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Biomedical subjects

J N Moore

Publications and source records attributed to J N Moore.

At least 91 records · Page 5Linked to original sources

Effects of fenoldopam on cecal blood flow and mechanical activity in horses.

Lateral cecal arterial blood flow, carotid arterial pressure, heart rate, and mechanical activity in the duodenum, right ventral colon, cecal body, and cecal apex were measured in 6 conscious healthy horses for 60 minutes during and for 120 minutes after IV infusion of 0.9% NaCl solution (control) or fenoldopam. There were no significant changes in these measurements during or after infusion of 0.9% NaCl (saline) solution. Fenoldopam, a selective dopamine-1 receptor agonist, was administered in saline solution at dosages of 0.01, 0.05, and 0.1 micrograms/kg/min. Intravenous infusion of fenoldopam at 0.01 microgram/kg/min significantly increased heart rate, but did not change average carotid arterial pressure or lateral cecal arterial blood flow. Intravenous infusion of fenoldopam at both 0.05 and 0.1 microgram/kg/min significantly increased heart rate, significantly decreased average carotid arterial pressure, and significantly increased lateral cecal arterial blood flow. Intravenous infusion of fenoldopam at 0.01, 0.05, and 0.1 microgram/kg/min did not significantly change the mechanical activity measured by the area under the strain gauge deflection curve for the duodenum, right ventral colon, cecal body, or cecal apex. These results suggest that dopaminergic-1 receptors are present on the colonic vasculature of horses. There was no evidence, however, that dopaminergic-1 receptors exist on the visceral smooth muscle of the duodenum, right ventral colon, cecal body, or cecal apex of horses.

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

Comparative effects of cholera toxin, Salmonella typhimurium culture lysate, and viable Salmonella typhimurium in isolated colon segments in ponies.

Isolated segments of left dorsal colon and a side-to-side colocolostomy (between the left ventral colon and left dorsal colon) were surgically created in 6 adult ponies. Four segments, each separated by an empty segment, were inoculated (20 ml) with 1 of the following 4 solutions: phosphate buffered saline solution (PBSS)/1% polyethylene glycol (PEG); purified cholera toxin in PBSS/1% PEG (5 micrograms cholera toxin/ml of PBSS/1% PEG); lyophilized Salmonella typhimurium UCD 1755 culture lysate, reconstituted in PBSS/1% PEG; and viable S typhimurium UCD 1755 (10(8) organisms/ml of PBSS/1% PEG). Twenty hours following inoculation of the treatment solutions into the isolated colon segments, the ponies were reanesthetized. Fluid accumulation in the isolated segments was measured, and tissue samples from isolated segments were taken for examination by light microscopy and electron microscopy, and for measurement of mucosal cyclic adenosine monophosphate levels. There was fluid accumulation in segments inoculated with cholera toxin in 4 ponies (29.5 +/- 12.7 ml), and in segments inoculated with S typhimurium UCD 1755 culture lysate in 3 ponies (14.0 +/- 8.7 ml). There was no fluid accumulation in segments inoculated with either the control solution (PBSS/1% PEG) or viable S typhimurium UCD 1755. There was significantly (P less than 0.05) less cyclic adenosine monophosphate in segments inoculated with cholera toxin, Salmonella lysate, and viable Salmonella, compared with control segments. Histologically, there were minimal changes in control segments, consisting of mild to moderate submucosal edema and capillary congestion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of immunity to core lipopolysaccharides (LPS) on the production of thromboxane and prostacyclin by equine peritoneal macrophages.

An experiment was designed to determine whether a change in the ability of macrophages to respond to lipopolysaccharides (LPS) of gram-negative bacteria was involved in the development of cross-reactive immunity to endotoxemia. The endotoxin-induced production of thromboxane A2(TxA2) and prostacyclin (PGI2) by peritoneal macrophages from horses which were hyperimmunized against the common core region of LPS were compared to those in unimmunized horses. Bacterins used for induction of core LPS immunity were prepared from the J-5 mutant of Escherichia coli 0111:B4, and the R 595 mutant of Salmonella minnesota. Serum antibody titers to core LPS were determined by an indirect enzyme-linked immunosorbent assay. Immunized horses had a marked increase in titer to core LPS (p less than 0.05), while there was no change in titer in unimmunized control horses. The only significant difference in the in vitro LPS-induced production of TxA2 and PGI2 by peritoneal macrophages between immunized and control horses was a greater production of TxA2 by macrophages from immunized horses in response to 10 ng/ml LPS (p less than 0.05). Results of this experiment do not support the concept that cross-reactive immunity to LPS is attended by reduced production of TxA2 and PGI2 by equine peritoneal macrophages.

