The influence of intramammary lipopolysaccharide infusion on serum Ca, P, vitamin D, cytokines and cortisol concentrations in lactating sows

Ten multiparous lactating sows were used to investigate whether intramammary infusion of lipopolysaccharides (LPS; Escherichia coli 0111:B4; 2.0 microg/kg of body weight) would affect the circulating concentrations of Ca, P, 25-hydroxyvitamin D (25-OHD), tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and cortisol. The sows were randomly allotted to either control group (control) or LPS-treated group with five individuals per group and were infused with either physiological saline solution or LPS solution. The rectal temperature and udder quarter appearance were recorded at 0 (just before infusion), 1, 3, 7, 12 or 24 h after infusion. Blood samples were taken at 0, 1, 3, 7, 12 or 24 h after infusion. Before infusion, the rectal temperatures of all sows were below 39.2 degrees C. At 3 and 7 h after infusion, the sows in the LPS group had a rectal temperature over 39.4 degrees C. At 24 h after infusion, the rectal temperatures returned to pre-infusion levels. Serum Ca and P concentrations in the LPS group decreased (P < 0.05) after LPS infusion compared with the control group at 1 h after infusion. No significant differences (P > 0.05) in the concentrations of 25-OHD were observed between groups control and LPS at any sampling time. Increased (P < 0.01) concentrations of serum TNF-alpha, IL-6 and cortisol were observed in the LPS group compared with the control group at 3 and 7 h after infusion respectively. In conclusion, the elevation of serum concentrations of TNF-alpha, IL-6 and cortisol and the alterations of circulating concentrations of Ca and P following LPS infusion indicate that the immune system has been activated and immune activation may affect macromineral homeostatic regulation, which might have important implications for metabolic health of lactating sows. Lowered serum Ca and P following immune activation also shows a causative mechanism whereby immune activation increases the risk of secondary disorders such as mastitis-metritis-agalactia syndrome. However, immune activation did not affect circulating concentrations of vitamin D metabolites.     

Gentamicin concentrations in synovial fluid and joint tissues during intravenous administration or continuous intra-articular infusion of the tarsocrural joint of clinically normal horses

OBJECTIVE: To compare gentamicin concentrations achieved in synovial fluid and joint tissues during IV administration and continuous intra-articular (IA) infusion of the tarsocrural joint in horses. ANIMALS: 18 horses with clinically normal tarsocrural joints. PROCEDURE: Horses were assigned to 3 groups (6 horses/group) and administered gentamicin (6.6 mg/kg, IV, q 24 h for 4 days; group 1), a continuous IA infusion of gentamicin into the tarsocrural joint (50 mg/h for 73 hours; group 2), or both treatments (group 3). Serum, synovial fluid, and joint tissue samples were collected for measurement of gentamicin at various time points during and 73 hours after initiation of treatment. Gentamicin concentrations were compared by use of a Kruskal-Wallis ANOVA. RESULTS: At 73 hours, mean +/- SE gentamicin concentrations in synovial fluid, synovial membrane, joint capsule, subchondral bone, and collateral ligament of group 1 horses were 11.5 +/- 1.5 microg/mL, 21.1 +/- 3.0 microg/g, 17.1 +/- 1.4 microg/g, 9.8 +/- 2.0 microg/g, and 5.9 +/- 0.7 microg/g, respectively. Corresponding concentrations in group 2 horses were 458.7 +/- 130.3 microg/mL, 496.8 +/- 126.5 microg/g, 128.5 +/- 74.2 microg/g, 99.4 +/- 47.3 microg/g, and 13.5 +/- 7.6 microg/g, respectively. Gentamicin concentrations in synovial fluid, synovial membrane, and joint capsule of group 1 horses were significantly lower than concentrations in those samples for horses in groups 2 and 3. CONCLUSIONS AND CLINICAL RELEVANCE: Continuous IA infusion of gentamicin achieves higher drug concentrations in joint tissues of normal tarsocrural joints of horses, compared with concentrations after IV administration.     

