Inhibition of bone resorption in vitro by a cartilage-derived anticollagenase factor.

A cartilage-derived factor containing a specific collagenous inhibitor was found to block reversibly parathyroid hormone-stimulated 45Ca release from fetal rat bone in vitro. Morphologic and quantitative histometric examination revealed that this factor modulates osteoclastic activities.

Bone resorbing activity in supernatant fluid from cultured human peripheral blood leukocytes.

A new soluble mediator was found in supernatant fluid from cultures of human peripheral blood leukocytes that were stimulated by phytohemagglutinin, or by antigenic material present in human dental plaque deposits. This soluble Jactor produced bone resorption in organ cultures of fetal rat bones as measured by increased release of calcium-45, and also increased the number of active osteoclasts.

Effect of osteoclast activating factor from human leukocytes on bone metabolism.

The effects of osteoclast activating factor (OAF) released by normal human peripheral blood leukocytes cultured with phytohemagglutinin have been examined in organ culture. Like parathyroid hormone (PTH), OAF causes a rapid increased in the release of previously incorporated 45Ca from fetal rat bone after brief or continuous exposure; the bones also lose stable calcium and collagen content. The resorption response to OAF also resembles that of PTH in having a steep dose response curve and being only transiently inhibited by calcitonin and partially inhibited by increasing medium phosphate concentration. OAF-stimulated resorption was inhibited more effectively by cortisol than was PTH stimulation. The response to maximally effective doses of OAF was not enhanced by PTH or prostaglandin E2, but submaximal doses gave additive effects. Both OAF and PTH inhibit collagen synthesis in fetal rat calvaria at the concentrations that stimulate bone resorption.

Platelet factor 4 regulates osteoclastic bone resorption in vitro.

Platelet factor 4, which inhibits collagenases derived from both human skin and granulocytic extracts, was found to block reversibly parathyroid hormone-stimulated 45Ca release from fetal rat bone in vitro. The inhibitory property was equally effective in both actively resorbing bones and in bones stimulated to initiate resorption.

Investigations on in vitro bone resorbing activity from athymic (nude) and euthymic mouse splenic leukocytes.

T-lymphocyte dependence of the production of in vitro bone resorbing activity was examined using athymic (nu/nu) and euthymic (nu/+) mouse splenic leukocytes. Conditioned medium (CM) from unstimulated splenic leukocytes of nu/nu mice had greater in vitro bone resorbing activity compared to CM from nu/+ mice (1.7- as compared to 1.2-fold increase of 45Ca release in mouse calvaria). CM from concanavalin A (Con A)-treated nu/nu and nu/+ leukocytes had 1.8-fold and no increase in 45Ca release, respectively. CM from both nu/nu and nu/+ phytohemagglutinin (PHA)-treated leukocytes had a 1.7-fold increase in 45Ca release. Bone resorbing activity from nu/nu CM was inhibited by interferon-tau (10 & 100 IU/mL) and indomethacin (2 x 10(-6) M). CM (untreated or Con A-treated) from nu/nu leukocytes had higher levels of prostaglandin E (PGE) as compared to CM from nu/+ leukocytes, and indomethacin decreased PGE levels in nu/nu CM. Leukocytes from nu/+ mice had increased mitogenesis when stimulated with PHA (1, 3, & 10 micrograms/mL) or Con A (1 and 10 micrograms/mL), whereas leukocytes from nu/nu mice were nonresponsive or had significant inhibition of mitogenesis with PHA and Con A.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of bone turnover in athymic (nude) and euthymic mice: biochemical, histomorphometric, bone ash and in vitro studies.

