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The influence of restricted feeding on site and extent of digestion and flow of nitrogenous compounds to the duodenum in steers.

The effects of restricted feeding on site and extent of digestion, flow of N-containing compounds to the duodenum, and ruminal metabolism were determined. In Trial 1, corn silage-based diets were fed at one of three intakes to three ruminally and duodenally fistulated steers (420 +/- 4.4 kg BW) in a repeated 3 x 3 Latin square experiment. Feeding levels were 100% of ad libitum intake, 90% of ad libitum intake, and 80% of ad libitum intake. Site of digestion was not affected by restricted feeding; however, extent of DM, NDF, and apparent N digestion were increased (P < .03) 2.8, 4.1, and 6.2 percentage units for each 1-kg restriction in DM intake. Restricted feeding increased (P < .06) ruminal pH and ammonia concentrations, decreased (P < .05) ruminal liquid dilution rate, and had no major effects on bacterial concentrations. In Trial 2, all-concentrate diets based on whole shelled corn were fed at 100, 90, or 80% of ad libitum intake to six ruminally and duodenally fistulated steers (440 +/- 4.1 kg BW) in a replicated 3 x 3 Latin square experiment. Restricted feeding increased (P < .06) apparent ruminal DM digestion; however, true ruminal OM digestibility was not affected. Extent of apparent N digestion increased 3.0 percentage units for each 1-kg restriction in DMI. Ruminal pH was not affected by restricted feeding; however, ruminal ammonia concentrations increased (P < .06) and ruminal liquid dilution rate decreased (P < .04) with restricted feeding. In both Trials, total N flow to the duodenum was approximately 100% of N intake for the 80% of ad libitum intake. Flow of N exceeded N intake in a linear (P < .01) manner as DMI increased. Decreases in duodenal N flow when intake was restricted resulted from decreases (P < .01) in bacterial N flowing to the duodenum, and also in decreases (P < .01) in non-ammonia, non-bacterial N flow when whole shelled corn-based diets were fed. We concluded that restrictions in digestible energy intake are less than the DM restriction when corn silage-based diets are fed but are equal to the DM restriction when whole shelled corn-based diets are fed. Also, restricted feeding strategies reduce the flow of N to the duodenum from both bacterial and feed origins.

Animal Feed↗

Glucose metabolism in isolated adipocytes from ad Libitum- and restricted-fed lean and obese Zucker rats at two different ages.

Chronic food restriction in Sprague-Dawley rats has been shown to alter adipose glucose metabolism. In the present study, lean and obese male Zucker rats were food restricted from 5 weeks until either 10 or 26 weeks of age and adipocyte glucose metabolism was measured. Adipocytes from restricted-fed lean and obese Zucker rats converted more glucose to CO2 and fatty acids than those from their ad libitum-fed counterparts in both the absence and the presence of increasing doses of insulin at 10 weeks of age. At the highest insulin dose, adipocytes from restricted-fed obese rats converted significantly more glucose to CO2 and fatty acids than did those from restricted-fed lean rats. Basal glyceride-glycerol values were similar in all groups at this age. At the 0.4 and 2.0 ng/ml insulin levels, glyceride-glycerol production was highest in restricted-fed lean rats; restricted-fed obese and ad libitum-fed lean rats had similar values; and ad libitum-fed obese rats had the lowest. At the 20 ng/ml dose, glyceride-glycerol values of restricted-fed rats were higher than those of ad libitum-fed rats. Basal and insulin-stimulated values were compared within each group. Most basal versus insulin-stimulated values were significantly different for the two lean groups. For ad libitum-fed obese rats, only 0 versus 20 ng/ml insulin values were significant. Restricted-fed obese rats had significant increases in 0 versus both 2 and 20 ng/ml insulin values. Restricted-fed obese rats had significantly lower serum insulin levels relative to ad libitum-fed obese rats at 10 weeks of age. Adipocytes from all rats at 26 weeks of age had similar basal rates of conversion of glucose metabolism to all three metabolites. In the presence of insulin, adipocytes from restricted-fed lean rats metabolized significantly more glucose to CO2 and glyceride-glycerol than adipocytes prepared from the three other groups. Fatty acid production was similar in all groups at each insulin level. Only restricted-fed lean rats showed consistent significant responses to insulin stimulation for the three metabolites. Whether these results are due to age, length of food restriction, or serum insulin levels remains to be determined.

