Monitoring of pancreatic islets transplanted to colon mesentery.
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Biomedical subjects
Publications and source records attributed to I Licińska.
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BACKGROUND: The unique mechanism of dithizone action in the interior of the viable pancreatic islet suggests the possible development of a specific radiopharmaceutical that may have a potential clinical application in the diagnosis of the pancreatic organ allografts or islets rejection. The radiodiagnostic properties of the newly developed radioactive analogue of dithizone, i.e. Dithizone-[(131)I]-Histamine conjugate have been evaluated in the present study. METHODS: The four islet cells transplantation models were chosen for this purpose. The most important feature of the Dithizone-[(131)I]-Histamine conjugate is its possessed ability of zinc chelation. As was presented in the recent study, the conjugate stains pink-reddish the isolated pancreatic islets in vitro. Among the studied transplantation models, only the islets grafting under testis capsule enabled determination of the pancreatic islets in rats by radioactive Dithizone-[(131)I]-Histamine conjugate. The level of the radioactivity in the recipient testis (right) was almost two times higher compared to the controls (0.24 vs. 0.13% ID/g, respectively). CONCLUSIONS: These preliminary data demonstrate the ability of the developed radioactive analogue of dithizone for in vivo identification of transplanted pancreatic islets, and suggests a potential clinical application of the radiodithizone in the diagnosis of the pancreatic islet rejection.
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Transplantation of whole pancreas or pancreatic islets remains a promising approach to treatment of diabetes mellitus. Since there is no efficient method presently known for in vivo detection of pancreatic islet rejection, we have utilized dithizone [DTZ] to monitor the survival of transplanted islet allografts following the induction of tolerance by a new strategy of deliberate introduction of donor antigens into the adult thymus. In this study, we examined the morphology of islet allografts in vivo and in vitro following pretreatment with intrathymic (IT) inoculation of 2 mg soluble Ag obtained from 3M KCl extracts of resting T-cells with or without ALS immunosuppression in the WF-to-Lewis combination. Fresh isolated rat islets stained pink 3-5 minutes following exposure to medium containing 0.12 mM DTZ solution in DMSO. Intravenous (i.v.) injection of DTZ solution into unmodified recipients of islet allografts that had rejected their grafts showed massive degranulation of islets which did not stain pink with DTZ. This was confirmed by microscopic finding of fibrosis and lymphocytic infiltration. In contrast, i.v. injection of DTZ solution into long-term recipients of islet allografts at 50, 100, and 150 days after transplantation showed viable islet cells which stained crimson red with DTZ and the findings were confirmed with microscopic sections. This study demonstrates that DTZ is an effective means of in vivo and in vitro identification of transplanted pancreatic islets and suggests that this strategy may have potential clinical application in the diagnosis of the pancreatic islet rejection.
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The mono and diiodo-derivatives of dithizone labelled with radioactive 131I isotope were obtained. Those compounds can be used for diagnostic of pancreas and other organs to monitor pathological states.
A simple, one-step method of preparation of human albumin microspheres by thermal denaturation of protein aerosol in a gas medium is described. These microspheres were easily labelled with technetium-99m and iodine-131, and were characterized by short biological clearance and high lung uptake.
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Dithizone (DTZ) which selectively stains islets of Langerhans in vitro has a diagnostic potential in the in vivo identification of viable transplanted pancreatic islets. In the present study, we compared the use of DTZ, and a synthetic iodo-derivative of DTZ (I-DTZ) as a potential radioactive marker for identification of viable transplanted pancreatic islet cells. Fresh islets isolated from Lewis rat donors were transplanted beneath the kidney capsule into each diabetic syngeneic (Lewis) recipient rat. DTZ(I-DTZ) solution was injected intravenously (i.v.) at a dose 10 mg/kg body weight (b.w.) for macro and microscopic identification of surviving transplanted islets. The recipients were nephrectomized to confirm that the normoglycemic state was maintained by the islet grafts. In addition, we administered i.v. at the same time concentrations of DTZ (I-DTZ) to test for toxicity. The results show that following i.v. or intraductal (i.d.) injection of low concentrations does not damage pancreatic islet function as determined by insulin secretion or glucose levels. Angiogenesis and microvascularization were observed for 10-12 days after transplantation, and the histologic and biochemical studies showed no pathological changes in injected rats in organ examined. The human pancreatic islets harvested from multiorgan donors stain red ex vivo in the same way as DTZ or I-DTZ administered i.v. in rats. The results indicate that DTZ has a diagnostic potential in monitoring the survival of transplanted pancreatic islets and possibly in the early diagnosis by radioisotopic detection of pancreatic endocrine diseases.