Effect of a tumour-derived lipid-mobilising factor on glucose and lipid metabolism in vivo

Treatment of ex-breeder male NMRI mice with lipid mobilising factor isolated from the urine of cachectic cancer patients, caused a significant increase in glucose oxidation to CO2, compared with control mice receiving phosphate buffered saline. Glucose utilisation by various tissues was determined by the 2-deoxyglucose tracer technique and shown to be elevated in brain, heart, brown adipose tissue and gastrocnemius muscle. The tissue glucose metabolic rate was increased almost three-fold in brain, accounting for the ability of lipid mobilising factor to decrease blood glucose levels. Lipid mobilising factor also increased overall lipid oxidation, as determined by the production of 14CO2 from [14C carboxy] triolein, being 67% greater than phosphate buffered saline controls over a 24 h period. There was a significant increase in [14C] lipid accumulation in plasma, liver and white and brown adipose tissue after administration of lipid mobilising factor. These results suggest that changes in carbohydrate metabolism and loss of adipose tissue, together with an increased whole body fatty acid oxidation in cachectic cancer patients, may arise from tumour production of lipid mobilising factor. © 2002 Cancer Research UK.

Expression of uncoupling proteins-1,-2 and-3 mRNA is induced by an adenocarcinoma-derived lipid-mobilizing factor

The abnormalities of lipid metabolism observed in cancer cachexia may be induced by a lipid-mobilizing factor produced by adenocarcinomas. The specific molecules and metabolic pathways that mediate the actions of lipid-mobilizing factor are not known. The mitochondrial uncoupling proteins-1, -2 and -3 are suggested to play essential roles in energy dissipation and disposal of excess lipid. Here, we studied the effects of lipid-mobilizing factor on the expression of uncoupling proteins-1, -2 and -3 in normal mice. Lipid-mobilizing factor isolated from the urine of cancer patients was injected intravenously into mice over a 52-h period, while vehicle was similarly given to controls. Lipid-mobilizing factor caused significant reductions in body weight (-10%, P=0.03) and fat mass (-20%, P<0.01) accompanied by a marked decrease in plasma leptin (-59%, P<0.01) and heavy lipid deposition in the liver. In brown adipose tissue, uncoupling protein-1 mRNA levels were elevated in lipid-mobilizing factor-treated mice (+96%, P<0.01), as were uncoupling proteins-2 and -3 (+57% and +37%, both P<0.05). Lipid-mobilizing factor increased uncoupling protein-2 mRNA in both skeletal muscle (+146%, P<0.05) and liver (+142%, P=0.03). The protein levels of uncoupling protein-1 in brown adipose tissue and uncoupling protein-2 in liver were also increased with lipid-mobilizing factor administration (+49% and +67%, both P=0.02). Upregulation by lipid-mobilizing factor of uncoupling proteins-1, -2 and -3 in brown adipose tissue, and of uncoupling protein-2 in skeletal muscle and liver, suggests that these uncoupling proteins may serve to utilize excess lipid mobilized during fat catabolism in cancer cachexia.

B2B e-marketplaces in the airline industry:process drivers and performance indicators

Competitive pressures are increasing within and between different strategically oriented groups of airlines. This paper focuses on the level of efficiency improvements gained by using e-Marketplaces in the procurement process. Findings from a survey among 88 international airlines reveal that the use of Business-to-Business (B2B) e-Marketplaces does play different roles across the various airline groupings. Airlines that are involved in strategic alliances show higher joint procurement activities than airlines that are not involved in strategic alliances. However, alliances are probably viewed as loose arrangements and thus airlines may be reluctant to share information on procurement prices and processes with another airline that could also be acting as a competitor. The financial involvement in or initiation of e-Marketplaces by airlines is very low. Low cost airlines show high use of e-Marketplaces, but demonstrate little financial involvement in contrast. Overall, the categories of spares and repairs, office supplies, tools and ground support equipment (GSE) show the greatest potential for reducing costs and increasing procurement process efficiencies. The intense competitive pressures facing carriers will make their search for tools to realise even incremental savings and efficiency gains ever more urgent. There is evidence that e-Marketplaces are one tool to improve such performance indicators.

