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Heterophile antibodies. Part III. Evidence for linkage of high responder activity to sheep red blood cells and the formation of specific antibodies to HBsAg.

Group A, B and O subjects who produce immune antibodies to group A1 or B red blood cells also produce high titer antibodies to sheep red blood cells. Sheep red blood cells appear to possess AB-like as well as non-AB determinants on their surface membranes, each capable of producing and reacting with antibodies of their respective specificities. The antibodies against AB-like determinants preferentially agglutinate A or B cells whereas non-AB-like determinants preferentially stimulate hemolytic antibodies. Human antibodies reacting with these two kinds of determinants on sheep red blood cells may be produced in response to microorganisms possessing very similar factors on their membranes. Individuals who possess AB-like determinants in their secretions, similar to the determinants present on sheep red blood cells (or microorganisms), often make weaker antibodies to these red blood cells. Subjects lacking corresponding anti-sheep inhibitors in their secretions generally produce stronger sheep red blood cell antibodies. There is a positive correlation between the formation of antibodies to HBsAg and strong agglutinating antibodies to sheep red blood cells, indicating that similar determinants may be found on HBsAg virus and on sheep red blood cells. No such correlation was found for anti-tetanus antibodies.

ABO Blood-Group System↗

Sheep as a new experimental host for Babesia divergens.

Babesia divergens was cultivated in sheep erythrocytes in RPMI 1640 supplemented with 10% Fetal Calf Serum (FCS) or sheep serum. In vitro cultures in sheep red blood cells were initiated with human erythrocytes infected in vitro with B. divergens Rouen 1987 or with gerbil blood infected with several isolates from bovine origin. After the first subcultures on sheep erythrocytes, a ten-fold multiplication of the parasites was obtained within 48 h. Erythrocytes from three splenectomized sheep were infected in vitro with B. divergens; when parasitaemia reached 10%, the animals were inoculated with homologous parasitized erythrocytes. All sheep expressed hyperthermia with a peak between the 6th and the 9th day post-infection (p-i) and a transitory parasitaemia 10 days p-i. In vitro primary cultures were performed on two of these sheep, demonstrating the parasite persistence at very low parasitaemia in the infected animals. Splenectomized sheep can be used as a new model for B. divergens chronic infection.

Animals↗

Metabolism of valine and the exchange of amino acids across the hind-limb muscles of fed and starved sheep.

A combination of the isotope-dilution and arterio-venous (AV) difference techniques was used to study simultaneously the metabolism of valine in the whole body and in the hind-limb muscles of fed and starved (40 h) sheep. The net exchange of gluconeogenic amino acids across hind-limb muscles was also studied. Valine entry rate was unaffected by nutritional status. There was significant extraction of valine by hind-limb muscles in both fed and starved sheep. The percentage of valine uptake decarboxylated was higher (P less than 0.05) in fed sheep but the amount of valine decarboxylated was not significantly different. The proportion of valine uptake that was transaminated was about 30 times higher in starved sheep. About 54% of valine taken up by hind-limb muscle of starved sheep was metabolized. The corresponding value for fed sheep was 21%. The contribution of CO2 from valine decarboxylation to total hind-limb muscle CO2 output was about 0.2%. The output of alanine in both fed and starved sheep was low but the output of glutamine was relatively high and roughly equivalent to the amounts of aspartate, glutamate and branched-chain amino acids that were catabolized. This study has confirmed that valine is catabolized in sheep skeletal muscle, and shown that glutamine is a major carrier of amino nitrogen out of muscle.

Amino Acids↗

Developmental capacity, energy metabolism and ultrastructure of mature oocytes from prepubertal and adult sheep.

Development to the blastocyst stage was assessed for oocytes obtained from prepubertal and adult sheep matured and fertilized in vitro. The proportion of cleaved oocytes reaching the blastocyst stage was significantly lower for oocytes derived from prepubertal sheep than for those from adult sheep (7.4% and 24.6% respectively). There were no differences in the metabolism of glucose, glutamine or pyruvate between oocytes matured in vivo and in vitro, or of glucose or pyruvate between oocytes from prepubertal and adult sheep. Glutamine metabolism by mature oocytes from prepubertal sheep was significantly lower than that by oocytes from adult sheep. Ultrastructural studies revealed no differences in the morphology of cytoplasmic organelles of oocytes matured in vitro from prepubertal and adult sheep, but differences in the volume fraction and size of mitochondria and cortical granules were observed. These data suggest that mature oocytes from prepubertal sheep do not possess the developmental potential of their adult-derived counterparts, and this phenomenon may be associated with metabolic and ultrastructural anomalies.

