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Biomedical subjects

Gianni Angelini

Publications and source records attributed to Gianni Angelini.

18 recordsLinked to original sources
PubMed2006

Human cardiac myosin autoantibodies impair myocyte contractility: a cause-and-effect relationship.

The functional relevance of autoantibodies (Abs) against cardiac myosin (CM) in clinical idiopathic dilated cardiomyopathy (DCM) remains controversial. The study sought to determine effects of human Abs affinity-purified (AF) by immunoaffinity column chromotography on excitation-contraction coupling in isolated myocytes. Effects of CM-Abs from heart failure patients with DCM (n=19) and ischemic heart disease (IHD, n=19) on contractility, L-type Ca2+ current, and Ca2+ transients in continuously perfused rat ventricular myocytes were studied. Immunofluorescence studies using confocal microscopy were carried out to determine whether Abs were internalized. AF-Abs from either group did not differ in IgG titer but differed in their elution profiles. The IgG3 subclass response was higher in AF fractions from DCM (21%) than IHD (5%) patients. The Abs reduced the capacity of field-stimulated myocytes to contract in a dose-dependent manner. Inhibition of contraction, as a percentage of untreated cells, was greater with DCM than IHD-Abs (P=0.004), and the effect was independent of Ab titer. An increase in frequency of the beating myocytes (0.2 to 3.0 Hz) raised peak systolic and diastolic levels of [Ca2+]i of cells treated with DCM but not IHD-Abs (P<0.005). The AF-Abs were not internalized by myocytes and had no effect on L-type Ca2+ currents. The altered sensitivity of the myofilaments to [Ca2+]i by CM-Abs may represent a potential mechanism of autoantibody-mediated impairment in clinical DCM.

Adult↗
PubMed2006

Penicillamine administration reverses the inhibitory effect of hyperhomocysteinaemia on endothelium-dependent relaxation in the corpus cavernosum in the rabbit.

OBJECTIVE: To elucidate the role of copper in mediating the impact of homocysteine on vasculogenic erectile dysfunction (VED), by investigating the effect of dietary supplementation with the copper-chelator penicillamine to rabbits rendered hyperhomocysteinaemic (HHC) with a methionine-rich diet, as a raised plasma level of homocysteine might be a risk factor for VED. MATERIALS AND METHODS: Homocysteine inhibits the nitric oxide (NO)-dependent relaxation of the corpus cavernosum (CC), an effect which appears to be mediated via the generation of superoxide (O2*-), and H2O2. Copper is a catalyst for the generation of H2O2 in the presence of homocysteine and in the presence of copper, H2O2 undergoes reactions resulting in the generation of O2*-, which reacts with NO to produce peroxynitrite (ONOO-), thereby reducing the bioavailability of NO and impairing NO-mediated relaxation of CC. Smooth muscle strips from CC were obtained from two groups of adult New Zealand White rabbits, one rendered HHC with a diet supplemented with methionine (group 1) and another HHC group that had additional dietary supplementation with penicillamine (group 2). Tissue O2*- levels were measured in each group. After pre-contraction with phenylephrine, relaxation responses of CC strips to carbachol were also assessed in both groups. RESULTS: Methionine supplementation led to profound HHC in all rabbits. Penicillamine in group 2 reduced the total plasma Cu2+ compared to group 1. There was a markedly lower carbachol-stimulated relaxation of CC from HHC rabbits in group 1, with a mean (sem) maximum relaxation of 37 (4)% (six samples), than in group 2, at 58 (6)%. CONCLUSION: These data show that elevated levels in vivo of homocysteine in the rabbit markedly impair NO-dependent relaxation of the CC. Furthermore, this effect appears to be augmented by copper. Further clinical studies on homocysteine and copper status in patients with VED are warranted.

Animals↗
PubMed2005

Plaque rupture after short periods of fat feeding in the apolipoprotein E-knockout mouse: model characterization and effects of pravastatin treatment.