Effect of low doses of cosyntropin on serum cortisol concentrations in clinically normal dogs

OBJECTIVE: To determine the lowest of 5 doses of cosyntropin (1.0, 0.5, 0.1, 0.05, or 0.01 microg/kg) administered IV that stimulates maximal cortisol secretion in clinically normal dogs. ANIMALS: 10 clinically normal dogs. PROCEDURES: 5 dose-response experiments were performed in each of the dogs. Each dog received 5 doses of cosyntropin (1.0, 0.5, 0.1, 0.05, and 0.01 microg/kg) IV in random order (2-week interval between each dose). Serum samples for determination of cortisol concentrations were obtained before (baseline) and at 10, 20, 30, 40, 50, 60, 120, and 240 minutes after cosyntropin administration. RESULTS: Compared with baseline values, mean serum cortisol concentration in the study dogs increased significantly after administration of each of the 5 cosyntropin doses. Mean peak serum cortisol concentration was significantly lower after administration of 0.01, 0.05, and 0.1 microg of cosyntropin/kg, compared with findings after administration of 0.5 and 1.0 microg of cosyntropin/kg. After administration of 0.5 and 1.0 microg of cosyntropin/kg, mean peak serum cortisol concentration did not differ significantly; higher doses of cosyntropin resulted in more sustained increases in serum cortisol concentration, and peak response developed after a longer interval. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of cosyntropin IV at a dose of 0.5 microg/kg induced maximal cortisol secretion in healthy dogs. Serum cortisol concentration was reliably increased in all dogs after the administration of each of the 5 doses of cosyntropin. These data should be useful in subsequent studies to evaluate the hypothalamic-pituitary-adrenal axis in healthy and critically ill dogs.     

Pharmacokinetics of voriconazole following intravenous and oral administration and body fluid concentrations of voriconazole following repeated oral administration in horses

OBJECTIVE: To determine the pharmacokinetics of voriconazole following IV and PO administration and assess the distribution of voriconazole into body fluids following repeated PO administration in horses. ANIMALS: 6 clinically normal adult horses. PROCEDURES: All horses received voriconazole (10 mg/kg) IV and PO (2-week interval between treatments). Plasma voriconazole concentrations were determined prior to and at intervals following administration. Subsequently, voriconazole was administered PO (3 mg/kg) twice daily for 10 days to all horses; plasma, synovial fluid, CSF, urine, and preocular tear film concentrations of voriconazole were then assessed. RESULTS: Mean +/- SD volume of distribution at steady state was 1,604.9 +/- 406.4 mL/kg. Systemic bioavailability of voriconazole following PO administration was 95 +/- 19%; the highest plasma concentration of 6.1 +/- 1.4 microg/mL was attained at 0.6 to 2.3 hours. Mean peak plasma concentration was 2.57 microg/mL, and mean trough plasma concentration was 1.32 microg/mL. Mean plasma, CSF, synovial fluid, urine, and preocular tear film concentrations of voriconazole after long-term PO administration were 5.163 +/- 1.594 microg/mL, 2.508 +/- 1.616 microg/mL, 3.073 +/- 2.093 microg/mL, 4.422 +/- 0.8095 microg/mL, and 3.376 +/- 1.297 microg/mL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that voriconazole distributed quickly and widely in the body; following a single IV dose, initial plasma concentrations were high with a steady and early decrease in plasma concentration. Absorption of voriconazole after PO administration was excellent, compared with absorption after IV administration. Voriconazole appears to be another option for the treatment of fungal infections in horses.     

Comparison of transdermal administration of fentanyl versus intramuscular administration of butorphanol for analgesia after onychectomy in cats

OBJECTIVE: To compare postoperative discomfort assessed by subjective pain score and plasma cortisol concentrations in cats undergoing onychectomy that received analgesia by use of transdermal fentanyl (TDF) patches or an i.m. injection of butorphanol. DESIGN: Randomized prospective clinical trial. ANIMALS: 22 client-owned cats weighing 2.2 to 5 kg (4.84 to 11 lb) undergoing onychectomy. PROCEDURE: Researchers were blinded to which cats received a TDF patch (25 microg/h) 18 to 24 hours prior to surgery or an i.m. injection of butorphanol (0.2 mg/kg (0.09 mg/lb]) at the time of sedation, immediately following extubation, and at 4-hour intervals thereafter for 12 hours. Clinical variables, plasma cortisol concentration, and pain scores were evaluated and recorded 24 hours prior to surgery, at extubation, and 2, 4, 8, 12, 24, 36, and 48 hours after surgery. RESULTS: The TDF group had a lower pain score than the butorphanol group only at 8 hours after surgery. Both groups had significantly lower mean plasma cortisol concentrations 0, 24, 36, and 48 hours after surgery, compared with mean plasma cortisol concentrations prior to surgery. No significant differences in appetite or response to handling the feet were observed between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Our data did not reveal a difference in pain relief between administration of TDF and butorphanol. Plasma cortisol concentrations were not different between groups. Fentanyl appeared to provide equivalent analgesia to butorphanol in cats undergoing onychectomy. The primary advantage of using a TDF patch is that repeated injections are not required.     

