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R C Boston

Publications and source records attributed to R C Boston.

At least 19 recordsLinked to original sources

Obesity and diet affect glucose dynamics and insulin sensitivity in Thoroughbred geldings.

Insulin resistance is considered a risk factor in obesity, laminitis, exertional rhabdomyolysis, and osteochondrosis. The objective was to use the minimal model to estimate glucose effectiveness (Sg) and insulin sensitivity (Si) in nonobese to obese horses initially adapted to forage only, then adapted to forage plus supplements rich in starch and sugar (SS) or fiber and fat (FF). Ten Thoroughbred geldings, with BCS of 5 (nonobese), 6 (moderately obese), and 7 to 8 (obese), were adapted to pasture and hay, allocated to two groups, and fed SS or FF in a switch-back design with 8 wk of adaptation. Modified frequent-sampling i.v. glucose tolerance tests were applied after adaptation to forage, SS, and FF. For the tolerance tests, horses were kept in stalls overnight and provided hay, and venous catheters were placed the next morning. Baseline samples were collected, 0.3 g of glucose/kg of BW was given i.v., and blood was sampled at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, and 19 min. At 20 min, 30 mU of insulin/kg of BW was given, followed by sampling at 22, 23, 24, 25, 27, 30, 35, 40, 50, 60, 70, 80, 90, 100, 120, 150, and 180 min. Plasma was analyzed for glucose and insulin, and Si, Sg, acute insulin response to glucose, and the disposition index were calculated. Normality was tested using the Shapiro-Wilk statistic. Body condition effects were analyzed using a mixed model with repeated measures. Diet effects were analyzed using a Wilcoxon signed rank test. The Sg was higher in obese than nonobese (P = 0.003) and moderately obese (P = 0.007) horses; Si was lower in obese than nonobese (P = 0.008) horses, and acute insulin response to glucose was higher in obese than nonobese (P = 0.039) horses. Effects of diet were likely confounded by body condition, but horses had lower Si (P = 0.066) when fed SS compared with FF, especially when nonobese. In conclusion, the minimal model effectively estimated Sg, Si, acute insulin response to glucose, and disposition index in horses. Obese geldings were insulin-resistant and seemed to rely primarily on Sg for glucose disposal. Feeding a diet rich in sugar and starch decreased insulin sensitivity of horses. Maintenance of body condition and avoidance of grain-based meals rich in sugar and starch would be beneficial to decrease the risk of developing insulin resistance and associated metabolic syndromes in horses, especially for horses at risk for these syndromes.

Animal Feed↗

Effect of hydroxyethyl starch infusion on colloid oncotic pressure in hypoproteinemic horses.

OBJECTIVE: To determine the effect of hydroxyethyl starch (HES) on colloid oncotic pressure (pi) during fluid resuscitation of hypoproteinemic horses and to evaluate the clinical usefulness of direct and indirect methods for determination of pi before and after infusion of a synthetic colloid. DESIGN: Prospective clinical study. ANIMALS: 11 hypoproteinemic horses. PROCEDURE: Horses received IV infusions of 8 to 10 ml of a 6% solution of HES/kg (3.6 to 4.5 ml/lb) of body weight during fluid resuscitation. Blood samples were obtained for determination of plasma measured colloid oncotic pressure (pi meas) and plasma total protein and albumin (A) concentrations. Plasma globulin concentration (G) was calculated as the difference between plasma total protein and albumin concentrations. Calculated values for colloid oncotic pressure (piA + G) were determined by use of a predictive nomogram previously developed for horses. RESULTS: There was no significant difference between the means of pi meas and piA + G at the beginning of HES infusion. After HES infusion, the mean of pi meas was increased significantly from baseline for 6 hours. Mean plasma total protein and albumin concentrations and piA + G were decreased significantly from baseline for 24 hours. Differences between mean pi meas and piA + G after HES infusion were significant for 24 hours. CONCLUSIONS AND CLINICAL RELEVANCE: There was good agreement between plasma pi meas and piA + G in blood samples obtained from hypoproteinemic horses immediately before infusion of HES. Use of a predictive nomogram did not, however, account for the oncotic effect of HES. Results of comparison of pi meas to piA + G after HES infusion suggest that a significant oncotic effect was maintained for 24 hours in the study horses.

Animals↗

Physiologic modeling of the intravenous glucose tolerance test in type 2 diabetes: a new approach to the insulin compartment.

