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Biomedical subjects

S Saccani

Publications and source records attributed to S Saccani.

At least 19 recordsLinked to original sources
PubMed2002

Thoracic aortic stents: a combined solution for complex cases.

OBJECTIVES: The combination of endovascular and standard surgical techniques may facilitate the management of complex aortic disease although the long-term durability of this approach needs to be confirmed. DESIGN: A retrospective review of our experience in the treatment of patients with complex aortic pathology using a combined endovascular and surgical approach. MATERIALS AND METHODS: Between 1998 and 2001, 27 patients with thoracic aortic aneurysm underwent stent-graft implantation. Eight required combined endovascular and surgical procedure because of complex pathology. In 3 cases, combined repair was carried out for a concomitant abdominal aortic aneurysm or aorto-iliac-femoral occlusive disease. In the other 5 cases, vessel relocation was performed to obtain safe landing zones: left subclavian artery to left carotid artery translocation in 3 patients, celiac trunk to superior mesenteric artery translocation in one and aorto-celiac-mesenteric bypass grafting in one. RESULTS: One of the 8 patients died on 12th post-operative day of intestinal bleeding and bowel infarction. No neurological sequelae were reported. The other patients are currently well at 11 months mean follow-up time. CONCLUSIONS: Simultaneous surgical and endovascular procedure is a feasible and may be a valuable adjunct to the treatment of complex aortic and peripheral vessel anatomy.

Adult↗
PubMed2002

New perspectives for the treatment of thoracic aortic aneurysm with self-expanding endoprostheses. Preliminary experience.

We present our preliminary experience with the application of covered aortic stents to treat aneurysms and dissections of the thoracic artery, a technique that was developed in 1996. Seven selected patients were treated with World Medical Talent bare spring tip endoprostheses and followed up for a total of 67 months. All prostheses were implanted at the Parma General Hospital Cardiovascular Department. Seven patients, average age 57.8 years, range 44-73 years, were treated; a total of 11 prosthetic segments were implanted. Aortic pathologies included: 2 isthmic atherosclerotic aneurysms, 2 chronic dissections, 1 acute dissection, 1 thoracic aneurysm associated with an aneurysm of the abdominal aorta below the renal arteries. Dilation diameters ranged from 6-9 cm, lengths from 4-12 cm. All patients underwent computerized tomography and angiography before stent implantation. The procedure was carried out in an operating room with the patient under general anesthesia and in controlled hypotension. In 2 cases the common iliac artery, prepared for the extraperitoneal route by application of a No. 10 Dacron introducer sheath, was used as the insertion site; in 4 cases the common femoral artery was used, in the case of the double aneurysm the traditional surgical route was used to correct the abdominal aneurysm, and the thoracic aneurysm was repaired through the abdominal prosthesis. All patients were released in good condition; thrombosis of the aneurysm surrounding the graft was immediate in all cases except one which required the application of a second segment shortly after the initial procedure. There were no major complications; one case of iatrogenic dissection of the femoral artery used as the access site required a prosthetic bypass. No implant-related complications were observed during follow-up. Our initial experience has been favorable and demonstrates that stents can be utilized for aortic pathologies of varying etiologies; we had no mortality or major complications, and hospital stays were short. Long term results must be confirmed before the therapeutic potential of this technique can be fully evaluated.

Adult↗
PubMed2001

Two waves of nuclear factor kappaB recruitment to target promoters.

Proinflammatory stimuli induce the rapid and transient translocation of nuclear factor (NF)-kappaB to the nucleus, where it activates transcription from several genes, including those encoding inflammatory cytokines and chemokines, adhesion molecules, and cytoprotective proteins. Using chromatin immunoprecipitation, we show that after an acute stimulation two distinct waves of NF-kappaB recruitment to target promoters occur: a fast recruitment to constitutively and immediately accessible (CIA) promoters and a late recruitment to promoters requiring stimulus-dependent modifications in chromatin structure to make NF-kappaB sites accessible (promoters with regulated and late accessibility [RLA]). Our results suggest that a mechanism of specificity in NF-kappaB-dependent transcriptional responses relies on the ability of individual stimuli to make RLA promoters accessible to NF-kappaB before its rapid extrusion from the nucleus.

Acetylation↗
PubMed2001

Age-related changes in cytokine production by leukocytes in rhesus monkeys.

