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Neurobehavioral effects of dietary restriction in rats.

The effects of reduced body weight gain on nervous system function of young male Fischer 344 rats were examined. The rats were fed 15% ('mild') or 50% ('severe') less than the controls. Mild and severe dietary restriction resulted in 9% and 38% lower body weight compared to the controls. Mild dietary restriction caused slight changes in flash evoked potentials, auditory brainstem responses, caudal nerve action potentials, and body temperature. Severe dietary restriction increased the magnitude of the effects noted in the mild group, as well as causing a significant decrease in grip strength. Somatosensory evoked responses were not affected by either mild or severe restriction. Diet restricted rats were more excitable while restrained for testing. Thus, dietary restriction has significant effects on numerous behavioral and neurophysiological parameters that should be considered in the interpretation of neurotoxicological data when body weight differences are present.

Animals↗

PubMed2005

A systematic review of the association between factor V Leiden or prothrombin gene variant and intrauterine growth restriction.

OBJECTIVE: The purpose of this study was to conduct a systematic review of the literature of studies that examined the association between factor V Leiden and/or prothrombin gene variant and intrauterine growth restriction. STUDY DESIGN: This systematic review of studies assesses the association between factor V Leiden and/or prothrombin gene variant and intrauterine growth restriction. RESULTS: Ten case-control studies fulfilled the selection criteria for inclusion in the meta-analysis. There was a significant association between factor V Leiden and intrauterine growth restriction (odds ratio, 2.7; 95% CI, 1.3-5.5) and prothrombin gene variant and intrauterine growth restriction (odds ratio, 2.5; 95% CI, 1.3-5.0). Five cohort studies were identified in the systematic review; 3 studies were prospective (2 full publications), and 2 studies were retrospective (1 full publication). Combining the 2 full publication prospective studies yields a summary relative risk of 0.99 (95% CI, 0.5-1.9). CONCLUSION: This meta-analysis of case-control studies suggests that the factor V Leiden and prothrombin gene variant both confer an increased risk of giving birth to an intrauterine growth restricted infant, although this may be driven by small, poor-quality studies that demonstrated extreme associations. Large well-conducted prospective cohort studies are required to determine definitively whether an association between thrombophilia and intrauterine growth restriction is present.

Case-Control Studies↗

PubMed2006

Reactive oxygen species are involved in lipopolysaccharide-induced intrauterine growth restriction and skeletal development retardation in mice.

OBJECTIVE: Maternal infection is a cause of adverse developmental outcomes including embryonic resorption, intrauterine fetal death, and preterm labor. Lipopolysaccharide-induced developmental toxicity at early gestational stages has been well characterized. The purpose of the present study was to investigate the effects of maternal lipopolysaccharide exposure at late gestational stages on intrauterine fetal growth and skeletal development and to assess the potential role of reactive oxygen species in lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation. STUDY DESIGN: The timed pregnant CD-1 mice were intraperitoneally injected with lipopolysaccharide (25 to 75 microg/kg per day) on gestational day 15 to 17. To investigate the role of reactive oxygen species on lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation, the pregnant mice were injected with alpha-phenyl-N-t-butylnitrone (100 mg/kg, intraperitoneally) at 30 minutes before lipopolysaccharide (75 microg/kg per day, intraperitoneally), followed by an additional dose of alpha-phenyl-N-t-butylnitrone (50 mg/kg, intraperitoneally) at 3 hours after lipopolysaccharide. The number of live fetuses, dead fetuses, and resorption sites was counted on gestational day 18. Live fetuses in each litter were weighed. Crown-rump and tail lengths were examined and skeletal development was evaluated. RESULTS: Maternal lipopolysaccharide exposure significantly increased fetal mortality, reduced fetal weight and crown-rump and tail lengths of live fetuses, and retarded skeletal ossification in caudal vertebrae, anterior and posterior phalanges, and supraoccipital bone in a dose-dependent manner. Alpha-phenyl-N-t-butylnitrone, a free radical spin-trapping agent, almost completely blocked lipopolysaccharide-induced fetal death (63.2% in lipopolysaccharide group versus 6.5% in alpha-phenyl-N-t-butylnitrone + lipopolysaccharide group, P < .01). In addition, alpha-phenyl-N-t-butylnitrone significantly reversed lipopolysaccharide-induced intrauterine growth restriction and skeletal development retardation. However, aminoguanidine, a selective inhibitor of inducible nitric oxide synthase, had little effect. Furthermore, lipopolysaccharide-induced intrauterine fetal death, intrauterine fetal growth restriction, and skeletal development retardation were associated with lipid peroxidation and glutathione depletion in maternal liver, placenta, and fetal liver. Alpha-phenyl-N-t-butylnitrone significantly attenuated lipopolysaccharide-induced lipid peroxidation and glutathione depletion in maternal liver, placenta, and fetal liver. CONCLUSION: Maternal lipopolysaccharide exposure at late gestational stages results in intrauterine fetal growth restriction and skeletal development retardation in mice. Reactive oxygen species might be, at least in part, involved in lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation.

