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1.
The aim of this study was to evaluate the long-term effects of a combined periodontal treatment of scaling and root planing (SRP) and Nd:YAG laser (NDL) in chronic periodontitis (CP) patients. This was accomplished by determining the periodontal indices and the interleukin-1beta (IL-1β) and matrix metalloproteinase-8 (MMP-8) levels of the gingival crevicular fluid (GCF). This study was performed according to a random split-mouth-design, controlled clinical trial for sulcular debridement on 40 teeth from 20 patients with generalized moderate chronic periodontitis. The periodontal healing outcomes were compared after periodontal treatment with either SRP + NDL at 1 W (test side) or SRP (control side). Plaque index (PI), gingival index (GI), probing pocket depth (PPD), and clinical attachment level (CAL) were recorded, and samples of gingival crevicular fluid (GCF) were taken at baseline and post-therapy (3 and 9 months after treatment). The GCF samples were analyzed for IL-1β and MMP-8. There was postoperative improvement of all clinical parameters in both groups, but test side GI, PPD, and CAL recovery was higher than that of the control side (p < 0.05). Although levels of IL-1β and MMP-8 in GCF after treatment were lower in the test side than the control side, there was not a statistically significant difference (p > 0.05). In the long term, we found that SRP + NDL treatment of periodontal pockets was more effective than SRP alone in reducing PPD, CAL, GI, and GCF values.  相似文献   

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3.
In recent years, the use of laser radiation has been investigated as an alternative or adjunctive tool to conventional procedures employed in the treatment of periodontal disease. Various beneficial characteristics of Nd:YAG laser radiation, such as hemostatic and bactericidal effects, might lead to improved treatment outcomes. The objective of the present study was to examine the clinical, microbiological, and anti-inflammatory efficacy of Nd:YAG laser periodontal pocket irradiation as an adjunct to scaling and root planing (SRP). Thirty patients with chronic periodontitis (CP) were randomly assigned in parallel groups to receive SRP alone or SRP followed by Nd:YAG laser (λ = 1,064 nm) (SRP+NDL). Probing pocket depth (PPD), bleeding on probing (BOP), and plaque index (PI) were recorded, and samples of gingival crevicular fluid (GCF) and subgingival microbiota were taken at baseline and post-therapy (4 and 8 weeks after treatment). The laser therapy was performed 1 day after the SRP procedure. The GCF samples were analyzed for interleukin-1beta (IL-1β), tumor necrosis factor alpha (TNF-α), and total antioxidative status (TAS). Microbiological samples were cultured and analyzed for ten bacteria. No statistically significant differences were detected for clinical or microbiological variables between SRP and SRP+NDL treatments. However, levels of IL-1 β in GCF were significantly lower after SRP+NDL treatment when compared to IL-1 β levels obtained by SRP alone after 4 weeks of treatment. Levels of TNF-α were significantly lower after the SRP+NDL treatment during post-therapy. TAS of GCF increased during post-therapy after the SRP+NDL treatment. However, after SRP alone, it remained constant. In this short-term clinical study Nd:YAG laser radiation in the treatment of CP is showed to be a potential adjunct to conventional SRP.  相似文献   

4.
The aim of this study was to investigate if coherence length is of importance in laser phototherapy. Twenty patients with moderate periodontitis were selected. After oral hygiene instructions, scaling and root planing (SRP), one side of the upper jaw was randomly selected for HeNe (632.8 nm, 3 mW) or InGaAlP (650 nm, 3 mW) laser irradiation. One week after SRP, the following parameters were measured: pocket depth, gingival index, plaque index, gingival crevicular fluid volume, matrix metalloproteinase (MMP-8), interleukin (IL-8) and subgingival microflora. The irradiation (180 s per point, energy 0.54 J) was then performed once a week for 6 weeks. At the follow up examination, all clinical parameters had improved significantly in both groups. A more pronounced decrease of clinical inflammation was observed after HeNe treatment. MMP-8 levels were considerably reduced on the HeNe side, while there was no difference for IL-8 or microflora. Coherence length appears to be an important factor in laser phototherapy.  相似文献   

