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Biomedical subjects

R Romanelli

Publications and source records attributed to R Romanelli.

At least 19 recordsLinked to original sources

Activation of neutrophil collagenase in periodontitis.

Neutrophil collagenase (matrix metalloproteinase 8 [MMP-8]) is an important mediator of tissue destruction in inflammatory diseases. Studies of anaerobic periodontal infections have shown that active MMP-8 in gingival crevicular fluid is associated with the degradation of periodontal tissues in progressive periodontitis whereas the latent enzyme is predominant in gingivitis. Since the activation of MMP-8 appears to be a crucial step in periodontitis, we have examined the activation of MMP-8 in gingival crevicular fluid samples by using a soluble biotinylated collagen substrate. Analysis of gingival crevicular fluid in periodontitis, gingivitis, and controls revealed sixfold (P < 0.001)-higher levels of active collagenase in periodontitis (n = 12) samples compared to gingivitis (n = 17) samples, which exhibited low levels of activity, while controls (n = 25) showed no activity. After gingival crevicular fluid was collected, no further activation of latent collagenase occurred in vitro. Although both MMP-1 and MMP-8, but not MMP-13, could be detected by immunoblots, blocking antibodies to MMP-1 showed that collagenase activity was largely contributed by MMP-8, which was localized to the matrix of diseased tissues. The MMP-8 in gingival crevicular fluid migrated primarily as a 60-kDa form with smaller amounts of a 78-kDa species, whereas MMP-8 isolated from peripheral neutrophils migrated at 70 and 89 kDa, corresponding to active and latent forms of the enzyme, respectively. Most of the MMP-8 in the 60- and 70-kDa bands selectively bound to tissue inhibitor of metalloproteinase 2 and collagen, indicating that most, but not all, of the enzyme in these bands was in an activated form. However, the amounts of the 78- and 60-kDa forms from gingival crevicular fluid in different samples did not correlate (r2 = 0.028) with the latent and active enzyme measured by collagenase assay. Collectively, these studies have identified distinct forms of latent and active MMP-8 in gingival crevicular fluid that appear to result from a unique activation mechanism that occurs in periodontitis. The complexity of MMP-8 activation is further indicated by the presence of latent, activated, and superactivated forms of MMP-8 in the 60- and 70-kDa bands obtained from gingival crevicular fluid and neutrophil samples, respectively.

Case-Control Studies↗

Assessment of a novel screening test for neutrophil collagenase activity in the diagnosis of periodontal diseases.

BACKGROUND: Increased levels of active neutrophil collagenase (MMP-8) in the gingival crevicular fluid (GCF) are associated with progressive periodontitis. The measurement of this enzyme in GCF could facilitate diagnosis. However, assays with sufficient sensitivity to detect collagenase in whole-mouth GCF currently use radiolabeled substrates and require several days to complete. To provide more rapid analyses of collagenase activity that are better adapted to clinical studies, we developed and validated a novel assay (soluble biotinylated-collagen assay: SBA) based on chemiluminescent detection of biotinylated collagen digestion products. METHODS: The concordance of the novel SBA assay with a radioactive collagen substrate assay was assessed by parallel analyses of enzyme from 35 neutrophil preparations and from 41 samples of GCF from periodontitis patients, followed by Pearson correlation analysis. To test whether the assay appropriately measured MMP-8 activity, enzyme activity was assessed after incubation with specific collagenase blockers. We examined the diagnostic utility of the SBA in cross-sectional and longitudinal analyses of 125 patients with adult periodontitis, 5 patients with early-onset periodontitis, 1 edentulous patient, and in 32 control patients without periodontitis. RESULTS: The assay detected <56 pg collagen degraded/hour/microl sample, which is comparable to the most sensitive radioactive assay. The total assay time was 22 hours and reproducibility on replicate measurements was high (r = 0.96). In direct comparisons of MMP-8 activity in GCF with enzyme from peripheral blood neutrophils using the SBA and radioactive assays, there was a high correlation (r = 0.97). As expected, EDTA and TIMP-1 and -2, known inhibitors of MMP-8, completely blocked enzyme activity with this assay. Cross-sectional and longitudinal analyses of GCF showed that MMP-8 activity was >18-fold higher in severe periodontitis than in stable periodontitis and decreased to <25% of pretreatment levels following therapy. Based on measurements of collagenase activity in different disease groups, we estimated a value of 80 nano units as a threshold for severe periodontitis. CONCLUSIONS: These results indicate that active MMP-8 is detected in GCF by a novel assay that is specific, simple, rapid, and reproducible and which may facilitate diagnostic discrimination between stable and progressive lesions.

