Effects of postpartum treatment with non-steroidal anti-inflammatory drugs on milk production and culling risk in dairy cattle

Dairy Research, 2014 is known as Dairy Day, 2014Inflammation during early lactation is common in dairy cattle, and a high degree of inflammation during this time has recently been associated with both lower productivity and greater risk of disease during that lactation. Early lactation treatments with two non-steroidal anti-inflammatory drugs were compared with a placebo treatment to evaluate effects on whole-lactation productivity and retention in the herd. Both meloxicam and sodium salicylate increased whole-lactation milk and milk protein yields by 6 to 9%, despite being administered for only 1 or 3 days in early lactation, respectively. In addition, meloxicam treatment tended to decrease the risk of cows leaving the herd during the lactation. These results indicate that postpartum inflammatory signals have long-lasting effects on lactation in dairy cattle

Physical properties of thermoelectric zinc antimonide using first-principles calculations

We report first principles calculations of the structural, electronic, elastic and vibrational properties of the semiconducting orthorhombic ZnSb compound. We study also the intrinsic point defects in order to eventually improve the thermoelectric properties of this already very promising thermoelectric material. Concerning the electronic properties, in addition to the band structure, we show that the Zn (Sb) crystallographically equivalent atoms are not exactly equivalent from the electronic point of view. Lattice dynamics, elastic and thermodynamic properties are found to be in good agreement with experiments and they confirm the non equivalency of the zinc and antimony atoms from the vibrational point of view. The calculated elastic properties show a relatively weak anisotropy and the hardest direction is the y direction. We observe the presence of low energy modes involving both Zn and Sb atoms at about 5-6 meV, similarly to what has been found in Zn4Sb3 and we suggest that the interactions of these modes with acoustic phonons could explain the relatively low thermal conductivity of ZnSb. Zinc vacancies are the most stable defects and this explains the intrinsic p-type conductivity of ZnSb.Comment: 33 pages, 8 figure

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

Power corrections to the π0γ\pi^0\gamma transition form factor and pion distribution amplitudes

Employing the standard hard-scattering approach and the running coupling method we calculate a class of power-suppressed corrections $\sim 1/Q^{2n},n=1,2,3,...$ to the electromagnetic $\pi^0\gamma$ transition form factor (FF) $Q^2F_{\pi\gamma}(Q^2)$ arising from the end-point $x \to 0,1$ integration regions. In the investigations we use a hard-scattering amplitude of the subprocess $\gamma+\gamma^{*} \to q +\bar{q}$, symmetrized under exchange $\mu_R^2 \leftrightarrow \bar{\mu}_R^2$ important for exclusive processes containing two external photons. In the computations the pion model distribution amplitudes (DA's) with one and two non-asymptotic terms are employed. The obtained predictions are compared with the CLEO data and constraints on the DA parameters $b_2(\mu_0^2)$ and $b_4(\mu_0^2)$ at the normalization point $\mu_0^2=1 GeV^2$ are extracted. Further restrictions on the pion DA's are deduced from the experimental data on the electromagnetic FF $F_{\pi}(Q^2)$.Comment: 23 pages, 6 figures; the version published in Phys. Rev. D69, 094010 (2004

Состояние микрофлоры кишечника у госпитализированных детей с острыми кишечными инфекциями