Plasma cortisol concentrations following cortisone infusion in dogs before and after treatment with cortisone acetate

OBJECTIVE: To evaluate effects of iatrogenic hyperadrenocorticism on plasma cortisol concentrations produced by an infusion of hydrocortisone in dogs. PROCEDURE: Plasma cortisol concentrations were measured regularly during a 6 h infusion of hydrocortisone sodium succinate at two dose rates. The infusions were performed before and after treatment for 30 d with oral cortisone acetate at 10 mg/kg/24 h, divided thrice daily. Adrenal activity during the experimental period was assessed by weekly ACTH stimulation tests. RESULTS: Both infusion rates produced lower plasma cortisol concentrations after treatment for 30 d with cortisone. CONCLUSION: Prior exposure to high concentrations of glucocorticoids may result in accelerated metabolism of glucocorticoids administered subsequently. This may necessitate increased dosages when using glucocorticoids to support inadequate adrenal function.     

Effect of medetomidine and its antagonism with atipamezole on stress-related hormones, metabolites, physiologic responses, sedation, and mechanical threshold in goats

OBJECTIVE: To evaluate the effects of medetomidine and its antagonism with atipamezole in goats. STUDY DESIGN: Prospective randomized crossover study with 1 week between treatments. ANIMALS: Six healthy 3-year-old neutered goats (three male and three female) weighing 39.1-90.9 kg (60.0 +/- 18 kg, mean +/- SD). METHODS: Goats were given medetomidine (20 microg kg(-1), IV) followed, 25 minutes later, by either atipamezole (100 microg kg(-1), IV) or saline. Heart and respiratory rate, rectal temperature, indirect blood pressure, and mechanical threshold were measured, and sedation and posture were scored and blood samples obtained to measure epinephrine, norepinephrine, free fatty acids, glucose, and cortisol concentrations at baseline (immediately before medetomidine), 5 and 25 minutes after medetomidine administration, and at 5, 30, 60, and 120 minutes after the administration of antagonist or saline. Parametric and nonparametric tests were used to evaluate data; p < 0.05 was considered significant. RESULTS: Medetomidine decreased body temperature, heart rate, and respiratory rate and increased mean arterial blood pressure, cortisol, and glucose. Recumbency occurred 89 +/- 50 seconds after medetomidine administration. All goats were standing 86 +/- 24 seconds after atipamezole administration whereas all goats administered saline were sedate and recumbent at 2 hours. Tolerance to compression of the withers and metacarpus increased with medetomidine. From 5 to 120 minutes after saline or atipamezole administration, there were differences in body temperature, glucose, and cortisol but none in heart rate or blood pressure. Three of the six goats receiving saline developed bloat; five of six urinated. After atipamezole, four of six goats developed piloerection and all goats were agitated and vocalized. CONCLUSION: At the doses used, atipamezole antagonized the effects of medetomidine on recumbency, sedation, mechanical threshold, and the increase in glucose. Atipamezole increased the rate of return of cortisol toward baseline, and prevented further decline in rectal body temperature. CLINICAL RELEVANCE: Atipamezole may be used to antagonize some, but not all effects of medetomidine.     

