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PubMed2001

Dietary restriction impairs neutrophil exudation by reducing CD11b/CD18 expression and chemokine production.

HYPOTHESIS: Patients with malnutrition are susceptible to infection. Polymorphonuclear neutrophils (PMNs) are the major effector of the nonspecific immune response in host resistance to infection. Dietary restriction may impair PMN-mediated immunity in the peritoneal cavity by reducing PMN exudation, adhesion molecule expression on PMNs, and chemokine production. DESIGN: Randomized study of murine glycogen-induced peritonitis with dietary restriction. SETTING: University research laboratory. MATERIALS: Male C57BL/6J mice. INTERVENTIONS: Mice (N = 204) were assigned to ad libitum, moderate, and severe diet-restricted groups receiving mouse chow ad libitum (132 g/kg, 66 g/kg, and 33 g/kg daily for 7 days, respectively). After dietary restriction with or without 1 day of refeeding, mice were administered glycogen intraperitoneally to induce cell exudation. MAIN OUTCOME MEASURES: CD11b, CD18, and CD62L expressions on circulating PMNs, phagocytosis, and reactive oxygen intermediate production by exudative PMNs were measured after glycogen installation. The levels of PMN-specific chemokine, macrophage inflammatory protein 2 (MIP-2), in peritoneal lavage fluid were also measured. These parameters were measured after glycogen installation in the refeeding experiment. RESULTS: Seven days of dietary restriction decreased CD11b/CD18 expression on circulating PMNs, MIP-2 levels in peritoneal lavage fluid, and subsequent PMN exudation into the peritoneal cavity early in peritonitis. Both CD11b and CD18 expression on circulating PMNs and MIP-2 levels correlated significantly with numbers of exudative PMNs. Seven days of dietary restriction also impaired phagocytosis, while up-regulating reactive oxygen intermediate production by exudative PMNs. Only 1 day of ad libitum refeeding normalized CD11b/CD18 expression with PMN exudation into the peritoneal cavity. CONCLUSIONS: Short-term dietary restriction impairs PMN exudation into local inflammatory sites in murine peritonitis by reducing CD11b/CD18 expression and MIP-2 production. Even brief nutritional replenishment in diet-restricted patients may improve host defense via restoring these PMN functions and chemokine production at local inflammatory sites.

Animals↗

PubMed2000

Association between household and workplace smoking restrictions and adolescent smoking.

CONTEXT: Recent marked increases in adolescent smoking indicate a need for new prevention approaches. Whether workplace and home smoking restrictions play a role in such prevention is unknown. OBJECTIVE: To assess the association between workplace and home smoking restrictions and adolescent smoking. DESIGN, SETTING, AND SUBJECTS: Data were analyzed from 2 large national population-based surveys, the Current Population Surveys of 1992-1993 and 1995-1996, which included 17,185 adolescents aged 15 to 17 years. MAIN OUTCOME MEASURES: Smoking status of the adolescents surveyed, compared by presence of home and workplace smoking restrictions. RESULTS: After adjusting for demographics and other smokers in the household, adolescents who lived in smoke-free households were 74% (95% confidence interval [CI], 62%-88%) as likely to be smokers as adolescents who lived in households with no smoking restrictions. Similarly, adolescents who worked in smoke-free workplaces were 68% (95% CI, 51%-90%) as likely to be smokers as adolescents who worked in a workplace with no smoking restrictions. Adolescent smokers were 1.80 (95% CI, 1.23-2.65) times more likely to be former smokers if they lived in smoke-free homes. The most marked relationship of home smoking restrictions to current adolescent smoking occurred in households where all other members were never-smokers. Current smoking prevalence among adolescents in homes without smoking restrictions approached that among adolescents in homes with a current smoker but with smoking restrictions. CONCLUSIONS: Parents with minor children should be encouraged to adopt smoke-free homes. Smoke-free workplaces can also augment smoking prevention. These findings emphasize the importance of tobacco control strategies aimed at the entire population rather than at youth alone. JAMA. 2000;284:717-722

Adolescent↗

PubMed1994

Severe restrictive lung disease in systemic sclerosis.

