Plasma concentrations of sodium benzylpenicillin after intrauterine infusion in pony mares

Plasma concentrations of sodium benzylpenicillin were measured following intrauterine infusion at a dose rate of 22,000 u/kg (250,000 u/ml). The reproductive status of the mare at the time of infusion did not appear to influence plasma concentrations of penicillin, but preswabbing the endometrium for bacteriological culture resulted in peak plasma concentrations which were nearly twice those found in unswabbed mares.     

Endometrial and serum gentamicin concentrations in pony mares given repeated intrauterine infusions

Endometrial tissue and blood serum gentamicin (GT) concentrations were determined in 6 ovariectomized pony mares given intrauterine infusions (50 ml of a 5% commercial aqueous solution of GT) each day for 5 consecutive days. The mares were subjected to the following 3 treatments: (1) GT infusion only (trial A, control); (2) progesterone plus GT (trial B, P + G); and (3) estradiol plus GT (trial C, E + G). Endometrial tissue concentrations of GT (micrograms/g) at 24 and 120 hours were significantly higher (P less than 0.05) in trials B (65.54 +/- 15.57 and 100.33 +/- 19.27) and C (73.33 +/- 22.53 and 74.09 +/- 8.60) than in trial A (4.23 +/- 0.70). Endometrial concentration for trial A at 120 hours was also significantly higher than trial A at 24 hours. There was no significant difference (P greater than 0.05) in endometrial concentrations among trials A, B, and C at 120 hours. Serum GT concentrations were significantly lower than endometrial tissue concentrations. The highest serum concentrations of GT found in every trial occurred at 6 hours after each intrauterine infusion of GT. The highest overall serum concentration of GT (micrograms/ml) determined occurred in trial B (8.30 +/- 1.28) at 78 hours. There was no significant difference in serum concentrations of GT between days of treatment, except for trial A at 78 and 102 hours, respectively. Serum concentrations of GT were significantly higher (P less than 0.05) than trial A at 30, 54, 78, and 102 hours in trial B, and at 78 and 102 hours in trial C. There was no significant difference in serum concentrations of GT between trials B and C.     

Effect of intrauterine infusion of Escherichia coli endotoxin in postpartum pony mares

Fifteen pony mares were assigned to 1 of 3 treatment groups after foaling: Group 1, 35 ml of sterile saline solution was infused into the uterine lumen within 24 hours after parturition (6 mares); group 2, 300 mg of Escherichia coli endotoxin was infused into the uterine lumen within 24 hours after parturition (6 mares); and group 3, 300 mg of E coli endotoxin was infused into the uterine lumen between 72 and 96 hours after parturition (3 mares). Rectal temperatures were taken at -1, -0.5, 0, 0.5, 1, 1.5, 2, 3, 4, and 5 hours after treatment. Venous blood samples were also taken at these times for routine WBC counts. Data were analyzed as a repeated measurement design with linear and quadratic orthogonal contrasts performed where significant time and interaction with time occurred. Pretreatment averages of total WBC and neutrophil counts were compared with their nadir posttreatment averages by a t test when treatment-by-time interaction was significant for the parameter. Rectal temperature (37.9 +/- 0.1 C) remained stable and did not vary among treatment groups after intrauterine infusions. In contrast, total WBC and neutrophil counts did vary among treatment groups across time. However, for treatment groups 1 and 3, neither blood total WBC count nor neutrophil count after intrauterine infusions was different from pretreatment observations. In group 2, total WBC count decreased (P less than 0.10) from a pretreatment average of 11.5 +/- 0.4 X 10(3) cells/mm3 to a nadir concentration of 10.0 +/- 0.6 X 10(3) cells/mm3 by 60 minutes after infusion of endotoxin into the uterus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tissue and serum concentrations of amikacin after intramuscular and intrauterine administration to mares in estrus.

