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Biomedical subjects

E Lalla

Publications and source records attributed to E Lalla.

At least 19 recordsLinked to original sources
PubMed2006

Infection with a periodontal pathogen induces procoagulant effects in human aortic endothelial cells.

BACKGROUND: Multiple studies have demonstrated a link between periodontal infections and vascular disease. Porphyromonas gingivalis, a major periodontal pathogen, has been shown to adhere to and invade endothelial cells. OBJECTIVE: In order to dissect mechanisms underlying these observations, we assessed the role of P. gingivalis infection in modulating properties of endothelial cells linked to atherothrombosis. METHODS: Primary human aortic endothelial cells (HAEC) were infected with either P. gingivalis 381 or its non-invasive fimbriae-deficient mutant, DPG3. Markers of coagulation and thrombosis were assessed 8 h and 18 h postinfection in cell lysates and supernatants. RESULTS: Infection with P. gingivalis 381 significantly enhanced tissue factor expression and activity, and suppressed levels of tissue factor pathway inhibitor. Furthermore, P. gingivalis infection decreased levels and activity of tissue plasminogen activator, and enhanced plasminogen activator inhibitor-1 antigen and activity. Consistent with an important role for bacterial adhesion/invasion in this setting, infection with DPG3 failed to induce procoagulant properties in HAEC. Most of the above effects of P. gingivalis 381 were more apparent at the later time point (18 h postinfection). This suggests that P. gingivalis infection, rather than having an immediate and direct effect, might activate pathways that, in turn, trigger endothelial procoagulant mechanisms. CONCLUSIONS: Taken together these data demonstrate for the first time that infection with a periodontal pathogen induces procoagulant responses in HAEC.

Aorta↗
PubMed2004

Longitudinal stability of serum immunoglobulin G responses to periodontal bacteria.

BACKGROUND: The value of seroepidemiology in the study of periodontal infections has not been adequately explored. This study examined serum immunoglobulin (IgG) responses to periodontal bacteria in patients with periodontitis and periodontitis-free individuals over a 30-month period. METHODS: Eighty-nine patients with chronic periodontitis and 42 control subjects with no deep periodontal pockets and no or minimal attachment loss (30-72 years old, 43% men) were included. Patients were examined at baseline, after completed periodontal therapy 4 months post-baseline, and at 30 months, and controls, at baseline and 30 months. IgG antibodies to 19 periodontal species were determined by checkerboard immunoblotting. RESULTS: On average, patients displayed at baseline up to 800-fold higher titers than controls to all but three species. Over the 30-month period, titers remained stable at low levels in controls. In patients, periodontal conditions improved from a baseline mean probing depth of 3.6 mm, bleeding on probing of 62% and an average of 21.5 pockets of=6 mm/person, to 2.5 mm mean pocket depth, 30% bleeding on probing, and 1.2 deep pockets, at 30 months. Over time, antibody titers showed a modest decline in patients, but remained significantly elevated at 30 months in comparison with controls. Antibody-level changes over time were not significantly different between subjects that did and did not receive adjunctive systemic antibiotics. CONCLUSIONS: Conspicuous differences in IgG titers to periodontal bacteria exist between periodontitis patients and periodontally healthy controls. Despite successful periodontal therapy, titers remained elevated over a 30-month period, suggesting that serology may mark the history of past periodontal infection.

Adult↗
PubMed2002

RAGE is a multiligand receptor of the immunoglobulin superfamily: implications for homeostasis and chronic disease.

Receptor for AGE (RAGE) is a member of the immunoglobulin superfamily that engages distinct classes of ligands. The biology of RAGE is driven by the settings in which these ligands accumulate, such as diabetes, inflammation, neurodegenerative disorders and tumors. In this review, we discuss the context of each of these classes of ligands, including advance glycation end-products, amyloid beta peptide and the family of beta sheet fibrils, S100/calgranulins and amphoterin. Implications for the role of these ligands interacting with RAGE in homeostasis and disease will be considered.

Alzheimer Disease↗
PubMed2002

RAGE and arthritis: the G82S polymorphism amplifies the inflammatory response.

