Hematological and Biochemical Assessment of Two Species of Freshwater Mussels, Quadrula quadrula and Amblema plicata, Following Translocation.

Nondestructive, sublethal, and sensitive health monitoring tools are needed to assess the health of freshwater mussels (family Unionidae). Recent developments to standardize hemocyte characterization have assisted in the hematologic assessment of wild and captive freshwater mussels. In this study, preliminary baseline hematological reference ranges were established for wild mapleleaf mussels Quadrula quadrula (n = 14) and threeridge mussels Amblema plicata (n = 20) collected from the Muskingum River in Devola, Ohio. Mussels were collected from the wild, and hemolymph was sampled from each mussel in the field upon capture (baseline sample). They were then transported live to a propagation facility. Subsequent hemolymph samples were collected at 2 and 4 weeks and quarterly thereafter for 11 months following translocation. Hemocyte counts, hemocyte morphology, and hemolymph chemistry (Na+ , Cl- , Mg2+ , P3- , K+ , Ca2+ , glucose, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase]) were measured from each sample on each sampling occasion. Hemocyte counts were consistently greater in Q. quadrula than in A. plicata following transfer to captivity. Baseline hemocyte morphology and hemolymph chemistry varied between species. This study provides a foundation of reference ranges for hemocyte characterization for Q. quadrula, and A. plicata and a preliminary understanding of how hemocyte character might be expected to change when wild mussels are translocated into captivity, and thus be a useful technique for monitoring the health of freshwater mussels.

Machine learning based unfolding of x-ray spectra from filter stack spectrometer data.

We demonstrate the application of neural networks to perform x-ray spectra unfolding from data collected by filter stack spectrometers. A filter stack spectrometer consists of a series of filter-detector pairs, where the detectors behind each filter measure the energy deposition through each layer as photo-stimulated luminescence (PSL). The network is trained on synthetic data, assuming x-rays of energies <1 MeV and of two different distribution functions (Maxwellian and Gaussian) and the corresponding measured PSL values obtained from five different filter stack spectrometer designs. Predicted unfolds of single distributions are near identical reproductions of the ground truth spectra, with differences in the values lower than 20% at the higher energy end in some cases. The neural network has also demonstrated robustness to experimental measurement errors of <5% and some capability of performing unfolds for linear combinations of the two distributions without previous training. The network can perform unfolds at rates >1 Hz, ideal for application to some high-repetition-rate systems.

Reduced-order model to approximate response matrices for filter stack spectrometers.

We present a reduced-order model to calculate response matrices rapidly for filter stack spectrometers (FSSs). The reduced-order model allows response matrices to be built modularly from a set of pre-computed photon and electron transport and scattering calculations through various filter and detector materials. While these modular response matrices are not appropriate for high-fidelity analysis of experimental data, they encode sufficient physics to be used as a forward model in design optimization studies of FSSs, particularly for machine learning approaches that require sampling and testing a large number of FSS designs.

Robust unfolding of MeV x-ray spectra from filter stack spectrometer data.

We present an inversion method capable of robustly unfolding MeV x-ray spectra from filter stack spectrometer (FSS) data without requiring an a priori specification of a spectral shape or arbitrary termination of the algorithm. Our inversion method is based upon the perturbative minimization (PM) algorithm, which has previously been shown to be capable of unfolding x-ray transmission data, albeit for a limited regime in which the x-ray mass attenuation coefficient of the filter material increases monotonically with x-ray energy. Our inversion method improves upon the PM algorithm through regular smoothing of the candidate spectrum and by adding stochasticity to the search. With these additions, the inversion method does not require a physics model for an initial guess, fitting, or user-selected termination of the search. Instead, the only assumption made by the inversion method is that the x-ray spectrum should be near a smooth curve. Testing with synthetic data shows that the inversion method can successfully recover the primary large-scale features of MeV x-ray spectra, including the number of x-rays in energy bins of several-MeV widths to within 10%. Fine-scale features, however, are more difficult to recover accurately. Examples of unfolding experimental FSS data obtained at the Texas Petawatt Laser Facility and the OMEGA EP laser facility are also presented.

Impact of two types of complete pelleted, wild ungulate feeds and two pelleted feed to hay ratios on the development of urolithogenic compounds in meat goats as a model for giraffes.

