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M D'Silva

Publications and source records attributed to M D'Silva.

At least 37 records · Page 2Linked to original sources
PubMed1995

The immunomodulatory effect of leflunomide in rat cardiac allotransplantation.

Leflunomide, a novel immunosuppressant, has been the subject of recent preclinical studies using solid organ allo- and xenotransplantation models. The objectives of this study were to evaluate the efficacy and toxicity of leflunomide using a rat cardiac allotransplant model in two different strain combinations (DA x PVG and DA x Lew). Leflunomide, at doses ranging between 5 and 30 mg/kg, prolonged graft survival in both strain combinations as effectively as CsA and FK506 1 mg/kg (P < 0.05). A dose-dependent effect was seen only after a longer treatment course. When ongoing rejection was intercepted early (postoperative day 2), 5 mg/kg was as effective as 1 mg/kg FK506 (P > 0.05) but was inferior to CsA in the DA x PVG combination (P < 0.05). However, in the DA x Lew combination, leflunomide was equally as efficacious as 15 mg/kg CsA and 1 mg/kg FK506 (P > 0.05). If ongoing rejection was treated at postoperative day 4, 10 mg/kg leflunomide was not only as effective as 15 mg/kg CsA and 1 mg/kg FK506, but demonstrated a dose-dependent increase in graft survival in both strain combinations. The toxicity of leflunomide at doses of especially 5-20 mg/kg was minimal in comparison to therapeutic doses of CsA and FK506 using body weight and biochemical parameters of renal and liver function. These in vivo observations convincingly show leflunomide to be equally as potent an immunosuppressant as CsA and FK506 in transplant rejection. It is also well tolerated on long-term administration and, by virtue of this fact, is a potentially suitable candidate for clinical transplantation.

Animals↗
PubMed1995

Transplantation of reproductive organs.

A historical review of the literature concerning replantation and transplantation of reproductive organs has included studies from this laboratory, using rats, over the past 25 years. From the basic observation of ischemic and traumatic injury due to the transplantation, syngeneic testicle transplants, resulting in a partner's impregnation and histological restoration of the testicles, led to human testicular transplantation. As to the ovarian transplants, granulosa-theca cell tumors may transform into malignancies if followed for a prolonged period as intrasplenic ovaries, and high doses (15 to 20 mg/kg b.w.) of azathioprine can produce such malignant tumors in a shorter period. By caval-portal shunt, ovarian hormones enter directly into the portal blood stream and no typical granulosa-theca cell tumors were produced, owing to the fact that the liver cannot degrade all the hormones secreted by both ovaries. While en-bloc vagino-utero-ovarian transplantation in the rat is possible, no impregnation has been yet achieved. Finally, it is hypothesized that those who have acquired microsurgical techniques and have a full understanding of the anatomy of the reproductive system will not only be able to perform replantation of the penis, but also will be capable of allogeneic transplantation of genital organs, whether ethically approved or not, and sooner than one may think. In such cases a penile part may be obtained at a sex-change surgery or from a cadaveric donor, similar to other vital organ transplantation practices.

Animals↗
PubMed1995

Rat heart-aorta cluster transplantation: a novel model to study transplant rejection.

The purpose of this study was to develop a microsurgical cluster model of heart plus entire thoracic aorta transplantation and to compare it to the isolated model of heart transplantation as a tool to study transplant rejection. Thirty-six syngeneic (DA x DA and Lew x Lew) and allogeneic (DA x PVG and DA x Lew) cluster heart-aorta transplants were compared to 43 syngeneic and allogeneic isolated heart grafts. Graft survival, recipient survival and histological data on myocardial and aortic tissues were assessed. There was no statistically significant difference in graft survival between the two models studied (P > 0.05). In the cluster transplants, the aortic component was spared the severity of acute rejection noted for the myocardial counterpart. In conclusion, the results demonstrated that the cluster model was technically feasible and highly reproducible. Additionally, it was possible to apply this model to the study of experimental allograft rejection using novel immunosuppressants. The success of the cluster model in strongly mismatched transplant strain combinations underscores its potential for application in slower rejection combinations, making it particularly suited for chronic rejection studies. The inherent capacity for sampling a broader range of vessel sizes in one animal makes the cluster model more suitable than the isolated models of aorta or heart for application to experimental protocols.

Animals↗
PubMed1994

The immunomodulatory effects of a novel agent, leflunomide, in rat cardiac allotransplantation.

We assessed the immunomodulatory effect of leflunomide (LEF) in a heterotopic abdominal model of rat heart transplantation using a major histocompatibility mismatch (DA X LEW). The endpoint of this study was cardiac rejection assessed by abdominal palpation of the ventricular impulse and confirmed by laparotomy and histology. In this study, LF was investigated using four dosages (5, 10, 20 and 30 mg/kg per day orally) against cyclosporine (CsA) (15 mg/kg per day orally) and FK 506 (1 mg/kg per day orally). The ability of LEF to prevent rejection and reverse ongoing acute rejection was assessed. The results showed that untreated hearts were fully rejected by day 5 and that LEF at 5 mg/kg was significantly better than any other dose tested, was superior to FK 1 mg/kg, and was as effective as CsA 15 mg/kg in preventing rejection after a short course of treatment. After a longer course, 10 and 20 mg/kg LEF proved more effective than 5 mg/kg in controlling rejection and as efficacious as 1 mg/kg FK and 15 mg/kg CsA. In the control of ongoing established early rejection. LEF proved to be equally effective, even at lower doses (5 mg/kg), to CsA 15 mg/kg and FK 1 mg/kg. In the control of ongoing established late rejection, 20 mg/kg LEF proved to be superior to 10 mg/kg LEF and 15 mg/kg CsA, and was as effective as FK 1 mg/kg. However, when higher doses of CsA (25 mg/kg) and FK (2 mg/kg) were tested against 20 mg/kg LEF in this mode of rescue, LEF proved as effective as CsA and superior to FK. In the assessment of drug toxicity using body weight as a parameter, 20 mg/kg LEF proved safer than any other LEF dose tested, and safer than 15 mg/kg CsA and 1 mg/kg FK in both short- and long term administration. We conclude that LEF is a relatively safe and potent immunosuppressant with promising clinical potential.

