Oxidant and antioxidant profile of hyperketonemic ewes affected by pregnancy toxemia

Background: Negative energy balance during late pregnancy in ewes is an important cause of hyperketonemia. Ketone bodies can generate superoxide radicals and cause oxidative stress and cellular dysfunction, as noted in cows with subclinical ketosis or in diabetic people. Objective: The aim of this study was to evaluate the role of hyperketonemia in initiating the process of lipid peroxidation. Methods: The study included 10 pregnant ewes (aged 3.5–6 years) with pregnancy toxemia, 10 clinically healthy pregnant ewes, and 10 clinically healthy nonpregnant ewes. Serum concentrations of β‐hydroxybutyrate (BHB), cortisol, and glucose, plasma activities of glutathione peroxidase, superoxide dismutase, and catalase, and plasma concentrations of thiobarbituric acid reactive substances (TBARS), markers of lipid peroxidation, and reduced glutathione were measured. Data from the 3 groups were statistically analyzed and compared. Results: Serum concentrations of BHB, cortisol, and TBARS were significantly higher in ewes with pregnancy toxemia when compared with concentrations in healthy pregnant and nonpregnant groups (P≤.05). In ewes with pregnancy toxemia, a strong positive correlation was found between concentrations of TBARS and BHB (r=.80; P=.002) and between concentrations of BHB and cortisol (r=.76; P=.005). Conclusions: Oxidative stress and lipid peroxidation are involved in the development and complications of pregnancy toxemia. An association between hyperketonemia and the products of lipid peroxidation has also been demonstrated, suggesting that ketosis is a risk factor in the development of lipid peroxidation and oxidative stress in ewes affected by pregnancy toxemia.     

Influence of reproductive state on pituitary-adrenal activity in the ewe.

Plasma corticosteroid concentrations are altered in pregnancy, during the reproductive cycle and by ovariectomy in many species. This study was designed to examine basal ACTH and cortisol in ewes of four different reproductive statuses: ovariectomized, nonpregnant cycling, nonpregnant noncycling, and pregnant. Blood samples were drawn every 4 hr for 48 hr from ewes during quiet, undisturbed conditions and analyzed for plasma ACTH, cortisol and progesterone concentrations. There were no significant changes in ACTH, cortisol or progesterone over time. Mean progesterone concentrations were significantly greater in the pregnant ewes than in all other ewes, and were greater in cycling ewes than noncycling or ovariectomized ewes. Mean ACTH was significantly greater in pregnant ewes than noncycling ewes, and mean cortisol was significantly greater in cycling ewes than in nonpregnant cycling or noncycling ewes. Ovariectomized ewes also had significantly greater mean cortisol concentrations than cycling ewes. The results demonstrate that there is an increase in basal ACTH and cortisol in ovine pregnancy.     

Maintenance of the corpus luteum of early pregnancy in the ewe. III. Differences between pregnant and nonpregnant ewes in luteal responsiveness to prostaglandin F2 alpha

The effects of pregnancy and number of corpora lutea on luteal regression induced with prostaglandin F2 alpha (PGF2 alpha) were examined in 93 ewes. Bred and nonpregnant ewes were assigned randomly to receive a single im injection of PGF2 alpha: 0, 2, 4, 6, 8 or 10 mg/58 kg body weight. Injections were given on d 13 postestrus. The concentration of progesterone in serum 24 h after PGF2 alpha injection was affected by dose (P less than .001). The effect of pregnancy and the interaction of pregnancy with number of corpora lutea on levels of progesterone in serum were significant (P less than .05); therefore, data were partitioned according to pregnancy status and analyzed separately. There was an effect of number of corpora lutea on serum concentration of progesterone in pregnant (P less than .01) but not nonpregnant ewes (P greater than .10). Similar relationships among groups were observed for the concentration of progesterone in luteal tissue. In nonpregnant ewes the minimum dose of PGF2 alpha to produce a significant suppression of progesterone in serum (P less than .05) was 4 mg/58 kg body weight. In pregnant ewes with one or two corpora lutea, the minimum effective doses were 6 and 10 mg/58 kg body weight, respectively. The concentration of 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) in serum was related to the dose of PGF2 alpha injected. There were no differences in the concentration of PGFM in serum between pregnant and nonpregnant ewes either before or after injection. Corpora lutea of early pregnancy appear to be resistant to the luteolytic effect of PGF2 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in ovine maternal temperature, and serum cortisol and interleukin-6 concentrations after challenge with Escherichia coli lipopolysaccharide during pregnancy and early lactation

