Abstract: BACKGROUND: Fibroblasts are actually considered pivotal in inflammation and tissue remodelling process and for these reasons they are involved in the pathogenesis of autoimmune disorders such as celiac disease. Investigations to define the role of fibroblasts in celiac diseases are obstructed by the absence of specific models. Our objective is to isolate and culture primary fibroblasts from endoscopic duodenal biopsies of celiac and non-celiac subjects, to analyze their growth patterns and the morphometric characteristics. METHODS: 60 duodenal bioptic specimens from 20 celiac patients and 114 from 38 non-celiac subjects were mechanically chopped and enzymatically digested in order to obtain primary cell cultures. Growth patterns, karyotype (Q-banding analysis), expression of typing proteins (fibroblast surface protein and cytokeratin 20) and morphometric parameters (diameters and their ratio, perimeter, area and perimeter/area ratio at computerised image analysis) were investigated on cultured cells. RESULTS: Primary cells were successfully cultured in 78% of the collected duodenal biopsies. Cultured cells, expressing the fibroblast surface protein, were negative for cytokeratine 20 and maintained a normal kariotype. Cells grew slowly without differences between the celiac and the non celiac group. Morphometric analysis of celiac fibroblasts revealed significantly increased dimensions, with a preserved diameters ratio, and a reduced perimeter/area ratio. CONCLUSION: For the first time this study demonstrates the feasibility of culturing primary fibroblast cell from endoscopic duodenal biopsies in celiac and non-celiac subjects, opening a new window of opportunity in studies intended to establish the role of fibroblasts as a possible partaker in the pathogenesis of the celiac mucosal damage.
Abstract: Cardiac performance after myocardial infarction is compromised by ventricular remodeling, which represents a major cause of late infarct-related chronic heart failure and death. In recent years, the scientists' interest has focused on the hypothesis that the administration of bone marrow progenitors, following myocardial infarction, could ameliorate left ventricular remodeling by continuing to differentiate along the haematopoietic lineage. This approach has been developed minding to the consolidated use of transfusions to restore lost or depleted blood components and, therefore, as an enriched dose of various progenitors, generally autologous, injected peripherally or directly in the infarcted area. Since the safety of this therapy was not yet established, for ethical reasons pioneering researchers involved in these studies used animal models as surrogate of the human biologic system. Herein this hypothesis of therapy resulted in an increased use of living animals and in the reappraisal of models of myocardial damage with limited discussion on the theoretical basis of animal models applied to cell-based therapies. Recently, the European Union and its commission for surveillance of laboratory animals advanced a new proposal to restrict the use of living animals. This review will focus on the history of models utilization in biomedicine, with particular attention to animal models, and delineate an operative comparison between the two best known models of myocardial injury, namely coronary ligation and cryodamage, in the perspective of adult stem cell research applied to cardiovascular regenerative medicine.
Abstract: OBJECTIVE: To compare the effects of the angiotensin II receptor antagonist candesartan with the angiotensin-converting enzyme inhibitor enalapril on myocardial fibrosis evaluated by echoreflectivity analysis. METHODS: Hypertensive patients (n = 196) with echocardigraphically documented left ventricular hypertrophy were randomized to candesartan 8-16 mg/day (n = 91) or enalapril 10-20 mg/day (n = 105) with possible addition of hydrochlorothiazide (12.5-25 mg/day) for 48 weeks. Echoreflectivity analysis was performed on ultrasound two-dimensional tracings of the midapex septum with a specifically designed and validated software. Colour histograms were obtained; the primary outcome variable was the treatment-related change in histogram width (broadband), previously shown to correlate with collagen volume on endomyocardial biopsy; changes in mean colour scale were secondary outcome variable. RESULTS: Echoreflectivity analysis was feasible in 84 patients (48 candesartan, 36 enalapril). Broadband decreased significantly in the candesartan (-8.0 colour levels) and in the enalapril group (-12.9 colour levels) with no significant difference between treatments (P = 0.409); no significant changes occurred in mean colour scale. Patients under monotherapy (n = 46) showed similar trends as the larger intention to treat cohort, without significant difference between treatments. CONCLUSION: In hypertensive patients with left ventricular hypertrophy, both candesartan and enalapril induce a moderate but statistically significant reduction in an echoreflectivity index of myocardial fibrosis.
Abstract: ABSTRACT: Bronchopleural fistula following pneumonectomy is a serious and frightening complication in chest surgery with a high mortality rate. The possibility of curing this complication using a conservative treatment is extremely poor. Below we describe a case of a patient affected by left pleural empyema due to a postpneumonectomy bronchopleural fistula. The patient had previously undergone an aortic prosthesis implantation. He was successfully treated using omental pedicle in order to cover the bronchial stump, to fill the pleural space and to protect the aortic prosthesis. He also underwent thoracoplasty to collapse the residual pleural space. The postoperative course was uneventful. During the follow-up, after thirty months, the patient was asymptomatic, and no recurrence of the fistula was present.