Adipose Tissue↗

Dietary restrictions for patients with neutropenia: a survey of institutional practices.

PURPOSE/OBJECTIVES: To describe institutional practices related to dietary restrictions for patients with neutropenia to determine whether restrictions are used and when they are implemented and discontinued. DESIGN: Descriptive survey. SAMPLE: 156 institutions belonging to the Association of Community Cancer Centers. METHODS: Mailed survey. FINDINGS: Of the institutions surveyed, 78% (n = 120) placed patients with neutropenia on restricted diets. Participating institutions responded that patients were placed on restricted diets at a variety of different white blood cell and neutrophil counts, including neutrophils < 1,000 (43%) and < 500 (46%). The majority of institutions (92%) placed patients on restricted diets once neutropenia was documented, while only 9% of institutions restricted diets when cancer treatment was initiated. Of the participating institutions, 83% (n = 96) restricted diets only when patients were neutropenic rather than throughout the duration of the chemotherapy regimen. The most commonly restricted foods were fresh fruits and juices (92%), fresh vegetables (95%), and raw eggs (74%). Few institutions restricted tap water (12%). Wine was restricted at 39% of institutions, and beer was restricted at 40% of institutions. CONCLUSIONS: The role of diet in the development of infection in patients with neutropenia is unclear. This unclear role contributes to the variation in dietary restrictions among institutions. IMPLICATIONS FOR NURSING PRACTICE: Additional research should focus on dietary factors contributing to neutropenic infections and establishing criteria for implementation of specific dietary modifications. Nursing assessment should include nutritional status and risk factors for neutropenia and bacterial translocation. Nursing protocols for neutropenic dietary restrictions should be based on research findings.

Bacterial Infections↗

Restricted driver licensing for medical impairments: does it work?

BACKGROUND: Medical conditions may adversely affect driving ability. Many North American jurisdictions provide restricted driving licences that permit people with certain medical conditions to drive under limited conditions, but the effectiveness of such programs has not yet been determined. The objectives of this study were to evaluate the rates of crashes and traffic violations among drivers with a restricted licence, compared with the rates in the general driving population, and to compare the crash and traffic violation rates before and after driving restrictions were imposed. METHODS: We retrospectively analyzed a cohort of all licensed Saskatchewan drivers registered from Jan. 1, 1992, to Apr. 19, 1999. The cohort was divided into those with a restricted licence and those with an unrestricted general licence. We used multivariate Poisson regression to calculate incidence rate ratios (IRRs) for at-fault crashes and traffic violations, adjusting for age, sex and residence (urban v. rural). We used interventional time series analysis to compare rates of crashes and traffic violations before and after the imposition of driving restrictions. RESULTS: Of the 703,758 drivers in the study, 23,185 (3.3%) had a restricted licence. Restricted licence holders had a higher crash rate than drivers without restrictions (adjusted IRR 1.13, 95% confidence interval [CI] 1.11-1.17). However, this rate was lower than that among male drivers (adjusted IRR 2.01, 95% CI 1.99-2.02) and urban drivers (adjusted IRR 1.38, 95% CI 1.37-1.39). Drivers with restricted licences had a lower traffic violation rate than those without restrictions (adjusted IRR 0.93, 95% CI 0.91-0.95). At-fault crash rates decreased by 12.8% (95% CI 2.4%-23.2%) and adjusted traffic violation rates decreased by 10.0% (95% CI 4.4%-15.7%) after restrictions were imposed. During the study period, licence restrictions likely averted up to 816 crashes and 751 traffic violations. INTERPRETATION: Province-wide population data suggest that a restricted licensing program appears to provide a significant decrease in the rates of crashes and traffic violations.

Accidents, Traffic↗

ELISA detection of restriction site polymorphisms in the pig ryanodine receptor locus.

