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Biomedical subjects

J C Ng

Publications and source records attributed to J C Ng.

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

Kinetics, dose response, tachyphylaxis and cross-tachyphylaxis of vascular leakage induced by endotoxin, zymosan-activated plasma and platelet-activating factor in the horse.

Vascular leakage induced by intradermal injection of endotoxin, zymosan-activated plasma (ZAP) and platelet-activating factor (PAF) was measured in nine Thoroughbreds using 125-iodine human serum albumin (125I-HSA) as a marker in the blood. ZAP and PAF produced dose-dependent increases in vascular permeability with the maximum occurring within the first 15 min after injection. The vascular leakage induced by endotoxin was also dose-dependent, but the maximum occurred 2 h after intradermal injection. Intradermal sites previously injected with endotoxin were refractory to a second injection of endotoxin for up to 5 days. However, sites injected with endotoxin and re-injected with either ZAP or PAF remained responsive with increased vascular leakage compared to saline injected control sites re-injected with either ZAP or PAF. Diminished response to endotoxin challenge may contribute to the poor prognosis of endotoxaemia in the horse.

Animals↗
PubMed1995

Phenylbutazone in racing greyhounds: plasma and urinary residues 24 and 48 hours after a single intravenous administration.

The concentrations of phenylbutazone (PBZ), oxyphenbutazone (OPBZ) and gammahydroxyphenylbutazone (OHPBZ) in plasma and urine from 50 Greyhounds 24 and 48 h after the intravenous administration of a single dose of PBZ (30 mg/kg) were measured. The 24 h plasma concentrations of OPBZ and OHPBZ, the 48 h plasma concentration of OHPBZ and the 24 h urinary concentration of PBZ were normally distributed, while log transformations were required before the 24 h plasma concentration of PBZ and the 24 and 48 h urinary concentrations of OPBZ and OHPBZ became normally distributed. The 95%, 99%, 99.9% and 99.99% upper predicted confidence intervals for both 24 h and 48 h plasma and urinary concentrations demonstrated wide potential variation in the concentration of the analytes should PBZ be administered to Greyhounds. The 24 h plasma and urinary concentrations of PBZ were weakly correlated, but no similar relationship existed for OPBZ or OHPBZ. The urinary concentrations of each analyte were not affected by the trainer or sex of the Greyhound or the urinary pH. We conclude that it would be impossible to predict the timing of the PBZ administration or the plasma concentration of PBZ from the measurement of the concentration of PBZ in a single sample of urine.

Animals↗
PubMed1994

The magical and medicinal usage of Stangeria eriopus in South Africa.

The underground caudex of the cycad Stangeria eriopus is used extensively by several ethnic groups in South Africa, mainly as an ingredient in magical potions but also as an emetic. An assessment of two main outlets showed that 3410 plants were sold in the month of July 1992; continued usage of this material now threatens the remaining plant populations. A proximate analysis of the caudex material gives high carbohydrate content with only small percentages of fat, protein, fibre and ash. An unusually high content of sodium sulphate may explain the efficacy of Stangeria-containing preparations as an emetic. The phytosterols sitosterol and stigmasterol are present in a 4:1 ratio while the fatty acid component comprises palmitic, oleic, stearic and arachidic acids. Twelve amino acids were identified in the material, including the non-protein amino acids beta-alanine, gamma-aminobutyric acid and pyroglutamic acid. The candidate neurotoxin beta-N-methylamino-L-alanine could not be detected but cycasin is present at the levels of 0.17% and 0.21% in fresh and dry caudex material, respectively and appears to be accompanied by the related toxin, macrozamin.

Attitude to Health↗
PubMed1994

Concentration of ptaquiloside, a major carcinogen in bracken fern (Pteridium spp.), from eastern Australia and from a cultivated worldwide collection held in Sydney, Australia.

Two surveys of bracken fern for the concentration of the carcinogen ptaquiloside (PT) have been carried out, one of bracken fern from the eastern side of Australia and the other from a worldwide collection of bracken clones held in Sydney Australia. Bracken from eastern Australia contained concentrations of ptaquiloside ranging from 0 to 12,945 micrograms PT/g. From 91 samples 15% contained greater than 5,000 micrograms PT/g and 57% of samples contained more than 1,000 micrograms PT/g bracken on the dry weight basis. Ptaquiloside concentrations were highest in Pteridium revolutum and from P. esculentum from areas where bovine enzootic haematuria was known to occur. Bracken from the cultivated bracken clone collection from world-wide sources tended to have lower concentrations of ptaquiloside ranging from 0 to 9,776 micrograms PT/g. From 77 samples, 8% contained more than 5,000 micrograms PT/g and 35% contained more than 1,000 micrograms PT/g bracken. Samples from both the eastern Australia survey and the Australian representatives in the worldwide collection showed significantly higher concentrations of PT in the P. esculentum collected from the more southern states. In samples from the worldwide collection there were no statistical differences in the concentrations of PT in bracken between taxa.

