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1.
New Phytol ; 197(1): 19-35, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23110592

ABSTRACT

Resprouting as a response to disturbance is now widely recognized as a key functional trait among woody plants and as the basis for the persistence niche. However, the underlying mechanisms that define resprouting responses to disturbance are poorly conceptualized. Resprouting ability is constrained by the interaction of the disturbance regime that depletes the buds and resources needed to fund resprouting, and the environment that drives growth and resource allocation. We develop a buds-protection-resources (BPR) framework for understanding resprouting in fire-prone ecosystems, based on bud bank location, bud protection, and how buds are resourced. Using this framework we go beyond earlier emphases on basal resprouting and highlight the importance of apical, epicormic and below-ground resprouting to the persistence niche. The BPR framework provides insights into: resprouting typologies that include both fire resisters (i.e. survive fire but do not resprout) and fire resprouters; the methods by which buds escape fire effects, such as thick bark; and the predictability of community assembly of resprouting types in relation to site productivity, disturbance regime and competition. Furthermore, predicting the consequences of global change is enhanced by the BPR framework because it potentially forecasts the retention or loss of above-ground biomass.


Subject(s)
Fires , Germination , Plant Development , Plant Physiological Phenomena , Carbohydrate Metabolism , Carbon/metabolism , Climate Change , Ecosystem , Plant Roots/metabolism , Plant Roots/physiology , Plant Stems/metabolism , Plant Stems/physiology , Plants/metabolism , Seeds/metabolism , Seeds/physiology , Species Specificity , Wood/metabolism , Wood/physiology
2.
Ann Bot ; 99(4): 609-23, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17272303

ABSTRACT

BACKGROUND AND AIMS: The branch-base xylem structure of the endangered Wollemia nobilis was anatomically investigated. Wollemia nobilis is probably the only extant tree species that produces only first-order branches and where all branches are cleanly abscised. An investigation was carried out to see if these unusual features might influence branch-base xylem structure and water supply to the foliage. METHODS: The xylem was sectioned at various distances along the branch bases of 6-year-old saplings. Huber values and relative theoretical hydraulic conductivities were calculated for various regions of the branch base. KEY RESULTS: The most proximal branch base featured a pronounced xylem constriction. The constriction had only 14-31 % (average 21 %) of the cross-sectional area and 20-42 % (average 28 %) of the theoretical hydraulic conductivity of the more distal branch xylem. Wollemia nobilis had extremely low Huber values for a conifer. CONCLUSIONS: The branch-base xylem constriction would appear to facilitate branch abscission, while the associated Huber values show that W. nobilis supplies a relatively large leaf area through a relatively small diameter 'pipe'. It is tempting to suggest that the pronounced decline of W. nobilis in the Tertiary is related to its unusual branch-base structure but physiological studies of whole plant conductance are still needed.


Subject(s)
Tracheophyta/anatomy & histology , Water/metabolism , Extinction, Biological , Microscopy, Electron, Scanning , Tracheophyta/growth & development , Tracheophyta/metabolism , Xylem/anatomy & histology , Xylem/growth & development , Xylem/metabolism
3.
Ann Bot ; 92(6): 835-44, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14612379

ABSTRACT

Intact trees of Wollemia nobilis Jones, Hill and Allen (Araucariaceae) routinely develop multiple coppice shoots as well as orthotropic epicormic shoots that become replacement or additional leaders. As these are unusual architectural features for the Araucariaceae, an investigation was made of the axillary meristems of the main stem and their role in the production of epicormic and possibly coppice shoots. Leaf axils, excised from the apex to the base of 2-m-high W. nobilis plants (seedling origin, ex situ grown), were examined anatomically. Small, endogenous, undifferentiated (no leaf primordia, no vascular or provascular connections) meristems were found in the axils from near the shoot apex. In the more proximal positions about half the meristems sampled did not differentiate further, but became tangentially elongated to compensate for increases in stem diameter. In the remaining axils the meristems slowly developed into bud primordia, although these buds usually developed few leaf primordia and their apical 'domes' were wide and flat. Associated vascular development was generally restricted to provascular dedifferentiation of the cortical parenchyma, with the procambium usually forming a 'closed loop' that did not extend back to the secondary vascular tissues. Development of the meristems was very uneven with adjacent axils often at widely differing stages of development into buds. The study shows that, unlike most conifers, W. nobilis possesses long-lived meristematic potential in most, if not all, leaf axils. Unlike other araucarias that have been investigated, many of the meristems in the orthotropic main stem will slowly develop into bud primordia beneath the bark in intact plants. It appears likely that this slow but continued development provides a ready source of additional or replacement leaders and thus new branches and leaves.


