Biomedical subjects
Publications and source records attributed to A Romagnoli.
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Mitochondrial Ca2+ uptake controls cellular functions as diverse as aerobic metabolism, cytosolic Ca2+signalling and mitochondrial participation in apoptosis. Modulatory inputs converging on the organelle can regulate this process, determining the final outcome of Ca2+-mediated cell stimulation. We investigated in HeLa cells and primary skeletal myotubes the effect on Ca2+ signalling of the transcriptional peroxisome-proliferator-activated-receptor-gamma-coactivator-1alpha (PGC-1alpha), which triggers organelle biogenesis and modifies the mitochondrial proteome. PGC-1alpha selectively reduced mitochondrial Ca2+ responses to cell stimulation by reducing the efficacy of mitochondrial Ca2+ uptake sites and increasing organelle volume. In turn, this affected ER Ca2+ release and cytosolic responses in HeLa cells. Most importantly, the modulation of mitochondrial Ca2+ uptake significantly reduced cellular sensitivity to the Ca2+-mediated proapoptotic effect of C2 ceramide. These results reveal a primary role of PGC-1alpha in shaping mitochondrial participation in calcium signalling, that underlies its protective role against stress and proapoptotic stimuli in pathophysiological conditions.
BACKGROUND: Computed tomography has been shown to be useful in the evaluation of aortocoronary bypass grafts (CABG). This is the first prospective study to evaluate the accuracy of a new-generation scanner in the detection of patency and significant stenoses (>50% decrease in diameter) of venous and arterial grafts in patients with previous CABG. METHODS AND RESULTS: In 96 patients (80 males, mean age 62 years) with previous CABG, a multislice computed tomography (MSCT) scan was performed (collimation 16x0.625 mm). Patients with atrial fibrillation, renal failure, severe respiratory disease, severe heart failure, heart rate >70 bpm despite therapy, or unstable angina were excluded. A total of 285 conduits implanted on the native coronary arteries at the time of CABG were evaluated. MSCT data were analyzed by 2 independent radiologists and compared with the results of conventional angiography. Three patients were excluded from analysis. All conduits were judged evaluable in 84 patients. Among these patients, MSCT correctly diagnosed 54 occluded grafts and 4 significant stenoses on the body of the grafts. Of the 17 significant anastomotic lesions, MSCT correctly diagnosed 15. For these 84 patients, diagnostic accuracy was 99%, sensitivity was 97%, and specificity was 100%. When all 93 patients were considered, the sensitivity of MSCT in diagnosing significant stenoses was 96%. CONCLUSIONS: MSCT with the new-generation scanner allows for accurate assessment of venous and arterial conduits in patients with previous CABG with a high degree of sensitivity and specificity. Exclusion criteria and radiation exposure remain limitations of the method.
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Several studies in patients with chronic kidney diseases have shown that men have a more rapid disease progression than women. Also, with ageing, men exhibit greater decrements in renal function and increased glomerular sclerosis than women. Data from meta-analysis studies indicate that women with several non-diabetic renal diseases such as membranous nephropathy, IgA nephropathy and polycystic kidney disease present a slower progression, but in diabetic renal disease this is not yet established. Thus, men appear to be at greater risk for renal injury than are women, but the underlying mechanisms are unknown. Sex hormones may mediate the effects of gender on chronic renal disease, through the interaction with the renin-angiotensin system, the modulation of nitric oxide synthesis and the downregulation of collagen degradation. New observations indicate that androgens may contribute to continuous loss of kidney cells though the stimulation of apoptotic pathways. Apoptosis is an unique type of programmed cell death which is activated in several chronic kidney diseases. Studies in vitro indicate that androgens prime a Fas/FasL dependent apoptotic pathway in kidney tubule cells. This apoptotic cell death pathway is receptor-linked and interacts with the mitochondrial pathway, which may be activated by other mechanisms, such as toxins and ischemia. Therefore, the mechanisms to cell death which are primed by androgens may interact with others occurring in several conditions leading to the loss of renal cells. These findings are consistent with a role for androgens to promote chronic renal injury in men.
Piriformis muscle syndrome (PMS) is a cause of sciatica, leg or buttock pain and disability. The pain is usually increased by muscular contraction, palpation or prolonged sitting. The aim of our paper was to evaluate the feasibility of CT-guided percutaneous botulinic toxin (BTX) injection for the purpose of PMS treatment. Thirty patients suffering from PMS, suspected with clinical and electrophysiological criteria, after imaging examinations excluding other causes of sciatic pain, resulted positive at the lidocaine test and were treated by intramuscular injection of BTX type A under CT guidance. The follow-up (12 months) was performed with clinical examination in all cases and with MR 3 months after the procedure in 9 patients to evaluate the denervative process entity of the treated muscle. In 26 cases relief of symptoms was obtained after 5-7 days. In 4 patients an insufficient relief of pain justified a second percutaneous treatment which was clinically successful. No complications or side effects were recorded after BTX injection. The MR examination showed a signal intensity change of the treated muscle in 7 patients due to the denervative process of PM, whereas in the remaining 2 cases only an atrophy of the treated muscle was detected. Larger series are necessary to confirm these MRI preliminary results. The CT-guided BTX injection in the PMS is an emergent and feasible technique that obtains an excellent local therapeutic effect without risk of imprecise inoculation.