Analysis of Variance↗
PubMed1993

Vascular leakage induced by histamine, bradykinin, serotonin and prostaglandin E2 in greyhounds.

Vascular leakage induced by intradermal injection of histamine, bradykinin and serotonin alone and co-injected with prostaglandin E2 was measured in Greyhounds using 125iodine-labelled human serum albumin (125I-HSA) as a marker in the blood. Histamine and bradykinin produced dose-dependent vascular leakage. At equimolar concentrations, histamine was more than twice as potent as bradykinin. Serotonin did not induce vascular leakage and was irritant. Prostaglandin E2 did not induce significant vascular leakage (maximum 5 microL) when injected alone, but when co-injected with histamine and bradykinin, the vascular leakage of both histamine and bradykinin was increased. This effect was more pronounced if lower concentrations of histamine and bradykinin were injected. The induced vascular leakage was greatest during the first five minutes of lesion development for histamine, during the second five minutes of lesion development for bradykinin, and the synergistic effect of prostaglandin E2 was maximal during the third five minute period of lesion development.

Animals↗
PubMed1993

Free radical oxidation products in plasma and synovial fluid of horses with synovial inflammation.

Free radical oxidation products, namely conjugated dienes, ultraviolet fluorescence (excitation 325 nm, emission 395 nm) and visible fluorescence (excitation 360 nm, emission 460 nm) were measured in equine synovial fluid exposed to free radicals in vitro and in the plasma and synovial fluids of horses with synovial effusions. The synovial effusions were induced by intra-articularly administered carrageenin (0.3 ml, 1%), which rarely resulted in clinical lameness. The free radicals were generated in vitro by mixtures of iron and ethylene diamine tetra acetate (Fe/EDTA) or mixtures of hypoxanthine and xanthine oxidase (HX/XO). The conjugated diene concentrations and intensity of ultraviolet fluorescence were negligible in plasma and synovial fluid specimens. No increase resulted from incubation of synovial fluids with either a free radical generating system or as a result of the induced inflammation. The intensity of visible fluorescence did not increase in specimens incubated with Fe/EDTA. However, the intensity of visible fluorescence increased in specimens incubated with HX/XO, in synovial effusions induced by carrageenin, in plasma and in synovial fluids aspirated from saline injected controls. The results indicate that the intensity of visible fluorescence of equine synovial fluid increases after exposure to free radicals and during synovitis in the horse, suggesting a possible role for free radicals in the pathogenesis of equine inflammatory joint disease.

Acute Disease↗
PubMed1992

Specific activation of glucuronide prodrugs by antibody-targeted enzyme conjugates for cancer therapy.

Cancer chemotherapy may be improved by increasing antineoplastic drug specificity for tumor cells. We have synthesized a glucuronide prodrug that can be enzymatically converted to an antineoplastic agent at tumor cells that are able to bind beta-glucuronidase-monoclonal antibody conjugates. The glucuronide prodrug BHAMG, the tetra-n-butyl ammonium salt of (p-di-2-chloroethylaminophenyl-beta-D-glucopyranoside) uronic acid, was 150 times less toxic than the parent drug, N,N-di-(2-chloroethyl)-4-hydroxyaniline, to HepG2 human hepatoma cells and over 1000-fold less toxic than the parent drug to AS-30D rat hepatoma cells in vitro. In the presence of beta-glucuronidase, BHAMG was activated and became as toxic as the parent drug N,N-di-(2-chloroethyl)4-hydroxyaniline. A conjugate (RH1-beta G) was formed by linking beta-glucuronidase to a monoclonal antibody which binds to an antigen expressed on the surface of AS-30D cells. The concentration of BHAMG causing 50% inhibition of AS-30D cellular protein synthesis was reduced over 1000-fold, from greater than 770 microM to less than 0.74 microM after these cells were preincubated with RH1-beta G. Specificity of BHAMG activation at antigen-positive cells was shown by monoclonal antibody RH1 blocking of RH1-beta G conversion of BHAMG to toxic drug and by the inability of BHAMG to be converted to active drug when antigen-negative control cells were preincubated with RH1-beta G. Our results show that the targeted-beta-glucuronidase activation of BHAMG can increase the specificity of chemotherapy for rat hepatoma in vitro and suggest that the targeted activation of glucuronide prodrugs may be useful for cancer therapy.