Subject(s)
Tracheophyta/growth & development , Australia , Flowers/growth & development , Germination , Meristem/cytology , Meristem/growth & development , Seeds/physiology
5.
Vet Hum Toxicol ; 41(2): 67-70, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10192132

ABSTRACT

Sixteen Western Whiteface ewes were divided into 2 groups to determine the effects of plant maturity on liver function and weight gains. They were allowed to graze a greater than 95% pure stand of Kochia scoparia for 72 or 55 d. Four additional sheep (controls) were placed on weedy Bermuda grass pasture with the same water supply as the kochia-fed sheep. Body weights were determined on June 5, 1996 and on removal from the kochia pasture. Blood samples were collected at approximately 7-d intervals for serum chemistry profiles. Kochia scoparia plant samples were also randomly collected at 5-6 w intervals, oven dried, identified by date of collection and stored for later nutrient, oxalate, nitrate and sulfate analysis. Liver biopsies were performed pre-, mid- and post-study to assess morphologic changes. An almost exclusive diet (> 95%) of Kochia scoparia resulted in minimal elevations in serum GGT, suggesting mild hepatocellular injury, but was not associated with overt hepatic lesions or clinical disease. Other serum chemistry measurements were within normal ranges. Unlike for other domestic animal species, Kochia scoparia may be a useful grazing forage for sheep, offering little risk of toxicosis.


Subject(s)
Chenopodiaceae/toxicity , Liver/drug effects , Sheep/metabolism , Weight Gain/drug effects , Animal Feed , Animals , Female , Liver Glycogen/metabolism , Oxalates/metabolism , Sulfates/metabolism , gamma-Glutamyltransferase/blood
6.
Thromb Res ; 85(6): 455-64, 1997 Mar 15.
Article in English | MEDLINE | ID: mdl-9101638

ABSTRACT

Although hormone replacement therapy (HRT) appears to protect women from ischaemic heart disease (IHD), its use is associated with increased factor clotting activity (VIIc), an independent risk factor for IHD. The nature of this factor VII rise was therefore examined in a cross-sectional study of 279 women aged between 40 and 65 years. Ninety-four were pre-menopausal, 44 were post-menopausal and taking HRT, whilst 141 were post-menopausal non-users. For those women on oestrogen-only HRT, the mean factor VIIc was 144%, compared to 130% for post-menopausal non-users, and 116% for those on combined HRT. These differences were significant (p = 0.01). Oestrogen-only users also had significantly higher mean levels of factor VIIa (3.3 ng/ml) compared to non-users (2.2 ng/ml) and those on oestrogen-progestogen HRT (2.2 ng/ml-p = 0.015). In contrast for factor VII antigen the mean values of the three groups were similar. Analysis of the age-regression slopes showed a significant age-related rise in factor VIIc of 1.2% per annum (p < 0.01) for post-menopausal non-users. There was a similar increase in factor VII antigen (2.1%) but no rise in factor VIIa. For all HRT users there was no change with age for any of the factor VII measures. Thus the age-related rise in factor VIIc appears to be due to an increase in factor VII zymogen alone, and taking HRT seems to abolish such a rise. In contrast, the increased factor VIIc seen with oestrogen-only HRT appears to be secondary to factor VII activation.


