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Biomedical subjects

C Chimenti

Publications and source records attributed to C Chimenti.

At least 19 recordsLinked to original sources

Alterations of energy metabolism and glutathione levels of HL-60 cells induced by methacrylates present in composite resins.

OBJECTIVES: Methacrylic compounds such as 2-hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacrylate (TEGDMA) and bisphenol A glycerolate (1 glycerol/phenol) dimethacrylate (Bis-GMA) are largely present in auto- or photopolymerizable composite resins. Since the polymerization reaction is never complete, these molecules are released into the oral cavity tissues and biological fluids where they could cause local adverse effects. The aim of this work was to verify the hypothesis that the biological effects of HEMA, TEGDMA and Bis-GMA - at a non-cytotoxic concentration - depend on the interaction with mitochondria and exert consequent alterations of energy metabolism, GSH levels and the related pathways in human promyelocytic cell line (HL-60). METHODS: The biological effects of methacrylic monomers were determined by analyzing the following parameters: GSH concentration, glucose-6-phosphate dehydrogenase (G6PDH) and glutathione reductase (GR) activity, oxygen and glucose consumption and lactate production along with cell differentiation and proliferation. RESULTS: All monomers induced both cellular differentiation and decrease in oxygen consumption. Cells treated with TEGDMA and Bis-GMA showed a significant enhancement of glucose consumption and lactate production. TEGDMA and HEMA induced GSH depletion stimulating G6PDH and GR activity. CONCLUSIONS: All the monomers under study affect the metabolism of HL-60 cells and show differentiating activity. Since alterations in cellular metabolism occurred at compound concentrations well below cytotoxic levels, the changes in energy metabolism and glutathione redox balance could be considered as potential mechanisms for inducing clinical and sub-clinical adverse effects and thus providing useful parameters when testing biocompatibility of dental materials.

Bisphenol A-Glycidyl Methacrylate↗

Immunosuppressive treatment of chronic non-viral myocarditis.

Inflammatory cardiomyopathy defined as myocarditis associated with cardiac dysfunction, represents a main cause of heart failure. Despite the improvement of diagnostic techniques, a specific standardized treatment of myocarditis is not yet available. The immunohistochemical detection of myocardial HLA up-regulation has been demonstrated useful in the identification of a sub-group of autoimmune inflammatory dilated cardiomyopathy (DCM) in part susceptible to immunosuppression. Recently, in a retrospective study, we defined the virologic and immunologic profile of responders and non-responders to immunosuppressive therapy of active lymphocytic myocarditis and chronic heart failure in patients who had failed to benefit from conventional supportive treatment. Non-responders were characterized by high prevalence (85%) of viral genomes in the myocardium and no detectable cardiac autoantibodies in the serum. Conversely, 90% of responders were positive for autoantibodies, while only 3 (15%) of them presented viral particles at PCR analysis on frozen endomyocardial tissue. With regard to the type of virus involved in non-responders, enterovirus, adenovirus, or their combination was associated with the worst clinical outcome. Hepatitis C virus (HCV) was the only viral agent of our series associated with detectable cardiac autoantibodies, suggesting a relevant immunomediated mechanism of damage by HCV and explaining the relief of myocardial inflammation after immunosuppressive treatment. The assessment of virologic and immunologic features of patients with biopsy-proven inflammatory cardiomyopathy may allow us to identify a specific treatment leading to recovery of cardiac function.

Chronic Disease↗

In vitro comparison of the cytotoxicity of two orthodontic composite resins.

AIM: Several studies have reported that dental resin-based materials release substances with biological activity: for this reason in this study we evaluated the in vitro cytopathic effects of a self-curing and a light-curing orthodontic composite resins by a cytotoxicity test. METHODS: The cytotoxic potential of specimens, prepared according to the manufacturer instructions, was evaluated using the thiazolyl blue tetrazolium bromide (MTT) assay on the mouse fibroblast cell line (3T3 Swiss) with 2 cells-material contact systems: the 24 h extracts method and the indirect toxicity method. RESULTS: The results obtained in this study elicit a close agreement between the 2 procedures; from the data obtained in the reported experimental conditions, it was possible to establish that the examined chemical-cured material is more cytotoxic than the light-cured one. CONCLUSIONS: From a clinical point of view, the photo-polymerizable resins are undoubtedly more useful in the daily practice, because of the larger precision of the bonding obtainable by the greater period available for setting the brackets before their lock. The results obtained in this study, even considering the limits of the in vitro tests, represent a further favourable feature of the light-curing composite resins. However, further investigations about the influence of polymerization methods of the materials on the biological effects are suggested to contribute to the determination of the best clinical operative conditions.

