Platelet-derived growth factor (PDGF) is considered a decisive mediator of fibroblast growth and ... more Platelet-derived growth factor (PDGF) is considered a decisive mediator of fibroblast growth and phenotype within the lung. The cellular sources of PDGF within the lung remain undefined. The ability of lung fibroblasts themselves to produce PDGF in vitro was therefore investigated. Northern and Western blot analyses revealed the expression of PDGF-A mRNA and secretion of A-chain containing proteins by fibroblasts derived from adult and fetal rat lung. PDGF-A gene or protein expression were below the limits of detection in two human lung fibroblast lines examined in a similar manner. PDGF-B transcripts or proteins were not detected in any lung fibroblast line examined. Conditioned medium (CM) was collected from these same lung fibroblast lines and tested for its ability to promote cell growth using human fetal lung fibroblasts as targets. Both adult and fetal rat lung fibroblasts were found to produce a potent and efficacious stimulus for cell growth. Growth-promoting activity in rat fibroblast-derived CM functioned as a "competence" factor and was partially inhibited by anti-PDGF antibody. Thus rat lung fibroblasts in vitro produce potent growth factors of which at least one appears to be PDGF-AA. Differences in the expression of PDGF-AA between rat and human lung fibroblasts exist. Growth factor-producing fibroblasts may play a role in lung repair and remodeling through production PDGF-AA in vivo.
The explosion and subsequent blowout of the Deepwater Horizon (DWH) offshore drilling rig on Apri... more The explosion and subsequent blowout of the Deepwater Horizon (DWH) offshore drilling rig on April 20, 2010, led to the largest accidental offshore oil spill since the advent of the petroleum industry, dwarfed only by the deliberate release of crude oil by Iraqi forces during the Persian Gulf War. Over the time until the well was capped on July 15, approximately 200 million gallons of oil spilled into the Gulf of Mexico from the ocean floor beneath the well site located approximately 50 miles off the coast of Louisiana. For perspective, this amount is nearly 20 times the amount of oil discharged during the Exxon Valdez incident in Alaska. As a result, massive mitigation efforts took place during and after the flow of oil which entailed mechanical recovery, controlled burning, and chemical dispersion. As a result unprecedented application of oil dispersant agents was employed by BP during this time until their use was curtailed by the EPA on May 26, 2010. Overall, about 17 20% of the...
Accumulation of basic drugs by pulmonary tissue is well known. The cationic amphiphilic nature of... more Accumulation of basic drugs by pulmonary tissue is well known. The cationic amphiphilic nature of many of these compounds suggests that they may be sequestered within an acidic and/or phospholipid-rich compartment. We described previously receptor-independent, concentrative, temperature- and pH-dependent sequestration of the beta adrenergic antagonists [125I]iodocyanopindolol and [125I]iodopindolol by intact rat type II pneumocytes in primary culture. The present study reveals that type II pneumocytes sequester [125I]iodocyanopindolol to an extent greater than other cell types (type II cells greater than polymorphonuclear leukocytes greater than S49) within 80-min incubations. Localization of fluorescence into large granular structures was observed after incubation of type II cells with 9-aminoacridine-propranolol (9-AAP). The distribution of fluorescence coincides with surfactant-containing lamellar bodies (LB) visualized with tannic acid/osmium staining. The large granule localiza...
American Journal of Physiology-Lung Cellular and Molecular Physiology
Control of growth and phenotypic expression of interstitial fibroblasts is a critical determinant... more Control of growth and phenotypic expression of interstitial fibroblasts is a critical determinant of lung architecture and physiology during processes of growth and remodeling. We examined the ability of lung fibroblasts to produce transforming growth factor-beta (TGF-beta), a cytokine that is known to modulate proliferation and phenotypic expression of mesenchymal cells. Cultures of fibroblasts isolated from rat lungs spontaneously secrete TGF-beta as measured in the standard bioassay of anchorage-independent growth of normal rat kidney (NRK) cells in soft agar. Rat lung fibroblasts secrete TGF-beta in an inactive precursor form. Fibroblasts cultured from adult and fetal rat lungs produced comparable amounts of TGF-beta. The ability of lung fibroblast supernatant fluids to induce colony formation in soft agar could be completely neutralized by preincubation of samples with anti-TGF-beta immunoglobulin (Ig). Anti-platelet-derived growth factor IgG had no effect on anchorage-independ...
