[Total Hip and Knee Arthroplasty - Utilization of Postoperative Rehabilitation]. / Implantation einer Hüft- oder Knietotalendoprothese und die Inanspruchnahme einer Anschlussrehabilitation.

BACKGROUND: After total hip and knee arthroplasty, patients have different options of subsequent treatment: an early postoperative rehabilitation, with or without a period at home, or only outpatient services. The aim of this study was to identify factors predicting the utilization of an early postoperative rehabilitation. METHODS: This cross-sectoral analysis is based on claims data of AOK Baden-Württemberg (Statutory Health Insurance), Deutsche Rentenversicherung Bund and Deutsche Rentenversicherung Baden-Württemberg (German Pension Insurance). Predictors for participation in an early postoperative rehabilitation and for an interim period were determined using logistic regression analysis. RESULTS: 82.6% of 9 232 patients were going to an early postoperative rehabilitation after total hip arthroplasty. After total knee arthroplasty, 83.9% of 7 656 patients were utilizing postoperative rehabilitation. Moreover, there was less utilization of postoperative rehabilitation in young, male and foreign patients. The analysis shows that the utilization of post-acute rehabilitation was significantly predicted by sociodemographic variables (age, sex, nationality) as well as comorbidity, outpatient treatment and medication. CONCLUSION: The results provide an indication of higher severity of patients in group "postoperative rehabilitation without a period at home". Nevertheless there are some indications for under-utilization of certain patient groups.

Estimating the residual risk for HIV, HCV and HBV in different types of platelet concentrates in Germany.

BACKGROUND AND OBJECTIVES: We estimated and compared the residual risks due to window-period donations for pooled and apheresis platelets in Germany using a modification of a previously described statistical model. This model directly utilizes the reported interdonation intervals before a positive donation and reflects in this aspect the look-back procedures used in haemovigilance. MATERIALS AND METHODS: Data from the German National Blood Donor Surveillance System for the years 2006-2012, including reports about donations from repeat donors with confirmed positive test results for HIV, HCV and HBV, were used to estimate the risk of undetected infectious units for both pooled and apheresis platelets. RESULTS: Demographics of whole-blood and apheresis donors differed in age, gender, catchment area and interdonation interval. These differences impact on the prevalence and incidence of transfusion relevant infections and consequently the residual risk. The estimates for the residual risks for pooled and apheresis platelets were comparable. For HIV, there was no significant difference, for HCV apheresis platelets had a lower residual risk, whereas pooled platelets had a lower risk for undetected HBV infections. CONCLUSION: These findings do not support calls for a shift to an apheresis platelets-only policy in Germany.

Fate of D3 mouse embryonic stem cells exposed to X-rays or carbon ions.

The risk of radiation exposure during embryonic development is still a major problem in radiotoxicology. In this study we investigated the response of the murine embryonic stem cell (mESC) line D3 to two radiation qualities: sparsely ionizing X-rays and densely ionizing carbon ions. We analyzed clonogenic cell survival, proliferation, induction of chromosome aberrations as well as the capability of cells to differentiate to beating cardiomyocytes up to 3 days after exposure. Our results show that, for all endpoints investigated, carbon ions are more effective than X-rays at the same radiation dose. Additionally, in long term studies (≥8 days post-irradiation) chromosomal damage and the pluripotency state were investigated. These studies reveal that pluripotency markers are present in the progeny of cells surviving the exposure to both radiation types. However, only in the progeny of X-ray exposed cells the aberration frequency was comparable to that of the control population, while the progeny of carbon ion irradiated cells harbored significantly more aberrations than the control, generally translocations. We conclude that cells surviving the radiation exposure maintain pluripotency but may carry stable chromosomal rearrangements after densely ionizing radiation.

[HIV, HCV, HBV and syphilis surveillance among blood donors in Germany 2008-2010]. / HIV-, HCV-, HBV- und Syphilissurveillance unter Blutspendern in Deutschland 2008-2010.