5.
In 30 patients with periodontitis, a total of 278 teeth exhibiting bleeding on probing, subgingival calculus, and a probing depth between 3–6 mm were examined. For each participant, two treatment types were alternatively applied on the contralateral quadrants: scaling and root planing (SRP) as control, and SRP followed by Er,Cr:YSGG laser application (SRP+laser), as a test method. Five clinical parameters: plaque level, bleeding on probing, probing depth, gingival recession and clinical attachment level were examined at baseline and at 2, 3, 6, 12 months after treatment. Of the total of 1,668 sites examined in all patients, 1,088 sites were found with a probing depth of 3–6 mm. In these sites, differences in clinical parameters between SRP and SRP+laser-treated quadrants were analyzed, assuming the level of p < 0.05 as significant. After 2 months from baseline, the mean probing depth reduction and the clinical attachment level gain were significantly greater in SRP+laser than in SRP quadrants, and remained so throughout the study (p < 0.001). A marked reduction of the bleeding scores occurred in all examined sites, irrespective of the treatment method. However, after 12 months, significantly less teeth exhibited bleeding on probing in SRP+laser quadrants than in SRP quadrants (p < 0.001). The mean plaque and gingival recession levels did not differ between the SRP and SRP+laser quadrants neither before nor after the treatment. The periodontal procedures either using Er,Cr:YSGG laser after SRP or SRP alone, lead to significant improvements in all clinical parameters investigated. However, laser application, as an adjunct to SRP, appeared to be more advantageous.  相似文献   

6.
Periodontal disease is a chronic progressive inflammatory process leading to damage of tooth-supporting tissues. This comparative study assessed the effect of PhotoBioModulation (PBM) versus conventional therapy, and investigated biomarkers involved in the healing process. The test group comprised twenty systemically-healthy non-smoking subjects with chronic periodontitis with the presence of two matched contro-lateral premolar sites (probing depth > 5 mm); twenty subjects without chronic periodontitis (CP) served as control group. Patients were treated at baseline, either with scaling and root planing (SRP group) or with a procedure entailing SRP supported by PBM (PBM group). The laser used was a diode laser operating at 645 nm wavelength, 10 J/cm2, and 0.5 W/cm2 with a 600 μm fiber optic. Crevicular fluid levels of bradykinin (BK), vascular endothelial growth factor (VEGF), and epidermal growth factor z (EGF) were determined at both sites. Crevicular fluid specimens from both groups were analyzed with the ELISA TEST. Clinical differences in analyzed outcomes were observed in favor of PBM treatment. Taking average values as 100%, the reduction in BK concentration was 47.68% with SRP and 68.43% with PBM on day 3; the VEGF concentration decreased by 35.73% with SRP and 48.59% with PBM on day 7; the EGF concentration increased by 55.58% with SRP and by 58.11% with PBM on day 21. Clinical parameters improved significantly in both groups (pooled mean values of probing depth decreased from 5.6 to 4.5 mm; gingival index from 1.92 to 1.1; and bleeding on probing from 49.67 to 23.23) but did not vary significantly between the PBM and the SRP group. The results confirmed that PBM have beneficial effects in the early phases of the healing process playing a role in modulation of BK, EGF, and VEGF in gingival crevicular fluid levels; both groups had significant clinical improvement over control but there was no significant difference between them, only a trend for PBM group. The overall results of the study suggest a potential benefit of PBM in conjunction with SRP in treating chronic periodontitis.  相似文献   

