Brain lesions of naturally occurring pregnancy toxemia of sheep.

The neuropathology and biochemical features of 17 sheep with clinical signs and gross necropsy features of naturally occurring pregnancy toxemia were retrospectively evaluated. The sheep ranged in age from 3 to 6 years and were of seven different breeds and three breed crosses. Thirteen sheep (case Nos. 1-4, 6-9, 11-14, 16) showed astrocytic nuclear swelling, hypertrophy and proliferation, and cerebrocortical neuronal necrosis. Seven of these sheep had Purkinje cell necrosis (case Nos. 2, 3, 6, 11, 12, 14, 16), and seven had vacuolation of cerebral and cerebellar sub-cortical white matter (case Nos. 1-4, 9, 12, 13). The neuropathologic features were similar to those of naturally occurring hypoglycemia of human beings and experimentally induced hypoglycemia of primates and the rat. The lesions seen in the sheep studied may have been caused by cerebral hypoglycemia, but data for blood or cerebral glucose concentrations were not available.     

羊妊娠毒血症的防治

羊妊娠毒血症是怀孕末期母羊由于碳水化合物和挥发性脂肪酸代谢障碍而发生的亚急性代谢病,以低血糖、酮病、虚弱和失明为主要特征.主要临床表现为精神沉郁,食欲减退,运动失调,呆滞凝视,卧地不起,甚而昏睡等.近半年来,我站门诊已治该病1 3例,其中绵羊11例,山羊2例.治愈10例,药物引产2例,死亡1例.     

Metabolic profiles in goat does in late pregnancy with and without subclinical pregnancy toxemia

Background: Pregnant goat does can develop various metabolic diseases during late pregnancy that may have profound effects on their health and productivity, including subclinical pregnancy toxemia. Objectives: This study was performed to evaluate serum biochemical findings in goats in late pregnancy with and without subclinical pregnancy toxemia. Methods: Serum samples were obtained from 153 clinically healthy goats in the last trimester of pregnancy from 14 herds in central and northern Jordan. Serum was analyzed for the following constituents: 3‐hydroxybutyrate (3‐HB), glucose, total protein, albumin, urea, creatinine, aspartate aminotransferase, alkaline phosphatase, cholesterol, triglycerides, cortisol, T3, T4, total calcium, magnesium, and phosphorus, using commercially available kits. Goats were classified as having subclinical pregnancy toxemia or as controls on the basis of 3‐HB results. Biochemical results were compared between the 2 groups using nonparametric statistical tests. Results: Fifty‐three does had subclinical pregnancy toxemia (3‐HB>0.86 mmol/L) and 100 were pregnant control does (3‐HB≤0.86 mmol/L). Does with subclinical pregnancy toxemia had significantly lower glucose concentrations (P<.001) and significantly higher urea (P=.042) and total protein (P=.048) concentrations compared with pregnant control does. 3‐HB concentration was significantly correlated with glucose (r=0.290, P=.035), phosphorus (r=0.351, P=.01), and cortisol (r=0.394, P=.004) concentrations in goats with subclinical toxemia. Conclusions: Results of this study indicate that the biochemical profile of does with subclinical pregnancy toxemia differs from that of other pregnant goats. 3‐HB should be measured in pregnant does in late stages of gestation with hypoglycemia or with elevated urea and total protein concentrations.     

Pregnancy toxemia in a flock of sheep

A high prevalence of metabolic disease was evident in a large flock of sheep early in the lambing season. Pregnancy toxemia and secondary hypocalcemia were diagnosed on the basis of history, physical examination findings, and results of serum biochemical analyses. To decrease costs to the owner, pooled serum samples were used to determine the metabolic health status of the flock. Ewes close to the time of lambing were found to be in severe negative energy balance, which resulted in excessive fat mobilization as well as clinical signs associated with pregnancy toxemia and hepatic lipidosis. By nutrient analysis, it was determined that the ewes had an inadequate amount of fermentable carbohydrates, which provide glucose to support the additional nutrition required during late gestation. The diet provided to sheep during late gestation should contain sufficient glucose precursors to maintain adequate glucose availability to maternal and fetal tissues. To minimize the physiologic decline in dry-matter intake during late gestation (which results in accentuation of negative energy balance), high-quality feed ingredients should be fed to ewes during this period.     

