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Biomedical subjects

A Gaspari

Publications and source records attributed to A Gaspari.

At least 19 recordsLinked to original sources
PubMed2006

[Immunomodulation after combined spleen and kidney transplantation in swine].

AIM: Organ transplantation is the most effective treatment for several degenerative end-stage diseases. While the mainstream immunosuppression can achieve satisfactory results, the therapy has either side effects and flaws. The golden target to reach should be a stable tolerance with the transplanted organ accepted without a long term drug administration. Recent studies demonstrated a tolerogenic effect of spleen cells. Aim of this study is to evaluate a model of combined spleen and whole organ transplantation in a significant preclinical setting in swine. METHODS: Twenty-five outbred Landrace/Large-White swine underwent combined spleen/kidney transplantation (SKTx). The experiments were stratified into 3 groups per randomization. Group 1 (N=7) received kidney transplantation (KTx) alone with no immunosuppressive treatment. Group 2 (N=9) had a combined KTx and whole graft spleen Tx. Group 3 (N=9) had KTx and spleen cells (DST), injected through the portal vein. Renal lab tests were collected to evaluate the onset of rejection. Survivals were evaluated as well. The end-point of the study was at onset of kidney failure or at the limit of 60 postoperative day (POD) in non-rejecting animals. Tissue samples were collected to evaluate grade and severity of rejection. RESULTS: Controls died from kidney failure within 10(th) POD. Group 2 and 3, had a delayed renal graft rejection and an overall prolonged graft survival. Whole graft and spleen cells injection share this effect, while spleen administration through the portal route proved a superior effect, which is significant compared to controls (Kaplan Meier survival analysis P<0.05). CONCLUSIONS: These results, from a non immunosuppressed setting, suggest that spleen plays a key role as an immunomodulatory organ.

Animals↗
PubMed2006

[Liver transplantation in swine: a model for tolerance induction].

AIM: The liver as a solid graft has a known immunological privilege. Its tolerogenic property has been demonstrated in rodents. In humans the onset of chronic rejection and the severity of such complication is less frequent after liver transplantation compared to other organs. The underlying events whose effect is graft acceptance instead of rejection should be further investigated. Their control could open new ways to decrease the need for long-term immunosuppression after transplantation of other organs. Aim of this study is to evaluate a model of liver transplantation in swine as a preliminary step for immunological studies. METHODS: Ten outbred Landrace/Large White mismatched swine underwent to liver transplantation with a simple passive portocaval jugular bypass. The onset of rejection was monitored daily by liver function test. After death or sacrifice the liver parenchyma was studied to evaluate tissue damage and inflammatory infiltrate. RESULTS: The postoperative liver function showed a critical period for organ rejection about postoperative day 5. The animals that survived longer were sacrificed with a normal biochemical hepatic function. However, histology consistently showed a pattern of mild rejection in a still preserved architecture. CONCLUSIONS: The evidence of a prolonged liver function in a rejecting model of liver transplantation makes this model suitable for studies of tolerance induction.

Animals↗
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↗
PubMed2003

Modulation of blood circulating immune cells by radiofrequency tumor ablation.

Tumor ablation by radiofrequency (RFA) is an appealing therapeutical strategy for the treatment of liver tumors (hepatocarcinoma and metastatic lesions) to be used as valid alternative to the surgical resection that often is appropriate and feasible in only a minority of patients. RFA induces the localised and controlled disruption of the tumor by heating the tissue causing its coagulative necrosis. Such therapy results as a pathogenic "noxa" for the body, inducing a strong inflammatory response. We wanted to ascertain whether the inflammatory response induced by RFA was similar in patients with hepatocarcinoma and in patients with liver metastasis. We considered body temperature, leucocyte counts at different time points as inflammatory parameters. We observed that RFA treatment produced the inflammatory systemic effects as expected (fever, increase of neutrophils) only in the patients with liver metastasis, while no such effect could be seen in the HCC patients. On the other hand the circulating monocytes increased after RFA in both groups of patients. These preliminary results suggest that RFA tratment can exert different effects on the immune system depending the etiopathogenesis of the treated neoplastic liver lesions.

Body Temperature↗
PubMed2001

Follicular mycosis fungoides: a case report and review of the literature.