7.
Broad methodological heterogeneity makes the literature on the clinical effects of laser treatment in periodontitis, both as monotherapy and adjunct to non-surgical therapy, which is difficult to interpret. The present split-mouth study was performed: (i) to determine the efficacy and safety of a photoablative-photodynamic diode laser therapy, including antiseptic LED irradiation, in adjunct to scaling and root planing (iPAPD+SRP) vs. sham-treatment+SRP for the treatment of diffuse severe periodontitis and (ii) to estimate the patient-reported outcomes. Twenty-four patients with severe periodontitis were treated with iPAPD+SRP or sham-treatment+SRP. iPAPD+SRP consisted of the following: (1) intra-/extra-pocket de-epithelization with photoablative λ 810 nm laser, (2) disinfection with λ 405 nm LED, (3) SRP, and (4) 10 weekly antiseptic/anti-inflammatory photodynamic treatments with λ 635 nm laser and 0.1% toluidine blue as photosensitizer. Clinical and cytofluorescent periodontal markers and patient-reported results were analyzed. At 1-year follow-up, both groups showed a significant reduction of several severity markers of periodontitis, namely probing depth (PD) and bleeding on probing (BoP), as well as of bacteria, polymorphonuclear cells, erythrocytes and damaged epithelial cells in exfoliative samples, as compared with day 0. The quadrants subjected to iPAPD+SRP showed significantly better values of these parameters as well as of clinical attachment level (CAL) as compared with those undergoing sham-treatment+SRP. The patients’ perceived pain/discomfort, and overall liking was also in favor of the iPAPD+SRP treatment. This study confirms the efficacy of combined phototherapy in adjunct to SRP which had emerged from previous clinical trials, extending its field of application to severe periodontitis.  相似文献   

8.
BACKGROUND: The addition of phosphorothioate (PS) groups to natural phosphodiester (PD) antisense oligodeoxynucleotides (oligo) prevents their in vivo hydrolysis by nucleases allowing an RNase-dependent elimination of targeted mRNA. To further improve oligo function 2'-methoxyethyl (ME) groups were attached to selected nucleotides at the 3'-end because ME groups block RNase activity. METHODS/RESULTS: ME modification of PS- or PD/PS-oligo targeting human intracellular adhesion molecule (ICAM)-1 mRNA significantly increased the degree and duration of the in vitro inhibitory effects without compromising selectivity and specificity. A 7-day intravenous or oral therapy with rat ME/PS-modified ICAM-1 antisense oligo extended the survivals of kidney allografts. In addition, ME/PS-modified ICAM-1 antisense oligo reduced ischemic-reperfusion injury in kidneys, as measured by glomerular filtration rate, creatinine levels, and infiltration with leukocytes. Finally, a 14-day treatment with cyclosporine (CsA)-induced nephrotoxicity in syngeneic kidney transplants correlated with both increased ICAM-1 protein expression and infiltration with leukocytes. Graft perfusion and treatment of recipients with ICAM-1 antisense ME/PS-oligo alleviated the nephrotoxic effect and decreased ICAM-1 expression and leukocyte infiltration. CONCLUSIONS: ME/PS-modified ICAM-1 antisense oligo is very effective in inhibiting the ICAM-1-dependent mechanism of graft infiltration and tissue damage involved in allograft rejection, ischemic-reperfusion injury, and CsA-induced nephrotoxicity.  相似文献   

9.
用组织块移植法对兔颅骨细胞进行分离培养。相差显微镜观察,组织化学染色,免疫组织化学染色,mRNA原位杂交及体外钙化检测表明该细胞群符合成骨样细胞的特点。在此基础上用免疫组织化学SP法观察了c─Fos,c─Jun在成骨样细胞内的表达及其与骨钙素合成的关系。结果显示c─Fos,c─Jun从第一代到第十一代成骨样细胞内均有表达,且早期表达较多,可位于胞核、核膜及胞浆内。第六代以后的细胞仅胞浆着色。在c─Fos,c─Jun高表达时骨钙素合成减少,c─Fos,c─Jun低表达时骨钙素合成增加,提示c─Fos,c─Jun对骨钙素具有负调控作用。本实验结果为c─Fos,c─Jun参与骨代谢提供了直接证据,同时也为观测成骨细胞生长分化及其影响因素提供了有价值的指标,有助于促进牙周炎牙槽骨骨吸收机理及其它骨代谢相关研究。  相似文献   