We compare two strategies for ELISA detection of restriction site polymorphisms (EDRSP) that are suitable for high-throughput genotyping of the pig ryanodine receptor point mutation (RYR1(hal)). In both procedures, target DNA is amplified by PCR with one primer that is 5' biotinylated and a second primer that is 5' fluoresceinylated. PCR products are captured in duplicate wells on a streptavidin-coated, 96-well plate. The duplicates may be treated in two ways. In a single restriction enzyme assay, one duplicate is exposed to a restriction enzyme that cuts one allele specifically, and the second duplicate is exposed to no restriction enzyme. In a dual restriction enzyme assay, the second replicate is exposed to a second restriction enzyme that cuts the alternate allele specifically. Thereafter, the two procedures are similar; anti-fluorescein antibodies conjugated to peroxidase are allowed to bind to the fluoresceinylated ends, the plate is washed, and a substrate is converted to a colored end product. The ratio of the absorbances in the two wells is used to classify subjects by genotype. When the dual restriction enzyme assay is run, three genotype groups are easily distinguishable. When the single restriction enzyme assay is run, heterozygotes generate values that may overlap with those of the homozygotes that are not cut by the restriction enzyme. Dual restriction enzyme assays are more accurate than single restriction enzyme assays; however, single restriction enzyme assays are sufficient for identifying pigs that carry RYR1(hal).

Animals↗

Carbohydrate restriction does not change mitochondrial free radical generation and oxidative DNA damage.

Many previous investigations have consistently reported that caloric restriction (40%), which increases maximum longevity, decreases mitochondrial reactive species (ROS) generation and oxidative damage to mitochondrial DNA (mtDNA) in laboratory rodents. These decreases take place in rat liver after only seven weeks of caloric restriction. Moreover, it has been found that seven weeks of 40% protein restriction, independently of caloric restriction, also decrease these two parameters, whereas they are not changed after seven weeks of 40% lipid restriction. This is interesting since it is known that protein restriction can extend longevity in rodents, whereas lipid restriction does not have such effect. However, before concluding that the ameliorating effects of caloric restriction on mitochondrial oxidative stress are due to restriction in protein intake, studies on the third energetic component of the diet, carbohydrates, are needed. In the present study, using semipurified diets, the carbohydrate ingestion of male Wistar rats was decreased by 40% below controls without changing the level of intake of the other dietary components. After seven weeks of treatment the liver mitochondria of the carbohydrate restricted animals did not show changes in the rate of mitochondrial ROS production, mitochondrial oxygen consumption or percent free radical leak with any substrate (complex I- or complex II-linked) studied. In agreement with this, the levels of oxidative damage in hepatic mtDNA and nuclear DNA were not modified in carbohydrate restricted animals. Oxidative damage in mtDNA was one order of magnitude higher than that in nuclear DNA in both dietary groups. These results, together with previous ones, discard lipids and carbohydrates, and indicate that the lowered ingestion of dietary proteins is responsible for the decrease in mitochondrial ROS production and oxidative damage in mtDNA that occurs during caloric restriction.

8-Hydroxy-2'-Deoxyguanosine↗

Aging and lifelong calorie restriction result in adaptations of skeletal muscle apoptosis repressor, apoptosis-inducing factor, X-linked inhibitor of apoptosis, caspase-3, and caspase-12.

