Characterisation and in vitro and in vivo evaluation of supercritical-CO2-foamed ß-TCP/PLCL composites for bone applications.

Most synthetic bone grafts are either hard and brittle ceramics or paste-like materials that differ in applicability from the gold standard autologous bone graft, which restricts their widespread use. Therefore, the aim of the study was to develop an elastic, highly porous and biodegradable ß-tricalciumphosphate/poly(L-lactide-co-ε-caprolactone) (ß-TCP/PLCL) composite for bone applications using supercritical CO2 foaming. Ability to support osteogenic differentiation was tested in human adipose stem cell (hASC) culture for 21 d. Biocompatibility was evaluated for 24 weeks in a rabbit femur-defect model. Foamed composites had a high ceramic content (50 wt%) and porosity (65-67 %). After 50 % compression, in an aqueous environment at 37 °C, tested samples returned to 95 % of their original height. Hydrolytic degradation of ß-TCP/PLCL composite, during the 24-week follow-up, was very similar to that of porous PLCL scaffold both in vitro and in vivo. Osteogenic differentiation of hASCs was demonstrated by alkaline phosphatase activity analysis, alizarin red staining, soluble collagen analysis, immunocytochemical staining and qRT-PCR. In vitro, hASCs formed a pronounced mineralised collagen matrix. A rabbit femur defect model confirmed biocompatibility of the composite. According to histological Masson-Goldner's trichrome staining and micro-computed tomography, ß-TCP/PLCL composite did not elicit infection, formation of fibrous capsule or cysts. Finally, native bone tissue at 4 weeks was already able to grow on and in the ß-TCP/PLCL composite. The elastic and highly porous ß-TCP/PLCL composite is a promising bone substitute because it is osteoconductive and easy-to-use and mould intraoperatively.

Lymphotoxin alpha LTA+496C allele is a risk factor for periodontitis in patients with coronary artery disease.

Periodontitis and coronary artery disease (CAD) are inflammatory diseases and associated with each other. The major histocompatibility complex (MHC) region carries genes involved in immune response and inflammation. We investigated whether the MHC genes correlate with the presence of periodontitis or with the occurrence of periodontal pathogens in patients with CAD. Blood and saliva samples from CAD patients (n = 106) were collected at the time of hospitalization. Nine MHC genetic markers [human leukocyte antigen (HLA)-A, HLA-B, HLA-DRB1, lymphotoxin alpha (LTA) +253(a/g), +496(C/T), +633(c/g), +724(C/A), C4A and C4B)] were typed. Based on panoramic tomography, patients were categorized into nonperiodontitis and periodontitis groups. Two major periodontal pathogens, Aggregatibacter (Actinobacillus) actinomycetemcomitans and Porphyromonas gingivalis, were cultivated and polymerase chain reaction-amplified from salivary samples. Serum immunoglobulin (Ig)A and IgG antibody levels to these pathogens were measured. In the univariate analysis, LTA+496C allele (OR = 5.29; 95% CI = 2.07-13.51, P = 0.00027), and the occurrence of P. gingivalis in saliva (OR = 4.74; 95% CI = 1.64-13.70; P = 0.002) were more frequent in periodontitis when compared with nonperiodontitis. Similarly, serum IgA antibody level against the pathogen was increased in periodontitis (P = 0.048). In the multiple logistic regression analysis, when a wide range of covariates was included, the LTA+496C allele (OR = 10.87; 95% CI = 3.23-36.60; P = 0.00012) and the elevated serum IgA antibody level against P. gingivalis (OR = 1.56; 95% CI = 1.05-2.30; P = 0.026) remained as significant risk factors for periodontitis. In conclusion, the major finding of this study is that the LTA+496C allele is associated with periodontitis in patients with CAD.

Complement and c4 null alleles in severe chronic adult periodontitis.