Pharmacokinetics and pharmacodynamics of epsilon-aminocaproic acid in horses

OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of epsilon-aminocaproic acid (EACA), including the effects of EACA on coagulation and fibrinolysis in healthy horses. ANIMALS: 6 adult horses. PROCEDURES: Each horse received 3.5 mg of EACA/kg/min for 20 minutes, i.v. Plasma EACA concentration was measured before (time 0), during, and after infusion. Coagulation variables and plasma alpha(2)-antiplasmin activity were evaluated at time 0 and 4 hours after infusion; viscoelastic properties of clot formation were assessed at time 0 and 0.5, 1, and 4 hours after infusion. Plasma concentration versus time data were evaluated by use of a pharmacokinetic analysis computer program. RESULTS: Drug disposition was best described by a 2-compartment model with a rapid distribution phase, an elimination half-life of 2.3 hours, and mean residence time of 2.5 +/- 0.5 hours. Peak plasma EACA concentration was 462.9 +/- 70.1 microg/mL; after the end of the infusion, EACA concentration remained greater than the proposed therapeutic concentration (130 microg/mL) for 1 hour. Compared with findings at 0 minutes, EACA administration resulted in no significant change in plasma alpha(2)-antiplasmin activity at 1 or 4 hours after infusion. Thirty minutes after infusion, platelet function was significantly different from that at time 0 and 1 and 4 hours after infusion. The continuous rate infusion that would maintain proposed therapeutic plasma concentrations of EACA was predicted (ie, 3.5 mg/kg/min for 15 minutes, then 0.25 mg/kg/min). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that EACA has potential clinical use in horses for which improved clot maintenance is desired.     

Partial prostaglandin-mediated mechanism controlling the release of cortisol in plasma after intravenous administration of endotoxins

In a first series of experiments we studied the influence of E. coli endotoxins or lipopolysaccharides (LPS) administered either intravenously (i.v.) or intramammarily (i.mam.) to lactating goats on plasma cortisol and rectal temperature (RT). Differences in the magnitude of the cortisol release and shape of the fever curve were observed. In both models maximal pyrexia and fever index (FI) were comparable.

In a second series of experiments the influence of LPS on the plasma cortisol and RT was studied after i.v. injection of increasing doses of LPS : low (25 ng/kg), moderate (200 ng/kg) and relatively high (500 ng/kg). Although the cortisol response was dose dependent, the effect was not correlated with FI. The administration of flurbiprofen, a non steroidal anti-inflammatory drug (NSAID), resulted in a complete inhibition of fever at all LPS doses and the cortisol release after administration of low doses LPS. This indicates a prostaglandin mediation. With moderate and high doses LPS the cortisol release was only partially inhibited and delayed suggesting a non prostaglandin mediated mechanism.

In a third series of experiments the influence of flurbiprofen on fever and cortisol release was studied after i.mam. LPS administration. The observed increase of plasma cortisol and RT were completely abolished after flurbiprofen treatment.

It is concluded that: 1) the increase of plasma cortisol after LPS administration in lactating goats is not related to hyperthermia per se, 2) the control of fever and cortisol release may, to some extent, differ according to the LPS dose and method of administration, 3) the cortisol release observed after moderate and high doses of LPS is probably controlled by two phenomena. The first being induced by cyclo-oxygenase metabolites, the second by intermediary mediators other than prostaglandins or by LPS itself. 4) Although an eight-fold higher dose of LPS was given i.mam., a cortisol release comparable to the lowest dose of LPS (25 ng/kg) was observed. These differences in cortisol release can be ascribed to 1) a detoxification of LPS at the level of the mammary gland or 2) a slower resorption of LPS from the mammary gland.     

Pharmacokinetics and adverse effects of butorphanol administered by single intravenous injection or continuous intravenous infusion in horses

