Avaliação do sistema integrado de controle parasitário em uma criação semi-intensiva de caprinos na região de Santa Catarina / Evaluation of the integrated parasite control in a semi-intensive goat farming in the region of Santa Catarina

O objetivo deste trabalho foi subsidiar um programa sustentável de controle parasitário em um rebanho caprino em São Francisco do Sul, SC, aplicando o Sistema Integrado de Controle Parasitário (SICOPA). Foram utilizados 63 caprinos, distribuídos em nove grupos para teste de eficácia de anti-helmínticos, exames de contagem de ovos por grama de fezes (OPG), coprocultura, grau Famacha, micro-hematócrito, escore corporal e contagem de larvas no pasto. A redução da OPG 15 dias pós-tratamento com closantel, albendazole, nitroxinil, levamisole, ivermectina+levamisole+albendazol, moxidectina, ivermectina, abamectina e sulfóxido de albendazol foi de 89, 83, 65, 63, 57, 37, 31, 0 e 0%, respectivamente. A média de graus Famacha 1 e 2 no estudo foi de 81%, e de graus 3, 4 e 5 foi de 19%, e não se observou correlação com os valores do micro-hematócrito em razão da prevalência de Trichostrongylus sp. (92%). A contagem de larvas infectantes (L3) na pastagem apresentou valores abaixo de 1000 L3/kg/MS, predominando Trichostrongylus sp. Nenhuma das drogas testadas foi considerada eficaz, evidenciando resistência parasitária múltipla. A aplicação de ferramentas do SICOPA e a adoção de estratégias de manejo e nutrição adequados são fundamentais para estabelecer um programa sanitário sustentável.

The objective of this study was to subsidize a sustainable parasite control program in a flock of goats in São Francisco do Sul, SC, Brazil, applying the integrated system for parasite control. Sixty three adult animals were used in nine groups to perform an anthelmintic efficacy test, faecal egg count (FEC), Famacha method, haematocrit, body condition score, coproculture, and the presence of larvae on pasture. Drug efficacy measured by FEC 15 days post-treatment with closantel, ivermectin + Levamisole + albendazole, albendazole, nitroxinyl, levamisol, abamectin, ivermectin, moxidectin and albendazole was 85, 57, 83, 65, 63, 31, 28, 24 and 0%, respectively. The Famacha score 1 or 2 was given to 81% and scores 3, 4 or 5 were given to 19%, without significant correlation with haematocrit values since the predominant was Trichostrongylus sp. (92%). The count of infective larvae levels on pasture revealed values below 1000 L3/kg/DM predominantly Trichostrongylus sp. None of the tested drugs was effective, showing multiple parasitic resistance. The correct application of the SICOPA and adoption of management strategies and proper nutrition are essential to establish a sustainable health program.

Clinical evidence for immunomodulatory effects of probiotic bacteria.

Close, tightly orchestrated interactions between the intestinal epithelium and the mucosa-associated immune system are critical for normal intestinal absorptive and immunological functions. Recent data indicate that commensal intestinal microbiota represents a major modulator of intestinal homeostasis. This review analyzes the process of intestinal colonization and the interaction of microbiota with the intestinal epithelium and mucosal immune system, with special reference to the first years of extrauterine life. Dysregulation of the symbiotic interaction between intestinal microbiota and the mucosa may result in a pathological condition with potential clinical repercussions. Based on the concept that there is a beneficial and symbiotic relation between the host and endogenous microbiota, strategies aimed at directly modulating intestinal microbiota with regard to disease prevention or treatment have been developed. One strategy involves administering viable probiotic bacteria. Clinical evidence for the beneficial effect of probiotics in the prevention and/or treatment of necrotizing enterocolitis, infectious and antibiotic-associated diarrhea, allergic diseases, and inflammatory bowel disorders is reviewed herein.

The nutritional phenotype in the age of metabolomics.