Animals↗
PubMed1993

Effect of caval-portal shunt on ovarian tissue in rats: I. Histological observation.

Forty-three female Sprague Dawley rats were divided into five groups, with groups 1-4 subjected to end-to-side caval-portal shunt (CPS). In addition to CPS, group 1 (n = 13), group 2 (n = 10), and group 3 (n = 7) rats had undergone removal of the right ovary and one-half of the left ovary, the left ovary, and one-half of the left ovary, respectively. Group 4 (n = 6) rats were not subjected to ovariectomy. Group 5 (n = 7) animals were not subjected to CPS but underwent left ovarian hemiresection. The ovarian volume of the hemiresected ovaries increased to 393.00 +/- 4.83 mm3 and 126.00 +/- 44.3 mm3 from 18.40 +/- 0.54 mm3 and 18.40 +/- 0.59 mm in groups 1 and 3, respectively, at the end of three postoperative months. The nonresected ovaries enlarged to 339.98 +/- 5.09 mm3 and 226.3 +/- 46.2 mm3 from 36.79 +/- 1.09 mm3 in groups 2 and 3, respectively. When no ovaries were resected, the CPS animals in group 4 showed an increment of ovarian volume of 1.75-2.2 times as much as the preoperative ones. In the animals that had undergone simple hemiovariectomy (group 5), the contralateral ovaries showed a significant increase in volume (40.2 +/- 8.3 mm3 to 243.1 +/- 114.8 mm3) at 3 months. The hemiresected ovarian volume increased from 27.1 +/- 5.5 mm3 to 44.1 +/- 11.8 mm3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Flexible technique for multiple organ procurement in rats: a training and research tool in transplantation.

Multiple organ procurement techniques are increasingly popular in many transplant centers. This paper describes a technique for multiorgan unit(s) explantation in rats. The procedure involves in situ preliminary dissection, cold perfusion of the thoracic and abdominal organ units as separate procedures, explantation, and finally the ex situ isolation of various organ units as single and/or multiple organ combination units. The procedure is feasible, allows for flexibility in the separation of combination organ units, and is reproducible. The exercise is provided as a training and research tool for clinical and research transplant surgeons. The technique is also presented as an animal model for clinical organ sharing.

Animals↗
PubMed1993

Relevance of tumor necrosis factor to graft-versus-host disease after small bowel transplantation.

The small bowel (SB), an organ replete with lymphocytes, may provoke graft-versus-host disease (GVHD) after transplantation (Tx). Since tumor necrosis factor (TNF) has been suspected of mediating the tissue lesions of GVHD, we sought to determine whether TNF could be detected in the serum of rats undergoing GVHD after SBTx or lymphocyte transfer. For this purpose, postoperative serum TNF activity was determined in Lewis x Brown Norway (LBNF1) hybrid rats suffering from GVHD after undergoing transplantation of an entire (group 1; n = 8) or a segmental (group 2; n = 4) Lew SB, or after i.p. injection with lethal doses (500 x 10(6)) of Lew lymphocytes (group 3; n = 3). Control LBNF1 received i.p. small doses (50 x 10(6)) of Lew lymphocytes (group 4; n = 4). Serum TNF activity was assessed using the WEHI bioassay. In rats with acute and lethal GVHD after entire SBTx (group 1) or injection with large doses of lymphocytes (group 3), TNF activity gradually increased and reached high levels by the time the rats were agonal. In segmental SBTx rats (group 2), GVHD was less severe than in entire SBTx rats. Similarly, the increase in TNF activity was less intense and only transient since it had returned to control levels by the time the rats had completely recovered from GVHD. In control rats primed with small doses of lymphocytes (group 4), GVHD did not occur and no increase in TNF activity was detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

Misdiagnosed malignancy in transplanted organs.

The case reports of three patients who received cancer-bearing organs at this institution are presented. A fourth recipient, who was to be transplanted with a cancerous kidney, was spared this disastrous complication. The relevant data regarding the donors is also alluded to, with special reference to the type and site of the primary malignancy. Following these case reports, the implications of these issues, their possible prevention, and further management are discussed.

Adult↗
PubMed1991

Multiorgan transplantation in the rat: development of a new microsurgical model.

Although transplantation of multiple abdominal viscera (MOTx) has been performed in humans, reproducible animal models and extensive laboratory work are needed to explore the physiological and immunological aspects of this new transplant procedure. We therefore developed a microsurgical model that allows en bloc transplantation of three major abdominal viscera. Using isogeneic rat strain combinations, 30% of the liver, pancreas, and duodenum and a segment of small bowel (SB) were heterotopically transplanted. A segment of aorta that included the celiac axis and the superior mesenteric artery provided the blood supply to the graft. Venous outflow occurred via the graft suprahepatic vena cava into the recipient's infrahepatic vena cava. The graft SB was anastomosed to the native SB. After a training period (N = 15), we could achieve a success rate of 83% (N = 23). Mean operation time was 105 minutes. Macroscopic and microscopic appearance of transplanted organs was normal. This study documents the feasibility of MOTx in the rat and provides a microsurgical model that should facilitate preclinical experimental research in this area.

Animals↗