Young Adult Sheep Research Articles

An integrated pharmacodynamic analysis of erythropoietin, reticulocyte, and hemoglobin responses in acute anemia.

To determine by pharmacodynamic (PD) analysis physiologically relevant parameters of the cellular kinetics of erythropoiesis in acute anemia. The PD relationships among erythropoietin (EPO), reticulocyte, and RBC (Hb) responses were investigated in young adult sheep in acute anemia induced twice by two controlled phlebotomies separated by a 4-week recovery period. The phlebotomies resulted in rapid increases in plasma EPO, with maximal levels occurring at 3 to 8 days, followed by a reticulocyte response with a delay of 0.5 to 1.5 days. The Hb returned to prephlebotomy base line at the end of the 4-week recovery period. The EPO, reticulocyte count, and Hb responses were well described by a PK/PD model (r = 0.975) with the following cellular kinetics parameters: the lag time between EPO activation of erythroid progenitor cells and reticulocyte formation; the reticulocyte-to-RBC maturation time; the reticulocyte and Hb formation efficacy coefficients, quantifying EPO's efficacy in stimulating the formation of reticulocytes and Hb, respectively; the C50 PK/PD transduction parameter defined as the EPO level resulting in half the maximum rate of erythropoiesis. Physiologically relevant cellular kinetics parameters can be obtained by an endogenous PK/PD analysis of phlebotomy data and are useful for elucidating the pathophysiologic etiology of various anemias.

Pasture intake and digestibility by young and non-breeding adult sheep: the extent of genetic variation and relationships with productivity

The objectives of this study were to estimate the genetic variation in pasture intake and digestibility of the selected diet by young and by adult sheep, and to determine the genetic relationships between pasture intake and productivity traits. The pasture intakes of groups of young and adult sheep, each containing sheep from 11 bloodlines, were measured using the paired alkane technique. The wool grown, and its fibre diameter, over the intake measurement period were also estimated, as were liveweight and fat depth. Differences in pasture intake between bloodlines were largely related to liveweight in both groups of sheep, and were repeatable ( t=0.8) between the groups. The repeatability of wool growth and wool growth efficiency was a little higher ( t>0.9). Combining all the known estimates improved the precision of the genetic parameter estimates. The pooled estimates of heritability of DOMI, wool growth, wool growth efficiency and fibre diameter were 0.12±0.04, 0.37±0.05, 0.25±0.05 and 0.66±0.08, respectively. The genetic relationships of wool growth efficiency with wool growth and fibre diameter were 0.84±0.20 and −0.03±0.12, respectively, while those for feed intake (as DOMI) with wool growth and fibre diameter were −0.02±0.17 and 0.40±0.15.

Tolerance to the nephrotoxic component of Narthecium ossifragum in sheep: the effects of repeated oral doses of plant extracts.

Young adult sheep were dosed with extracts of Narthecium ossifragum plants by the oral or parenteral routes and the resulting nephrotoxicity was assessed from the increases in the concentrations of creatinine and urea in the serum. Following single intraruminal or intraperitoneal doses of extracts derived from 30 g N. ossifragum (wet weight) per kg live weight (kg lw), serum creatinine concentrations increased from about 100 micromol/L to between 260 and 510 micromol/L. The serum urea concentrations increased from about 5-8 mmol/L to between 11 and 66 mmol/L in individual sheep. Daily intraruminal administration of 5-30 g/kg lw to three sheep over a 10- or 15-day period increased creatinine concentrations from 100 micromol/L to 300-760 micromol/L, and urea concentrations from 5-8 mmol/L to 35 mmol/L. A single intraperitoneal challenge dose of 30 g/kg lw, delivered 7 or 12 days after the final intraruminal dose, did not lead to increased serum creatinine or urea concentrations, indicating that oral treatment had apparently resulted in an increased tolerance to the nephrotoxic principle(s) in N. ossifragum.

Persistent colonization of sheep by Escherichia coli O157:H7 and other E. coli pathotypes.