Using a variety of experimental rodent and human models, age-related alterations in cytokine production by immune cells have been described extensively. While the precise mechanism(s) responsible for such age-related changes in cytokine responses remain unclear, it seems likely that these changes may have a significant effect on immune cell function. In an attempt to clarify such changes in aging primates, we examined cytokine production by white cells derived from a controlled colony of rhesus monkeys (Macaca mulatta). Non-fractionated whole blood and peripheral blood mononuclear cells (PBMCs) were obtained from male monkeys of different ages (6-28 years), and were subsequently evaluated for their ability to express mRNA and protein for the cytokines, IL-10, IL-6, IFNgamma, IL-1beta, and TNFalpha, following in vitro stimulation with polyclonal mitogens. Our results suggest that white blood cells derived from aged rhesus monkeys exhibit a significant increase in their ability to produce the Th2-associated cytokine, IL-10, upon stimulation with lipopolysaccharide (LPS) when compared to white cells derived from younger counterparts. Similarly, a significant age-related decrease in the expression of the Th1-associated cytokine, IFNgamma, was also observed using phytohemagglutinin (PHA)-stimulated PBMCs. No significant age-related differences in the production of IL-1beta or TNFalpha were observed in response to any stimulation, but there was limited evidence of an age-related increase in IL-6 production. Overall, our results suggest that a possible systemic change from a Th0/Th1 to a Th2-like cytokine profile occurs in circulating leukocytes derived from aging primates. We believe that such age-related alterations in cytokine production may play a role in the reduced immune responses observed in elderly human populations.

Aging↗
PubMed2001

Surgical repair of thoracic aortic aneurysms: results and complications.

Between January 1990 and February 2001 a total of 323 patients underwent following operations at our Institution: respectively 256 on the ascending aorta, 13 on the transverse arch and 54 on thoracic descending aorta. Sixteen patients with thoracic aortic aneurysms underwent endovascular stent graft implantation. The overall in-hospital mortality was respectively: 7% for ascending aortic aneurysms, 7.7% in the aortic arch aneurysms group and 5.5% for descending aortic aneurysms. The mortality was greater in case of emergency surgery and in the subgroup of patients with acute type A dissection. Stroke with permanent dysfunction occurred in 1.5% of ascending aneurysms, 7.7% of arch aneurysms and in 3.7% of thoracic descending aneurysms. In the latter group, all the major neurological events were related to conventional surgical procedures only: really no mortality or neurological morbidity occurred with endovascular stent graft implantation. Even if modern physiologic monitoring devices and new surgical techniques have been developed in the last years, the treatment of thoracic aortic aneurysms remains challenging. Endoluminal placement of stent grafts has developed as an alternative procedure for the treatment of thoracic aortic aneurysms, even if longer term follow-up is still necessary to fully define the efficacy of this approach.

Adolescent↗
PubMed2000

Redox regulation of chemokine receptor expression.

Cytokines and reactive oxygen intermediates (ROI) are frequent companions at sites of acute inflammation. We have shown previously that in human monocytes, bacterial lipopolysaccharide, IL-1, and tumor necrosis factor-alpha induce a rapid down-regulation of the monocyte chemotactic protein-1 receptor CCR2 (CC chemokine receptor-2). These stimuli also induce production of ROI. In this paper, we investigate the influence of antioxidants and/or ROI on chemokine-receptor expression. In human monocytes, the antioxidant pyrrolidine dithiocarbamate (PDTC) rapidly inhibited CCR2 (95-100% of inhibition) and CCR5 (77-100% of inhibition) mRNA expression by strongly decreasing transcript stability. CCR2 half-life was decreased from 1.5 h to 45 min; CCR5 half-life was decreased from 2 h to 70 min. This inhibitory activity also included CXCR4 (CXC chemokine receptor-4) but not CXCR2 receptor and, although to a lesser extent, was shared by the antioxidants N-acetyl-l-cysteine and 2-mercaptoethanol. In contrast, the ROI-generating system xanthine/xanthine oxidase increased CCR5 and CXCR4 mRNA expression and counteracted the inhibitory effect of PDTC. Accordingly, H(2)O(2) and the glutathione-depleting drug buthionine sulfoximine increased to different extents CCR2, CCR5, and CXCR4 mRNA expression. The PDTC-mediated inhibition of CCR5 and CXCR4 mRNA expression was associated with decreased chemotactic responsiveness (>90% inhibition) and with a marked inhibition of surface-receptor expression. In contrast, xanthine/xanthine oxidase opposed the bacterial lipopolysaccharide- and tumor necrosis factor-alpha-mediated inhibition of CCR5 and CXCR4 mRNA expression and increased both the CCR5 surface expression and the cell migration (3-fold) in response to macrophage inflammatory protein-1beta. These results suggest that the redox status of cells is a crucial determinant in the regulation of the chemokine system.

