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PubMed1997

Mutations in the Res subunit of the EcoPI restriction enzyme that affect ATP-dependent reactions.

The Res subunits of the type III restriction-modification enzymes share a statistically significant amino acid sequence similarity with several RNA and DNA helicases of the so-called DEAD family. It was postulated that in type III restriction enzymes a DNA helicase activity may be required for local unwinding at the cleavage site. The members of this family share seven conserved motifs, all of which are found in the Res subunit of the type III restriction enzymes. To determine the contribution, if any, of these motifs in DNA cleavage by EcoPI, a type III restriction enzyme, we have made changes in motifs I and II. While mutations in motif I (GTGKT) clearly affected ATP hydrolysis and resulted in loss of DNA cleavage activity, mutation in motif II (DEPH) significantly decreased ATP hydrolysis but had no effect on DNA cleavage. The double mutant R.EcoPIK90R-H229K showed no significant ATPase or DNA restriction activity though ATP binding was not affected. These results imply that there are at least two ATPase reaction centres in EcoPI restriction enzyme. Motif I appears to be involved in coupling DNA restriction to ATP hydrolysis. Our results indicate that EcoPI restriction enzyme does not have a strand separation activity. We suggest that these motifs play a role in the ATP-dependent translocation that has been proposed to occur in the type III restriction enzymes.

Adenosine Triphosphate↗

PubMed1999

Mechanisms by which energy restriction inhibits carcinogenesis.

Cancer that occurs at numerous organ sites, including the colon and breast, is inhibited by energy restriction, and the inhibition is proportional to the degree of restriction imposed. In an effort to identify the mechanism(s) by which energy restriction exerts this effect, a short term model system of experimentally induced mammary carcinogenesis was used. Given that carcinogenesis is known to involve a dysregulation to tissue size homeostasis in which cell proliferation and cell death are in dysequilibrium, we hypothesized that energy restriction exerts its effect by altering one or more aspects of cell cycle regulation. It was observed that energy restriction inhibited cell proliferation and increased cell death due to apoptosis. Thus attention was next focused on aspects of cell cycle regulation that might be affected by energy restriction. It was observed that the amount of p27 protein, one member of the Cip/Kip family of genes that are involved in cell cycle arrest, was increased dose dependently by energy restriction. Based on this and related observations, the hypothesis is advanced that energy restriction inhibits carcinogenesis, at least in part, by delaying cell cycle progression via shifting cell populations into a G(0)/G(1)state. Ongoing work indicates that corticosteroids, which are produced in increased amounts in response to energy restriction, may be involved in mediating this effect.

Animals↗

PubMed1995

Effects of water restriction during growth and adulthood on renal function of bobwhite quail, Colinus virginianus.

Renal function and osmoregulation were studied in bobwhite quail (Colinus virginianus) raised with unrestricted water (chronically unrestricted group) or restricted water (chronically restricted group). There was no difference in urine concentrating ability between adult and juvenile (3.5 or 7.5 week-old) quail. A filtration marker (polyethylene glycol) was infused into adult quail via osmotic minipumps and responses to the following regimens studied: ad libitum water intake, short-term (4-day) water restriction, and acute (1-day) dehydration (withdrawal of all drinking water). Chronically restricted quail had higher urine-to-plasma ratios of polyethylene glycol and lower urine flow rates during short-term restriction. A greater proportion of the reduction in urine flow rate during dehydration was attributable to enhanced tubular reabsorption, rather than reduced rates of filtration, in chronically restricted than in chronically unrestricted birds. Chronically restricted birds also had higher maximum urine-to-plasma ratios of polyethylene glycol (but not higher urine osmolality). These differences occurred in the face of arginine vasotocin concentrations that were not different in the two groups of birds (approximately 15 pg.ml-1 during hydration, and 45 pg.ml-1 during water restriction or dehydration). These observations suggest that chronically restricted quail have an enhanced responsiveness of tubular reabsorption to dehydration, a finding consistent with previous observations of tubule hypertrophy and hyperplasia in these birds (Goldstein and Ellis 1991). Despite this, no difference was found in medullary cAMP levels, either basal or arginine vasotocin- or forskolin-stimulated, in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1991

Dietary restriction reduces the incidence of 3-methylcholanthrene-induced tumors in mice: close correlation with its potentiating effect on host T cell functions.

