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openaire: EC/H2020/676580/EU//NoMaD | openaire: EC/H2020/951786/EU//NOMAD CoE Funding Information: This work received funding from the European Union’s Horizon 2020 Research and Innovation Programme (Grant Agreement No. 676580), and from the Deutsche Forschungsgemeinschaft (DFG), projects 414984028 (SFB 1404, FONDA) and 460197019 (NFDI consortium FAIRmat). Funding Information: This work was funded by the Austrian Science Fund (FWF) [J 4522-N] (JW), the Federal Ministry of Education and Research (BMBF) for the Berlin Center for Machine Learning/BIFOLD (01IS18037A) (KTS), and the UKRI Future Leaders Fellowship programme (MR/S016023/1) (RJM). MG works at the BASLEARN-TU Berlin/BASF Joint Lab for Machine Learning, co-financed by TU Berlin and BASF SE. Funding Information: Financial support by the Deutsche Forschungsgemeinschaft (DFG) through Project C1 of the collaborative research centre SFB/TR 103 ‘From Atoms to Turbine Blades—A Scientific Basis for a new Generation of Single-Crystal Superalloys’ is acknowledged. Funding Information: The work performed by OI was made possible by the Office of Naval Research (ONR) through support provided by the Energetic Materials Program (MURI Grant No. N00014-21-1-2476). This work was performed, in part, at the Center for Integrated Nanotechnologies, an Office of Science User Facility operated for the US Department of Energy (DOE) Office of Science. This research is part of the Frontera computing project at the Texas Advanced Computing Center. Frontera is made possible by the National Science Foundation award OAC-1818253. Funding Information: HJK acknowledges generous support by the Office of Naval Research under Grant Numbers N00014-17-1-2956, N00014-18-1-2434, and N00014-20-1-2150, DARPA Grant D18AP00039, the Department of Energy under Grant Numbers DE-SC0018096 and DE-SC0012702, the National Science Foundation under Grant Numbers CBET-1704266 and CBET-1846426, an AAAS Marion Milligan Mason Award, and a Career Award at the Scientific Interface from the Burroughs Wellcome Fund. The author also thanks Adam H Steeves for providing a critical reading. Funding Information: PVB thanks Huozhi Zhou, Lav Varshney, and Yangfeng Ji for insightful discussions. Research was sponsored by the Defense Advanced Research Project Agency (DARPA) and The Army Research Office and was accomplished under Grant Number W911NF-20-1-0289. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of DARPA, the Army Research Office, or the U.S. Government. The U.S. Government is authorized to reproduce and distribute reprints for Government purposes not with standing any copyright notation herein. Funding Information: This work was supported by KAKENHI Grant No. JP20J20845 from Japan Society for the Promotion of Science. Part of the calculation was performed at the Supercomputer System B and C at the Institute for Solid State Physics, the University of Tokyo. Funding Information: This work was performed as part of a user project at the Molecular Foundry, Lawrence Berkeley National Laboratory, supported by the Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract No. DE-AC02–05CH11231. CB performed work at the NRC under the auspices of the AI4D Program. IT acknowledges NSERC Funding Information: KB acknowledges NSF Grant No. CHE 1856165 and BK acknowledges NSF Grant No. DGE 1633631. Funding Information: The authors thank Frisco Rose and Michael J Mehl for fruitful discussions, and acknowledge support by DOD-ONR (N00014-17-1-2090, N00014-17-1-2876) and by the National Science Foundation under DMREF Grant No. DMR-1921909. Funding Information: The authors would like to acknowledge support from the NCCR MARVEL, funded by the Swiss National Science Foundation (SNSF) (Grant Agreement ID 51NF40-182892). Funding Information: I acknowledge Jilles Vreeken, Angelo Ziletti, and Matthias Scheffler for insightful discussions. This work received funding from the European Union’s Horizon 2020 Research and Innovation Programme (Grant Agreement No. 676580 and No. 951786), the NOMAD laboratory CoE, and ERC:TEC1P (No. 740233). Funding Information: We acknowledge funding and support from the European Research Commission (Grant No. ERC CoG 772230), the Berlin Mathematics Research Center MATH+ (Project Nos. AA2-8, EF1-2, and AA2-22), and the German Ministry of Education and Research (Grant No. 01IS18037J, BIFOLD–BZML). Funding Information: We acknowledge Luca Ghiringhelli, Lucas Foppa, Claudia Draxl, Wray Buntine, and Daniel Schmidt for insightful discussions and, in particular, thank Luca Ghiringhelli and Lucas Foppa for critically reading the manuscript. This work received funding from the European Union’s Horizon 2020 Research and Innovation Programme (Grant Agreement No. 951786), the NOMAD CoE, and ERC: TEC1P (No. 740233) as well as from the Australian Research Council (DP210100045). Publisher Copyright: © 2022 The Author(s). Published by IOP Publishing Ltd. In recent years, we have been witnessing a paradigm shift in computational materials science. In fact, traditional methods, mostly developed in the second half of the XXth century, are being complemented, extended, and sometimes even completely replaced by faster, simpler, and often more accurate approaches. The new approaches, that we collectively label by machine learning, have their origins in the fields of informatics and artificial intelligence, but are making rapid inroads in all other branches of science. With this in mind, this Roadmap article, consisting of multiple contributions from experts across the field, discusses the use of machine learning in materials science, and share perspectives on current and future challenges in problems as diverse as the prediction of materials properties, the construction of force-fields, the development of exchange correlation functionals for density-functional theory, the solution of the many-body problem, and more. In spite of the already numerous and exciting success stories, we are just at the beginning of a long path that will reshape materials science for the many challenges of the XXIth century.

We previously showed that digitoxin prolongs the survival of rats with heart failure due to myocardial infarction (MI). In this study, we evaluated the effect of digitoxin on myocardial structure, ventricular function, and proteins involved in calcium kinetics. Seventy-two rats with MI >35% of the left ventricle were randomly assigned to 4 treatment groups: sham (n = 15), digitoxin (n = 11), infarction (n = 20), and infarction + digitoxin (n = 26). The rats were assessed 120 days after surgery by echocardiogram, hemodynamics, papillary muscle mechanics, collagen content, cardiomyocyte nuclear volume, and Western blot analysis of proteins involved in calcium kinetics. Digitoxin was administered via the rat chow. Two-way analysis of variance was used for comparisons. Myocardial infarction caused inotropic impairment, pulmonary congestion, increase of nuclear volume, myocardial collagen, and Na+/Ca2+ exchanger levels, and decreased SERCA2 and phosphorylated phospholamban levels. Treatment with digitoxin showed improvements in cardiac remodeling, inotropism, ventricular performance, pulmonary congestion, collagen accumulation, nuclear volume, and proteins involved in calcium kinetics. In rats with heart failure due to MI, long-term treatment with digitoxin attenuates congestive heart failure, mitigates myocardial remodeling and contractile impairment, and preserves myocardial levels of proteins involved in calcium kinetics.

