Glucose modulates food‐related salience coding of midbrain neurons in humans

Although early rat studies demonstrated that administration of glucose diminishes dopaminergic midbrain activity, evidence in humans has been lacking so far. In the present functional magnetic resonance imaging study, glucose was intravenously infused in healthy human male participants while seeing images depicting low‐caloric food (LC), high‐caloric food (HC), and non‐food (NF) during a food/NF discrimination task. Analysis of brain activation focused on the ventral tegmental area (VTA) as the origin of the mesolimbic system involved in salience coding. Under unmodulated fasting baseline conditions, VTA activation was greater during HC compared with LC food cues. Subsequent to infusion of glucose, this difference in VTA activation as a function of caloric load leveled off and even reversed. In a control group not receiving glucose, VTA activation during HC relative to LC cues remained stable throughout the course of the experiment. Similar treatment‐specific patterns of brain activation were observed for the hypothalamus. The present findings show for the first time in humans that glucose infusion modulates salience coding mediated by the VTA. Hum Brain Mapp 37:4376–4384, 2016. © 2016 Wiley Periodicals, Inc.     

Depression increasingly predicts mortality in the course of congestive heart failure

BACKGROUND: Congestive heart failure (CHF) is frequently associated with depression. However, the impact of depression on prognosis has not yet been sufficiently established. AIMS: To prospectively investigate the influence of depression on mortality in patients with CHF. METHODS: In 209 CHF patients depression was assessed by the Hospital Anxiety and Depression Scale (HADS-D). RESULTS: Compared to survivors (n=164), non-survivors (n=45) were characterized by a higher New York Heart Association (NYHA) functional class (2.8+/-0.7 vs. 2.5+/-0.6), and a lower left ventricular ejection fraction (LVEF) (18+/-8 vs. 23+/-10%) and peakVO(2) (13.1+/-4.5 vs. 15.4+/-5.2 ml/kg/min) at baseline. Furthermore, non-survivors had a higher depression score (7.5+/-4.0 vs. 6.1+/-4.3) (all P<0.05). After a mean follow-up of 24.8 months the depression score was identified as a significant indicator of mortality (P<0.01). In multivariate analysis the depression score predicted mortality independent from NYHA functional class, LVEF and peakVO(2). Combination of depression score, LVEF and peakVO(2) allowed for a better risk stratification than combination of LVEF and peakVO(2) alone. The risk ratio for mortality in patients with an elevated depression score (i.e. above the median) rose over time to 8.2 after 30 months (CI 2.62-25.84). CONCLUSIONS: The depression score predicts mortality independent of somatic parameters in CHF patients not treated for depression. Its prognostic power increases over time and should, thus, be accounted for in risk stratification and therapy.     

Extrahepatic bile ducts in healthy subjects,in patients with cholelithiasis,and in postcholecystectomy patients: A prospective ultrasonic study

To determine the average diameter and the upper normal limit of the common bile duct in healthy man, 830 blood donors were examined by ultrasound. The mean diameter was 2.5 ± 1.1 mm (SD) at the porta hepatis and 2.8 ± 1.2 mm (SD) at the widest point, the regression coefficient between both diameters being r = 0.84. None of the healthy subjects had a diameter larger than 7 mm at any site, and in 95% of all subjects the diameters were less than 4 mm at both sites of measurement. The diameters were significantly correlated with age (r = 0.16) and weight (r = 0.11), but not with sex, height, and body surface area. In 73 patients with cholelithiasis and in 55 patients after cholecystectomy, all of whom lacked clinical or laboratory signs of biliary obstruction, the average diameters at the porta hepatis were 3.8 ± 2.0 mm and 5.2 ± 2.3 mm, and at the widest point 4.8 ± 2.2 mm and 6.2 ± 2.5 mm, respectively. It is concluded that a common bile duct with any sonographic diameter larger than 4 mm should be followed closely and evaluated further with clinical examinations such as intravenous cholangiography unless cholecystectomy has been performed.     

Multicenter evaluation of a fully mechanized soluble transferrin receptor assay on the Hitachi and cobas integra analyzers. the determination of reference ranges.

