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Biomedical subjects

R W Welch

Publications and source records attributed to R W Welch.

At least 19 recordsLinked to original sources
PubMed2001

The effects of yoghurt containing a novel fat emulsion on energy and macronutrient intakes in non-overweight, overweight and obese subjects.

OBJECTIVE: To investigate the effects of a yoghurt containing a novel fat emulsion on energy and macronutrient intakes up to 8 h post-consumption in non-overweight, overweight and obese subjects, and to assess energy compensation over the following 24 h. DESIGN: A double-blind, placebo-controlled, within-subject crossover design was used. Twenty (10 female, 10 male) non-overweight (body mass index (BMI) 20-24.9 kg/m(2)), 20 (10 female, 10 male) overweight (BMI 25-29.9 kg/m(2)) and 20 (13 female, 7 male) obese (BMI>30 kg/m(2)) subjects participated in the study. Subjects were given in random order, 7 days apart, either a 200 g portion of a test (5 g of a novel fat emulsion+1 g milk fat) or control (6 g milk fat) yoghurt at 09:00 h. At 4 and 8 h post-consumption subjects were given ad libitum access to a range of foods. Amounts of food consumed were determined by pre and post-covert weighing of individual serving dishes. Over the following 24 h subjects weighed and recorded all food intakes. RESULTS: Mean energy intakes were significantly lower after the test yoghurt compared with the control yoghurt in non-overweight (3.79 vs 5.43 MJ; P<0.01) and overweight (4.43 vs 6.12 MJ; P<0.001) subjects 4 h post-consumption and in non-overweight (3.82 vs 5.38 MJ; P<0.001), overweight (3.94 vs 5.80 MJ; P<0.001) and obese (4.91 vs 6.26 MJ; P<0.01) subjects 8 h post-consumption. The corresponding macronutrient intakes were also significantly reduced in non-overweight and overweight subjects (P<0.01) at 4 h post-consumption and in all subjects 8 h post-consumption (P<0.01). In the total group, energy intakes over the following 24 h were also significantly reduced (6.35 vs 7.70 MJ; P<0.01) after the test yoghurt relative to the control yoghurt. CONCLUSIONS: These results suggest that the effects of this novel fat emulsion are maintained at least up to 8 h and are evident in non-overweight, overweight and obese subjects.

Adult↗
PubMed2000

Short-term effects of yoghurt containing a novel fat emulsion on energy and macronutrient intakes in non-obese subjects.

BACKGROUND: The satiating properties of fat remain poorly understood, particularly with reference to its physicochemical characteristics. OBJECTIVE: To investigate the short-term effects of consumption of yoghurt containing either a novel fat emulsion or normal milk fat, on the energy and macronutrient intakes of non-obese subjects. DESIGN: Two double-blind, placebo-controlled, within-subject crossover studies were conducted three months apart. Twenty-nine (15 F, 14 M) and thirty (16 F, 14 M) subjects participated in Study 1 and Study 2 respectively. In each study, subjects were given in random order, 7 days apart, either a 200g portion of a test (5g of a novel fat emulsion + 1 g milk fat) or control (6g milk fat) yoghurt at 1300 h. At 4h post-consumption subjects were given ad libitum access to a range of foods. Amounts of food consumed by individuals were determined by pre- and post-covert weighing of individual serving dishes. RESULTS: Mean energy intakes were significantly lower after the test yoghurt compared with the control yoghurt in Study 1 (6.4 vs 7.6 MJ; P< 0.001), Study 2 (6.9 vs 7.9 MJ; P<0.001), and for both studies combined (6.7 vs 7.7 MJ; P<0.001). The corresponding fat intakes in Study 1, Study 2 and in the combined studies were all significantly reduced (P< 0.001). Protein and carbohydrate intakes were also significantly reduced in Study 1 (P< 0.05), Study 2 (P< 0.01), and for the combined studies (P< 0.001). CONCLUSIONS: These results suggest that the physicochemical characteristics of small amounts of dietary fat affect short-term satiety.

Adult↗
PubMed2000

Food processing: a century of change.

