The use of periodontal membranes in the field of periodontology: spotlight on collagen membranes.

Periodontal regenerative techniques are performed to accomplish the restitution of soft and hard teeth-supporting tissues that have been lost due to trauma or inflammatory disease. Periodontal membranes are used for these techniques to provide support and a framework for cell growth and tissue regeneration. They act as a temporary and selective barrier to cell proliferation. Easy clinical handling, biomechanical specifications, high biocompatibility, cell-occlusivity, and satisfactory bioresorption rate are essential properties a membrane needs to be effective. The creation and maintenance of a secluded space is also a fundamental rule in periodontal regenerative techniques. The use of barrier membranes in the field of restorative dentistry has progressed toward the use of minimally invasive approaches optimizing wound closure and limiting patient morbidity. This review intends to provide an overview of the major cellular events in the surgical wound and membrane surface. It was also performed to assess, from literature data, the pertinence of using non-resorbable and resorbable membranes for this regenerative purpose. Special attention will be given to collagen membranes.

[Inflammation in the perivascular adipose tissue and atherosclerosis]. / Inflammation dans le tissu adipeux péri-artériel et athérome.

In atherosclerosis studies, there are few data, especially in men, on the biology of perivascular adipose tissue (PVAT) compared to that of other adipose tissue (AT), on amendments in obesity, and its possible role in the development of atherosclerosis. We conducted an ex vivo human study on pericarotid adipose tissue-collected in the immediate vicinity (PVATp) and away from the plate (tapas)-and subcutaneous (SC) neck gathered during surgery from patients suffering from atheromatous carotid disease. In addition, we conducted a study in obese Zucker rats (models of obesity and insulin resistance) and Wistar rats subjected to moderate stress. In these models, we collected renal adipose tissue (RAT), epididymal adipose tissue (EAT), and TAPA samples. On all samples, we measured mRNA levels encoding for proinflammatory cytokines (TNFα, IL-6, IL-1ß, MCP-1). Our results showed an increase in mRNA MCP-1, TNF and IL-6 in the adipose tissue around atherosclerotic plaques, an increase that was greater in diabetics than in non-diabetic subjects; we noted for the mRNA of MCP-1 in the TAPAp, 3.49×10-2±1.17×10-2ng/ug 18S in diabetic patients compared to 7.26×10-3±1.00×10-3ng/ug 18S (**P<0.01) in non-diabetic patients. In the obese Zucker rat, we found a significant increase in IL-6 in TAPA in obese animals compared to the corresponding controls (4.24×10-5±1.75×10-6ng/µg 18S vs 1.29×10-5±1.55×10-6ng/ug 18S). In stressed rats, we recorded a TNFα mRNA increase in the PVAT and EAT in the stressed rats compared to fatty tissue of control animals, we note respectively, 7.52×10-3±2.8×10-3ng/µg 18S vs 2.62×10-3±0.57×10-3ng/18S and 4.78×10-3±1.52×10-3ng/µg 18S vs 2.02×10-3±0.3×10-3ng/ug 18S. In summary, our work shows an inflammatory state of the TAPA surrounding the atheromatous plaques in diabetic patients. An obesity or stress state promotes an inflammatory profile of PVAT.

Mutual amplification of corticosteroids and angiotensin systems in human vascular smooth muscle cells and carotid atheroma.