All mice treated with 3-methylcholanthrene (MC) suffered with tumor 114 days after treatment. However, 40% dietary restriction caused a great inhibition of tumor incidence. In order to understand the mechanisms by which dietary restriction decreased the occurrence of tumor in mice, we investigated the correlation between tumor incidence and host T cell immune responses. At 114 days after MC administration, the mice were sacrificed and their T cell immune responses were assessed. Flow cytometry studies demonstrated that dietary restriction caused a marked increase of the proportion of Thy 1.2+, L3T4+ T cells in MC-treated diet-restricted mice. Consistent with this result, T cell responses against concanavalin A and interleukin-2 were also potentiated in spleen cells obtained from MC-treated diet-restricted mice, while spleen cells obtained from MC-treated unrestricted mice showed decreased T cell responses because of their tumor burden. Such potentiation of T cell functions by dietary restriction was also observed at earlier stages of MC-induced tumorigenesis. During the course of carcinogenesis, spleen cells obtained from diet-restricted mice showed decreased natural killer activity in vivo. However, in vitro induction of cytotoxic T cells was markedly augmented in MC-treated diet-restricted mice compared with unrestricted mice. These results strongly suggest that the increase of host T cell immune responses might be one of the major causes for the reduction of tumor occurrence by dietary restriction.

Animals↗

PubMed1995

Cerebellar growth in normal and growth-restricted fetuses of multiple gestations.

OBJECTIVE: Our purpose was to evaluate growth of the cerebellum in growth-restricted fetuses of twin and triplet gestations versus growth in normal in utero sibling(s) and in singleton gestations. STUDY DESIGN: An ultrasonographic study was conducted in a population of pregnant women with twin and triplet gestations. The control group was either the normal in utero sibling(s) when one fetus was growth restricted or normal twin and singleton pregnancies. Standard biometric measurements were obtained on all fetuses throughout pregnancy, including the transverse cerebellar diameter. However, only the last measurement was used for the analysis. Statistical analyses were conducted comparing growth of the transverse cerebellar diameter among the growth-restricted fetuses versus growth in the normal in utero fetal sibling(s) or other normal twin and singleton gestations. RESULTS: Pregnancies were categorized on the basis of the growth status of women with twin and triplet gestations: Group 1 (151) contained women with two fetuses appropriately grown for gestational age; group 2 (52) had one appropriately grown fetus and one with intrauterine growth restriction; group 3 (19) had two fetuses with intrauterine growth restriction. In addition, there were 30 triplet gestations (group 4), five of which had growth-restricted fetuses, and group 5 contained 1405 singleton pregnancies. In all five groups there was a statistically significant relationship between transverse cerebellar diameter and gestational age (p < 0.0001). There was also no significant difference between growth of the transverse cerebellar diameter in the appropriately grown and growth-restricted siblings and among normal singleton and twin pregnancy groups. In most cases of growth-restricted fetuses, except for the transverse cerebellar diameter measurements, all other biometric parameters were < 10th percentile. CONCLUSION: These data confirm the relative preservation of normal cerebellar growth in growth-restricted fetuses and a similar rate of growth in singleton and multifetal gestations. The transverse cerebellar diameter therefore represents an independent biometric parameter that can be used in both singleton and multifetal pregnancies to assess normal and deviant fetal growth.

Biometry↗

PubMed1991

Effects of food restriction on the length of lactational diestrus in rats.

The effect of food restriction (60% of an ad lib ration) for the first 14 days postpartum on serum progesterone levels and the duration of lactational diestrus was determined in rat dams nursing litters of eight pups. Food restricted dams showed a longer period of lactational diestrus than ad lib fed dams. Food restriction also caused an increase in progesterone levels that was maintained beyond the period of food restriction itself. Treatment with the dopamine agonist bromocryptine mesylate (0.5 mg/day) either from Day 1 or Day 9 postpartum onward induced early termination of lactational diestrus in both ad lib and food restricted dams but the effect was more rapid in the ad lib fed than in the food restricted females. In both cases, however, the effects of bromocryptine administration on milk delivery showed a similar time course providing indirect evidence that prolactin suppression was equivalent under both diet conditions. These data suggest that food restriction during lactation results in increased progesterone levels that most likely result from increased prolactin release. Further, while prolactin suppression in food restricted dams reduces the duration of lactational diestrus, the latency to do so is somewhat longer than that seen in ad lib fed females, suggesting that some other mechanism may also be operating to suppress ovulation in the food restricted female.

