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Steep slope negative capacitance MOSFETs with HfYOx ferroelectric on FDSOI were experimentally demonstrated. An average SS of 30 mV/dec was achieved over 3 decades of drain current. The negative capacitance is believed to be a transient phenomenon because a strong polarization switching is needed for the steep slope. We found that the sub-thermal SS degrades with the cycling measurements, which is assumed to be caused by the trap charging in the ferroelectric oxide layer. The tradeoff between polarization and charge trapping is responsible for the subthreshold behavior of the device.

The subthreshold behavior of floating-gate MOSFETs connected with ferroelectric capacitors (FeCs) was investigated experimentally and theoretically. We found that the subthreshold swing (SS) decreases with decreasing ferroelectric capacitance (i.e., with the decreasing FeC area), in contrast to the voltage dividing effect of regular dielectric capacitors. The ferroelectric polarization switching counteracts the effect of voltage dividing by introducing an additional charge onto the floating gate, which improves the SS and leads to the observed SS dependence. The SS improvement caused by the polarization switching is different from the negative capacitance effect, which is helpful to further understand the ferroelectric transistor.

The reactor safety research of the Helmholtz Association is an integral part of the national provident research. It focuses on the safety of nuclear power plants in Germany and abroad as well as on safety aspects of internationally developed innovative reactor concepts. The research in the three involved Helmholtz centers Forschungszentrum Jülich, Helmholtz-Zentrum Dresden-Rossendorf and Karlsruhe Institute of Technology covers important areas of design basis and beyond design basis accidents. A unique combination of code and model development supported by own large-scale experiments ensures the active preservation of the reactor safety competences. The research that is embedded in a strong international co-operation will be continued after the completion of the national phase-out from the use of nuclear energy for electricity production in 2022.

To proceed the miniaturization of electronic devices new materials and new device designs are needed. A promising candidate for future gate dielectrics are ternary rare earth oxides which exhibit permittivities up to 40. Such amorphous oxides (e.g. GdScO3 and LaLuO3) were introduced in silicon based MOSFETs and showed good performance according electron and hole mobility or steep subthreshold slopes down to 65 mV/dec [1-3]. They are also used in SiGe or Ge based devices with the same good performance [4]. The ternary rare earth oxides GdScO3 (GSO) and LaLuO3 (LLO) are deposited epitaxial and amorphous by PLD on α-GaN deposited by MOVPE on sapphire (Al2O3) substrates c.f. Hardtdegen et al. [5] and Y2O3 deposited on Si(111) by molecular beam epitaxy analogous to the approach of Tarnawska et al. [6] at different temperatures. Depending on the growth temperatures and the substratethe amorphous, orthorhombic, hexagonal or cubic phase is formed. On GaN GSO grows hexagonal proofed by a Θ-2Θ scan exhibiting beside the peaks of GaN and sapphire two peaks corresponding to the reflections of (0002) and (0004) hexagonal GSO (Figure 1). Furthermore the hexagonal structure was confirmed by TEM and the lattice constants determined from the diffraction pattern are a=0.36 nm and c=0.58 nm. The layers were electrical characterized by CV measurements using Al pads as top electrode. CET plots were made with different layer thicknesses and the permittivity (k) was extracted from inverses of the slope of the fitted lines. The k of hexagonal GSO on GaN is 27. Furthermore GSO was grown on Y2O3. Depending on the thickness of Y2O3 GSO grows hexagonal on 1 nm layers and cubic on 7 nm layers. Hexagonal GSO and cubic GSO deposited on Y2O3 on Si exhibit a k of 24 and 14, respectively. LLO was grown on GaN and exhibits a hexagonal structure at a growth temperature of 600°C and cubic structure at 900 °C The transition temperature seems to be 860 °C at which the cubic and the hexagonal crystal structure both are present. The rocking curve displays a FWHM of 0.15° for the hexagonal and the cubic structure. The lattice constants measured by XRD of the hexagonal and the cubic crystal structure are a=0.375 nm, c=0.612 nm and a=1.086 nm, respectively. Also on the Y2O3 LLO grows epitaxial. At low temperatures the hexagonal structure and high temperatures the cubic structure forms, too. The lattice constants determined by XRD and TEM are a=0.375 nm and c=0.612 nm for the hexagonal structure and a=1.086 nm for the cubic structure. LLO exhibits a k of 26 and 23 for hexagonal LLO and cubic LLO on Y2O3on Si, respectively. Finally we will present our recent results about GSO and LLO deposited by PLD especially the crystal structure and the electrical properties. Therefore we will show the dependence of the material properties to the growth conditions. References 1. E. Durgun Özben, J.M.J.L., A. Nichau, M. Schnee, S. Lenk, A. Besmehn, K. K. Bourdelle, and J.S. Q. T. Zhao, and S. Mantl, Integration of LaLuO3( k∼30) as High- k Dielectric on Strained and Unstrained SOI MOSFETs With a Replacement Gate Process. IEEE ELECTRON DEVICE LETTERS,, 2011. 32: p. 15-17. 2. Lopes, J.M.J., et al., Amorphous ternary rare-earth gate oxides for future integration in MOSFETs. Microelectronic Engineering, 2009. 86(7-9): p. 1646-1649. 3. Roeckerath, M., et al., Gadolinium scandate as an alternative gate dielectric in field effect transistors on conventional and strained silicon. Applied Physics A, 2009. 94(3): p. 521-524. 4. Minamisawa, R.A., et al., High mobility strained Si0.5Ge0.5/SSOI short channel field effect transistors with TiN/GdScO3 gate stack. Microelectronic Engineering, 2011. 88(9): p. 2955-2958. 5. Hardtdegen, H., et al., Uniform III-nitride growth in single wafer horizontal MOVPE reactors. physica status solidi (a), 2005. 202(5): p. 744-748. 6. Tarnawska, L., et al., Single crystalline Sc2O3/Y2O3 heterostructures as novel engineered buffer approach for GaN integration on Si (111). Journal of Applied Physics, 2010. 108(6): p. 063502. Figure 1

Aims: The present study investigated the effect of different frequencies (three and five times a week) on electron transport chain and oxidative stress after 8 weeks of run training. Methods: Eighteen male mice (CF1, 30-35g) were distributed into the following groups (n=6): untrained (UT); trained three-time per week (T3) and trained five- time per week (T5). All training sessions were at the same intensity and duration (45min/day) in a treadmill for small animals. Forty-eight hours after the last training session, the animals were killed by decapitation and quadriceps (red portion) was removed and stored at -70ºC. Succinate dehydrogenase (SDH), complexes I, II, II-III, IV and hydroperoxides were measured. Results: Training sessions for five times per week were more effective in increasing the mitochondrial respiratory chain enzyme activities (SDH, complexes I, II, II-III, IV) as well as in decreasing the formation hydroperoxides than sessions performed for three times training per week (p

Steep slope negative capacitance MOSFETs with HfYOx ferroelectric on FDSOI were experimentally demonstrated. An average SS of 30 mV/dec was achieved over 3 decades of drain current. We found that the subthermal SS degrades with the sweeping numbers, which is assumed to be caused by the traps in the ferroelectric oxide layer.