Subject(s)
Aging/metabolism , Antigens/metabolism , Estrogen Replacement Therapy , Factor VII/metabolism , Adult , Aged , Body Mass Index , Drug Therapy, Combination , Estrogens/administration & dosage , Estrogens/therapeutic use , Factor VIIa/metabolism , Female , Humans , Mass Screening , Menopause , Middle Aged , Myocardial Ischemia/epidemiology , Progestins/administration & dosage , Progestins/therapeutic use , Risk Factors
7.
Nat Toxins ; 5(3): 115-20, 1997.
Article in English | MEDLINE | ID: mdl-9285916

ABSTRACT

The objective of this study was to assess the performance of chick embryo motoneuron cultures for the study of neurotoxicants. The response of motoneurons to the cytotoxic effects of picrotoxin, strychnine, bulbocapnine, and the naturally occurring excitatory amino acids, N-methyl D-aspartate (NMDA) and L-glutamate was studied by using a colorimetric viability assay using a vital dye. Selective cellular responses other than cell death were evaluated using a spectrofluorometric assay based on the response of an electrochromic styryl dye (Di-4-Anneps) to determine the expression of receptors for glycine, gamma-aminobutyric acid (GABA), NMDA, and L-glutamate by motoneurons in culture. The performance of chick embryo motoneurons (E7) in culture was useful and informative in neurotoxicologic studies. Motoneurons (E7) were found to express receptors for glycine, GABA, NMDA, and dopamine. The presence of the receptors and the inherent characteristics of motoneurons to generate action potential at an early embryonic stage (E4) makes this culture system a reliable model to conduct mechanistic studies as well as for predictive screening tests for agents of pharmacologic and toxicologic potential.


Subject(s)
Motor Neurons , Neurotoxins/toxicity , Spinal Cord/cytology , Animals , Cell Culture Techniques/methods , Chick Embryo , Membrane Potentials , Motor Neurons/pathology , Motor Neurons/physiology , Neurotoxins/analysis
8.
J Vet Pharmacol Ther ; 19(5): 376-81, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8905572

ABSTRACT

The effect of bacterial infection on antibiotic activity and penetration of parenterally administered ceftiofur into implanted tissue chambers was studied in cattle. Tissue chambers were implanted subcutaneously in the paralumbar fossae of eight calves (256-290 kg body weight). Approximately 80 days after implantation, the two chambers on one side of each animal were inoculated with Pasteurella haemolytica (10(6) CFU/chamber). Eighteen hours after inoculation, ceftiofur sodium was administered intravenously (5 mg/kg) to each of the calves. Non-infected chamber fluid, infected chamber fluid and heparinized blood samples were collected immediately before and at 1, 3, 6, 12 and 24 h after drug administration. Concentrations of ceftiofur and desfuroylceftiofur metabolites and ceftiofur-equivalent microbiological activity were measured by high-pressure liquid chromatography and microbiological assay respectively. Concentrations of ceftiofur and desfuroylceftiofur metabolites and anti-microbial activity in P. haemolytica-infected tissue chambers were significantly higher than those in non-infected tissue chambers at all sampling times, indicating that ceftiofur, regardless of the method used for analysis, localizes at higher concentrations at tissue sites infected with P. haemolytica. Antibiotic activity-concentration ratios were lower in plasma and infected chamber fluid compared with non-infected chamber fluid, suggesting that antibiotic was bound to proteins. However, higher antimicrobial activity in the infected chamber fluid compared with the non-infected chamber fluid, suggests that active drug is reversibly bound to proteins. Protein-bound desfuroylceftiofur may represent a reservoir for release of active drug at the site of infection in the animal.


