Minor Negative Effects Research Articles

High-fat Diets Improve the Performance of Growing-Finishing Pigs

A growth experiment was conducted to evaluate the effect of high-fat diets (10% added fat) for growing-finishing pigs. The experiment comprised 40 growing-finishing pigs from 10 litters with an average initial weight of 23.4 kg and average final weight of 104.1 kg. The experiment consisted of a growing period from week 0 to 7 and a finishing period from week 8 to slaughter. During the growing, finishing and overall periods, the high-fat diet gave a significantly higher average daily gain (ADG) and better feed efficiency as kg feed per kg of weight gain (F/G) compared with a low-fat diet (1.5% added fat). Overall, the high-fat diet also gave higher ADG, lower total feed intake, better feed/gain and a shorter time to market of 6.3 days (P<0.01), compared with the low-fat diet. There were no significant differences between diets for P2 backfat thickness, lean percentage (GP2Q), carcass meatiness or meat area in cutlet, but the high-fat diets tended to reduce the fat area in the cutlet. Carcass quality determined by the primal cut method, however, revealed a significantly lower lean percentage and a significantly higher fat percentage of pigs fed with high-fat diets. In conclusion, the use of high-fat diets improved growth performance with only minor negative effects on carcass quality. Thus, the addition of 10% rendered fat to diets had a positive effect on growth performance, but led to a slight increase in the fat content of the carcass.

An Epidemiologic and Economic Study of Respiratory Diseases in Two Conventional Danish Swine Herds. II: Associations Between Lesions Present at Slaughter and Mean Daily Gains During Specific Intervals of the Growth Period

A total of 578 slaughter pigs from 2 Danish conventional farrow-to-finish operations (Herds a and B) were followed from an age of 14 days to slaughter. Pigs were weighted at 3 weeks intervals and at slaughter and extended post mortem examination of the plucks was done. Regression models with second and third order interaction terms demonstrated that Mycoplasma-like pneumonia, complicated pneumonia, anterior-ventral pleuritis, pericarditis, fissures and atrophic rhinitis, separately and through interactions with other lesions, significantly reduced mean daily gains during specific intervals of the growth period in 2 conventional swine herds. It is likely that the periods of reduced growth reflect the times when the diseases were in the acute and early recovery stages. Maximum estimated reductions in daily gains associated with the combined lesions were 82 grams and 283 grams during the interval 120-140 days in Herds A and B, respectively. Although dorso-caudal pleuritis and parietal pleuritis had minor negative effects during 2 intervals neither had a significant adverse effect on total growth rate in either herd (Paisley et al. 1993). R2 values for the regression models were less than 0.27 showing that the lesions present at slaughter explained less than 27% of the variation in herd mean daily gains during any interval.

Long-term feeding of rapeseed meal and full-fat rapeseed of double low cultivars to dairy cows

Long-term effects on dairy cow performances of feeding different levels of rapeseed meal and heattreated and crushed full-fate rapeseed, both of double low cultivars, were studied. The study included the first three lactations of 85 dairy cows. Even at the highest inclusion levels of rapeseed products, 2.5 kg DM rapeseed meal plus 0.9 kg DM full-fat rapeseed per day, there were no negative effects on animal health, feed intake, feed conversion, milk production and milk composition. Compared with other protein and fat supplements, i.e. soybean meal, cotton seed meal and tallow, the milk protein content and production tended to increase (P<0.10), while milk urea content decreased (P<0.05). Medium (1.2–1.4 kg DM) as well as high levels of rapeseed products resulted in a significant increase in thiocyanate content but a decrease in iodine content of the milk. However, milk from the rapeseedfed cows did not cause any metabolic disturbances when fed to rats. Milk fatty acid composition was affected by the inclusion of full-fat rapeseed, whereby the concentrations of C18:0 and C18:1 increased and C16:0 decreased compared to when tallow was fed. Preliminary results from studies on the fertility of the cows indicated minor negative effects on primiparous cows fed the highest amounts of rapeseed products.

Specific valylation identity of turnip yellow mosaic virus RNA by yeast valyl‐tRNA synthetase is directed by the anticodon in a kinetic rather than affinity‐based discrimination

Variants with mutations in three parts of the tRNA-like structure of turnip yellow mosaic virus RNA (the anticodon, the discriminator position in the amino acid acceptor stem, and in the variable loop) were created via site-directed mutagenesis of a cDNA clone and transcription with T7 RNA polymerase. The valylation properties of transcripts were studied in the presence of pure yeast valyl-tRNA synthetase. Mutation of the central position of the anticodon triplet resulted in a quasi-total loss of valylation activity, indicating that the anticodon is a principal determinant for valylation of the turnip yellow mosaic virus tRNA-like structure. These anticodon mutants interacted with yeast valyl-tRNA synthetase with affinities comparable to those of the wild-type RNA and behaved as competitive inhibitors in the valylation reaction of yeast tRNAVal. The defective aminoacylation of these mutants therefore results from kinetic rather than affinity effects. Minor negative effects on valylation efficiency were observed for mutants with substitutions at the two other sites studied, suggesting a structural role or a limited contribution to the valine identity of the tRNA-like molecule.