Aniline Mustard↗
PubMed1991

Prediction in road safety studies: an empirical inquiry.

Studies about the road safety effect of interventions are usually retrospective quasi-experiments. In these, one key task is to predict what would have been the safety of the treated group without the intervention. Such predictions can be made by several methods, one of which is to use a "comparison group." We use 26 yearly counts of reported injury accidents for the Canadian provinces to examine which of several simple methods of prediction would have historically predicted best. We find that the use of more data does not always improve prediction. How well one predicts depends not only on the amount of data used but also on the extent to which the prediction method is in accord with the unknown time trend behind the accident counts. We also find that the use of a comparison group to predict is not always better than predicting that this year's count will be the same as last year's. In addition, the intuitive notion that a good comparison group is that which is thought similar to the treated group is too simple. Both similarity and size (as measured by the number of accidents) are important. Moreover, whatever preconceived notions of similarity we had, were contradicted by the data. If the history of accident counts on the treatment group and on several possible comparison groups is available, a simple method to select the most suitable comparison group is suggested.

Accidents, Traffic↗
PubMed1991

Assessment of histamine, bradykinin, prostaglandins E1 and E2 and carrageenin as vascular permeability agents in the horse.

The vascular leakage induced by histamine, bradykinin, serotonin and prostaglandin E1 and E2 was assessed. The test agents were injected intradermally into the shaved thoracic skin of horses and the vascular leakage estimated either semi-quantitatively by recording the diameter of the lesions or by measuring the actual volume of extravasated plasma in microliters using iodine-125-labelled human serum albumin (125I-HSA) as a marker in the blood plasma. Using the latter method, the vascular leakage induced by carrageenin and the effect of coadministered prostaglandins E1 and E2 upon the vascular leakage of both histamine and bradykinin were also investigated. No obvious lesions resulted when serotonin (10(-2) mol/l) was injected but histamine and bradykinin produced circular lesions which increased in diameter for approximately 30 min. The size of the lesions and volume of extravasated plasma was dose dependent. On a molar basis, bradykinin (10(-6) mol/l, 10(-5) mol/l) was more potent than histamine but they were equipotent at 10(-4) mol/l. The size of the lesions induced by carrageenin were independent of their anatomical location on the thorax. Except for the second hour, the hourly volume of vascular leakage increased until the fifth hour when the experiment was concluded. The maximum vascular leakage resulting from the injection of prostaglandin E1 or E2 (1, 10, 100 or 1000 ng) was 7 microliters but when co-administered with bradykinin (10(-6) mol/l), the volume of leaked plasma increased from 29 to 78 microliters. No synergy was observed when either prostaglandin was co-administered with histamine (10(-5) mol/l).

Administration, Cutaneous↗
PubMed1990

Superoxide production by stimulated equine polymorphonuclear leukocytes--inhibition by anti-inflammatory drugs.

Polymorphonuclear leukocytes (PMNLs) were isolated from an inflammatory exudate induced in the intercarpal joints of horses by an administration of carrageenin. Their superoxide production at rest and following stimulation with either serum-treated zymosan (STZ) or phorbol myristate acetate (PMA) was measured by cytochrome-c reduction. Stimulation of the cells increased the cytochrome-c reduction 10-15 times that of resting cells. The maxima were 20 nmol of reduced cytochrome-c per 10(6) cells per ml at 120 min (STZ) and 35 nmol of reduced cytochrome-c per 10(6) cells per ml at 60 min (PMA). The maximum inhibition of the cytochrome-c reduction by superoxide dismutase (Palosein) was 83.6% (STZ stimulation) and 72.1% (PMA stimulation). The non-steroidal anti-inflammatory drugs, phenylbutazone, salicylic acid, aspirin, sodium salicylate in addition to D-penicillamine and dimethylsulfoxide caused dose-dependent inhibition of the cytochrome-c reduction when the cells were stimulated by PMA. The maximum inhibitions were 64% and 36% for aspirin (10(-2) M), 32% and 17% for phenylbutazone (10(-3) M), 15% and 31% for dimethylsulfoxide (6.4 x 10(-1) M), 32% and 19% for salicylic acid (10(-2) M), 0% and 17% for sodium salicylate (10(-2) M) and 2.2% and 2.5% for D-penicillamine (10(-4) M) when the cells were stimulated by STZ and PMA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Copper salicylate and copper phenylbutazone as topically applied anti-inflammatory agents in the rat and horse.

