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Biomedical subjects

T L Pazdernik

Publications and source records attributed to T L Pazdernik.

At least 55 records · Page 3Linked to original sources
PubMed1984

Soman induced changes in brain regional glucose use.

Soman, a potent central acetylcholine esterase inhibitor, has a greater impact on brain regional glucose use than other organophosphates, such as diisopropylfluorophosphate (DFP) or phospholinium iodide. At near-lethal doses soman induced explosive persistent seizures that were associated with a greater than fourfold increase of glucose use in many brain structures. Single near-lethal doses of soman lead to conspicuous neuronal damage and a marked reduction in brain activity, 1 to 3 days after exposure. When soman (2 X LD50) was given to TAB (an antidotal mixture of trimedoxime, atropine, and benactyzine ) pretreated rats, there was a greater than twofold reduction of glucose use in almost every brain region. We suggest that soman seizures are mediated via activation of muscarinic receptors; also, the substantia nigra has a key role in the initiation/propagation of seizures. Soman has in addition, a depressive effect on some brain components which appears not to involve muscarinic receptors. We suggest that the conspicuous pathology that follows a single, near-lethal dose of soman results from a depletion of energy flow along with an influx of Ca2+ which sets into motion a cascade of destructive reactions, such as activation of proteases.

Animals↗
PubMed1984

Topographical distribution of down-regulated muscarinic receptors in rat brains after repeated exposure to diisopropyl phosphorofluoridate.

Quantitative receptor autoradiography demonstrated that muscarinic receptors were down-regulated in Wistar rats after repeated exposure to diisopropyl phosphorofluoridate. The density of receptors was decreased to 60-85% of the controls. Reductions in muscarinic receptor binding were observed in cortex, caudate-putamen, lateral septum, hippocampal formation, superior colliculus, and pons. The density of muscarinic receptors was unchanged in thalamic and hypothalamic nuclei, periaqueductal grey, cerebellum, inferior colliculus and reticular formation of the brain stem. The down-regulation of muscarinic receptors in forebrain structures, such as cortex, caudate-putamen and hippocampus, may be important in the adaptation to the behavioral effects of organophosphate poisons.

Animals↗
PubMed1984

Topographical distribution of decrements and recovery in muscarinic receptors from rat brains repeatedly exposed to sublethal doses of soman.

[3H]Quinuclidinyl benzilate binding to rat brain muscarinic receptors decreased after repeated exposure to soman, a potent organophosphorus cholinesterase inhibitor. The topographical distribution of this decrement was analyzed by quantitative receptor autoradiography. After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey. Minor or no decreases were observed in thalamic or hypothalamic nuclei, reticular formation, pontine nuclei, inferior colliculus, nucleus of the seventh nerve, and cerebellum. Scatchard analyses of saturation curves using frontal cortex sections from soman-treated rats revealed a decrease in maximal quinuclidinyl benzilate binding from that in control rats and a return toward control levels by 24 days without any significant change in affinity. These brain areas showing significant decrements in muscarinic receptors recovered with a similar time course. An estimate of the time for 50% recovery for some of the brain areas was 14 days for superior colliculus, 16 days for cortex, and 19 days for hippocampal body. The application of quantitative receptor autoradiography to analyze receptor alterations has been valuable in localizing the telencephalon as a region more susceptible to change in receptor concentration.

Animals↗
PubMed1983

Cadmium-induced immunotoxicity.