The Robert Koch Institute collects and evaluates data on the prevalence and incidence of HIV, hepatitis C (HCV), hepatitis B (HBV) and syphilis infections among blood and plasma donors in Germany according to article 22 of the Transfusion Act. This report includes data from all blood donation services in Germany for 2008-2010. The prevalence for HIV ranged from 6.6-7.0/100,000, for HCV from 68.9-81.6/100,000, for HBV from 116.2-136.6/100,000 and for syphilis from 31.0-42.1/100,000 donations. The proportion of incident infections per 100,000 donations ranged from 0.8-0.9 for HIV, 0.8-1.0 for HCV, 0.3-0.5 for HBV and 1.4-1.6 for syphilis. Since 2001 the prevalence and incidence of HBV and HCV among blood has declined whereas incident HIV infections reached a peak in 2008 and 2010 and show an increasing trend. Also, the proportion of syphilis infections among first time donors was highest in 2010. Significant differences in infection prevalence and incidence were found between the sexes, different age groups and different donation types. In order to optimise donor selection a validated donor questionnaire should be used and confidentiality in all steps of donation should be assured. The possibility of a confidential self-exclusion should be explicitly pointed out to donors.

[Demography and donation frequencies of blood and plasma donor populations in Germany. Update 2010 and 5-year comparison]. / Demografie und Spendeaktivität von Blut- und Plasmaspendern in Deutschland. Update 2010 und 5-Jahres-Vergleich.

The Robert Koch Institute collects and evaluates nationwide data on the incidence and prevalence of transfusion-relevant infections among blood and plasma donors in Germany. Since 2006 data not only on the number of donations tested but also on the number of the respective donors have become available. The demographic profile and donation frequencies of German whole blood, plasma and platelet donors in 2010 and the percentages among the general population are described and compared to data from 2006. Although the general population eligible to donate blood is on the decline since 2003, with a loss of 2% between 2006 and 2010, this has not led to a decrease in the number of blood donors and donations. Instead, the number of new and repeat whole blood donors increased by 8% and 7%, respectively. At the same time, the number of new plasma donors grew by 23%, that of repeat plasma donors by 41%. In 2010 more than 4.3% of the population aged 18-68 years was active as repeat whole blood donors; 0.4% repeatedly donated plasma or platelets. Since 2006 the percentage of donors among the general population increased significantly, especially among the youngest age group (18-24 years). Donation frequency varied depending on donor age and sex, with an average of 1.9 per year for whole blood donations, 12.5 for plasmapheresis and 5.0 for plateletpheresis. While the donation frequency for whole blood remained unchanged since 2006, the frequency of apheresis donations increased, especially among older donors. By recruiting more new donors and retaining and reactivating existing ones more effectively, the number of whole blood and apheresis donations was augmented.

Circadian integration of sleep-wake and feeding requires NPY receptor-expressing neurons in the mediobasal hypothalamus.

Sleep and feeding rhythms are highly coordinated across the circadian cycle, but the brain sites responsible for this coordination are unknown. We examined the role of neuropeptide Y (NPY) receptor-expressing neurons in the mediobasal hypothalamus (MBH) in this process by injecting the targeted toxin, NPY-saporin (NPY-SAP), into the arcuate nucleus (Arc). NPY-SAP-lesioned rats were initially hyperphagic, became obese, exhibited sustained disruption of circadian feeding patterns, and had abnormal circadian distribution of sleep-wake patterns. Total amounts of rapid eye movement sleep (REMS) and non-REMS (NREMS) were not altered by NPY-SAP lesions, but a peak amount of REMS was permanently displaced to the dark period, and circadian variation in NREMS was eliminated. The phase reversal of REMS to the dark period by the lesion suggests that REMS timing is independently linked to the function of MBH NPY receptor-expressing neurons and is not dependent on NREMS pattern, which was altered but not phase reversed by the lesion. Sleep-wake patterns were altered in controls by restricting feeding to the light period, but were not altered in NPY-SAP rats by restricting feeding to either the light or dark period, indicating that disturbed sleep-wake patterns in lesioned rats were not secondary to changes in food intake. Sleep abnormalities persisted even after hyperphagia abated during the static phase of the lesion. Results suggest that the MBH is required for the essential task of integrating sleep-wake and feeding rhythms, a function that allows animals to accommodate changeable patterns of food availability. NPY receptor-expressing neurons are key components of this integrative function.

Remote entanglement between a single atom and a Bose-Einstein condensate.

Entanglement between stationary systems at remote locations is a key resource for quantum networks. We report on the experimental generation of remote entanglement between a single atom inside an optical cavity and a Bose-Einstein condensate (BEC). To produce this, a single photon is created in the atom-cavity system, thereby generating atom-photon entanglement. The photon is transported to the BEC and converted into a collective excitation in the BEC, thus establishing matter-matter entanglement. After a variable delay, this entanglement is converted into photon-photon entanglement. The matter-matter entanglement lifetime of 100 µs exceeds the photon duration by 2 orders of magnitude. The total fidelity of all concatenated operations is 95%. This hybrid system opens up promising perspectives in the field of quantum information.

