Vengai Mavangira

The nexus between nutrient metabolism, oxidative stress and inflammation in transition cows

Increased incidence of several economically important diseases (i.e. mastitis, metritis, displaced abomasum and ketosis) causes significant animal welfare problems and production losses in transition dairy cattle and decreases the availability of safe and nutritious food for a growing global population. A major underlying factor responsible for the development of transition cow disorders is metabolic stress, which occurs when cows fail to adapt physiologically to an increase in nutrient requirements needed for parturition and the onset of copious milk synthesis and secretion. Metabolic stress can be characterised as resulting from the combined effects of altered nutrient metabolism, dysfunctional inflammatory responses, and oxidative stress. Together, these factors form destructive feedback loops that exacerbate metabolic stress and cause health disorders in transition cows. A better understanding of how nutrition and immunology interact to influence metabolic stress will facilitate the development of control programs to improve transition cow health. The ability to detect signs of metabolic stress early enough in the dry period to implement needed management adjustments before calving will be the key to successful monitoring and intervention programs.

Effect of ammonium chloride supplementation on urine pH and urinary fractional excretion of electrolytes in goats

OBJECTIVEnTo determine whether dietary supplementation with ammonium chloride would affect urine pH or urinary fractional excretion (FE) of electrolytes in goats fed grass hay.nnnDESIGNnClinical trial.nnnANIMALSn15 yearling castrated male goats.nnnPROCEDURESnIn the dose response study, 3 yearling goats fed orchard grass hay and water ad libitum were administered ammonium chloride at either 200, 400, or 500 mg/kg (91, 182, or 227 mg/lb), PO, every 24 hours. In the FE study, 8 goats fed orchard grass hay were randomly divided into either a treatment (n=4) or a control group (4). In the treatment group, ammonium chloride was administered at 450 mg/kg (2.25% of dry matter intake [DMI]), PO, every 24 hours for 8 days. The FE of electrolytes was compared between groups; FE measurements were also determined for 4 client-owned goats fed alfalfa hay.nnnRESULTSnAmmonium chloride administered at 450 mg/kg (2.25% of DMI) achieved and maintained urine pH<6.5 for 24 hours. Goats fed orchard grass hay with ammonium chloride supplementation had significantly higher FE of calcium and chloride than did goats fed orchard grass hay without supplemental ammonium chloride.nnnCONCLUSIONS AND CLINICAL RELEVANCEnDietary ammonium chloride supplementation at a dose of 450 mg/kg may be necessary to achieve a urine pH<6.5 in goats. Further studies of ammonium chloride supplementation and urolithiasis in goats fed low-calcium diets are indicated.

Polyunsaturated fatty acids influence differential biosynthesis of oxylipids and other lipid mediators during bovine coliform mastitis

Coliform mastitis is a severe and sometimes fatal disease characterized by an unregulated inflammatory response. The initiation, progression, and resolution of inflammatory responses are regulated, in part, by potent oxylipid metabolites derived from polyunsaturated fatty acids. The purpose of this study was to characterize the biosynthesis and diversity of oxylipid metabolites during acute bovine coliform mastitis. Eleven cows diagnosed with naturally occurring acute systemic coliform mastitis and 13 healthy control cows, matched for lactation number and days in milk, were selected for comparison of oxylipid and free fatty acid concentrations in both milk and plasma. Oxylipids and free fatty acids were quantified using liquid chromatography-tandem mass spectrometry. All polyunsaturated fatty acids quantified in milk were elevated during coliform mastitis with linoleic acid being the most abundant. Oxylipids synthesized through the lipoxygenase and cytochrome P450 pathways accounted for the majority of the oxylipid biosynthesis. This study demonstrated a complex and diverse oxylipid network, most pronounced at the level of the mammary gland. Substrate availability, biosynthetic pathways, and degree of metabolism influence the biosynthesis of oxylipids during bovine coliform mastitis. Further studies are required to identify targets for novel interventions that modulate oxylipid biosynthesis during coliform mastitis to optimize inflammation.

Malignant Melanoma of the Horn Base in a Pygora Goat

A case of malignant melanoma, originating at the base of the left horn, was diagnosed in a white 11-year-old Pygora doe. At necropsy, the goat had an ulcerated, black-pigmented, 2.5-cm mass at the base of the left horn. Firm masses diffusely black on the cut surface were present at the left horn base, subcutaneously over the frontal bones, and infiltrating into the frontal sinuses, the submandibular lymph node, and left parotid salivary gland. The left maxillary premolars and molars were loosened from the periodontia. Multiple black foci of metastasis were observed in the liver. Histologically, the masses consisted predominantly of moderately pleomorphic, polyhedral to spindle cells that contained variable amounts of dark brown intracytoplasmic pigment granules. The tumor cells were positive for Melan A by immunohistochemical staining.