Animals↗

PubMed2005

Eliminating analgesic meperidine use with a supported formulary restriction.

PURPOSE: Meperidine is a commonly used analgesic despite unique disadvantages compared with other opioid analgesics. The objective of this study was to measure the effects of a meperidine formulary restriction on the prescribing of parenteral opioid analgesics. MATERIALS AND METHODS: The study was performed at a single 750-bed tertiary care teaching hospital in Rochester, NY. The formulary restriction limited meperidine to use exclusively for rigors or procedural sedation and was supported by an educational initiative and a computerized order entry system. Independent computerized pharmacy records were used to capture all doses of parenteral morphine, meperidine, and hydromorphone administered to patients in the emergency department or on a medical or surgical inpatient floor during data-collection periods. Baseline data were collected during two 3-day periods before the formulary restriction; then comparison data were collected during three 3-day periods over 15 months after the formulary restriction. RESULTS: The number of administered doses of meperidine per day decreased from 37.5 (20.8% of parenteral opioid doses before the restriction) to 0.22 (0.1% of parenteral opioid doses, P = .001). The total number of opioid doses and morphine doses given did not change, whereas the number of hydromorphone doses increased significantly postrestriction, from 16.0 doses per day (8.9% of total) to 59.7 doses per day (29.5%) (P = .009). CONCLUSION: Meperidine formulary restriction, supported by an educational program and computerized order entry, effectively eliminated analgesic meperidine use. Hydromorphone use increased proportionately to offset the decreased use of meperidine.

Analgesics, Opioid↗

PubMed2006

Dietary restriction protects against chronic-ethanol-induced changes in exploratory behavior in Wistar rats.

Chronic ethanol intake causes various types of neural damage and behavioral impairments, probably acting through oxidative stress and excitotoxicity, while dietary restriction is considered by some authors to protect the central nervous system from these kinds of damage. In the present study, a factorial experimental design was used to investigate the effects of chronic ethanol and dietary restriction treatments, associated or not, on Wistar rats' exploratory behavior, spatial memory aspects and cortical and hippocampal acetylcholinesterase (AChE) activity. Dietary restriction lasted for the whole experiment, while ethanol treatment lasted for only 3 weeks. Despite the short ethanol treatment duration, for two behavior categories assessed, moving and rearing, an interaction was observed between the effects of chronic ethanol and dietary restriction. There were no significant differences in AChE activities among the groups. Cerebellar neural nitric oxide synthase (nNOs) activity was measured as a first step to assess oxidative stress. Dietary restriction significantly reduced NO formation. The present results indicate that dietary restriction might exert a protective effect against chronic-ethanol-induced changes in exploratory behavior. It is hypothesized that the mechanisms underlying this protection can involve prevention of oxidative stress.

Acetylcholinesterase↗

PubMed2004

A new murine tumor model for studying HLA-A2-restricted anti-tumor immunity.