Aging↗

A comparison of the voluntary intake and digestion of a range of forages at different times of the year by the sheep and the red deer (Cervus elaphus).

1. Comparisons were made between castrated male Scottish Blackface sheep and red deer (Cervus elaphus) of voluntary forage intake (VFI), digestibility and the mean retention time (MRT) of a particulate-phase marker (103Ru-phenanthroline) in the alimentary tract, when a range of forages: dried-grass pellets, chopped dried grass, fresh-frozen Agrostis-Festuca spp. and heather (Calluna vulgaris, L. Hull) were given at different times of the year. 2. On both the dried-grass-pellet and chopped dried-grass diets the red deer and sheep ate similar quantities. Both species had a higher VFI of dried-grass pellets in July than in November. The sheep digested the dried-grass-pellet diet better than the red deer and this was associated with a longer MRT of the particulate-phase marker in the alimentary tract. 3. The VFI of Agrostis-Festuca spp. and heather by the red deer was twice that of the sheep. The VFI of heather by the sheep increased by 32% between January and April, and the VFI of both the Agrostis--Festuca spp. and heather diets by the red deer increased by 65--70%. The sheep digested the Agrostis--Festuca spp. better than the red deer but the red deer digested the heather slightly better than the sheep. MRT of the particulate-phase marker was greater for the sheep than for the red deer on both the diets. The digestibility and MRT of both diets in the red deer did not decrease with the seasonal increase in VFI, suggesting a possible hypertrophy of the alimentary tract.

Animal Feed↗

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).

Animal Feed↗

Role of rumen protozoa in nitrogen digestion in sheep given two isonitrogenous diets.

1. The effect of protozoa on digestion in the rumen was studied using either defaunated or faunated sheep. 2. Six wethers, each fitted with rumen and simple duodenal cannulas, were given two isonitrogenous diets containing either lucerne (Medicago sativa) hay (diet L) or sodium hydroxide-treated wheat straw (diet S). The diets were given in eight equal portions per day at 3-h intervals. The mean intake of dry matter, 53 g/kg body-weight0.75 per d, was similar for the two diets and each diet had a similar digestible organic matter content. Diet L promoted a large protozoal population and was rich in nitrogen sources of low rumen-degradability, while diet S supported a smaller protozoal population and was rich in rumen-degradable N. 3. Digesta flow at the duodenum was estimated by means of a dual-marker technique using chromium-mordanted lucerne hay and polyethylene glycol as markers. The microbial flow at the duodenum was estimated using diaminopimelic acid (DAPA), nucleic-acid purine bases (PB) and 35S incorporation simultaneously. The different microbial markers were compared in the defaunated sheep. Protozoal N contribution was estimated in faunated sheep. 4. Defaunated sheep had lower rumen ammonia concentrations and molar proportions of butyric acid than faunated sheep, but they had higher molar proportions of propionic acid. 5. Rumen organic matter digestion was reduced by defaunation, but this decrease was compensated for by increased intestinal digestion. 6. There was a net increase of N flow (approximately 10 g/d) between mouth and duodenum in defaunated sheep. This was explained by increases in both microbial and dietary N flows from the rumen compared with faunated sheep. 7. The influence of protozoa on solid- and liquid-phase retention times in the rumen is discussed, as well as the protozoal contribution to microbial N flow in the duodenum of faunated sheep.

Animals↗

Chronic airway disease: deteriorating pulmonary function in sheep associated with repeated challenges of house dust mite.

The aim of this work was to characterize lung function and cellular responses in a large animal model for chronic asthma. All sheep were sensitized to house dust mite (HDM) by subcutaneous injection of HDM before lung challenges. Groups of sheep were given weekly lung challenges with either HDM (n = 12) or saline (control, n = 5) for 3 months. Post challenge, there were significant increases in lung resistance in 7 out of 12 HDM-challenged sheep, compared to control sheep. In HDM-responding sheep, there was a progressive increase in the magnitude of HDM-induced resistance throughout the trial. All HDM-challenged sheep developed BAL eosinophilia and bronchial hyperresponsiveness. In conclusion, sheep chronically challenged intralung with HDM consistently develop airway hyperresponsiveness and eosinophilia, whereas allergen-specific bronchoconstriction is observed in just over half of these sheep.

