Bovine Leukemia Virus Infection in Dairy Cattle: Effect on Serological Response to Immunization against J5 Escherichia coli Bacterin

Thirteen bovine leukemia virus- (BLV-) negative and 22 BLV-positive Holstein cows were immunized with J5 Escherichia coli bacterin at dry off, three weeks before calving, during the second week after calving, and three weeks after the third immunization. Serum was collected before the initial immunization, immediately before the third and fourth immunizations, and 21 days after the fourth immunization. Anti-J5 E. coli IgM, IgG1, and IgG2 titers were determined by ELISA. Anti-J5 E. coli IgM titers did not differ significantly (P = .98) between groups. Increases in anti-J5 E. coli IgG1 titers were higher in the BLV-negative cows (P = .057). Geometric mean anti-J5 E. coli IgG2 titers increased fourfold in the BLV-negative cows, which was significantly higher (P = .007) than the twofold increase in the BLV-positive cows. Cattle infected with BLV may have impaired serologic responses following immunization with J5 bacterin, and response may differ according to antibody isotype

Cabergoline treatment at dry-off accelerated mammary involution as indicated by mammary secretion composition changes in dairy cows

In ruminants, the early phase of drying-off is a period of mammary gland involution that is marked by the cessation of prolactin (PRL) release. The speed at which the bovine mammary gland involutes following the abrupt cessation of lactation is directly related to the risk of new intramammary infections.ObjectivesOur aim was to assess the effect of PRL inhibition by cabergoline on the speed of the mammary gland involution, through analysis of the changes of mammary secretion composition.Materials and methodsFourteen Holstein dairy cows were injected with a single i.m. administration of 5.6 mg cabergoline (n=7) (Velactis ®, Ceva Sante Animale) or placebo (n=7) at the first day of dryingoff (D0). Mammary secretion samples were collected using a teat-cannula once during lactation (D-6) and at D1, D2, D3, D4, D8 and D14 after the drying-off. The mammary secretion samples were used for milk fat, lactose, true protein, alpha-lactalbumin and SCC analysis. Mammary biopsy samples were collected one week before drying-off (D-6), at D1 and at D8 and used for RNA extraction and RT-PCR analyses.ResultsAs expected, SCC progressively increased whereas lactose content decreased in mammary secretions after drying-off (P < 0.001). The increase in SCC was 2.4 fold higher in cabergoline treated cows than in control cows (P < 0.01). The decrease of lactose content in mammary secretions progressively decreased during involution and was associated with paralleled change in GLUT-1 mRNA level coding the main glucose transporter in the udder. These decreases were faster in cabergoline treated cows compared to controls with lower lactose content in cabergoline treated cows already by D1 than in controls (P < 0.05) and significant decrease in GLUT-1 mRNA levels at D1 and D8 respectively for cabergoline and control treatments compared to D-6 (P ≤ 0.05). Cabergoline treatment tended to increase fat content at D3 after drying-off (P < 0.10). No significant effects of cabergoline treatment were observed both in true protein and in alpha-lactalbumin contents in mammary secretions or in alphalactalbumin and kappa-casein mRNA levels in mammary tissues.ConclusionsThe changes in lactose, SCC and fat in mammary secretions and GLUT-1 mRNA level in the udder, indicate that cabergoline treatment was efficient to hasten the mammary gland involution without affecting milk protein synthesis in the mammary tissue. Cabergoline could facilitate dairy management at the time of dry-off

Anti-inflammatory salicylate treatment alters the metabolic adaptations to lactation in dairy cattle