10.
The aim of this randomized, parallel, controlled clinical trial was to examine the clinical and biochemical efficacy of diode laser as an adjunct to scaling and root planing (SRP). Thirty chronic periodontitis patients were randomly assigned into two groups to receive SRP alone (control) or SRP followed by diode laser (test). Plaque index, gingival index, bleeding on probing, probing depth, and clinical attachment level were measured at baseline and at 1, 3, and 6 months after treatment. The gingival crevicular fluid levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-8 (MMP-8) and tissue inhibitor matrix metalloproteinase-1 (TIMP-1) were analyzed by enzyme-linked immunosorbent assay. Test group showed significantly a better outcome compared to the control group in full-mouth clinical parameters. MMP-1, MMP-8, and TIMP-1 showed significant differences between groups after treatment compared to baseline (p?<?0.05). The total amount of IL-1β, IL-6, MMP-1, MMP-8, and TIMP-1 decreased (p?<?0.05) and IL-8 increased after treatment in both test and control groups (p?<?0.05). Diode laser provided significant improvements in clinical parameters and MMP-8 was significantly impacted by the adjunctive laser treatment at first month providing an insight to how lasers can enhance the outcomes of the nonsurgical periodontal therapy.  相似文献   

11.
In order to evaluate whether nonsurgical periodontal treatment with/without diode laser (DL) decontamination improves clinical parameters, the levels of IL-1β, IL-6, IL-8, intercellular adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM) in gingival crevicular fluid and metabolic control (HbA1c) in chronic periodontitis (CP) patients with diabetes mellitus type 2 (DM2). Sixty patients with DM2 and CP were randomly assigned into two groups to receive scaling and root planing (SRP, n?=?30) or SRP followed by diode laser application (SRP?+?DL, n?=?30). Clinical periodontal and gingival crevicular fluid (GCF) parameters were assessed at baseline, 1, and 3 months after periodontal treatment. HbA1c levels were evaluated at baseline and 3 months post-therapy. Total amounts of cytokines and molecules were analyzed by ELISA. Nonsurgical periodontal treatment with/without DL appeared to improve clinical, biochemical parameters, and glycemic control in DM2 patients (BMI?<?25 kg/m2) with CP. The SRP?+?DL group provided better reductions in probing depth (PD) and clinical attachment level (CAL) parameters compared to the SRP group (P?<?0.05). Significant reductions were found in the total amounts of GCF levels of IL-1, IL-6, IL-8, ICAM, and VCAM after treatment (P?<?0.05). HbA1c levels decreased significantly at 3 months after treatment (P?<?0.05). SRP?+?DL reduced HbA1c levels more significantly compared to SRP alone (0.41 vs. 0.22 %, P?<?0.05). SRP, especially in combination with DL, shows improvement of glycemic control for DM2 patients with CP.  相似文献   

12.
Achilles tendon problems are commonly encountered in sports medicine and low‐level laser therapy (LLLT) is widely used in rehabilitative applications to decrease pain, reduce inflammatory processes, and promote tissue healing. This study examined the effects on the proliferation of porcine Achilles tendon fibroblasts and gene expression, using different doses of low‐level laser irradiation (LLLI). Four groups of identically cultured fibroblasts were exposed to LLLI and harvested after 24 h. The control group (Group 1) was subjected to no LLLI. Other groups received 1 J/cm2 (Group 2), 2 J/cm2 (Group 3), and 3 J/cm2 (Group 4), respectively. Cell proliferation and mRNA expressions of type I collagen and decorin were then measured. When compared to the control group, the cell proliferation of irradiated Achilles tendon fibroblasts in the other three groups increased significantly by 13% ± 0.8% (Group 2), 30% ± 0.4% (Group 3), and 12% ± 0.6% (Group 4) respectively. But progressively higher laser intensity did not achieve a correspondingly higher cell proliferation effect in Achilles tendon fibroblasts. The mRNA expressions of decorin and type I collagen in fibroblasts with LLLI were significantly higher (p < 0.05). Therefore, suitable dosages of LLLI may result in more effective tissue healing by promoting type I collagen and decorin synthesis. However, these positive effects of LLLI on the repair of the Achilles tendon in humans should be further investigated in clinic. Published by Wiley Periodicals, Inc. J Orthop Res 27: 646–650, 2009  相似文献   

