Description of lesions in lambs intoxicated with sodium selenite included in intraruminal boluses: Lambs intoxicated with selenium.

Selenium is an essential micronutrient for ruminants, which participates in the optimal functioning of proteins and enzymes that can combat oxidative stress in the body; however, its toxicity is documented in different species. The objective of this work was to describe macroscopic and microscopic lesions in lambs intoxicated with selenium administered through intraruminal boluses. The main lesions at necropsy were pulmonary oedema; the myocardial surface presented multifocal pale areas; the thyroid and thymus glands were decreased in size, and areas of necrosis, haemorrhage and hyperkeratosis were observed in the reticulum and rumen. At the microscopic level, congestion, haemorrhage, oedema and hyaline membranes were observed in the lung; hepatic congestion, haemorrhage, degeneration and necrosis; degeneration and necrosis of the reticulum mucosa, as well as areas of hyperplasia and hyperkeratosis; myocardial degeneration, necrosis and fibrosis; congestion, haemorrhage, degeneration and renal tubular necrosis; thyroid follicular atrophy and thymic cortical atrophy. This study evidenced the main lesions related to selenium poisoning in lambs supplemented with the mineral through intraruminal boluses.

Aflatoxin B1 as a complicit in intestinal damage caused by Eimeria ovinoidalis in lambs: Novel insights to reveal parasite-gut battle.

Mycotoxins, unavoidable contaminants in feed and feed ingredients, have the potential to influence the incidence and severity of various diseases upon ingestion. Sheep coccidiosis is an enteric disease caused by protozoa of Eimeria spp. However, the extent to which the presence of aflatoxin b1 (AFB1) synergistically exacerbates damage to intestinal health in lambs with Eimeria remains unclear. 50-day-old female lambs were randomly assigned to a 2 × 2 factorial arrangement of treatments for 15 days to assess the impact of AFB1 exposure on lambs with or without Eimeria (E.) ovinoidalis infection. Our findings reveal that AFB1 synergistically intensifies damage to intestinal health in lambs challenged by E. ovinoidalis. This is evidenced by disruptions to the intestinal microbiota and reductions in the production of short-chain fatty acids. AFB1 further aggravates damage to the cecal mechanical barrier. Additionally, AFB1 contributes to the entry of lipopolysaccharide into the bloodstream, activating the inflammatory response. Interestingly, AFB1 exposure history results in an early peak of oocyst excretion and a decreased number of oocyst excretion in E. ovinoidalis infected lambs. This may be closely linked to the destruction of the intestinal epithelial cell structure and its apoptosis, as indicated by a decreased ratio of Bcl-2 to Bax and increased caspase-3 levels. Mechanistically, proteomics analysis identified mitochondrial dysfunction (inhibition of the oxidative phosphorylation pathway) as the primary factor intensifying intestinal epithelial cell destruction caused by coccidia, exacerbated by AFB1 through the inhibiting the conversion of NADH to NAD+ in the cecum of lambs via down-regulation of the PGC-1α/NRF1/TFAM pathway. Overall, these results offer novel insights into the AFB1 complicity in accelerating intestinal damage caused by E. ovinoidalis in lambs. Targeting the mitochondrial oxidative phosphorylation pathway of the intestine may represent a new therapeutic strategy against the detrimental effects of mycotoxin and coccidia.

Chronic inflammation decreases arcuate kisspeptin expression in male sheep.

