Clinical results after nonsurgical therapy in aggressive and chronic periodontitis.

AIM: This study aims to analyze factors influencing treatment results in aggressive (AgP) and chronic (ChP) periodontitis. METHODS: ChP [probing pocket depth (PPD) ≥ 3.5 mm, attachment loss ≥ 5 mm at >30 % of sites; age > 35 years] and AgP (clinically healthy; PPD ≥ 3.5 mm at >30 % of sites, radiographic bone loss ≥ 50 % at 2 teeth; age ≤ 35 years) were examined prior and 3 months after nonsurgical therapy according to the full-mouth disinfection concept. Adjunctive systemic antibiotics were used if Aggregatibacter actinomycetemcomitans had been detected at baseline. RESULTS: In 31 ChP (12 female, 10 smokers; 4,808 sites) and 28 AgP (16 female, 9 smokers; 4,769 sites), overall mean PPD reductions were less favorable in AgP (0.9 ± 0.5 mm) than in ChP (1.3 ± 0.4 mm; p = 0.033). PPD reductions and relative vertical probing attachment level gain were more favorable at sites with initial PPD ≥ 6 mm, bleeding on probing, and for adjunctive systemic antibiotics. Furthermore, PPD reductions were more favorable for increased baseline tooth mobility and maxillary teeth, whereas AgP, female sex, and multirooted teeth were associated with less favorable PPD reduction. CONCLUSION: Regarding PPD reduction, AgP responded less favorably to nonsurgical treatment than ChP.

Non-surgical periodontal therapy decreases serum elastase levels in aggressive but not in chronic periodontitis.

AIM: Assessment of the effect of non-surgical periodontal therapy (SRP) on serum inflammatory parameters in patients with untreated aggressive (AgP) and chronic (ChP) periodontitis. METHODS: Overall, 31 ChP and 29 AgP were examined clinically prior to and 12 weeks after SRP (subgingival scaling of all pockets within 2 days) with systemic antibiotics for patients positive for Aggregatibacter actinomycetemcomitans (14 AgP, 9 ChP). Blood was sampled prior to, one day, 6, and 12 weeks after the first SRP visit. Serum elastase, C-reactive protein (CRP), lipopolysaccharide-binding protein (LBP), interleukin (IL) 6, 8, and leukocyte counts were assessed. RESULTS: At baseline, serum elastase, CRP, and LBP were significantly (p < 0.01) higher in AgP than ChP. Serum elastase, CRP, LBP, and IL-6 were significantly (p < 0.001) elevated one day after scaling in both groups. Both groups showed significant clinical improvement (p < 0.001). A significant difference was observed regarding change of serum elastase 12 weeks after SRP between AgP and ChP (p = 0.015). Multiple regression analysis revealed AgP, African origin, and bleeding on probing to be associated with more pronounced elastase reduction. CRP reduction was associated with African origin, systemic antibiotics, and baseline probing pocket depth. CONCLUSION: SRP results in serum elastase reduction in AgP but not in ChP.

Increased systemic elastase and C-reactive protein in aggressive periodontitis (CLOI-D-00160R2).

The inflammatory mediators, serum elastase and C-reactive protein (CRP), are associated with an increased risk for coronary heart disease. Thus, the aim of this study is to compare systemic inflammatory mediators in periodontally healthy controls (C), patients with untreated aggressive (AgP) and chronic (ChP) periodontitis. C [periodontal pocket probing depth (PPD) <3.6 or <5 mm without bleeding (BOP), BOP < 10%], ChP (PDD ≥ 3.6 mm and probing attachment loss ≥5 mm at >30% of sites; age >35 years), and AgP (clinically healthy; PDD ≥ 3.6 mm at >30% of sites, bone loss ≥50% at ≥2 teeth; age ≤35 years) were examined clinically, and the body mass index was assessed. Blood was sampled for assessment of serum levels of elastase, CRP, lipopolysaccharide binding protein (LBP), interleukin (IL) 6, 8, and leukocyte counts. Thirty C, 31 ChP, and 29 AgP were analyzed. Elastase, CRP, LBP, and IL-6 levels were elevated in AgP compared to C (p < 0.013), whereas leukocyte counts and IL-8 were similar. Multiple regression analysis identified AgP (p < 0.001) and education level (p < 0.001) to explain 47% of the variation of elastase. AgP (p = 0.003), African origin (p = 0.006), female sex (p = 0.002), and BMI (p < 0.001) explained 39% of the variation of CRP. Serum elastase and CRP are significantly elevated in AgP compared to C. AgP patients exhibit a stronger systemic inflammatory burden than C patients.

