methylcellulose and Thrombocytopenia

Topics: Animals; Catheter Ablation; Electromagnetic Phenomena; Hypersplenism; Liver Cirrhosis, Experimental; Methylcellulose; Rats; Splenectomy; Thioacetamide; Thrombocytopenia; Time Factors

Thrombocytopenia due to hypersplenism is usually a serious condition in cirrhotic patients who have undergone invasive procedures. We designed a new treatment method using a high-frequency alternating electromagnetic force to treat the disease condition in a rat model.. Sprague-Dawley rats were given thioacetamide in drinking water and injected with methylcellulose intraperitoneally to create a cirrhotic hypersplenism model. Spleen volume was determined using the Carlson method. The Control Group consisted of 14 rats, 15 weeks old, that were used to determine the normal platelet count and normal spleen size. Experimental Group I, consisting of 15 rats, received electromagnetic thermoablation of their spleens, after which the spleen was returned to the abdomen. Group II consisted of 13 rats, receiving the same electromagnetic thermoablation as Group I, but the ablated portion was removed. Group III consisted of 14 rats receiving total splenectomies.. Cirrhotic hypersplenism was confirmed during laparotomy and pathological examination. Spleen volume enlarged from 1513 +/- 375 mm(3) (Control Group) to 7943 +/- 2822 mm(3) (experimental groups). Platelet counts increased from 0.35 +/- 0.21 x 10(6)/mm(3) to 0.87 +/- 0.24 x 10(6)/mm(3) for Group I, from 0.52 +/- 0.23 x 10(6)/mm(3) to 1.10 +/- 0.20 x 10(6)/mm(3) for Group II, and from 0.47 +/- 0.23 x 10(6)/mm(3) to 1.18 +/- 0.26 x 10(6)/mm(3) for Group III. No rats died due to the treatment in any of the experimental groups.. Our animal model performed successfully and our proposed electromagnetic thermotherapy effectively treated thrombocytopenia due to cirrhotic hypersplenism.

Topics: Animals; Catheter Ablation; Electromagnetic Phenomena; Hypersplenism; Liver Cirrhosis, Experimental; Male; Methylcellulose; Platelet Count; Rats; Rats, Sprague-Dawley; Splenectomy; Thioacetamide; Thrombocytopenia; Time Factors

The innate immune response to intraportally infused adenoviral vector was evaluated in rhesus monkeys. A first-generation adenovirus-expressing lacZ (Ad-lacZ) was administered at a dose just below that which causes severe morbidity. The response to vector was evaluated for the initial 24 h following infusion. Clinical findings during this time were primarily limited to petechiae, consistent with the development of thrombocytopenia and biochemical evidence of disseminated intravascular coagulation. Serum transaminases were elevated and a lymphopenia developed. Tracking of fluorescent-labeled vector demonstrated distribution to macrophages and dendritic cells of the spleen and Kupffer cells of the liver. A systemic release of the cytokine IL-6 occurred soon after vector infusion. Analysis of splenic cells revealed acute activation of macrophages and dendritic cells followed by massive apoptosis. Bone marrow cultures demonstrated normal erythroid and primitive progenitors with a significant decrease in myeloid progenitors. Similar findings, except the abnormality in bone marrow cultures, were observed in monkeys who received an identical dose of Ad-lacZ in which vector genes were inactivated with psoralen and UV irradiation. These data suggest that inadvertent targeting of antigen-presenting cells following intraportal infusion of vector leads to a systemic cytokine syndrome which may be triggered by the viral capsid proteins.

Topics: Adenoviridae; Animals; Apoptosis; beta-Galactosidase; Bone Marrow Cells; Cells, Cultured; Dendritic Cells; Ficusin; Flow Cytometry; Fluorescent Dyes; Genetic Vectors; Interleukin-6; Kupffer Cells; Lac Operon; Liver; Lymphopenia; Macaca mulatta; Macrophages; Male; Methylcellulose; Microscopy, Electron; Models, Biological; Spleen; Thrombocytopenia; Time Factors; Tissue Distribution; Transaminases; Ultraviolet Rays

Topics: Antigens, CD; Antigens, CD34; Blood Cells; Bone Marrow Transplantation; Breast Neoplasms; Cells, Cultured; Colony-Forming Units Assay; Female; Fibrin; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; In Vitro Techniques; Leukapheresis; Megakaryocytes; Methylcellulose; Thrombocytopenia; Transplantation, Autologous

Topics: Animals; B-Lymphocytes; Hypersplenism; Leukocyte Count; Leukopenia; Methylcellulose; Rats; Rats, Inbred Strains; Spleen; Splenomegaly; T-Lymphocytes; Thrombocytopenia

Extensive hepatic erythropoiesis, granulocytopoiesis and megakaryocytopoiesis occur in adult mice given methylcellulose (MC). This appears to be a compensatory response to MC induced hemolytic anemia and thrombocytopenia. The present study was undertaken to evaluate the effects of whole body irradiation (WBI) upon established hepatic hematopoiesis (HH) as well as its effect when given before the induction of HH. Established hepatic erythroid and granulocytic foci were significantly decreased 24 hours after 100 or 300 rads. The DO for erythroid and granulocytic foci was 107 +/- 10 rads and 95 +/- 20 rads respectively, similar to those reported for murine marrow and spleen cell CFUS. Megakaryocytes were more radioresistant, gradually declining over 7 days to 50% of control values following 100 rads and with a DO of 347 +/- 7 rads; suggesting a differential radiation sensitivity compared to erythroid and granulocytic foci. WBI, 100 and 300 rads, given before MC failed to prevent subsequent development of HH although both marrow and spleen responses were reduced. Hepatic granulocytic foci and marrow peroxidase positive cells were reduced by such treatment while erythroid and megakaryocytic foci were similar to controls. This suggests that irradiation damaged stem cells responded to MC with increased erythropoiesis and megakaryocytopoiesis at the expense of granulopoiesis.

Topics: Anemia, Hemolytic; Animals; Dose-Response Relationship, Radiation; Erythropoiesis; Female; Granulocytes; Hematopoiesis; Liver; Megakaryocytes; Methylcellulose; Mice; Organ Size; Radiation Dosage; Thrombocytopenia

Topics: Animals; Blood Platelets; Chromium Isotopes; Exchange Transfusion, Whole Blood; Methylcellulose; Rats; Splenomegaly; Thrombocytopenia