Parathyroid hormone-related protein in the colostrum of paretic post parturient dairy cows.
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Animals↗
Biomedical subjects
M Wanner
Publications and source records attributed to M Wanner.
The "supercharged" posterior calf fasciocutaneous flap.
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Adult↗
Sprayed medicated feed with sulfadimidine for piglets.
The bioavailability of two different forms of medicated feed containing 2000 mg sulfadimidine (SDM) per kg was determined in three groups of eight piglets. In the first group, pharmacokinetic parameters of SDM were determined after a single intravenous dose of 10 mg/kg body weight and after single oral doses of 45 mg/kg body weight ingested either as an oleus solution sprayed directly onto the feed pellets ready for use (SPR) or as a commercially available premix incorporated into the feed before pelletising (PMX). After the single intravenous administration, the mean +/- SD of the volume of distribution was 0.34 +/- 0.05 l/kg, the total body clearance 0.37 +/- 0.07 ml/min.kg, the mean residence time 15.5 +/- 2.5 h, and the elimination half-life 11.1 +/- 2.0 h. Although no statistical significance existed, a single meal with PMX was associated with slightly higher mean values for the maximum serum concentration (Cmax), the time to reach Cmax, and the bioavailability (52.98 +/- 6.60 micrograms/ml, 6.8 +/- 1.1 h, 59.7 +/- 12.1%, respectively, vs. 40.04 +/- 13.19 micrograms/ml, 6.0 +/- 1.4 h, 49.0 +/- 18.6 for SPR). The remaining two groups of piglets received medicated feed with either SPR or PMX during a 3-day period both with restrictive (twice-daily) or ad libitum feeding according to a cross-over design. In all four cases, potentially efficacious plasma SDM concentrations between 50 and 150 micrograms/ml were obtained within 24 h after initiation of the treatment. With PMX, plasma concentrations tended to be higher than with SPR with both feeding regimens. Ad libitum feeding was associated with a significantly higher food intake and hence a higher SDM intake resulting in higher plasma concentrations. Additionally, plasma concentrations were more constant over time with ad libitum feeding whereas they declined considerably between meals in restrictively fed animals. In vitro dissolution tests of the two types of medicated feed revealed that SDM was rapidly released from SPR (58% within 15 min) and that SDM release from PMX was markedly slower (3% within 15 min). Despite the relatively slow rate of in vitro dissolution, in vivo absorption of SDM was satisfactory. It is concluded that both forms of SDM medicated feed may be considered bioequivalent and potentially efficacious in piglets.
Administration, Oral↗
Clarithromycin pharmacokinetics after oral administration with or without fasting in crossbred beagles.
Clarithromycin was administered to eight dogs intravenously and orally. A suspension or a tablet was given to animals both immediately after feeding and on an empty stomach. Neither the formulation nor the time of administration in relation to feeding significantly influenced the pharmacokinetic parameters. The lowest mean (+/-SD) maximum plasma concentration (Cmax) of 3.0 +/- 0.6 micrograms/ml, the lowest bioavailability (F) of approximately 69 per cent and the shortest time above the proposed breakpoint of susceptibility (L) of 2.9 +/- 1.3 hours were observed with the suspension after feeding. The highest Cmax of 3.6 +/- 0.8 micrograms/ml, the highest F of 83 per cent and the longest L of 4.5 +/- 2.0 hours were observed with the suspension in the fasted group. The mean time at which Cmax occurred (tmax) was between one and two hours after administration. In conclusion, clarithromycin is potentially suitable for therapeutic use in dogs, pending species-specific studies of safety and therapeutic efficacy.
Administration, Oral↗
The concentration of ionized magnesium in serum during the periparturient period of non-paretic dairy cows.
Ion-selective electrodes have recently been designed for determining the ionized concentration of magnesium (Mg2+) in serum. This development may allow new insights into some metabolic diseases of cattle. For this report, the concentrations of Mg2+, total magnesium (Mgtot), ionized calcium (Ca2+), total calcium (Catot), and inorganic phosphate (P(i)) were determined in sera from seventeen 3- to 16-year-old Brown Swiss and crossed Simmental/Red Holstein cows during the periparturient period. In each animal, a transient increase of Mg2+ and Mgtot serum concentrations was observed in association with the transient decrease in serum concentrations of Ca2+, Catot and P(i) after parturition. On average, throughout the study, the serum Mg2+ concentrations were 68.5% of those of Mgtot, whereas the serum Ca2+ concentrations were 52% of those of Catot. The possible mechanisms involved in the transient increase of Mg2+ and Mgtot serum concentrations are discussed.