BACKGROUND: These studies examined the early time course of plaque development and destabilization in the brachiocephalic artery of the apolipoprotein E-knockout mouse, the effects of pravastatin thereon, and the effects of pravastatin on established unstable plaques. METHODS AND RESULTS: Male apolipoprotein E-knockout mice were fed a high-fat, cholesterol-enriched diet from the age of 8 weeks. Animals were euthanized at 1-week intervals between 4 and 9 weeks of fat feeding. Acutely ruptured plaques were observed in the brachiocephalic arteries of 3% of animals up to and including 7 weeks of fat feeding but in 62% of animals after 8 weeks, which suggests that there is a sharp increase in the number of plaque ruptures at 8 weeks. These acute plaque ruptures then appear to heal and form buried fibrous caps; after 9 weeks of fat feeding, mice had 1.05+/-0.15 buried fibrous caps at a single site in the brachiocephalic artery. Pravastatin (40 mg/kg of body weight per day for 9 weeks; resultant plasma concentration 16+/-4 nmol/L) had no effect on plasma cholesterol concentration in fat-fed apolipoprotein E-knockout mice but reduced the number of buried fibrous caps by 43% (P<0.0001). In longer-term experiments, the delay of pravastatin treatment until unstable plaques had developed reduced the incidence of acute plaque rupture by 36% (P<0.0001). CONCLUSIONS: Plaque rupture occurs at high frequency in the brachiocephalic arteries of male apolipoprotein E-knockout mice after 8 weeks of fat feeding. Pravastatin treatment inhibits early plaque rupture and is also effective when begun after unstable plaques have developed.

Animals↗
PubMed2005

Prosthetic valve endocarditis.

Prosthetic valve endocarditis is a catastrophic complication of cardiac valve replacement, associated with high mortality rates. Medical treatment is effective in a few instances of endocarditis involving the leaflets alone in bioprostheses. However, accurate diagnosis, better myocardial protection, and improved surgical strategies have led to better survival in patients undergoing surgery after failed conservative therapy. This comprehensive review addresses various issues involved in the management of this complication.

Anti-Bacterial Agents↗
PubMed2005

Nickel contact allergy and menstrual cycle.

According to some reports in the literature, the hormonal fluctuations which occur during the menstrual cycle may affect the clinical expression of contact allergy to a greater or lesser degree. In clinical practice, too, patient history often shows exacerbation of the contact dermatitis during the days immediately preceding menstruation. On the contrary, the follicular phase of the cycle seems to have a temporary protective role in inhibiting the eliciting phase of allergic contact dermatitis. One possible explanation for this phenomenon is of immunological type: it has been demonstrated that oestradiol induces inhibition of delayed hypersensitivity type reactions, probably by acting indirectly on cells having a regulatory function in cell-mediated immunity. To investigate any inhibitory effect of the ovulatory phase of the menstrual cycle on contact sensitization, 30 selected fertile women, allergic to nickel sulfate and with a regular menstrual cycle lasting between 25 and 32 days, were enrolled. Patch tests were performed with a series of 10 serial aqueous dilutions of nickel sulfate, from 5% to 0.0013%. The 30 women were tested at 2 different times, in the ovulatory phase (demonstrated by transvaginal ultrasound) and the progestinic phase; they were subdivided into 2 groups of 15 women: in one group, the tests were made first in the ovulatory phase, and in the other, first in the progestinic phase of the menstrual cycle. There was a minimum interval of 5 weeks between the 2 test phases. The study shows that during ovulation the patch tests elicited significantly less intense responses than in the progestinic phase. These data therefore suggest that the ovulatory phase of the cycle has a significant inhibitory role on delayed hypersensitivity type reactions. For this reason, negative responses to patch tests executed in this phase could likely be false-negatives, and after careful evaluation of the phenomenon and of the clinical condition and patient history, it may be considered advisable to repeat the tests during the progestinic phase of the menstrual cycle.

Adult↗
PubMed2004

Nitroaspirins and morpholinosydnonimine but not aspirin inhibit the formation of superoxide and the expression of gp91phox induced by endotoxin and cytokines in pig pulmonary artery vascular smooth muscle cells and endothelial cells.

BACKGROUND: Although nonsteroidal antiinflammatory drugs (NSAIDs) are ineffective in treating acute respiratory distress syndrome (ARDS), inhalational NO has proved to be useful. NO-donating NSAIDs may therefore be more effective in treating ARDS than NSAIDs alone. Because oxidant stress is central to the pathophysiology of ARDS, the effect of nitroaspirins (NCX 4016, NCX 4040, and NCX 4050) compared with morpholinosydnonimine (SIN-1; an NO donor) and aspirin (ASA) on superoxide (O2*-) formation and gp91phox (an active catalytic subunit of NADPH oxidase) expression in pig pulmonary artery vascular smooth muscle cells (PAVSMCs) and endothelial cells (PAECs) was investigated. METHODS AND RESULTS: Cultured PAVSMCs and PAECs were incubated with lipopolysaccharide (LPS), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1alpha (with or without NO-ASA, SIN-1, or ASA) for 16 hours, and O2*- release was measured by use of the reduction of ferricytochrome c. The expression of gp91(phox) was assessed by use of Western blotting. LPS, TNF-alpha, and IL-1alpha all stimulated the formation of O2*- and expression of gp91(phox) in both PAVSMCs and PAECs, an effect inhibited by NADPH oxidase inhibitors, diphenyleneiodonium, and apocynin. SIN-1, NCX 4016, and NCX 4050 but not ASA alone inhibited the formation of O2*- and expression of gp91(phox). CONCLUSIONS: LPS and cytokines promote the formation of O2*- in PAVSMCs and PAECs through an augmentation of NADPH oxidase activity, which in turn is prevented by NO. Thus, NO may play a protective role in preventing excess O2*- formation, but its negation by O2*- may augment the progress of ARDS. The inhibitory effect of nitroaspirins suggests that they may be therapeutically useful in treating ARDS through the suppression of NADPH oxidase upregulation and O2*- formation.