Adult↗

Left anterior descending coronary artery bridge. A cause of early death after cardiac transplantation.

Immediately following orthotopic transplantation, a patient suffered left pump failure, which resulted in death. Autopsy of the donor heart revealed a proximal left anterior descending artery bridge with a thrombus causing segmental distal anteroseptal infarction. In this case report, myocardial coronary bridges and their clinical implications are reviewed. Myocardial bridging and acute coronary obstruction should be considered in the differential diagnosis of patients with acute pump dysfunction following orthotopic cardiac transplantation.

Coronary Thrombosis↗

Malakoplakia of the appendix.

A case of a malakoplakia of the appendix in a sixty-year-old woman is reported. No involvement of the organs or important general diseases were present and the patient, after the appendicectomy, promptly recovered. Only three cases of malakoplakia of the appendix have previously been described in the literature and they are briefly summarized.

Appendectomy↗

[Multiple coronary aneurysms of an atherosclerotic nature in a patient with an abdominal aortic aneurysm: presentation of an anatomo-clinical case].

We describe the case of a 71-year-old man with history of inferior wall myocardial infarction and abdominal aortic aneurysm surgically treated. The patient, admitted to hospital for chest pain, after 24 hours suddenly dead for ventricular fibrillation and cardiac arrest. Chest X Ray, echocardiogram and Computed Tomography had shown a very large paracardiac mass. At the autopsy, three large saccular aneurysms were found, one for each coronary artery and lumen completely filled with thrombi.

Aged↗

Synthesis and biological profile of the enantiomers of [4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-cis-octahydroquinoxalin- 1-yl]furan-2-ylmethanone (cyclazosin), a potent competitive alpha 1B- adrenoceptor antagonist.

The enantiomers of [4-(4-amino-6, 7-dimethoxyquinazolin-2-yl)-cis-octahydroquinoxalin-1-yl]-fu ran- 2-ylmethanone (cyclazosin, 1) were synthesized from the chiral furan-2-yl(cis-octahydroquinoxalin-1-yl)methanone [(+)-2 and (-)-2], which were obtained by resolution of the racemic amine with (S)-(+)- and (R)-(-)-mandelic acid. The binding profile of the enantiomers of 1 was assessed at alpha 1-, alpha 2-, D2, and 5-HT1A receptors as well as at native alpha 1A- and alpha 1B- and cloned alpha 1a-, alpha 1b-, and alpha 1d-adrenoceptor subtypes in comparison with prazosin, spiperone, and AH11110A. (+)-1 displayed a 40-90-fold selectivity for the alpha 1B(alpha 1b)-adrenoceptor relative to alpha 1A(alpha 1a) and alpha 1d subtypes. A significant enantioselectivity was observed at the alpha 1A(alpha 1a)-adrenoceptor and particularly at alpha 1d-adrenoceptors since (-)-1 was 11-14- and 47-fold, respectively, more potent than (+)-1. Furthermore the enantiomer (+)-1 displayed selectivities of 1100-, 19000-, and 12000-fold in binding to alpha 1b-adrenoceptors relative to alpha 2-adrenoceptors and 5-HT1A and D2 receptors. These results indicate that (+)-1, [(+)-cyclazosin] is the most potent and selective ligand for the alpha 1B-adrenoceptor subtype so far described and may be a valuable tool in the characterization of alpha 1-adrenoceptor subtypes.

Adrenergic alpha-1 Receptor Antagonists↗

Subarachnoid hemorrhage simulating myocardial infarction.

We describe a patient with a subarachnoid hemorrhage that presented with electrocardiographic evidence of transmural myocardial infarction. The patient was found to have normal coronaries and on autopsy revealed generalized myocytolysis with no evidence of transmural myocardial infarction. This case illustrates the value of acute coronary angiography in patients with altered mental status and suspected myocardial infarction.

Adult↗

Remodeling of human myocardial collagen in idiopathic dilated cardiomyopathy. Role of metalloproteinases and pyridinoline cross-links.

A major contribution to the mechanical strength of the heart is provided by a continuous fibrillar collagen network embracing individual myocytes and forming an interstitial and perivascular framework. This study explores the possibility that idiopathic dilated cardiomyopathy may involve extensive changes in this collagenous framework. Idiopathic dilated cardiomyopathy hearts were obtained at transplant and compared with control hearts from autopsy. Idiopathic dilated cardiomyopathy showed a doubling of collagen concentration and a quadrupling of the total collagen per heart, whereas the stable mature cross-link, pyridinoline, diminished from 2.07 mol/mol of collagen to 1.0. Neutrophil-type collagenase activity is elevated approximately 30-fold as is the activity of gelatinase. Tissue inhibitor of metalloproteinase activity falls to negligible levels in idiopathic dilated cardiomyopathy, whereas alpha 2-macroglobulin is high. It is postulated that collagen critical to mechanical stability of the heart is degraded by metalloproteinase activity and is replaced by fibrous intercellular deposits of poorly cross-linked collagen. These changes contribute to weakening and dilatation of the ventricular wall.