Acrylic Resins↗

Transanal rectocele repair using EndoGIA: short-term results of a prospective study.

BACKGROUND: The surgical treatment of symptomatic rectocele may be carried out by means of endorectal techniques. Results depend on a correct etiologic evaluation of associated diseases. We report the preliminary results of an original endorectal technique applied to selected patients. METHODS: Fifteen women (median age, 57 years; range, 38-73 years) underwent transanal rectocele resection by a 60 mm endo-GIA and subsequent plication of the anterior rectal wall. All patients had a primary isolated anterior medium sublevator rectocele with obstructed defecation symptoms. They were prospectively evaluated by questionnaire, defecation diary, clinical examination, defecography and anal manometry were performed preoperatively. All patients had less than three weekly bowel motions. Postoperative follow-up included clinical examination and symptoms questionnaire with defecation diary at one week, one month and three months; defecography was performed at three months. RESULTS: The time required to repair the rectocele was approximately 20 min. The mean time spent in hospital after the operation was 37 h. Postoperative pain was low or moderate in all cases, one patient had acute urinary retention, 11 had minor rectal bleeding, and 5 had temporary urgency. Abolition of excessive straining, feeling of incomplete evacuation, enemas and self-digitations was achieved in all patients; stool frequency at three months was 7 per week in 10 patients, 5-6 per week in 3 patients and 4-6 in 2 patients (p<0.001). Defecography at three months did not show any rectocele recurrence. CONCLUSIONS: Transanal rectocele repair with linear stapler applied in selected patients is safe and easy to perform. Short-term results are safisfactory. Complete investigations of impaired defecation and selection of patients are needed to achieve satisfactory results.

Adult↗

[Biomechanical aspects of the space gaining therapy according to Cetlin].

The non extraction technique according to N. Cetlin for the treatment of crowded and protrusive dentitions in class I and class II malocclusions is assessed. The intent of this article is to outline the approach to non extraction treatment with the following major clinical objectives: 1) space gaining in both maxillary and mandibular arches; 2) anchorage preservation throughout treatment and 3) intrusion of the maxillary incisors.

Biomechanical Phenomena↗

Retinol-induced apoptosis in larval pancreas of Bufo bufo.

Tadpoles of Bufo bufo at the end of premetamorphosis were exposed to the action of retinol diluted in the rearing water at two concentrations: 20 and 40 microM, for 48 h. Assuming that retinol causes growth suppression by cell death induction, the TUNEL reaction for the detection of apoptotic cells was performed on paraffin sections of pancreas. The results showed that retinol induced a significant dose-dependent increase of number of apoptotic cells with respect to controls, in which apoptosis was scarce. Electron microscopic observations of treated specimens showed that the effects of retinol mostly occurred on exocrine cells: condensed crescent-shaped nuclear chromatin, dark cytoplasm with long projections; conversely, mitochondria and endoplasmic reticulum appeared unaffected.

Animals↗

Inflammatory left ventricular microaneurysms as a cause of apparently idiopathic ventricular tachyarrhythmias.

