Pharmacokinetics and pharmacokinetic/pharmacodynamic relationships for angiotensin-converting enzyme inhibitors

The pharmacokinetic (PK) properties and the pharmacokinetic/pharmacodynamic (PK/PD) relationships for the angiotensin-converting enzyme (ACE) inhibitors (ACEIs), such as enalaprilat, benazeprilat, imidaprilat and ramiprilat, differ from those of conventional drugs. This is because of their immediate and saturable binding to an ACE pool which is partly circulating (and contributing to the measured plasma concentration), and partly noncirculating (tissular), being anchored to the endothelium of vessels and not measurable by the analytical technique. A physiologically based model is required to allow appropriate interpretation of the different phases of the disposition curve of ACEI. The protracted terminal phase observed for all ACEIs is not a conventional elimination phase but a phase dependent on ACEI dissociation from ACE. In contrast, the phase which reflects ACEI elimination (and which is interpreted as a distribution phase for a conventional drug) has a short half-life, thus explaining the absence of drug accumulation during repeated dosing and mild kidney failure. ACE inhibition is the surrogate endpoint generally selected for establishing a PK/PD relationship and for simulating dosage regimen scenarios in order to decide on the appropriate dosage regimen for ACEIs.     

Effects of mushroom and herb polysaccharides, as alternatives for an antibiotic, on growth performance of broilers

(1) This in vivo trial was conducted to study the effects of polysaccharide extracts of two mushrooms, Lentinus edodes (LenE) and Tremella fuciformis (TreE), and a herb, Astragalus membranaceus (AstE) on growth performance, and the weights of organs and the gastrointestinal tract (GIT) of broiler chickens. (2) Three extracts (LenE, TreE and AstE) were supplemented at inclusion rates of 0.5, 1, 2, 3 and 4 g/kg from 7 to 14 d of age and compared with an antibiotic treatment group (20 mg/kg, virginiamycin (VRG) as well as a group of non-supplemented birds. (3) Body weight (BW) gain, feed intake and feed conversion ratio (FCR) of the extract-supplemented groups were not significantly different from those of the antibiotic group. Significant effects of type of extract and concentration on growth performance were found from 7 to 28 d of age. Generally, birds fed with LenE showed higher BW gain and lower FCR from 7 to 28 d of age than those fed with TreE and AstE and 2 g/kg LenE was considered the optimal inclusion rate for enhanced broiler growth. However, the extracts had no significant effect on the relative weights of organs and GIT compared with the antibiotic group. (4) The birds fed the extracts showed better growth performance than the non-supplemented birds, but were not significantly different from those fed VRG. Of the three extracts, LenE appeared to be a potential growth promoter. Future studies are needed to investigate whether the extracts can be used as alternatives for antibiotic growth promoters in challenged birds, and to elucidate the mechanisms for potentially enhanced growth performance in poultry.     

The adipocyte as an endocrine cell

Communication between adipose and other tissues has been hypothesized since at least the 1940s to be bidirectional. Despite this expectation, early progress was largely limited to adipose tissue's role in metabolism and storage of fatty acids, its development, and its response to endocrine and neural cues. However, efforts of the last decade have identified several molecules that are secreted from adipocytes, apparently for the purpose of signaling to other tissues. Cloning of the mouse obesity gene in 1994 is perhaps the most famous impetus for recognition that adipocytes are active in the regulation of multiple body functions. The product of this gene, leptin, has since been found to inhibit feeding, enhance energy expenditure, and stimulate gonadotropes. Evidence for the roles of other adipocyte-derived signals is being generated. Resistin is a protein that can cause whole-body insulin resistance. Its expression is correlated with body fatness and is inhibited by thiazolidinediones, perhaps mediating the association of type 2 diabetes with obesity, and the effectiveness of these drugs. Resistin and a related molecule, RELM alpha, can also inhibit differentiation of preadipocytes. Adiponectin/Acrp30 secretion from adipocytes is diminished in obese states. This protein can enhance use of fatty acids in lean tissues, inhibit glucose production by liver, and consequently decrease both blood glucose and BW. Adiponectin may also be responsible for the effectiveness of thiazolidinediones, given that these drugs promote adiponectin secretion. Secretion of complement proteins has been observed in adipocytes, and these interact to generate a signal called acylation-stimulating protein, which can promote triacylglycerol synthesis. These signals seem to be largely unique to adipocytes. Other signals are derived from adipose tissue, and it is unlikely that all the adipocyte's endocrine signals have been identified. Certainly, there is much to learn about how these signals function; however, it is clear that these biomedical research discoveries comprise a useful model for our study of growth and development in livestock.     

A regional evaluation of chromium tripicolinate supplementation of diets fed to reproducing sows

A cooperative research study involving 353 litters was conducted at three stations to determine the effects of graded levels of supplemental Cr from chromium tripicolinate (CrPic) on reproductive performance of sows and preweaning performance of their pigs. Primiparous and multiparous sows were fed fortified corn-soybean meal diets with supplemental levels of 0, 200, 600, or 1,000 ppb Cr (as-fed basis). Each station used at least three of the supplemental Cr levels, with two of those levels being 0 and 200 ppb. Station effects were observed for sow gestation weight gain, lactation weight change, lactation feed intake, litter size at birth and weaning, and pig weight at birth and weaning (P = 0.001 to 0.087). Supplemental Cr increased the number of pigs born live per litter (9.49, 9.82, 10.94, and 10.07; quadratic, P = 0.05) and sow lactation weight change (-0.2, 0.8, -4.1, and -3.9 kg; linear, P = 0.01) but decreased individual birth weight of total pigs born (1.61, 1.57, 1.47, and 1.56 kg; quadratic, P = 0.10). Tissues were obtained from a subset of sows from one station after they had completed three parities on the study. The content of Cr in the adrenal gland (16.4, 20.0, 34.0, and 48.4 ppb), kidney (35.8, 56.4, 132.6, and 176.0 ppb), and liver (22.8, 37.4, 87.6, and 92.2 ppb) was increased linearly (P = 0.001 to 0.005) by increasing CrPic supplementation. The results suggest that the supplementation level that maximizes the biological response is above that currently allowed. Additionally, supplementation of Cr at 1,000 ppb (five times currently permitted supplementation levels) was not detrimental to sow performance, even when fed continuously for three parities. There may be merit to continued research to evaluate higher supplementation rates.