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Effects of the nonsteroidal antiinflammatory agent sodium salicylate on endotoxin-induced mastitis were evaluated in lactating cows. Escherichia coli endotoxin was administered to a mammary quarter 1 h after initiation of a 12-h i.v. infusion of sodium salicylate. Milk SCC, BSA concentrations in milk, mammary inflammation, rectal temperature, appetite, milk production, and plasma and lymph PGF2 alpha were monitored. Gross mammary inflammation was not reduced by salicylate infusion, nor did sodium salicylate prevent increased milk SCC or BSA concentrations in milk, although treatment tended to decrease the magnitude of these responses. Sodium salicylate decreased subcutaneous abdominal vein PGF2 alpha metabolite, and PGF2 alpha metabolite tended to be reduced in lymph during the acute phase of inflammation. The increased rectal temperature after endotoxin infusion was reduced in cows treated with sodium salicylate. Appetite was reduced after endotoxin infusion in untreated cows and those treated with sodium salicylate. Milk production declined after endotoxin challenge in all cows. Although sodium salicylate did not substantially reduce mammary inflammation, it had an antipyretic effect and reduced PGF2 alpha metabolite in mammary blood.

In the present study the effect of Flunixin meglumine (FM), a cyclooxygenase inhibitor, was investigated on postpartal prostaglandin production and uterine activity in the cow. For that purpose 8 cows were given FM in a dose of 2.2 mg/Kg b.w. twice daily (08.00 and 16.00 h) for the first 10 days p.p. Blood samples were collected at various times before, during and after parturition and the concentrations of 15-keto-13,14-dihydro-PGF2 alpha (PGFM), progesterone as well as adrenaline and noradrenaline determined. Eight cows served as controls. Uterine activity was measured by means of pressure microsensors and electrodes which were surgically implanted into the uterine wall before parturition. During the whole treatment period FM inhibited endogenous PG-production by more than 80% (p < 0.05). The suppressive effect of FM was maximal 4 h after the last injection and lasted no longer than 8 h. PGF2 alpha-suppression clearly decreased spontaneous uterine motility and reduced the myometrial response to ocytocin (5 IU i.v.) and PGF2 alpha (15 mg i.v.). Treatment with FM did not interfere with uterine involution, the return to cyclicity and the first postpartal cycle length. Also, no obvious effects were seen on catecholamine concentrations which fluctuated during parturition without regularly representing the actual stress situation. Our results demonstrate that FM is able to effectively inhibit PGF2 alpha-secretion as well as uterine activity in the cow. Further evaluation of FM as a tocolyticum or in the treatment of uterine infections is required.

Oxytetracycline (OTC) was administered by constant IV infusion to 3 healthy postpartum cows at rates predicted to approach a steady-state plasma concentration of 5 micrograms/ml. After 8 hours of constant IV infusion, genital tissues were surgically removed. The mean plasma-to-tissue ratios of concentrations of OTC were 0.95, 1.33, 1.88, and 1.04 (2 cows only) for caruncles, endometrium, uterine wall, and ovaries, respectively. Differences between the ratios of any 2 of the uterine tissues were statistically significant (P less than 0.05). Intrauterine (IU) infusions of 5.5 mg of OTC/kg were administered to 3 healthy postpartum cows and 3 postpartum cows with metritis. The mean values of the fraction of the drug absorbed from the uteri of cows given IU infusions of OTC were 0.50 and 0.23 for healthy postpartum cows and postpartum cows with metritis, respectively. Concentrations of OTC were high in the caruncles and endometrium of all cows at 24 hours after IU infusions of the drug. Concentrations in the plasma, uterine wall, and ovaries were low, with mean concentrations of OTC in these tissues in postpartum cows with metritis being lower than those in the same tissues of healthy postpartum cows. Computer-simulated genital tissue concentrations of OTC after twice daily IV doses of 11 mg/kg indicated that this dosage regimen would provide postpartum uterine tissue concentrations greater than 5 micrograms/g throughout the dosage interval in all tissues, except the uterine wall.

