The effect of consuming low- versus high-glycemic index meals after exercise on postprandial blood lipid response following a next-day high-fat meal.

BACKGROUND/OBJECTIVES: Exercise performed shortly before (that is, within half a day of) a high-fat meal is beneficial for stimulating fat oxidation after the meal and reducing postprandial triglycerides (TG). This benefit of exercise is unfortunately negated if the after-exercise food choice to replace the calories expended during exercise is one containing high-glycemic index (HGI) carbohydrates. We determined the effect of consuming low-glycemic index (LGI) carbohydrates after an exercise session on fat oxidation and TG after a subsequent high-fat meal. SUBJECTS/METHODS: Using a randomized, counterbalanced crossover design, 23 overweight or obese individuals (body mass index ⩾25 kg m(-2)) performed: walking exercise (90 min) at 1800 h followed by no meal (EX); exercise followed by a meal with LGI carbohydrates (that is, lentils, EX-LGI); exercise followed by a meal with HGI carbohydrates (that is, instant potatoes, white bread, EX-HGI); and a control condition with no exercise or meal. After a 10-h overnight fast, participants were given a standardized high-fat meal. Fat oxidation was estimated before and for 6 h after this meal from respiratory gas measures and TG determined from blood samples. RESULTS: Fat oxidation (mean±s.d.) was higher with EX (6.9±1.7 g h(-1)) than EX-HGI (6.3±1.6 g h(-1); P=0.007) and Control (5.9±1.7 g h(-1); P=0.00002), and EX-LGI (6.6±1.7 g h(-1)) was higher than Control (P=0.002). TG total area under the curve was 18-32% lower with EX and EX-LGI compared with control (P=0.0005 and P=0.0001, respectively) and EX-HGI (P=0.05 and P=0.021, respectively). CONCLUSIONS: A meal containing HGI carbohydrates consumed after an evening exercise session cancels the beneficial effect of exercise for stimulating fat oxidation and lowering TG after a subsequent high-fat meal, whereas consuming a post-exercise meal with LGI carbohydrates retains the positive effect of exercise.

Blood concentrations of D- and L-lactate in healthy rabbits.

OBJECTIVES: To determine whole blood and serum concentrations of l-lactate and serum concentrations of d-lactate in healthy rabbits and compare three methods of analysis for l-lactate measurement. METHODS: Prospective study using 25 rabbits. Concentrations of whole blood l-lactate were measured using a portable analyser and a blood gas analyser. The remainder of the sample was allowed to clot for centrifugation. Serum was stored at -20°C for determination of l- and d- lactate by high-performance liquid chromatography. RESULTS: d-lactate values by high-performance liquid chromatography were 0 · 17 ± 0 · 08 mmol/L. l-lactate values were 5 · 1 (±2 · 1) mmol/L by high-performance liquid chromatography, 6 · 9 (±2 · 7) mmol/L with the portable analyser and 7 · 1 (±1 · 6) mmol/L with the blood gas analyser. No significant difference (P > 0 · 05) was found between the two analysers. Significant difference existed between serum l-lactate values obtained by high-performance liquid chromatography and the whole blood values obtained with the blood gas analyser (P < 0 · 01) and portable analyser (P < 0 · 05). CLINICAL SIGNIFICANCE: Serum concentrations of d-lactate in healthy rabbits are in the range of those of other mammals. l-lactate values in healthy rabbits are higher compared with other mammals. Good correlation was found between the portable and blood gas analysers for whole blood l-lactate measurement in healthy rabbits.

Serum D-lactate concentrations in cats with gastrointestinal disease.

