[The subanalysis of Rheuma-VOR demonstrates a considerable need for rheumatological care]. / Die Subanalyse von Rheuma-VOR zeigt den erheblichen Bedarf der rheumatologischen Versorgung auf.

BACKGROUND: Early diagnosis and treatment of inflammatory rheumatic diseases can prevent consequential damage such as permanently limited mobility and joint or organ damage. Simultaneously, there is an increasing deficit in medical care owing to the lack of rheumatological capacity. Rural regions are particularly affected. OBJECTIVES: The available unconfirmed diagnoses of the study Rheuma-VOR were analysed regarding another definitive inflammatory rheumatic disease. MATERIALS AND METHODS: The returned questionnaires of the rheumatologists participating in Rheuma-VOR were screened for definitive inflammatory rheumatic diseases other than the required diagnosis of rheumatoid arthritis, psoriatic arthritis or spondyloarthritis. RESULTS: Of 910 unconfirmed diagnoses, in 245 patients another definitive diagnosis could be confirmed. A total of 29.8% of the diagnoses corresponded to degenerative joint changes or chronic pain syndrome, whereas 26.1% involved different forms of inflammatory arthritis. The majority of diagnoses (40.5%) were collagenosis or vasculitis, DISCUSSION: The available data show that a rheumatological presentation was indicated for the majority of patients. Owing to the increasing deficits in medical care a prior selection of the patients is crucial to make optimal use of restricted rheumatological capacities.

[Severe polyneuropathy in primary Sjögren's syndrome : Sjögren's syndrome should be considered in patients with motor neuropathy]. / Schwere Polyneuropathie bei primärem Sjögren-Syndrom : Bei Patienten mit motorischen Neuropathien auch an Sjögren-Syndrom denken!

A 64-year-old male patient developed over a period of 20 years a peripheral neuropathy symmetrically affecting the upper and lower limbs. The histological examination of a sural nerve biopsy revealed a severe axonal neuropathy. Despite extensive laboratory investigations including immunological and metabolic tests the origin could not be identified. Finally, a Schirmer test revealed xerophthalmia. A subsequent salivary gland biopsy from the lower lip revealed a grade III lymphocytic inflammation according to Chisholm and Mason and confirmed the diagnosis of Sjögren's syndrome.

Self-Calibrating Vector Atomic Magnetometry through Microwave Polarization Reconstruction.

Atomic magnetometry is one of the most sensitive ways to measure magnetic fields. We present a method for converting a naturally scalar atomic magnetometer into a vector magnetometer by exploiting the polarization dependence of hyperfine transitions in rubidium atoms. First, we fully determine the polarization ellipse of an applied microwave field using a self-calibrating method, i.e., a method in which the light-atom interaction provides everything required to know the field in an orthogonal laboratory frame. We then measure the direction of an applied static field using the polarization ellipse as a three-dimensional reference defined by Maxwell's equations. Although demonstrated with trapped atoms, this technique could be applied to atomic vapors, or a variety of atomlike systems.

Platelet transfusion to reverse antiplatelet therapy before decompressive surgery in patients with intracranial haemorrhage.

BACKGROUND: Platelet concentrates (PC) are transfused to improve primary haemostasis before urgent neurosurgery in patients with intracranial haemorrhage (ICH) receiving antiplatelet therapy (APT). It is unresolved, whether PCs increase the risk for major cardio- and cerebrovascular adverse events. We evaluated a standardized transfusion regimen to reverse APT in patients with ICH who required decompressive neurosurgery. METHODS: Analysed were consecutive patients between 2012 and 2014. The primary outcome was the frequency of new arterial thrombotic complications. The secondary outcome was the frequency of recurrent ICH. RESULTS: Of 72 patients, 14 received acetylsalicylic acid and a P2Y12 inhibitor, 53 received acetylsalicylic acid and five clopidogrel. No acute coronary syndrome (95% CI: 0-5·07) and one ischaemic stroke occurred (1·4%; 95% CI: 0·25-7·46). In contrast, 26·4% of patients developed recurrent ICH (95% CI: 17·59-37·58). The risk of bleeding was significantly higher compared to the risk of arterial thrombosis (P < 0·00001) and was increased for patients with chronic ICH (OR: 4·78; 95% CI: 1·57-14·55) and those receiving clopidogrel (OR: 2·78; 95% CI: 0·90-8·57). CONCLUSION: Platelet concentrate transfusion before cranial decompressive surgery in patients with ICH complicating APT showed a low risk for cardio-cerebral thrombotic complications. However, the risk of rebleeding remains high, especially in patients with chronic ICH and those pretreated with clopidogrel.