Animals↗

PubMed1992

Ultrastructural morphometry of matrical changes induced by exercise and food restriction in the rat calcaneal tendon.

The ultrastructural morphometry of collagen fibril populations in 24 calcaneal tendons obtained from 12 Fischer 344 rats were studied to elucidate matrical changes induced by food restriction and/or endurance exercise. Rats were randomly assigned to four equal groups: ad libitum control (AC), ad libitum exercise (AE), restricted diet control (RC) and restricted diet exercise (RE) groups. Beginning from 6 weeks of age, animals in the two food restriction groups were fed 60% of the mean food consumption of ad libitum fed rats. Then, starting from 6-7 months of age, the rats in the two exercise groups performed 40-50 min of treadmill running at 1.2-1.6 miles h-1 every day for a total of 10 weeks. Endurance training did not significantly alter body weight, but food restriction with or without exercise resulted in a significant loss of body weight. In ad libitum fed controls, food restriction alone did not significantly alter the mean collagen fibril CSA, but predisposed a preponderance of small-sized collagen fibrils. Endurance training per se induced a significant (32%) increase in mean fibril CSA (P less than 0.05), but this adaptive response to exercise was prevented by food restriction, as indicated by a 33% decline in fibril CSA (P less than 0.05). These findings demonstrate that dietary restriction modifies the adaptation of tendon collagen morphometry in response to endurance training, and that weight loss is better achieved with food restriction than endurance exercise.

Animal Nutritional Physiological Phenomena↗

PubMed1994

Serum glucose, glucose tolerance, corticosterone and free fatty acids during aging in energy restricted mice.

Energy restriction, the only method known to increase maximum life span in laboratory animals, was used as a tool to test hypotheses regarding possible mechanisms of aging. Serum glucose and corticosterone (CS) concentrations in mice of a long-lived hybrid mouse strain, aged 7, 17, and 29 months, and on 50%, 80%, and 100% of ad libitum intake, were measured. Serum glucose and CS concentrations were also measured in response to intraperitoneal (i.p.) glucose challenge in mice at ages 7 and 29 months. Serum glucose and CS concentrations were also measured at several time points over 36 h, to assess their diurnal variation. There were no differences in single fasting glucose concentrations in 7- and 29-month-old mice at the same degree of energy restriction, but energy restriction decreased glucose concentrations. Serum CS concentrations were generally increased restricted animals with respect to fully fed ones. Average serum glucose concentrations were found to be significantly decreased by dietary restriction. Glucose tolerance curves were unchanged by age in ad libitum fed or 50% restricted animals, but in 80% ad libitum groups, older animals showed evidence of decreased glucose tolerance with respect to young animals. For each age, peak serum glucose concentrations after i.p. glucose loading varied with degree of energy restriction, with more severely restricted animals showing less glucose tolerance. Average serum CS concentrations were elevated at 7 months by restriction, especially at night and long after feeding, but we found no differences with age or diet in average CS concentrations. Our serum glucose results support the hypothesis that nonenzymatic glycation is mechanistically involved in normal aging. Our serum CS results do not support the hypothesis that CS contributes significantly to the pathophysiology of normal aging in mice.

Aging↗

PubMed1983

Expression of ultraviolet-induced restriction alleviation in Escherichia coli K-12. Detection of a lambda phage fraction with a retarded mode of DNA injection.

Ultraviolet-induced restriction alleviation is an SOS function which partially relieves the K-12-specific DNA restriction in Escherichia coli. Restriction alleviation is determined by observing elevated survival of unmodified phage lambda in cells irradiated with ultraviolet prior to infection. We demonstrate that restriction of lambda is also relieved when log-phase cells are irradiated as late as 50 min after adsorption of lambda. At this time more than 60% of the lambda DNA is already released as acid-soluble material from the cells. Experiments involving reextraction of lambda DNA from infected cells and a mild detergent treatment removing absorbed phages from the cellular surface showed that only a small specific fraction of all lambda infections is destined to escape restriction due to restriction alleviation. This fraction (10-20%) has a retarded mode of DNA injection (60 min or longer) after adsorption which allows the expression of the restriction alleviation function before the phage DNA is exposed to restriction endonucleases. This behaviour of a fraction of lambda phages explains why the SOS function restriction alleviation could initially be discovered. We show that the retarded mode of DNA injection is not required for another SOS function acting on lambda DNA, the increased repair of ultraviolet-irradiated DNA (Weigle reactivation).