Urolith formation has been documented in giraffes and goats. As research in giraffes poses logistical challenges, 16 buck goats were used as a model. The impact of two commercially available, pelleted feeds used for giraffes, ADF-16 and Wild Herbivore (WH), as well as the impact of alfalfa hay and pellet proportions (20% hay:80% pellets, 80P or 80% hay:20% pellet, 20P) on the formation of urolithogenic precursors in goat urine was accomplished in a 2 × 2 factorial balance study. Complete diets contained 0.60, 0.32, 0.35 and 0.26% phosphorus (P) with calcium:P ratios of 1.60, 4.16, 3.06 and 5.23, for 80P-ADF-16, 20P-ADF-16, 80P-WH and 20P-WH respectively. Total faeces and urine were collected over two 5-day periods to assess N and mineral balance. Fresh urine samples were collected and evaluated microscopically for urolithic crystal content. Urinary nitrogen (N) was lower and N retention was higher in goats fed 80P diets (p < 0.05). Intake of P was greatest for goats fed 80P-ADF-16; however, urinary P excretion and P retention were not affected by treatment. Crystal scores were higher in animals receiving 80P diets (p = 0.08), with crystals being composed predominantly of calcium phosphate. Urine pH was alkaline (>8) for all treatments. Urinary P concentration, a risk factor for urolithiasis, was highest (p ≤ 0.06) in the 80P-ADF-16 treatment (0.38 vs. 0.01, 0.02 and 0.04 mg/dl for 20P-ADF-16, 80P-WH and 20P-WH respectively), reflecting its highest dietary P level. Further investigation is recommended to determine the long-term effects of these diets on urolithogenic compound formation.

Gender differences in binge eating and behavioral correlates among college students.

PURPOSE: The purpose of this study was to investigate gender differences in binge eating and associated behavioral correlates in college students. METHODS: A webbased survey was conducted with 2073 students (mean age 19.8 yr; range 18-23 yr). Multiple logistic regression was used to calculate odds ratios and 95% confidence intervals for the factors associated with binge eating. RESULTS: Twenty-nine percent of students reported recent bingeing. Factors associated with binge eating included being female, having a higher body mass index, current tobacco use, and exercising to lose weight. Women were more likely to binge eat (73.8%; χ(2)=32.3; p≤0.001), report loss of control (45%; χ(2)=16.3; p≤0.001), self induced vomiting (20.7%; χ(2)=15.9; p≤0.001), and laxative use (6.7%; χ(2)=8.93; p≤0.001). CONCLUSIONS: Results generated from this study suggest that gender-disparate behaviors are potential targets for future tailored interventions.

Measurement of the positive muon lifetime and determination of the Fermi constant to part-per-million precision.

We report a measurement of the positive muon lifetime to a precision of 1.0 ppm; it is the most precise particle lifetime ever measured. The experiment used a time-structured, low-energy muon beam and a segmented plastic scintillator array to record more than 2×10(12) decays. Two different stopping target configurations were employed in independent data-taking periods. The combined results give τ(µ(+)) (MuLan)=2 196 980.3(2.2) ps, more than 15 times as precise as any previous experiment. The muon lifetime gives the most precise value for the Fermi constant: G(F) (MuLan)=1.166 378 8(7)×10(-5) GeV(-2) (0.6 ppm). It is also used to extract the µ(-)p singlet capture rate, which determines the proton's weak induced pseudoscalar coupling g(P).

Evaluating temporal patterns of metals concentrations in floodplain lakes of the Athabasca Delta (Canada) relative to pre-industrial baselines.

Sediment quality monitoring is widely used to quantify extent of river pollution, but requires knowledge of pre-disturbance conditions in the potentially altered landscape. This has long been identified as a critical aspect to develop for addressing concerns of river pollution in the Alberta Oil Sands Region. Here, we use analyses of sediment cores from eight floodplain lakes spanning a 67 river-km transect across the Athabasca Delta to define pre-1920 (pre-industrial) baseline concentrations for vanadium and five primary pollutants. We then evaluate if sediment metals concentrations have become enriched above baseline since onset of oil sands development and other industrial activities. Results demonstrate no enrichment of metals concentrations (except zinc at one lake) and absence of consistent temporal increases above pre-industrial baselines. Thus, natural processes continue to dominate metal deposition in floodplain lakes of the Athabasca Delta -- an important finding to inform stewardship decisions. The pre-1920 metals concentrations baselines offer a useful tool for ongoing sediment monitoring in aquatic ecosystems of the Athabasca Delta.

beta1- and beta2-Adrenergic receptors in rat cerebral cortex are independently regulated.