Acetophenones↗
PubMed2004

Upper gastrointestinal haemorrhage following cardiac surgery: a comparative study with vascular surgery patients from a single centre.

OBJECTIVE: To compare the frequency and outcome of upper gastrointestinal haemorrhage (UGH) patients who had undergone cardiac surgery with a control group of vascular surgery patients. PATIENTS: Patients who had undergone cardiac or vascular surgery from January 1999 to December 2000 were identified from departmental records. The inclusion criteria used were haematemesis and/or melaena in the post-operative period. RESULTS: Only 20 of the 2274 (0.9%) cardiac operations were complicated by UGH compared to eight of 708 (1.1%) vascular operations. Among those with UGH, 90% of the cardiac and 43% of the vascular patients were taking aspirin, warfarin or both. The mean interval between surgery and the UGH was 9.6 days (range 1-30) for the cardiac and 6 days (range 0-15) for the vascular patients. Duodenal and gastric ulcers were the most common cause of UGH (60%) in the cardiac group. Despite endoscopic intervention, more than one third of ulcer associated haemorrhages required surgical over-sewing, but none of the patients who had surgery died. The overall mortality on the cardiac surgery patients who experienced UGH was 15%, significantly higher than the 2.3% for the whole cardiac surgery group during the study period (P = 0.00075, OR = 8, 95% confidence interval 2.3-28). However, even this mortality is less than that of general inpatients who suffer UGH (33%). CONCLUSIONS: Cardiac and vascular surgical patients have similar low post-operative rate of UGH. Post-operative UGH is associated with increased mortality after primary surgery. Early surgical intervention appears to be life saving in those patients who are too ill to compensate for the haemodynamic disturbance of untreated UGH.

Aged↗
PubMed2004

Midterm results after septal reshaping for anteroseptal scars.

BACKGROUND: Midterm clinical and morphologic results of the septal-reshaping exclusion of anteroseptal dyskinetic or akinetic areas were evaluated. METHODS: From January to June 2003, 44 patients with myocardial infarction following left anterior descending coronary artery (LAD) occlusion underwent septal reshaping. The mean (+/- SD) New York Heart Association (NYHA) class of the patients at admission was 2.7 +/- 0.9. Angina was referred in 21 cases. The incision was started at the apex and directed parallel to the LAD toward the base of the heart. The septum was rebuilt with 1 or 2 U-stitches passed from the inside to join the anterior wall to the septum by starting as high as possible where the scar began and continuing in an oblique direction toward the new apex. An oval polyethylene terephthalate fiber (Dacron) patch was then sutured from the septum (at the end of the direct suture through the border with the inferior septum) to the anterior wall (between the healthy wall and the scarred wall) and up to the new apex. RESULTS: The 30-day mortality rate was 2.2% (1 patient, due to the failure of a previously implanted defibrillator). Three patients experienced acute renal failure. No patient had restrictive syndrome. After a mean follow-up period of 8.5 +/- 4.9 months (range, 4-22 months), the mean NYHA class improved from 2.7 +/- 0.9 to 1.6 +/- 0.5 (P < .001). The 18- month survival rate and the probability of being alive in NYHA class I or II were 93.2% +/- 2.0% and 90.9% +/- 4.3%, respectively. Echocardiographic results showed reductions in the left ventricle volume with a normalization of the stroke volume. The diastolic longitudinal length remained unchanged, and the diastolic sphericity index was reduced but not significantly. CONCLUSIONS: At 1 year after surgery, the good clinical and morphologic results demonstrate the safety and effectiveness of septal reshaping for anteroseptal scars.

Adult↗
PubMed2003

The role of 3-dimethylaminopropylamine and amidoamine in contact allergy to cocamidopropylbetaine.