AIMS To evaluate the expression of genes and proteins involved in the urethral components: vessels, nerves, and extracellular matrix, in female rats after trauma by vaginal distension (VD) and after electrical stimulation therapy (electrotherapy). METHODS We analyzed the urethras of three groups of 18 female rats 30 days posttrauma by VD: control (no interventions); trauma (animals that had VD); and electrotherapy group (those that had VD and were treated with electrical stimulation). We compared the expression of vascular endothelial growth factor (VEGF), nerve growth factor (NGF), collagen types I and III (COL1a1 and COL3a1), and lysyl-oxidase like 1 (LOXL1) among the groups. Real-time reverse transcription-polymerase chain reaction, Western blot, and immunohistochemistry were used for molecule quantification. We used the Kruskal-Wallis test and analysis of variance for statistical analyses with p

H. Jokinen työryhmän jäsenenä. Introduction: Numerous diagnostic criteria have tried to tackle the variability in clinical manifestations and problematic diagnosis of vascular cognitive impairment (VCI) but none have been universally accepted. These criteria have not been readily comparable, impacting on clinical diagnosis rates and in turn prevalence estimates, research, and treatment. Methods: The Vascular Impairment of Cognition Classification Consensus Study (VICCCS) involved participants (81% academic researchers) from 27 countries in an online Delphi consensus study. Participants reviewed previously proposed concepts to develop new guidelines. Results: VICCCS had a mean of 122 (98-153) respondents across the study and a 67% threshold to represent consensus. VICCCS redefined VCI including classification of mild and major forms of VCI and subtypes. It proposes new standardized VCI-associated terminology and future research priorities to address gaps in current knowledge. Discussion: VICCCS proposes a consensus-based updated conceptualization of VCI intended to facilitate standardization in research. (C) 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Our purpose was to verify if alcohol causes alterations on translocation of Ca2+ and tension induced by KCl or noradrenaline in vas deferens of periadolescent Wistar rats. A single dose of alcohol (i.p. 3.0 g/kg) or saline as control, was given 4 h before sacrifice. Longitudinal strips of prostatic portion were mounted in vitro for simultaneous measurements of intracellular Ca2+ and contractions. Fluorescence and tension were measured in strips loaded with the fluorescent dye fura-2. The mean values (±S.E.M.) of fluorescence ratios (F340/380) evoked by KCl were significantly lower by about 70% after alcohol, in relation to control. It was about 50% lower when evoked by noradrenaline. In relation to tension, the respective mean values (±S.E.M.) were lower by about 60% in organs treated with KCl or by about 80% after noradrenaline. In some experiments, before noradrenaline contraction, the vas deferens was incubated with verapamil 10−6 M for 30 min. In these experiments, contractions by noradrenaline in the presence of verapamil were decreased by about 70% by alcohol. Alcohol decreases cytosolic calcium and contractility after KCl and noradrenaline, as compared with controls. In addition, alcohol promoted damage of lumen structures. Prostatic portion showed no striking morphometric change after treatment, but the number of TUNEL positive cells in muscular layer, basal lamina and lumen were increased by alcohol, indicating apoptosis, compared with controls. This investigation shows that alcohol treatment alters signaling of calcium which in turn compromises the contraction associated with a process of apoptosis of periadolescent rats.

In chronic liver diseases of different etiologies, including viral hepatitis, genotoxic effects of oxidative stress have been shown, both in clinical and in experimental conditions, suggesting that this mechanism may contribute to the evolution of the disease.To evaluate DNA damage in the peripheral blood of untreated non-diabetic patients with chronic hepatitis C and control subjects, and its correlation with demographic, anthropometric, biochemical, and histological parameters in the patient sample.This study comprised 100 subjects of both genders, 60 of whom were treatment-naïve patients with positive serology for genotype 1 hepatitis C. The remaining 40 were blood donors with negative serology for hepatitis who were used as control subjects, and matched by gender, age, weight, and BMI. DNA damage was determined using the comet assay in the total peripheral blood.The DNA damage evaluated by the comet assay revealed higher values in the group of patients with hepatitis compared with that in the control group. The relationships of the comet assay with the studied variables were assessed using multivariate analysis; significant correlations were only identified with insulin (r = 0.343, p = 0.008) and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) (r = 0.331, p = 0.011).Patients with genotype 1 chronic hepatitis C have higher rates of DNA damage, as determined by comet assay and this alteration is correlated with the HOMA index of insulin resistance.

Background: activation of the Wnt pathway by mutated APC gene is considered the initial event in colorectal carcinogenesis. The identification of these mutations can improve the specific treatment of the adenocarcinoma. Objective: detect and evaluate wild-type APC protein in tissue from colorectal adenoma, adenocarcinoma and adjacent mucosa. Methods: 42 patients that underwent surgery for adenocarcinoma and 53 patients with resected adenomas were studied. Tissue samples from the adenocarcinoma were obtained from the tumor and from adjacent non-neoplastic mucosa located 10 cm from the proximal margin of the tumor. Adenoma tissue was obtained from representative areas. Blocks of tissue microarray (TMA) were submitted to immunohistochemistry with anti-APC, with readings of positivity and intensity of immunostaining and the score of immune expression of APC protein was obtained. Results: the APC protein immune expression score showed a significantly lower expression of APC protein in the adenoma when compared with the adenocarcinoma (p < 0.0001) and adjacent mucosa (p < 0.0001). The APC protein immune expression score in the colorectal mucosa and adjacent to the adenocarcinoma showed no significant difference (p = 0.24). Conclusions: the finding of decreased expression of APC protein in adenoma tissue may indicate that the mutated APC gene may contribute to the changes in the adenoma-carcinoma process of carcinogenesis sequence. The strong expression of protein APC in tissues from the carcinoma and adjacent mucosa suggests that in most patients in this series, the mutation of the APC gene did not participate in the oncogenesis mechanism. Resumo: Racional: a ativação da via Wnt pelo gene APC mutado é considerado evento inicial da carcinogênese colorretal. A identificação dessas mutações pode tornar o tratamento do adenocarcinoma mais específico. Objetivo: detectar e avaliar a proteína APC não mutada em tecidos de adenoma, adenocarcinoma e mucosa adjacente. Método: estudados 42 doentes operados de adenocarcinoma e 53 com adenomas ressecados. Tecidos de adenocarcinoma foram obtidas da neoplasia e da mucosa adjacente não neoplásica situadas a 10 cm da margem proximal do tumor. Tecidos do adenoma foram obtidas de área representativa. Blocos de tissue microarray (TMA) foram submetidos a imuno-histoquímica com anticorpo anti-APC. Avaliadas a positividade e intensidade da expressão e obtidos escores da imunoexpressão da proteína APC. Resultados: o escore da imunoexpressão da proteína APC no adenoma foi significantemente menor do que no adenocarcinoma (p < 0,0001) e na mucosa adjacente (p < 0,0001). O escore da imunoexpressão da proteína APC na mucosa adjacente e no adenocarcinoma não mostraram diferença significante (p = 0,24). Conclusões: a menor expressão da proteína APC no adenoma pode indicar que o gene APC mutado participa das alterações do processo adenoma-carcinoma. A forte expressão da proteína APC no CCR e na mucosa adjacente sugerem que a mutação do gene APC não participou da oncogênese. Keywords: Colorectal neoplasms Carcinoma, Adenoma APC Gene, Immunohistochemistry Biological tumor markers, Palavras-chave: Neoplasias colorretais Carcinoma, Adenoma Gene APC, Imunoistoquímica, Marcadores biológicos de tumor