BACKGROUND: Increased D-lactate concentrations cause neurological signs in humans with gastrointestinal disease. HYPOTHESIS/OBJECTIVES: To determine if serum D-lactate concentrations are increased in cats with gastrointestinal disease compared to healthy controls, and if concentrations correlate with specific neurological or gastrointestinal abnormalities. ANIMALS: Systematically selected serum samples submitted to the Gastrointestinal Laboratory at Texas A&M University from 100 cats with clinical signs of gastrointestinal disease and abnormal gastrointestinal function tests, and 30 healthy cats. METHODS: Case-control study in which serum D- and L-lactate concentrations and retrospective data on clinical signs were compared between 30 healthy cats and 100 cats with gastrointestinal disease. Association of D-lactate concentration with tests of GI dysfunction and neurological signs was evaluated by multivariate linear and logistic regression analyses, respectively. RESULTS: All 100 cats had a history of abnormal gastrointestinal signs and abnormal gastrointestinal function test results. Thirty-one cats had definitive or subjective neurological abnormalities. D-lactate concentrations of cats with gastrointestinal disease (median 0.36, range 0.04-8.33 mmol/L) were significantly higher than those in healthy controls (median 0.22, range 0.04-0.87 mmol/L; P = .022). L-lactate concentrations were not significantly different between the 2 groups of cats with gastrointestinal disease and healthy controls. D-lactate concentrations were not significantly associated with fPLI, fTLI, cobalamin, folate, or neurological abnormalities (P > .05). CONCLUSIONS AND CLINICAL IMPORTANCE: D-lactate concentrations can be increased in cats with gastrointestinal disease. These findings warrant additional investigations into the role of intestinal microbiota derangements in cats with gastrointestinal disease, and the association of D-lactate and neurological abnormalities.

Diets supplemented with chickpea or its main oligosaccharide component raffinose modify faecal microbial composition in healthy adults.

The effects of diets supplemented with either chickpea or its main oligosaccharide raffinose on the composition of the faecal microbial community were examined in 12 healthy adults (18-65 years) in a randomised crossover intervention study. Subjects consumed their usual diet supplemented with soups and desserts that were unfortified, or fortified with either 200 g/d of canned chickpeas or 5 g/d of raffinose for 3 week periods. Changes in faecal bacterial populations of subjects were examined using 16S rRNA-based terminal restriction fragment length polymorphisms (T-RFLP) and clone libraries generated from the diet pools. Classification of the clone libraries and T-RFLP analysis revealed that Faecalibacterium prausnitzii, reported to be an efficient butyrate producer and a highly metabolically active bacterium in the human intestinal microbiota, was more abundant in the raffinose diet and the chickpea diet compared to the control diet. However, no significant difference was observed in the faecal total short chain fatty acid concentration or in the levels of the components (butyrate, acetate and propionate) with the chickpea diet or the raffinose diet compared to the control diet. Bifidobacterium species were detected by T-RFLP in all three diet groups and quantitative real-time PCR (qPCR) analysis showed a marginal increase in 16S rRNA gene copies of Bifidobacterium with the raffinose diet compared to control (P>0.05). The number of individuals showing TRFs for the Clostridium histolyticum - Clostridum lituseburense groups, which include pathogenic bacteria species and putrefactive bacteria, were lower in the chickpea diet compared to the other two treatments. Diet appeared to affect colonisation by a high ammonia-producing bacterial isolate which was detected in 83%, 92% and 42% of individuals in the control, raffinose and chickpea groups, respectively. Our results indicate that chickpea and raffinose have the potential to modulate the intestinal microbial composition to promote intestinal health in humans.

Anticonvulsants containing the N-(3-aryl-2-propenoyl) amido pharmacophore.

A series of 1-(3-aryl-2-propenoyl)-4-oxopiperidines (1) as well as some related semicarbazones (2) and thiosemicarbazones (3) were prepared in order to determine whether the relative locations of aryl rings and amidic groups would lead to novel anticonvulsant agents. Initially the compounds were administered intraperitoneally to mice and examined in the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and neurotoxicity (NT) screens. The biodata revealed that anticonvulsant properties were displayed by most of the compounds in series (1), in half of the semicarbazones (2) while protection was absent by members of series (3). Molecular modeling was utilized in order to compare the positions of a phenyl ring in relation to amidic groups in representative compounds in series (1-3) with previously reported anticonvulsant agents. Molecular simplification of 4-oxo-1-(3-phenyl-2-propenoyl)piperidine (la) led to 1-(3-phenyl-2-propenoyl)piperidine (7) and N,N-diethylcinnamamide (8) with retention of anticonvulsant properties. Both (la) and (8) afforded protection in the hippocampal kindling screen in rats. When administered orally to rats, (la) and (8) demonstrated activity in the MES screen and in the case of (8), a huge protection index was observed revealing it to be an important lead compound. The IC50 values of all of the compounds towards murine P388 cells were in excess of 50 microM while several compounds displayed cytotoxicity towards Mycobacterium tuberculosis.

