The influence of portal blood upon lipid metabolism in normal and diabetic dogs and baboons

It has been reported that hyperlipidemia can be alleviated in human beings with an end to side portacaval shunt. Understanding the mechanism of the effect has important implications, including the possibility of devising other ways of lowering serum lipid levels. In this investigation, the influence of splanchnic venous blood on lipid metabolism was evaluated in dogs and baboons by altering the portal venous inflow to all, or portions, of the liver and by measuring the effects on different end points, including the serum lipid concentrations and the rate of hepatic lipid synthesis. In other studies, analyses have been made regarding the effect of alloxan induced insulinopenia and of total pancreatectomy on these processes. The results indicate that the effect of complete portal diversion upon serum lipids is mainly due to diversion of the hormone rich venous return from the upper splanchnic organs, although the bypass of the nutritionally rich blood returning from the intestines may play a secondary role. Therefore, a reduction of hepatic lipid synthesis is an important, although not necessarily the sole, factor in the antilipidemic influence of portacaval shunt. The effects upon synthesis and blood lipids are due more to the diversion of endogenous hormones than to the bypass of intestinal nutrients. The substances in portal venous blood that subserve hepatic lipid metabolism are presumably largely the same as the hepatotrophic factors which have been described before as profoundly affecting hepatic structure, function, and the capacity for regeneration. These portal blood factors are multiple and interrelated, but the single most important one seems to be insulin

The effect of diabetes mellitus on portal blood hepatotrophic factors in dogs

Ten nondiabetic dogs were submitted to a procedure called splanchnic division which directed the nutrient rich venous return from the intestines into the left lobes of the liver and the hormone rich pancreatico gastroduodeno splenic venous return into the right lobes. Two mth later, the right lobes had undergone the expected gross and microscopic hypertrophy. Compared with the abnormal shrunken and glycogen depleted hepatocytes of the left lobes, the large and otherwise normal hepatocytes of the right lobes had a higher rate of cell division as judged by microscopic examination, measurements of deoxyribonucleic acid synthesis and the results of autoradiography. Both sides had greater cell replication than in the livers of normal unaltered dogs. The dominance of the right lobes following splanchnic division was almost completely eliminated by the prior creation of alloxan induced diabetes in 4 dogs and by the performance of total pancreatectomy at the same time as splanchnic division in 6 dogs. In these 10 diabetic dogs, which were treated with Sc administered insulin for the 2 mth period of the postoperative study, hepatic lobar and cell size were nearly equal on both sides. By light and electron microscopy, the hepatocytes on both sides had abnormalities, somewhat less pronounced on the right. However, the most active cell division was now transferred to the left lobes. The results with alloxan induced diabetes were similar to those after total pancreatectomy, except that lipid deposits were less on both liver sides in the alloxan experiments, and the glycogen was selectively reduced in the right lobes. The latter finding presumably was due to the continued action of glucagon in dogs made diabetic with alloxan. 12 nondiabetic dogs had a procedure called partial portacaval transposition which directed systemic venous blood from the hindquarters, kidneys and adrenal glands into the left lobes of the liver and the total splanchnic venous return into the right lobes. Two mth later, the degree of relative hypertrophy and hyperplasia of the glycogen rich right lobes was even greater than after splanchnic division, as was the morphologic damage to the left lobar hepatocytes. The degree of right lobar hypertrophy following partial portacaval transposition was reduced but not eliminated by pre existing alloxan induced diabetes in 4 dogs and by concomitant total pancreatectomy in 6 more dogs. The dogs were Sc treated with insulin. Structurally, the hepatocytes on the right side after 2 mth were in better condition than were those on the left, although both were abnormal. The dominance of cell division on the right side was reduced, as judged by standard microscopy and by autoradiography, but there was not a shifting of sides. The biochemical analyses reflected the presence or absence of glucagon. These findings are consistent with the earlier multifactorial hypothesis which holds that portal hepatotrophic factors are mainly interreacting hormones generated by splanchnic organs and delivered straight to the liver and that the hormone interrelationships might have augmented significance because of the high concentration of nutritional substrate in the same venous blood. The observations also substantiate by direct testing the suggestion that insulin is the most important hepatotrophic factor and that it profoundly affects many aspects of liver cell structure, division and function

Is lymphovascular invasion a powerful predictor for biochemical recurrence in pT3 N0 prostate cancer?: Results from the K-CaP database

To assess the impact of lymphovascular invasion (LVI) on the risk of biochemical recurrence (BCR) in pT3 N0 prostate cancer, clinical data were extracted from 1,622 patients with pT3 N0 prostate cancer from the K-CaP database. Patients with neoadjuvant androgen deprivation therapy (n = 325) or insufficient pathologic or follow-up data (n = 87) were excluded. The primary endpoint was the oncologic importance of LVI, and the secondary endpoint was the hierarchical relationships for estimating BCR between the evaluated variables. LVI was noted in 260 patients (21.5%) and was significantly associated with other adverse clinicopathologic features. In the multivariate Cox regression analysis, LVI was significantly associated with an increased risk of BCR after adjusting for known prognostic factors. In the Bayesian belief network analysis, LVI and pathologic Gleason score were found to be first-degree associates of BCR, whereas prostate-specific antigen (PSA) level, seminal vesicle invasion, perineural invasion, and high-grade prostatic intraepithelial neoplasia were considered second-degree associates. In the random survival forest, pathologic Gleason score, LVI, and PSA level were three most important variables in determining BCR of patients with pT3 N0 prostate cancer. In conclusion, LVI is one of the most powerful adverse prognostic factors for BCR in patients with pT3 N0 prostate cancer.1132Ysciescopu