Lipopolysaccharide (LPS) from Gram-negative bacteria induces an immune response and impairs reproduction through suppression of gonadotropin releasing hormone (GnRH), subsequently luteinizing hormone (LH) secretion. While there is evidence that acute inflammation inhibits kisspeptin, little is known about the impact of chronic inflammation on this key reproductive neuropeptide in livestock species. Thus, we sought to examine a central mechanism whereby LPS suppresses LH secretion in sheep. Twenty wethers were randomly assigned to one of five treatment groups: control (CON; n=4), single acute IV LPS dose (SAD; n=4), daily acute IV LPS dose (DAD; n=4), daily increasing IV LPS dose (DID; n=4), and chronic subcutaneous LPS dose (CSD; n=4). On Days 1 and 7, blood samples were collected every 12 minutes for 360 minutes using jugular venipuncture. Following blood collection on Day 7, all animals were euthanized, brain tissue was perfused with 4% paraformaldehyde, and hypothalamic blocks were removed and processed for immunohistochemistry. On Day 1, LH pulse frequency was significantly lower (p=0.02) in SAD (0.25 ± 0.1 pulses/hour), DAD (0.25 ± 0.1 pulses/hour), DID (0.35 ± 0.1 pulses/hour), and CSD (0.40 ± 0.1 pulses/hour) compared to CON (0.70 ±0.1 pulses/hour). On Day 7, only DID animals (0.35 ± 0.1 pulses/hour) had significantly lower (p=0.049) LH pulse frequency compared to controls (0.85 ± 0.1 pulse/hour). Furthermore, only DID animals (33.3 ± 10.9 cells/section/animal) had significantly fewer (p=0.001) kisspeptin-immunopositive cells compared to controls (82.6 ± 13.6 cells/section/animal). Taken together, we suggest that daily increasing doses of LPS is a powerful inhibitor of kisspeptin neurons in young male sheep and a physiologically relevant model to examine the impact of chronic inflammation on the reproductive axis in livestock.

Poisonings in ruminants by Cenostigma pyramidale (Tul.) Gagnon & G.P.Lewis (Fabaceae): A mini-review of teratogenic potential and phytochemical evidence.

Teratogenic plants can be found in pastures in different parts of the world and represent a threat to the reproduction of ruminants. In the northeast region of Brazil, several studies have indicated that Cenostigma pyramidale (Tul.) Gagnon & G.P.Lewis is one of the main poisonous plants that causes reproductive problems in sheep and goats. In this context, the present study reviewed spontaneous and experimental poisonings reports by C. pyramidale in sheep and goats, as well as analyzing the phytochemical evidence related to this species. The scientific documents were retrieved from different databases and, after applying the selection criteria, a total of 16 articles published between 2000 and 2024 were included in this review. Cenostigma pyramidale causes embryonic loss, abortion, and congenital malformations in pregnant sheep and goats in the Brazilian semi-arid region. The main malformations observed in newborn animals are arthrogryposis, scoliosis, micrognathia, multiple skull deformities, cleft palate, and brachygnathism. Many secondary metabolites have already been isolated from C. pyramidale, however, to date, no evidence has been found regarding the possible teratogenic compounds that occur in this plant. From this perspective, new phytochemical studies are necessary to help unravel the mechanisms of action of embryotoxic agents from C. pyramidale.

Expression analysis of TLR signaling pathway genes under lipopolysaccharide-induced and E. coli F17-infected sheep intestinal epithelial cells.

Escherichia coli (E. coli) F17 is one of the main pathogens causing diarrhea in young livestock. The specific F17 fimbriae and lipopolysaccharide (LPS) in the surface components of E. coli F17 induces immune activation via interacting with the intestinal epithelial cells (IECs)-expressed innate immune toll-like receptors (TLRs) signaling pathway. In this study, the expression patterns of eight canonical genes from the TLR signaling pathway (IL-6, IL-8, IL-1ß, TLR4, MyD88, CD14, TNF-α and TRAF6) were analyzed in LPS-induced IECs, E. coli F17-infected IECs and ileum tissue of E. coli F17-infected lambs. The results showed that increased expression levels of all the studied genes were observed following post-LPS-induced and E. coli F17-infected treatment, with TLR4 having the highest up-regulated expression multiple (compared to NC, fold change = 17.94 and 20.11, respectively), and CD14 having the lowest up-regulated expression multiple (fold change = 2.68 and 1.59, respectively), and higher expression levels of all the studied TLR signaling pathway genes were observed in ileum tissue of E. coli F17 antagonistic (AN) lambs than in E. coli F17 sensitive (SE) lambs. Furthermore, when compared to LPS-induced IECs, E. coli F17-infected IECs showed a more pronounced increase in the expression of IL6, TLR4 and TNF-α, indicating the different roles of these genes in the IECs resistance to E. coli F17 infection. Our results demonstrate that the TLR signaling pathway likely promotes immune activation and provide the first evidence that TLRs have a significant potential to protect against E. coli F17 infections.

