Added thermogenic and satiety effects of a mixed nutrient vs a sugar-only beverage.

OBJECTIVE: To examine the effects of a sugar-only (SO) beverage vs one containing a mixed-nutrient (MN) composition on energy expenditure and feelings of hunger and satiety. HYPOTHESIS: A beverage containing a mixed macronutrient composition will lead to greater thermic effect of food and feelings of fullness than an isocaloric beverage containing only sugar. RESEARCH METHODS AND PROCEDURES: Adults were randomly assigned to receive a 2510 kJ (600 kcal) SO liquid formula followed by an isovolumic, isoenergetic, MN liquid formula with an energy distribution of 17% protein, 67% carbohydrates as sucrose and corn syrup solids, and 16% fat, or vice versa, in a crossover design. The carbohydrate source in the two beverages was identical: 1:1 ratio of sucrose and corn syrup solids (25 dextrose equivalents). The thermic response was calculated as the 7 h deviation from resting metabolic rate (RMR). Subjects provided hunger/satiety ratings and other related information by visual analog scales at regular intervals throughout the study period. RESULTS: In all, 20 subjects completed the protocol; one was removed from the thermic effect analysis due to discrepant RMRs. Following beverage ingestion, SO and MN liquid meals produced 7 h thermic effects of (X+/-s.e.m.) 274.1+/-27.6 kJ (65.5+/-6.6 kcal) and 372.0+/-33.9 kJ (88.9+/-8.1 kcal), respectively, resulting in a significant (P<0.01) difference between meals (Delta=97.9+/-35.1 kJ [23.4+/-8.4 kcal]). Analysis of satiety ratings using area under the curve analysis showed greater feelings of satiety (P<0.05) with MN compared to SO consumption. Also, subjects felt that they could eat less (P<0.05) after consumption of the MN vs SO beverage. DISCUSSION: In comparison to MN beverages, SO beverages are associated with a relatively high-energy retention without accompanying subjective hunger/fullness compensations, suggesting a basis for their role in long-term unintentional weight gain in healthy adults.

Gastric emptying, pulmonary function, gas exchange, and respiratory quotient after feeding a moderate versus high fat enteral formula meal in chronic obstructive pulmonary disease patients.

High fat enteral formulas have been advocated for the nutritional support of chronic obstructive pulmonary disease (COPD) patients because dietary fat utilization under ideal conditions produces less CO2 per O2 consumed than carbohydrate. No data exist for these patients comparing the effects of a moderate fat vs. a high fat enteral formula on gastric emptying times (GE) and subsequent CO2 production (VCO2), oxygen consumption (VO2), respiratory quotient (RQ), and pulmonary function. Our double-blind crossover study compared these parameters after feeding a 355 mL (530 kcal) meal with either 41% fat calories (Respalor) or 55% fat calories (Pulmocare). Thirty-six COPD outpatients with a forced expiratory volume in 1 s (FEV1) < 60% of predicted were studied after an overnight fast. Gastric emptying half-time (GE t1/2) was measured using the 99MTc-radionuclide technique; VCO2, VO2, RQ, and other pulmonary functions were measured at 0, 30, 90, and 150 min postprandial using the Canopy Mode of the Deltatrac Metabolic Monitor and the Renaissance Spirometry System. We observed a significantly (p = 0.0001) longer GE t1/2 of the high fat meal when compared to the moderate fat meal (134.1 vs. 108.6 min) At 30 and 90, but not at 150 min postprandial, the VCO2 and VO2 for patients fed the moderate-fat formula were significantly (p = 0.05) higher than for those fed the high-fat formula; no differences were observed for the other pulmonary functions. Although RQ increased significantly (p = 0.01) after both meals, no differences between formulas were noted at all postprandial times tested. Compared to the high-fat meal, the moderate-fat meal significantly enhanced gastric emptying. The earlier rise in VCO2 and VO2 after the moderate-fat meal did not impact pulmonary function and reflected the earlier utilization of the moderate-fat meal. The fact that RQ was not different between the two meals at all postprandial times tested suggest that the higher rise in VCO2 and VO2 after the moderate-fat meal was most likely due to earlier gastric emptying of the moderate-fat meal rather than the difference of the fat-to-carbohydrate ratio between the two tested meals. The impact of these findings on long-term management of COPD patients awaits long-term prospective studies.