OBJECTIVE: To determine an infusion rate of butorphanol tartrate in horses that would maintain therapeutic plasma drug concentrations while minimizing development of adverse behavioral and gastrointestinal tract effects. ANIMALS: 10 healthy adult horses. PROCEDURE: Plasma butorphanol concentrations were determined by use of high-performance liquid chromatography following administration of butorphanol by single IV injection (0.1 to 0.13 mg/kg of body weight) or continuous IV infusion (loading dose, 17.8 microg/kg; infusion dosage, 23.7 microg/kg/h for 24 hours). Pharmacokinetic variables were calculated, and changes in physical examination data, gastrointestinal tract transit time, and behavior were determined over time. RESULTS: A single IV injection of butorphanol was associated with adverse behavioral and gastrointestinal tract effects including ataxia, decreased borborygmi, and decreased defecation. Elimination half-life of butorphanol was brief (44.37 minutes). Adverse gastrointestinal tract effects were less apparent during continuous 24-hour infusion of butorphanol at a dosage that resulted in a mean plasma concentration of 29 ng/ml, compared with effects after a single IV injection. No adverse behavioral effects were observed during or after continuous infusion. CONCLUSIONS AND CLINICAL RELEVANCE: Continuous IV infusion of butorphanol for 24 hours maintained plasma butorphanol concentrations within a range associated with analgesia. Adverse behavioral and gastrointestinal tract effects were minimized during infusion, compared with a single injection of butorphanol. Continuous infusion of butorphanol may be a useful treatment to induce analgesia in horses.     

Pharmacokinetics of flunixin meglumine in lactating cattle after single and multiple intramuscular and intravenous administrations

The pharmacokinetics of flunixin were studied in 6 adult lactating cattle after administration of single IV and IM doses at 1.1 mg/kg of body weight. A crossover design was used, with route of first administration in each cow determined randomly. Plasma and milk concentrations of total flunixin were determined by use of high-pressure liquid chromatography, using an assay with a lower limit of detection of 50 ng of flunixin/ml. The pharmacokinetics of flunixin were best described by a 2-compartment, open model. After IV administration, mean plasma flunixin concentrations rapidly decreased from initial concentrations of greater than 10 micrograms/ml to nondetectable concentrations at 12 hours after administration. The distribution phase was short (t1/2 alpha, harmonic mean = 0.16 hours) and the elimination phase was more prolonged (t1/2 beta, harmonic mean = 3.14 hours). Mean +/- SD clearance after IV administration was 2.51 +/- 0.96 ml/kg/min. After IM administration, the harmonic mean for the elimination phase (t1/2 beta) was prolonged at 5.20 hours. Bioavailability after IM dosing gave a mean +/- SD (n = 5) of 76.0 +/- 28.0%. Adult, lactating cows (n = 6) were challenge inoculated with endotoxin as a model of acute coliform mastitis. After multiple administration (total of 7 doses; first IV, remainder IM) of 1.1 mg/kg doses of flunixin at 8-hour intervals, plasma flunixin concentrations were approximately 1 microgram/ml at 2 hours after each dosing and 0.5 micrograms/ml just prior to each dosing. Flunixin was not detected in milk at any sampling during the study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of subanesthetic doses of ketamine on hemodynamic and immunologic variables in dogs with experimentally induced endotoxemia

OBJECTIVE: To determine the effects of ketamine hydrochloride on hemodynamic and immunologic alterations associated with experimentally induced endotoxemia in dogs. ANIMALS: 9 mixed-breed dogs. PROCEDURES: In a crossover study, dogs were randomly allocated to receive ketamine (0.5 mg/kg, IV, followed by IV infusion at a rate of 0.12 mg/kg/h for 2.5 hours) or control solution (saline [0.9% NaCl] solution, 0.25 mL, IV, followed by IV infusion at a rate of 0.5 mL/h for 2.5 hours). Onset of infusion was time 0. At 30 minutes, lipopolysaccharide (LPS; 1 microg/kg, IV) was administered. Heart rate (HR), systolic arterial blood pressure (SAP), plasma tumor necrosis factor (TNF)-alpha activity, and a CBC were evaluated. RESULTS: Mean SAP was significantly reduced in dogs administered ketamine or saline solution at 2 and 2.5 hours, compared with values at time 0. However, there was no significant difference between treatments. At 1, 2, and 2.5 hours, dogs administered ketamine had a significantly lower HR than dogs administered saline solution. Although plasma TNF-alpha activity significantly increased, compared with values at time 0 for both groups, ketamine-treated dogs had significantly lower peak plasma TNF-alpha activity 1.5 hours after LPS administration. All dogs had significant leukopenia and neutropenia after LPS administration, with no differences detected between ketamine and saline solution treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of a subanesthetic dose of ketamine had immunomodulating effects in dogs with experimentally induced endotoxemia (namely, blunting of plasma TNF-alpha activity). However, it had little effect on hemodynamic stability and no effect on WBC counts.     