Age-associated decline in skeletal muscle mass and strength is associated with oxidative stress and Ca(2+) homeostasis disturbance. Exercise should be considered a viable modality to combat aging of skeletal muscle. This study aimed to investigate whether continuous and fractionated training could be useful tools to attenuate oxidative damage and retain calcium-handling proteins. We conducted the study using 24-month-old male Wistar rats, divided into control, continuous, and fractionated groups. Animals ran at 13 m min(-1) for five consecutive days (except weekends) for 6 weeks, for a total period of 42 days. Each session comprised 45 min of exercise, either continuous or divided into three daily sessions of 15 min each. Metabolic and oxidative stress markers, protein levels of mitochondrial transcription factors, and calcium-handling proteins were analyzed. Continuous exercise resulted in reduced ROS production as well as showed a decrease in TBARS levels and carbonyl content. On the other hand, fractionated training increased the antioxidant enzyme activities. The ryanodine receptor and phospholamban protein were regulated by continuous training while sodium calcium exchange protein was increased by the fractionated training. These data suggest that intracellular Ca(2+) can be modulated by various training stimuli. In addition, the modulation of oxidative stress by continuous and fractionated training may play an important regulatory role in the muscular contraction mechanism of aged rats, due to changes in calcium metabolism.

Patient: Female, 13 Final Diagnosis: Multiorgan failure as a sequelae of advanced liver disease Symptoms: A lysosomal enzyme defect • abnormal bilirubin level • abnormal lipid profile • cardiovascular complications • Child-Pugh A/B • cholestasis and/or gallbladder dysfunction • chronic and florid fibroplastic cholecystitis • frequent diarrhoea • greatly elevated hepatic content of cholesteryl esters • hepatic fibrosis • hepatomegaly • hepatosplenomegaly with thrombocytopenia • increasing jaundice • increasing transaminases • Lab-MELD 14 cirrhosis • malabsorption • oesophageal varices (Grade III) • orange-yellow liver • pressure in the right epigastrium • steatorrhoea • symptomatic gallstones • Vitamin D deficiency Medication: — Clinical Procedure: — Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: Cholesteryl ester storage disease (CESD), also known as lysosomal acid lipase deficiency (LAL-D), is a rare autosomal-recessive inheritable lysosomal storage disease. Since 2015, a causal treatment with sebelipase alfa, which replaces the missing LAL enzyme, has been approved. We report a fatal course of LAL-D in a female patient. Case Report: In 1979, CESD was first diagnosed in a 13-year-old female with marked hepatomegaly. At that time, no specific treatment for CESD was available and the spontaneous course of the disease had to be awaited. In 2013, a laparoscopic cholecystectomy for symptomatic gallstones was performed. The patient’s CESD had caused a Child-Pugh A/B and Lab-MELD 14 cirrhosis with esophageal varices (grade III), a solitary fundal varix, as well as hepatosplenomegaly with thrombocytopenia. In 2016, the patient was admitted with compensated cirrhosis and splenomegaly for a ligature of esophageal varices which was complicated by vomiting of blood followed by severe coagulopathy and hemorrhagic shock. The dried blood test showed reduced acid lipase (0.03 nmol/spot*3 hours; reference range 0.2–2) and beta-galactosidase (0.08 nmol/spot*21 hours; reference range 0.5–3.2). Then 15 days after the esophageal varices bleed, the patient died due to multiorgan failure as a sequelae of advanced liver disease. Conclusions: LAL-D should be included in the differential diagnosis of lipid metabolism disorder, hepatomegaly, and non-alcoholic fatty liver disease with fibrosis or cirrhosis. Causal treatment with sebelipase alfa should be introduced even in patients who have LAL-D and many years of clinically mild symptoms of this disease to prevent the serious sequelae of cirrhosis or cardiovascular complications.

The purpose of the present study was to investigate the effects of taurine supplementation on muscle performance, oxidative stress, and inflammation response after eccentric exercise (EE) in males. Twenty-one participants (mean age, 21 ± 6 years; weight, 78.2 ± 5 kg; height, 176 ± 7 cm) were selected and randomly divided into two groups: placebo (n = 10) and taurine (n = 11). Fourteen days after starting supplementation, subjects performed EE (3 sets until exhaustion, with EE of the elbow flexors on the Scott bench, 80% 1 repetition maximum (RM)). Blood samples were collected and muscle performance was measured on days 1, 14, 16, 18, and 21 after starting the supplements. Then, performance, muscle damage, oxidative stress, and inflammatory markers were analyzed. The taurine supplementation resulted in increased strength levels and thiol total content and decreased muscle soreness, lactate dehydrogenase level, creatine kinase activity, and oxidative damage (xylenol and protein carbonyl). Antioxidant enzymes (superoxide dismutase, catalase, and gluthatione peroxidase) and inflammatory markers (tumor necrosis factor, interleukin-1β (IL-1β), and interleukin-10 (IL-10)) were not altered during the recovery period compared with the placebo group. The results suggest that taurine supplementation represents an important factor in improving performance and decreasing muscle damage and oxidative stress but does not decrease the inflammatory response after EE.

III–V nitrides are interesting materials for a very wide variety of electronic and optoelectronic devices. In this study, their interaction with GdScO3 (GSO), a ternary rare earth oxide, is investigated for MOS applications.We compare pulsed laser deposited amorphous and crystalline epitaxial GdScO3 in terms of their band alignment with the underlying GaN substrate and the resulting electrical characteristics of the MOS stack. The crystal structure of GdScO3 and GaN is investigated by means of x-ray diffraction, showing that crystalline oxide is growing epitaxially on GaN. X-ray photoelectron spectroscopy analysis shows a staggered band alignment with a GdScO3-GaN valence band offset of 3.6–3.7 eV, which is reflected in a very asymmetric current-voltage behaviour of the MOS capacitors: breakdown at positive bias, significantly earlier for the crystalline oxide (around 5MV/cm) compared to the amorphous oxide (around 8MV/cm), and no breakdown up to a field of 14 MV/cm at negative bias. Transmission electron microscopy images show a crystalline, two-atom thick interface layer between GaN and both crystalline and amorphous GdScO3, which is thought to be an electron barrier between GSO and GaN and a possible source of the staggered band alignment. The electrical behaviour can be exploited for asymmetric nano-electronic devices. Published by AIP Publishing.