UNLABELLED: The involvement of the renin-angiotensin-aldosterone system (RAAS) and cortisol in increased cardiovascular risk is well known. If numerous relationships between RAAS and corticosteroids have been described, their interactions within the arterial wall, especially during the transdifferentiation of vascular smooth muscle cells (VSMCs) and the atheroma formation, are not established. Here, we clarified the relationships between mRNA levels of corticosteroid and angiotensin system components using cortisol, fludrocortisone, and angiotensin II treatments of cultured VSMCs maintained in a contractile phenotype or induced to a lipid storing phenotype. We then determined the quantitative relationships between the mRNA content of these components measured with reverse transcription polymerase chain reaction (RT-PCR), in the atheroma plaque and nearby macroscopically intact tissue (MIT) from 27 human carotid endarterectomy samples. In both VSMC phenotypes, cortisol markedly increased both angiotensinogen (AGT) and AT1-receptor (AT1R) mRNA levels. These effects of cortisol were mediated via glucocorticoid receptor-α (GRα) without any illicit activation of the mineralocorticoid receptor (MR). Angiotensin II increased GRα, 11ßHSD1, CYP11B1, as well as CYP11B2 mRNAs and decreased AT1R in contractile VSMC; only GRα and CYP11B2 were increased in lipid storing VSMCs, while MR and AGT mRNAs decreased. In endarterectomy specimens, positive correlations between mRNA levels of AGT and aldosterone synthase or 11ßHSD1 in MIT and of AT1R and MR in atheroma were detected. The arterial tissue angiotensin system is a target for local glucocorticoids and arterial glucocorticoids for angiotensin II. Both systems appear activated in lipid storing VSMCs and strongly correlated in vivo, and their mutual amplification may contribute to the development of atheroma. KEY MESSAGE: Cortisol increases angiotensin II signaling in VSMCs via GRα. Angiotensin II stimulates cortisol signaling through increased GRα and 11ß-HSD1. Corticoid and angiotensin receptors are strongly correlated in the arterial wall. These correlations are maintained at different stages of atheroma development. An auto-amplification loop between angiotensin and cortisol signaling favors atherogenesis.

Auto-amplification of cortisol actions in human carotid atheroma is linked to arterial remodeling and stroke.

High cortisol and aldosterone levels increase cardiovascular risk, but the respective roles of each hormone within the arterial wall remain controversial. We tested the hypothesis that cortisol production within the arterial wall may contribute to atherosclerotic remodeling and act through illicit activation of the mineralocorticoid receptor (MR). Gene expression studies of the corticoid system components and marker genes of the atherosclerotic process in human carotid atheroma plaque and nearby macroscopically intact tissue (MIT) were considered together with clinical data and compared with pharmacological stimulations of human vascular smooth muscle cells (VSMCs) in contractile or lipid-storing phenotypes. The components of corticoid production and action were present and active within the human carotid wall and VSMCs. Atheroma plaque and lipid-storing VSMCs expressed 11ß-hydroxysteroid deshydrogenase-1 (11ß-HSD1) at two- to tenfold higher levels than MIT or contractile VSMCs. The 11ß-HSD1 expression was stimulated by cortisol and cortisone, especially in lipid-storing VSMCs. MR mRNA level was lower in atheroma and lipid-storing VSMCs and downregulated via MR by fludrocortisone and cortisol. Cortisol upregulated collagen1 and MCP-1 mRNAs via the glucocorticoid receptor (GRα), in both VSMC phenotypes, whereas fludrocortisone stimulated the collagen1 expression only in lipid-storing VSMCs. The GRα mRNA level in MIT was higher in patients with previous stroke and correlated positively with the collagen1 mRNA but negatively with diastolic blood pressure. Local cortisol production by 11ß-HSD1, and its action via high parietal GRα could be relevant from the first step of atherosclerotic remodeling and auto-amplify with transdifferentiation of VSMCs during atheroma progression.

[Respective roles of cortisol, aldosterone and angiotensin II during pathophysiology of atherosclerosis]. / Rôles respectifs du cortisol, de l'aldostérone et de l'angiotensine II dans la physiopathologie de l'athérosclérose.

The involvement of angiotensin II, cortisol and aldosterone in increased cardiovascular risk is well known but their interactions within arterial wall and during atheroma formation are not established. In fact, mild cortisol excess is associated with a higher prevalence of cardiovascular events, increased intima media thickness, a higher frequency of atherosclerotic plaques and increased mortality. Conversely, remission from hypercortisolism is followed by improvement in cardiovascular risk markers as intima-media thickness or arterial distensibility, suggesting a strong link between cortisol excess and adverse vascular remodeling. On the other hand, implication of renin-angiotensin system (RAS) in atheromatous remodeling is well documented. The RAS also includes aldosterone, a mineralocorticoid which secretion is mainly and strongly stimulated by angiotensin II, and which receptor (MR) can also be activated by cortisol given that MR affinity is similar for both aldosterone and cortisol. The role of aldosterone in arterial remodeling is still very controversial. Aldosterone treatment associated with a high salt diet induced not only hypertension but also oxidative stress, collagen synthesis and vascular inflammation. However in models without salt loading or arterial hypertension, such as the treatment with deoxycorticosterone acetate in dogs, no alterations in aortic structure were observed and moreover, the MR blockade with eplerenone did not attenuate atherosclerosis in the aorta of diabetic Apo-E KO mice. It stems that among the different effects and mechanisms described in cell experiments, it is not known which are indeed operating in situ in human vessels and thus, if local cortisol is deleterious or beneficial and, if activation of MR by aldosterone or cortisol is important in vascular remodeling and atherogenesis. RAS blocker treatment would be particularly beneficial in essential hypertensive patients with low plasma renin, to attenuate both angiotensin II and also cortisol up-regulation.