Effect of continuous intravenous administration of a 50% dextrose solution on phosphorus homeostasis in dairy cows

OBJECTIVE: To determine the effect of continuous IV administration of 50% dextrose solution on phosphorus homeostasis in lactating dairy cows. DESIGN: Clinical trial. ANIMALS: 4 multiparous Jersey cows. PROCEDURES: Cows were administered 50% dextrose solution IV (0.3 g/kg/h [0.14 g/lb/h]) for 5 days. Plasma concentrations of glucose, immune-reactive insulin (IRI), and phosphorus were determined before, during, and for 72 hours after dextrose infusion. Phosphorus intake and losses of phosphorus in urine, feces, and milk were determined. Each cow received a sham treatment that included instrumentation and sampling but not administration of dextrose. RESULTS: Plasma glucose, IRI, and phosphorus concentrations were stable during sham treatment. Plasma phosphorus concentration decreased rapidly after onset of dextrose infusion, reaching a nadir in 24 hours and remaining less than baseline value for 36 hours. Plasma phosphorus concentration increased after dextrose infusion was stopped, peaking in 6 hours. Urinary phosphorus excretion did not change during dextrose infusion, but phosphorus intake decreased because of reduced feed intake, followed by decreased fecal phosphorus loss and milk yield. Rapid changes in plasma phosphorus concentration at the start and end of dextrose infusion were temporally associated with changes in plasma glucose and IRI concentrations and most likely caused by compartmental shifts of phosphorus. CONCLUSIONS AND CLINICAL RELEVANCE: Hypophosphatemia developed in response to hyperglycemia or hyperinsulinemia in dairy cows administered dextrose via continuous IV infusion. Veterinarians should monitor plasma phosphorus concentration when administering dextrose in this manner, particularly in cows with decreased appetite or preexisting hypophosphatemia.     

Comparison of pharmacokinetics of fentanyl after intravenous and transdermal administration in cats

OBJECTIVE: To compare pharmacokinetic and pharmacodynamic characteristics of fentanyl citrate after IV or transdermal administration in cats. ANIMALS: 6 healthy adult cats with a mean weight of 3.78 kg. PROCEDURE: Each cat was given fentanyl IV (25 mg/cat; mean +/- SD dosage, 7.19 +/- 1.17 mg/kg of body weight) and via a transdermal patch (25 microg of fentanyl/h). Plasma concentrations of fentanyl were measured by use of radioimmunoassay. Pharmacokinetic analyses of plasma drug concentrations were conducted, using an automated curve-stripping process followed by nonlinear, least-squares regression. Transdermal delivery of drug was calculated by use of IV pharmacokinetic data. RESULTS: Plasma concentrations of fentanyl given IV decreased rapidly (mean elimination half-life, 2.35 +/- 0.57 hours). Mean +/- SEM calculated rate of transdermal delivery of fentanyl was 8.48 +/- 1.7 mg/h (< 36% of the theoretical 25 mg/h). Median steady-state concentration of fentanyl 12 to 100 hours after application of the transdermal patch was 1.58 ng/ml. Plasma concentrations of fentanyl < 1.0 ng/ml were detected in 4 of 6 cats 12 hours after patch application, 5 of 6 cats 18 and 24 hours after application, and 6 of 6 cats 36 hours after application. CONCLUSIONS AND CLINICAL RELEVANCE: In cats, transdermal administration provides sustained plasma concentrations of fentanyl citrate throughout a 5-day period. Variation of plasma drug concentrations with transdermal absorption for each cat was pronounced. Transdermal administration of fentanyl has potential for use in cats for long-term control of pain after surgery or chronic pain associated with cancer.     