In 1900, the population was beset with poverty, and infectious and deficiency diseases were common. The first half of the century was blighted by world wars, economic depression and post-war austerity. Nevertheless, a combination of enlightened social policy and the application of medical, nutritional and food science, resulted in substantial improvements in health, such that, by 1950, many hitherto common infectious diseases were under control, and the diet was generally nutritionally adequate. The second half of the century saw increasing economic prosperity, and unprecedented social and scientific advances. The impact on food processing was manifold: nascent technologies such as freezing and chilling were increasingly exploited, and the consumer became the major focus of a food industry that became more sophisticated, embracing automation, computerisation and new developments in, for example, drying, heat processing, controlled and modified atmosphere packaging, ingredients and quality assurance. By 1999, this had led to an industry which provided foods that were not only safe, nutritious and palatable, but which were also increasingly convenient and healthy.

Bread↗
PubMed1999

Specificity of ascorbate analogs for ascorbate transport. Synthesis and detection of [(125)I]6-deoxy-6-iodo-L-ascorbic acid and characterization of its ascorbate-specific transport properties.

Cellular ascorbic acid accumulation occurs in vitro by two distinct mechanisms: transport of ascorbate itself or transport and subsequent intracellular reduction of its oxidized product, dehydroascorbic acid. It is unclear which mechanism predominates in vivo. An easily detectable compound resembling ascorbate but not dehydroascorbic acid could be a powerful tool to distinguish the two transport activities. To identify compounds, 21 ascorbate analogs were tested for inhibition of ascorbate or dehydroascorbic acid transport in human fibroblasts. The most effective analogs, competitive inhibitors of ascorbate transport with K(i) values of 3 microM, were 6-deoxy-6-bromo-, 6-deoxy-6-chloro-, and 6-deoxy-6-iodo-L-ascorbate. No analog inhibited dehydroascorbic acid transport. Using substitution chemistry, [(125)I]6-deoxy-6-iodo-L-ascorbate (1.4 x 10(4) mCi/mmol) was synthesized. HPLC detection methods were developed for radiolabeled and nonradiolabeled compounds, and transport kinetics of both compounds were characterized. Transport was sodium-dependent, inhibited by excess ascorbate, and similar to that of ascorbate. Transport of oxidized ascorbate and oxidized 6-deoxy-6-iodo-L-ascorbate was investigated using Xenopus laevis oocytes expressing glucose transporter isoform GLUT1 or GLUT3. Oxidation of ascorbate or its analog in media increased uptake of ascorbate in oocytes by 6-13-fold compared with control but not that of 6-deoxy-6-iodo-L-ascorbate. Therefore, 6-deoxy-6-iodo-L-ascorbate, although an effective inhibitor of ascorbate transport, either in its reduced or oxidized form was not a substrate for dehydroascorbic acid transport. Thus, radiolabeled and nonradiolabeled 6-deoxy-6-iodo-L-ascorbate provide a new means for discriminating dehydroascorbic acid and ascorbate transport in ascorbate recycling.

Animals↗
PubMed1999

Dietary antioxidant supplementation and DNA damage in smokers and nonsmokers.

Deficiencies of antioxidant nutrients have been implicated in the etiology of lung and other cancers. However, most intervention trials with antioxidant nutrients have not shown beneficial effects, and some have indicated that beta-carotene may be deleterious. This randomized, double-blind, placebo-controlled study evaluated the effects of five short-term (4-wk) antioxidant nutrient supplement regimens [ascorbic acid (350 mg), RRR-alpha-tocopherol (250 mg), beta-carotene (60 mg), selenium (80 micrograms as sodium selenite), ascorbic acid (350 mg) + RRR-alpha-tocopherol (250 mg)] on plasma antioxidants and mononuclear leukocyte DNA damage in male smokers (n = 9) and nonsmokers (n = 12). Plasma concentrations of ascorbic acid and tocopherol were significantly increased by supplementation, but there was no significant change in plasma beta-carotene or blood glutathione peroxidase activity after supplementation with beta-carotene or selenium. DNA damage in mononuclear leukocytes, as assessed by comet assay, was not affected by any supplementation regimen. DNA damage, as assessed by 8-hydroxydeoxyguanosine in mononuclear leukocytes, was not influenced by ascorbic acid, alpha-tocopherol, or selenium supplementation in smokers or nonsmokers, but beta-carotene supplementation resulted in significant differences between smokers and nonsmokers in the level of oxidative DNA damage, with decreases in smokers and increases in smokers. This is a further indication of the differential effects of supplemental beta-carotene in smokers and nonsmokers.