HLA-A2/K(b) transgenic mice have been powerful tools for studying HLA-A2-restricted anti-tumor immunity. Two tumor lines were established from an aged HLA-A2/K(b) transgenic mouse that developed spontaneous tumors in the right limb and lung. Histopathologic analysis of the tumor was consistent with an osteosarcoma that had metastasized to the lung. The cells from the primary tumor and the lung metastasis were adapted to culture and are designated Ag201P and Ag201M, respectively. Both Ag201P and Ag201M induced tumors in mice, indicating that the established cell lines are tumorigenic. Both tumor lines expressed HLA-A2/K(b) as assessed by RT-PCR and immunofluorescence analysis. Furthermore, the HLA-A2/K(b) molecules were functional on both tumor lines as demonstrated by their ability to present exogenously loaded HLA-A2-restricted peptides to human HLA-A2-restricted T cells. More importantly, endogenously expressed HLA-A2-restricted epitopes were processed and presented in the context of HLA-A2/K(b) in Ag201P and Ag201M cells to human HLA-A2-restricted T cells. Thus, Ag201P and Ag201M are two new murine tumor lines that express functional HLA-A2/K(b), and represent potentially invaluable tools to study HLA-A2-restricted anti-tumor immunity in mice.

Animals↗

PubMed2006

Restrictive mitral inflow pattern is a strong independent predictor of lack of viable myocardium after a first acute myocardial infarction.

In patients with acute myocardial infarction (AMI) a restrictive mitral inflow pattern successfully predicts clinical outcome. The impact of myocardial viability on the mitral inflow velocities, however, is unknown. One hundred and forty-one patients with a first AMI underwent two-dimensional, Doppler and dobutamine stress echocardiography (DSE). Patients were classified into two groups based on Doppler measurement of left ventricular filling: a restrictive group (18 patients), and a non-restrictive group (123 patients). In the non-restrictive group, myocardial viability at DSE was found in 56 patients, while in the restrictive group only three patients showed contractile reserve (46% vs. 16%, p<0.03). The multivariate logistic regression analysis demonstrated that restrictive mitral inflow pattern was a strong independent predictor of lack of viable myocardium (OR=12.45, p<0.001).

Adult↗

PubMed2005

Employment restrictions among persons with ICD-10 anxiety disorders: characteristics from a population survey.

Disability, employment, and employment restrictions among persons with ICD-10 anxiety disorders were investigated at a population level in comparison to persons without disability or long-term health conditions. Data were provided by the Australian Bureau of Statistics (ABS) collected in a 1998 national survey. Multistage sampling obtained a probability sample of 37,580 individuals in the household component of the survey. Trained lay interviewers using ICD-10 computer-assisted interviews identified household residents with anxiety disorders. Details of employment restrictions are reported and discussed. The four most commonly reported restrictions were: restricted in the type of job (24.0%); need for a support person (23.3%); difficulty changing jobs (18.6%); and restricted in the number of hours (15.4%). The nature and extent of employment restrictions characterizing persons with anxiety disorders indicates a need for strengthened disability and health condition screening at application for Government income support and at gateways to public funded vocational assistance.

Adolescent↗

PubMed2006

A simple classification system was recommended for patients with restricted shoulder or neck range of motion.

OBJECTIVE: To construct an empirical classification of patients with shoulder complaints, and then to investigate the relationship between the empirical classification and the setting in which the patients were recruited, their demographic and clinical characteristics, and the original diagnostic categories. STUDY DESIGN AND SETTING: A latent class analysis was performed on the combined data of two previous studies. RESULTS: Four clusters of patients emerged, one with patients who have a small chance of any restriction of the motion of the shoulder and a moderate chance of restriction of the motions of the neck, a second with patients who have a high chance of restriction of the motions of the shoulder and a moderate chance of restriction of motions of the neck, a third with patients who have a low to moderate chance of restriction of all motions, and a fourth with patients who have a high chance of restriction of all of the motions. Patients recruited from a clinic for rheumatology and rehabilitation and from the orthopedic clinic were more present in the second cluster. Patients in the third cluster were on average younger than those in the other clusters. There appeared to be little agreement between the clusters found and the classification of patients according to the original diagnostic categories. CONCLUSION: Patients experiencing shoulder pain can be classified in a simple way into four categories, reflecting the distinction between problems of the shoulder and those of the neck. A simple classification rule is proposed with which almost all patients can be classified into the four clusters.

Adolescent↗

PubMed2005

Impact of restricting fluoroquinolone prescription on bacterial resistance in an intensive care unit.