Subject(s)
Cephalosporins/blood , Cephalosporins/pharmacokinetics , Pasteurella Infections/physiopathology , Animals , Cattle , Cattle Diseases , Cephalosporins/administration & dosage , Chromatography, High Pressure Liquid/veterinary , Diffusion Chambers, Culture , Dose-Response Relationship, Drug , Injections, Intravenous/veterinary , Pasteurella Infections/metabolism , Protein Binding , Software
9.
Vet Hum Toxicol ; 38(5): 329-32, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8888533

ABSTRACT

The pharmacokinetic disposition, urinary excretion and toxicity of tolonium chloride were determined after i.v. administration to sheep. Pretreatment with sodium nitrite significantly decreased the volume of the central compartment, apparent volume of distribution, area under the concentration-time curve, and total body clearance of tolonium chloride. Urinary excretion of tolonium chloride and its metabolite, leucotolonium chloride, together accounted for less than 15% of the administered dose in sheep receiving sodium nitrite and less than 10% of the administered dose in control sheep. The LD50 of tolonium chloride was 10 mg/kg with a 95% confidence interval of 7.35-13.60 mg/kg. Comparison with previously published data describing the pharmacokinetics and toxicity of a related compound, methylene blue, indicated that tolonium chloride has a higher volume of distribution and a narrower therapeutic index.


Subject(s)
Coloring Agents/pharmacokinetics , Sheep/blood , Tolonium Chloride/pharmacokinetics , Animals , Blood Chemical Analysis , Coloring Agents/administration & dosage , Coloring Agents/metabolism , Dose-Response Relationship, Drug , Female , Injections, Intravenous , Lethal Dose 50 , Oxidation-Reduction , Regression Analysis , Tolonium Chloride/administration & dosage , Tolonium Chloride/metabolism , Urine/chemistry
10.
Vet Hum Toxicol ; 38(1): 19-23, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8825743

ABSTRACT

Six groups of 4 rabbits each were treated as follows: Control; phenobarbital (PB); 3-methylcholanthrene (3MC); proadifen hydrochloride (SKF-525A); Artemisia filifolia and Helenium flexuosum. Prototype P450 inducers (PB and 3MC) increased basal hepatic cytochrome P450 content by 2-3 fold whereas the P450 inhibitor (SKF-525A) had no effect on basal cytochrome P450 content. PB-induction of hepatic microsomes significantly increased the rate of dealkylation of long alkyl chain alkoxyresorufin ethers, benzyloxyresorufin and pentoxyresorufin 47-fold and 17-fold, respectively, but had little or no effect on short alkyl chains. 3MC-induction of microsomes increased dealkylation of all alkoxyresorufin ethers tested, preferentially dealkylating ethers with short alkyl chain in the order: methoxy > ethoxy > propoxy. Artemisia filifolia or Helenium flexuosum had no effect on basal hepatic cytochrome P450 content. However, microsomal dealkylation activity of short alkyl chain alkoxyresorufin ethers (methoxy, ethoxy and propoxy) was inhibited approximately 50%. When these plants are eaten for several days, they may inhibit biotransformation processes in herbivores through the same isoenzymes induced by 3MC.


Subject(s)
Artemisia , Cytochrome P-450 Enzyme System/metabolism , Enzyme Inhibitors/toxicity , Isoenzymes/metabolism , Microsomes, Liver/drug effects , Plants, Medicinal , Plants, Toxic , Animal Feed , Animals , Biotransformation/drug effects , Cytochrome P-450 Enzyme System/drug effects , Enzyme Induction/drug effects , Enzyme Inhibitors/administration & dosage , Isoenzymes/drug effects , Liver/drug effects , Liver/enzymology , Male , Methylcholanthrene/administration & dosage , Methylcholanthrene/toxicity , Microsomes, Liver/enzymology , Phenobarbital/administration & dosage , Phenobarbital/toxicity , Proadifen/administration & dosage , Proadifen/toxicity , Rabbits
12.
Vet Hum Toxicol ; 37(1): 47-9, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7709592