Animals↗

Evaluation of the opsonic capacity of core lipopolysaccharide antiserum of equine origin against smooth Escherichia coli 0111:B4, using macrophage chemiluminescence.

A study was performed to determine whether equine antiserum to core lipopolysaccharide (LPS) would enhance phagocytosis of smooth gram-negative (GN) organisms by equine macrophages. Five healthy adult horses (group A) were immunized with a bacterin prepared from the J-5 mutant of Escherichia coli 0111:B4 and Salmonella minnesota R595 to produce antibodies to core LPS. Five horses (group B) served as nonimmunized controls and were given physiologic saline solution instead of the rough mutant bacterin. Serum antibody titers to core LPS and to smooth E coli 0111:B4 were determined by indirect ELISA. Four serum pools were prepared: pool 1 = sera from horses in group B prior to immunization; pool 2 = sera from horses in group A prior to immunization (preimmune serum); pool 3 = sera from horses in group B, 7 days after the last saline injection; pool 4 = sera from horses in group A, 7 days after the last immunization (core LPS antiserum). The serum pools, either unheated or heated 30 minutes at 56 C, in 3 dilutions (1/50, 1/100, 1/500) were used to opsonize smooth E coli 0111:B4 in an assay of equine peritoneal macrophage chemiluminescence (CL). Peritoneal fluid was collected from clinically normal horses and the macrophages were purified by adherence to borosilicate glass scintillation vials. Each serum type and dilution was added to triplicate vials containing 10(7) colony-forming units of E coli 0111:B4. Luminol-dependent CL was measured with a liquid scintillation counter in the out-of-coincidence mode. Each serum dilution was tested in duplicate vials without bacteria to asses serum-induced nonspecific CL.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In vitro reactivity of digital arteries and veins to vasoconstrictive mediators in healthy horses and in horses with early laminitis.

The in vitro reactivity of vasoconstrictive mediators that are implicated in acute laminitis was determined in palmar and plantar digital arteries and veins obtained from healthy horses and in palmar digital vessels of horses with early laminitis (Obel grade I). To obtain baseline reactivity data, 3 experiments were conducted, using healthy horses: (1) the reactivity of palmar and plantar digital arteries and veins to angiotensin II, norepinephrine, and 5-hydroxytryptamine (serotonin) were compared; (2) the direct effects of bacterial endotoxin on vascular reactivity were assessed; and (3) the reactivity of palmar digital arteries and veins to angiotensin II, norepinephrine, prostaglandin F2 alpha (PGF2 alpha), serotonin, and a thromboxane-endoperoxide analog (U46619) were determined. The vascular reactivity of these same 5 vasoconstrictors then was determined in horses with early laminitis and was compared with data from healthy (control) horses. Obel grade-I laminitis was experimentally induced in horses, using carbohydrate overload. Dose responses were conducted for each agent at concentrations between 10(-8)M and 10(-4)M. The potency of a drug was defined as the mean effective concentration necessary to induce 50% of maximal contraction (EC50). There were no differences in EC50 concentrations and in maximal contractions between forelimb and hind limb arteries and veins for angiotensin II, norepinephrine, and serotonin. Incubation with endotoxin had no effect on the reactivity of arteries and veins to angiotensin II, norepinephrine, and serotonin.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Effects of dopamine administration on cecal mechanical activity and cecal blood flow in conscious healthy horses.

Lateral cecal arterial blood flow, carotid arterial pressure, heart rate, and mechanical activity of the circular and longitudinal muscle layers of the cecal body were measured in 7 conscious healthy horses during IV infusion of physiologic saline solution for 60 minutes (control), during a 60-minute IV infusion of dopamine (at dosages of 1, 2.5, and 5 micrograms/kg/min), and for 60 minutes after IV infusion of dopamine. The mean values for lateral cecal arterial blood flow during IV infusion of dopamine at a dosage of either 1 or 2.5 micrograms/kg/min were not significantly different from the mean values for lateral cecal arterial blood flow during IV infusion of saline solution. The mean values for lateral cecal arterial blood flow, however, were significantly greater during IV infusion of dopamine at a dosage of 5 micrograms/kg/min than the mean values for lateral cecal arterial blood flow during IV infusion of saline solution. Intravenous infusion of dopamine at 1 and 2.5 micrograms/kg/min did not significantly change the mean values for carotid arterial pressure. In contrast, the mean values for carotid arterial pressure were significantly less during IV infusion of dopamine at dosages of 2.5 and 5 micrograms/kg/min than during infusion of saline solution. The mean values for heart rate were not significantly altered by infusion of dopamine at a dosage of either 1 or 2.5 micrograms/kg/min, but infusion of dopamine at a dosage of 5 micrograms/kg/min significantly increased heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Recognition and treatment of endotoxemia.

