Individual and Diurnal Variations in Rectal Temperature,Respiration, and Heart Rate of Pack Donkeys during the Early Rainy Season

Six Nubian pack donkeys were used to determine variations in rectal temperature (RT), respiratory rate (RR), and heart rate (HR) during the early rainy season. The donkeys exhibited a diurnal range of RT, RR, and HR of 34.7 to 38.7°C, 15 to 75 breaths/minute, and 36 to 72 beats/minute, respectively, with peak mean values at 2:00 pm and a trough shortly after sunrise (7:00 am). The amplitude of the diurnal rhythm of RT and RR was not correlated with the diurnal range of ambient temperature (AT) and relative humidity (RH). Although mean diurnal RTs were positively correlated with corresponding ATs, mean daily RTs were not significantly correlated with corresponding ATs. Diurnal and daily variations in RT of donkeys, like those of other ungulates, therefore, appear to reflect an endogenous rhythm, which may be largely independent of fluctuations in environmental thermal load. The mean maximum AT and RH, and the corresponding RR and HR values, fell above the normal range for donkeys in the tropics. The season was meteorologically stressful to the donkeys, imposing significant changes in the RT, RR, and HR parameters requiring responses to maintain homeostasis. The values of the amplitude in RT, RR, and HR obtained in individual donkeys were higher than the corresponding values obtained during the hourly recordings, indicating that it is more important to evaluate the individual's vital parameters in reaching conclusion of fitness for work in donkeys. The hourly recordings have shown the hours of the day (11:00 am to 4:00 pm) that are potentially meteorologically stressful for donkeys to be used for packing during the season.     

Effect of the Depth of Insertion of the Thermometer on the Rectal Temperature of Donkeys During the Hot-Dry Season in a Tropical Savannah

The objective of the present study was to evaluate the effect of the depth of insertion and environmental parameters on the rectal temperature (RT) in donkeys during the hot-dry season in a tropical savannah zone of Nigeria. The experimental subjects were comprised of thirty donkeys divided into three groups based on age: group I, 10 foals (40.67 ± 2.20 kg; 1.50 ± 0.02 months); group II, 10 yearlings (91.53 ± 0.54 kg; 1.51 ± 0.01 years); and group III, 10 adults (140 ± 0.71 kg; 8.03 ± 0.06 years). Each group was divided into 5 male and 5 female donkeys. Measurements of the RT were recorded with a digital thermometer probe (model HI935007, Hanna Instruments), which was inserted into the rectum at varying depths of 3.5, 7, 10.5, and 14 cm in the same animal in each group. There was a gradual increase in the RT in donkeys as the depth of insertion was increased from 3.5 cm (36.60°C) to 14 cm (38.40°C). Data obtained from the study were subjected to repeated-measures analysis of variance, followed by Tukey's post-hoc test to compare mean values between different depths of RT measurements. Overall, there was a variation in the RT by the depth of insertion with the shallow depth of 3.5 cm having a lower RT than the depths of 7, 10.5, and 14 cm. The variation of the RT observed in donkeys showed that there is need to standardize the probe-insertion depth in veterinary clinical practice for accurate measurement of the RT in donkeys in the Northern Guinea savannah zone of Nigeria.     

Effect of Heat Stress on Milk Production,Rectal Temperature,Respiratory Rate and Blood Chemistry in Holstein,Jersey and Australian Milking Zebu Cows