The mechanisms of apoptosis in the loss of myocytes in skeletal muscle with age and the role of mitochondrial and sarcoplasmic reticulum-mediated pathways of apoptosis are unknown. Moreover, it is unknown whether lifelong calorie restriction prevents apoptosis in skeletal muscle and reverses age-related alterations in apoptosis signaling. We investigated key apoptotic regulatory proteins in the gastrocnemius muscle of 12 and 26 month old ad libitum fed and 26 month old calorie-restricted male Fischer-344 rats. We found that apoptosis increased with age and that calorie-restricted rats showed less apoptosis compared with their age-matched cohorts. Moreover, pro- and cleaved caspase-3 levels increased significantly with age and calorie-restricted rats had significantly lower levels than the aged ad libitum group. Neither age nor calorie restriction had any effect on muscle caspase-3 enzyme activity, but the levels of X-linked inhibitor of apoptosis, particularly an inhibitor of caspase-3, increased with age and were reduced significantly in the 26 month old calorie-restricted cohort. The apoptotic inhibitor apoptosis repressor with a caspase recruitment domain (ARC), which inhibits cytochrome c release, underwent an age-associated decline in the cytosol but increased with calorie restriction. In contrast, mitochondrial ARC levels increased with age and were lower in calorie-restricted rats than in age-matched controls, suggesting a translocation of this protein to attenuate oxidative stress. The translocation of ARC may explain the reduction in cytosolic cytochrome c levels observed with age and calorie restriction. Moreover, we found a striking approximately 350% increase in the expression of procaspase-12 (caspase located at the sarcoplasmic reticulum) with age which was significantly lower in the 26 month old calorie-restricted group. The total protein level of apoptosis-inducing factor in the plantaris muscle increased with age and was reduced calorie-restricted rats compared with age-matched controls, but there were no significant changes in this pro-apoptotic protein in the isolated nuclei. Calorie restriction is able to lower the apoptotic potential in aged skeletal muscle by altering several key apoptotic proteins toward cellular survival, thereby reducing the potential for sarcopenia.

Aging↗

Effects of amino acid restriction during starter and grower periods on subsequent performance and incidence of leg disorders in two strains of male large white turkeys.

Male turkeys of two commercial Large White strains (Nicholas 88, BUT 6) were subjected to growth restriction by means of reducing amino acid (AA) content of diets to a minimum of 75% of NRC (1994) suggested levels. There were three periods when diets containing 75% of NRC recommended AA for that age period were fed ad libitum: 0 to 3 wk, 0 to 6 wk, or 6 to 12 wk. A fourth (control) group was not restricted in AA content at any time. When turkeys were not fed the AA-restricted diets they were fed diets formulated to meet a minimum of 100, 110, or 120% of NRC (1994) AA recommendations, which resulted in a 3 x 4 factorial arrangement of treatments with three AA levels by four restriction times. Four pens of 12 males each were fed each AA by restriction time combination. At 18 wk, all birds were scored individually for leg condition and representative samples of turkeys were processed for parts yield. Birds fed restricted diets from 0 to 6 or 6 to 12 wk had significantly lower BW at 18 wk than control birds. Birds fed the restricted diets from 0 to 3 wk did not differ significantly in 18-wk BW compared to control birds but the magnitude of difference was similar to that observed at the end of the restriction period. Feed utilization was not improved by early AA restriction. Restricting early growth resulted in a significantly higher incidence of birds with no leg disorders and a lower incidence of birds with moderate leg disorders than control birds. Feeding higher AA levels during realimentation resulted in a greater severity of leg disorders. Breast meat yield was depressed significantly as severity of early restriction increased. Increasing dietary AA above NRC (1994) recommended levels generally improved performance during realimentation but was not able to compensate for reduced gains during restriction.

Amino Acids↗

Fluid restriction in anorexia nervosa: a neglected symptom or new phenomenon?

OBJECTIVE: The deliberate restriction of fluids to control weight is even more dangerous than food restriction since it results in several serious medical complications. However, there has been scant attention given to the anorexia nervosa patient's manipulation of fluids. It is our clinical impression that fluid restriction in this illness is more common than previously thought. METHOD: We summarize the demographic and clinical features of six cases of anorexia nervosa and one case of eating disorder not otherwise specified (ED-NOS) (subthreshold anorexia nervosa), where fluid restriction was a major behavioral problem. We then describe two of the anorexia nervosa cases in more detail. All were treated at a dieting disorders unit affiliated with the University of Sydney. Their preadmission history, psychological and physical status on admission, results of physical investigations, the beginning of the fluid restriction, fluid and food intake throughout treatment, and the resolution of the fluid restriction were assessed. RESULTS: Patterns emerged in the relationship between eating and drinking. In all cases, food restriction was severe prior to the onset of fluid restriction but, notably, fluid intake recommenced prior to food intake. The reasons given by patients for restricting fluid were that it contained calories and that it made them feel full. Most anorexic patients equate feeling full with "feeling fat." Furthermore, they feel fully in control when they restrict fluid as well as food and this produces a strong motivation to maintain the behavior. DISCUSSION: The cases illustrate the insidious nature and serious consequences of fluid restriction and the difficulties managing dieting-disordered patients who undertake it. Careful attention must be given to assessment and clinicians should be aware of fluid restriction as an important aspect of anorexic behavior.