This study analyzes oxidative stress in skeletal muscle using different resisted training protocols. We hypothesize that different types of training produce different specifics. To test our hypothesis, we defined 3 resistance training protocols and investigated the respective biochemical responses in muscle. Twenty-four male Wistar rats were distributed in 4 groups: untrained (UT), muscular resistance training (RT), hypertrophy training (HT), and strength training (ST). After 12 weeks of training on alternate days, the red portion of the brachioradialis was removed and the following parameters were assessed: lactate and glycogen content, superoxide production, antioxidant enzyme content, and activities (superoxide dismutase, SOD; catalase, CAT; GPx, glutathione peroxidase). Thiobarbituric acid-reactive substances (TBARS), carbonyl, and thiol groups were also measured. Results showed increased superoxide production (UT = 5.348 ± 0.889; RT = 5.117 ± 0,651; HT = 8.412 ± 0.431; ST = 6.354 ± 0.552), SOD (UT = 0.078 ± 0.0163; RT = 0.101 ± 0.013; HT = 0.533 ± 0.109; ST = 0.388 ± 0.058), GPx (UT = 0.290 ± 0.023; RT = 0.348 ± 0.014; HT = 0.529 ± 0.049; ST = 0.384 ± 0.038) activities, and content of GPx (HT = 3.8 times; ST = 3.0 times) compared with the UT group. CAT activity was lower (UT = 3.966 ± 0.670; RT = 3.474 ± 0.583; HT = 2.276 ± 0.302; ST = 2.028 ± 0.471) in HT and ST groups. Oxidative damage was observed in the HT group (TBARS = 0.082 ± 0.009; carbonyl = 0.73 ± 0.053; thiol = 12.78 ± 0.917) compared with the UT group. These findings indicate that HT causes an imbalance in oxidative parameters in favor of pro-oxidants, causing oxidative stress in skeletal muscle.

Aim Physical exercise is important in the prevention and treatment of cardiovascular diseases. Nevertheless, controversy remains around type and intensity of effort required for significant biochemical protective changes. This study investigates two exercise protocols on ventricular oxidative parameters in rats post-infarction. Main methods Thirty-six 2-month-old male Wistar rats were divided in two groups (n = 18): Sham and acute myocardial infarction (AMI) conducted by blocking the coronary artery. Thirty days after AMI, animals were divided in 6 subgroups (n = 6): sham, sham + continuous training (60 min), sham + interval training, AMI, AMI + continuous training, and AMI + interval training. Training was conducted in water (30–32 °C) 5 times a week for 6 weeks. Animals were sacrificed 48 h after the last exercise routine. Left ventricles were used for oxidative stress analyses (antioxidant enzyme activity and level, oxidative damage) and HIF1α and cit c oxidase expression. Key findings After AMI, both exercise models decreased superoxide levels significantly. Training routines did not alter SOD expression and activity, though CAT expression increased with continuous training and GPX level diminished in both training groups, which coincided with the increase in GPX activity. Lipid damage decreased only in the continuous training group, while protein damage decreased only in the interval training group. Cytochrome C increased in both groups, while HIF-1 α dropped significantly after both exercise protocols. Significance Significant improvement occurred in myocardium redox status in rats challenged with AMI after different training routines. However, continuous training seems to be more efficient in improving the parameters analyzed.

Background: Mesalamine suppositories are first-line therapy in active ulcerative proctitis; the standard regime still recommends multiple doses per day. The primary objective of this study was to show the noninferiority of once-daily administration of a novel 1 g mesalamine suppository versus thrice-daily administration of the 0.5 g mesalamine suppository. Methods: This was a single-blind (investigator-blinded), randomized, multicenter, comparative, Phase III clinical trial. Patients with mild to moderately active ulcerative proctitis inserted either one mesalamine 1 g suppository at bedtime or one mesalamine 0.5 g suppository thrice daily over a 6-week period. The primary endpoint was rate of remission (Disease Activity Index below 4). Results: In all, 354 patients were evaluable for safety and per-protocol analysis. The new regimen demonstrated noninferiority: The percentage of patients with remission was 87.9% for the once-daily 1 g mesalamine suppository and 90.7% for the thrice-daily 0.5 g mesalamine suppository. Each regimen resulted in prompt cessation of clinical symptoms (e.g., median time to ≤3 stools per day (all without blood): 5 days in the 1 g mesalamine once-daily and 7 days in the 0.5 g mesalamine thrice-daily group). Patients preferred applying suppositories once a day. Conclusions: In active ulcerative proctitis the once-daily administration of a 1 g mesalamine suppository is as effective and safe, yet considerably more convenient, than the standard thrice-daily administration of a 0.5 g mesalamine suppository. (Inflamm Bowel Dis 2010)

To analyze the dosimetric and clinical benefit of a forward planned technique to optimize dose distribution in whole-breast irradation (WBI) using additional partial-volume segments (PVSeg).: In two separate treatment periods, 265 breast cancer patients received tangential-field WBI and were retrospectively analyzed. Between 02/2004 and 03/2006, 96 patients were treated with one to two additional low-weighted PVSeg to reduce dose peaks within the target volume. 169 patients treated between 01/2000 and 12/2001 before implementation of this PVSeg technique served as comparison group. Total dose was 50-50.4 Gy (single dose, 1.8-2 Gy). The planning target volume (PTV) receiving at least 95%, 105% and 110% of the reference dose (V(95-110%)) and frequency of moist skin desquamation during radiotherapy were compared uni- and multivariately with patient- and treatment-related variables.: The mean PTV was 1,144 ml (range, 235-2,365 ml). Moist skin desquamations developed in 16 patients (17%) with PVSeg compared to 30 patients (18%) without PVSeg (p = 0.482). In breast volumes1,100 ml, the corresponding figures were 19% versus 29% (p = 0.133). V(105%) was significantly reduced by the use of PVSeg (82 +/- 51 ml vs. 143 +/- 129 ml; p0.0001). In univariate analysis, the following variables had significant influence on the development of moist skin desquamation: V(95%) (p0.0001), V(105%) (p0.001), V(110%) (p = 0.012) adjuvant chemotherapy (p = 0.02), and single dose (p = 0.009). In multivariate analysis, only V(95%) (p = 0.002) remained significant.: The use of PVSeg in WBI reduced dose peaks within the PTV while breast volumes1,100 ml benefited most. V(95%) was strongly correlated to the risk of developing moist skin desquamations.

UNLABELLED Previous studies have shown high inter- and intraindividual variation coefficients (Vkinter; Vkintra) of the gastric emptying time t(end) determined by sonographical antrum planimetry. PURPOSE Are there new parameters reflecting the functional process of gastric emptying? METHOD Gastric emptying of 300 ml water was studied in 20 healthy volunteers by sonographical antrum planimetry. 10 volunteers were examined a second time on another day. RESULTS High variation coefficients Vkinter (42%) and Vkintra (31%) could be demonstrated. Moreover, a correlation of r = +0.922 between tend and the maximal percentual increase of the antral area was evident. This relation is introduced as the functional-emptying-line (FEL). CONCLUSION Using the functional aspects of FEL, gastric emptying can be studied sonographically under functional aspects.