Shiga toxin-producing Escherichia coli (STEC) is an important cause of food-borne illness in humans. Ruminants appear to be more frequently colonized by STEC than are other animals, but the reason(s) for this is unknown. We compared the frequency, magnitude, duration, and transmissibility of colonization of sheep by E. coli O157:H7 to that by other pathotypes of E. coli. Young adult sheep were simultaneously inoculated with a cocktail consisting of two strains of E. coli O157:H7, two strains of enterotoxigenic E. coli (ETEC), and one strain of enteropathogenic E. coli. Both STEC strains and ETEC 2041 were given at either 10(7) or 10(10) CFU/strain/animal. The other strains were given only at 10(10) CFU/strain. We found no consistent differences among pathotypes in the frequency, magnitude, and transmissibility of colonization. However, the STEC strains tended to persist to 2 weeks and 2 months postinoculation more frequently than did the other pathotypes. The tendency for persistence of the STEC strains was apparent following an inoculation dose of either 10(7) or 10(10) CFU. One of the ETEC strains also persisted when inoculated at 10(10) CFU. However, in contrast to the STEC strains, it did not persist when inoculated at 10(7) CFU. These results support the hypothesis that STEC is better adapted to persist in the alimentary tracts of sheep than are other pathotypes of E. coli.

Effect of unilateral condylectomy on the sheep temporomandibular joint

Unilateral condylectomy was performed on five young adult sheep. The animals were killed at three months and both joints and the excised condyles were examined macroscopically and histologically. All five showed pronounced regeneration of the condylar head on the operated side. The articular surface was fibrous and fused to the disc. Four of the five opposite joints showed medial remodelling. Young sheep have a higher regenerative capability than human adults of equivalent age, and similar reactions to those of children.

Sympathetic responses to cardiopulmonary vagal afferent stimulation during development.

Previous work in our laboratory has demonstrated impairment of cardiopulmonary reflex control of renal sympathetic nerve activity (RSNA) during the newborn period. The present study was designed to test the hypothesis that this delayed maturation is secondary to incomplete central integration of vagal afferent input. Term fetal (135-140 days; n = 6), newborn (3-7 days of age; n = 8), and young adult (6-8 wk old; n = 8) sheep anesthetized with alpha-chloralose underwent vagal afferent nerve stimulation. All animals had undergone prior sinoaortic denervation to eliminate influences from the arterial baroreceptors. After determination of optimal stimulation parameters, RSNA responses to gradual increases in stimulation frequency (1.0-16 Hz) were recorded and compared by one-way ANOVA. RSNA decreased progressively with increased frequency of stimulation in all three groups of animals. When comparing the three groups at any given frequency of stimulation, reflex withdrawal of RSNA tended to be more pronounced in newborn lambs (P < 0.05 for 1 and 4 Hz). Heart rate (HR) was also noted to decrease significantly with vagal afferent stimulation in each of the groups, but no significant differences in the reflex decreases in HR were noted among the three groups of animals. These results demonstrate that central integration of vagal afferent input is intact in fetal and newborn sheep. These results suggest that the delayed maturation of cardiopulmonary reflex-mediated changes in RSNA seen early in development appears to depend on intrinsic alterations in baroreceptor function rather than incomplete central integration.

Ossifying fibroma in a sheep

A young adult sheep from a commercial feedlot was presented for necropsy because of a firm mass protruding from the rostral mandible which impaired mastication, resulting in weight loss. The mass was diagnosed as ossifying fibroma. Ossifying fibroma is an uncommon benign tumor of the jaw which is most frequently diagnosed in the horse, and which may be underreported in ruminants. To our knowledge, this is the first published report of ossifying fibroma in a sheep. Surgical removal of ossifying fibroma is usually curative. Treatment of ossifying fibroma could be warranted in valuable young ruminants including those used in research and breeding programs.

Multiple segmental gradual distraction of facial skeleton: an experimental study.

The method of distraction osteogenesis was used to move several facial segments in different directions with formation of new bone. On 3 young adult sheep a Le Fort II osteotomy, combined with circumferential orbital osteotomies, was performed. The periosteum over the osteotomies was preserved. Titanium bone screws were placed as bone markers. The segments were fixed with pins and plates to a combined distraction apparatus in order to advance the segments in different directions. By a gradual distraction, the midface was advanced forward by 30 mm. The left orbit was moved laterally 20 mm and the right orbit was moved forward 20 mm. In both orbits there was a concomitant globe movement. New bone formation in the distracted area was obvious radiographically, clinically, and histologically. In conclusion, multiple segmental distraction is possible in the adult sheep face and may offer three-dimensional (3D), controlled correction of complex face deformities.