Peripheral neuropathy caused by fenugreek (Trigonella foenum-graecum) straw intoxication in cattle and experimental reproduction in sheep and goats.

Trigonella foenum-graecum (fenugreek) is a legume widely used as a food supplement in humans and less frequently in ruminants. Toxicity has been described sporadically in ruminants grazing mature fenugreek plants or stubble; however, the pathological features are unclear. This report describes a natural outbreak of intoxication in cattle fed fenugreek straw and the experimental reproduction using 8 sheep and 8 goats. Affected cattle presented clinical signs approximately 1 month after consuming the straw and 100 of 400 cattle (25%) were affected, of which 60 of 100 (60%) died or were euthanized. Clinical signs were characterized by proprioceptive positioning defects with abnormal postures and weakness of hindlimbs. Forelimbs were also affected in severely affected animals, and cattle became recumbent. Locomotion was characterized by trembling, and some cattle showed high-stepping movements of their forelimbs and knuckled over in their fetlocks. Experimental intoxication induced clinical signs only in sheep and were similar to cattle, although with signs starting in the forelegs. Gross and microscopic lesions were similar in spontaneous and experimental intoxications. Macroscopic changes corresponded with muscular hemorrhages and edema, mainly surrounding the peripheral nerves. Microscopic examination only demonstrated lesions in the distal peripheral nerves, which included edema, hemorrhages, and Wallerian degeneration. Neurofilament immunohistochemistry revealed altered axon labeling and S100 showed a decrease in myelin intensity and loss of its typical compact arrangement around axons. Biochemical and hematological abnormalities included elevated levels of muscle and liver enzymes and thrombocytopenia. These findings indicate that fenugreek straw induces peripheral neuropathy in cattle and sheep, but not in goats.

Anthelmintic intoxication in goats and sheep: A systematic review.

The objective of this study was to conduct research of the literature available in electronic media on anthelmintic intoxication in sheep and goats. The search for primary studies was carried out in five electronic databases: ScienceDirect, PubMed, Scopus, Web of Science, and SciELO. The search terms used were (antihelmintic OR antiparasitic OR vermifuge) AND (poisoning OR toxicity OR overdose OR intoxication) AND (goat OR sheep). A total of 2361 articles were identified from the five databases: Science Direct (n = 1869), PubMed (n = 434), Scopus (n = 37), Web of Science (n = 16), and SciELO (n = 5). As 111 articles were found in duplicates, 2250 were left for review of the title and abstracts, of which 115 were read in full, and 28 were included in the systematic review. Of the 28 articles, 16 involved sheep, 9 involved goats, and 3 involved both species. Twelve drugs were identified in intoxication reports: albendazole (2), closantel (14), disophenol (1), ivermectin (1), levamisole (2), moxidectin (1), netobimin (1), nitroxinil (1), oxfendazole (2), parbendazole (2), tetramizole (1), and thiabendazole (1). The most prevalent symptoms of anthelmintic intoxication reported were showed involvement of the nervous, locomotor, and renal systems, as well as teratogenic influences. Data from this review underscore the need of the care required in the control of parasitic infections through the safe use of antiparasitic drugs to avoid cases of intoxication.

Un-fractionated heparin counteracts the systemic inflammatory responses and multiple organ damages caused by endotoxaemia in sheep.