History and clinical findings A 18-year-old girl suffered from chronic active ulcerative colitis for ten years with growth retardation, primary amenorrhoea and osteopenia, so that total colectomy had been discussed as a possible treatment option. However, clinical remission was reached using a medication with budesonide (9 mg), mesalazine (3 g) and azathioprine (100 mg) when a painful ulcer occurred at the right lower leg. Investigations The clinical examination revealed an ulcer of 7 cm diameter with a red-bluish margin at the right lower leg. The typical clinical features led to the diagnosis of pyoderma gangrenosum. Treatment and course High doses of orally administered prednisolone induced the healing of the pyoderma gangrenosum within 2 months. After another 2 months systemic steroids were discontinued. Further laboratory tests confirmed secondary adrenal and ovarian failure (negative CRH-GnRH-test). Change of drug therapy to hydrocortisone (25 mg) in combination with mesalazine (3 g) and azathioprine (100 mg) improved the clinical course. Hydrocortisone was gradually reduced until CRH-GnRH-response returned to normal. Conclusion Drug therapy with azathioprine can be regarded as a treatment option in pediatric patients with chronic active inflammatory bowel disease. It can be concluded from this case report that faced with controversial therapeutic options in adolescent patients the decision mainly depends on the clinical experience of the physician than on the results of controlled clinical trials.

An investigation was conducted on 21 patients (16 men and five women; mean age 48.2 [34-67] years) with cirrhosis of the liver of various aetiologies to determine whether molsidomine, which selectively reduces pre-load with-out the development of tolerance, effects portal and cardiac haemodynamics in liver cirrhosis and portal hypertension. Intravenous injection of 2 mg molsidomine reduced the hepatic vein closing pressure after 30 min by 8% (P less than 0.05) and the hepatic vein closing pressure gradient by 13.4% (P less than 0.002). The cardiac output fell by 5.8% (P less than 0.02) and the mean systemic arterial pressure by 4.2% (P less than 0.003). The reduction in hepatic venous closing pressure gradient did not correlate with the fall in cardiac output and mean arterial pressure. In 15 of 21 patients the hepatic venous pressure fell, but in six patients (28.6%) the pressure was not reduced (non-responders). The latter failure of response was associated with marked ascites, significant functional liver decompensation and alcoholic liver cirrhosis. Preliminary long-term observations with molsidomine point to a reduction in portal pressure by as much as 40%. This suggests that the drug is suitable for preventing bleeding from oesophageal varices.

The acute effect of metoclopramide on oesophageal motility was investigated prospectively in 33 consecutive patients (20 men and 13 women; mean age 60.5 +/- 12.6 years) with type I (n = 8) or type II (n = 25) diabetes. 15 patients had a peripheral sensory-motor polyneuropathy only and three just an autonomic cardial neuropathy. Both lesions were present in ten, none in five. No patient had oesophago-gastroduodenal lesions. Sphincter pressure, relaxation time, contraction amplitude and propulsion velocity of bolus-induced oesophageal peristalsis were measured manometrically after intravenous administration of 10 mg metoclopramide. Resting pressure in the lower oesophageal sphincter rose significantly by 26.7%, contraction amplitude in the tubular portion of the oesophagus by more than 30%, and propulsion velocity by more than 20% (P for each < 0.05). At the same time the amount of segmental and aperistaltic oesophageal contractions regressed significantly. The effect of metoclopramide was demonstrated regardless of the type of diabetes, duration of diabetes and any manifestation of autonomic cardial or peripheral sensory-motor neuropathy.

In 124 patients with Crohn's disease (69 women, 55 men; mean age 33.7 [11-66] years) and 53 with ulcerative colitis (30 women, 23 men; mean age 36.2 [19-74] years) the incidence of lactose intolerance, as measured by the H2 breath test and blood sugar concentration, was determined prospectively. To exclude abnormal bacterial colonization of the small intestine or rapid small-intestine transit after partial resection of the small intestine as a cause of lactose intolerance, the oro-caecal transit time for lactulose (H2 breath test) was measured. While 21 of 124 patients with Crohn's disease (16.9%) had the expected incidence of lactose intolerance, this was present in only 2 of 53 patients with ulcerative colitis (3.8%; P < 0.05). The lactose intolerance was independent of the site of any inflammatory changes, disease activity and extent of small-intestine resection. Oro-caecal transit time for lactose was similar for all patients. There was no lactose intolerance in two patients with abnormal small-intestinal bacterial colonization.--Because of their considerable diagnostic and prognostic significance, tests for lactose intolerance should be performed routinely in all cases of Crohn's disease or ulcerative colitis.

In the very unlikely case of a core melt accident in a nuclear power plant, the reactor pressure vessel could fail and corium melt could be released into the reactor cavity. Subsequent processes could result in a threat of the containment integrity. As a counter-measure the implementation of a core-catcher device in nuclear power plants is envisaged. Such a core-catcher concept has been developed at the Forschungszentrum Karlsruhe (FZK, Germany) within the COMET project. It is based on water injection into the melt layer from the bottom, yielding rapid fragmentation of the corium, porosity formation and thus coolability. Detailed large scale experiments with sustained heating of melts have highlighted the sequences of flooding and cooling and have been used to optimise the COMET concept. The open porosities and large surfaces that are generated during melt solidification form a porous permeable structure that is permanently filled with the evaporating coolant water and thus allows efficient short-term and long-term removal of the decay heat. Two variants of the bottom flooding concept have been developed and seem technically mature for reactor application. Corium layers up to 0.5 m high are safely arrested and cooled by water supply with 0.2 bar overpressure. The conceptual and experimental work at FZK is accompanied by theoretical investigations at IKE, University of Stuttgart. These investigations address porosity formation as well as quenching and long-term coolability of layers with resulting porosities. The aim of the theoretical work is to get a better understanding of the underlying processes of porosity formation in order to generally support the applicability of the concept for real conditions and to allow checks and optimisation for various conditions. A model for porosity formation is presented, which assumes that this process is essentially determined by strong local pressure buildup from strong evaporation due to water injection from below and the restriction of steam removal by friction in the melt. The effect of key parameters is investigated and compared to experimental results. Agreement about the influence and importance of these parameters as well as essential quantitative effects is found.

Background Collagenous colitis is clinically characterized by watery diarrhoea and can histologically be diagnosed by a thickening of the subepithelial collagen layer and an inflammatory infiltrate in the lamina propria. So far, the pathogenesis of collagenous colitis and the role of luminal factors remain unclear. Methods This clinical pilot investigation was conducted with an open-label design to monitor the clinical effects of EcN on stool frequency and stool consistency in 14 patients (11 female, 3male; age: 58.1 +/- 9.6 years). Due to the open-label protocol EcN was administered at different doses (1 - 6 capsules/day containing 2.5 - 25 x 10 (9) viable bacteria each). Except for two patients who discontinued treatment, therapy duration was at least 4 weeks. Results The results indicate a marked clinical response to the oral administration of EcN with a reduction of the stool frequency > or = 50 % in 9/14 (64 %) patients. Stool frequency clearly (p = 0.034) decreased from 7.6 +/- 4.8/day to 3.7 +/- 5.8/day at the end of therapy (between 4 and 18 weeks). Moreover, stool consistency changed in 7/14 patients from watery or slimy to soft (6 pts) and normal (1 pt), respectively. Conclusion With respect to the preliminary data from this trial, the probiotic E. coli strain Nissle 1917 (EcN) seems to be of therapeutic clinical benefit in collagenous colitis. This may be explained with the recently shown antagonistic effect of EcN against Yersinia species, since a relevant number of patients suffering from collagenous colitis showed positive titres of serum IgG and IgA antibodies against Yersinia species. Further studies on the effects of EcN on mucosal collagen metabolism and long-term follow-up are warranted.