American journal of physiology. Lung cellular and molecular physiology, 2003
Programmed cell death (apoptosis) functions as a mechanism to eliminate unwanted or irreparably d... more Programmed cell death (apoptosis) functions as a mechanism to eliminate unwanted or irreparably damaged cells ultimately leading to their orderly phagocytosis in the absence of calamitous inflammatory responses. Recent studies have demonstrated that the generation of free radical intermediates and subsequent oxidative stress are implicated as part of the apoptotic execution process. Oxidative stress may simply be an unavoidable yet trivial byproduct of the apoptotic machinery; alternatively, intermediates or products of oxidative stress may act as essential signals for the execution of the apoptotic program. This review is focused on the specific role of oxidative stress in apoptotic signaling, which is realized via phosphatidylserine-dependent pathways leading to recognition of apoptotic cells and their effective clearance. In particular, the mechanisms involved in selective phosphatidylserine oxidation in the plasma membrane during apoptosis and its association with disturbances o...
Etoposide (VP-16) is extensively used to treat cancer, yet its efficacy is calamitously associate... more Etoposide (VP-16) is extensively used to treat cancer, yet its efficacy is calamitously associated with an increased risk of secondary acute myelogenous leukemia. The mechanisms for the extremely high susceptibility of myeloid stem cells to the leukemogenic effects of etoposide have not been elucidated. We propose a mechanism to account for the etoposide-induced secondary acute myelogenous leukemia and nutritional strategies to prevent this complication of etoposide therapy. We hypothesize that etoposide phenoxyl radicals (etoposide-O(.)) formed from etoposide by myeloperoxidase are responsible for its genotoxic effects in bone marrow progenitor cells, which contain constitutively high myeloperoxidase activity. Here, we used purified human myeloperoxidase, as well as human leukemia HL60 cells with high myeloperoxidase activity and provide evidence of the following. 1) Etoposide undergoes one-electron oxidation to etoposide-O(.) catalyzed by both purified myeloperoxidase and myeloper...
Loss of differentiated function by type II pneumocytes plated on plastic surfaces was demonstrate... more Loss of differentiated function by type II pneumocytes plated on plastic surfaces was demonstrated by decreased lamellar body content, increased cellular protein, and rapid cellular flattening, changes that were retarded modestly by plating cells on laminin-coated surfaces. Laminin surfaces also inhibited [3H]thymidine (THM) incorporation into cellular DNA by 40% compared with plastic at 40 h, but did not alter an additional mitogenic effect of rat serum over fetal calf serum. In contrast, cells plated on the laminin-rich basement membrane-like gel formed from an extract of EHS mouse sarcoma, matrix gel (MG), maintained a high content of intracellular lipids in lamellar inclusions and retained a rounded morphology for at least 3 days. MG markedly inhibited THM incorporation and morphological changes when cells were cultured on this surface or when MG was formed over cells initially plated on plastic for various intervals. The importance of the laminin component of MG was demonstrate...
Numerous studies indicate that synthesis and secretion of surfactant by type II pneumocytes are m... more Numerous studies indicate that synthesis and secretion of surfactant by type II pneumocytes are modulated by the interaction of beta-adrenergic agonists with specific cell surface receptors. Two 125I-labeled beta-adrenergic ligands, l-iodopindolol (IPIN) and l-iodocyanopindolol (ICYP), were thus employed to investigate the properties of type II cell beta-receptors. Saturable, high-affinity, stereospecific binding to crude membrane fractions from whole rat lungs was exhibited by both ligands (IPIN, KD 283 pM, Bmax 508 fmol/mg protein; ICYP, KD 18 pM, Bmax 404). Type II cell membranes obtained by N2 cavitation also revealed stereospecific, saturable, high-affinity binding. In intact cells (37 degrees C) however, rapid, highly concentrative (cell/media greater than 1000), nonspecific ligand uptake compromised estimates of specific binding (specific/total binding less than 0.1). Total ligand uptake was inhibited at 4 degrees C, by decreasing pH within the physiological range (7-8) and b...