BACKGROUND: Follicular mycosis fungoides is an unusual variant of mycosis fungoides (MF). Unlike classic MF where atypical lymphocytes show a predilection for the epidermis (epidermotropism), follicular MF displays a malignant lymphocytic infiltrate tropic for hair follicles (folliculotropism). This malignant lymphocytic infiltrate results in follicular disruption typically manifesting clinically as plaques, comedones and follicular papules. METHODS: This report describes a 40-year-old patient with follicular MF presenting as nodules on the face and chest. Histologic examination of the patient's biopsy revealed a folliculocentric infiltrate of atypical lymphocytes with sparing of the epidermis. RESULTS AND CONCLUSIONS: Our case is discussed in the context of previously reported cases of follicular MF; we also include a review of all cases of follicular MF published to date that meet the strict criterion for this diagnosis.

Administration, Topical↗
PubMed2000

[Transplantation of the intestines and bacterial translocation].

Infections, sepsis and multiple organ failure syndrome are associated with high morbidity and mortality in human and experimental small bowel transplantation (SBTx). These complications are attributed to bacterial translocation demonstrated in animal and human studies. Bacterial translocation (BT) is defined as the passage of viable bacteria from the intestinal lumen to other tissues or organs. BT has been associated with different clinical and experimental situations, hemorrhagic shock, trauma, bowel obstruction, immunodepression, total parenteral nutrition, antibiotics. Although BT has been investigated in several small and large animal models of SBTx, precise information on the mechanisms involved are not available. It is possible that the operative procedure by itself may promote BT for the interaction of a number of factors such as preservation, ischemia/reperfusion, abnormal motility, lymphatic disruption and aberrant systemic venous drainage, acute or chronic rejection and antibiotic therapy. Furthermore, the potent immunosuppressive therapy used in these patients may augment the deleterious effects caused by BT. In this review we examined the existing literature concerning BT with particular regard to intestinal transplantation, to better understand the alterations in the symbiotic relationship between immunocompromised host and his gut microflora after SBTx.

Animals↗
PubMed1999

Liver ischemia modifies the concentration of plasmatic catecholamines after reperfusion in the rat.

Pulmonary hypertension is one of the most frequent and severe consequences of liver ischemia. The aim of this study is to evaluate the presence of humoral vasoactive mediators, generated during liver ischemia, which could be able to determine the onset of pulmonary hypertension. Thus, we evaluated the plasmatic concentration of catecholamines (adrenaline, noradrenaline, dopamine) during the immediate reperfusion period. Wistar rats were used. Animals (n = 89) were divided into four groups. Group 1 served as control (sham-operated). In group 2 animals underwent 60 min of left hepatic exclusion. In group 3 animals underwent to bilateral adrenectomy. In group 4 animals had both bilateral adrenectomy and liver ischemia. Ischemia in group 2 and 4 was induced by interrupting the vascular supply to the left and median lobes, so avoiding the use of a portal shunt. Blood samples were collected from the suprahepatic inferior caval vein immediately after reperfusion. Strips of the main pulmonary artery were put into an isolated organ bath and tested for the response to noradrenaline, adrenaline and plasma samples. Plasma samples collected after ischemia caused a significantly greater (p < 0.01) contraction of the pulmonary artery compared to controls. Plasma samples collected after adrenectomy caused a weak contraction which was not different from that obtained in the adrenectomy + ischemia group. Plasma concentrations of catecholamines after liver ischemia were significantly increased in the control group (p < 0. 01). In adrenectomized rats only the adrenaline level was greatly reduced. However ischemia did not increase plasma catecholamines as it occurred in sham-operated rats.

Animals↗
PubMed1999

[Whole pancreatic transplantation and islet transplantation. Experiment notes].