A previous study from our laboratory showed that maternal food restriction (MFR) delays thermoregulation in newborn rats. In neonates brown adipose tissue (BAT) is essential for thermogenesis due to the presence of uncoupling proteins (UCPs). The aim of this study was to evaluate the influence of MFR on the UCPs mRNA and protein expression in BAT and skeletal muscle (SM) of the newborn rat. Female Wistar EPM-1 control rats (CON) received chow ad libitum during pregnancy, whereas food-restricted dams (RES) received 50% of the amount ingested by CON. Fifteen hours after birth, the litters were weighed and sacrificed. Blood was collected for hormonal analysis. BAT and SM were used for determination of UCPs mRNA and protein expression, and Ca 2+ -ATPase sarcoplasmic reticulum (SERCA1). RES pups showed a significant reduction in body weight and fat content at birth. MFR caused a significant increase in the expression of UCP1 and UCP2 in BAT, without changes in UCP3 and SERCA1 expression in BAT and SM. No differences between groups were found for leptin, T4 and glucose levels. RES pups showed increased insulin and decreased T3 levels. The delay in development of thermoregulation previously described in RES animals appears not to result from impairment in thermogenesis, but from an increase in heat loss, since MFR caused low birth weight in pups, leading to greater surface/volume ratio. The higher expression of UCP1 and UCP2 in BAT suggests a compensatory mechanism to increased thermogenesis.

To evaluate the grading of fibrosis and immunohistochemical expression of MPL in bone marrow biopsies of ET and PMF. Fibrosis in bone marrow biopsies (BMBs) was evaluated according to the European Consensus for grading of fibrosis, according to reticulin proliferation. Immunohistochemical analysis was performed in samples from 18 ET and 38 PMF patients: 19 were classified as pre-fibrotic and 19 were classified as fibrotic according to the World Health Organization (WHO) criteria, by means of the MPL antibody. Six bone marrow donors' biopsies were used as controls. Average reticulin (p

The goal of the present study was to investigate whether subchronic treatment with grape juice concentrate is able to protect liver and peripheral blood cells against cholesterol-induced injury in rats. The effects of the grape juice concentrate treatment on histopathological changes, immunohistochemistry for cyclo-oxygenase-2 (COX-2), and basal and oxidative DNA damage induced by H2O2 using a single-cell gel (comet) assay were evaluated. Male Wistar rats (n 18) were divided into three groups: group 1 – negative control; group 2 – cholesterol at 1 % (w/w) in their diet, treated for 5 weeks; group 3 – cholesterol at 1 % in their chow, treated for 5 weeks, and grape juice concentrate at 222 mg/d in their drinking-water in the final week only. The results indicated that the treatment with grape juice concentrate did not show remarkable differences regarding liver tissue in group 3 compared with group 2. However, grape juice concentrate was able to decrease oxidative DNA damage induced by H2O2 in peripheral blood cells, as depicted by the tail moment results. COX-2 expression in the liver did not show statistically significant differences (P>0·05) between groups. Taken together, the present results suggest that the administration of subchronic grape juice concentrate prevents oxidative DNA damage in peripheral blood cells.

Type 2 diabetes mellitus is a complex disorder with a worldwide prevalence estimated to be in the range of 1–5%, with greatest impact in developing nations (King et al. 1998). According to the latest report from the National Health and Nutrition Examination Survey (NHANES), type 2 diabetes has a 12.9% prevalence among individuals aged 20 years or more, and over 40% of the adult population may present any hyperglycemic disorder (prediabetes plus diabetes) (Cowie et al. 2009). Micro- and macrovascular complications account for the disease-related morbidity and mortality of type 2 diabetes (Stirban & Tschoepe 2008), and diabetic retinopathy has been reported as the most common cause of blindness in adults (King et al. 1998). In experimental animals, diabetes occurs either spontaneously or by chemical, surgical, genetic or combined techniques, and these models share many clinical characteristics of the human disease (Srinivasan & Ramarao 2007; Chatzigeorgiou et al. 2009). However, there are limitations to the use of such models in research, including animal availability, costs, long periods of induction, heterogeneity in the degree of glucose disturbances and high mortality rates. Chemically induced diabetes obtained using alloxan or streptozotocin promotes irreversible toxic effects on beta cells, with insulin deficiency. However, the increment in blood glucose may not be uniform (Rees & Alcolado 2005; Lenzen 2008; Szkudelski 2001). Non-rodent animal models (swine and non-human primates) have been used to depict spontaneous type 2 diabetes, but they are expensive and require sophisticated animal facilities (Wagner et al. 2006). Models of diet-induced impaired glucose tolerance or type 2 diabetes in rodents are scarce in the literature. Yin et al. (2002) induced hyperglycaemia in rabbits by adding sucrose 37% and lard 10% to the standard laboratory chow and showed mild hyperglycaemia, hyperinsulinaemia and dyslipidaemia, increased lipid peroxidation, decreased NO/NOS levels and aortic atherosclerosis. However, involvement of other target organs was not assessed. Most of what is known about diabetes complications in rabbits derives from models of alloxan-induced diabetes. Oxidative stress and non-enzymatic glycosylation are considered major factors contributing to the extent of chronic complications of diabetes in the kidneys, liver and pancreas (Szkudelski 2001; Griesmacher et al. 1995; Bulut et al. 2001; Sochor et al. 1979; Mir & Darzi 2009). Retinopathy seems to be a consequence of glucose toxicity and increased oxidative stress. Early cellular and molecular changes in the retinal vasculature have been related to glucose-associated mechanisms of toxicity, alterations in vascular permeability and capillary obliteration (Kvanta 2006). The United Kingdom Prospective Diabetes Study (UKPDS) has shown that LDL-cholesterol, followed by HDL-cholesterol, is the main risk factor for cardiovascular events (Turner et al. 1998). To assess initial complications of hyperglycaemia, we modified the protocol of Yin et al. (2002) by adding cholesterol to the diet given chronically to rabbits. To obtain a more comprehensive model, we evaluated these animals 24 weeks after diet-induced hyperglycaemia/hypercholesterolaemia for early functional and/or morphologic alterations in the kidneys, pancreas, liver, aortas and, particularly, to examine retinopathy.

