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PubMed1983

Increases in hyperlipoproteinemia, disturbances in cholesterol metabolism and atherosclerosis induced by dietary restriction in rabbits fed a cholesterol-rich diet.

The influence of dietary restriction on cholesterol transport and metabolism was investigated in rabbits given standard or cholesterol-rich diets (0.2 g cholesterol/kg body weight daily) either ad libitum or with 50% caloric ration. Dietary restriction which has only a slight influence in control rabbits markedly aggravated the disturbances induced by exogenous cholesterol. With limited feeding, control rabbits presented a moderate increase in plasma cholesterol, whereas marked aggravation of hypercholesterolemia was observed in cholesterol-fed rabbits. Analysis of the lipoprotein profile showed that the excess of plasma cholesterol with the restricted cholesterol-rich diet corresponded to an increase in the concentration of very low density lipoprotein (VLDL) and low density lipoproteins (LDL) without any additional changes in the composition of these lipoproteins. No significant change appeared in the high density lipoprotein (HDL) concentration. The parameters of cholesterol metabolism were determined, from the curves of [3H]cholesterol radioactivity decrease, using a two-pool model. The increase in cholesterol turnover rate induced by the cholesterol-rich diet was accentuated by dietary restriction, whereas rabbits on standard restricted diet showed a slight decrease. The large increase in the size of both pools A and B in cholesterol-fed rabbits was even more pronounced with limited feeding. Dietary restriction induced additional accumulation of cholesterol in the aortic wall and the grade of the lesions was also aggravated.

Animals↗

PubMed1990

Modulation of free radicals and superoxide dismutases by age and dietary restriction.

Reducing dietary intake has been shown to be the most effective means for modulating aging processes in laboratory rodents. Dietary restriction has also been shown to be a modulator of membrane lipid peroxidation and cytosolic antioxidant status. In the present study, anti-radical action of dietary restriction was investigated further by quantitating the formation of the superoxide radical, hydroxyl radical and hydrogen peroxide by liver microsomes from rats of various ages. The results show that the ad libitum fed group maintained a higher production of superoxide and hydroxyl radicals when compared to the food restricted group of the same age. Hydrogen peroxide formation followed the same trend but was statistically greater only at 3 and 6 months of age. The food restricted group tended to show a higher superoxide dismutase (SOD) activity in both cytosolic and mitochondrial fractions than ad libitum fed controls. These data indicate that the free radical activity observed in the liver microsomes of ad libitum fed rats can be attenuated by dietary restriction, thereby providing a possible biochemical mechanism for its anti-lipoxidative action on membrane lipid peroxidation as reported in an earlier study. This action may in part underlie the life span-prolonging action of food restriction.

Aging↗

PubMed1995

Is late-life caloric restriction beneficial?

Caloric restriction initiated in young mice and rats results in increases in mean and median life span. When caloric restriction is implemented in older animals, an increase in life span is still observed; however, the magnitude of the increase is not as great as that observed in animals calorie restricted since they were young. Here we report the results of a pilot study in which caloric restriction was initiated in mature, older rats. Survival rates and terminal pathology were characterized and compared between a cohort of 17 continually ad libitum fed Long Evans rats and a cohort of 18 Long Evans rats, which were gradually introduced to 33% restriction in diet consumption at 18 months of age. No difference in the median life span was observed between the two groups. The data suggest there may be a level of maturity, or a stage in the aging process, after which caloric restriction no longer increases longevity.

Aging↗

PubMed2001

The relationship between participation restrictions and selected clinical measures following anterior cruciate ligament reconstruction.