高精料诱导的SARA对泌乳期山羊血液和瘤胃液中皮质醇的影响

选择7只装有永久性瘤胃瘘管的泌乳中期山羊,2×2拉丁方设计,分别饲喂精粗比为6∶4和4∶6的饲料,通过饲喂精粗比6∶4饲料建立泌乳期山羊瘤胃亚急性酸中毒(subacute ruminal acidosis, SARA)模型,研究SARA时山羊血液和瘤胃液中皮质醇浓度、肝脏皮质醇受体(glucocorticoid receptor, GR)mRNA表达及其他相关指标的变化。结果表明,精粗比6∶4日粮饲喂2周后成功诱导SARA状态(SARA组),采食后瘤胃液pH值低于5.8持续时间约6 h,而精粗比为4∶6组山羊瘤胃液pH均高于6.0 (对照组)。高精料日粮处理对瘤胃pH和乳酸以及瘤胃液和血浆内的脂多糖、皮质醇浓度有显著性影响(P<0.05),采食前SARA组山羊瘤胃液中乳酸浓度显著高于对照组(P<0.05),采食后0~4 h乳酸含量下降,6~10 h时逐渐增加并极显著高于对照组(P<0.01);2组间瘤胃液中脂多糖浓度无显著性差异(P>0.05),SARA组血浆脂多糖浓度在采食前和采食后6 h均显著高于对照组(P<0.05);采食前SARA组山羊血液中皮质醇浓度高于对照组(P=0.05),但采食后6 h两组间无显著差异(P>0.05); 2组山羊瘤胃液中皮质醇浓度在采食后2,4和6 h分别显著高于对照组(P<0.05),但在采食前和采食后10 h无显著差异(P>0.05)。Real-time PCR结果显示,SARA组山羊肝脏中GR mRNA表达显著下调(P<0.05)。本研究结果显示,泌乳期山羊发生SARA时糖皮质激素水平升高,负反馈下调肝脏GR的表达水平,提示SARA时机体处于应激状态,可能引起肝脏的物质代谢和营养物质重分配的改变。     

Tumor necrosis factor-alpha, interleukin-6, serum amyloid A, haptoglobin, and cortisol concentrations in sows following intramammary inoculation of Escherichia coli

OBJECTIVE: To determine whether concentrations of proinflammatory cytokines, acute-phase proteins, and cortisol differ at parturition among 3 categories of sows (noninoculated, clinically affected and nonaffected following intramammary inoculation with Escherichia coll). ANIMALS: 16 sows. PROCEDURE: Sows were allocated to inoculated (n = 12) or noninoculated (4) groups. Inoculated sows received intramammary administration of E coli (serotype O127) during the 24-hour period preceding parturition. Blood samples were collected from noninoculated and inoculated sows for 3 consecutive days within 3 to 11 days before farrowing and inoculation. Samples were also collected 0, 24, 48, 72, and 96 hours after farrowing and inoculation. Inoculated sows were further categorized as affected (4 sows) or nonaffected (8 sows) based on clinical signs of disease. Serum tumor necrosis factor (TNF)-alpha, plasma interleukin (IL)-6, and serum amyloid A (SAA) concentrations were measured by use of ELISA; serum haptoglobin concentration was assayed by use of a hemoglobin-binding method; and plasma cortisol concentration was determined by use of radioimmunoassay. RESULTS: Plasma or serum concentrations of TNF-alpha, IL-6, and SAA of both categories of inoculated sows were significantly increased by 24 hours after intramammary inoculation of E coli, compared with concentrations in noninoculated sows. Concentrations of serum TNF-alpha and plasma IL-6 were significantly higher in inoculated sows that developed clinical mastitis than in nonaffected inoculated sows. CONCLUSIONS AND CLINICAL RELEVANCE: Concentrations of TNF-alpha and IL-6 are promising markers for the identification of periparturient sows with subclinical coliform mastitis. Identification of such sows should help improve the health and survival of piglets.     

Pharmacokinetics of fluconazole following intravenous and oral administration and body fluid concentrations of fluconazole following repeated oral dosing in horses