Bone turnover in T-cell deficient mice was investigated by comparing parameters of bone physiology in athymic (nude) and euthymic mice. Static and dynamic bone histomorphometry, serum biochemical assays, body weight and tibia length measurements, and bone ash determination were completed in 6- and 12-wk-old athymic (nude) mice (NIH: Swiss nu/nu) and euthymic mice (nu/+) (10 mice/group). In vitro bone resorbing activity stimulated by parathyroid hormone (PTH) or prostaglandin E2 (PGE2) was measured in calvaria of neonatal athymic and euthymic mice. Athymic mice had smaller vertebral tissue area (p less than 0.01), tibia length (p less than 0.001), and less body weight (p less than 0.01) than euthymic mice. The percent double labeled surface (p less than 0.05) and mineralizing perimeter (p less than 0.01) were reduced in athymic as compared to age-matched euthymic mice. Osteoclast number was reduced in the 6-wk athymic mice as compared to 6-wk euthymic mice. Osteoclastic perimeter was reduced in the 12-wk-old mice (athymic and euthymic) as compared to the 6-wk-old mice. Serum calcium was lower at both ages in athymic mice (p less than 0.01) as compared to euthymic mice. Serum alkaline phosphatase levels were reduced (p less than 0.01) in 12-wk-old athymic mice as compared to age-matched euthymic mice, and were greater in 6-wk-old mice than 12-wk-old mice. Athymic mice had greater femur density than euthymic mice (p less than 0.01), and lower (p less than 0.001) percent ash weight of dry bone compared to euthymic mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypercalcemia associated with T-cell lymphoma-leukemia.

Two adults who had T-cell lymphoma-leukemia and recurrent hypercalcemia in the absence of radiographic evidence of bone disease are described. Bone histopathology showed marked osteoclastic activation. Bone resorbing factors, including both prostaglandin E and a material produced in the presence of a prostaglandin synthetase inhibitor, were detected in the in-vitro culture fluids of malignant cells of one of the patients. Serum levels of parathyroid hormone were not elevated. These findings suggest that hypercalcemia resulted from in-vitro osteoclast activation by tumor cell product(s), one of which may be similar, if not identical, to the lymphocyte product osteoclast-activating factor. Two other patients having T-cell lymphoma-leukemia and hypercalcemia have been identified in the literature: the malignant cells of one of these patients also released a calcium-mobilizing factor in vitro.

Progesterone facilitates the acquisition of avoidance learning and protects against subcortical neuronal death following prefrontal cortex ablation in the rat.

Following a cortical injury, neurons in areas near and connected to the site of injury begin to degenerate. The observed neuronal death may contribute to the severity of the observed behavioral impairments. The purpose of the present study was to examine if progesterone, a hormone known for its effectiveness at reducing cerebral edema, could protect against secondary neuronal death and facilitate the acquisition of an avoidance learning task in an ablation model of cortical injury. Rats served as sham controls or received bilateral ablation of the medial prefrontal cortex followed by a 10-day regimen of progesterone (4 mg/kg) or oil vehicle (1 ml/kg) beginning 1 h after cortical lesions. Progesterone-treated lesion rats showed a significant facilitation of avoidance learning compared to oil-treated lesion controls. In addition, progesterone-treated lesion animals did not differ from either progesterone- or oil-treated sham controls in avoidance learning. Anatomical analysis revealed that progesterone treatment decreased the amount of neuronal death seen in the striatum and the mediodorsal nucleus of the thalamus. The findings are consistent with the notion that progesterone is an effective neuroprotective agent and suggest that the hormone can reduce the behavioral impairments associated with frontal cortical ablation injury.

Skeletal manifestations in cutaneous T-cell lymphomas.

The clinical course of three patients with cutaneous T-cell lymphoma (CTCL) in whom skeletal disease developed is presented and the literature on skeletal involvement in these disorders is reviewed. Three separate types of skeletal manifestations occurred: (1) osteolytic lesions, (2) osteoblastic lesions, and (3) diffuse osteoporosis. Hypercalcemia was present in two cases. Tumor cells from two patients in short-term culture secreted osteoclast-activating factor(s). Both of these patients had pathologic evidence of osteoclast activation in bone sections. Thus, the tumor cells in certain patients with CTCL may derive from a monoclonal proliferation of a T-cell subset capable of producing humoral bone-resorbing factor(s) similar to those demonstrated in cultures of mitogen- and antigen-activated normal lymphocytes. Since skeletal lesions are unusual, it would follow that other T-cell subsets account for pathologic cell proliferation in most patients with CTCL.