Adolescent↗

Selective amino acid restriction targets mitochondria to induce apoptosis of androgen-independent prostate cancer cells.

Relative specific amino acid dependency is one of the metabolic abnormalities of cancer cells, and restriction of specific amino acids induces apoptosis of prostate cancer cells. This study shows that restriction of tyrosine and phenylalanine (Tyr/Phe), glutamine (Gln), or methionine (Met), modulates Raf and Akt survival pathways and affects the function of mitochondria in DU145 and PC3, in vitro. These three restrictions inhibit energy production (ATP synthesis) and induce generation of reactive oxygen species (ROS). Restriction of Tyr/Phe or Met in DU145 and Met in PC3 reduces mitochondrial membrane potential (DeltaPsim) and induces caspase-dependent and -independent apoptosis. In DU145, Tyr/Phe or Met restriction reduces activity of Akt, mitochondrial distribution of phosphorylated Raf and apoptosis inducing factor (AIF), and increases mitochondrial distribution of Bak. Mitochondrial Bcl-XL is increased in Tyr/Phe-restricted but decreased in Met-restricted cells. Under Tyr/Phe or Met restriction, reduced mitochondrial Raf does not inactivate the pro-apoptotic function of Bak. Tyr/Phe restriction also inhibits Bcl-2 and Met restriction inhibits Bcl-XL in mitochondria. These comprehensive actions damage the integrity of the mitochondria and induce apoptosis of DU145. In PC3, apoptosis induced by Met restriction was not associated with alterations in intracellular distribution of Raf, Bcl-2 family proteins, or AIF. All of the amino acid restrictions inhibited Akt activity in this cell line. We conclude that specific amino acid restriction differentially interferes with homeostasis/balance between the Raf and Akt survival pathways and with the interaction of Raf and Bcl-2 family proteins in mitochondria to induce apoptosis of DU145 and PC3 cells.

Adenosine Triphosphate↗

Quantification of epitope-specific MHC class-II-restricted T cells following lymphocytic choriomeningitis virus infection.

CD4(+) T cells are critical for the control of many viruses; however, the numbers of virus-specific CD4(+) cells that are expanded following infection are unknown. We have addressed this issue by enumerating virus-specific, MHC class-II-restricted T cells following infection of mice with lymphocytic choriomeningitis virus (LCMV). We have found that the numbers of T cells that produce interferon-gamma in response to stimulation with three different class-II-restricted LCMV epitopes increase from undetectable numbers in noninfected animals to between 4 x 10(5) and 2 x 10(6) cells per spleen at the peak of the T cell response. This contrasts with the numbers of virus-specific class-I-restricted T cells which expand to 1 x 10(7) to 2 x 10(7) cells per spleen during the same time period. We could not reproducibly detect virus-specific class-I-restricted or class-II-restricted T cells that produced interleukin-4 at any time following LCMV infection, indicating that infection with this virus induces a predominantly type 1 cytokine response. In contrast to the rapid decrease in the numbers of class-I-restricted T cells, the numbers of LCMV-specific class-II-restricted T cells declined gradually following the peak of the T cell response. We demonstrate, therefore, that following infection with LCMV there is expansion of both class-I-restricted and class-II-restricted virus-specific T cells; however, the degree of expansion of class-II-restricted T cells is substantially less than that observed for class-I-restricted cells. Furthermore, the downregulation phase of the class-II-restricted response is protracted compared with the precipitous contraction of the antiviral CD8(+) T cell response.

Amino Acid Sequence↗

Alleviation of EcoK DNA restriction in Escherichia coli and involvement of umuDC activity.