Nuclear factor kappa-B (NFkappaB) plays a crucial role in diseases associated with dysregulated immune response. NFkappaB inhibitor alpha downregulates the activity of NFkappaB.To evaluate the contribution of the NFkappaB inhibitor alpha gene in Crohn's disease single nucleotide polymorphisms in the 3'-UTR and at position -420 in the promoter were studied in 259 patients with Crohn's disease genotyped for the variations of the CARD15 gene in comparison to 441 healthy controls. Additionally we screened the coding region of the NFkappaB inhibitor alpha gene for polymorphisms by SSCP analysis.In comparison to controls the A allele and the AA genotype frequencies of the single nucleotide polymorphisms in the 3'-UTR were significantly increased only in Crohn's disease patients without a variation in the CARD15 gene. Similarly, the difference between patients harboring no predisposing CARD15 alleles and patients harboring such a variation was significant.The findings indicate that the phenotype Crohn's disease is to be substructured with respect to genetic susceptibility.

Anamnese und klinischer Befund: Ein 61-jahriger Patient stellte sich mit diffusen Oberbauchbeschwerden und den Symptomen einer progredienten Belastungsdyspnoe stationar vor. Klinisch imponierten die Zeichen einer Rechtsherzbelastung und eine ausgepragte Kyphoskoliose. Therapie und Verlauf: Mittels Einschwemmkatheteruntersuchung konnte eine pulmonale Hypertonie mit Ausschluss einer kardialen Genese diagnostiziert werden. Eine obstruktive Atemwegserkrankung und eine Lungenembolie wurden durch eine Lungenfunktionsanalyse bzw. durch eine Spiralcomputertomographie des Thorax ausgeschlossen. Die Kyphoskoliose blieb somit als alleinige Ursache der pulmonalen Hypertonie bestehen. Da der Patient einer nichtinvasiven Beatmung als Therapie der Wahl ablehnend gegenuberstand, konnte alternativ unter einer medikamentosen Therapie mit Calciumantagonisten und ACE-Hemmern und nachfolgender Sauerstofftherapie der pulmonalvaskulare Widerstand effektiv gesenkt werden (746 vs. 332 dyn*s*cm−5). Schlussfolgerung: Eine Kyphoskoliose kann eine betrachtliche pulmonalarterielle Widerstandserhohung hervorrufen. Diese lasst sich durch eine medikamentose Therapie und eine Sauerstofftherapie effektiv senken.

Collagenous colitis is an idiopathic microscopic colitis characterized by chronic watery diarrhea, a typical subepithelial collagen layer, and lymphoplasmacellular infiltration. We investigated the effect of budesonide on symptoms and histology in patients with collagenous colitis in a randomized, double-blind, placebo-controlled multicenter trial.Patients with chronic diarrhea and histologically proven collagenous colitis were randomized to receive either oral budesonide (Entocort capsules; AstraZeneca, Sodertalje, Sweden) 9 mg/day for 6 weeks or placebo. Complete colonoscopy was performed before and after treatment. Histopathology was assessed by a single pathologist blinded to the patients' treatment. Clinical symptoms were assessed by standardized questionnaires.Fifty-one patients were randomized; 45 patients were available for per protocol analysis. The rate of clinical remission was significantly higher (P0.001) in the budesonide group than in the placebo group (per protocol 86.9% vs. 13.6%, respectively; intention-to-treat 76.9% vs. 12.0%, respectively). Histologic improvement was observed in 14 patients of the budesonide group (60.9%) and in 1 patient of the placebo group (4.5%; P0.001). Two patients in the budesonide group (7.7%) and 1 patient in the placebo group (4.0%) discontinued treatment prematurely because of side effects.Oral budesonide (Entocort capsules) is an effective and safe treatment modality for patients with collagenous colitis. Long-term follow-up of these patients is necessary to investigate whether clinical and histologic remission is sustained.

Doped HfO2 has become a promising candidate for non-volatile memory devices since it can beeasily integrated into existing CMOS technology. Many dopants like Y, Gd, and Sr have beeninvestigated for the stabilization of ferroelectric HfO2. Here, we report the fabrication of capacitorscomprising ferroelectric HfO2 metal-insulator-metal structures with TiN bottom and top electrodesusing the dopant Lu. Amorphous 5% Lu doped HfO2 was deposited by pulsed laser deposition andafterwards annealed to achieve the ferroelectric, orthorhombic phase (space group Pbc21). Thepolarization of the layers was confirmed by capacitance-voltage, polarization-voltage, and currentvoltagemeasurements. Depending on the anneal temperature, the remanent polarization changesand the initial state of the oxide varies. The layer exhibits initially a pinched hysteresis up to anannealing temperature of 600 °C and an unpinched hysteresis at 700 °C. The maximum polarizationis about 11 lC/cm2 which is measured after 104 cycles and stable up to 106 cycles. The influence ofthe layer thickness on the oxide properties is investigated for 10–40 nm thick HfLuO; however, athickness dependence of the ferroelectric properties is not observed. Published by AIP Publishing.

Studies have confirmed an increased prevalence for developing microscopic colitis in patients with sprue, and vice versa (1– 3). For collagenous colitis, the reported prevalence of sprue is 3.46% (1). In patients with confirmed sprue who continue to have symptoms in spite of adherence to their restriction diet, collagenous colitis and lymphocytic colitis should always be excluded.

In the context of severe accidents, large R&D efforts throughout the world are currently directed towards ex-vessel corium behaviour. Among the mitigation means which can be envisaged, the European industries and utilities are considering the implementation of a core-catcher outside the reactor pressure vessel in order to prevent basemat erosion and to stabilize and control the corium within the containment. The CSC project focused on two key phenomena for external core-catcher efficiency, reliability and safety: spreading and coolability. An experimental programme, covering different scenarios and including both simulant and real materials provided a lot of results which now constitute a large database and which enabled the qualification of computer codes.

Hintergrund: Die primar sklerosierende Cholangitis und die Sarkoidose sind Erkrankungen, die nur selten in Kombination miteinander auftreten. Fallbeschreibung: Wir berichten den Fall einer 42-jahrigen Frau mit einer primar sklerosierenden Cholangitis, die endoskopisch-cholangiographisch, histologisch sowie durch den Nachweis antineutrophiler zytoplasmatischer Antikorper mit perinuklearem Fluoreszenzmuster diagnostiziert wurde. Radiologisch sowie histologisch fand sich eine pulmonale sowie hepatische Manifestation einer Sarkoidose, zudem fielen eine Alopecia areata sowie eine Choledocholithiasis auf. Schlussfolgerung: Die vorliegende Kasuistik gibt einen Uberblick uber die in der Literatur beschriebenen Falle, erortert die Theorien zur bisherigen ungeklarten Atiologie beider Erkrankungen und berichtet uber den derzeitigen Stand der Diagnostik und Therapiemoglichkeiten der Erkrankungen.