Intrauterine pressure (IUP) changes were recorded in nonlactating, cyclic dairy cows using transcervically placed intraluminal pressure microtransducers. Spontaneous activity was recorded for the first 30 min. Prostaglandins (PG) F(2alpha) (5 mug/kg), E(2) (5 mug/kg), or cloprostenol (0.1 mug/kg) were then injected intravenously (i.v.) at diestrus, proestrus, estrus, and metestrus, and their effects were recorded. The drug administrations did not alter the duration of the estrous cycle of the cows. Single doses of PGF(2alpha) and E(2) significantly increased uterine activity at all stages of the estrous cycle, while cloprostenol had no effect. PGF(2alpha) and PGE(2) increased IUP, frequency, and amplitude during all stages of the estrous cycle. The spontaneous pattern resumed within 20 min postinjection. Partial uterine refractoriness occurred with both PGs. The results indicate that low doses of natural prostaglandins stimulate uterine activity during the estrous cycle in cattle.

The endocrine function of the individual components of the hypothalamo-hypophyseal-ovarian axis of the postweaning anestrous sow was evaluated by monitoring the sow's response to exogenous estradiol, gonadotropin releasing hormone (GnRH), and gonadotropins. Sows (4 to 6/group) not returning to estrus by 42.8 +/- 3.1 days after weaning were assigned to 1 of the following treatments: 10 micrograms of estradiol benzoate (EB)/kg of body weight; 200 micrograms of GnRH, 1,000 IU of pregnant mare's serum gonadotropin (PMSG); 1,000 IU of human chorionic gonadotropin (HCG); or 4 ml of saline solution plus 2 ml of corn oil. A preovulatory-like surge of luteinizing hormone [(LH) greater than 12 hours in duration] was observed in all weaned sows treated with EB. All EB-treated sows exhibited estrus and ovulated but none conceived. Sows given GnRH had transiently increased (less than 3 hours) LH concentrations that were not associated with estrus or ovulation. Treatment with PMSG caused an increase in peripheral concentrations of 17 beta-estradiol that was followed by an LH surge, estrus, ovulation, and conception. Treatment with HCG caused an increase in circulating concentrations of 17 beta-estradiol that was accompanied by a surge of LH in some sows and ovulation in all sows. Not all sows treated with HCG exhibited estrous behavior, but conception occurred in 2 of 3 sows that were mated at estrus. None of the sows treated with saline plus corn oil had consistent changes in circulatory concentrations of 17 beta-estradiol or LH and none exhibited estrus or ovulated.(ABSTRACT TRUNCATED AT 250 WORDS)

A catheter-backpack system was developed for repeated blood collection in pigs. Castrated male pigs (n = 12) were maintained in pairs in outdoor pens and later in a slotted-floor confinement finishing house. Blood collection required no restraint and appeared to be stress free. Serum cortisol concentration was unchanged by mode of maintenance. However, diurnal variation of cortisol was more pronounced when pigs were housed. A significant decrease (P less than 0.05) in serum norepinephrine concentration occurred during the housing period.

This study describes a method for measuring intrauterine pressure (IUP) changes and uterine motility in cows. Spontaneous uterine motility was recorded during the estrous cycle in stanchioned, nonlactating dairy cows using a pair of miniature pressure transducers mounted 15 cm apart at the distal end of a dacron catheter placed in one uterine horn via the cervix. Clinical examination of ovarian status and determination of the peripheral plasma levels of estradiol-17beta and progesterone were used to determine the stages of the cycle. The pressure sensors recorded variations in muscular resting tension (tone) and the occurrence, spatial distribution, and force of the uterine contractions. Both tone and uterine activity varied significantly during the cycle. They were minimal during diestrus, increased during proestrus, reached maximal values at estrus, and then decreased. The highest synchronized motor activity with presence of peristaltic-antiperistaltic movements occurred during estrus. The prevailing direction of the uterine contractions during late estrus (immediate preovulatory period) was cervico-tubal.

A mixture of amphoteric surfactants with antimicrobial properties, C31G, was evaluated as a teat dip by a modified excised teat model. The model was modified to avoid misinterpretation of results from indigenous bacterial microflora on teats. In three experiments, bacterial numbers recovered from teats dipped in .75, 1.5, and 3.0% solutions of C31G were compared with bacteria recovered from undipped teats (negative controls) and teats dipped with 1.0% iodophor (an effective teat dip). Mean log reductions of teat end concentrations of Staphylococcus, aureus, Streptococcus fecalis, and Escherichia coli were determined in each experiment. Efficacy was greatest for the 3.0% solution of C31G with mean log reductions (Log reduction = Log 10 of controls - Log 10 of dipped teats) 3.53 for Staphylococcus aureus, 2.89 for Streptococcus fecalis, and 3.16 for Escherichia coli. Iodophor (1%) yielded mean log reductions of 3.26 for Staphylococcus aureus, 2.16 for Streptococcus fecalis, and 2.83 for Escherichia coli. For all three organisms, number of viable organisms decreased with increasing concentrations of C31G. The efficacy of C31G should be evaluated in vivo.