The association of polymorphisms affecting lipid metabolism with the risk of myocardial infarction (MI) in type 2 diabetes mellitus was investigated. The Genetics, Outcomes and Lipids in type 2 Diabetes (GOLD) Study is a prospective, multicenter study, conducted on 990 patients presenting diabetes and MI (n = 386), or diabetes without previous manifestation of stroke, peripheral or coronary arterial disease (n = 604), recruited from 27 institutions in Brazil. APO A1 (A/G −75 and C/T +83) and APO C3 (C/G 3’UTR) non-coding sequences, CETP (Taq 1B), LPL (D9N), APO E (ɛ2, ɛ3, ɛ4,), PON-1 (Q192R), and two LCAT variants Arg147 → Trp and Tyr171 → Stop were tested by PCR-RFLP. There was a higher prevalence of LPL DN genotype (19% vs.12%, p = 0.03) and a higher frequency of the N allele (11% vs. 7%) among subjects with MI when compared to controls, with an odds ratio of MI for carriers of 9N allele of 2.46 (95% CI = 1.79–3.39, p

Several gastrointestinal symptoms associated with prolonged intense exercise (IE) have been reported, although the mechanisms underlying its effects on the intestine remain poorly understood. The aim of the present study was to investigate whether IE may induce oxidative stress in the intestine, as well as its possible relationship with intestinal signaling impairments, leading to contractile disturbances. C57BL/6 mice were submitted to 4 days (EX.4D) and 10 days (EX.10D) of IE. The daily exercise session consisted of a running session until exhaustion, with the treadmill speed set at 85% of each animal's maximum velocity. The decrease in exhaustion time was exponential, and the reduction in the maximum velocity, as assessed by an incremental test, was higher in EX.4D than in EX.10D animals. The ileum mucosa layer was partially destroyed after 4 days of IE, where 37% and 11% muscle layer atrophies were observed in EX.4D and EX.10D animals, respectively. Ileum contractility was significantly impaired in the EX.4D animal group, with reduced efficacy for carbachol, bradykinin, and KCl signaling associated with a decrease in lipid peroxidation and with no alteration of protein oxidation. Intestinal myocytes from EX.10D animals displayed areas containing structurally disorganized mitochondria, which were associated with increased levels of protein oxidation, without alteration of contractility, except for a reduction in the potency of bradykinin signaling. Finally, no clear relationship between ileum contractility and oxidative stress was shown. Together, these results argue in favor of significant functional, biochemical, and morphological disturbances caused by exercise, thus demonstrating that intestinal tissue is very sensitive to exercise.

This study investigated the influence of a moderate exercise training program on the intestinal contractility based on the hypothesis that this organ may endure repetitive periods of ischemia-reperfusion events during moderate aerobic training (10, 25, 40, and 55 days of 60-min treadmill running at 13-21 m/min, 5 days/week). The adaptation of the animal to this program was assessed by significant increase of animal physical performance associated with a mild increase in the wet heart mass-to-body mass ratio. The endurance exercise training caused functional changes of the C57BL/6 ileum contractility, mainly causing a significant reduction of the efficacy of both the electro- (KCl) and pharmacomechanical (acetylcholine, [2-lysine]-angiotensin II, and bradykinin) couplings after 55 days of moderate treadmill running. The level of ileum lipid peroxidation, evaluated by an indirect method, significantly decreased after 10 days of moderate aerobic training, remaining at this lower level throughout the 55 days of training. Altogether, these data demonstrate that the murine ileum is an important target for aerobic moderate exercise training program by causing impairment of the contractility in response to either agonists or depolarization, and that endurance exercise exerts a remarkable protective effect against tissue oxidative stress.

There is little information regarding the time of hypolipidemic treatment of changes in atherosclerotic plaque, tissue cholesterol content, and also for the recovery of endothelial function. To assess the early effects of lipid-lowering treatment on these parameters, six groups of New Zealand male rabbits were studied. Animals in groups I and II were fed regular chow; groups III and IV received a 12-week 0.5% cholesterol diet followed by 12 weeks of 0.05% cholesterol diet. Finally, groups V and VI were fed a 12-week 0.5% cholesterol diet and were then shifted to a regular diet for 12 weeks. During the last four weeks, the rabbits in groups I, III, and V received low-dose pravastatin (2 mg/day), added to the diet. Group IV animals had the highest cholesterol plasma levels (vs. groups I, II, III, and V, p < 0.01) and presented atherosclerotic plaques in a more advanced stage. Nonatherogenic diet was insufficient to restore endothelial function in animals previously fed cholesterol-enriched diets (groups IV and VI). Conversely, pravastatin treatment promoted significant improvement in endothelial function and reduced the progression of atherosclerosis. Marked increase in cholesterol content was seen in aorta and liver in response to the atherogenic diet. However, neither treatment with pravastatin nor nonatherogenic diet was capable of modifying the tissue cholesterol content. Our study supports the hypothesis that the early use of statins can attenuate the progression of atherosclerosis and ameliorate endothelial function. In addition, significant changes in the tissue cholesterol pool probably need a longer period of treatment.

Objective: The aim of this work was to demonstrate a possible relationship between anti-latency-associated peptide human latent transforming growth factor beta 1 (latent TGF-β1) expression in megakaryocytes and microvascular density in bone marrow biopsies from patients with essential thrombocythemia and primary myelofibrosis. Methods: Microvascular density was evaluated by immunohistochemical analysis and the expression of latent TGF-β1 in samples (100 megakaryocytes per bone marrow sample) from 18 essential thrombocythemia and 38 primary myelofibrosis (19 prefibrotic and 19 fibrotic) patients. Six bone marrow donor biopsies were used as controls. Fibrosis in the bone marrow biopsies was evaluated according to the European Consensus. Results: The average fibrosis grade differed between essential thrombocythemia and primary myelofibrosis groups when compared to the control group. Latent TGF-β1 expression differed significantly between the fibrotic primary myelofibrosis (PMF) group and the control group (p-value < 0.01). A high degree of neo-angiogenesis (demonstrated by analysis of CD34 expression) was detected in patients with myelofibrosis. There were correlations between latent TGF-β1 expression and microvascular density (r = 0.45; p-value < 0.0009) and between degree of microvascular density and fibrosis grade (r = 0.80; p-value < 0.0001). Remarkable differences for neo-angiogenesis were not observed between patients with essential thrombocythemia and controls. Conclusion: Angiogenesis participates in the pathogenesis of primary myelofibrosis, in both the prefibrotic and fibrotic stages, while latent TGF-β is differentially expressed only in the prefibrotic stage.