UNLABELLED Numerous extraintestinal manifestations in various organ systems have been reported to be associated with inflammatory bowel disease (IBD). Aim of the present paper was to evaluate the frequency of cutaneous manifestations in Crohn's disease (CD) and ulcerative colitis (UC) with respect to their location, the activity and location of the underlying disease, the treatment options and the time to remission. METHODS The medical records of 1043 inpatients with CD and UC were screened retrospectively for extraintestinal symptoms with special regard to cutaneous manifestations. RESULTS The prevalence of cutaneous manifestations in IBD was 22/1043 (2.1%; 18 women, 4 men; age: 31.41 +/- 9.9 [21-51] yrs.). In 15/22 patients (68.2%) the cutaneous manifestations were associated with CD, in 7/22 patients (31.8%) UC was confirmed. In 6/22 patients (27.3%) pyoderma gangrenosum (PG) was diagnosed, in 16/22 patients (72.7%) erythema nodosum (EN). EN and PG predominately occurred at the lower legs: in 68.1% the tibia was the main affection site. Other locations like breast or anus were rare. In 16/22 patients (72.7%) an acute phase of the underlying disease was evident, in 6/22 patients (27.3%) CD or UC were in remission. In patients with CD a colonic involvement was found in 86.7%. Arthritis was the most frequent coexisting extraintestinal manifestation in CD (53.3%) and UC (28.8%). Drug treatment was performed with high doses of glucocorticoids and salicylates. The time to remission in patients with EN was significantly shorter as compared to PG (5.3 +/- 1.8 vs. 19.6 +/- 14.2 weeks; p < 0.001). In 5/22 patients (22.7%) cutaneous manifestations reoccurred after a symptom-free interval. All efflorescenses reoccurred during an active phase of the underlying disease at the same manifestation site as the initial presentation. CONCLUSION In this series the prevalence of cutaneous manifestations in IBD was 22/1043 (2.1%). EN and PG were more frequent in women with IBD, in CD, and during the acute phases of the underlying disease. EN and PG predominately affect the lower legs. Cutaneous manifestations respond well to an acute phase therapy of the underlying disease. The time to remission was significantly shorter in EN as compared to PG. However, relapses have to be considered in a relevant subgroup of patients.

The overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis is a rare condition and only few cases have been published, partly associated with ulcerative colitis, but not with Crohn's disease. We report an autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome in a female patient with Crohn's disease. In addition, a second case of overlap syndrome is reported in a man without inflammatory bowel disease. A 24-year-old woman was referred with a 10-month history of diarrhoea and biochemical changes including elevated serum levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and immunoglobulin G. Enzyme linked immunosorbent assay showed that antinuclear autoantibodies were elevated. Immunofluorescence for perinuclear-staining antineutrophil cytoplasmatic antibodies was positive. Diagnostic criteria of definite autoimmune hepatitis according to the International Autoimmune Hepatitis Group were fulfilled. Liver biopsy simultaneously showed criteria of autoimmune hepatitis and primary sclerosing cholangitis. Endoscopic retrograde cholangiography demonstrated features of primary sclerosing cholangitis. Colonoscopy and colonoscopic biopsies indicated an active Crohn's disease affecting the terminal ileum and the ascending and transverse colon. Furthermore, we report the case of a 28-year-old man with known primary sclerosing cholangitis for the previous 6 years, and who developed jaundice and a marked increase of aspartate aminotransferase, alanine aminotransferase and immunoglobulin G, leading to the diagnosis of definite autoimmune hepatitis. A review of the literature revealed only 16 cases of an autoimmune hepatitis/primary sclerosing cholangitis syndrome in patients without inflammatory bowel disease or in association with ulcerative colitis. We report two additional cases, one case showing an association with Crohn's disease.

OBJECTIVE: Collagenous colitis is a chronic watery diarrhea disorder characterized by a subepithelial collagen layer and a lymphoplasmacytic infiltration within the lamina propria. However, no standard treatment has been introduced by controlled clinical trials. Aim of the present pilot trial was to investigate the clinical effects of orally administered budesonide (3 mg t.i.d.) in 7 patients with collagenous colitis. In addition, the histomorphological changes after budesonide treatment were described in a group of 3 patients. METHODS: The study was performed as an open label pilot trial. Study end point was the clinical remission of collagenous colitis defined by stool frequency and stool consistency. RESULTS: The results indicate a rapid and sustained clinical response in all patients. Stool frequency significantly decreased (p < 0.001) from 10.43 ± 5.56 per day (4–20 per day) to 3.3 ± 1.2 (1–5 per day) after 10 days and to 1.86 ± 0.69 per day (1–3 per day) after 10 wk. Moreover stool consistency changed from watery (6 patients) or soft (1 patient) to soft (1 patient) or solid (6 patients). Clinical improvement was achieved within the first 10 days in all patients and maintained after dose reduction. In 3 patients no diarrhea recurred within 7, 12, or 15 months after treatment with budesonide was terminated. In these patients control biopsies were taken and showed a marked regression of both characteristics, the collagen band and the lymphoplasmacytic infiltration. CONCLUSIONS: With respect to the preliminary data from this pilot trial, budesonide with its high topical and low systemic effects seems to be of therapeutic clinical benefit in collagenous colitis. A therapeutic effect could be demonstrated for both therapeutic goals, the clinical response and morphological changes. Further studies on the effects of budesonide on mucosal collagen metabolism and long-term follow-up are warranted.

Recently, increased serum levels of vascularendothelial growth factor (VEGF) have been shown inpatients with inflammatory bowel disease. The origins ofthe circulating VEGF are still not described. Monocytes play an important role in the inflammatoryprocess. VEGF binding to monocytes mediates monocyterecruitment and activation. The present studyinvestigates the VEGF production of peripheral bloodmononuclear cells and the ability of peripheral monocytesto bind VEGF165 in patients with Crohn'sdisease. Nineteen patients with Crohn's disease and 10healthy volunteers were studied. VEGF165labeling of CD14+ monocytes was measured using two-color flow cytometry.Density of VEGF labeling was expressed as the meanfluorescence intensity (MFI). Furthermore, VEGF levelswere determined in culture supernatants of unstimulated peripheral blood mononuclear cells. VEGF inculture supernatants was measured using a solid-phaseenzyme-linked immunosorbent assay. There was asignificantly decreased VEGF165 labeling ofmonocytes of patients with active Crohn's disease (MFI:369.9 ± 121.6, N = 7, P < 0.002) compared topatients with inactive disease (MFI: 457.7 ±74.5, N = 6) and healthy controls (MFI: 542.9 ±96.2, N = 10). Unstimulated peripheral blood mononuclear cellsof patients with active Crohn's disease producedsignificantly higher amounts of VEGF (1142.6 ±483.9 pg/ml, N = 12, P < 0.001) compared withperipheral blood mononuclear cells of healthy volunteers(113.4 ± 101.8 pg/ml, N = 10). VEGF production byperipheral blood mononuclear cells of patients withactive disease was significantly increased compared to patients with quiescent disease (261.6± 254.8 pg/ml, N = 7, P < 0.001). Inconclusion, our data describe peripheral bloodmononuclear cells as one of the origins of the elevatedVEGF serum levels in patients with active Crohn's disease.Furthermore, a decrease in VEGF165 bindingsites on peripheral monocytes of patients with activeCrohn's disease has been shown. The study underlines theimportant role of VEGF in Crohn's disease.