Antimycobacterial arylidenecyclohexanones and related Mannich bases.

Several series of 2-arylidenecyclohexanones and related Mannich bases as well as various 2,6-bis(arylidene)cyclohexanones were evaluated against Mycobacterium tuberculosis H37Rv. Using a concentration of 12.5 microg/ml, nearly half of the unsaturated ketones inhibited the growth of the microorganism by 21-66% while all of the Mannich bases achieved 99% or greater inhibition. The relative hydrophobicities and widths of the molecules may have been contributing factors as to whether bioactivity was present or absent. Two of the Mannich bases demonstrated noteworthy potencies towards Mycobacterium avium. The conclusion was drawn that Mannich bases of 2-arylidenecyclohexanones represent a novel class of antimycobacterials.

Cytotoxic and topographical properties of 6-arylidene-2-dimethylaminomethylcyclohexanone hydrochlorides and related compounds.

A number of 2-arylidenecyclohexanones (1a-h) were converted into the corresponding Mannich bases (2a-h) and (3a,f). Evaluation against murine L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes revealed the marked cytotoxicity of the Mannich bases and also the fact that almost invariably these compounds were more potent than the precursor enones (1a-h). Further evaluation of most of the Mannich bases towards a panel of nearly 60 human tumour cell lines confirmed their utility as potent cytotoxins. In this assay, the compounds showed growth-inhibiting properties greater than the anticancer alkylator melphalan. QSAR studies revealed that in some cell lines compounds possessing small electron-attracting aryl substituents showed the greatest potencies. Molecular modeling and X-ray crystallography demonstrated that various interatomic distances and torsion angles correlated with cytotoxicity. A representative compound (2a) demonstrated weak inhibiting properties towards human N-myristoyltransferase and stimulated a tyrosine protein kinase. A single dose of 100 mg/kg of most of the compounds did not prove to be lethal in mice.

Cytotoxic mannich bases of 1-arylidene-2-tetralones.

Various 1-arylidene-2-tetralones 1 had been shown previously to possess moderate cytotoxic properties unaccompanied by murine toxicity. The objective of the present investigation was to undertake different molecular modifications of representative members of series 1 with a view to discerning those structural features leading to increased potencies. All compounds were evaluated using human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells. The Mannich bases 2, 4, 5 and 7 possessed increased potencies compared to the corresponding unsaturated ketones 1 and in general were potent cytotoxics having IC50 values in the 0.2-10 microM range. QSAR using the cytotoxicity data for 2a-e suggested that potency was positively correlated with the size of the substituents in the arylidene aryl ring. Compounds 2a-f were evaluated using a panel of approximately 53 human tumour cell lines and, when all cell lines were considered, were more potent than the reference drug melphalan. In particular, marked antileukemic activity was displayed. Molecular modeling was utilized in order to evaluate whether the shapes of the different compounds contributed to the varying potencies observed. Representative compounds demonstrated minimal or no inhibiting properties towards human N-myristoyltransferase (NMT) and did not bind to calf thymus DNA. This study has revealed a number of unique lead molecules as candidate anti-neoplastic agents serving as prototypes for future development.

3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones: a novel group of cytotoxic agents.

A series of novel 3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones 3 have been synthesized which displayed potent cytotoxicity towards human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells. In contrast, the related N-arylmaleamic acids 4 possessed little or no cytotoxicity in these four screens. Molecular modeling revealed certain interplanar and bond angles and interatomic distances which were perceived to contribute to the observed bioactivity as well as providing suggestions for future structural modifications of the piperidones 3. Evaluation of representative compounds in series 3 and 4 on the activity of human N-myristoyltransferase revealed that, at the maximum concentration utilized, namely 250 microM, only weak inhibiting properties were displayed by some of the compounds in series 4. Various members of series 3 and 4 were well tolerated in mice.