Abstract: BACKGROUND: Solitary fibrous tumor of the pleura is a rarely encountered clinical entity which may have different clinical pictures. Although the majority of these neoplasms have a benign course, the malignant form has also been reported. CASE PRESENTATION: We herein describe a case of 72 year-old man with head, facial, and thoracic traumas caused by neurally-mediated situational syncope when coughing. The diagnostic work-up including chest x-ray, CT and PET, revealed a large solitary mass of the left hemithorax. Radical surgical resection of the mass was performed through a left lateral thoracotomy and completed with a wedge resection of the lingula. Hystological examination of the surgical specimen showed an encapsulated mass measuring 12 x 11.5 x 6 cm consistent with a solitary fibrous tumor of the pleura. It's surgical removal definitively resolved the neurologic manifestations. The patient had no postoperative complications. At two years follow-up the patient is free from recurrence and without clinical manifestations. CONCLUSION: In our case its resection definitively resolved the episodes of situational syncope due, in our opinion, to the large thoracic mass compressing the phrenic nerve.
Abstract: BACKGROUND: Bone Marrow (BM) progenitor cells can target the site of myocardial injury, contributing to tissue repair by neovascolarization and/or by a possible direct paracrine effect on the inflammatory cascade. Angiotensin Converting Enzyme inhibitors (ACE-I) are effective in reducing mortality and preventing left ventricular (LV) function deterioration after myocardial infarction. METHODS: We investigated the short term effects of BM mononuclear cells (BMMNCs) therapy on the pro-inflammatory cytokines (pro-CKs) and on LV remodelling and compared these effects over a standard ACE-I therapy in a rat model of myocardial cryodamage.Forty two adult inbread Fisher-F344 rats were randomized into three groups: untreated (UT; n = 12), pharmacological therapy (ACE-I; n = 14, receiving quinapril), and cellular therapy (BMMNCs; n = 16, receiving BMMNCs infusion). Rats underwent to a standard echocardiogram in the acute setting and 14 days after the damage, before the sacrifice. Pro-CKs analysis (interleukin (IL)1beta, IL-6, tumor necrosis factor (TNF)alpha was performed (multiplex proteome arrays) on blood samples obtained by direct aorta puncture before the sacrifice; a control group of 6 rats was considered as reference. RESULTS: Concerning the extension of the infarcted area as well as the LV dimensions, no differences were observed among the animal groups; treated rats had lower left atrial diameters and higher indexes of LV function. Pro-Cks were increased in infarcted-UT rats if compared with controls, and significantly reduced by BMMNCs and ACE-I ; TNFalpha inversely correlated with LV fractional shortening. CONCLUSION: After myocardial infarction, both BMMNCs and ACE-I reduce the pattern of pro-Ck response, probably contributing to prevent the deterioration of LV function observed in UT rats.
Abstract: AIM : This study investigates the effects of surgery on collagen turnover in patients affected by Crohn's disease (CD). METHODS : Fifteen patients affected by active CD, assessed according to the Crohn's disease activity index, and confirmed by histology, with different pharmacological treatments, were enrolled in the study. N-Terminal propeptide of type III collagen was assessed on peripheral blood before and 6 months after surgery, as an index of collagen turnover. A control group of 15 healthy age- and sex-matched subjects was also studied. RESULTS : In CD patients peripheral N-terminal propeptide of type III collagen serum levels were significantly higher than in controls before surgery (5.0 +/- 1.8 vs 2.7 +/- 0.7 microg/l, respectively; p = 0.0001). Six months after these values were significantly reduced (from 5.0 +/- 1.8 to 3.1 +/- 0.8 microg/l; p = 0.003). Independently on the pretreatment regimen and the duration of the disease, an improvement in the patients' symptoms was observed. CONCLUSIONS : The surgical resection of the affected intestinal segment in CD patients seems to be able to break down the collagen synthesis processes. Peripheral N-terminal propeptide of type III collagen could be seen as an additive marker to clinical and endoscopic observations after surgery.
Abstract: BACKGROUND: There is only one previous case report of a poorly differentiated carcinoma arising from an adenolymphoma of the parotid gland (Warthin's tumour). The absence of clinical symptoms, and the aspecificity of the radiological pattern make the diagnosis very difficult. CASE PRESENTATION: We here report the case of a 73-year-old man with Warthin's tumour who was brought to our attention because of a swelling in the parotid region. CONCLUSIONS: In this case with an atypical clinical presentation, the intra-operative examination of a frozen section of the parotid mass allowed us to diagnose the malignant tumour correctly and consequently undertake its radical excision.
