@article{SunHuangMengetal.2012, author = {Sun, Sheng-Yun and Huang, Jin and Meng, Min-Jie and Lu, Jia-Hai and Hocher, Berthold and Liu, Kang-Li and Yang, Qin-He and Zhu, Xiao-Feng}, title = {Improvement of lipid profile and reduction of body weight by Shan He Jian Fei Granules in high fat diet-induced obese rats}, series = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, volume = {58}, journal = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, number = {1-2}, publisher = {Clin Lab Publ., Verl. Klinisches Labor}, address = {Heidelberg}, issn = {1433-6510}, pages = {81 -- 87}, year = {2012}, abstract = {Background: The goal was to study lipid profiles (TG, TC, LDL, HDL), effects on serum leptin, and fat tissue adiponectin, and resistin as well as body weight effects of Shan He Jian Fei Granules (SHJFG) in rats on a high fat diet. Methods: Rats were randomly divided into five groups: normal control group fed with normal fat diet, rats on high fat diet receiving low dosage, middle dosage, high dosage of Shan He Jian Fei Granules (SHJFG) as well as a high fat diet group receiving placebo. Rats were treated for 8 weeks. Body weight and naso-anal length of each rat were recorded and Lee's index was calculated. Serum TG, TC, LDL, HDL and leptin concentrations were analyzed. The gene expressions of adiponectin and resistin in adipose tissues were tested by RT-PCR. Results: Compared to the high-fat diet group, body weights, Lee's indexes, weight of fat tissues and serum TG, TC, LDL and leptin of SHJFG groups significantly decreased (p<0.05), whereas mRNA expressions of adiponectin and resistin of SHJFG groups significantly increased (p<0.05). Conclusions: SHJFG could significantly lower body weight and serum TG, TC, and LDL of obese rats. The effects of SHJFG in lowering leptin synthesis and raising mRNA expression of adiponectin and resistin in fat tissues may act as part of the mechanisms in lowering body weight of obese rats. Further studies are needed to demonstrate whether SHJFG may also reduce overall cardiovascular morbidity and mortality like other lipid lowering drugs.}, language = {en} } @inproceedings{EspeRailaHenzeetal.2012, author = {Espe, Katharina M. and Raila, Jens and Henze, Andrea and Blouin, Katja and Schneider, A. and Schmiedeke, D. and Krane, Vera and Schweigert, Florian J. and Hocher, Berthold and Wanner, Christoph and Drechsler, Christiane}, title = {Low vitamin E plasma levels are associated with cerebrovascular events and mortality in hemodialysis patients}, series = {Annals of nutrition \& metabolism : journal of nutrition, metabolic diseases and dietetics ; an official journal of International Union of Nutritional Sciences (IUNS)}, volume = {60}, booktitle = {Annals of nutrition \& metabolism : journal of nutrition, metabolic diseases and dietetics ; an official journal of International Union of Nutritional Sciences (IUNS)}, number = {2}, publisher = {Karger}, address = {Basel}, issn = {0250-6807}, pages = {137 -- 137}, year = {2012}, language = {en} } @article{ChenLiWangetal.2012, author = {Chen, You-Peng and Li, Jian and Wang, Zi-Neng and Reichetzeder, Christoph and Xu, Hao and Gong, Jian and Chen, Guang-Ji and Pfab, Thiemo and Xiao, Xiao-Min and Hocher, Berthold}, title = {Renin angiotensin aldosterone system and glycemia in pregnancy}, series = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, volume = {58}, journal = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, number = {5-6}, publisher = {Clin Lab Publ., Verl. Klinisches Labor}, address = {Heidelberg}, issn = {1433-6510}, pages = {527 -- 533}, year = {2012}, abstract = {Background: The renin-angiotensin-aldosterone system (RAAS) is involved in the pathogenesis of insulin resistance and type 2 diabetes in the general population. The RAAS is activated during pregnancy. However, it is unknown whether the RAAS contributes to glycemia in pregnant women. Methods: Plasma renin activity (PRA) and plasma aldosterone levels were quantified at delivery in 689 Chinese mothers. An oral glucose tolerance test in fasted women was performed in the second trimester of pregnancy. The diagnosis of gestational diabetes mellitus (GDM) and impaired glucose tolerance during pregnancy were made according to the guidelines of the Chinese Society of Obstetrics. Results: Plasma aldosterone was significantly higher in pregnant women with GDM as compared to those without impairment of glycemic control (normal pregnancies: 0.27 +/- 0.21 ng/mL, GDM: 0.36 +/- 0.30 ng/mL; p<0.05). Regression analyses revealed that PRA was negatively correlated with fasting blood glucose (FBG) (R-2 = 0.03, p = 0.007), whereas plasma aldosterone and aldosterone/PRA ratio were positively correlated with FBG (R-2 = 0.05, p<0.001 and R-2 = 0.03, p = 0.007, respectively). Multivariable regression analysis models considering relevant confounding factors confirmed these findings. Conclusions: This study demonstrated that fasting blood glucose in pregnant women is inversely correlated with the PRA, whereas plasma aldosterone showed a highly significant positive correlation with fasting blood glucose during pregnancy. Moreover, plasma aldosterone is significantly higher in pregnant women with GDM as compared to those women with normal glucose tolerance during pregnancy. Although causality cannot be proven in association studies, these data may indicate that the RAAS during pregnancy contributes to the pathogenesis of insulin resistance/new onset of diabetes during pregnancy.