BACKGROUND: Endotoxaemia is believed to be a major cause of mortality and there are several therapeutic regimens for the treatment of this situation. OBJECTIVES: The present experimental study was conducted to evaluate acute phase response, cardiovascular and hepatorenal damages following the treatment of Ovine experimental endotoxaemia model employing unfractionated heparin (UFH). MATERIALS AND METHODS: Twenty clinically healthy 1-year-old fat-tailed ewes were randomly divided into four equal groups, comprising UFH 200, UFH 400, Ctrl+ and Ctrl-. Lipopolysaccharide (LPS) from Escherichia coli serotype O55:B5 at 0.4 µg/kg was administered intravenously to the ewes. UFH (at 200 and 400 IU/kg) was administrated to the UFH 200 and UFH 400 groups, respectively. All the ewes were evaluated clinically before and 1.5, 3, 4.5, 6 and 24 hours after LPS injection. Blood samplings were also performed at those hours. We measured serum concentrations of haptoglobin, interferon-gamma, total antioxidant status, malondialdehyde, cardiac lactate dehydrogenase, cardiac troponin-I, total bilirubin, alanine transaminase and creatinine. Serum concentrations of acute phase response, cardiovascular, hepatic and renal biomarkers and clinical parameters increased significantly following the induction of endotoxaemia in the groups receiving LPS. RESULTS: The significantly lowest concentrations of these parameters at hours 4.5 and 6 among the treatment groups belonged to the UFH 400 sheep. CONCLUSIONS: UFH could act as an anti-inflammatory mediator by decreasing inflammatory cytokines and acute phase proteins, modulating oxidative stress biomarkers and reducing multiple organ dysfunction following endotoxaemia in a dose-dependent manner. Furthermore, the anti-inflammatory effects of UFH at 400 IU/kg were significantly higher than another dose. This research examined the effect of two doses of UFH and higher doses may have more anti-inflammatory effects that require further studies.

Animal safety of a tall fescue endophyte (Epichloë sp.) in a perennial ryegrass (Lolium perenne) host.

AIMS: To assess animal health and production in sheep grazing perennial ryegrass (Lolium perenne) infected with a tall fescue endophyte (Epichloë sp.). METHODS: Three replicates of pure perennial ryegrass pastures infected with AR501 tall fescue endophyte (AR501 HE), AR1, AR37 or standard endophyte (STD) (all >85% infection) and a low endophyte control (AR501 LE) were grazed by 10 lambs for 7 weeks during late summer/early autumn, 2017. AR501 HE and AR501 LE were in the same tetraploid cultivar and the remaining treatments were in the same diploid cultivar. Lambs were weighed on Days 0, 19, 37 and 48 and assessed for ryegrass staggers on a 0-4 tremor scale nine times from Day 13. On Days 14 and 20, rectal temperatures and respiration rates were measured in lambs grazing AR501 HE, AR501 LE and STD under heat load. Pasture samples from each treatment were taken regularly (8 times) for analysis of known endophyte secondary metabolites. RESULTS: Peak mean ryegrass staggers scores for lambs grazing STD and AR37 treatments were 3.9 and 2.7, respectively, indicating environmental conditions were conducive to toxicity. Lambs grazing AR501 HE showed no ryegrass staggers at any date. The liveweight of STD lambs was up to 6.6 kg less than some or all other treatments on Days 19, 34 and 48, but there was no evidence of a difference between the liveweight of AR501 HE lambs and AR501 LE, AR37 or AR1 lambs on any date. Rectal temperatures and respiration rates of STD lambs were higher than AR501 HE lambs by 0.2°C and 26 breaths/minute, respectively. Apart from lower rectal temperature of AR501 HE lambs on Day 14, there was no evidence of differences between the AR501 HE and AR501 LE lambs. N-Formylloline was the only loline present in AR501 HE herbage (350-860 mg/kg). Peramine in AR501 HE herbage (42-77 mg/kg) was greater than that in STD and AR1 herbage on five and seven of the eight sampling dates, respectively. CONCLUSION: Lambs grazing AR501 HE showed no ryegrass staggers, exacerbated heat stress or suppressed liveweight gain compared with lambs grazing AR501 LE in a season when endophyte-induced toxicity was evident in STD and AR37 pastures. This suggests AR501 tall fescue endophyte does not produce toxic concentrations of secondary metabolites. CLINICAL RELEVANCE: This study suggests that there are no secondary metabolites produced by the tall fescue AR501 endophyte-perennial ryegrass association which affect animal health or production.