The concept of the nutritional phenotype is proposed as a defined and integrated set of genetic, proteomic, metabolomic, functional, and behavioral factors that, when measured, form the basis for assessment of human nutritional status. The nutritional phenotype integrates the effects of diet on disease/wellness and is the quantitative indication of the paths by which genes and environment exert their effects on health. Advances in technology and in fundamental biological knowledge make it possible to define and measure the nutritional phenotype accurately in a cross section of individuals with various states of health and disease. This growing base of data and knowledge could serve as a resource for all scientific disciplines involved in human health. Nutritional sciences should be a prime mover in making key decisions that include: what environmental inputs (in addition to diet) are needed; what genes/proteins/metabolites should be measured; what end-point phenotypes should be included; and what informatics tools are available to ask nutritionally relevant questions. Nutrition should be the major discipline establishing how the elements of the nutritional phenotype vary as a function of diet. Nutritional sciences should also be instrumental in linking the elements that are responsive to diet with the functional outcomes in organisms that derive from them. As the first step in this initiative, a prioritized list of genomic, proteomic, and metabolomic as well as functional and behavioral measures that defines a practically useful subset of the nutritional phenotype for use in clinical and epidemiological investigations must be developed. From this list, analytic platforms must then be identified that are capable of delivering highly quantitative data on these endpoints. This conceptualization of a nutritional phenotype provides a concrete form and substance to the recognized future of nutritional sciences as a field addressing diet, integrated metabolism, and health.

Binding of tritiated and radioiodinated ZM241,385 to brain A2A adenosine receptors.

Autoradiography on rat brain using tritiated (1*), mono- (2*) and di-radioiodinated (3*) derivatives of the A(2A) adenosine receptor antagonist ZM241,385 showed high receptor density in striatum. K(D)s of 1*, 2* and 3* were 0.4, 2.2 and 15 nM and nonspecific binding was 5, 40 and 50% of total binding. Striatal uptake of 2* in mice was approximately 0.2% ID/g 60 min post-injection; blocking by 2 was insignificant. Poor penetration of the blood brain barrier and high nonspecific binding make 2* unsuitable for imaging striatal receptors.

Evaluation of radioiodinated 8-Cyclopentyl-3-[(E)-3-iodoprop-2-en-1-yl]-1-propylxanthine ([*I]CPIPX) as a new potential A1 adenosine receptor antagonist for SPECT.

8-Cyclopentyl-3-[(E)-3-[(131)I]iodoprop-2-en-1-yl]-1-propylxanthine (2*) was generated by iododestannylation of the tributyl-stannyl-precursor with [(131)I]NaI and chloramine T. The radiochemical yield of 2* was 82 +/- 4%, and the purity exceeded 98%. The specific activity was 33 +/- 19 GBq/micromol. Affinities for rat, pig and human A(1) adenosine receptors (A(1)ARs) were in the low nanomolar range, but poor selectivity for the human A(1)AR over the A(2A)AR was found. Additionally, in vitro and ex vivo autoradiographic studies revealed high unspecific binding which makes this ligand unsuitable for SPECT imaging.

Maternal and infant factors associated with failure to thrive in children with vertically transmitted human immunodeficiency virus-1 infection: the prospective, P2C2 human immunodeficiency virus multicenter study.

OBJECTIVE: Many children with human immunodeficiency virus-1 (HIV-1) have chronic problems with growth and nutrition, yet limited information is available to identify infected children at high risk for growth abnormalities. Using data from the prospective, multicenter P2C2 HIV study, we evaluated the relationships between maternal and infant clinical and laboratory factors and impaired growth in this cohort. METHODS: Children of HIV-1-infected women were enrolled prenatally or within the first 28 days of life. Failure to thrive (FTT) was defined as an age- and sex-adjusted weight z score < or =-2.0 SD. Maternal baseline covariates included age, race, illicit drug use, zidovudine use, CD4+ T-cell count, and smoking. Infant baseline predictors included sex, race, CD4+ T-cell count, Centers for Disease Control stage, HIV-1 RNA, antiretroviral therapy, pneumonia, heart rate, cytomegalovirus, and Epstein-Barr virus infection status. RESULTS: The study cohort included 92 HIV-1-infected and 439 uninfected children. Infected children had a lower mean gestational age, but birth weights, lengths, and head circumferences in the 2 groups were similar. Mothers of growth-delayed infants were more likely to have smoked tobacco and used illicit drugs during pregnancy. In repeated-measures analyses of weight and length or height z scores, the means of the HIV-1-infected group were significantly lower at 6 months of age (P <.001) and remained lower throughout the first 5 years of life. In a multivariable Cox regression analysis, FTT was associated with a history of pneumonia (relative risk [RR] = 8.78; 95% confidence interval [CI]: 3.59-21.44), maternal use of cocaine, crack, or heroin during pregnancy (RR = 3.17; 95% CI: 1.51-6.66), infant CD4+ T-cell count z score (RR = 2.13 per 1 SD decrease; 95% CI: 1.25-3.57), and any antiretroviral therapy by 3 months of age (RR = 2.77; 95% CI: 1.16-6.65). After adjustment for pneumonia and antiretroviral therapy, HIV-1 RNA load remained associated with FTT in the subset of children whose serum was available for viral load analysis. CONCLUSIONS: Clinical and laboratory factors associated with FTT among HIV-1-infected children include history of pneumonia, maternal illicit drug use during pregnancy, lower infant CD4+ T-cell count, exposure to antiretroviral therapy by 3 months of age (non-protease inhibitor), and HIV-1 RNA viral load.