Transfusion-transmitted CMV infection - current knowledge and future perspectives.

Transmission of human cytomegalovirus (CMV) via transfusion (TT-CMV) may still occur and remains a challenge in the treatment of immunocompromised CMV-seronegative patients, e.g. after stem cell transplantation, and for low birthweight infants. Measures to reduce the risk of TT-CMV have been evaluated in clinical studies, including leucocyte depletion of cellular blood products and/or the selection of CMV-IgG-negative donations. Studies in large blood donor cohorts indicate that donations from newly CMV-IgG-positive donors should bear the highest risk for transmitting CMV infections because they contain the highest levels of CMV-DNA, and early CMV antibodies cannot neutralise CMV. Based on this knowledge, rational strategies to reduce the residual risk of TT-CMV using leucoreduced blood products could be designed. However, there is a lack of evidence that CMV is still transmitted by transfusion of leucoreduced units. In low birthweight infants, most (if not all) CMV infections are caused by breast milk feeding or congenital transmission rather than by transfusion of leucoreduced blood products. For other patients at risk, no definitive data exist about the relative importance of alternative transmission routes of CMV compared to blood transfusion. As a result, only the conduction of well-designed studies addressing strategies to prevent TT-CMV and the thorough examination of presumed cases of TT-CMV will achieve guidance for the best transfusion regimen in patients at risk.

Implications of a switch to a 100% apheresis platelet supply for patients and for blood donors: a risk benefit analysis.

BACKGROUND: A 100% apheresis platelet supply is considered to increase transfusion safety by lowering donor exposures for transfusion recipients. We performed a risk benefit analysis to contrast the reduction of donor exposures and the risk of contaminated blood products in the nation-wide inventory with the donor risks associated with a switch to a 100% apheresis platelet supply in Germany. METHODS: Donor exposures and the number of contaminated blood products resulting from HIV-like, HBV-like, HCV-like pathogens and two theoretical agents with infection rates of 10 and 1000 in 100 000, respectively, were calculated for a 100% apheresis platelet supply in Germany based on the 2006-2012 hemovigilance reports. These numbers were compared with the current mixed platelet supply of pooled and apheresis platelets. Moreover, additional donation time and apheresis donor complications resulting from a 100% apheresis platelet supply were estimated. RESULTS: Per million total blood products (red cells, platelets, fresh frozen plasma), a 100% apheresis platelet supply would reduce donor exposures by 87 100 and the number of contaminated blood products ranging from 0·8 to 871·1. On the other hand, this requires additional 29 478 apheresis donations, 3·4 years additional donor time, and would be associated with 58 additional donor complications, respectively. CONCLUSIONS: A 100% apheresis platelet supply would reduce donor exposures and the number of contaminated blood products in the inventory, but would increase apheresis complications in donors. Potential risks for patients must be carefully weighed against the risks for donors, dependent on the specific pathogen scenario.

Tolerance of platelet concentrates treated with UVC-light only for pathogen reduction--a phase I clinical trial.

BACKGROUND: The THERAFLEX UV-Platelets pathogen reduction system for platelet concentrates (PCs) operates with ultraviolet C light (UVC; 254 nm) only without addition of photosensitizers. This phase I study evaluated safety and tolerability of autologous UVC-irradiated PCs in healthy volunteers. METHODS: Eleven volunteers underwent two single (series 1 and 2) and one double apheresis (series 3). PCs were treated with UVC, stored for 48 h and retransfused in a dose-escalation scheme: 12·5, 25% and 50% of a PC (series 1); one complete PC (series 2); two PCs (series 3). Platelet counts, fibrinogen, activated partial thromboplastin time, prothrombin time, D-dimer, standard haematology, temperature, heart rate, blood pressure and clinical chemistry parameters were measured. One- and 24-h corrected count increments were determined in series 2 and 3. Platelet-specific antibodies were assessed before and at the end of the study. RESULTS: Neither adverse reactions related to transfusions nor antibodies against UVC-treated platelets were observed. Corrected count increments did not differ between series 2 and 3. CONCLUSIONS: Repeated transfusions of autologous UVC-treated PCs were well tolerated and did not induce antibody responses in all volunteers studied. EudraCT No. 2010-023404-26.