BACKGROUND: The results of pancreas transplantation have greatly improved in recent years. The path to further improvements goes through extensive experimental researches. METHODS: This study describes the effects of different procedures as hemodynamic asset and postoperative outcome. Twenty-nine swine underwent a total pancreatectomy, and were stratified into five groups. Group one (n = 5) served as control. Group two (n = 7) was autotransplanted. Group three (n = 6) and group four (n = 6) underwent allotransplantation; the first without immunosuppression and the second treated with cyclosporine and steroids. In group five (n = 5) Langerhans Islets transplantation was performed. RESULTS: Survival was different depending on which methodology was applied. The postoperative survival was 7 +/- 2 days in group one, 24 +/- 16 days in group two, 17 +/- 7 days in group three, 27 +/- 8 days in group four and 12 +/- 6 days in group five. CONCLUSIONS: The postoperative glucose control was normal in group two and group four while a severe diabetes appeared in group one (group 1 vs group 2: p < 0.05) and in group three during acute graft rejection after the 12th postoperative day (group 3 vs group 4: p < 0.05). Glycemia was slightly controlled in group five. The intraoperative hemodynamic status was evaluated at the time of pancreatectomy, harvesting, revascularization, and when surgery was over. Among the different parameters studied (mean arterial and pulmonary pressure, pulmonary wedge pressure, central venous pressure, cardiac output, oxygen extraction ratio, systemic vascular resistance, oxygen delivery and oxygen consumption), a statistically significant difference between group one and group five (p < 0.05) was observed.

Animals↗
PubMed1999

[Microsurgical repair of iatrogenic injuries of the recurrent laryngeal nerve].

In this retrospective study the functional results of microsurgical repair of iatrogenic recurrent nerve lesions (10 patients) faced during years 1983 through 1995 have been analysed. Different parameters were considered (thyroid disease, previous thyroid surgery, microsurgical reconstruction technique, time between surgical damage and microsurgery). Furthermore, a thorough review has been made on the medical literature on subjects such as surgical anatomy of the cervical region, microsurgical nerve repair techniques, and clinical results of microsurgery in different authors experiences.

Adult↗
PubMed1998

[Treatment of the nephrotoxicity of immunosuppressive drugs with insulin-like growth factor-I].

BACKGROUND: Delayed graft function is a common and severe complication after cadaveric kidney transplantation. Besides a more complicated postoperative course, DGF can worsen the overall graft survival. In particular, DGF enhances the nephrotoxicity of mainstream immunosuppressants cyclosporine and FK506. This study evaluates a new therapeutical approach to the treatment of DGF related nephrotoxicity, based on the administration of IGF-I. METHODS: Sixty inbred Lewis rats underwent a bilateral clamping of the renal pedicles (20') as standard damage. The animals were stratified in six groups, according to the postoperative treatment. Group 1 served as control and received only the standard ischemic injury. Cyclosporine and FK506 were added in groups 3 and 5. Groups 2, 4 and 6 had the same treatment of groups 1, 3, 5 respectively, plus the administration of IGF-I. Blood samples were drawn daily to evaluate creatinine and BUN for 7 days. RESULTS: The rats treated with IGF-I had significantly better values compared to the respective controls (2-way ANOVA, p < 0.05). CONCLUSIONS: In conclusion, IGF-I improves the nephrotoxicity of mainstream immunosuppressants in this model. Its use is potentially beneficial for transplantation.

Animals↗
PubMed1998

[The hemodynamic effects of the in-vivo administration of insulin-like growth-factor I].

BACKGROUND: Recent studies have demonstrated that IGF-I has several biological activities that correlate with the GH axis, by acting as a cell protecting factor and a promoting compound in different tissues and organs. Our latest findings have demonstrated a potential application of IGF-I in the treatment of postischemic renal injury, which frequently appears after a kidney transplant. The beneficial effect of the renal postoperative recovery probably correlates with the regulation of the vascular tone, in which IGF-I plays a role with other cytokines. However, this rises the question whether IGF-I has any effect on the general hemodynamic status. This study was designed to underline the intraoperative hemodynamic effect of exogenous IGF-I in an experimental setting of renal transplantation in swine. METHODS: Twelve female swine underwent a left renal autotransplantation. At the reperfusion the animals were separated in two groups. Group one served as control. Group two received 400 micrograms of IGF-I (added to the flushing solution). The animals were kept under complete hemodynamic monitoring over the operation. RESULTS: Among the different parameters studied (mean arterial pressure, mean pulmonary arterial pressure, pulmonary wedge pressure, central venous pressure, cardiac output, oxygen extraction ratio, systemic vascular resistance, oxygen delivery and oxygen consumption), any statistically significant difference between group one and two were observed. CONCLUSIONS: While the clinical administration of IGF-I requires further studies, the in vivo administration of this peptide is apparently well tolerated, and does not cause any hemodynamic instability to the operation.