15-F2t-Isoprostane Concentrations and Oxidant Status in Lactating Dairy Cattle with Acute Coliform Mastitis

Background Severe mammary tissue damage during acute coliform mastitis in cattle is partially caused by oxidative stress. Although considered a gold standard biomarker in some human conditions, the utility of 15‐F2t‐Isoprostanes (15‐F2t‐Isop) in detecting oxidative stress in dairy cattle has not been validated. Hypothesis Concentrations of 15‐F2t‐Isop in plasma, urine, and milk correlate with changes in oxidant status during severe coliform mastitis in cattle. Animals Eleven lactating Holstein‐Friesian dairy cows in their 3rd–6th lactation. Methods A case–control study using cows with acute coliform mastitis and matched healthy controls were enrolled into this study. Measures of inflammation, oxidant status, and redox status in plasma and milk samples were quantified using commercial assays. Plasma, urine, and milk 15‐F2t‐Isop were quantified by liquid chromatography/tandem mass spectrometry (LC‐MS/MS) and ELISA assays. Data were analyzed by Wilcoxon rank sum tests (α = 0.05). Results Plasma 15‐F2t‐Isop quantified by LC‐MS/MS was positively correlated with systemic oxidant status (r = 0.83; P = .01). Urine 15‐F2t‐Isop quantified by LC‐MS/MS did not correlate with systemic oxidant status, but was negatively correlated with redox status variables (r = −0.83; P = .01). Milk 15‐F2t‐Isop quantified by LC‐MS/MS was negatively correlated (r = −0.86; P = .007) with local oxidant status. Total 15‐F2t‐Isop in milk quantified by a commercial ELISA (cbELISA) was positively correlated with oxidant status in milk (r = 0.98; P < .001). Conclusions and Clinical Importance Free plasma 15‐F2t‐Isop quantified by LC‐MS/MS and total milk 15‐F2t‐Isop quantified by cbELISA are accurate biomarkers of systemic and mammary gland oxidant status, respectively. Establishing reference intervals for free and total 15‐F2t‐Isops for evaluating oxidative stress in dairy cows should currently be based on the LC‐MS/MS method.

Periparturient lipolysis and oxylipid biosynthesis in bovine adipose tissues

The periparturient period of dairy cows is characterized by intense lipolysis in adipose tissues (AT), which induces the release of free fatty acids (FFA) into circulation. Among FFA, polyunsaturated fatty acids are susceptible to oxidation and can modulate inflammatory responses during lipolysis within AT. Linoleic and arachidonic acid oxidized products (oxylipids) such as hydroxy-octadecadienoic acids (HODE) and hydroxy-eicosatetraenoic acids (HETE), were recently identified as products of lipolysis that could modulate AT inflammation during lipolysis. However, the effect of lipolysis intensity during the transition from gestation to lactation on fatty acid substrate availability and subsequent AT oxylipid biosynthesis is currently unknown. We hypothesized that in periparturient dairy cows, alterations in AT and plasma fatty acids and oxylipid profiles coincide with changes in lipolysis intensity and stage of lactation. Blood and subcutaneous AT samples were collected from periparturient cows at -27±7 (G1) and -10±5 (G2) d prepartum and at 8±3 d postpartum (PP). Targeted lipidomic analysis was performed on plasma and AT using HPLC-MS/MS. We report that FFA concentrations increased as parturition approached and were highest at PP. Cows exhibiting high lipolysis rate at PP (FFA>1.0 mEq/L) had higher body condition scores at G1 compared to cows with low lipolysis rate (FFA<1.0 mEq/L). Concentrations of plasma linoleic and arachidonic acids were increased at PP. In AT, 13-HODE, and 5-, 11- and 15-HETE were increased at PP compared to G1 and G2. Concentrations of beta hydroxybutyrate were positively correlated with those of 13-HODE and 15-HETE in AT. Plasma concentrations of 5- and 20-HETE were increased at PP. These data demonstrate that prepartum adiposity predisposes cows to intense lipolysis post-partum and may exacerbate AT inflammation because of increased production of pro-inflammatory oxylipids including 5- and 15-HETE and 13-HODE. These results support a role for certain linoleic and arachidonic acid-derived oxylipids as positive and negative modulators of AT inflammation during periparturient lipolysis.

Differences in the Oxylipid Profiles of Bovine Milk and Plasma at Different Stages of Lactation

Mastitis is caused by a bacterial infection of the mammary gland, which reduces both milk quality and quantity produced for human consumption. The incidence and severity of bovine mastitis are greatest during the periparturient period that results from dysfunctional inflammatory responses and causes damage to milk synthesizing tissues. Oxylipids are potent fatty acid-derived mediators that control the onset and resolution of the inflammatory response. The purpose of this study was to investigate how oxylipid profiles change in bovine milk at different stages of the lactation cycle. Results showed significantly lower concentrations of both milk polyunsaturated fatty acid content and total oxylipid biosynthesis during early lactation when compared to mid- or late-lactation. The only oxylipid that was higher during early lactation was 20-hydroxyeicosatetraenoic acid (HETE), which is often associated with inflammatory-based diseases. Milk oxylipid profiles during the different stages of lactation differed from plasma profiles. As such, plasma fatty acid and oxylipid concentrations are not a proxy for local changes in the mammary gland during the lactation cycle.

