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PubMed2002

Mechanisms by which discharge modulates diastolic depolarization in sheep and dog Purkinje fibers.

For reasons unknown, a fast drive is prone to induce overdrive excitation in sheep Purkinje fibers under conditions that still induce overdrive suppression in dog Purkinje fibers. Our aim was to study by means of a microelectrode technique diastolic depolarization (DD) and its changes with overdrive in sheep and dog Purkinje fibers perfused in vitro under identical conditions. The major results are: (a) At a slow rate, diastolic depolarization is much faster and larger in sheep than in dog Purkinje fibers. (b) Faster rates increase DD slope and amplitude in sheep and decrease them in dog Purkinje fibers. (c) DD slope and amplitude increase in sheep and decrease in dog if the same number of action potentials are separated by a shorter diastole. (d) The change in DD slope and amplitude induced by a fast drive persists after a subsequent slow drive of approximately 20 s. (e) The fastest drives can induce an oscillatory potential superimposed on early DD in sheep. (f) In both species, high [Ca(2+)](o) increases and low [Ca(2+)](o) decreases DD slope and amplitude. (g) Neither high nor low [Ca(2+)](o) change the DD rate-dependence patterns peculiar to either species. (h) DD amplitude in dog in high [Ca(2+)](o) is still smaller than that in sheep in Tyrode solution. (i) Caffeine prevents the steepening of early DD by drive, but not the subsequent increase which can lead to overdrive excitation in both species. (j) TTX decreases DD slope and amplitude in both species. (k) Cs(+) markedly reduces DD slope and amplitude and more so at faster rates, especially in the sheep. We conclude that the differences in diastolic depolarization and the different behavior of DD with overdrive in the two species account for the propensity of sheep Purkinje fibers to develop overdrive excitation and for that of dog Purkinje fibers to develop overdrive suppression.

Animals↗
PubMed2002

Autologous tissue-engineered trachea with sheep nasal chondrocytes.

OBJECTIVE: This study was designed to evaluate the ability of autologous tissue-engineered trachea shaped in a helix to form the structural component of a functional tracheal replacement. METHODS: Nasal septum were harvested from six 2-month-old sheep. Chondrocytes and fibroblasts were isolated from tissue and cultured in media for 2 weeks. Both types of cells were seeded onto separate nonwoven meshes of polyglycolic acid. The chondrocyte-seeded mesh was wound around a 20-mm-diameter x 50-mm-long helical template and then covered with the fibroblast-seeded mesh. In 2 separate studies the implants were placed either in a subcutaneous pocket in the nude rat (rat tissue-engineered trachea) or in the neck of a sheep (sheep tissue-engineered trachea). Rat tissue-engineered tracheas were harvested after 8 weeks and analyzed by means of histology and biochemistry. Sheep tissue-engineered tracheas were harvested from the neck at 8 weeks and anastomosed into a 5-cm defect in the sheep trachea. RESULTS: Sheep receiving tissue-engineered trachea grafts survived for 2 to 7 days after implantation. Gross morphology and tissue morphology were similar to that of native tracheas. Hematoxylin-and-eosin staining of rat tissue-engineered tracheas and sheep tissue-engineered tracheas revealed the presence of mature cartilage surrounded by connective tissue. Safranin-O staining showed that rat tissue-engineered tracheas and sheep tissue-engineered tracheas had similar morphologies to native tracheal cartilage. Collagen, proteoglycan, and cell contents were similar to those seen in native tracheal tissue in rat tissue-engineered tracheas. Collagen and cell contents of sheep tissue-engineered tracheas were elevated compared with that of normal tracheas, whereas proteoglycan content was less than that found in normal tracheas. CONCLUSIONS: This study demonstrated the feasibility of recreating the cartilage and fibrous portion of the trachea with autologous tissue harvested from single procedure. This approach might provide a benefit to individuals needing tracheal resection.

Animals↗
PubMed1985

The role of condensed tannins in the nutritional value of Lotus pedunculatus for sheep. Rates of body and wool growth.