OBJECTIVE: We sought to identify risk factors for developing severe restrictive lung disease and to determine the time of onset and rate of progression in patients with systemic sclerosis (SSc). METHODS: Using the University of Pittsburgh Scleroderma Databank, we grouped patients according to their lowest forced vital capacity (FVC) value: > 75% predicted, 50-75% predicted, and < 50% predicted. In patients with severe restrictive disease, we examined serial pulmonary function test (PFT) results to determine the rate of loss of lung volume over time. RESULTS: Of 890 SSc patients, 60% (n = 531) never had an FVC < or = 75% predicted; 27% (n = 243) had moderate restrictive disease, with an FVC value of 50-75% predicted; and only 13% (n = 116) of the patients had severe restrictive disease, with FVC < or = 50% predicted. Black race, male sex, early disease, and primary cardiac involvement due to SSc were the features most frequently associated with severe restrictive lung disease (by multiple logistic regression). Fifty-five patients with severe restrictive lung disease had their first of at least 2 PFTs during the first 5 years after onset of any SSc (not pulmonary) symptoms. In 30 patients, the FVC declined by 32% per year in the first 2 years of illness, in 16 patients the annual loss was 12% in years 2-4 after disease onset, and in 9 patients annual loss was 3% during years 4-6 of disease (P < 0.005 by 1-way analysis of variance). CONCLUSION: In SSc patients, black men with early disease who have cardiac involvement are the most likely to have factors associated with the development of severe restrictive lung disease (which is increasingly becoming a major cause of death). Disease subtype (diffuse versus limited cutaneous) and serum anti-topoisomerase I antibody do not differentiate between moderate and severe restrictive disease. Careful monitoring of pulmonary function early in the disease, when the greatest loss of lung function occurs, may help identify patients likely to respond to new therapy.

Adult↗

PubMed2005

Effects of feed restriction during organogenesis on embryo-fetal development in rabbit.

BACKGROUND: Appropriate maternal nutrition and body weight gain during pregnancy is well established as a major factor in healthy prenatal development in humans. Given the role of nutrition and body weight gain in normal development, pharmaceuticals intended to reduce appetite and promote weight loss will generate developmental toxicity data that may be challenging to interpret. To aid with this, the effects of feed restriction, and subsequent reduction in maternal body weight gain, on embryo-fetal development was investigated in the rabbit. METHODS: Groups of 15 pregnant New Zealand White rabbits were offered 150 (control), 110, 75, 55, 35, and 15 g feed/day from gestation day (GD) 7-19. Cesarean sections were carried out on GD 29 and fetuses were examined for external, visceral, and skeletal development. RESULTS: Maternal body weights at the end of the feed restriction period (GD 20) were 0.97, 0.98, 0.93, 0.94, and 0.86 x control for the 110, 75, 55, 35, and 15 g feed/day groups, respectively. Only at 15 g feed/day was there a net maternal body weight loss (the GD 20 body weight was 0.93 x the GD 6 body weight) at the end of the feed restriction period. Six does aborted in the 15 g feed/day group; there were no other abortions associated with feed restriction. Fetal body weight was significantly reduced at 75, 55, 35, and 15 g feed/day (0.95, 0.90, 0.86, and 0.84 x control, respectively). There were no external or visceral malformations or variations, and no skeletal malformations associated with feed restriction. The incidence of fetuses with sternebrae 5 or 6 unossified was increased at feed levels < or = 75 g/day. At a feed level of 35 g/day there was an increase in unossified metatarsals and metacarpals, and an increase in the number of fetuses with a reduced number of caudal vertebrae ossified. Although these findings were not increased at a feed level of 15 g/day, the lack of dose response was likely due to increased abortion and subsequent decrease in fetuses available for evaluation at 15 g feed/day. CONCLUSION: These data demonstrate that feed restriction to feed levels that produce substantial reductions in maternal body weight gain can result in developmental toxicity expressed by abortion, reduced fetal weight, and alterations in ossification. Abortion only occurred when feed was restricted to an amount that produced maternal body weight loss (15 g feed/day) whereas reduced fetal weight and increased incidence of fetuses with unossified sternebrae, metatarsals, metacarpals, or caudal vertebrae were noted at feed levels of < or = 75 g/day. There were no fetal malformations associated with feed restriction.