Soluble transferrin receptor (sTfR) is reported to be a reliable marker for the diagnosis of iron deficiency, especially when iron metabolism is influenced by inflammatory disorders such as infection, chronic inflammation and cancer-related anemia. In the present multicenter study the analytical performance of a recently introduced, latex-enhanced immunoturbidimetric assay for the determination of soluble transferrin receptor (Tina quant [a] sTfR, Roche Diagnostics) on different fully mechanized analyzers such as Hitachi 917 and 911, and Cobas Integra 400 and 700 was evaluated. Within-run and between-run imprecision showed good results (CV<5% and <7%, respectively). The assay was found to be linear over a wide measuring range (0.4-35 mg/l). Endogenous substances did not interfere with the test results. Comparison of serum sTfR concentrations with those of heparinized plasma revealed good correlation (r>0.976). Method comparison with an existing fully mechanized method as well as with ELISA tests for sTfR showed very good correlation (r>0.987). Because of the lack of international standardization the results differed from each other up to 2.5-fold. The 95% of serum levels in healthy individuals ranged from 1.9 to 4.4 mg/l (n=427). However, the reference ranges should be reported in a sex-dependent manner, as 2.2-5.0 mg/l for men (n=211) and as 1.9-4.4 mg/l for premenopausal (n=216) and postmenopausal (n=45) women. The Tina quant [a] sTfR assay enables the precise, accurate, rapid and convenient determination of sTfR concentrations for routine clinical chemistry purposes.     

Myocardial fatty acid metabolism during acute cardiac allograft rejection

Fatty acids are promptly taken up, metabolised and eliminated by healthy cardiomyocytes. Cardiomyopathy, coronary heart disease and chronic rejection are known to be associated with an impaired fatty acid metabolism. It was the aim of this study to investigate fatty acid metabolism in a rat heart transplant model and to correlate scintigraphic findings with histological changes. After right-side nephrectomy of Lewis recipients Brown Norway cardiac allografts were anastomosed to the renal vessels. Animals were given no immunosuppression. The metabolism of carrier-free 17-¹²³ jodo-heptadecanoic acid (¹²³J-HDA) with a specific activity of >2×10¹⁷ Bq/ml was scintigraphically measured between days 1 and 11. An increase in the grade of rejection was observed over time. Fifty-six frames of 30 s duration each were recorded. For the region of interest (native heart, transplanted heart, left kidney) frames 10–56 were superimposed, time-activity curves generated and monoexponentially fitted. Furthermore, elimination half-life and intercepts were calculated. Following scintigraphic evaluation the animals were killed and graft as well as native hearts excised for histological examination. The uptake of the tracer identified severe grades of rejection. Elimination half-life of the tracer was twice as long from hearts with mild rejection and more than 14 times as long in severe rejection compared with no rejection. Elimination half-life and amplitude did not permit discrimination between grades 1, 2 and 3 a, but significantly decreased in groups 3 b and 4. This method therefore seems to be a valuable tool for the noninvasive detection of severe acute cardiac allograft rejection. Since fatty acid metabolism is clearly stress-dependent it remains to be seen whether this method allows detection of earlier rejection in loaded hearts.     

Comparison of the influence of volume-oriented training and high-intensity interval training on serum homocysteine and its cofactors in young, healthy swimmers.

BACKGROUND: Since homocysteine (Hcy) is a risk factor for cardiovascular and other diseases, it is important to know how exercise can modify it. Previous studies have suggested that endurance training influences Hcy. However, little is known about the effect of training intensity on Hcy. MATERIALS AND METHODS: We investigated Hcy, vitamin B12, vitamin B6, folate and methylmalonic acid (MMA) before and after 3 weeks of volume-oriented training (VOL) (30 km/week) and high-intensity interval training (HIT) (20 km/week) in 20 young swimmers (16 +/- 2 years). Afterward, the athletes completed 5 days of recovery training. RESULTS: The training induced a Hcy increase in HIT and VOL (6.47 +/- 0.95 micromol/l vs. 7.44 +/- 1.17 micromol/l and 7.33 +/- 1.92 micromol/l vs. 8.28 +/- 1.42 micromol/l, respectively) that persisted during the recovery period (8.02 +/- 1.69 micromol/l and 8.00 +/- 1.81 micromol/l, respectively). Vitamin B12 was unchanged after the training (539 +/- 166 ng/l vs. 556 +/- 192 ng/l and 480 +/- 144 ng/l vs. 491 +/- 124 ng/l, respectively) but decreased during the recovery period (459 +/- 134 ng/l and 451 +/- 116 ng/l, respectively). Folate showed an increase during the training (9.07 +/- 2.01 microg/l vs. 11.71 +/- 4.08 microg/l and 10.34 +/- 2.32 microg/l vs. 11.13 +/- 4.64 microg/l, respectively), which was reversible by the end of the recovery training (8.57 +/- 1.98 microg/l and 9.60 +/- 2.38 microg/l, respectively). Vitamin B6 and MMA did not change. For none of the measured parameters were there significant differences between HIT and VOL. CONCLUSION: Three weeks of strenuous swimming caused a prolonged Hcy increase, which was accompanied by changes in vitamin B12 and folate. The magnitude of these effects was not influenced by the training intensity.     