}, language = {en} } @article{HocherGroenSchumannetal.2012, author = {Hocher, Berthold and Groen, Hans J{\"u}rgen and Schumann, Claudia and Tsuprykov, Oleg and Seifert, Susanne and Hitzler, Walter E. and Armbruster, Franz Paul}, title = {Vitamin D status from dried capillary blood samples}, series = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, volume = {58}, journal = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, number = {7-8}, publisher = {Clin Lab Publ., Verl. Klinisches Labor}, address = {Heidelberg}, issn = {1433-6510}, doi = {10.7754/Clin.Lab.2012.120429}, pages = {851 -- 855}, year = {2012}, abstract = {Background: Given the huge impact of vitamin D deficiency on a broad spectrum of diseases such as rickets, osteoporosis, mineral bone disease-vascular calcification syndrome, infectious diseases, but also several types of cancer and CNS diseases, reliable and simple methods to analyze the vitamin D status are urgently needed. Methods: We developed an easy technique to determine the 25-OH vitamin D status from dried blood samples on filter paper. This allows determination of the 25-OH vitamin D status independently of venous blood taking, since only sampling of capillary blood is required for this new method. We compared the results of vitamin D measurements from venous blood of 96 healthy blood donors with those from capillary blood taken from the same patients at the same time. The capillary blood was dried on filter paper using the D-Vital ID dry-blood collection system. Results: 25-OH vitamin D concentration data from extracted dried capillary blood filters correlated very well with data obtained after direct measurement of venous blood samples of the same blood donor (R: 0.7936; p<0.0001). The correlation was linear over the whole range of 25-OH vitamin D concentrations seen in this study. A Bland-Altman plot revealed good agreement between both tests. Conclusions: The D-Vital ID dry-blood collection system showed an excellent performance as compared to the classical way of 25-OH vitamin D measurement from venous blood. This new technique will facilitate easy and reliable measurement for vitamin D status, in particular, in rural or isolated areas, developing countries, and field studies.}, language = {en} } @article{VickersCheethamBirminghametal.2012, author = {Vickers, Steven P. and Cheetham, Sharon C. and Birmingham, Gareth D. and Rowley, Helen L. and Headland, Katie R. and Dickinson, Keith and Grempler, Rolf and Hocher, Berthold and Mark, Michael and Klein, Thomas}, title = {Effects of the DPP-4 Inhibitor, Linagliptin, in Diet-Induced obese rats a comparison in Naive and Exenatide-Treated Animals}, series = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, volume = {58}, journal = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, number = {7-8}, publisher = {Clin Lab Publ., Verl. Klinisches Labor}, address = {Heidelberg}, issn = {1433-6510}, doi = {10.7754/Clin.Lab.2011.110919}, pages = {787 -- 799}, year = {2012}, abstract = {Background: To assess the chronic effect of the DPP-4 inhibitor, linagliptin, alone, in combination with exenatide, and during exenatide withdrawal, in diet-induced obese (DIO) rats. Methods: Female Wistar rats were exposed to a cafeteria diet to induce obesity. Animals were then dosed with vehicle or linagliptin (3 mg/kg PO) orally once-daily for a 28 day period. In a subsequent study, rats received exenatide (either 3 or 30 mu g/kg/day) or vehicle by osmotic mini-pump for 28 days. In addition, groups of animals were dosed orally with linagliptin either alone or in combination with a 3 mu g/kg/day exenatide dose for the study duration. In a final study, rats were administered exenatide (30 mu g/kg/day) or vehicle by osmotic mini-pump for eleven days. Subsequently, exenatide-treated animals were transferred to vehicle or continued exenatide infusion for a further ten days. Animals transferred from exenatide to vehicle were also dosed orally with either vehicle or linagliptin. In all studies, body weight, food and water intake were recorded daily and relevant plasma parameters and carcass composition were determined. Results: In contrast to exenatide, linagliptin did not significantly reduce body weight or carcass fat in DIO rats versus controls. Linagliptin augmented the effect of exenatide to reduce body fat when given in combination but did not affect the body weight response. In rats withdrawn from exenatide, weight regain was observed such that body weight was not significantly different to controls. Linagliptin reduced weight regain after withdrawal of exenatide such that a significant difference from controls was evident. Conclusions: These data demonstrate that linagliptin does not significantly alter body weight in either untreated or exenatide-treated DIO rats, although it delays weight gain after exenatide withdrawal. This finding may suggest the utility of DPP-4 inhibitors in reducing body weight during periods of weight gain.