High-fat diet causes an imbalance in the colonic serotonergic system promoting adipose tissue enlargement and dysplasia in rats

A high-fat (HF) diet, the serotonergic system and stromal elements have all been implicated in colon carcinogenesis. We investigated whether the colonic serotonergic system could play a main role in the development of colonic dysplasia and stromal reactivity in carcinogen-treated rats under HF diet. For this, dimethylhydrazine-treated rats were fed with standard diet and a HF diet. Fat distribution was quantified by computerized tomography exam, serotonergic activity was analyzed by high-performance liquid chromatography, gene expression, and immunohistochemistry, which along with histopathological technique enabled us to enumerate dysplasia, microvessels density, cell proliferation and COX-2 expression. We found that the HF diet induced an increase in the amount of viscera! adipose tissue, even without expressive changes in the average body weight. This was correlated with a loss of serotonergic balance in colon tissue. Moreover, the HF diet promoted dysplasia and microvessel density in association with increased proliferation and COX-2 expression within pericryptal colonic stroma. Our current findings suggest that a HF diet promotes the enlargement of adipose tissue via loss of control in colon serotonergic activity, which enhances colonic dysplasia by supporting microvessel development. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

The Banhado Alkaline Complex, Southeastern Brazil: source and evolution of potassic SiO2-undersaturated high-Ca and low-Ca magmatic series

The Cretaceous Banhado alkaline complex in southeastern Brazil presents two potassic SiO2-undersaturated series. The high-Ca magmatic series consist of initially fractionated olivine (Fo(92-91)) + diopside (Wo(48-43)En(49-35)Ae(0-7)), as evidenced by the presence of xenocrysts and xenoliths. In that sequence, diopside (Wo(47-38)En(46-37)Ae(0-8)) + phlogopite + apatite + perovskite (Prv(> 92)) crystallized to form the phlogopite melteigite and led to the Ca enrichment of the magma. Diopside (Wo(47-41)En(32-24) Ae(3-14)) continued to crystallize as an early mafic mineral, followed by nepheline (Ne(74.8-70.1)Ks(26.3-21.2)Qz(7.6-0.9)) and leucite (Lc(65-56)) and subsequently by melanite and potassic feldspar (Or(85-99)Ab(1-7)) to form melanite ijolites, wollastonite-melanite urtites and melanite-nepheline syenites. Melanite-pseudoleucite-nepheline syenites are interpreted to be a leucite accumulation. Melanite nephelinite dykes are believed to represent some of the magmatic differentiation steps. The low-Ca magmatic series is representative of a typical fractionation of aegirine-augite (Wo(36-29)En(25-4)Ae(39-18)) + alkali feldspar (Or(57-96)Ab(3-43)) + nepheline (Ne(76.5-69.0)Ks(19.9-14.4)Qz(15.1-7.7)) + titanite from phonolite magma. The evolution of this series from potassic nepheline syenites to sodic sodalite syenites and sodalitolites is attributed to an extensive fractionation of potassic feldspar, which led to an increase of the NaCl activity in the melt during the final stages forming sodalite-rich rocks. Phonolite dykes followed a similar evolutionary process and also registered some crustal assimilation. The mesocratic nepheline syenites showed interactions with phlogopite melteigites, such as compatible trace element enrichments and the presence of diopside xenocrysts, which were interpreted to be due to a mixing/mingling process of phonolite and nephelinite magmas. The geochemical data show higher TiO2 and P2O5 contents and lower SiO2 contents for the high-Ca series and different LILE evolution trends and REE chondrite-normalized patterns as compared to the low-Ca series. The Sr-87/Sr-86, Nd-143/Nd-144, Pb-206/Pb-204 and Pb-208/Pb-204 initial ratios for the high-Ca series (0.70407-0.70526, 0.51242-0.51251, 17.782-19.266 and 38.051-39.521, respectively) were slightly different from those of the low-Ca series (0.70542-0.70583, 0.51232-0.51240, 17.758-17.772 and 38.021-38.061, respectively). For both series, a CO2-rich potassic metasomatized lithospheric mantle enriched the source with rutile-bearing phlogopite clinopyroxenite veins. Kamafugite-like parental magma is attributed to the high-Ca series with major contributions from the melting of the veins. Potassic nephelinite-like parental magma is assigned to the low-Ca series, where the metasomatized wall-rock played a more significant role in the melting process.