Citation:Farney, J. K., Mamedova, L. K., Coetzee, J. F., KuKanich, B., Sordillo, L. M., Stoakes, S. K., … Bradford, B. J. (2013). Anti-inflammatory salicylate treatment alters the metabolic adaptations to lactation in dairy cattle. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 305(2), R110–R117. https://doi.org/10.1152/ajpregu.00152.2013Adapting to the lactating state requires metabolic adjustments in multiple tissues, especially in the dairy cow, which must meet glucose demands that can exceed 5 kg/day in the face of negligible gastrointestinal glucose absorption. These challenges are met through the process of homeorhesis, the alteration of metabolic setpoints to adapt to a shift in physiological state. To investigate the role of inflammation-associated pathways in these homeorhetic adaptations, we treated cows with the nonsteroidal anti-inflammatory drug sodium salicylate (SS) for the first 7 days of lactation. Administration of SS decreased liver TNF-α mRNA and marginally decreased plasma TNF-α concentration, but plasma eicosanoids and liver NF-κB activity were unaltered during treatment. Despite the mild impact on these inflammatory markers, SS clearly altered metabolic function. Plasma glucose concentration was decreased by SS, but this was not explained by a shift in hepatic gluconeogenic gene expression or by altered milk lactose secretion. Insulin concentrations decreased in SS-treated cows on day 7 compared with controls, which was consistent with the decline in plasma glucose concentration. The revised quantitative insulin sensitivity check index (RQUICKI) was then used to assess whether altered insulin sensitivity may have influenced glucose utilization rate with SS. The RQUICKI estimate of insulin sensitivity was significantly elevated by SS on day 7, coincident with the decline in plasma glucose concentration. Salicylate prevented postpartum insulin resistance, likely causing excessive glucose utilization in peripheral tissues and hypoglycemia. These results represent the first evidence that inflammation-associated pathways are involved in homeorhetic adaptations to lactation.the transition from late pregnancy to lactation is a time of great physiological stress, especially for the dairy cow. The decline in feed intake that accompanies parturition, coupled with the rapid increase in energy requirements during lactogenesis, requires a dramatic shift in nutrient fluxes to release stored nutrients and direct them to the mammary gland. This programmed shift in metabolic setpoints is an archetypal example of homeorhesis, defined as the “coordinated changes in metabolism of body tissues necessary to support a physiological state” (4).Mechanisms underlying homeorhetic adaptions to lactation have been described to some extent. The somatotropic axis is decoupled during this time, resulting in dramatic elevations of plasma growth hormone concentrations without the expected rise in insulin-like growth factor 1 secretion (11, 51). Likewise, insulin sensitivity declines substantially from late gestation (5, 48). These endocrine shifts are critical for promoting the mobilization of stored nutrients and sparing glucose for use by the mammary gland. This conservation of glucose is particularly important in ruminants. The microbes that inhabit the rumen ferment most dietary carbohydrate to volatile fatty acids, leaving very little glucose to be absorbed in the small intestine. As a result, lactating cows absorb almost no glucose from the gastrointestinal tract and must synthesize as much as 5 kg of glucose in the liver daily (2).The homeorhetic adaptations that allow cows to increase milk production to 40 kg/day within days after parturition can stress the metabolic system. Rapid lipolysis can increase plasma nonesterified fatty acid (NEFA) concentrations by as much as 10-fold within a few days after parturition (21), and both hypoglycemia and hypocalcemia are common, as nutrients are drawn into the mammary gland. Ketosis and fatty liver (FL) are common metabolic diseases that result during this time; in fact, nearly 90% of all metabolic diseases in dairy cattle occur during the first 4 wk of the 305-day lactation (24).Despite their reliance on mobilized lipid as an energy source, dairy cattle entering lactation with greater adipose mass are at greater risk of developing metabolic diseases (34). It has become clear in the past decade that animals with excessive adiposity exhibit a low-grade inflammation (23), suggesting that perhaps inflammation underlies metabolic disturbances in obese dairy cows. In support of this hypothesis, cows with moderate or severe FL have increased levels of the inflammatory cytokine TNF-α (41). Inflammatory cytokines cause myriad metabolic changes in dairy cattle, including anorexia, lipomobilization, impaired insulin sensitivity, and reduced milk yield (7, 26, 27), all of which are associated with FL and ketosis. Furthermore, daily injection of TNF-α for 7 days increased liver triglyceride content independent of effects on feed intake, and this effect was accompanied by changes in hepatic gene expression consistent with both inflammation and a shift from fatty acid oxidation to triglyceride synthesis (8).These recent findings suggest that exogenous inflammatory agents are sufficient to induce metabolic dysfunction. Whether inflammation is a necessary causative factor in the natural progression of bovine FL and ketosis, however, remains unclear. To address this broad question, we used the nonsteroidal anti-inflammatory drug (NSAID) sodium salicylate (SS). Sodium salicylate is a weak inhibitor of cyclooxygenase (COX)-1 and COX-2 (31), and its probable mode of action is that it inhibits phosphorylation of the NF-κB inhibitor IκB-α (53). Phosphorylation of IκB results in its degradation, allowing NF-κB to be released for translocation into the nucleus and subsequent activation of an inflammatory transcription program (3). The specific hypothesis for this study was that SS would slow liver triglyceride accumulation, promote gluconeogenesis, and limit metabolic disease in dairy cows entering lactation. In contrast, our findings suggest that inflammatory signals may contribute to homeorhetic adaptations to lactation, especially regulation of glucose metabolism and modulation of lipolysis and ketogenesis as animals return to positive energy balance