Effect of bleomycin-induced fibrosis on pulmonary metabolism of selected xenobiotics.

Few studies are available characterizing the effects of fibrosis on pulmonary disposition of drugs or environmental pollutants. Two model substrates, p-nitroanisole and carbofuran, were selected to evaluate the effect of bleomycin-induced fibrosis on pulmonary disposition and metabolism using the isolated perfused lung and in vitro enzyme preparations. The rate of p-nitroanisole oxidation in the isolated perfused lung was significantly lower in fibrotic (k = 0.0334 min-1) than in control (k = 0.0493 min-1) lungs. However, there was no difference in the amount of p-nitrophenol formed between control (38 +/- 4 micrograms) and fibrotic (47 +/- 7 micrograms) lungs. Carbofuran clearance was similar in control (t1/2 = 91 min, ke = 0.008 min-1) and fibrotic (t1/2 = 75 min, ke = 0.009 min-1) lungs and was consistent with a one-compartment model. The Km value for p-nitrophenol formation in microsomes (0.185 +/- 0.095 mM) from control lungs was similar to fibrotic lungs (0.054 +/- 0.014 mM); however, Vmax was significantly higher in healthy (34.6 +/- 6.3 pmoles/min per mg microsomal protein) than in fibrotic (11.16 +/- 3.19 pmoles/min per mg microsomal protein) lungs. In vitro carbofuran studies indicated limited metabolism of carbofuran in both healthy and fibrotic microsomal enzyme preparations (< 5% of the administered dose). Lower p-nitroanisole metabolism in fibrotic lungs was consistent with lower levels of cytochrome P-450 2B1/B2 measured in bleomycin-treated lungs. Results suggest that individuals with bleomycin-induced pulmonary fibrosis may be at greater risk when exposed to certain toxic environmental chemicals or drugs that require detoxification by pulmonary microsomal enzymes.

Alu-PCR: characterization of a chromosome 6-specific hybrid mapping panel and cloning of chromosome-specific markers.

The Alu-polymerase chain reaction (Alu-PCR) was applied to selectively amplify DNA sequences from human chromosome 6 using a single primer (A1) directed to the human Alu consensus sequence. A specific amplification pattern was demonstrated for a panel of eight somatic cell hybrids containing different portions of chromosome 6. This PCR pattern permits the identification of submicroscopic DNA alterations and can be utilized as a reference for additional chromosome 6-specific hybrids. To obtain new chromosome 6-specific markers we established two libraries from PCR-amplified sequences using two somatic cell hybrids (MCH381.2D and 640-5A). Out of a total of 109 clones that were found to be chromosome 6 specific, 13 clones were regionally assigned. We also included a procedure that allows the isolation of chromosome 6-specific markers from hybrids that contain human chromosomes other than 6. Our results will contribute to the molecular characterization of chromosome 6 by fostering characterization of somatic cell hybrids and by the generation of new regionally assigned DNA markers.

Two-generation reproduction study of hydrotreated shale oil vapors.

Two generations of Sprague-Dawley rats were each exposed to vapors generated by countercurrent distillation (50 degrees C) at 0, 0.5, 2.5, and 5.0 mg/liter, for 6 hr/day, 5 days/week, for 124-126 days prior to mating. After mating, exposure was continuous except for the last day of gestation through lactation for F0 dams, and the last day of gestation through Day 6 of lactation for F1 dams. F1 pups were not exposed during lactation; F2 pups were exposed via nursing only. Body weights were recorded weekly before mating; organ and body weights were recorded on Days 1, 13, and 30 of gestation and on Days 1, 4, and 21 of lactation. Histopathology, reproductive performance, and certain sperm parameters were evaluated. The test material significantly (p less than 0.05) depressed body weights of F0 males and brain and lung weights of F1 weanling males at 5.0 mg/liter. Testicular weights of F1 weanling males were depressed at the 0.5 and 5.0 mg/liter concentrations. While a dose-related decrease in sperm count and sperm ATP levels and an increase in ATP/sperm ratios were observed in F0 males at 2.5 and 5.0 mg/liter, there was no adverse effect on overall reproductive performance.