Severe forms of chronic periodontitis affect up to 10% of adults. Tumour necrosis factor and lymphotoxin-alpha genes in the major histocompatibility complex are associated with severe periodontitis. Complement factor C4 is a nearby, polymorphic, functionally relevant gene region. Although associated with chronic mucosal infections, C4 deficiencies have not been assessed in adult periodontitis patients. We tested whether complement levels are systemically altered and C4 deficiencies associated with severe chronic periodontitis. In a case-control study, we analysed levels of plasma C3, and C4, serum classical pathway haemolytic activity, C4 allotypes and C4 gene numbers in 37 patients with severe chronic periodontitis and in 150 voluntary controls. Plasma levels of C3 were higher, and classical pathway haemolytic activity was lower in patients than in controls. Partial C4 gene deficiencies were more frequent in patients than in controls (odds ratio 2.4, 95% confidence interval 1.1-5.5, P = 0.032). Changes in complement levels may reflect chronic, recurring inflammation. C4 gene deficiencies are associated with predisposition to chronic periodontitis.

Localization of heat shock proteins in clinical Actinobacillus actinomycetemcomitans strains and their effects on epithelial cell proliferation.

Actinobacillus actinomycetemcomitans is an important pathogen in periodontitis. In the present study we localized the GroEL- and DnaK-like heat shock proteins (Hsp) in subcellular fractions of 12 A. actinomycetemcomitans strains of various clinical origin and compared their effects on periodontal epithelial cell proliferation and viability. In all strains, GroEL-like protein was found in the membrane, cytoplasm, and periplasm, whereas DnaK-like protein was present in the cytoplasm and periplasm. No correlation was observed between the Hsp expression and the serotype or origin of A. actinomycetemcomitans strains. The bacterial membrane fractions that expressed the GroEL-like protein moderately or strongly induced epithelial cell proliferation more strongly than strains that expressed the protein weakly. The results suggest that GroEL-like Hsp may play a role in the virulence of A. actinomycetemcomitans by increasing epithelial proliferation.

Role of infection as a risk factor for atherosclerosis, myocardial infarction, and stroke.

An increasing body of evidence has linked infections to atherosclerosis and thrombosis. Herpesviruses cause atherosclerosis in experimental animals. Herpesviruses can also be detected in atherosclerotic lesions in humans. Cytomegalovirus may play a role in arteriosclerosis in transplanted hearts, and this virus, together with tumor suppressor protein p53, can be found in restenosis lesions following angioplasty. Chlamydia pneumoniae and dental infections are associated with coronary heart disease in cross-sectional and longitudinal studies, and preceding respiratory infections are associated with ischemic stroke. Infections may favor formation of atherosclerosis and thrombosis by elevation of blood levels of fibrinogen, leukocytes, clotting factor, and cytokines and by alteration of the metabolism and functions of endothelial cells and monocyte macrophages. Low-grade infections may also be one of the causes of the inflammatory reaction observed in atherosclerotic lesions and acute ischemic symptoms, reflected in elevated levels of C-reactive protein. These observations warrant further studies in this field.

Acute tongue abscess: report of two cases.

Tongue abscesses are extremely rare. Two cases caused by periodontal pathogens are presented.

Value of some laboratory and clinical measurements in the treatment plan for advanced periodontitis.

In our previous study, we reported that only 13 of 46 adult patients with advanced periodontitis responded well to initial non-surgical periodontal therapy. In the present follow-up study, the remaining 33 patients were randomly treated further using either modified Widman flap surgery or systemic metronidazole. The patients responding unsatisfactorily to this 2nd treatment phase, received supplementary systemic chemotherapy or surgery, respectively. By using this study design, we determined which baseline clinical variables and/or laboratory findings predicted the treatment outcome in these study patients. Clinical variables included the assessment of bleeding, suppuration, probing pocket depth, furcation lesions, relative attachment level and radiographic infrabony defects. Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were cultured from subgingival plaque samples. The specific IgG and IgA antibody levels against 5 serotypes of A. actinomycetemcomitans were determined in serum and saliva. Elastase-like, trypsin-like and general protease activities were assessed from saliva. The bivariate statistical analyses showed that the most pronounced difference between the patients responding well to initial non-surgical therapy (group MC, n = 13), to either supplementary surgery or chemotherapy (group FT1, n = 11), or those responding to the complex therapy (group FT2, n = 17), was the prior extent of periodontal destruction expressed as the proportion of > or = 6 mm deep periodontal pockets. When multiple linear regression was used to investigate the influence of clinical and laboratory findings on the variation of treatment response between the 3 groups, the most significant explanatory factor was the simultaneous presence of subgingival A. actinomycetemcomitans and multiple deep periodontal pockets. None of the immunological or biochemical variables used had any further influence in the model. Pretreatment microbiological examination, especially for the detection of A. actinomycetemcomitans, seems to be a valuable laboratory screening method for identifying complex treatment need in adult patients with advanced periodontitis. However, the evaluation of the extent and pattern of periodontal breakdown remains crucial for choosing the treatment strategy including surgery and/or chemotherapy in A. actinomycetemcomitans-infected adult periodontitis patients.