Lotus pedunculatus (cv. Grasslands Maku) grown on acid low-fertility soil and containing high concentrations of condensed tannin (76-90 g/kg dry matter (DM] was grazed by growing sheep for 31-42 d periods in three experiments. In Expt 2 an additional group of lambs grazed areas oversown with white clover (Trifolium repens) and red clover (Trifolium pratense). Lambs were transferred from grazing ryegrass (Lolium perenne)-white clover straight on to lotus in all experiments (unconditioned sheep). In Expt 3 a second group was included which had grazed high-tannin lotus for a pre-experimental period of 8 weeks (conditioned sheep). Effects of condensed tannin on body and wool growth were assessed by studying responses to daily oral administration of polyethylene glycol (PEG; molecular weight 3350, 75-100 g/d). PEG forms a complex with condensed tannin, which is assumed to be inert in its passage through the digestive system, and so effectively reduces the nutritional effects attributable to high condensed-tannin concentrations. Live-weight gain (LWG) in the absence of PEG was low (27-125 g/d) for sheep grazing high-tannin lotus, and PEG administration increased LWG by 41-61 g/d and increased wool growth. In Expt 3, responses to PEG supplementation tended to be less with conditioned than with unconditioned sheep, indicating that conditioned sheep had partially adapted to the high-tannin diet. PEG supplementation had no effect on either LWG or wool growth of sheep grazing areas oversown with mixed clovers, confirming its effects as specific to forages containing condensed tannins. These experiments therefore conclusively show that high concentrations of condensed tannin induced by growing Lotus pedunculatus under low soil fertility conditions prevent maximum expression of LWG and wool growth in grazing sheep. These results contrast with high LWG (153-315 g/d) observed in growing sheep grazing the same lotus cultivar grown in high fertility soil and containing 20 g condensed tannin/kg DM, a level considered to be nutritionally beneficial.

Administration, Oral↗
PubMed1987

Absorption and secretion of 65Zn in the stomach and intestinal tract of sheep exchanging digesta via duodenal re-entrant cannulas.

The absorption and secretion of 65Zn in the stomach and intestinal tract regions was studied in sets of two and three sheep which were exchanging digesta via re-entrant cannulas in the proximal duodenum. One sheep from each of the three three-sheep sets was dosed intraruminally with the radioisotope. One sheep from the three two-sheep sets received an intravenous dose. Measurements of 65Zn in blood plasma from intraruminally dosed sheep showed that there was no apparent absorption from the stomach region. Measurements from sheep receiving radioactive digesta intraduodenally showed that mean apparent absorption of 65Zn was 0.07 and mean true absorption was 0.103. There was a large variation in endogenous recycling of 65Zn into the stomach region. Secretion of 65Zn into the stomach and intestinal regions in the intravenously dosed sheep of the two-sheep sets was calculated on the basis of total recovery over 10 d in the digesta and faeces. The present study showed that for every 1 molecule Zn secreted into the stomach region, 2.1 molecules were secreted into the intestinal tract region.

Animals↗
PubMed1996

The effects of condensed tannins from Desmodium intortum and Calliandra calothyrsus on protein and carbohydrate digestion in sheep and goats.