Novel calibration tools and validation concepts for microarray-based platforms used in molecular diagnostics and food safety control.

Commercial platforms consisting of ready-to-use microarrays printed with target-specific DNA probes, a microarray scanner, and software for data analysis are available for different applications in medical diagnostics and food analysis, detecting, e.g., viral and bacteriological DNA sequences. The transfer of these tools from basic research to routine analysis, their broad acceptance in regulated areas, and their use in medical practice requires suitable calibration tools for regular control of instrument performance in addition to internal assay controls. Here, we present the development of a novel assay-adapted calibration slide for a commercialized DNA-based assay platform, consisting of precisely arranged fluorescent areas of various intensities obtained by incorporating different concentrations of a "green" dye and a "red" dye in a polymer matrix. These dyes present "Cy3" and "Cy5" analogues with improved photostability, chosen based upon their spectroscopic properties closely matching those of common labels for the green and red channel of microarray scanners. This simple tool allows to efficiently and regularly assess and control the performance of the microarray scanner provided with the biochip platform and to compare different scanners. It will be eventually used as fluorescence intensity scale for referencing of assays results and to enhance the overall comparability of diagnostic tests.

[Hemostatic management of patients undergoing ear-nose-throat-surgery]. / Perioperatives Hämostasemanagement bei HNO-Eingriffen.

Perioperative hemostatic management is increasingly important in Otolaryngology. This review summarizes the key elements of perioperative risk stratification, thromboprophylaxis, and therapies for bridging of antithrombotic treatment. It gives a practical advise based on the current literature with an emphasis for patients undergoing ear-nose-throat surgery.

Driving Rydberg-Rydberg transitions from a coplanar microwave waveguide.

The coherent interaction between ensembles of helium Rydberg atoms and microwave fields in the vicinity of a solid-state coplanar waveguide is reported. Rydberg-Rydberg transitions, at frequencies between 25 and 38 GHz, have been studied for states with principal quantum numbers in the range 30-35 by selective electric-field ionization. An experimental apparatus cooled to 100 K was used to reduce effects of blackbody radiation. Inhomogeneous, stray electric fields emanating from the surface of the waveguide have been characterized in frequency- and time-resolved measurements and coherence times of the Rydberg atoms on the order of 250 ns have been determined. These results represent a key element in the development of an experimental architecture to interface Rydberg atoms with solid-state devices.

Demonstration of a state-insensitive, compensated nanofiber trap.

We report the experimental realization of an optical trap that localizes single Cs atoms ≃215 nm from the surface of a dielectric nanofiber. By operating at magic wavelengths for pairs of counterpropagating red- and blue-detuned trapping beams, differential scalar light shifts are eliminated, and vector shifts are suppressed by ≈250. We thereby measure an absorption linewidth Γ/2π=5.7±0.1 MHz for the Cs 6S(1/2), F=4→6P(3/2), F'=5 transition, where Γ0/2π=5.2 MHz in free space. An optical depth d≃66 is observed, corresponding to an optical depth per atom d1≃0.08. These advances provide an important capability for the implementation of functional quantum optical networks and precision atomic spectroscopy near dielectric surfaces.

Selenium deficiency is associated with polyneuropathy in primary Sjögren's syndrome.

BACKGROUND: Selenium plays an important role in the regulation of the immune system. Selenium deficiency is associated with Hashimoto's thyroiditis, a common comorbidity in primary Sjögren's syndrome (pSS). Therefore we aimed to identify whether or not selenium deficiency is also associated with pSS. METHODS: 107 consecutive female patients with pSS and, as a control, 59 female patients with axial spondyloarthritis were recruited. Later, 11 male pSS patients, 5 of these suffering from polyneuropathy, and 15 male axSpA patients were additionally recruited in order to confirm the results from the female patients. All patients were consulted about their diet and food intolerances and their plasma selenium concentrations were analyzed. Current and previous extraglandular manifestations of pSS were recorded. Patients complaining of misperceptions and tingling paraesthesia underwent measurement of nerve conduction velocity. The proportion of patients and controls with a selenium deficiency was compared using Fisher's exact test. RESULTS: The proportion of female pSS patients with a low selenium concentration <0.63 µmol/L (22.4%) was significantly higher than of the controls (1.7%) (p < 0.001). Within the group of female patients with pSS, selenium deficiency was significantly associated with the presence of polyneuropathy (45.8% with vs 14.5% without polyneuropathy, p = 0.003) and particularly polyneuropathy with motor nerve involvement measured by nerve conduction velocity (41.7% with vs 10.8% without motor neuropathy, p = 0.001). The mean selenium concentrations of the 5 male pSS patients with polyneuropathy were significantly lower compared to the 6 pSS patients without polyneuropathy and to the 15 male axSpA controls. CONCLUSIONS: PSS and in particular its complication polyneuropathy is associated with selenium deficiency. Measurement of the selenium concentration in blood is advisable in patients with pSS and in particular in the subset of patients with polyneuropathy. Substitution of selenium may be a possible therapy of polyneuropathy associated with pSS.