Effects of induced moulting on immune responses of hens.

1. The potential for induced moult to be a stressor and therefore alter the immune response in hens was examined. Spent hens from White Leghorn and White Rock layer flocks were induced into a moult by withdrawal of food and the effects on the humoral and cellular immune responses of these birds were examined. 2. Lymphocyte numbers were lower in moulted birds compared with nonmoulted controls. 3. Antibody responses to sheep red blood cells or Brucella abortus antigen were largely unaffected. 4. The delayed type hypersensitivity response to the skin sensitiser dinitrofluorobenzene (DNFB) was depressed during the period of food withdrawal but recovered when feeding resumed. 5. Induced moulting probably has a negative effect on the cellular component of the immune system of the moulted birds.     

Effects of protein supply and reproductive status on local and systemic immune responses to Teladorsagia circumcincta in sheep

The effects of protein supply and reproductive status on circulating antibody responses and local inflammatory cell counts were investigated in parasitized sheep, with local immune responses assessed through a recently refined abomasal cannulation methodology. We hypothesized that if breakdown of immunity has a nutritional basis, then protein scarcity would result in a breakdown of immunity to Teladorsagia circumcincta in both periparturient and non-reproducing (barren) ewes. Twin-bearing and barren, abomasally cannulated ewes were fed at either 0.8 or 1.3 times protein requirements from 3 weeks before until 6 weeks after parturition (n = 6). All sheep were trickle infected at a rate of 10,000 infective larvae (L3) per day, for 3 days per week throughout the experiment. Faecal egg counts remained virtually zero in all barren ewes, whilst protein supplementation reduced faecal egg counts in the periparturient ewes during most of the periparturient period. Final worm burdens, taken at 6 weeks into lactation, were lower for the barren ewes than for the lactating ewes, whilst protein supplementation reduced worm burdens in the latter. Protein supply did not affect mucosal mast cell counts, which were consistently higher for the barren ewes than the periparturient ewes, but were temporarily decreased around parturition. Barren ewes and protein supplemented lactating ewes had higher globule leukocyte counts than the unsupplemented lactating ewes. Protein supplementation increased eosinophil counts in the lactating ewes though only during the later part of the lactation period. Plasma IgA anti-L3 antibody was similar for all ewes, but IgE anti-L3 antibody was higher for the protein supplemented periparturient ewes compared to the unsupplemented periparturient ewes and all barren ewes. It is likely that the combination of low protein requirements and large body protein reserves did not result in breakdown of immunity to T. circumcincta for the barren ewes. These results suggest that changes in mucosal mast cell and eosinophil counts are not necessarily associated with changes in host resistance to T. circumcincta. However, the data support the view that increased globule leukocyte counts and plasma IgE anti-L3 antibody may be associated with nutritionally improved expression of immunity in periparturient ewes.     

Characterization of immune responses caused by bovine leukemia virus envelope peptides in sheep.

To study the immunomodulative activity caused by bovine leukemia virus envelope (BLV Env) peptide, sheep were immunized with two kinds of Th-epitope peptides, peptide 98 (BLV Env 98-117), and 61 (BLV Env 61-78). Four of eight immunized sheep showed specific proliferative responses against both of the peptide stimulations. To characterize the cells responding to the peptides, peptide-specific cells were established from the responding sheep by the continuous stimulation of peripheral blood mononuclear cells (PBMCs) with either peptide 98 or 61 in vitro. The peptide 98-specific cells consisted of CD4-positive cells, whereas the peptide 61-specific cells consisted of CD8-positive cells and MHC class II-positive cells. In addition, cytokine profile analysis indicated that the peptide 98-stimulated cells expressed IFN-gamma but not IL-10, although the peptide 61-stimulated cells expressed IL-10 but not IFN-gamma. These results show that BLV envelope peptides 98 and 61 can modulate immune responses of sheep lymphocytes in different ways and may contribute to the pathogenesis of BLV infection.     