A hazai vállalatok nyitottsága az elektronikus beszerzésre (E-procurement Responsivess of the Hungarian Companies')

A Versenyképesség Kutató Központ 2004-ben a "Versenyben a világgal 1995-97" kutatási program és az 1999-es vállalati versenyképességi kérdőíves felmérés hagyományait folytatva, valamint azok tapasztalataira építve, egy hároméves kutatási programot kezdett el "Versenyben a világgal 2004-2006 – Gazdasági versenyképességünk vállalati nézőpontból" címmel. A kérdőíves felmérés nyomán létrejött adatbázist hasonló témában elemezték a szerzők 2005-ben. A korábbi eredményeken okulva, valamint a kérdőívelemzés kiterjesztésével azt kívánták felmérni, hogy az elektronikus beszerzés iránti nyitottság növekedett-e hazánkban, illetve milyen egyéb összefüggések fedezhetők fel a beszerzési szervezet, a beszerzés vállalati kapcsolatai, valamint az elektronikus beszerzés értelmezésében az egyes válaszadóknál. A kutatás továbbra is eltér a hagyományos megoldásoktól, azaz nem kívánja vizsgálni a hazai vállalati honlapok elterjedtségét, azonban a korábbiaktól eltérően több információtechnológiával kapcsolatos információt kér a válaszadóktól. A cél a belső vállalati folyamatok, a vevő-szállító kapcsolatok, az informatikai háttér elektronikus beszerzéssel való kapcsolatának felismerése. Meg szeretnék tudni, hogy az elektronikus beszerzés milyen hatékonyságnövelési lehetőséget hordoz és a hazai információs társadalmi fejlettség figyelembevételével mennyire nyitottak erre a beszerzők és a pályázók. Az elektronikus beszerzés és versenyképesség kapcsolata különösen a 2000-es évek eleje óta foglalkoztatja a kutatókat. Vita az elektronikus beszerzés beszerzési költségre gyakorolt hatásával, valamint a kormányzati politika hatásával kapcsolatban alakult ki, melyet a közbeszerzés, mint speciálisan szabályozott beszerzési tevékenység és az e-beszerzés kapcsolatára fejt ki. A vállalatok versenyképességének és az elektronikus beszerzés folyamatosan. / === / The Competitiveness Research Center based on the experience of the „ In Global Competition 1995-1997” research program and continuing the company competitiveness survey (1999) has begun a three-year research program with the following title: „In Global Competition 2004- 2006” Our economic competitiveness from company point of view”. The authors had analyzed a database generated on the basis of a questionnaire survey with a similar theme in 2005. Drawing the lessons from earlier researches and expanding the questionnaire, they now seek to find out how far receptiveness to electronic procurement has increased in Hungary and what other relations can be observed in responses concerning the interpretation of procurement organizations, the corporate aspects of procurement and electronic procurement. The new research project continues to differ from traditional solutions insofar as it does not intend to examine the penetration of corporate web pages, but, in contrast to earlier practice, it does want responders to provide information on their IT technology. The objectives are thus to understand how electronic procurement relates to corporate processes, purchaser-supplier relations and IT base, and to see what opportunities of increasing efficiency there are in electronic procurement and how far procurers and bidders are open to this at the current level of information society development in Hungary. Researchers have focused on the relation between electronic procurement and competitiveness since the early 2000s. What is debated is how electronic procurement influences procurement costs, and how government policies influence the relation between public procurement as a specially regulated procurement activity and electronic procurement. The relation between corporate competitiveness and the continually increasing means of electronic procurement is beyond doubt, evidenced by their research findings as well.