Hypertension is one of the major precursors of atherosclerotic vascular disease, and vascular smooth muscle abnormal cell replication is a key feature of plaque formation. The present study was conducted to examine the relationship between hypertension and smooth muscle cell proliferation after balloon injury and to correlate neointima formation with resting membrane potential of uninjured smooth muscle cells, since it has been suggested that altered vascular function in hypertension may be related to the resetting of the resting membrane potential in spontaneously hypertensive rats (SHR). Neointima formation was induced by balloon injury to the carotid arteries of SHR and renovascular hypertensive rats (1K-1C), as well as in their normotensive controls, i.e., Wistar Kyoto (WKY) and normal Wistar (NWR) rats. After 14 days the animals were killed and the carotid arteries were submitted to histomorphometric and immunohistochemical analyses. Resting membrane potential measurements showed that uninjured carotid arteries from SHR smooth muscle cells were significantly depolarized (-46.5 +/- 1.9 mV) compared to NWR (-69 +/- 1.4 mV), NWR 1K-1C (-60.8 +/- 1.6 mV), WKY (-67.1 +/- 3.2 mV) and WKY 1K-1C (-56.9 +/- 1.2 mV). The SHR arteries responded to balloon injury with an enhanced neointima formation (neo/media = 3.97 +/- 0.86) when compared to arteries of all the other groups (NWR 0.93 +/- 0.65, NWR 1K-1C 1.24 +/- 0.45, WKY 1.22 +/- 0.32, WKY 1K-1C 1.15 +/- 0.74). Our results indicate that the increased fibroproliferative response observed in SHR is not related to the hypertensive state but could be associated with the resetting of the carotid smooth muscle cell resting membrane potential to a more depolarized state.

The purpose of the present study was to examine the importance of magnesium in endothelial function after arterial balloon injury. Male Wistar rats were fed normal, high or low concentrations of magnesium. Three weeks later the animals underwent endothelial injury of the thoracic aorta by a balloon catheter or a sham operation. Biochemical, histological and endothelial function analysis were performed 15 days after the surgical treatment. The animals fed a low magnesium diet presented the lowest level of serum magnesium and the highest ionized blood calcium levels. Histomorphometric analysis revealed no differences among groups neither regarding the magnitude of intimal thickening nor the recovery of endothelial coverage. However, when vasoreactivity responses were compared in the balloon-injured group, those animals fed a high magnesium diet had the better endothelium-dependent vascular relaxation. In conclusion, a higher magnesium level in the diet was beneficial to vessels that underwent endothelial injury by balloon catheter. © 1998 Elsevier Science Ireland Ltd. All rights reserved.

We report theoretical and experimental studies on the tuning characteristics of a diode-pumped single-longitudinal-mode Cr:LiSrAlF/sub 6/ laser with external optical feedback from a diffraction grating. The results of theoretical analysis explained the mechanism of wavelength tuning and agreed well with the measured characteristics. The simple relation, which describes the dependence of the threshold power on the reflectivity of the output coupler and on the feedback from the grating, was derived taking account of the wavelength dependence of the Cr:LiSrAlF/sub 6/ emission cross section. From these results we could optimize the reflectivity of the coupler for achieving broad-band tuning. It was found that the tuning range of 200 nm is possible if the feedback ratio from the grating is increased to 35%.

This study aimed at assessing the effects of Kefir, a probiotic fermented milk, on oxidative stress in diabetic animals. The induction of diabetes was achieved in adult male Wistar rats using streptozotocin (STZ). The animals were distributed into four groups as follows: control (CTL); control Kefir (CTLK); diabetic (DM) and diabetic Kefir (DMK). Starting on the 5th day of diabetes, Kefir was administered by daily gavage at a dose of 1.8mL/day for 8weeks. Before and after Kefir treatment, the rats were placed in individual metabolic cages to obtain blood and urine samples to evaluate urea, creatinine, proteinuria, nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) and C-reactive protein (CRP). After sacrificing the animals, the renal cortex was removed for histology, oxidative stress and NOS evaluation. When compared to CTL rats, DM rats showed increased levels of glycemia, plasmatic urea, proteinuria, renal NO, superoxide anion, TBARS, and plasmatic CRP; also demonstrated a reduction in urinary urea, creatinine, and NO. However, DMK rats showed a significant improvement in most of these parameters. Despite the lack of differences observed in the expression of endothelial NO synthase (eNOS), the expression of inducible NO synthase (iNOS) was significantly lower in the DMK group when compared to DM rats, as assessed by Western blot analysis. Moreover, the DMK group presented a significant reduction of glycogen accumulation within the renal tubules when compared to the DM group. These results indicate that Kefir treatment may contribute to better control of glycemia and oxidative stress, which is associated with the amelioration of renal function, suggesting its use as a non-pharmacological adjuvant to delay the progression of diabetic complications.

To assess collagen content and types in the rectus abdominis muscle of cadavers of different ages. Forty fresh adult male cadavers within 24 h of death were obtained from an Institute of Legal Medicine and divided by age at death into Group 1 (mean age, 23.3 years; range, 18–30 years; n = 20) and Group 2 (mean age, 46.2 years; range, 31–60 years; n = 20). From each cadaver, samples of the rectus abdominis muscle measuring 1 cm2 were collected 3 cm superiorly and 2 cm inferiorly to the umbilicus. Histological sections were prepared and stained with picrosirius red and Masson’s trichrome stain for visualization of total collagen fibers, and immunohistochemical analysis was performed to distinguish types I, II, III, IV and V collagen. No significant differences in total collagen were found between groups by Masson’s trichrome staining. However, picrosirius red staining revealed a significantly greater amount and higher concentration of total collagen and types I and III collagen in Group 1 than in Group 2 (P

PURPOSE: To examine histological and histomorphometric techniques for measuring collagen in skeletal muscle. METHODS: The following staining methods were used in the study: hematoxylin and eosin, Masson's trichrome, reticulin, and picrosirius red, and immunostaining for collagen types I, II, III, IV, and V. Histomorphometric measurements were performed using Corel PhotoPaint and UTHSCSA Image Tool 3.0 software. RESULTS: Both the Masson's trichrome and picrosirius red staining provided the best visualization for the measurement of collagen content. CONCLUSION: This methodology is important for the identification and quantification of the different types of collagen in muscles and can be used in the investigation of the qualitative and quantitative influence of collagen on physical activities, aging, and diseases. OBJETIVO: Examinar os procedimentos empregados na quantificação do colágeno por métodos histológicos e histomorfométricos. MÉTODOS: Foram utilizadas colorações histológicas por HE, Tricrômico de Masson, Reticulina, Picrossírius e reação imuno-histoquímica para colágeno I, II, III, IV e V. A quantificação histomorfométrica foi realizada utilizando-se os programas Corel PhotoPaint e Image Tool versão 3.0. RESULTADOS: Os métodos histológicos de Masson e Picrossírius apresentaram uma maior facilidade na quantificação do colágeno. CONCLUSÃO: Este modelo é importante para que possa ser identificado e quantificado os diferentes tipos de colágenos nos músculos e relacionar com a atividade física, envelhecimento e doenças.

Specific heat and DC magnetization measurements have been performed on spinel compounds Li(V 1-x Cr x ) 2 O 4 (0≤x≤0.3). It is found that the heavy Fermi liquid-like state seen in LiV 2 O 4 disappears and a spin-glass state is realized for x≥0.1, due to the partially resolved spin frustration geometrically inherent in the V sublattice. Such a feature is analogous to that seen in another 3d heavy fermion compound Y 0.95 Sc 0.05 Mn 2 .