Repeated administration of the tricyclic antidepressant desmethylimipramine to adult rats for 10 days caused a 40% decrease in the density of beta1-adrenergic receptors in the cerebral cortex but had no effect on the density of beta2-adrenergic receptors. Conversely, destruction of noradrenergic neurons by administration of 6-hydroxydopamine to neonatal rats caused a 64% increase in the density of beta1-adrenergic receptors in adult cerebral cortex with no change in the density of beta2-adrenergic receptors. These results suggest that the beta-adrenergic receptors in rat cortex involved in neuronal function are primarily of the beta1 subtype.

beta-Adrenergic receptor involvement in 6-hydroxydopamine-induced supersensitivity in rat cerebral cortex.

The intraventricular administration of 6-hydroxydopamine, a procedure which destroys noradrenergic nerve terminals in the central nervous system, caused an increase in the density of beta-adrenergic receptors in rat cerebral cortex, without affecting their affinity for isoproterenol. The results suggest that changes in the density of adrenergic receptors are involved in 6-hydroxydopamine-induced supersensitivity at central noradrenergic synapses.

Effects of cyclosporine immunosuppression in insulin-dependent diabetes mellitus of recent onset.

Type I diabetes may be an autoimmune disorder, although the evidence is largely circumstantial. The natural history of the disease after diagnosis includes partial remission in most patients, but only about 3 percent achieve transient insulin independence. beta Cell function, as indicated by the plasma concentration of C-peptide, is lost over 6 to 30 months and islet cell antibodies disappeared over 1 to 2 years. This article describes a pilot study in which 41 patients were treated with the immunosuppressive agent cyclosporine for 2 to 12 months. Of 30 patients treated within 6 weeks of diagnosis, 16 became insulin independent with concentrations of plasma C-peptide in the normal range and decreasing titers of islet cell antibodies. Of 11 patients who entered the study 8 to 44 weeks after diagnosis, two achieved this state. These results indicate that a controlled trial of the effects of cyclosporine in type I diabetes should be conducted.

Adiposopathy and bariatric surgery: is 'sick fat' a surgical disease?

OBJECTIVE: To review how bariatric surgery in obese patients may effectively treat adiposopathy (pathogenic adipose tissue or 'sick fat'), and to provide clinicians a rationale as to why bariatric surgery is a potential treatment option for overweight patients with type 2 diabetes, hypertension, and dyslipidaemia. METHODS: A group of clinicians, researchers, and surgeons, all with a background in treating obesity and the adverse metabolic consequences of excessive body fat, reviewed the medical literature regarding the improvement in metabolic disease with bariatric surgery. RESULTS: Bariatric surgery improves metabolic disease through multiple, likely interrelated mechanisms including: (i) initial acute fasting and diminished caloric intake inherent with many gastrointestinal surgical procedures; (ii) favourable alterations in gastrointestinal endocrine and immune responses, especially with bariatric surgeries that reroute nutrient gastrointestinal delivery such as gastric bypass procedures; and (iii) a decrease in adipose tissue mass. Regarding adipose tissue mass, during positive caloric balance, impaired adipogenesis (resulting in limitations in adipocyte number or size) and visceral adiposity are anatomic manifestations of pathogenic adipose tissue (adiposopathy). This may cause adverse adipose tissue endocrine and immune responses that lead to metabolic disease. A decrease in adipocyte size and decrease in visceral adiposity, as often occurs with bariatric surgery, may effectively improve adiposopathy, and thus effectively treat metabolic disease. It is the relationship between bariatric surgery and its effects upon pathogenic adipose tissue that is the focus of this discussion. CONCLUSIONS: In selective obese patients with metabolic disease who are refractory to medical management, adiposopathy is a surgical disease.

Artificial insemination in deer and non-domestic bovids.

Artificial insemination technology has revolutionized the domestic cattle breeding industry and allowed for the dissemination of valuable genetics worldwide. This technology has been adapted for use in many other taxa for the conservation of threatened and endangered species, but its use for the genetic management of small populations of deer, antelope and other non-domestic bovids has met numerous challenges and limited success. In practice, adaptation of domestic bovine AI protocols to other artiodactylids for genetic management has been limited by: (1) a lack of understanding of species-specific reproductive characteristics; (2) the inability to minimize handling stress; (3) pregnancy losses; and (4) regulatory challenges in semen importation. To date, AI protocols have been developed for seven species of cervid and 14 species of non-domestic bovids; recent developments in this technology has allowed greater use of AI for dissemination of genetics in farmed deer species. However, despite decades of research in the use of assisted reproduction for the conservation of antelope and other non-domestic bovids, even this simplest technique has not been used repeatedly for genetic management.