Felsőoktatási intézmények közbeszerzési sajátosságai = Public Procurement Characteristics of Higher Education Institutions

A kutatók a 2000-es évek eleje óta foglalkoznak a közbeszerzés és a versenyképesség kapcsolatával. A két terület közötti összefüggés egyértelmű, melyet vizsgálatainak is megerősítenek. Az Európai Unió tagállamainak jogalkotón folyamatos a nyomás, hogy a közbeszerzést különböző célokra használják fel. Mindez segít a közbeszerzés értelmezési körének kitágításában, de felhívja a figyelmet arra, hogy a jogalkotóknak elsősorban néhány kiemelt témára kell összpontosítaniuk, mint az innováció vagy a fenntarthatóság. A felsőoktatási intézmények közbeszerzésben betöltött szerepén túl fontosságuk a konzorciális beszerzések, a közbeszerzés képzés, továbbá az innovatív termékek, technológiák beszerzési gyakorlatában betöltött szerepük miatt kiemelkedő. Hazánkban ez az első alkalom, hogy feltárjuk kifejezetten nagy közbeszerző felsőoktatási intézményeik piaci szerepét és elemezzük közbeszerzési gyakorlatuk sajátosságait, viszonyítjuk eddigi kutatási eredményeinkhez. ______ Researchers have focused on the relation between public procurement and competitiveness since the early 2000s. The relation between corporate competitiveness and public procurement is beyond doubt, evidenced by our research findings. There is growing pressure on the legislators of EU Member States to use public procurement for certain purposes. This helps to widen the scope of procurement, but the regulators have to focus on several priorities like innovation and sustainability. The importance of universities in the development of consortial purchasing, purchasing education, procurement of innovative goods and technologies is unquestionable. It is the first opportunity in Hungary to analyze the role of large contracting authorities, participants of the higher educational market in public procurement and to explore the characteristics of their public procurement practice in order to make comparison between universities and other public procurement market players.

A hazai vállalatok elektronikus beszerzés iránti nyitottsága = E-procurement Responsiveness of the Hungarian Companies’

A Versenyképesség Kutató Központ 2004-ben a „Versenyben a világgal 1995-97.” kutatási program és az 1999-es vállalati versenyképességi kérdőíves felmérés hagyományait folytatva, valamint azok tapasztalataira építve egy hároméves kutatási programot kezdett el „Versenyben a világgal 2004-2006 − Gazdasági versenyképességünk vállalati nézőpontból” címmel. A kérdőíves felmérés nyomán létrejött adatbázist elemeztük hasonló témában 2005-ben. A korábbi eredményeken okulva, a kérdőív-elemzés kiterjesztésével azt kívántuk felmérni, hogy az elektronikus beszerzés iránti nyitottság növekedett-e hazánkban, illetve milyen egyéb összefüggések fedezhetők fel a beszerzési szervezet, a beszerzés vállalati kapcsolatai, valamint az elektronikus beszerzés értelmezésében az egyes válaszadóknál. A kutatás továbbra is eltér a hagyományos megoldásoktól, azaz nem kívánja vizsgálni a hazai vállalati honlapok elterjedtségét, azonban a korábbiaktól eltérően több információ-technológiával kapcsolatos információt kíván a válaszadóktól. A cél, tehát belső vállalati folyamatok, vevő-szállító kapcsolatok, az informatikai háttér elektronikus beszerzéssel való kapcsolatának feltárása és következtetéseink levonása volt annak érdekében, hogy megtudjuk milyen hatékonyságnövelési lehetőséget hordoz az elektronikus beszerzés és a hazai információs társadalmi fejlettség figyelembe vételével mennyire nyitottak erre a beszerzők és a pályázók egyaránt. Az elektronikus beszerzés és versenyképesség kapcsolata különösen a 2000-es éves eleje óta foglalkoztatja a kutatókat. Vita az elektronikus beszerzés beszerzési költségre gyakorolt hatásában, valamint a kormányzati politika által gyakorolt hatás jellegében van, melyet a közbeszerzés mint speciálisan szabályozott beszerzési tevékenység és az e-beszerzés kapcsolatára fejt ki. A vállalatok versenyképességének és az elektronikus beszerzés folyamatosan bővülő és fejlődő eszközrendszerének kapcsolata azonban nem kérdéses, ezt kutatási eredményeink is megerősítik. _________ The Competitiveness Research Center based on the experience of the „ In Global Competition 1995-1997” research programme and continuing the company competitiveness survey (1999) has begun a three-year research programme with the following title: „In Global Competition 2004-2006” Our economic competitiveness, company point of view”. We had analyzed a database generated on the basis of a questionnaire survey with a similar theme in 2005. Drawing the lessons from earlier researches and expanding the questionnaire examination, we now seek to find out how far receptiveness to electronic procurement has increased in Hungary and what other relations can be observed in responses concerning the interpretation of procurement organizations, the corporate aspects of procurement and electronic procurement. The new research project continues to differ from traditional solutions insofar as it does not intend to examine the currency of corporate web pages, but, in contrast to earlier practice, it does want responders to provide information on IT technology. The objectives are thus to understand how electronic procurement relates to corporate processes, purchaser-supplier relations and IT base, and to see what opportunities of increasing efficiency there are in electronic procurement and how far procurers and bidders are open to this at the level of information society development in Hungary. Researchers have focused on the relation between electronic procurement and competitiveness since the early 2000s. What is debated is how electronic procurement influences procurement costs, and how government policies influence the relation between public procurement as a specially regulated procurement activity and electronic procurement. The relation between corporate competitiveness and the continually increasing means of electronic procurement is beyond doubt, evidenced by our research findings.