Endotoxemia occurs secondary to several diseases that disrupt the mucosal barrier to bacteria or their toxins. The effects of endotoxemia are varied and are mediated by a wide variety of proinflammatory substances. Although evidence certainly exists to incriminate the cyclooxygenase-derived products of arachidonic acid in the early responses to endotoxemia, various other mediators must also be considered. Treatment presently involves fluid replacement, correction of acid-base abnormalities, augmentation of cardiovascular function, and inhibition of cyclooxygenase activity.

Animals↗

Composite speech spectrum for hearing and gain prescriptions.

Average long-term RMS 1/3-octave band speech spectra were generated for 30 male and 30 female talkers. The two spectra were significantly different in both low and high frequency bands but were similar in the mid-frequency region. It was concluded that a single spectrum could validly be used to represent both male and female speech in the frequency region important for hearing aid gain prescriptions: 250 Hz through 6300 Hz. In addition, the male and female spectra were compared with analogous spectra reported by Byrne (1977) and Pearsons, Bennett, and Fidell (1977). For each sex, significant differences were found among the three spectra in a few frequency bands. The best estimate of the average speech spectrum for each sex was obtained from a weighted average of the three sets of data, excluding the significantly different data points. The long-term RMS 1/3-octave band speech spectrum for male and female talkers combined was derived for use in hearing aid gain prescriptions.

Adult↗

Iron-carbonyl bond geometries of carboxymyoglobin and carboxyhemoglobin in solution determined by picosecond time-resolved infrared spectroscopy.

The iron-carbonyl geometries in carboxymyoglobin (MbCO) and carboxyhemoglobin (HbCO) in ambient temperature solution have been investigated using picosecond time-resolved infrared spectroscopy. Polarized infrared and visible beams were used to monitor the change in infrared absorbance of the bound CO stretch bands on photodissociation of the ligand. The ratio of the change in absorbance for perpendicular and parallel relative polarizations of the photolysis and infrared probe beams is directly related to the angle between the ligand bond axis and the normal to the heme plane. Ratios, and hence the angles, have been obtained for the configurations giving rise to the principal CO stretch infrared absorption bands of HbCO and MbCO: 18 degrees for the 1951 cm-1 band of HbCO; 20 degrees and 35 degrees, respectively, for the 1944 cm-1 and 1933 cm-1 bands of MbCO. Structures consistent with x-ray diffraction and the picosecond experiments reported here are proposed for MbCO and HbCO in which the Fe-C bond tilts to the heme normal and the Fe-C-O angle differs significantly from 180 degrees.

Carbon Monoxide↗

Distribution of short-term rms levels in conversational speech.

For 30 male and 30 female talkers, distributions of short-term rms speech levels, relative to the corresponding long-term rms levels, were determined in each of eight 1/3-oct bands for six short-term measurement intervals. Consecutive, Hanning-windowed, 20-ms time records were combined to produce nominal measurement intervals ranging from 20 to 120 ms. For each measurement interval, mean distributions of short-term rms speech levels relative to long-term levels were very similar for male and female talkers, and intertalker differences were small, especially for short-term amplitudes above the median level. The distribution of short-term rms speech levels relative to long-term rms speech levels varied with measurement interval for the short-term measurements. The effects of measurement interval was least for the highest amplitude speech levels and increased as speech levels decreased. For short-term amplitudes above the median level, the effect of measurement interval was greater in higher frequency regions, whereas for short-term amplitudes below the median level, measurement interval had the greatest effect on the lower frequency bands. These data may facilitate comparisons among investigations using different measurement intervals. In addition, they have implications for amplification strategies.

Female↗

Endotoxin-induced procoagulant activity in equine peripheral blood monocytes.