This study examined the relationship between participation restrictions in activities of daily living and sports following anterior cruciate ligament reconstruction (ACLR) and the status of knee structures, performance-based activity limitations, and impairments. Fifty subjects (36 men, 14 women, age=20.6 +/- 1.3 years) at a mean of 31.0 +/- 16.3 months following ACLR participated in this study. Participation restrictions in activities of daily living and sports were measured by the combined scores of the Knee Outcome Survey Activities of Daily Living Scale and Sports Activity Scale. The status of knee structures was assessed by determining the number of previously injured structures in the knee and the time from the most recent ACLR to testing. Performance-based activity limitations were assessed with the single leg hop for distance test. Impairments included isokinetic quadriceps function and anterior tibiofemoral joint laxity. Forward stepwise regression analysis revealed that while the number of injured knee structures alone accounted for 47% of the variability in patient-reported participation restrictions, the combination of the number of injured knee structures, time from ACLR, and the hop index provided the most effective estimate of participation restrictions. Isokinetic quadriceps function and KT-1000 side-to-side differences were not entered into the regression model and were not significant predictors of participation restrictions. We recommend that clinicians use caution in assuming that isokinetic quadriceps function and anterior tibiofemoral joint laxity provide an effective estimate of participation restrictions.

Activities of Daily Living↗

PubMed2006

The impact of restricted diet on brain function using BOLD-fMRI.

We investigated the effect of a restricted diet model on activity in the human motor cortex using functional magnetic resonance imaging (fMRI). Two series of blood oxygenation level-dependent (BOLD)-fMRI measurements were made in healthy subjects performing simple motor tasks using their right hands. The first series was done 5-10 days prior to the restricted diet schedule (controls), and the second series was performed after 25-28 days of restricted diet, in the form of a religious fast (Ramadan). The size and intensity of the activated area in the motor cortex increased during the time of restricted diet versus the controls. We conclude that restricted diet has a significant effect on cerebral activity, as shown by BOLD-fMRI, although the exact relationship between the images and neuronal activity due to the restricted diet is still to be determined.

Adult↗

PubMed2001

The effect of formulary restriction in the use of antibiotics in an Italian hospital.

OBJECTIVE: To compare the expenditure and usage of antibiotics at the San Martino Teaching Hospital, a 2500-bed hospital in Genoa, Italy, before and after the implementation of an antibiotic control program that streamlined the hospital formulary and the creation of a restricted group of antibiotics requiring approval before use. METHODS: Usage and expenditure data for all antibiotics were collected from 1996 to 1998. Antibiotic usage was standardised by defined daily doses (DDDs) per 100/patient-days. Cost data were expressed in Euros. Changes in antibiotic usage was determined by comparing the mean usage during 1996 and 1997, the period before the implementation of the antibiotic control program, to 1998 when the streamlined formulary and restricted group of antibiotics, controlled by the Infectious Disease Team (IDT). were initiated. The Wilcoxon rank sign test was used to determine statistical significance of the changes in overall antibiotic use; a P value of less than 0.05 was considered significant. RESULTS: After the implementation of the antibiotic control program, overall antibiotic usage decreased by 8.5%, 28.00 DDD/100 patient-days during 1996-1997 to 25.62 DDD/100 patient-days during 1998. The control program resulted in overall savings of 342,927 Euros after the first year of implementation. The usage and expenditure in the restricted group of antibiotics decreased by 78.5% and 53.5%, respectively, (P=0.03). Restricting the use of ceftazidime and imipenem accounted for the majority of the decreased usage and savings. In the non-restricted group of antibiotics, usage increased only by 32.6% resulting in a net reduction of 46.3% in all antibiotic use. CONCLUSION: Although antibiotic control programs have been successful in other countries, this represents the first attempt at successful antibiotic control in a large Italian teaching hospital. Streamlining the formulary to control antibiotic choices and the creation of a restriction program using the expertise of infectious disease physicians resulted in significant reductions in the use of and expenditure for antibiotics.

Anti-Bacterial Agents↗

PubMed1996

HLA-A2-restricted peripheral blood cytolytic T lymphocyte response to HPV type 16 proteins E6 and E7 from patients with neoplastic cervical lesions.

