Controversial problems in the nosology of atherosclerosis

Atherogenic dislipoproteinemia and the disturbances of vascular permeability are considered to be the main etiologic factors of atherosclerosis according to the current concept of the pathogenesis of this disease. The authors suggest that the following nozological forms of atherosclerosis should be distinguished (basing on relevant morphological features): classical (Anichkow-Khalatov disease), autoimmune, genetically predetermined, and symptomatic secondary atherosclerosis. Each form has its special leading pathogenetic link and particular morphologic development. This requires a differential approach to the choice of treatment and prevention in each individual case of atherosclerosis.     

Role of the monocytes and IgG in the development of atherosclerotic lesions in the aorta of rabbits

In experimental hypercholesterinemia in rabbits, immune autoradiographic studies showed that lesions in the endothelial monolayer of the aorta developed in parallel with IgG deposition in the cytoplasm of the affected endothelial cells and in different parts of atherosclerotic plaques. This process was accompanied by active replacement of blood monocytes into the internal sheath of the aorta in the zone of IgG deposition which appeared to be due to the presence in these cells of Fc-receptors for immunoglobulins. Incomplete catabolism of lipids in the cytoplasm of macrophages of monocytic genesis is one of the key events of atherosclerosis morphogenesis.     

The role of cytokines in a Porphyromonas gingivalis-induced murine abscess model

INTRODUCTION: Porphyromonas gingivalis is an important periodontopathic bacterium that is strongly associated with periodontal disease and is part of human dental plaque. Periodontal disease results from the interaction of the host with bacterial products, and T-cell-derived cytokines remain critical in the immunoregulation of periodontal disease. METHODS: The aim of this study was to examine the role of T helper type 1 [interleukin-12p40 (IL-12p40), interferon-gamma, tumour necrosis factor (TNF)] and type 2 (IL-4, IL-10) cytokines in the immune response to a subcutaneous challenge with P. gingivalis using a well-established murine abscess model, in genetically modified cytokine-specific knockout mice. RESULTS: IL-12p40(-/-) mice exhibited more advanced tissue destruction and a reduced inflammatory cell infiltrate after subcutaneous P. gingivalis challenge. Deficiency of IL-4 or IL-10 did not result in increased susceptibility to P. gingivalis-mediated tissue destruction. Furthermore, TNF deficiency appeared to reduce local tissue destruction. Interestingly, serum-specific antibodies suggested a strong T helper type 2 response. CONCLUSION: The results of our study indicate an important role for IL-12 in a primary P. gingivalis subcutaneous challenge.     

High-temperature protein G is essential for activity of the Escherichia coli clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system

Prokaryotic DNA arrays arranged as clustered regularly interspaced short palindromic repeats (CRISPR), along with their associated proteins, provide prokaryotes with adaptive immunity by RNA-mediated targeting of alien DNA or RNA matching the sequences between the repeats. Here, we present a thorough screening system for the identification of bacterial proteins participating in immunity conferred by the Escherichia coli CRISPR system. We describe the identification of one such protein, high-temperature protein G (HtpG), a homolog of the eukaryotic chaperone heat-shock protein 90. We demonstrate that in the absence of htpG, the E. coli CRISPR system loses its suicidal activity against λ prophage and its ability to provide immunity from lysogenization. Transcomplementation of htpG restores CRISPR activity. We further show that inactivity of the CRISPR system attributable to htpG deficiency can be suppressed by expression of Cas3, a protein that is essential for its activity. Accordingly, we also find that the steady-state level of overexpressed Cas3 is significantly enhanced following HtpG expression. We conclude that HtpG is a newly identified positive modulator of the CRISPR system that is essential for maintaining functional levels of Cas3.     