The purpose of this study was to study the state of the intestinal microflora in young children who received inpatient treatment for acute intestinal infections. A study of the microflora in 183 children aged 0 months. up to 3 years of life. At the same time, 43 (23.5%) children received breast milk, 53 (29.0%) were artificially fed and 87 (47.5%) mixed-fed children. All children were examined by bacteriological method. Conditionally pathogenic flora among hospitalized patients was detected in 114 (62.3%), Candida was mainly detected in 67.5% of cases, in 57 patients (50.0%) in association with other opportunistic microorganisms — Candida + St. aureus — in 32 (28.1%), Candida + P. vulgaris — in 9 (7.9%), Candida + + P. vulgaris + St. aureus — in 12 (10.5%), Candida + St. aureus + Ps. aeroginosa — in 4 (3.5%). As a result of studying the composition of the intestinal microflora in patients hospitalized with intestinal infection, a decrease in the number of E. coli and B. bifidum was found, 43.7% and 63.4%, respectively.Целью данного исследования явилось изучение состояния микрофлоры кишечника у детей раннего возраста, получавших стационарное лечение по поводу острых кишечных инфекций. Проведено исследование состояния микрофлоры у 183 детей в возрасте от 0 мес. до 3 лет жизни. При этом 43 (23,5%) ребенка получали грудное молоко, 53 (29,0%) находились на искусственном и 87 (47,5%) детей на смешанном вскармливании. Все дети обследовались бактериологическим методом. Среди госпитализированных детей условно-патогенная флора была выявлена у 114 (62,3%) больных, в основном определялась Candida — в 67,5% случаях , у 57 больных (50,0%) — в ассоциации с другими условно-патогенными микроорганизмами — Candida + St. aureus — у 32 (28,1%), Candida + P. vulgaris — у 9 (7,9%), Candida + P. vulgaris + St. aureus — у 12 (10,5%), Candida + St. aureus + Ps. aeroginosa — у 4 (3,5%). В результате изучения состава микрофлоры кишечника у госпитализированных с кишечной инфекцией больных установлено снижение количества E. coli и B. bifidum, соответственно в 43,7% и 63,4% случаев

P2Y2 and P2Y6 receptor activation elicits intracellular calcium responses in human adipose-derived mesenchymal stromal cells

Adipose tissue contains self-renewing multipotent cells termed mesenchymal stromal cells. In situ, these cells serve to expand adipose tissue by adipogenesis, but their multipotency has gained interest for use in tissue regeneration. Little is known regarding the repertoire of receptors expressed by adipose-derived mesenchymal stromal cells (AD-MSCs). The purpose of this study was to undertake a comprehensive analysis of purinergic receptor expression. Mesenchymal stromal cells were isolated from human subcutaneous adipose tissue and confirmed by flow cytometry. The expression profile of purinergic receptors was determined by quantitative real-time PCR and immunocytochemistry. The molecular basis for adenine and uracil nucleotide-evoked intracellular calcium responses was determined using Fura-2 measurements. All the known subtypes of P2X and P2Y receptors, excluding P2X2, P2X3 and P2Y12 receptors, were detected at the mRNA and protein level. ATP, ADP and UTP elicited concentration-dependent calcium responses in mesenchymal cells (N = 7–9 donors), with a potency ranking ADP (EC50 1.3 ± 1.0 μM) > ATP (EC50 2.2 ± 1.1 μM) = UTP (3.2 ± 2.8 μM). Cells were unresponsive to UDP (< 30 μM) and UDP-glucose (< 30 μM). ATP responses were attenuated by selective P2Y2 receptor antagonism (AR-C118925XX; IC50 1.1 ± 0.8 μM, 73.0 ± 8.5% max inhibition; N = 7 donors), and UTP responses were abolished. ADP responses were attenuated by the selective P2Y6 receptor antagonist, MRS2587 (IC50 437 ± 133nM, 81.0 ± 8.4% max inhibition; N = 6 donors). These data demonstrate that adenine and uracil nucleotides elicit intracellular calcium responses in human AD-MSCs with a predominant role for P2Y2 and P2Y6 receptor activation. This study furthers understanding about how human adipose-derived mesenchymal stromal cells can respond to external signalling cues

Quantum dots coordinated with conjugated organic ligands: new nanomaterials with novel photophysics