The purpose of this study was to assess the effect of reducing prescription of fluoroquinolones in an intensive care unit (ICU) upon bacterial resistance, particularly as regards Pseudomonas aeruginosa. For six months between January 2001 and June 2001, administration of fluoroquinolones was kept to a minimum. A bacteriological screening of patients was performed to assess the incidence of fluoroquinolone-resistant bacteria. There was a 75.8% restriction in prescriptions of fluoroquinolones. There was no significant change in bacterial ecology between the periods preceding (12 months) and following (12 months) restriction. There was a significant recovery of sensitivity of P. aeruginosa to ciprofloxacin (P<or=0.01), with a decrease in resistant strains from 71.3% in the pre-restriction period to 52.4% in the post-restriction period. Regarding clinical data, no significant differences were noted between the pre-restriction and the post-restriction periods, except for the number of cases of ventilator-associated pneumonia with P. aeruginosa resistant to ciprofloxacin. This study demonstrated the possibility of introducing rotation of antibiotics in an ICU.

Bacterial Infections↗

PubMed2004

Engineering strand-specific DNA nicking enzymes from the type IIS restriction endonucleases BsaI, BsmBI, and BsmAI.

More than 80 type IIA/IIS restriction endonucleases with different recognition specificities are now known. In contrast, only a limited number of strand-specific nicking endonucleases are currently available. To overcome this limitation, a novel genetic screening method was devised to convert type IIS restriction endonucleases into strand-specific nicking endonucleases. The genetic screen consisted of four steps: (1) random mutagenesis to create a plasmid library, each bearing an inactivated endonuclease gene; (2) restriction digestion of plasmids containing the wild-type and the mutagenized endonuclease gene; (3) back-crosses with the wild-type gene by ligation to the wild-type N-terminal or C-terminal fragment; (4) transformation of the ligated DNA into a pre-modified host and screening for nicking endonuclease activity in total cell culture or cell extracts of the transformants. Nt.BsaI and Nb.BsaI nicking endonucleases were isolated from BsaI using this genetic screen. In addition, site-directed mutagenesis was carried out to isolate BsaI nicking variants with minimal double-stranded DNA cleavage activity. The equivalent amino acid substitutions were introduced into BsmBI and BsmAI restriction endonucleases with similar recognition sequence and significant amino acid sequence identity and their nicking variants were successfully isolated. This work provides strong evidence that some type IIS restriction endonucleases carry two separate active sites. When one of the active sites is inactivated, the type IIS restriction endonuclease may nick only one strand.

Amino Acid Sequence↗

PubMed2005

Efficient differentiation and integration of lineage-restricted neural precursors in the traumatically injured adult cat spinal cord.

Several recent studies have shown that highly undifferentiated neural stem cells (NSCs) grafted into the intact or injured adult spinal cord of animal either remain undifferentiated or show fate restriction to a astrocytic lineage. This indicates that functionally diverse roles expected of cellular replacement cannot be performed by the transplantation of highly immature precursors; rather, more differentiated or appropriate mixtures of more restricted neural precursors may be important in replacement strategies. In this study, we investigated the ability of lineage-restricted neural progenitors derived from adult mouse periventricular subependymal zone (SEZ) to integrate and differentiate into the chronically injured adult spinal cord. To this end, NSCs were grown as adherent cultures followed by expansion in non-adhesive dishes. This allowed us to grow NSCs as colonies of restricted neural precursors, illustrated by NCAM, nestin, Sox-2, A2B5, and GFAP immunostaining. The mixture of lineage-restricted precursors was directly implanted into the chronically injured spinal cord of immunosuppressed cats. The fate of the cells was traced with GFP fluorescence and immunocytochemistry for neural markers such as beta-III-tubulin, GFAP, and Ng2. After four weeks, transplanted cells survived, giving rise to neurons and in addition to cells with an astrocytic phenotype. We conclude that a mixture of more restricted neural precursors may be better suited than highly immature NSCs for neural replacement strategies after central nervous system (CNS) injuries.

Animals↗

PubMed2005

Leptin enhances ovulation and attenuates the effects produced by food restriction.