PURPOSE: To evaluate the feasibility of a contrast enhanced MR angiography (MRA) technique, using the latest 1.5 T MR tomoscan, to obtain optimal imaging of the portal system and compare the angiographic images with those obtained by color-Doppler and DSA. MATERIAL AND METHODS: Thirty patients (9 women and 21 men: average 53 years old) underwent contrast MRA of the portal vein, after portal hypertension had been diagnosed on the basis of clinical and chemical data and by color-Doppler. We used a dynamic 3D FFE T1-weighted breath - hold sequence during the arterial and venous phase after administering. 0.2 mmol/Kg of gadolinium-DTPA were at the rate of 2 ml/s. The contrast bolus was monitored using a 2D FFE T1-weighted sequence on a coronal plane. A FFE T1-weighted sequence was performed on axial plane before and after the dynamic sequence to obtain evaluate the a hepatic parenchyma. In the post processing phase MIP (maximum intensity projection) were reconstructed. We considered the patency of the portal venous system and the presence of cavernomatous and collateral circles; portal thrombosis was classified as partial or complete and as proximal or distal. RESULTS: Good quality MR angiographic images were obtained in 28 of the 30 cases examined; in 2 patients movement artefacts compromised the image quality. We observed a concordance between MRA and Doppler ultrasound in 79 vessels out of 84 (94%). A 97.5% concordance was found between MRA and DSA (82 vessels out of 84) with a sensitivity of 100% and a specificity of 97.3%. MRA was superior to DSA and Doppler ultrasound for evaluating large collateral shunts, above all gastro-esophageal and paraumbilical shunts, and complex anatomical conditions. CONCLUSIONS: Where available, advanced MRA technology with contrast enhancement should be used as a routine modality to study the anatomy and pathology and the portal system in all patients in whom Doppler ultrasound has yielded doubtful information. MRA is well-suited to obtain good vascular imaging before surgical or interventional procedures.
In this paper two cases of abdomino-scrotal hydrocele are described. One of these cases resulted really singular due to its rare dimensions as well as to its secondary renal obstruction. After a careful description of the cases a detailed review of the literature as well as of the etiopathogenetic theories of this rare pathology are reported.
The periurethral injection of polytetrafluoroethylene in the treatment of stress urinary incontinence is a therapeutic option introduced more than 30 years ago which is considered rapid, effective and burdened with low complications. This particular therapeutic option when utilized for the treatment of post-prostatectomy incontinence, presents some problems due to the oncologic follow-up of these patients with particular regard to the presence of local recurrences. In fact these injections should not interfere with the standard methods of evaluation of the urethro-vescical anastomosis (DRE and TRUS). The polytetrafluoroethylene in our experience does not accomplish with these requirements because it modifies the palpatory and sonographic findings hindering a reliable evaluation of that region.
The pseudocontact shifts of NMR signals, which arise from the magnetic susceptibility anisotropy of paramagnetic molecules, have been used as structural constraints under the form of a pseudopotential in the SANDER module of the AMBER 4.1 molecular dynamics software package. With this procedure, restrained energy minimization (REM) and restrained molecular dynamics (RMD) calculations can be performed on structural models by using pseudocontact shifts. The structure of the cyanide adduct of the Met80Ala mutant of the yeast iso-1-cytochrome c has been used for successfully testing the calculations. For this protein, a family of structures is available, which was obtained by using NOE and pseudocontact shifts as constraints in a distance geometry program. The structures obtained by REM and RMD calculations with the inclusion of pseudocontact shifts are analyzed.
Typically, blood loss after operations requiring cardiopulmonary bypass is estimated from the sum of blood on sponges and drapes, in the suction system reservoir, and in chest drainage bottles. Prime of the extracorporeal circuit is usually returned to the patient, but no accounting is made of blood remaining in the circuit. In 50 patients, we examined 25 bubble and 25 membrane oxygenator circuits after completion of cardiopulmonary bypass and after return of all prime to the patients. Saline solution was added to each circuit and recirculated for 3 minutes, after which the volume and hematocrit of the recirculated saline were determined. From these values, we estimated that 92.0 +/- 18.1 mL of red blood cells remained in the bubble oxygenators and 100 +/- 11.6 mL in the membrane oxygenators. This volume of red cells is equivalent to 250 mL of whole blood with 35% hematocrit or 30 grams of hemoglobin at 12 gm% concentration. We conclude that blood loss after operations requiring cardiopulmonary bypass is systematically underestimated by the approximately 250 mL left as red cells on the walls and filters of the extracorporeal circuit after return of all prime to the patient.