KAAD-cyclopamine augmented TRAIL-mediated apoptosis in malignant glioma cells by modulating the intrinsic and extrinsic apoptotic pathway.

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic. The main obstacle in TRAIL-based therapy is that many glioma cells are resistant. In this study glioblastoma cell lines, human glioblastoma short-term cultures and human astrocytes were treated with 3-keto-N-aminoethylaminoethylcaproyldihydrocinnamoyl cyclopamine (KAAD-cyclopamine), tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) or the combination of both. Single treatment with KAAD-cyclopamine or TRAIL does not induce cytotoxicity in malignant glioma cells. However, treatment with KAAD-cyclopamine in combination with TRAIL induces rapid apoptosis in TRAIL-resistant glioma cells. Notably, normal human astrocytes were not affected by the combination treatment consisting of KAAD-cyclopamine and TRAIL. KAAD-cyclopamine led to an upregulation of death receptor 4 and 5 and down-regulation of bcl-2 and c-FLIP. Furthermore, overexpression of both bcl-2 and c-FLIP attenuated KAAD-cyclopamine facilitated TRAIL-mediated apoptosis. Taken together,we provided evidence that KAAD-cyclopamine facilitated TRAIL-mediated apoptosis at the level of the intrinsic and extrinsic apoptotic pathways in malignant glioma cells.

Genistein enhances proteasomal degradation of the short isoform of FLIP in malignant glioma cells and thereby augments TRAIL-mediated apoptosis.

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer drug. One obstacle in TRAIL-based therapies is that many cancer cells, including gliomas, are resistant towards TRAIL. In this study one glioblastoma cell line, one human short-term glioblastoma culture and human astrocytes were treated with genistein, tumour necrosis factor-related apoptosis-inducing ligand or the combination of both. Single treatment with genistein or TRAIL does not induce cytotoxicity in malignant glioma cells. However, treatment with genistein in combination with TRAIL induces rapid apoptosis in TRAIL-resistant glioma cells. Notably, normal human astrocytes were not affected by the combination treatment consisting of genistein and TRAIL. Genistein enhanced proteasomal degradation of the short isoform of c-FLIP. Importantly, over-expression of only the short isoform of c-FLIP attenuated genistein TRAIL-mediated cytotoxicity. Taken together, we gave evidence that genistein facilitated TRAIL-mediated apoptosis at the level of the extrinsic apoptotic pathways in malignant glioma cells.

Palmitic acid and DGAT1 deficiency enhance osteoclastogenesis, while oleic acid-induced triglyceride formation prevents it.

Both obesity and diabetes mellitus are associated with alterations in lipid metabolism as well as a change in bone homeostasis and osteoclastogenesis. We hypothesized that increased fatty acid levels affect bone health by altering precursor cell differentiation and osteoclast activation. Here we show that palmitic acid (PA, 16:0) enhances receptor activator of NF-κB ligand (RANKL)-stimulated osteoclastogenesis and is sufficient to induce osteoclast differentiation even in the absence of RANKL. TNFα expression is crucial for PA-induced osteoclastogenesis, as shown by increased TNFα mRNA levels in PA-treated cells and abrogation of PA-stimulated osteoclastogenesis by TNFα neutralizing antibodies. In contrast, oleic acid (OA, 18:1) does not enhance osteoclast differentiation, leads to increased intracellular triglyceride accumulation, and inhibits PA-induced osteoclastogenesis. Adenovirus-mediated expression of diacylglycerol acyl transferase 1 (DGAT1), a gene involved in triglyceride synthesis, also inhibits PA-induced osteoclastogenesis, suggesting a protective role of DGAT1 for bone health. Accordingly, Dgat1 knockout mice have larger bone marrow-derived osteoclasts and decreased bone mass indices. In line with these findings, mice on a high-fat PA-enriched diet have a greater reduction in bone mass and structure than mice on a high-fat OA-enriched diet. Thus, we propose that TNFα mediates saturated fatty acid-induced osteoclastogenesis that can be prevented by DGAT activation or supplementation with OA.