Mechanisms of Nausea and Vomiting: Current Knowledge and Recent Advances in Intracellular Emetic Signaling Systems

Nausea and vomiting are common gastrointestinal complaints that can be triggered by diverse emetic stimuli through central and/or peripheral nervous systems. Both nausea and vomiting are considered as defense mechanisms when threatening toxins/drugs/bacteria/viruses/fungi enter the body either via the enteral (e.g., the gastrointestinal tract) or parenteral routes, including the blood, skin, and respiratory systems. While vomiting is the act of forceful removal of gastrointestinal contents, nausea is believed to be a subjective sensation that is more difficult to study in nonhuman species. In this review, the authors discuss the anatomical structures, neurotransmitters/mediators, and corresponding receptors, as well as intracellular emetic signaling pathways involved in the processes of nausea and vomiting in diverse animal models as well as humans. While blockade of emetic receptors in the prevention of vomiting is fairly well understood, the potential of new classes of antiemetics altering postreceptor signal transduction mechanisms is currently evolving, which is also reviewed. Finally, future directions within the field will be discussed in terms of important questions that remain to be resolved and advances in technology that may help provide potential answers.     

Alternatives to linear analysis of energy balance data from lactating dairy cows

The current energy requirements system used in the United Kingdom for lactating dairy cows utilizes key parameters such as metabolizable energy intake (MEI) at maintenance (MEm), the efficiency of utilization of MEI for 1) maintenance, 2) milk production (kl), 3) growth (kg), and the efficiency of utilization of body stores for milk production (kt). Traditionally, these have been determined using linear regression methods to analyze energy balance data from calorimetry experiments. Many studies have highlighted a number of concerns over current energy feeding systems particularly in relation to these key parameters, and the linear models used for analyzing. Therefore, a database containing 652 dairy cow observations was assembled from calorimetry studies in the United Kingdom. Five functions for analyzing energy balance data were considered: straight line, two diminishing returns functions, (the Mitscherlich and the rectangular hyperbola), and two sigmoidal functions (the logistic and the Gompertz). Meta-analysis of the data was conducted to estimate kg and kt. Values of 0.83 to 0.86 and 0.66 to 0.69 were obtained for kg and kt using all the functions (with standard errors of 0.028 and 0.027), respectively, which were considerably different from previous reports of 0.60 to 0.75 for kg and 0.82 to 0.84 for kt. Using the estimated values of kg and kt, the data were corrected to allow for body tissue changes. Based on the definition of kl as the derivative of the ratio of milk energy derived from MEI to MEI directed towards milk production, MEm and kl were determined. Meta-analysis of the pooled data showed that the average kl ranged from 0.50 to 0.58 and MEm ranged between 0.34 and 0.64 MJ/kg of BW0.75 per day. Although the constrained Mitscherlich fitted the data as good as the straight line, more observations at high energy intakes (above 2.4 MJ/kg of BW0.75 per day) are required to determine conclusively whether milk energy is related to MEI linearly or not.     

Effects of abomasal vegetable oil infusion on splanchnic nutrient metabolism in lactating dairy cows

Changes in the metabolism of nutrients by the portal-drained viscera (PDV) and liver may contribute to the reduction in dry matter intake (DMI) and other production responses generally observed in lactating dairy cows fed supplemental long-chain fatty acids (LCFA). In the present study, effects of a 7-d abomasal infusion of vegetable oil on arterial concentration and splanchnic (PDV and liver) metabolism of nutrients were measured in six cows at 55 (early lactation [ELAC]) and 111 (midlactation [MLAC]) d postpartum. Cows were fed for ad libitum DMI at 8-h intervals, and blood samples for measurement of splanchnic metabolism were obtained over 8 h beginning 2 h before feeding at 0830 h. Blood flow for the PDV and liver was increased by oil infusion and was greater in ELAC, despite similar-feed DMI during blood sampling. Increased blood flow in ELAC was associated with greater liver oxygen removal and glucose release that accompanied greater milk yield. In contrast, oil infusion had no effect on splanchnic oxygen use. Greater blood flow during oil infusion may have been due to specific effects of intestinal LCFA supply on PDV blood flow. Net PDV release and liver removal of branched-chain volatile fatty acids (VFA) and ammonia were increased by oil infusion. Net PDV release of longer-chain (4 and 5 C) VFA and NEFA was greater in ELAC, but net PDV flux of other nutrients was not affected by lactation stage, possibly due to the similarity of feed DMI. Oil infusion increased arterial concentration and net PDV release and liver removal of NEFA, and it decreased net liver release and arterial concentration of glucose. Effects of oil infusion on liver glucose release were associated with decreased daily DMI. In ELAC, arterial concentration and net liver removal of NEFA were also increased, but liver release of glucose was greater than in MLAC. Oil infusion and ELAC both increased net liver removal of L-lactate. The resulting decrease in net total splanchnic release of L-lactate in ELAC reflects decreased tissue energy balance of the cows. Generally, stage of lactation and relative milk yield had greater effects on metabolism of the liver than the PDV, in which metabolism was largely dictated by DMI. In the present study, there was little evidence to suggest an effect of stage of lactation on the metabolic response ofthe PDV and liver to postruminal LCFA supply.     