Major changes in maternal physiology during pregnancy and lactation can have a large impact on the immune and neuroendocrine systems. One of the most significant changes, observed in rats and mice, is hyporesponsiveness of the hypothalamic pituitary adrenal axis (HPAA) in response to inflammation, restraint, and other psychological stressors during late pregnancy and lactation. This attenuation, however, has not been well characterized in ruminant animals and may be relevant to their susceptibility to inflammatory diseases during these periods. Thus, the intent of this study was to characterize responsiveness of the ovine HPAA to inflammatory challenge during pregnancy and lactation. Ewes from early (33 d), middle (55 d), and late (138 d) pregnancy, as well as early lactation (10 d), were challenged i.v. with a bolus dose of 400 ng of Escherichia coli lipopolysaccharide (LPS)/kg of BW or saline. A corresponding group of nonpregnant ewes was also challenged with LPS to serve as positive control animals for each pregnancy and lactation study. Responsiveness of the HPAA was assessed by measuring the 4-h change in serum cortisol concentration after LPS challenge. The cortisol increase after LPS challenge was elevated (P < 0.01) in pregnant ewes during late pregnancy over that of nonpregnant animals. In contrast, the characteristic temperature response associated with systemic LPS challenge was decreased (P < 0.01) during early pregnancy and lactation compared with nonpregnant or nonlactating animals. Serum IL-6 concentrations were measured to assess whether changes in HPAA responsiveness during pregnancy or lactation were attributed to changes in proinflammatory signaling to the HPAA. Interestingly, enhanced cortisol responsiveness during late pregnancy was correlated with increased (P < 0.01) serum IL-6 concentrations, indicating that IL-6 may contribute to enhanced HPAA responsiveness during this period. Serum IL-6 concentrations during early and midpregnancy did not increase in response to LPS challenge, indicating that HPAA activation during periods of pregnancy may be independent of IL-6 production.     

Pancreatic insulin release and peripheral insulin sensitivity in German black headed mutton and Finish Landrace ewes: evaluation of the role of insulin resistance in the susceptibility to ovine pregnancy toxemia

German black headed mutton (GBM) ewes are recognized as being highly susceptible to ovine pregnancy toxemia (OPT). The present trial was performed to evaluate whether a breed-dependent gestational diabetes mellitus-like insulin resistance during late pregnancy might be responsible for the high incidence of OPT in the GBM breed. Modified frequently sampled intravenous glucose tolerance tests (300 mg glucose and 0.03 IU insulin per kg of BW) were performed during mid and late pregnancy, the periparturient, and the dry period in polytocous 3.5-yr-old GBM and Finnish Landrace (FL) ewes fed according to their requirements. The corresponding blood samples were analyzed for plasma concentrations of glucose, insulin, nonesterified fatty acids (NEFAs) and β-hydroxybutyrate (β-HB). In addition, the baseline plasma cortisol concentrations were determined during late pregnancy. The BW gain during pregnancy and the rearing success did not differ between the GBM and FL ewes. In both breeds, late pregnancy was associated with decreased basal plasma glucose concentrations and enhanced glucose disposal, as well as elevated baseline β-HB values. Only in the GBM ewes did the plasma NEFA concentrations increase significantly during advancing pregnancy. Moreover, significantly higher baseline plasma NEFA concentrations as well as lower (P < 0.05) basal plasma glucose values were recorded during late pregnancy in the GBM than in the FL ewes. The first-phase insulin secretion, the peripheral insulin sensitivity, and the baseline plasma cortisol values did not differ between both breeds during late pregnancy. It is concluded that increased lipolysis during late pregnancy is a characteristic of the GBM breed. Moreover, elevated plasma NEFA concentrations may contribute to impaired pancreatic insulin response and peripheral insulin resistance in GBM ewes and thus promote OPT.     