Alpha-Particle Exposure Induces Mainly Unstable Complex Chromosome Aberrations which do not Contribute to Radiation-Associated Cytogenetic Risk.

The mechanism underlying the carcinogenic potential of α radiation is not fully understood, considering that cell inactivation (e.g., mitotic cell death) as a main consequence of exposure efficiently counteracts the spreading of heritable DNA damage. The aim of this study is to improve our understanding of the effectiveness of α particles in inducing different types of chromosomal aberrations, to determine the respective values of the relative biological effectiveness (RBE) and to interpret the results with respect to exposure risk. Human peripheral blood lymphocytes (PBLs) from a single donor were exposed ex vivo to doses of 0-6 Gy X rays or 0-2 Gy α particles. Cells were harvested at two different times after irradiation to account for the mitotic delay of heavily damaged cells, which is known to occur after exposure to high-LET radiation (including α particles). Analysis of the kinetics of cells reaching first or second (and higher) mitosis after irradiation and aberration data obtained by the multiplex fluorescence in situ hybridization (mFISH) technique are used to determine of the cytogenetic risk, i.e., the probability for transmissible aberrations in surviving lymphocytes. The analysis shows that the cytogenetic risk after α exposure is lower than after X rays. This indicates that the actually observed higher carcinogenic effect of α radiation is likely to stem from small scale mutations that are induced effectively by high-LET radiation but cannot be resolved by mFISH analysis.

Emission properties and photon statistics of a single quantum dot laser.

A theoretical description for a single quantum-dot emitter in a microcavity is developed.We analyze for increasing steady-state pump rate the transition from the strong-coupling regime with photon antibunching to the weak-coupling regime with coherent emission. It is demonstrated how Coulomb interaction of excited carriers and excitation-induced dephasing can strongly modify the emission properties. Our theoretical investigations are based on a direct solution of the Liouville-von Neumann equation for the coupled carrier-photon system. We include multiple carrier excitations in the quantum dot, their Coulomb interaction, as well as excitation-induced dephasing and screening. Similarities and differences to atomic systems are discussed and results in the regime of recent experiments are interpreted.

Lossless state detection of single neutral atoms.

We introduce lossless state detection of trapped neutral atoms based on cavity-enhanced fluorescence. In an experiment with a single 87Rb atom, a hyperfine-state-detection fidelity of 99.4% is achieved in 85 µs. The quantum bit is interrogated many hundreds of times without loss of the atom while a result is obtained in every readout attempt. The fidelity proves robust against atomic frequency shifts induced by the trapping potential. Our scheme does not require strong coupling between the atom and cavity and can be generalized to other systems with an optically accessible quantum bit.

[Epidemiological data on infections among blood donors in Germany 2007]. / Infektionsepidemiologische Daten von Blutspendern in Deutschland 2007.

The Robert Koch Institute collects and evaluates data on the prevalence and incidence of HIV, hepatitis C (HCV), hepatitis B (HBV), and syphilis infections among blood and plasma donors in Germany according to §22 of the Transfusion Act ("Transfusiongesetz"). The surveillance data permit an assessment of the occurrence of infections in the blood donor population and consequently the safety of the collected donations. This report includes data from all blood donation services in Germany for 2007. Due to the revision of the Transfusion Act in 2005, not only the number of donations but also the number of donors is now available for analysis. Nearly 550,000 donations or blood samples from new donors and more than 6.24 million donations collected from approximately 2.43 million repeat donors were tested for transfusion-relevant infections in 2007. The prevalence for HIV was 8.0/100,000, for HCV 70.0/100,000, for HBV 132.5/100,000, and for syphilis 36.8/100,000 donations. The proportion of seroconversions/100,000 donations was 0.6 for HIV, 1.1 for HCV, 0.6 for HBV, and 1.7 for syphilis. The analysis showed a very low incidence of HIV, HBV, and syphilis with marginal changes compared to previous years. The prevalence and incidence of HCV among blood donors was once again declining.

A susceptibility gene for type 2 diabetes confers substantial risk for diabetes complicating cystic fibrosis.