Effect of tolbutamide and glyburide on pyruvate kinase flux in isolated rat hepatocytes.

The effects of two representative sulfonylureas, tolbutamide and glyburide, on pyruvate kinase (PK) flux were examined in fasted rat hepatocytes. PK flux was estimated by trapping 14C from NaH14CO3 in a 2 mM lactate pool, accounting for any incomplete trapping by parallel incubations with L-[1-14C]alanine. Glyburide (20 microM) and tolbutamide (1 mM) decreased glucose formation by 34.9% and 54.8%, respectively, from 2 mM lactate. This decrease in glucose formation was associated with a proportional decrease in pyruvate carboxylase (PCOX) flux (32.7% and 50.5%, respectively). Under these conditions, no net change in PK flux was observed. When hepatocytes were preincubated with lactate and/or sulfonylurea addition for 30 min prior to radiolabeling with NaH14CO3, the metabolic state of the cells changed markedly. Glyburide produced a 34.6% decrease in glucose formation and a 31.3% decrease in PCOX flux, but no change in PK flux. In contrast, tolbutamide decreased glucose formation by 12.5% and increased PK flux by 53.2%, but no change in PCOX flux was observed. Such an increase in PK flux may be linked to tolbutamide-mediated increases in fructose-1,6-bisphosphate (F16P) via fructose-2,6-bisphosphate (F26P). These findings demonstrate that tolbutamide and glyburide decrease hepatic glucose production through various alterations in carbohydrate metabolism, depending upon the metabolic state of the cell. In addition, F26P may play a larger role in the hypoglycemic mechanism of action of tolbutamide than glyburide, since pyruvate carboxylase accounted for most of the decrease in glucose formation observed with glyburide and because preincubation with tolbutamide resulted in an activation of PK.

Obstructive sleep apnea: a comparison of continuous positive airway pressure and surgical treatment.

Since earlier descriptions of the syndrome of obstructive sleep apnea (OSA), various treatment alternatives have included a variety of medical regimens, continuous positive airway pressure (CPAP), tracheostomy, and other surgical options. A lack of acceptable criteria for surgical intervention remains an important concern for the surgeon. in an attempt to resolve some of the controversies pertaining to various therapeutic modalities, we performed a retrospective analysis--from 1983 to the present--of posttreatment results in patients who underwent surgical therapy and those who were treated primarily with CPAP at this institution. Of 400 patients diagnosed with OSA, only 66 underwent surgical treatment, including uvulopalatopharyngoplasty. CPAP was the mainstay of treatment in the majority of our patients. Post-treatment data were available for 50 patients treated with CPAP and for 45 patients treated surgically. A comparative analysis of polysomnographic studies revealed superior cures with CPAP, although long-term compliance remains a significant problem. We advocate CPAP as initial therapy in patients with no clinically apparent causes for obstruction (e.g., nasal polyps, deviated nasal septum, or obstructive tonsillar hypertrophy) because of the predictability of success, and lower costs and complication rates. Long-term followup of OSA patients is indicated, regardless of treatment modality.

Criteria to evaluate bone mineralization in cattle: II. Noninvasive techniques.