A comprehensive review on endemic and experimental fluorosis in sheep: Its diverse effects and prevention.

Fluoride is a natural element widely distributed in the environment and plays an important role in the growth of humans and animals. However, in many species, high concentrations of fluoride induce several problems, such as dental, skeletal, and non-skeletal fluorosis. Sheep living in endemic areas are sensitive to the chronic toxicity of fluoride, and they have been found to suffer not only from teeth and bone problems but also from other organs. Studies indicating the chronic harmful effects of fluoride on teeth, bones, blood biochemical parameters, kidney, liver, heart, reproductive system and growth in sheep have been clearly summarized in this review. Besides, this work also includes updated progress in terms of prevention or reduction of fluoride toxicity in this species.

Detection of aluminium hydroxide-induced granulomas in sheep by computed tomography: A feasible approach for small ruminant lentiviruses diagnosis and research.

Aluminium (Al) hydroxide use as adjuvant induces local formation of long-lasting subcutaneous granulomas in sheep. Macrophages within these granulomas have been identified as a new small ruminant lentivirus (SRLV) replication site in naturally infected animals. Diagnosis of Al hydroxide-induced granulomas in sheep is mostly based on postmortem observations but little information is available on in vivo detection. Computed tomography (CT) is used for studying these reactions in other animal species. To determine if CT could be a tool for in vivo diagnosis and research of subcutaneous Al hydroxide-induced granulomas in sheep. A retrospective survey on thoracic CT scans was performed on 46 adult sheep. Analysis included absence or presence, number and location of subcutaneous nodules. Thoracic CT scans and pathological studies were prescribed to two further sheep. Single or multiple subcutaneous nodules were detected in 26 (56.52%) sheep. One or two nodules per animal were most often observed (36.95%). Size ranged between 1.5 and 4.5 cm. Pre-contrast two-dimensional (2D) CT images showed focal or multifocal increases in subcutaneous tissue thickness. Post-contrast 2D CT images revealed hypointense areas in the centre. Histopathology indicated the presence of granulomas composed by a large number of activated macrophages, surrounding a central core of necrosis. Large intracytoplasmic Al-positive aggregates were demonstrated by lumogallion staining. CT is a useful tool to detect subcutaneous Al hydroxide-induced granulomas in vivo in sheep. CT provides a diagnostic and research tool that can be very useful in future works in Al hydroxide-induced pathology, SRLV infection, or both.

Hepatogenous photosensitization in ruminants and horses caused by the ingestion of Chamaecrista serpens in Brazil.