Adolescent↗

[Complete regression of Barrett's esophagus after drug therapy].

Barrett's esophagus is defined as a disorder in which the normal stratified squamous mucosa of the esophagus is replaced by columnar epithelium. Patients with Barrett's esophagus are at risk to develop an adenocarcinoma of the esophagus. Pathologic gastroesophageal reflux is correlated to the disease and therapeutical options must aim to stop this noxa in order to prevent columnar metaplasia, and subsequent dysplasia and/or neoplasia. The Authors report the case of a patient in whom the complete regression of the metaplasia was observed after medical therapy.

Anti-Ulcer Agents↗

Intramural left anterior descending coronary artery: significance of the depth of the muscular tunnel.

To establish whether an intramural left anterior descending coronary artery (LADA) is a simple anatomic or a singularly pathologic variant we studied 39 hearts, each with an intramural course of the LADA and no coronary artery disease, valvular derangement, cardiomyopathy, or congenital anomaly. Seventeen of the 39 hearts had no myocardial lesions, while 22 had gross and/or microscopic alterations in the myocardial territory supplied by the intramural LADA. The myocardial lesions consisted of one or more of the following: interstitial fibrosis, replacement fibrosis, contraction band necrosis, and/or increased vascular density in areas of focal fibrosis. The coronary anatomy of the 22 hearts with myocardial lesions (group 1) was compared with that of the 17 hearts without myocardial changes (group 2). Each of the group 1 hearts had an intramural LADA deeply placed within the ventricular wall and attenuation of potential collateral blood flow because of a co-existing intramural course of the posterior descending artery, other epicardial coronary arteries, and/or a diminutive right coronary artery. The myocardial changes in group 1 hearts and their absence in group 2 hearts suggest that the deep, intramural LADA of the group 1 hearts is abnormal rather than a simple anatomic variant of normal. Furthermore, the deep intramural LADA may be associated with sudden death since 13 of the 22 group 1 hearts were from sudden death victims. Six of these 13 persons died suddenly during vigorous exercise.

Adult↗

[The assessment of glucose tolerance in hypertensive subjects treated with amlodipine].

The authors studied the side effects of amlodipine on glucose metabolism, carrying out an oral glucose tolerance test before and after 8-10 days of treatment, in a group of subjects with normal glucose tolerance. No significant variation in the average plasma glucose and insulin levels was observed. Nevertheless, in some cases, during amlodipine therapy, a decrease in glucose plasma level was found.

Amlodipine↗

Myxoid heart disease: an assessment of extravalvular cardiac pathology in severe mitral valve prolapse.

Because of the microscopic features of the affected leaflets in mitral valve prolapse (MVP), myxoid degeneration of the valve is a common pathologic designation applied to this condition. We undertook this study as a means of gaining an insight into the occurrence and prevalence of extravalvular cardiac alterations in hearts with severe MVP. Tissues of 24 hearts with severe myxomatous transformation of the mitral valve as the sole cardiac abnormality were examined. Eighteen of the 24 subjects with severe MVP died suddenly. Only two of these had pathologic evidence of severe mitral insufficiency. Twenty-four normal hearts served as controls. The two groups of hearts came from victims of homicide, suicide, accident, or natural death. Sections of the mitral valve, working myocardium, conduction system, and cardiac nerves and ganglia were studied by routine and special connective tissue and proteoglycan stains. Similar to the findings in severely affected mitral valves, prominent deposits of proteoglycans in neural and conduction tissue readily distinguished hearts with myxomatous valve changes from the control hearts. We conclude that the commonly recognized local derangement of valvular tissue in MVP is but one specific reflection of a more general myxomatous alteration in cardiac connective tissue.

Adolescent↗

Pigmented papillary carcinoma of the male breast.

A case of highly pigmented papillary carcinoma originating in the breast of a 70-year-old man is presented. The tumor was located in the subareolar region and did not affect the overlying skin, which was normally pigmented. The significance of the presence of melanocytes in the tumor and of melanin pigment in the cytoplasm of its cells is discussed.

Aged↗