Animals↗
Parathyroid hormone-related protein and calcium concentrations in milk and blood of ewes.
Parathyroid hormone-related protein (PTHrP) and calcium (Ca) concentrations were measured 2 to 3 months postpartum in milk and plasma or serum of 22 ewes by the use of commercial radioimmunoassay kits for PTHrP concentration, colorimetry for serum total Ca concentration (Catot), and atomic absorption spectrophotometry for milk total Ca concentration. Scatter plots did not reveal dependency between milk Ca and Catot, Catot and plasma PTHrP, milk Ca and milk PTHrP, and milk PTHrP and plasma PTHrP. Thus, the systemic and mammary effects of PTHrP are not major determinants of the endocrine, paracrine, and autocrine regulation of Ca homeostasis during lactation in ewes.
Animals↗
Postparturient hypocalcemia of dairy cows: a model for the study of the interdependence of Ca, Pi, and Mg homeostasis.
Disorders of calcium, phosphorus and magnesium homeostasis in ruminants provide natural models for the study of the physiology and pathophysiology of these minerals. The knowledge that can be acquired with a better understanding of the pathogenesis of these diseases could give useful clues in the puzzle of human osteoporosis. In the present study, the case of parturient paresis of dairy cows is reexamined with a newly developed technique for the measurements of serum ionized magnesium concentrations (Mg2+). The concentrations of total magnesium (Mgtot), ionized calcium (Ca2+), total calcium (Catot), and inorganic phosphate (Pi) were also determined in the sera of seventeen 3- to 16-year-old Brown Swiss and crossed Simmental/Red Holstein cows during the periparturient period. In each animal, a transient increase of Mg2+ and Mgtot serum concentrations was observed in association with the transient decrease after parturition of Ca2+, Catot and Pi serum concentrations. On average, throughout the study, serum Mg2+ concentrations were 68.5% of those of Mgtot whereas serum Ca2+ concentrations were 52% of those of Catot. The possible mechanisms involved in the transient increase of Mg2+ and Mgtot serum concentrations are discussed and the relevance of this data for osteoporosis is outlined.
Analysis of Variance↗
Effect of the interval between feeding and drug administration on oral ampicillin absorption in dogs.
Eight dogs of various breeds received single oral doses of 20 mg/kg bodyweight ampicillin at four different time intervals relative to feeding a meal. In treatment A the dogs were fasted for 12 hours before and after ampicillin administration. In treatment B the dogs received ampicillin immediately after, in treatment C one hour before and in treatment D two hours after the meal. Each dog received these treatments during a period of feeding dry and canned dog food according to an 8 x 8 Latin square design. Blood samples were taken at specified time intervals after drug administration by jugular venepuncture. Antibiotic concentrations in plasma were determined by microbiological assay. Non-compartmental pharmacokinetic parameters were calculated from the individual concentration-time curves and were compared by non-parametric statistic tests between treatments and types of food. With both dry and canned food ampicillin absorption was impaired when the drug and food were given at the same time (treatment B) as compared to the absorption in fasting dogs (treatment A and C). On dry food, drug absorption was also decreased in treatment D. It is recommended for clinical purposes to give ampicillin to fasted dogs, and to wait at least one hour before feeding. After a meal (dry food) waiting two hours until drug administration is not sufficient to avoid impaired ampicillin absorption.
Administration, Oral↗
Reevaluation of the growth-permissive substrate properties of goldfish optic nerve myelin and myelin proteins.