An experiment was conducted to evaluate the capabilities of dual photon absorptiometry (PA), radiographic photometry (RP), and ultrasound (U) to estimate bone mineral content (BMC) and bone strength of a group of bovine third metacarpals (McIII). Metacarpals were chosen for evaluating BMC and bone strength because of their accessibility and susceptibility to biomechanical stress. The right and left McIII of 14 Angus heifers (24 to 32 mo of age) were collected at slaughter and all soft tissues (including periosteum) were removed. The BMC was estimated at both the midpoint and 3 cm proximal to the midpoint on the McIII diaphysis. Metacarpals then were tested by three-point bending to determine breaking load (BL) and breaking strength (BS). Bones were reassembled and two 2-cm sections were removed, one at the midpoint and one 1 cm proximal to the midpoint section. Sections then were ashed and ash content was expressed as grams per 2-cm slice and defined as BMC. Correlation coefficients (r) between BMC vs PA, RP, and U were .908 (P less than .0001), .967 (P less than .0001), and .565 (P less than .0001), respectively; r values between BS vs PA, RP, and U were .406 (P less than .05), .429 (P less than .05), and .499 (P less than .01), respectively, and r values between BL vs PA, RP, and U were .870 (P less than .0001), .865 (P less than .0001), and .588 (P less than .001), respectively. These data indicate that noninvasive techniques are useful in predicting BMC and BL in the bovine.

Criteria to evaluate bone mineralization in cattle: I. Effect of dietary phosphorus on chemical, physical, and mechanical properties.

Fourteen Angus heifers (210 +/- 6 kg initial BW) were allotted randomly to either a low P (LP: .12% P, DM basis) or an adequate P (AP: .20% P, DM basis) diet fed for 14 to 16 mo under drylot conditions on concrete floors to determine the influence of dietary P on chemical, physical, and mechanical properties of bone. Three weeks postpartum, after 14 to 16 mo on their diets, heifers were slaughtered and the right and left third metacarpals (McIII) were excised; soft tissue was removed and metacarpals were frozen in .9% saline. Metacarpals were subjected to a three-point flexure test using an Instron Testing Machine with a crossload speed of 50 mm/min to determine mechanical properties. Broken McIII were reassembled and a 2-cm section was removed at point of loading for determination of chemical and physical properties. Breaking load (BL) was greater (P less than .05) for McIII from the AP than for those from LP heifers (1,348 vs 1,179 kg). Breaking strength (BS) was greater (P less than .05) for AP than for LP heifers (202.5 vs 189.2 MPa). Animals receiving AP diets had greater (P less than .01) bone mineral content (12.6 vs 11.2 g/2-cm slice) and percentage of bone ash (68.0 vs 67.2%) than did LP animals. No differences (P greater than .10) were observed between treatment groups in Ca, P, or Mg percentage in bone ash. Circular, elliptical, radiographic, and planimeter area indices all were greater (P less than .05) in AP than in LP animals (1,048, 729, 1,069, and 570 vs 932, 660, 957, and 523 mm2, respectively). These data indicate that mechanical properties of bovine third metacarpals are sensitive to dietary P and reflect P status in the bovine. Mineral content of bone was highly correlated with its mechanical and physical properties.

Chemicals, cancer, and risk assessment.

Cancer rates in Louisiana in particular, and the United States in general, especially as they relate to exposure to synthetic chemicals, have been a subject of great interest to the general public. Physicians are asked many difficult questions on this subject by their patients. This article provides an objective overview of cancer mortality rates and cancer risk assessment techniques with the intent of assisting physicians in providing knowledgeable responses to these questions. Prominent findings contained in this article include: (1) with the exception of lung cancer, due to consumption of tobacco products, cancer mortality rates are declining; (2) Louisiana ranks 16th among the 50 states in overall cancer mortality; (3) cancer risk assessment techniques used by the United States government are intentionally very conservative and overestimate real cancer risks, particularly for low level exposures; (4) the vast majority of cancers is related to individually controllable lifestyle factors; a small percentage is related to occupational or environmental exposures.

Cytotoxicity of three novel fluoropyrimidines in cultured L1210 murine lymphocytic leukemia cells.