This study assessed the effects of cadmium on functional lymphopoietic precursor cells and cell size in both spleen and bone marrow. Splenic plaque-forming cell (S-PFC) precursors were stimulated by a thymus independent immunogen (TNP-LPS) and by a thymus dependent immunogen (TNP-BSA plus dextran sulfate). Bone marrow plaque-forming cell (M-PFC) precursors were stimulated by TNP-LPS plus dextran sulfate. Male C57Bl/6J mice received either a single ip injection of 5.9 mg/kg CdCl2, and were sacrificed 3 days later (ip group), or 5 daily sc injections of 3.26 mg/kg CdCl2, and were sacrificed either 2 days later (7 day sc group) or 7 days later (12 day sc group). The ip group showed an increase in spleen cellularity which resulted in an enhanced S-PFC (TNP-LPS) response per spleen and compensated for a depressed S-PFC (TNP-BSA) response per 10(6) cells cultured. Bone marrow cellularity was not significantly decreased but the M-PFC response was drastically depressed. Similar results were obtained in the 7 day sc group. However, a significant increase in spleen cellularity was not seen, resulting in a noncompensated decrease in S-PFC (TNP-BSA) response. The S-PFC (TNP-LPS) response per 10(6) cells cultured was increased in this group. Responses were similar to controls in the 12 day sc group, but bone marrow cellularity was decreased. The ip and 7 day sc groups showed substantial cadmium-induced shifts in bone marrow cell size distribution profile to larger diameters. Changes in spleen cell size distribution were not as significant. Partial recovery was evident in the 12 day sc group. This study demonstrated that in vivo exposure to cadmium has a greater effect on the in vitro function of immature B-cells in the bone marrow than on more mature B-cells found in the spleen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

A computer-assisted teaching system in pharmacology for health professionals.

In this report the authors describe experiences with a computer-assisted teaching system in teaching pharmacology to medical students and other health professionals. The system is composed of both computer-assisted instruction and computer-managed instruction. The "Keller Plan" philosophy was adopted, and the pharmacology course was organized into modules. Students were required to meet minimum proficiency requirements in each module and have multiple chances to reach this or higher levels. The advantages of this system are numerous. The department can provide both scheduled and independent study courses in basic pharmacology to students of different educational levels. Students can progress through a course at various speeds; that is, achievement is constant, but time is variable. Both the students and instructors are provided with frequent and rapid feedback. Most importantly, students with low aptitudes achieve significantly higher scores on the pharmacology portion of the examination of the National Board of Medical Examiners.

Computer-Assisted Instruction↗
PubMed1983

Dopamine and 5-HT uptake by synaptosomes after pretreatment with p-chlorophenylalanine.

5-Hydroxytryptamine (5-HT) and dopamine uptake were studied in rat hypothalamic and striatal synaptosomes, respectively, after a single-dose or repeated doses of p-chlorophenylalanine (PCPA), and after withdrawal of the drug. 5-HT uptake did not change 24 h after a single large dose of PCPA (300 mg/kg). Uptake of neither amine changed 12 h or 7 days after treatment with 300 mg/kg PCPA every third day, for 2 weeks. In all cases, the kinetic parameters remained identical. These results indicate that depletion of 5-HT levels by PCPA and the resulting decrease in serotoninergic activity do not induce changes in 5-HT or dopamine uptake. Hence, reported changes in transmitter uptake due to clinical or experimental manipulations must not be directly related to synaptic activity.

Animals↗
PubMed1983

Soman-induced depression of brain activity in TAB-pretreated rats: 2-deoxyglucose study.

Administration of large doses of Soman (2xLD50) to rats protected with TAB, a mixture of trimedoxime (TMB-4), atropine and benactyzine, results in approximately 2-fold reductions of local cerebral glucose utilization (LCGU) in most brain regions. This is in contrast to the marked increase in LCGU that is observed in conjunction with the seizures associated with an LD50 dose of Soman given to unprotected rats. This study reveals that TAB is effective in protecting against Soman-induced seizures, but only at the expense of a severe decrease in LCGU after Soman exposure.

Animals↗
PubMed1982

Superior colliculus activation by retinal nicotinic ganglion cells: a 2-deoxyglucose study.

Systemic injection of the acetylcholinesterase inhibitor, di-isopropylfluorophosphate, in rats causes a marked increase in glucose use in the superficial layers of the superior colliculus. This activation of the superior colliculus is largely a retinal effect. Furthermore, since this response can be blocked by intraocular as well as systemic injections of mecamylamine, it is postulated that retinal nicotinic receptors are involved.

Animals↗
PubMed1980

Role of chloramphenicol reduction products in aplastic anemia.

Oral administration of chloramphenicol did not significantly alter the early stage of chronic hypoplastic marrow failure induced by busulfan. Chloramphenicol reduction products were most suppressive to antigen-reactive cells detected by the Mishell-Dutton plaque-forming cell assay. This reduction in immunocompetence may be an important parameter in the initial phases of the etiology of chloramphenicol-induced aplastic anemia.