}, language = {en} } @article{AlterKretschmerVonWebskyetal.2012, author = {Alter, Markus L. and Kretschmer, Axel and Von Websky, Karoline and Tsuprykov, Oleg and Reichetzeder, Christoph and Simon, Alexandra and Stasch, Johannes-Peter and Hocher, Berthold}, title = {Early urinary and plasma biomarkers for experimental diabetic Nephropathy}, series = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, volume = {58}, journal = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, number = {7-8}, publisher = {Clin Lab Publ., Verl. Klinisches Labor}, address = {Heidelberg}, issn = {1433-6510}, doi = {10.7754/Clin.Lab.2011.111010}, pages = {659 -- 671}, year = {2012}, abstract = {Background: As the prevalence of diabetes rises, its complications such as diabetic nephropathy affect an increaseing number of patients. Consequently, the need for biomarkers in rodent models which reflect the stage and course of diabetic nephropathy is high. This article focuses on Heart-type fatty acid binding protein (H-FABP), osteopontin (OPN), nephrin, and Neutrophil gelatinase-associated lipocalin (NGAL) in urine, and kidney injury molecule (KIM)-1, clusterin, and tissue inhibitior of metalloproteinases (TIMP) 1 in plasma in uni-nephrectomized rats with streptocotozin-induced type 1 diabetes mellitus, a common animal model to explore renal impairment in the setting of diabetes mellitus. Methods: 23 male Wistar rats were uni-nephrectomized and subsequently divided into two study groups. The diabetic group received streptozotocin (STZ) via tail-vein injection, the non-diabetic group received citrate buffer without STZ. Subsequently, blood glucose, body weight, and blood pressure were checked regularly. After 18 weeks, animals were placed in metabolic cages, blood and urine obtained and subsequently organs were harvested after sacrifice. Results: Blood glucose levels were highly increased in diabetic animals throughout the experiment, whereas systolic blood pressure did not differ between the study groups. At study end, classical biomarkers such as urinary albumin and protein and plasma cystatin c were only slightly but not significantly different between groups indicating a very early disease state. In contrast, urinary excretion of H-FABP, OPN, nephrin, and NGAL were highly increased in diabetic animals with a highly significant p-value (p<0.01 each) compared to non-diabetic animals. In plasma, differences were found for calbindin, KIM-1, clusterin, TIMP-1, and OPN. These findings were confirmed by means of the area under the receiver operating characteristic curve (ROC-AUC) analysis. Conclusions: In summary, our study revealed elevated levels of new plasma and urinary biomarkers (urinary osteopontin, urinary nephrin, urinary NGAL, urinary H-FABP, plasma KIM-1, plasma TIMP-1) in uni-nephrectomized diabetic rats, an established rat model of diabetic nephropathy. These biomarkers appeared even before the classical biomarkers of diabetic nephropathy such as albuminuria and urinary protein excretion. The new biomarkers might offer advantage to urinary albumin and plasma cystatin c with respect to early detection.}, language = {en} } @article{SchmerbachKalkWengenmayeretal.2012, author = {Schmerbach, K. and Kalk, Philipp. and Wengenmayer, Christina and Lucht, K. and Unger, T. and Hocher, Berthold and Thoene-Reineke, C.}, title = {Renal outcome in equipotent Antihypertensive Treatment with Telmisartan, Ramipril and in combination in SHR-SP Rats}, series = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, volume = {58}, journal = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, number = {7-8}, publisher = {Clin Lab Publ., Verl. Klinisches Labor}, address = {Heidelberg}, issn = {1433-6510}, doi = {10.7754/Clin.Lab.2011.110622}, pages = {625 -- 633}, year = {2012}, abstract = {Background: The ONTARGET trial revealed an association of ACEI/ARB combination treatment (telmisartan and ramipril) with adverse renal outcome versus respective monotherapy; preclinical evidence regarding renal outcome in ACEI/ARB combination treatment is scarce. Methods: Spontaneously hypertensive stroke prone rats (SHR-SP) rats on a salt-rich diet were randomly allocated to 4 groups: SHR (untreated, n = 24), SHR + telmisartan (SHR-T, 2.39 +/- 0.69 mg/kg bw; n = 27), SHR + ramipril (SHR-R, 6.28 +/- 3.48 mg/kg bw; n = 27) and combination treatment (SHR-TR, 0.51 +/- 0.14 mg/kg bw; same dose for telmisartan and ramipril; n = 26). Study duration was 12 weeks, blood pressure was assessed weekly and doses were adjusted to maintain equal blood pressure. Finally, blood and urine samples were obtained and kidneys were harvested for histological studies. Results: Blood pressure in untreated rats rose to a maximum of 239 mmHg, whereas in all treatment groups it remained stable betvveen 140 and 150 mmHg. Mortality was 50\% in the untreated group, whereas all treatment groups survived completely. Renal function - as indicated by plasma urea and cystatin c - was significantly worse in SHR-TR animals compared to all other groups. With plasma creatinine a similar trend was observed. All treatment options significantly decreased albuminuria. Renal glomerulosclerosis was decreased by monotherapy, whereas combination therapy failed to have a significant effect. Interstitial fibrosis was decreased to a similar extent by all treatment options. Conclusions: ACEI/ARB combination treatment failed to render significant additional benefits on renal outcome in hypertensive rats when compared to monotherapy. Instead our data indicate that dual RAAS blockade might have an adverse effect on kidney function and histology when compared to monotherapy in salt-loaded SHR-SP.