Pharmacokinetics of ivermectin in pregnant and nonpregnant sheep

The plasma kinetic profile of ivermectin during the last trimester of pregnancy was studied in ewes after a single subcutaneous administration of 0.2 mg/kg body weight (BW). Sheep were randomly distributed into two groups. Ewes in group 1 (control, n=6) were left unmated, whereas in group 2 (pregnant, n=6) ewes were estrus-synchronized and mated with rams. Both groups were housed under similar conditions of management and feeding. At 120 days of pregnancy, both groups were given a subcutaneous injection of 0.2 mg/kg BW of ivermectin. Blood samples were taken by jugular puncture according to a fixed protocol between 1 h and 40 days post-treatment. After plasma extraction and derivatization, samples were analyzed by high performance liquid chromatography with fluorescence detection. A computerized pharmacokinetic analysis was performed, and the data were compared by means of the Student t-test. The results showed that plasma concentrations of ivermectin remained longer in the pregnant than in the control group. The mean values of pharmacokinetic parameters C(max), t(max), and area under the concentration-time curve (AUC) were similar for both groups of sheep. The mean residence time (MRT) values for the pregnant group (8.8+/-1.4 days) were higher (P<0.05) than those observed in the control group (5.3+/-1.9 days). It can be concluded that pregnancy increases the residence time of ivermectin in the plasma of pregnant sheep when it is administered subcutaneously.     

A Comparison of Inulin, Paraaminohippuric Acid, and Endogenous Creatinine Clearances as Measures of Renal Function in Neonatal Foals

The glomerular filtration rate (GFR) was estimated in eight full-term neonatal foals by the single injection inulin plasma clearance method at two days of age, the continuous infusion plasma and urinary clearance methods at three days of age, and the 12-hour endogenous creatinine clearance method at four days of age. The effective renal plasma flow (ERPF) was estimated simultaneously by the single injection para-aminohippuric acid (PAH) plasma clearance method in the eight two-day old foals and the continuous PAH infusion plasma and urinary clearance method in the eight three-day old foals. The GFR (+/- 1 SEM), as determined from the single injection plasma clearance method, was 2.30 +/- 0.34 mL/kg/min; by continuous infusion plasma clearance 2.56 +/- 0.30 mL/kg/min; by continuous infusion urinary clearance 2.82 +/- 0.32 mL/kg/min; and by 12-hour endogenous creatinine clearance 2.81 +/- 0.55 mL/kg/min. Effective renal plasma flow (+/- 1 SEM) measured by the single injection plasma clearance method was 15.22 +/- 1.5 mL/kg/min, by continuous infusion plasma clearance was 18.21 +/- 2.0 mL/kg/min. and by continuous infusion urinary clearance it was 11.95 +/- 1.9 mL/kg/min. The results of these methods were not statistically different. On a per kilogram body weight basis, the full-term neonatal foal's GFR and ERPF was determined to be comparable with adult equine GFR and ERPF.     

Cortisol in pregnancy toxaemia of sheep

Of 31 pregnant ewes with clinical signs of pregnancy toxaemia, 24 had hypoglycaemia and hyperketonaemia at the time that a single blood sample was obtained. Twenty-five of these had a plasma cortisol concentration in excess of 10 ng/ml and six had a value below this. All the seven animals which did not show both hypoglycaemia and hyperketonaemia had a plasma cortisol concentration in excess of 10 ng/ml. Taking all the sheep together, 80% had a high plasma cortisol concentration. This could be the consequence of increased adrenal output or reduced excretion by the liver.     

Insulin Sensitivity during Late Gestation in Ewes Affected by Pregnancy Toxemia and in Ewes with High and Low Susceptibility to this Disorder

Background

Insulin resistance during late gestation might act as 1 etiologic factor causing pregnancy toxemia in ewes.

Objective

Evaluation of pancreatic insulin secretion and peripheral insulin sensitivity in ewes with differing susceptibility to pregnancy toxemia and in ketotic ewes.

Animals

Pregnant ewes suffering from (PT, n = 5) and ewes with high (HR, n = 7) and low risk (LR, n = 5) of being affected by pregnancy toxemia.

Methods

In a case‐control study, the pancreatic insulin release and the peripheral insulin sensitivity were assessed by means of the intravenous glucose tolerance test with subsequent measurement of the plasma concentrations of glucose, insulin, nonesterified fatty acids (NEFA), and β‐hydroxybutyrate (β‐HB). The ewes were tested during late pregnancy within 5 and 15 days antepartum.

Results

The insulin secretion after glucose administration was significantly lower in the HR and PT than in the LR ewes. The baseline rate of lipolysis was significantly increased in the HR ewes, but the NEFA clearance was similar in both risk groups, albeit delayed in the PT ewes. The baseline β‐HB concentration was significantly higher in the PT than in the HR and LR ewes. In the HR and in the PT ewes, the plasma β‐HB concentrations did not decrease after glucose administration.