Concentrations of amikacin in endometrial tissue and plasma were studied in mares in estrus after intrauterine infusion of 1.0 or 2.0 g once a day for 3 consecutive d, and after 9.7 or 14.5 mg/kg body weight (BW) had been injected intramuscularly once a day for 3 consecutive d to determine concentrations of amikacin sulfate in plasma and endometrial tissues, and whether parenteral administration provides any advantages over intramuscular infusion. No amikacin was detected in serum at the 1.0 g dose. At the infusion dose of 2.0 g once a day, very low levels of serum amikacin were detected at 1 and 4 h postinfusion on the 1st treatment day. Amikacin was found to penetrate the endometrium after intramuscular injection; however, the levels attained were not as high as those achieved following intrauterine infusion. Based on the tissue and serum concentrations of amikacin, an intrauterine infusion at a dose of 4.4 mg/kg BW/d would appear to be an appropriate therapeutic regimen for the treatment of gram-negative endometritis.     

Endometrial candidiasis in five mares

Five cases of endometritis caused by yeast were seen at Texas A & M University, and are presented in this paper. Possible methods of diagnosis and therapy are discussed. A guarded prognosis for future reproductive performance should be expected if this syndrome occurs in concert with poor perineal conformation.     

Efficacy of intrauterine infusion of plasma for treatment of infertility and endometritis in mares

We evaluated the efficacy of intrauterine plasma infusion in mares as a treatment for infertility caused by endometritis and distinguished the effects of intrauterine infusion of plasma vs saline solution. Forty-three subfertile mares were randomly assigned to 1 of 3 treatment groups: untreated controls (n = 14), those treated by saline infusion (n = 14), and those treated by plasma infusion (n = 15). Reproductive status was assessed daily by transrectal ultrasonography. Uterine aspirates and biopsy specimens were obtained 8 days after ovulation for cytologic and histologic evaluation, and mares were treated on days 12 to 16. Uterine aspirates and biopsy specimens were obtained again on day 8 of the next estrous cycle, and the mares were bred at the subsequent estrus. A postovulation intrauterine infusion of either plasma or saline solution was administered to mares in their respective treatment groups. Biopsy specimens were scored from 1 (no indications of inflammation) to 6 (severe inflammation). The pregnancy rate was lower (P less than 0.005) for mares with scores 5 and 6 (0/5) than for those with scores 1 to 4 (17/35). There was no significant effect of treatment nor a treatment by biopsy score interaction on pregnancy rate; however, the pregnancy rate for mares treated with plasma or saline solution (9/27) tended to be lower than for the control (untreated) mares (8/13). There was no change in mean biopsy score between specimens obtained before treatment and those obtained after treatment for the control group and the group treated with saline solution; however, there was a significant increase (P less than 0.05) in scores in the group treated with plasma.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of teasing, mechanical stimulation and the intrauterine infusion of saline on uterine contractions in mares

Uterine motility may have significance for the transportation of spermatozoa and the elimination of the ejaculate and inflammatory products after mares have been covered. The effect of some of the component stimuli of coitus on uterine contractions was investigated by using M-mode ultrasound. The number, amplitude and duration of the uterine contractions of each uterine horn and of the uterine body were measured in oestrous mares for four minutes before and four minutes after teasing by a stallion, mechanical stimulation of the vagina and cervix, the intrauterine infusion of 80 ml of sterile saline, the intrauterine infusion of 10 ml of sterile saline, the intrauterine infusion of 150 ml of sterile saline, and the transcervical passage of a uterine catheter. Teasing by a stallion did not affect the total number, mean amplitude or mean duration of the uterine contractions. Mechanical stimulation of the vagina and cervix increased the total number of uterine contractions, but did not affect the amplitude or duration of the contractions. The intrauterine infusion of 80 ml of sterile saline resulted in an increase in the total number of contractions and a significant increase in the mean amplitude and the mean duration of the contractions in the uterine horns but not the uterine body. The intrauterine infusion of 10 ml of sterile saline caused a significant decrease in the number of uterine contractions in the uterine horns, but had no effect on the contractions of the uterine body. The infusion of 150 ml of sterile saline reduced the number of contractions in the uterine horns but not the uterine body, and did not affect the mean amplitude and mean duration of the contractions. The transcervical insertion of a catheter reduced the number of contractions in the uterine horns, but did not affect the amplitude or duration of the uterine contractions.     