Cellular immune responses in the skin of sheep infected with larvae of Lucilia cuprina, the sheep blowfly.

Cellular immune responses were observed in the skin of sheep after primary and secondary infection with sheep blowfly (Lucilia cuprina) larvae. Both primary and secondary infections resulted in a massive cellular infiltration within 48 h of wound initiation, with the majority of cells having the CD45 phenotype. Neutrophils comprised the major cell type at the skin surface. In the dermis, the number of CD4+ T helper, gamma delta-TCR+ cells and T19+ (CD4-, CD8-) T cells also increased significantly in skin during both primary and secondary infections compared with control sites. However, there was no significant difference in the numbers of these cells between primary and secondary infections. An increase in the expression of the CD1 antigen on Langerhans/dendritic cells was observed, along with an apparent increase in the number of these cells in secondary lesions, with the majority of the cells being concentrated in the upper dermis and epidermis. While there was no increase in mast cells, eosinophils increased significantly during infection compared with control sites. The cellular infiltration observed following primary and secondary infections suggests polyclonal activation of T cells and their selective recruitment to the lesion site.     

Systemic responses to challenge infection withHaemonchus contortus in immune Merino sheep

Some systemic responses to single-dose infection with 10 000Haemonchus contortus infective larvae were examined in sheep already shown to have protective immunity against the parasite. The major haematological finding was a neutrophil leukocytosis that occurred after the infections became patent but not during the pre-patent period. There was no definitive eosinophilia and no discernible change in the erythrocyte parameters. Systemic hyperthermia was not conclusively evident during the pre-patent period. Enzyme-linked-immunosorbent assays (ELISA) were used to measure the secondary anti-helminth antibody response in serum during the pre-patent period when the establishment of patent infection is resisted. These ELISAs employed preparations from adult worms to represent the parasitic stages of the worm, preparations from infective larvae to represent the pre-parasitic stages of the worm, and exsheathing fluid, which is the soluble material obtained whenH. contortus larvae undergo ecdysis and transform from the pre-parasitic to the parasitic phase. Antibody responses to the three preparations differed qualitatively, indicating the presence of three different but perhaps overlapping sets of antigens. The three peaks in antibody against exsheathing fluid may reflect the pulses of antigen delivered to sheep as the parasite undergoes its three moults within the host.Abbreviations ELISA enzyme-linked immunosorbent assay - EDTA ethylene diamine tetraacetate     

Early pregnancy alters the metabolic responses to restricted nutrition in sheep

This study investigated whether a 27-day period of nutrition at half-maintenance during early pregnancy (up to Day 14) could alter maternal endocrine responses. Forty-six ewes were fed all or half of their maintenance requirements and slaughtered on Day 14 of the oestrous cycle or pregnancy. We used real time RT-PCR to study gene expression of growth hormone receptor (GHR) and leptin in adipose tissue and GHR, GHR1A and of the insulin-like growth factor I (IGF-I) in the liver. Blood profiles of metabolites and metabolic hormones were also determined. Throughout the experiment, underfed animals presented lower body weight and body condition, greater plasma concentrations of non-esterified fatty acids (NEFA), and lower plasma concentrations of leptin, compared to adequately fed animals. Undernutrition affected the patterns of gene expression in adipose and hepatic tissues, and the responses differed between pregnant and non-pregnant ewes. In adequately fed ewes, pregnancy up-regulated leptin mRNA expression in adipose tissue, a response that was impaired in underfed ewes. The hepatic expression of IGF-I mRNA was increased by pregnancy in underfed animals while no effect was observed in adequately fed ewes. It remains to be determined whether the changes in the endocrine milieu are paralleled by modifications in uterine gene expression that could alter the environment of the embryo during early pregnancy.     