Conclusion and Clinical Importance

There is reduced pancreatic first‐phase insulin response and impaired insulin‐dependent inhibition of the ketone body formation during late pregnancy in the HR and PT ewes. This insulin resistance might represent 1 causative factor in the pathogenesis of ovine pregnancy toxemia.     

Digesta kinetics, ruminal fermentation characteristics and serum metabolites of pregnant and lactating ewes fed chopped alfalfa hay

Eight ruminally cannulated ewes (four control and four bred; average BW = 85.7 kg), limit-fed alfalfa hay (1.86% BW), were used in two experiments to determine the effects of pregnancy and lactation on digestive function and serum metabolites. Seven-day sampling periods were used starting on d 102, 118 and 132 of gestation (Exp. 1) and d 14 and 32 of lactation (Exp. 2). Particulate (6.8 vs 4.9%/h; PPR) and fluid passage rates (13.9 vs 10.9%/h) were greater (P less than .05) and gastrointestinal mean retention time (28.9 vs 35.7 h) and fluid turnover time (FTT, 7.5 vs 9.5 h) were lesser (P less than .05) in pregnant than in nonpregnant ewes, respectively. Isobutyrate concentration was lower (P less than .05) in pregnant (1.7 mol/100 mol) than in nonpregnant (1.9 mol/100 mol) ewes. No differences (P greater than .10) were noted for any other ruminal fermentation measures between pregnant and nonpregnant ewes. In Exp. 2, no differences (P greater than .10) were noted in digesta kinetics or ruminal fermentation measures except for isobutyrate and isovalerate molar proportions and serum urea N (SUN) concentration. Isobutyrate, isovalerate and SUN concentrations (21.8 vs 26.1 mg/dl) were lower (P less than .05) in lactating ewes than in nonlactating ewes. Gastrointestinal fill (5.7 vs 7.7 g/kg BW) and FTT (9.3 vs 12.7 h) were lesser and DM digestion (66.7 vs 57.4%) was greater (P less than .05) in lactating than in nonlactating ewes. Data suggest that, during pregnancy, passage rate increases occur without affecting DM digestion and that, during lactation, PPR is not affected when ewes are limit-fed.     

Pharmacokinetics of gentamicin in mares in late pregnancy and early lactation

The disposition of drugs may differ between pregnant and nonpregnant animals, necessitating a change in dosage. We hypothesized that volume of distribution or clearance may be different for aminoglycoside antibiotics in pregnant mares vs. nonpregnant lactating mares. To examine this hypothesis, we administered gentamicin sulfate to seven Thoroughbred and Quarterhorse mares on two occasions, followed by plasma drug gentamicin assay and pharmacokinetic analysis. The first dose was administered 1-4 weeks before parturition (mean weight 578 kg) and the second dose was administered in the period 1-4 weeks after parturition (mean weight 518 kg). The dose administered at each time was approximately 6.6 mg/kg, intravenously (i.v.). Plasma gentamicin concentrations were determined using fluorescence polarization immunoassay and pharmacokinetic analysis was performed using a two-compartment open model. The plasma concentration vs. time profiles and total area-under-the-curve were almost identical for mares at late gestation vs. early lactation. Mean volume of distribution at steady-state was 0.15 (+/-0.02) and 0.16 (+/-0.03) L/kg, systemic clearance was 1.06 (+/-0.17) and 1.11 (+/-0.17) mL/kg/min, and mean (harmonic) elimination half-life was 2.2 and 2.1 h, for pregnant and nonpregnant mares, respectively. We concluded that there were no differences in drug distribution and clearance between pregnant and nonpregnant lactating mares. Gentamicin was also assayed in plasma of newborn foals after an injection of 6.6 mg/kg to three of the mares within 60 min of parturition. Gentamicin was undetectable in plasma samples from these foals and, therefore, apparently does not cross the placenta of mares at term.     