To determine whether optic nerve myelin of goldfish carries mammalian-like neurite growth inhibitory proteins which can be neutralized by the antibody IN-1, myelin fractions of fish optic nerves were used as substrates for fish retinal ganglion cell axons and rat dorsal root ganglia (DRG). Axonal growth was monitored and compared with that of IN-1 treated preparations. Growth of fish retinal axons and rat DRG neurites was substantial on goldfish optic nerve myelin and no improvement was observed with IN-1. In contrast, rat CNS myelin allowed only poor growth, and number of axons and length of DRG neurites increased significantly with IN-1. In addition, proteins of fish optic nerve myelin and bovine CNS myelin were extracted, reconstituted in liposomes and applied to growth cones. When goldfish myelin proteins in liposomes were seeded onto growth cones, 77% of fish and 89% of rat DRG growth cones continued to elongate, and the proportion of elongating fish growth cones (80%) did not significantly change when liposomes were pretreated with IN-1. But 73% of fish and 93% of rat growth cones collapsed with liposomes containing proteins from bovine CNS myelin. Upon IN-1 treatment, only 24% of fish growth cones collapsed. Thus, axon growth in vitro indicates that goldfish optic nerves, which permit successful axon regeneration in vivo, lack mammalian-like neurite growth inhibitors which are neutralized by IN-1.
Animals↗
[Parathyroid hormone related-protein and calcium homeostasis].
Recently, parathyroid hormone-related protein (PTHrP) was identified as one of the major causes of humoral hypercalcemia of malignancy in several species. The hormone probably has an important role in the physiology and pathophysiology of mammals and birds. Many endocrine, paracrine and autocrine functions are attributed to PTHrP. Parathormone shares the same receptor with PTHrP. This receptor was isolated in many tissues. PTHrP could be an important fetal growth factor. The influence of PTHrP on calcium homeostasis is presently the object of active research. PTHrP stimulates calcium transfer through the placenta and maintains a concentration gradient between the dam's blood and the fetus. The hormone is produced in large quantities in milk. However, its exact and principal function in lactation has not yet been determined. Among other effects, PTHrP might stimulate the secretion of calcium, phosphate and magnesium in milk and might foster the development of the mammary gland. A role of PTHrP in the pathogenesis of postparturient paresis in dairy cows has been hypothesized. Results of recent trials demonstrate that despite an important role in calcium homeostasis, PTHrP is not pivotal in the development of milk fever.
Amino Acid Sequence↗
Parathyroid hormone-related protein and calcium homeostasis during the periparturient period of dairy cows.
Plasma and milk concentrations of parathyroid hormone-related protein (PTHrP) at various stages of pregnancy and lactation were determined in thirty-nine 3- to 16-year-old Brown Swiss and Red Holstein x Simmental dairy cows originating from 4 herds. Eighteen of the cows were separated into 2 groups: low-parity (LP, n = 8) cows if they were in their first or second pregnancy and high-parity (HP, n = 10) cows if they were in their third or greater pregnancy. Blood samples were collected from each cow on 1 occasion, 15 to 5 days before calving, and blood and milk samples were collected daily during 6 days after calving. Serum total and ionized calcium (Ca(tot) and Ca2+, respectively) and milk Ca(tot) concentrations were also quantified. A transient postpartum decrease of serum Ca(tot) and Ca2+ concentrations was observed, whereas milk Ca(tot) concentration was constant. Plasma concentration of PTHrP was detected in 11 of 21 cows by use of an immunoradiometric assay (range, 0.45 to 1.82 pmol/L). Daily mean (+/- SD) colostrum and milk PTHrP concentrations ranged from 3.25 (+/- 3.23) to 4.69 (+/- 1.36) nmol/L in LP cows and 2.74 (+/- 0.5) to 5.95 (+/- 0.33) nmol/L in HP cows. In all cows of the HP group and most cows of the LP group, milk PTHrP concentration was highest in the day-1 sample. Milk PTHrP concentration correlated positively with milk Ca(tot) concentration in HP cows (r = 0.5959, P < 0.0001). In contrast, there was a negative relation between milk PTHrP and milk Ca(tot) concentrations in LP cows (r = -0.3285, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of Variance↗
Bioavailability of different forms of amoxycillin administered orally to dogs.