Exercise training improves relaxation response and SOD-1 expression in aortic and mesenteric rings from high caloric diet-fed rats

Abstract Background Obesity has been associated with a variety of disease such as type II diabetes mellitus, arterial hypertension and atherosclerosis. Evidences have shown that exercise training promotes beneficial effects on these disorders, but the underlying mechanisms are not fully understood. The aim of this study was to investigate whether physical preconditioning prevents the deleterious effect of high caloric diet in vascular reactivity of rat aortic and mesenteric rings. Methods Male Wistar rats were divided into sedentary (SD); trained (TR); sedentary diet (SDD) and trained diet (TRD) groups. Run training (RT) was performed in sessions of 60 min, 5 days/week for 12 weeks (70–80% VO2max). Triglycerides, glucose, insulin and nitrite/nitrate concentrations (NOx-) were measured. Concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained. Expression of Cu/Zn superoxide dismutase (SOD-1) was assessed by Western blotting. Results High caloric diet increased triglycerides concentration (SDD: 216 ± 25 mg/dl) and exercise training restored to the baseline value (TRD: 89 ± 9 mg/dl). Physical preconditioning significantly reduced insulin levels in both groups (TR: 0.54 ± 0.1 and TRD: 1.24 ± 0.3 ng/ml) as compared to sedentary animals (SD: 0.87 ± 0.1 and SDD: 2.57 ± 0.3 ng/ml). On the other hand, glucose concentration was slightly increased by high caloric diet, and RT did not modify this parameter (SD: 126 ± 6; TR: 140 ± 8; SDD: 156 ± 8 and TRD 153 ± 9 mg/dl). Neither high caloric diet nor RT modified NOx- levels (SD: 27 ± 4; TR: 28 ± 6; SDD: 27 ± 3 and TRD: 30 ± 2 μM). Functional assays showed that high caloric diet impaired the relaxing response to ACh in mesenteric (about 13%), but not in aortic rings. RT improved the relaxing responses to ACh either in aortic (28%, for TR and 16%, to TRD groups) or mesenteric rings (10%, for TR and 17%, to TRD groups) that was accompanied by up-regulation of SOD-1 expression and reduction in triglycerides levels. Conclusion The improvement in endothelial function by physical preconditioning in mesenteric and aortic arteries from high caloric fed-rats was directly related to an increase in NO bioavailability to the smooth muscle mostly due to SOD-1 up regulation.