ABSTRACT

The objectives of the present experiment were to determine the effects of Artemisia filifolia or Helenium flexuosum ingestion on antipyrine disposition as an indirect index of mixed function oxidase (MFO) activity and to evaluate the rabbit as an animal model for assessing the impact of xenobiotics in food. Twelve adult male New Zealand white rabbits were acclimated and maintained on commercial rabbit pellets for 1 w before treatment commenced. On day 1, all rabbits were given 25 mg antipyrine/kg iv. Beginning on day 14, 6 of the rabbits were fed A filifolia and the other 6 were fed H flexuosum at 250 mg/kg daily for 5 d. Antipyrine injection was repeated in all rabbits on day 19. Serial blood samples were taken following each antipyrine administration and serum concentrations determined and subjected to pharmacokinetic analysis. Administration of H flexuosum significantly increased antipyrine half-life elimination from 99.5 +/- 15 min to 215.5 +/- 28 min, typical of an inhibitory-type effect on MFO. Administration of A filifolia was not accompanied by a significant change in antipyrine disposition. Rabbits appear to be appropriate animal models for evaluating the effect of plant ingestion on hepatic biotransformation.


Subject(s)
Animal Feed , Antipyrine/metabolism , Plants, Edible/physiology , Animals , Male , Mixed Function Oxygenases/metabolism , Rabbits
13.
J Vet Pharmacol Ther ; 17(5): 389-93, 1994 Oct.
Article in English | MEDLINE | ID: mdl-7853465

ABSTRACT

Phenylbutazone given during the perisurgical period has been reported to increase the intensity and duration of thiamylal anaesthesia in horses. A possible mechanism of competitive plasma protein binding has been suggested. The purpose of the present study was to experimentally reproduce the phenomenon of increased intensity and/or duration of thiamylal anaesthesia and to determine if there is competitive displacement of plasma protein bound thiamylal by phenylbutazone. Six ponies each received one of three treatments, 11 mg/kg intravenous (i.v.) thiamylal; 8.8 mg/kg i.v. phenylbutazone; and 11 mg/kg i.v. thiamylal with 8.8 mg/kg i.v. phenylbutazone given 9 min later. Thirteen blood samples were collected from 0 time through 600 min following drug administration and plasma drug concentrations quantified by high performance liquid chromatography. The pharmacokinetics of thiamylal and phenylbutazone were best described by three- and two-compartment models, respectively. There were no significant differences in pharmacokinetic parameters for thiamylal in the presence of phenylbutazone. However, there were differences in phenylbutazone pharmacokinetics when preceded by thiamylal administration. Unbound phenylbutazone concentrations were increased at 171, 231 and 351 min when given with thiamylal, accompanied by decreases in per cent bound phenylbutazone (P < 0.05). There were also significant (P < 0.05) changes in per cent plasma protein binding of thiamylal and phenylbutazone between 120 and 360 min, when in combination. No changes in intensity or duration of anaesthesia were observed.


Subject(s)
Anesthesia/veterinary , Horses/physiology , Phenylbutazone/pharmacology , Thiamylal/pharmacokinetics , Animals , Binding, Competitive/drug effects , Blood Proteins/metabolism , Chromatography, High Pressure Liquid/veterinary , Cross-Over Studies , Drug Interactions , Female , Injections, Intravenous/veterinary , Male , Models, Biological , Normal Distribution , Phenylbutazone/administration & dosage , Phenylbutazone/blood , Phenylbutazone/pharmacokinetics , Protein Binding/drug effects , Thiamylal/administration & dosage , Thiamylal/blood
14.
Br J Haematol ; 85(2): 348-51, 1993 Oct.
Article in English | MEDLINE | ID: mdl-8280607

ABSTRACT

A close inter-relationship between raised factor VII clotting activity and elevated blood lipids, particularly serum triglycerides, is well established. A study of factor VII, its activation state and of plasma lipids has been undertaken in two groups of healthy middle-aged males to elucidate this mechanism. A control group with normal factor VII levels were closely matched for age and body-mass index with a second group with elevated levels. Factor VII assays, using rabbit and bovine thromboplastin and a factor VII Ag method, were employed. Triglycerides correlated with the rabbit factor VII thromboplastin assay and factor VII Ag (P < 0.05) but not with the bovine thromboplastin method. Higher HDL-cholesterol and apolipoprotein A-I levels were found in subjects with increased factor VII (P < 0.001) and appeared to be due to differences in alcohol consumption. Cholesterol levels were significantly higher with elevated factor VII. Differential testing suggests that higher factor VII is predominantly mediated through a rise in total VII, rather than an increase in its activity state.