In-situ upgrading of Napier grass pyrolysis vapour over microporous and hierarchical mesoporous zeolites

This study presents in-situ upgrading of pyrolysis vapour derived from Napier grass over microporous and mesoporous ZSM-5 catalysts. It evaluates effect of process variables such catalyst–biomass ratio and catalyst type in a vertical fixed bed pyrolysis system at 600 °C, 50 °C/min under 5 L/min nitrogen flow. Increasing catalyst–biomass ratio during the catalytic process with microporous structure reduced production of organic phase bio-oil by approximately 7.0 wt%. Using mesoporous catalyst promoted nearly 4.0 wt% higher organic yield relative to microporous catalyst, which translate to only about 3.0 wt% reduction in organic phase compared to the yield of organic phase from non-catalytic process. GC–MS analysis of bio-oil organic phase revealed maximum degree of deoxygenation of about 36.9% with microporous catalyst compared to the mesoporous catalysts, which had between 39 and 43%. Mesoporous catalysts promoted production olefins and alkanes, normal phenol, monoaromatic hydrocarbons while microporous catalyst favoured the production of alkenes and polyaromatic hydrocarbons. There was no significant increase in the production of normal phenols over microporous catalyst due to its inability to transform the methoxyphenols and methoxy aromatics. This study demonstrated that upgrading of Napier grass pyrolysis vapour over mesoporous ZSM-5 produced bio-oil with improved physicochemical properties

Homeobox gene Dlx-2 is implicated in metabolic stress-induced necrosis

<p>Abstract</p> <p>Background</p> <p>In contrast to tumor-suppressive apoptosis and autophagic cell death, necrosis promotes tumor progression by releasing the pro-inflammatory and tumor-promoting cytokine high mobility group box 1 (HMGB1), and its presence in tumor patients is associated with poor prognosis. Thus, necrosis has important clinical implications in tumor development; however, its molecular mechanism remains poorly understood.</p> <p>Results</p> <p>In the present study, we show that Distal-less 2 (Dlx-2), a homeobox gene of the Dlx family that is involved in embryonic development, is induced in cancer cell lines dependently of reactive oxygen species (ROS) in response to glucose deprivation (GD), one of the metabolic stresses occurring in solid tumors. Increased Dlx-2 expression was also detected in the inner regions, which experience metabolic stress, of human tumors and of a multicellular tumor spheroid, an <it>in vitro </it>model of solid tumors. Dlx-2 short hairpin RNA (shRNA) inhibited metabolic stress-induced increase in propidium iodide-positive cell population and HMGB1 and lactate dehydrogenase (LDH) release, indicating the important role(s) of Dlx-2 in metabolic stress-induced necrosis. Dlx-2 shRNA appeared to exert its anti-necrotic effects by preventing metabolic stress-induced increases in mitochondrial ROS, which are responsible for triggering necrosis.</p> <p>Conclusions</p> <p>These results suggest that Dlx-2 may be involved in tumor progression via the regulation of metabolic stress-induced necrosis.</p

Thermodynamics of String Field Theory Motivated Nonlocal Models

We investigate the thermodynamic properties of the nonlocal tachyon motivated by their nonlocal structure in string field theory. We use previously developed perturbative methods for nonlocal fields to calculate the partition function and the equation of state in the high temperature limit. We find that in these models the tachyons undergo a second order phase transition. We compare our results with those of ordinary scalar field theory. We also calculate the one loop finite temperature effective potential.Comment: 31 pages, 9 figure

Elizabethkingia anophelis bacteremia is associated with clinically significant infections and high mortality

published_or_final_versio

Joint PDF modelling of turbulent flow and dispersion in an urban street canyon

The joint probability density function (PDF) of turbulent velocity and concentration of a passive scalar in an urban street canyon is computed using a newly developed particle-in-cell Monte Carlo method. Compared to moment closures, the PDF methodology provides the full one-point one-time PDF of the underlying fields containing all higher moments and correlations. The small-scale mixing of the scalar released from a concentrated source at the street level is modelled by the interaction by exchange with the conditional mean (IECM) model, with a micro-mixing time scale designed for geometrically complex settings. The boundary layer along no-slip walls (building sides and tops) is fully resolved using an elliptic relaxation technique, which captures the high anisotropy and inhomogeneity of the Reynolds stress tensor in these regions. A less computationally intensive technique based on wall functions to represent boundary layers and its effect on the solution are also explored. The calculated statistics are compared to experimental data and large-eddy simulation. The present work can be considered as the first example of computation of the full joint PDF of velocity and a transported passive scalar in an urban setting. The methodology proves successful in providing high level statistical information on the turbulence and pollutant concentration fields in complex urban scenarios.Comment: Accepted in Boundary-Layer Meteorology, Feb. 19, 200