This study aimed to describe the first reports of outbreaks of hepatogenous photosensitization in cattle, sheep, and horses caused by spontaneous ingestion of Chamaecrista serpens, as well as to reproduce poisoning in sheep experimentally. Eleven photodermatitis outbreaks of unknown cause occurred in cattle, sheep and horses on nine farms in the semiarid region of Bahia, northeastern Brazil, between July 2017 and July 2020. Cutaneous lesions of photosensitization initiated until one week after the animals were introduced in paddocks invaded by the plant at the beginning of the rainy season. The photosensitive skin lesions were progressive and consisted of hyperemia, edema, ulcerative-crusted lesions with necrosis, especially in non-pigmented skin areas. The lesions in young animals were more severe. The animals avoided the sun and exhibited hyporexia, weight loss, restlessness, irritability, and severe itching. An experimental study was made using seven sheep, and resulted in photodermatitis, similar to that observed in the natural poisoning, seven days after the beginning of plant ingestion. Two sheep were reserved for the control group. Serum biochemistry changes indicated liver injury caused by the plant. Skin biopsies and liver biopsy guided by ultrasound were performed. The one sheep that had more pronounced skin lesions was euthanized and necropsied. At the necropsy, the liver was enlarged, diffusely pale, and firm, with an evident lobular pattern and an empty gallbladder. Histopathology revealed similar skin and liver lesions in samples from biopsies and the necropsy. There was a marked disorganization of the cords of hepatocytes associated with degenerative necrotic changes on the liver. The cutaneous injuries included orthokeratotic hyperkeratosis, hypergranulosis, acanthosis, and extensive areas of epidermic necrosis and ulceration. Three sheep were protected from sunlight and the lesions regressed within 45 days after the plant's consumption ceased. In conclusion, C. serpens causes hepatogenous photosensitization in ruminants and horses, and should be included in the list of differential diagnoses in cases of photosensitive dermatitis.

Chronic facial eczema in sheep: description of gross and histological changes in the liver and association with serum gamma-glutamyltransferase activity at the time of sporidesmin intoxication.

AIMS: To determine the gross and histological changes developing in the liver of sheep 8 months after a single period of exposure to sporidesmin and to examine associations between the severity of gross and histological changes to the liver and the activity of gamma-glutamyltransferase (GGT) measured in serum in the sheep at the time of intoxication. METHODS: A group of 50 Romney ewes grazing a mixed ryegrass/white clover pasture were accidentally exposed to sporidesmin for up to 5 weeks. Seventeen sheep showed photosensitisation and four were subject to euthanasia. The remaining sheep were moved to safer pasture and a blood sample collected and analysed for serum GGT activity. The sheep were slaughtered 8 months later. Livers were classified into grossly normal, moderately affected, or severely affected and histology performed to assess portal fibrosis, biliary hyperplasia, portal inflammation, and hepatocellular necrosis. RESULTS: Serum GGT activity ranged from 59 to 1571 IU/L (reference range 32-70 IU/L). Thirteen of the 46 sheep developed clinical signs of facial eczema. However, at slaughter all except four sheep had grossly detectable changes to the shape of the liver including atrophy of the left lobe and the lateral part of the right lobe. Hypertrophy was typically limited to the medial part of the right lobe. In severely affected sheep the liver hypertrophy formed a nodular bulging mass. Changes in the liver shape were classified as severe in 25 and moderate in 17 sheep. Severely affected livers contained significantly more fibrosis than moderately affected livers (p = 0.001, Cliff's delta (d) = 0.68). While there was significantly greater fibrosis and biliary hyperplasia in the left than right lobes, histological changes were present throughout all samples taken of affected livers. Serum GGT activity taken during acute intoxication were correlated to subsequent fibrosis and biliary hyperplasia. CONCLUSIONS: Hepatic fibrosis develops in sheep after a single episode of sporidesmin intoxication, even in sheep with only mildly elevated GGT activity at the time of intoxication. Furthermore, the severity of the subsequent hepatic fibrosis was predicted by the degree of elevation of serum GGT activity during intoxication. CLINICAL RELEVANCE: More research is required to determine how the presence and severity of hepatic fibrosis affect animal production. However, if hepatic fibrosis does decrease production, the consistent development of fibrosis after sporidesmin ingestion reinforces the importance of avoiding exposure of livestock to sporidesmin. ABBREVIATIONS: GGT: Gamma-glutamyltransferase; d: Cliff's delta.

Replication of Small Ruminant Lentiviruses in Aluminum Hydroxide-Induced Granulomas in Sheep: a Potential New Factor for Viral Dissemination.