The receptor for advanced glycation end products (RAGE) and its proinflammatory S100/calgranulin ligands are enriched in joints of subjects with rheumatoid arthritis (RA) and amplify the immune/inflammatory response. In a model of inflammatory arthritis, blockade of RAGE in mice immunized and challenged with bovine type II collagen suppressed clinical and histologic evidence of arthritis, in parallel with diminished levels of TNF-alpha, IL-6, and matrix metalloproteinases (MMP) 3, 9 and 13 in affected tissues. Allelic variation within key domains of RAGE may influence these proinflammatory mechanisms, thereby predisposing individuals to heightened inflammatory responses. A polymorphism of the RAGE gene within the ligand-binding domain of the receptor has been identified, consisting of a glycine to serine change at position 82. Cells bearing the RAGE 82S allele displayed enhanced binding and cytokine/MMP generation following ligation by a prototypic S100/calgranulin compared with cells expressing the RAGE 82G allele. In human subjects, a case-control study demonstrated an increased prevalence of the 82S allele in patients with RA compared with control subjects. These data suggest that RAGE 82S upregulates the inflammatory response upon engagement of S100/calgranulins, and, thereby, may contribute to enhanced proinflammatory mechanisms in immune/inflammatory diseases.

Alleles↗
PubMed2001

Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model.

Although hyperhomocysteinemia (HHcy) is a well-known risk factor for the development of cardiovascular disease, the underlying molecular mechanisms are not fully elucidated. Here we show that induction of HHcy in apoE-null mice by a diet enriched in methionine but depleted in folate and vitamins B6 and B12 increased atherosclerotic lesion area and complexity, and enhanced expression of receptor for advanced glycation end products (RAGE), VCAM-1, tissue factor, and MMP-9 in the vasculature. These homocysteine-mediated (HC-mediated) effects were significantly suppressed, in parallel with decreased levels of plasma HC, upon dietary supplementation with folate and vitamins B6/B12. These findings implicate HHcy in atherosclerotic plaque progression and stability, and they suggest that dietary enrichment in vitamins essential for the metabolism of HC may impart protective effects in the vasculature.

Animals↗
PubMed2001

Receptor for advanced glycation end products, inflammation, and accelerated periodontal disease in diabetes: mechanisms and insights into therapeutic modalities.

In hyperglycemic states found in diabetics, a nonenzymatic glycation and oxidation of proteins and lipids occurs. As a result, advanced glycation end products (AGEs), particularly N epsilon-(carboxymethyl)lysine, accumulate in the plasma and tissues of diabetic subjects. This accumulation has been linked to the development of pathogenic complications of diabetes. Many of the effects of AGEs are receptor-dependent and involve a multi-ligand member of the immunoglobulin superfamily of cell surface molecules. The best characterized of these is the receptor for advanced glycation end products (RAGE), which is expressed by multiple cell types including endothelium and mononuclear phagocytes. Based on data from a variety of sources, including studies of RAGE-deficient mice, it appears that RAGE plays a central role in oral infection, exaggerated inflammatory host responses, and destruction of alveolar bone in diabetes. It is possible that antagonists of RAGE might have a valuable adjunctive therapeutic role for the management of periodontal disease found in diabetics.

Alveolar Bone Loss↗
PubMed2000

Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases.

The receptor for advanced glycation end products (RAGE), a multi-ligand member of the immunoglobulin superfamily of cell surface molecules, interacts with distinct molecules implicated in homeostasis, development and inflammation, and certain diseases such as diabetes and Alzheimer's disease. Engagement of RAGE by a ligand triggers activation of key cell signalling pathways, such as p21ras, MAP kinases, NF-kappaB and cdc42/rac, thereby reprogramming cellular properties. RAGE is a central cell surface receptor for amphoterin, a polypeptide linked to outgrowth of cultured cortical neurons derived from developing brain. Indeed, the co-localization of RAGE and amphoterin at the leading edge of advancing neurites indicated their potential contribution to cellular migration, and in pathologies such as tumour invasion. Here we demonstrate that blockade of RAGE-amphoterin decreased growth and metastases of both implanted tumours and tumours developing spontaneously in susceptible mice. Inhibition of the RAGE-amphoterin interaction suppressed activation of p44/p42, p38 and SAP/JNK MAP kinases; molecular effector mechanisms importantly linked to tumour proliferation, invasion and expression of matrix metalloproteinases.