Cytotoxic 4'-aminochalcones and related compounds.

A series of 4'-aminochalcones 1 and related maleamic acids 2 and Schiff bases 3 were designed and synthesized as candidate cytotoxic agents. The atomic charges on different atoms of representative compounds were calculated. Evaluation of the enones 1-3 against human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells revealed that approximately 40% of the IC50 values generated were less than 10 microM. In some cases cytotoxicity was correlated with the Hammett sigma values of the aryl substituents and less frequently with the aryl Hansch pi values. Evidence was obtained that in general these compounds displayed selective toxicity for certain malignant cells and were well tolerated in mice. This study has revealed various directions whereby the project may be amplified in the future with a view to finding compounds with increased cytotoxicity to tumour cells.

A toxicological evaluation of 2-dimethylaminomethyl-1-phenyl-2-propen-1-one hydrochloride.

2-Dimethylaminomethyl-1-phenyl-2-propen-1-one hydrochloride (3) is a novel cytotoxic and anticancer agent. The objective of this study was to obtain information pertaining to possible toxic symptoms detected by in vivo evaluations in mice and an in vitro test for mutagenicity. The data obtained revealed that 3 had no effect on alanine transaminase, aspartate transaminase, HDL cholesterol and protein concentrations in sera nor were variations in the numbers of red and white blood cells detected. Furthermore autopsies of treated mice revealed no pathological symptoms in the heart, kidney, brain, spleen and testes. However elevation of the concentrations of total cholesterol, triglycerides, creatinine and urea were noted in treated mice as well as inflammation of the liver and lungs. Chromosomal aberrations were detected in a micronuclei test. In the Ames test, compound 3 was converted into one or more mutagens in the presence (but not the absence) of a murine liver homogenate. Thus future molecular modifications of 3 should bear in mind approaches to reduce or minimize unwanted side effects.

Self-reported calcium intake and bone mineral content in children and adolescents.

OBJECTIVE: We examined the relationship between self-reported calcium (Ca) intake and bone mineral content (BMC) in children and adolescents. We hypothesized that an expression of Ca adjusted for energy intake (EI), i.e., Ca density, would be a better predictor of BMC than unadjusted Ca because of underreporting of EI. METHODS: Data were obtained on dietary intakes (repeated 24-hour recalls) and BMC (by DEXA) in a cross-section of 227 children aged 8 to 17 years. Bivariate and multivariate analyses were used to examine the relationship between Ca. Ca density, and the dependent variables total body BMC and lumbar spine BMC. Covariates included were height, weight, bone area. maturity age, activity score and EI. RESULTS: Reported EI compared to estimated basal metabolic rate suggested underreporting of EI. Total body and lumbar spine BMC were significantly associated with EI, but not Ca or Ca density, in bivariate analyses. After controlling for size and maturity, multiple linear regression analysis revealed unadjusted Ca to be a predictor of BMC in males in the total body (p = 0.08) and lumbar spine (p = 0.01)). Unadjusted Ca was not a predictor of BMC at either site in females. Ca density was not a better predictor of BMC at either site in males or females. CONCLUSIONS: The relationship observed in male adolescents in this study between Ca intake and BMC is similar to that seen in clinical trials. Ca density did not enable us to see a relationship between Ca intake and BMC in females, which may reflect systematic reporting errors or that diet is not a limiting factor in this group of healthy adolescents.

Both L- and D-lactate contribute to metabolic acidosis in diarrheic calves.

Diarrhea in neonates is often complicated by metabolic acidosis. We used blood gas analysis and HPLC to determine whether bacterial fermentation might contribute to acidosis in diarrheic calves. Diarrheic calves (n = 21) had significantly lower pH, PCO(2), HCO(3)(-) and a higher anion gap than healthy calves (n = 21). Serum concentrations (mean +/- SD, mmol/L) of DL-, L- and D-lactate were also significantly higher in diarrheic (8.9 +/- 5.1, 4.1 +/- 3.4 and 5.2 +/- 5.7) than in healthy calves (1.7 +/- 1.2, 2.0 +/- 1.1 and too low to quantify). D- and L-lactate accounted for 64% anion gap increase in diarrheic calves. Fecal D- and L-lactate concentrations were also significantly higher in diarrheic calves (9.4 +/- 3.0 and 11.9 +/- 2.7 mmol/L) than healthy calves (1.1 +/- 0.1 and 1.6 +/- 0.1 mmol/L). The elevated concentrations of serum and fecal D-lactate suggest gut bacterial fermentation contributes to the development of acidosis in diarrhea.