AIMS/HYPOTHESIS: Insulin-requiring diabetes affects 25-50% of young adults with cystic fibrosis (CF). Although the cause of diabetes in CF is unknown, recent heritability studies in CF twins and siblings indicate that genetic modifiers play a substantial role. We sought to assess whether genes conferring risk for diabetes in the general population may play a risk modifying role in CF. METHODS: We tested whether a family history of type 2 diabetes affected diabetes risk in CF patients in 539 families in the CF Twin and Sibling family-based study. A type 2 diabetes susceptibility gene (transcription factor 7-like 2, or TCF7L2) was evaluated for association with diabetes in CF using 998 patients from the family-based study and 802 unrelated CF patients in an independent case-control study. RESULTS: Family history of type 2 diabetes increased the risk of diabetes in CF (OR 3.1; p = 0.0009). A variant in TCF7L2 associated with type 2 diabetes (the T allele at rs7903146) was associated with diabetes in CF in the family study (p = 0.004) and in the case-control study (p = 0.02; combined p = 0.0002). In the family-based study, variation in TCF7L2 increased the risk of diabetes about three-fold (HR 1.75 per allele, 95% CI 1.3-2.4; p = 0.0006), and decreased the mean age at diabetes diagnosis by 7 years. In CF patients not treated with systemic glucocorticoids, the effect of TCF7L2 was even greater (HR 2.9 per allele, 95% CI 1.7-4.9, p = 0.00011). CONCLUSIONS/INTERPRETATION: A genetic variant conferring risk for type 2 diabetes in the general population is a modifier of risk for diabetes in CF.

No evidence for DNA and early cytogenetic damage in bystander cells after heavy-ion microirradiation at two facilities.

The occurrence of bystander effects has challenged the evaluation of risk for heavy ions, mainly in the context of space exploration and the increasing application of carbon ions in radiotherapy. In the present study, we addressed whether heavy-ion-induced DNA and cytogenetic damage is detectable in bystander cells. The formation of gamma-H2AX foci, sister chromatid exchanges and micronuclei were used as markers of damage to DNA. Normal human fibroblasts were exposed to low fluences of carbon and uranium ions, and alternatively single cells were targeted with heavy ions using the GSI microbeam. We did not observe a significant increase in the bystander formation of gamma-H2AX foci, sister chromatid exchanges or micronuclei. In addition, we performed for the first time parallel experiments at two microbeam facilities (GSI, JAEA) using the same cell line, culture conditions and irradiation protocols. No significant enhancement of the micronucleus frequencies in bystander cells was detected after targeted carbon-ion irradiation, confirming the results. Details regarding the history, culture conditions or support of the cells might be affecting the detection of bystander effects. On the other hand, the potential X-ray- and heavy-ion-induced bystander effects investigated herein clearly do not exceed the experimental error and thus are either lacking or are less pronounced than the effects reported in the literature for similar end points after alpha-particle and X-ray exposure.

Cell cycle arrest and aberration yield in normal human fibroblasts. II: Effects of 11 MeV u-1 C ions and 9.9 MeV u-1 Ni ions.

PURPOSE: To investigate further the relationship between high linear energy transfer (LET) induced cell cycle arrests and the yield of chromosome aberrations observable in normal human fibroblasts at the first post-irradiation mitosis. MATERIALS AND METHODS: Normal human fibroblasts (AG01,522C) were exposed in G0/G1 to either 11 MeV u(-1) C ions (LET = 153.5 keV microm(-1)) or 9.9 MeV u(-1) Ni ions (LET = 2,455 keV microm(-1)), subcultured in medium containing 5-Bromo-2'-deoxyuridine (BrdU) and at multiple time-points post-irradiation the yield of chromosomal damage, the mitotic index and the cumulative BrdU-labelling index were determined. Furthermore, a mathematical approach was used to analyse the entire cell population. RESULTS: Following high LET exposure normal fibroblasts suffer a transient delay into S-phase and into mitosis as well as a prolonged, probably permanent cell cycle arrest in the initial G0/G1-phase. Cells that reach the first mitosis at early times carried less aberrations than those collected at later times indicating a relationship between cell cycle delay and the number of aberrations. However, with respect to the whole cell population, only a few aberrant fibroblasts are able to progress to the first mitosis. For all endpoints studied the relative biological effectiveness (RBE) of C ions is in the range of 2 - 4, while for Ni ions RBE < 1 is estimated. In contrast, when compared on a per particle basis Ni ions with the higher ionization density were found to be more effective. CONCLUSIONS: Detailed analysis of the data demonstrates that the number of fibroblasts at risk for neoplastic transformation is significantly reduced by a chronic cell cycle arrest in the initial G0/G1-phase and, for the first time, the LET-dependence of this effect has been shown.