Animals↗
PubMed2000

Blockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice.

Diabetes is associated with increased prevalence, severity, and progression of periodontal disease. To test the hypothesis that activation of RAGE (Receptor for Advanced Glycation End products) contributes to the pathogenesis of diabetes-associated periodontitis, we treated diabetic mice, infected with the human periodontal pathogen Porphyromonas gingivalis, with soluble RAGE (sRAGE). sRAGE is the extracellular domain of the receptor, which binds ligand and blocks interaction with, and activation of, cell-surface RAGE. Blockade of RAGE diminished alveolar bone loss in a dose-dependent manner. Moreover, we noted decreased generation of the proinflammatory cytokines TNF-alpha and IL-6 in gingival tissue, as well as decreased levels of matrix metalloproteinases. Gingival AGEs were also reduced in mice treated with sRAGE, paralleling the observed suppression in alveolar bone loss. These findings link RAGE and exaggerated inflammatory responses to the pathogenesis of destructive periodontal disease in diabetes.

Alveolar Bone Loss↗
PubMed1999

Periodontitis and systemic disease.

Recent evidence suggests that periodontal disease may play an etiologic role in the pathogenesis of several systemic illnesses, such as cardiovascular disease and preterm birth. This article reviews proposed mechanisms for such associations and outlines studies currently underway aimed at clarifying this issue. Results from this line of research may fundamentally change the way we approach our periodontitis patients.

Cardiovascular Diseases↗
PubMed1998

A murine model of accelerated periodontal disease in diabetes.

Diabetes is a risk factor for periodontal disease in humans. In hyperglycemia, glycoxidation of proteins and lipids results in the formation of advanced glycation endproducts, or AGEs. The accumulation of AGEs in the plasma and tissues, and their interaction with their cellular receptor for AGE (RAGE), has been implicated in diabetic complications. In order to establish a model with which to delineate the specific host response factors that underlie the development of periodontal disease in diabetes, male C57BL/6J mice were rendered diabetic with streptozotocin. One month after documentation of diabetes or control state, mice were inoculated with the human periodontal pathogen Porphyromonas gingivalis, strain 381 (P. gingivalis) or treated with vehicle. Infection with P. gingivalis was achieved, as demonstrated by infiltration of gingival tissue with granulocytes, presence of DNA specific for P. gingivalis as well as increased serum antibody titer to P. gingivalis. At 2 and 3 months after infection, increased alveolar bone loss was demonstrated in P. gingivalis-inoculated diabetic vs. non-diabetic mice, along with enhanced tissue-destructive capacity, as demonstrated by increased collagenolytic activity in gingival extracts. Consistent with an important role for AGE-RAGE interaction, increased AGE deposition and expression of vascular and monocyte RAGE were demonstrated in diabetic gingiva compared with non-diabetic controls. Taken together, these data indicate that we have established a murine model of enhanced periodontal disease in diabetes. This model will serve to delineate molecular mechanisms which account for the increased susceptibility of diabetic patients to periodontal disease.

Alveolar Bone Loss↗
PubMed1998

Enhanced interaction of advanced glycation end products with their cellular receptor RAGE: implications for the pathogenesis of accelerated periodontal disease in diabetes.