Amoxycillin was administered to six dogs intravenously (as the sodium salt at 20 mg/kg bodyweight) and orally (as the trihydrate at 20 mg/kg). The oral treatments followed a Latin square pattern, each dog receiving amoxycillin as a 60 ml suspension by stomach tube, or as 3 ml of drops or in the form of tablets. The concentration of the drug in the plasma was measured microbiologically and its pharmacokinetic parameters were calculated by the use of statistical moments. After intravenous administration the mean +/- sd apparent volume of distribution was 0.312 +/- 0.102 litre/kg, the steady state rate of clearance was 3.4 +/- 1.1 ml/min/kg and the mean residence time was 1.6 +/- 0.4 hours. After oral administration the liquid forms of the drug tended to be more readily absorbed than the tablets, as indicated by their higher bioavailabilities (suspension 76.8 +/- 16.7 per cent, drops 68.2 +/- 25.8 per cent, tablets 64.2 +/- 17.9 per cent). However, the differences between their pharmacokinetic parameters were not statistically significant. The respective values of Cmax for the tablets, drops and suspension were 18.6 +/- 5.3 micrograms/ml, 18.1 +/- 2.4 micrograms/ml and 20.7 +/- 2.2 micrograms/ml, of tmax 2.0 +/- 1.0 hours, 1.4 +/- 0.6 hours and 1.4 +/- 0.5 hours and of the AUC 69.5 +/- 22.5 micrograms/ml hours, 71.8 +/- 21.0 micrograms/ml hours and 80.6 +/- 21.8 micrograms/ml hours. The two useful drug products (drops and tablets) had similar pharmacokinetic profiles in the dogs and can therefore be regarded as equivalent in this species.
Administration, Oral↗
Pharmacokinetics of sulphadoxine and trimethoprim in sows: influence of lactation.
A potentiated sulpha drug was administered intravenously to 12 sows on the 17th day of lactation and to 4 sows in early pregnancy to study the influence of lactation on its disposition kinetics. The dose-rate of sulphadoxine (SDX) used was 12 mg/kg b.w. while that of trimethoprim (TMP) was 2.4 mg/kg b.w. The pharmacokinetic parameters of SDX showed no significant difference between lactating and pregnant sows (Vss, 0.24 +/- 0.04 L/kg; Cls, 0.25 +/- 0.05 ml/min per kg: MRT, 17.08 +/- 4.48 h). SDX did not accumulate in milk, the concentrations in milk being less than the concentrations in serum at the same time. Of the pharmacokinetic parameters for TMP, only the mean residence time was significantly different between the two groups (Vss, 1.60 +/- 0.31 L/kg; Cls, 4.62 +/- 1.07 ml/min per kg: MRTlactating, 5.43 +/- 1.26 h; MRTpregnant, 7.74 +/- 1.72 h). TMP was excreted in milk to a considerable extent, the ratio of its concentration in milk to that in serum at the same time being over 2.2. These two substances show a completely different pharmacokinetic behaviour. Even though TMP is excreted more quickly in lactating sows, adjusting the dose of this potentiated sulpha drug does not seem to be appropriate.
Animals↗
[Pharmacokinetics of baytril (enrofloxacin) in dogs].
Baytril with the active ingredient enrofloxacin was given to four dogs in a single intravenous and oral dose of 5 mg/kg body weight. Measured plasma concentrations were different depending on the method of analysis used. Using high performance liquid chromatography quantitative determination of both enrofloxacin and its main metabolite ciprofloxacin is possible whereas antimicrobially active substance is measured by bioassay. Ciprofloxacin occurred early in the concentration-time curves after intravenous and oral administration of the parent drug enrofloxacin with cmax 0.2 and 0.3 microgram/ml, respectively, at tmax 2 and 4 h, respectively. Areas under the curve (AUC) calculated from concentration-time-curves with bioassay data are overestimated, because ciprofloxacin may be more active than enrofloxacin against E. coli 14 (ICB 4004) used in this test. Thus, pharmacokinetic parameters which are derived from AUC-values are overestimated, too. Oral bioavailability calculated with bioassay results was more than 100% whereas availability of enrofloxacin was only 53%. Clearance was 10.3 ml/min.kg (antimicrobially active substance) and 27.1 ml/min.kg (enrofloxacin). Elimination half life was 3.7 and 2.4 h, respectively.