Metronidazole in the treatment of localized juvenile periodontitis.

Systemic metronidazole and tetracycline were compared as adjunctive agents in the treatment of localized juvenile periodontitis (LJP). 27 patients with Actinobacillus actinomycetemcomitans-positive (Aa) LJP were treated with scaling and rootplaning, control of oral hygiene and periodontal surgery if indicated. The patients were randomly divided into 3 equal groups: the 1st group had metronidazole 200 mg x 3 x 10 days, the 2nd tetracycline 250 mg x 4 x 12 days, the 3rd group received no medication and served as a control. 6 patients had periodontal surgery. 4 sites with the most advanced bone loss as determined on radiographs were selected in each subject for test sites. Gingival index, gingival bleeding after probing (GB), probing depth (PD), suppuration, and radiographic bone loss were registered, and subgingival Aa was selectively cultured. GB and PD > or = 4 mm were registered in the whole dentition as well. All parameters were monitored at baseline and at 6 and 18 months after treatment. By the end of the study, Aa was suppressed to below detection level at all test sites only in the metronidazole group, at 17/26 sites (4 patients) in the tetracycline group and at 19/26 sites (6 patients) in the control group. Clinically, all groups showed improvement. In conclusion, metronidazole was more effective than tetracycline in the suppression of Aa and the suppression of Aa appeared to produce better clinical results.

The long-term efficacy of systemic doxycycline medication in the treatment of localized juvenile periodontitis.

The presence of Actinobacillus actinomycetemcomitans in the deep periodontal pockets of patients with localized juvenile periodontitis has been causally associated with active periodontal destruction. Thus, eradication of this microorganism has become the goal of treatment. It has been postulated that such eradication cannot be achieved without systemic antimicrobial treatment. The efficacy of a semisynthetic tetracycline (doxycycline) in a double-blind follow-up study of 14 patients with localized juvenile periodontitis was evaluated. For assessment of the periodontal status, probing depth and bleeding after probing at 4 sites of all teeth were recorded. The treatment consisted of instruction in oral hygiene, scaling and root planing, periodontal surgery and systemic medication for 2 weeks with either doxycycline (Doximycin) or placebo. A. actinomycetemcomitans was cultivated from subgingival samples taken from 4 sites. The periodontal condition and the prevalence of A. actinomycetemcomitans were monitored at the baseline and at 2, 8 and 20 months. The periodontal condition improved in both groups; the only significant difference was a greater reduction in the prevalence of A. actinomycetemcomitans 8 months after treatment with doxycycline as compared with the placebo.

Treatment of juvenile periodontitis without antibiotics. A follow-up study.

20 patients with juvenile periodontitis (JP) were treated with oral hygiene instruction, scaling and root planing, possibly with flap surgery but with no antibiotics. The patients were monitored after 6 to 12 years. Re-examination revealed that no probing depth of 7 mm or more existed any longer, and that sites with probing depth of 4 to 6 mm had decreased from 237 to 46. The bone loss scores had changed from 18% (range 2.0 to 48.1) to 14% (range 0 to 44.4) and the bleeding on probing scores from 39% (range 0 to 100) to 10% (range 0 to 40). Actinobacillus actinomycetemcomitans (A.a.) had neither been cultivated nor serologically tested at the initial examination. At the re-examination, it was found in 2 patients out of 20 at 5 sites. 7 patients, the 2 with positive cultures included, had elevated titers to A.a. strain Y4 in whole or parotid saliva or both. It is concluded that there is a marked improvement in the periodontal condition of these patients, and that good periodontal health in patients with JP can be reached without antibiotics.