The activity of the EcoK DNA restriction system of Escherichia coli reduces both the plating efficiency of unmodified phage lambda and the transforming ability of unmodified pBR322 plasmid DNA. However, restriction can be alleviated in wild-type cells, by UV irradiation and expression of the SOS response, so that 10(3)- to 10(4)-fold increases in phage growth and fourfold increases in plasmid transformation occurred with unmodified DNA. Restriction alleviation was found to be a transient effect because induced cells, which initially failed to restrict unmodified plasmid DNA, later restricted unmodified phage lambda. Although the SOS response was needed for restriction alleviation, constitutive SOS induction, elicited genetically with a recA730 mutation, did not alleviate restriction and UV irradiation was still needed. A hitherto unsuspected involvement of the umuDC operon in this alleviation of restriction is characterized and, by differential complementation, was separated from the better known role of umuDC in mutagenic DNA repair. The need for cleavage of UmuD for restriction alleviation was shown with plasmids encoding cleavable, cleaved, and non-cleavable forms of UmuD. However, UV irradiation was still needed even when cleaved UmuD was provided. The possibility that restriction alleviation occurs by a general inhibition of the EcoK restriction/modification complex was tested and discounted because modification of lambda was not reduced by UV irradiation. An alternative idea, that restriction activity was competitively reduced by an increase in EcoK modification, was also discounted by the lack of any increase in the modification of lambda Ral-, a naturally undermodified phage. Other possible mechanisms for restriction alleviation are discussed.

Bacterial Proteins↗

Rewarding and locomotor-activating effects of direct dopamine receptor agonists are augmented by chronic food restriction in rats.

RATIONALE: Previous studies indicate that chronic food restriction augments the rewarding and motor-activating effects of diverse drugs of abuse. The drugs that have so far proved susceptible to the augmenting effect of food restriction all increase synaptic concentrations of dopamine (DA). It is not known whether behavioral effects of selective, direct DA receptor agonists are also subject to the augmenting effect of food restriction. OBJECTIVES: The first objective of this study was to investigate whether the rewarding and locomotor-activating effects of the D1 agonist, A77636, and the D2 agonist, quinpirole are augmented by chronic food restriction. The second purpose was to investigate whether the augmented rewarding and locomotor-activating effects of d-amphetamine in food-restricted rats are reversed by the D1 antagonist, SCH23390. METHODS: Rewarding effects of drugs were measured in terms of their ability to lower the threshold for lateral hypothalamic self-stimulation (LHSS) using a rate-frequency method. Locomotor-activating effects were measured in terms of the number of midline crossings exhibited by rats in a shuttle apparatus. RESULTS: A77636 (1.0 and 2.5 mg/kg, i.p.) produced a greater threshold-lowering effect in food-restricted than ad libitum fed rats but produced variable effects on locomotor activity with no difference between groups. Quinpirole (0.2 and 0.5 mg/kg, i.p.) produced a marginally greater threshold-lowering effect in food-restricted rats and a dramatic locomotor response that was exclusive to food-restricted rats. The D1 antagonist, SCH23390, at a dose of 0.01 mg/kg (i.p.), had no effect on the lowering of LHSS threshold by amphetamine (0.5 mg/kg, i.p.) in ad libitum fed rats but blocked the augmentation otherwise observed in food-restricted rats. SCH23390, at a dose of 0.025 mg/kg, had no effect on locomotor activity induced by amphetamine (0.5 mg/kg) in ad libitum fed rats but blocked the augmentation otherwise observed in food-restricted rats. CONCLUSIONS: These results indicate that the augmentation of reward by food restriction extends to drugs that bypass the DA terminal and act postsynaptically. When taken together with prior immunohistochemical and behavioral findings, these results suggest that food restriction may increase the "enabling" effect of the D1 receptor on DA-mediated behaviors.

Adamantane↗

Ovarian and hormonal responses to a progesterone-releasing controlled internal drug releasing treatment in dietary-restricted goats.