Summary Both vitamin E and coenzyme Q possess distinct lipoprotective antioxidant properties in ... more Summary Both vitamin E and coenzyme Q possess distinct lipoprotective antioxidant properties in biological membranes. Their combined antioxidant activity, however, is markedly synergistic when both are present together. While it is likely that vitamin E represents the initial chain-breaking antioxidant during lipid peroxidation, both fully reduced CoQH2 (ubiquinol) and semireduced CoQH. (ubisemiquinone) appear to efficiently recycle the resultant vitamin E phenoxyl
A permanent reduction in seizure threshold due to repeated subconvulsive electrical stimulation o... more A permanent reduction in seizure threshold due to repeated subconvulsive electrical stimulation of the amygdala characterizes the kindling model of epilepsy. Since kindling may involve neurochemical alterations, cerebral amino acids were studied in this induced seizure state. Minimal changes were found in the levels of amino acids in the cerebellum, frontal cortex and brain stem of amygdaloid kindled rats when measured one week after the last seizure. The uptake of taurine into synaptosomes prepared from the cerebellum of kindled rats was significantly elevated, suggesting that alterations in synaptic action of this inhibitory neurotransmitter may play a role in the development of kindling.
To test the hypothesis that enhanced oxidative stress during pregnancies complicated by preeclamp... more To test the hypothesis that enhanced oxidative stress during pregnancies complicated by preeclampsia is associated with improper copper (Cu) binding by plasma albumin, resulting in enhanced Cu redox-cycling activity and that altered Cu binding, in turn, is caused by interactions of excessive amounts of free fatty acids with albumin. We studied binding and redox-cycling activity of Cu in 17 normal pregnancy and 17 preeclampsia plasma samples. Binding of exogenous Cu in plasma samples was quantified indirectly using spectrophotometric measurements of its complex with a specific chelator of Cu(I), bathocuproine disulfonate. Redox-cycling activity of Cu in plasma samples was estimated by electron paramagnetic resonance (EPR) spectroscopy of ascorbate radicals formed during one-electron oxidation of ascorbate by redox-active catalytic Cu. Formation of Cu/albumin complexes in model systems in the presence and absence of fatty acids was studied using EPR spectroscopy of Cu(II)/albumin. We found that preeclampsia plasma (as compared to normal pregnancy plasma) (1) displays elevated endogenous ascorbate redox-cycling that is normalized by a Cu(II) chelator, cuprizone I, (2) has lowered capacity to bind and redox-regulate exogenously added Cu, and (3) responds to treatment with fatty-acid-free albumin by diminished ascorbate oxidizing activity. Conversely, addition of free fatty acid (oleic acid) to normal pregnancy plasma sample yields increased ascorbate redox-cycling activity. Our model experiments showed that Cu-dependent redox-cycling activity of purified human serum albumin is significantly increased by excess free fatty acids. Mishandling of Cu by albumin contributes to oxidative stress in preeclampsia. Cu chelators may represent promising mechanism-based antioxidants to attenuate oxidative stress in preeclampsia.
ABSTRACT The kindling model of epileptogenesis is characterized by the induction of a persistent ... more ABSTRACT The kindling model of epileptogenesis is characterized by the induction of a persistent reduction of seizure threshold after repeated exposures of the brain to stimuli which were initially subconvulsive. We studied the ability of repeated injections of pentylenetetrazol (PTZ) to induce kindling. Subconvulsive doses of PTZ (20–25 mg/kg, i.p.) were administered to rats every 4 days for a total of 21 treatments. The convulsive response score of PTZ-treated rats remained elevated upon challenge with 22.5 mg/kg PTZ after a 3-week PTZ-free period. Studies on the mechanisms involved in PTZ-induced kindling revealed that hepatic microsomal P-450 concentrations were unchanged after chronic PTZ treatment. No significant changes in brain amino acids, including GABA and taurine, two neuroinhibitory amino acids which have been implicated in the regulation of seizure phenomena, were found in PTZ-kindled animals.