Animal Feed↗

PubMed1991

Comparison of class I- and II-restricted T cell recognition of the identical peptide.

There is structural and functional evidence that both class I- and II-restricted T cells recognize short processed peptides bound to MHC molecules. Although the structural conformation of bound peptides remains unknown, no evidence of distinct structural motifs of class I- or class II-restricted peptides has been described. Conversely, two algorithms proposed to predict T cell epitopes, and based on primary amino acid sequence or tertiary structure, are both compatible with many observed class I- and class II-restricted peptides. We previously identified eight class I-restricted peptides which were also recognized by class II-restricted T cells. Based on functional and direct binding studies, additional examples of peptides with both class I and II restrictions have been identified. In this study, we have directly compared the fine specificity of T cell recognition of a single epitope in a single mouse strain in the context of both class I- and class II-restricted responses. Based on a panel of analogue peptides with amino acid substitutions and peptides of various lengths, we observed several striking similarities in the recognition patterns of both class I- and class II-restricted T cells. In addition, some characteristics of recognition were different in the two systems indicating that the recognition processes were similar but not identical.

Amino Acid Sequence↗

PubMed2002

Food restriction modulates amphetamine-conditioned place preference and nucleus accumbens dopamine release in the rat.

Food restriction has been shown to increase self-administration of psychostimulants, including cocaine and amphetamine (AMPH). Consistent with this, food-restricted rats are more sensitized to the rewarding effects of cocaine as measured by conditioned place preference (CPP). This study investigated whether moderate food restriction in rats (15 g/day) results in an increased CPP, relative to ad libitum-fed controls, to a second psychostimulant, AMPH. Conditioning trials consisted of six alternating injections of i.p. AMPH (0.425-6.8 mg/kg) and i.p. saline, paired with distinct environments. On Day 7, a drug-free 20-min choice test for environment was carried out to assess CPP. 0.85 mg/kg AMPH significantly increased CPP in food-restricted vs. ad libitum-fed rats. At 1.7 and 3.4 mg/kg AMPH, food-restricted rats showed decreased CPP, but increased locomotor activity, relative to ad libitum fed controls. To evaluate whether an alteration in extracellular fluid DA levels in the nucleus accumbens (NAc) core could account for these behavioral alterations, DA release was measured by microdialysis. DA release to a single acute i.p. injection of either 0.85 or 1.7 mg/kg AMPH was comparable in food-restricted and ad libitum fed rats. However, ad libitum fed rats demonstrated conditioned DA release after an AMPH conditioning paradigm analogous to the CPP paradigm, whereas food-restricted rats demonstrated no conditioned DA release. In conclusion, altered DA release in the nucleus accumbens core is not a primary effect of moderate food restriction and cannot completely account for either the altered CPP behavior or enhanced locomotor activity observed in this study.

Amphetamine↗

PubMed1999

Restricting access to foods and children's eating.

This study evaluated maternal restriction of children's access to snack foods as a predictor of children's intake of those foods when they were made freely available. In addition, child and parent eating-related "risk" factors were used to predict maternal reports of restricting access. Participants were 71, 3-to-5-year-old children (36 boys, 35 girls) and their parents. Children's snack food intake was measured immediately following a meal, in a setting offering free access to palatable snack foods. Child and maternal reports of restricting children's access to those snack foods were obtained. In addition, information on child and parent adiposity as well as parents' restrained and disinhibited eating was used to examine "risk" factors for restricting access. For girls only, child and maternal reports of restricting access predicted girls' snack food intake, with higher levels of restriction predicting higher levels of snack food intake. Maternal restriction, in turn, was predicted by children's adiposity. Additionally, parents' own restrained eating style predicted maternal restriction of girls' access to snack foods.