The aims of this study were to investigate the effects of chronic feed deprivation on the ovulatory process, and to assess whether leptin administration is able to alter these effects. Prepuberal rats subjected to food restriction and primed with gonadotrophins were used. Body and ovarian weights were significantly decreased in proportion to the severity of the food restriction. Only the most severe feed deprivation was able to inhibit the ovulation rate. Either buffer or leptin was daily administrated to prepuberal rats fed either ad libitum or with a severe food restriction. Serum progesterone, ovulation rate and ovarian prostaglandin E2 were reduced in rats subjected to food restriction and stimulated by daily administration of leptin in rats fed ad libitum. Negative effects produced by a severe food restriction were partially reversed by chronic administration of leptin. The ovarian endothelium nitric oxide synthase expression was strongly inhibited in rats with food restriction and once again, leptin administration reversed this effect. In summary, the ovulatory process was significantly inhibited in response to a severe decrease in food intake, at least in part, to the direct or indirect impairment of some ovarian factors production as prostaglandins and nitric oxide. Chronic treatment with leptin enhanced the ovulatory process in comparison with control animals, and partially prevented these negative effects produced by a severe malnutrition.

Animals↗

PubMed2006

Auditory processing deficits in growth restricted fetuses affect later language development.

An increased risk for language deficits in infants born growth restricted has been reported in follow-up studies for more than 20 years, suggesting a relation between fetal auditory system development and later language learning. Work with animal models indicate that there are at least two ways in which growth restriction could affect the development of auditory perception in human fetuses: a delay in myelination or conduction and an increase in sensorineural threshold. Systematic study of auditory function in growth restricted human fetuses has not been reported. However, results of studies employing low-risk fetuses delivering as healthy full-term infants demonstrate that, by late gestation, the fetus can hear, sound properties modulate behavior, and sensory information is available from both inside (e.g., maternal vascular) and outside (e.g., noise, voices, music) of the maternal body. These data provide substantive evidence that the auditory system is functioning and that environmental sounds are available for shaping neural networks and laying the foundation for language acquisition before birth. We hypothesize that fetal growth restriction affects auditory system development, resulting in atypical auditory information processing in growth restricted fetuses compared to healthy, appropriately-grown-for-gestational-age fetuses. Speech perception that lays the foundation for later language competence will differ in growth restricted compared to normally grown fetuses and be associated with later language abilities.

Child↗

PubMed2004

Suppressive effects on delayed type hypersensitivity by fasting and dietary restriction in ICR mice.

Dietary restriction improves declining physiologic functions, prevents or lessens the severity of neoplasms and autoimmune diseases, and attenuates various inflammatory reactions. In the present study, we compared the effect on allergic dermatitis from repeated short-term fasting (every 3 days), and from moderate dietary restriction receiving 60% of the amount of food consumed by an ad libitum feeding group. In addition, we attempted to verify the involvement of corticosteroids and oxidative stress during nutritional deprivation. The overall food intake in mice undergoing moderate dietary restriction was less than that in mice undergoing repeated fasting. Nonetheless, moderate dietary restriction and repeated fasting showed similar suppressive effects on dermatitis. Furthermore, both the restricted-diet and fasted mice showed less oxidative stress than the mice fed ad libitum. In RU486 (a glucocorticoid receptor antagonist)-injected mice, no suppressive effect of fasting on dermatitis was seen. In conclusion, repeated fasting and moderate dietary restriction suppressed dermatitis in similar ways. Hypercorticism and reduced oxidative stress is associated with the suppression of dermatitis.

Animals↗

PubMed1997

Increased placental apoptosis in intrauterine growth restriction.

OBJECTIVES: Our purpose was to investigate a possible role for apoptosis in the pathophysiologic mechanisms of intrauterine growth restriction. STUDY DESIGN: Placental samples were obtained from 43 uncomplicated third-trimester pregnancies and from 26 pregnancies complicated by intrauterine growth restriction. The definition used to identify cases of intrauterine growth restriction depended on three criteria: clinical evidence of suboptimal growth, ultrasonographic evidence of deviation from an appropriate growth percentile, and individualized birth weight ratios <10th percentile. Light microscopy was used to quantify the incidence of apoptosis. Electron microscopy and TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) staining were used to confirm the occurrence of apoptosis. RESULTS: Quantification of apoptosis (medians and interquartile ranges) resulted in the following values: normal third trimester (n = 43) 0.14% of cells (0.08% to 0.20%) and intrauterine growth restriction third trimester (n = 26) 0.24% of cells (0.16% to 0.29%). The incidence of apoptosis was significantly higher in placentas from pregnancies with intrauterine growth restriction compared with normal third-trimester placentas (p < 0.01, Mann Whitney U test). CONCLUSIONS: These results suggest that apoptosis may play a role in the pathophysiologic mechanisms of intrauterine growth restriction.