The effect of heat stress on changes in milk production, rectal temperature, respiratory rate and blood chemistry was evaluated in three groups of six mature Holstein, Jersey and Australian Milking Zebu (AMZ) dairy cows. These animals were subjected to a cool environment when the mean temperature-humidity index (THI) was 72+/-1.4 (dry bulb temperature of 22.2-24.4 degrees C and relative humidity of 100-60%) during the month of December. This experiment was repeated during the hotter month of July of the following year, when the mean THI was 93+/-3.1 (dry bulb temperature of 35.6-43.9 degrees C and relative humidity 95-35%). Holstein cows produced more (p <0.01) milk than AMZ and Jersey cows during the cooler months of the year and all the cows were dry during the hotter months from June until September. Heat stress increased (p<0.01) rectal temperature and respiratory rate in all three breeds. Heat stress had no effect on blood pH in Holstein and AMZ cows but lowered (p <0.01) blood pH from 7.42 to 7.34 in Jersey cows. In addition, heat stress lowered (p <0.01) blood pCO2 (kPa), bicarbonate (HCO3, mmol/L), base excess (BE, mmol/L) and plasma chloride (Cl-, mmol/L) in all three breeds. The total haemoglobin (THb, g/dl) was elevated (p <0.01) in all three breeds when they were subjected to heat stress. Heat stress increased (p<0.01) oxygen saturation (O2SAT, %) in Jersey and AMZ cows but lowered it (p <0.01) in Holstein cows. On the other hand, heat stress increased (p <0.01)pO2 (kPa) in Holstein and Jersey cows but lowered it (p <0.01) in AMZ cows. Heat stress increased (p <0.01) plasma potassium (K, mmol/L) and calcium (Ca, mmol/L) only in Holstein and Jersey cows but lowered them (p<0.01) in AMZ cows. The plasma glucose (GLU, mmol/L) increased (p<0.01) with heat stress in Holstein and AMZ cows but decreased (p <0.01) in Jersey cows. Heat stress increased (p<0.01) plasma creatinine (CR, (mol/L) but lowered (p<0.01) plasma creatinine phosphokinase (CPK, IU/L), aspartate aminotransferase (AST, IU/L) and blood urea nitrogen (BUN, mmol/L) in all three breeds. These results indicate that heat-stressed Holstein and AMZ cows were able to maintain their acid-base balance with a marginal change in their pH of 0.02 when their rectal temperatures increased by 0.47 and 0.38 degrees C, respectively. When heat stress increased the rectal temperature in Jersey cows by 0.70 degrees C, the pH decreased (p<0.01) from 7.42 to 7.34. However, even with this decrease 0.08 the pH is still within the lower physiological limit of 7.31.     

Quantitative Analysis of Stress Echocardiograms in Healthy Horses with 2‐Dimensional (2D) Echocardiography,Anatomical M‐Mode,Tissue Doppler Imaging,and 2D Speckle Tracking

Background: Stress echocardiography is used to diagnose myocardial dysfunction in horses, but current methods are not well standardized. The influence of heart rate (HR) on measurements is largely unknown. Objectives: To investigate the use of 2‐dimensional echocardiography (2DE), anatomical M‐mode (AMM), tissue Doppler imaging (TDI), and 2D speckle tracking (2DST) at rest and after exercise for quantification of regional and global left‐ventricular (LV) function. Animals: Five athletic Warmblood horses; 11.6 ± 3.6 years; 529 ± 48 kg. Methods: Prospective study. Three separate echocardiographic examinations were performed before (baseline) and over 5 minutes after treadmill exercise with 2DE (1st, short‐axis view; 2nd, long‐axis view) and pulsed‐wave TDI (3rd examination). Offline analyses were performed at baseline and after exercise at HR 120, 110, 100, 90, and 80 minute^?1. Global and segmental measurements were compared by analysis of variance. Results: Quantitative analyses of stress echocardiograms were feasible in all horses. None of the AMM indices changed significantly after exercise. Stroke volume and ejection fraction by 2DE and strain by 2DST decreased, whereas strain rate by 2DST increased significantly at HR > 100 minute^?1. TDI analyses were technically difficult and provided little additional information. Conclusions and Clinical Importance: Volumetric indices by 2DE and strain and strain rate by 2DST are applicable for quantitative assessment of stress echocardiograms. In healthy horses, they are significantly altered at a HR > 100 minute^?1 and need to be evaluated in view of the instantaneous HR. Further investigations are needed to define the clinical value of stress echocardiography in horses with cardiac disease.     

Effect of a carbohydrase admixture in growing pigs fed wheat-based diets in thermoneutral and heat stress conditions