Vascular endothelial growth factor (VEGF) is a potent angiogenic, vascular permeability-enhancing, and calcium-dependent enzyme-modulating cytokine with overexpression in various pathologic disorders, including granulomatous inflammation, tissue repair, delayed hypersensitivity reactions, rheumatoid arthritis, and tissue ischemia. The present study investigates the role of VEGF in chronic inflammatory bowel disease.Thirty-one patients with Crohn's disease, 15 patients with ulcerative colitis, and 9 healthy volunteers were studied. VEGF serum levels were measured with a solid-phase enzyme-linked immunosorbent assay.Significantly increased VEGF serum levels were observed in both active Crohn's disease and active ulcerative colitis when compared with healthy controls. Patients with active Crohn's disease and active ulcerative colitis showed significantly higher VEGF serum levels than patients with quiescent disease. No difference was observed between inactive disease and healthy controls. In addition, strongly increased VEGF serum levels were found in patients with Crohn's disease with fistulas in the absence of clinical, endoscopic, histologic, and laboratory findings of disease activity.Significantly increased VEGF serum levels were observed in patients with active Crohn's disease and ulcerative colitis, which suggests that VEGF has an important role in chronic inflammatory bowel disease. Its possible association with fistulas has yet to be determined.

□ In der vorliegenden Ubersichtsarbeit werden die bronchopulmonalen Manifestationen bei gastroosophagealer Refluxkrankheit und chronisch entzundlichen Darmerkrankungen sowie das hepatopulmonale Syndrom bei Leberzirrhose beschrieben sowie deren mogliche Ursachen bzw. Therapie dargestellt. Etwa 20% der Patienten mit chronisch obstruktiver Atemwegserkrankung weisen Symptome einergastroosophagealen Refluxkrankheit auf. In pathophysiologischer Hinsicht scheint die Reflexbronchokonstriktion im Vergleich zur Mikroaspiration der bedeutsamere und haufigere Mechanismus zu sein. Erste Studien zeigen den positiven Effekt einer saurehemmenden Therapie auf die refluxassoziierte Atemnot.

Background and aims. Linkage of inflammatory bowel diseases to chromosome 12p13.2–q24.1 (IBD2) has been confirmed in several genome wide screens. The STAT6 gene is located within this chromosomal region. The transcription factor STAT6 is involved in the regulation of the TH1/TH2 immune response. Increased production of TH1 cytokines is crucial in the pathogenesis of Crohn's disease. Patients and methods. Therefore, we genotyped a single nucleotide polymorphism in the 3′ untranslated region of the STAT6 gene (G2964A) in 243 patients with Crohn's disease, 100 patients with ulcerative colitis and 548 healthy controls. Results. In comparison to controls, the G allele and the GG genotype frequencies were significantly increased only in Crohn's disease patients without a variation in the CARD15 gene (p Conclusions. Alterations in the STAT6 pathway may play a crucial role in the pathogenesis of distinct subgroups of patients with Crohn's disease.

A core catcher concept is proposed to be integrated into a new PWR design based on the standard German PWR. The core catcher achieves coolability by spreading and fragmentation of the ex-vessel core-melt based on the process of water inlet from the bottom through the melt. To ge more detailed information on the very important process of water penetrating into the melt, simulant experiments have been conducted using a transparent plastic and a solder melt representing the oxidic and metallic part of the core-melt. It appears from the results that fragmentation of the melts can be achieved by proper selection of water supply pressure and water feed cross-section. The important part of the transient medium scale experiments with thermite melts, conducted since mid 1993, is to get information on the process of evaporation of water by water ingression in hot melts from below and to investigate whether there is a possibility of strong melt-water interactions, or even steam explosions. The experimental set-up represents a section of the core catcher. A thermite melt is located on the catcher plate with water supply from the bottom. After ignition of the melt, the upper sacrificial layer is eroded until water penetrates into the melt from the bottom through the holes in the supporting plate and fragmentation and simultaneous solidification of the melt occurs. The experiments, up to now, show that flooding and early coolability of the melt by water addition from the bottom are achieved. These experiments serve also as pretests for the COMET-H experiments with sustained heating planned to be conducted in the BETA-facility at the beginning of next year.

One of the problems which must be solved in severe accidents is the melt-concrete interaction which does occur when the core debris penetrates the lower pressure vessel head and contacts the basement. To prevent these accident consequences, a core catcher concept is proposed to be integrated into a new pressurized-water reactor design. The core catcher achieves coolability by spreading and fragmentation of the ex-vessel core melt based on the process of water inlet from the bottom. In order to justify the dominant process during flooding of the melt from the bottom, prototypic experiments with thermite melts in laboratory scale have been carried out. In these experiments flooding and early coolability of the melt is demonstrated. To obtain more detailed information on the important process of water penetration into the melt, a simulant experiment has been conducted using a transparent plastic melt with the typical viscosity behaviour of an oxidic corium melt and a temperature allowing evaporation of water. In every experiment the melt is flooded, and complete freezing in the form of a porous layer occurs within a few minutes only.

The motivation of the work performed within the work package “Corium and Debris Coolability” of the Severe Accident Research Network of Excellence (SARNET) is to reduce or possibly solve the remaining uncertainties on the efficiency of cooling reactor core structures and materials during severe accidents, either in the core, in the vessel lower head or in the reactor cavity, so as to limit the progression of the accident. This can be achieved either by ensuring corium retention within the reactor pressure vessel or at least by limiting the corium progression and the rate of corium release into the cavity. These issues are to be covered within the scope of accident management for existing reactors and within the scope of design and safety evaluation of future reactors. The specific objectives are to create and enhance the database on debris formation, debris coolability and corium behavior in the lower head, to develop and validate the models and computer codes for simulation of in-vessel debris bed and melt pool behavior, to perform reactor scale analysis for in-vessel corium coolability and to assess the influence of severe accident management measures on in-vessel coolability. The work being performed within this work package comprises experimental and modeling activities with strong cross coupling between the tasks. Substantial knowledge and understanding of governing phenomena concerning coolability of intact rod-like reactor core geometry was obtained in previous projects. Hence the main thrust of experimental and modeling efforts concentrates mainly on the study of formation and cooling of debris beds in order to demonstrate effective cooling modes, cooling rates and coolability limits. Modeling efforts have been aimed at assessing and validating the models in system-level and detailed codes for core degradation, oxidation and debris behavior. The paper describes the work performed up to now and summarizes the main results achieved so far.Copyright © 2012 by ASME

