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Biomedical subjects

A Delfino

Publications and source records attributed to A Delfino.

At least 19 recordsLinked to original sources
PubMed2005

[Blockade of B7:CD28 costimulatory pathway reduces the vascular damage in an experimental model of chronic rejection].

AIM: Costimulatory blockade and donor specific transfusion (DST) can catalyze tolerance of transplanted organs through a multistep adaptation between the recipient and donor immune systems. Such an in vivo process may prolong graft survival. Aim of this study was to evaluate the outcome of aortic transplantation under CTLA4Ig and DST in a mismatched model in rats. METHODS: Orthotopic aortic transplantation was performed in recipients Lewis from Wistar-Furth rats. The animals were stratified into 3 groups, according to the postoperative treatment. Group 1 had aortic transplantation only (controls, n=6), while group 2 (n=7) had a load of donor splenocytes (DST). Group 3 was treated with DST and CTLA4Ig. All the animals were sacrificed at the 60th postoperative day and the aortic specimens were prepared for histology. Intimal cells, muscular cells and lymphocyte cell infiltration were evaluated by serial counts. RESULTS: In Group 1 there was a severe chronic rejection, while group 2 showed a slower onset of chronic rejection with less inflammatory infiltrate than group 1 (P<0.05). Group 3 had the best overall outcome with lower infiltration and minimal alterations compared with groups 1 and 2. CONCLUSIONS: Costimulatory blockade and DST load can prevent the onset of chronic rejection in this experimental setting. Despite the wide availability of immunosuppressors, which makes transplantation a today's clinical routine, the solution to chronic rejection is still elusive. The synergistic role of splenocytes and costimulatory blockade raises interesting perspectives about the immunomodulatory role of spleen in tolerance induction.

Animals↗
PubMed2004

Serum lamivudine levels in the presence of a lamivudine-resistant HBV mutant.

BACKGROUND/AIMS: Lamivudine efficiently inhibits hepatitis B virus replication and has been used to treat hepatitis B virus recurrence after orthotopic liver transplantation. Although effective, its use is hampered by viral breakthrough due to the appearance of hepatitis B virus drug-resistant strains. Aims of this work were to evaluate the inter- and intra-individual variations of lamivudine serum levels and the effects on the drug levels of the lamivudine-resistant hepatitis B virus mutant infection. METHODS: Serum lamivudine concentration was measured by high-performance liquid chromatography. Polymerase chain reaction analysis and sequencing analysis of the reverse transcriptase area of the polymerase was performed on each sample using specific primers. A polymerase chain reaction-enzyme-linked immunosorbent assay was used to differentiate between wild-type hepatitis B virus and lamivudine-resistant hepatitis B virus strain. RESULTS: Lamivudine serum levels presented minor inter- and intra-individual fluctuations along time, with an important increase at the time of the hepatitis flare-up due to the hepatitis B virus mutant presence. When the wild-type hepatitis B virus briefly reappeared as a mixed population, the titre of lamivudine dropped to below the detection level. CONCLUSIONS: While lamivudine serum levels appears stable when the anti-viral efficacy is fully achieved, important fluctuations are present according to the type of viral population, with a considerable decrease possibly due to the presence of the wild-type virus.

Anti-HIV Agents↗
PubMed2004

Kinetics of soluble tumour necrosis factor (TNF)-alpha receptors and cytokines in the early phase of treatment for chronic hepatitis C: comparison between interferon (IFN)-alpha alone, IFN-alpha plus amantadine or plus ribavirin.