Since it has been found that all subjects with contact allergy to cocamidopropylbetaine (CAPB) have positive reactions to 3-dimethylaminopropylamine (DMAPA), and reports have appeared in literature of the sensitizing action of amidoamine in products containing CAPB, we aimed to verify the possibility that pure amidoamine may have a sensitizing role in subjects with positive reactions to CAPB. To this end, in 10 patients with contact allergy to a commercial CAPB, we tested DMAPA 1% aq. and a pure amidoamine in concentrations ranging from 0.5% aq. to 0.1% aq. The study showed that all patients with positive reactions to DMAPA reacted to amidoamine at 0.5% and 0.25% aq., while 4 of the 10 also had positive reactions to amidoamine at 0.1% aq. We consider that simultaneous allergic reaction to DMAPA and amidoamine represents cross-reactivity and hypothesize that DMAPA is in fact the true sensitizing substance, while amidoamine, which may in any case release DMAPA in vivo as a result of enzymatic hydrolysis, may favour the transepidermal penetration of the sensitizing agent. In addition, we advise that testing of CAPB be suspended, because, as suggested by chemico-structural analyses and demonstrated in vivo, when thoroughly purified, it no longer has a sensitizing action.

Allergens↗
PubMed2003

Nickel, chromium and cobalt in consumer products: revisiting safe levels in the new millennium.

The transition metals nickel (Ni), chromium (Cr) and cobalt (Co) are common causes of allergic contact dermatitis (ACD). Given the high frequency with which these allergens can be associated with hand eczema in those responsible for domestic work, it has been suggested that contamination of household consumer products with these metals may be of relevance to the causation/chronicity of hand dermatitis. Dose-response studies using 48 h occlusive patch test conditions in sensitized individuals show that >/=90% of sensitized patients fail to react below 1 p.p.m., even on irritated skin. Assessment under more realistic exposure conditions has shown that in the presence of irritants and/or following repeated exposures, such individuals rarely react to levels below 10 p.p.m. On the basis of this information, it was recommended a decade ago that household (and other consumer) products should not contain more than 5 p.p.m. of each of Ni, Cr or Co and that, for an even greater degree of protection, the ultimate target level should be 1 p.p.m. The data generated since the original recommendations were made serve to reinforce the validity of these recommendations. Indeed, it is our view that typically the level of each of these transition metals should not normally exceed 1 p.p.m. Then, where consumer products meet this guideline fully, modern quantitative risk assessment shows clearly that elicitation of ACD is highly improbable, and the chance of the induction of sensitization is even lower.

Chromium↗
PubMed2002

The geometry of unstented and stented pig common carotid artery bypass grafts.

The long-term success of arterial bypass grafting with autologous saphenous veins is limited by neointimal hyperplasia (NIH), which seemingly develops preferentially at sites where hydrodynamic wall shear is low. Placement of a loose-fitting, porous stent around end-to-end, or end-to-side, autologous saphenous vein grafts on the porcine common carotid artery has been found significantly to reduce NIH, but the mechanism is unclear. In a preliminary study, we implanted autologous saphenous vein grafts bilaterally on the common carotid arteries of pigs, placing a stent around one graft and leaving the contralateral graft unstented. At sacrifice 1 month post implantation, the grafts were pressure fixed in situ and resin casts were made. Unstented graft geometry was highly irregular, with non-uniform dilatation, substantial axial lengthening, curvature, kinking, and possible long-pitch helical distortion. In contrast, stented grafts showed no major dilatation, lengthening or curvature, but there was commonly fine corrugation, occasional slight kinking or narrowing of segments, and possible long-pitch helical distortion. Axial growth of grafts against effectively tethered anastomoses could account for these changes. CFD studies are planned, using 3D MR reconstructions, on the effects of graft geometry on the flow. Abnormality of the flow could favour the development of vascular pathology, including NIH.

Animals↗
PubMedDate not supplied

Tolerance to calcitriol and tacalcitol in three patients with allergic contact dermatitis to calcipotriol.

We describe 3 cases of psoriatic patients who developed a severe eczematous eruption after the use of calcipotriol ointment. For all of them, the dermatitis recovered after the suspension of the calcipotriol ointment and topical application of corticosteroids. We performed patch tests with the standard series of SIDAPA (Italian Society of Environmental, Occupational and Allergological Dermatology), with an integrative series of vehicles and preservatives, with the commercial ointment containing calcipotriol, with its excipients and, finally, with a series of diluted calcipotriol in isopropanol and petrolatum. They all revealed a strong allergic reaction to calcipotriol and also to its dilution in isopropanol (for all patients) and in petrolatum (only one patient). It is interesting to underline that the reactions always occurred on the legs, even if the patients had applied the ointment elsewhere. We can hypothesize that the venom stasis dermatitis of the legs, associated with xerosis, may have favored the penetration of the drug through the skin, increasing the risk of allergic contact sensitization. Finally, cross-reactivity to other vitamin D3 analogue, tacalcitol, and calcitriol was excluded.

Administration, Cutaneous↗