Comprehensive Analysis of 1-Year-Old Female Apolipoprotein E-Deficient Mice Reveals Advanced Atherosclerosis with Vulnerable Plaque Characteristics.

Apolipoprotein E-knockout (Apoe-/-) mice constitute the most widely employed animal model of atherosclerosis. Deletion of Apoe induces profound hypercholesterolemia and promotes the development of atherosclerosis. However, despite its widespread use, the Apoe-/- mouse model remains incompletely characterized, especially at late time points and advanced disease stages. Thus, it is unclear how late atherosclerotic plaques compare to earlier ones in terms of lipid deposition, calcification, macrophage accumulation, smooth muscle cell presence, or plaque necrosis. Additionally, it is unknown how cardiac function and hemodynamic parameters are affected at late disease stages. Here, we used a comprehensive analysis based on histology, fluorescence microscopy, and Doppler ultrasonography to show that in normal chow diet-fed Apoe-/- mice, atherosclerotic lesions at the level of the aortic valve evolve from a more cellular macrophage-rich phenotype at 26 weeks to an acellular, lipid-rich, and more necrotic phenotype at 52 weeks of age, also marked by enhanced lipid deposition and calcification. Coronary artery atherosclerotic lesions are sparse at 26 weeks but ubiquitous and extensive at 52 weeks; yet, left ventricular function was not significantly affected. These findings demonstrate that atherosclerosis in Apoe-/- mice is a highly dynamic process, with atherosclerotic plaques evolving over time. At late disease stages, histopathological characteristics of increased plaque vulnerability predominate in combination with frequent and extensive coronary artery lesions, which nevertheless may not necessarily result in impaired cardiac function.

Therapeutic human monoclonal antibodies in inflammatory diseases.

Monoclonal antibodies (mAbs) are antibodies of a single antigen specificity produced by identical immune cells, i.e., clones of a common germ cell. They offer unprecedented opportunities to drug development because of their ability to target almost any cell surface or secreted molecule with remarkable efficacy and safety. In this chapter, the application of human mAbs in the treatment of inflammatory diseases is reviewed. We discuss in detail several mAb-based drugs such as anti-tumor necrosis factor (anti-TNF), anti-interleukin-1 (anti-IL-1) receptor, anti-IL-6 receptor, anti-α4 integrin subunit, and anti-CD20 agents, all of which have been documented by clinical trials to be efficacious and have been approved for the therapy of several inflammatory and immune diseases, including rheumatoid arthritis, Crohn's disease, ulcerative colitis, spondyloarthropathies, juvenile arthritis, psoriasis, psoriatic arthritis, and others. These novel drugs can be used either as a monotherapy or in combination with other conventional therapeutic modalities, particularly if the disease under treatment is refractory to therapy using solely conventional techniques. As a large variety of mAb-based agents targeting a plethora of cytokines, chemokines, adhesion and co-stimulatory molecules, receptors, as well as diverse cell types, are presently under investigation, the therapeutic armamentarium of the clinician is expected to greatly broaden in the near future, providing improved patient care for a wide range of devastating diseases of our times.

The use of platelet-rich plasma combined with demineralized freeze-dried bone allograft in the treatment of periodontal endosseous defects: a report of two clinical cases.

BACKGROUND: On the basis of systematic reviews and randomized controlled trials, the authors provide reports of two cases in which platelet-rich plasma (PRP) combined with demineralized freeze-dried bone allograft (DFDBA) was used to treat periodontal endosseous defects. CASE DESCRIPTION: Clinicians treated two circumferential endosseous defects with a probing pocket depth of 5 and 8 millimeters, respectively (case 1), and a combined 1-2-3-wall endosseous defect with a probing pocket depth of 6 mm (case 2) by using the combination of PRP and DFDBA. At six months, complete periodontal pocket resolution occurred in all defects, and clinical attachment level and radiographic defect fill in all defects exhibited significant improvement compared with presurgical values. CLINICAL IMPLICATIONS: The combination of PRP and DFDBA may be clinically and radiographically efficacious in the treatment of periodontal endosseous defects.

A systematic review and meta-analysis on the effect of implant length on the survival of rough-surface dental implants.

BACKGROUND: A meta-analysis on the survival of short implants compared to conventional implants has never been performed. Therefore, the aim of this study was to address the focused question "Is there a significant difference in survival between short (or=10 mm) rough-surface dental implants placed in 1) totally or 2) partially edentulous patients?" by conducting a systematic review and meta-analysis of prospective studies published in the dental literature in the English language up to and including August 2007. METHODS: PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were scanned electronically, and seven journals were searched manually. In the first phase of selection, titles and abstracts, and in the second phase, full texts, were evaluated autonomously and in duplicate by two reviewers. Extensive contact with authors was carried out in search of missing, unclear, or unpublished data. RESULTS: The electronic and manual search provided, respectively, 1,056 and 14,417 titles and abstracts. In the second phase of selection, the complete text of 300 articles was examined, and 37 articles reporting on 22 patient cohorts were selected. Meta-analyses revealed no statistically significant difference in survival between short (or=10 mm) rough-surface implants placed in totally or partially edentulous patients. CONCLUSIONS: Within the limitations of this systematic review, the placement of short rough-surface implants is not a less efficacious treatment modality compared to the placement of conventional rough-surface implants for the replacement of missing teeth in either totally or partially edentulous patients.

Therapy of peri-implantitis: a systematic review.