Prediction of dose response for radiation induced exchange aberrations taking cell cycle delays into account.

Chromosomal aberrations (CAs) are regarded as one of the most sensitive biological indicators of genetic alterations. The aberration frequency is routinely determined in the first metaphase. Yet, the data interpretation can be complicated due to radiation induced mitotic delays. To investigate the effect of delays on CA frequency in the first mitosis, human lymphocytes were irradiated with X rays and Giemsa detectable CAs were measured at different sampling times. Besides, a computer simulation was performed reproducing the main effects under investigation, that is, CA induction and cell progression through the mitotic cycle. The CA formation model takes into account the structural organisation of interphase chromosomes in a lymphocyte nucleus, DNA double-strand break (DSB) induction and their rejoining/misrejoining. Lymphocyte transition through the cell cycle was simulated by a Monte Carlo technique. The delay was proposed to result from DNA DSBs. The predicted ratios of first/second/third cycle metaphases agree with the experimental data for control and irradiated samples. Both experimental and calculated CA frequencies in the first mitosis were nearly time-independent. This was proposed to result from de-synchronisation of the lymphocyte population.

Multiple retinoids alter liver bile salt-independent retinyl ester-hydrolase activity, serum vitamin A and serum retinol-binding protein of rats.

Liver bile salt-independent retinyl ester hydrolase (BSI-REH) has been suggested to play a significant role in the hydrolysis of chylomicron derived retinyl esters. Studies were conducted to investigate the individual effects of N-(4-hydroxyphenyl)retinamide (HPR), retinoic acid, 13-cis-retinoic acid, Acitretin and Temarotene on BSI-REH, serum retinol, and serum retinol-binding protein (RBP) concentrations. We have demonstrated that micromolar concentrations of HPR, retinoic acid, 13-cis-retinoic acid or Acitretin significantly reduced the in vitro hydrolysis of retinyl palmitate. In contrast, Temarotene stimulated retinyl palmitate hydrolysis by BSI-REH. Retinoic acid and 13-cis-retinoic acid produced transient, but significant, depressions of both serum retinol and RBP concentrations, when the individual retinoids were administered orally to rats. The duration of the depression was shorter than we previously observed with acute HPR administration. Furthermore, Acitretin appeared to function with bimodal activity, producing significant depression of serum retinol at 2 h and 24 h. No effect of Acitretin or Temarotene on serum RBP concentration was observed. The alterations observed in BSI-REH activity, serum retinol and RBP concentrations provide evidence that these retinoids can alter liver retinyl ester hydrolysis, but the effects observed on serum retinol concentration can only be partially explained by the BSI-REH activity.

Retinol-binding protein secretion from the liver of N-(4-hydroxyphenyl) retinamide-treated rats.

N-(4-Hydroxyphenyl)retinamide (HPR; Fenretinide), a synthetic retinoid possessing antitumor activity, depresses plasma retinol and retinol-binding protein (RBP) concentrations. In study 1, the ability of retinol or HPR to induce RBP secretion from the livers of vitamin A-deficient rats was compared. A large apoRBP pool accumulated in the liver rough microsomes of these rats. Following retinol repletion, 80% of the accumulated RBP was rapidly secreted into the plasma. In contrast, HPR treatment only induced two-thirds of the RBP secretion observed with retinol. Prior colchicine treatment caused a large RBP accumulation in the Golgi-enriched fraction following retinol repletion. HPR plus colchicine treatment produced significantly less accumulation of RBP in the Golgi-enriched fraction than did retinol. In study 2, HPR treatment of vitamin A-adequate rats caused RBP to accumulate in the liver rough microsomes. When vitamin A-adequate rats were treated with colchicine, the concentration of RBP in the Golgi-enriched fraction increased 2.9-fold. However, significantly less RBP accumulated in the Golgi following HPR treatment. These studies demonstrate that HPR will induce liver RBP secretion, but to a lesser degree than retinol. Further, more RBP remained in the rough microsomes of HPR treated, vitamin A-adequate rats, indicating that HPR depressed the amount of RBP secreted.

The complex between retinol and retinol-binding protein is formed in the rough microsomes of liver following repletion of vitamin A-depleted rats.

