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J N Moore

Publications and source records attributed to J N Moore.

At least 37 records · Page 2Linked to original sources
PubMed1995

Increased phospholipid mass with decreased arachidonoyl molecular species is associated with decreased eicosanoid synthesis and increased tumor necrosis factor synthesis by thioglycollate-elicited rat peritoneal macrophages.

Because the activation state of macrophages may alter their response to endotoxin, we compared phospholipid arachidonic acid content, and synthesis of eicosanoids and tumor necrosis factor by resident and thioglycollate-elicited rat peritoneal macrophages. Thioglycollate elicitation increased macrophage phospholipid mass twofold, increased the relative percentages of 16:0-20:4 diacylglycerophosphocholine (PtdCho) and 18:0-20:4 diacylglycerophosphoethanolamine (PtdEtn), and decreased the relative percentages of 18:0-20:4 alkenylacylglycerophosphoethanolamine (PlsEtn) and 18:0-20:4 alkylacylglycerophosphocholine (PakCho) compared with resident peritoneal macrophages. Thioglycollate-elicited macrophages synthesized significantly less thromboxane B2, 6-keto-prostaglandin F1 alpha, and prostaglandin E2 and more tumor necrosis factor (TNF) activity in response to both endotoxin and A23187 than did resident macrophages. These results suggest that thioglycollate elicitation decreases specific arachidonic acid-containing molecular species in PlsEtn and PakCho, which may, in part, explain the decrease in eicosanoid and increase in TNF synthesis by thioglycollate-elicited macrophages. The differences between resident and thioglycollate-elicited macrophages in the synthesis of the eicosanoids and TNF activity was not altered by increasing either the concentration of either stimulus or the incubation time.

Animals↗
PubMed1995

Pharmacokinetics of heparin and its pharmacodynamic effect on plasma lipoprotein lipase activity and coagulation in healthy horses.

We evaluated the pharmacokinetics of IV administered sodium heparin and the pharmacodynamic effect of heparin on lipoprotein lipase (LPL) activity. Horses were allotted to 3 groups. Plasma samples were obtained from each horse before and at various times for 6 hours after heparin administration for determination of heparin concentration, LPL activity, and activated partial thromboplastin time (APTT). The disposition of heparin was dose dependent. The area under the plasma heparin concentration vs time curve (AUC) increased more than proportionally with dose, indicating that heparin elimination was nonlinear. Total clearance of heparin was similar after the 40 and 80 IU/kg of body weight dosages, averaging 0.45 and 0.36 IU/kg/min, respectively. However, after administration of the 120 IU/kg dose, clearance was significantly less than that after the 40 IU/kg dose. The half-life of heparin averaged 53, 70, and 136 minutes after 40, 80, and 120 IU/kg, respectively, with significant differences observed between the low and high doses. In contrast to heparin, the area under the plasma concentration vs time curve for LPL activity increased less than proportionally with dose. Maximal LPL activity observed was independent of dose, averaging 4.8 mumol of free fatty acids/ml/h. The APTT was significantly prolonged for 120 minutes after administration of the 40 IU/kg dose. Correlation coefficients for LPL activity vs either plasma heparin concentration or APTT were less than 0.7, indicating that neither laboratory measure can be used to accurately predict plasma LPL activity.

Analysis of Variance↗
PubMed1994

Anti-inflammatory and immune support in endotoxemia and septicemia.

Endotoxemia and septicemia are encountered frequently in equine veterinary practice. The deleterious effects of endotoxin are related to the severity of the response of the host's inflammatory system. Consequently, it is imperative that appropriate steps be taken to identify animals at risk of developing endotoxemia or septicemia, and to initiate treatments that will reduce the inflammatory response. This article discusses the anti-inflammatory and immune support of horses and foals with endotoxemia and septicemia.

Animals↗
PubMed1994

Dietary source of omega-3 fatty acids affects endotoxin-induced peritoneal macrophage tumor necrosis factor and eicosanoid synthesis.

The effect of 8 weeks of feeding diets enriched with corn oil, linseed oil, or menhaden oil on endotoxin- and calcium ionophore (A23187)-induced tumor necrosis factor (TNF) and eicosanoid synthesis by rat peritoneal macrophages was determined. The fatty acid composition of macrophage phospholipids and TNF activity and eicosanoid synthesis in response to endotoxin and A23187 were determined. The ratio of omega-6/omega-3 fatty acids in macrophages from linseed oil or menhaden oil-fed rats decreased approximately 24- and 55-fold, respectively. Basal and endotoxin-induced synthesis of TNF was increased by ingestion of the menhaden oil diet but not by the linseed oil diet. Ingestion of the menhaden oil and linseed oil diets significantly reduced basal, endotoxin-, and A23187-induced synthesis of eicosanoids compared with the corn oil group. Ingestion of the menhaden oil diet resulted in a greater decrease in eicosanoid synthesis than the linseed oil diet.

