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Biomedical subjects

T L Pazdernik

Publications and source records attributed to T L Pazdernik.

At least 73 records · Page 4Linked to original sources

Cyclophosphamide. I. Effects of survival and colony-forming cells in BDF1 L-1210-bearing mice.

A new technique is described in which L-1210 colony-forming cells and myelopoietic colony-forming cells can be assessed simultaneously from hemopoietic organs of L-1210-bearing mice. This technique was utilized to evaluate the effects of cyclophosphamide on the recovery of myelopoietic function in tumor-bearing mice. In general, changes in L-1210 colony-forming cells in bone marrows and spleens of cyclophosphamide-treated L-1210-bearing mice correlated with their mean survival time. Injection of L-1210 cells alone enhanced myelopoiesis in the spleen and injection of both cyclophosphamide and L-1210 cells resulted in a synergistic enhancement of myelopoiesis in the spleen. The results in this paper are also compatible with the hypothesis that the host defense system does regulate the growth of L-1210 cells in BDF mice.

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Podophyllotoxin analogs. 1. Synthesis and biological evaluation of certain trans-2-aryl-trans-6-hydroxymethyl-3-cyclohexenecarboxylic acid gamma-lactones as antimitotic agents.

A series of cis and trans bicyclic lactones was prepared as congeners of podophyllotoxin (1) and evaluated as antimitotic agents both in cell cultures grown in vitro and in an in vitro protein binding assay. All compounds displayed insignificant activity-a result which may reflect insufficient structural similarity to podophyllotoxin or which may be interpreted as in agreement with previous observations of the stereochemical requirements for antimitotic activity defined for 1.

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Conformationally rigid amphetamine analogs as inhibitors of monoamine uptake by brain synaptosomes.

Four 3-phenyl-2-amino-trans-decalin isomers were synthesized in order to obtain derivatives of phenylethylamine with a rigid conformation between the phenyl ring and the amino function. The stereoisomers were tested as inhibitors of catecholamine uptake by rat brain synaptosomes, and their potency was compared with that of amphetamine. The most potent inhibitor of catecholamine uptake was the diaxial 2(a)-amino-3(a)-phenyl-trans-decalin, which was one-fourth to one-third as potent as (+/)-amphetamine. As a dopamine uptake inhibitor in the stiatum, this compound was competitive. The results differ from those obtained earlier with similar analogs with a norepinephrine moiety incorporated into the decalin structure, since a gauche derivative [2(a)-amino-3(e)-3,4-dihydroxyphenyl-3-trans-decalol] was then the most potent and over 20 times as potent as the diaxial anti derivative. It remains to be seen whether this indicates that the mode of binding of phenylethylamines is different from that of catecholamines.

2-Naphthylamine↗

Toxicity of antitumor agents on hemopoietic colony forming cells.

The effects of selected antitumor agents--methotrexate, 6-mercaptopurine, cyclophosphamide, hydroxyurea and cytosine arabinoside on hemopoietic progenitor cells were determined by femoral and splenic colony forming cell (CFC) content after single and multiple injections of the agents. Mice were injected in groups of three with the agents on different days and killed on the same day. Major findings were: 1) All the antitumor agents (by single or multiple injections), with the exception of 6-mercaptopurine, caused an early reduction in the number of CFC per femur and an increase in CFC levels per spleen on day 7.2)CFC levels per 10(5) cells were significantly lower at 1 hour after single injections of hydroxyurea or methotrexate than at 24 hours after a single injection of either drug. 3) Multiple vs. single doses of hydroxyurea and cytosine arabinoside showed that multiple doses were more effective in reducing femoral CFC levels on day 1 and elevating splenic CFC content on day 7 than were single doses. 4) Multiple doses of 6-mercaptopurine were more effective than single doses in lowering femoral CFC levels on day 1, but all doses of 6-mercaptopurine failed to evoke a change in splenic CFC levels. 5) Multiple doses of methotrexate were not more effective than single doses in decreasing femoral CFC content and raising splenic CFC levels.

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Effects of allogenic and effector cells on the development of antibody-producing cells, in vitro.

Effects of allogenic and effector spleen cells on the development of anti-SRBC plaque-forming cells from target spleen cells in vitro were studied. Addition of allogeneic cells resulted in various degrees of suppression of target cell PFC production. This allogeneic suppression could be abolished by pretreating the cells with either uv or X irradiation. Addition of effector cells to target spleen cell cultures markedly suppressed PFC production. Effector cell suppression of PFC production was anti-BAtheta serum-sensitive and radiation-resistant.

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Hemoperfusion and pharmacokinetic studies with methamidophos in the rat.

A gas chromatographic method for quantifying methamidophos in plasma was developed and used to study the kinetics of methamidophos in the rat and to evaluate the efficacy of hemoperfusion therapy for treating organophosphate insecticide poisoned individuals. Intravenous administration of methamidophos resulted in a plasma decay curve which corresponded to a one compartment pharmacokinetic model with the following pharmacokinetic parameters: t1/2 = 1.5 hr; Vd = 0.81 L/kg; C1 = 5.8 mL/min/kg; kel = 0.45 hr-1. Hemoperfusion with activated charcoal effectively removed methamidophos from the blood of intoxicated rats, and significantly decreased the body burden of methamidophos; 27% of the administered dose of methamidophos was removed during five hours of perfusion. Despite a rapid reduction in the body burden of the insecticide, rats were not protected against a lethal dose of the insecticide. Because of the rapid and slowly reversible inhibition of acetylcholinesterase by organophosphate insecticides, hemoperfusion alone will not improve the clinical status of organophosphate insecticide poisoned patients.

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Reactive oxidant species in piriform cortex extracellular fluid during seizures induced by systemic kainic acid in rats.

Kainic acid (KA) administered systemically to rats produces seizures and brain damage. We measured an increase in reactive oxidant species (ROS) during KA-induced seizures in the extracellular fluid (ECF) of the piriform cortex, a brain region known to be subsequently damaged. Intracerebral microdialysis samples were collected and assayed for isoluminol-dependent chemiluminescence before and after injection of KA (16 mg/kg, i.p.). Hydrogen peroxide (H2O2) concentrations were calculated from catalase-sensitive chemiluminescence, the difference between total and catalase-resistant chemiluminescence. During generalized tonic-clonic seizures, both total and catalase-resistant chemiluminescence increased significantly in samples from brain ECF. Catalase-resistant chemiluminescence, most likely produced by ascorbic acid, increased for a full hour during sustained seizure activity. H2O2 concentrations showed a trend towards elevation during seizures. Increased ROS suggest that oxidative stress occurs in brain ECF during sustained seizure activity.

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