Objective. To test the hypothesis that enhanced oxidative stress during pregnancies complicated b... more Objective. To test the hypothesis that enhanced oxidative stress during pregnancies complicated by preeclampsia is associated with improper copper (Cu) binding by plasma albumin, resulting in enhanced Cu redox-cycling activity and that altered Cu binding, in ...
Etoposide (VP-16) is extensively used to treat cancer, yet its efficacy is calamitously associate... more Etoposide (VP-16) is extensively used to treat cancer, yet its efficacy is calamitously associated with an increased risk of secondary acute myelogenous leukemia. The mechanisms for the extremely high susceptibility of myeloid stem cells to the ...
... Transforming Growth Factor-3 Production by Lung Macrophages and Fibroblasts* Jason Keiley, MD... more ... Transforming Growth Factor-3 Production by Lung Macrophages and Fibroblasts* Jason Keiley, MD; Elizabethj Kovacs, Ph.D.; Kieran Nicholson, MB.; and James P Bibisiak, Ph.D. ... TGF-release during the course of pulmonary injury. REFERENCES 1 Roberts AB, Spurn MB. ...
... Transforming Growth Factor-3 Production by Lung Macrophages and Fibroblasts* Jason Keiley, MD... more ... Transforming Growth Factor-3 Production by Lung Macrophages and Fibroblasts* Jason Keiley, MD; Elizabethj Kovacs, Ph.D.; Kieran Nicholson, MB.; and James P Bibisiak, Ph.D. ... TGF-release during the course of pulmonary injury. REFERENCES 1 Roberts AB, Spurn MB. ...
Platelet-derived growth factor (PDGF) is considered a decisive mediator of fibroblast growth and ... more Platelet-derived growth factor (PDGF) is considered a decisive mediator of fibroblast growth and phenotype within the lung. The cellular sources of PDGF within the lung remain undefined. The ability of lung fibroblasts themselves to produce PDGF in vitro was therefore investigated. Northern and Western blot analyses revealed the expression of PDGF-A mRNA and secretion of A-chain containing proteins by fibroblasts derived from adult and fetal rat lung. PDGF-A gene or protein expression were below the limits of detection in two human lung fibroblast lines examined in a similar manner. PDGF-B transcripts or proteins were not detected in any lung fibroblast line examined. Conditioned medium (CM) was collected from these same lung fibroblast lines and tested for its ability to promote cell growth using human fetal lung fibroblasts as targets. Both adult and fetal rat lung fibroblasts were found to produce a potent and efficacious stimulus for cell growth. Growth-promoting activity in rat fibroblast-derived CM functioned as a "competence" factor and was partially inhibited by anti-PDGF antibody. Thus rat lung fibroblasts in vitro produce potent growth factors of which at least one appears to be PDGF-AA. Differences in the expression of PDGF-AA between rat and human lung fibroblasts exist. Growth factor-producing fibroblasts may play a role in lung repair and remodeling through production PDGF-AA in vivo.
The explosion and subsequent blowout of the Deepwater Horizon (DWH) offshore drilling rig on Apri... more The explosion and subsequent blowout of the Deepwater Horizon (DWH) offshore drilling rig on April 20, 2010, led to the largest accidental offshore oil spill since the advent of the petroleum industry, dwarfed only by the deliberate release of crude oil by Iraqi forces during the Persian Gulf War. Over the time until the well was capped on July 15, approximately 200 million gallons of oil spilled into the Gulf of Mexico from the ocean floor beneath the well site located approximately 50 miles off the coast of Louisiana. For perspective, this amount is nearly 20 times the amount of oil discharged during the Exxon Valdez incident in Alaska. As a result, massive mitigation efforts took place during and after the flow of oil which entailed mechanical recovery, controlled burning, and chemical dispersion. As a result unprecedented application of oil dispersant agents was employed by BP during this time until their use was curtailed by the EPA on May 26, 2010. Overall, about 17 20% of the...