OBJECTIVE: To determine the pharmacokinetics of fluconazole in horses. ANIMALS: 6 clinically normal adult horses. PROCEDURE: Fluconazole (10 mg/kg of body weight) was administered intravenously or orally with 2 weeks between treatments. Plasma fluconazole concentrations were determined prior to and 10, 20, 30, 40, and 60 minutes and 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after administration. A long-term oral dosing regimen was designed in which all horses received a loading dose of fluconazole (14 mg/kg) followed by 5 mg/kg every 24 hours for 10 days. Fluconazole concentrations were determined in aqueous humor, plasma, CSF, synovial fluid, and urine after administration of the final dose. RESULTS: Mean (+/- SD) apparent volume of distribution of fluconazole at steady state was 1.21+/-0.01 L/kg. Systemic availability and time to maximum plasma concentration following oral administration were 101.24+/-27.50% and 1.97+/-1.68 hours, respectively. Maximum plasma concentrations and terminal half-lives after IV and oral administration were similar. Plasma, CSF, synovial fluid, aqueous humor, and urine concentrations of fluconazole after long-term oral administration of fluconazole were 30.50+/-23.88, 14.99+/-1.86, 14.19+/-5.07, 11.39+/-2.83, and 56.99+/-32.87 microg/ml, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Bioavailability of fluconazole was high after oral administration to horses. Long-term oral administration maintained plasma and body fluid concentrations of fluconazole above the mean inhibitory concentration (8.0 mg/ml) reported for fungal pathogens in horses. Fluconazole may be an appropriate agent for treatment of fungal infections in horses.     

Evaluation of plasma aldosterone concentrations before and after ACTH administration in clinically normal dogs and in dogs with various diseases

Plasma aldosterone concentrations were measured in response to adrenocorticotropic hormone (ACTH) gel administration in clinically normal dogs, in dogs with hypoadrenocorticism, and in dogs (with electrolyte abnormalities) that did not have hypoadrenocorticism. Baseline plasma aldosterone concentrations were determined from specimens obtained every 10 minutes for 3 hours from 2 dogs and every 30 minutes for 7.5 hours from 2 other dogs. During the evaluation period, plasma aldosterone concentrations varied by at least 50% in each dog. A randomized crossover design was used to compare changes in plasma aldosterone concentrations after administration of ACTH gel and physiologic NaCl solution. Dogs had significantly (P = 0.002) higher plasma aldosterone concentrations after administration of ACTH gel than after administration of NaCl solution. Plasma cortisol concentrations increased as expected after ACTH gel administration. Analysis of cortisol and aldosterone concentrations in the same specimens obtained at 7 sample collection times did not reveal significant linear correlation, and scatterplots did not indicate a nonlinear association. In addition, plasma aldosterone concentrations were determined in response to ACTH administration alone and to ACTH combined with a high dose of dexamethasone (0.1 mg/kg, IV). The plasma aldosterone response to ACTH alone was not significantly different from the response to ACTH combined with dexamethasone. For both tests, plasma aldosterone concentrations at 60 and 120 minutes after ACTH administration were significantly (P less than 0.0005 and P = 0.0001, respectively, increased, compared with base-line values. Six dogs with adrenocortical hypofunction, as determined by plasma cortisol concentrations before and after ACTH administration, had plasma aldosterone concentrations that were diminished or did not increase after ACTH administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum concentrations of cortisol, sex hormones of adrenal origin, and adrenocortical steroid intermediates in healthy dogs following stimulation with two doses of cosyntropin

OBJECTIVE: To compare the effects of 2 doses of cosyntropin (5 microg/kg vs 250 microg, IV) on serum concentrations of cortisol, sex hormones of adrenal origin, and adrenocortical steroid intermediates and determine the optimal sample collection time after adrenal stimulation with cosyntropin. ANIMALS: 10 healthy, privately owned, neutered dogs. PROCEDURE:Dogs were randomly assigned to initially receive cosyntropin at 5 microg/kg or as a total dose of 250 microg, IV. Dogs received the alternate dose 1 to 2 weeks later. Serum was obtained from blood samples collected before (0 minutes) and 30, 60, 90, and 120 minutes after cosyntropin administration. RESULTS:Maximum stimulation of cortisol, androstenedione, progesterone, and 17-hydroxyprogesterone production was achieved at 60 minutes following IV administration of cosyntropin at 5 microg/kg or as a total dose of 250 microg. Serum estradiol concentration did not increase in response to either cosyntropin dose. For all hormones, no significant difference in serum hormone concentrations was found among sample collection times of 0, 30, 60, and 90 minutes when comparing the 2 doses of cosyntropin. CONCLUSIONS AND CLINICAL RELEVANCE: Cosyntropin, when administered at 5 microg/kg, IV, effectively stimulated maximum production of cortisol, sex hormones of adrenal origin, and adrenocortical steroid intermediates at 1 hour after administration.