Phagocytosis is an important non-specific defense mechanism. Uterine phagocytosis is reviewed emphasizing factors which may alter the uterine phagocytic responses including the estrous cycle, pregnancy and the puerperium, and the presence of an intrauterine device. Implications of phagocytosis in therapy of and recovery from intrauterine infections are considered.

The purpose in this experiment was to determine the relationship between subclinical mastitis and the estrous cycle. Subclinical mastitis was defined as a quarter in which milk had a somatic cell concentration greater than 500,000/ml and was bacteriologic culture-positive on 2 consecutive examinations. Normal quarters were defined as quarters from which milk had a somatic cell concentration less than 500,000/ml and was bacteriologic culture-negative on 2 consecutive examinations. Selected biochemical and cytologic characteristics of milk from 10 cows with subclinical mastitis were measured at 5-day intervals during the estrous cycle. Milk and blood progesterone concentrations were determined. Analysis of variance of dependent variables was performed, using a model with the following factors: cows, treatments, days of estrous cycle, and interaction of treatment with day of the estrous cycle. Treatment consisted of comparison of normal and subclinically mastitic quarters. Clinical signs of mastitis tended to occur more often during estrus (days 0 and 20) than during diestrus (day 10). Day of the estrous cycle was a significant source of variation for bovine serum albumin concentrations in milk. Somatic cell concentrations, electrical conductivity, milk bacterial concentrations, and log10 milk bacterial concentrations did not vary significantly during days of the estrous cycle. A significant treatment-by-day interaction occurred for milk progesterone concentrations; blood progesterone concentrations were not similarly affected. Milk progesterone concentrations for mastitic and normal quarters were similar at estrus (days 0 and 20) and metestrus (day 5). Milk progesterone concentrations for mastitic quarters were significantly decreased on day 15 of the estrous cycle, compared with values from normal quarters.

An investigation was conducted on changes in sperm morphology along the excurrent duct of bulls. The study comprised 20 bulls with proven fertility and normal semen picture, and 10 bulls with pathologic semen. The morphology of spermatozoa was evaluated on ejaculates and on postslaughter collected contents from the excurrent duct. The incidence of pathologic sperm heads decreased along the duct in both groups of bulls. The main decrease generally occurred in caput epididymidis. In bulls with pathologic semen, the decrease continued in lower regions of epididymis and was deferens. The rate and pattern of sperm removal seem to primarily depend on the quality of spermatozoa entering the excurrent duct. The removal was clearly selective and is assumed to be associated with phagocytosis of spermatozoa mainly in the efferent ductules and proximal part of caput epididymis. Proximal cytoplasmic droplets were present on almost all sperm in the efferent ductules. The incidence decreased during passage along the genital tract. Migration of cytoplasmic droplets from a proximal to a distal position took place between regions C and D of the caput epididymidis. The incidence of middle-piece abnormalities decreased during passage along the genital tract, while the incidence of sperm tail abnormalities increased in the corpus and cauda epididymidis in all bulls.

The aim of this investigation was to study the effects of various concentrations and combinations of prostaglandins (PG) on sperm migration in cervical mucus collected from estrous ewes. Semen from six rams was pooled and extended in Tes-tris-yolk-glycerol to 500 x 10(6) sperm per ml, cooled and held at 5 degrees C for three hours. Aliquots of the semen were supplemented with various concentrations of PGF(2alpha) or PGE(1), combinations of PGF(2alpha) + E(1), or PGE(1) + E(2) + E(3) + F(1alpha) + F(2alpha). The semen was filled into 0.25-ml French straws and immediately frozen in liquid nitrogen vapor. The semen was thawed in a 35 degrees C water bath for two minutes. Cervical mucus was collected from 30 ewes, pooled and filled in the capillary tubes. Frozen-thawed ram semen with PG added was brought into contact with cervical mucus, held at 37 degrees C and evaluated for sperm migration in the capillary tube at 15, 30, 60, 120, and 180 minutes under a phase-contrast microscope. At 180 minutes, sperm numbers were counted and sperm motility was graded at 20, 30, 40, 50, and 60-mm distances in the capillary tube. Analysis of the results showed that sperm migration distance increased with time, but there was no difference between the controls and samples with PG. At 180 minutes, sperm motility and number decreased, while distance of migration in the capillary tube increased. This sperm response was similar, whether the supplementation of semen was with any of several individual PGs, or a combination of two or five PGs.