The adherence to bone by cytoplasmic elements of osteoclast.

The intimate association observed between osteoclasts and bone has suggested that these cells may be adherent to the bony surface. We investigated this cell-surface relationship in parathyroid hormone-stimulated bone explants following applications of biophysically-induced cell detachment forces. Bone surfaces adjacent to disrupted osteoclasts were examined with transmission electron microscopy for the presence of residual cell membrane elements. Results of this study provide evidence for the adherence of osteoclasts to bony surfaces and implicate elements of both clear zone and ruffled border as cell-membrane bonded sites.

Apparent cytotoxicity of base metal casting alloys.

The cytotoxic potentials of three Ni-Cr based alloys and an Fe-Cr based alloy were assessed. In tissue culture, casting of all four test materials and powders of the Fe-Cr based material did not elicit adverse cellular changes. However, cultures containing Ni-Cr powders showed prominent zones of lysis and cell alteration. The cytotoxic potential of products obtained from the surfaces of casting alloys may offer an expedient means for estimation of long-term clinical toxicity.

Medial prefrontal lesion deficits involving or sparing the prelimbic area in the rat.

The rat medial prefrontal cortex (PFC) is believed to play a central role in working memory and selective attention processes. More recently, it has been shown that the effects of large PFC lesions on working memory may be due to the prelimbic area of the PFC. The aim of the present study was to compare the effects of lesions of the prelimbic area with PFC lesions that involved or spared the prelimbic area on shuttlebox avoidance and radial maze learning in rats. The findings indicate that rats with PFC lesions that spared the prelimbic area were impaired at avoidance but not radial arm maze learning, whereas rats with prelimbic lesions or PFC lesions that included this area were impaired on the radial arm maze but not the avoidance learning task. Results support the notion that the medial frontal cortex of the rat is a functionally dissociable region and suggest that the prelimbic area appears to be critical for working memory, but less so for attention processes.

Clinical evaluation and comparison of 2 topical anesthetics for pain caused by needle sticks and scaling and root planing.

BACKGROUND: Pain generated by needle sticks (Ns) for the delivery of local anesthetic and/or scaling and root planing (SRP) instrumentation is commonly addressed by the use of topical anesthetics, such as a benzocaine-gel preparation (BGP). Pain suppression following such use has been highly variable. Development of medicine-containing patches and adhesives for intraoral use have led to a new approach for topical anesthesia in the form of a transoral lidocaine delivery system (LDS). The purpose of this double-blind study was to evaluate the efficacy of the LDS and also to compare LDS with BGP for pain suppression to Ns and SRP. METHODS: One group of 20 subjects randomly received in both maxillary and mandibular molar-bicuspid areas LDS or BGP on one side and non-anesthetic control on the other side. A second group of 20 subjects compared the effectiveness of LDS directly with BGP in molar-bicuspid areas of both arches. Random order determined the selection for each anesthetic tested between the arches and bilateral. Pain perception was separately scored to a pain-inducing Ns simulation without anesthetic injection at each area and subsequently also to SRP using both a verbal pain scale (VPS) and a visual analog scale (VAS). RESULTS: VPS and VAS results analyzed by Bonferroni-adjusted Wilcoxon matched-pairs signed-rank tests found pain suppression scores significantly (P < 0.005) reduced for Ns by LDS to controls and to BGP. Comparing LDS directly with BGP, LDS was significantly (P < 0.05) more effective in reducing pain to Ns in both arches, to SRP in the maxillary arch, and equally effective as BGP in the mandibular arch. CONCLUSIONS: LDS is more effective than BGP for topical pain suppression to Ns and SRP in both arches.

The effectiveness of a disposable tooth cleansing device on plaque.