Animals↗
PubMed1994

Regulation of equine fibrinolysis in blood and peritoneal fluid based on a study of colic cases and induced endotoxaemia.

Much of the pathophysiology associated with equine gastrointestinal diseases is attributed to the effects of endotoxin on haemostasis. Because little is known about the responses of the equine fibrinolytic system to endotoxin, regulation of the system was investigated. Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) were identified as the primary plasminogen activator and plasminogen activator inhibitor, respectively, in equine blood. Under experimental conditions, the equine fibrinolytic system responded to endotoxin in a manner similar to that reported in man, with an early, transient increase in t-PA activity followed by an overwhelming and prolonged increase in activity of PAI-1. To investigate the response of the equine fibrinolytic system to clinical endotoxaemia, endotoxin concentrations were measured in plasma and peritoneal fluid, and activities of t-PA and PAI-1 were compared between healthy horses (n = 38) and horses with naturally occurring gastrointestinal diseases (n = 150). It was observed that plasma PAI-1 and peritoneal t-PA were increased concurrently in abnormal horses; and that these increases were associated with the presence of endotoxin. The results of this study suggest that 1) fibrinolysis is regulated in horses in a manner similar to that in man; 2) regulation of fibrinolysis is altered in endotoxaemic horses with gastrointestinal diseases; 3) events occurring in the vascular system may not reflect those in the peritoneal cavity; and 4) t-PA activity is increased in the peritoneal fluid of endotoxaemic horses with gastrointestinal diseases.

Animals↗
PubMed1994

Pentoxifylline inhibits mediator synthesis in an equine in vitro whole blood model of endotoxemia.

Whole blood from 10 healthy horses was aseptically collected into heparin or citrate anticoagulant and incubated in vitro for 6 hr in the absence (saline control) or presence of 1 ng endotoxin/ml blood. Pentoxifylline (0.1, 1, 10, or 100 micrograms/ml blood) was added 1 hr before, at the same time, or 1 hr after endotoxin. As compared to saline controls, pentoxifylline alone had no effect on mediator production, with the exception of significantly increasing 6-ketoprostaglandin F1 alpha concentration. Pentoxifylline inhibited endotoxin-induced increases in tumor necrosis factor (TNF) and interleukin-6 (IL-6) activity in a dose-related fashion, whether added before, at the same time, or after endotoxin. Pentoxifylline significantly inhibited tissue factor activity, but only when added before endotoxin. Pentoxifylline had no effect on endotoxin-induced 6-keto-prostaglandin F1 alpha production, but significantly inhibited thromboxane B2 (TxB2) production. The results of this study indicate that pentoxifylline, at blood concentrations consistent with those achieved in vivo, has effects that may be beneficial in the treatment of endotoxemia.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Comparison of the effects of ketoprofen and flunixin meglumine on the in vitro response of equine peripheral blood monocytes to bacterial endotoxin.

The purpose of this study was to investigate the in vitro effects of flunixin meglumine, a cyclo-oxygenase inhibitor, and ketoprofen, a reported cyclo-oxygenase and lipoxygenase inhibitor, on the synthesis of cyclo-oxygenase end-products thromboxane B2 and prostaglandin E2, lipoxygenase derived 12-hydroxyeicosatetraenoic acid, tumor necrosis factor and tissue factor. Six adult horses were each randomly administered flunixin meglumine (1.1 mg/kg) or ketoprofen (2.2 mg/kg) intravenously every 12 hours with the drug treatments separated by two weeks. Blood samples were obtained prior to initiating treatment, the last day of treatment and for two consecutive days after the termination of treatment for measurement of serum concentrations of thromboxane B2 as well as isolation of peripheral blood monocytes. Quantitation of unstimulated, endotoxin- and calcium ionophore-induced synthesis of thromboxane B2, prostaglandin E2, 12-hydroxyeicosatetraenoic acid, tumor necrosis factor and tissue factor by peripheral blood monocytes was performed in vitro. Both flunixin meglumine and ketoprofen significantly decreased serum concentrations of thromboxane B2 demonstrating in vivo cyclo-oxygenase inhibition. There were no significant differences between drug treatment groups in the in vitro production of thromboxane B2, prostaglandin E2, 12-hydroxy-eicosatetraenoic acid, tumor necrosis factor or tissue factor. This study does not identify significant differences between the effects of flunixin meglumine and ketoprofen.