Considering the nutritional ecology of the spruce budworm in its management

To successfully manage spruce budworm ( Choristoneura fumiferana (Clemens)) populations, we need more knowledge about the insect's nutritional ecology. Here we address this issue by considering variations in host suitability for the budworm due to tree species, age, nutrient levels, defensive compounds, inducible defenses, and stress. Tree age has minor effects on foliar nutritional quality. Nitrogen levels (as an index of protein) in the diet appear to be the most significant factor affecting performance both in the field and laboratory. Tannins/phenolics, and supraoptimal levels of calcium in host foliage may interfere with the bioavailability of some minerals such as iron. Monoterpenes can be toxic at very high levels but otherwise seem to have minor negative effects on budworm performance. There is little evidence of short-term inducible defenses in fir foliage. Likewise, there is little evidence that drought stress makes fir trees more nutritionally favorable for spruce budworm. However, drought-induced flowering may be very important to larval survival. Neither is there evidence for substantial variation among trees in their inherent susceptibility to budworm. We hypothesize that variations in host-plant quality are less important in regulating budworm dynamics than other factors, such as the physical environment and natural enemies. However, spruce-budworm/host-plant phenological synchrony and host flowering status may be very important variables that deserve more research. Management of budworm will require more detailed knowledge about the entire complex of community factors that contribute to the increased likelihood of outbreak development.

Distinct cis-acting regions in U3 regulate trans-activation of the human spumaretrovirus long terminal repeat by the viral bel1 gene product.

The human spumaretrovirus (HSRV) genome contains, in addition to coding information for the structural proteins, open reading frames (ORFs) for at least three additional genes termed bel1, bel2 and bel3. We report here the localization of the transcriptional activator of HSRV to the bel1 ORF. In reporter-based transient expression assays in COS cells utilizing the bacterial CAT gene linked to HSRV LTR sequences between -710 and +309 with respect to the transcriptional initiation site, co-expression of the bel1 gene product alone caused an over 100 to 300-fold increase in the level of LTR activity. High-level trans-activation by bel1 was specific for the HSRV LTR, as relatively minor positive and negative regulatory effects were observed on HIV-1 LTR and RSV LTR expression, respectively, whereas HTLV-1 LTR activity remained unaffected. Distinct regions of the HSRV LTR were found to be involved in bel1-induced trans-activation. Specifically, deletions between -500 and -389 and between -136 and -62 in the U3 region resulted in a 4- and 30 to 35-fold decline, respectively, in the response to bel1. Limited mutagenesis of the bel1 ORF indicated that most of the bel1 coding region, except for the carboxy-terminal 27 residues, is essential for the activation function.

AHR-16303B, a Novel Antagonist of 5-HT2 Receptors and Voltage-Sensitive Calcium Channels

In vivo and in vitro methods were used to characterize AHR-16303B, a novel compound with antagonistic action at 5-HT2 receptors and voltage-sensitive calcium channels. The 5-HT2 receptor-antagonistic properties of AHR-16303B were demonstrated by inhibition of (a) [3H]ketanserin binding to rat cerebral cortical membranes (IC50 = 165 nM); (b) 5-hydroxytryptamine (5-HT)-induced foot edema in rats (minimum effective dose, (MED) = 0.32 mg/kg orally, p.o.); (c) 5-HT-induced vasopressor responses in spontaneously hypertensive rats (SHR) (ID50 = 0.18 mg/kg intravenously (i.v.), 1.8 mg/kg p.o.), (d) 5-HT-induced antidiuresis in rats (MED = 1 mg/kg p.o.), and (e) platelet aggregation induced by 5-HT + ADP (IC50 = 1.5 mM). The calcium antagonist properties of AHR-16303B were demonstrated by inhibition of (a) [3H]nimodipine binding to voltage-sensitive calcium channels on rabbit skeletal muscle membranes (IC50 = 15 nM), (b) KCl-stimulated calcium flux into cultured PC12 cells (IC50 = 81 nM), and (c) CaCl2-induced contractions of rabbit thoracic aortic strips (pA2 = 8.84). AHR-16303B had little or no effect on binding of radioligands to dopamine2 (DA2) alpha 1, alpha 2, H1, 5-HT1 alpha, beta 2, muscarinic M1, or sigma opioid receptors; had no effect on 5-HT3 receptor-mediated vagal bradycardia; and had only minor negative inotropic, chronotropic, and dromotropic effects on isolated guinea pig atria. In conscious SHR, 30 mg/kg p.o. AHR-16303B completely prevented the vasopressor responses to i.v. 5-HT, and decreased blood pressure (BP) by 24% 3 h after dosing.

Uncorrected pre-ejection period: a simple non-invasive measurement for pharmacodynamic screening of inotropic activity.

Since heart rate (HR) is an important determinant of the duration of systole, systolic time intervals (STI) from 8 healthy subjects were examined after infusion of atropine. As no overall correlation was found between HR and pre-ejection period (PEP), the results confirm the need for individual estimates of the correction of the left ventricular ejection time (LVET) and the total electromechanical systole (OS2). In the same subjects the sensitivity of PEP to minor negative inotropic effects of mexiletine and disopyramide measured at Cmax was confirmed. Thus, in addition to its simplicity and reliability, the sensitivity of the uncorrected PEP should encourage use of this technique as part of any screening system for the early detection of an inotropic effect of new chemical entities.