We have previously studied the effect of three different treatment regimens with interferon (IFN)-alpha alone or in combination with amantadine or ribavirin on viral kinetics in the first month of therapy. To understand the regulation of cytokine immune response during early inhibition of HCV replication, we analysed the longitudinal profile of proinflammatory markers (soluble TNFRs), of type 1 cytokines [IFN-gamma and interleukin (IL-12)], and of a type 2 cytokine (IL-10). Twenty-two chronic hepatitis C patients received daily therapy for 6 months. Sera were collected at baseline, at 6, 12, 24, 30 and 48 h and at the 3rd, 7th, 15th and 30th days of treatment. All cytokines and receptors were evaluated by enzyme linked immunosorbent assay (ELISA). At baseline, a correlation was found between the two soluble TNFRs (P < 0.0001) and between the soluble TNFRs and ALT levels (P < 0.003), as shown previously. Regardless of the type of treatment, lower levels of soluble TNFR-p75 were present from day 3 in patients who had significant virus decay at day 30 (P < 0.01). Baseline IL-10 levels correlated with TNFR-p75 (P < 0.01) and with treatment response (P < 0.05) and a significant IL-10 reduction from baseline was observed from day 3 among responders, irrespective of the type of treatments (P < 0.05). IL-12 and IFN-gamma levels did not differ according to treatment or outcome. These findings suggest a pivotal role for IL-10 in orchestrating the antiviral immune response. Its early decline can favour the shift from a Th2 to a Th1 immune response, which has been shown to be associated with a long-term virological response to treatment.

Adult↗
PubMed2002

Fabricated hyalS micropatterns and surface guidance of NCTC 2544 continuous cell line: an in vitro study.

Surface topography is important in establishing tissue organisation adjacent to implants, smooth surfaces generally being associated with fibrous encapsulation. By virtue of its large hydrated molecular volume and its capacity to form molecular matrix, hyaluronic acid can expand the interfibrillar collagen spaces to allow the movement of cells, although it can also hamper their locomotion. Low molecular-weight hyaluronan can also stimulate cell proliferation, especially at low concentrations. The aim of the present work was to evaluate in vitro the growth and migratory behaviour of NCTC 2544 keratinocytes cultured on different materials microstructured with hyaluronic acid or sulfated hyaluronic acid to assess the possibility of using these devices in the repair process of soft tissues. Ultrastructural morphological analyses, morphometric evaluations and detection of cytoskeletal elements were performed. Our observations provide evidence that micrometer-size parallel grooves of hyaluronic acid can influence cell growth behaviour since cells seeded onto the microstructured substrate arranged themselves according to a shape and an orientation that clearly reflected the chemotropism exerted on them by the two forms of acid. These data also highlight the importance of accurate microtexture fabrication. We intend to follow up these in vitro studies with in vivo experimental applications using PET and gelatin substrates structured with HyalS to evaluate wound healing responses, and to extend our investigations of the cytoskeletal modifications induced by different microstructures.

Adjuvants, Immunologic↗
PubMed2001

Isospin asymmetry in the pseudospin dynamical symmetry.

Pseudospin symmetry in nuclei is investigated considering the Dirac equation with a Lorentz structured Woods-Saxon potential. The isospin correlation of the energy splittings of pseudospin partners with the nuclear potential parameters is studied. We show that, in an isotopic chain, the pseudospin symmetry is better realized for neutrons than for protons. This behavior comes from balance effects among the central nuclear potential parameters. In general, we found an isospin asymmetry of the nuclear pseudospin interaction, opposed to the nuclear spin-orbit interaction which is quasi-isospin symmetric.

Journal Article↗
PubMed1997

Residual strain effects on the stress field in a thick wall finite element model of the human carotid bifurcation.

A three-dimensional finite element model of the carotid artery bifurcation was constructed in order to determine the stress field and assess the modification of the stress field when residual strain is taken into account. Residual strain in the carotid bifurcation was characterized by experimental observations. According to these observations, a geometrical model of the carotid artery was constructed to exhibit a state free of strain. Appropriate boundary conditions were applied to yield the correct geometry in the unloaded state, and physiological levels of pressure and axial stretching were applied. The model took into account the varying thickness of the arterial wall along the bifurcation. For modeling purposes, the material was considered to be hyperelastic, incompressible, homogenous and isotropic. For comparison, a similar model of the carotid artery which does not include the effects of residual strain was also created. The results demonstrate that in the model of the carotid artery bifurcation with residual strain, the distribution of maximum principal stress along the inner wall and the circumferential stress throughout the wall is much more uniform than in the model without residual strain. The ratio between the stress at the inner and the outer walls is highest at the lateral wall of the carotid sinus; this is the same location known to be a site of low and oscillatory fluid wall shear stress, and the principal location of early intimal thickening. These results suggest that the localization of atherosclerosis in the carotid artery may be due to local variations in both fluid wall shear stress and solid wall stress.

Animals↗
PubMed1996

The effects of time-varying curvature on velocity profiles in a model of the coronary arteries.