BACKGROUND: We sought to investigate the arrhythmogenic role, incidence, treatment, and prognosis of inflammatory left ventricular (LV) microaneurysms in patients with apparently idiopathic ventricular tachyarrhythmias. Methods and Results-- We studied 156 consecutive patients (71 men, 85 women; mean age, 44.1+/-11.8 years) with severe ventricular arrhythmias and normal 2D echo cardiac parameters by coronary and ventricular angiography, biventricular endomyocardial biopsy, and electrophysiological study. Polymerase chain reaction was used to detect genomic sequences of enterovirus, adenovirus, Epstein Barr virus, cytomegalovirus, herpes simplex viruses, influenza A and B viruses, and hepatitis C virus in frozen endomyocardial samples. Of these patients, 15 (9.6%) showed angiographic evidence of single or multiple LV microaneurysms. All 15 patients had recurrent episodes of ventricular tachycardia with right bundle-branch block morphology, and the arrhythmias originated within or close to the aneurysms in those patients (n=6) undergoing ventricular mapping. A lymphocytic myocarditis was observed in LV biopsies of all patients and in the right ventricles of 3 patients. Polymerase chain reaction analysis was performed in 12 and viral genomes were found in 5 (42%): hepatitis C virus in 2, enterovirus in 2, and influenza virus A in 1. The patients were treated with antiarrhythmics, and cardiac function was preserved for the next 47+/-39.5 months of follow-up. No major clinical event was registered, and arrhythmias were successfully treated by antiarrhythmics. CONCLUSIONS: Inflammatory LV microaneurysms, often of viral origin, are a consistent cause of apparently idiopathic ventricular arrhythmias. Their prognosis so far has been benign, and aggressive therapeutic strategies have been unnecessary.

Adolescent↗

Programmed cell death in the pancreas of Bufo bufo during metamorphosis.

Programmed cell death or apoptosis occurred in anuran amphibian larval pancreas as a remodelling agent, and was responsible for the reduction of the gland volume during metamorphosis. Apoptotic cells were recognisable by their morphological characteristics and could be immunocytochemically detected by means of the TUNEL reaction, which evidenced nuclear DNA fragmentation. During the last stages of prometamorphosis, that is in the period of hindlimb differentiation, only a few TUNEL positive cells occurred, whereas they increased at the beginning of metamorphic climax, that is at forelimb emergence and during tail regression. Under the electron microscope, the typical morphological characteristics of apoptosis were observed: decrease in size, and the presence of wide intercellular spaces and nuclei with dense chromatin masses arranged in crescents. The fragmentation of these cells produced the so-called 'apoptotic bodies': portions of cytoplasm lined by a membrane, containing nuclear fragments and cytoplasmic organites. Dead cell elimination is hypothesised to occur by phagocytic ingestion.

Animals↗

Myocardial cell death in human diabetes.

The renin-angiotensin system is upregulated with diabetes, and this may contribute to the development of a dilated myopathy. Angiotensin II (Ang II) locally may lead to oxidative damage, activating cardiac cell death. Moreover, diabetes and hypertension could synergistically impair myocardial structure and function. Therefore, apoptosis and necrosis were measured in ventricular myocardial biopsies obtained from diabetic and diabetic-hypertensive patients. Accumulation of a marker of oxidative stress, nitrotyrosine, and Ang II labeling were evaluated quantitatively. The diabetic heart showed cardiac hypertrophy, cavitary dilation, and depressed ventricular performance. These alterations were more severe with diabetes and hypertension. Diabetes was characterized by an 85-fold, 61-fold, and 26-fold increase in apoptosis of myocytes, endothelial cells, and fibroblasts, respectively. Apoptosis in cardiac cells did not increase additionally with diabetes and hypertension. Diabetes increased necrosis by 4-fold in myocytes, 9-fold in endothelial cells, and 6-fold in fibroblasts. However, diabetes and hypertension increased necrosis by 7-fold in myocytes and 18-fold in endothelial cells. Similarly, Ang II labeling in myocytes and endothelial cells increased more with diabetes and hypertension than with diabetes alone. Nitrotyrosine localization in cardiac cells followed a comparable pattern. In spite of the difference in the number of nitrotyrosine-positive cells with diabetes and with diabetes and hypertension, apoptosis and necrosis of myocytes, endothelial cells, and fibroblasts were detected only in cells containing this modified amino acid. In conclusion, local increases in Ang II with diabetes and with diabetes and hypertension may enhance oxidative damage, activating cardiac cell apoptosis and necrosis.

Angiotensin II↗

Giant cell myocarditis responding to immunosuppressive therapy.

An unusual case of giant cell myocarditis presenting with cardiogenic shock that dramatically responded to conventional dose of steroids and azathioprine is reported. Cardiac recovery was rapid, complete (left ventricular ejection fraction rose to 55% from 10%), and was accompanied by the disappearance of the inflammatory infiltrates including giant cells in the control endomyocardial biopsy. Maintenance of the recovery at 16 months of follow-up on a low dose of azathioprine suggests that giant cell myocarditis might be a heterogeneous disease having either a negative untreatable trend necessitating cardiac transplantation, or a curable substrate responding to immunosuppressive drugs.