Midface advancement in sheep by gradual distraction: A 1-year follow-up study

Purpose: The purpose of this study was to find a solution to the unsafistactory postoperative maxillary relapse after major maxillary advancement or inferior repositioning of the maxilla. Materials and Methods: Major midface advancement by gradual distraction was performed on three young adult sheep over 21 days. Using an external device, the midface was advanced 36 mm in the nasofrontal area and 43 mm in the lateral aspect of the maxilla. The apparatus remained as an external fixation device for 6 weeks after the distraction to allow better ossification. After removal of the device, a 1-year clinical and radiographic follow-up was conducted. Results: Direct measurements between the markers showed 2- to 3-mm relapse after 1 year. Radiologic measurements demonstrated that the relapse occurred during the first 3 months after removal of the distraction apparatus. Conclusion: It was concluded that midface advancement by gradual distraction may obviate the need for bone grafting and offer a greater movement of bone segments with good skeletal stability.

Response of the hypertrophied left ventricle to tachycardia: importance of maturation

Pressure overload left ventricular (LV) hypertrophy (LVH) induces ventricular dysfunction during stress, which is commonly attributed to diminished myocardial capillary density and ischemia. Immature hearts with LVH have a normal coronary flow reserve and capillary density. The purpose of this study was to determine 1) whether young lambs with LVH had an abnormal response to chronotropic stress, 2) whether nonischemic mechanisms contributed to the abnormal response, and 3) whether the age at which LVH was induced affected the response. We assessed LV endomyocardial function, perfusion, and Ca(2+)-adenosinetriphosphatase (ATPase) mRNA levels in chronically instrumented lambs with and without LVH and adult sheep with and without LVH. Rapid pacing induced diastolic dysfunction, increased time constant of isovolumic relaxation using an iterative fit (tM), and elevated LV diastolic pressures in young lambs and adult sheep with LVH. During pacing, tM was greater in the adult sheep with LVH than in the young lambs with LVH. Ca(2+)-ATPase mRNA levels were 79% less in adult sheep with LVH than in those without. Ca(2+)-ATPase mRNA levels in lambs with and without LVH and adult sheep without LVH were similar. Diastolic dysfunction occurred in the absence of subendomyocardial hypoperfusion, suggesting a nonischemic mechanism. In adult sheep with LVH diastolic dysfunction was associated with a marked reduction in Ca(2+)-ATPase mRNA levels.

Midface advancement by gradual distraction

Midface osteotomy was performed on 5 young adult sheep aged 10–12 months.In 4 animals midface advancement by gradual distraction was performed using an external device; one animal served as a control. The midface was advanced by 2 mm per day for 21 days. The amount of advancement was 36 mm in the nasofrontal area and 43 mm on the lateral aspect of the maxilla. After the period of active distraction the midface was maintained with external fixation for an additional 6 weeks to allow for ossification. Radiographs were obtained immediately postoperatively, after 21 days of distraction, and at the end of the 6 week fixation period. New bone formation in the distracted area was obvious radiographically, clinically and histologically. In conclusion, midface advancement by osteotomy and gradual distraction is possible in the sheep model and may offer controlled correction of deformity, obviating the need for bone grafting.

Yersiniaspecies infection of lambs and cull cows at an abattoir

The rectal contents of 330 cull cows and 66 lambs were sampled over the 1984-1985 killing season at a New Zealand freezing works for the presence of Yersinia species. Samples from the cows revealed one isolation of Y. pseudotuberculosis and one isolation of Y. intermedia. Samples from the lambs gave thirteen isolates of Y. enterocolitica, three of Y. inter-media, two of Y. pseudotuberculosis and one of Y. frederiksenii. Two of the isolates of Y. enterocolitica were shown to be serotype 0:3. Although no parallel studies were carried out on young cattle or adult sheep, these findings are consistent with the hypothesis that Yersinia infection primarily involves young animals. Thus there exists the potential for transmission of the above species of Yersinia from young animals to man which needs further detailed study.

The electron microscopic immunohistochemistry of elastase-treated aorta and nuchal ligament of fetal and postnatal sheep.