Accumulation of basic drugs by pulmonary tissue is well known. The cationic amphiphilic nature of... more Accumulation of basic drugs by pulmonary tissue is well known. The cationic amphiphilic nature of many of these compounds suggests that they may be sequestered within an acidic and/or phospholipid-rich compartment. We described previously receptor-independent, concentrative, temperature- and pH-dependent sequestration of the beta adrenergic antagonists [125I]iodocyanopindolol and [125I]iodopindolol by intact rat type II pneumocytes in primary culture. The present study reveals that type II pneumocytes sequester [125I]iodocyanopindolol to an extent greater than other cell types (type II cells greater than polymorphonuclear leukocytes greater than S49) within 80-min incubations. Localization of fluorescence into large granular structures was observed after incubation of type II cells with 9-aminoacridine-propranolol (9-AAP). The distribution of fluorescence coincides with surfactant-containing lamellar bodies (LB) visualized with tannic acid/osmium staining. The large granule localiza...
American Journal of Physiology-Lung Cellular and Molecular Physiology
Control of growth and phenotypic expression of interstitial fibroblasts is a critical determinant... more Control of growth and phenotypic expression of interstitial fibroblasts is a critical determinant of lung architecture and physiology during processes of growth and remodeling. We examined the ability of lung fibroblasts to produce transforming growth factor-beta (TGF-beta), a cytokine that is known to modulate proliferation and phenotypic expression of mesenchymal cells. Cultures of fibroblasts isolated from rat lungs spontaneously secrete TGF-beta as measured in the standard bioassay of anchorage-independent growth of normal rat kidney (NRK) cells in soft agar. Rat lung fibroblasts secrete TGF-beta in an inactive precursor form. Fibroblasts cultured from adult and fetal rat lungs produced comparable amounts of TGF-beta. The ability of lung fibroblast supernatant fluids to induce colony formation in soft agar could be completely neutralized by preincubation of samples with anti-TGF-beta immunoglobulin (Ig). Anti-platelet-derived growth factor IgG had no effect on anchorage-independ...
American journal of physiology. Lung cellular and molecular physiology, 2003
Programmed cell death (apoptosis) functions as a mechanism to eliminate unwanted or irreparably d... more Programmed cell death (apoptosis) functions as a mechanism to eliminate unwanted or irreparably damaged cells ultimately leading to their orderly phagocytosis in the absence of calamitous inflammatory responses. Recent studies have demonstrated that the generation of free radical intermediates and subsequent oxidative stress are implicated as part of the apoptotic execution process. Oxidative stress may simply be an unavoidable yet trivial byproduct of the apoptotic machinery; alternatively, intermediates or products of oxidative stress may act as essential signals for the execution of the apoptotic program. This review is focused on the specific role of oxidative stress in apoptotic signaling, which is realized via phosphatidylserine-dependent pathways leading to recognition of apoptotic cells and their effective clearance. In particular, the mechanisms involved in selective phosphatidylserine oxidation in the plasma membrane during apoptosis and its association with disturbances o...
Etoposide (VP-16) is extensively used to treat cancer, yet its efficacy is calamitously associate... more Etoposide (VP-16) is extensively used to treat cancer, yet its efficacy is calamitously associated with an increased risk of secondary acute myelogenous leukemia. The mechanisms for the extremely high susceptibility of myeloid stem cells to the leukemogenic effects of etoposide have not been elucidated. We propose a mechanism to account for the etoposide-induced secondary acute myelogenous leukemia and nutritional strategies to prevent this complication of etoposide therapy. We hypothesize that etoposide phenoxyl radicals (etoposide-O(.)) formed from etoposide by myeloperoxidase are responsible for its genotoxic effects in bone marrow progenitor cells, which contain constitutively high myeloperoxidase activity. Here, we used purified human myeloperoxidase, as well as human leukemia HL60 cells with high myeloperoxidase activity and provide evidence of the following. 1) Etoposide undergoes one-electron oxidation to etoposide-O(.) catalyzed by both purified myeloperoxidase and myeloper...