Aluminum (Al)-based salts are widely used adjuvants in ruminants and other species to strengthen the immune response elicited against vaccine antigen(s). However, they can lead to the formation of long-lasting granulomas composed of abundant activated macrophages. Small ruminant lentiviruses (SRLV) are widely distributed macrophage-tropic retroviruses that cause persistent infections in sheep and goats. Infected monocytes/macrophages and dendritic cells establish an inflammatory microenvironment that eventually leads to clinical manifestations. The aim of this work was to study the effect of Al-induced granulomas in the replication and pathogenesis of SRLV. Eleven adult, naturally SRLV-infected sheep showing clinical arthritis were distributed in vaccine (n = 6), adjuvant-only (n = 3), and control (n = 2) groups and inoculated with commercial Al-based vaccines, Al hydroxide adjuvant alone, or phosphate-buffered saline, respectively. In vitro studies demonstrated viral replication in Al-induced granulomas in 5 out of 10 sheep. Immunohistochemistry (IHC) evinced granular, intracytoplasmic SRLV presence in macrophages within granulomas. Viral sequences obtained from granulomas, blood monocytes, and other tissues were highly similar in most animals, suggesting virus circulation among body compartments. However, notable differences between isolated strains in granulomas and other tissues in specific animals were also noted. Interestingly, the B2 subtype was the most commonly found SRLV genotype, reaching a wider body distribution than previously described. Recombination events between genotypes B2 and A3 along the gag region were identified in two sheep. Our results indicate that Al-hydroxide-derived granulomas may represent an ideal compartment for SRLV replication, perhaps altering natural SRLV infection by providing a new, suitable target tissue.IMPORTANCE Granulomas are inflammation-derived structures elicited by foreign bodies or certain infections. Aluminum adjuvants included in vaccines induce granulomas in many species. In sheep, these are persistent and consist of activated macrophages. Small ruminant lentiviruses (SRLV), which are macrophage-tropic lentiviruses, cause a chronic wasting disease affecting animal welfare and production. Here, we studied the occurrence of SRLV in postvaccination granulomas retrieved from naturally infected ewes after vaccination or inoculation with aluminum only. SRLV infection was confirmed in granulomas by identification of viral proteins, genomic fragments, and enzymatic activity. The infecting SRLV strain, previously found exclusively in carpal joints, reached the central nervous system, suggesting that occurrence of SRLV in postvaccination granulomas may broaden tissue tropism. SRLV recombination was detected in inoculated animals, a rare event in sheep lentiviruses. Potentially, virus-host interactions within granulomas may modify viral pathogenesis and lead to more widespread infection.

Effects of Nano-Copper Poisoning on Immune and Antioxidant Function in the Wumeng Semi-Fine Wool Sheep.

The Wumeng semi-fine wool sheep is vital to the production system of the Wumeng mountainous area in Southwest China. To study the effect of nano-copper poisoning in the Wumeng semi-fine wool sheep, nano-copper poisoning model was established in sheep. We determined blood physiological and biochemical parameters, immune indexes, and antioxidant indicators. The results showed that Hb, RBC, and PCV levels in blood from the nano-copper group were markedly lower (P < 0.01) than those in the control group. Serum LDH, AST, ALT, CPK, and Cp from the nano-copper group were significantly higher (P < 0.01) than those in control animals. Serum SOD, GSH-Px, CAT, and T-AOC from the nano-copper group were significantly lower (P < 0.01) than those in control sheep, and MDA content in serum from the nano-copper group were markedly higher (P < 0.01) than those in control sheep. The levels of IL-2, IL-6, IL-1ß, IgA, IgM, and IgG from the nano-copper group were significantly lower (P < 0.01) than those in the control group. It was concluded that nano-copper poisoning could not only affect the immune function of Wumeng semi-fine wool sheep but also reduce the antioxidant capacity.

Developmental Programming: Contribution of Epigenetic Enzymes to Antral Follicular Defects in the Sheep Model of PCOS.