Airway Resistance↗

A comparative study of nutrient digestibility, kinetics of digestion and passage and rumen fermentation pattern in goats and sheep offered medium quality forages at the maintenance level of feeding.

The in vivo digestibility and the rates of degradation and passage of alfalfa hay (AH) and vetch straw (VS) were compared in three Granadina goats and three Segureña wethers fed at approximately maintenance level, using a change over design. The nylon bag technique was used to estimate the fractional rate of degradation of the feeds in the rumen. The fractional outflow rate of hay and straw particles was determined with chromium as a marker. No significant differences in the digestibility coefficients of nutrients between animal species were found. Nitrogen retention expressed as coefficients of both nitrogen intake and digested nitrogen was lower (P < 0.01) in goats than in sheep when VS was offered. There was no significant difference between goats and sheep in the effective degradability (measured at outflow rates in the range of 0.027 to 0.032 h-1) of dry matter (DM) for either forage. However, the effective degradabilities of the neutral detergent fibre (NDF) and crude protein (CP) of VS were lower (P < 0.01 and P < 0.001, respectively), in goats than in sheep. The degradation rates of DM, NDF and CP were not significantly different (P > 0.05) between goats and sheep. Also, the fractional rate of passage of particles from the rumen was not different (P = 0.056) between species, although there was a tendency for an increased outflow rate in goats. In a second experiment the effects of animal species, type of diet and frequency of feeding on rumen fermentation pattern were studied following a factorial design. Four goats and four wethers were used. They were randomly allocated to three dietary treatments: AH, VS or a 50:50 mixture of AH and VS (AH/VS). Rations were offered in two or three meals daily and samples of rumen content were obtained at 09.00, 11.00, 13.00, 15.00, 17.00 and 19.00 h. No difference in rumen pH was found between goats and sheep. Total volatile fatty acids and ammonia concentrations were higher (P < 0.001) in sheep than in goats. The molar proportions of acetate and isovalerate were higher (P < 0.01 and P < 0.001, respectively) in goats than in sheep, whereas the opposite was true for the molar proportion of n-butyrate. Feeding frequency had a slight effect on the rumen parameters measured. It is concluded that only minor differences in the digestive capacity and rumen activity of sheep and goats can be expected when they are fed on medium quality forages.

Animal Feed↗

Influence of diet on amino acid absorption in beef cattle and sheep.

Six sheep and three steers were fed pelleted alfalfa hay prior to and during the first blood sampling period (BSP) and then switched to an 85% concentrate (HC) diet at least 28 days before a second BSP. Portal plasma flow rates were higher in steers than sheep (7.9 versus 5.0 liters/hr per kg0.75). With HC feeding, sheep and cattle had higher plasma femoral arterial concentrations of glycine and 3-methylhistidine and lower concentrations of valine and isoleucine than when fed hay. When fed HC diets, sheep, but not cattle, had lower glutamate and histidine and higher serine concentrations than when fed hay. Sheep had higher concentrations of aspartate, asparagine, threonine, glycine, tyrosine, phenylalanine, valine, leucine, citrulline, arginine, lysine, 3-methylhistidine and histidine than cattle. Diet did not affect the portal venous-arterial concentration difference or the net portal amino acid appearance (NPAAA) rate of any of the amino acids in sheep or cattle. With sheep, there was a tendency for the NPAAA rate to be higher for all amino acids, except aspartate, with HC compared to hay feeding. Expressed on the basis of metabolic body size, NPAAA rate was qualitatively and quantitatively similar between sheep and cattle.

Absorption↗

Lung vascular permeability after reversal of fibronectin deficiency in septic sheep. Correlation with patient studies.