Animals↗
PubMed1993

Analysis of hemostasis in horses with colic.

Eight tests of hemostasis were measured in 233 horses with colic. Blood samples were obtained at admission and for 4 consecutive days of hospitalization. Data were analyzed retrospectively by outcome, by broad-category diagnosis group, by small intestinal disorder, and by smaller categories for comparing specific diseases. Nonsurviving horses and horses with the most severe forms of intestinal ischemia had changes interpreted as hypercoagulative, the intensity of which was increased on the first and second mornings (sample times 2 and 3) after admission, when most significant differences for results of specific tests were detected. Nonsurvivors had decreased antithrombin III activity and prolonged prothrombin and activated partial thromboplastin times; those with strangulating obstructions also had decreased protein C and plasminogen activities. During hospitalization and with survival, these changes tended to reverse. In most horses, regardless of diagnosis or outcome, concentration of fibrin degradation products and fibrinogen, and alpha 2-antiplasmin activity increased over time. Whether these changes reflected specific effects of colic or of the acute-phase response was not determined. In comparisons of small intestinal disorders (proximal enteritis, strangulations, and impactions), diagnostically distinguishing features were not found. Likewise, in comparisons of specific diseases (small vs large intestinal impaction, proximal enteritis vs colitis, small vs large intestinal obstruction), diagnostically distinguishing features were not found.

Animals↗
PubMed1993

Thromboxane A2 receptors in equine monocytes: identification of a new subclass of TXA2 receptors.

Thromboxane (TX) A2 has been implicated as an important pathophysiologic mediator of a variety of cardiovascular diseases. Monocytes synthesize TXA2 and it modulates their function. This study sought to characterize monocyte TXA2 receptors. Radioligand binding studies were performed on membranes prepared from equine peripheral blood monocytes using [125I]BOP, a TXA2 receptor agonist. [125I]BOP bound to a single class of binding sites (Kd = 1.0 +/- 0.3 nM and Bmax = 389 +/- 191 fmol/mg protein; n = 5). Several TXA2 receptor agonists and antagonists competed for binding with [125I]BOP. I-BOP produced a concentration-dependent inhibition of endotoxin-induced tumor necrosis factor (TNF) activity (IC50 = 9.6 +/- 2.5 nM; n = 5). In contrast to its effects in platelets and vascular smooth muscle, I-BOP significantly increased cAMP formation in monocytes (EC50 = 22 +/- 3.6 nM; n = 4). The TXA2 receptor antagonists SQ29548 (5.6 microM) and L657925 (0.13 microM) significantly blocked I-BOP-stimulated cAMP formation but did not block 250 nM prostaglandin E2-stimulated cAMP formation. These data support the presence of a TXA2 receptor in equine peripheral blood monocytes. Activation of this receptor results in suppression of endotoxin-induced TNF formation and stimulation of cAMP production. Increased cAMP production after receptor activation suggests that this receptor may represent a unique subclass of TXA2 receptors.

Animals↗
PubMed1993

Administration of a receptor antagonist for platelet-activating factor during equine endotoxaemia.

Platelet-activating factor (PAF) is an important mediator of endotoxaemia and various PAF receptor antagonists prevent many of the adverse effects of experimental endotoxaemia in laboratory animals. In this study a specific PAF receptor antagonist was used to investigate the role of PAF in equine endotoxaemia. At an interval of not greater than 10 days, 6 horses were each challenged with endotoxin and endotoxin with concurrent administration of SRI 63-441, a PAF receptor antagonist. The order of the treatments was randomised. Clinical signs, serum biochemical and coagulation profiles, and platelet aggregation in vitro were monitored in all horses for 24 h after treatment. Challenge with endotoxin increased maximal platelet aggregation induced by PAF. This response was blocked by administration of SRI 63-441 concurrently with endotoxin. No changes in percentage maximal platelet aggregation to ADP or collagen were noted after administration of endotoxin. The PAF receptor antagonist delayed the onset of fever, tachycardia, leucopenia and lactic acidaemia. Lack of more profound beneficial alterations of the horses' responses to endotoxin may have been due to the low dose of endotoxin administered in this model or to only partial effectiveness of SRI 63-441 in blocking the effects of endotoxin-induced PAF.

Animals↗
PubMed1993

Antagonism of a specific dopaminergic receptor agonist with metoclopramide in horses.