Retinol-binding protein (RBP), the plasma transport protein for vitamin A, is primarily synthesized in the rough endoplasmic reticulum of the liver. RBP then passes through the smooth endoplasmic reticulum and into the Golgi apparatus where vesicles form and transport the protein to the cell membrane. When rats were depleted of their vitamin A stores, RBP accumulated in the liver microsomes, particularly in the rough microsomes. To identify the organelle(s) where retinol initially binds to RBP, vitamin A-depleted rats were given an i.v. injection of [3H]retinol suspended in Tween 40. After intervals of 2, 3, 4, 5, 6, 8, 10, 15 and 20 min, liver fractions enriched in rough and smooth microsomes and Golgi apparatus were prepared. The retinol/RBP complex (holoRBP) was detected in the rough microsomes within 3 min post injection. HoloRBP later appeared in the smooth microsomes and Golgi fraction, and then the serum at time intervals consistent with the known secretion rate for RBP. HoloRBP was detected in the rough microsomes at all times after 3 min, whether or not the complex was present in the other subcellular fractions. Thus, the holoRBP complex can form in the rough endoplasmic reticulum of the liver.

Repeated 2-deoxy-D-glucose-induced glucoprivation attenuates Fos expression and glucoregulatory responses during subsequent glucoprivation.

A condition of reduced responsiveness to hypoglycemia, known as hypoglycemia-associated autonomic failure (HAAF), occurs in diabetic patients in the wake of a prior hypoglycemic episode. This condition suggests that hypoglycemia alters central glucose-sensing mechanisms. This experiment examined the effects of repeated 2-deoxy-D-glucose (2DG)-induced glucoprivation on subsequent 2DG-induced feeding and hyperglycemic responses in rats. Fos immunoreactivity (ir) in adrenal medulla and brain sites involved in these responses was also examined. Rats were injected daily for 10 days with 2DG (200 mg/kg) or saline (0.9%) or were handled. On day 11, rats were injected with 2DG (200 mg/kg). After injection, food intake was measured in one group. In another group, food was withheld, and multiple blood samples were collected for glucose determination. In a third group, food was withheld, and rats were killed after 2 h for evaluation of Fos-ir. Prior repeated glucoprivation reduced subsequent feeding and hyperglycemia responses to 2DG to baseline levels. Double-label immunohistochemistry showed that Fos-ir was reduced or abolished in catecholamine cell groups A1, A1/C1, C1, C3, and A6 and in the paraventricular nucleus of the hypothalamus and adrenal medulla. In other brain sites, 2DG-induced Fos-ir was diminished or unaffected by prior glucoprivation. Sites in which Fos-ir was abolished have been implicated previously in glucoprivic control of feeding and adrenal medullary secretion. Therefore, the present findings may identify crucial neuroanatomical sites that are altered by prior glucoprivation and that mediate some of the physiological deficits observed in HAAF.

Acute 2DG-induced glucoprivation or dexamethasone abolishes 2DG-induced glucoregulatory responses to subsequent glucoprivation.

Behavioral, neuroendocrine, and autonomic responses to glucoprivation are impaired after a glucoprivic episode. A life-threatening manifestation of this effect, known as hypoglycemia-associated autonomic failure (HAAF), occurs in diabetic patients as a result of prior inadvertent hypoglycemia resulting from insulin therapy. Glucocorticoids, which are elevated by glucoprivation, have been implicated in the pathogenesis of HAAF. The goal of the present study was to examine the effect of glucocorticoids on glucoregulatory responses in a rat model of HAAF. 2-deoxy-D-glucose (2DG; 200 mg/kg) was used to induce glucoprivation. Rats were injected with saline, 2DG, or the synthetic glucocorticoid, dexamethasone (DEX; 250 microg/rat) in the morning. Then 6 h later, rats were injected with 2DG, and their feeding and hyperglycemic responses were measured. Both 2DG and DEX in the morning eliminated glucoprivic feeding and hyperglycemic responses in the afternoon test. Epinephrine (0.3 mg/kg) administration in the afternoon elicited marked hyperglycemia in animals given 2DG that morning, demonstrating that glycogen depletion from morning glucoprivation was not responsible for the absence of the hyperglycemic response in the afternoon test. The effects of prior saline or 2DG treatment on subsequent glucoprivic feeding were also examined in adrenalectomized rats in which the source of endogenous glucocorticoids was removed. In these animals, prior glucoprivation did not attenuate 2DG-induced feeding in the afternoon test. These findings demonstrate that a single glucoprivic episode is sufficient to cause impairment in glucoregulatory responses to a second glucoprivic episode in the same day. In addition, these results strongly implicate glucocorticoids in the pathogenesis of HAAF.