The DNA from human papillomavirus (HPV) can be detected in 90% of cervical carcinomas. To address whether patients infected with HPV can mount efficient T cell responses to this pathogen we examined the cytotoxic T lymphocyte (CTL) response of peripheral blood mononuclear cells (PBMC) from patients with abnormal genital epithelial cells. PBMC from 11 HLA-A2+ patients were stimulated with CaSki, a cervical carcinoma cell line that is HPV 16+ and HLA-A2+. The CTL were screened for reactivity to the cervical carcinoma cell line C33A (HPV-, HLA-A2+) transfected with the HPV 16 E6 or E7 genes or the plasmid without insert. The CTL of 1 patient showed particularly strong CaSki and HPV E6 or E7 protein-specific cytotoxicity in a HLA-A2+-restricted fashion. In contrast, these CTL lysed neither a vector-only transfectant, the natural killer cell (NK) target, K562 nor the lymphokine-activated killer cell (LAK) target, Daudi. HLA-A2 restriction was demonstrated by the lack of recognition of a HLA-A2- CaSki cell line developed in our laboratory. The CTL line was cloned and 99 clones were harvested and screened; 51 clones lysed CaSki, of which 17 did not lyse the A2- CaSki. Of these HLA-A2- restricted clones, 8 did not lyse C33A transfectants, 6 lysed all C33A transfectants, 3 lysed C33A-E7 only and none lysed C33A-E6 only. These data imply that, within the bulk CTL line, HLA-A2-restricted recognition of antigens was restricted to CaSki antigens, antigens common to cervical carcinoma (CaSki plus C33A), or HPV-16-E7-derived antigen on the clonal level. The E7-restricted clones were negative for recognition of known HLA-A2-binding peptides from E7.

Base Sequence↗

PubMed2004

Effects of age and dietary restriction on oxidative DNA damage, antioxidant protection and DNA repair in rats.

BACKGROUND: Experimentally imposed dietary restriction is known to extend the lifespan of rodents, perhaps by slowing the accumulation of oxidative damage that is thought to be one of the causes of aging. AIM OF THE STUDY: We examined the effects of restricted total food intake, and protein and calorie restriction, on DNA oxidation and related biomarkers in rats. METHODS: From 1 to 17 months, rats in group 1 received normal diet ad libitum. Group 2 received 70% of the quantity consumed by the first group. Group 3 had the same quantity as group 2, but with a reduction in protein (from 18% to 10% of the diet by weight), and group 4 were further restricted with a 30% decrease in calories. Lymphocytes were isolated from blood samples taken every two months. DNA breaks, oxidised pyrimidines, resistance to H2O2-induced damage, and strand break repair were measured with the comet assay. Organs were isolated from rats killed at 17 months, with 1 month-old rats for comparison; DNA oxidation and antioxidant enzyme activities were measured. RESULTS: DNA breaks in lymphocytes increased from 1 to 3 months but thereafter declined with age, except in ad libitum fed rats. Oxidised pyrimidines did not change significantly. Resistance to H2O2-induced damage was least at 3 months, and increased with age. Repair of DNA strand breaks was efficient at all ages. Diet had little effect on these endpoints. Diet had no influence on 8-oxo-7.8-dihydroguanine levels in DNA from liver, testis and brain of 17 month old rats. Combining data from all four groups, the levels in brain and liver were significantly higher at 17 months compared with 1 month. Antioxidant enzyme activities tended to increase between 1 and 17 months; effects of diet were not so consistent. CONCLUSIONS: While DNA damage shows a modest increase with age in some organs, antioxidant status and DNA strand break repair do not decline with age. Restricted diets (including protein and calorie restriction) have no effect on any of these markers of genetic stability.

Aging↗

PubMed2002

Postural restrictions in labyrintholithiasis.

Benign paroxysmal positional vertigo (BPPV) is the most frequent labyrinthopathy in humans. Treatment consists mainly of liberatory maneuvers aiming to remove otolithic debris and subsequent postural restrictions in order to prevent debris from returning into the canal. The reappearance of symptoms after an effective liberatory maneuver was studied in a group subjected to restrictions and in a second group free from restrictions. The effects of these restrictions were evaluated. No statistically significant difference was found between the groups. Accordingly, restrictions seem to have no effect upon symptom recurrence. The slight supremacy of the Semont maneuver and the prevalence of subsequent relapse compared with the Epley maneuver suggests that these maneuvers could operate on different disorders (cupulolithiasis versus canalolithiasis). Finally, late recognition of relapse in patients who undergo restrictions might even make the liberatory maneuver less effective.

Adolescent↗

PubMed2003

Monte-Carlo prediction of changes in areas of west Cumbria requiring restrictions on sheep following the Chernobyl accident.