Protein/amino acid metabolism and nutrition in very low birth weight infants.

A large number of studies in recent years have described protein and nitrogen metabolism in the neonate. However, the majority of these data are difficult to interpret because of a number of confounding variables, particularly in very low birth weight (VLBW) infants. In contrast, application of state-of-the-art tracer isotopic and molecular biology methods in isolated cell system and whole animals has resulted in major advances in our understanding of the regulation of protein breakdown, synthesis, and protein accretion. The following workshop summary reviews the recent developments in basic physiology of protein metabolism in cellular and animal models in relation to human preterm infants, and identifies the important areas toward which future basic and clinical research should be directed to provide for optimal nitrogen accretion and growth of the VLBW infant.

Glucose production, gluconeogenesis, and insulin sensitivity in children and adolescents: an evaluation of their reproducibility.

The prevalence of overweight and obese children has doubled, and the incidence of type 2 diabetes in children (0-19 y) has increased 4-fold during the past several decades. As a result we can anticipate an increased number of metabolic studies in children. There are few data on measures of glucose metabolism in normal children, and virtually none relating to their reproducibility. The aims of this study were 1) to provide new data on energy expenditure and glucose, lipid, and protein metabolism in nonobese, healthy children and adolescents; 2) to evaluate their reproducibility; and 3) on the basis of these data, to perform power calculations for metabolic studies. Eight nonobese subjects (8-16 y) were studied on two occasions, preceded by 7 d of a diet with identical energy content and macronutrient distribution. Gluconeogenesis, measured by deuterium oxide, accounted for 50% of glucose production. Insulin sensitivity, measured by the labeled minimal model, averaged 4.9 x 10(-4) mL(mU x min)(-1). Glucose appearance rate was significantly higher (p < 0.01) in the children than in the adolescents. Furthermore, we demonstrated that for energy intake and expenditure, plasma concentrations of glucose and C-peptide, and rates of appearance of glucose and leucine, a 10% difference can be detected in fewer than five subjects with a power of 80% and a type I error of 5%. Insulin concentration, gluconeogenesis, insulin secretory indices, insulin sensitivity, and glucose effectiveness were more variable, but with the above power a difference of 25% could be detected in 7-11 subjects using a paired study design.

Sympathomimetic effects of MIBG: comparison with tyramine.

UNLABELLED: Because nothing is known about whether metaiodobenzylguanidine (MIBG) has tyramine-like actions, the sympathomimetic effects of MIBG were determined in the isolated rabbit heart and compared with those of tyramine. METHODS: Spontaneously beating rabbit hearts were perfused with Tyrode's solution (Langendorff technique; 37 degrees C; 26 mL/min), and the heart rate as well as the norepinephrine and dopamine overflow into the perfusate was measured before and after doses of MIBG or tyramine (0.03-10 micromol) given as bolus injections (100 microL) into the aortic cannula. Km and Vmax values for the neuronal uptake (uptake1) of 125I-MIBG and 14C-tyramine were obtained in human neuroblastoma (SK-N-SH) cells. The Ki of MIBG for inhibition of the 3H-catecholamine uptake mediated by the vesicular monoamine transporter was determined in membrane vesicles obtained from bovine chromaffin granules and compared with the previously reported Ki value for tyramine determined under identical experimental conditions. RESULTS: By producing increases in heart rate and norepinephrine overflow, both compounds had dose-dependent sympathomimetic effects in the rabbit heart. MIBG was much less effective than tyramine in increasing heart rate (maximum effect 59 versus 156 beats/min) and norepinephrine overflow (maximum effect 35 versus 218 pmol/g). Tyramine also caused increases in dopamine overflow, whereas MIBG was a poor dopamine releaser. At a dose of 10 micromol, the increase in heart rate lasted more than 60 min after MIBG and about 20 min after tyramine injection. Accordingly, the norepinephrine overflow caused by 10 micromol MIBG and tyramine declined with half-lives of 57.8 and 2.2 min, respectively. The effects of both drugs were drastically reduced in hearts exposed to 2 micromol/L desipramine. The kinetic parameters characterizing the saturation of neuronal uptake by 125I-MIBG and 14C-tyramine were similar for the two compounds: Km values of MIBG and tyramine were 1.6 and 1.7 micromol/L, respectively, and Vmax values of MIBG and tyramine were 43 and 37 pmol/mg protein/min, respectively. However, in inhibiting the vesicular 3H-catecholamine uptake, MIBG was eight times less potent than tyramine. CONCLUSION: MIBG is much less effective than tyramine as an indirect sympathomimetic agent. This is probably a result of its relatively low affinity for the vesicular monoamine transporter and explains the relatively poor ability of the drug to mobilize norepinephrine stored in synaptic vesicles. The long duration of MIBG action results primarily from the drug not being metabolized by monoamine oxidase. The sympathomimetic effects of MIBG described here are not likely to come into play in patients given diagnostic or common therapeutic doses of radioiodinated MIBG.