Relationship between pain and anxiety in rats

Clinically, it is well known that neuropathic pain often induces comorbid symptoms such as anxiety. In turn, also anxiety has been associated with a heightened experience of pain. Although, the link between pain and anxiety is well recognized in humans, the neurobiological basis of this relationship remains unclear. Therefore, the aim of the current study was to investigate the influence of neuropathic pain on anxiety and vice versa in rats by assessing not only pain-related behaviour but also by discovering possible key substrates which are responsible for the interrelation of pain and anxiety.rnIn rats with a chronic constriction of the sciatic nerve (CCI model) anxiety-like behaviour was observed. Since anxiety behaviour could be completely abolished after the treatment of the pure analgesic drugs gabapentin and morphine, we concluded that anxiety was caused by the strong persistent pain. Furthermore, we found that the neuropeptides oxytocin and vasopressin were upregulated in the amygdala of CCI rats, and the intra-amygdala treatment of an oxytocin antagonist but not the vasopressin antagonist could reduce anxiety-like behaviour in these animals, while no effect on mechanical hypersensitivity was observed. These data indicate that oxytocin is implicated in the underlying neuronal processes of pain-induced anxiety and helps to elucidate the pathophysiological mechanisms of neuropathic pain. rnTo assess the influence of trait anxiety on pain sensation in rats, we determined mechanical hypersensitivity after sciatic nerve lesion (CCI) in animals selectively bred for high anxiety or low anxiety behaviour. The paw withdrawal thresholds were significantly decreased in high anxiety animals in comparison to low anxiety animals 2 and 3 weeks after surgery. In a second model state anxiety was induced by the sub-chronic injection of the anxiogenic drug pentylentetrazol in naive rats. Pain response to mechanical stimuli was increased after pharmacologically-induced anxiety. These results provided evidence for the influence of both trait and state anxiety on pain sensation. rnThe studies contribute to the elucidation of the relationship between pain and anxiety. We investigated that the neuropathic pain model displays sensory as well as emotional factors of peripheral neuropathy. Changes in expression levels of neuropeptides in the central nervous system due to neuropathic pain may contribute to the pathophysiology of neuropathic pain and its related symptoms in animals which might also be relevant for human scenarios. The results of the current study also confirm that anxiety plays an important role in the perception of pain. rnA better understanding of pain behaviour in animals might improve the preclinical profiling of analgesic drugs during development. The study highlights the potential use of the rat model as a new preclinical tool to further investigate the link between pain and anxiety by determining not only the sensory reflexes after painful stimuli but also the more complex pain-related behaviour such as anxiety.rn

Increased IL-4 and decreased regulatory cytokine production following relocation of Icelandic horses from a high to low endoparasite environment

Insect bite hypersensitivity (IBH) is an IgE-mediated dermatitis of horses caused by bites of Culicoides spp. IBH does not occur in Iceland where Culicoides are absent. However, following importation into continental Europe where Culicoides are present, >or=50% of Icelandic horses (1st generation) develop IBH but and allergens induce Th2 responses, we investigated whether horses domiciled in Iceland are Th2-biased, and whether this is determined by helminth infection. We compared the parasite burden and T cell responses between Icelandic horses living in Iceland or Switzerland. Horses in Iceland have higher faecal egg counts, higher tapeworm-specific IgG(T) levels and higher total serum IgE levels than horses in Switzerland. Nevertheless, horses in Iceland displayed a low proportion of IL-4-producing cells in PBMC cultures after polyclonal or parasite extracts stimulation. No IL-4-producing cells were found in PBMC from horses after stimulation by Culicoides extract. Addition of anti-IL-10 and anti-TGF-beta1 to PBMC cultures of horses in Iceland increased the proportion of IL-4-producing cells after polyclonal or parasite antigens stimulation but not stimulation with Culicoides extract. This paralleled the high levels of IL-10 and TGF-beta1 found in supernatants from PBMC cultures of horses in Iceland. Collectively, horses living in Iceland have a high parasite burden but low IL-4 production. This supports the hypothesis that heavy helminth infections have a suppressive effect on IL-4 production mediated by IL-10 and TGF-beta1.

Perioperative fluid management: comparison of high, medium and low fluid volume on tissue oxygen pressure in the small bowel and colon

BACKGROUND AND OBJECTIVE: Insufficient blood flow and oxygenation in the intestinal tract is associated with increased incidence of postoperative complications after bowel surgery. High fluid volume administration may prevent occult regional hypoperfusion and intestinal tissue hypoxia. We tested the hypothesis that high intraoperative fluid volume administration increases intestinal wall tissue oxygen pressure during laparotomy. METHODS: In all, 27 pigs were anaesthetized, ventilated and randomly assigned to one of the three treatment groups (n = 9 in each) receiving low (3 mL kg-1 h-1), medium (7 mL kg-1 h-1) or high (20 mL kg-1 h-1) fluid volume treatment with lactated Ringer's solution. All animals received 30% and 100% inspired oxygen in random order. Cardiac index was measured with thermodilution and tissue oxygen pressure with a micro-oximetry system in the jejunum and colon wall and subcutaneous tissue. RESULTS: Groups receiving low and medium fluid volume treatment had similar systemic haemodynamics. The high fluid volume group had significantly higher mean arterial pressure, cardiac index and subcutaneous tissue oxygenation. Tissue oxygen pressures in the jejunum and colon were comparable in all three groups. CONCLUSIONS: The three different fluid volume regimens tested did not affect tissue oxygen pressure in the jejunum and colon, suggesting efficient autoregulation of intestinal blood flow in healthy subjects undergoing uncomplicated abdominal surgery.