A conformational and structure-activity relationship study of cytotoxic 3,5-bis(arylidene)-4-piperidones and related N-acryloyl analogues.

A series of 3,5-bis(arylidene)-4-piperidones 1 and related N-acryloyl analogues 2 were prepared as candidate cytotoxic agents with a view to discerning those structural features which contributed to bioactivity. A number of the compounds were markedly cytotoxic toward murine P388 and L1210 leukemic cells and also to human Molt 4/C8 and CEM neoplasms. Approximately 40% of the IC50 values generated were lower than the figures obtained for melphalan. In virtually all cases, the N-acyl compounds were significantly more bioactive than the analogues 1. In general, structure-activity relationships revealed that the cytotoxicity of series 1 was correlated positively with the size of the aryl substituents, while in series 2, a -sigma relationship was established. In particular, various angles and interatomic distances were obtained by molecular modeling, and the presence of an acryloyl group on the piperidyl nitrogen atom in series 2 affected the relative locations of the two aryl rings. This observation, along with some differences in distances between various atoms in series 1 and 2, may have contributed to the disparity in cytotoxicity between 1 and 2. The results obtained by X-ray crystallography of representative compounds were mainly in accordance with the observations noted by molecular modeling. Selected compounds interfered with the biosynthesis of DNA, RNA, and protein in murine L1210 cells, while others were shown to cause apoptosis in the human Jurkat leukemic cell line. This study has revealed the potential of these molecules for development as cytotoxic and anticancer agents.

Body composition in nutritionally adequate ambulatory and non-ambulatory children with cerebral palsy and a healthy reference group.

Bone-mineral content (BMC; g) and density (BMD; g/cm2) were measured by dual energy X-ray absorptiometry in the proximal femur, femoral neck, and total body of nutritionally adequate children (n=17; 11 girls, six boys; aged 7.6 to 13.8 years) with spastic cerebral palsy (CP). Bone-mineral-free lean tissue (BMFL; g) and fat mass (FM; g) were obtained from total body scans. Chronological and developmental age-based z scores for the children with CP were derived from a pediatric database (n=894). Children with CP had BMC z scores from -1.8 (total body) to -3.2 (femoral neck) SDs below the normative sample. Non-independent ambulators had lower z scores for total body BMD, femoral neck BMD, and BMC than independent ambulators. The BMFL z score of individuals with CP was 2 SDs below that of the reference group and higher in the independent ambulators than in the non-independent ambulators, whereas FM deviated little. These findings suggest that non-nutritional factors, such as ambulation, account for the low BMC, BMD, and BMFL tissue observed in this population.

Oral rehydration solution therapy in the management of children with rotavirus diarrhea.

Rotavirus infections are the most common cause of gastroenteritis among children younger than 3 years of age and are associated with sporadic outbreaks of diarrhea in elderly and immunocompromised patients. Oral rehydration solutions (ORS) are formulated to correct dehydration and acidosis. Currently, ORS do not promote intestinal healing; however, investigators are examining the role of nutrition in promoting intestinal healing. This article reviews the composition of several ORS in human medicine and summarizes our current knowledge of the nutritional treatment of rotavirus diarrhea and intestinal healing.

The effect of a weight-bearing physical activity program on bone mineral content and estimated volumetric density in children with spastic cerebral palsy.

After an 8-month physical activity intervention in children with cerebral palsy, increases in femoral neck bone mineral content (BMC) (9.6%), volumetric bone mineral density (v BMD) (5.6%), and total proximal femur BMC (11.5%) were observed in the intervention group (n = 9) compared with control subjects (n = 9; femoral neck BMC, -5. 8%; v BMD, -6.3%; total proximal femur BMC, 3.5%).