Increasing evidence has demonstrated the importance of monocyte procoagulant activity (PCA) in the pathogenesis of coagulopathies in a variety of diseases. Because endotoxin precipitated coagulopathies are common sequelae to intestinal ischemia/endotoxemia in the equine species, we investigated the ability of equine peripheral blood monocytes to express PCA. Monocytes isolated from five healthy adult horses were incubated in vitro with Escherichia coli endotoxin (10 micrograms), and the PCA was measured by the ability of cellular lysates to accelerate the clotting times of equine plasma in a modified one-stage recalcification assay. Equine monocyte PCA was identified as thromboplastin based on lack of clot formation in factor VII-deficient plasma. The induction of PCA occurred as early as 2 hr after endotoxin exposure, peaked at 6 hr (396% increase), and then gradually declined. The amount of PCA was proportional to the dose of endotoxin (0.01 to 100 micrograms) and the number of monocytes. Neither platelets nor neutrophils produced PCA, either in the absence or presence of endotoxin (1 microgram). Lymphocytes at a concentration of 4 x 10(6)/ml RPMI did produce a significant amount of PCA, compared to the time-matched controls. Co-incubation of neutrophils or lymphocytes with monocytes did not alter the PCA, whereas coincubation of platelets and monocytes significantly enhanced the expression of PCA. This effect was further augmented by the addition of endotoxin (1 microgram).

Animals↗

Effects of xylazine on cecal mechanical activity and cecal blood flow in healthy horses.

Mechanical activity of the cecal body, lateral cecal arterial blood flow, carotid arterial pressure, and heart rate were measured in 6 conscious healthy horses 30 minutes before and for 120 minutes after IV administration of xylazine at dosages of 1.1 mg/kg of body weight, 0.55 mg/kg, and 0.275 mg/kg. Xylazine at a dosage of 1.1 mg/kg reduced the mean motility index (the product of the mean amplitude of contractions and the total duration of contractile activity divided by the recording time) of the circular and longitudinal muscle layers for the first, second, third, and fourth 30-minute periods after administration of xylazine. Xylazine at a dosage of 0.55 mg/kg reduced the motility index of the circular and longitudinal muscle layers for the first and second 30-minute periods after administration of xylazine. Xylazine at a dosage of 0.275 mg/kg reduced the motility index of the circular and longitudinal muscle layers for the first 30-minute period after administration of xylazine. Mean lateral cecal arterial blood flow was significantly (P less than 0.05) lower than the base-line value at 2 and 4 minutes after administration of all 3 xylazine dosages and at 8 minutes after administration of xylazine dosages of 1.1 mg/kg and 0.55 mg/kg. All dosages of xylazine caused transient hypertension and bradycardia, followed by hypotension.

Animals↗

Effects of multiple low doses of flunixin meglumine on repeated endotoxin challenge in the horse.

Previous work has shown repeated low doses of flunixin meglumine (FM) inhibit thromboxane production in normal horses. Enhanced concentrations of thromboxane in serum occurred after the drug therapy was discontinued. Our study was performed to evaluate the effects of low doses of FM in horses repeatedly challenged with endotoxin. Group I horses received E. coli endotoxin (0.1 microgram/kg IV) at 0 and 90 h. Group II horses received endotoxin and were also treated with FM (0.25 mg/kg IV) at 2, 10, 18, 26, 34, and 42 h after the initial administration of endotoxin. Clinical signs of endotoxemia were observed in all horses, but FM treated horses recovered more rapidly. The leukopenic response after endotoxin was attenuated in Group II following the second dose. Serum thromboxane (TxB2) decreased after the initial administration of endotoxin and remained below baseline values throughout the study. Serum TxB2 concentrations were not different between the groups. Plasma TxB2 and 6-keto-PGF1 alpha concentrations were increased after the initial endotoxin injection. In Group II, plasma TxB2 levels declined rapidly after FM administration and remained low. After the second dose of endotoxin, Group I horses had a mild rise and decline in TxB2 and 6-keto-PGF1 alpha concentrations, respectively. Thromboxane B2 levels in Group II changed little after the second dose of endotoxin, but a dramatic increase in 6-keto-PGF1 alpha concentrations occurred. These results suggest that multiple low doses of FM to horses with endotoxemia cause a selective and sustained suppression of TxB2 production and an enhancement of 6-keto-PGF1 alpha.

6-Ketoprostaglandin F1 alpha↗

Low dose flunixin meglumine: effects on eicosanoid production and clinical signs induced by experimental endotoxaemia in horses.

The efficacy of low doses of flunixin meglumine in reducing eicosanoid generation and clinical signs in response to experimentally induced endotoxaemia was investigated. Thromboxane B2 and 6-keto-prostaglandin F1 alpha were measured in serum and plasma by radioimmunoassay. Plasma flunixin concentrations were determined by high performance liquid chromatography and pharmacokinetic parameters derived non-compartmentally. In horses administered flunixin meglumine before endotoxin challenge, a significant suppression in plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha generation was observed. Elevations in blood lactate were significantly suppressed in horses pretreated with 0.25 mg/kg bodyweight flunixin meglumine. Reduction of the clinical signs of endotoxaemia by flunixin meglumine was dose dependent. Low doses of flunixin inhibited eicosanoid production without masking all of the physical manifestations of endotoxaemia necessary for accurate clinical evaluation of the horse's status.

