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Objective: Changes in lipid profiles, Lp(a) lipoprotein, and acute phase reactants are associated with early atherosclerosis in rheumatoid arthritis (RA). The associations of Lp(a) levels with atherosclerotic disorders, diabetes, RA, and renal diseases suggest that Lp(a) might be involved in autoimmune reactions. Methods: Eighty-seven women with RA diagnosed according to American Rheumatism Association criteria (mean age 45.4±9.4 years) were recruited and 50 healthy women (mean age 44±10.7 years) included as a control group. Serum Lp(a), total cholesterol (TC), triglyceride (TG), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and C-reactive protein levels were analyzed. Results: In the RA and C groups, serum Lp(a) levels were 39.2±20.6 mg/dl and 14.8±9.7 mg/dl, respectively (P0.05), TG levels were 124.5±50.1 mg/dl and 94.6±24.9 mg/dl (P0.05). While serum CRP levels showed a positive correlation with Lp(a), they correlated negatively with HDL-C levels (r=0.83 and P

In the present study, both the effects of intracerebroventricular (i.c.v.) injection of cytidine-5'-diphosphate choline (CDP-choline) on plasma vasopressin levels and the choline involvement of these effects were investigated. I.c.v. administration of CDP-choline (0.5, 1.0 and 2.0 micromol) increased plasma vasopressin levels dose- and time-dependently. I.c.v. injection of equimolar dose of choline (1 micromol) produced similar vasopressin response. However equimolar dose of cytidine (1 micromol; i.c.v.), the other hydrolysis product of CDP-choline, did not affect plasma vasopressin levels. Pretreatment of rats with hemicholinium-3, neuronal high affinity choline uptake inhibitor (20 microg; i.c.v.) blocked the vasopressin response to i.c.v. CDP-choline (1 micromol). Pretreatment of rats with mecamylamine (50 microg; i.c.v.), a nonselective nicotinic receptor antagonist, abolished the increase in plasma vasopressin induced by CDP-choline while atropine (10 microg; i.c.v.), nonselective muscarinic receptor antagonist, failed to change the response. In conclusion, intracerebroventricularly injected CDP-choline can increase plasma vasopressin levels by activating central nicotinic cholinergic receptors through the activation of presynaptic cholinergic mechanisms.

The T cell receptor excision DNA circle (TREC) level is an independent predictor of HIV-1 disease prognosis. We studied the temporal changes in TREC levels prior to and after highly active antiretroviral therapy (HAART) in a cohort of 131 Greek men with hemophilia who were followed up for up to 20 years since seroconversion (SC). TREC levels were determined in all available cryopreserved samples of peripheral blood mononuclear cells (PBMCs) using a multiplex real-time polymerase chain reaction (PCR) assay. Trends in log 10 TREC values were described using random effects models. Prior to HAART initiation TREC levels tended to decrease over time (mean rate of drop 19% per year 95% CI: 16-22%). Initial TREC values were higher with younger age at SC, but the subsequent rate of drop did not differ significantly by age at SC. There was a monotonic relationship between baseline HIV-RNA levels and TREC slopes with steeper slopes at higher levels of HIV-RNA. The TREC slopes differed significantly by clinical outcome being steeper in subjects who progressed to AIDS sooner. After HAART initiation, TREC values tended to increase on average by 35% per year (95% CI: -7-94%) but the increase was evident only in subjects with a pre-HAART CD4 count below 80 cells/μl. TREC values, which likely represent a simple indicator of naive T-lymphocyte reserve, may be a clinically useful marker for long-term prognosis of HTV-1 infection and for immune reconstitution after successful HAART. 20 47 54 Cited By :12

Although there is a general consensus concerning the lower risk for cardiovascular disease in moderate drinkers, the mechanisms responsible for the cardioprotective effect of red wine remain unknown. It has been proposed that increased serum paraoxonase activity may be a mechanism of action underlying reduced cardiovascular disease risk in moderate drinkers, since paraoxonase inhibits lipoprotein oxidation. The aim of this study was to investigate the effects of red wine consumption on serum paraoxonase/arylesterase activities and on lipoprotein oxidizability in healthy-men. Fourteen healthy-men were included in the study. The subjects consumed 0.375 g alcohol / kg body weight for 3 weeks. Paraoxonase and arylesterase activities were studied spectrophotometrically. Oxidizability of apolipoprotein B-containing lipoproteins were determined, after separating them with precipitation method, by incubating with copper-sulfate. Paraoxonase activity did not change, however arylesterase activity significantly decreased after red wine consumption (P < 0.01). There was a reduced susceptibility of apolipoprotein B-containing lipoproteins to copper-sulfate induced oxidation after red wine consumption (P < 0.01). Our results support that red wine protects lipoproteins against oxidation, however there was not any significant change in serum paraoxonase activity after red wine consumption.