}, language = {en} } @article{AlterOttvonWebskyetal.2012, author = {Alter, Markus L. and Ott, Ina M. and von Websky, Karoline and Tsuprykov, Oleg and Sharkovska, Yuliya and Krause-Relle, Katharina and Raila, Jens and Henze, Andrea and Klein, Thomas and Hocher, Berthold}, title = {DPP-4 Inhibition on top of angiotensin receptor blockade offers a new therapeutic approach for diabetic nephropathy}, series = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie}, volume = {36}, journal = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie}, number = {1}, publisher = {Karger}, address = {Basel}, issn = {1420-4096}, doi = {10.1159/000341487}, pages = {119 -- 130}, year = {2012}, abstract = {Background: The need for an improved treatment for diabetic nephropathy is greatest in patients who do not adequately respond to angiotensin II receptor blockers (ARBs). This study investigated the effect of the novel dipeptidyl peptidase-4 inhibitor linagliptin alone and in combination with the ARB telmisartan on the progression of diabetic nephropathy in diabetic endothelial nitric oxide synthase (eNOS) knockout mice. Methods: Sixty male eNOS knockout C57BL/6J mice were divided into four groups after receiving intraperitoneal high-dose streptozotocin: telmisartan (1 mg/kg), linagliptin (3 mg/kg), linagliptin + telmisartan (3 mg/kg + 1 mg/kg) and vehicle. Fourteen mice were used as non-diabetic controls. Results: After 12 weeks, urine and blood were obtained and blood pressure measured. Glucose concentrations were increased and similar in all diabetic groups. Telmisartan alone reduced systolic blood pressure by 5.9 mmHg versus diabetic controls (111.2 +/- 2.3 mmHg vs 117.1 +/- 2.2 mmHg; mean +/- SEM; P = 0.071). Combined treatment significantly reduced albuminuria compared with diabetic controls (71.7 +/- 15.3 mu g/24 h vs 170.8 +/- 34.2 mu g/24 h; P = 0.017), whereas the effects of single treatment with either telmisartan (97.8 +/- 26.4 mu g/24 h) or linagliptin (120.8 +/- 37.7 mu g/24 h) were not statistically significant. DPP-4 inhibition, alone and in combination, led to significantly lower plasma osteopontin levels compared with telmisartan alone. Histological analysis revealed reduced glomerulosclerosis after Linagliptin alone and in combination with telmisartan in comparison to non treated diabetic animals (p < 0.01 and p < 0.05). Kidney malonaldehyde immune-reactivity, a marker of oxidative stress, was significantly lower in animals treated with linagliptin. Conclusions: DPP-4 inhibition on top of ARB treatment significantly reduced urinary albumin excretion and oxidative stress in diabetic eNOS knockout mice. Linagliptin on top of an angiotensin II receptor blocker may offer a new therapeutic approach for patients with diabetic nephropathy.}, language = {en} } @misc{HocherReichetzederAlter2012, author = {Hocher, Berthold and Reichetzeder, Christoph and Alter, Markus L.}, title = {Renal and cardiac effects of DPP-4 inhibitors - from preclinical development to clinical research}, series = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie}, volume = {36}, journal = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie}, number = {1}, publisher = {Karger}, address = {Basel}, issn = {1420-4096}, doi = {10.1159/000339028}, pages = {65 -- 84}, year = {2012}, abstract = {Inhibitors of type 4 dipeptidyl peptidase (DDP-4) were developed and approved for the oral treatment of type 2 diabetes. Its mode of action is to inhibit the degradation of incretins, such as type 1 glucagon like peptide (GLP-1), and GIP. GLP-1 stimulates glucose-dependent insulin secretion from pancreatic beta-cells and suppresses glucagon release from alpha-cells, thereby improving glucose control. Besides its action on the pancreas type 1 glucagon like peptide has direct effects on the heart, vessels and kidney mainly via the type 1 glucagon like peptide receptor (GLP-1R). Moreover, there are substrates of DPP-4 beyond incretins that have proven renal and cardiovascular effects such as BNP/ANP, NPY, PYY or SDF-1 alpha. Preclinical evidence suggests that DPP-4 inhibitors may be effective in acute and chronic renal failure as well as in cardiac diseases like myocardial infarction and heart failure. Interestingly, large cardiovascular meta-analyses of combined Phase II/III clinical trials with DPP-4 inhibitors point all in the same direction: a potential reduction of cardiovascular events in patients treated with these agents. A pooled analysis of pivotal Phase III, placebo-controlled, registration studies of linagliptin further showed a significant reduction of urinary albumin excretion after 24 weeks of treatment. The observation suggests direct renoprotective effects of DPP-4 inhibition that may go beyond its glucose-lowering potential. Type 4 dipeptidyl peptidase inhibitors have been shown to be very well tolerated in general, but for those excreted via the kidney dose adjustments according to renal function are needed to avoid side effects. In conclusion, the direct cardiac and renal effects seen in preclinical studies as well as meta-analysis of clinical trials may offer additional potentials - beyond improvement of glycemic control - for this newer class of drugs, such as acute kidney failure, chronic kidney failure as well as acute myocardial infarction and heart failure.