Serum protein pattern in ewe with pregnancy toxemia

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

Systemic innate immune responses following intrapulmonary delivery of CpG oligodeoxynucleotides in sheep

Mucosal delivery of CpG oligodeoxynucleotide (ODN) in mice has been shown to induce potent innate immunostimulatory responses and protection against infection. We evaluated the efficacy of CpG ODN in stimulating systemic innate immune responses in sheep following delivery to the pulmonary mucosa. Intrapulmonary (IPM) administration of B-Class CpG ODN in saline induced transient systemic responses which included increased rectal temperatures, elevated serum 2'5'-A synthetase and haptoglobin concentrations. The ODN dose required to induce detectable systemic responses following IPM delivery could be reduced by approximately 80% if the CpG ODN was administered in 30% emulsigen instead of saline. Intrapulmonary B-Class CpG ODN formulated in 30% emulsigen produced similar effects when compared to those seen following SC injection. These responses were CpG ODN-specific since control GpC ODN did not induce any detectable response. Intrapulmonary administration of both B-Class and the newly described C-Class CpG ODN produced similar effects indicating that both classes of CpG ODN were comparably effective in stimulating innate immune system following mucosal delivery. Administration of CpG ODN directly into the lungs or delivery of CpG ODN via an intratracheal (IT) infusion also produced similar systemic responses. These observations support the conclusion that mucosal delivery of CpG ODN is an effective route for induction of systemic acute phase responses and antiviral effector molecules in large animals, and may be helpful in controlling systemic infections.     

Effects of chemotherapy on immune responses in dogs with cancer

Chemotherapy is assumed to be immunosuppressive; yet to the authors' knowledge, the effects of common chemotherapy protocols on adaptive immune responses in dogs with cancer have not been fully evaluated. Therefore, a study was conducted to evaluate the effects of 2 common chemotherapy protocols on T- and B-cell numbers and humoral immune responses to de novo vaccination in dogs with cancer. Twenty-one dogs with cancer (12 with lymphoma, 9 with osteosarcoma) were enrolled in a prospective study to assess effects of doxorubicin versus multi-drug chemotherapy on adaptive immunity. Numbers of circulating T and B cells were assessed by flow cytometry, and antibody responses to de novo vaccination were assessed before, during, and after chemotherapy. The T- and B-cell numbers before treatment also were compared with those of healthy, age-matched, control dogs. Prior to treatment, dogs with cancer had significantly fewer (P < .05) CD4+ T cells and CD8+ T cells than did healthy dogs. Doxorubicin treatment did not cause a significant decrease in T- or B-cell numbers, whereas treatment with combination chemotherapy caused a significant and persistent decrease in B-cell numbers. Antibody titers after vaccination were not significantly different between control and chemotherapy-treated dogs. These findings suggest that chemotherapy may have less impact on T-cell numbers and ability to mount antibody responses in dogs with cancer than was previously anticipated, though dogs with lymphoma or osteosarcoma appear to be relatively T-cell deficient before initiation of chemotherapy.     

Humoral and cellular immune responses in cattle and sheep inoculated with Sarcocystis

Cattle inoculated with Sarcocystis bovicanis (= Sarcocystis cruzi) and sheep inoculated with Sarcocystis ovicanis were monitored for the appearance of Sarcocystis-specific antibodies and lymphocytes in the peripheral circulation. Anti-Sarcocystis antibody was identified by enzyme-linked immunosorbent assay, whereas antigen-reactive lymphocytes were discerned by an in vitro lymphocyte blastogenic assay. The antigens used were the soluble fraction recovered from disrupted bradyzoites of mature sarcocysts. Cattle developed anti-Sarcocystis immunoglobulin (Ig)M responses, beginning 3 to 4 weeks after inoculation, and IgG1 antibody responses, beginning 5 to 6 weeks after inoculation. The increase in IgM antibody was relatively brief, returning to near preinfection levels in 2 to 3 months. In contrast, IgG1 antibody levels remained high for at least 5 to 6 months. Neither IgG2 nor IgA antibody responses were demonstrable in cattle. In sheep, the IgG antibody levels followed a time course similar to that seen in cattle, except that the increase was slightly delayed (6 to 8 weeks after inoculation was done). Measurable IgM antibody response was not seen in sheep. Cellular immunoresponsiveness as judged by in vitro lymphocyte blastogenesis in cattle was different from that in sheep. Sarcocystis-specific lymphocytes were demonstrable in the circulation of cattle within 15 days after they were inoculated, but the activity decreased rapidly. In sheep, reactive cells were not evident until 3 to 4 weeks after inoculation were done, but peripheral blood lymphocytes taken from these sheep as long as 5 to 6 weeks after the inoculations remained capable of mounting strong blastogenic responses. Neither the enzyme-linked immunosorbent assay nor the blastogenic assay showed species specificity. Animals immunized with a given species of Sarcocystis gave similar in vitro responses to antigens from the immunizing species and to other species of Sarcocystis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Higher whole-blood selenium is associated with improved immune responses in footrot-affected sheep