Blood flow patterns in the coronary arteries are of interest due to their possible involvement in atherosclerosis localization. Spatial variations in hemodynamic flow patterns are predominantly determined by the vessel geometry. The coronary arteries represent a unique situation in the cardiovascular system because their geometry undergoes large dynamic variations during each cardiac cycle due to the contraction of the heart. This study was initiated to analyze the effects of time-varying curvature on flow velocity profiles in a curved tube model of the coronary arteries. An in vitro flow model was constructed, which consisted of a flexible curved tube through which fluid flowed under a steady imposed pressure gradient. The radius of curvature of the tube was varied in time using a stepper motor and carriage. Two different deformation configurations were used to determine if variations in center of curvature displacement affected the velocity profiles. It was found in both cases that the skewing of the axial velocity profile depended on the instantaneous dynamic vessel movement, with maximal skewing occurring when the radius of curvature was in transition from the minimum to the maximum value. The change in skewing was greater for the case where carriage moved obliquely to the main direction of flow than when the carriage moved perpendicularly. Although this study was limited to relatively low values of the radius of curvature and change in curvature, an initial understanding of this flow situation was obtained which may lead to the development of more physiologic models.

Animals↗
PubMed1995

Cervical intraepithelial neoplasia and human papillomavirus related lesions of the genital tract in HIV positive and negative women.

Two hundred and twenty one women at high risk for HIV (intravenous drug users and/or those with infected partners) were investigated, through a self-filled questionnaire and gynaecological examination, to define the relationship between genital Human Papilloma Virus (HPV) infections, preneoplastic cervical intraepithelial lesions (CIN) and behavioural risk factors. In the 121 HIV positive women, 58 (47%) had HPV lesions at colposcopic and/or cytologic examination and, out of these 58, 23 (40%) had CIN 1, CIN 2 or CIN 3. Six out of the 16 cases with CIN 1 and CIN 2 (37%) followed-up showed a rapid progression of the lesion to CIN 3; in 3 women the interval was 6 months, in the other 3 about 12 months. Only 5 (7%) of the remaining 66 women without HPV lesions had a CIN lesion, with an obviously significant difference on comparison with HPV positive subjects. Sixty two women out of the 121 (52%) had a previous diagnosis of condylomata. In the 100 HIV negative women, 23 (23%) had HPV lesions and, among these 23, 6 (26%) had CIN 1, CIN 2 or CIN 3; 1 of them had rapid progression from CIN 1 to CIN 3 within a year. Only 5 (3%) without HPV infection showed any kind of CIN. 33 women out of 100 (33%) had a previous clinical history of condylomata. Our findings strongly suggest that HIV infection is associated with HPV lesions and that cervical cytological abnormalities develop in this situation. There is a need for short interval cytological and colposcopic follow-up for women at high risk of HIV infection.

Adult↗
PubMed1994

Preliminary analysis of the effects of blood vessel movement on blood flow patterns in the coronary arteries.

Blood flow patterns are believed to be involved in the formation and progression of arterial diseases. It is possible that the normal physiologic movement of blood vessels during the cardiac cycle affects blood flow patterns significantly. For example, the contraction of the heart in systole and subsequent relaxation in diastole create movements of the coronary arteries, as evidenced in real-time angiography. The effects of this movement on coronary artery flow patterns have never been previously analyzed. This work was undertaken to provide a preliminary estimate of the importance of the effects of such physiologic movements on blood flow patterns in the coronary arteries. A Womersley-type solution was used to determine the effect of axial movement on the wall shear rate in a simplified model of the coronary arteries. The pulsatile pressure gradient was derived from previously published coronary artery flow waveforms. The axial movement function was obtained from a three-dimensional reconstruction of a biplanar coronary angiogram. Significant changes in wall shear rate were noted when the movement was taken into account. The maximum and minimum wall shear rates were 10 percent smaller and 107 percent larger in magnitude respectively, and the Oscillatory Shear Index (OSI) was doubled. Most of the changes in wall shear rate were observed in systole, when the pressure gradient is minimal and the movement is strongest. The results indicate that blood vessel movement during the cardiac cycle has a significant effect on hemodynamic phenomena which have been associated with the development of atherosclerosis.

Arteriosclerosis↗