In patients affected by benign or malignant inoperable airway obstructions, therapeutical options include endoscopic treatment by Nd-YAG laser therapy, tracheobronchial dilatations with rigid or flexible bronchoscope, and inflating balloon dilators. Metal self-expanding or silicone stents allow to obtain stable results. Our experience is based on the use of 14 stents (10 Dumon and 4 Wallstent) in 13 cases of stenosis either due to vegetating malignant tumours not amenable to surgery or benign stenosis. In the following 24-48 hours both subjective and objective changes of the pulmonary function, blood gas analysis and radiologic aspects were observed. The results showed an improvement in the respiratory parameters and a sensible improvement in the quality of life.
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Idrapril is the prototype of a new class of ACE inhibitors, characterised by the presence of a hydroxdmic group. Six untreated in-patients with essential hypertension were given single oral doses of the calcium salt of idrapril, idrapril calcium (200 mg) and placebo according to a double blind, randomised experimental design. Supine and upright blood pressure, heart rate, plasma idrapril serum UCE, active renin and angiotensin II were measured at timed intervals for 24 hours after dosing. Plasma idrapril reached a peak after 2 hours (3.01 microgm x ml(-1)), and by 12 hours the compound had almost disappeared (67 ng x ml(-1)). Derived t1/2 was 1.4-2.2 h. ACE activity was suppressed [from 77.9 to 3.3 after 2 hours and 11.8 after 12 hours nmol(-1) x min(-1) x ml] and angiotensin II production inhibited [from 8.8 to 3.1 (after 1 hour) and 7.5 (after 24 hours) pg x ml(-1)]. Compared to placebo, idrapril calcium significantly lowered both supine blood pressure starting at 4 hours (idrapril calcium 140/93 mmHg; placebo 157/101 mmHg; placebo 147/100 mmHg), and upright blood pressure starting at 3 hours (idrapril calcium 135/95 mmHg; placebo 147/100 mmHg) up to 24 hours (idrapril calcium 132/92 mmHg; placebo 145/100 mmHg). Idrapril calcium appears to be an effective ACE inhibitor in essential hypertension, with a hypotensive action for up to 24 h.
The Authors report a case of endobronchial lipoma, a rare, benign lung lesion. Literature data show that a correct preoperative diagnosis of nature is possible in less than 50% of all the cases and a thoracotomy is mandatory in 85% of the patients because FNAB or brushing rarely allow a certain cytological diagnosis. When a benign tumor is suspected, an endobronchial resection is the treatment of choice, allowing a correct histological diagnosis and in the same time a definitive therapy with resolution of symptoms. Surgical option is reserved for the not certainly determined benign or malignant lesions.
The authors prepared an experimental animal model of ischemia and reperfusion of the limbs to evaluate in vivo the reactive oxygen species involvement and protective role of coenzyme Q10 in reperfusion injury. A group of male rabbits (untreated group) underwent clamping of abdominal aorta for 3 hr and then declamping; at intervals blood sampling was drawn for coenzyme Q10, vitamin E, lactic acid and creatine kinase assays. Another group of male rabbits (treated group) underwent the same ischemia period but before declamping coenzyme Q10 was administered intra aorta. In untreated group, coenzyme Q10 and vitamin E plasma levels decreased while lactic acid and creatine kinase plasma levels increased during reperfusion. These data demonstrate that, after only 3 hr of ischemia, the extremities show a biochemical reperfusion injury, and this involves an increased consumption of antioxidants such as coenzyme Q10 and vitamin E. In the treated group, the increase of creatine kinase plasma levels during reperfusion was not significant, while the decrease in vitamin E was more marked.
Isolated systolic hypertension (ISH) is a definite risk factor for cardiovascular complications (i.e., cardiac failure, coronary artery disease, and stroke) independent of diastolic elevation. The prevalence of ISH is estimated to be approximately 15-20% in the population above the age of 60 years, and increases with advancing age. The Systolic Hypertension in the Elderly (SHELL) study is planned to evaluate the efficacy and tolerability of lacidipine, matched with the diuretic chlorthalidone, in treatment of ISH in elderly hypertensive patients (EHP). One hundred fifteen Italian centers will participate in the study. Fifty centers are associated with the Società Italiana di Geriatria Ospedaliera and 65 centers are departments of internal medicine or outpatient clinics for management of hypertension. A total of 4,800 patients will be enrolled in the trial. Two subprojects will consist of periodical echocardiographic evaluation and 24-h ambulatory blood pressure monitoring. The primary end point of the SHELL study is the incidence of cardiovascular and cerebrovascular events in EHP with ISH, treated with either lacidipine or chlorthalidone. In particular, the SHELL trial is intended to determine whether lacidipine treatment will significantly reduce fatal myocardial events and total cardiovascular mortality.
Loss of hearing due to chronic noise exposition is a well-known pathology and many nations have regulations for the protection of workers with periodical audiometry and ONT check-ups. For the last 15 years, the authors have followed state railway workers of the Milan area who were professionally exposed to noise. All were periodically examined by ONT specialists and submitted to audiometry. The findings underscore the importance of these periodical examinations and their efficacy for the prevention of hearing loss due to noise.