Bacteriophage lambda↗

PubMed1983

Differential effects of dietary caloric and protein restriction in the aging rat.

Numerous studies have shown caloric restriction retards the physiological decline and increases the life span of animals. However, in these studies protein consumption was also reduced; thus, whether the beneficial effects were due to caloric or to protein restriction is unclear. To examine independently the effects of caloric and protein restriction on growth, renal function, and survival, caloric restricted male rats were fed 18, 30 or 42 percent casein diets that provided two-thirds of the quantity of diet consumed by groups fed 12, 20, or 28 percent casein diets ad libitum, respectively. Hence, caloric restricted groups consumed the same amount of protein as their paired ad libitum fed groups but one-third fewer calories. The results showed that caloric restriction decreased mature body weight, increased the rate of attaining mature body weight, retarded the age-associated decline in renal function, and increased survival. Protein restriction had no effect on mature body weight, decreased maturation rate, improved renal function, and decreased survival. Thus, protein restriction did not contribute to the survival-promoting effects of caloric restriction in rats.

Aging↗

PubMed2005

Fatigue, sleep restriction and driving performance.

We ran a randomized cross-over design study under sleep-deprived and non-sleep-deprived driving conditions to test the effects of sleep restriction on real driving performance. The study was performed in a sleep laboratory and on an open French highway. Twenty-two healthy male subjects (age = 21.5 +/- 2 years; distance driven per year = 12,225 +/- 4739 km (7641 +/- 2962 miles) [mean +/- S.D.]) drove 1000 km (625 miles) over 10 h during five 105 min sessions on an open highway. Self-rated fatigue and sleepiness before each session, number of inappropriate line crossings from video recordings and simple reaction time (RT) were measured. Total crossings increased after sleep restriction (535 crossings in the sleep-restricted condition versus 66 after non-restricted sleep (incidence rate ratio (IRR): 8.1; 95% confidence interval (95% CI): 3.2-20.5; p < 0.001)), from the first driving session. The interaction between the two factors (conditionxtime of day) was also significant (F(5, 105) = 3.229; p < 0.05). Increasing sleepiness score was associated with increasing crossings during the next driving session in the sleep-restricted (IRR: 1.9; 95% CI: 1.4-2.4) but not in the non-restricted condition (IRR: 1.0; 95% CI: 0.8-1.3). Increasing self-perceived fatigue was not associated with increasing crossings in either condition (IRR: 0.95; 95% CI: 0.93-0.98 and IRR: 1.0; 95% CI: 0.98-1.02). Rested subjects drove 1000 km with four shorts breaks with only a minor performance decrease. Sleep restriction induced important performance degradation even though time awake (8h) and session driving times (105 min) were relatively short. Major inter-individual differences were observed under sleep restriction. Performance degradation was associated with sleepiness and not fatigue. Sleepiness combined with fatigue significantly affected RT. Road safety campaigns should encourage drivers to avoid driving after sleep restriction, even on relatively short trips especially if they feel sleepy.

Adolescent↗

PubMed2004

Graduated driver licensing restrictions: awareness, compliance, and enforcement in North Carolina.

PROBLEM: This study examined the extent to which critical restrictions in North Carolina's graduated driver licensing (GDL) system are known, adhered to, and enforced. METHOD: Teenagers and their parents were recruited as they applied for either an intermediate or full license at 1 of 23 licensing offices. Telephone interviews were conducted with 900 teenagers and their parents. RESULTS: Awareness of North Carolina's night and passenger restrictions was very high among both parents and teenagers. Ten percent of teenagers reported violating the night restriction without their parents' knowledge, and 15% had done so with their parents' approval. Only 4% of parents reported allowing their teenagers to drive with more than one teenage passenger, but 19% of teenagers reported that they were allowed to do this. Violations of the passenger restriction without parental knowledge were more common than violations of the night restriction (22% vs. 10%, respectively). Among teenagers who violated restrictions without their parents' knowledge, most reported doing so only once or a few times. Teenagers expressed little concern about detection, although a majority reported driving more carefully to avoid police notice. Neither parents nor teenagers knew much about police enforcement of GDL restrictions. To obtain a sense of the views of law enforcement officers, informal interviews were conducted with 20 officers from five diverse communities and the state highway patrol. These officers were highly supportive of GDL but unfamiliar with many of the specific provisions. Moreover, enforcement of GDL restrictions did not appear to be a high priority. IMPACT ON INDUSTRY: There is a need to increase the belief among teens (and parents) that police are enforcing GDL restrictions in their community; law enforcement participation in well-publicized traffic safety enforcement efforts would likely produce this result.