Effect of a povidone-iodine intrauterine infusion on progesterone levels and endometrial steroid receptor expression in mares

Background

Intrauterine infusions have been widely used for the treatment of endometritis in the mare. Nevertheless, their consequences on endocrine and endometrial molecular aspects are unknown. We studied the effect of a 1% povidone-iodine solution intrauterine infusion on progesterone levels, endometrial histology and estrogen (ERα) and progesterone (PR) receptor distribution by immunohistochemistry.

Methods

Fourteen healthy mares were used in this study. Estruses were synchronized and seven mares were treated with intrauterine infusions at days 0 and 2 post ovulation of two consecutive estrous cycles. Uterine biopsy samples were taken on days 6 and 15 post ovulation.

Results

The treatment did not induce an inflammatory response indicating endometritis, neither affected the ERα. However, it reduced the percentage of PR positive cells (PPC) on day 6 (deep glandular epithelium, control: 95.7 vs. infused: 61.5, P < 0.05). Treated mares tended to have lower progesterone levels on day 2 (3.9 ng/ml vs. 6.6 ng/ml, P = 0.07), and higher levels on day 15 compared with controls (4.4 ng/ml vs. 1.3 ng/ml, P = 0.07).

Conclusion

a 1% povidone-iodine infusion during days 0 and 2 post ovulation in healthy mares did not induce histological changes indicating endometritis, but altered progesterone concentrations and reduced the expression of endometrial PR at day 6 without affecting the ERα. These changes could reduce embryo survival.     

Conception in mares following intrauterine therapy with amikacin

The semisynthetic aminoglycoside amikacin is a potentially valuable antibiotic in broodmare practice due to its efficiency against Gram negative bacteria which have developed resistance to gentamicin. Each of 4 mares conceived when amikacin at 200 ug/ml in buffered extender was used in artificial insemination or as a prebreeding infusion. After intrauterine infusion of 2 g amikacin in 200 ml saline, 4 mares conceived to natural service or insemination with untreated semen after seven hours. In unbuffered saline solutions, amikacin (1 g/100 ml) and gentamicin (1 mg/ml) were spermicidal in vitro.     

Plasma prolactin concentrations in mares and their neonates after oxytocin induction of parturition

Studies were undertaken to investigate the effects of oxytocin induction on prolactin release in term (Group II) and preterm (Group III) mares and to compare these effects to spontaneously foaling mares (Group I). Since physiological concentrations of prolactin in blood have not been measured in the neonatal foal, experiments were designed to monitor prolactin in the cord artery and jugular blood of the foals from all groups of mares. Although prolactin levels varied in term mares (Group I and II) during the last 11 days of pregnancy, an increase was observed between Day -6 and Day 0 (2.7 and 11.9 ng/ml respectively; P less than 0.1). The average concentration of prolactin over the last 4 days (Days -3 to 0) had increased by 40% when compared to the average concentration on Days -6, -5, and -4. These findings indicate a rising trend which appears to occur concomitantly with changes in concentrations of 2 mammary components tested, sodium and potassium. Prolactin concentrations did not significantly increase in term mares after oxytocin treatment or in spontaneously foaling mares. However, the preterm induced mares had higher prolactin concentrations during the first stage of labor (19.3 +/- 7.2 ng/ml) than prior to treatment with oxytocin (4.7 +/- 2.0 ng/ml; P less than 0.01). Levels of prolactin in all groups significantly declined by 20-min post-placental expulsion. For the first 30 min after birth, prolactin concentrations in foals from oxytocin-induced mares appeared to be 2-fold higher than those from spontaneously foaling mares. Thereafter, prolactin values declined to baseline values by 48 hrs. When comparing cord arterial plasma with cord venous plasma in each group, prolactin concentrations were similar. However, the average prolactin levels in both the cord artery and vein appeared higher (ave: 1.1 ng/ml) in Group II and III than in Group I (less than 0.5 ng/ml). From these results, the authors suggest that 1) prolactin may have a role in regulating mammary secretory products in mares just prior to parturition; 2) oxytocin may increase prolactin secretion in preterm induced mares; 3) oxytocin induction may have a short term effect to increase circulatory prolactin concentrations in neonates in utero regardless whether their dams were treated preterm or term.     