High-performance liquid chromatographic assay of (+/-)-lactic acid and its enantiomers in calf serum.

Two high-performance liquid chromatographic methods are described for the determination of lactic acid and its enantiomers in calf serum. A 300x8.0 mm I.D. column packed with sulfonated styrene-divinylbenzene copolymer and a 50x4.6 mm ODS column with N,N-dioctyl-L-alanine were used. UV detection was at 205 and 236 nm for the non-chiral and chiral assays, respectively. Both assays demonstrated excellent linear relationships between peak area ratios and serum concentrations over a range of 0.5 to 20 mM, based on 100 microl bovine serum. Recovery was complete. Inter- and within-batch bias and relative standard deviation were <15%.

Examination of metabolism of viscera drained by the portal vein in neonatal calves, using short-term intravenous infusions of glutamine and other nutrients.

OBJECTIVE: To quantify glutamine use in viscera drained by the portal vein in neonatal calves and to assess the relative nutritional importance of glutamine, glucose, and acetate for enterocytes. ANIMALS: 5 healthy neonatal calves. PROCEDURE: A femoral artery, jugular vein, and the portal vein were surgically cannulated in each calf. Blood flow in the portal vein was measured by use of an ultrasonographic transit-time flow probe. A series of solutions was infused on 4 days for each calf. On the infusion days, acetate, glucose, glutamine, and saline (0.9% NaCl; control) solutions were administered IV during 1-hour periods via the jugular vein. Venous and arterial blood samples were collected during the last 15 minutes of each 1-hour infusion. RESULTS: Uptake of glutamine and glucose by viscera drained by the portal vein was 0.3+/-1.1 and 1.9+/-3.1 micromol/kg0.75/min, respectively, during saline infusion. During acetate, glucose, and saline infusions, glucose was a greater source of energy for the intestines than was glutamine. However, during glutamine infusion, uptake of glutamine by viscera drained by the portal vein increased significantly (29.9+/-11.2 micromol/kg0.75/min), which was associated with an increase in ammonia production (7.0+/-0.5 micromol/kg0.75/min). Toxicosis was not associated with IV administration of glutamine. CONCLUSION: Glutamine infusion resulted in an increase in glutamine uptake by viscera drained by the portal vein, which was associated with an increase in ammonia production and a slight increase in oxygen consumption. CLINICAL RELEVANCE: These solutions may be used to develop treatments that enhance healing of intestines of diarrheic calves.

Nutrient uptake by viscera drained by the portal vein in neonatal calves during intravenous infusion of glutamine.

OBJECTIVE: To quantify glutamine use by viscera drained by the portal vein in neonatal calves and to determine whether uptake could be stimulated by long-term IV infusion or long-term use of oral supplements. ANIMALS: 4 healthy neonatal calves. PROCEDURE: A femoral artery, jugular vein, and the portal vein were surgically cannulated in each calf. Blood flow in the portal vein was measured, using an ultrasonic transit-time flow probe. Calves were given an IV infusion of glutamine on days 6, 8, and 10 after surgery. Before the first infusion, calves were fed a diet of milk only. The diet was supplemented with glutamine for the second and third infusions. Glutamine was administered via the jugular vein during a 5-hour period. Venous and arterial blood samples were collected every hour for 5 hours. RESULTS: During glutamine infusion, uptake of glutamine by viscera drained by the portal vein increased in association with increased production of ammonia. Glutamine supplementation of the diet did not alter glutamine uptake. Glutamine infusion did not increase viscera uptake of indispensable amino acids. Long-term use of glutamine supplements or infusion of glutamine for periods of more than 1 hour increased glutamine uptake by viscera. Arterial leucine concentration and uptake of leucine by the viscera decreased during glutamine infusion, indicating that leucine became the limiting factor. CONCLUSION: Glutamine administration (supplements or infusions) to calves may require that a mixture of amino acids be provided to improve effectiveness. CLINICAL RELEVANCE: Glutamine may be beneficial in treatments designed to promote intestinal healing in diarrheic calves.