Changes in lateral cecal arterial blood flow, mean internal carotid arterial pressure, and heart rate caused by nasogastric administration of fenoldopam (3, 6, and 9 mg/kg of body weight), a selective agonist of dopaminergic receptors, were recorded in 7 healthy horses. Cecal arterial blood flow was significantly increased within 30 minutes after administration of fenoldopam at all 3 dosages, with the peak increases from baseline (67.8 +/- 17.5 ml/min) being 125 +/- 28, 120 +/- 22, and 153 +/- 32 ml/min for 3, 6, and 9 mg/kg, respectively. Although carotid arterial pressure did not change significantly after administration of fenoldopam at the dosage of 3 mg/kg, administration of fenoldopam at the dosages of 6 and 9 mg/kg significantly reduced carotid arterial pressure from 113 +/- 10 to 88 +/- 3 and 81 +/- 5 mm of Hg, respectively. Intravenous infusion of metoclopramide, a dopaminergic receptor antagonist, at the rate of 0.125 mg/kg/h, blocked the effect of fenoldopam on cecal arterial blood flow and carotid arterial pressure. It was concluded that dopaminergic receptors mediate alterations in local blood flow and systemic pressure in horses.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Blockade of endotoxin-induced cecal hypoperfusion and ileus with an alpha 2 antagonist in horses.

Stimulation of alpha 2 adrenergic receptors inhibits colonic motility and may constrict some peripheral vascular beds. Endotoxemia elicits release of sympathetic neurotransmitters and increases sympathetic nerve activity, which may result in stimulation of alpha 2 adrenergic receptors. The objective of this study was to determine whether blockade of alpha 2 adrenergic receptors would restore cecal motility and blood flow during endotoxemia in horses. Strain-gauge force transducers and ultrasonic flow probes were used to measure cecal and colonic mechanical activity and lateral cecal arterial blood flow. Intravenous infusion of endotoxin (cumulative dose of 0.03 mg/kg) significantly decreased cecal and right ventral colon contractile activity and lateral cecal arterial blood flow. Slow IV infusion of yohimbine (cumulative dose of 75 micrograms/kg) significantly attenuated those effects of endotoxin. On the basis of our findings, we concluded that endotoxemia causes cecal and proximal colonic ileus and cecal hypoperfusion via a mechanism that involves alpha 2 adrenergic receptors.

Analysis of Variance↗
PubMed1992

Equine tumor necrosis factor alpha: cloning and expression in Escherichia coli, generation of monoclonal antibodies, and development of a sensitive enzyme-linked immunosorbent assay.

We describe the production and purification of recombinant equine tumor necrosis factor alpha (rETNF alpha), generation and characterization of murine monoclonal antibodies (Mabs) and rabbit polyclonal antibodies (Pabs) against ETNF alpha, and development of a sensitive enzyme-linked immunosorbent assay (ELISA). Genomic-derived DNA sequences encoding mature ETNF alpha were reconstructed by the polymerase chain reaction (PCR) and oligonucleotide-directed mutagenesis and were cloned into the vector pFLAG-1 for expression in Escherichia coli. rETNF alpha was purified by anti-FLAG immunoaffinity chromatography and then used as immunogen for production of murine Mabs and rabbit Pabs. Three Mabs (6H4, 9B10, and 12F6) were obtained from one fusion. All three Mabs recognized rETNF alpha on western blots. Mabs 6H4 and 9B10 recognized similar epitopes on rENTF alpha and neutralized both rETNF alpha and native ETNF alpha (nETNF alpha) in a WEHI cell cytotoxicity assay. A sensitive ELISA was developed using Mab 6H4 and biotin-labeled rabbit Pabs. The ELISA was shown to detect levels of ENTF alpha as low as 100 pg/ml and was used to demonstrate the induction of ETNF alpha in horses with experimental endotoxemia. The rETNF alpha, antibodies, and ELISA developed in this report should be useful tools for studies of TNF-mediated diseases in horses.

Animals↗
PubMed1992

Endotoxin-induced production of interleukin 6 by equine peritoneal macrophages in vitro.

A study was performed to determine whether equine peritoneal macrophages produce interleukin 6 (IL-6) in vitro in response to endotoxin. Peritoneal fluid was collected from 14 clinically normal adult horses and was used as the source of peritoneal macrophages. Macrophages from each horse were isolated and cultured separately in vitro in the absence or presence of various concentrations (0.5, 5, 500 ng/ml) of endotoxin (lipopolysaccharide from Escherichia coli 055:B5). Culture medium supernatants were collected after 3, 6, 12, and 24 hours' incubation and were frozen at -70 C until assayed for IL-6 activity. Supernatant IL-6 activity was determined by use of a modified colorimetric assay and the murine hybridoma cell line B 13.29 clone B.9, which is dependent on IL-6 for survival. Results indicated that equine peritoneal macrophages produce IL-6 in vitro and that supernatant medium IL-6 activity was significantly (P less than 0.05) increased by exposure to endotoxin. Significant (P less than 0.05) time and treatment effects on macrophage IL-6 production were apparent. The IL-6 activity peaked at 6 or 12 hours' incubation, then remained high through 24 hours' incubation, regardless of endotoxin exposure. Medium IL-6 activity during 3 and 6 hours' incubation was significantly (P less than 0.05) greater in macrophages exposed to 5 or 500 ng of endotoxin/ml than in those exposed to 0.5 ng of endotoxin/ml; however peak IL-6 activity was similar among all endotoxin concentrations. Endotoxin concentration did not have an effect on medium IL-6 activity from macrophages exposed to endotoxin for 12 or 24 hours.