Subject(s)
Factor VII/analysis , Lipids/blood , Adult , Antigens/analysis , Apolipoproteins/analysis , Cholesterol/blood , Factor VII/immunology , Factor VIIa/analysis , Humans , Male , Middle Aged , Triglycerides/blood
15.
J Vet Diagn Invest ; 5(4): 541-7, 1993 Oct.
Article in English | MEDLINE | ID: mdl-8286452

ABSTRACT

Gram-negative bacterial isolates (635) obtained from routine submissions to the Oklahoma Animal Disease Diagnostic Laboratory during 1983-1987 were tested for antimicrobial susceptibility. Minimal inhibitory concentrations (MICs) were determined for the following antimicrobials using commercially prepared microdilution assay materials: ampicillin, cephalothin, chloramphenicol, erythromycin, gentamicin, kanamycin, oxytetracycline, penicillin G, spectinomycin, sulfachlorpyridazine, sulfadimethoxine, and tylosin. Results for isolates from cattle, dogs, horses, and pigs are presented. In only a few instances were differences in MICs apparent among bacterial isolates from different tissues. Aminocyclitol MICs for equine uterine isolates of Klebsiella pneumoniae differed from MICs for isolates from other tissues, and ampicillin, kanamycin, and spectinomycin MICs for bovine fecal isolates of Escherichia coli differed from MICs for isolates obtained from other tissues. In several instances, bimodal distribution of susceptibilities was apparent for ampicillin, kanamycin, and/or oxytetracycline. There was also a bimodal distribution pattern for erythromycin against Pasteurella haemolytica of bovine origin.


Subject(s)
Anti-Bacterial Agents/toxicity , Bacterial Infections/veterinary , Gram-Negative Bacteria/drug effects , Microbial Sensitivity Tests/veterinary , Animals , Bacterial Infections/microbiology , Cattle , Cattle Diseases , Dog Diseases , Dogs , Enterobacter/drug effects , Enterobacter/isolation & purification , Escherichia coli/drug effects , Escherichia coli/isolation & purification , Gram-Negative Bacteria/isolation & purification , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/isolation & purification , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/isolation & purification , Salmonella/drug effects , Salmonella/isolation & purification , Swine , Swine Diseases
16.
J Clin Microbiol ; 31(9): 2303-8, 1993 Sep.
Article in English | MEDLINE | ID: mdl-7691872

ABSTRACT

Pasteurella haemolytica serotype A1 isolates were collected from cattle within a feedlot during an outbreak of bovine respiratory disease. Genetic heterogeneity among the isolates was examined by restriction endonuclease analysis (REA), ribotyping, and analysis of plasmid content. The susceptibilities of isolates to several antibiotics were also examined. Five different REA patterns and three different ribotypes were observed among the isolates. Fifty percent of the isolates had an identical REA type, ribotype, and plasmid profile. Examination of the plasmid content of the isolates revealed that most (73%) carry a single plasmid which encodes beta-lactamase, 13.5% carry two plasmids, and 13.5% carry no plasmid. The data reveal the presence of genetic differences among isolates of P. haemolytica A1, associated with shipping fever pneumonia within a closed feedlot, and suggest that a combination of REA, ribotyping, plasmid analysis, and antibiotic susceptibility determination will be useful in analyzing the molecular epidemiology of this disease.