Plasma fibronectin deficiency and opsonic dysfunction exist in critically ill septic surgical, trauma, and burn patients with multiple organ failure. Fibronectin deficiency can be reversed by infusion of fresh plasma cryoprecipitate. The influence of therapy with human cryoprecipitate on lung vascular permeability in septic sheep with plasma fibronectin deficiency following surgery was evaluated. Additionally, selected studies on pulmonary function in septic surgical and trauma patients after infusion of plasma cryoprecipitate were completed. In patients, ventilation-perfusion balance appeared to improve as measured by the multiple inert gas elimination technique. With the lung lymph fistula preparation in fibronectin deficient sheep, infusion of human plasma cryoprecipitate (10 units; 250 ml) delayed the onset and minimized the increase in lung vascular permeability during postoperative Pseudomonas sepsis (5 X 10(9) bacteria, I.V.; 5 X 10(10) bacteria, I.P.). For example, in a first group of sheep, the transvascular protein clearance (TPC) at 2 hrs in septic sheep (n = 4) treated with only saline (volume control) was 20.1 +/- 3.1 ml/hr, compared to 11.23 +/- 0.83 ml/hr in the sheep (n =a 4) treated with fibronectin-rich cryoprecipitate (p less than 0.05). In a second group of sheep, cryoprecipitate depleted of fibronectin by affinity chromatography was used as the control solution. It also did not manifest this protective effect with respect to lung vascular permeability. Thus, at 2 hrs the lymph flow (Qlym) was 30.2 ml/hr and the transvascular protein clearance (TPC) was 18.0 ml/hr in septic sheep given fibronectin-deficient cryoprecipitate. In contrast, in the fibronectin-rich cryoprecipitate treated sheep, the Qlym was 14.8 ml/hr and the TPC was 8.12 ml/hr. It is suggested that fibronectin may influence lung vascular integrity during sepsis following surgery and trauma.

Adolescent↗

Effects of serotonin antagonists on blood pressure in mineralocorticoid hypertensive sheep.

The serotonin antagonist methysergide has a partial agonistic action on isolated vascular smooth muscle from hypertensive animals, whereas ketanserin, another serotonin antagonist, does not. The goal of this study was to determine the effects of these two agents on blood pressure in the conscious, deoxycorticosterone acetate (DOCA) hypertensive sheep. Adult sheep maintained on a standard laboratory diet and 0.1% NaCl/0.25% KCl drinking water developed hypertension following DOCA implantation (mean arterial pressure: control = 83 mm Hg, DOCA = 108 mm Hg). Methysergide (40 micrograms/kg--i.v. bolus) produced a greater pressor response in hypertensive sheep than in normotensive sheep (control = 8 +/- 1 mm Hg, DOCA = 18 +/- 3 mm Hg). Ketanserin (50 micrograms/kg--i.v. bolus), on the other hand, caused a similar decrease in blood pressure (approximately -16 mm Hg) in both control and DOCA sheep. Pressor responses to infusions of serotonin were greater in DOCA sheep compared with controls. Both methysergide and ketanserin were equally effective antagonists of a serotonin-induced pressor response (75% inhibition) in control and DOCA sheep. Methysergide had no effect on a norepinephrine-induced pressor response, but ketanserin caused a 20% attenuation of this response. These results demonstrate an enhanced responsiveness to serotonin and methysergide in DOCA hypertensive sheep.

Animals↗

Successful transpedicular lumbar interbody fusion by means of a composite of osteogenic protein-1 (rhBMP-7) and hydroxyapatite carrier: a comparison with autograft and hydroxyapatite in the sheep spine.

STUDY DESIGN: Transpedicular lumbar interbody fusion (TLIF) was performed in a sheep model comparing three treatment groups: a composite of osteogenic protein (OP)-1 and hydroxyapatite carrier (HA), HA without OP-1, and autograft. OBJECTIVE: To evaluate the efficacy of the composite of OP-1 and HA (HA-OP-1) in achieving reliable TLIF. SUMMARY OF BACKGROUND DATA: Anterior fusion techniques directly address disc-related problems and achieve primary axial stability. However, they are characterized by high morbidity. Alternatively, the theoretically advantageous posterior TLIF technique using autograft fails clinically because it lacks compressive stability. METHODS: In 36 sheep, lumbar vertebrae L4 to L6 were instrumented posteriorly. Endoscopically assisted TLIF of L4 to L5 was performed. In 12 sheep, the defect was filled with injectable HA-OP-1. Another 12 sheep were treated with HA and another 12 with autograft. Animals were killed at 8 weeks and evaluated by radiologic, histologic, and histomorphometric analysis and by fluorochrome labeling. RESULTS: Only 10 autograft sheep were available for evaluation. Radiologically and histologically, TLIF with HA-OP-1 led to a fusion rate of 10 in 12 compared with autograft (one in 10 fused) and HA (two in 12 fused) ( = 0.0016). Semiquantitative radiologic and histologic scoring also revealed significant differences with superiority of HA-OP-1 ( = 0.0011). Compared with HA, HA-OP-1 presented significantly more ossification at the bone-cement interface ( = 0.0003) and less cement resorption ( = 0.0209). In four of 12 HA sheep, excessive resorption was responsible for local aseptic inflammation. CONCLUSIONS: Biointegration of the osteoconductive HA does not occur, because shear forces cause early HA fracture, subsequent fragmentation, and gross resorption (initiating severe inflammation in four of 12 sheep). In contrast, osteoinductive effects of HA-OP-1 enable bio-integration, resulting in full osseous composite sheathing and solid fusion. By use of this composite, TLIF is successfully applied in sheep. Harvesting autograft and the anterior approach are avoided.