Following the 1986 Chernobyl accident radiocaesium levels in sheep meat in some upland areas of the United Kingdom were above the national intervention limit. West Cumbria was one of these areas and restrictions are currently still in place. In addition to deposition from the Chernobyl accident, Cumbria has been subject to radiocaesium deposition from atmospheric nuclear weapons tests, the 1957 Windscale accident and routine releases from the Sellafield nuclear reprocessing plant. A Monte-Carlo approach has been used to try to predict areas in west Cumbria where radiocaesium activity concentrations in lamb meat would require the imposition of restrictions at different times after the Chernobyl accident. The approach models the transfer of radiocaesium from soil to vegetation, based upon soil organic matter, and from vegetation to lamb meat. Spatial inputs are soil organic matter and total post-Chernobyl (137)Cs and (134)Cs deposition; a ratio of Chernobyl (137)Cs to (134)Cs deposition has been used to differentiate Chernobyl and pre-Chernobyl (137)Cs deposition. Comparisons of predicted radiocaesium transfer from soil-vegetation and the spatial variation in lamb (137)Cs activity concentrations are good and predicted restricted areas with time after Chernobyl compare well to the restricted areas set by UK government. We predict that restrictions may be required until 2024 and that in some areas the contribution of pre-Chernobyl (137)Cs to predicted lamb radiocaesium activity concentrations is significant, such that restrictions may only have been required until 1994 as a consequence of Chernobyl radiocaesium deposition alone. This work represents a novel implementation of a spatial radioecological model using a Monte-Carlo approach.

Animal Feed↗

PubMed2006

The suppressive effects of dietary protein restriction on the progression of renal impairment in OLETF rats.

BACKGROUND: The suppressive effect of dietary protein restriction on the progression of diabetic nephropathy remains controversial. We investigated the effects of protein and energy restrictions on both albuminuria and morphology using diabetic-prone Otsuka Long-Evans Tokushima fatty (OLETF) rats. METHODS: In this study, male OLETF rats were divided into two groups according to their energy intake. They were then further divided into three subgroups based on their amount of dietary protein, which ranged between 10% and 30% of their total intake. Urinary albumin excretion (UAE) was used as a marker of renal impairment, and body weight fasting (F) and postchallenge (P), blood glucose (BG) levels, and systolic blood pressure (SBP) were all measured during various experimental periods up to 28 weeks of age. RESULTS: The OLETF rats fed with the high-calorie diet started to gain weight at 12 weeks, and their FBG and PBG were elevated at 22 weeks, while SBP did not differ between the two groups. In addition, UAE increased significantly in the rats fed with the high-calorie diet. However, the increasing rates of UAE with age were higher in the rats with a higher protein diet within the same energy groups. UAE correlated well with the amounts of dietary energy and protein at 16 and 28 weeks of age, while it correlated with both the FBG and PBG at only 28 weeks of age. A linear regression analysis, using the data obtained at 28 weeks, showed that the amount of protein intake and FBG explained 63.4% and 23.9% of the variation in UAE, respectively. Histological studies revealed that protein and energy restriction markedly reduced the sclerotic changes of the glomeruli. CONCLUSION: Dietary protein restriction starting very early in the life of OLETF rats, in combination with energy restriction, clearly suppressed UAE and the typical morphological changes that otherwise occurred at around 16 weeks of age. This method also seemed to be more effective than energy restriction alone in slowing down any increase in UAE. The influence of BG levels on UAE was lower at an early age, while it became an increasingly important factor at later ages in the experimental rat model.

Albuminuria↗

PubMed1983

Cardiac output and uteroplacental blood flow in diet-restricted and diet-repleted pregnant rats.