Subject(s)
DNA Restriction Enzymes , DNA, Bacterial/analysis , Mannheimia haemolytica/genetics , Pasteurellosis, Pneumonic/microbiology , RNA, Ribosomal/genetics , Animals , Bacterial Typing Techniques , Cattle , Drug Resistance, Microbial , Mannheimia haemolytica/classification , Plasmids , Polymorphism, Restriction Fragment Length , RNA Probes , RNA, Bacterial/genetics , Serotyping
17.
Vet Hum Toxicol ; 35(3): 229-30, 1993 Jun.
Article in English | MEDLINE | ID: mdl-8351795

ABSTRACT

Horses develop severe and often fatal hemolytic anemia after ingesting dried leaves from red maple (Acer rubrum) trees. Toxicosis appears related to an unknown oxidant present in the dried or wilted leaves. This case report describes 2 horses that aborted and developed fatal hemolytic anemia after consuming wilted leaves from red maple (Acer rubrum). While an absolute diagnosis was not confirmed due to lack of proper antemortem and postmortem examinations, red maple toxicosis appeared a reasonable diagnosis based on clinical signs and laboratory findings. Other differentials include equine infectious anemia, autoimmune hemolytic anemia, piroplasmosis, leptospirosis, ehrlichiosis, and other plant or chemical sources of oxidants (onion, garlic, kale, phenothiazines).


Subject(s)
Abortion, Veterinary/etiology , Horse Diseases/etiology , Plant Poisoning/veterinary , Animals , Female , Horses , Plant Poisoning/complications , Pregnancy
19.
Am J Vet Res ; 53(12): 2292-5, 1992 Dec.
Article in English | MEDLINE | ID: mdl-1476310

ABSTRACT

Single-dose pharmacokinetic variables of pyrimethamine were studied in horses. Pyrimethamine (1 mg/kg of body weight) was administered IV and orally to 6 adult horses, and plasma samples were obtained at frequent intervals thereafter. Plasma pyrimethamine concentration was assayed by gas chromatography, and concentration-time data were analyzed, using a pharmacokinetic computer program. The IV and oral administration data were best described by 3-compartment and 1-compartment models, respectively. The median volume of distribution at steady state after IV administration was 1,521 ml/kg and the median elimination half-time was 12.06 hours. Mean plasma concentration after oral administration fluctuated between a maximal concentration of 0.18 microgram/ml and 0.09 microgram/ml (24 hours after dosing). Bioavailability after oral administration was 56%.


Subject(s)
Horses/metabolism , Pyrimethamine/pharmacokinetics , Administration, Oral , Animals , Chromatography, Gas/veterinary , Female , Injections, Intravenous/veterinary , Male , Models, Biological , Pyrimethamine/blood
20.
Am J Vet Res ; 53(12): 2296-9, 1992 Dec.
Article in English | MEDLINE | ID: mdl-1476311

ABSTRACT

Pharmacokinetics, CSF penetration, and hematologic effects of oral administration of pyrimethamine were studied after multiple dosing. Pyrimethamine (1 mg/kg of body weight) was administered orally once a day for 10 days to 5 adult horses, and blood samples were collected frequently after the first, fifth, and tenth doses. The CSF samples were obtained by cisternal puncture 4 to 6 hours after administration of the first, third, seventh, and tenth doses. Pyrimethamine concentration in plasma and CSF was quantified by gas chromatography, and plasma concentration-time data were analyzed, using a pharmacokinetic computer program. Repeated daily dosing resulted in accumulation of pyrimethamine in plasma, with steady state being achieved within 5 days, when the mean peak plasma concentration was more than twice that measured after the first dose. Pyrimethamine concentration in CSF was 25 to 50% of corresponding plasma concentration and did not appear to accumulate with successive administration of doses. Blood samples collected during and after the dosing regimen were submitted for hematologic analysis; neutrophil numbers decreased slightly, but remained within normal range for adult horses.


Subject(s)
Horses/blood , Pyrimethamine/pharmacokinetics , Administration, Oral , Animals , Blood Cell Count/drug effects , Blood Cell Count/veterinary , Female , Horses/metabolism , Male , Models, Biological , Pyrimethamine/administration & dosage , Pyrimethamine/cerebrospinal fluid , Pyrimethamine/pharmacology
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