The efficacy of exogenous carbohydrases in pig diets has been suggested to depend on enzyme activity and dietary fiber composition, but recent evidence suggests other factors such as ambient temperature might be important as well. Therefore, we investigated the effect of heat stress (HS) on the efficacy of a multienzyme carbohydrase blend in growing pigs. Ninety-six (barrows: gilts; 1:1) growing pigs with initial body weight (BW) of 20.15 ± 0.18 kg were randomly assigned to six treatments, with eight replicates of two pigs per pen in a 3 × 2 factorial arrangement: three levels of carbohydrase (0, 1X, or 2X) at two environmental temperatures (20 °C or cyclical 28 °C nighttime and 35 °C day time). The 1X dose (50 g/tonne) provided 1,250 viscosimetry unit (visco-units) endo-β-1,4-xylanase, 4,600 units α-l-arabinofuranosidase and 860 visco-units endo-1,3(4)-β-glucanase per kilogram of feed. Pigs were fed ad libitum for 28 d and 1 pig per pen was sacrificed on day 28. There was no enzyme × temperature interaction on any response criteria; thus, only main effects are reported. Enzyme treatment quadratically increased (P < 0.05) BW on day 28, average daily gain (ADG) (P < 0.05), and average daily feed intake (ADFI) (P < 0.05) with the 1X level being highest. HS reduced the BW at day 14 (P < 0.01) and day 28 (P < 0.01), ADG (P < 0.01), and ADFI (P<0.001). There was a trend of increased feed efficiency (G:F) (P < 0.1) in the HS pigs. HS increased apparent jejunal digestibility of energy (P < 0.05) and apparent ileal digestibility of calcium (P < 0.01). At day 1, HS reduced serum glucose (P < 0.001) but increased nonesterified fatty acid (P < 0.01). In the jejunum, there was a trend of increased villi height by carbohydrases (P < 0.1), whereas HS reduced villi height (P < 0.05). HS increased the jejunal mRNA abundance of IL1β in the jejunum (P < 0.001). There was a trend for a reduction in ileal MUC2 (P < 0.1) and occludin (P < 0.1) by HS, and a trend for increased PEPT1 (P < 0.1). There was no effect of HS on alpha diversity and beta diversity of the fecal microbiome, but there was an increase in the abundance of pathogenic bacteria in the HS group. In conclusion, HS did not alter the efficacy of carbohydrases. This suggests that carbohydrases and HS modulate pig performance independently.     

Seasonal,sex and live weight variations in feed and water consumptions of adult captive African Giant rats (Cricetomys gambianus,Waterhouse – 1840) kept individually in cages

Adult African Giant rats (Cricetomys gambianus, Waterhouse) (AGRs) (n = 231) of both sexes (117 bucks, 114 does) were live‐trapped in the wild in Zaria, Nigeria. Live weight (LW), daily feed consumption (FC) and water consumption (WC) of the AGRs were measured during the cold‐dry (CDS), hot‐dry (HDS) and rainy (RS) seasons for 2 years with the aim of determining seasonal, sex and LW variations. Feed consumption was significantly different (p < 0.001) between all the seasons, with the lowest mean value recorded during the HDS, while the highest was obtained during the RS. Water consumption was also lowest (p < 0.001) during the HDS but did not differ significantly (p > 0.05) between the CDS and RS. Both feed and water consumptions were higher (p < 0.01) in the males (bucks) than the females (does) during the CDS and HDS, but the sex difference was not significant (p > 0.05) during the RS. Feed consumption correlated positively (p < 0.0001) with WC and relative humidity, but negatively (p < 0.0001) with LW, ambient temperature and heat index. In conclusion, both feed and water consumptions in AGRs decrease with increased seasonal heat and adult LW and are lower in does than in bucks during the dry seasons (CDS and HDS). Intervention may be indicated during the HDS to improve feed and water consumptions for optimal performance of the AGRs.     

Immunological study of an attenuated Salmonella Typhimurium expressing ApxIA,ApxIIA, ApxIIIA and OmpA of Actinobacillus pleuropneumoniae in a mouse model

Salmonella Typhimurium strain expressing the Actinobacillus pleuropneumoniae antigens, ApxIA, ApxIIA, ApxIIIA and OmpA, was previously constructed as a vaccine candidate for porcine pleuropneumonia. This strain was a live attenuated (∆lon∆cpxR∆asd)Salmonella as a delivery host and contained a vector containing asd. An immunological study of lymphocyte proliferation, T-lymphocyte subsets and cytokines in the splenocytes of a mouse model was carried out after stimulation with the candidate Salmonella Typhimurium by intranasal inoculation. The splenic lymphocyte proliferation and the levels of IL-4, IL-6 and IL-12 of the inoculated mice were significantly increased, and the T- and B-cell populations were also elevated. Collectively, the candidate may efficiently induce the Th1- and Th2-type immune responses.     