A factorial experiment was conducted to study the effects of condensed tannins (CT) from the tropical legumes Desmodium intortum and Calliandra calothyrsus on the digestion and utilization of protein and carbohydrate in sheep and goats. CT-free Centrosema pubescens was also fed for comparison with the CT legumes, and each legume was included (300 g/kg DM) in a basal diet of pangola grass (Digitaria decumbens). Pangola grass alone was used as a control diet. There were no significant (P > 0.05) differences between sheep and goats for the efficiency of digestion of N (0.574, SE 0.013), organic matter (OM; 0.519, SE 0.010), neutral-detergent fibre (NDF; 0.524, SE 0.011) and acid-detergent fibre (ADF; 0.407, SE 0.016). Diets containing desmodium and calliandra were digested less well in the rumen (64 and 62% of total OM digested) when compared with the pangola and centrosema diets (74 and 73% of total OM digested in rumen). There was an apparent net gain of 30% in ADF across the digestive tract of sheep and goats given calliandra, and this gain was ascribed to the formation of 'artifact' fibre as a result of fibre-tannin interaction. Overall, inclusion of legume at 300 g/kg in the diet significantly increased (P < 0.05) the concentration of acetic acid and decreased butyric acid concentration in the rumen fluid of sheep and goats. Significantly higher proportions of dietary N apparently reached the abomasum of animals given the diets containing desmodium (50%) and calliandra (56%) when compared with animals given the centrosema and pangola diets (35%). Sheep and goats given the CT diets also had higher excretions of faecal N. This increment of faecal N (14%) did not affect post-rumen N digestion (P > 0.05) since animals given CT diets absorbed more N (19%) per kg total OM digested than those given the control diets. It was concluded that whilst the low levels of CT provided in desmodium (1.0%) and calliandra (2.3%) diets protected dietary protein from degradation in the rumen, there were no overall beneficial or detrimental effects of CT in these diets for sheep or goats. A method was developed to categorize CT into fractions representative of their forms (free, protein-bound, and fibre-bound) during the digestion process. A quantitative model of CT metabolism during passage through the digestive tract was developed from the measured exchanges of CT between free, protein-bound and fibre-bound pools in the rumen and lower digestive tract. CT interchange mainly occurred in the reticulo-rumen of both animal species. Desmodium and calliandra free CT showed net losses of 68 and 78% in the rumen respectively and 57 and 68% of the fibre-bound CT was lost in the same site for sheep and goats respectively. However, protein-bound CT increased across the rumen by 73 and 56% for both animal species. Post-rumen losses of the total CT abomasal flow were 86 and 83% (free CT) for sheep and goats respectively, 70 and 66% (protein-bound CT), whilst 28% loss of fibre-bound CT occurred in sheep and goats respectively.

Animals↗
PubMed1996

Transmission of human T cell leukemia virus type I to sheep: antibody profile and detection of viral DNA sequences.

Lambs were inoculated intraperitoneally with either 1.8 x 10(7) live peripheral blood cells from an HTLV-I-infected person (five lambs) or with 8 x 10(7) live cells from the HTLV-I-producing cell lines MT-2 (four lambs) or C10 MJ (five lambs). Four control lambs were inoculated with minimal essential medium supplemented with fetal calf serum. The animals were monitored during a period of 24 months. Beginning at 5 to 12 months after inoculation, four of the five lambs inoculated with the fresh HTLV-I-infected peripheral blood cells began to develop detectable levels of antibodies to a recombinant HTLV-I gp21env antigen, as determined by an enzyme-linked immunoassay (ELISA). The anti-gp21 antibodies persisted for the remaining observation period. These antibodies were not detected in the sera from the other sheep. Absorption and blocking experiments demonstrated the specificity of the gp21 reactivity. This reactivity was also confirmed by Western blot (WB). With the exception of the serum of an MT-2-inoculated sheep that formed a weak band with p19 by WB, none of the sera of the four gp21-positive sheep or of the other experimental sheep reacted with other structural or regulatory HTLV-I proteins, as determined by ELISA, WB, and radioimmunoassay. PCR analyses demonstrated the presence of the HTLV-I provirus in peripheral blood leukocytes of the four sheep showing antibodies to gp21env. The remaining sheep were negative. PCR analyses failed to detect BLV sequences in any of the experimental sheep. None of the sheep showed clinical abnormalities during the observation period. The potential value of the sheep model for studying atypical virus-host interactions in infected people is discussed.

Animals↗
PubMed2001

Branched-chain amino acid aminotransferase activity decreases during development in skeletal muscles of sheep.