}, language = {en} } @article{WeinertWieseRaweletal.2012, author = {Weinert, Christoph H. and Wiese, Stefanie and Rawel, Harshadrai Manilal and Esatbeyoglu, Tuba and Winterhalter, Peter and Homann, Thomas and Kulling, Sabine E.}, title = {Methylation of catechins and procyanidins by rat and human Catechol-O-Methyltransferase metabolite profiling and molecular modeling studies}, series = {Drug metabolism and disposition : the biological fate of chemicals}, volume = {40}, journal = {Drug metabolism and disposition : the biological fate of chemicals}, number = {2}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, address = {Bethesda}, issn = {0090-9556}, doi = {10.1124/dmd.111.041871}, pages = {353 -- 359}, year = {2012}, abstract = {Catechins and procyanidins are major polyphenols in plant-derived foods. Despite intensive studies in recent years, neither their biochemical nor their toxicological properties have been clarified sufficiently. This study aimed to compare the methylation of catechins and procyanidins by the enzyme catechol-O-methyltransferase (COMT) in vitro. We conducted incubations with rat liver cytosol and human placental cytosol including S-adenosyl-L-methionine. The set of substrates comprised the catechins (-)-epicatechin (EC) and (+)catechin (CAT), the procyanidin dimers B1, B2, B3, B4, B5, and B7 as well as procyanidin trimer C1. After extraction, metabolites were analyzed by means of liquid chromatography-electrospray ionizationmass spectrometry and liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry. EC and CAT were converted to two monomethylated metabolites each by human and rat COMT, with the 3'-O-methyl derivatives being consistently the main metabolites. Furthermore, the flavanyl units of procyanidins were methylated consecutively, leading to monomethylated and dimethylated dimeric metabolites as well as monomethylated, dimethylated, and trimethylated C1 metabolites. The methylation status of each flavanyl unit was determined by means of mass spectrometric quinone-methide fragmentation patterns. In addition, molecular modeling studies were performed with the aim to predict the preferred site of methylation and to verify the experimental data. In conclusion, our results indicate that the degree and position of methylation depend clearly on the three-dimensional structure of the entire substrate molecule.}, language = {en} } @article{ThierbachFlorianWolfrumetal.2012, author = {Thierbach, Rene and Florian, Simone and Wolfrum, Katharina and Voigt, Anja and Drewes, Gunnar and Blume, Urte and Bannasch, Peter and Ristow, Michael and Steinberg, Pablo}, title = {Specific alterations of carbohydrate metabolism are associated with hepatocarcinogenesis in mitochondrially impaired mice}, series = {Human molecular genetics}, volume = {21}, journal = {Human molecular genetics}, number = {3}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {0964-6906}, doi = {10.1093/hmg/ddr499}, pages = {656 -- 663}, year = {2012}, abstract = {Friedreich's ataxia is an inherited neurodegenerative disease caused by the reduced expression of the mitochondrially active protein frataxin. We have previously shown that mice with a hepatocyte-specific frataxin knockout (AlbFxn(-/-)) develop multiple hepatic tumors in later life. In the present study, hepatic carbohydrate metabolism in AlbFxn(-/-) mice at an early and late life stage was analyzed. In young (5-week-old) AlbFxn(-/-) mice hepatic ATP, glucose-6-phosphate and glycogen levels were found to be reduced by similar to 74, 80 and 88\%, respectively, when compared with control animals. This pronounced ATP, G6P and glycogen depletion in the livers of young mice reverted in older animals: while half of the mice die before 30 weeks of age, the other half reaches 17 months of age and exhibits glycogen, G6P and ATP levels similar to those in age-matched controls. A key event in this respect seems to be the up-regulation of GLUT1, the predominant glucose transporter in fetal liver parenchyma, which became evident in AlbFxn(-/-) mice being 5-12 weeks of age. The most significant histological findings in animals being 17 or 22 months of age were the appearance of multiple clear cell, mixed cell and basophilic foci throughout the liver parenchyma as well as the development of hepatocellular adenomas and carcinomas. The hepatocarcinogenic process in AlbFxn 2/2 mice shows remarkable differences regarding carbohydrate metabolism alterations when compared with all other chemically and virally driven liver cancer models described up to now.