Effect of water deprivation on absorption (oral, intramuscular) and disposition of ampicillin in sheep

The effects of a 72 h water deprivation on the absorption--intramuscular (i.m.) and oral and disposition of ampicillin, inulin and para-aminohippuric acid (PAH) were investigated in six sheep. After intravenous (i.v.) administration of ampicillin sodium (10 mg/kg), the water deprivation decreased slightly the initial volume of distribution (0.082 +/- 0.033 vs. 0.055 +/- 0.030 l/kg) but not the steady state volume of distribution. The plasma clearance was significantly decreased (6.21 +/- 1.94 vs. 3.90 +/- 1.92 ml/min/kg) and the mean residence time (MRT) was increased from 22.25 +/- 4.91 to 33.36 +/- 8.16 min. After i.m. administration of ampicillin sodium (20 mg/kg), ampicillin concentrations were systematically higher after a 3-day period of water deprivation than during the control period but the muscular absorption rate was not modified. After oral administration of ampicillin trihydrate (1 g in toto) plasma concentrations were much lower and more persistent than after an i.m. administration and the systemic availability remained low whatever the hydration status. Influences of water deprivation on ampicillin disposition were linked to adaptation of renal function as assessed by inulin and PAH clearances. The therapeutic relevance of the results are discussed for a better definition of dosage regimens for sheep reared in arid environments.     

A comparative study of the pharmacokinetics of thiopental in the rabbit, sheep and dog

The central arterial pharmacokinetics of thiopental were studied in six rabbits, six sheep and six dogs after a short infusion at approximately 10 mg/kg min. Thiopental was infused to a defined electro-encephalographic endpoint (EEG burst suppression). The time to reach early burst suppression was longer in the dog (3.9 +/- 0.5 min) compared with the sheep (3.0 +/- 0.6 min) and the rabbit (2.5 +/- 0.5 min). The total dose required to produce the same level of EEG activity was higher in the dog (35.9 +/- 6.8 mg/kg) compared with the sheep (24.3 +/- 5.3 mg/kg) and the rabbit (21.6 +/- 6.8 mg/kg). The plasma concentration-time data for each animal was fitted using non-linear regression to a bi- or tri-exponential function. In all animals, the plasma-time profile was best described as a tri-exponential decay. The initial volume of distribution was similar in all three species (rabbit, 38.6 +/- 10.0 mg/kg; sheep, 44.5 +/- 9.1 ml/kg; dog, 38.1 +/- 18.4 ml/kg). The maximum arterial plasma thiopental concentration achieved at EEG burst suppression was higher in the sheep (221.8 +/- 27.9 micrograms/ml) than the dog (164.7 +/- 29.9 micrograms/ml) or the rabbit (112.3 +/- 15.1 micrograms/ml). Thiopental distribution clearance was slower in the sheep (43.6 +/- 15.1 ml/min/kg) compared with the rabbit (110.5 +/- 18.7 ml/min kg) and the dog (97.2 +/- 47.2 ml/min kg). Elimination half-life was extended in the sheep (251.9 +/- 107.8 min) and dog (182.4 +/- 57.9 min) relative to the rabbit (43.1 +/- 3.4 min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of zearalenone on early pregnancy in guinea pigs

Female guinea pigs were tested to determine whether they could serve as a model of zearalenone (ZEN) toxicosis during early pregnancy, as observed in domestic swine. Only 1 of 4 female guinea pigs that were given 21 mg of ZEN/kg of body weight orally during the first 8 days after mating was pregnant when examined 22 days after mating. Guinea pigs that were given 7 or 14 mg of ZEN/kg had normal fetal development. Serum concentrations of progesterone were less than 12 ng/ml in all guinea pigs 8 and 15 days after mating. Serum concentrations of progesterone were greater than 100 ng/ml in pregnant guinea pigs on day 22, but remained less than 12 ng/ml in nonpregnant guinea pigs. Three of 5 guinea pigs treated with 20 mg of ZEN/kg and only 1 of 4 guinea pigs given 30 mg of ZEN/kg on days 1 to 3 after mating were pregnant 22 days after mating. Female guinea pigs treated with 20 or 30 mg of ZEN/kg on days 4 to 5 or 6 to 8 after mating and female guinea pigs treated with 60 or 90 mg of ZEN/kg on days 4 and 5 after mating had normal pregnancies. Serum concentrations of progesterone were less than 10 ng/ml in all guinea pigs on day 15 and remained low on day 22 only in nonpregnant guinea pigs.(ABSTRACT TRUNCATED AT 250 WORDS)     