Adult↗
PubMed1997

Use of a new vitamin C-deficient diet in a depletion/repletion clinical trial.

To conduct an inpatient study on the recommended dietary allowance (RDA) for vitamin C, we developed a unique vitamin C-deficient diet using a nutrient database and selective menus. Fourteen different menus were developed offering > 300 items with 0-2.4 mg vitamin C per serving. During the 4-6 mo volunteers were hospitalized, daily dietary vitamin C was restricted to < or = 5.0 mg. The mean daily dietary vitamin C intake was < 3.9 mg for the seven study subjects. With concurrent supplementation, the diet provided > or = 85% of the RDA for 17 essential nutrients. Within 3 wk of admission the diet induced vitamin C deficiency as indicated by plasma concentrations, which decreased from 23 +/- 6.9 to 6.9 +/- 2.0 mumol/L. Daily intake of vitamin C and five other nutrients was determined by nutrient database analyses. Mean energy, protein, the iron were 105-185% of the RDA and total and saturated fat were 32% and 10% of energy, respectively. Weight and nutritionally relevant indexes remained normal. Dietary adherence, calculated by the number of days with < or = 5.0 mg vitamin C per total study days, was 88-98% per repletion dose. Computer analyses of menu selections permitted individual preferences to be met while restricting vitamin C intake to < or = 5.0 mg/d. There were no complications from the diet during the depletion and repletion phase. With this diet, ascorbic acid pharmacokinetics for escalating doses could be determined in healthy volunteers.

Ascorbic Acid↗
PubMed1996

Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance.

Determinants of the recommended dietary allowance (RDA) for vitamin C include the relationship between vitamin C dose and steady-state plasma concentration, bioavailability, urinary excretion, cell concentration, and potential adverse effects. Because current data are inadequate, an in-hospital depletion-repletion study was conducted. Seven healthy volunteers were hospitalized for 4-6 months and consumed a diet containing <5 mg of vitamin C daily. Steady-state plasma and tissue concentrations were determined at seven daily doses of vitamin C from 30 to 2500 mg. Vitamin C steady-state plasma concentrations as a function of dose displayed sigmoid kinetics. The steep portion of the curve occurred between the 30- and 100-mg daily dose, the current RDA of 60 mg daily was on the lower third of the curve, the first dose beyond the sigmoid portion of the curve was 200 mg daily, and complete plasma saturation occurred at 1000 mg daily. Neutrophils, monocytes, and lymphocytes saturated at 100 mg daily and contained concentrations at least 14-fold higher than plasma. Bioavailability was complete for 200 mg of vitamin C as a single dose. No vitamin C was excreted in urine of six of seven volunteers until the 100-mg dose. At single doses of 500 mg and higher, bioavailability declined and the absorbed amount was excreted. Oxalate and urate excretion were elevated at 1000 mg of vitamin C daily compared to lower doses. Based on these data and Institute of Medicine criteria, the current RDA of 60 mg daily should be increased to 200 mg daily, which can be obtained from fruits and vegetables. Safe doses of vitamin C are less than 1000 mg daily, and vitamin C daily doses above 400 mg have no evident value.

Adult↗
PubMed1995

Accumulation of vitamin C (ascorbate) and its oxidized metabolite dehydroascorbic acid occurs by separate mechanisms.