A disposable polyester foam sponge on a stick, impregnated with a non-foaming dentifrice, has been widely dispensed to hospitalized and nursing home patients for intraoral cleansing and refreshing. Since no information was found relative to tooth cleansing capabilities, we have evaluated its effectiveness in the removal of accumulated plaque and also in prevention of plaque accumulation. Removal of 72 hours of accumulated plaque was assessed in a cross-over design study comparing the device with a commercially-available toothbrush by two different groups of 13 and 29 adult, healthy subjects who used each instrument for 1 and 3 minutes respectively. No significant differences were found between mean scores assessed by Turesky's modification of the Quigley-Hein plaque index by either group using either instrument at either time period (P > 0.05). Prevention of plaque accumulation was assessed in a third group of 25 subjects who used each instrument an average of 3 times a day for 1 week in a cross-over study. While the toothbrush was found significantly more effective in retarding the accumulation of plaque from a plaque-free baseline on both facial and lingual surfaces (P < 0.02), the tooth cleansing device still retained plaque-preventive capabilities by maintaining plaque formation below 2 mm at the cervical margin of the tooth. Results of this study indicate the tooth cleansing device may be a viable alternative to conventional toothbrushes.

Retained "hopeless" teeth. Effects on the proximal periodontium of adjacent teeth.

The retention of teeth diagnosed as periodontally "hopeless" may accelerate the destruction of the adjacent proximal periodontium. Studies determining the influence these teeth have on the health status of adjacent teeth appear nonexistent. It was the intent of this retrospective study to assess the status of the periodontium in adjacent teeth proximal to the periodontium of "hopeless" teeth. We evaluated 17 teeth, each being mesially adjacent to one "hopeless" tooth, in 17 subjects treated for periodontal disease. In each case, the "hopeless" and the adjacent teeth received the same treatment. Probing depths (P-D), radiographic alveolar bone level (R-BL) and the width of the periodontal ligament space (W-PL) were measured for both the adjacent interproximal and the nonadjacent interproximal surface for each hopeless tooth. At both pretherapy and posttherapy, there were no significant differences for any of the variables (P-D, R-BL and W-PL) for the adjacent interproximal surfaces with the nonadjacent interproximal surfaces. However, there was a significant reduction in the mean probing depth for the adjacent interproximal surfaces, pretherapy to posttherapy. No other significant changes were found in any of the other variables for either the adjacent or nonadjacent interproximal surfaces. These data suggest that teeth considered periodontally "hopeless" and retained have no effect on the proximal periodontium of adjacent teeth prior to and following therapy.

Plaque score changes based primarily on patient performance at specific time intervals.

Patient plaque removal is a major component of periodontal therapy and should be continuously monitored during and following treatment. There do not appear to be studies which address plaque score changes achieved primarily by patient performance from the time of initial presentation to, during, and following active therapy. We assessed individual tooth surfaces and segment plaque scores for 24 adult subjects presenting with periodontitis, the majority of which was ADA case types III and IV, at 3 time points (initial presentation, post-initial preparation, and at 3 months following active therapy), using the O'Leary Plaque Index. The assessments describing surfaces and segments were made prior to any professional intervention. Analysis of buccal (B), interproximal (I), and lingual (L) plaque retentive surfaces at t-0 indicated the mean plaque index on B and L surfaces (30.7% and 41.9% respectively) was less than that on I surfaces (79.6%). At t-1 and t-2, the mean plaque index on all three surfaces was significantly (P less than 0.05) less than at t-0. Analysis of plaque indices in each of 6 segments at each time point revealed that plaque scores in all segments, except the mandibular right segment, were analogously reduced from t-0 to t-1 and to t-2. Our results indicate that plaque reduction for all subjects based primarily on patient performance consistently approaches or exceeds 50% on all surfaces and that interproximal surfaces present with and retain more plaque than buccal and lingual surfaces. Furthermore, patient plaque performance achieved at the time of post-initial preparation may be a predictor of the plaque control achievable during therapy based on patient performance.

Effect of soluble extracts from periodontal dressings on human granulocytic leukocytes in vitro.