Undermodeling affects minimal model indexes: insights from a two-compartment model.

The classic (hereafter cold) and the labeled (hereafter hot) minimal models are powerful tools to investigate glucose metabolism. The cold model provides, from intravenous glucose tolerance test (IVGTT) data, indexes of glucose effectiveness (SG) and insulin sensitivity (SI) that measure the effect of glucose and insulin, respectively, to enhance glucose disappearance and inhibit endogenous glucose production. The hot model provides, from hot IVGTT data, indexes of glucose effectiveness (SG*) and insulin sensitivity (SI*) that, respectively, measure the effects of glucose and insulin on glucose disappearance only. Recent reports call for a reexamination of some of the assumptions of the minimal models. We have previously pointed out the criticality of the single-compartment description of glucose kinetics on which both the minimal models are founded. In this paper we evaluate the impact of single-compartment undermodeling on SG, SI*, and by using a two-compartment model to describe the glucose system. The relationships of the minimal model indexes to the analogous indexes measured with the glucose clamp technique are also examined. Theoretical analysis and simulation studies indicate that cold indexes are more affected than hot indexes by undermodeling. In particular, care must be exercised in the physiological interpretation of SG, because this index is a local descriptor of events taking place in the initial portion of the IVGTT. As a consequence, SG not only reflects glucose effect on glucose uptake and production but also the rapid exchange of glucose between the accessible and nonaccessible glucose pools that occurs in the early part of the test.

Gluconeogenesis in very low birth weight infants receiving total parenteral nutrition.

Very low birth weight (VLBW) infants are dependent on total parenteral nutrition (TPN) to prevent hypoglycemia and provide a sufficient energy intake. However, diminished tolerance for parenteral glucose delivered at high rates frequently provokes hyperglycemia. We hypothesized that when their glucose supply is reduced to prevent hyperglycemia, VLBW infants can maintain normoglycemia via gluconeogenesis from glycerol and amino acids. Twenty infants born at 27 +/- 0.2 (mean +/- SE) gestational weeks and having a birth weight of 996 +/- 28 g, received lipids (1.6 +/- 0.1 mg x kg(-1) x min(-1)), protein (2.2 +/- 0.1 mg x kg(-1) x min(-1)), and glucose (3.1 +/- 0.1 mg x kg(-1) x min(-1) [17.1 +/- 0.2 micromol x kg(-1) x min(-1)]) parenterally over a period of 8-12 h on day 5.0 +/- 0.2 of life. Gluconeogenesis was estimated using [U-13C]glucose (n = 8) or [2-(13)C] glycerol (n = 6) and mass isotopomer distribution analysis (MIDA), or 2H2O (n = 6) and the rate of deuterium incorporation in carbon 6 of glucose. Blood glucose averaged 3.0 +/- 0.1 mmol/l; plasma glucose appearance rate (glucose Ra), 28.8 +/- 1.1 micromol x kg(-1) x min(-1); and glucose production rate (GPR), 10.7 +/- 1.0 micromol x kg(-1) x min(-1). The [U-13C]glucose and [2-(13)C]glycerol tracers provided similar estimates of gluconeogenesis, averaging 28 +/- 2 and 26 +/- 2% of glucose Ra and 72 +/- 5 and 73 +/- 9% of GPR, respectively. Glycerol contributed 64 +/- 5% of total gluconeogenesis. Gluconeogenesis measured by 2H2O, which does not include the contribution from glycerol, was comparable to the nonglycerol fraction of gluconeogenesis derived by the [2-(13)C]glycerol MIDA. We conclude that in VLBW infants receiving TPN, normoglycemia was maintained during reduced glucose infusion by glucose production primarily derived from gluconeogenesis, and that glycerol was the principal gluconeogenic substrate.

