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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.


MONTGOMERY, DAVID WESLEY. January 1986 (has links)
Didemnin B (DB) is a seven amino acid cyclic polypeptide (NSC-325319), MW 1112, isolated from a Caribbean tunicate of the family didemnidae (Trididemnum genus). In vitro assays of murine splenic mononuclear cell (MNC) proliferation showed that DB potently inhibited the mixed lymphocyte reaction (IC₅₀ = < 10 pg/ml), concanavalin A (Con A; IC₅₀ = 50 pg/ml) and lipopolysaccharide (IC₅₀ = < 100 pg/ml) mitogenesis. Proliferation induced by phorbol esters, calcium ionophore and Con A were equipotently inhibited by DB, suggesting that the drug acts upon an intracellular pathway common to these mitogens. Since DB did not produce lymphocytotoxicity, nor inhibit ongoing DNA, RNA or protein synthesis at immunosuppressive concentrations, it was concluded that this agent may affect lymphocyte activation processes. Investigation of the mechanisms of DB action showed that it failed to alter interleukin 2 (Il-2) production by MNC in vitro. However DB was found to block binding of the hormone prolactin (PRL) to both human lymphocytes and a PRL-dependent cell line, the Nb 2 node lymphoma. As PRL plays an important regulatory role in the immune response, abrogation of PRL-MNC interaction may represent a site of DB immunosuppressive action. In vivo, DB demonstrated a potent, inhibitory effect upon alloantigen-driven proliferation in the murine graft-versus-host reaction but hemagglutinating antibody responses in mice to sheep red blood cells were strongly enhanced by DB treatment (4.6-fold). Further, DB treatment of mice in vivo was not bone marrow suppressive, but increased organ cellularity, ongoing DNA synthesis and circulating levels of lymphocytes and granulocytes. DB also exerted significant toxicity in vivo. High doses caused losses in body weight (18%) and mortality (20%), but no mortality occurred at doses of 0.1 mg/kg/day x 7 days. DB did not significantly alter indices of renal function but high dose treatment produced significant but reversible hepatotoxicity. DB also induced ornithine decarboxylase activity in various rat tissues, with adrenal > liver > kidney = spleen > thymus > heart. This correlated with increased organ to body weight ratios for liver and spleen, suggesting a trophic response of these organs to DB. The data presented here show that DB exerts potent inhibitory activity toward cell mediated immunity in vivo and in vitro suggesting that DB might also inhibit rejection of solid organ grafts. In addition, humoral responses and bone marrow function are markedly enhanced by DB treatment in vivo, suggesting that resistance to infectious organisms might be increased by this drug.


McKee, Preston Harold, 1942- January 1975 (has links)
No description available.

Pharmacokinetic and biopharmaceutical studies of cyclosporine in the dog and of salicylate in humans.

Abdallah, Hisham Youssef. January 1989 (has links)
Cyclosporine (CsA) is commercially available for oral administration as a solution in olive oil with alcohol and an emulsifier. This formulation suffers from the disadvantages of poor and highly variable absorption, objectionable taste and difficulty in measuring the prescribed dose by visually impaired patients. Several oral formulations were prepared and tested in vitro and in vivo in dogs. Based on these preliminary results the dosage form chosen for evaluation was a tablet formulation prepared by direct compression. These tablets were compared to the commercial oil solution placed into soft gelatin capsules. In order to determine absolute bioavailability and to avoid the concern of time-dependent clearance, an intravenous tracer dose of ³H-CsA was simultaneously administered with each oral test product on each of two occasions. Absolute bioavailability was 46.0 ± 11.1% and 45.4 ± 9.9% for the capsules and tablets, respectively. C(max), t(max) and MRT were not significantly different between the two products. No differences were observed in the pharmacokinetics of the intravenously administered CsA in the two experiments which were separated by 8-13 days. The elderly, usually defined as people over 65 years of age, constitute about 12% of the U.S. population. It has been estimated that one out of four elderly people is arthritic and is, therefore, a candidate for chronic salicylate therapy. The pharmacokinetics of salicylate following a single oral solution dose of 600 mg of sodium salicylate were investigated in 22 healthy, nonsmoking male subjects. The plasma concentration and urinary excretion of salicylic acid and its metabolite, salicyluric acid, as well as the urinary excretion of salicyl glucuronides were monitored. Urinary recovery essentially accounted for the administered dose and was not influenced by age, nor was the apparent oral clearance of salicylic acid. Assuming no presystemic elimination, it could be concluded that systemic availability is unaffected by age. An increase in the apparent volume of distribution, V(area), and a decrease in the maximum plasma salicylic acid concentration with age were observed. Renal clearance of salicyluric acid decreased significantly with age and was found to correlate significantly with creatinine clearance.