It is unknown whether ascorbate alone (vitamin C), its oxidized metabolite dehydroascorbic acid alone, or both species are transported into human cells. This problem was addressed using specific assays for each compound, freshly synthesized pure dehydroascorbic acid, the specially synthesized analog 6-chloroascorbate, and a new assay for 6-chloroascorbate. Ascorbate and dehydroascorbic acid were transported and accumulated distinctly; neither competed with the other. Ascorbate was accumulated as ascorbate by sodium-dependent carrier-mediated active transport. Dehydroascorbic acid transport and accumulation as ascorbate was at least 10-fold faster than ascorbate transport and was sodium-independent. Once transported, dehydroascorbic acid was immediately reduced intracellularly to ascorbate. The analog 6-chloroascorbate had no effect on dehydroascorbic acid transport but was a competitive inhibitor of ascorbate transport. The Ki for 6-chloroascorbate (2.9-4.4 microM) was similar to the Km for ascorbate transport (9.8-12.6 microM). 6-Chloroascorbate was itself transported and accumulated in fibroblasts by a sodium-dependent transporter. These data provide new information that ascorbate and dehydroascorbic acid are transported into human neutrophils and fibroblasts by two distinct mechanisms and that the compound available for intracellular utilization is ascorbate.

Ascorbic Acid↗
PubMed1995

Determination of optimal vitamin C requirements in humans.

Although the recommended dietary allowance provides an estimate for vitamin C ingestion in humans, optimal vitamin C requirements are unknown. We define optimal vitamin C requirements operationally based on the following: dose-function relations, availability in the food supply, steady state concentrations in plasma and tissues achieved at each dose of vitamin C, urinary excretion, bioavailability, toxicity, and epidemiologic observations. Optimal vitamin C requirements can be estimated when information is available for at least some of these criteria.

Ascorbic Acid↗
PubMed1994

Can dietary oats promote health?

Current consumption levels of oat products are low. However, oats are a nutritious foodstuff, supplying protein of relatively good quality and significant quantities of vitamins and minerals. As a bland and nutritious foodstuff, oats are valuable for the nutrition of infants and the sustenance of adults. Oats are generally consumed as oatmeal or rolled oats, but oat bran has become available in recent years. In addition to their nutritional attributes, dietary oat products exert a number of physiological effects that may be beneficial in the prevention or amelioration of pathophysiological states, including improvements in gastro-intestinal function, modulation of glucose metabolism, and decreasing blood cholesterol status. The latter effects have attracted considerable attention and a critical review of the data indicates that dietary oats have the ability to lower blood cholesterol and that they are most effective at high dose levels in hypercholesterolaemic individuals. Although the soluble fibre, beta-glucan gum appears to be the major hypocholesterolaemic agent, its mode of action is not fully understood.

Avena↗
PubMed1994

Iron status, blood lipids and endogenous antioxidants in response to dietary iron levels in male and female rats.

The effect of dietary iron levels on iron status, blood lipids and endogenous antioxidants was investigated in male and female rats. Diets low in iron (15 mg/kg Fe; LFe) or high in iron (400 mg/kg Fe; HFe) were given to groups of male (n = 6) and female (n = 6) weanling rats for six weeks. In a second experiment the same dietary iron levels were fed to groups (n = 12) of males and females for seven months, during which colon tumours were induced. Indices of iron status, blood lipid levels and antioxidant enzyme activities were measured in both experiments. In the first experiment, indices of iron status were significantly higher in HFe rats and in females compared with males. Cholesterol and triglycerides were significantly higher in HFe rats and cholesterol was significantly higher in males. Plasma albumin and bilirubin levels and plasma caeruloplasmin activity were significantly higher in female rats. The second experiment confirmed the higher indices of iron status in HFe rats and in female rats, and also showed that plasma cholesterol levels were significantly higher in HFe rats. There were no consistent, significant differences over both experiments in activities of the antioxidant enzymes measured. Results show that higher dietary iron levels are associated with higher cholesterol levels in male and female rats. However cholesterol was found to be higher in male rats while iron status was higher in female rats. This indicates that factors other than iron status are responsible for the differences in cholesterol in male and female rats.

Animals↗
PubMed1993

Ascorbic acid accumulation and transport in human fibroblasts.