[Heparin-induced thrombocytopenia]. / Heparininduzierte Thrombozytopenie.

Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction that carries an increased risk of thromboembolic complications. HIT is caused by platelet-activating antibodies directed against a complex of platelet factor 4 (PF4) and heparin. HIT typically manifests in the second week after initiation of heparin therapy with a platelet count reduction of more than 50% of the highest level after the start of heparin administration as well as thromboembolic events. The clinical probability can be calculated by the 4 T's score. The laboratory diagnosis of HIT is based on confirmation of PF4/heparin antibodies or on functional tests that provide evidence of heparin-dependent platelet-activating antibodies. A low 4 T's score and negative HIT test virtually rule out the presence of HIT. Patients with acute HIT require anticoagulation with a compatible anticoagulant in a therapeutic dose. The drugs currently available for this include the direct thrombin inhibitors argatroban, lepirudin, bivalirudin, and desirudin and the indirect factor Xa inhibitors danaparoid and fondaparinux.

Preoperative platelet transfusions to reverse antiplatelet therapy for urgent non-cardiac surgery: an observational cohort study.

Essentials An increasing number of patients requiring surgery receive antiplatelet therapy (APT). We analyzed 181 patients receiving presurgery platelet transfusions to reverse APT. No coronary thrombosis occurred after platelet transfusion. This justifies a prospective trial to test preoperative platelet transfusions to reverse APT. SUMMARY: Background Patients receiving antiplatelet therapy (APT) have an increased risk of perioperative bleeding and cardiac adverse events (CAE). Preoperative platelet transfusions may reduce the bleeding risk but may also increase the risk of CAE, particularly coronary thrombosis in patients after recent stent implantation. Objectives To analyze the incidence of perioperative CAE and bleeding in patients undergoing non-cardiac surgery using a standardized management of transfusing two platelet concentrates preoperatively and restart of APT within 24-72 h after surgery. Methods A cohort of consecutive patients on APT treated with two platelet concentrates before non-cardiac surgery between January 2012 and December 2014 was retrospectively identified. Patients were stratified by the risk of major adverse cardiac and cerebrovascular events (MACCE). The primary objective was the incidence of CAE (myocardial infarction, acute heart failure and cardiac troponine T increase). Secondary objectives were incidences of other thromboembolic events, bleedings, transfusions and mortality. Results Among 181 patients, 88 received aspirin, 21 clopidogrel and 72 dual APT. MACCE risk was high in 63, moderate in 103 and low in 15 patients; 67 had cardiac stents. Ten patients (5.5%; 95% CI, 3.0-9.9%) developed a CAE (three myocardial infarctions, four cardiac failures and three troponin T increases). None was caused by coronary thrombosis. Surgery-related bleeding occurred in 22 patients (12.2%; 95% CI, 8.2-17.7%), making 12 re-interventions necessary (6.6%; 95% CI, 3.8-11.2%). Conclusion Preoperative platelet transfusions and early restart of APT allowed urgent surgery and did not cause coronary thromboses, but non-thrombotic CAEs and re-bleeding occurred. Randomized trials are warranted to test platelet transfusion against other management strategies.

Corticotropin releasing factor-1 receptor antagonist, CP-154,526, blocks the expression of ethanol-induced behavioral sensitization in DBA/2J mice.