Inhibition of lectin-induced mitogenic response of murine lymphoid cells by the Chinese drug Tianhuafen.

January 1981 (has links)
by Poon Suet Ping, Cycles. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1981. / Bibliography: leaves 117-129.

Synthetic approaches to the tricarbonyl subunit of rapamycin

LaMunyon, James B. 19 March 1998 (has links)
Graduation date: 1998

A synthetic approach to FR901483

Sha, Li, January 2001 (has links)
Thesis (M.S.)--West Virginia University, 2001. / Title from document title page. Document formatted into pages; contains vii, 57 p. : ill. Includes abstract. Includes bibliographical references (p. 55-57).

Effect of immunosuppressive agents on drug metabolism in rats /

Bai, Shuang, January 2001 (has links)
Thesis (Ph. D.)--University of Texas at Austin, 2001. / Vita. Includes bibliographical references (leaves 187-270). Available also in a digital version from Dissertation Abstracts.

Applications of ring-closing metathesis in construction of alkaloid natural products : synthetic studies on the immunosuppressant FR901483 and lundurines A-C

Simila, Suvi Tuula, 1978- 02 October 2012 (has links)
Ring-closing metathesis (RCM) has proven to be a valuable tool for constructing alkaloid-like, poly-cyclic compounds. The syntheses of alkaloid structures we were interested in developing, could utilize RCM to construct a spirocyclic structure for the immunosuppressant FR901483 and the tetracyclic framework of lundurines A-C asymmetrically. The azaspirane core of FR901483 was obtained via an addition of an allylsilane to an N-acyl iminium ion, and a RCM. Other key functional group manipulations were a stereoselective hydroboration and a subsequent lactonization that provided a precursor for a lactone-lactam rearrangement. This rearrangement provided the azatricyclic core of FR901483. In the enantioselective approach to FR901483 a new mildly cleavable protecting group was developed. Addition of a zinc nucleophile to a chiral N-acyl iminium ion, and a RCM provided the desired precursor for the hydroboration/lactone-lactam rearrangement sequence but without a sufficient stereoselection. A novel approach toward the total synthesis of lundurines A-C has been developed. The key features of the approach involve an intramolecular cyclopropanation of the indole C(2)-C(3) double bond, an enantioselective tandem RCM to construct the tetracyclic core and a concise synthesis to access the RCM precursor. An Ugi reaction was utilized with both cyclic and acyclic ketones, 2-vinyltryptamine derivative, a carboxylic acid and an isocyanide to access diverse compounds, including RCM precursors. An alternative reductive amination route to construct the RCM precursor for the lundurines was found to be more efficient and high yielding than the Ugi approach. An RCM was utilized to affect the closure of the five-and eight-membered rings of the tetracyclic core. This constitutes as the first example of RCM of a 2-vinylindole derivative to give an indole-fused eight-membered ring. / text

Effect of immunosuppressive agents on drug metabolism in rats

Bai, Shuang 28 August 2008 (has links)
Not available / text

The parameters of Cyclosporine A induced inhibition of a T cell dependent antibody response

Schilke, Angela J. January 1990 (has links)
Cyclosporine A (CsA) is a widely used immunosuppressive drug which has novel, clinically beneficial effects on the immune system. Substantial evidence indicates that CsA acts preferentially by impairing T cell lymphokine production, but there is some evidence that CsA may also affect B cells and other antigen presenting cells directly. Using an in vitro antibody response to sheep red blood cells, we have examined the effect CsA has on different populations of mouse lymphocytes. CsA appears to have a direct inhibitory effect on highly purified B cells from naive animals in a dose dependent manner at physiologically achievable levels in vitro. Even antigen stimulated B cells were found to be sensitive to the late addition of CsA when the drug was added simultaneously with lymphokine. B cells and T cells briefly pulsed with CsA do not recover to produce antibody when CsA is removed. Indeed, B cells from naive animals treated in vivo with CsA and stimulated in vitro with lymphokine and SRBC to produce antibody are profoundly inhibited from producing PFC despite the absence of CsA in culture. These findings suggest that CsA has direct irreversible, fast acting inhibitory effects on B lymphocytes aside from or in addition to its effects on T cells. / Department of Biology

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