The aim of this study was to perform an immunohistochemical analysis from 100 megakaryocytes per sample, analyzing positivity and intensity levels of anti-LAP human TGF-β1 (or Latent TGF-β1) and anti-TGF-β1 (or Active TGF-β1) antibodies from 18 essential thrombocythemia (ET) and 38 primary myelofibrosis (PMF) patients (being 19 pre-fibrotic and 19 fibrotic). Six bone marrow donor biopsies were used as controls. Fibrosis in bone marrow biopsies (BMB) was evaluated according to the European Consensus. The average fibrosis grade differed between each group (P = 0.001 or P = 0.003). Latent TGF-β1 values differed significantly between pre-fibrotic (P = 0.018) and fibrotic (P = 0.031) groups when compared with the control group. The high immunoexpression level of Latent TGF-β1 in the megakaryocytes from patients with myelofibrosis, which was not observed in patients with essential thrombocythemia, may be associated with the development of bone marrow fibrosis.

Aim: Euterpe Oleracea (acai) is a fruit from the Amazon region whose chemical composition may be beneficial for individuals with atherosclerosis. We hypothesized that consumption of Euterpe Oleracea would reduce atherosclerosis development by decreasing cholesterol absorption and synthesis.Methods: Male New Zealand rabbits were fed a cholesterol-enriched diet (0.5%) for 12 weeks, when they were randomized to receive Euterpe Oleracea extract (n = 15) or water (n = 12) plus a 0.05% cholesterol-enriched diet for an additional 12 weeks. Plasma phytosterols and desmosterol were determined by ultra-performance liquid chromatography and mass spectrometry. Atherosclerotic lesions were estimated by computerized planimetry and histomorphometry.Results: At sacrifice, animals treated with Euterpe Oleracea had lower levels of total cholesterol (p =0.03), non-HDL-cholesterol (p = 0.03) and triglycerides (p = 0.02) than controls. These animals had smaller atherosclerotic plaque area in their aortas (p = 0.001) and a smaller intima/media ratio (p = 0.002) than controls, without differences in plaque composition. At the end of the study, campesterol, β-sitosterol, and desmosterol plasma levels did not differ between groups; however, animals treated with Euterpe Oleracea showed lower desmosterol/campesterol (p = 0.026) and desmosterol/ β-sitosterol (p =0.006) ratios than controls.Conclusions: Consumption of Euterpe Oleracea extract markedly improved the lipid profile and attenuated atherosclerosis. These effects were related in part to a better balance in the synthesis and absorption of sterols.

The goal of this study was to investigate the expression of some metalloendopeptidases in squamous cell carcinomas of the oropharynx as well as its relation to histological differentiation, staging of disease, and prognosis. Paraffin blocks from 21 primary tumors were obtained from archives of the Department of Pathology, Paulista Medical School, Federal University of Sao Paulo, UNIFESP/EPM. Immunohistochemistry was used to detect the expression of EP24.15 and EP24.16 by means of tissue microarrays. Expression of EP24.15 or EP24.16 was not correlated with the stage of disease, histopathological grading or recurrence in squamous cell carcinomas of the oropharynx. In summary, our results support the notion that EP24.15 and EP24.16 are expressed in carcinoma of the oropharynx; however, these do not appear to be suitable biomarkers for histological grading, disease stage or recurrence as depicted by tissue microarrays and immunohistochemistry.

The goal of this study was to investigate whether daily administration of green tea is able to protect the liver injury induced by cholesterol. Male Wistar rats (n = 24) were distributed into four groups: group 1, negative control; group 2, cholesterol at 1% (w/w) in the diet treated for 5 weeks; group 3, cholesterol at 1% treated for 5 weeks and green tea at 1% (w/v) in drinking water in the last week only and group 4, cholesterol and green tea at 1% in drinking water for 5 weeks. The results pointed out that treatment with green tea in the last week (group 3) showed mild degenerative changes of liver tissue in cholesterol exposed group when compared to group 2. Green tea aqueous extract was not able to reduce cholesterol levels, that is, no significant statistical differences (p > 0.05) were noticed when compared to positive control group. Nevertheless, green tea was able to decrease oxidative deoxyribonucleic acid (DNA) damage either to peripheral blood or to liver cells as depicted by significant statistical differences (p

OBJETIVO: Avaliar o colágeno no músculo reto do abdome em cadáveres de diferentes faixas etárias. MÉTODOS: Foram dissecados 40 cadáveres adultos masculinos, não fixados, com tempo de óbito de até 24 horas, em temperatura ambiente, provenientes do Instituto Médico-Legal de Franca (SP - Brasil). Os cadáveres foram distribuídos em dois grupos: GRUPO A (n=20) - 18 a 30 anos e GRUPO B (n=20) -31 a 60 anos. Realizou-se incisão na porção mediana da lâmina anterior da bainha do músculo reto a 3 cm superiormente e 2 cm inferiormente ao umbigo em ambos os lados, sendo retirados quatro fragmentos de músculo reto do abdome. Esse material foi conservado em formalina tamponado a 10% e enviado para imuno-histoquímica para determinação do tipo de colágeno. RESULTADOS: Na Imunihistoquímica os colágenos I e III foram estatisticamente maiores no grupo A, porém não houve diferença entre os grupos em relação ao colágeno IV. CONCLUSÃO: A quantidade de colágeno tipo I e III foi maior no grupo A. PURPOSE: To assess the collagen content and types in the rectus abdominis muscle of cadavers of different ages. METHODS: Forty fresh adult male cadavers, at room temperature, were obtained from the Institute of Legal Medicine of Franca and dissected within 24 hours of death. The cadavers were divided into two groups: Group A (n=20), 18 to 30 years of age, and Group B (n=20), 31 to 60 years of age. Bilateral incisions were made in the middle portion of anterior rectus sheath 3 cm superiorly and 2 cm inferiorly to the umbilicus and four fragments of the rectus abdominis muscle were dissected. The samples were fixed in 10% buffered formalin and sent for immunohistochemical analysis to determine collagen content and types. RESULTS: Immunohistochemical results revealed higher amounts of type I and type III collagen in Group A. However, no difference in the amount of type IV collagen was found between the groups. CONCLUSION: The amount of type I and type III collagen was higher in group A. UNINOVE Department of Physical Therapy UNIFESP Universidade Federal de São Paulo (UNIFESP) Department of Pathology UNIFESP Head of the Department of Surgery UNIFESP, Department of Pathology UNIFESP, Head of the Department of Surgery SciELO

Aim: Based on evidence that ionizing radiation can ameliorate chronic and autoimmune diseases in patients and experimental animals, we investigated the effects of radiation on the induction and development of experimental atherogenesis.Methods: Male New Zealand rabbits were divided into 5 groups and given an atherogenic diet for 90 days. Peritoneal and thoracic areas (9 Gy) were irradiated on the 1st and 45th days for groups 1 and 2, the 45th day for groups 3 and 4, and not at all for group 5. Prior to irradiation, the peritoneal cavity of animals from groups 1 and 3 was washed with buffered saline. Cells collected by peritoneal washing were reinfused into the peritoneal cavity of the same animal after irradiation. Animals from groups 2 and 4 were intraperitoneally injected with saline as a control.Results: Despite similar lipid profiles among the experimental groups, the percentage of aortas covered by plaques was remarkably reduced (p