Adult↗

PubMed2000

Chronic food restriction increases fos-like immunoreactivity (FLI) induced in rat forebrain by intraventricular amphetamine.

Chronic food restriction enhances behavioral responsiveness to amphetamine and other abused drugs. Because this effect is evident when drugs are administered intracerebroventricularly (i.c.v.) as well as systemically, it would seem to reflect increased sensitivity of a neural substrate rather than a change in drug disposition. In the present study, c-Fos immunohistochemistry was used to evaluate whether the magnitude and pattern of cellular activation induced by i.c.v. amphetamine is altered by a regimen of food restriction previously shown to potentiate amphetamine reward. In the absence of amphetamine challenge, there was generally no difference in brain Fos-like immunoreactivity (FLI) between ad libitum fed and food-restricted rats. In response to amphetamine (50 microg), both groups displayed increased FLI in caudate-putamen, nucleus accumbens, bed nucleus of the stria terminalis, ventral pallidum, central nucleus of the amygdala, and cingulate cortex. With the exception of cingulate cortex and caudal caudate-putamen, a significantly greater response was observed in brain regions of food-restricted rats. These results indicate that food restriction augments a cellular immediate early gene (IEG) response to acute amphetamine in brain regions known to mediate rewarding and other behavioral effects of psychostimulants. The difference between these results and those produced by sensitizing regimens of psychostimulant exposure are discussed, as are possible endocrine factors that could be involved in the modulatory effect of food restriction on cellular and behavioral responses to amphetamine.

Amphetamine↗

PubMed1997

Reciprocal regional changes in brain NPY receptor density during dietary restriction and dietary-induced obesity in the rat.

Neuropeptide Y (NPY) potently induces feeding, reduces thermogenesis and induces obesity in rats when injected into the cerebral ventricles. Groups of male Wistar rats were either restricted to 60% of their normal daily food intake over 10 days or made obese by presenting them with a high-calorie diet rich in sugars and fat over 6 weeks. Food restricted rats lost up to 20% of their body weight, compared with control rats and had large reductions in their body fat mass. By contrast, rats with dietary-induced obesity weighed 26% more than controls due mainly to increased body fat mass. Quantitative receptor autoradiography demonstrated reduced [(125)I]PYY binding in the hypothalamic lateral (perifornical) and dorsal areas, hypothalamic ventromedial, arcuate and dorsomedial nuclei, hippocampal CA3 region, centromedial amygdaloid nucleus and thalamic paraventricular and reuniens nuclei in dietary restricted rats compared with controls. By contrast, regional [(125)I]PYY binding was significantly increased in hypothalamic lateral and dorsal areas, hypothalamic arcuate and dorsomedial nuclei, amygdaloid medial and centromedial nuclei, thalamic centromedial and paraventricular nuclei of dietary obese rats versus controls. Masking NPY Y1 receptors with 1 microM BIBP3226, a selective Y1 receptor antagonist, revealed that the changes in [(125)I]PYY binding in brains of food-restricted and dietary-obese rats were due to changes in BIBP3226-insensitive binding sites, presumably Y2 or Y5 NPY receptors. These data suggest that dietary-restriction stimulates NPY release resulting in down-regulation of NPY Y5 'feeding' and/or Y2 receptors and reduced BAT thermogenesis thereby providing an increased drive to eat to restore normal caloric intake whilst reducing thermogenesis in order to conserve fat reserves. By contrast, the up-regulation of NPY Y5 and/or Y2 receptors in dietary-induced obesity is consistent with inhibition of NPY release in the hypothalamus, amygdala and thalamus. Overall, we suggest that there is a regional increase in NPY release during negative energy balance, such as during food-restriction and a reduced regional release of NPY in positive energy balance, such as during hyperphagia associated with the development of obesity.

Amygdala↗