Genes and networks expressed in perioperative omental adipose tissue are correlated with weight loss from Roux-en-Y gastric bypass.

CONTEXT: Gastric bypass surgery is the most commonly performed bariatric surgical procedure in the United States. Variable weight loss following this relatively standardized intervention has been reported. To date, a method for reliable profiling of patients who will successfully sustain weight loss for the long term has not been established. In addition, the mechanisms of action in accomplishing major weight loss as well as the explanation for the variable weight loss have not been established. OBJECTIVE: To examine whether gene expression in perioperative omental adipose is associated with gastric bypass-induced weight loss. DESIGN: Cross-sectional study of gene expression in perisurgical omental adipose tissues taken/available at the time of operation and total excess weight loss (EWL). SUBJECTS: Fifteen overweight individuals who underwent Roux-en-Y gastric bypass (RYGB) surgery at the University of California Davis Medical Center (BMI: 40.6-72.8 kg/m(2)). MEASUREMENTS: Body weight before and following weight stabilization 18-42 months after surgery. Perioperative omental adipose RNA isolated from 15 subjects was hybridized to Affymetrix HG-U133A chips for 22,283 transcript expression measurements. RESULTS: Downstream analysis identified a set of genes whose expression was significantly correlated with RYGB-induced weight loss. The significant individual genes include acyl-coenzyme A oxidase 1 (ACOX1), phosphodiesterase 3A cGMP-inhibited (PDE3A) and protein kinase, AMP-activated, beta 1 non-catalytic subunit (PRKAB1). Specifically, ACOX1 plays a role in fatty acid metabolism. PDE3A is involved in purine metabolism and hormone-stimulated lipolysis. PRKAB1 is involved in adipocytokine signaling pathway. Gene network analysis revealed that pathways for glycerolipid metabolism, breast cancer and apoptosis were significantly correlated with long-term weight loss. CONCLUSION: This study demonstrates that RNA expression profiles from perioperative adipose tissue are associated with weight loss outcome following RYGB surgery. Our data suggest that EWL could be predicted from preoperative samples, which would allow for informed decisions about whether or not to proceed to surgery.

Fission yeast Clp1p phosphatase regulates G2/M transition and coordination of cytokinesis with cell cycle progression.

BACKGROUND: In Saccharomyces cerevisiae the mitotic-exit network (MEN) functions in anaphase to promote the release of the Cdc14p phosphatase from the nucleolus. This release causes mitotic exit via inactivation of the cyclin-dependent kinase (Cdk). Cdc14p-like proteins are highly conserved; however, it is unclear if these proteins regulate mitotic exit as in S. cerevisiae. In Schizosaccharomyces pombe a signaling pathway homologous to the MEN and termed the septation initiation network (SIN) is required not for mitotic exit, but for initiation of cytokinesis and for a cytokinesis checkpoint that inhibits further cell cycle progression until cytokinesis is complete. RESULTS: We have identified the S. pombe Cdc14p homolog, Clp1p, and show that it is not required for mitotic exit but rather functions together with the SIN in coordinating cytokinesis with the nuclear-division cycle. As cells enter mitosis, Clp1p relocalizes from the nucleolus to the spindle and site of cell division. Clp1p exit from the nucleolus does not depend on the SIN, but the SIN is required for keeping Clp1p out of the nucleolus until completion of cytokinesis. Clp1p, in turn, may promote the activation of the SIN by antagonizing Cdk activity until cytokinesis is complete and thus ensuring that cytokinesis is completed prior to the initiation of the next cell cycle. In addition to its roles in anaphase, Clp1p regulates the G2/M transition since cells deleted for clp1 enter mitosis precociously and cells overexpressing Clp1p delay mitotic entry. Unlike Cdc14p, Clp1p appears to antagonize Cdk activity by preventing dephosphorylation of Cdc2p on tyrosine. CONCLUSIONS: S. pombe Clp1p affects cell cycle progression in a markedly different manner than its S. cerevisiae homolog, Cdc14p. This finding raises the possibility that related phosphatases in animal cells will prove to have important roles in coordinating the onset of cytokinesis with the events of mitosis.