ABSTRACT: We reported previously that sheep affected with footrot (FR) have lower whole-blood selenium (WB-Se) concentrations and that parenteral Se-supplementation in conjunction with routine control practices accelerates recovery from FR. The purpose of this follow-up study was to investigate the mechanisms by which Se facilitates recovery from FR. Sheep affected with FR (n = 38) were injected monthly for 15 months with either 5 mg Se (FR-Se) or saline (FR-Sal), whereas 19 healthy sheep received no treatment. Adaptive immune function was evaluated after 3 months of Se supplementation by immunizing all sheep with a novel protein, keyhole limpet hemocyanin (KLH). The antibody titer and delayed-type hypersensitivity (DTH) skin test to KLH were used to assess humoral immunity and cell-mediated immunity, respectively. Innate immunity was evaluated after 3 months of Se supplementation by measuring intradermal responses to histamine 30 min after injection compared to KLH and saline, and after 15 months of Se supplementation by isolating neutrophils and measuring their bacterial killing ability and relative abundance of mRNA for genes associated with neutrophil migration. Compared to healthy sheep, immune responses to a novel protein were suppressed in FR-affected sheep with smaller decreases in FR-affected sheep that received Se or had WB-Se concentrations above 250 ng/mL at the time of the immune assays. Neutrophil function was suppressed in FR-affected sheep, but was not changed by Se supplementation or WB-Se status. Sheep FR is associated with depressed immune responses to a novel protein, which may be partly restored by improving WB-Se status (> 250 ng/mL).     

Effects of pulsed or continuous infusion of cortisol on immune function in sheep

It was postulated that frequent pulses of cortisol such as might be induced by a repeated or chronic stressor, could induce immune suppression and that the effect would be greater than in animals subjected to less frequent increases. Four groups of nine adult Scottish Blackface ewes were infused for 14 d with saline or hydrocortisone hemisuccinate (cortisol) delivered continuously or in pulses. Plasma concentrations of cortisol were significantly elevated (to between approximately 100 and 1000 nmol/liter; P < 0.001) for about 30 or 75 min after infusion of pulses of hydrocortisone hemisuccinate at intervals of 1 hr (P1) or 6 hr (P6), respectively. In animals continuously infused (CI), they were consistently elevated (P < 0.001), compared with concentrations in control animals infused with saline only (S), to approximately 1000 nmol/liter or more. Antibody production in response to ovalbumin injection was not affected by any of the infusion regimes. At Days 10, 24, and 31 after injection of ovalbumin and initiation of the infusion, rates of multiplication of unstimulated lymphocytes, in vitro, were greater (P < 0.05) in P6 animals than in saline-infused, control animals and this resulted in a reduction in the stimulated lymphocyte response. As a consequence of the increased basal lymphocyte activity, after Day 0, the corrected, stimulated lymphocyte response of P6 animals was consistently below that of controls (P < 0.05 at Day 24). Both mean basal and stimulated lymphocyte activities in CI and P1 animals were similar to those of controls. The gamma interferon (IFN-gamma) response was generally small and not affected by treatment. It is concluded that large, relatively infrequent increases in circulating cortisol concentrations can modify the cell mediated immune response such that the response to a specific antigen challenge is compromised but smaller, more frequent pulses had no effect. Elevated cortisol concentrations per se did not have a significant inhibitory effect on the immune system.