Child Behavior↗

PubMed1997

HLA-A locus-restricted and tumor-specific CTLs in tumor-infiltrating lymphocytes of patients with non-small cell lung cancer.

HLA class I restriction and tumor specificity of cytotoxicity in the IL-2-activated tumor-infiltrating lymphocytes from 16 patients with non-small cell lung cancer were investigated. Six HLA class I-restricted and tumor-specific CTL lines were established: (i) HLA A2-restricted and adenocarcinoma-specific CTLs in three (two A0201+ and one A0206+) patients with adenocarcinoma, (ii) HLA A3101- and A3302-restricted and adenocarcinoma-specific CTLs in an HLA A3101/3302+ patient with adenocarcinoma, and (iii) HLA A3302-restricted CTLs and (iv) HLA A2402-restricted CTLs recognizing tumors with different types of histology in an HLA A3302+ patient with adenocarcinoma and an HLA A2402+ patient with squamous cell carcinoma (SCC), respectively. The three HLA A2-restricted CTL lines recognized 4, 4, or 6 of 15 HLA A2+ adenocarcinoma cell lines that originated from lung, stomach, colon, and breast with different subtypes (HLA A0201, A0206, and A0207), respectively. Furthermore, the CTLs of an HLA A0206+ patient recognized five different fractions of peptides eluted from an HLA A0201+ adenocarcinoma cell line. These results showed evidence of the existence of HLA class I-restricted and tumor-specific CTLs recognizing peptide antigens on HLA-A alleles of adenocarcinoma or SCC in tumor sites of a substantial number of patients with non-small cell lung cancer.

Adenocarcinoma↗

PubMed2000

Cardiac natriuretic peptide response to water restriction in the hormonal adaptation of two semidesert rodents from West Africa (Steatomys caurinus, Taterillus gracilis).

Two African rodents, Taterillus gracilis and Steatomys caurinus, native to regions of alternate dry and wet seasons, were studied under laboratory conditions. These species differ in estivation behavior, one undergoing pseudoestivation and the other strong estivation. One group of animals of each species was provided with unlimited access to seed and vegetables rich in water, mimicking the food availability of the wet season (control group). A second group of animals of each species was subjected to water restriction for 8 days, mimicking the natural drought that occurs during the dry-hot season. The effects of water restriction on osmoregulation and body water content were assessed from hematocrit, and plasma and urinary osmolalities (PO, UO). Whether the natriuretic peptide system was modified by the osmoregulator adaptation to aridity of these semidesert rodents was examined from measurements of atrial natriuretic peptide (ANP) levels in plasma, atria, and ventricles, in parallel with morphological studies. In both species, UO was increased by water restriction. In water-deprived T. gracilis, ANP levels were about twice (right atria: 1.08 +/- 0.16 microg/mg protein vs control: 0.40 +/- 0.06 microg/mg protein) and plasma concentrations half (0.28 +/- 0.06 ng/ml vs control: 0.64 +/- 0.07 ng/ml) those in control animals. In S. caurinus these variables were not affected by water availability (right atria water restricted: 2. 20 +/- 0.15 microg/mg protein vs control: 2.86 +/- 0.37 microg/mg protein; plasma ANP water restricted: 0.80 +/- 0.12 ng/ml vs control: 0.90 +/- 0.16 ng/ml). Consistent with these quantitative results, immunohistochemical and ultrastructural observations showed an increase in immunostaining for both the N- and the C-terminal ANP and a larger number of granules in the atria of T. gracilis following water restriction, whereas there was no visible change in S. caurinus. Thus, water restriction induced a decrease in ANP secretion in T. gracilis, increasing cardiac storage alongside a reduced urine production. In contrast, in S. caurinus, the natriuretic system was not affected by an 8-day period of water restriction.