The catabolism of branched-chain amino acid (BCAA) differs between sheep and monogastric animals. The transamination of BCAA seems to be affected by development of the sheep. We studied the developmental changes in the activity and expression of the BCAA aminotransferase (BCAT) isoenzymes in skeletal muscle of sheep. Five muscles were taken from fetus, newborn, preruminant and ruminant lambs. BCAT specific activity and the contribution of each BCAT isoenzyme [mitochondrial and cytosolic (BCATm and BCATc, respectively)] were quantified using radioenzymatic and immunoprecipitation assays. BCATm and BCATc mRNAs were assessed by real-time reverse transcription-polymerase chain reaction. BCAT specific activities were 62% (diaphragma) to 83% (longissimus dorsi) lower in the ruminant lamb than in the fetal sheep. BCATm and BCATc were both expressed in sheep skeletal muscle at all developmental stages. BCATc was mainly responsible for the developmental decrease in BCAT specific activity. BCATc specific activities were 77% (diaphragma) to 92% (longissimus dorsi) lower in the ruminant lamb than in the fetal sheep, whereas BCATm specific activities were only 36% (semimembranosus) to 56% (longissimus dorsi) lower. BCATc and BCATm mRNAs in the longissimus dorsi were not affected by development of the sheep. The developmental decrease in BCATc activity, and to a lesser extent in BCATm activity, probably involves posttranscriptional mechanisms in sheep. The present results are consistent with lower in vivo metabolism of BCAA in ruminant than in the fetal sheep.

Animals↗
PubMed1988

Structural organization of the beta-globin locus of B-haplotype sheep.

Goats and some sheep synthesize a juvenile hemoglobin, Hb C (alpha 2 beta C2), at birth and produce this hemoglobin exclusively during severe anemia. Sheep that synthesize this juvenile hemoglobin are of the A haplotype. Other sheep, belonging to a separate group, the B haplotype, do not synthesize hemoglobin C and during anemia continue to produce their adult hemoglobin. To understand the basis for this difference we have determined the structural organization of the beta-globin locus of B-type sheep by constructing and isolating overlapping genomic clones. These clones have allowed us to establish the linkage map 5' epsilon I-epsilon II-psi beta I-beta B-epsilon III-epsilon IV-psi beta II-beta F3' in this haplotype. Thus, B sheep lack four genes, including the BC gene, and have only eight genes, compared with the 12 found in the goat globin locus. The goat beta-globin locus is as follows: 5' epsilon I-epsilon II-psi beta X-beta C-epsilon III-epsilon IV-psi beta Z-beta A-epsilon V-epsilon VI-psi beta Y-beta F3'. Southern blot analysis of A-type sheep reveals that these animals have a beta-globin locus similar to that of goat, i.e., 12 globin genes. Thus, the beta-globin locus of B-haplotype sheep resembles that of cows and may have retained the duplicated locus of the ancestor of cows and sheep. Alternatively, the B-sheep locus arrangement may be the result of a deletion of a four-gene set from the triplicated locus.

Amino Acid Sequence↗
PubMed2002

Molecular analysis of wild and domestic sheep questions current nomenclature and provides evidence for domestication from two different subspecies.

Complete mitochondrial DNA (mtDNA) control regions (CR) were sequenced and analysed in order to investigate wild sheep taxonomy and the origin of domestic sheep (Ovis aries). The dataset for phylogenetic analyses includes 63 unique CR sequences from wild sheep of the mouflon (O. musimon, O. orientalis), urial (O. vignei), argali (O. ammon) and bighorn (O. canadensis) groups, and from domestic sheep of Asia, Europe and New Zealand. Domestic sheep occurred in two clearly separated branches with mouflon (O. musimon) mixed into one of the domestic sheep clusters. Genetic distances and molecular datings based on O. canadensis CR and mtDNA protein-coding sequences provide strong evidence for domestications from two mouflon subspecies. Other wild sheep sequences are in two additional well-separated branches. Ovis ammon collium and O. ammon nigrimontana are joined with a specimen from the transkaspian Ust-Urt plateau currently named O. vignei arkal. Ovis ammon ammon, O. ammon darwini and O. vignei bochariensis represent a separate clade and the earliest divergence from the mouflon group. Therefore, O. musimon, O. vignei bochariensis and Ust-Urt sheep are not members of a 'moufloniform' or O. orientalis species, but belong to different clades. Furthermore, Ust-Urt sheep could be a hybrid population or an O. ammon subspecies closely related to O. ammon nigrimontana.

Animals↗
PubMed2005

Airway remodelling and inflammation in sheep lungs after chronic airway challenge with house dust mite.