Adolescent↗

PubMed2004

Effects of food restriction on peroxisome proliferator-activated receptor-gamma and glucocorticoid receptor signaling in adipose tissues of normal rats.

In adipocytes, peroxisome proliferator-activated receptor (PPAR)-gamma activates adipocyte differentiation and glucocorticoid (GC) stimulates the expression of PPAR-gamma mRNA. The local tissue concentrations of GC, in turn, are modulated by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). To clarify the change of energy metabolism in condition of reduced energy intake, we investigated whether food restriction alters the adipocyte size and levels of PPAR-gamma, GC receptor (GR), and 11beta-HSD1 mRNA expression in the white adipose tissues of normal rats. Male Wistar rats weighing 340 g were housed under free feeding or 20% reduction of food intake for 2 or 14 days. We found that 2-day food restriction did not cause any change in the mean size or number of adipocytes in the omentum, while 14-day food restriction decreased the size and increased the number of adipocytes. In addition, the levels of PPAR-gamma2, GR, and 11beta-HSD1 mRNA expression in the omentum were lower in the food-restricted rats after 2 days, while they did not differ after 14 days. Also, after both 2 and 14 days, plasma concentrations of free fatty acid (FFA) were higher in the food-restricted rats than in control rats. Finally, plasma concentrations of adrenocorticotropin (ACTH) and corticosterone were the same in the both groups after 2 days, although they were higher in the food-restricted rats after 14 days. These results suggest that adipocyte differentiation in the omentum of food-restricted rats is attenuated after 2 days but recovers after 14 days, resulting in an increase in the number of small adipocytes. It is also likely that lipolysis induced during the 14-day period of food restriction decreased the size of adipocytes. Further, food restriction may affect the efficiency of local GC effects by altering GR and 11beta-HSD1 mRNA expression. Also, higher levels of plasma GC and recovery of GR and 11beta-HSD1 mRNA expression may contribute to the recovery of the levels of PPAR-gamma2 mRNA expression in the omentum and result in the recovery of adipocyte differentiation.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗

PubMed2004

Chronic food restriction increases D-1 dopamine receptor agonist-induced phosphorylation of extracellular signal-regulated kinase 1/2 and cyclic AMP response element-binding protein in caudate-putamen and nucleus accumbens.

Results of behavioral and c-fos immunohistochemical studies have suggested that chronic food restriction and maintenance of animals at 75-80% of free-feeding body weight may increase d-1 dopamine (DA) receptor function. The purpose of the present study was to determine whether D-1 DA receptor binding and/or mitogen-activated protein kinase (MAPK) signaling in caudate-putamen (CPu) and nucleus accumbens (NAc) are increased in food-restricted subjects. In the first experiment, saturation binding of the D-1 DA receptor antagonist [3H]SCH-23390 indicated no difference between food-restricted and ad libitum fed rats with regard to density or affinity of d-1 binding sites in CPu or NAc. In the second experiment, activation of extracellular signal-regulated kinases (ERK1/2) and cyclic AMP response element-binding protein (CREB) by i.c.v. injection of the D-1 DA receptor agonist SKF-82958 (20 microg) were markedly greater in food-restricted than ad libitum fed rats. Given a prior finding that SKF-82958 does not differentially stimulate adenylyl cyclase in CPu or NAc of food-restricted versus ad libitum fed subjects, the present results suggest that increased D-1 DA receptor-mediated ERK1/2 MAP kinase signaling may mediate the enhanced downstream activation of CREB, c-fos, and behavioral responses in food-restricted subjects. It is of interest that food restriction also increased the activation of c-Jun N-terminal protein kinase/stress-activated protein kinase, but this effect was no greater in rats injected with SKF-82958 than in those injected with saline vehicle. This represents additional evidence of increased striatal cell signaling in food-restricted subjects, presumably in response to the i.c.v. injection procedure, although the underlying receptor mechanisms remain to be determined. There were no differences between feeding groups in protein levels of the major phosphatases, MKP-2 and PP1. The upregulation of striatal MAP kinase signaling in food-restricted animals may adaptively serve to facilitate associative learning but, at the same time, increase vulnerability to the rewarding and addictive properties of abused drugs.