An experiment was conducted to evaluate the effects of dietary restriction on ovarian, endocrine (ovarian steroids and luteinizing hormone (LH) pulse) and metabolic (glucose, insulin and non-esterified fatty acid (NEFA)) profiles in goats treated with a progesterone-releasing controlled internal drug releasing (CIDR-G) device. Cycling goats were offered either a maintenance or a restricted (30% of requirement; n =4 per treatment) level of feeding. The dietary restriction was started on the day following ovulation. At 30-32 days after the start of food restriction, the goats received a prostaglandin F(2alpha) (2mg of dinoprost) injection followed by 10 days of CIDR-G treatment. Ovarian ultrasonographic images were monitored daily throughout the experiment and blood samples were collected daily just before the morning feeding for analysis of endocrine and metabolic profiles. Frequent blood samples (1 ml) were also collected at 10 min intervals for 8 h from -8 h to CIDR-G removal, and from 32 to 40 h after CIDR-G removal for analysis of LH pulses. Body weight was significantly (P < 0.05) decreased in the food-restricted animals. Oestrous behaviour and ovulation followed by a rise of plasma progesterone concentration were observed after the CIDR-G removal in all control animals but not in any of the food-restricted animals within 12 days after CIDR-G removal. The LH pulse frequency from 32 to 40 h after the CIDR-G removal was significantly (P < 0.05) lower in the food-restricted animals than in control animals (1.5 +/- 0.6 versus 3.8 +/- 0.5 pulses for 8 h). There was no significant difference in the glucose concentration in weekly plasma samples between control and food-restricted animals. Insulin concentrations from 2 weeks after the start of feed restriction were significantly (P < 0.05) lower in restricted animals than in control animals. The NEFA concentration in restricted animals was significantly (P < 0.05) increased after the start of feed restriction, and then decreased gradually to the basal level. The present results suggest that nutritionally induced anovulation after CIDR-G treatment is associated with a reduction in the frequency of LH pulses, and that insulin and NEFA, rather than the glucose concentration in the circulation, may be associated with the metabolic suppression of LH pulses.

Animals↗

Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model.

Diet and lifestyle produce major effects on tumour incidence, prevalence, and natural history. Moderate dietary restriction has long been recognised as a natural therapy that improves health, promotes longevity, and reduces both the incidence and growth of many tumour types. Dietary restriction differs from fasting or starvation by reducing total food and caloric intake without causing nutritional deficiencies. No prior studies have evaluated the responsiveness of malignant brain cancer to dietary restriction. We found that a moderate dietary restriction of 30-40% significantly inhibited the intracerebral growth of the CT-2A syngeneic malignant mouse astrocytoma by almost 80%. The total dietary intake for the ad libitum control group (n=9) and the dietary restriction experimental group (n=10) was about 20 and 13 Kcal x day(-1), respectively. Overall health and vitality was better in the dietary restriction-fed mice than in the ad libitum-fed mice. Tumour microvessel density (Factor VIII immunostaining) was two-fold less in the dietary restriction mice than in the ad libitum mice, whereas the tumour apoptotic index (TUNEL assay) was three-fold greater in the dietary restriction mice than in the ad libitum mice. CT-2A tumour cell-induced vascularity was also less in the dietary restriction mice than in the ad libitum mice in the in vivo Matrigel plug assay. These findings indicate that dietary restriction inhibited CT-2A growth by reducing angiogenesis and by enhancing apoptosis. Dietary restriction may shift the tumour microenvironment from a proangiogenic to an antiangiogenic state through multiple effects on the tumour cells and the tumour-associated host cells. Our data suggest that moderate dietary restriction may be an effective antiangiogenic therapy for recurrent malignant brain cancers.

Animals↗

Effects of growth restriction in early childhood on growth, IQ, and cognition at age 11 to 12 years and the benefits of nutritional supplementation and psychosocial stimulation.