HIGH PERFORMANCE, LOW COST SUBSPACE DECOMPOSITION AND POLYNOMIAL ROOTING FOR REAL TIME DIRECTION OF ARRIVAL ESTIMATION: ANALYSIS AND IMPLEMENTATION

This thesis develops high performance real-time signal processing modules for direction of arrival (DOA) estimation for localization systems. It proposes highly parallel algorithms for performing subspace decomposition and polynomial rooting, which are otherwise traditionally implemented using sequential algorithms. The proposed algorithms address the emerging need for real-time localization for a wide range of applications. As the antenna array size increases, the complexity of signal processing algorithms increases, making it increasingly difficult to satisfy the real-time constraints. This thesis addresses real-time implementation by proposing parallel algorithms, that maintain considerable improvement over traditional algorithms, especially for systems with larger number of antenna array elements. Singular value decomposition (SVD) and polynomial rooting are two computationally complex steps and act as the bottleneck to achieving real-time performance. The proposed algorithms are suitable for implementation on field programmable gated arrays (FPGAs), single instruction multiple data (SIMD) hardware or application specific integrated chips (ASICs), which offer large number of processing elements that can be exploited for parallel processing. The designs proposed in this thesis are modular, easily expandable and easy to implement. Firstly, this thesis proposes a fast converging SVD algorithm. The proposed method reduces the number of iterations it takes to converge to correct singular values, thus achieving closer to real-time performance. A general algorithm and a modular system design are provided making it easy for designers to replicate and extend the design to larger matrix sizes. Moreover, the method is highly parallel, which can be exploited in various hardware platforms mentioned earlier. A fixed point implementation of proposed SVD algorithm is presented. The FPGA design is pipelined to the maximum extent to increase the maximum achievable frequency of operation. The system was developed with the objective of achieving high throughput. Various modern cores available in FPGAs were used to maximize the performance and details of these modules are presented in detail. Finally, a parallel polynomial rooting technique based on Newton’s method applicable exclusively to root-MUSIC polynomials is proposed. Unique characteristics of root-MUSIC polynomial’s complex dynamics were exploited to derive this polynomial rooting method. The technique exhibits parallelism and converges to the desired root within fixed number of iterations, making this suitable for polynomial rooting of large degree polynomials. We believe this is the first time that complex dynamics of root-MUSIC polynomial were analyzed to propose an algorithm. In all, the thesis addresses two major bottlenecks in a direction of arrival estimation system, by providing simple, high throughput, parallel algorithms.

Effects of Supplementing High or Low Quality Forages with Corn or Corn Processing Co-Products Upon Digestibility of Dry Matter and Energy by Steers

A digestibility trial, utilizing eight crossbred steers weighing initially 741 lbs. was conducted in an 8 x 8 Latin square design. High-fiber corn by-products were compared with corn as energy sources when fed in mixed diets with either lowor high-quality forage. Ground, dry corn stover and ground alfalfa hay were both fed alone or with corn grain, dried corn gluten feed (CGF), and dried corn distillers grains plus solubles (DDG) in a 1:1 ratio (dry basis). Total tract dry matter digestibility (DMD) was increased for both forages when fed with concentrates. Total tract DMD was similar in stover-based and alfalfa-based diets fed with CGF and DDG. However, stover+corn was lower in DMD than either stover+CGF and stover+DDG. Conversely, alfalfa+corn was higher in DMD than alfalfa+CGF or alfalfa+DDG. Feeding stover with corn tended to decrease digestibility of neutral detergent fiber (NDF), while feeding stover with CGF or DDG increased NDFD. There was no effect upon NDF digestion of alfalfa-based diets when fed with any of the concentrates. Feeding either forage with a concentrate increased digestible energy (DE). Stover+CGF and stover+DDG were similar in DE and were both higher in DE than stover+corn. Alfalfa+DDG tended to be higher than alfalfa+CGF and was similar to alfalfa+corn in DE. Alfalfa+CGF was lower in DE compared with alfalfa+corn. Results are interpreted to indicate that stover is more susceptible to negative feed interactions caused by corn grain than is alfalfa. Additionally, highfiber corn co-products fed with stover resulted in a positive associative effect but essentially had no associative effect when fed with alfalfa.