Report of the first workshop on the genetic map of bovine chromosome 1

Allergic bronchopulmonary aspergillosis (ABPA), occurring primarily in patients with asthma or cystic fibrosis (CF), is a hypersensitivity reaction to Aspergillus fumigatus (Af), and is characterized by increased serum IgE levels and peripheral blood and pulmonary eosinophilia. We evaluated the IgE and cytokine profile in ABPA through enzyme-linked immunosorbent assay (ELISA), and evaluated eosinophil activity with the eosinophil peroxidase (EPO) assay. IgE and cytokines were measured in supernatants from cultures of peripheral blood mononuclear cells (PBMC) from three subject groups: ABPA patients, patients with asthma, and healthy individuals. All cultures for the three subject groups were studied in the presence and absence of two purified Af antigens (the 35-kD antigen and heat shock protein 1). We found that increased in vitro levels of IgE in unstimulated PBMC culture supernatants correlated significantly with serum IgE concentrations in ABPA patients. We measured a decrease in IgE levels of up to 75% of baseline values in supernatants from PBMC cultured with Af antigens. Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) concentrations in cultures with Af were increased in ABPA, whereas concentrations of IL-4 did not differ in the three subject groups. An inverse relation was noted between the changes in IgE and IFN-gamma measured in 4 of 5 ABPA patients. The PBMC supernatants also promoted EPO activity in purified eosinophils from ABPA patients, and to a lesser extent in purified eosinophils from healthy subjects. These results show that the 35-kD antigen and HSP1 from Af downregulate IgE in vitro but are capable of inducing eosinophilia in ABPA. Further studies could result in the characterization of epitopes leading to these disparate effects. An identification of the IgE-down-regulating epitopes in Af antigens might have therapeutic significance.     

Effect of method of application of a fibrolytic enzyme product on digestive processes and milk production in Holstein-Friesian cows

Four multiparous cows with cannulas in the rumen and proximal duodenum were used in early lactation in a 4 x 4 Latin square experiment to investigate the effect of method of application of a fibrolytic enzyme product on digestive processes and milk production. The cows were given ad libitum a total mixed ration (TMR) composed of 57% (dry matter basis) forage (3:1 corn silage:grass silage) and 43% concentrates. The TMR contained (g/kg dry matter): 274 neutral detergent fiber, 295 starch, 180 crude protein. Treatments were TMR alone or TMR with the enzyme product added (2 kg/1000 kg TMR dry matter) either sprayed on the TMR 1 h before the morning feed (TMR-E), sprayed only on the concentrate the day before feeding (Concs-E), or infused into the rumen for 14 h/d (Rumen-E). There was no significant effect on either feed intake or milk yield but both were highest on TMR-E. Rumen digestibility of dry matter, organic matter, and starch was unaffected by the enzyme. Digestibility of NDF was lowest on TMR-E in the rumen but highest postruminally. Total tract digestibility was highest on TMR-E for dry matter, organic matter, and starch but treatment differences were nonsignificant for neutral detergent fiber. Corn silage stover retention time in the rumen was reduced by all enzyme treatments but postruminal transit time was increased so the decline in total tract retention time with enzymes was not significant. It is suggested that the tendency for enzymes to reduce particle retention time in the rumen may, by reducing the time available for fibrolysis to occur, at least partly explain the variability in the reported responses to enzyme treatment.     

Splanchnic metabolism of dairy cows during the transition from late gestation through early lactation

Blood flow and net nutrient fluxes for portal-drained viscera (PDV) and liver (total splanchnic tissues) were measured at 19 and 9 d prepartum and at 11, 21, 33, and 83 d in milk (DIM) in 5 multiparous Holstein-Friesian cows. Cows were fed a grass silage-based gestation ration initially and a corn silage-based lactation ration peripartum and postpartum. Meals were fed at 8-h intervals and hourly (n = 8) measures of splanchnic metabolism were started before (0730 h and 0830 h) feeding at 0830 h. Dry matter intakes (DMI) at 19 and 9 d prepartum were not different. Metabolism changes measured from 19 to 9 d prepartum were lower arterial insulin and acetate, higher arterial nonesterified fatty acids and increased net liver removal of glycerol. After calving, PDV and liver blood flow and oxygen consumption more than doubled as DMI and milk yield increased, but 85 and 93% of the respective increases in PDV and liver blood flow at 83 DIM had occurred by 11 DIM. Therefore, factors additional to DMI must also contribute to increased blood flow in early lactation. Most postpartum changes in net PDV and liver metabolism could be attributed to increases in DMI and digestion or increased milk yield and tissue energy loss. Glucose release was increasingly greater than calculated requirements as DIM increased, presumably as tissue energy balance increased. Potential contributions of lactate, alanine, and glycerol to liver glucose synthesis were greatest at 11 DIM but decreased by 83 DIM. Excluding alanine, there was no evidence of an increased contribution of amino acids to liver glucose synthesis is required in early lactation. Increased net liver removal of propionate (69%), lactate (20%), alanine (8%), and glycerol (4%) can account for increased liver glucose release in transition cows from 9 d before to 11 d after calving.     