Adaptation, Physiological↗

PubMed1994

Restrictive smoking policies in the workplace: effects on smoking prevalence and cigarette consumption.

BACKGROUND: Thirty-two worksites participating in a randomized trial of worksite health promotion aimed at reducing smoking and obesity were categorized at baseline and 2 years later as having either restrictive or unrestrictive smoking policies. Between the two assessment points, 16 sites received health promotion interventions. RESULTS: At baseline 15 sites had restrictive policies and 17 unrestrictive policies. Smoking restrictions were associated with significantly lower smoking prevalence and higher lifetime quit rates among ever smokers. They also were associated with more recent quit attempts and lower daily cigarette consumption, although these effects were not significant. Between baseline and follow-up, 9 of the 17 worksites that had few smoking restrictions at baseline became restrictive. Although neither baseline smoking policies nor changes in smoking policy predicted change in smoking prevalence or in the frequency of quit attempts, smokers in sites changing from unrestrictive to restrictive policies reported a significant reduction in daily cigarette consumption. CONCLUSIONS: The worksite health promotion program was successful in reducing smoking prevalence in intervention sites compared to controls. However, the existence of restrictive smoking policies neither helped nor hindered these intervention efforts. The present data are believed to support the idea that restrictive smoking policies have beneficial effects on the smoking habits of employees, but that the magnitude of this effect is modest.

Analysis of Variance↗

PubMed1996

Modification of catecholamine-induced changes in heart function by food restriction in rats.

In view of the common practice of dieting for weight reduction, the influence of severe food restriction (about 25% of ad libitum intake) on adrenergic mechanisms was studied. Cardiac norepinephrine and epinephrine concentrations as well as plasma norepinephrine levels, were increased upon feeding a restricted diet to rats for 14 days in comparison with control rats that ingested about 30 g food/ day. Bradycardia as well as characteristic electrocardiographic abnormalities, including prolongation of the QRS and QT intervals, were observed in food-restricted rats. Diet-restricted rats did not develop ventricular arrhythmias in response to epinephrine injections as readily as control rats. Depression in both + dP/dt and -dP/dt of the heart in situ as well as reductions in the inotropic responses to epinephrine were evident in diet-restricted rats. Beta-adrenergic binding studies revealed a significant decrease in receptor density, but the dissociation constant for binding was also depressed in the food-restricted rat heart. Downregulation of the beta-adrenergic receptors in the heart may explain the lack of an epinephrine-induced increase in contractile force development as well as arrhythmias in food-restricted rats. These data demonstrate that severe food restriction has marked effects on adrenergic mechanisms and heart function, and thus some caution should be exercised at early periods of this therapy for weight reduction.

Animals↗

PubMed1983

Genetic and physical studies of restriction-deficient mutants of the Inc FIV plasmids R124 and R124/3.

R124 and R124/3 are R plasmids that carry the genes for two different restriction and modification systems. The phenotype of strains carrying either of these plasmids along with the F'lac+ plasmid, is restriction-deficient (Res-). The Res- phenotype is not due to selection of pre-existing mutants but rather to a complex mutational event caused by the F plasmid. Restriction-deficient mutants carry extensive deletions and other DNA rearrangements. Tn7 insertion is used to locate the restriction gene. Many of the Res- mutants are genetically unstable and revert at exceptionally high frequencies. Reversion is accompanied by DNA rearrangements which result in a net gain of 9 kb of DNA. F derivates of F+ which do not cause restriction-deficiency but do cause deletion were used to distinguish between the DNA rearrangements associated with restriction-deficiency and those associated with deletion. From Res+ revertants of strains carrying F'lac+ and R124 or R124/3 we have isolated F plasmids that now carry the genes for the R124 or R124/3 restriction and modification systems. It is suggested that interaction between part of the F plasmid and that segment of the R plasmid which controls the switch in Res-Mod specificity which has been observed (Glover et al. 1983) is responsible for the production of restriction-deficiency.