OBJECTIVES: (1) To determine whether benefits to growth and cognition remain after intervention in growth-restricted children who received psychosocial stimulation and nutritional supplementation in early childhood. (2) To investigate the extent of the differences in IQ and cognition at age 11 to 12 years between growth-restricted and non-growth-restricted children. STUDY DESIGN: Growth-restricted and non-growth-restricted children were identified at age 9 to 24 months, at which time the growth-restricted children participated in a 2-year randomized trial of nutritional supplementation and psychosocial stimulation. Eight years after the interventions ended, the children's growth, IQ, and cognitive functions were measured. RESULTS: There were no significant benefits from supplementation to growth or cognition. Children who had received stimulation had higher scores on the Weschler Intelligence Scales for Children-Revised full-scale (IQ) and verbal scale and tests of vocabulary and reasoning (all P <.05). The growth-restricted children had significantly lower scores than the non-growth-restricted children on 10 of 11 cognitive tests. CONCLUSIONS: Psychosocial stimulation had small but significant long-term benefits on cognition in growth-restricted children. Growth-restricted children had significantly poorer performance than non-growth-restricted children on a wide range of cognitive tests, supporting the conclusion that growth restriction has long-term functional consequences.

Child↗

Effects of photostimulation at 18, 24 and 30 weeks of age on the productivity of female turkeys fed ad libitum or restricted until point of lay.

1. Turkey females were fed ad libitum or restricted from 6 weeks of age to achieve mean body weights of 0.6 of ad libitum fed birds on photostimulation at 18, 24 or 30 weeks of age. Body weight, food intake, egg production and hatchability were recorded to 54 weeks of age. 2. Restricted turkeys were fed ad libitum after first egg or 36 weeks of age. Food intake after 30 weeks of age averaged 170 g/bird/d and was similar for all treatments. At 54 weeks of age, restricted turkeys photostimulated at 24 and 30 weeks were not as heavy as turkeys photostimulated at 18 weeks and ad libitum fed turkeys. 3. A large proportion of restricted turkeys photostimulated at 18 weeks of age did not commence lay until 30 to 40 weeks and a significant number of restricted birds photostimulated at 24 weeks had short laying cycles. Restricted birds photostimulated at 30 weeks came into lay and showed similar persistency of lay to ad libitum fed turkeys. 4. Ad libitum fed turkeys laid 115.0, 122.0 and 101.0 and restricted turkeys 92.4, 99.5 and 103.4 eggs when photostimulated at 18, 24 and 30 weeks, respectively. The number of non-settable eggs was lower in restricted compared with ad libitum fed turkeys and declined with age at photostimulation. 5. Egg size at the end of the experiment was similar for ad libitum fed turkeys and restricted birds photostimulated at 18 weeks but was 2.3 g lower for restricted birds photostimulated at 24 and 30 weeks of age. 6. Hatchability was higher, and the proportion of second quality poults was lower with eggs from restricted turkeys. The mean numbers of poults hatched were 59.9, 75.1 and 66.0 for ad libitum fed and 71.7, 65.7 and 79.4 for restricted turkeys photostimulated at 18, 24 and 30 weeks of age.

Age Factors↗

Alterations in hepatic microsomal mixed-function oxidase system during different levels of food restriction in adult male and female rats.

Wistar strain adult male and female rats were given 25, 50 and 75% less food than an ad libitum-fed group of rats for 45 d and the effects of food restriction on hepatic drug metabolizing enzymes, microsomal electron transport components, NADPH-dependent lipid peroxidation and glutathione-S-transferase activities were studied. Compared to ad libitum-fed controls, the cytochrome P-450 levels were higher in food restricted male rats, while they were lower in food restricted females. The activities of NADPH cytochrome c reductase were lower in food restricted females than in ad libitum-fed controls. The activities of drug metabolizing enzymes, aminopyrine N-demethylase and acetanilide hydroxylase were higher in food restricted males, whereas in food restricted females these activities were lower than in respective groups fed ad libitum. Microsomal, NADPH-dependent lipid peroxidation was higher in 25 and 50% food restricted females while in 50 and 75% food restricted males it was lower than in ad libitum controls of the same sex. The cytosolic glutathione-S-transferase activities were lower in food restricted rats of both the sexes than in the same sexed controls. Another group of male and female rats were given 75% less food than the ad libitum-fed rats and refed for 3 d prior to killing. Here also, the effects of restriction were different between sexes. It is concluded that hepatic microsomal mixed-function oxidase system (MFOS) is altered due to feed restriction and food restriction followed by refeeding, in a sex-related manner.

Animals↗