Slow Isotope Turnover Rates and Low Discrimination Values in the American Alligator: Implications for Interpretation of Ectotherm Stable Isotope Data

Stable isotope analysis has become a standard ecological tool for elucidating feeding relationships of organisms and determining food web structure and connectivity. There remain important questions concerning rates at which stable isotope values are incorporated into tissues (turnover rates) and the change in isotope value between a tissue and a food source (discrimination values). These gaps in our understanding necessitate experimental studies to adequately interpret field data. Tissue turnover rates and discrimination values vary among species and have been investigated in a broad array of taxa. However, little attention has been paid to ectothermic top predators in this regard. We quantified the turnover rates and discrimination values for three tissues (scutes, red blood cells, and plasma) in American alligators (Alligator mississippiensis). Plasma turned over faster than scutes or red blood cells, but turnover rates of all three tissues were very slow in comparison to those in endothermic species. Alligator δ15N discrimination values were surprisingly low in comparison to those of other top predators and varied between experimental and control alligators. The variability of δ15N discrimination values highlights the difficulties in using δ15N to assign absolute and possibly even relative trophic levels in field studies. Our results suggest that interpreting stable isotope data based on parameter estimates from other species can be problematic and that large ectothermic tetrapod tissues may be characterized by unique stable isotope dynamics relative to species occupying lower trophic levels and endothermic tetrapods.

Seawater carbonate chemistry and biological processed during experiments with corals Porites sp. & Stylophora pistillata, 2010

Uptake of anthropogenic CO2 by the oceans is altering seawater chemistry with potentially serious consequences for coral reef ecosystems due to the reduction of seawater pH and aragonite saturation state (omega arag). The objectives of this long-term study were to investigate the viability of two ecologically important reef-building coral species, massive Porites sp. and Stylophora pistilata, exposed to high pCO2(or low pH) conditions and to observe possible changes in physiologically related parameters as well as skeletal isotopic composition. Fragments of Porites sp. and S. pistilata were kept for 6-14 months under controlled aquarium conditions characterized by normal and elevated pCO2 conditions, corresponding to pHTvalues of 8.09, 7.49, and 7.19, respectively. In contrast with shorter, and therefore more transient experiments, the long experimental timescale achieved in this study ensures complete equilibration and steady state with the experimental environment and guarantees that the data provide insights into viable and stably growing corals. During the experiments, all coral fragments survived and added new skeleton, even at seawater omega arag <1, implying that the coral skeleton is formed by mechanisms under strong biological control. Measurements of boron (B), carbon (C) and oxygen (O) isotopic composition of skeleton, C isotopic composition of coral tissue and symbiont zooxanthellae, along with physiological data (such as skeletal growth, tissue biomass, zooxanthellae cell density and chlorophyll concentration) allow for a direct comparison with corals living under normal conditions and sampled simultaneously. Skeletal growth and zooxanthellae density were found to decrease, whereas coral tissue biomass (measured as protein concentration) and zooxanthellae chlorophyll concentrations increased under high pCO2 (low pH) conditions. Both species showed similar trends of delta11B depletion and delta18O enrichment under reduced pH, whereas the delta13C results imply species-specific metabolic response to high pCO2 conditions. The skeletal delta11B values plot above seawater delta11B vs. pH borate fractionation curves calculated using either the theoretically derived deltaB value of 1.0194 (Kakihana et al., Bull. Chem. Soc. Jpn. 50(1977), 158) or the empirical deltaB value of 1.0272 (Klochko et al., EPSL 248 (2006), 261). However, the effective deltaB must be greater than 1.0200 in order to yield calculated coral skeletal delta11B values for pH conditions where omega arag >1. The delta11B vs. pH offset from the literature seawater delta11B vs. pH fractionation curves suggests a change in the ratio of skeletal material laid down during dark and light calcification and/or an internal pH regulation, presumably controlled by ion-transport enzymes. Finally, seawater pH significantly influences skeletal delta13C and delta18O. This must be taken into consideration when reconstructing paleo-environmental conditions from coral skeleton