Glucose production during an IVGTT by deconvolution: validation with the tracer-to-tracee clamp technique.

Recently, a new method, based on a two-compartment minimal model and deconvolution [A. Caumo and C. Cobelli. Am. J. Physiol 264 (Endocrinol. Metab. 37): E829-E841, 1993; P. Vicini, G. Sparacino, A. Caumo, and C. Cobelli. Comput. Meth. Prog. Biomed. 52: 147-156, 1997], has been proposed to estimate endogenous glucose production (EGP) from labeled intravenous glucose tolerance test (IVGTT) data. Our aim here is to compare this EGP profile with that independently obtained with the reference method, based on the tracer-to-tracee ratio (TTR) clamp. An insulin-modified (0.03 U/kg body wt infused over 5 min) [6,6-2H2]glucose-labeled IVGTT (0.33 g/kg of glucose) was performed in 10 normal subjects. A second tracer ([U-13C]glucose) was also infused during the test in a variable fashion to clamp endogenous glucose TTR. The TTR clamp was quite successful. As a result, the EGP profile, reconstructed from [U-13C]glucose data with the models of Steele and Radziuk, were almost superimposable. The deconvolution-obtained EGP profile, calculated from [6,6-2H2]glucose data, showed remarkable agreement with that obtained from the TTR clamp. Some differences between the two profiles were noted in the estimated basal EGP and in the initial modalities of EGP inhibition. A high interindividual variability was also observed with both methods in the resumption of EGP to baseline; variability was high in both the timing and the extent of resumption. In conclusion, the use of the two-compartment minimal model of the IVGTT and deconvolution allows the estimation of a profile of EGP that is in very good agreement with that independently obtained with a TTR clamp.

Methods for measuring iodine in urine and serum.

The most important information in the determination of the status of iodine nutrition of a population comes from the measurement of the urinary excretion of iodine. Several methods are available for measuring urinary iodine. The choice among methods depends on the intended application, the number of samples, the cost and the technical capability. Epidemiological field studies demand simple, rapid and cost-effective methods. Suitable for these applications are the rapid urinary iodide test and the ammonium persulfate oxidation method which gives comparable results to the chloric acid method without having the drawbacks of being hazardous and explosive. In research studies however, sophisticated automated technology like the Technicon Autoanalyzer or Paired-Ion Reversed Phase HPLC are used in which the high cost of instrumentation are outweighed by the benefits of processing a large number of samples with high accuracy and minimal technician time. For determining serum inorganic iodide (SII) the HPLC assay is the method of choice, because contaminations from the protein bound iodine fraction do not interfere with the detection process. The clinical relevance of the measurement of SII is limited, but allows the calculation of the absolute iodine uptake which has great value in pathophysiologic studies.

Rapid urinary iodide test.

Assessment of iodine deficiency and monitoring of iodine supplementation programs demands rapid, simple and cost-effective methods for the determination of urinary iodide concentrations. We propose a rapid test based on the iodide-catalyzed oxidation of 3,3',5,5'-tetramethylbenzidine by peracetic acid/H2O2 to yield colored products. The color of the chemical reaction is compared with color categories of a pictogram corresponding to three ranges (<10, 10-30, and >>30 microg/100 mL) of iodide concentrations. The test is very easy to perform and does not require any instrumentation or apparatus. Sample preparation is simple and consists in the removal of interfering substances by disposable columns, 65 x 10.5 mm, packed with specifically prepared activated charcoal. For comparison with a reference method for measuring urinary iodide (HPLC), we determined the iodide concentrations of 370 random (untimed) urine samples from consecutive patients by both HPLC and the rapid test. The results obtained by both methods are in close agreement with respect to classification of the samples according to the above three ranges, with a maximum difference of <5% for each range. This rapid test is therefore very well suited to epidemiological surveys of iodine deficiency especially in developing countries.