SOI-bipolar transistors were fabricated by Si epitaxial layers on MgO.Al 2 O 3 epitaxial layers grown on Si wafers. Leakage current increased due to crystalline defects on the Si layer. By using solid-phase epitaxy (SPE) or seedless zone melting recrystallization (ZMR), crystalline defects were reduced. Stacking faults were reduced from 10 8 /cm 2 to less than 10 2 /cm 2 by solid-phase epitaxial growth of the amorphous Si layer. The leakage current of a bipolar transistor fabricated on a defect-reduced Si layer was less than 1 nA at 10 V

Unrepaired cyclobutane-type pyrimidine dimers of DNA extracted from human skin tumours were examined by an immunoblotting method using polyclonal antibodies raised against UV-irradiated calf thymus DNA. A total of 40 DNA samples extracted from seven SCC lesions, two AK lesions, two lymphomas, one basal cell epithelioma, one eccrine poroma, one neurofibroma of Recklinghausen's disease, on verruca vulgaris, four femoral normal skins and white blood cells of 21 humans were studied by immunoblotting using this antibody. Two of the 40 DNAs examined, one from facial actinic keratosis (AK) and one from a squamous cell carcinoma (SCC) which developed form facial AK formed immunoprecipitates. It was found, using photoreactivation enzyme plus visible light, that both immunoprecipitates were cyclobutane-type pyrimidine dimers. In addition, immunofluorescent studies on AK tissue were positive in an immunoblotting assay and revealed that the unremoved photodamage in DNA remained in the nucleus of AK cells. These findings indicate that these tumour cells may be deficient in the enzyme function for repairing photoproduct damage. The unrepaired cyclobutane-type pyrimidine dimer in AK cells might reflect the genetic process in multistage carcinogenesis as well as in xeroderma pigmentosum.

1982年より1989年までの直腸癌治癒切除160例に対し,組織学的進行度を参考にしてfollow upプロトコールを作製し,理学的所見や腫瘍マーカーの測定の他に種々の画像診断を加えて局所再発の早期発見に努めた,follow upしえた症例のうち25例に局所再発が認められた.群別再発率はA群(lowrisk)が0%,B群(intermedeate risk)が11.3%,C群(high risk)が23.2%とC群の再発率が高率であった.局所再発の初回診断法は括約筋温存群ではEUS,内視鏡検査によるものが多く,確定診断は内視鏡下生検によって行われたものが14例中10例と最も多かった.直腸切断群では初回診断はMRI,CTによって行われたものが多く,組織学的確診は11例中8例がCT下生検によって行われた。各種画像診断の特徴では,とくにMRI緩和時間により局所再発巣と術後瘢痕組織の鑑別の可能性が示唆された.これらの検討より,直腸癌術後症例に対してはCT,USなどの画像診断を加えた定期的スクリーニングを行い,疑診例にはMRIによる精査を行ったのちにCT下生検による確定診断を行うのが最も良い方法と考えられた.

過去4年間に,直腸癌Miles術後の局所再発と診断された17症例(切除群4例,非切除群13例)を臨床病理学的に検討した,原発癌が下部直腸で,腫瘍長径5cm以上,壁深達度a2以上,ew 2mm以下の症例に多く再発し,再発までの期間は平均32.9±24.2カ月であった.症状は会陰部痛が最も多く,診断にはCTとMRI診断が有用であった.治療別の比較では,切除群に2年以上の晩期再発が多く,再発巣が6cm以下と小さいもので,症状も軽くCEA値の低い時期に診断されていた.再発因子別では,ew因子によると思われる再発8症例中2例が切除群となっていたのに対し,n因子による4症例はすべて非切除群となっていた.非切除の局所要因としては,仙骨S1以上の上方浸潤が最も多く,ついで側方浸潤が多かった.切除群には多くの術後合併症を認めたが,その予後は比較的良好であり,非切除群では大部分が2年未満に死亡し,quality of lifeも不良な症例が多かった.

過去22年間に経験したCrohn病手術例35例の治療成績と術後経過について検討した.対象例の男女比は27:8,初回手術時平均年齢は29歳,病型は小腸型17例,小腸大腸型10例,大腸型8例で,平均観察期間は12年であった.初回手術の手術適応は35例中24例(69%)が閉塞であったのに対して,再手術ではのべ29回のうち閉塞10回(34%),瘻孔18回(62%)と瘻孔によるものが多かった.手術術式は35例中33例が腸切除術(広範囲腸切除術15例,小範囲腸切除術18例)で,病変部空置兼粘液瘻造設術は初回に1例,再手術に4例行われていた.術式別の手術施行5年後までにおける累積再手術率は,広範囲腸切除術は25%,小範囲腸切除術は50%であった.また病変部空置兼粘液瘻造設術は5例と症例数は少ない.ものの,その再手術率は20%であったことより,本術式は症例を選んで施行すれば良好な結果を期待しうると考えられた.

We studied an effect of preoperative radiation upon the change of tumor volume in rectal carcinomas. As a preliminary study, tumor volume of 15 cases of rectal carcinoma with no preoperative irradiation was estimated preoperatively using transrectal ultrasonography, and were compared with those determined by resected specimens after operation. As a result, there was a pallarel relasionship between the two values, and a mean estimation error rate was 14.6%. Next, the same method was applied to 15 patients with rectal carcinoma who underwent preoperative radiation in order to detect the reduction rate of tumor volume after radiation therapy (42.6 Gy). As a consequence, 80% of cases exhibited the reduction rate of more than 40% with an average of 55.1%. It was suggested that the determination of pre and postoperative tumor volume would be beneficial to evaluation of preoperative radiation therapy as well as decision of the optimal dose of radiation in rectal carcinomas.

Twenty eight early rectal cancers (11 mucosal and 17 submucosal ones) treated between January 1973 to October 1988 were retrospectively evaluated, which were found in 11 males and 17 females with the average age of 62.0 years. The half of the patients complained of bloody stool, while five had no symptoms. The mucosal cancers were located equally over the all rectal regions, but almost of all submucosal cancers were placed on the lower rectum. Almost of all mucosal cancers occurred as focal cancers in adenomas, and many of submucosal cancers did not have any adenomatous components. Intrarectal ultrasonic examination was valuable in diagnosing the depth of invasion of early rectal cancer. Webelive that intrarectal ultrasonic examination is necessary for deciding the protocol of treatment for rectal cancers.

大腸癌肝転移のhigh risk group (高危険度群) を判別するため, 大腸癌症例407例に認められた肝転移症例78例 (同時性51例, 異時性27例) についてその臨床病理学的特徴を検討した.肝転移群の原発巣平均最大径は53.9mmであり, その中でも同時性のものは56.1mmと大きく, 全大腸癌症例の49.3mmに比べて有意に大きかった.占居部位別にみた肝転移率は各部位間に差を認めなかったが, 肉眼型別比較では3型 (40.5%) が2型 (20.7%) に比べ有意に高率であった.病理組織学的検討によると, 組織型では中分化腺癌, 深達度ではs, a2以上, リンパ節転移程度ではn2以上, リンパ管侵襲程度ではly3以上, 静脈侵襲程度ではv2以上の症例に肝転移率が高率で, これらの所見を呈する症例が肝転移high risk groupと考えられた.大腸癌肝転移の予測には, これらの病理学的所見を含めた多因子による総合的判断が重要である.