The minimal model of Bergman et al has been used to yield estimates of insulin sensitivity (Si) and glucose effectiveness (Sg) in type 2 diabetes by incorporating exogenous insulin protocols into the regular intravenous glucose tolerance test (IVGTT). These estimates, however, are influenced by the degree to which the dose of exogenous insulin is greater than the physiologic response to a glucose load. Moreover, most studies have related to type 2 diabetes subjects whose diabetes was relatively mild in terms of therapeutic requirements. To develop a "minimal disturbance" approach in estimating Si and Sg in type 2 diabetes, we have used a reduced glucose load (200 mg/kg) and a "physiologic" insulin infusion throughout the IVGTT in a series of 8 patients, 5 of whom were insulin-requiring. Data from this approach were analyzed using the modelling program CONSAM to apply the Bergman model, either unmodified (BMM), or incorporating an additional delay element between the plasma and "remote" insulin compartments (MMD). Application of the MMD and extension of the IVGTT from 3 to 5 hours improved successful resolution of Si and Sg from 37.5% (BMM, 3-hour IVGTT) to 100% (MMD, 5-hour IVGTT). Si was reduced in these type 2 diabetes patients compared with normal subjects (1.86 +/- 0.60 v. 8.65 +/- 2.27 min(-1) x microU(-1) x mL x 10(4) P <.01). The results were validated in the type 2 diabetes group using a 2-stage euglycemic clamp ((Si)CLAMP = 2.02 +/- 0.42 min(-1) x microU(-1) x mL x 10(4) P >.4). Sg was not significantly reduced (2.00 +/- 0.25 type 2 diabetes v. 1.55 +/- 0.26 normal min(-1) x 10(2)). Data from a group of normal nondiabetic subjects was then analyzed using the MMD, but this approach did not enhance the fit of the model compared with the BMM. This result indicates that the delay in insulin action in type 2 diabetes represents an abnormality whereby the onset of insulin action cannot be described as a single phase in the transfer of insulin from plasma to the remote compartment. It is postulated that the physiologic basis for this delayed action may relate to transcapillary endothelial transfer of insulin, this process limiting the rate of onset of insulin action.

Blood Glucose↗

Obese premenopausal African-American women with normal and impaired glucose tolerance have a similar degree of insulin resistance but differ in beta-cell function.

OBJECTIVE: To determine whether insulin resistance and secretion differ in obese premenopausal African-American women with and without glucose intolerance. RESEARCH DESIGN AND METHODS: A total of 63 women underwent oral glucose tolerance tests (OGTTs). A total of 48 women underwent frequently sampled intravenous glucose tolerance tests (FSIGTs). Insulin resistance was determined from the insulin sensitivity index (S(I)) from the FSIGT. Insulin secretion during the OGTT was determined by (I(30 min) - I(0 min))/(G(30 min) - G(0 min)) and during the FSIGT by the acute insulin response to glucose (AIRg). The disposition index, the product of AIRg and S(I), was used to determine whether AIRg was adequate to compensate for insulin resistance. Statistical analyses included one-way analysis of variance with Bonferroni corrections for multiple comparisons and regression analyses. RESULTS: The women were divided into three groups: nonobese glucose tolerant (n = 32), obese glucose tolerant (n = 17), and obese glucose intolerant (n = 14). The BMI of the three groups were 24.8 +/- 2.3, 37.8 +/- 5.5, and 42.0 +/- 7.6 kg/m(2) (mean +/- SD), respectively (P < 0.0001). The ages of the three groups were 34.9 +/- 8.4, 32.1 +/- 5.0, and 41.1 +/- 6.3 years (P = 0.011). S(I) was higher in the nonobese women than in the obese glucose-tolerant women (3.99 +/- 1.44 vs. 2.66 +/- 2.14 l x mU(-1) x min(-1), P = 0.03). S(I) was similar in the obese glucose-intolerant and obese glucose-tolerant women (2.12 +/- 1.27 vs. 2.66 +/- 2.14 l x mU(-1) x min(-1), P = 0.9). OGTT showed that insulin secretion was lower in the glucose-intolerant than the obese glucose-tolerant women (1.73 +/- 1.38 vs. 3.62 +/- 2.11, P = 0.005). FSIGT showed that AIRg was not significantly lower in glucose-intolerant than in obese glucose-tolerant women (807 +/- 665 vs. 1,253 +/- 655 mU x l(-1) x min, P = 0.078). The disposition index was lower in glucose-intolerant than in obese glucose-tolerant women (1,324 +/- 1,061 vs. 2,656 +/- 1,415, P = 0.014). CONCLUSIONS: Obese premenopausal African-American women with and without glucose intolerance have a similar degree of insulin resistance but differ in insulin secretion.