Cultured L1210 murine lymphocytic leukemia cells were used to compare metabolic activation and cytotoxicity of 5-fluorouracil (FU), Ftorafur (FT), and three novel FU-sulfur analogues. These analogues, 1-(2'-tetrahydrothienyl)-5-fluorouracil (FUS), 1-(2'-tetrahydrothienyl)-5- fluorouracil-1'-oxide (FUSO), and 1-(2'-tetrahydrothienyl)-5-fluorouracil-1'-1'-dioxide (FUSO2), have yet to be fully evaluated for potential therapeutic value based on in vitro cytotoxicity. The role of these FU analogues as prodrugs was evaluated by comparing metabolism of normal pyrimidine pathways and activation by hepatic mixed function oxidases (MFO). Significant differences in biochemical activity and cytotoxicity were measured between FU and FU analogues. FU and FU analogues were cytotoxic to L1210 cells (63-92% growth inhibition of 100 microM concentrations after 72 hr of incubation). However, at equimolar concentration cytotoxicity of the FU analogues after MFO activation (56-66% growth inhibition) was greater than FU (47% growth inhibition). Hypoxanthine, a purine precursor, did not significantly alter fluoropyrimidine cytotoxicity with or without MFO. Thymidine and uridine, pyrimidine precursors, reduced FT and FUS cytotoxicities in the presence (27, 40%) and absence (25, 15%) of MFO but did not modify FU, FUSO, or FUSO2 cytotoxicities.

Comparative acute toxicity of shale and petroleum derived distillates.

In anticipation of the commercialization of its shale oil retorting and upgrading process, Unocal Corp. conducted a testing program aimed at better defining potential health impacts of a shale industry. Acute toxicity studies using rats and rabbits compared the effects of naphtha, Jet-A, JP-4, diesel and "residual" distillate fractions of both petroleum derived crude oils and hydrotreated shale oil. No differences in the acute oral (greater than 5 g/kg LD50) and dermal (greater than 2 g/kg LD50) toxicities were noted between the shale and petroleum derived distillates and none of the samples were more than mildly irritating to the eyes. Shale and petroleum products caused similar degrees of mild to moderate skin irritation. None of the materials produced sensitization reactions. The LC50 after acute inhalation exposure to Jet-A, shale naphtha, (greater than 5 mg/L) and JP-4 distillate fractions of petroleum and shale oils was greater than 5 mg/L. The LC50 of petroleum naphtha (greater than 4.8 mg/L) and raw shale oil (greater than 3.95 mg/L) also indicated low toxicity. Results demonstrate that shale oil products are of low acute toxicity, mild to moderately irritating and similar to their petroleum counterparts. The results further demonstrate that hydrotreatment reduces the irritancy of raw shale oil.

Comparative dermal carcinogenesis of shale and petroleum-derived distillates.

Ten test materials derived from petroleum or hydrotreated shale oils were applied 3 times/week for up to 105 weeks to the shaved skin of 25 male and 25 female C3H/HeN mice per group. Mineral oil and benzo(a) pyrene (0.15%) were control materials. Clinical observations were recorded during the study. At death, histopathologic examination was conducted on skin, internal organs and any gross lesions. Exposures to some materials were ended midway in the study due to severe irritation. Chronic toxicity of all materials was limited to inflammatory and degenerative skin changes. Significant increases over control incidence of skin tumors (squamous cell carcinoma and fibrosarcoma) occurred with both petroleum and shale-derived naphtha (21%, 50%), Jet A (26%, 28%), JP-4 (26%, 50%), and crude oils (84%, 54%). Severely hydrotreated shale oil and petroleum and shale-derived diesel distillates were not considered tumorigenic. Results indicate that toxicity of comparable petroleum and shale-derived fractions was qualitatively similar and confirm earlier findings that hydrotreating reduces or eliminates carcinogenicity of raw shale oil.

Wheat fiber and laxation: dose response and equilibration time.

We studied the dose response to soft white winter wheat fiber on fecal output in a group of healthy volunteers whose breakfasts consisted of wheat fiber cereals in amounts that provided 0.3 g, 5.6 g, 9.5 g, 11.2 g, 19.0 g, and 28.4 g dietary fiber per day for 14 days; no other aspects of their diet were altered. A linear dose response was observed between the six levels of fiber intake (r = 0.983, p less than 0.01) with a 1-g increase in wheat fiber, producing a mean 2.7-g increase in fecal weight. This increase was independent of the initial daily fecal weight of the volunteer (mean 117 +/- 64 g/day, range 5-297 g/day, n = 73). The maximum increase in fecal output due to cereal fiber was reached after the first week on the supplement. These data support the use of graded amounts of cereal fiber in the management of constipation.