Serial blood samples were collected and plasma concentrations of florfenicol (FLO) were measured following the administration of an intravenous bolus of 50 mg/kg FLO to five healthy non-lactating dairy cows. A triexponential equation provided the best fit of the data for four of the five cows. The mean value for beta corresponded to a half-life of 3.2 h. The mean apparent volume of distribution was 0.67 l/kg, and the mean body clearance was 0.15 l/kg/h. The extent of binding of FLO to bovine plasma proteins was determined in vitro at concentrations of 5 micrograms/ml and 50 micrograms/ml by equilibrium dialysis and ultrafiltration. The drug was 18% and 19% bound by equilibrium dialysis, and 23% and 19% bound by ultrafiltration, at 5 micrograms/ml and 50 micrograms/ml, respectively. Phagocytosis of 32phosphorus-labelled Staphylococcus aureus by bovine blood neutrophils was compared in vitro between neutrophils incubated in phosphate-buffered saline alone or in combination with 5, 125, or 1000 micrograms/ml chloramphenicol or FLO. There was no significant effect of chloramphenicol at any concentration. Florfenicol significantly inhibited phagocytosis at all concentrations, but the percentage inhibition was small. The clinical significance, if any, of this effect of FLO remains to be demonstrated.

Concentrations of prostaglandin F2 alpha (PGF2 alpha) and thromboxane B2 (TXB2) were evaluated in the milk of cows with naturally occurring (n = 3) and experimentally induced (n = 5) acute coliform mastitis. These arachidonic acid metabolites were measured by radioimmunoassay in unextracted milk. Experimental infections were induced by inoculating 600 to 1,200 colony-forming units of Escherichia coli into 1 mammary quarter per experimental cow. In the experimental cows, milk was collected before inoculation and at 12, 24, 36, 48, 60, and 72 hours after inoculation. Somatic cell concentrations, bovine serum albumin, and concentrations of PGF2 alpha and TXB2 were determined in milk collected at each sampling. Mild-to-moderate increases in milk PGF2 alpha and TXB2 concentrations were observed in cows with naturally occurring mastitis. the increases corresponded to the clinical severity and course of mastitis. In the experimental cows, increases in milk PGF2 alpha and TXB2 concentrations were observed, but the increases were not significant, using a statistical model that included factors of treatment, cows, hours after inoculation, cows-by-treatment and hours-by-treatment interactions, and random error (residual). Results of the present study indicated a large biological variability in milk arachidonic acid metabolite concentrations in cows with acute coliform mastitis, and that arachidonic acid metabolites may be important in the pathophysiologic process of acute coliform mastitis.

Spontaneous and drug-induced uterine motility (UM) was recorded in 5 nonanesthetized bitches for 2 to 4 days. Catheter-tip pressure transducers were surgically implanted in 1 uterine horn, tunneled subcutaneously to exit from the skin over the dorsal lumbar area, and protected by a bandage. On the day after implantation, spontaneous UM was recorded in the awake bitch. Effects of IV prostaglandin (PG) F2 alpha (5 micrograms/kg of body weight) and oxytocin (0.05 USP U/kg) and IM PGF2 alpha (25 micrograms/kg) were measured. Estradiol (1 to 25 micrograms/kg) was administered and the study was repeated 24 hours later. In awake bitches, spontaneous UM was 190% greater than UM in anesthetized bitches. Uterine motility was increased by more than 100% after IV PGF2 alpha or oxytocin and by 52% after IM PGF2 alpha. Estradiol abolished spontaneous UM, but did not affect drug-induced responses. Seemingly, spontaneous and drug-induced UM can be documented in the nonanesthetized bitch.

Effects of beta-endorphin and naloxone on bovine uterine motility were tested both in vivo and in vitro. Six cyclic Holstein cows were used to study in vivo effects of beta-endorphin and naloxone on uterine motility during estrus and diestrus. Intrauterine pressure changes were recorded by a microtip pressure transducer before and after treatment. Blood samples were taken every 10 min during the recording periods for beta-endorphin assay. The results revealed that beta-endorphin anc naloxone had no effect on intrauterine pressure in vivo. The effects of beta-endorphin and naloxone on myometrial contractility were also examined in vitro. Beta-endorphin and naloxone were added to tissue baths containing estrous and diestrous uterine strips. The results showed no significant effect of beta-endorphin and naloxone on bovine myometrial contractility. The role of beta-endorphin in bovine reproductive physiology is still not clearly understood, and additional studies are needed.