Absorptiometry, Photon↗

Effects of enrofloxacin and magnesium deficiency on matrix metabolism in equine articular cartilage.

OBJECTIVE: To investigate the effects of enrofloxacin and magnesium deficiency on explants of equine articular cartilage. SAMPLE POPULATION: Articular cartilage explants and cultured chondrocytes obtained from adult and neonatal horses. PROCEDURE: Full-thickness explants and cultured chondrocytes were incubated in complete or magnesium-deficient media containing enrofloxacin at concentrations of 0, 1, 5, 25, 100, and 500 microg/ml. Incorporation and release of sulfate 35S over 24 hours were used to assess glycosaminoglycan (GAG) synthesis and degradation. An assay that measured binding of dimethylmethylene blue dye was used to compare total GAG content between groups. Northern blots of RNA from cultured chondrocytes were probed with equine cDNA of aggrecan, type-II collagen, biglycan, decorin, link protein, matrix metalloproteinases 1, 3, and 13, and tissue inhibitor of metalloproteinase 1. RESULTS: A dose-dependent suppression of 35S incorporation was observed. In cartilage of neonates, 35S incorporation was substantially decreased at enrofloxacin concentrations of 25 mg/ml. In cartilage of adult horses, 35S incorporation was decreased only at enrofloxacin concentrations of > or =100 microg/ml. Magnesium deficiency caused suppression of 35S incorporation. Enrofloxacin or magnesium deficiency did not affect GAG degradation or endogenous GAG content. Specific effects of enrofloxacin on steady-state mRNA for the various genes were not observed. CONCLUSION AND CLINICAL RELEVANCE: Enrofloxacin may have a detrimental effect on cartilage metabolism in horses, especially in neonates.

Age Factors↗

Early risk factors for increased adiposity: a cohort study of African American subjects followed from birth to young adulthood.

BACKGROUND: Obesity is an increasing concern in the United States. Effective prevention of obesity requires the risk factors to be well defined. African Americans have a high risk of obesity. OBJECTIVE: The objective of this study was to identify risk factors, present at birth, for increased adiposity in adulthood in an African American population. DESIGN: In this retrospective analysis of a prospective cohort study, anthropometric and socioeconomic variables were collected at birth. A representative sample of 447 African American subjects was followed up until young adulthood, when skinfold thickness was measured. Associations between the independent variables and increased adiposity (skinfold thickness above the 85th percentile) were explored by using unadjusted and adjusted analyses. RESULTS: Three variables measured at birth were independently associated with adiposity in young adulthood, explaining 12% of the variance. The odds ratios (with 95% CIs) of these variables for increased adiposity were 2.7 (1.2, 6.2) for female sex, 4.0 (1.4, 11. 2) for first-born status, and 1.15 (1.06, 1.25) for each unit increment in maternal prepregnancy body mass index (BMI; in kg/m(2)). After adjustment for these variables, birth weight for gestational age and socioeconomic variables were not associated with adiposity. CONCLUSIONS: This cohort study of African American subjects was the first to identify first-born status as an independent risk factor for increased adiposity in adulthood in a US population. The results of the study strengthen previous reports of the effect of female sex and maternal BMI on adulthood obesity. Identification of risk factors early in life may help target prevention toward high-risk children and allow healthy lifestyles to be established before the onset of obesity.

Adolescent↗

Gait and speed as exercise components of risk factors associated with onset of fatigue injury of the third metacarpal bone in 2-year-old Thoroughbred racehorses.