Electrophoresis, Agar Gel↗

PubMed1984

Mutant HLA-A2 antigens as restricting elements for virus-specific cytotoxic T cells.

Mutants of the EB virus-transformed cell line T5-1 (HLA-A1, 2; B8, 27), bearing well-characterized alterations in HLA-A2 antigen expression and unable to bind the HLA-A2-specific monoclonal antibody BB7.2, have been tested for their susceptibility to EB virus-specific cytolysis using effector T-cell preparations functionally restricted through relevant HLA antigens. Initial experiments first confirmed that the parent line T5-1 was susceptible to cytolysis by both "common" A2-restricted and B27-restricted effector cells. While those T5-1 mutants with little or no surface A2 expression were not lysed by A2-restricted effectors, those targets with quantitatively normal expression of mutant A2 molecules were as susceptible to A2-restricted lysis as the parent line itself. In contrast, all the T5-1 mutant lines were susceptible to B27-restricted cytolysis. The results demonstrate that experimentally induced mutations of HLA-A2 antigen structure, affecting a serologically defined site on the molecule, can occur without altering that same molecule's expression of the T cell-restricting determinant(s). Such experimentally induced mutations are quite different from the naturally occurring "variant" A2 antigens which are present within the serologically defined A2 antigen group and which show changes at the T cell-restricting site.

Antibodies, Monoclonal↗

PubMed2000

[Effects of restrictions on use of vancomycin in a German university hospital].

BACKGROUND: Recently, increasing antibiotic resistance has been observed among gram-positive bacteria. However, only few isolates were found to be resistant against glycopeptides. Therefore, internationally accepted guidelines recommend a restricted use of vancomycin and other glycopeptide antibiotics in order to prevent the development of resistance against these clinically important antibiotics. In many countries, the hospital pharmacies play a key role in control and reinforcement of antibiotic formulary restrictions. In Germany, however, the hospital pharmacies usually do not take over such control functions, and most wards keep a stock of regularly used drugs including antibiotics, which makes reinforcement of restrictions difficult. METHODS: In an attempt to achieve a restriction of vancomycin use, the pharmacy of our university hospital was advised to deliver vancomycin to the wards only on request with a special order form signed by an attending, individually for every patient who should receive vancomycin. The efficacy of this restriction measure was evaluated in 3-month periods before and after the restriction became effective. RESULTS: Hospitalwide, this led to a 20.1% reduction of i.v. vancomycin and an 85.7% reduction of oral vancomycin use per 1000 patient days. If the hematology/oncology units were not considered, the reduction of i.v. vancomycin use was 41.8%, and the total use after the restriction 24.2 g per 1000 patient days. Microbiology results which justified the use of vancomycin decreased by 8.3% (10.9% hematology/oncology units not considered) between the 2 observation periods. Assuming a 7-day mean course of i.v. vancomycin therapy, the empirical use of i.v. vancomycin decreased from 39.9% to 8% after the restriction had been instituted. CONCLUSION: Allowing only experienced physicians (attendings) to decide on the use of vancomycin therapy, proved in our experience to be an effective measure to reduce unnecessary vancomycin use.

Drug Utilization↗

PubMed2004

Maternal dietary vitamin restriction increases body fat content but not insulin resistance in WNIN rat offspring up to 6 months of age.