Effects of a short‐term supranutritional selenium supplementation on redox balance,physiology and insulin‐related metabolism in heat‐stressed pigs

Heat stress (HS) disrupts redox balance and insulin‐related metabolism. Supplementation with supranutritional amounts of selenium (Se) may enhance glutathione peroxidase (GPX) activity and reduce oxidative stress, but may trigger insulin resistance. Therefore, the aim of this experiment was to investigate the effects of a short‐term high Se supplementation on physiology, oxidative stress and insulin‐related metabolism in heat‐stressed pigs. Twenty‐four gilts were fed either a control (0.20 ppm Se) or a high Se (1.0 ppm Se yeast, HiSe) diet for 2 weeks. Pigs were then housed in thermoneutral (20°C) or HS (35°C) conditions for 8 days. Blood samples were collected to study blood Se and oxidative stress markers. An oral glucose tolerance test (OGTT) was conducted on day 8 of thermal exposure. The HS conditions increased rectal temperature and respiration rate (both p < .001). The HiSe diet increased blood Se by 12% (p < .05) and ameliorated the increase in rectal temperature (p < .05). Heat stress increased oxidative stress as evidenced by a 48% increase in plasma advanced oxidized protein products (AOPPs; p < .05), which may be associated with the reductions in plasma biological antioxidant potential (BAP) and erythrocyte GPX activity (both p < .05). The HiSe diet did not alleviate the reduction in plasma BAP or increase in AOPPs observed during HS, although it tended to increase erythrocyte GPX activity by 13% (p = .068). Without affecting insulin, HS attenuated lipid mobilization, as evidenced by a lower fasting NEFA concentration (p < .05), which was not mitigated by the HiSe diet. The HiSe diet increased insulin AUC, suggesting it potentiated insulin resistance, although this only occurred under TN conditions (p = .066). In summary, HS induced oxidative stress and attenuated lipid mobilization in pigs. The short‐term supranutritional Se supplementation alleviated hyperthermia, but did not protect against oxidative stress in heat‐stressed pigs.     

Effects of a skullcap root supplement on haematology,serum parameters and antioxidant enzymes in rabbits on a high‐cholesterol diet

We studied the effects of Scutellaria baicalensis root on blood parameters and antioxidant enzyme activities in rabbits fed a high‐cholesterol diet. Thirty‐two New Zealand White rabbits were divided into four groups of eight animals each. They were fed a standard diet (C group), a diet with a 1% pure cholesterol supplement (CH group), a diet with a 1% pure cholesterol supplement and a 9% skullcap root supplement (CH + SR group), or a diet with a 9% skullcap root supplement (SR group). After 6 weeks, the rabbits fed the high‐cholesterol diet had significantly decreased RBC and Hb levels and significantly increased MCV, MCH and Fe levels (p ≤ 0.05). The skullcap root supplement had no adverse effects on the haematological parameters. The values for RBC, Hb, HCT, MCV, MCH and MCHC were similar in the skullcap root‐treated and control rabbits. We also observed a remarkable elevation in the serum TC, LDL and TG levels at the end of the 6‐week period. The rabbits fed the cholesterol diet showed decreased activity of the erythrocyte GSH‐Px compared with the rabbits fed the basal diet. The GSH‐Px activity was significantly higher in the rabbits fed the CH + SR diet than in those on the CH diet. The erythrocyte SOD activity was also significantly decreased in the rabbits on the CH diet. However, the CH + SR group rabbits showed significantly enhanced erythrocyte SOD activity. The SOD level in the CH + SR rabbits was 34.91 U/ml, which was a 23% increase (p ≤ 0.05) in relation to the results for the CH group and only 15% diminished in relation to the control group. These results suggest that the dietary supplementation of skullcap root may improve rabbit antioxidant systems and protect against the risks from a high‐cholesterol diet.     

Comparison of bacterial endotoxin lipopolysaccharide concentrations in the blood,ovarian follicular fluid and uterine fluid: a clinical case of bovine metritis

We investigated the concentration of the bacterial endotoxin lipopolysaccharide (LPS) in the blood, ovarian follicular fluid and uterine fluid of a clinical case of bovine metritis. A 2-year-old lactating Holstein cow exhibited continuous fever >39.5°C for more than 2 weeks after normal calving. The cow produced a fetid, watery, red-brown uterine discharge from the vagina and was diagnosed with metritis. The LPS concentrations in plasma and uterine fluid were 0.94 and 6.34 endotoxin units (EU)/ml, respectively. One of seven follicles showed an extremely high level of LPS (12.40 EU/ml) compared to the other follicles (0.62–0.97 EU/ml). These results might suggest the presence of high concentration of LPS in follicles in cows with postpartum metritis.     