Identification of two genes potentially associated in iron-heme homeostasis in human carotid plaque using microarray analysis.

Classic characteristics are poor predictors of the risk of thromboembolism. Thus, better markers for the carotid atheroma plaque formation and symptom causing are needed. Our objective was to study by microarray analysis gene expression of genes involved in homeostasis of iron and heme in carotid atheroma plaque from the same patient. mRNA gene expression was measured by an Affymetrix GeneChip Human Gene 1.0 ST arrays (Affymetrix, Santa Clara, CA, USA) using RNA prepared from 68 specimens of endarteriectomy from 34 patients. Two genes involved in iron-heme homeostasis, CD163 and heme oxygenase (HO-1), were analysed in 34 plaques. CD163 (2.18, p01.45E-08) and HO-1 (fold-change 2.67, p02.07E-09) mRNAs were induced. We suggest that atheroma plaques show a more pronounced induction of CD163 and HO-1. Although further evidence is needed, our results support previous data. To our knowledge, this is the first report comparing gene expression between intact arterial tissue and carotid plaque using microarray analysis.

[Recurrent staphylococcal infection of the face associated with the development of anti-Dsg3 antibody response]. / Récidive d'une staphylococcie de la face associée à l'apparition d'une réponse anticorps anti-Dsg3.

The etiopathogenesis of the Tunisian pemphigus is still ambiguous. Indeed, the complete mechanism, which goes from the causal agent until the final targets, is unknown. Nevertheless, two types of factors were associated in the etiopathogenesis of the pemphigus: genetic and/or environmental factors. We focused our intention in bacterial infectious etiology due to staphylococcus. We report a 42-year-old man presenting staphylococcal infection: anti-desmogleines antibody (1 and 3) at the first infection was negative. Surprisingly, he became positive for anti-Dsg3 antibodies after having relapsed.

[Role of staphylococcal infections in the occurrence of endemic Tunisian pemphigus]. / Rôle des infections à staphylocoques dans la survenue de pemphigus endémique tunisien.

Pemphigus is a severe autoimmune blistering disorder, in which immunoglobulin G autoantibodies are directed against desmosomal glycoproteins. The antibodies against desmogleine1 are prevalent in normal subjects living in Tunisia, that suggests the role of environment in the pathogenesis of this endemic type of pemphigus and the need for additional factors to switch from a subclinical form to a clinical form of the disease. The aim of this study was to investigate explanatory environmental factors. We tested the hypothesis that normal subjects whom presented staphylococcal infections have antibodies against desmoglein. We recruited 29 patients with staphylococcal infections from the dermatology department of the university hospital of Tunis. 29 controls healthy subjects are used to compare the prevalence of anti-desmoglein1 and 3 between these two groups. We used a specific and sensitive enzyme linked immunosorbent assay to detect autoantibodies against Dsg1. (10.3% versus 7% in healthy Tunisian blood donors: p < 0.05). Conversely, we observed a significant association with antibodies against Dsg3 (20.78% versus 3% in healthy Tunisian blood donors: p < 0.05). Subclasses analysis of anti-desmoglein antibodies showed that they were almost exclusively the IgG 1, 2 and 3 subclasses in positive normal sera. The antibodies against desmogleins binding activity of these positive sera were confirmed by indirect immunofluorescence analysis and by immunobloting using human epidermal extract. In conclusion, we detected autoantibodies in the sera of patients with staphylococcal infections and found elevated levels of autoantibodies against Dsg 3.