Arachidonic acid metabolites (AAM) were measured in milk and plasma during the course of acute endotoxin-induced mastitis in 12 lactating cows. Mastitis was induced by intramammary challenge exposure with 10 micrograms of Escherichia coli (026:B6) endotoxin. Endotoxin was injected into the teat cistern via the teat canal of a single randomly selected rear quarter of each cow. Concentrations of prostaglandin (PG) F2 alpha and thromboxane (Tx) B2 in fat-free unextracted milk and of 15-keto-13,14-dihydro-PGF2 alpha in plasma were measured by radioimmunoassay. Total production of AAM in milk was determined by measuring quarter milk production. The AAM were compared in 6 cows administered flunixin meglumine (1.1 mg/kg of body weight) and in 6 cows administered saline solution. Concentrations of TxB2 in milk were significantly (P less than 0.001) increased during the early course of acute mastitis in endotoxin-treated quarters of cows not administered flunixin meglumine. Peak concentrations of TxB2 in milk occurred at 8 hours after endotoxin inoculation. Flunixin meglumine treatment produced significant (P less than 0.05) reductions in milk TxB2 and plasma 15-keto-13,14-dihydro-PGF2 alpha concentrations. Concentrations of PGF2 alpha in milk and total PGF2 alpha and TxB2 production per quarter per milking were not significantly influenced by endotoxin challenge or by flunixin meglumine treatment.

Intrauterine pressure (IUP) was recorded in nonlactating dairy cows using an intraluminal catheter with two micropressure transducers located 15 cm apart at the distal end. There was a significant increase (P < 0.05) in IUP following administration of xylazine and oxytocin at all four stages of the estrous cycle. The most significant increase in IUP occurred during proestrus for both drugs. The effect of pretreatment with adrenoceptor-blocking agents on IUP changes induced by xylazine and oxytoxin was evaluated. Alpha-1 adrenoceptor blockade (prazosin) had no effect on IUP following xylazine treatment. However, alpha-2 adrenoceptor blockade (yohimbine) resulted in a reduction (P < 0.05) in IUP compared to controls. Neither prazosin or yohimbine affected oxytocin-induced IUP.

In a 270-cow dairy herd, milk samples from all cows with acute mastitis were cultured during a 12-month period. Of 119 isolates (from 166 quarters), 49% were gram-positive organisms, 39% were gram-negative organisms, and 12% were yeasts. Of all samples from cows with acute mastitis, 40% failed to produce colonies on culture media. Recovery of the common gram-positive pathogens, Staphylococcus aureus (11% of isolations) and Streptococcus agalactiae (1% of isolations), was rather low. However, S epidermidis (14% of isolations) and streptococci other than Str agalactiae (9% of isolations) were recovered more frequently than expected, particularly in recently calved cows. Coliform organisms accounted for 35% of the total isolates and were the single most important cause of acute mastitis. Of 42 cows with coliform mastitis, 6 died despite intensive antibiotic and electrolyte therapy. There was no death loss among cows with mastitis caused by gram-positive organisms. Antimicrobial susceptibilities of 95 isolates to 11 antimicrobials was determined by standardized methods. Organisms were most often susceptible to chloramphenicol, cephalothin, and gentamicin. A treatment regimen consisting primarily of oxytetracycline and/or sulfonamides systemically in conjunction with intramammary infusions of cephapirin was evaluated. Treatment response in 37 quarters was determined by culturing before treatment and at 4 or more days after treatment. Of 23 quarters initially culture-positive, 22 were negative on reculture. Treatment response appeared to agree with the results of the susceptibility testing.

The influence on sperm morphology of different methods for preparation of semen and of storage in a fixative solution was examined in 27 beef bulls subjected to a regular breeding health examination. Sperm head morphology under light microscopy did not differ between smears of fresh semen stained with carbol-fuchsin-eosin (Williams staining) or Nigrosin-Eosin. Nor was there any difference between samples stained immediately after collection and those stained after 1 month of storage at + 4 degrees C in buffered formal-saline solution. Formol-saline fixed spermatozoa examined in wet preparations under phase contrast microscopy had a higher prevalence of acrosome defects and cytoplasmic droplets than stained smears of fresh semen under light microscopy. One month of storage in formol-saline did not affect the prevalence of acrosome defects or cytoplasmic droplets. There was no influence of fixation method (wet or dry), staining, examination technique, or storage time on midpiece or sperm tail morphology. The affinity of spermatozoa to eosin at staining with Nigrosin-Eosin ("live and dead count") did not differ between fresh semen and spermatozoa that had been stored in formol-saline for 1 month. It is concluded that bull semen can be stored for at least 1 month at + 4 degrees C in buffered formal-saline without major changes in sperm morphology. Furthermore, examination of wet preparations of fixed spermatozoa under phase contrast microscope is likely to yield the most accurate results for morphological characteristics like acrosome morphology and cytoplasmic droplets.