BACKGROUND: Remodelling of airway walls is a significant morbidity factor in patients suffering from chronic asthma. The relationship between airway remodelling and the inflammatory response is not well defined. Sheep have been used extensively to model airway disease in humans and represent a suitable model to examine airway remodelling. OBJECTIVE: The aim of the present study was to develop a model for airway remodelling in sheep after repeated challenge with a relevant human allergen to assess the relationship of airway remodelling with inflammation. METHODS: Repeated challenges of house dust mite (HDM) extract or saline (control) were administered to local lung segments of sheep for a period of 6 months. After the last challenge, lung tissues from both challenged and unchallenged lung compartments of the same sheep were compared using morphometric image analysis and (immuno) histological studies. RESULTS: All HDM-challenged sheep developed significant bronchoalveolar lavage eosinophilia during challenge. At the end of the challenge period, significant increases in airway collagen and airway smooth muscle content were found in a proportion (3/7) of the HDM-challenged sheep. Hyperplasia of goblet cells and epithelial cells were observed in small bronchi and bronchioles exposed to allergen. Irrespective of airway remodelling changes, all HDM-challenged, but no saline-challenged sheep, displayed significant increases in mast cells in alveolar septa and airway walls of challenged lungs compared with untreated lung compartments of the same sheep. Significant increases were also observed in CD5 and gamma delta T cell subpopulations in all allergen-exposed lung parenchyma. CONCLUSION: A proportion of atopic sheep develop typical airway remodelling changes after chronic allergen challenge, which is not directly related to the level of allergic inflammation.

Allergens↗
PubMed1996

Maintenance of atrial fibrillation in anesthetized and unanesthetized sheep using cholinergic drive.

Atrial fibrillation (AF) was induced electrically and the duration of AF was measured in six isoflurane-anesthetized sheep (weight range 54.5-72.7 kg), and in five unanesthetized sheep (weight range 60-75 kg). In the anesthetized sheep, AF was induced by direct electrical stimulation of the right atrium with a catheter electrode and the duration of AF was determined. Intravenous neostigmine (10 micrograms/kg IV) was administered and the duration of AF was again measured. Then cholinergic drive was increased by bilateral electrical vagal stimulation; AF was induced and the duration of AF was measured. In the anesthetized animals with no neostigmine or vagal stimulation, 34% of the episodes of AF lasted 10 seconds, 11% lasted 20 seconds, and only 1% lasted 200 seconds. However, in one anesthetized animal AF was sustained for 4,800 seconds with no drug or vagal support. The administration of neostigmine alone in 3 anesthetized animals more than doubled the average duration of AF. In the animals with vagal stimulation (after neostigmine), AF persisted throughout stimulation, but ceased shortly after vagal stimulation was terminated at 2,220, 4,500, and 3,840 seconds. The AF frequency ranged from 325-750/min. The unanesthetized sheep were lightly sedated with a small dose (200 micrograms/kg IM) of xylazine to make them less sensitive to environmental noise; then AF was induced and its duration was timed. After these measurements, neostigmine was administered (30 micrograms/kg IM) and cholinergic drive was produced reflexly by intravenous injection of 60-2,000 micrograms of phenylephrine. AF was electrically induced at the time of maximum reflex slowing in heart rate. For the control (no drug) studies, 64% of the AF episodes lasted 10 seconds, 20% lasted 20 seconds, and only 2% of the episodes lasted as long as 140 seconds. When phenylephrine was injected after neostigmine to provide increased cholinergic drive, the duration of fibrillation depended on the dose of phenylephrine. In a 60-kg sheep, the duration of AF increased from 1 second with an intravenous dose of 60 micrograms to 700 seconds with an intravenous dose of 2,000 micrograms. However, there was a considerable range in responsiveness to the reflex cholinergic drive provided by the intravenous phenylephrine; for example a single intravenous 500-micrograms dose produced AF ranging from 190-540 seconds among the sheep. The duration of AF was most controllable in the anesthetized sheep, following neostigmine administration and with bilateral vagal stimulation. In the unanesthetized sheep, AF could generally be sustained for more than the duration of the half-life (about 4 minutes) of phenylephrine following neostigmine. However, there was a large variation in the duration of AF among the animals for the same dose of phenylephrine. This study identifies two methods (direct vagal stimulation and reflex vagal stimulation) for providing the cholinergic drive needed to sustain AF in the adult sheep. The duration of AF is sufficiently long to enable the measurement of electrical atrial defibrillation threshold.