Body fluid and endometrial concentrations of ketoconazole in mares after intravenous injection or repeated gavage

After single oral administration of ketoconazole (30 mg/kg bodyweight [bwt]) in 50 ml of corn syrup to a healthy mare, the drug was not detected in serum. Ketoconazole in 0.2 N HC1 was administered intragastrically to six healthy adult horses in five consecutive doses of 30 mg/kg bwt at 12 h intervals. Ketoconazole concentrations were measured in serum, synovial fluid, peritoneal fluid, cerebrospinal fluid (CSF), urine and endometrium. Mean peak serum ketoconazole concentration was 3.76 micrograms/ml at 1.5 to 2 h after intragastric administration. Mean peak synovial concentration was 0.87 micrograms/ml 3 h after the fifth dose. Similarly, mean peritoneal concentration peaked 3 h after the fifth dose at 1.62 micrograms/ml. Mean endometrial concentrations peaked at 2.73 micrograms/ml 2 h after the fifth dose. Ketoconazole was detected in the CSF of only one of the six mares at a concentration of 0.28 micrograms/ml 3 h after the fifth dose. The highest measured concentration of ketoconazole in urine was 6.15 micrograms/ml 2 h after the fifth dose. A single intravenous injection of ketoconazole (10 mg/kg bwt) was given to one of the six mares; the overall elimination rate constant was estimated at 0.22/h and bioavailability after oral administration was 23 per cent.     

Serum concentrations and pharmacokinetics of enrofloxacin after intravenous and intragastric administration to mares.

Serum concentrations and pharmacokinetics of enrofloxacin were studied in 6 mares after intravenous (IV) and intragastric (IG) administration at a single dose rate of 7.5 mg/kg body weight. In experiment 1, an injectable formulation of enrofloxacin (100 mg/mL) was given IV. At 5 min after injection, mean serum concentration was 9.04 microg/mL and decreased to 0.09 microg/mL by 24 h. Elimination half-life was 5.33 +/- 1.05 h and the area under the serum concentration vs time curve (AUC) was 21.03 +/- 5.19 mg x h/L. In experiment 2, the same injectable formulation was given IG. The mean peak serum concentration was 0.94 +/- 0.97 microg/mL at 4 h after administration and declined to 0.29 +/- 0.12 microg/mL by 24 h. Absorption of this enrofloxacin preparation after IG administration was highly variable, and for this reason, pharmacokinetic values for each mare could not be determined. In experiment 3, a poultry formulation (32.3 mg/mL) was given IG. The mean peak serum concentration was 1.85 +/- 1.47 microg/mL at 45 min after administration and declined to 0.19 +/- 0.06 microg/mL by 24 h. Elimination half-life was 10.62 +/- 5.33 h and AUC was 16.30 +/- 4.69 mg x h/L. Bioavailability was calculated at 78.29 +/- 16.55%. Minimum inhibitory concentrations of enrofloxacin were determined for equine bacterial culture specimens submitted to the microbiology laboratory over an 11-month period. The minimum inhibitory concentration of enrofloxacin required to inhibit 90% of isolates (MIC90) was 0.25 microg/mL for Staphylococcus aureus, Escherichia coli, Salmonella spp., Klebsiella spp., and Pasteurella spp. The poultry formulation was well tolerated and could be potentially useful in the treatment of susceptible bacterial infections in adult horses. The injectable enrofloxacin solution should not be used orally.     