Effects of low dosage progestin-only administration upon plasma triglycerides and lipoprotein metabolism in postmenopausal women.

Oral administration to five postmenopausal women of dl-norgestrel (0.075 mg/d for 7 wk) reduced mean fasting plasma levels of triglycerides by 29% (P < 0.001), VLDL triglycerides by 39% (P < 0.01), and VLDL apo B by 26% (P < 0.05), while lowering mean total cholesterol by 7% (P < 0.06). To explain these observations the kinetics of VLDL and LDL apo B turnover were studied by injecting autologous 125I-labeled VLDL and 131I-labeled LDL under control conditions and again in the fourth week of a 7-wk course of dl-norgestrel. VLDL apo B pool size fell by an average of 27% (1.2 vs 1.7 mg/kg, P < 0.06) and production of apo B by 18% (18 vs 22 mg/kg per d, P < 0.05) with unchanged fractional catabolic rate. Production of LDL apo B increased 36% with dl-norgestrel (12 vs 9.4 mg/kg per d, P < 0.05), but this was compensated by a 36% increase in fractional catabolic rate of LDL apo B (0.33 vs 0.25 pools/d, P < 0.005), thereby maintaining pool size. Lipoprotein (a) fell by an average of 12% (16 vs 18 mg/dl, P < 0.06). dl-Norgestrel reduced VLDL triglycerides (40 vs 64 mg/dl, P < 0.05), intermediate density lipoprotein cholesterol (14 vs 19 mg/dl, P < 0.02), IDL apo B (5.3 vs 7.2 mg/dl, P < 0.05), and VLDL cholesterol (3.1 vs 5.1 mg/dl, 0.10 > P > 0.05), in parallel with the reductions in VLDL apo B production and pool size. dl-Norgestrel significantly lowered the production rate of VLDL apo B, thereby decreasing plasma VLDL and intermediate density lipoprotein concentrations.

Effects of combined estrogen and progestin administration on plasma lipoprotein metabolism in postmenopausal women.

Treatment of postmenopausal women with low doses of estradiol-17 beta (1 mg/d) and dl-norgestrel (0.075 [corrected] mg/d) significantly reduced fasting serum levels of low density lipoprotein (LDL) cholesterol and lowered very low density lipoprotein (VLDL) triglycerides in four of five subjects. To explain these results, the kinetics of VLDL and LDL apolipoprotein (apo) B turnover were studied by injecting autologous 125I-labeled VLDL and 131I-labeled LDL into subjects before discontinuing long-term (4-yr) treatment with the estradiol-17 beta and dl-norgestrel and again 7 wk after stopping treatment. The 24% mean decrease in VLDL apo B pool size during treatment was associated with a significant increase in VLDL apo B fractional catabolic rate (15 +/- 1 vs. 11 +/- 1 pools/d), whereas production rate was similar to control (24 +/- 3 vs. 21 +/- 2 mg/kg per d). There was a significant 25% mean decrease in LDL apo B pool size (27 +/- 2 vs. 36 +/- 3 mg/kg) due to a significant decrease in total (8.3 +/- 0.3 vs. 11 +/- 1 mg/kg per d) and independent (3.3 +/- 0.5 vs. 6.6 +/- 0.8 mg/kg per d, P less than 0.05) LDL apo B production. Estradiol-17 beta together with dl-norgestrel lowered plasma VLDL by enhancing their clearance and LDL by reducing their production.

Effects of intravenously administered fructose and glucose on splanchnic amino acid and carbohydrate metabolism in hypertriglyceridemic men.