Animals↗

Differential effects of prolonged septicemia on isolated pulmonary arteries and veins from sheep.

Isolated third-order pulmonary arteries and veins from sheep were examined for the effects of septicemia on norepinephrine-induced contractions, nitric oxide (NO)-mediated dilation, and basal cyclic GMP levels. The groups studied were as follows: control sheep (n = 7); sheep given live Pseudomonas aeruginosa (Ps, n = 6) for 48 h; and sheep given NG-mono-methyl-L-arginine during the last 24 h of Ps infusion (Ps-L-NMMA, n = 4). The norepinephrine-induced contractions were significantly greater (p < .05) in arteries from septic (Ps and Ps-L-NMMA) sheep. Basal cyclic GMP levels were similar in all of the arteries. The norepinephrine-induced contractions were significantly depressed (p < .05) in veins from septic (Ps and Ps-L-NMMA) sheep. Basal cyclic GMP levels in veins from Ps sheep were markedly elevated (p < .01). N omega-nitro-L-arginine methyl ester (L-NAME) ex vivo decreased cyclic GMP in both arteries and veins. Removal of endothelium enhanced contractions and decreased cyclic GMP in arteries and veins only from control sheep. The results show that septicemia differently affects the pulmonary artery and vein. The enhanced vasoconstriction of the artery is due to decreased endothelium-dependent NO release; the attenuated vasoconstriction of the vein is associated with NO-mediated increased cyclic GMP levels.

ADP Ribose Transferases↗

Scrapie epidemic in a fully PrP-genotyped sheep flock.

In scrapie-affected sheep flocks, host PrP genotype plays a vital role in determining which sheep will succumb to scrapie and the incubation period. Consequently, within-flock scrapie dynamics is best understood within the context of the genotype profile of the flock. Here we describe a 17 month epidemic of scrapie in a commercially farmed flock of 230 genotyped Texel sheep. At the start of the study, 70% of the sheep were of three genotypes only: ARR/ARQ, ARH/ARQ and ARQ/ARQ. Only 15% of sheep encoded the disease-associated VRQ allele and only a single sheep (0.4%) was of the most susceptible VRQ/VRQ genotype. For susceptible genotypes there was a marked deficit (P<0.025) of older animals (> or =3 years), implying that some cases of scrapie had occurred previously. In the ensuing 17 months, 18 sheep of known genotype were confirmed positive for the disease: seven VRQ/ARQ, six VRQ/ARH, two VRQ/ARR, three ARQ/ARQ. Median ages at death were 2.7, 2.8, 4.2 and 3.8 years respectively. Mortality rates were 55, 86, 13 and 3% respectively. Survival analysis revealed a highly significant effect of genotype on survivorship, but no difference between VRQ/ARQ and VRQ/ARH, or between VRQ/ARR and ARQ/ARQ. There was no difference in the survivorship of middle- and older-age cohorts of susceptible sheep. Scrapie risk group (as defined by PrP genotype) was not associated with submission as a scrapie suspect but later found to be negative, or with dying of unknown causes on the farm.

Age Factors↗

Phenotype of disease-associated PrP accumulation in the brain of bovine spongiform encephalopathy experimentally infected sheep.

In view of the established link between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease and of the susceptibility of sheep to experimental BSE, the detection of potential cases of naturally occurring BSE in sheep has become of great importance. In this study, the immunohistochemical (IHC) phenotype of disease-associated prion protein (PrP(d)) accumulation has been determined in the brain of 64 sheep, of various breeds and PrP genotypes, that had developed neurological disease after experimental BSE challenge with different inocula by a range of routes. Sheep BSE was characterized by neuron-associated intra- and extracellular PrP(d) aggregates and by conspicuous and consistent deposits in the cytoplasm of microglia-like cells. The stellate PrP(d) type was also prominent in most brain areas and marked linear deposits in the striatum and midbrain were distinctive. Sheep of the ARR/ARR and ARQ/AHQ genotypes displayed lower levels of PrP(d) than other sheep, and intracerebral BSE challenge resulted in higher levels of PrP(d) accumulating in the brain compared with other routes. The PrP genotype and the route of challenge also appeared to affect the incubation period of the disease, giving rise to complex combinations of magnitude of PrP(d) accumulation and incubation period. Despite these differences, the phenotype of PrP(d) accumulation was found to be very consistent across the different factors tested (notably after subpassage of BSE in sheep), thus highlighting the importance of detailed IHC examination of the brain of clinically affected sheep for the identification of potential naturally occurring ovine BSE.