Anesthesia, General↗
PubMed1977

Chronic copper poisoning in sheep. ii. The distribution of soluble copper-, molybdenum-, and zinc-binding proteins from liver and kidney.

The concentrations of copper, molybdenum, and zinc in the soluble protein fraction from sheep liver and kidney were determined after gel filtration. Samples from grazing sheep as well as from copper poisoned sheep were tested. In normal sheep the copper-binding proteins were separated into 3 different fractions. In copper poisoned sheep, as well as in grazing sheep with high copper concentrations, only 2 main fractions were seen. Molybdenum was only found in the high molecular weight protein fraction. The distribution of the zinc-binding proteins varied according to the degree of copper accumulation. The low molecular weight zinc-binding protein fraction was only seen in sheep with liver copper concentrations lower that 40 mug/g wet weight. In copper poisoned sheep a major part of the kidney copper was found in the low molecular weight protein fraction. At post mortem the bile copper concentrations in the copper poisoned sheep were only 2-4 times higher than those of the control animals.

Animals↗
PubMed1989

An epidemiological study of sheep deaths before and during export by sea from Western Australia.

A study was conducted to record the deaths that occurred during export, and to examine the temporal pattern of pellet feeding in the feedlot and ascertain the variation in mortality between groups of sheep from different farms. Between November 1985 and April 1987, 5 cohorts of sheep were selected on arrival at a feedlot before live export by sea from Western Australia to the Middle East. Each cohort consisted of 4,118 to 9,612 Merino wethers from 15 to 35 farms (lines). There were few deaths during trucking to the feedlot (rate 0.9, range 0.0 to 3.0 per 10,000 sheep) and during lot-feeding (rate 6.2, range 1.2 to 12.2 per 10,000 sheep). Most of the deaths occurred aboard ship (rate 210.7, range 152.7 to 271.5 per 10,000 sheep). The proportion of sheep that ate pelleted feed increased with increasing length of time in the feedlot. By the end of lot-feeding the percentage of sheep that had not eaten pellets was 23.3, 4.4, 1.2, 2.1 and 0.2 in a representative sample of each of the 5 cohorts. It was considered that offering hay throughout lot-feeding was undesirable for the purpose of maximising the number of sheep that ate pellets before loading on the ship. Half of the deaths aboard ship occurred in 25% of 133 lines of sheep in the 5 cohorts. In each cohort the median per cent death rate (and range) per line was 1.3 (0.3 to 11.9), 1.1 (0.0 to 5.7), 1.8 (0.0 to 6.8), 2.3 (0.0 to 14.3) and 0.9 (0.1 to 5.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Husbandry↗
PubMed1976

Changes in arterial blood pressure, heart rate and haematocrit during acute hyperkalaemia in conscious sheep.

The systolic, diastolic and mean arterial blood pressures, heart rate and haematocrit were measured at 15 minute intervals before, during and after 2 hour infusions of 0-4 mol.l-1 NaCl at 2-2 ml min-1 into conscious intact sheep and 0-4 mol. l-1 KCl at 2-2 ml. min-1 into conscious sheep which were either intact or adrenalectomized. The haemotocrit was also measured in splenectomized sheep receiving 0-4 mol. l-1 KCl. The NaCl infusion had no significant effect on blood pressure(BP), heart rate and haematocrit. Both intact and adrenalectomized sheep were able to withstand an increase in plasma potassium concentration in excess of 50% of the preinfusion concentration before any substantial fall in BP occurred. In intact and adrenalectomized sheep, heart rate and haematocrit increased rapidly and progressively throughout the potassium infusions and at maximum plasma potassium concentration the mean increments in these parameters for both groups of sheep were 21-6+/-2-69 beats/min and 7-5+/-0-47% respectively. Heart rate and haematocrit were more closely correlated with the plasma potassium concentration than with any other variable measured in these experiments. Adrenalectomy did not reduce the ability of the sheep to maintain their BP or to increase their heart rate and haematocrit. As the mean increase in haematocrit during potassium infusion into splenectomized sheep was 1-3+/-0-45% most of the increase in haematocrit observed in the potassium-infused intact and adrenalectomized sheep was caused by ejection of red cells from the spleen into the circulation.

