betadex and Hyperplasia

The present article describes an unusual proliferative islet finding observed incidentally in a young male Wistar rat in a 2-week toxicity study. Histologically, the islet lesion was characterized by diffuse enlargement of the islets, which consisted of peripheral proliferation of non-insulin-containing islet cells surrounding normal-appearing insulin-containing cells in the center. To the authors' knowledge, this is the first report of spontaneous proliferative islet lesion composed of non-insulin-containing cells in young rats.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; beta-Cyclodextrins; Blood Glucose; Cell Proliferation; Female; Hyperplasia; Injections, Subcutaneous; Insulin; Islets of Langerhans; Male; Plasma; Rats; Rats, Wistar

Epidermal permeability barrier formation depends upon lamellar body (LB) secretion/fusion with the apical plasma membrane (APM) of outermost stratum granulosum (SG) cell, creating cholesterol/glycosphingolipid-enriched lipid rafts-like domains. We found that the dimensions of these domains are comparable to lipid raft in other cell types; and that acute barrier disruption regulates their size and dynamics. To assess the function of these LB-derived raft-like domains, we assessed APM dynamics and barrier recovery in methyl-beta-cyclodextrin (MbetaCD)-treated hairless mice and caveolin-1 knockouts (cav-1(-/-)). MbetaCD treatment impaired APM raft-like domain formation and barrier recovery. Accelerated barrier recovery is observed in cav-1(-/-) in parallel with expansion of raft-like domains. Barrier abrogation of normal epidermis resulted in translocation of cav-1 from the cytoplasm to raft-like membrane domains, restricting further raft-like domain formation and initiating terminal differentiation. Inhibition of LB secretion by monensin and absence of cav-1 delayed terminal differentiation. Furthermore, cav-1(-/-) mice exhibited an increased propensity to develop experimentally induced epidermal hyperplasia correlating with lipid raft persistence. Finally, the epidermal hyperplasia in psoriasis and Netherton syndrome is paralleled by increased lipid raft formation. These studies demonstrate that cav-1 delivery to the APM by LB trafficking to APM "brakes" further LB secretion, signals terminal differentiation, and regulates epidermal hyperproliferation.

Topics: Animals; beta-Cyclodextrins; Caveolae; Caveolin 1; Epidermis; Homeostasis; Hyperplasia; Male; Membrane Microdomains; Mice; Mice, Hairless; Permeability

Beta-Cyclodextrin tetradecasulfate binds fibroblast growth factors and possesses anticoagulant properties. This study was designed to assess the separate and combined effects of local intramural delivery and intravenous administration of beta-cyclodextrin tetrade-casulfate on neointimal formation and arterial damage following angioplasty.. Fifty-two pigs randomized into four groups underwent coronary artery angioplasty: 1) control, 2) continuous intravenous infusion of 100 mg/kg/d of beta-cyclodextrin tetradecasulfate, 3) intramural delivery of 1250 mg beta-cyclodextrin tetradecasulfate, 4) intramural delivery of 1250 mg beta-cyclodextrin tetradecasulfate followed by continuous intravenous infusion of 100 mg/kg/d. Fourteen days after injury, morphometric analysis revealed that arteries randomized to the intravenous beta-cyclodextrin tetradecasulfate groups had a decreased normalized neointima area: control, 3.03 +/- 0.75 mm(2); intravenous, 1.67 +/- 0.73 mm(2) (40% decrease; P < 10(-7)); intravenous plus local, 1.95 +/- 0.76 mm(2) (30% decrease; P < 10(-5)). There was no difference in neointimal response following local beta-cyclodextrin tetradecasulfate delivery only (2.82 +/- 1.14 mm(2)). Coronary arterial damage, defined as aneurysm, dissection, adventitial rupture, and retromedial hematoma was similar in all groups (12% in control and local groups, 10% in the intravenous group, 14% in the intravenous plus local; NS). Bleeding complications were more frequent in the intravenous and intravenous plus local groups compared to the local and control groups (23%vs 7.6% and 0%, respectively; P < 0.05).. Continuous intravenous administration of beta-cyclodextrin tetradecasulfate substantially reduced intimal hyperplasia, while intramural delivery had no effect, indicating that a single bolus of beta-cyclodextrin tetradecasulfate did not reduce intimal hyperplasia. There was no additive effect of local intramural delivery of beta-cyclodextrin tetradecasulfate. However, local delivery of beta-cyclodextrin tetradecasulfate induced less bleeding complications and did not lead to additional arterial injury, indicating that local delivery of an anticoagulant does not cause additional arterial injury.

Topics: Angioplasty, Balloon, Coronary; Animals; beta-Cyclodextrins; Coronary Vessels; Cyclodextrins; Electrocardiography; Hyperplasia; Infusions, Intravenous; Injections, Intravenous; Random Allocation; Swine; Tunica Intima

A monoclonal antibody, NR-2 MAb, against one of the rat renal cell tumor-associated antigens was developed. NR-2 MAb belonged to IgM class and recognized a polypeptide of 81,000 daltons designated as NR-2 antigen, which is of non-glycoprotein nature with a pI of 4.6. NR-2 MAb was employed to probe the histogenesis of renal cell tumors in rats treated with N-ethyl-N-hydroxyethylnitrosamine followed by trisodium nitrilotriacetate monohydrate. Immunohistochemical analysis indicated that NR-2 antigen was expressed in simple hyperplasia, adenomatous hyperplasia and renal cell tumors. Both clear cells and basophilic cells of the simple hyperplasia showed equally strong positive reactions with NR-2 MAb, whereas the vacuolated epithelium was negative. Furthermore, the proximal tubules in nontumorous areas also expressed NR-2 antigen, suggesting that the hyperplastic lesions which eventually lead to renal cell tumors may derive from epithelia of proximal tubules and not directly from vacuolated epithelium. Such NR-2 antigen-positive epithelia of proximal tubules seem to be initiated cells. NR-2 MAb also cross-reacted with preneoplastic liver lesions.

Topics: Animals; Antibodies, Monoclonal; Antigens, Neoplasm; beta-Cyclodextrins; Biomarkers, Tumor; Carcinoma, Renal Cell; Cyclodextrins; Hyperplasia; Kidney Neoplasms; Liver; Male; Molecular Weight; Neoplasm Proteins; Rats; Rats, Inbred Strains