Animals↗

Red cell glutathione deficiency: clinical and biochemical investigations using sheep as an experimental model system.

The biochemical properties of red cells from normal sheep and sheep with three types of red cell glutathione (GSH)-deficiency were compared. One deficiency was due to an impaired transport system for amino acids (lesion 1), one was the result of a diminished activity of gamma-glutamyl cysteine synthetase (GC-S) (lesion 2) and the third was a combined deficiency produced by selective breeding to give animals with both lesions 1 and 2. Under normal husbandry conditions no clinical symptoms were apparent in sheep with lesion 2, but red cells from sheep with lesion 1 and lesions 1 + 2 showed an increased osmotic fragility, a greater tendency to form Heinz bodies and a shorter potential life span than normal. These deficiencies were not found in tissues other than blood. Normal and GSH-deficient red cells had the expected low concentrations of 5-oxoproline. The effects of the toxic agents phenylhydrazine, s-methylcysteine sulphoxide and nitrite in vivo were measured in sheep of the different types. GSH-deficient sheep responded earlier and more dramatically than normal sheep, showing greater methaemoglobin formation, and for phenylhydrazine and s-methylcysteine sulphoxide, more severe anaemia. Sheep with the combined lesions were in general the most susceptible, but even they had the ability to recover from moderately severe oxidative challenge.

Anemia↗

Regional differences in the effects of various doses of cerulein upon the small-intestinal migrating motor complex in fasted and non-fasted sheep.

There are no precise data concerning the effect of cerulein on the small-intestinal migrating motor complex (MMC) in sheep. Thus, the effort was directed towards the elucidation of the role of cerulein, a cholecystokinin (CCK) amphibian analogue, in the regulation of MMC cycle in conscious fasted and non-fasted sheep in various regions of the small intestine. In six sheep, equipped with bipolar electrodes in the entire small intestine and with one duodenal strain gauge force transducer in four of these animals, the continuous myoelectric and motor activity recordings were performed. During control period, two normal consecutive MMC cycles were recorded in fasted and non-fasted animals and then cerulein was slowly injected at the dose 1 (during 30 s), 10 (during 30 s or 60 s) or 100 ng/kg (during 30 s, 60 s or 120 s) or infused at the dose 0.5 or 1.5 ng/kg/min during 60 min. After cerulein administration at least two consecutive MMC cycles were also recorded. It was found that cerulein in moderate and higher doses injected in both fasted and non-fasted animals, especially during phase 2a or 2b MMC, inhibited phase 3 in the duodenum in at least one-third of the experiments and significantly increased the MMC cycle duration. The application of 100 ng/kg of cerulein during 120 s in the course of phase 2b MMC prolonged cycle duration from 70 +/- 21 to 113 +/- 19 min (p < 0.05) or from 51 +/- 18 to 113 +/- 19 min (p < 0.01) in fasted and non-fasted sheep respectively. The first phase 3 MMC arriving after cerulein administration at the highest dose was usually abnormal in approximately 60% of the experiments. The second phase 3 observed following the hormone injection was abnormal much less frequently and to the lesser extent. Furthermore, both cerulein doses significantly shortened the duration of phase 3 MMC either in fasted (from approximately 5.5-6.5 cpm to 4-5 cpm) or in non-fasted sheep (from approximately 4.5-5.5 to 3-4.5 cpm). The effects of cerulein exhibited the dose-response character. They were more pronounced when cerulein was injected during phase 2b or 2a MMC when compared with phase 1 MMC. The effects of cerulein on the ileal MMC were less evident, although the inhibition of the ileal phase 3 in response to both higher injected doses was observed occasionally. Infusions of cerulein in non-fasted sheep exerted similar effects as cerulein injections. It was stated that cerulein exerts marked regulatory effect upon the small-intestinal MMC in sheep. Although it remains uncertain whether the efficient doses of cerulein used in the present study correspond to physiological or pharmacological doses of CCK it seems likely that most of these doses were physiological. Thus, it is concluded that cerulein participates in the control of MMC cycles in the digestive and interdigestive states in sheep. It is possible that CCK is a physiological regulator of the ovine small-intestinal MMC.

Animals↗