}, language = {en} } @article{ChupeerachTungtrongchitrPhonratetal.2012, author = {Chupeerach, Chaowanee and Tungtrongchitr, Anchalee and Phonrat, Benjaluck and Schweigert, Florian J. and Tungtrongchitr, Rungsunn and Preutthipan, Sangchai}, title = {Association of Thr420Lys polymorphism in DBP gene with fat-soluble vitamins and low radial bone mineral density in postmenopausal Thai women}, series = {Biomarkers in medicine}, volume = {6}, journal = {Biomarkers in medicine}, number = {1}, publisher = {Future Medicine}, address = {London}, issn = {1752-0363}, doi = {10.2217/BMM.11.88}, pages = {103 -- 108}, year = {2012}, abstract = {Aims: To investigate the genetic markers for osteoporosis bone mineral density by the genotyping of rs7041, rs4588 and rs1352845 in the DBP gene with either bone mineral density or serum 25-hydroxycholecalciferol, retinol and alpha-tocopherol, among 365 postmenopausal Thai women. Materials \& methods: The DBP genotypes were analyzed by a PCR restriction fragment-length polymorphism method. Serum 25-hydroxycholecalciferol was assessed using a commercial chemiluminescent immunoassay. Serum retinol and alpha-tocopherol were measured by reverse-phase high-performance liquid chromatography. Results: After adjustment for age >50 years, elder Thai subjects with low BMI (<= 25 kg/m(2)) and carrying the rs4588 CC genotype had a higher risk of radial bone mineral density osteoporosis (odds ratio: 6.29; p = 0.048). The rs1352845 genotype also had a statistical association with total hip bone mineral density; however, it disappeared after adjustment for age and BMI. No association was found in fat-soluble vitamins with bone mineral density. Conclusion: DBP genotypes may influence the osteoporosis bone mineral density in postmenopausal Thai women.}, language = {en} } @article{DorenkampBonaventuraSohnsetal.2012, author = {Dorenkamp, Marc and Bonaventura, Klaus and Sohns, Christian and Becker, Christoph R. and Leber, Alexander W.}, title = {Direct costs and cost-effectiveness of dual-source computed tomography and invasive coronary angiography in patients with an intermediate pretest likelihood for coronary artery disease}, series = {Heart}, volume = {98}, journal = {Heart}, number = {6}, publisher = {BMJ Publ. Group}, address = {London}, issn = {1355-6037}, doi = {10.1136/heartjnl-2011-300149}, pages = {460 -- 467}, year = {2012}, abstract = {Aims The study aims to determine the direct costs and comparative cost-effectiveness of latest-generation dual-source computed tomography (DSCT) and invasive coronary angiography for diagnosing coronary artery disease (CAD) in patients suspected of having this disease. Methods The study was based on a previously elaborated cohort with an intermediate pretest likelihood for CAD and on complementary clinical data. Cost calculations were based on a detailed analysis of direct costs, and generally accepted accounting principles were applied. Based on Bayes' theorem, a mathematical model was used to compare the cost-effectiveness of both diagnostic approaches. Total costs included direct costs, induced costs and costs of complications. Effectiveness was defined as the ability of a diagnostic test to accurately identify a patient with CAD. Results Direct costs amounted to (sic)98.60 for DSCT and to (sic)317.75 for invasive coronary angiography. Analysis of model calculations indicated that cost-effectiveness grew hyperbolically with increasing prevalence of CAD. Given the prevalence of CAD in the study cohort (24\%), DSCT was found to be more cost-effective than invasive coronary angiography ((sic)970 vs (sic)1354 for one patient correctly diagnosed as having CAD). At a disease prevalence of 49\%, DSCT and invasive angiography were equally effective with costs of (sic)633. Above a threshold value of disease prevalence of 55\%, proceeding directly to invasive coronary angiography was more cost-effective than DSCT. Conclusions With proper patient selection and consideration of disease prevalence, DSCT coronary angiography is cost-effective for diagnosing CAD in patients with an intermediate pretest likelihood for it. However, the range of eligible patients may be smaller than previously reported.}, language = {en} } @article{KemperLutzBaehretal.2012, author = {Kemper, Christoph J. and Lutz, Johannes and B{\"a}hr, Tobias and R{\"u}ddel, Heinz and Hock, Michael}, title = {Construct validity of the anxiety sensitivity index-3 in clinical samples}, series = {Assessment}, volume = {19}, journal = {Assessment}, number = {1}, publisher = {Sage Publ.}, address = {Thousand Oaks}, issn = {1073-1911}, doi = {10.1177/1073191111429389}, pages = {89 -- 100}, year = {2012}, abstract = {Using two clinical samples of patients, the presented studies examined the construct validity of the recently revised Anxiety Sensitivity Index-3 (ASI-3). Confirmatory factor analyses established a clear three-factor structure that corresponds to the postulated subdivision of the construct into correlated somatic, social, and cognitive components. Participants with different primary clinical diagnoses differed from each other on the ASI-3 subscales in theoretically meaningful ways. Specifically, the ASI-3 successfully discriminated patients with anxiety disorders from patients with nonanxiety disorders. Moreover, patients with panic disorder or agoraphobia manifested more somatic concerns than patients with other anxiety disorders and patients with nonanxiety disorders. Finally, correlations of the ASI-3 scales with other measures of clinical symptoms and negative affect substantiated convergent and discriminant validity. Substantial positive correlations were found between the ASI-3 Somatic Concerns and body vigilance, between Social Concerns and fear of negative evaluation and socially inhibited behavior, and between Cognitive Concerns and depression symptoms, anxiety, fear of negative evaluation, and subjective complaints. Moreover, Social Concerns correlated negatively with dominant and intrusive behavior. Results are discussed with respect to the contribution of the ASI-3 to the assessment of anxiety-related disorders.