13.
The purpose of this split-mouth, single-blind, controlled clinical study was to evaluate the impact of low-level laser therapy (LLLT) as an adjunct to non-surgical treatment of chronic periodontitis. Twenty-five systemically healthy and non-smoking adults with chronic periodontitis who had at least two bilateral premolar teeth with probing pocket depth (PPD) of 7?≥?x?≥?5 mm were included in the study. In the periodontal examination of these patients, PPD, gingival index (GI), plaque index (PI), clinical attachment level (CAL), and bleeding on probing (BOP) were recorded at the baseline, first, third, and sixth months after treatment. Gingival crevicular fluid (GCF) samples were taken at the baseline, first week, and first month after treatment. The collected GCF samples were analyzed using the MAGPIX? system with a Bio-Plex Pro? Human Cytokine 27-plex kit. After non-surgical periodontal treatment, LLLT with an energy density of 7.64 J/cm2 was performed four times: immediately after scaling and root planning (SRP) and on the first, third, and seventh day after treatment. In the first month, PPD levels were significantly (p?<?0.05) lower in the SRP?+?LLLT group than in the SRP group. At the third and sixth months, CAL, PPD, and GI were significantly (p?<?0.05) lower in the SRP?+?LLLT group than in the SRP group. Differences in GCF cytokines levels among the group were not statistically significant. Within the limitations of this study, it is indicated that LLLT as an adjunct to non-surgical periodontal treatment has a positive impact on clinical parameters.  相似文献   

14.
Adjunctive treatments to scaling and root planing (SRP) such as lasers, have been utilized in the treatment of chronic periodontitis, mainly aiming to suppress and eliminate the bacteria, as well as enhancing the healing response. Eighty gingival papilla biopsy samples were obtained from 60 patients diagnosed with chronic advanced periodontitis; randomly assigned to three treatment groups (n = 20), as well as 20 subjects with no periodontal disease [group A]. Group B received SRP on a single quadrant/day for four consecutive days. On day 5, all quadrants were rescaled. Groups C and D received the same treatment as group B plus laser application with the low-level diode laser (630-670 nm, 1.875 J/cm2) for five and ten consecutive days, respectively. Papilla biopsies were obtained from subjects and evaluated by RT-PCR for expression of COX-2. The values in the control group were 0.028 0.014 and baseline values for the examined groups were 0.16 0.18. Significantly decreased level of COX-2 expression for groups C and D was found after treatment, while lowest average expression was found in the group that had the 10 laser treatments supplemental to SRP (0,035 0,014). The results of this study show suppression of COX-2 in gingival tissue after low-level laser treatment as adjunct to SRP.  相似文献   