Adrenal Glands↗
PubMed1991

Species-specific transfer of plasma albumin from blood into different cerebrospinal fluid compartments in the fetal sheep.

1. The blood-cerebrospinal fluid (CSF) transfer of endogenous sheep albumin and several exogenous species of albumin has been investigated in different CSF compartments of the immature fetal sheep brain, at an early stage of development (60 days gestation, term is 150 days) when the CSF concentration of total protein is high. 2. There were marked differences in the steady-state CSF/plasma ratios for all species of albumin (including endogenous sheep albumin) between different CSF compartments. Ratios measured in the cisterna magna were significantly higher than those in the dorsal subarachnoid space, which in turn were higher than those in the lateral ventricles. The ratios for endogenous sheep albumin were (%; mean +/- S.E.M.): lateral ventricle (LV), 4.0 +/- 0.03; dorsal subarachnoid (DSA), 6.1 +/- 1.0; cisterna magna (CM), 13.7 +/- 0.8. 3. Three hours after I.V. injection, the CSF/plasma ratios for bovine albumin (LV, 2.0 +/- 0.2; DSA, 2.4 +/- 0.1; CM, 7.2 +/- 0.7%) were significantly lower than the ratio for endogenous sheep albumin in all three compartments. The ratios for human albumin (LV, 0.7 +/- 0.2; DSA, 1.0 +/- 0.2; CM, 3.9 +/- 0.4%) were significantly lower than those for bovine albumin. 4. In all three CSF compartments, the endogenous sheep albumin ratios were higher than would be expected on the basis of transfer by passive mechanisms. Conversely, steady-state CSF/plasma ratios for [3H]sucrose and [14C]inulin were consistent with passive transfer, and there were no differences between the ratios for these markers measured in each of the three CSF regions. 5. Goat albumin and [35S]sheep albumin ratios were not significantly different, 5 h after injection, from the endogenous sheep albumin levels in each of the three CSF compartments. 6. It is concluded that in the 60-day-old fetal sheep, all of the endogenous albumin in CSF is derived from the plasma by a specific transfer mechanism that can distinguish between different species of the same protein. There is also some evidence of a small passive component of blood-CSF albumin transfer. 7. Immunocytochemical evidence suggests that the route of transfer from blood to CSF is transcellular, through the choroid plexus epithelial cells. 8. Regional variations in albumin ratios are probably due to differences in specific transfer into each CSF compartment. This is reflected in a differential immunocytochemical staining for albumin in choroid plexus epithelial cells from different regions of the brain. 9. The results are discussed in terms of differences in albumin amino acid sequences, structural homologies, and transfer by a specific transcellular mechanism.

Albumins↗
PubMed2006

Sheep-passaged bovine spongiform encephalopathy agent exhibits altered pathobiological properties in bovine-PrP transgenic mice.

Sheep can be experimentally infected with bovine spongiform encephalopathy (BSE), and the ensuing disease is similar to scrapie in terms of pathogenesis and clinical signs. BSE infection in sheep is an animal and human health concern. In this study, the transmission in BoPrP-Tg110 mice of prions from BSE-infected sheep was examined and compared to the transmission of original cattle BSE in cattle and sheep scrapie prions. Our results indicate no transmission barrier for sheep BSE prions to infect BoPrP-Tg110 mice, but the course of the disease is accelerated compared to the effects of the original BSE isolate. The shortened incubation period of sheep BSE in the model was conserved in subsequent passage in BoPrP-Tg110 mice, indicating that it is not related to infectious titer differences. Biochemical signature, lesion profile, and PrP(Sc) deposition pattern of both cattle and sheep BSE were similar. In contrast, all three sheep scrapie isolates tested showed an evident transmission barrier and further adaptation in subsequent passage. Taken together, those data indicate that BSE agent can be altered by crossing a species barrier, raising concerns about the virulence of this new prion towards other species, including humans. The BoPrP-Tg110 mouse bioassay should be considered as a valuable tool for discriminating scrapie and BSE in sheep.