Forty-three organisations from 22 countries network their capacities of research in SARNET (Severe Accident Research NETwork of excellence) to resolve the most important remaining uncertainties and safety issues on severe accidents in existing and future water-cooled nuclear power plants (NPP). After a first project in the 6th Framework Programme (FP6) of the European Commission, the SARNET2 project, coordinated by IRSN, started in April 2009 for 4 years in the FP7 frame. After 2,5 years, some main outcomes of joint research (modelling and experiments) by the network members on the highest priority issues are presented: in-vessel degraded core coolability, molten-corium-concrete- interaction, containment phenomena (water spray, hydrogen combustion⋯), source term issues (mainly iodine behaviour). The ASTEC integral computer code, jointly developed by IRSN and GRS to predict the NPP SA behaviour, capitalizes in terms of models the knowledge produced in the network: a few validation results are presented. For dissemination of knowledge, an educational 1-week course was organized for young researchers or students in January 2011, and a two-day course is planned mid-2012 for senior staff. Mobility of young researchers or students between the European partners is being promoted. The ERMSAR conference is becoming the major worldwide conference on SA research. © 2012 Jean-Pierre Van Dorsselaere et al.

To investigate the effects physical training exerts on markers of oxidative stress in rats with chronic kidney disease (CKD).Twenty-four male Wistar rats were divided into four groups (n=6): sham, CKD, exercise-sham and exercise-CKD. Surgical reduction of the renal mass was performed (5/6 nephrectomized) and exercise was conducted on a treadmill (50 min/day up to 1 km/h for, 5 days/week for eight weeks). Forty-eight hours after the last exercise session, blood (1 mL) was collected from the abdominal aorta and animals were decapitated. The left kidney was surgically removed and stored at -70 °C for subsequent analysis.An increase was observed in creatinine and urea levels, superoxide production, antioxidant enzymes, and oxidative damage in the CKD group, as compared to sham animals (p0.05). Physical training made superoxide production and oxidative damage decrease in the CKD group (p0.05), increasing SOD and GPX activity, though it did not increase the antioxidant effects of CAT, and renal parameters.Even without altering renal function in animals induced to CKD model, the results show that physical training is an important component in the treatment of CKD, because it exerted a positive influence on oxidative stress parameters, especially on the reduction in superoxide production and oxidative damage, as well as an improvement in the antioxidant defense system, like SOD and GPX.

Background & Aims Comparative data on budesonide vs mesalamine for the treatment of mild-to-moderately active Crohn's disease (CD) are sparse. We assessed the efficacy and safety of each therapy in patients with mildly to moderately active CD. Methods We performed a randomized, double-blind, double-dummy, 8-week, multicenter study in which 309 patients with mildly to moderately active CD received pH-modified-release oral budesonide (9 mg/day once daily or 3 mg/day 3 times daily) or Eudragit-L–coated oral mesalamine (4.5 g/day). Results The primary efficacy variable, clinical remission (defined as Crohn's Disease Activity Index ≤150), at the final visit occurred in 69.5% (107 of 154) of patients given budesonide vs 62.1% (95 of 153) of patients given mesalamine (difference, 7.4%; 95% repeated confidence interval, −4.6% to 18.0%; P = .001 for noninferiority). Clinical remission rates did not differ significantly between the 2 budesonide groups. Treatment response, defined as Crohn's Disease Activity Index of 150 or less and/or a decrease of 70 or more (Δ70) or 100 or more (Δ100) points from baseline to final visit, did not differ significantly between patients given budesonide vs mesalamine (Δ70, P = .11; Δ100, P = .15), or between the 2 budesonide groups (Δ70, P = .38; Δ100, P = .78). No other efficacy end points differed significantly between groups. Discontinuation because of adverse events occurred in 3% and 5% of budesonide- and mesalamine-treated patients, respectively. There were no clinically relevant differences in adverse events between the 2 budesonide groups. Conclusions Budesonide (9 mg/day) was numerically, but not statistically, more effective than Eudragit-L–coated mesalamine (4.5 g/day) in patients with mildly to moderately active CD. Budesonide (9 mg/day), administered once daily, was as effective as the standard (3 times daily) regimen.

Objective Inflammatory bowel diseases (IBD) are multifactorial disorders, characterized by failure to limit the inflammatory response to luminal antigens. Genetic factors play an important role in the pathogenesis, but little is known about the accountable genes. Increased secretion of pro-inflammatory cytokines appears crucial in the initiation of the inflammatory response. Methods To evaluate the role of the IL-6 gene in IBD, a functionally relevant polymorphism in the promoter region (G/C at position -174) has been genotyped in 169 patients with Crohn's disease (CD), 133 patients with ulcerative colitis (UC) and 440 healthy controls by using restriction fragment length polymorphism (RFLP) analysis. Results No significant differences were apparent in the allele, genotype and carrier frequencies between patients and controls. Conclusion High secretion of IL-6 does not seem to play a major role in the genetic predisposition to IBD.

In a prospective study we compared the usefulness of various laboratory tests (albumin, alpha-1-proteinase inhibitor (A1PI), cholinesterase (CHE), C-reactive protein, erythrocyte sedimentation rate, hematocrit) and activity indices (CDAI, VHAI) in relation to the disease activity by endoscopic criteria. Except for hematocrit highly significant differences (p less than 0.0005) of the mean values of all test results were found for patients without or with slight mucosal lesions compared with patients with severe inflammation of the mucosa. Further analysis of the data indicates the highest test efficiency (84%), sensitivity (80%), and specificity (88.6%) for CHE. CHE showed good correlations to all other tests; the highest correlation was found between CHE and VHAI (r = -0.78). We suggest that a suppression of CHE synthesis mediated by endotoxins and cytokines rather than an increased intestinal loss explains the decreased CHE in severe Crohn's disease. It is concluded from the data that CHE is a useful test to assess the inflammatory activity of Crohn's disease.

The pharmacokinetics and bioavailability of hydrocortisone after rectal administration of a hydrocortisone acetate foam were determined after single and multiple dosing in healthy subjects as well as in patients with inflammatory bowel disease. Endogenous hydrocortisone was suppressed by dexamethasone administration. Plasma levels were compared with those observed after intravenous administration of hydrocortisone. Only a very small part of the rectal dose (100 mg) was absorbed; the mean absolute bioavailability was 3.1% in healthy volunteers and 4.5% in patients. There was substantial intersubject variability. Although maximum hydrocortisone levels after single or multiple doses were significantly higher (about 70%) in the patient group, the systemic bioavailability is very low so that the risk of systemic side effects after rectal administration of hydrocortisone acetate foam has to be considered very low.