Cardiac output and uteroplacental blood flow were measured with 15 mu radioactive microspheres in anesthetized pregnant rats which were fed: (1) ad libitum throughout gestation; (2) a 50% restricted diet from day 5 of gestation; and (3) a 50% restricted diet from days 5 to 13 of gestation and ad libitum from day 14 of gestation. An additional group of nonpregnant rats fed ad libitum was also used. Dietary restriction caused a net maternal weight loss and a 20% reduction in mean fetal weight and mean placental weight by day 21 of gestation. Restricted dams fed ad libitum during the last week of gestation showed a net maternal weight gain, while mean fetal weight, but not placental weight, was near that of the ad libitum--fed controls. In the diet-restricted rats, total cardiac output was reduced 30% relative to controls by days 20 and 21 of gestation, but cardiac output per unit maternal body weight was not significantly different. Dietary restriction decreased both total uterine and placental blood flow by about 65%. Diet repletion late in gestation did not significantly increase total cardiac output or cardiac output per unit body weight. Total uterine and placental blood flows were near those of controls, primarily because of an increased fraction of cardiac output distributed to the uterus.

Animals↗

PubMed1987

Influence of dietary restriction on accumulation of heat-labile enzyme molecules in the liver and brain of mice.

The influence of dietary restriction on alterations of two aminoacyl-tRNA synthetases was investigated in mouse tissues. Mice were fed a restricted diet (first 80% and then 60% of the ad libitum intake) from 23.5 months of age for 70 days. Before dietary restriction, about 35 and 25% of these enzymes in the brain and liver, respectively, were heat-labile. Dietary restriction resulted in a decrease in the percentage of heat-labile enzyme in both tissues: After 40 and 70 days of dietary restriction the percentage of heat-labile enzyme decreased to about 20 and 10%, respectively, in the brain and to undetectable or very low levels in the liver. These results suggest an interesting possibility that prolongation of the life span by dietary restriction is due to reduction in the level of altered enzyme molecules whose accumulation may be detrimental to cellular functions.

Amino Acyl-tRNA Synthetases↗

PubMed1993

Elbow joint restriction: effect on functional upper limb motion during performance of three feeding activities.

This study was conducted to quantify and compare changes in upper limb joint motion during different feeding tasks when the elbow joint was restricted. Ten male and nine female volunteer subjects age 18 to 50 years participated; all were healthy, right dominant, with no upper limb pathology. A splint was used to restrict elbow joint motion. Three feeding tasks under both unrestricted and restricted conditions were randomly assigned; motion was recorded by a video-based three-dimensional motion analysis system. Elbow restriction resulted in significantly (p < .05) larger arcs of motion in shoulder flexion and internal rotation. Differences between feeding types were similar during both unrestricted and restricted conditions. Increased shoulder joint motion resulting from elbow joint restriction may require greater activity of shoulder girdle muscles increasing the risk of soft tissue problems and degenerative joint disease. Decisions regarding elbow immobilization should take into consideration potential effects upon total upper limb motion.

Activities of Daily Living↗

PubMed1988

Age-related changes in lipid metabolism in rats: the consequence of moderate food restriction.

Male Sprague-Dawley rats, 3 weeks of age, received one of the four following dietary manipulations until 9 months of age: group AD, fed ad libitum; group R, restricted to 75% of food intake of group AD; group RAD, restricted until 5 months of age and then fed ad libitum; group ADR, fed ad libitum until 5 months of age and then restricted. The concentration of serum total and HDL cholesterol tended to be higher in group AD than in all groups that had experienced food restriction. Liver cholesterol was higher in groups AD and RAD than in groups R and ADR. Activity of hepatic microsomal hydroxymethylglutaryl-CoA reductase was comparable, whereas sterol synthesis from mevalonate was significantly higher in groups R and ADR than in groups AD and RAD. Cholesterol 7 alpha-hydroxylase activity also tended to be higher in groups R and ADR. It seems likely that hepatic cholesterol homeostasis functions effectively even when moderate food restriction was started after the growing period. In addition, food restriction reduced the ratio of arachidonate to linoleate, suggesting inhibition of the desaturation system.

Aging↗

PubMed1993

Effects of triiodothyronine administration on dietary [14C]triolein partitioning between deposition in adipose tissue and oxidation to [14C]CO2 in ad libitum-fed or food-restricted rats.