Size-Fractionated Nitrogen Uptake Measurements in the Equatorial Pacific and Confirmation of the Low Si-High-Nitrate Low-Chlorophyll Condition

The equatorial Pacific Ocean is the largest natural source of CO(2) to the atmosphere, and it significantly impacts the global carbon cycle. Much of the large flux of upwelled CO(2) to the atmosphere is due to incomplete use of the available nitrate (NO(3)) and low net productivity. This high-nutrient low-chlorophyll (HNLC) condition of the equatorial upwelling zone (EUZ) has been interpreted from modeling efforts to be due to low levels of silicate ( Si( OH) 4) that limit the new production of diatoms. These ideas were incorporated into an ecosystem model, CoSINE. This model predicted production by the larger phytoplankton and the picoplankton and effects on air-sea CO(2) fluxes in the Pacific Ocean. However, there were no size-fractionated rates available for verification. Here we report the first size-fractionated new and regenerated production rates (obtained with (15)N - NO(3) and (15)N - NH(4) incubations) for the EUZ with the objective of validating the conceptual basis and functioning of the CoSINE model. Specifically, the larger phytoplankton ( with cell diameters > 5 mu m) had greater rates of new production and higher f-ratios (i.e., the proportion of NO(3) to the sum of NO(3) and NH(4) uptake) than the picoplankton that had high rates of NH(4) uptake and low f-ratios. The way that the larger primary producers are regulated in the EUZ is discussed using a continuous chemostat approach. This combines control of Si(OH)(4) production by supply rate (bottom-up) and control of growth rate ( or dilution) by grazing ( top-down control).

High Hepatic and Extrahepatic Mortality and Low Treatment Uptake in HCV-coinfected Persons in the Swiss HIV Cohort Study between 2001 and 2013

BACKGROUND & AIMS The landscape of HCV treatments is changing dramatically. At the beginning of this new era, we highlight the challenges for HCV-therapy by assessing the long-term epidemiological trends in treatment uptake, efficacy and mortality among HIV/HCV-coinfected people since the availability of HCV therapy. METHODS We included all SHCS participants with detectable HCV RNA between 2001 and 2013. To identify predictors for treatment uptake uni- and multivariable Poisson regression models were applied. We further used survival analyses with Kaplan-Meier curves and Cox regression with drop-out as competing risk. RESULTS Of 12,401 participants 2107 (17%) were HCV RNA positive. Of those, 636 (30%) started treatment with an incidence of 5.8/100 person years (PY) (95% CI 5.3-6.2). Sustained virological response (SVR) with pegylated interferon/ribavirin was achieved in 50% of treated patients, representing 15% of all participants with replicating HCV infection. 344 of 2107 (16%) HCV RNA positive persons died, 59% from extrahepatic causes. Mortality/100 PY was 2.9 (95% CI 2.6-3.2) in untreated patients, 1.3 (1.0-1.8) in those treated with failure, and 0.6 (0.4-1.0) in patients with SVR. In 2013, 869/2107 (41%) participants remained HCV RNA positive. CONCLUSIONS Over the last 13 years HCV treatment uptake was low and by the end of 2013, a large number of persons remain to be treated. Mortality was high, particularly in untreated patients, and mainly due to non-liver related causes. Accordingly, in HIV/HCV-coinfected patients, integrative care including the diagnosis and therapy of somatic and psychiatric disorders is important to achieve mortality rates similar to HIV-monoinfected patients.