(Table 3, Page 417) Table 3. The concentrations of Zn, Cu, Pb, Cd, Ni, Co, Ag, Mn and Fe in a soluble in 1M HCl fraction of ferromanganese nodules of Slupsk Furrow in the southern Baltic sea

The concentration of Zn, Cu, Pb, Cd, Ni, Co, Ag, Mn, Fe, Ca, Mg, K and Na in molluscs Macoma balthica, Mya arenaria, Cardium glaucum, Mytilus edulis and Astarte borealis from the southern Baltic was determined. The surface sediments and ferromanganese concretions associated with the molluscs were also analysed for concentration of these metals. Species- and region-dependent differences in the metal levels of the organisms were observed. The properties of molluscs analysed which have a tendency toward elevated biological tolerance of selected trace metals were specified. The interelement relationship between metal concentrations in the soft tissue and the shell was estimated and was discussed.

Proteomic analysis of coronary sinus serum reveals leucine-rich α2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure

BACKGROUND: Heart failure (HF) prevention strategies require biomarkers that identify disease manifestation. Increases in B-type natriuretic peptide (BNP) correlate with increased risk of cardiovascular events and HF development. We hypothesize that coronary sinus serum from a high BNP hypertensive population reflects an active pathological process and can be used for biomarker exploration. Our aim was to discover differentially expressed disease-associated proteins that identify patients with ventricular dysfunction and HF.

METHODS AND RESULTS: Coronary sinus serum from 11 asymptomatic, hypertensive patients underwent quantitative differential protein expression analysis by 2-dimensional difference gel electrophoresis. Proteins were identified using mass spectrometry and then studied by enzyme-linked immunosorbent assay in sera from 40 asymptomatic, hypertensive patients and 105 patients across the spectrum of ventricular dysfunction (32 asymptomatic left ventricular diastolic dysfunction, 26 diastolic HF, and 47 systolic HF patients). Leucine-rich α2-glycoprotein (LRG) was consistently overexpressed in high BNP serum. LRG levels correlate significantly with BNP in hypertensive, asymptomatic left ventricular diastolic dysfunction, diastolic HF, and systolic HF patient groups (P≤0.05). LRG levels were able to identify HF independent of BNP. LRG correlates with coronary sinus serum levels of tumor necrosis factor-α (P=0.009) and interleukin-6 (P=0.021). LRG is expressed in myocardial tissue and correlates with transforming growth factor-βR1 (P<0.001) and α-smooth muscle actin (P=0.025) expression.

CONCLUSIONS: LRG was identified as a serum biomarker that accurately identifies patients with HF. Multivariable modeling confirmed that LRG is a stronger identifier of HF than BNP and this is independent of age, sex, creatinine, ischemia, β-blocker therapy, and BNP.