Animals↗
PubMed1992

Effect of experimentally induced endotoxemia on serum interleukin-6 activity in horses.

A study was conducted to determine whether serum interleukin-6 (IL-6) activity increased in horses during experimentally induced endotoxemia and whether serum IL-6 activity correlated to changes in clinical or laboratory data. Six clinically normal horses were given endotoxin IV (30 ng/kg of body weight) in 0.9% NaCl solution over 1 hour. Five of these and 1 additional horse served as controls and were given only 0.9% NaCl solution. Venous blood, for determination of serum IL-6 activity and WBC count, was collected before and at various times through 8 hours after the start of endotoxin or NaCl infusion. Rectal temperature and heart and respiratory rates were recorded throughout the study period. Serum IL-6 activity was determined by bioassay of proliferation of the B13.29 clone B.9 hybridoma cell line. From 1.5 through 5 hours after start of the infusion, serum IL-6 activity was significantly (P less than 0.05) increased in horses given endotoxin. Mean peak serum IL-6 activity was observed between 3 and 4 hours. In response to endotoxin infusion, horses became lethargic, tachycardic, and febrile. Leukopenia developed by 1 hour, followed by leukocytosis at 8 hours. Significant (P less than 0.05) positive association and linear correlation were apparent between mean serum IL-6 activity and mean rectal temperature in the group of horses that were given endotoxin. Changes from baseline were not evident in any of the clinical or laboratory values in horses given only NaCl solution.

Animals↗
PubMed1992

Vowel production in a prelinguistic child following cochlear implantation.

Formant frequencies were determined from vocalic utterances of a prelinguistically deafened child implanted with a Nucleus 22-channel device at age 5 years. Speech samples were obtained from recordings of speech made 5 and 2 months prior to implantation and at 6, 12, 18, 24, and 36 months post implantation. Prior to implantation, first formant values showed a greater range than those of normal hearing children of comparable age, and second formant values showed a greatly reduced range and clustered around a mean of 1800 Hz. By 36 months post implantation, first formant values approximated age-matched norms. By 6 months post implantation, higher second formant values were apparent. A progressive shift in second formant values was noted through 36 months post implantation when the vocalic space most closely corresponded to age-matched normative data.

Child↗
PubMed1992

Reduced endotoxin-induced production of tumor necrosis factor activity by equine peritoneal macrophages exposed to the dual inhibitor of arachidonic acid metabolism, SK & F 86002.

The purpose of this study was to determine if a structurally novel dual inhibitor of arachidonic acid metabolism, SK & F 86002, would inhibit the endotoxin-induced production of tumor necrosis factor (TNF) activity by equine peritoneal macrophages. Equine peritoneal macrophages were variously pretreated for 0, 0.5 and 2 h with SK & F 86002 at 10(-9) to 10(-4) molar final concentrations or were left untreated. Then, the macrophages were cultured in vitro in the presence of endotoxin (5 ng/mL). Supernatant media were collected after 4 h and stored at -70 degrees C until assayed for TNF activity and immunoreactive thromboxane B2 (iTxB2). Macrophage supernatant TNF activities were estimated by an in vitro cytotoxicity bioassay using the murine fibrosarcoma cell line, WEHI 164 clone 13. Concentrations of iTxB2 were quantitated by radioimmunoassay. Coincubation of macrophages with SK & F 86002 significantly decreased the subsequent supernatant TNF activity. Concentrations of SK & F 86002 from 10(-7) to 10(-4) molar effectively reduced TNF production when added to macrophages 0 and 0.5 h prior to endotoxin. After 2 h of preincubation, SK & F 86002 significantly reduced supernatant TNF activity at 10(-5) and 10(-4) M concentrations. Supernatant concentrations of iTxB2 were reduced when SK & F 86002 was added at 10(-6) to 10(-4) M concentrations, 0 and 0.5 h prior to endotoxin, and at all concentrations (10(-9) to 10(-4)) when preincubated with macrophages for 2 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