6-Ketoprostaglandin F1 alpha↗

Endotoxin-induced production of thromboxane and prostacyclin by equine peritoneal macrophages.

Equine peritoneal macrophages were isolated and cultured in vitro to assess their ability to produce thromboxane (TxA2) and prostacyclin (PGI2) in response to endotoxin. Peritoneal macrophages (2.5 x 10(6)/ml) were incubated in tissue culture media, containing 1) no additive (nonstimulated control), 2) endotoxin (0.5 to 100 ng/ml) or 3) the calcium ionophore, A23187 (0.95 microM) for two and six h. Concentrations of the stable metabolites of TxA2 and PGI2 thromboxane B2 (TxB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), in the incubation media were determined by radioimmunoassay. The concentrations of both metabolites increased from two to six h incubation. Endotoxin increased the production of TxA2 and PGI2 over the nonstimulated control values at both two and six h and endotoxin-induced concentrations of 6-keto-PGF1 alpha were higher at six than at two h. The response of macrophages to A23187 was similar to endotoxin. Mean eicosanoid concentrations did not differ among the range of endotoxin concentrations at either time; however there was significant curvilinear regression between endotoxin concentration and TxB2 at both times, and between endotoxin and 6-keto-PGF1 alpha at two h. The results indicate that equine macrophages may be a significant source of TxA2 and PGI2 during endotoxemia.

6-Ketoprostaglandin F1 alpha↗

Effects of a specific thromboxane synthetase inhibitor in equine endotoxaemia.

Thromboxane A2 may play a major role in circulatory shock. In some species, thromboxane synthetase inhibitors have a beneficial effect on shock induced by endotoxin, trauma, sepsis and administration of arachidonate. In some shock models, however, results with thromboxane synthetase inhibitors have been conflicting. The effect of UK-38,485, a selective thromboxane inhibitor, was evaluated in ponies injected with endotoxin intraperitoneally. Four groups of ponies were used to compare the effects of endotoxin alone, UK-38,485 alone, treatment with UK-38,485 before endotoxin challenge and treatment with UK-38,485 after endotoxin challenge. Haematological, metabolic, eicosanoid and clinical responses in each group were evaluated. The results indicated that UK-38,485 is an effective inhibitor of thromboxane A2 generation following endotoxin challenge. Prostacyclin values were elevated compared with baseline in ponies administered UK-38,485 and endotoxin. However, prostacyclin values were not significantly different from those of ponies receiving endotoxin alone. Furthermore, UK-38,485 failed to attenuate the haematological, metabolic and clinical manifestations commonly seen in the pony after endotoxin challenge.

6-Ketoprostaglandin F1 alpha↗

HPLC determination and pharmacokinetics of thiabendazole and its major metabolite 5-OH thiabendazole in equine plasma.

Separate high performance liquid chromatographic methods were developed for thiabendazole (TBZ) and 5-hydroxy thiabendazole (5-OH-TBZ) determination in horse plasma using 1-methyl-2-phenyl benzimidazole (MPBZ) as an internal standard. In both methods TBZ and 5-OH-TBZ were extracted from plasma using organic solvents, injected on to a C-18 column, and eluents monitored by a fluorescence detector. However, mobile phase composition, extraction solvent as well as detector wavelength differed in the two methods. The linear range for TBZ was 0.02 to 0.77 microgram ml-1 while that for 5-OH-TBZ was 0.96 to 8.0 micrograms ml-1. A commercially available TBZ oral suspension was administered to four thoroughbred horses in the following manner: days 1 and 2, 44 mg kg-1; days 4 and 5, 440 mg kg-1. Blood samples were collected during the 24 hours after administration and then analysed for TBZ and 5-OH-TBZ. Half-lives (t1/2), maximum plasma concentrations (Cmax), area under plasma concentration time curves (AUC O-alpha), and relative apparent bioavailability (F), were determined using pharmacokinetic equations. The pharmacokinetic parameters varied in the following manner: 1.16 to 13.63 hours (t1/2), 12 to 131 micrograms ml-1 X hours (AUC O-alpha), 3.33 to 8.90 micrograms ml-1 (Cmax), 1.38 to 0.12 (F) after 44 mg kg-1 and 440 mg kg-1 doses, respectively. The ratios of concentrations of TBZ to 5-OH-TBZ after oral administration of TBZ, were significantly lower for 44 mg kg-1 than 440 mg kg-1 doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