Effects of management practices prior to and during ensiling and concentrate type on nitrogen utilization in dairy cows

Three experiments with a total of 18 multiparous Holstein-Friesian dairy cows in early to mid lactation were used in incomplete changeover designs with four periods consisting of 4 wk each. The objectives of the experiments were to investigate the effects of 1) grass management practices prior to ensiling and 2) concentrate energy sources on animal performance and N utilization and suggest ways in which the annual N excretion can be reduced. In the first experiment, four silages were prepared as early-cut material from grass that was fertilized with either 75 or 150 kg of N/ha. Two other silages were prepared from the latter but harvested 2 wk later. Within each silage type, both direct cut and wilted silages were produced. In the second experiment, starch-based and fiber-based concentrates were offered with the three wilted silages used in the previous experiment. In the third experiment, barley-based and corn-based concentrates were offered with three silages that had been treated with different additives at the time of ensiling. Neither dry matter intake nor milk yield were significantly affected by either silage or concentrate type. Milk protein content and yield, however, were higher in silages made from medium fertilized grass and also increased with increased starch content of the concentrate. Grass management and diet affected the amount and form of N excreted. Use of nitrogen fertilizer at lower than 75 kg of N/ha and feeding less degradable starch concentrate is recommended for mitigation of N pollution, especially in the form of urine N by dairy cows in intensive farming.     

Nitrogen pollution by dairy cows and its mitigation by dietary manipulation

One of the major contributions to atmospheric pollution comes from nitrogen (N) derived from cattle and especially dairy cows. Although most estimates of ammonia volitilization are based on total N excretion, it has been repeatedly shown that urinary N is a much more important source of pollution than faecal N, specially under grazing conditions. A model was developed to predict the amount and form of N excreted under different production systems. Analysis of N pollution was based on data collected from Holstein/Friesian cows fed 30 different diet types consisting of 10 grass silages and 6 concentrates. While there was a strong correlation between N intake and N output in general, urinary N was exponentially correlated with N intake and the model predicted about 80% loss of N in urine for levels of N consumption above 500 g N/d. On the other hand, outputs of faecal and milk N increased by less than 20% per unit increase in N intake. Model predictions also agreed well with published data and provided reasonable estimates of the form in which N was excreted. Concentrate composition with respect to energy type and its degradation and protein degradability and silage type had significant effects on the amount and form of N excreted. It is concluded that N pollution may be ameliorated by using grass grown with moderate fertiliser application, and maize-based energy supplements, formulated to provide low degradable protein and with N intakes of less than 400 g/d for average yielding cows. This revised version was published online in August 2006 with corrections to the Cover Date.     

Manipulation of fermentation in the rumen

Artificial saliva (4 litres/day) was infused into the rumen of sheep fed a semi-purified diet at hourly intervals. Dilution rate and the efficiency of synthesis of microbial protein in vivo were increased. The pattern of rumen fermentation was altered; the molar proportion of propionic acid decreased (32–20%) and acetic acid increased (58–66%) with infusion, and there was an increased flow of total amino acids into the duodenum.     

The influence of insulin and amino acid supply on amino acid uptake by the lactating bovine mammary gland.

Four lactating dairy cows received arterial infusions of insulin (1.41 U/h), an AA mixture (threonine, methionine, leucine, phenylalanine, and lysine at 5.87, 1.90, 3.55, 2.17, and 4.21 mmol/h, respectively), and a combination of the two in a 4 x 4 Latin square. The infusions were performed over a 3-d period directly into the extra pudic artery on both sides of the mammary gland, and samples were taken simultaneously of the downstream extra pudic arterial blood and also of subcutaneous abdominal venous blood. Blood flow was measured by dye dilution using p-amino-hippuric acid and was increased by 37% by infusion of insulin plus AA (P less than .05). Infusions of AA tended to increase the arteriovenous difference and uptake of the infused AA (P less than .05 for phenylalanine) and had varying effects on the uninfused AA. Inclusion of insulin in the AA infusion tended to increase uptake of infused AA, whereas infusions of insulin alone tended to decrease uptake. There were no significant effects of infusion on milk yield or composition.