Loss of differentiated function by type II pneumocytes plated on plastic surfaces was demonstrate... more Loss of differentiated function by type II pneumocytes plated on plastic surfaces was demonstrated by decreased lamellar body content, increased cellular protein, and rapid cellular flattening, changes that were retarded modestly by plating cells on laminin-coated surfaces. Laminin surfaces also inhibited [3H]thymidine (THM) incorporation into cellular DNA by 40% compared with plastic at 40 h, but did not alter an additional mitogenic effect of rat serum over fetal calf serum. In contrast, cells plated on the laminin-rich basement membrane-like gel formed from an extract of EHS mouse sarcoma, matrix gel (MG), maintained a high content of intracellular lipids in lamellar inclusions and retained a rounded morphology for at least 3 days. MG markedly inhibited THM incorporation and morphological changes when cells were cultured on this surface or when MG was formed over cells initially plated on plastic for various intervals. The importance of the laminin component of MG was demonstrate...
Numerous studies indicate that synthesis and secretion of surfactant by type II pneumocytes are m... more Numerous studies indicate that synthesis and secretion of surfactant by type II pneumocytes are modulated by the interaction of beta-adrenergic agonists with specific cell surface receptors. Two 125I-labeled beta-adrenergic ligands, l-iodopindolol (IPIN) and l-iodocyanopindolol (ICYP), were thus employed to investigate the properties of type II cell beta-receptors. Saturable, high-affinity, stereospecific binding to crude membrane fractions from whole rat lungs was exhibited by both ligands (IPIN, KD 283 pM, Bmax 508 fmol/mg protein; ICYP, KD 18 pM, Bmax 404). Type II cell membranes obtained by N2 cavitation also revealed stereospecific, saturable, high-affinity binding. In intact cells (37 degrees C) however, rapid, highly concentrative (cell/media greater than 1000), nonspecific ligand uptake compromised estimates of specific binding (specific/total binding less than 0.1). Total ligand uptake was inhibited at 4 degrees C, by decreasing pH within the physiological range (7-8) and b...
Summary Both vitamin E and coenzyme Q possess distinct lipoprotective antioxidant properties in ... more Summary Both vitamin E and coenzyme Q possess distinct lipoprotective antioxidant properties in biological membranes. Their combined antioxidant activity, however, is markedly synergistic when both are present together. While it is likely that vitamin E represents the initial chain-breaking antioxidant during lipid peroxidation, both fully reduced CoQH2 (ubiquinol) and semireduced CoQH. (ubisemiquinone) appear to efficiently recycle the resultant vitamin E phenoxyl
A permanent reduction in seizure threshold due to repeated subconvulsive electrical stimulation o... more A permanent reduction in seizure threshold due to repeated subconvulsive electrical stimulation of the amygdala characterizes the kindling model of epilepsy. Since kindling may involve neurochemical alterations, cerebral amino acids were studied in this induced seizure state. Minimal changes were found in the levels of amino acids in the cerebellum, frontal cortex and brain stem of amygdaloid kindled rats when measured one week after the last seizure. The uptake of taurine into synaptosomes prepared from the cerebellum of kindled rats was significantly elevated, suggesting that alterations in synaptic action of this inhibitory neurotransmitter may play a role in the development of kindling.