(See the Major Article by Gwamaka et al, on pages 1137–44.) It is noteworthy that micronutrient malnutrition, including iron (Fe) deficiency (ID), is usually highly prevalent in malaria endemic areas. Since the 1960s, it was believed that micronutrient deficiencies are associated with increased morbidity and mortality from malaria and that malaria, in turn, may contribute to poor nutritional status, thus reflecting the classic vicious cycle of malnutrition and infection [1]. Worldwide, ID (usually defined as a ferritin level

Objective: The objective of the study was to compare pro-hepcidin, hemoglobin (Hb) concentration, hematocrit (Hct), C-reactive protein (CRP), IL-6 and iron status parameters in preeclamptic (PE) and healthy pregnant women, and to examine the relationship between serum pro-hepcidin levels and iron parameters of preeclampsia (PE). Methods: In a prospective controlled study, we collected serum from women with normal pregnancy (n=37) and from women with PE (n=30) at the Department of Obstetrics and Gynecology at Turgut Ozal University between February 2010 and January 2013. Pro-hepcidin, hemoglobin (Hb) concentration, hematocrit (Hct), CRP, IL-6 and iron status parameters were measured in all patients and compared between groups. Results: Levels of serum prohepcidin in PE and control groups were similar and amount 69.4±19.7 and 71.9±22.1ng/ml, respectively. The difference was not statistically significant (p: 0.694). On the other hand, the study group had a statistically lower iron binding capacity (IBC), total iron binding capacity, transferin, total protein, albumin levels (p

This study was designed to determine serum human leukocyte antigen-G (HLA-G) levels and establish whether serum HLA-G level is related with insulin resistance, oxidative stress, dyslipidemia and ovarian hyperandrogenism in women with polycystic ovary syndrome (PCOS). Twenty-five patients with PCOS and 23 healthy control women were evaluated in this study. Serum HLA-G, lipid fractions, glucose, insulin, malondialdehyde (MDA), glutathione (GSH), white blood cell (WBC), sex hormone-binding globulin (SHBG) and other hormone (gonadotropins and androgens) levels were measured. The estimate of insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Serum luteinizing hormone (LH), total testosterone, fasting insulin, WBC levels and LH/follicle-stimulating hormone (FSH) ratio, free androgen index (FAI) and HOMA-IR values were significantly higher in patients with PCOS compared with healthy women. However, the women with PCOS had considerably lower serum FSH, SHBG, MDA, GSH and HLA-G levels than healthy subjects. HLA-G was inversely related with HOMA-IR, FAI, LH/FSH ratio and WBC, but positively with high-density lipoprotein cholesterol. Decreased serum HLA-G level may be related with insulin resistance, ovarian hyperandrogenism and oxidative stress in women with PCOS. Nevertheless, the exact role of HLA-G in the pathogenesis of the disease remains to be elucidated. © 2014 Informa UK Ltd.

The early diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI) is very important for treatment research and patient care purposes. Few biomarkers are currently considered in clinical settings, and their use is still optional. The objective of this work was to determine whether multimodal and nonpreviously AD associated features could improve the classification accuracy between AD, MCI, and healthy controls, which may impact future AD biomarkers. For this, Alzheimer's Disease Neuroimaging Initiative database was mined for case-control candidates. At least 652 baseline features extracted from MRI and PET analyses, biological samples, and clinical data up to February 2014 were used. A feature selection methodology that includes a genetic algorithm search coupled to a logistic regression classifier and forward and backward selection strategies was used to explore combinations of features. This generated diagnostic models with sizes ranging from 3 to 8, including well documented AD biomarkers, as well as unexplored image, biochemical, and clinical features. Accuracies of 0.85, 0.79, and 0.80 were achieved for HC-AD, HC-MCI, and MCI-AD classifications, respectively, when evaluated using a blind test set. In conclusion, a set of features provided additional and independent information to well-established AD biomarkers, aiding in the classification of MCI and AD. © 2015 Antonio Martínez-Torteya et al.

Background: It has been suggested that off-pump coronaryartery bypass grafting (CABG) surgery reduces myocardialischemia-reperfusion injury, postoperative systemicinflammatory response, and oxidative stress. The aim of thisstudy was to measure serum malondialdehyde (MDA), highsensitivityC-reactive protein (hs-CRP), M30, and M65 levelsand to investigate the relationship between M30 levels andoxidative stress and inflammation in patients undergoing onandoff-pump CABG surgery.Methods: Fifty patients were randomly assigned to onpumpor off-pump CABG surgery (25 patients off-pump and25 on-pump CABG surgery), and blood samples were collectedprior to surgery, and 30 minutes, 60 minutes, 6 hours,and 24 hours after CABG surgery.Results: Compared to the on-pump group, serum MDAlevels at 30 minutes, 60 minutes, 6 hours, and 24 hours afterthe CABG surgery were significantly lower in the off-pumpgroup (P = .001, P = .001, P = .001, and P = .001, respectively).Serum M30 levels were found to be elevated in both groups,returning to baseline at 24 hours. When compared to baseline,the hs-CRP level reached its peak at 24 hours at 13.28 ±5.32 mg/dL in the on-pump group, and 15.44 ± 4.02 mg/dLin the off-pump group.Conclusion: CABG surgery is associated with an increasein inflammatory markers and serum M30 levels, indicatingepithelial/endothelial apoptosis in the early period.