Gangrenous mastitis caused by Bacillus species in six goats

CASE DESCRIPTIONn6 lactating dairy goats were examined because of acute mastitis.nnnCLINICAL FINDINGSnGoats were considered to have endotoxemia on the basis of physical examination and clinicopathologic findings. The affected udder halves had gangrenous discolored distal portions with sharp demarcations from grossly normal tissue proximally. Udder secretions from the affected sides were serosanguineous in all cases. A Bacillus sp was isolated in pure cultures in all cases. In 1 case, the Bacillus sp was identified as Bacillus cereus.nnnTREATMENT AND OUTCOMEnGoats were treated for mastitis and endotoxemia with polyionic IV fluid therapy, systemic and intramammary antimicrobial administration, anti-inflammatory drug administration, and other supportive treatment. All goats survived to discharge. All except 1 goat had follow-up information available. The affected udder halves sloughed in 1 to 2 months following discharge. In subsequent lactations after the mastitis episodes, milk production in 2 of 5 goats was above the mean, as determined on the basis of Dairy Herd Improvement records, and 3 of 5 goats were voluntarily withdrawn from lactation. All 5 goats had successful kiddings after the Bacillus mastitis episode.nnnCONCLUSIONS AND CLINICAL RELEVANCEnBacillus sp should be considered as a causative agent in goats with gangrenous mastitis, especially when the Bacillus sp is isolated in a pure culture. Antimicrobial sensitivity testing is recommended for selection of an appropriate antimicrobial for treatment. Prognosis for survival appears to be good, although milk production may be decreased.

Role of lipid mediators in the regulation of oxidative stress and inflammatory responses in dairy cattle

Periparturient dairy cows experience an increased incidence and severity of several inflammatory-based diseases such as mastitis and metritis. Factors associated with the physiological adaptation to the onset of lactation can impact the efficiency of the inflammatory response at a time when it is most needed to eliminate infectious pathogens that cause these economically important diseases. Oxidative stress, for example, occurs when there is an imbalance between the production of oxygen radicals during periods of high metabolic demand and the reduced capabilities of the hosts antioxidant defenses. The progressive development of oxidative stress in early lactation cows is thought to be a significant underlying factor leading to dysfunctional inflammatory responses. Reactive oxygen species (ROS) are also produced by leukocytes during inflammation resulting in positive feedback loops that can further escalate oxidative stress during the periparturient period. During oxidative stress, ROS can modify polyunsaturated fatty acids (PUFA) associated with cellular membranes, resulting in the biosynthesis of oxidized products called oxylipids. Depending on the PUFA substrate and oxidation pathway, oxylipids have the capacity of either enhancing or resolving inflammation. In mediating their effects, oxylipids can directly or indirectly target sites of ROS production and thus control the degree of oxidative stress. This review discusses the evidence supporting the roles of oxylipids in the regulation of oxidative stress and the subsequent development of uncontrolled inflammatory responses. Further, the utility of some of the oxylipids as oxidative stress markers that can be exploited in developing and monitoring therapies for inflammatory-based diseases in dairy cattle is discussed. Understanding of the link between some oxylipids and the development or resolution of oxidative stress could provide novel therapeutic targets to limit immunopathology, reduce antibiotic usage, and optimize the resolution of inflammatory-based diseases in periparturient dairy cows.

Relationships between demographic variables and lead toxicosis in cattle evaluated at North American veterinary teaching hospitals

OBJECTIVEnTo determine associations between age, sex, breed, and month and year of admission and the diagnosis of lead toxicosis in cattle.nnnDESIGNnRetrospective case-control study. Sample Population-Records of all cattle evaluated at North American veterinary teaching hospitals during the years 1963 to 2002, which were available through the Veterinary Medical Database.nnnPROCEDURESnLogistic regression was used to evaluate the associations between postulated risk factors and the occurrence of lead toxicosis in cattle and predict the occurrence of the diagnosis of lead toxicosis in cattle.nnnRESULTSn413 cases of lead intoxication and 202,363 control cattle were identified and met the inclusion criteria. Cattle < 4 years of age were at increased risk for the diagnosis of lead intoxication relative to cattle > or = 4 years of age. Cattle > or = 2 months and < 6 months of age had the greatest risk for lead intoxication (odds ratio, 12.3). Angus cattle were at greater risk for toxicosis (odds ratio, 1.95), compared with other breeds. The risk of lead toxicosis was greater before 1985 (odds ratio, 1.94) than the risk thereafter. The risk of lead toxicosis diagnosis was greatest in the months of May, June, July, and August.nnnCONCLUSIONS AND CLINICAL RELEVANCEnLead toxicosis in cattle was associated with age < 4 years and the Angus breed. A seasonal pattern existed with peak occurrence in the late spring and summer. The occurrence of lead toxicosis has declined over time.