Anemia, Aplastic↗
PubMed1980

Immunopharmacology: regulation of precursor cells.

A new area of immunopharmacology is described which deals with the regulation of the neogenesis of blood-forming cells. Hemo/immunopoiesis is the process which describes the differentiative and proliferative status of cells as they progress from the most primitive pluripotent stem cell to the most mature functional end-stage cells (erythrocytes, myeloid cells and lymphocytes). This so-called "hemic cell renewal" system is under intricate control mechanisms which can be modulated by the "hemopoietic-inductive microenvironment", cell-cell interactions, hemopoietins, cyclic nucleotides, calcium, prostaglandins and pharmacological agents. Hopefully, the interesting findings that have occurred in this area of research over the past decade can be translated into useful clinical modalities for the treatment of hematological and immunological disorders.

Calcium↗
PubMed1979

Effects of cyclophosphamide on hemic precursor cells in mouse bone marrow and spleen.

Cyclophosphamide severely inhibits the function of various hemic precursor cells in mice. In these studies we compared the effects of Cy on early B-lymphocytic precursor cells in mouse bone marrow to those effects on bone marrow myeloid precursor cells and splenic lymphoid precursor cells. These studies demonstrated that: 1) Pre-ARC in the bone marrow were extremely sensitive to even low doses of Cy (50 mg/kg) with virtually no renewal of this precursor population 11 days after injection of 200 mg/kg. 2) The sensitivity of pre-ARC to Cy along with the lack of their renewal was exemplified by the virtual absence of functional ARC in the spleen when assessed 11 days after injection of 200 mg/kg of Cy. 3) A rapid multiphasic renewal pattern was observed for myelocytic progenitor cells. 4) In general, LPS responsive cells were suppressed to a greater extent than were Con A responsive cells, especially with lower doses of Cy.

Animals↗
PubMed1979

Toxicity of platinum complexes on hemopoietic precursor cells.

Four platinum compounds, cis-dichlorodiammineplatinum, dichloro- 1,2-benzenediamine-N,N'-platinum, cis-dichlorobis-(cyclohexylamine)platinum and cis-dichlorobis(cyclopentylamine)platinum, were studied for their toxicity toward myelocytic progenitor cells (CFC assay) and pre-antigen reactive cells (P-PFC assay) in murine bone marrow and toward antigen reactive cells in the mouse spleen (MD-PFC assay). It was demonstrated that each of the platinum compounds markedly suppressed the ability of splenic antigen reactive cells to generate antibody producing cells (MD-PFC) 3 days after i.v. injection. At the same time, certain doses of each of the platinum compounds induced selective recovery of the preantigen reactive cells (P-PFC) and myelocytic progenitor cells (CFC) in the bone marrow with a pattern that was unique for each compound. It was also demonstrated with cis-dichlorodiammineplatinum that the recovery for both bone marrow precursor cell populations was multiphasic with time. In general, the results indicated that the platinum compounds induced unique patterns of immunosuppression with relatively minor hemopoietic toxicity.

Animals↗
PubMed1978

Radiosensitivity of different B and T subpopulations of lymphocytes in the mouse spleen.

X-irradiation was used as a tool to investigate the radiosensitivity of different B and T precursor subpopulations as detected by three in vitro culture systems. The culture systems utilized in this study included antigen reactive cell assays (ARCA), polyclonal mitogen assays (PMA), and polyclonal effector cell assays (PECA). The order of radiosensitivity of these systems in both the B and T cell series was ARCA greater than PMA greater than PECA (D37 values for B cell responses: ARCA = 88.8 R, PMA = 125 R, PECA = 223 R; D37 values for T cell responses: ARCA = 160 R, PMA = 441 R and PECA = 1095 R). With all assay systems the B cell response was more radiosensitive than the T cell response. The extrapolation number (n) from the radiation survival curves was approximately 2.0 for T cell responses and approximately 1.0 for B cell responses. The value of 1.0 for B cell responses suggest that their extreme radiosensitivity may be due in part to a lack of repair mechanisms. These findings also suggest that the more primitive precursor cells are more apt to undergo cellular proliferation upon activation and that this event is more radiosensitive than is the final differentiation event of precursor cells into a progeny of functional end-stage cells.

Animals↗