Acetylcysteine↗
PubMed2000

Human cytomegalovirus harbors its own unique IL-10 homolog (cmvIL-10).

We identified a viral IL-10 homolog encoded by an ORF (UL111a) within the human cytomegalovirus (CMV) genome, which we designated cmvIL-10. cmvIL-10 can bind to the human IL-10 receptor and can compete with human IL-10 for binding sites, despite the fact that these two proteins are only 27% identical. cmvIL-10 requires both subunits of the IL-10 receptor complex to induce signal transduction events and biological activities. The structure of the cmvIL-10 gene is unique by itself. The gene retained two of four introns of the IL-10 gene, but the length of the introns was reduced. We demonstrated that cmvIL-10 is expressed in CMV-infected cells. Thus, expression of cmvIL-10 extends the range of counter measures developed by CMV to circumvent detection and destruction by the host immune system.

Amino Acid Sequence↗
PubMed2000

[Endoluminal repair of aortic aneurysms. Our experience].

From February 1998 and March 2000 fourteen patients underwent "custom made" aortic self-expanding endoprostheses implantation (World Medical Talent Sunrise): nine of them for dilative pathology of thoracic aorta and 5 for abdominal aortic aneurysm below renal arteries. The etiology was degenerative in 8 patients, false aneurysm in 2, chronic dissection in 2 cases, acute dissection in one patient and post traumatic in the last one. All patients underwent preoperative Computed Tomography and Substraction Angiography studies. Stent-graft implantation was successful in all cases but one who required the conversion of the endovascular procedure in traditional surgery for technical problems. There were no perioperative deaths or major complications. We registered 2 cases of dissection of the femoral artery used to introduce the stent-graft, and treated with an iliac-femoral prosthetic bypass. There were no cases of paraplegia or renal failure or bowel ischemia. With the exception of one patient, died for a car accident, the others are alive and continue their scheduled follow-up controls. Our experience shows that this procedure is safe, allowing favorable results, if compared to traditional surgery, even if it requires further long-term evaluations.

Adult↗
PubMed1999

Divergent effects of dithiocarbamates on AP-1-containing and AP-1-less NFAT sites.

Changes in the redox status of cells affect NF-kappaB and activator protein (AP)-1 nuclear expression and activity. In particular, antioxidants decrease NF-kappaB and increase AP-1 transcriptional activity, thereby regulating gene expression. In T cells, low concentrations of antioxidants enhance IL-2 and inhibit IL-4 expression. Since NFAT binding sites play an essential role in regulating IL-2 and IL-4 gene transcription, we studied the effects of dithiocarbamates, using the pyrrolidine derivative of dithiocarbamate (PDTC), on the activity of the distinct AP-1-containing IL-2 NFAT and AP-1-less IL-4 NFAT enhancers elements. Consistent with the presence of AP-1 proteins within the IL-2 NFAT complex, PDTC strongly enhanced phorbol 12-myristate 13-acetate/phytohemagglutinin-induced NFAT binding to the IL-2 NFAT enhancer and transcriptional activity of a reporter plasmid driven by this NFAT enhancer. In contrast, the activity of the IL-4 NFp enhancer, which does not bind AP-1, was abolished by PDTC treatment. In the Jurkat T cell line treated with PDTC, co-expression of the Ca2+/calmodulin-dependent phosphatase, calcineurin, completely restored the IL-4 NFp enhancer activity. Our data indicate that calcineurin-mediated NFAT activity is a target for antioxidants and provides new insights into the molecular mechanisms controlling differential cytokine gene expression.

Antioxidants↗
PubMed1998

The human toll signaling pathway: divergence of nuclear factor kappaB and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6).

The human homologue of Drosophila Toll (hToll) is a recently cloned receptor of the interleukin 1 receptor (IL-1R) superfamily, and has been implicated in the activation of adaptive immunity. Signaling by hToll is shown to occur through sequential recruitment of the adapter molecule MyD88 and the IL-1R-associated kinase. Tumor necrosis factor receptor-activated factor 6 (TRAF6) and the nuclear factor kappaB (NF-kappaB)-inducing kinase (NIK) are both involved in subsequent steps of NF-kappaB activation. Conversely, a dominant negative version of TRAF6 failed to block hToll-induced activation of stress-activated protein kinase/c-Jun NH2-terminal kinases, thus suggesting an early divergence of the two pathways.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Divergent effects of LPS on expression of IL-1 receptor family members in mononuclear phagocytes in vitro and in vivo.