Background Sustained β-adrenoreceptor activation promotes cardiac hypertrophy and cellular injury. Aims To evaluate the cardioprotective effect of exercise on damage induced by β-adrenergic hyperactivity. Methods Male Wistar rats were randomised into four groups (n=8 per group): sedentary non-treated control (C), sedentary treated with isoproterenol 0.3 mg/kg/day administered subcutaneously for 8 days (I), exercised non-treated (E) and exercised plus isoproterenol administered during the last eight days of exercise (IE). Exercised animals ran on a treadmill for 1 h daily 6 times a week for 13 weeks. Results Isoproterenol caused increases in left ventricle (LV) wet and dry weight/body weight ratio, LV water content and cardiomyocyte transverse diameter. Additionally, isoproterenol induced severe cellular lesions, necrosis, and apoptosis, increased collagen content and reduced capillary and fibre fractional areas. Notably, all of these abnormalities were completely prevented by exercise. Conclusion Our data have demonstrated that complete cardioprotection is possible through exercise training; by preventing β-adrenergic hyperactivity-induced cardiac hypertrophy and structural injury.

Aging and aerobic exercise are two conditions known to interfere with health and quality of life, most likely by inducing oxidative stress to the organism. We studied the effects of aging on the morphological and functional properties of skeletal, cardiac, and intestinal muscles and their corresponding oxidative status in C57BL/6 mice and investigated whether a lifelong moderate exercise program would exert a protective effect against some deleterious effects of aging. As expected, aged animals presented a significant reduction of physical performance, accompanied by a decrease of gastrocnemius cross-sectional area and cardiac hypertrophy. However, most interesting was that aging dramatically interfered with the intestinal structure, causing a significant thickening of the ileum muscular layer. Senescent intestinal myocytes displayed many mitochondria with disorganized cristae and the presence of cytosolic lamellar corpuscles. Lipid peroxidation of ileum and gastrocnemius muscle, but not of the heart, increased in aged mice, thus suggesting enhanced oxidative stress. With exception of the intestinal muscle responsiveness, animals submitted to a daily session of 60 min, 5 days/wk, at 13 up to 21 m/min of moderate running in treadmill during animal life span exhibited a reversion of all the observed aging effects on intestinal, skeletal, and heart muscles. the introduction of this lifelong exercise protocol prevented the enhancement of lipid peroxidation and sarcopenia and also preserved cellular and ultracellular structures of the ileum This is the first time that the protective effect of a lifelong regular aerobic physical activity against the deleterious effects of aging on intestinal muscle was demonstrated. Universidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04023062 São Paulo, Brazil Universidade Federal de São Paulo, Escola Paulista Med, Dept Physiol, BR-04023062 São Paulo, Brazil Universidade Federal de São Paulo, Escola Paulista Med, Dept Pathol, BR-04023062 São Paulo, Brazil Universidade Federal de São Paulo, Escola Paulista Med, Dept Morphol, BR-04023062 São Paulo, Brazil Universidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04023062 São Paulo, Brazil Universidade Federal de São Paulo, Escola Paulista Med, Dept Physiol, BR-04023062 São Paulo, Brazil Universidade Federal de São Paulo, Escola Paulista Med, Dept Pathol, BR-04023062 São Paulo, Brazil Universidade Federal de São Paulo, Escola Paulista Med, Dept Morphol, BR-04023062 São Paulo, Brazil Web of Science

Japan Oil, Gas and Metals National Corporation (JOGMEC), which is a former Japan National Oil Corporation (JNOC), has been developing natural gas to liquids (GTL) conversion technology since the year of 1998 in collaboration with five private Japanese companies, namely; JAPEX Co. Ltd., Chiyoda Corp., COSMO Oil Co. Ltd., Nippon Steel Corp., and INPEX Corp. Our new GTL process is particularly effective when it is applied to natural gas feed stock containing 20-40mol% of CO2. It does not require the three expensive items; (1) an oxygen supply plant, (2) a unit for CO2 separation from natural gas, and (3) a H2 separation unit to optimize gas composition. The reduction of these facilities, which are indispensable to the conventional GTL process, would results in less CAPEX and OPEX. For our new GTL process, the most preferable CO2 content in feed natural gas is around 30mol%. Therefore, in case that the CO2 content is less than 30mol%, some amount of CO2 can be supplied from other CO2 sources, such as flare gas, associated gas, remaining CO2 of EOR and exhausted gas from oil refinery and LNG plant. This paper aims to present applications of our new GTL process to enable an economic exploitation of gas reserves in South East Asia and Australia, by taking into account the operation results of the Yufutsu GTL pilot plant of 7BPSD located at Tomakomai city in Hokkaido of Japan, and the study results of process simulation and the economics. We present an attractive combination scheme for our new GTL process with LNG plant by utilizing CO2 exhausted from LNG plant. It reduces initial project's investment compared with a stand-alone GTL plant located in South East Asia and Australia, where infrastructure of an LNG plant can be for common use with our GTL plant.

OBJECTIVE: This study assessed whether the consumption of soy milk could add significantly to the lipid profile and lipid peroxidation in comparison with non-fat milk. METHODS: A double-blind, randomized, crossover study was conducted on 60 outpatients with primary hypercholesterolemia following a lipid-lowering diet for at least 6 wk. Lipid profile was obtained at baseline and at 6 and 12 wk, with the patients randomly assigned to receive initially 1 L/d of soy milk or non-fat cow milk for 6 wk. Lipid peroxidation was estimated by plasma thiobarbituric reactive substances. Apolipoprotein E genotypes were examined by polymerase chain reaction restriction fragment length polymorphism. RESULTS: The soy milk diet was associated with low-density lipoprotein cholesterol reduction (baseline 157 5 mg/dL; soy milk 148 4 mg/dL; non-fat cow milk 158 4 mg/dL; P 0.05, soy milk versus other treatments) and with high-density lipoprotein cholesterol increase (baseline 58 2 mg/dL; soy milk 62 2 mg/dL; non-fat cow milk 57 2 mg/dL; P 0.05, soy milk versus other treatments). In addition, plasma thiobarbituric reactive substances were reduced by the soy milk diet (baseline 1.82 0.12 nM/L; soy milk 1.49 0.09 nM/L; non-fat cow milk 1.91 0.11 nM/mL; P 0.05, soy milk versus non-fat cow milk). Changes in lipid profile were not influenced by APOE genotypes. CONCLUSIONS: These results indicate that soy milk as part of a lipid-lowering diet has beneficial effects in improving lipid profile and reducing lipid peroxidation. Nutrition 2004;20:200 ‐204. ©Elsevier Inc. 2004