CdSe quantum dots functionalized with oligo-(phenylene vinylene) (OPV) ligands (CdSe-OPV nanostructures) represent a new class of composite nanomaterials with significantly modified photophysics relative to bulk blends or isolated components. Single-molecule spectroscopy on these species have revealed novel photophysics such as enhanced energy transfer, spectral stability, and strongly modified excited state lifetimes and blinking statistics. Here, we review the role of ligands in quantum dot applications and summarize some of our recent efforts probing energy and charge transfer in hybrid CdSe-OPV composite nanostructures

Structural and functional evolution of the P2Y12-like receptor group

Metabotropic pyrimidine and purine nucleotide receptors (P2Y receptors) belong to the superfamily of G protein-coupled receptors (GPCR). They are distinguishable from adenosine receptors (P1) as they bind adenine and/or uracil nucleotide triphosphates or diphosphates depending on the subtype. Over the past decade, P2Y receptors have been cloned from a variety of tissues and species, and as many as eight functional subtypes have been characterized. Most recently, several members of the P2Y12-like receptor group, which includes the clopidogrel-sensitive ADP receptor P2Y12, have been deorphanized. The P2Y12-like receptor group comprises several structurally related GPCR which, however, display heterogeneous agonist specificity including nucleotides, their derivatives, and lipids. Besides the established function of P2Y12 in platelet activation, expression in macrophages, neuronal and glial cells as well as recent results from functional studies implicate that several members of this group may have specific functions in neurotransmission, inflammation, chemotaxis, and response to tissue injury. This review focuses specifically on the structure-function relation and shortly summarizes some aspects of the physiological relevance of P2Y12-like receptor members

Особенности получения биодизеля первого поколения в аппарате с вихревым слоем

The possibility of intensifying the process of transesterification of triglycerides of carboxylic acids of vegetable oils with alcohols C1-C3 in the presence of potassium hydroxide in an apparatus with a vortex sheet is shown. Analysis of the composition of mixtures of methyl esters of carboxylic acids of sunflower oil showed that the redistribution of hydrogen and the destructive transformation in the system take place along with the transesterification reactions. This results in the expenditure of octadecyl acid ether.Показана возможность интенсификации процесса переэтерификации триглицеридов карбоновых кислот растительных масел спиртами С1-С3 в присутствии гидроксида калия в аппарате с вихревым слоем. Анализ состава смесей метиловых эфиров карбоновых кислот подсолнечного масла показал, что наряду с переэтерификацией в системе протекают реакции перераспределения водорода и деструктивные превращения, приводящие к исчезновению в биодизеле метилового эфира октадеценовой кислоты

Development of selective agonists and antagonists of P2Y receptors

Although elucidation of the medicinal chemistry of agonists and antagonists of the P2Y receptors has lagged behind that of many other members of group A G protein-coupled receptors, detailed qualitative and quantitative structure–activity relationships (SARs) were recently constructed for several of the subtypes. Agonists selective for P2Y1, P2Y2, and P2Y6 receptors and nucleotide antagonists selective for P2Y1 and P2Y12 receptors are now known. Selective nonnucleotide antagonists were reported for P2Y1, P2Y2, P2Y6, P2Y11, P2Y12, and P2Y13 receptors. At the P2Y1 and P2Y12 receptors, nucleotide agonists (5′-diphosphate derivatives) were converted into antagonists of nanomolar affinity by altering the phosphate moieties, with a focus particularly on the ribose conformation and substitution pattern. Nucleotide analogues with conformationally constrained ribose-like rings were introduced as selective receptor probes for P2Y1 and P2Y6 receptors. Screening chemically diverse compound libraries has begun to yield new lead compounds for the development of P2Y receptor antagonists, such as competitive P2Y12 receptor antagonists with antithrombotic activity. Selective agonists for the P2Y4, P2Y11, and P2Y13 receptors and selective antagonists for P2Y4 and P2Y14 receptors have not yet been identified. The P2Y14 receptor appears to be the most restrictive of the class with respect to modification of the nucleobase, ribose, and phosphate moieties. The continuing process of ligand design for the P2Y receptors will aid in the identification of new clinical targets