Origin of a pair of red-crowned cranes (Grus japonensis) found in Sarobetsu Wetland,northwestern Hokkaido,Japan: a possible crossbreeding between the island and the mainland population

Red-crowned cranes Grus japonensis, which are an endangered species, have two separate populations, a mainland population in the Eurasian continent and an island population in eastern Hokkaido, Japan. Island cranes showed three haplotypes (Gj1, Gj2 and Gj13), whereas ten haplotypes (Gj3–Gj12) were confirmed in captive cranes and stray cranes. We found Gj5 haplotype in feathers of two cranes as well as four new haplotypes in seven wild crane feathers collected in South Korea. We also found feathers in the nest in Sarobetsu Wetland in northwestern Hokkaido. While the haplotype of female-derived feathers was Gj2, that of male-derived feathers was Gj5. The results suggest that there has been crossbreeding between cranes in the island population and cranes in the mainland population.     

Presence of a Temperature Gradient Among Genital Tract Portions and the Thermal Changes Within These Portions Over the Estrous Cycle in Beef Cows

The aim of the present study was to describe the temperature of the different portions of the female genital tract and their relation to rectal temperature and to investigate the effect of steroid hormones profiles on these variables over the estrous cycle in cattle. Four nonpregnant Japanese Black cows were investigated daily over two successive estrous cycles using a digital thermometer with a long probe and rounded-end sensor to record the temperature of the rectum (RT), vagina (VT), cervix (CT), uterine body (UBT) and uterine horns (UHT). Blood samples were collected immediately before temperature recording to assay peripheral levels of progesterone (P₄) and estradiol-17β (E₂). Moreover, transrectal ultrasonography was carried out after temperature recording to monitor the ovulatory follicle and track ovulation. During the experiment, the ambient temperature and relative humidity were recorded for further calculation of the temperature humidity index (THI). The temperature within the genital tracts in these cows progressively increased towards the uterine horns from the vagina. The VT, CT, UBT and UHTs were significantly higher in association with peripheral P₄ concentrations greater than 4 ng/ml (mid-luteal phase) when compared with lower peripheral P₄ concentrations. The VT was more significantly (P<0.01) correlated to the CT, UBT and UHTs than RT. In conclusion, a temperature gradient was present among the vagina, cervix and uterus over the estrous cycle, and changes in peripheral P₄ concentrations were associated with the thermal variations within these portions. The VT could be more beneficial than RT in monitoring temperature of deeper portions of the female genital tract in bovine.     

Improvement of bacterial clearance and relief of clinical signs of Salmonella enterica serovar Typhimurium infection in pigs through upregulation of Th 1-specific responses by administration of a combination of two silicate minerals,biotite and bentonite

Biotite and bentonite are phyllosilicate minerals that were originally used inindustrial applications. Several beneficial activities of them have recently beenreported, especially regulation of the immune system and antimicrobial effects. Therefore,we investigated the immune-enhancing and bacterial clearance effects of a biotite andbentonite mixture (BBM) on experimental infection of Salmonella entericaserovar Typhimurium (S. Typhimurium) to determine whether the BBM couldbe used as an alternative antibiotic. We administered 1% or 2% BBM as a feed supplement.We then evaluated the bacterial clearance effects of the BBM against S.Typhimurium. We also evaluated the immune-enhancing effect of the BBM through severalimmunological experiments that included examination of the lysozyme activity,CD4⁺/CD8⁺ T lymphocyte ratio and the T-helper type 1 (Th 1)cytokine profile. The clinical signs of S. Typhimurium and the number ofviable bacteria in feces and tissues were significantly decreased in both BBM groups,especially in the 2% BBM group. The BBM also markedly enhanced the lysozyme activity,CD4⁺/CD8⁺ T lymphocyte ratio and expression levels of IFN-γ andIL-12 in S. Typhimurium-challenged pigs. Therefore, the BBM could be agood candidate as an alternative antibiotic that improves Th 1-specific immune responsesand the bacterial clearance effect.     