Dimeric inhibin concentrations in mares with granulosa-theca cell tumors

OBJECTIVE: To determine whether concentrations of dimeric inhibin (CaCA) are greater in plasma and tumor fluid from mares with granulosa-theca cell tumors (GTCT), compared with concentrations in plasma and equine follicular fluid (eFF) from control mares. ANIMALS: 6 mares with GTCT and 12 clinically normal mares. PROCEDURE: The alphabetaA immunoradiometric assay used 2 antibodies, one against each subunit of inhibin (alpha and betaA subunits). Tumor tissue, tumor fluid, and a single blood sample were collected at the time of surgical removal of the GTCT. A single blood sample was collected from 7 control mares during various stages of the estrous cycle. Five other control mares were ovariectomized when their ovaries contained growing follicles of 25 to 35 mm in diameter. A blood sample and eFF from the largest follicle were collected at the time of ovariectomy. RESULTS: Mares with GTCT had significantly greater plasma concentrations of betabetaA (mean +/- SEM, 0.86 +/- 0.53 ng of recombinant human-alphabetaA/ml), compared with control mares (0.14+/-0.02 ng/ml). Concentrations of alphabetaA in tumor fluid and eFF were similar. Concentrations of alphabetaA were significantly lower after ovariectomy. CONCLUSIONS AND CLINICAL RELEVANCE: Dimeric inhibin concentration was higher in plasma from mares with GTCT than in plasma from control mares. Increased granulosa cell mass and loss of mechanisms regulating alphabetaA release in mares with GTCT likely accounted for the increase in plasma concentrations. Measurement of alphabetaA concentrations may be useful for identifying mares with GTCT.     

Probenecid infusion in mares: effect on para-aminohippuric acid clearance

Para-aminohippuric acid (PAHA, 0.1 mg/min/kg of body weight) was infused IV into 2 mares, followed by concurrent IV infusion of PAHA and probenecid (0.075, 0.15, 0.25, or 0.35 mg of probenecid/min/kg). Probenecid infusion reduced the clearance of PAHA at serum probenecid concentrations greater than 55 micrograms/ml. At 12-hour intervals, probenecid (in 5 repeated doses - 50, 75, 100, or 200 mg/kg) was administered by gavage to 2 mares. Mean serum probenecid concentration was greater than 55 micrograms/ml for all dosages. At dosages less than 200 mg/kg, accumulation of probenecid in the serum was minimal from the 1st to the 5th dose. At a dosage of 200 mg/kg, probenecid accumulated in the serum from the 1st to the 5th dose. Intragastric administration of 5 doses of probenecid (75 mg/kg) at 12-hour intervals to 6 mares reduced the clearance of PAHA by 50%. Bioavailability of probenecid was 117 and 102% for 2 mares after a single intragastric dose, compared with a single IV dose.     

Amikacin sulfate in mares: pharmacokinetics and body fluid and endometrial concentrations after repeated intramuscular administration

Six mares were given 5 IM injections (at 12-hour intervals between doses) of amikacin sulfate at a dosage of 7 mg/kg of body weight. Serum amikacin concentrations were measured serially throughout the study; synovial, peritoneal, endometrial, and urine concentrations were determined after the last injection. Amikacin concentrations of the CSF were measured serially in 3 of the 6 mares; 1 of the 3 mares had septic meningitis. Mean serum amikacin concentrations peaked at 1 to 2 hours after IM injection. The highest mean serum concentration was 19.2 micrograms/ml (1.5 hours after the 5th injection). The highest mean synovial concentration was 10.8 micrograms/ml at 2 hours after the 5th injection; the highest mean peritoneal concentration was 16.2 micrograms/ml at 3 hours after the 5th injection. The mean endometrial amikacin concentration was 2.5 micrograms/g (1.5 hours after the 5th injection). Amikacin reached a CSF concentration of 0.97 micrograms/ml in the mare with meningitis, but amikacin was not detected in CSF of healthy mares. Urine concentrations reached 1,458 micrograms/ml. Pharmacokinetic values were estimated after the 1st injection (elimination rate constant = 0.31/hour; half-life = 2.3 hours; apparent volume of distribution = 0.26 L/kg), and after the 5th injection (elimination rate constant = 0.28/hour; half-life = 2.6 hours; apparent volume of distribution = 0.30 L/kg); significant differences were not observed.