Abstract: Established methods for evaluating cardiac function in small animals involve surgical manoeuvres. We describe a method for evaluating left ventricular volume (LVV) and pressure (LVP) in anaesthetised adult rats. Under fluoroscopic control a 23 G needle was inserted into the left ventricular cavity of anaesthetised normotensive WKY rats. LVV was determined by biplane angiography and LVP was measured directly. Surface electrocardiograms were recorded throughout the procedure. In 8 animals the study was repeated three times, one week apart. Animals were then sacrificed and tissues harvested for histological examination. In 8 rats, the technique was found to be reproducible and there was no evidence of functional (ECG) or pathological myocardial damage following repeated measurements. In conclusion this technique provides a reproducible method of measuring LVV and LVP, allowing longitudinal haemodynamic studies in anaesthetised rats.
Abstract: Mammals must adapt to gravity on passing from the intrauterine to the extrauterine environment. In order to evaluate the cardiovascular effects of gravity in the first phases of extrauterine life, the effects of passive orthostatism on the cardiac filling volume were investigated through longitudinal haemodynamic studies in 14 normal healthy males before (6 months) and after (18 months) acquiring the ability to stand. Left ventricular diameter (by echocardiographic measurement), arterial blood pressure (by sphygmomanometry) and heart rate were measured in the supine and upright position at both ages. At 6 months the left ventricular end diastolic volume was not modified by a change in posture [supine 6(SEM 3) ml, upright 6(3) ml], so heart rate was minimally altered [supine 128(9), upright 130(11) beats.min-1] and blood pressure remained stable [supine 74(6), upright 73(5) mm Hg]. After the acquisition of the erect posture (18 months) left ventricular end diastolic volume was reduced [supine 14(3), upright 8(2) ml], heart rate increased [supine 110(11), upright 127(12) beats.min-1] and blood pressure remained constant [supine 80(6), upright 79(7) mm Hg]. The assumption of the erect posture therefore represents a phase when, for the first time in the natural history of the cardiovascular system, translocation of intravascular volume from the cardiopulmonary area to the periphery stimulates nervous and humoral responses to control the dynamics of body fluids and arterial blood pressure in a gravitational environment.
Abstract: Angiotensin is a potent coronary vasoconstrictor, but little is known of the effects of long-term activation of the renin-angiotensin system on coronary reserve in humans. The effects of exercise on coronary hemodynamics were determined in eight patients with mild essential uncomplicated hypertension, before and after treatment with furosemide (50 mg, to ensure activation of the renin-angiotensin system). Coronary sinus blood flow was measured by thermodilution technique, intra-arterial blood pressure was measured from the ascending aorta, and plasma renin activity was determined by radioimmunoassay. Oxygen supply and demand were derived (using coronary sinus blood flow multiplied by the arteriovenous oxygen difference to equal oxygen supply and heart rate multiplied by the mean systolic blood pressure to equal oxygen demand) both at rest and during isometric exercise (handgrip to 50 percent of maximal effort for three minutes). The study was a single-blind crossover (furosemide versus placebo) design. Furosemide produced a significant reduction in coronary sinus blood flow, associated with an increase in coronary vascular resistance. Changes in mean arterial pressure and heart rate were insignificant. Slight reductions in plasma volume and mean right atrial pressure were observed. During isometric exercise, the increase in oxygen supply for a given increment in oxygen demand was attenuated by furosemide. The contribution of the renin-angiotensin system to this effect was determined by the short-term administration of 25 mg of the angiotensin converting enzyme inhibitor captopril. Forty-five minutes after oral captopril, coronary reserve was restored to pretreatment values. In conclusion, furosemide modulates coronary reserve, and it is likely that this is because furosemide mediates activation of renin-angiotensin system, thus reducing the vasodilatory capacity of the coronary arteries.
Abstract: The purpose of this study was to evaluate whether the heart can induce high blood pressure by maintaining an inappropriately elevated cardiac output/body weight ratio during growth. Direct (femoral artery) mean arterial pressure (MAP), heart rate, cardiac output/body weight ratio (as defined by M-mode echocardiography), and total peripheral vascular resistance were measured and calculated every 2 months in nine conscious dogs during development from 2 to 10 months of age. In four dogs a J-shaped catheter for atrial pacing was chronically implanted at the age of 3 months, and their hearts were permanently paced at 130 beats/min until maturity. The aim of atrial pacing was to prevent the natural slowing of the heart rate and, consequently, to maintain a cardiac output/body weight ratio that was inappropriately high in relation to age during growth. Five dogs were studied as controls. No hemodynamic differences were observed until the age of 4 months. From the age of 5 to 10 months heart rate was kept at 130 beats/min by atrial pacing in the atrially paced group, and the mean cardiac output/body weight ratio did not decrease (196 +/- 24 vs 191 +/- 34 [SE] ml/min/kg). MAP rose from 62 +/- 4 to 116 +/- 8 mm Hg, and total peripheral resistance increased from 0.34 +/- 0.07 to to 0.61 +/- 0.09 mm Hg/ml/min/kg.(ABSTRACT TRUNCATED AT 250 WORDS)