Allergen sensitization is associated with increased dna methylation in older men

Background: Variation in epigenetic modifications, arising from either environmental exposures or internal physiological changes, can influence gene expression and may ultimately contribute to complex diseases such as asthma and allergies. We examined the association of asthma and allergic phenotypes with DNA methylation levels of retrotransposon-derived elements. Methods: We used data from 704 men (mean age 73 years) in the longitudinal Normative Aging Study to assess the relationship between asthma, allergic phenotypes and DNA methylation levels of the retrotransposon-derived elements Alu and long interspersed nuclear element (LINE)-1. Retrotransposons represent a large fraction of the genome (>30%) and are heavily methylated to prevent expression. Percent methylation of Alu and LINE-1 elements in peripheral white blood cells was quantified using PCR pyrosequencing. Data on sensitization to common allergens from skin prick testing, asthma and methacholine responsiveness were gathered approximately 8 years prior to DNA methylation analysis. Results: Prior allergen sensitization was associated with increased methylation of Alu (\u3b2 = 0.32 for sensitized vs. nonsensitized patients; p = 0.003) in models adjusted for pack-years of smoking, body mass index, current smoking, air pollutants, percentage of eosinophils, white blood cell count and age. Of the men interviewed, 5% of subjects reported a diagnosis of asthma. Neither Alu nor LINE-1 methylation was associated with asthma. Conclusions: These data suggest that increased DNA methylation of repetitive elements may be associated with allergen sensitization but does not appear to be associated with asthma. Future work is needed to identify potential underlying mechanisms for these relationships

Expression of SMARCD1 interacts with age in association with asthma control on inhaled corticosteroid therapy.

BackgroundGlobal gene expression levels are known to be highly dependent upon gross demographic features including age, yet identification of age-related genomic indicators has yet to be comprehensively undertaken in a disease and treatment-specific context.MethodsWe used gene expression data from CD4+ lymphocytes in the Asthma BioRepository for Integrative Genomic Exploration (Asthma BRIDGE), an open-access collection of subjects participating in genetic studies of asthma with available gene expression data. Replication population participants were Puerto Rico islanders recruited as part of the ongoing Genes environments &amp; Admixture in Latino Americans (GALA II), who provided nasal brushings for transcript sequencing. The main outcome measure was chronic asthma control as derived by questionnaires. Genomic associations were performed using regression of chronic asthma control score on gene expression with age in years as a covariate, including a multiplicative interaction term for gene expression times age.ResultsThe SMARCD1 gene (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1) interacted with age to influence chronic asthma control on inhaled corticosteroids, with a doubling of expression leading to an increase of 1.3 units of chronic asthma control per year (95% CI [0.86, 1.74], p = 6 × 10- 9), suggesting worsening asthma control with increasing age. This result replicated in GALA II (p = 3.8 × 10- 8). Cellular assays confirmed the role of SMARCD1 in glucocorticoid response in airway epithelial cells.ConclusionFocusing on age-dependent factors may help identify novel indicators of asthma medication response. Age appears to modulate the effect of SMARCD1 on asthma control with inhaled corticosteroids

Plasma metabolite profiles in children with current asthma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146270/1/cea13183.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146270/2/cea13183_am.pd

Resurgence of vaccine-preventable diseases in Venezuela as a regional public health threat in the Americas

Venezuela’s tumbling economy and authoritarian rule have precipitated an unprecedented humanitarian crisis. Hyperinflation rates now exceed 45,000%, and Venezuela’s health system is in free fall. The country is experiencing a massive exodus of biomedical scientists and qualified healthcare professionals. Reemergence of arthropod-borne and vaccine-preventable diseases has sparked serious epidemics that also affect neighboring countries. In this article, we discuss the ongoing epidemics of measles and diphtheria in Venezuela and their disproportionate impact on indigenous populations. We also discuss the potential for reemergence of poliomyelitis and conclude that action to halt the spread of vaccine-preventable diseases within Venezuela is a matter of urgency for the country and the region. We further provide specific recommendations for addressing this crisis. © 2019 Centers for Disease Control and Prevention (CDC). All rights reserved