To test the hypothesis that enhanced oxidative stress during pregnancies complicated by preeclamp... more To test the hypothesis that enhanced oxidative stress during pregnancies complicated by preeclampsia is associated with improper copper (Cu) binding by plasma albumin, resulting in enhanced Cu redox-cycling activity and that altered Cu binding, in turn, is caused by interactions of excessive amounts of free fatty acids with albumin. We studied binding and redox-cycling activity of Cu in 17 normal pregnancy and 17 preeclampsia plasma samples. Binding of exogenous Cu in plasma samples was quantified indirectly using spectrophotometric measurements of its complex with a specific chelator of Cu(I), bathocuproine disulfonate. Redox-cycling activity of Cu in plasma samples was estimated by electron paramagnetic resonance (EPR) spectroscopy of ascorbate radicals formed during one-electron oxidation of ascorbate by redox-active catalytic Cu. Formation of Cu/albumin complexes in model systems in the presence and absence of fatty acids was studied using EPR spectroscopy of Cu(II)/albumin. We found that preeclampsia plasma (as compared to normal pregnancy plasma) (1) displays elevated endogenous ascorbate redox-cycling that is normalized by a Cu(II) chelator, cuprizone I, (2) has lowered capacity to bind and redox-regulate exogenously added Cu, and (3) responds to treatment with fatty-acid-free albumin by diminished ascorbate oxidizing activity. Conversely, addition of free fatty acid (oleic acid) to normal pregnancy plasma sample yields increased ascorbate redox-cycling activity. Our model experiments showed that Cu-dependent redox-cycling activity of purified human serum albumin is significantly increased by excess free fatty acids. Mishandling of Cu by albumin contributes to oxidative stress in preeclampsia. Cu chelators may represent promising mechanism-based antioxidants to attenuate oxidative stress in preeclampsia.
ABSTRACT The kindling model of epileptogenesis is characterized by the induction of a persistent ... more ABSTRACT The kindling model of epileptogenesis is characterized by the induction of a persistent reduction of seizure threshold after repeated exposures of the brain to stimuli which were initially subconvulsive. We studied the ability of repeated injections of pentylenetetrazol (PTZ) to induce kindling. Subconvulsive doses of PTZ (20–25 mg/kg, i.p.) were administered to rats every 4 days for a total of 21 treatments. The convulsive response score of PTZ-treated rats remained elevated upon challenge with 22.5 mg/kg PTZ after a 3-week PTZ-free period. Studies on the mechanisms involved in PTZ-induced kindling revealed that hepatic microsomal P-450 concentrations were unchanged after chronic PTZ treatment. No significant changes in brain amino acids, including GABA and taurine, two neuroinhibitory amino acids which have been implicated in the regulation of seizure phenomena, were found in PTZ-kindled animals.
Objective. To test the hypothesis that enhanced oxidative stress during pregnancies complicated b... more Objective. To test the hypothesis that enhanced oxidative stress during pregnancies complicated by preeclampsia is associated with improper copper (Cu) binding by plasma albumin, resulting in enhanced Cu redox-cycling activity and that altered Cu binding, in ...
Etoposide (VP-16) is extensively used to treat cancer, yet its efficacy is calamitously associate... more Etoposide (VP-16) is extensively used to treat cancer, yet its efficacy is calamitously associated with an increased risk of secondary acute myelogenous leukemia. The mechanisms for the extremely high susceptibility of myeloid stem cells to the ...
... Transforming Growth Factor-3 Production by Lung Macrophages and Fibroblasts* Jason Keiley, MD... more ... Transforming Growth Factor-3 Production by Lung Macrophages and Fibroblasts* Jason Keiley, MD; Elizabethj Kovacs, Ph.D.; Kieran Nicholson, MB.; and James P Bibisiak, Ph.D. ... TGF-release during the course of pulmonary injury. REFERENCES 1 Roberts AB, Spurn MB. ...
... Transforming Growth Factor-3 Production by Lung Macrophages and Fibroblasts* Jason Keiley, MD... more ... Transforming Growth Factor-3 Production by Lung Macrophages and Fibroblasts* Jason Keiley, MD; Elizabethj Kovacs, Ph.D.; Kieran Nicholson, MB.; and James P Bibisiak, Ph.D. ... TGF-release during the course of pulmonary injury. REFERENCES 1 Roberts AB, Spurn MB. ...
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