used to specifically examine the modulation of PR8 virus-specific cytokine responses by CORT. RST suppressed the PR8 virus- specific production of Th1-type (IL-2 and IFN-gamma) and Th2-type IL-10) cytokines by cells from the regional lymph nodes and spleens. In addition, IL-6 production by splenocytes was inhibited by RST; however, IL-6 production by cells from the regional lymph nodes was enhanced. Treatment of mice with RU486 prevented the effects of RST, suggesting that the RST-induced alterations in cytokine responses were mediated by CORT. Furthermore, CORT was shown to inhibit the PR8 virus-specific production of both Thl-type and Th2-type cytokines in vitro at doses corresponding to the physiologic range of free plasma CORT following hypothalamic-pituitary-adrenal axis activation.

Transforming growth factor-alpha overexpression in proliferative verrucous leukoplakia and oral squamous cell carcinoma: an immunohistochemical study.

Proliferative verrucous leukoplakia is a unique type of oral leukoplakia that has a high risk of malignant transformation. The aim of this study was to examine the expression of transforming growth factor-alpha in proliferative verrucous leukoplakia, oral squamous cell carcinoma, and normal mucosa. Transforming growth factor-alpha, a potent mitogen, is known to play an important role in various neoplasms including oral squamous cell carcinoma. Immunohistochemical localization of transforming growth factor-alpha in archival paraffin-embedded sections was performed with commercially available monoclonal antibodies. Ten cases each of normal mucosa, proliferative verrucous leukoplakia, and oral squamous cell carcinoma were stained. Quantification of the staining intensity, expressed as the cytoplasmic optical density, was done with the Roche Image Analysis System. The data were statistically analyzed with the one-way analysis of variance and Tukey tests. Notably, the mean cytoplasmic optical density of proliferative verrucous leukoplakia was significantly higher than the mean cytoplasmic optical density of normal mucosa (p < 0.01). The mean cytoplasmic optical density of proliferative verrucous leukoplakia was slightly higher than that of oral squamous cell carcinoma, however, this difference was not significant (p > 0.05). The mean cytoplasmic optical density values demonstrate that increased transforming growth factor-alpha immunoreactivity occurs in proliferative verrucous leukoplakia and oral squamous cell carcinoma relative to normal mucosa.

pH changes observed in the inflamed gingival crevice modulate human polymorphonuclear leukocyte activation in vitro.

Previous studies have noted a positive correlation between gingival inflammation and crevicular pH, which reportedly varies from 6.5 to 8.5. In the present study, we characterized the manner in which deviation from the "physiological" pH of blood (7.2) influences activation of chemotaxis, phagocytosis, superoxide generation, and degranulation by human polymorphonuclear leukocytes (PMNs). Purified PMNs were suspended in HEPES-buffered balanced salts solutions adjusted to pH 6.7, 7.2, 7.7, or 8.2. In a modified Boyden chamber, the chemotactic response to fMet-Leu-Phe was maximal at pH 7.2. In comparison, chemotaxis was significantly depressed at pH 7.7 and pH 8.2 (P < 0.05), but was not significantly different at pH 6.7. Activation of the respiratory burst by fMet-Leu-Phe was optimal at pH 7.2, but was significantly depressed at pH 6.7 and 8.2 (P < 0.05). pH had little effect on N-acetyl-beta-glucosaminidase release from primary granules. However, lactoferrin release from the secondary granules of fMet-Leu-Phe-activated PMNs was significantly lower at pH 7.2 than at pH 6.7 or 8.2 (P < 0.05). Moreover, phagocytosis of opsonized bacteria was significantly lower at pH 7.2 than at pH 7.7. In addition to these effects on functional activation, extracellular pH influenced the magnitude of intracellular Ca2+ mobilization. Peak fMet-Leu-Phe-induced Ca2+ levels were significantly higher at pH 8.2 than at pH 7.2 (P < 0.01). These findings suggest that the pH of the periodontal environment can selectively influence PMN activation, thereby altering the balance between bacteria and the host response.