An Ex Vivo Model for Studying Hepatic Schistosomiasis and the Effect of Released Protein from Dying Eggs

BACKGROUND: We report the use of an ex vivo precision cut liver slice (PCLS) mouse model for studying hepatic schistosomiasis. In this system, liver tissue is unfixed, unfrozen, and alive for maintenance in culture and subsequent molecular analysis.

METHODS AND FINDINGS: Using thick naive mouse liver tissue and sterile culture conditions, the addition of soluble egg antigen (SEA) derived from Schistosoma japonicum eggs, followed 4, 24 and 48 hrs time points. Tissue was collected for transcriptional analysis and supernatants collected to quantitate liver enzymes, cytokines and chemokines. No significant hepatotoxicity was demonstrated by supernatant liver enzymes due to the presence of SEA. A proinflammatory response was observed both at the transcriptional level and at the protein level by cytokine and chemokine bead assay. Key genes observed elevated transcription in response to the addition of SEA included: IL1-α and IL1-β, IL6, all associated with inflammation. The recruitment of antigen presenting cells was reflected in increases in transcription of CD40, CCL4 and CSF1. Indications of tissue remodeling were seen in elevated gene expression of various Matrix MetalloProteinases (MMP3, 9, 10, 13) and delayed increases in TIMP1. Collagen deposition was significantly reduced in the presence of SEA as shown in COL1A1 expression by qPCR after 24 hrs culture. Cytokine and chemokine analysis of the culture supernatants confirmed the elevation of proteins including IL6, CCL3, CCL4 and CXCL5.

CONCLUSIONS: This ex vivo model system for the synchronised delivery of parasite antigen to liver tissue provides an insight into the early phase of hepatic schistosomiasis, corresponding with the release of soluble proteins from dying schistosome eggs.

ARB: Phase II window of opportunity study of short-term preoperative treatment with enzalutamide in ER-positive and triple-negative breast cancer

The androgen receptor (AR) is expressed in 60-80% of breast cancers (BC) across all molecular phenotypes, with a higher incidence in oestrogen receptor positive (ER+) BC compared to ER negative tumours. In ER+ disease, AR-expression has been linked to endocrine resistance which might be reversed with combined treatment targeting ER and AR. In triple negative BCs (TNBC), preclinical and clinical investigations have described a subset of patients that express the AR and are sensitive to androgen blockade, providing a novel therapeutic target. Enzalutamide, a potent 2nd generation anti-androgen, has demonstrated substantial preclinical and clinical anti-tumour activity in AR+ breast cancer. Short-term preoperative window of opportunity studies are a validated strategy for novel treatments to provide proof-of-concept and define the most appropriate patient population by directly assessing treatment effects in tumour tissue before and after treatment. The ARB study aims to assess the anti-tumour effects of enzalutamide in early ER+ breast cancer and TNBC, to identify the optimal target population for further studies and to directly explore the biologic effects of enzalutamide on BC and stromal cells. Methods: ARB is an international, investigator sponsored WOO phase II study in women with newly diagnosed primary ER+ BC or AR+ TNBC of ≥ 1cm. The study has two cohorts. In the ER+ cohort, postmenopausal patients will be randomised 2:1 to receive either enzalutamide (160mg OD) plus exemestane (50mg OD) or exemestane (25mg OD). In the TNBC cohort, AR+ will receive single agent treatment with enzalutamide (160mg OD). Study treatment is planned for 15–29 days, followed by surgery or neo-adjuvant therapy. Tissue and blood samples are collected before treatment and on the last day of study treatment. The primary endpoint is inhibition of tumour-cell proliferation, as measured by change in Ki67 expression, determined centrally by 2 investigators. Secondary endpoints include induction of apoptosis (Caspase3), circulating hormone levels and safety. ARB aims to recruit ≈235 patients from ≈40 sites in the UK, Germany, Spain and USA. The study is open to recruitment.