Adult↗

Coronary angiodysplasia of epicardial and intramural vessels.

A case of coronary angiodysplasia combining large aneurysms of epicardial arteries with diffuse malformation of intramural vessels is reported. Clinical presentation may mimic a vascularized cardiac tumor. Although leaking of the aneurysms in the pericardial space may occur, this entity seems to have a benign prognosis not requiring surgical repair.

Adult↗

Prognostic significance of left ventricular aneurysms with normal global function caused by myocarditis.

OBJECTIVES: To evaluate the prognosis of left ventricular (LV) aneurysms with normal global function caused by myocarditis. BACKGROUND: LV aneurysms may result from idiopathic or viral myocarditis. The prognosis of inflammatory LV aneurysms when associated with a normal cardiac function is unknown. METHODS: Among 353 patients with a histologic diagnosis of myocarditis, 12 (3.3%) had single or multiple localized LV aneurysms (length, 10.6 +/- 3.1 mm; width, 7.4 +/- 4.2 mm) with normal cardiac function. Presenting symptoms were ventricular tachycardia (VT) in nine patients and unexplained chest pain in three. All patients underwent laboratory tests and noninvasive and invasive cardiac examinations, including biventricular endomyocardial biopsy. RESULTS: In all patients, LV endomyocardial biopsy specimen showed a lymphocytic myocarditis with focal intense myocytolysis or damage of intramural vessels, whereas right ventricular biopsy was diagnostic for myocarditis only in three. Serologic study suggested a viral infection in 3 patients and an immunologic disorder in 2, although it was negative in 7. Treatment included antiarrhythmics in 9 patients with VT, ss-blockers in 1 with chest pain, and immunosuppression (prednisone and azathioprine for 5 months) in 4 with active myocarditis (2 with chest pain and 2 with VT). At intermediate-term follow-up (mean, 53 months; range, 12 to 120 months), LV function was persistently normal in all patients, with an LV aneurysm occlusion being observed in two patients. All patients were asymptomatic, with no VT recurrence or major clinical events. None required implantable electrical devices or a surgical intervention. CONCLUSIONS: LV aneurysms with normal global function caused by myocarditis are an uncommon benign entity in which major therapeutic regimens are usually unnecessary.

Adolescent↗

Cell death in acromegalic cardiomyopathy.

BACKGROUND: Prolonged untreated acromegaly leads to a nonspecific myopathy characterized by ventricular dysfunction and failure. However, the mechanisms responsible for the alterations of cardiac pump function remain to be defined. Because cell death is implicated in most cardiac disease processes, the possibility has been raised that myocyte apoptosis may occur in the acromegalic heart, contributing to the deterioration of ventricular hemodynamics. METHODS AND RESULTS: Ten acromegalic patients with diastolic dysfunction and 4 also with systolic dysfunction were subjected to electrocardiography, Holter monitoring, 2-dimensional echocardiography, cardiac catheterization, and biventricular and coronary angiography before surgical removal of a growth hormone-secreting pituitary adenoma. Endomyocardial biopsies were obtained and analyzed quantitatively in terms of tissue scarring and myocyte and nonmyocyte apoptosis. Myocardial samples from papillary muscles of patients who underwent valve replacement for mitral stenosis were used for comparison. The presence of apoptosis in myocytes and interstitial cells was determined by confocal microscopy with the use of 2 histochemical methods, consisting of terminal deoxynucleotidyl transferase (TdT) assay and Taq probe in situ ligation. Acromegaly was characterized by a 495-fold and 305-fold increase in apoptosis of myocytes and nonmyocytes, respectively. The magnitude of myocyte apoptosis correlated with the extent of impairment in ejection fraction and the duration of the disease. A similar correlation was found with the magnitude of collagen accumulation, indicative of previous myocyte necrosis. Myocyte death was independent from the hormonal levels of growth hormone and insulin-like growth factor-1. Apoptosis of interstitial cells did not correlate with ejection fraction. CONCLUSIONS: Myocyte cell death, apoptotic and necrotic in nature, may be critical for the development of ventricular dysfunction and its progression to cardiac failure with acromegaly.