RATIONALE: Manipulation of glucocorticoid receptor signaling has been shown to alter the acquisition and expression of ethanol-induced locomotor sensitization in mice. It is unknown if other components of the hypothalamic-pituitary-adrenal (HPA)-axis modulate locomotor sensitization resulting from repeated ethanol administration. In the present investigation, we determined if pretreatment with an i.p. injection of CP-154,526, a selective corticotropin releasing factor (CRF) type-1 receptor antagonist, would block the acquisition and/or expression of ethanol-induced locomotor sensitization in male DBA/2J mice. METHODS: To assess the role of the CRF1 receptor in the acquisition of behavioral sensitization, mice were pretreated with an i.p. injection of CP-154,526 30 min before each of 10 sensitizing i.p. injections of ethanol. To determine the role of the CRF1 receptor in modulating the expression of ethanol-induced sensitization, mice that had previously been sensitized to the locomotor stimulant effects of ethanol were pretreated with CP-154,526 30 min before an i.p. injection of ethanol on the test day. In a third study, ethanol-naïve mice were pretreated with CP-154,526 30 min before an initial i.p. injection of ethanol to determine the combined effects of the CRF1 receptor antagonist and ethanol on locomotor activity. Blood ethanol concentrations were assessed at the termination of sensitization studies. RESULTS: Pretreatment with CP-154,526 blocked the expression of ethanol-induced locomotor sensitization in DBA/2J mice but did not prevent the acquisition of sensitization. The ability of CP-154,526 to block the expression of ethanol-induced locomotor sensitization was not attributable to alterations in blood ethanol levels or possible sedative effects produced by the combined administration of CP-154,526 and ethanol. CONCLUSIONS: These data provide novel evidence that CRF1 receptor signaling modulates the expression of ethanol-induced locomotor sensitization, and add to a growing literature suggesting a role for neurochemicals and hormones associated with the HPA-axis in behavioral sensitization resulting from repeated exposure to drugs of abuse.

Very low rates of Helicobacter pylori infection in organ transplant recipients presenting with peptic ulcer disease.

BACKGROUND: Leading causative factors of peptic ulcer disease (PUD) in the general population are infection with Helicobacter pylori (HP) and exposure to non-steroidal anti-inflammatory drugs (NSAID). We hypothesized that this may be different in transplant recipients given increased exposure of immunosuppressive and anti-microbial drugs. METHODS: We performed a retrospective single center analysis of all patients presenting with PUD to the endoscopy unit at a tertiary care and transplant center in Germany between 2006 and 2013. PUD was diagnosed by upper endoscopy. HP was identified by biopsy and histology. Organ transplant recipients were compared to non-transplant recipients (control group). RESULTS: 66 patients with PUD were identified in the study period. 12% (44/366) had previously received an organ transplant. 7% (3/44) of transplant recipients were found to be positive for HP compared to 25% (81/322) in the control group (p=0.007). Even when excluding patients taking proton-pump-inhibitors (PPI) from the analysis rates were similar with 30% (65/214) of the ulcers being HP positive in the control group compared to 14% (1/7) in transplant recipients (p=0.006). Furthermore, in the transplant recipient group rates of being in intensive care, concurrent PPI and concurrent antibiotic medication were significantly higher than in the control group. CONCLUSION: Organ transplant recipients with PUD have lower rates of Helicobacter pylori positivity compared to the general population.

Diagnosing peri-implant disease using the tongue as a 24/7 detector.

Our ability of screening broad communities for clinically asymptomatic diseases critically drives population health. Sensory chewing gums are presented targeting the tongue as 24/7 detector allowing diagnosis by "anyone, anywhere, anytime". The chewing gum contains peptide sensors consisting of a protease cleavable linker in between a bitter substance and a microparticle. Matrix metalloproteinases in the oral cavity, as upregulated in peri-implant disease, specifically target the protease cleavable linker while chewing the gum, thereby generating bitterness for detection by the tongue. The peptide sensors prove significant success in discriminating saliva collected from patients with peri-implant disease versus clinically asymptomatic volunteers. Superior outcome is demonstrated over commercially available protease-based tests in saliva. "Anyone, anywhere, anytime" diagnostics are within reach for oral inflammation. Expanding this platform technology to other diseases in the future features this diagnostic as a massive screening tool potentially maximizing impact on population health.Early detection of gum inflammation caused by dental implants helps prevent tissue damage. Here, the authors present a peptide sensor that generates a bitter taste when cleaved by proteases present in peri-implant disease, embed it in a chewing gum, and compare the probe to existing sensors using patient saliva.

Involvement of protein kinase A in ethanol-induced locomotor activity and sensitization.