The distribution of gentamicin (G) in plasma and uterine lumen was studied following intramuscular (i.m.) and intrauterine (i.u.) treatment. A Foley catheter was inserted into one uterine horn and retained in place by inflation of the cuff. This provided a closed system for collection of uterine lumen samples and analysis of the concentration of gentamicin for 6 h following treatment. Four normal cycling and healthy cows in dioestrus were given i.m. injections of 4 mg gentamicin/kg BW and another two were given i.m. injections of 2 mg gentamicin/kg BW gentamicin. The uteri were infused with 50 ml saline containing phenolsulphonphthalein (PSP) indicator. Blood and infused solution (IS) samples were periodically collected during the 6-h period following i.m. administration. Six hours after injection, approximately 183.7 micrograms gentamicin and 39.4 micrograms gentamicin were accumulated in the uterine lumen of cows receiving 4 mg gentamicin/kg BW and 2 mg gentamicin/kg BW, respectively. The amount of gentamicin reaching the blood stream after i.m. administration of 4 mg gentamicin/kg BW was 2.89 times that reached after administration of 2 mg gentamicin/kg BW based on the area under the curve of plots of plasma concentration of gentamicin versus time. Four normal-cycling and healthy cows in dioestrus were given i.u. infusions of gentamicin (225-275 mg) diluted in 50 ml saline containing PSP indicator using a Foley catheter in a closed system. Samples from the IS and blood were collected at various intervals for 6 h after infusion. Following i.u. infusion of gentamicin, an average of 29.4% of the dose was absorbed into the bloodstream. The majority of the dose of gentamicin (70.6%) remained in the uterine lumen throughout the 6-h period.

Milk whey immunoglobulins (Ig) and phagocytosis of staphylococci by milk polymorphonuclear neutrophilic leukocytes (PMN) were measured in 12 cows (allotted to 6 pairs) during acute bovine mastitis induced by intramammary inoculation of endotoxin. Six of these cows (or 1 in each pair) were treated with flunixin meglumine and were compared with the others (given only saline solution). The endotoxin inoculation comprised 10 micrograms of Escherichia coli O26:B6 lipopolysaccharide injected into one of the rear quarters (mammae). Flunixin meglumine was administered parenterally at a dosage of 1.1 mg/kg every 8 hours (total of 7 doses) beginning at 2 hours after endotoxin was injected. Milk samples were obtained, and whey samples were prepared from each quarter of each cow 3 times before inoculation and at 2, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 336 hours after endotoxin was inoculated. Significant increases (P less than 0.05) in milk whey IgG1, IgG2, IgM, and IgA concentrations were observed in whey samples from endotoxin-inoculated quarters. Greatest relative increase was seen for IgG2. Increased whey Ig concentrations were not observed in quarters which were not inoculated with endotoxin. Concentrations of whey IgG1 and IgM in endotoxin-inoculated quarters were significantly (P less than 0.05) decreased in flunixin meglumine-treated cows, compared with those in saline solution-treated cows. Significant increases in phagocytosis of staphylococci by milk PMN were observed in whey samples from endotoxin-inoculated quarters. Significant differences in PMN phagocytosis were not found in whey samples from cows given flunixin meglumine when compared with whey samples from cows given saline solution.

The clinical effect of flunixin meglumine administration was determined in cows with acute mastitis induced by intramammary administration of endotoxin. In 12 lactating cows, 10 micrograms of Escherichia coli 026:B6 endotoxin were administered via a teat cannula into the teat cistern of single randomly selected rear quarters. Cows were challenge exposed as pairs. One cow in each pair was administered parenteral flunixin meglumine (6 cows) and 1 cow per pair was administered saline solution (6 cows). Multiple doses (7) of 1.1 mg of flunixin meglumine/kg of body weight or saline solution were administered at 8-hour intervals beginning 2 hours after endotoxin. Cow and quarter clinical signs as well as milk somatic cell concentrations, bovine serum albumin, electrical conductivity, and milk production were determined before and for 14 days after endotoxin inoculation. Intramammary endotoxin produced signs characteristic of acute coliform mastitis. Quarter and systemic abnormalities occurred and milk production was reduced by approximately 50% at 12 hours after endotoxin. Flunixin meglumine therapy significantly (P less than or equal to 0.05) reduced rectal temperatures and quarter signs of inflammation and improved clinically graded depression when compared with these signs in saline solution-treated controls. Milk production and laboratory indicators of inflammation in milk were not significantly (P greater than 0.05) different for flunixin meglumine vs saline solution controls. The clinical response observed was consistent with the antipyretic, analgesic, and anti-inflammatory properties of flunixin meglumine.