The Diurnal Variation of Urea in Cow’s Milk and how Milk Fat Content,Storage and Preservation Affects Analysis by a Flow Injection Technique

Six Swedish Red and White dairy cows, producing 20-39 kg of 4% fat-corrected milk were given a ration balanced in energy and protein. They had access to feed from 05.15 to 09.00 and from 13.00 to 16.30 and were milked at 06.15 and 15.30. The milk was analysed for urea with a FIA technique.There was a significant diurnal variation in milk urea. The highest values were found 3–5 h after the beginning of the morning feeding and the lowest values (down to 60% of the max. values) during late night. Within 1 h after the start of the morning feeding the urea values had increased significantly, but they had decreased within the same time after the start of the afternoon feeding. Since there was a pronounced diurnal variation in the milk fat content, the urea concentration was also recalculated to concentration in the water phase of the milk. It was higher in that phase, but the pattern of the diurnal variation was not changed significantly. However, analyses on milk with a very high fat content may give misleading results.There were no important differences in the milk urea concentration of different udder quarters. When calculated as concentration in the water phase of the milk, no differences in urea concentration were found between the beginning and the end of milking. The analytical method had a good precision (coefficient of variation max. 3%). The milk urea concentration was not changed significantly after storage during 10 days at 4°C when no preservative was added; but after 17 days the milk had turned sour and the urea value had increased. When a preservative (bronopole) was added the urea concentration remained unchanged during 17 days. Deepfreezing did not influence the urea concentration.     

A subjective descriptive study of the warm‐up and turn to a fence,approach, take‐off,suspension, landing and move‐off in 10 showjumpers

There is limited knowledge about causes of musculoskeletal injury in showjumpers. The objectives were to describe features of the turn, approach and jump in a group of experienced showjumpers believed by their riders to be sound, to relate these findings to clinical findings, and to identify features that may predispose to injury. Ten experienced showjumpers in normal competition training jumped an upright and a parallel fence four times off the left and right reins respectively, after a rider‐defined period of warm‐up. Real‐time and high‐speed motion capture was undertaken. Detailed subjective assessment of the gait was performed during the warm‐up, on the turn and approach to the jump and all phases of the jump. Six horses had thoracolumbar pain or epaxial muscle tension. Six horses exhibited a poor‐quality canter. The mean duration of warm‐up was 7 min (range 5–10 min). All horses had lean of the trunk and hindlimbs >45° on the turn. The inside hindlimb was placed in front of the outside hindlimb in 75% of the turns. Sideways oscillations of the hocks during stance were seen in all horses on the turn and on the straight approach in five horses. The inside hindlimb had greater magnitude of oscillation than the outside hindlimb on the turns. Repeated asynchronous push‐off with the hindlimbs at take‐off was seen in three horses. The hindlimbs drifted to the left or right during the ascent‐phase of suspension in four horses, reflecting asymmetrical push‐off. Only two horses landed consistently with the correct forelimb leading relative to the direction in which the horse had to turn after the fence. Four horses landed seven (n = 2) or eight (n = 2) times each with the left (n = 2) and right (n = 2) forelimbs respectively. Repetitive overload through asymmetrical use of the left and right canter leads, inadequate warm‐up, and limb instability could potentially predispose to injury.     

Development of a genotyping tool for a functionally relevant CYP2C19 allele (Phe100Asn,Ala103Val and Ile112Leu) in cynomolgus macaques

In cynomolgus macaques, which are widely used in drug metabolism studies, CYP2C19(formerly known as CYP2C75) is abundantly expressed in liver, metabolizes human CYP2Csubstrates and is thus an important drug-metabolizing enzyme. One of the cynomolgusCYP2C19 alleles (p.Phe100Asn, p.Ala103Val and p.Ile112Leu) results insubstantially reduced metabolic activity and thus is an important allele in drugmetabolism studies. For this allele, a genotyping tool was developed using allele-specificTaqMan probe. Genotyping 40 Cambodian cynomolgus macaques using this tool found 1homozygote, 17 heterozygotes and 22 wild type animals, and the result was confirmed bydirect-sequencing. Interestingly, this allele frequency was similar to that of Chinesecynomolgus macaques. The genotyping tool established is useful for drug metabolism studiesusing cynomolgus macaques.