15.
BACKGROUND: Chemokines are involved in the regulation of the cellular renal infiltrate in glomerulonephritis; however, it is unclear to which degree resident glomerular cells or infiltrating leukocytes contribute to the formation of chemokines in glomerular inflammatory lesions. We therefore examined whether monocytes/macrophages play a role in the expression of the C-C chemokines MCP-1/CCL2 and RANTES/CCL5 in renal tissue in a lipopolysaccharide (LPS)-induced model of inflammation, where previously we have shown increased glomerular RANTES expression and glomerular infiltration of ED-1-positive cells. METHODS: Inflammatory lesions were induced by an intraperitoneal injection of LPS. The infiltration of monocytes into the glomerulus was reduced by two experimental approaches. First, rats were depleted of monocytes by the use of specific monocyte-antisera or by cytotoxic drugs. Second, the infiltration of monocytes into the kidney was reduced by using intercellular adhesion molecule-1 (ICAM-1) knockout mice. RESULTS: Both experimental approaches demonstrated a significant reduction in the number of infiltrating monocytes/macrophages after lipopolysaccharide injection. This reduction in the infiltration of inflammatory cells was associated with significantly reduced RANTES/CCL5 mRNA expression. However, MCP-1/CCL2 mRNA expression was not inhibited after the LPS injection by monocyte/macrophage depletion. Also, the increase in nuclear factor-kappaB (NF-kappaB) binding activity after the LPS injection was not reduced in pretreated animals. The experiments therefore demonstrate that infiltrating monocytes/macrophages contribute to increased RANTES/CCL5 mRNA expression in inflammatory renal lesions, whereas MCP-1/CCL2 mRNA expression and NF-kappaB activation were not reduced by monocyte/macrophage depletion. CONCLUSION: MCP-1/CCL2 released from renal tissue upon stimulation plays a major role in the regulation of monocyte/macrophage infiltration, which contributes significantly to increased renal RANTES/CCL5 expression. This cross-talk between resident renal cells and monocytes/macrophages is therefore likely to boost the number of infiltrating inflammatory cells.  相似文献   

16.
This study sought to evaluate the effect of low-level laser treatment combined with scaling and root planing (SRP) on gingival tissue levels of TNF-alpha in subjects with periodontal disease. Eighty gingival papilla biopsy samples were obtained from 60 patients diagnosed with chronic advanced periodontitis; randomly assigned to three treatment groups (n = 20), as well as 20 subjects with no periodontal disease (group A). Group B received SRP on a single quadrant/day for four consecutive days. On day 5, all quadrants were rescaled. Groups C and D received the same treatment as group B plus laser application with the low-level diode laser (630–670 nm, 1.875 J/cm2) for five and ten consecutive days, respectively. Papilla biopsies were obtained from subjects and evaluated by ELISA for levels of TNF-alpha. The values in the control group were 5.2 ± 3.21 pg/mg and baseline values for the examined groups were 46.01 ± 16.69. Significantly decreased level of TNF-alpha for groups C and D was found after treatment, while group B demonstrated reduction of TNF-alpha of 31.34%. The results of this study show suppression of TNF-alpha in gingival tissue after low-level laser treatment as adjunct to SRP. Data may suggest beneficial anti-inflammatory effects of the laser treatment when used as adjunctive periodontal treatment.  相似文献   

17.
BACKGROUND: The upregulated renal expression of intercellular adhesion molecule 1 (ICAM-1) is associated with glomerular and interstitial infiltration of leukocytes. AIM: To test the hypothesis that renal expression of ICAM-1 may be predictive in the highly variable IgA nephropathy (IgAN). METHODS: ICAM-1 (CD54) in tubular epithelium and interstitial leukocytes, macrophages (CD14), and T cells (CD3) were assessed using avidin-biotin-peroxidase in renal biopsy specimens from 45 patients with IgAN and from 29 patients with no glomerulonephritis. RESULTS: In IgAN, tubular ICAM-1+ was seen in 25 of 45 (55%) biopsy specimens, associated with glomerular hypercellularity, glomerulosclerosis involving less than 50% of the glomerular area, interstitial cellular infiltration, tubular atrophy, and proteinuria (U = 44, p = 0.005). Interstitial ICAM-1+ leukocytes were correlated with glomerulosclerosis involving less and more than 50% of the glomerular area, tubular atrophy, interstitial fibrosis, and serum creatinine concentration (r = 0.6343, p < 0.001). In patients with an increase of 50% in the serum creatinine concentration, interstitial ICAM-1+ leukocytes and CD14+ and CD3+ cells were significantly more numerous than in patients with a stable creatinine concentration. In patients with no glomerulonephritis, tubular ICAM-1+ was seen in 7 of 29 (24%) biopsy specimens, inversely correlated with the number of normal glomeruli and associated with glomerulosclerosis covering more than 50% of the glomerular area, tubular atrophy, and creatinine. CONCLUSIONS: Tubular and interstitial expression of ICAM-1 can be a marker of tubulointerstitial disturbance in IgAN. Interstitial ICAM-1 may be an adverse predictor of disease progression.  相似文献   