As the initial step in the use of fibroblasts as a model system for 'in situ kinetics', ascorbic acid (vitamin C) accumulation in normal human fibroblasts was investigated for the first time. Ascorbic acid was transported into fibroblasts and accumulated against a concentration gradient up to 20-fold, as measured by h.p.l.c. with coulometric electrochemical detection. Ascorbic acid accumulation was mediated by two concentration-dependent transport activities. The first was a high-affinity activity with an apparent Km of 6 microM and an apparent Vmax. of 203 microM/h, and the second was a low-affinity activity with an apparent Km of 5 mM and an apparent Vmax. of 1.8 mM/h. Both activities were inhibited by metabolic inhibitors and inhibitors of ascorbic acid transport in human neutrophils. The low-affinity transporter could not be accounted for by diffusion. Although the high-affinity transport activity was comparable with that described for human neutrophils, the low-affinity transporter was different. These data provide the first evidence that two-component ascorbic acid transport may be a generalized mechanism for accumulation of this vitamin in humans.

2,4-Dinitrophenol↗
PubMed1993

Coulometric electrochemical detection of hydroxyproline using 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole.

A new method for detection of hydroxyproline has been developed. Hydroxyproline was derivatized using 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole; separation and detection were accomplished using HPLC with coulometric electrochemical detection. Derivatized hydroxyproline was initially detected using a 16 channel coulometric electrochemical array system. The assay was slightly modified for use with a simpler 2-channel coulometric electrochemical detector. Both detectors are sensitive into the upper fmol range. Derivatization of hydroxyproline occurs in 5 min and the derivative is stable for several hours at 0 degrees C. The techniques were used to quantitate hydroxyproline in purified type I collagen and other biological samples.

4-Chloro-7-nitrobenzofurazan↗
PubMed1991

Cloning of an NADH-dependent butanol dehydrogenase gene from Clostridium acetobutylicum.

The acetone-butanol fermentation of C. acetobutylicum is characterized by the unique shift from acid to solvent production. The mechanism of the solventogenic switch involves the induction of several enzymes, including NADH-dependent butanol dehydrogenase (BDH) at the onset of solventogenesis. This enzyme is responsible for the final conversion of butyraldehyde to butanol, and is distinct from the NADPH-dependent alcohol dehydrogenase (ADH) also present in the organism. To characterize the genetic control of this gene, we have cloned and expressed it in E. coli. A lambda EMBL3 phage library of C. acetobutylicum DNA was screened via plaque hybridization using a [32P]-radiolabeled, 32-fold degenerate, 62-mer oligonucleotide probe. The probe was designed by reverse translation of the NH2-terminal amino acid sequence of purified BDH II. Southern blot experiments indicate that the phage insert was of clostridial origin and had no homology with the previously cloned NADPH-dependent ADH. Subcloning of DNA from purified positive plaques has localized the gene to a 3.5-kb EcoRI fragment from which the enzyme is well expressed. The sequence of the 25 NH2-terminal amino acids for the cloned enzyme purified from E. coli was determined and found to be identical to that for the clostridial NADH-dependent BDH II. Maxicell analysis of [35S]-radiolabeled plasmid-encoded proteins identified a species encoded by the clostridial insert with the expected Mr of 42 kD.

Alcohol Oxidoreductases↗
PubMed1991

Ascorbic acid accumulation in human skin fibroblasts.

The transport and accumulation of ascorbic acid in normal human skin fibroblasts in culture was investigated by using high-performance liquid chromatographic separation and coulometric electrochemical detection. Results measured as picomole ascorbic acid per microgram cell protein were expressed in molar amounts after determining the volume of skin fibroblasts. Confluent fibroblasts contained undetectable amounts of ascorbic acid. On incubation with micromole per liter amounts of ascorbic acid in the medium, cells showed increasing uptake of ascorbic acid with time, accumulating a 15-fold excess in 3.5 h. Kinetic experiments suggested two transport mechanisms, a high-affinity and a low-affinity transport activity. Both transport activities were temperature sensitive and accumulated ascorbic acid against a concentration gradient.

Ascorbic Acid↗