Early osseointegration to hydrophilic and hydrophobic implant surfaces in humans

Objective: To evaluate the rate and degree of osseointegration at chemically modified moderately rough, hydrophilic (SLActive) and moderately rough, hydrophobic (SLA) implant surfaces during early phases of healing in a human model. Material and methods: The devices used for this study of early healing were 4 mm long and 2.8 mm in diameter and had either an SLActive chemically modified or a moderately rough SLA surface configuration. These devices were surgically installed into the retro‐molar area of 49 human volunteers and retrieved after 7, 14, 28 and 42 days of submerged healing. A 5.2‐mm‐long specially designed trephine with a 4.9 mm inside diameter, allowing the circumferential sampling of 1 mm tissue together with the device was applied. Histologic ground sections were prepared and histometric analyses of the tissue components (i.e. old bone, new bone, bone debris and soft tissue) in contact with the device surfaces were performed. Results: All device sites healed uneventfully. All device surfaces were partially coated with bone debris. A significant fraction of this bone matrix coating became increasingly covered with newly formed bone. The process of new bone formation started already during the first week in the trabecular regions and increased gradually up to 42 days. The percentage of direct contact between newly formed bone and the device (bone‐to‐implant contact) after 2 and 4 weeks was more pronounced adjacent to the SLActive than to the SLA surface (14.8% vs. 12.2% and 48.3% vs. 32.4%, respectively), but after 42 days, these differences were no longer evident (61.6% vs. 61.5%). Conclusion: While healing showed similar characteristics with bone resorptive and appositional events for both SLActive and SLA surfaces between 7 and 42 days, the degree of osseointegration after 2 and 4 weeks was superior for the SLActive compared with the SLA surface. To cite this article :
Lang NP, Salvi GE, Huynh‐Ba G, Ivanovski S, Donos N, Bosshardt DD. Early osseointegration to hydrophilic and hydrophobic implant surfaces in humans.
Clin. Oral Impl. Res. 22 , 2011; 349–356. doi: 10.1111/j.1600‐0501.2011.02172.x     

Childhood-onset myasthenia gravis with thymoma

Juvenile myasthenia gravis is an acquired, autoimmune disease occurring before age 16 years. Thymoma is exceedingly rare in children, especially in association with juvenile myasthenia gravis. We describe a 14-year-old boy with juvenile myasthenia gravis and thymoma. He presented with difficulties chewing and swallowing, nasal speech, and fluctuating weakness of the leg muscles. Neurologic examination revealed masticatory and bulbar muscle weakness with nasal speech, proximal muscle weakness, fatigability of the arms and legs, and distal muscle weakness of the legs. A diagnosis of juvenile myasthenia gravis was confirmed by a positive neostigmine test, a decremental response on repetitive nerve stimulation, and increased titers of serum anti-acetylcholine receptor antibodies. The patient received anticholinesterases, corticosteroids, azathioprine, and thymectomy. A pathohistologic analysis of the thymus gland indicated thymoma, Masaoka grade II. After 2 years of an unstable disease course, remission was achieved. Because only 10 cases of thymoma-associated myasthenia gravis are described in the pediatric population, this report offers an important contribution to a better understanding of this rare association.     

The influence of surface microroughness and hydrophilicity of titanium on the up-regulation of TGFβ/BMP signalling in osteoblasts

The topography of titanium implants has been identified as an important factor affecting the osseointegration of surgically placed dental implants. Further modification to produce a hydrophilic microrough titanium implant surface has been shown to increase osseointegration compared with microrough topology alone. This study aimed to determine possible molecular mechanisms to explain this clinical observation by examining differences in the whole genome mRNA expression profile of primary human osteoblasts in response to sand-blasted acid-etched (SLA) and hydrophilic SLA (modSLA) titanium surfaces. A decrease in osteoblast proliferation associated with the titanium surfaces (modSLA > SLA > control) correlated with an increase in expression of the osteogenic differentiation markers BSPII and osteocalcin. Pathway analysis demonstrated that a number of genes associated with the TGFβ?BMP signalling cascade (BMP2, BMP6, SP1, CREBBP, RBL2, TBS3, ACVR1 and ZFYVE16) were significantly differentially up-regulated with culture on the modSLA surface. BMP2 was shown to have the largest fold change increase in expression which was subsequently confirmed at the protein level by ELISA. Several other genes associated with the functionally important mechanisms relevant to bone healing, such as Wnt signalling (CTNNA1, FBX4, FZD6), angiogenesis (KDR), osteoclastogenesis (HSF2, MCL1) and proteolysis (HEXB, TPP1), were also differentially regulated. These results suggest that chemical (hydrophilic) modification of the SLA surface may result in more successful osseointegration through BMP signalling.