Elevated serum levels of epithelial cell apoptosis-specific cytokeratin 18 neoepitope m30 in critically ill patients

Apoptosis of the epithelium is deemed to play a pivotal role in the pathogenesis of sepsis. A neoepitope in cytokeratin 18 (CK18), termed M30 neoantigen, becomes available at an early caspase cleavage event during apoptosis of epithelium-derived cells and is not detectable in vital or necrotic epithelial cells. A monoclonal antibody, M30, specifically recognizes a fragment of CK18 cleaved at Asp396 (M30 neoantigen). We used an enzyme-linked immunosorbent assay (ELISA) to measure M30 antigen levels in the sera of 15 septic patients. Healthy humans and critical ill patients suffering from severe trauma served as controls. Mann-Whitney U test was used to calculate significance, and a P value of <0.01 was considered to be statistically significant. Serum levels of the CK18 neoepitope M30 were significantly increased in septic patients (236.88 +/- 47.4 U/L) versus trauma (97.2 +/- 17.1 U/L) and healthy controls (66.9 +/- 9.2 U/L) (P < 0.01 and P < 0.008, respectively). The increased serum level of the CK18 neoepitope in septic patients indicates a heightened apoptotic turnover in epithelial cells as compared with trauma patients and healthy controls. Interestingly, nonsurviving trauma patients exhibited a significant increase in the M30 neoantigen as compared with survivors and healthy controls (P < 0.003 and P < 0.002, respectively). The detection of CK18 neoepitope M30 in the serum might be a useful marker in tracing apoptotic epithelium in septic patients.     

Immunoadsorption as a rescue therapy in systemic lupus erythematosus: considerations on safety and efficacy

OBJECTIVE: In SLE, extracorporeal procedures aiming at reduction of immunoglobulin (Ig) and immune complexes (IC) are used as a rescue therapy. Plasma exchange (PE) has not been proven overall effective in SLE, and long-term treatment in particular has been associated with severe bacterial and viral infections. Immunoadsorption (IAS), in contrast, selectively removes Ig and IC and may thus be safer. We therefore investigated the rate of infections in SLE patients who were undergoing long-term IAS. METHODS: 16 SLE patients were treated with > or = 10 courses of IAS, and nine patients with highly active disease received pulse cyclophosphamide (IVCP) therapy in parallel. We retrospectively analysed the records of all these patients for the occurrence of infections. Patients receiving IAS therapy plus IVCP were compared with 25 patients with similarly active disease treated with standard IVCP therapy within the same observation period. Patients receiving IAS without additional IVCP were compared with patients with similarly moderate disease activity receiving neither IAS nor IVCP. RESULTS: No potentially life-threatening viral infection occurred in IAS-treated patients and episodes of herpes zoster were equally distributed. No severe infection was observed during IAS without concomittant cyclophosphamide. As expected, more patients with highly active disease receiving IVCP experienced infections than those with less active disease (16 of 34 [47%] vs. 2 of 22 [9%], p < 0.04). On comparing the two groups with highly active disease, infections were similar (IAS+IVCP: 3 of 9 patients [33%], IVCP only: 5 of 25 [20%]), but one patient receiving IAS+IVCP died of septicaemia. Disease activity significantly decreased in both groups treated with IAS. CONCLUSION: IAS has an acceptable safety profile with regard to severe infections and appears safe with regard to severe viral disease. Highly active disease and IVCP therapy increase the risk of severe infections in SLE.     

Akutintervention (Primär-PCI) im Rahmen des Essener Herzinfarktverbundes

In a German city (Essen, 490,000 people), a new network system for patients with ST elevation myocardial infarction (STEMI) was established in 2004. This included a so-called integrated care model (IV model) by participation of insurance companies. In a cooperative structure between invasive and noninvasive hospitals, general practitioners and cardiologists as well as emergency systems it could be realized, that every patient with STEMI will be treated by primary percutaneous coronary intervention (PCI) as soon as possible according to the current guidelines. The patient characteristics (age, gender, comorbidity, medication) were comparable to other trials and registries.The primary success rate was high (96.4%). The acute in-hospital results demonstrated a low mortality (7.6%). The time periods of delay were comparable to other registries. The symptom-to-balloon time was 239 min, the medical contact-to-balloon time 95 min, the door-to-balloon time 60 min, and the puncture-to-balloon time 18 min (median values).The STEMI network system in Essen demonstrates the possibility of modern therapy in patients with myocardial infarction (primary PCI) in a cooperative modality between all participants in the health-care system.