AIMS/HYPOTHESIS: Epidemiological evidence suggests that some adult diseases like insulin resistance syndrome and diseases associated with it originate in fetal life. The role of maternal macronutrient malnutrition but not of micronutrients in the fetal origin of adult disease is well studied. We hypothesise that chronic maternal vitamin restriction predisposes the offspring to insulin resistance syndrome. METHODS: Female weanling Wistar/NIN rats received a control diet ( n=6) or a 50% vitamin-restricted diet ( n=14) for 12 weeks and mated with control males. Four dams on the restricted diet were shifted to the control diet from parturition. Pups born to the remaining 10 dams on the restricted diet were weaned on to control diet or continued on the restricted diet. All groups had 8 male pups from weaning onwards. RESULTS: Birthweights of pups were comparable among different groups. Weaning body weights were low in the restricted diet group, but on rehabilitation they caught up with control animals by post-natal day 100. None of the pups had impaired oral glucose tolerance and their insulin resistance status was comparable on days 40, 70, 100 and 180. Compared with offspring on the control diet, offspring on the restricted diet had a significantly higher percentage of body fat and higher plasma triglycerides, as well as lower lean body mass and fat-free mass. They also had increased oxidative stress. Rehabilitation from parturition or weaning prevented the changes in body fat percent, lean body mass, fat-free mass and oxidative stress. CONCLUSIONS/INTERPRETATION: Since changes in adiposity and fat metabolism are considered forerunners of insulin resistance syndrome, our observations suggest that maternal dietary vitamin restriction predisposes the offspring to insulin resistance syndrome in later life.

Adipose Tissue↗

PubMed2003

Effectiveness of non-invasive positive pressure ventilation differs between decompensated chronic restrictive and obstructive pulmonary disease patients.

OBJECTIVE: To compare the efficiency of non-invasive positive pressure ventilation (NPPV) in decompensated patients with either chronic obstructive pulmonary disease (COPD) or chronic restrictive pulmonary disease. DESIGN: Retrospective study. SETTING: A 17-bed intensive care unit in a university teaching hospital. SETTING: Sixty-four patients with COPD (age: 70+/-13 years, sex ratio: 37 male to 27 female patients, forced expiratory volume in 1 s: 31+/-13% predicted) and 20 patients with chronic restrictive pulmonary disease (age: 75+/-9 years, sex ratio: 9 male to 11 female patients, total lung capacity: 57+/-17% predicted) consecutively treated with NPPV (facial mask, pressure support ventilation (PSV) +/- PEEP) for acute respiratory failure. MEASUREMENTS AND RESULTS: There were no statistically significant differences between COPD and patients with chronic restrictive pulmonary disease in terms of cause of exacerbation, use of oxygen therapy or NPPV at home, severity of acute respiratory failure (ARF), mean delay from intensive care admission to initiation of NPPV and total duration of NPPV. Patients with chronic restrictive pulmonary disease had a lower success rate on NPPV (without need of tracheal intubation) than COPD (35% vs 67%, p=0.01). Causes of NPPV failure were not different between COPD and patients with restrictive disease. After 12 h of NPPV, restrictive patients who succeeded with NPPV had similar respiratory rate, minute ventilation and arterial blood gas to COPD patients. At the 3rd and 12th h of NPPV, improvements in pH and PaCO(2) were predictive of NPPV success in COPD, but not in restrictive patients. CONCLUSION: The results of this retrospective study suggest that the effectiveness of NPPV for acute decompensation is less in patients with chronic restrictive pulmonary disease as compared to COPD.

Aged↗

PubMed2004

A progressive ratio schedule of self-stimulation testing in rats reveals profound augmentation of d-amphetamine reward by food restriction but no effect of a "sensitizing" regimen of d-amphetamine.