Acromegaly↗

Global biventricular dysfunction in patients with asymptomatic coronary artery disease may be caused by myocarditis.

BACKGROUND: The causal role of asymptomatic critical coronary artery obstruction in patients presenting with severe global biventricular dysfunction but no evidence of myocardial infarction is uncertain. METHODS AND RESULTS: Among 291 patients aged >40 years undergoing a noninvasive (2-dimensional echocardiography) and invasive (catheterization, coronary angiography, and biventricular endomyocardial biopsy, 6 to 8 samples/patient) cardiac study because of progressive heart failure (New York Heart Association functional class III or IV) with global biventricular dysfunction and no history of myocardial ischemic events, 7 patients (2.4%; 7 men; mean age, 49+/-6.9 years) had severe coronary artery disease (3 vessels in 4 patients; 2 vessels in 1 patient, proximal occlusion of left anterior descending coronary artery in 2 patients). Left ventricular end-diastolic diameter and ejection fraction by 2-dimensional echocardiography were 73+/-10.5 mm and 23+/-6.5%, respectively, and right ventricular end-diastolic diameter and ejection fraction were 39+/-7 mm and 29+/-7.2%, respectively. Biopsy specimens showed extensive lymphocytic infiltrates with focal myocytolysis meeting the Dallas criteria for myocarditis in all patients (in 5 patients with and 2 patients without fibrosis). Cardiac autoantibodies were detected with indirect immunofluorescence in the serum of 2 patients with active myocarditis. The 2 patients with active inflammation received prednisone (1 mg. kg-1. d-1 for 4 weeks followed by 0.33 mg. kg-1. d-1 for 5 months) and azathioprine (2 mg. kg-1. d-1 for 5 months) in addition to conventional drug therapy for heart failure. At 8-month overall follow-up, cardiac volume and function improved considerably in immunosuppressed patients but remained unchanged in conventionally treated patients, of whom 1 died. CONCLUSIONS: Global biventricular dysfunction in patients with severe asymptomatic coronary artery disease and no evidence of previous myocardial infarction may be caused by myocarditis. Histologic findings may influence the treatment.

Adult↗

Marked elevation of myocardial trace elements in idiopathic dilated cardiomyopathy compared with secondary cardiac dysfunction.

OBJECTIVES: We sought to investigate the possible pathogenetic role of myocardial trace elements (TE) in patients with various forms of cardiac failure. BACKGROUND: Both myocardial TE accumulation and deficiency have been associated with the development of heart failure indistinguishable from an idiopathic dilated cardiomyopathy. METHODS: Myocardial and muscular content of 32 TE has been assessed in biopsy samples of 13 patients (pts) with clinical, hemodynamic and histologic diagnosis of idiopathic dilated cardiomyopathy (IDCM), all without past or current exposure to TE. One muscular and one left ventricular (LV) endomyocardial specimen from each patient, drawn with metal contamination-free technique, were analyzed by neutron activation analysis and compared with 1) similar surgical samples from patients with valvular (12 pts) and ischemic (13 pts) heart disease comparable for age and degree of LV dysfunction; 2) papillary and skeletal muscle surgical biopsies from 10 pts with mitral stenosis and normal LV function, and 3) LV endomyocardial biopsies from four normal subjects. RESULTS: A large increase (>10,000 times for mercury and antimony) of TE concentration has been observed in myocardial but not in muscular samples in all pts with IDCM. Patients with secondary cardiac dysfunction had mild increase (< or = 5 times) of myocardial TE and normal muscular TE. In particular, in pts with IDCM mean mercury concentration was 22,000 times (178,400 ng/g vs. 8 ng/g), antimony 12,000 times (19,260 ng/g vs. 1.5 ng/g), gold 11 times (26 ng/g vs. 2.3 ng/g), chromium 13 times (2,300 ng/g vs. 177 ng/g) and cobalt 4 times (86,5 ng/g vs. 20 ng/g) higher than in control subjects. CONCLUSIONS: A large, significant increase of myocardial TE is present in IDCM but not in secondary cardiac dysfunction. The increased concentration of TE in pts with IDCM may adversely affect mitochondrial activity and myocardial metabolism and worsen cellular function.

Adult↗