OBJECTIVE: To determine the degree to which components of the training program of 2-year-old Thoroughbred racehorses influence their susceptibility to fatigue injury of the third metacarpal bone (bucked shins). ANIMALS: 226 two-year-old Thoroughbred racehorses. PROCEDURE: Daily training information and health reports on 2-year-old Thoroughbreds were compiled from records provided from 5 commercial stables. For each horse, data (exercise variables) were collected that comprised distance jogged (approx speed of 5 m/s), galloped (approx 11 m/s), and breezed (approx 15 to 16 m/s) until a single instance of bucked shins was reported. Data were coded for analysis using cross-tabulation, graphic, and survival techniques. RESULTS: Of 226 horses, 56 had bucked shins, 9 completed the observation period without bucked shins, and 161 were lost to follow-up. Distinct training strategies were used at stables resulting in significantly different survival profiles among stables. Mean (+/- SD) allocation of exercise to breezing was 0.15 +/- 0.13 miles/wk (maximum, 0.64 miles/wk), to galloping was 4.47 +/- 1.52 miles/wk (maximum, 9.56 miles/wk), and to jogging was 2.34 +/- 1.70 miles/wk (maximum, 8.53 miles/wk). Survival (ie, lack of bucked shins during 1 year of monitoring) was found to be significantly reduced by exercise allocation to breezing, significantly increased by exercise allocation to galloping, and uninfluenced by exercise allocation to jogging. The log of the hazard ratio was reduced by 4.2 +/- 1.5/mile breezed and increased by 0.3 +/- 0.1/mile galloped. CONCLUSIONS AND CLINICAL RELEVANCE: Relationships between different gaits and speeds in the training regimen influence the incidence of bucked shins. To reduce the incidence of bucked shins, trainers should consider allocating more training effort to regular short-distance breezing and less to long-distance galloping.

Animals↗

Effect of daily floor treatment with sodium bisulfate on the fly population of horse stalls.

OBJECTIVE: To determine application rate and effectiveness of sodium bisulfate to decrease the fly population in a horse barn environment. SAMPLE POPULATION: 12 privately owned farms in southeastern Pennsylvania. PROCEDURE: Application rates of sodium bisulfate were approximately 2.3 kg/stall, 1.1 kg/stall, and 0.5 kg/stall. Two or 3 stalls were treated, and 1 or 2 stalls were not treated (control stalls) at each farm. Farm personnel applied sodium bisulfate in treated stalls daily for 7 days. Fly tapes were hung from the same site in treated and control stalls. After 24 hours, the fly tape was removed, flies adhering to the sticky surface were counted and recorded, and a new fly tape was hung. This procedure was repeated daily during each of the testing periods. RESULTS: Following the application of 2.3 kg of sodium bisulfate/stall, the numbers of flies collected on the fly tape were significantly decreased in treated stalls, compared with control stalls during the same time periods on 9 of the 12 farms evaluated. Following the application of 1.1 kg of sodium bisulfate/stall, fly numbers were significantly decreased in treated stalls on 6 of the 9 farms evaluated. Following the application of 0.5 kg of sodium bisulfate/stall, fly numbers were significantly decreased in the treated stalls on 3 of the 4 farms evaluated. CONCLUSIONS AND CLINICAL RELEVANCE: Our findings suggest that sodium bisulfate would be effective for fly control in horse barns.

Animals↗

Integrated MRI assessment of regional function and perfusion in canine myocardial infarction.

A single integrated examination using regional measurements of perfusion from contrast-enhanced MRI and three-dimensional (3D) strain from tissue-tagged MRI was developed to differentiate infarcted myocardium from adjacent tissue with functional abnormalities. Ten dogs were studied at baseline and 10 days after a 2-hour occlusion of the left anterior descending coronary artery (LAD). Strain was determined using a 3D finite element model. Two-dimensional measurements of hypoenhancing regions were highly correlated with myocardial viability (r = 0.96). Signal intensity versus time curves obtained from contrast-enhanced MRI were used for quantitative perfusion analysis. The remote and adjacent noninfarcted tissue of the dogs with LAD occlusion, as well as the infarcted tissue, exhibited abnormal deformation patterns as compared to normal dogs (positive predictive value (PPV) of strain determination of infarction = 66%). Integration of contrast-enhanced MRI results with 3D strain analysis enabled the delineation of the myocardial infarction (PPV = 100%) from functionally compromised myocardium. This integrated cardiac examination shows promise for noninvasive serial assessment of potentially jeopardized noninfarcted myocardium to study the process of infarct remodeling and expansion.

Animals↗

Distributing working versions of published mathematical models for biological systems via the Internet.