In conjunction with the immunoperoxidase and the immunoferritin methods, antielastin antibody was used to study the localization of elastin in untreated and elastase-treated elastic fibers of the nuchal ligament and the aorta of fetal and young adult sheep. In tissues not treated with elastase, the staining reaction for antielastin antibody was localized in the outer zones of the amorphous components and along the surfaces of the microfibrils ; the central zones of the amorphous components were unreactive. After mild elastase treatment, incompletely digested amorphous components showed staining both in their central and outer zones, and some of the microfibrils became unreactive. After extensive elastase treatment, small scattered amorphous components were still found in association with bundles of microfibrils. These components were stained diffusely by the antielastin antibody method but were not detectable by staining with uranyl acetate and lead citrate or with Kajikawa 's method for elastin; elastin was not detected on the surfaces of the microfibrils by any of the methods used. These findings were interpreted as indicating that the surfaces of the microfibrils are associated with small amounts of elastin, and that evenly stained amorphous components are composed of elastin, which is loosely arranged and allows the penetration of antielastin antibody. These observations support the concept that microfibrils serve an important role as a scaffold for elastin deposition in elastogenesis. Because of their high sensitivity, immunohistochemical methods for detecting elastin are useful to study partially degraded elastic fibers.

A study of bone proteins which can prevent hydroxyapatite formation

The ability of noncollagenous bone proteins (NCBP) to inhibit calcium phosphate precipitation in vitro raises the question as to the nature and the relative efficiency of such proteins in vivo. To investigate this question NCBP from young adult sheep bones were fractionated using nondegradative techniques. Their relative activity was measured by their efficiency in preventing hydroxyapatite growth. On a weight (of protein recovered) basis, the activity is about equally divided between the Gla-containing protein, osteocalcin, and a phosphorylated protein essentially the same as osteonectin. On a molecular weight basis, the activity of the phosphorylated protein is almost three times higher than that of the Gla-containing protein. Finally, the inhibitory activity of the phosphorylated protein is alkaline phosphatase sensitive. The properties of this protein could provide a means of regulating the solubility of bone mineral and maintaining an equilibrium of calcium between bone and blood.

1061 PULMONARY VASCULAR AND GRANULOCYTE RESPONSE TO GROUP B STREPTOCOCCAL (GBS) TOXIN

We have previously shown that a toxin isolated from GBS causes pulmonary hypertension, hypoxemia and fever in adult unanesthetized sheep. (Fed.Proc.37:854,1978) We have subsequently studied its effects on pulmonary vascular permeability and circulating granulocytes. Seven young adult sheep were instrumented to measure pulmonary artery and left atrial pressures, lung lymph flow and white blood cell and differential counts. Two mg of toxin caused an early phase of pulmonary hypertension and a late phase of increased lung vascular permeability. The granulocyte count fell to less than 10% of baseline values by 60 min and returned to near baseline by 5 hrs. The immature to total granulocyte ratio increased six fold by 5 hours. Granulocyte trapping and fragmentation in the pulmonary capillaries was demonstrated by electron microscopy in four sheep sacrificed during the second phase. To explore the role of prostaglandins we compared the response to GBS toxin alone with the response to the same dose of toxin during the infusion of indomethacin (IN) or methylprednisolone (MP). IN prevented the initial pulmonary hypertensive phase but did not modify the granulocytopenic response. In contrast, MP blocked the granulocytopenia but had little effect on the pulmonary hemodynamic changes. We concluded that the two components of the response seem to be independent. Biosynthesis of prostaglandin endoperoxides appears necessary for the acute pulmonary hypertensive response but not for the granulocytopenia. Sequestration of granulocytes may play an important role in the pathogenesis of the pulmonary vascular changes.

A note on the use of whole, moist barley treated with ammonia as a feed supplement for sheep

ABSTRACTWhole, moist barley treated with ammonia (A), whole, untreated barley (WU) and ground barley (G) were fed with hay and a little high protein, mixed concentrate. Digestibilities of dry matter, organic matter and crude fibre, assessed with young adult female sheep, were highest in diet A and lowest in diet G. The digestibilities of dry matter and crude fibre were also higher in diet WU than in diet G. Digestibility coefficients for dry matter and organic matter in barley, calculated by difference, appeared higher in A and in WU than in G. Young female sheep fed on the above diets from the age of 7 to 11 months ate more hay and gained more weight on A than on G; again diet WU was intermediate. Differences also occurred between the three groups as regards volatile fatty acids in the rumen fluid. Sheep on A or WU had a higher pH in the rumen fluid than those on G. Finally, sheep on A gave birth to more offspring than those on WU or G. All these differences were significant.

Phosphorus kinetics in the sheep.