High Rates of Smoking Especially in Female Crohn's Disease Patients and Low Use of Supportive Measures to Achieve Smoking Cessation--Data from the Swiss IBD Cohort Study

BACKGROUND AND AIMS Smoking is a crucial environmental factor in inflammatory bowel disease [IBD]. However, knowledge on patient characteristics associated with smoking, time trends of smoking rates, gender differences and supportive measures to cease smoking provided by physicians is scarce. We aimed to address these questions in Swiss IBD patients. METHODS Prospectively obtained data from patients participating in the Swiss IBD Cohort Study was analysed and compared with the general Swiss population [GSP] matched by age, sex and year. RESULTS Among a total of 1770 IBD patients analysed [49.1% male], 29% are current smokers. More than twice as many patients with Crohn's disease [CD] are active smokers compared with ulcerative colitis [UC] [UC, 39.6% vs CD 15.3%, p < 0.001]. In striking contrast to the GSP, significantly more women than men with CD smoke [42.8% vs 35.8%, p = 0.025], with also an overall significantly increased smoking rate compared with the GSP in women but not men. The vast majority of smoking IBD patients [90.5%] claim to never have received any support to achieve smoking cessation, significantly more in UC compared with CD. We identify a significantly negative association of smoking and primary sclerosing cholangitis, indicative of a protective effect. Psychological distress in CD is significantly higher in smokers compared with non-smokers, but does not differ in UC. CONCLUSIONS Despite well-established detrimental effects, smoking rates in CD are alarmingly high with persistent and stagnating elevations compared with the GSP, especially in female patients. Importantly, there appears to be an unacceptable underuse of supportive measures to achieve smoking cessation.

Cenozoic oxygen isotopic values for benthic foraminifera from DSDP and ODP low and high latitude marine sediment cores

The climate during the Cenozoic era changed in several steps from ice-free poles and warm conditions to ice-covered poles and cold conditions. Since the 1950s, a body of information on ice volume and temperature changes has been built up predominantly on the basis of measurements of the oxygen isotopic composition of shells of benthic foraminifera collected from marine sediment cores. The statistical methodology of time series analysis has also evolved, allowing more information to be extracted from these records. Here we provide a comprehensive view of Cenozoic climate evolution by means of a coherent and systematic application of time series analytical tools to each record from a compilation spanning the interval from 4 to 61 Myr ago. We quantitatively describe several prominent features of the oxygen isotope record, taking into account the various sources of uncertainty (including measurement, proxy noise, and dating errors). The estimated transition times and amplitudes allow us to assess causal climatological-tectonic influences on the following known features of the Cenozoic oxygen isotopic record: Paleocene-Eocene Thermal Maximum, Eocene-Oligocene Transition, Oligocene-Miocene Boundary, and the Middle Miocene Climate Optimum. We further describe and causally interpret the following features: Paleocene-Eocene warming trend, the two-step, long-term Eocene cooling, and the changes within the most recent interval (Miocene-Pliocene). We review the scope and methods of constructing Cenozoic stacks of benthic oxygen isotope records and present two new latitudinal stacks, which capture besides global ice volume also bottom water temperatures at low (less than 30°) and high latitudes. This review concludes with an identification of future directions for data collection, statistical method development, and climate modeling.

Loss model for a high frequency and low load DC/DC synchronous buck converter

This work presents a behavioral-analytical hybrid loss model for a buck converter. The model has been designed for a wide operating frequency range up to 4MHz and a low power range (below 20W). It is focused on the switching losses obtained in the power MOSFETs. Main advantages of the model are the fast calculation time and a good accuracy. It has been validated by simulation and experimentally with one Ga, power transistor and two Si MOSFETs. Results show good agreement between measurements and the model.