Mathematical models are useful tools for investigating complex systems. By representing physiological systems as models, theories can be tested quantitatively against data from the system. Models can be used to explore new theories prior to experimentation and to design studies to optimize experimental resources. They can also be used as teaching tools to illustrate physiochemical principles. In spite of their usefulness and the time invested in developing models, published models are often underused due to the difficulty in obtaining working versions of the model. To address this problem we have designed a library for mathematical models of biological systems on the Internet. The library contains published models of biological systems in formats compatible with several modeling packages, from the fields of physiology, metabolism, endocrinology, biochemistry, and chemistry. The models can be viewed graphically, model solutions can be viewed as plots against data, and models can be downloaded to be run with software on the user's own system. The address of the library is: http://biomodel.georgetown.edu/model/ Investigators are invited to submit working versions of published models to the library. Models can be submitted electronically at the time a manuscript is accepted for publication. As journals go online, articles containing models can be linked to working versions of the models in the library. By increasing access to working versions of models, more of the investment in kinetic studies and model development can be realized.

Computer Simulation↗

The effect of norepinephrine on insulin secretion and glucose effectiveness in non-insulin-dependent diabetes.

It has previously been shown that in normal subjects, physiological elevation of norepinephrine (NE) impairs insulin sensitivity (Si) but does not influence insulin secretion. The aim of this study was to determine the effect of short-term physiological elevation of NE on insulin secretion, Si, and glucose-mediated glucose disposal, or the glucose effectiveness index (Sg), in non-insulin-dependent diabetes mellitus (NIDDM). Two intravenous glucose tolerance tests (IVGTTs) were performed in eight well-controlled NIDDM patients, using a supplemental exogenous insulin infusion to achieve an approximation of normal endogenous insulin secretion. The IVGTTs were performed in random order after 30 minutes of either the saline (SAL) or NE (25 ng/kg/min) infusions, which were continued throughout the 3-hour IVGTT. Sg and Si were estimated by minimal model analysis of the IVGTT data as previously described. Plasma C-peptide was used to estimate insulin secretion rate using the ISEC program. NE infusion produced approximately a threefold increase in plasma NE, associated with (1) a significant reduction in glucose disposal ([KG] SAL v NE, 0.73 +/- 0.06 v 0.61 +/- 0.06 x 10(-2).min-1, P < .05), (2) no reduction in Si (2.33 +/- 0.8 v 2.62 +/- 0.9 x 10(-4).min-1/mU/L, NS), (3) a reduced mean second-phase insulin secretion rate (1.21 +/- 0.19 v 1.01 +/- 0.16 x 10(-3) pmol/kg/min per mmol/L glucose, P < .05), (4) a significant increase in Sg (0.89 +/- 0.08 v 1.63 +/- 0.2 x 10(-2).min-1, P < .05), and (5) a corresponding increase in glucose effectiveness at zero insulin ([GEZI] 0.55 +/- 0.13 v 1.30 +/- 0.33 x 10(-2).min-1, P < .05). These results show that in contrast to normal subjects, physiological elevation of NE in NIDDM does not result in a reduction in Si, but causes a reduction in glucose disposal related to inhibition of insulin secretion that is only partially compensated for by increased Sg.

Adult↗

A compartmental model depicting short-term kinetic changes in selenium metabolism in ewes fed hay containing normal or inadequate levels of selenium.

Changes in Se metabolism were studied in ewes fed hay containing normal or inadequate levels of Se. After intravenous injection of 75Se-sodium selenite, blood, feces and urine were collected at different times, and the concentrations of labeled and unlabeled Se were determined. Ewes were killed 1, 5, 9 or 14 d after tracer injection, and tissues were obtained for determination of radioactivity and Se concentration. The data were fitted to a compartmental model using the SAAM/CONSAM computer program, and kinetic parameters and steady-state transport rates were estimated. Daily Se intake (Vi) and fecal excretion (VF) were significantly (P < 0.001) higher in the ewes fed normal hay (6.06 +/- 1.09 and 3.36 +/- 0.88 mumol/d, respectively) than in those fed Se-deficient hay (0.64 +/- 0.18 and 0.26 +/- 0.15 mumol/d). The net absorption (Va) of Se was significantly higher in ewes fed normal hay [3.19 +/- 0.82 mumol/d by the balance method, Va = Vi-(VF -Vf) (Vf = endogenous fecal Se) and 1.05 +/- 0.38 mumol/d by using the model (plasma entry rate, U(1))] than in those fed hay deficient in Se [0.57 +/- 0.33 mumol/d (balance) and 0.28 +/- 0.08 mumol/d (model)]. The efficiency of absorption [alpha = U(1) divided by Vi] was significantly higher (0.46 +/- 0.19) in ewes fed Se-deficient hay than in those fed normal hay (0.18 +/- 0.09). Simultaneous fitting of the tracer data of both the groups showed that changes in hepatic extraction and urinary and fecal excretion were sufficient and necessary to account for the kinetic differences observed between treatments.