1. Ten castrated young adult sheep were brought indoors and given lucerne chaff (four animals with a phosphorus intake of 2 . 40 g/d) and fresh Ruanui ryegrass (six animals with a P intake of 3 . 72 g/d) to determine various kinetic indices of their P metabolism. 2. The results obtained from combined nutritional balance and 32P radioactivity measurements were analysed using the simulation, analysis and modelling computer (SAAM) program. Since the plasma P specific activity curve was described by at least four exponential terms, a four compartmental model (M1, M2, M3 and M4) was used to describe the experimental values. 3. The mean mass of the total exchangeable P pool (MT) for the lucerne chaff-fed and Ruanui ryegrass-fed sheep was 25 . 5 and 28 . 8 g respectively, while the total P transport (VT) to the exchangeable pool (MT) was markedly lower for sheep given lucerne chaff compared to those given Ruanui ryegrass (54 . 1 v. 111 . 3 mg/kg body-weight per d). Likewise the rate of P absorption (Va), faecal endogenous loss of P (Vf), urinary P excretion (Vu) as well as the movement of P to (Vo+) and from (Vo-) the skeleton and soft tissue was also lower in the lucerne chaff-fed sheep. 4. The availability of P, that is the proportion of ingested P which is absorbed, was 0 . 56 and 0 . 62 for the sheep given chaff and fresh herbage respectively. 5. The P metabolism of one sheep (sheep no. 30) differed from the other sheep in that its plasma inorganic P concentration was higher (95 v. 54 mg/l). This was associated with a larger first compartment (M1), a more rapid P transport between M1, and M2, an increase in (Vo) and a marked increase in (Vu).

Hemoglobin switching in sheep: a comparison of the erythropoietin- induced switch to HbC and the fetal to adult hemoglobin switch

Stimulation of sheep erythropoietic progenitor cells by erythropoietin (epo) has been studied with regard to its effect on the pattern of hemoglobin production. An analysis of hemoglobin (Hb) synthesis in BFU- E- and CFU-E-derived colonies from fetuses either homozygous for HbA (AA) (homozygous also for the beta c gene responsible for HbC production) or HbB (BB) (lacking the beta c gene) indicated the following. Colonies derived from precursor cells from 51- and 89-day fetuses exhibited small but detectable increments of HbB synthesis with prolonged incubation in vitro. This response was not dependent on the epo concentration. Erythropoietic precursor cells from a 124-day BB fetus were already committed to HbB synthesis, since HbF production was replaced by HbB on successive days in vitro as erythroid colonies matured; this switch was not affected by varying the epo concentration. In contrast, progenitor cells from a 124-day AA fetus responded to higher doses of epo by forming colonies in which more HbC was made at the expense of both HbF and HbA. Erythropoietic stress did not result in induction of HbF in vivo or in erythroid colonies derived from CFU-E in young adult BB sheep, whereas our prior studies had shown induction of HbC synthesis under analogous conditions in colonies derived from young adult AA sheep. We conclude that the epo-induced HbF (or HbA) to HbC switch and the fetal to adult hemoglobin switch are regulated by different mechanisms.

Hemoglobin Switching in Sheep: A Comparison of the Erythropoietin-Induced Switch to HbC and the Fetal to Adult Hemoglobin Switch

Stimulation of sheep erythropoietic progenitor cells by erythropoietin (epo) has been studied with regard to its effect on the pattern of hemoglobin production. An analysis of hemoglobin (Hb) synthesis in BFU-E- and CFU-E-derived colonies from fetuses either homozygous for HbA (AA) (homozygous also for the beta c gene responsible for HbC production) or HbB (BB) (lacking the beta c gene) indicated the following. Colonies derived from precursor cells from 51- and 89-day fetuses exhibited small but detectable increments of HbB synthesis with prolonged incubation in vitro. This response was not dependent on the epo concentration. Erythropoietic precursor cells from a 124-day BB fetus were already committed to HbB synthesis, since HbF production was replaced by HbB on successive days in vitro as erythroid colonies matured; this switch was not affected by varying the epo concentration. In contrast, progenitor cells from a 124-day AA fetus responded to higher doses of epo by forming colonies in which more HbC was made at the expense of both HbF and HbA. Erythropoietic stress did not result in induction of HbF in vivo or in erythroid colonies derived from CFU-E in young adult BB sheep, whereas our prior studies had shown induction of HbC synthesis under analogous conditions in colonies derived from young adult AA sheep. We conclude that the epo-induced HbF (or HbA) to HbC switch and the fetal to adult hemoglobin switch are regulated by different mechanisms.

Reaction of young adult sheep to vaccination and infection with myxovirus parainfluenza 3

An effect of vaccination against PI 3 virus by measuring the amount of virus excreted in the nasopharynx in vaccinated and in untreated sheep up to 5 days after challenge is described.