Analysis of Variance↗
PubMed1997

Insulin-like growth factor-I ameliorates delayed kidney graft function and the acute nephrotoxic effects of cyclosporine.

BACKGROUND: Delayed graft function (DGF) is a relatively common complication after cadaveric renal transplantation. The adverse effect of DGF on long-term graft survival has lead to intensive efforts to reduce ischemic graft injury. In this study we examined the effects of a new protective treatment based on insulin growth factor (IGF)-I. We evaluated the impact of the treatment on renal recovery and on the nephrotoxicity that is a common side effect of mainstream immunosuppressants. Because therapy with IGF-I or the analog des(1-3)IGF-I is effective in treating experimental ischemic renal failure, these peptides may be useful as perspective clinical treatments. METHODS: We have addressed three areas relating to the potential use of IGF-I and its analog des(1-3)IGF-I. First, because of the immunogenic properties of IGF-I, we assessed the effect of des(1-3)IGF-I on the rejection of skin allografts in Lewis rats. Next we determined whether treatment with des(1-3)IGF-I influences the early function of transplanted kidneys in a model of DGF induced by a combination of warm and cold ischemia. Finally we tested whether IGF-I protects against acute cyclosporine nephrotoxicity. RESULTS: Des(1-3)IGF-I did not accelerate the rejection of the skin grafts (P=0.57). The administration of this peptide in a model of syngenic renal transplant improved the early function of the graft. Postoperative values of creatinine and blood urea nitrogen were significantly better (P<0.05) in treated animals. IGF-I also ameliorated the nephrotoxicity of cyclosporine, with better values of creatinine and blood urea nitrogen (P<0.05). CONCLUSIONS: In evaluating this study it should be recognized that the animal models studied, although widely used, differ from the human condition. However, IGF-I and des(1-3)IGF-I exhibit properties that strongly suggest their value in preventing clinical DGF, and they deserve further studies.

Animals↗
PubMed1996

Expandable prosthesis for sutureless anastomosis in thoracic aorta prosthetic substitution.

OBJECTIVE: Most complications of descending aorta prosthetic substitution seem mainly to be related directly (ischemia to distal organs, i.e. liver, kidney, spinal cord) or indirectly (extracorporeal circulation or shunts and systemic heparinization complications) to the duration of blood flow interruption. the purpose of this study is to report the results of animal experimentation of a new device for sutureless prosthetic substitution of the descending thoracic aorta, with a very short cross-clamping phase. METHODS: The device consists of expandable loops of stainless steel wires, sewn to the proximal end of a Dacron prosthesis. The stainless steel wire loops can be expanded and tightened by activating a removable guide in such a way that the prosthesis varies its diameter, while maintaining a regular cylindrical shape. The device was prepared in two different configurations, one for long segments (expandable prosthesis end) and the other to be used for very short segments or as an anastomotic ring between prosthetic or vascular stumps (quick anastomotic ring). The expandable prosthesis end was tested in swine experiments by performing the prosthetic substitution of the first 10 cm of descending cross-clamped aorta, the prosthesis being fixed with the device both at the proximal and the distal ends (six experiments). All animals survived the procedure, that was accomplished with a very short cross-clamping time. The quick anastomotic ring was used to anastomose two prosthesis ends, at the middle of the prosthetic segment used for descending aorta substitution (two swine), to perform the distal anastomosis in the same model of descending aorta substitution (one swine) and simply to re-anastomose a subtotally transected descending aorta (one swine). RESULTS: The present experience proved the reliability of the device to carry out a sutureless, accurate, simple and quick anastomosis. Its advantage over an intraluminal ringed prosthesis is much easier insertion of the retracted wired end into the vascular stumps, thus allowing for a prosthetic diameter appropriate to the substituted vessel. CONCLUSIONS: The reduced cross-clamping feature of the device would suggest its use mainly in thoracic aorta prosthetic substitution for the prevention of ischemic damage to distal organs; it can also be used to advantage wherever an end-to-end vascular or prosthetic anastomosis is indicated, providing an accurate, stented anastomosis.

Anastomosis, Surgical↗