Previously determined pharmacokinetic parameters of the disposition of oxytetracycline (OTC) in cows were used to predict an IV priming dose and a rate of constant IV infusion of OTC sufficient to approach steady-state equilibrium of the drug between plasma and genital tissue concentrations in healthy postpartum cows and postpartum cows with endometritis. After 8 hours' constant IV infusion at rates calculated to maintain a plasma concentration of approximately 5 micrograms/ml, the mean concentrations of OTC in plasma (microgram/ml) and tissues (microgram/g) of healthy and infected postpartum cows, respectively, were: plasma, 4.95 and 5.23; uterine tissue, 3.65 and 4.18; and ovarian tissue, 4.57 and 4.53. The mean plasma to genital tissue ratios for healthy and infected postpartum cows, respectively, were 1.38 and 1.31 for uterine tissue and 1.09 and 1.16 for ovarian tissue. There were no significant differences (P greater than 0.28) between healthy and infected postpartum cows in any of the parameters investigated. However, plasma-to-genital tissue ratios of concentrations of OTC in postpartum cows as a group were significantly higher (P less than or equal to 0.03) than those previously determined in cycling cows. Computer-simulated uterine tissue concentrations of OTC, after twice daily IV doses of 11 mg of OTC/kg of body weight, indicated that this dosage regimen would provide postpartum uterine tissue concentrations greater than 5 micrograms/g during most of the dosage interval.

The objectives of this experiment were to compare the effects of prostaglandin F(2alpha) (PGF(2alpha)) and its synthetic analogue treatment on postpartum bovine myometrial activity with and without estrogen priming. Sixteen multiparous, normal postpartum Holstein cows were randomly assigned to the following four treatment groups: saline PGF(2alpha), cloprostenol and fenprostalene. Myometrial activity was recorded using a catheter containing a miniature pressure transducer placed in the previously gravid horn via the cervix. Spontaneous myometrial activity was recorded at 48 h post partum for 60 min in all cows. Saline (5 ml,i.m.), PGF(2alpha) (25 mg,i.m.), cloprostenol (500 ug,i.m.) or fenprostalene (1 mg, s.c.) was administered to the cows according to the group. Myometrial activity was recorded until it returned to baseline. At the end of myometrial activity recording, 10 mg of estradiol cypionate (ECP) was injected i.m. to each cow. The same treatment schedule was repeated 12 h later. Results from this study indicate that PGF(2alpha) or its analogues, with or without ECP priming, do not increase myometrial activity in the postpartum cow. After ECP administration, both spontaneous and drug-induced myometrial activity increased; however, this increased myometrial activity was not statistically significant.

Chloramphenicol was administered by constant IV infusion to 7 healthy postpartum cows at rates predicted to approach a steady-state plasma concentration of 5 micrograms/ml. After 8 hours of constant IV infusion, uterine tissues were removed surgically and were assayed for chloramphenicol concentrations. Mean plasma-to-tissue ratios of chloramphenicol concentrations were 3.05, 3.63 (6 cows only), and 3.22 for caruncles, endometrium, and uterine wall, respectively. Plasma-to-tissue ratios of the 3 tissues were not significantly different (P greater than 0.10). Intrauterine (IU) injections of chloramphenicol (20 mg/kg of body weight) were administered to 3 healthy post-partum cows. The mean value of the fraction of the drug absorbed from the uteri of these cows was 0.40. Mean concentrations of chloramphenicol were 43.8 micrograms/g in caruncles, 34.6 micrograms/g in endometrium, 2.8 micrograms/g in uterine wall, and 2.9 micrograms/ml in plasma 8 hours after IU injections. Chloramphenicol has now been banned for use in food-producing animals in the United States because of its potential for causing toxicosis in human beings. It is illegal to use chloramphenicol in food-producing animals in the United States and in some other countries as well. This includes use by the IU route of administration because chloramphenicol and most drugs are absorbed from the uterus into the bloodstream and are distributed to milk and tissues.