Three molecules, interleukin 1 (IL-1) receptor I (IL-1RI), IL-1 receptor II (IL-1RII or decoy) and IL-1 receptor accessory protein (IL-1R AcP or IL-1RIII), are involved in IL-1 binding and signal transduction. In addition, three homologous genes (T1/ST2, MyD88 and rsc786) have been identified. Expression of the signal transducing type I R and of the decoy type II R in human monocytes is regulated by pro- and anti-inflammatory signals. The present study was designed to evaluate comprehensively how a prototypic pro-inflammatory signal, bacterial lipopolysaccharide (LPS), affects expression of IL-1R family members in mononuclear phagocytes in vitro and in vivo. Resting human monocytes expressed high levels of IL-1RII, IL-1R AcP, MyD88 and rsc786, whereas low levels of IL-1RI and T1/ST2 were present. In vitro exposure to LPS augmented expression of IL-1RI, T1/ST2 and MyD88, whereas it inhibited that of IL-1RII and rsc786. Expression of IL-1R AcP in monocytes was less substantially affected by LPS. The expression of IL-1R family members was also studied in organs of mice given LPS. As expected on the basis of in vitro results, organs (e.g. spleen, lungs and peritoneal exudate cells) from LPS-treated mice showed increased levels of IL-1RI, T1/ST2 and MyD88. Intriguingly, while expression of IL-1RII was inhibited in peritoneal macrophages after LPS, in accordance with in vitro results, increased IL-1RII mRNA was observed in organs such as liver, lungs and spleen. This unexpected effect of LPS was drastically reduced in mice rendered neutropenic by 5-fluorouracil. Therefore, we conclude that the apparent induction of IL-1RII in certain organs of LPS-treated mice is due to recruitment of myeloid cells which express high levels of decoy RII. Therefore, members of IL-1R family are independently and divergently regulated in mononuclear phagocytes exposed to the prototypic pro-inflammatory signal LPS in vitro and in vivo.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Gene transfer-mediated expression of physiological numbers of the type II decoy receptor in a myelomonocytic cellular context dampens the response to interleukin-1.

Available information suggests that the type II IL-1 receptor (RII) is a nonsignaling molecule which acts as a decoy for IL-1. The decoy function model for RII was supported by gene transfer experiments in fibroblasts and keratinocytes. Therefore, inhibition of IL-1 responsiveness after decoy RII gene transfer could reflect a non-physiological cellular context and receptor number. In the present study, constructs encoding RII or a cytoplasmic deletion mutant (delta 372-398) were transfected into U937 cells which express only low levels of RI detectable by RT-PCR. Gene transfer resulted in receptor numbers (approximately equal to 10(3)/cell) of the same order of magnitude as that found in normal myelomonocytic cells. Transfer of RII or a cytoplasmic deletion mutant into U937 did not increase responsiveness to IL-1, as assessed by IL-8 expression and production; it actually considerably dampened it. These results are consistent with the view that in a myelomonocytic cellular context, RII does not contribute to signaling and represents a unique pathway of negative regulation of the IL-1 system.

Cell Line↗
PubMed1996

Regulated expression and release of the IL-1 decoy receptor in human mononuclear phagocytes.

The aim of this study was to investigate the expression and release of the IL-1 type II decoy receptor (R) in mononuclear phagocytes, which play a central role in immune and chronic inflammatory reactions. Human monocytes expressed both type I and type II R transcripts, the latter being two- to threefold more represented. By cross-linking and Ab blocking, the predominant surface IL-1-binding molecule was the decoy RII. IL-4, IL-13, and dexamethasone induced RI and RII transcripts and augmented the number of IL-1-binding sites with no modification of Kd values. The induced surface receptor was identified as the decoy RII. These stimuli induced the release of a soluble R with a m.w. of approximately 60 kDa, of which N-glycosylation contributed 22 kDa compared with 45 kDa released from polymorphonuclear leukocytes, of which N-glycosylation contributed 15 kDa. IL-13 and dexamethasone induced a release of 24 ng/ml/2 x 10(7) cells (from 8.7 to 43.2 ng/ml) and 25.6 ng/ml/2 x 10(7) cells (from 9.7 to 36.8 ng/ml) of decoy RII in 18 h, respectively (six donors). Thus, for instance, IL-13-treated (18 h) cells expressed 3.5 x 10(3) sites/cell and released 12 x 10(3) decoy RII/cell. The released decoy RII from monocytes bound IL-1apha and IL-1 receptor antagonist 30- and 2-fold less avidly than IL-1beta, respectively. In vitro-matured, monocyte-derived macrophages showed higher levels of surface expression and release of the IL-1 decoy RII. The results show that, on exposure to diverse molecules with anti-inflammatory properties, mononuclear phagocytes express and release copious amounts of a novel version of the soluble IL-1 decoy RII.