Animals↗

PubMed2006

Restrictive impairment in patients with asthma.

BACKGROUND: Patients with asthma have intermittent or persistent airflow obstruction, most often manifested spirometrically by reduced forced expiratory volume in 1s (FEV(1)) and FEV(1)/vital capacity (VC) ratio. In some patients, the VC may be reduced by air trapping, with an increase in functional residual capacity (FRC) and residual volume (RV) (pseudorestriction). We have reported 12 asthmatic patients with reduced VC and no increase in RV, i.e., a true restrictive impairment [Gill et al. True restrictive impairment in bronchial asthma. Am J Respir Crit Care Med 1999:159:A652]. OBJECTIVES: To confirm previous observations of true restrictive impairment (not attributable to air trapping) in patients with asthma, and to estimate its frequency in an asthmatic population. METHODS: Review of pulmonary function tests and clinical records of all post-pubertal patients diagnosed as asthma between January 2000 and September 2003 in a 184 bed inner city teaching hospital in Jamaica, Queens, New York. The clinical diagnosis of asthma was accepted when one or more of the following pulmonary function criteria were met: Positive bronchodilator response (BD), positive methacholine, repeated variability in spirometric values. Restriction was defined as decrease in total lung capacity (TLC) or decrease in VC with no increase in functional residual capacity (FRC) plus normal or high FEV(1)/FVC ratio. Patients with any clinical finding consistent with restriction, including a decreased diffusing capacity (DL) or obesity (BMI >30) were excluded. RESULTS: A total of 100 of 413 (24%) patients with asthma had restriction; 21 of these met all exclusions (including DL and BMI) and 11 (of 46) patients with an increased BMI and normal DL normalized their FVC on BD therapy, demonstrating that their pre-BD restrictive impairment could not be attributed to obesity. Plethysmographic FRC was measured in 81 of the 100 patients with restriction and was increased in only seven. CONCLUSION: True restrictive impairment was noted in at least 32 of 413 asthmatics (8%), consistent with previous observations in asthma and reactive airways dysfunction syndrome. This finding is not widely recognized and should not preclude the diagnosis of asthma, BD testing or appropriate therapy for asthma.

Adult↗

PubMed2000

Morbidity and mortality among very-low-birth-weight neonates with intrauterine growth restriction. The Vermont Oxford Network.

OBJECTIVE: We sought to determine the associations between intrauterine growth restriction and neonatal morbidity and mortality, as well as the impact of prenatal glucocorticoid administration on the frequency of specific complications of prematurity among neonates with intrauterine growth restriction. STUDY DESIGN: We examined the association between intrauterine growth restriction and adverse neonatal outcomes in a population of 19,759 singleton very-low-birth-weight neonates without major birth defects. We included neonates from 25 to 30 weeks' gestation entered in the Vermont Oxford Network database between 1991 and 1996 by 196 institutions. Intrauterine growth restriction was defined as the 10th percentile for birth weight according to the 1993 US national statistics. Odds ratios were estimated according to stepwise logistic regression for each neonatal outcome. Potential explanatory variables included gestational age, intrauterine growth restriction, race, prenatal care, prenatal glucocorticoid administration, route of delivery, fetal sex, and birth within versus postnatal transfer to a network institution. RESULTS: There was a statistically significant association of intrauterine growth restriction with neonatal death (odds ratio, 2.77; 95% confidence interval, 2.31-3. 33), necrotizing enterocolitis (odds ratio, 1.27; 95% confidence interval, 1.05-1.53), and respiratory distress syndrome (odds ratio, 1.19; 95% confidence interval, 1.03-1.36). There was a trend (P <. 10) toward association of intrauterine growth restriction with increased risks of intraventricular hemorrhage (odds ratio, 1.13; 95% confidence interval, 0.99-1.29) and severe intraventricular hemorrhage (grades III and IV; odds ratio, 1.25; 95% confidence interval, 0.98-1.59). Maternal prenatal glucocorticoid administration was associated with significantly lower risks of respiratory distress syndrome (odds ratio, 0.51; 95% confidence interval, 0.44-0.58), intraventricular hemorrhage (odds ratio, 0.67; 95% confidence interval, 0.61-0.73), severe intraventricular hemorrhage (odds ratio, 0.50; 95% confidence interval, 0.43-0.57), and death (odds ratio, 0.54; 95% confidence interval, 0.48-0.62). The benefits of prenatal glucocorticoid therapy for growth-restricted newborns were similar to those among normally grown infants. CONCLUSIONS: Intrauterine growth restriction within the range of 501 to 1500 g birth weight is associated with increased risks of neonatal death, necrotizing enterocolitis, and respiratory distress syndrome. Prenatal corticosteroid use was associated with decreased risks of all outcomes studied except necrotizing enterocolitis. We found no evidence that this benefit was dependent on fetal size.