18.
Abstract Objective: The aim of this study was to compare the clinical parameters and crevicular cell population, particularly leukocyte counts, changes after initial periodontal therapy with different instruments by a chairside laboratory technique, in severe periodontitis patients. Background data: Although scaling and root planing (SRP) with hand curettes or ultrasonic scalers may alter the subgingival microbial composition and improve clinical parameters, it is known that this effect decreases as the pocket depth (PD) increases. Material and methods: Thirty systemically healthy subjects with severe chronic periodontitis were randomly assigned to three groups (n=10), and were treated either with hand curettes, ultrasonic scalers, or Er:YAG laser alone. Clinical measurements were made before and 90 days after treatment. A total of four subgingival plaque samples were collected from pockets with a PD 4-6 and ≥7?mm and were analyzed with a phase-contrast microscopy for microorganism proportions and leukocyte counts at baseline and 7 and 90 days after treatment. Results: From day 0 to day 90, clinical parameters were significantly improved in all groups (p<0.01), but there were no significant differences among groups. Laboratory assessments revealed significant differences in all groups between baseline, day 7, and day 90. However, considering changes from day 7 to day 90, hand curettes were the most successful for maintaining the levels of micro-organisms and leukocytes. Conclusions: Although Er:YAG lasers are promising in treating periodontitis, the results of this study favor finishing SRP with hand curettes. Moreover, as there is a similar tendency between micro-organism and leukocyte count changes, leukocyte counts may be used as chairside marker to evaluate the efficacy of SRP.  相似文献   

19.
Prostaglandin estradiol (PGE(2)) stimulates bone resorption by a cyclic AMP (cAMP)-dependent mechanism that involves prostaglandin E receptors of the EP2 and EP4 subtypes. We tested a potent selective EP4 antagonist (EP4RA), which blocks PGE(2) binding to EP4 receptors. We examined the effects of EP4RA on osteoclastogenesis in murine marrow cultures, on cAMP production in primary osteoblastic (POb) cell cultures, and on bone resorption in organ cultures. EP4RA (1 micromol/L) decreased the number of tartrate-resistant acid phosphatase-positive multinucleated cells (TRAP(+) MNC) by 46%-48% in cultures treated with 0.1-1.0 micromol/L PGE(2) and by 96% in cultures treated with 0.01 micromol/L PGE(2). EP4RA also decreased TRAP(+) MNC formation by 60% in 1,25-dihydroxyvitamin D (1,25D)-treated cultures and by 62% in parathyroid hormone (PTH)-treated cultures. A chemically related analog of EP4RA that lacks antagonist activity did not inhibit TRAP(+) MNC formation. EP4RA decreased cAMP production in PGE(2)-treated POb by 44% but did not block cAMP response to PTH. EP4RA inhibited the increase in receptor activator of NF-kappaB ligand (RANKL) mRNA levels produced by PGE(2). In fetal rat long bone cultures, EP4RA decreased 45Ca release from control, unstimulated cultures by 12%-25% and from PGE(2)-stimulated cultures by 22%-37%. Because EP4RA partially inhibited osteoclastogenesis not only in response to PGE(2) but also in response to 1,25D and PTH, these results suggest that activation of the EP4 receptor may play a general role in osteoclastic bone resorption. EP4RA showed partial inhibition of PGE(2)-stimulated osteoclastogenesis at 1 micromol/L, but almost complete inhibition at 0.01 micromol/L PGE(2). This could be due to the limited efficacy of the antagonist at high concentrations of PGE(2), or an alternative pathway, such as activation of the EP2 receptor.  相似文献   

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