Amino Acid Sequence↗
PubMed1999

Effects of modest anemia on systemic and coronary circulation of septic sheep.

Although a lower transfusion trigger is generally recommended, little evidence is available about the physiological mechanisms of mild anemia in diseases with an imbalance between O2 supply and O2 demand such as sepsis. This study was undertaken to describe the systemic and coronary metabolic O2 reserve in an awake sheep model of hyperdynamic sepsis comparing two different hemoglobin levels. Twenty-four hours after sheep were rendered septic by cecal ligation and perforation (CLP), blood transfusion (n = 7, hemoglobin = 120 g/l) and isovolemic hemodilution (n = 8, hemoglobin = 70 g/l), respectively, were performed. Another 24 h later, we measured hemodynamics, organ blood flows, and systemic and myocardial O2 metabolism variables at baseline and through four stages of progressive hypoxia. Maximum coronary blood flow was 766.3 +/- 87.4 ml. min(-1). 100 g(-1) in hemodiluted sheep group versus 422.7 +/- 53.7 ml. min(-1). 100 g(-1) in the transfused sheep (P < 0.01). Myocardial O2 extraction was higher in the transfusion group (P = 0.03) throughout the whole hypoxia trial. In the hemodilution group, coronary blood flow increased more per increase in myocardial O(2) uptake than in transfused sheep (P < 0.01). This was accompanied by a lower left ventricular epicardial-to-endocardial flow ratio in hemodiluted sheep (1.13 +/- 0.07) than in transfused sheep (1.34 +/- 0.02, P < 0.05). We conclude that the lower coronary blood flow and greater myocardial O2 extraction in transfused septic sheep preserves transmyocardial O2 metabolism better in comparison to hemodiluted sheep.

Anemia↗
PubMed1983

Effects of 100% oxygen on lung vascular function in awake sheep.

The purpose of this study was to define the time course of pulmonary toxicity during continuous breathing of 100% oxygen in adult sheep. Sheep were prepared for chronic measurement of vascular pressures, cardiac output, gas exchange, and for collection of lung lymph. Tracheostomies allowed accurate delivery of either 100% oxygen, compressed air, or hypoxic gas. Six sheep breathed 100% oxygen for 72-96 h, and four sheep breathed compressed air for 96 h. In addition to hypoxic challenges [fractional concentration of inspired O2 (FIo2) = 0.12], some sheep received prostaglandin H2 (PGH2)-analogue infusions to further assess pulmonary vascular reactivity. Lung lymph and blood chemotactic activity were measured by granulocyte migration in modified Boyden chambers. Postmortem lung water content and light microscopy were used to measure pulmonary edema. All sheep breathing 100% oxygen died between 72 (n = 2) and 96 h (n = 4). Sheep breathing oxygen demonstrated lung toxicity by measurements of 1) a fourfold increase in flow of protein-rich lung lymph, 2) increased alveolar-arterial difference in Po2 (greater than 20 Torr on FIo2 = 0.21) and hypercapnic acidemia, and 3) a mean extravascular lung water/dry lung weight of 5.7 (controls = 3.3), and histological evidence of interstitial and alveolar edema. Chemotactic activity in lung lymph at base line increased eightfold within 72-96 h of oxygen breathing. In sheep breathing oxygen, the hypoxic pressor response decreased by 50% at 48 h, and by 72-96 h there was a total absence of hypoxic vasoconstriction. There was no increase in lung lymph prostacyclin metabolite, and sodium meclofenamate did not restore the pressor response. In sheep breathing compressed air none of these changes in pulmonary vascular reactivity, lymph flow, or chemotactic activity occurred. We conclude that prolonged breathing of pure oxygen causes pulmonary edema by increasing lung vascular permeability and that respiratory failure results from both edema and loss of pulmonary vascular reactivity.

Animals↗