Methodological and analytical aspects of simple methods for measuring iodine in urine. Comparison with HPLC and Technicon Autoanalyzer II.

This work describes an optimization of a simple photometric determination of iodine concentrations in urine using a modified ceric arsenite method with ammonium persulfate as oxidant. By means of this sensitive method iodine concentrations can be determined in very small specimens (50 microL). Urine samples (105) collected from a mixed population, were analyzed for urine iodine content by the optimized ammonium persulfate method, a Technicon Autoanalyzer II and a paired-ion-RP HPLC. We found that the precision of this optimized ammonium persulfate method yields inter assay CVs of <10% for urinary iodine concentrations >10 microg/dL. Recovery of [123I]iodide added to urine in vitro was 100.9 +/- 2.4%. The detection limit was 0.0029 microg iodine. There was a high correlation between all three methods (r > 0.94 in any case) and the interpretation of the results was consistent. We conclude that this simple, manual ammonium persulfate method is suitable for urinary iodine analysis and can be performed in any routine clinical laboratory.

X-ray fluorescence analysis (XFA) of thyroidal iodine content (TIC) with an improved measuring system.

X-ray fluorescence analysis is based on the principal that the electron structure of stable iodine in the thyroid is excited by Americium-241 gamma rays to emit a characteristic fluorescence radiation which is proportional to the amount of iodine present in the gland. A stationary measuring system consisting of a 11.1 GBq Am-241 source and a high-purity Germanium detector with spectrum analyser has been improved by a PC guided method for sonographic definition of the measuring volume. The lower limit of detectibility of the system corresponds to 0.01 mg of Iodine per ml of thyroid volume; the in vivo precision given as coefficient of variation amounts to 15%. The thyroid is exposed with a radiation dose of 6 microSv per measurement. First studies with this improved system carried out in 50 female volunteers between 20 and 40 years of age with normal thyroid volumes resulted in a mean iodine concentration of the thyroid of 0.665 +/- 0.304 mg/ml. The mean iodine excretion in urine was normal with 10.8 +/- 10.4 microg/dl.

Rapid urinary iodide test.

Assessment of iodine deficiency and monitoring of iodine supplementation programs demand rapid, simple, and cost-effective methods for the determination of urinary iodide concentrations. We propose a semiquantitative rapid test, based on the iodide-catalyzed oxidation of 3,3',5,5'-tetramethylbenzidine by peracetic acid/H2O2, to yield colored products. The color of the chemical reaction is compared with color categories of a pictogram corresponding to three ranges: <100, 100-300, and >300 microg/L (<0.79, 0.79-2.36, and >2.36 micromol/L) of iodide concentrations. The test is very easy to perform and does not require any instrumentation or apparatus. Sample preparation is simple and consists of the removal of interfering substances by disposable columns, 65 x 10.5 mm, packed with purified activated charcoal. For comparison with a reference method for measuring urinary iodide, by high-performance liquid chromatography, we determined the iodide concentrations of 370 random (untimed) urine samples from consecutive patients by both high-performance liquid chromatography and the rapid test. The results obtained by both methods are in close agreement, with respect to classification of the samples according to the above three ranges, with a maximum difference of less than 5% for each range. Median (y) values of a given distribution of urinary iodide concentrations can be calculated from the percent (x) of samples below 100 microg/L (0.79 micromol/L) using the regression equation: y = 179.78 - 1.60x. This rapid test, therefore, is suited to epidemiological surveys of iodine deficiency, especially in developing countries.

Stable isotopes in biosciences, their measurement and models for amino acid metabolism.

In order to follow the movement and quantify the metabolic fates of biologically important molecules in vivo, both tracers and kinetic modeling are required. For the study of intermediary metabolism in children, stable isotopically labeled substrates satisfy both the analytical and ethical requirements for tracer use in children. Stable isotope tracers have been proven safe over more than a half-century of use in humans. In addition, mass spectrometric analysis of stable nuclide molecular position and isotopic enrichment in biological molecules is both highly specific and extraordinarily precise. Using stable isotope data to develop models of biological system dynamics in vivo is an essential element of estimating substrate events that take place in cells or organs otherwise inaccessible for ethical sampling in children. Further, modeling is also a critical component in the development and the testing of hypotheses about the structure of the biological system in question and the mechanisms which control its operational parameters.