Synthesis and antitumor activity of a series of ftorafur analogues: the effect of varying electronegativity at the 1'-position.

To test the effect of changes in electronegativity within the alicyclic N-1 substituent 5-fluorouracil analogues on cytotoxic activity, a series of derivatives of ftorafur, 1-(2'-tetrahydrofuranyl)-5-fluorouracil, was synthesized and tested for antitumor activity in the P388 lymphocytic leukemia screen and cytotoxic activity in the L1210 cell culture screen. Two compounds of N-1 substituent with high electronegativity, the 2'-tetrahydrothiophene 1'-oxide and the 2'-tetrahydrothiophene 1',1'-dioxide derivatives, demonstrated the highest in vitro L1210 cell inhibition (84.5% and 92.0%, respectively). Furthermore, against P388 lymphocytic leukemia in vivo, the 2'-tetrahydrothiophene 1'-oxide derivative showed significant activity (T/C = 143). Other compounds of similar or lower electronegativity within the N-1 cyclic substituent were inactive against P388 lymphocytic leukemia and less active against L1210 cells.

Genetic, phenotypic and environmental relationships between sow body weight and sow productivity traits.

Yorkshire and Duroc litter records were used to estimate genetic, phenotypic and environmental relationships between sow body weight and sow productivity traits. Two data sets with two subsets each were used to complete this study; 663 and 460 records included litter traits only, while 522 and 359 records also contained sow body weight for Yorkshires and Durocs, respectively. Heritability estimates for number born (NB), number born alive (NBA), total birth weight of live pigs (BWLIT), litter weight at 3 wk (WT3WK), sow weight at parturition (WTDAMPAR) and sow weight at weaning (WTDAMWN) were .24 +/- .14, .21 +/- .14, .42 +/- .16, .19 +/- .14, .72 +/- .21 and .42 +/- .18, respectively, for Yorkshires and .05 +/- .10, .04 +/- .10, .21 +/- .14, .25 +/- .15, .85 +/- .25 and .87 +/- .26, respectively, for the Durocs. Repeatability estimates for NB, NBA, BWLIT, WT3WK, WTDAMPAR and WTDAMWN were .13 +/- .06, .17 +/- .06, .27 +/- .06, .13 +/- .06, .64 +/- .05 and .54 +/- .05, respectively, for Yorkshires and .17 +/- .06, .21 +/- .06, .14 +/- .06, .17 +/- .06, .28 +/- .07 and .39 +/- .07, respectively, for Durocs. Genetic correlations among litter traits were high and positive in the Yorkshire data. Genetic correlations between NBA and WTDAMPAR, NBA and WTDAMWN, WT3WK and WTDAMPAR, and WT3WK and WTDAMWN were .37 +/- .25, .18 +/- .34, .60 +/- .29 and .29 +/- .45, respectively, in the Yorkshire data. Genetic correlations among litter traits in the Duroc analysis had large standard errors but were generally similar to the estimates obtained from the Yorkshire data. The genetic correlation between WTDAMPAR and WTDAMWN was .93 +/- .09 for Yorkshire sows. The primary conclusion from this study is that as selection increases sow productivity traits, there will be a positive correlated response in sow body weight.

[14C]normacromerine fate in the rat.

The biological fate of [14C] normacromerine , a dimethoxylated phenethylamine derivative with putative hallucinogenic properties, was evaluated in male Sprague-Dawley rats at 100 mg/kg po. Urine was the primary elimination route accounting for 50% of administered carbon-14 after 24 h. Of this urine radioactivity, normacromerine comprised 30% at 8 h decreasing to nondetectable levels at 24h. Carbon-14 in feces represented less than 10% of the administered dose at 24 h, and 14CO2 expiration was not detected. Studies of normacromerine fate in comparison with previously studied phenethylamines may enhance evaluation of hallucinogenic potential of normacromerine .