Refeeding a chow meal containing [1-14C]triolein to food-restricted rats results in increased accumulation of [14C]lipid in carcass and epididymal adipose tissue and lower oxidation to [14C]CO2 compared to ad libitum-fed rats (Biochem. J. 285, 773-778, 1992). In the present experiments the effects of treatment with triiodothyronine (T3) for three days on lipid accumulation in refed food-restricted rats has been examined. T3 decreased accumulation of [14C]lipid in carcass and epididymal adipose tissue (32 and 77%, respectively) of food-restricted rats on refeeding the chow-[1-14C]triolein meal. This decreased accumulation of [14C]lipid was accompanied by increased [14C]CO2 production (77%) and decreased heparin-elutable lipoprotein lipase activity in the epididymal fat pad (90%) and subcutaneous adipose tissue (80%). Accumulation of [14C]lipid in the latter did not decrease significantly. In contrast, T3 treatment of ad libitum-fed rats increased [14C]lipid deposition in carcass (44%) and in subcutaneous adipose tissue (240%) on refeeding, when compared to untreated ad libitum rats. Lipoprotein lipase activity in the two adipose tissue depots of the refed ad libitum+T3 rats, however, decreased. Thus, the effects of T3 on [14C]lipid deposition are adipose-tissue-depot-specific and depend on the previous dietary intake (over 14 days) of the rat. T3-treatment increased the lipoprotein lipase activity released from perfused hearts to a similar extent in both food-restricted and ad libitum-fed rats compared to the corresponding untreated groups. The rates of lipogenesis in-vivo in liver, epididymal and subcutaneous adipose tissue of food-restricted rats refed chow were not altered by T3. It is concluded that the increased deposition of dietary lipid in the food-restricted rat can be partially reversed by treatment with T3, suggesting that the low-T3 state associated with this condition may be in part responsible.

Adipose Tissue↗

PubMed1994

Food restriction and stimulation of monooxygenation of p-nitroanisole in perfused rat liver.

This study assessed the effect of food restriction on the metabolism of model monooxygenase substrates in the perfused rat liver. Female Sprague-Dawley rats has access ad lib. to a Purina 5001 nonpurified diet (control) or were given 65% of the intake of controls for 3 weeks. Livers were perfused with oxygenated Krebs-Henseleit buffer using a non-recirculating system, and the rates of monooxygenation of p-nitroanisole and 7-ethoxycoumarin were measured. The results indicate that food restriction stimulated p-nitroanisole O-demethylation from 2.9 +/- 0.2 to 4.6 +/- 0.5 mumol/(g.hr) when saturating concentrations of p-nitroanisole were infused. Concomitantly, the ratio of beta-hydroxybutyrate to acetoacetate (B/A) and the rates of ketogenesis (B + A) were increased significantly by food restriction. Further, p-nitroanisole (200 mumol/L) increased hepatic malate concentration nearly 3-fold in liver extracts from food-restricted rats. However, infusion of either a low concentration of p-nitroanisole (50 mumol/L) or 7-ethoxycoumarin (200 mumol/L) did not alter these parameters. On the other hand, food restriction did not alter rates of monooxygenation in isolated microsomes supplemented with excess NADPH. Taken together, these data support the hypothesis that high concentrations of p-nitroanisole increased monooxygenation in food-restricted rats by stimulating fatty acid oxidation, which elevates the mitochondrial NADH/NAD+ ratio. This, in turn, increases the availability of reducing equivalents in the form of NADPH by a malate-pyruvate exchange system, leading to increased drug metabolism.

7-Alkoxycoumarin O-Dealkylase↗

PubMed1984

Delayed loss of striatal dopamine receptors during aging of dietarily restricted rats.

Dietary restriction by feeding every other day retards the normal age-associated loss of dopamine receptors from the corpus striatum of the rat. Ad libitum fed animals lose about 40% of the receptors labeled by [3H]spiperone between 3 and 24 months, while the loss is only about 20% over the same period in restricted rats. Ultimately, by 30 months of age, values for restricted animals drop to those of 24-month-old ad libitum-fed rats. The mean lifespan of restricted rats, however, is about 40% longer than the 22-24 months characteristic of ad libitum-fed counterparts. The effect of restriction appears to be chronic rather than acute since ad libitum-fed rats which are restricted for 2 weeks prior to sacrifice possess receptor levels comparable to 24-month-old rats maintained on ad libitum feeding for their entire lifetime.

Age Factors↗