DETERMINATION OF GLOMERULAR FILTRATION RATE IN DOGS USING CONTRAST-ENHANCED COMPUTED TOMOGRAPHY

The purpose of this project was to establish a procedure and reference values for glomerular filtration rate (GFR) using contrast-enhanced computed tomography (CT) in eight healthy dogs. A single section of the kidney was scanned sequentially after bolus injection (3 ml/s) of iohexol (300 mg/kg). Time-attenuation curves were constructed and the GFR per volume of kidney was calculated using Patlak graphical analysis software. The GFR was then converted from contrast clearance per unit volume (ml/min/ml) to contrast clearance per body weight (ml/min/kg). Individual kidney and global GFR were calculated using both CT and nuclear scintigraphy. Global GFR for each dog was also determined by plasma iohexol clearance. Contrast-enhanced CT underestimated the global GFR compared with the other two methods. The average global GFR was 2.57 +/- 0.33 ml/ min/kg using functional CT and 4.06 +/- 0.37 ml/min/kg using plasma iohexol clearance. There was significant (P < 0.05) interobserver variability of CT GFR of the right kidney and total GFR. There was decreased interobserver variability for the left kidney. There was no difference in the intraobserver variability for CT-determined individual kidney and global GFR. There was no difference between the motion corrected and nonmotion corrected values for individual and global CT GFR. Nuclear scintigraphy produced a slightly higher coefficient of variation than contrast-enhanced CT, 2.9% and 1.0%, respectively. It is hypothesized that altered renal blood flow, hematocrit of the small vessels, and nephrotoxicity play a role in the underestimation of GFR by contrast-enhanced CT.     

Pharmacokinetics of tulathromycin in fetal sheep and pregnant ewes

Macrolides are important antimicrobials frequently used in human and veterinary medicine in the treatment of pregnant women and pregnant livestock. They may be useful for the control of infectious ovine abortion, which has economic, animal health, and human health impacts. In this study, catheters were surgically placed in the fetal vasculature and amnion of pregnant ewes at 115 (±2) days of gestation. Ewes were given a single dose of 2.5 mg/kg tulathromycin subcutaneously, and drug concentrations were determined in fetal plasma, maternal plasma, and amniotic fluid at 4, 8, 12, 24, 36, 48, 72, 144, and 288 hr after drug administration. Pharmacokinetic parameters in maternal plasma were estimated using noncompartmental analysis and were similar to those previously reported in nonpregnant ewes. Tulathromycin was present in fetal plasma and amniotic fluid, indicating therapeutic potential for use against organisms in these compartments, though concentrations were lower than those in maternal plasma. Time‐course of drug concentrations in the fetus was quite different than that in the ewe, with plasma concentrations reaching a plateau at 4 hr and remaining at this concentration for the remainder of the sampling period (288 hr), raising questions about how tulathromycin may be transported into or metabolized and eliminated by the fetus.     

Measurement of glomerular filtration rate, renal plasma flow, and endogenous creatinine clearance in cheetahs (Acinonyx jubatus jubatus).

Glomerular filtration rate (GFR), renal plasma flow (RPF), and the endogenous creatinine clearance (CCr) rate were determined in 13 captive cheetahs, Acinonyx jubatus jubatus (seven females and six males, 1.5-7.5 yr of age, x = 5.02 yr), during general anesthesia with Telazol and isoflurane by measuring the urinary clearances of inulin, para-aminohipppuric acid, and endogenous creatinine, respectively. Methods to determine GFR, RPF, and endogenous CCr in captive cheetahs were evaluated, and the relationship between GFR and CCr for this species was determined. The GFR and the RPF were stable during the procedure, with mean values of 1.59+/-0.17 ml/min/kg body weight and 5.12+/-1.15 ml/min/kg body weight, respectively. Although the mean value for CCr (1.47+/-0.20 ml/min/kg body weight) was significantly less than the corresponding value for GFR, the mean difference (0.11+/-0.02 ml/min/kg weight) between the two measurements was slight, and the values were highly correlated (R2 = 0.928; P < 0.0001). The measurement of CCr in cheetahs should provide a reliable estimate of GFR, facilitating the early detection of renal disease in this species.     