}, language = {en} } @article{SakurabaBalazadehTanakaetal.2012, author = {Sakuraba, Yasuhito and Balazadeh, Salma and Tanaka, Ryouichi and M{\"u}ller-R{\"o}ber, Bernd and Tanaka, Ayumi}, title = {Overproduction of Chl b retards senescence through transcriptional reprogramming in arabidopsis}, series = {Plant \& cell physiology}, volume = {53}, journal = {Plant \& cell physiology}, number = {3}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {0032-0781}, doi = {10.1093/pcp/pcs006}, pages = {505 -- 517}, year = {2012}, abstract = {Leaf senescence is a developmentally and environmentally regulated process which includes global changes in gene expression. Using Arabidopsis as a model, we modified Chl arrangement in photosystems by overexpressing the catalytic domain (the C domain) of chlorophyllide a oxygenase (CAO) fused with the linker domain (the B domain) of CAO and green fluorescent protein (GFP). In these plants (referred to as the BCG plants for the B and C domains of CAO and GFP), the Chl a/b ratio was drastically decreased and Chl b was incorporated into core antenna complexes. The BCG plants exhibited a significant delay of both developmental and dark-induced leaf senescence. The photosynthetic apparatus, CO2 fixation enzymes and the chloroplast structure were lost in wild-type plants during senescence, while BCG plants retained them longer than the wild type. Large-scale quantitative real-time PCR analyses of 1,880 transcription factor (TF) genes showed that 241 TFs are differentially expressed between BCG plants and wild-type plants at senescence, similar to 40\% of which are known senescence-associated genes (SAGs). Expression profiling also revealed the down-regulation of a large number of additional non-TF SAGs. In contrast, genes involved in photosynthesis were up-regulated, while those encoding Chl degradation enzymes were down-regulated in BCG plants. These results demonstrate that alteration of pigment composition in the photosynthetic apparatus retards senescence through transcriptional reprogramming.}, language = {en} } @inproceedings{SchaperKietzmannKleuseretal.2012, author = {Schaper, K. and Kietzmann, M. and Kleuser, Burkhard and Baeumer, W.}, title = {Effects of sphingosine-1-phosphate and FTY720 on epidermal hyperproliferation and inflammation in an imiquimod induced mouse model of psoriasis}, series = {NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY}, volume = {385}, booktitle = {NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY}, number = {3}, publisher = {Springer}, address = {New York}, issn = {0028-1298}, pages = {80 -- 80}, year = {2012}, language = {en} } @inproceedings{BoehmPolzinLuethetal.2012, author = {Boehm, Andreas and Polzin, A. and Lueth, Anja and Kleuser, Burkhard and Rassaf, T. and Kelm, M. and Kroemer, H. K. and Schroer, K. and Rauch, B. H.}, title = {The release of sphingosine-1-phosphate from human platelets during acute coronary syndrome is attenuated by aspirin}, series = {NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY}, volume = {385}, booktitle = {NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY}, publisher = {Springer}, address = {New York}, issn = {0028-1298}, pages = {12 -- 12}, year = {2012}, language = {en} } @article{LiWangChenetal.2012, author = {Li, Jian and Wang, Zi-Neng and Chen, You-Peng and Dong, Yun-Peng and Shuai, Han-Lin and Xiao, Xiao-Min and Reichetzeder, Christoph and Hocher, Berthold}, title = {Late gestational maternal serum cortisol is inversely associated with fetal brain growth}, series = {Neuroscience \& biobehavioral reviews : official journal of the International Behavioral Neuroscience Society}, volume = {36}, journal = {Neuroscience \& biobehavioral reviews : official journal of the International Behavioral Neuroscience Society}, number = {3}, publisher = {Elsevier}, address = {Oxford}, issn = {0149-7634}, doi = {10.1016/j.neubiorev.2011.12.006}, pages = {1085 -- 1092}, year = {2012}, abstract = {To analyze the association between fetal brain growth and late gestational blood serum cortisol in normal pregnancy.Blood total cortisol was quantified at delivery in 432 Chinese mother/child pairs. Key inclusion criteria of the cohort were: no structural anomalies of the newborn, singleton pregnancy, no alcohol abuse, no drug abuse or history of smoking no hypertensive disorders and no impairment of glucose tolerance and no use of steroid medication during pregnancy. Differential ultrasound examination of the fetal body was done in early (gestational day 89.95 +/- 7.31), middle (gestational day 160.17 16.12) and late pregnancy (gestational day 268.89 +/- 12.42). Newborn's cortisol was not correlated with any of the ultrasound measurements