Prenatal testosterone (T)-treated sheep, similar to women with polycystic ovary syndrome (PCOS), manifest oligo-/anovulation, hyperandrogenism, and polyfollicular ovary. The polyfollicular ovarian morphology, a result of persistence of antral follicles, arises, in part, by transcriptional changes in key mediators of follicular development that, in turn, are driven by epigenetic mechanisms. We hypothesized that prenatal T excess induces, in a cell-specific manner, transcriptional changes in key mediators of follicular development associated with relevant changes in epigenetic machinery. Expression levels of key mediators of follicular development, DNA methyltransferases (DNMTs), and histone de-/methylases and de-/acetylases were determined in laser-capture microdissection-isolated antral follicular granulosa and theca and ovarian stromal cells from 21 months of age control and prenatal T-treated sheep (100 mg IM twice weekly from gestational day 30 to 90; term: 147 days). Changes in histone methylation were determined by immunofluorescence. Prenatal T treatment induced the following: (i) cell-specific changes in gene expression of key mediators of follicular development and steroidogenesis; (ii) granulosa, theca, and stromal cell-specific changes in DNMTs and histone de-/methylases and deacetylases, and (iii) increases in histone 3 trimethylation at lysine 9 in granulosa and histone 3 dimethylation at lysine 4 in theca cells. The pattern of histone methylation was consistent with the expression profile of histone de-/methylases in the respective cells. These findings suggest that changes in expression of key genes involved in the development of the polyfollicular phenotype in prenatal T-treated sheep are mediated, at least in part, by cell-specific changes in epigenetic-modifying enzymes.

Treatment with potassium bromide mitigates ataxia and reduces tremor in lambs with perennial ryegrass toxicosis.

Aims: To assess the use of potassium bromide (KBr) as a therapeutic intervention for perennial ryegrass toxicosis (PRGT) in lambs fed ryegrass seed containing lolitrem B. Methods: Male lambs aged 10-12 months (n = 43) were assigned to receive ryegrass seed containing lolitrem B, at a dose of 0.16 mg/kg/day (Groups 2, 3 and 4), or lucerne chaff and molasses (Groups 1 and 5). Lambs in Groups 2 and 3 were observed for clinical signs and gait changes until defined signs of PGRT were observed, when they were transferred, with lambs in Group 1, to the Testing phase of the trial. Lambs in Group 3 were then treated with a single oral dose of 300 mg/kg bromide. Lambs in Groups 4 and 5 received KBr daily from the start of the trial (540 mg/kg bromide over 3 days then 20 mg/kg daily) and were transferred to the Testing phase after 18 days. Clinical examination and gait assessment, and surface electromyography of the triceps muscle, measuring root-mean-square (RMS) voltages, were carried out on Days 0, 1 and 2 of the Testing phase followed by necropsy, histopathology, measurement of concentrations of bromide in serum and CSF and faecal cortisol metabolites (FCM). Results: In Group 3 lambs, mean composite gait scores decreased between Testing phase Day 0 and Days 1 and 2 (p < 0.001), but increased in lambs in Group 2 between Day 0 and Day 2 (p = 0.015). Scores for lambs in Group 3 on Day 2 were lower than for lambs in Group 2 (p < 0.001). Mean RMS voltages on Day 2 were higher in lambs in Group 2 than Group 3 (p = 0.045). Mean concentrations of bromide in serum were >800 µg/mL in lambs in Groups 3 and 4 on Day 2. Concentrations of FCM were higher in lambs from Group 2 than in Groups 1 or 5, but were similar in Groups 2, 3 and 4. Histopathological findings in the cerebellum of lambs from Groups 2, 3 and 4 were similar, showing pyknosis of neurons within the granular layer of the cerebellum and Purkinje neuron proximal axonal spheroid formation. Conclusions and clinical relevance: A single oral dose of 300 mg/kg bromide in lambs with neurological signs of PRGT resulted in reduced composite gait scores and reduced RMS voltages, indicating a significant improvement in clinical signs of ataxia, movement disorder and muscle tremor associated with the neurotoxic effects of lolitrem B.