Administration, Oral↗
Comparative pharmacokinetics of aditoprim in milk-fed and conventionally fed calves of different ages.
Aditoprim body disposition was described after intravenous and oral administration of 5 or 10 mg kg-1 bodyweight to milk-fed and conventionally fed calves with bodyweights of 80 kg, 160 kg and 210 kg. After intravenous administration to conventionally fed calves, aditoprim total body clearance increased and elimination half-life decreased with age. Oral administration of aditoprim with feed was associated with a longer absorption half-life and consequently longer elimination half-life in the older calves, because the drug was deposited in a functionally mature rumen. The weak base aditoprim is slowly absorbed from the rumen according to the pH partition hypothesis and probable binding to dietary fibres and other macromolecules. The favourable pharmacokinetics of aditoprim indicate a potential use for this antimicrobial in bovine practice, pending further studies on residue depletion profile, safety and therapeutic efficacy.
Administration, Oral↗
Comparison of an HPLC and bioassay method to determine antimicrobial concentrations after intravenous and oral administration of enrofloxacin in four dogs.
Plasma samples of dogs given 5 mg kg-1 bodyweight of a broad spectrum antimicrobial with the active ingredient enrofloxacin were assayed by two different methods (bioassay: Escherichia coli 14 ICB 4004 on ISO sensitest agar; high performance liquid chromatography with a RP C18 column). At concentrations up to 1000 ng ml-1 a linear correlation between values obtained by the two assay methods was found. At concentrations above 1000 ng ml-1 no correlation could be determined. The main metabolite of enrofloxacin, ciprofloxacin, is an important determinant of overall antimicrobial activity and hence influences bioassay results.
Administration, Oral↗
Doppler duplex for the evaluation of the degree of stenosis in carotid arteries in the rat.
This study evaluates the accuracy of the Doppler duplex technique for providing reliable information about the level of stenosis in microanastomoses. Stenoses ranging between 30 and 85 percent of the cross-sectional area of carotid arteries were evaluated in rats. Peak systolic velocities were measured in prestenotic, stenotic, and poststenotic segments, using the duplex technique. Surgical results with duplex measurements were expressed as percentage of stenosis (calculated from a ratio of two cross-sectional areas), and later correlated. The correlation coefficient between the two sets of measurements was 0.82 (p < 0.01), and the hypothesis of a simple linear relationship was clearly accepted (p = 0.92). Results of the study show that duplex measurements become increasingly unreliable in stenoses with severity less than 50 percent. With increasing degrees of stenosis (50 percent and above), the variance of measurements with duplex decreases. According to the data, the limiting value for the duplex method appears to lie at about 85 percent. When methods for continuous measurement of flap perfusion indicate a hindrance of inflow, Doppler duplex can provide valuable information about the causes. This technique can be used clinically for the evaluation of microanastomoses in 1-mm vessels. In clinical cases, if a 50 percent or more stenosis is diagnosed by duplex technique, the measurement should be repeated within 1 to 2 hr. If the stenosis persists or intensifies, revision should be considered.
Anastomosis, Surgical↗
Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after intravenous and oral administration of enrofloxacin in dogs.
Four dogs were given 5 mg/kg body weight enrofloxacin intravenously (i.v.) and orally (p.o.) in a cross-over study. Plasma concentrations of the active ingredient enrofloxacin and its main metabolite ciprofloxacin were determined by a reversed phase liquid chromatographic method. Pharmacokinetic parameters of both substances were calculated by use of statistical moments and were compared to those of enrofloxacin described in the veterinary literature. Mean enrofloxacin t1/2 lambda z was 2.4 h, mean Cls was 27.1 ml/min.kg, and mean Vss was 7.0 l/kg. After i.v. and p.o. administration, concentrations of ciprofloxacin exceeding minimal inhibitory concentrations of several microorganisms were reached (Cmax = 0.2 microgram/ml, tmax = 2.2 h after intravenous administration; Cmax = 0.2 microgram/ml, tmax = 3.6 h after oral administration). A considerable part of the antimicrobial activity is due to ciprofloxacin, the main metabolite of enrofloxacin.
Administration, Oral↗