during pregnancy nor with birth weight. Multivariable regression analysis, considering timing of the ultrasound examination, the child's sex, maternal BMI, maternal age, maternal body weight at delivery, the timing of cortisol measurement and maternal uterine contraction states, revealed that maternal serum total cortisol was significantly negative correlated with ultrasound parameters describing the fetal brain: late biparietal diameter (R-2 =0.512, p =0.009), late head circumference (R-2 = 0.498, p= 0.001), middle biparietal diameter (R-2= 0.819, p = 0.013), middle cerebellum transverse diameter R-2 = 0.76, p= 0.014) and early biparietal diameter(R-2 = 0.819, p = 0.013). The same analysis revealed that birth weight as well as ultrasound parameters such as abdominal circumference and femur length were not correlated to maternal cortisol levels. In conclusion, our study demonstrates that maternal cortisol secretion within physiological ranges may be inversely correlated to fetal brain growth but not to birth weight. It remains to be demonstrated whether maternal cortisol secretion negatively influencing fetal brain growth translates to adverse neurological outcomes in later life.}, language = {en} } @article{RailaEnjalbertMothesetal.2012, author = {Raila, Jens and Enjalbert, Francis and Mothes, Ralf and Hurtienne, Andrea and Schweigert, Florian J.}, title = {Validation of a new point-of-care assay for determination of ss-carotene concentration in bovine whole blood and plasma}, series = {Veterinary clinical pathology}, volume = {41}, journal = {Veterinary clinical pathology}, number = {1}, publisher = {Wiley-Blackwell}, address = {Malden}, issn = {0275-6382}, doi = {10.1111/j.1939-165X.2012.00400.x}, pages = {119 -- 122}, year = {2012}, abstract = {Background: beta-Carotene is an important precursor of vitamin A, and is associated with bovine fertility. beta-Carotene concentrations in plasma are used to optimize beta-carotene supplementation in cattle, but measurement requires specialized equipment to separate plasma and extract and measure beta-carotene, either using spectrophotometry or high performance liquid chromatography (HPLC). Objective: The objective of this study was to validate a new 2-step point-of-care (POC) assay for measuring beta-carotene in whole blood and plasma. Methods: beta-carotene concentrations in plasma from 166 cows were measured using HPLC and compared with results obtained using a POC assay, the iCheck-iEx-Carotene test kit. Whole blood samples from 23 of these cattle were also evaluated using the POC assay and compared with HPLC-plasma results from the same 23 animals. The POC assay includes an extraction vial (iEx Carotene) and hand-held photometer (iCheck Carotene). Results: Concentrations of beta-carotene in plasma measured using the POC assay ranged from 0.40 to 15.84 mg/L (n = 166). No differences were observed between methods for assay of plasma (mean +/- SD; n = 166): HPLC-plasma 4.23 +/- 2.35 mg/L; POC-plasma 4.49 +/- 2.36 mg/L. Similar good agreement was found when plasma analyzed using HPLC was compared with whole blood analyzed using the POC system (n = 23): HPLC-plasma 3.46 +/- 2.12 mg/L; POC-whole blood 3.67 +/- 2.29 mg/L. Conclusions: Concentrations of beta-carotene can be measured in blood and plasma from cattle easily and rapidly using a POC assay, and results are comparable to those obtained by the highly sophisticated HPLC method. Immediate feedback regarding beta-carotene deficiency facilitates rapid and appropriate optimization of beta-carotene supplementation in feed.}, language = {en} } @article{Schneider2012, author = {Schneider, Birgit}, title = {Climate model simulation visualization from a visual studies perspective}, series = {Wiley interdisciplinary reviews : Climate change}, volume = {3}, journal = {Wiley interdisciplinary reviews : Climate change}, number = {2}, publisher = {Wiley}, address = {Malden}, issn = {1757-7780}, doi = {10.1002/wcc.162}, pages = {185 -- 193}, year = {2012}, abstract = {The article gives an overview on the visualization of climate model data simulation from a visual studies perspective. On one hand the question is raised of what it means culturally when global images are used to communicate scenarios of a changing climate future beyond the field of climate research itself. The product of this process is one of the most widespread icons of climate change, the image of the blue planet that has turned red. On the other hand insights into how these visualizations are designed in the studio of a computer designer are given. The focus here is on the way in which specific visualization software shapes images of a changing global climate. The article takes as its starting point the perspective of visual and media studies, because images have become so crucial in communicating research results of climate science and convincing policy agents and the public. What is special about scientific images depicting climate change is that they have implicitly also become political images. As today various actors and recipient groups are making use of pictures depicting climate change, the article concerns climate science, media studies, computer visualization, cultural studies, and politics alike.}, language = {en} }