Single-injection method for evaluation of renal function with 3H-inulin and 14C-tetraethylammonium bromide in conscious unrestrained Sprague-Dawley rats

A single-injection, double-isotope method for simultaneously determining glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in conscious, unrestrained rats was evaluated. 3H-inulin and 14C-tetraethylammonium bromide were used to determine GFR and ERPF, respectively. Using a modified, single exponential, 1-compartment, mathematical model, solute clearance was estimated, using a plasma radioactivity disappearance curve constructed from samples collected during a 60-minute period. In 12 healthy, conscious, adult male Sprague-Dawley rats, the mean (+/- SEM) GFR, ERPF, and filtration fraction were 5.65 +/- 0.40 ml/min/kg, 13.92 +/- 0.82 ml/min/kg, and 0.41 +/- 0.03, respectively. In 7 adult male Sprague-Dawley rats that had undergone a three-quarter nephrectomy 6 weeks prior to study, the mean GFR, ERPF, and filtration fraction were 2.69 +/- 0.36 ml/min/kg, 7.02 +/- 0.90 ml/min/kg, and 0.39 +/- 0.03, respectively. In 37 adult male rats in various stages of renal disease, the mean GFR and ERPF correlated significantly (r = 0.85, P less than 0.001 and r = 0.83, P less than 0.001, respectively) with the reciprocal of plasma creatinine. The single-injection, double-isotope technique yielded functional values similar to those reported for healthy rats in which other clearance methods were used. Using this technique, we were able to detect alterations associated with various degrees of renal functional loss. The technique enabled us to evaluate conscious, unrestrained rats, eliminated the need to collect urine, and required short blood collection times (60 min) and small volumes (0.1 ml) of plasma.     

Serum protein pattern in ewe with pregnancy toxemia

Pregnancy toxemia is a metabolic disease of pregnant ewes which causes significant economic losses in sheep industry. The pathophysiology and metabolic changes of this disorder remain poorly understood. We conducted this study to describe the serum protein pattern associated with the pregnancy toxemia in ewes. In this study, the electrophoretic pattern of serum proteins of 15 ewes with naturally occuring pregnancy toxemia and 12 ewes with uncomplicated pregnant were investigated by Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE). Serum protein patterns were mainly characterized by four bands and located in the 76 kDa, 66 kDa, 55 kDa and 29 kDa both diseased and control groups. The percent of the 66 kDa, 55 kDa and 29 kDa proteins were decreased (P < 0.001 for 66 kDa; P < 0.01 for 55 kDa and P < 0.05 for 29 kDa) while 76 kDa (P < 0.05) protein was significantly increased (P < 0.001) in ewes with pregnancy toxemia relative to controls. Positive correlations were found between activities of liver enzymes and percentage of the distribution in 76 kDa, 55 kDa proteins. In contrast, there was a negative correlation between the 66 kDa protein and liver enzymes. In conclusion, the results of this study demonstrate that the percentages of the 76 kDa, 66 kDa, 55 kDa and 29 kDa proteins are significantly altered in ewes with pregnancy toxemia. However, further studies are needed to explore the potential role of these alterations in the pathophysiology in ewe with pregnancy toxemia.     

Maintenance of the corpus luteum of early pregnancy in the ewe. IV. Changes in luteal sensitivity to prostaglandin F2 alpha throughout early pregnancy

Two experiments were conducted to examine the temporal aspects of luteal resistance to the luteolytic effect of prostaglandin (PG) F2 alpha during early pregnancy. In Exp. 1, 14 pregnant and 12 nonpregnant ewes were treated with PGF2 alpha either on d 10 or 13 post-estrus. Jugular venous blood samples were collected at -30 min, 0, 6, 12, 18, 24, 30 and 36 h post-injection for quantification of progesterone. The difference (delta P) between pre-treatment and post-treatment concentrations of progesterone was calculated for each ewe. There was a significant interaction between pregnancy status and day of treatment on delta P (P less than .05). Pregnant and nonpregnant ewes treated on d 10 showed a large delta P. A large delta P also was observed in nonpregnant ewes treated on d 13 post-estrus. However, delta P in pregnant ewes treated on d 13 was smaller than in the other three groups (P less than .05). The temporal patterns of concentrations of progesterone in serum were different among treatment groups (P less than .05). A suppression in the concentration of progesterone was observed by 24 h post-injection in all four treatment groups. Progesterone returned to pre-treatment levels only in pregnant ewes treated on d 13. In Exp. 2, 47 pregnant ewes were treated with PGF2 alpha on d 10, 13, 16, 19, 22, 26 or 30 postestrus. Blood samples were collected and data were analyzed as described for Exp. 1.(ABSTRACT TRUNCATED AT 250 WORDS)