Animals↗

A compartmental model predicts that dietary potassium affects lithium dynamics in rats.

Lithium is the treatment of choice for manic depression, but therapy often results in nephrogenic diabetes insipidus and lithium intoxication. To investigate the effects of dietary potassium on potential side effects of lithium therapy, a mathematical model was built using the modeling program SAAM (Simulation, Analysis, And Modeling). Experimental data modeled were from adult male Sprague-Dawley rats fed diets with or without lithium and one of three levels of potassium for 17 d. A five-compartment model of lithium dynamics was built that was consistent with data from rats fed a lithium-containing diet adequate in potassium. This model was then compared with data from rats fed the other two lithium-containing diets. The model predicts that both the fractional transfer coefficient and rate of transport of lithium to the serum compartment from the kidney compartment are lower in rats fed the potassium-adequate diet than in those fed the potassium-deficient diet, and even lower in those fed the potassium-supplemented diet. In addition, fractional transfer coefficients into the serum compartment from the sampled and simulated tissue compartments changed differently with time depending on the amount of dietary potassium. The model also predicts that there would be less accumulation of lithium in the kidney, sampled tissue and simulated tissue compartments with supplemental dietary potassium. The model suggests that potassium supplementation, after a 7-d delay, protects against nephrogenic diabetes insipidus and the potentially toxic accumulation of lithium by decreasing the reabsorption of lithium from the kidneys and increasing lithium efflux from the tissues.

Absorption↗

A modelling procedure for the analysis of dynamic drug--DNA interactions probed during active transcription of the DNA.

A multicompartment simulation analysis (CONSAM) has been used to describe the in vitro inhibition of transcription of DNA by echinomycin. The model assumes that at all drug blockage sites the fractional amount of blocked RNA polymerase is defined by the relative drug occupancy at that site (and is released at a rate defined by the drug dissociation rate), with all remaining enzyme being rapidly transferred past that site. The solution to the 48 parameters (three per drug site, 16 sites), which fully described the echinomycin-DNA transcription data set, can readily be accomplished without manual intervention within an hour on a MS-DOS, 486D-based microcomputer, compared to several months for a similar solution by Monte-Carlo simulation (requiring repeated intervention). The adequacy of the parameters to describe the model was confirmed by four independent criteria. The approach is applicable to the analysis of any enzyme system where an inhibitor of any type (interacting in either a reversible or irreversible manner) prevents the processive movement of enzyme along the template.

Base Sequence↗

Clearance from plasma of triacylglycerol and cholesteryl ester after intravenous injection of chylomicron-like lipid emulsions in rats and man.

Chylomicrons transport fat and cholesterol via lymphatic vessels from the intestine into the bloodstream. The understanding of the metabolism of chylomicrons in man has been slowed by the difficulty of obtaining lymph chylomicrons for experimental studies. Acceptable methods for the study of chylomicron clearance in man are required, because the metabolism of chylomicrons may be abnormal in diseases such as diabetes mellitus. Metabolism of chylomicrons may also play a role in the development of atherosclerosis. In the present work, lipid emulsions were used as a physical model of chylomicrons. Triacylglycerol-rich lipid emulsions labelled with tracer amounts of radioactive triolein and cholesteryl oleate were prepared by sonication and purified by density gradient ultracentrifugation, then injected into unanaesthetized rats and normal human subjects. Plasma radioactivities were measured for 30 min in rats and 90 min in human subjects. Rat lymph chylomicrons were also injected into rats for comparison with the clearance of the lipid emulsions. The plasma clearance data for triacylglycerols and cholesteryl esters were fitted with a kinetic model using the SAAM/CONSAM programs. Multiple studies analysis of the individual studies in each group was used to obtain estimates of the parameter average values and variabilities. The plasma residence times of the lipid labels were obtained from the fitted clearance data. Our results suggest that information about chylomicron metabolism in man can be obtained by analysis of the plasma clearance data following the injection of suitably labelled chylomicron-like lipid emulsions. Our data provide a baseline for comparisons with individuals having abnormalities of lipid metabolism or risk factors for arteriosclerosis.

Animals↗

Application of models to determination of nutrient requirements: experimental techniques employing tracers.