The prevalence and severity of periodontal disease is increased in patients with both insulin-deficient and insulin-resistant forms of diabetes. While a number of underlying factors likely contribute to enhanced periodontal inflammation and alveolar bone loss in diabetes, a common characteristic of these disorders, regardless of etiology, is the presence of hyperglycemia. A critical consequence of hyperglycemia is non-enzymatic glycation and oxidation of proteins and lipids. After a series of reversible reactions which lead to the generation of Schiff bases/Amadori products, a further series of complex molecular rearrangements ensues which results in the formation of the irreversible advanced glycation end products, or AGEs. AGEs accumulate during the process of normal aging in the plasma and tissues, but to an accelerated degree in patients with diabetes. A central means by which AGEs are believed to impart their pathogenic effects is via interaction with specific cellular receptors; the best-characterized of these is receptor for AGE, or RAGE. RAGE, a member of the immunoglobulin superfamily of cell surface molecules, is present in increased levels on target cells in diabetes, such as endothelial cells and monocytes. One consequence of AGE-RAGE interaction is the generation of enhanced cellular oxidant stress, a means by which cell signaling pathways may be activated, thereby resulting in altered cellular phenotype and cellular dysfunction. In this report, we will review our studies to date on AGEs and RAGE and consider the implications of their enhanced interaction in the pathogenesis of accelerated periodontal disease in diabetes.

Animals↗
PubMed1996

Advanced glycation endproducts (AGEs) induce oxidant stress in the gingiva: a potential mechanism underlying accelerated periodontal disease associated with diabetes.

We hypothesized that one mechanism underlying advanced periodontal disease in diabetes may involve oxidant stress in the gingiva, induced by the effects of Advanced Glycation Endproducts (AGEs), the irreversible products of non-enzymatic glycation and oxidation of proteins and lipids which accumulate in diabetic plasma and tissue. Infusion of AGE albumin, a prototypic ligand, into mice resulted in increased generation of thiobarbituric acid reactive substances (TBARS) compared with infusion of non-glycated albumin in the gingiva, as well as in the lung, kidney and brain. Pretreatment of the animals with the antioxidants probucol or N-acetylcysteine (NAC) prevented the generation of TBARS in the gingiva. Affinity-purified antibody to AGEs demonstrated increased immunoreactivity for AGEs in the vasculature and connective tissues of the gingiva in streptozotocin-induced diabetic mice compared to non-diabetic controls. Increased immunoreactivity for AGEs was also demonstrated in the gingiva of diabetic humans compared with non-diabetic individuals via immunohistochemistry and ELISA. Consistent with these data, immunohistochemistry for heme oxygenase-1, a marker of enhanced oxidant stress, was increased in the gingival vasculature of diabetic mice and humans compared with non-diabetic controls. These data suggest that AGEs present in diabetic gingiva may be associated with a state of enhanced oxidant stress, a potential mechanism for accelerated tissue injury.

Adult↗
PubMedDate not supplied

[A modified Putti-Platt surgical method in the treatment of habitual luxation of the anterior shoulder: our experience].

Fifty cases of recurrent dislocation of the shoulder operated according to the Putti-Platt method modified by lateralization of the insertion of the coracoid processes are reported. Excellent results were obtained in 86% of the cases. There was neither incidence of recurrence, nor degenerative joint alteration. Mild limitation in extrarotation (less than 10 degrees) was observed in 7 cases.

Adolescent↗
PubMedDate not supplied

[Osteitis condensans ilii: therapy and diagnostic problems. Presentation of a case study].

The authors describe 4 female patients with Osteitis Condensans Ilii (OCI): 3 of them were pluriparous, ranging 32-36 years of age; while the remaining was nulliparous and 20 years old, with a previous trauma suffered in the iliac bone. Due to the inefficacy of the medical and physical treatment, two patients underwent surgical resection of the osteitic bone; then followed by a 45 days cast immobilization and a 3-4 months with restricted load. The other 2 patients were successfully treated with Indomethacin (a 100 mg/day cycle for a month, followed by a maintainance cycle with 300 mg/day for 3 months). The diagnostic aspects are then discussed, pointing out that absence of any peripheric neurologic damage, normal bone scan, female sex and younger age are the relevant characteristics for the diagnosis of OCI.

Adult↗
PubMedDate not supplied

[Instrumental diagnosis in shoulder instability].

The authors call attention to the pathology caused by glenohumeral instability and, in particular, to painful shoulders in athletes which so often cause problems in diagnosis. An instrumental protocol for diagnosis is suggested, based on several specific radiographic views, Ct scan and arthro-Ct scan, with double contrast medium, the latter having the task of determining lesion which would not otherwise be able to be studied.

Arthrography↗