AIM: The objective of this study was to provide a systematic review of randomized controlled and/or comparative clinical trials published in the international peer-reviewed literature in the English language, up to and including July 2007, concerning the efficacy of all treatment modalities implemented for the therapy of peri-implantitis. MATERIAL AND METHODS: PubMed and The Cochrane Library databases were searched electronically and numerous journals were examined manually. In the first phase of selection, the titles and abstracts, and in the second phase, complete papers were screened independently and in duplicate by three reviewers (S. K., I. K. K. and M. T.). RESULTS: The search yielded 1304 possibly relevant titles and abstracts. After the first phase of selection, 13 publications were singled out for a rigorous evaluation. Following the second phase, five studies were selected. CONCLUSIONS: The selected studies are too limited in number and exhibit small sample sizes and short follow-up periods. Therefore, there is a definite need for more well-designed, preferably longitudinal, randomized controlled clinical trials. Within the limitations of the selected studies, mechanical debridement combined with antiseptic/antibiotic therapy, the Er:YAG laser or regenerative techniques may be used for treating peri-implantitis, but the indications for each of these techniques have not been delineated clearly.

A comprehensive and critical review of dental implant prognosis in periodontally compromised partially edentulous patients.

OBJECTIVES: The outcome of implant treatment in periodontally compromised partially edentulous patients has not been completely clarified. Therefore, the aim of the present study was to perform, applying a systematic methodology, a comprehensive and critical review of the prospective studies published in English up to and including August 2006, regarding the short-term (<5 years) and long-term (>or=5 years) prognosis of osseointegrated implants placed in periodontally compromised partially edentulous patients. MATERIAL AND METHODS: Using The National Library Of Medicine and Cochrane Oral Health Group databases, a literature search for articles published up to and including August 2006 was performed. At the first phase of selection the titles and abstracts and at the second phase full papers were screened independently and in duplicate by the three reviewers (I. K. K., S. K., I. F.). RESULTS: The search provided 2987 potentially relevant titles and abstracts. At the first phase of evaluation, 2956 publications were rejected based on title and abstract. At the second phase, the full text of the remaining 31 publications was retrieved for more detailed evaluation. Finally, 15 prospective studies were selected, including seven short-term and eight long-term studies. Because of considerable discrepancies among these studies, meta-analysis was not performed. CONCLUSIONS: No statistically significant differences in both short-term and long-term implant survival exist between patients with a history of chronic periodontitis and periodontally healthy individuals. Patients with a history of chronic periodontitis may exhibit significantly greater long-term probing pocket depth, peri-implant marginal bone loss and incidence of peri-implantitis compared with periodontally healthy subjects. Even though the short-term implant prognosis for patients treated for aggressive periodontitis is acceptable, on a long-term basis the matter is open to question. Alterations in clinical parameters around implants and teeth in aggressive periodontitis patients may not follow the same pattern, in contrast to what has been reported for chronic periodontitis patients. However, as only three studies comprising patients treated for aggressive periodontitis were selected, more studies, specially designed, are required to evaluate implant prognosis in this subtype of periodontitis. As the selected publications exhibited considerable discrepancies, more studies, uniformly designed, preferably longitudinal, prospective and controlled, would be important.

A comprehensive and critical review of dental implant placement in diabetic animals and patients.

OBJECTIVES: A thorough and exhaustive analysis of the available studies concerning placement of endosseous dental implants in diabetic subjects has not been previously published. The aim of the present study was to perform a comprehensive and critical review of experimental and clinical studies published in the international peer-reviewed literature in the English language regarding endosseous implant installation in diabetic subjects and to draw evidence-based conclusions on the effectiveness and predictability of dental implant therapy in diabetic patients. MATERIAL AND METHODS: Literature search for articles published up to and including March 2005 in the English language was performed with a personal computer (PC) using The National Library Of Medicine (http://www.ncbi.nlm.nih.gov/PubMed) and Cochrane Oral Health Group databases. Search strategy included a specific series of terms and key words. The reference lists of identified publications, relevant texts and previous workshops were also scanned. Data sources also included several hand-searched journals and contact with experts, when it was considered appropriate. Search was conducted independently by the three reviewers (S. K., I. K. K., I. F.). At the first phase of selection the titles and abstracts and at the second phase full papers were screened independently by the three reviewers. Disagreement regarding inclusion of full papers was resolved by discussion among the reviewers. RESULTS: The search provided 227 potentially relevant titles and abstracts. At the first phase of evaluation, 199 publications were rejected based on title and abstract. At the second phase, the full text of the remaining 28 publications was retrieved for more detailed evaluation. These publications included 11 experimental studies and 16 clinical studies (one clinical study corresponded to two publications). Finally, 11 experimental and eight clinical studies were accepted. Clinical studies included four prospective and four retrospective studies. Because of the limited number of available studies and their heterogeneity, focusing on a specific predefined question to be answered by a systematic review was not feasible and therefore no meta-analysis was planned. CONCLUSION: Within the limits of the existing investigations, experimental studies seem to reveal an impaired bone healing response to implant placement in diabetic animals compared with non-diabetic controls, both quantitatively and qualitatively. The majority of clinical studies tend to indicate that diabetes is no contraindication for implant placement, on condition that it remains under metabolic control. However, definitive guidelines with objective criteria, such as type and duration of diabetes and glucosylated hemoglobin levels, need to be established in the future.