A phase I pharmacokinetic and pharmacodynamic study of the oral mitogen-activated protein kinase kinase (MEK) inhibitor, WX-554, in patients with advanced solid tumours

Purpose: We performed a multi-centre phase I study to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the orally available small molecule mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, WX-554, and to determine the optimal biological dose for subsequent trials.
Experimental design: Patients with treatment-refractory, advanced solid tumours, with adequate performance status and organ function were recruited to a dose-escalation study in a standard 3 + 3 design. The starting dose was 25 mg orally once weekly with toxicity, PK and PD guided dose-escalation with potential to explore alternative schedules.
Results: Forty-one patients with advanced solid tumours refractory to standard therapies and with adequate organ function were recruited in eight cohorts up to doses of 150 mg once weekly and 75 mg twice weekly. No dose-limiting toxicities were observed during the study, and a maximum tolerated dose (MTD) was not established. The highest dose cohorts demonstrated sustained inhibition of extracellular signal-regulated kinase (ERK) phosphorylation in peripheral blood mononuclear cells following ex-vivo phorbol 12-myristate 13-acetate stimulation. There was a decrease of 70 ± 26% in mean phosphorylated (p)ERK in C1 day 8 tumour biopsies when compared with pre-treatment tumour levels in the 75 mg twice a week cohort. Prolonged stable disease (>6 months) was seen in two patients, one with cervical cancer and one with ampullary carcinoma.
Conclusions: WX-554 was well tolerated, and an optimal biological dose was established for further investigation in either a once or twice weekly regimens. The recommended phase 2 dose is 75 mg twice weekly.

Perturbations in Blood Phosphatidylcholine and Sphingomyelin Fatty Acid Composition in a Sample Population of Cigarette Smokers

Docosahexaenoic (DHA) and arachidonic acids (AA) are polyunsaturated fatty acids (PUFAs), major components of brain tissue and neural systems, and the precursors of a number of biologically active metabolites with functions in inflammation resolution, neuroprotection and other actions. As PUFAs are highly susceptible to peroxidation, we hypothesised whether cigarette smokers would present altered PUFAs levels in plasma and erythrocyte phospholipids. Adult males from Indian, Sri-Lankan or Bangladeshi genetic backgrounds who reported smoking between 20 and 60 cigarettes per week were recruited. The control group consisted of matched non-smokers. A blood sample was taken, plasma and erythrocyte total lipids were extracted, phospholipids were separated by thin layer chromatography, and the fatty acid content analysed by gas chromatography. In smokers, dihomo-gamma-linolenic acid, the AA precursor, was significantly reduced in plasma and erythrocyte phosphatidylcholine. AA and DHA were significantly reduced in erythrocyte sphingomyelin. Relatively short term smoking has affected the fatty acid composition of plasma and erythrocyte phospholipids with functions in neural tissue composition, cell signalling, cell growth, intracellular trafficking, neuroprotection and inflammation, in a relatively young population. As lipid peroxidation is pivotal in the pathogenesis of atherosclerosis and neurodegenerative diseases such as Alzheimer disease, early effects of smoking may be relevant for the development of such conditions.

Exercise Training in Rats Impairs the Replenishment of White Adipose Tissue after Partial Lipectomy

The aim of this study was to evaluate the effect of exercise training on the metabolism of rats following the partial removal of fat pads. Three-month-old male Wistar rats were subjected to the partial removal (L) of retroperitoneal white adipose tissue (RET) and epididymal white adipose tissue (EPI), or a sham operation (Sh). Seven days after surgery, both sets of rats were subdivided into exercised (LE or ShE) (swimming 90 min/day, 5 days/week, 6 weeks) and sedentary (LS or ShS) groups. Partial removal of the fat pads increased the lipogenesis rates in both the RET and EPI and decreased the weight and lypolysis rate of the EPI, while the RET weight was not significantly affected by lipectomy. In both lipectomized and sham-operated groups, exercise training caused a reduction in carcass lipid content, food intake, RET and EPI weights, and RET lipogenesis rate. On the other hand, the exercise training increased the percentage of diet-derived lipid accumulation in both tissues, either in sham and lipectomized rats. These results confirmed that regrowth is not uniform and depends on the particular fat pad that is excised. They also demonstrated that exercise training following the partial removal of fat pads modified adipose tissue metabolism, impaired the replenishment of adipose tissue, and decrease body adiposity.