Cerebral Hemorrhage↗

PubMed1998

Neuroanatomical patterns of Fos-like immunoreactivity induced by naltrexone in food-restricted and ad libitum fed rats.

Chronic food restriction produces a variety of adaptive changes in physiology and behavior aimed at the preservation of energy homeostasis. The brain opioid system may be involved in the adaptation to food restriction since regional levels of opioid peptides, precursor mRNA, and receptor binding have previously been observed. In the present study, c-Fos immunohistochemistry was used to localize cells that are released from opioid-mediated inhibition by naltrexone under conditions of food restriction and ad libitum feeding. In the majority of hypothalamic and forebrain areas examined, Fos-like immunoreactivity (FLI) was higher in food-restricted rats regardless of injection treatment. This may reflect the persistent stress of underfeeding or the synchronizing effect of afternoon feeding on spontaneous c-fos mRNA expression in food-restricted rats. In two brain regions, bed nucleus of the stria terminalis (BNST) and central amygdala (CEA), naltrexone increased FLI in ad libitum fed rats, exclusively. This result suggests the presence of tonic opioid secretion under basal conditions that is suppressed by food restriction. Interestingly, work in other laboratories indicates that anorectic agents consistently increase FLI in BNST and CEA. In three brain regions--lateral (LH), dorsomedial (DMH) and arcuate hypothalamus (ARC)--naltrexone increased FLI in food-restricted rats, exclusively. This result suggests the presence of opioid secretion that is unique to the state of food restriction. The hypothalamic pattern of FLI is discussed in terms of NPY-opioid interactions that result from the ARC response to changes in circulating insulin, corticosterone and leptin levels during food restriction.

Adaptation, Physiological↗

PubMed1992

Sodium restriction versus daily maintenance replacement in very low birth weight premature neonates: a randomized, blind therapeutic trial.

To test the hypothesis that restriction of sodium intake during the first 3 to 5 days of life will prevent the occurrence of hypernatremia and the need for administration of large fluid volumes, we prospectively and randomly assigned 17 babies (mean +/- SD: 850 +/- 120 gm; 27 +/- 1 weeks of gestation) to receive in blind fashion either daily maintenance sodium or salt restriction with physician-prescribed parenteral fluid intake. Maintenance-group infants received 3 to 4 mEq of sodium per kilogram per day; restricted infants received no sodium supplement other than with such treatments as transfusion. Sodium balance studies conducted for 5 days demonstrated that maintenance salt intake resulted in a daily sodium balance near zero, whereas sodium-restricted infants continued to excrete urinary sodium at a high rate, which promoted a more negative balance (average daily sodium balance -0.30 +/- 1.78 SD in maintenance group vs -3.71 +/- 1.47 mEq/kg per day in restriction group; p less than 0.001). Care givers tended to prescribe daily increases in parenteral fluids for the salt-supplemented infants, perhaps because serum sodium concentrations were elevated in these infants after the first day of the study (p less than 0.001). Hypernatremia developed in two sodium-supplemented infants (greater than 150 mEq/L), and hyponatremia developed in two sodium-restricted infants (less than 130 mEq/L); however, the restricted infants were more likely to have normal serum osmolality (p less than 0.05). Both groups of infants produced urine that was neither concentrated nor dilute, with a high fractional excretion of sodium; renal failure was not observed. The mortality rate was not affected, but the incidence of bronchopulmonary dysplasia was significantly less in the sodium-restricted babies (p less than 0.02). We conclude that in tiny premature infants, a fluid regimen that restricts sodium may simplify parenteral fluid therapy targeted to prevent hypernatremia and excessive administration of parenteral fluids.

Fluid Therapy↗