Topically applied copper phenylbutazone, phenylbutazone, copper salicylate, salicylate and dimethylsulfoxide glycerol (80:20) were investigated as anti-inflammatory agents in rats and horses. Dimethylsulfoxide and glycerol (80:20) or dimethylsulfoxide, ethanol and glycerol (60:20:20) were used as the drug solvents. Subcutaneously administered carrageenin was used to induce inflammatory oedema, either in the paws of rats or the alar fold of the horse. The severity of the oedema and the anti-inflammatory effect of the drugs were assessed by measuring changes in the paw or alar-fold diameters. Copper salicylate and copper phenylbutazone were effective inhibitors of the inflammatory oedema in both species, but dimethylsulfoxide:glycerol (80:20) was not. In the rat, copper salicylate and copper phenylbutazone were superior anti-inflammatory agents compared to either salicylate or phenylbutazone, respectively. Following the topical application of four times the recommended daily dose of copper phenylbutazone to the horse for 5 days, minor skin irritation occurred and trace concentrations of phenylbutazone (maximum 0.6 microgram/ml) and negligible concentrations of oxyphenbutazone and gamma-hydroxyphenylbutazone were detected in the plasma.

Administration, Topical↗
PubMed1990

Effect of palosein (superoxide dismutase) and catalase upon oxygen derived free radical induced degradation of equine synovial fluid.

The effect of oxygen derived free radicals (ODFR) upon the specific viscosity of equine synovial fluid was studied. ODFR were generated either by a mixture of ferrous iron and EDTA (Fe/EDTA) or by a mixture of hypoxanthine and xanthine oxidase (HX/XO). Incubation of the synovial fluid with both free radical generating systems decreased its specific viscosity. When the synovial fluid was incubated with Fe/EDTA the specific viscosity of the synovial fluid was reduced rapidly. By 2 mins, it was 53 +/- 3 per cent of the original specific viscosity and by 30 mins it was reduced to 39 +/- 5 per cent. In the HX/XO system, the specific viscosity was 75 +/- 4 per cent of the original specific viscosity at 10 mins and by 50 mins it was reduced to 55 +/- 3 per cent. Palosein (superoxide dismutase) was an effective inhibitor of the free radical induced reduction of the viscosity of the synovial fluid when the free radicals were generated with HX/XO but not with Fe/EDTA. Catalase was moderately effective as an inhibitor of reduction in specific viscosity of the synovial fluid when the free radicals were generated by either system. Only minor synergy resulted when mixtures of Palosein and catalase were tested for inhibition of Fe/EDTA induced reduction in the specific viscosity of equine synovial fluid. The results indicate that Palosein may protect equine synovial fluid from the effects of the superoxide radical (O2-) but not from the hydroxyl radical (OH.).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Acute phase response in horses: changes in plasma cation concentrations after localised tissue injury.

An acute phase reaction was elicited in four horses to which Freund's adjuvant was administered intramuscularly. The localised inflammation was accompanied by changes in the plasma concentrations of copper, iron and zinc. The plasma copper concentration, the plasma ceruloplasmin copper concentration and the ceruloplasmin oxidase activity in the plasma steadily increased to a maximum 24 days after the administration of the adjuvant. At this time, the plasma copper concentration was 2.2 micrograms/ml, a 90 per cent increase over the baseline concentration. The ratio of the concentration of plasma ceruloplasmin copper to plasma copper remained constant, indicating that the non-ceruloplasmin bound copper component of the plasma is also an acute phase reactant in the horse. The plasma zinc and iron concentrations decreased to 59 per cent and 30 per cent of their respective baseline concentrations and the severity of the inflammation appeared to influence the plasma concentrations of each metal. Weak correlations between the plasma fibrinogen concentration and the plasma copper and zinc concentrations of 25 horses with plasma fibrinogen concentrations of 5 g/litre or greater indicated that a single measurement of plasma copper concentration is not useful in the diagnosis of non-specific inflammatory disorders of the horse. However, the results suggest that the plasma copper concentrations in serial samples may be used to monitor the resolution of inflammatory disorders in the horse.

Acute-Phase Reaction↗