Pharmacokinetic parameters of the disposition of oxytetracycline (OTC) were investigated in healthy cycling dairy cows after a single IV dose of 22 mg/kg of body weight. The biological half-life of OTC was 6.5 hours. These data were used to predict an IV priming dose and a rate of constant IV infusion of OTC sufficient to approach steady-state equilibrium of the drug between a plasma concentration of approximately 5 microgram/ml and a uterine tissue concentration. After 8 hours' constant IV infusion, the mean plasma concentration of OTC was 4.86 +/- 0.68 microgram/ml and the mean uterine tissue concentration of OTC was 4.50 +/- 0.45 microgram/ml. The mean ratio of plasma-to-uterine tissue OTC concentrations was 1.08. Computer-stimulated IV multiple doses of OTC at 11 mg/kg every 12 hours and 11 mg/kg every 24 hours suggested that the former dosage regimen could provide uterine tissue concentrations greater than 5 microgram/ml during the dosage interval, whereas the latter could provide such concentrations for only the first 12 hours of a 24-hour dosage interval.

The study of phagocytosis in the bovine uterus requires the collection of large numbers of uterine leukocytes. A method of stimulating polymorphonuclear neutrophil (PMN) invasion into the bovine uterus with oyster glycogen was tested. Following glycogen treatment, uterine aspirates contained large numbers (10(6)-10(9)) of viable uterine PMN. In Experiment 1, six cows were treated at one-week intervals by intrauterine infusion with 0.1, 1.0 and 10.0% oyster glycogen, respectively. Uterine lumens were lavaged at 0, 12, 24, 48, 72 and 168 hours post-infusion with each concentration of glycogen. The mean peak response for PMN was at 12 hours post-infusion of glycogen. In Experiment 2, uterine and peripheral blood PMN were collected from each of 12 cows. Phagocytosis was measured as the percent of (32)Phosphorus-labeled Staphylococcus aureus ingested by PMN during a one-hour incubation. Mean (+/- standard deviation) percent phagocytosis was not statistically different between blood (53.6 +/- 11.0%) and uterine (43.8 +/- 13.0%) PMN. This indicates that phagocytic activity was similar for PMN collected either from the uterine lumen or peripheral blood.

The distribution of oxytetracycline (OTC) in genital tissues, uterine secretions, milk, and plasma was examined after systemic (IM) and intrauterine (IU) administration at various intervals after administration in normal-cycling diestrous cows and in cows with chronic endometritis. The IM route resulted in OTC concentrations in endometrium and uterine secretions that were higher than were concentrations in plasma and milk over 72 hours. Twenty-four hours after IM administration, OTC concentrations in tissues of the genital tract (ovaries, oviducts, myometrium, serosa, cervix, and vagina), muscles, and udder were 100% higher than were concentrations in plasma. The IU administration resulted in a high concentration in the endometrium and uterine cavity over the 72-hour posttreatment period. The plasma concentrations were considerably lower than after the IM injection, indicating a lesser absorption from the uterus than from the IM injection site. This was more pronounced in cows with endometritis. Elimination from plasma and milk occurred in 24 hours. Contrary to results of the IM route, the IU route did not result in detectable concentrations in genital tissues apart from the endometrium 24 hours after administration.

Intrauterine fibroscopy was used in the clinical evaluation of 40 mares with established histories of subfertility. The average age of the mares was 12.2 years with a 2.8-year interval from last foaling in multiparous mares. Transluminal adhesions, endometrial cysts, diffuse fibrosis, fluid accumulation or myometrial tumours were found in 26 mares. When compared to other techniques, fibroscopy did not seem to be superior to uterine biopsy but had some advantage over rectal palpation as a single diagnostic technique. Only 3 mares failed to exhibit pathological findings when all 3 techniques were used. A second study was conducted to examine visually the effect of infusing various antibiotics and disinfectants into the uteri of clinically normal dioestrous mares. Fibre-optic examinations were performed before and after infusion of 3 mares/treatment. No gross pathological changes were seen 3 days after infusion of potassium penicillin, chloramphenicol succinate or a soluble oxytetracycline powder in a dextrose base. Lugol's solution caused severe inflammation, fibrin deposition, and ulceration of the endometrium. Ampicillin resulted in a white precipitate which adhered to the the endometrium for 10 days after treatment.