Adverse Side Effects Associated with Mexiletine

Mexiletine is a new antiar‐rhythmic drug that has minor negative inotropic effects even in patients with underlying left ventricular dysfunction. The drug can be used in patients with underlying conduction system disease although reports of worsening sinus node function or atrioventicular conduction abnormalities have been noted. Mexiletine may aggravate venticular arrhythmias. The drug can be used safely with other cardioactive agents. Side effects are frequent but can be minimized by starting with low doses and titrating the dosage as tolerated. Mexiletine should be administered with meals or a snack or with antacids or possibly cimetidine to reduce gastrointestinal side effects. Mexiletine can cause abnormal liver function tests, hematologic abnormalities, and elevated titers of antinuclear antibodies (ANA). Regular monitoring of these parameters is suggested.

Amiodarone: Electrophysiologic actions, pharmacokinetics and clinical effects

Interest in amiodarone has increased because of its remarkable efficacy as an antiarrhythmic agent. The purpose of this report is to review what is known about the electrophysiologic actions, hemodynamic effects, pharmacokinetics, alterations of thyroid function, response to treatment of supraventricular and ventricular tachyarrhythmias and adverse effects of amiodarone. Understanding the actions of amiodarone and its metabolism will provide more intelligent use of the drug and minimize the development of side effects. The mechanism by which amiodarone suppresses cardiac arrhythmias is not known and may relate to prolongation of refractoriness in all cardiac tissues, suppression of automaticity in some fibers, minimal slowing of conduction in fast channel-dependent tissue, or to interactions with the autonomic nervous system, alterations in thyroid metabolism or other factors. Amiodarone exerts definite but fairly minor negative inotropic effects that may be offset by its vasodilator actions. Amiodarone has a reduced clearance rate, large volume of distribution, low bioavailability and a long half-life that may last 2 months in patients receiving short-term therapy. Therapeutic serum concentrations range between 1.0 and 3.5 micrograms/ml. The drug suppresses recurrences of cardiac tachyarrhythmias in a high percent of patients, in the range of 80% or more for most supraventricular tachycardias and in about 66% of patients with ventricular tachyarrhythmias, sometimes requiring addition of a second antiarrhythmic agent. Side effects, particularly when high doses are used, may limit amiodarone's usefulness and include skin, corneal, thyroid, pulmonary, neurologic, gastrointestinal and hepatic dysfunction. Aggravation of cardiac arrhythmias occurs but serious arrhythmias are caused in less than 5% of patients. Amiodarone affects the metabolism of many other drugs and care must be used to reduce doses of agents combined with amiodarone.

The effects of the bradycardia-producing compound alinidine on action potentials and tension development in cardiac fibres.

Alinidine (ST 567, N-Allyl-Clonidine) exerted concentration-dependent negative chronotropic effects in isolated, spontaneously-beating sinus node cells and Purkinje fibres of guinea pigs and in ventricular strips of chick embryonic myocardium. Reduction of beat frequency by 30% was found after addition of 8.6 mumol/l alinidine in the former. A chronotropic effect was not seen during Ba2+-induced automaticity or triggered activity in guinea-pig papillary muscles and in enzymatically disaggregated cells of embryonic chick myocardium, which lose the beta-adrenoceptor responsiveness of the intact embryonic ventricle. In contrast to alinidine, D600 showed very pronounced and quinidine minor negative chronotropic effects in these latter experiments. Reduction of excitability, rate of rise of the action potential and velocity of repolarization as well as prolongation of the refractory period were seen after applications of very high concentrations of alinidine (285 mumol/l). In electrically-driven atria isometric peak tension was only slightly changed (increased by 85.5 mumol/l, decreased by 285 mumol/l) but it was reduced (to 36.8%) by alinidine (85.5 mumol/l) in papillary muscles. Both in atria and in papillary muscles, the maximum rate of rise of the action potential was unchanged by alinidine up to 85.5 mumol/l and the slight reduction following 285 mumol/l alinidine application was independent of the rate of stimulation. The present findings confirm the selectivity of the bradycardic effects of alinidine which has a main mode of action different to that of membrane stabilizing compounds or inhibitors of the slow inward current.

Effect of certain organic compounds on saliva secretion in sheep.

In two sheep fitted with esophageal cannulas the stimulation of resting saliva secretion by intrabuccal injections of volatile fatty acids (VFA) and of certain organic plant compounds was investigated. Volatile fatty acids, salicin and vanillin increased saliva flow rate by 100, 76 and 72% over 2.5 min after injection. Minor positive or negative effects were obtained with quercitrin, protocatechuic acid, grass juice, anethole and agaricinic acid. Injections of volatile fatty acids and of salicin induced chewing activities, which were significantly correlated with salivary flow rates. The results indicate that organic plant compounds can provide a stimulus for saliva secretion mediated in part by chewing activities.