RATIONALE: Prior research indicates that psychostimulant-induced sensitization is not expressed in lateral hypothalamic electrical self-stimulation (LHSS)-based measures of drug reward, although the augmenting effect of chronic food restriction is. Neuroadaptations within the brain dopamine system have been identified in both psychostimulant-sensitized and food-restricted animals. Consequently, a variant of the LHSS paradigm in which responding is particularly sensitive to changes in dopaminergic tone may be best suited to detect and compare effects of chronic d-amphetamine and food restriction. Instrumental responding on a progressive ratio (PR) schedule is more sensitive to dopaminergic manipulations than is responding on a continuous reinforcement (CRF) schedule, but has not previously been used to examine chronic psychostimulant and food restriction effects on LHSS-based measures of drug reward. OBJECTIVE: The first aim of this study was to determine whether a regimen of d-amphetamine treatment, that produces locomotor sensitization (5 mg/kg per day x5 days), increases the reward-potentiating effect of d-amphetamine in a PR LHSS protocol. The second aim, was to determine whether chronic food restriction produces a marked increase in the reward-potentiating effect of d-amphetamine in the PR LHSS protocol and, if so, whether it is reversible in parallel with body weight recovery when free feeding is restored. METHOD: Reward-potentiating effects of a challenge dose of d-amphetamine (0.25 mg/kg, IP) were measured in terms of the break point of LHSS responding on a PR schedule of reinforcement, in ad libitum fed and food-restricted rats. RESULTS: A regimen of d-amphetamine treatment that produced locomotor sensitization did not increase the break point for LHSS in the presence or absence of d-amphetamine. Chronic food restriction produced a marked increase in the break point-increasing effect of d-amphetamine (3-fold), which returned to baseline in parallel with body weight recovery over a 4-week period of restored free-feeding. CONCLUSIONS: A locomotor-sensitizing regimen of d-amphetamine treatment does not increase the rewarding effect of LH electrical stimulation or the reward-potentiating effect of d-amphetamine in a PR LHSS protocol. The augmenting effect of chronic food restriction on drug reward is mechanistically and functionally different from psychostimulant sensitization and may be controlled by signals associated with adipose depletion and repletion.

Animals↗

PubMed2000

Chronic food restriction in rats augments the central rewarding effect of cocaine and the delta1 opioid agonist, DPDPE, but not the delta2 agonist, deltorphin-II.

RATIONALE: Chronic food restriction augments the self-administration and locomotor stimulating effects of opiates, psychostimulants and NMDA antagonists. The extent to which these effects can be attributed to changes in drug pharmacokinetics and bioavailability versus sensitivity of the neuronal circuits that mediate the affected behavioral functions, has not been established. Recent studies point to central adaptive changes insofar as rewarding, locomotor and c-fos-inducing effects of amphetamine and MK-801, injected directly into the lateral ventricle, are greater in food-restricted than ad libitum fed rats. The increased expression of c-fos in nucleus accumbens (NAC) shell, in particular, suggests that food restriction may augment drug reward by modulating dopamine (DA) synaptic function in this area. OBJECTIVES: The first purpose of this study was to investigate whether the rewarding effects of cocaine and the delta1 opioid agonist DPDPE, both of which increase DA synaptic transmission, are augmented by food restriction. The second purpose was to determine whether the delta2 opioid agonist, deltorphin-II, which has been reported to exert DA-independent rewarding effects, is subject to the potentiating effect of food restriction. METHODS: Rewarding effects of drugs were measured in terms of their ability to lower the threshold for lateral hypothalamic self-stimulation (LHSS) using a rate-frequency method. RESULTS: In separate experiments, cocaine (50, 100 and 150 microg, ICV) and DPDPE (10 and 25 microg, ICV) produced greater threshold-lowering effects in food-restricted than ad libitum fed rats. Deltorphin-II (5.0, 10 and 25 microg, ICV) had no effect on reward thresholds, regardless of feeding regimen. CONCLUSIONS: While the reported DA-independence of deltorphin-II rewarding effects seemed to offer a means of testing the hypothesis that DA transmission is the critical modulated variable in food-restricted subjects, rewarding effects of this compound could not be demonstrated in the LHSS paradigm. The present results do, however, confirm and extend prior findings indicating that the enhanced self-administration of abused drugs by food-restricted subjects is due to enhanced sensitivity of a final common pathway for drug reward.

Animals↗