This paper concerns some issues involved in the design of tracer experiments for the development of whole-body compartmental models of nutrient metabolism. It focuses on tracer administration protocol, use of multiple tracers, sampling strategy, measurement types and experiment duration in a pragmatic approach to obtaining data suitable for analysis and interpretation with use of models.

Animals↗

A modified minimal model analysis of insulin sensitivity and glucose-mediated glucose disposal in insulin-dependent diabetes.

Although glucose utilization is impaired in insulin-dependent diabetes mellitus (IDDM), it is unclear whether this is due to reductions in insulin sensitivity (Si) and/or glucose-mediated glucose disposal (SG). The minimal model of Bergman et al can be applied to a frequently sampled intravenous glucose tolerance test (FSIGT) to simultaneously estimate Sl and SG, but cannot accommodate data from diabetics. Exogenous insulin approximating the normal pattern of insulin secretion was infused during FSIGTs in eight young non-obese C-peptide-negative IDDM subjects, but with the total dose modified to achieve sufficient glucose disappearance rates (KG) to allow analysis of data. The minimal model was modified to model the effects of the exogenous insulin on glucose kinetics to estimate SI and SG. Despite deliberately achieving supranormal plasma-free insulin levels during the FSIGT ("first-phase insulin" = 62 +/- 9 SE mU/L; "second phase insulin" = 34 +/- 9 mU/L), the diabetics showed low-normal KG values (1.3 +/- 0.29 min-1 X 10(2). Using the model, good parameter resolution (fractional SD [FSD] less than .5) was achieved (IDDM v controls: SI = 2.5 +/- 0.6 v 8.3 +/- 1.5 min-1.mU-1.L-1 X 10(4); SG = 1.6 +/- 0.5 v 2.6 +/- 0.2 min-1 X 10(2); P less than .05). This reduction in SG was confirmed in the same IDDM subjects by FSIGT during basal insulin infusion only (SG = 1.0 +/- 0.3 min-1 X 10(2)).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A new approach to the quantitative estimation of nitrogen metabolic pathways in the rumen.

Rumen nitrogen metabolism values were estimated by the use of a single injection of 15(NH4)2SO4 into the rumen of sheep and consecutive 15N enrichment measurements in the rumen ammonia pool, rumen non-NH3-N (NAN) pool, rumen purine pool and blood urea-N (BUN) pool for a period of 24 h. Synthesis and degradation of N compounds in the rumen and passage of N to and from the rumen were evaluated on a chemical rather than a microbial basis; microbial fractions were not separated. This model was examined in two experiments. In Expt 1 a ram (55 kg) was given a semi-synthetic diet (1067 g dry matter (DM), 22.8 g N) in which soya-bean meal provided over 90% of the N. In Expt 2, two rams (45 kg) were given in three consecutive periods a semi-synthetic basal diet containing: (1) roasted soya-bean meal (SBM, 725 g DM, 14.8 g N/d); or (2) fishmeal (FM, 728 g DM, 15.5 g N/d); or (3) raw soya-bean meal (RSBM, 724 g DM, 13.8 g N/d). In all these rations, the main protein source provided over 90% of the N. In Expt 1, 68.3% of N intake was degraded directly to NH3 in the rumen, 21.2% escaped rumen degradation and 10.5% was incorporated into stable N compounds in the rumen. Net NH3 transfer to the blood was 30.4%, NH3 flow from the rumen was 6.6% and rumen NAN output was 63% of N intake. In Expt 2, rumen NAN output was larger (7.67, 14.36 and 8.89 g N/d for diets containing SBM, FM and RSBM respectively; P less than 0.05) and net NH3 loss to the blood was smaller (6.1, 0.39 and 4.17 g N/d for diets SBM, FM and RSBM respectively; P less than 0.05) for diet FM as compared with the soya-bean diets. The percentage of rumen NAN that was synthesized from NH3 was larger for diet RSBM (36.4, 40.3 and 49.1 for diets SBM, FM and RSBM respectively; P less than 0.05) than for the other two rations. NH3 pool sizes (g N) were 0.463, 0.385 and 0.301 for diets SBM, FM and RSBM respectively (P less than 0.05), while their hourly turnover rates were 15.8, 26.1 and 5.12 for diets SBM, FM and RSBM respectively (P less than 0.01), indicating no correlation between pool size and its turnover rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Ammonia↗