RATIONALE: Mutant mice lacking the RIIbeta subunit of protein kinase A (regulatory subunit II beta(-/-)) show increased ethanol preference. Recent evidence suggests a relationship between heightened ethanol preference and susceptibility to ethanol-induced locomotor sensitization. It is currently unknown if protein kinase A signaling modulates the stimulant effects and/or behavioral sensitization caused by ethanol administration. To address this question, we examined the effects of repeated ethanol administration on locomotor activity RIIbeta(-/-) and littermate wild-type (RIIbeta(+/+)) mice on multiple genetic backgrounds. METHODS: Over three consecutive days, mice were given single i.p. saline injections and immediately placed in a locomotor activity apparatus to establish a composite baseline for locomotor activity. Next, mice maintained on a hybrid 129/SvEvxC57BL/6J or pure C57BL/6J genetic background were given 10 i.p. ethanol injections before being placed in the activity apparatus. Each ethanol injection was separated by 3-4 days. To determine if changes in behavior were specific to ethanol injection, naïve mice were tested following repeated daily saline injections. The effects of ethanol injection on locomotor behavior were also assessed using an alternate paradigm in which mice were given repeated ethanol injections in their home cage environment. RESULTS: Relative to RIIbeta(+/+) mice, RIIbeta(-/-) mice, regardless of genetic background, consistently showed significantly greater ethanol-induced locomotor activation. RIIbeta(-/-) mice also showed increased sensitivity to ethanol-induced locomotor sensitization resulting from repeated administration, an effect that was dependent on genetic background and testing paradigm. Increased locomotor activity by RIIbeta(-/-) mice was specific to ethanol injections, and was not related to altered blood ethanol levels. CONCLUSIONS: These data provide novel evidence implicating an influence of protein kinase A signaling on ethanol-induced locomotor activity and behavioral sensitization. The observation that RIIbeta(-/-) mice are more sensitive to the effects of repeated ethanol administration suggests that normal protein kinase A signaling limits, or is protective against, the stimulant effects of ethanol and the plastic alterations that underlie behavioral sensitization.

High ethanol consumption and low sensitivity to ethanol-induced sedation in protein kinase A-mutant mice.

Both in vitro and in vivo evidence indicate that cAMP-dependent protein kinase (PKA) mediates some of the acute and chronic cellular responses to alcohol. However, it is unclear whether PKA regulates voluntary alcohol consumption. We therefore studied alcohol consumption by mice that completely lack the regulatory IIbeta (RIIbeta) subunit of PKA as a result of targeted gene disruption. Here we report that RIIbeta knockout mice (RIIbeta-/-) showed incr eased consumption of solutions containing 6, 10, and 20% (v/v) ethanol when compared with wild-type mice (RIIbeta+/+). On the other hand, RIIbeta-/- mice showed normal consumption of solutions containing either sucrose or quinine. When compared with wild-type mice, the RIIbeta-/- mice were found to be less sensitive to the sedative effects of ethanol as measured by more rapid recovery from ethanol-induced sleep, even though plasma ethanol concentrations did not differ significantly from those of controls. Finally, both RIbeta- and catylatic subunit beta1-deficient mice showed normal voluntary consumption of ethanol, indicating that increased ethanol consumption is not a general characteristic associated with deletion of PKA subunits. These data demonstrate a role for the RIIbeta subunit of PKA in regulating voluntary consumption of alcohol and sensitivity to the intoxication effects that are produced by this drug.

Central leptin stimulates corticosterone secretion at the onset of the dark phase.

Leptin, a hormone secreted by adipose tissue in proportion to body adiposity, is proposed to be involved in the central nervous regulation of food intake and body weight. In addition, evidence is emerging that leptin regulates neuroendocrine and metabolic functions as well, presumably via its action in the central nervous system (CNS). To investigate this regulatory effect of leptin, we infused 3.5 microg of human leptin directly into the third cerebral ventricle (i3vt) of lean male Long-Evans rats, 90 min before the onset of their dark phase. Before and after infusion, blood samples were withdrawn through indwelling catheters for assessment of hormonal (plasma corticosterone, insulin, leptin), autonomic (plasma norepinephrine, epinephrine), and metabolic (plasma glucose) parameters. I3vt leptin caused an increase in plasma corticosterone and plasma leptin levels relative to the control condition. The effects of i3vt leptin on corticosterone secretion became particularly apparent after the onset of the dark phase. The results of the present study indicate that i3vt leptin stimulates the hypothalamo-pituitary-adrenal (HPA) axis, particularly when rats normally encounter their largest meals. These results are consistent with the possibility that high circulating leptin levels may underlie the increased activity of the HPA axis that is generally characteristic of human obesity and most animal models of obesity.