Splanchnic metabolism was studied in the fed state during prolonged intravenous administration (30 g/h) of either fructose or glucose to hypertriglyceridemic men who had been maintained on a high-carbohydrate diet for 2 wk. Splanchnic exchange of amino acids and carbohydrates was quantified by measurement of splanchnic flow and of blood or plasma arteriohepatic venous concentration gradients. Results obtained in subjects receiving fructose were compared with those obtained in (a) similar subjects receiving glucose and (b) postabsorptive controls maintained on isocaloric, balanced diets. Mean arterial plasma levels of alanine, glycine, serine, threonine, methionine, proline, valine, leucine, histidine, lysine, and ornithine were significantly higher in subjects given fructose than in those give glucose (P less than 0.05). The mean arterial concentration and splanchnic uptake of alanine were significantly higher in subjects given fructose than in postabsorptive controls, despite a significantly lower fractional extraction of alanine in the former (P less than 0.05). The mean arterial plasma levels of serine and ornithine were significantly lower in subjects receiving fructose than in postabsorptive controls (P less than 0.05). About half of the administered fructose or glucose was taken up in the splanchnic region, where approximately 15% was converted to CO2 and 10% to lactate. Half of the fructose taken up in the splanchnic region was converted to glucose released from the liver. The amount of hexose carbon remaining for hepatic synthesis of liquids in subjects given fructose was less than half of that of subjects given glucose. These studies demonstrate that fructose and glucose have divergent effects on amino acid metabolism and that during hypercaloric infusion of glucose (as with fructose), the human liver is a major site of lactate production.

Quantitative studies of the metabolism of chylomicron triglycerides and cholesterol by liver and extrahepatic tissues of sheep and dogs.

Unanesthetized sheep and dogs, previously fitted with indwelling catheters in the aorta, lower vena cava, mesenteric, portal, left hepatic and jugular veins, were given constant intravenous infusions of lymph in which the chylomicron lipids were variously labeled with (3)H or (14)C. Para-aminohippuric acid was infused into the mesenteric venous catheter for measurement of portal and hepatic venous blood flow. In some animals, alternately labeled free fatty acids bound to albumin were mixed with the lymph to be infused. In both species, chylomicron triglyceride fatty acids were taken up in the region drained by the lower vena cava and portal vein and free fatty acids derived from hydrolysis of these triglycerides were extensively recycled in the blood. Direct uptake of triglyceride fatty acids also occurred in liver and accounted for about 10% of the total triglyceride fatty acids removed from the blood in sheep and 22% in dogs. In sheep, 10% and, in dogs, about 40% of these triglyceride-fatty acids were released into the blood as free fatty acids. The free fatty acids recycled from various regions accounted for a substantial fraction of the chylomicron fat eventually deposited in each tissue. Uptake of chylomicron cholesterol from the blood of sheep occurred primarily in liver and to a small extent in certain tissues drained by the portal vein. The results obtained, together with other available data, demonstrate that chylomicron triglycerides are removed primarily in extrahepatic tissues of both species, while the liver removes cholesterol contained in chylomicron "skeletons" from which most of the triglycerides have been removed. The quantitative differences between transport of chylomicron lipid in sheep and dogs may be related to known differences in the structure of their hepatic sinusoids.

Mechanism of the hypolipemic effect of clofibrate in postabsorptive man.

Splanchnic metabolism of triglycerides and other major substrates was studied in the postabsorptive state in normotriglyceridemic and hypertriglyceridemic human subjects who received (1/2) g of clofibrate four times daily for 3 wk. Transport in blood plasma of triglycerides produced in the splanchnic region was quantified by three methods: (a) measurement of the transsplanchnic gradient of (14)C-labeled triglycerides during constant intravenous infusion of [1- (14)C] palmitate (b) chemical measurement of the transplanchnic gradient in concentration of triglycerides of very low density lipoproteins; and (c) determination of clearance of (14)C-labeled triglycerides in extrasplanchnic tissues. The first method measures only triglycerides derived from free fatty acids and the last two measure total splanchnic production. In hypertriglyceridemic subjects treated with clofibrate, average rates of total splanchnic production of triglycerides and production from free fatty acids were the same as those of comparable untreated subjects despite a consistent fall in plasma triglyceride levels. The hypotriglyceridemic effect of the drug was therefore accompanied by improved disposal of triglycerides in extrasplanchnic tissues. In treated normotriglyceridemic subjects, unlike their untreated counterparts, total splanchnic production was significantly higher than production from free fatty acids. Failure of clofibrate to reduce triglyceride levels in normotriglyceridemic subjects may have been related to increased total splanchnic production, coupled with improved extrasplanchnic disposal. Systemic transport and net splanchnic uptake of free fatty acids were similar in treated and control subjects but the fraction of [1-(14)C]palmitate converted to acetoacetate in splanchnic tissues was significantly higher in treated subjects. Net splanchnic extraction of plasma amino acids that enter the glucogenic pathway via pyruvate was increased in treated subjects and their arterial concentrations were reduced.