SARS-CoV-2 in the Amazon region

A medida que la pandemia del Síndrome Respiratorio Agudo Severo Coronavirus 2 (SARS-CoV-2) continúa expandiéndose, los recursos de atención médica a nivel mundial se han reducido. Ahora, la enfermedad es extendiéndose rápidamente por América del Sur, con consecuencias mortales en áreas con ya sistemas de salud pública debilitados. La región amazónica es particularmente susceptible a la devastación generalizada de la enfermedad por coronavirus 2019 (COVID-19) debido a sus habitantes amerindios nativos inmunológicamente frágiles y vulnerabilidades epidemiológicas. Aquí, nosotros discutir la situación actual y el impacto potencial de COVID-19 en la región amazónica y cómo una mayor propagación de la ola epidémica podría resultar devastadora para muchas personas amerindias que viven en la selva amazónicaAs the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic continues to expand, healthcare resources globally have been spread thin. Now, the disease is rapidly spreading across South America, with deadly consequences in areas with already weakened public health systems. The Amazon region is particularly susceptible to the widespread devastation from Coronavirus disease 2019 (COVID-19) because of its immunologically fragile native Amerindian inhabitants and epidemiologic vulnerabilities. Herein, we discuss the current situation and potential impact of COVID-19 in the Amazon region and how further spread of the epidemic wave could prove devastating for many Amerindian people living in the Amazon rainfores

Personal endotoxin exposure in a panel study of school children with asthma

<p>Abstract</p> <p>Background</p> <p>Endotoxin exposure has been associated with asthma exacerbations and increased asthma prevalence. However, there is little data regarding personal exposure to endotoxin in children at risk, or the relation of personal endotoxin exposure to residential or ambient airborne endotoxin. The relation between personal endotoxin and personal air pollution exposures is also unknown.</p> <p>Methods</p> <p>We characterized personal endotoxin exposures in 45 school children with asthma ages 9-18 years using 376 repeated measurements from a PM_2.5active personal exposure monitor. We also assayed endotoxin in PM_2.5samples collected from ambient regional sites (N = 97 days) and from a subset of 12 indoor and outdoor subject home sites (N = 109 and 111 days, respectively) in Riverside and Whittier, California. Endotoxin was measured using the Limulus Amoebocyte Lysate kinetic chromogenic assay. At the same time, we measured personal, home and ambient exposure to PM_2.5mass, elemental carbon (EC), and organic carbon (OC). To assess exposure relations we used both rank correlations and mixed linear regression models, adjusted for personal temperature and relative humidity.</p> <p>Results</p> <p>We found small positive correlations of personal endotoxin with personal PM_2.5EC and OC, but not personal PM_2.5mass or stationary site air pollutant measurements. Outdoor home, indoor home and ambient endotoxin were moderately to strongly correlated with each other. However, in mixed models, personal endotoxin was not associated with indoor home or outdoor home endotoxin, but was associated with ambient endotoxin. Dog and cat ownership were significantly associated with increased personal but not indoor endotoxin.</p> <p>Conclusions</p> <p>Daily fixed site measurements of endotoxin in the home environment may not predict daily personal exposure, although a larger sample size may be needed to assess this. This conclusion is relevant to short-term exposures involved in the acute exacerbation of asthma.</p

Perinatal paracetamol exposure in mice does not affect the development of allergic airways disease in early life

Background Current data concerning maternal paracetamol intake during pregnancy, or intake during infancy and risk of wheezing or asthma in childhood is inconclusive based on epidemiological studies. We have investigated whether there is a causal link between maternal paracetamol intake during pregnancy and lactation and the development of house dust mite (HDM) induced allergic airways disease (AAD) in offspring using a neonatal mouse model. Methods Pregnant mice were administered paracetamol or saline by oral gavage from the day of mating throughout pregnancy and/or lactation. Subsequently, their pups were exposed to intranasal HDM or saline from day 3 of life for up to 6 weeks. Assessments of airway hyper-responsiveness, inflammation and remodelling were made at weaning (3 weeks) and 6 weeks of age. Results Maternal paracetamol exposure either during pregnancy and/or lactation did not affect development of AAD in offspring at weaning or at 6 weeks. There were no effects of maternal paracetamol at any time point on airway remodelling or IgE levels. Conclusions Maternal paracetamol did not enhance HDM induced AAD in offspring. Our mechanistic data do not support the hypothesis that prenatal paracetamol exposure increases the risk of childhood asthma