Dexamethasone↗
PubMed1995

[Unilateral pulmonary embolectomy without extracorporeal circulation. A report of a clinical case].

The surgical treatment of pulmonary embolectomy is currently indicated for acute massive obstruction of the pulmonary artery with severe haemodynamic failure and, as in this case, when medical treatment with anticoagulants or thrombolytic drugs is contraindicated. In this work, the Authors focus on the technique of unilateral pulmonary embolectomy through a median sternotomy; this approach allowed an easier and safer embolectomy without extracorporeal circulation.

Embolectomy↗
PubMed1995

[Autotransfusion of the blood drained from mediastinum in the course of myocardial revascularization].

To determine if autotransfusion of unwashed shed mediastinal blood led to a reduction in the postoperative banked blood requirements were analyzed in a prospective study 82 patients undergoing myocardial revascularization during 1994 at Cardiovascular Surgery Center of Parma, randomized to receive (ATS) or not (noATS) the system. No differences were noted between two groups in terms of clinical parameters; likewise the operative characteristics were similar for the two groups. The mean 24-hours postoperative blood loss was 719.5 +/- 196 ml in the ATS group and 843 +/- 292 ml in the nonATS group (p = 0.027); the mean volume autotransfused in the ATS group was 416 +/- 167 ml. There were no reoperations for bleeding. In the nonATS group 65.8% of patients required postoperative homologous transfusions compared with 41.5% in the ATS group (p = 0.05). The mean immediate and 24-hour postoperative hemoglobin values were similar in the two groups, but at hospital discharge were 21.1 +/- 1.4 g/dL in the nonATS group and 11.3 +/- 1.4 g/dL in the ATS (p = 0.015). By logistic stepwise multiple analysis were identified as risk factors for banked blood requirement the variables: age, preoperative blood drawing patient, blood drawing before institution of cardiopulmonary bypass and postoperative blood loss. Non use of ATS was not a significant incremental risk factor for banked blood requirement, furthermore we think that use of ATS system is a primary blood volume support and confers to reduce homologous transfusions and their related complications after cardiac operations.

Aged↗
PubMed1995

[Combined cardiac surgery and aneurysm of subrenal abdominal aorta].

The authors explain their experience about the combined correction of cardiac pathology and infrarental aortic aneurysm repair. Seven patients of mean age of 63 years underwent simultaneous myocardial revascularization (5 cases) or aortic valve replacement (2 cases) and abdominal aortic aneurysm repair with bifurcated vascular prosthesis (6 cases) and tubular prosthesis (1 case) between 1987 and 1995. Cardiac operation was performed first with a mean number of 2.4 coronary artery by-pass grafts, with a mean by-pass time of 51 min, and a mean abdominal aortic cross-clamp time of 46 min. The mean total operating time was 231 min. All patients were managed postoperatively in the cardiac intensive care unit with a mean duration of 2.5 days and were transfused with a mean of 5 units of donor blood. The mean postoperative hospitalization was 9 days. One patient died for complication of postoperative myocardial infarction. The authors conclude that combined cardiac operation and abdominal aortic aneurysm repair is feasible in carefully selected patients.

Aged↗
PubMed1995

[Our experience in the surgery of thoracic aorta].

Particular interest was given to 61 cases of aneurysm and all possible risks and failures of the surgical procedures were discussed. The importance of how diagnostic, technical and instrumental investigations greatly improved therapy was emphasized. The largest group of patients investigated statistically was composed of patients suffering from acute aortic dissection. Emphasis was put on how modern diagnostic technology resulted in a faster and safe procedure, keeping in mind, however, that many severe cases were still unsuccessful. With regard to traumatic lesions of the aorta, typical of young patients, the importance of a complete clinical and surgical approach was stressed in order to treat the visceral and scheletral lesions that are often present.

Aortic Dissection↗