Purified populations of human polymorphonuclear granulocytic leukocytes were exposed in vitro to solubilized material(s) extracted from two commerical periodontal dressings. The composiitonof one dressing contained eugenol while that of the other lacked it. Extracts were prepared by placing each mixed dressing in isotonic saline for 18 to 24 hours. Granulocytic leukocytes received serial dilutions of each extract and were then evaluated at 15 minutes and at 3 hours of culture for changes in viability and elaboration of cyto-plasmic and lysosomal enzymes. High concentrations of extract from each dressing were toxic to the cultured granulocytes. Measurements for cell viability and release of cytoplasmic enzyme revealed that the toxic potential in the eugenol-free dressing was greater. With cell damage, extracellular release of the lysosomal enzymes was found to occur. Serially increased dilutions of either extract to nontoxic concentrations failed to selectively release lysosomal enzymes.

Effect of periodontal dressings on human gingiva fibroblasts in vitro.

In vitro cytotoxicity studies of periodontal dressings have not generally produced a result consistent with in vivo observations. These prior in vitro studies have not used human intraoral cell lines. We tested the effects of two eugenol containing and two non-eugenol periodontal dressings on cultured human gingival fibroblasts (HGF) (ATCC #1292). Replicate HGF cultures grown in microtiter plates were exposed to stock, 1:4 and 1:16 dilutions of extracts made from each of the four periodontal dressings. The HGF cultures were pulse labelled with tritiated thymidine (3HTdR) after 24, 48, and 72 hours. Incorporations of the labelled thymidine were measured using liquid scintillation counting and expressed as counts per minute. The results showed that undiluted extracts from all four periodontal dressings totally inhibited 3HTdR uptake (P less than 0.05). The 1:4 dilution of eugenol dressings inhibited 3HTdR uptake significantly more than non-eugenol dressings (P less than 0.05). Interestingly, at 72 hours the 1:16 dilution of the non-eugenol dressings caused significantly increased 3HTdR uptake which was not observed with the eugenol dressings. The present results suggest that the use of a human fibroblastic cell line for testing the effects of periodontal dressings may provide information about the relative biological effects of these dressings. Using this cell line, we have found that eugenol dressings inhibit fibroblast proliferation to a greater extent than non-eugenol dressings.

Retained "hopeless" teeth: lack of effect periodontally-treated teeth have on the proximal periodontium of adjacent teeth 8-years later.

We previously reported the lack of effect periodontally-treated teeth prognosed "hopeless" and retained for 3.4 +/- 1.5 years have on the proximal periodontium of adjacent teeth. We now report our findings for the same group of subjects following 8.4 +/- 0.7 years of "hopeless" tooth retention. Of the 17 "hopeless" and adjacent teeth originally measured in 17 subjects, 14 of the subjects were still available for re-evaluation. Measures used to assess the periodontium of proximal surfaces of adjacent teeth included pocket depths (PD), radiographic alveolar bone level (R-BL), and periodontal ligament space width (W-PL). Treatment for the subjects consisted of surgical therapy (N = 15) and scaling and root planing (N = 2). Of the 14 subjects re-examined, 2 were eliminated due to loss of adjacent tooth reference points and 2 due to extraction of the "hopeless" tooth (N = 10). Differences in measurements (i.e., nonadjacent to "hopeless" tooth value minus adjacent to "hopeless" tooth value) were analyzed using a repeated measures ANOVA. There were no significant differences for PD (P = 0.20), R-BL (P = 0.29), or W-PL (P = 0.16). These data confirm our original findings that retained periodontally "hopeless" teeth do not significantly affect the proximal periodontium of adjacent teeth following therapy.

Management of arthrogryposis multiplex congenita. A case report.

Arthrogryposis multiplex congenita is a rare disorder of skeletal muscle development which is characterized by deforming contractures of the joints, but seldom affects the temporomandibular joint. This report reviews the condition and reports the findings and periodontal management of a patient referred with arthrogryposis multiplex congenita which required treatment for severe dilantin gingival hyperplasia.