Simavli, Huseyin/0000-0003-1657-9099 WOS: 000374819800014 PubMed: 25264991 Purpose: Omentin, a member of the adipocytokines family, is derived from adipose tissue and a lower level of serum omentin is considered as a metabolic risk factor. The aim of the present study is to evaluate the serum levels of omentin in patients with pseudoexfoliation syndrome (PES). Materials and Methods: Patients without any systemic or ocular disease other than PES were included in the study. Age-matched and sex-matched healthy volunteers without PES were accepted as a control group. After detailed ophthalmologic examination, blood samples were obtained from a forearm vein. Serum levels of omentin were determined by the method of enzyme-linked immunosorbent assay. Results: The mean age of the PES group (12 females, 12 males, n = 24) was 75.2 +/- 8.4 years, and the control group (10 females, 10 males, n = 20) was 75 +/- 6.7 years. There was no difference between the groups in terms of age (P = 0.93) and sex (P = 0.9). The mean serum levels of omentin in the PES group were 801.5 +/- 317.1 ng/mL and in the control group were 1150.1 +/- 584.1 ng/mL. The mean serum omentin levels were significantly lower in patients with PES (P = 0.016). Conclusion: Lower levels of serum omentin in patients with PES compared with healthy subjects may support the theory of systemic nature of the disease.

Cellular therapy for end-stage liver failures using human mesenchymal stem cells (hMSCs)-derived hepatocytes is a potential alternative to liver transplantation. Hepatic trans-differentiation of hMSCs is routinely accomplished by induction with commercially available recombinant growth factors, which is of limited clinical applications. In the present study, we have evaluated the potential of sera from cardiac-failure-associated congestive/ischemic liver patients for hepatic trans-differentiation of hMSCs. Results from such experiments were confirmed through morphological changes and expression of hepatocyte-specific markers at molecular and cellular level. Furthermore, the process of mesenchymal-to-epithelial transition during hepatic trans-differentiation of hMSCs was confirmed by elevated expression of E-Cadherin and down-regulation of Snail. The functionality of hMSCs-derived hepatocytes was validated by various liver function tests such as albumin synthesis, urea release, glycogen accumulation and presence of a drug inducible cytochrome P450 system. Based on these findings, we conclude that sera from congestive/ischemic liver during cardiac failure support a liver specific microenvironment for effective hepatic trans-differentiation of hMSCs in vitro.

Background: A nationwide multicenter study was organized to establish reference intervals (RIs) in the Turkish population for 25 commonly tested biochemical analytes and to explore sources of variation in reference values, including regionality. Methods: Blood samples were collected nationwide in 28 laboratories from the seven regions (?400 samples/region, 3066 in all). The sera were collectively analyzed in Uludag University in Bursa using Abbott reagents and analyzer. Reference materials were used for standardization of test results. After secondary exclusion using the latent abnormal values exclusion method, RIs were derived by a parametric method employing the modified Box-Cox formula and compared with the RIs by the non-parametric method. Three-level nested ANOVA was used to evaluate variations among sexes, ages and regions. Associations between test results and age, body mass index (BMI) and region were determined by multiple regression analysis (MRA). Results: By ANOVA, differences of reference values among seven regions were significant in none of the 25 analytes. Significant sex-related and age-related differences were observed for 10 and seven analytes, respectively. MRA revealed BMI-related changes in results for uric acid, glucose, triglycerides, high-density lipoprotein (HDL)-cholesterol, alanine aminotransferase, and ?-glutamyltransferase. Their RIs were thus derived by applying stricter criteria excluding individuals with BMI >28 kg/m2. Ranges of RIs by non-parametric method were wider than those by parametric method especially for those analytes affected by BMI. Conclusions: With the lack of regional differences and the well-standardized status of test results, the RIs derived from this nationwide study can be used for the entire Turkish population. © by De Gruyter 2014., Applied Scientific Research Fund: :24256003:2012-2014 Japan Society for the Promotion of Science, Acknowledgments: This study was supported by Research Fund of Uludag Universty (UAP(T)-2011/48), IFCC C-RIDL, Scientific Research Fund (No:24256003:2012-2014) provided by the Japan Society for the Promotion of Science, Abbott Diagnostics and Becton Dickinson. We had invaluable input from the IFCC C-RIDL and the Turkish National Biochemical Association. We are very grateful to Uludag University Central Laboratory, We are thankful to David Ambruster from Abbott Diagnostics for his kind cooperation to realize this study. The final manuscript was edited with generous support by Prof. A. Myron Johnson.

The authors discuss in this paper the role of inflammatory, anti-inflammatory, and regulatory cytokines in patients infected with different species ofLeishmaniain Amazonas State, Brazil. A comparative analysis was made of serum concentrations of these cytokines in the peripheral blood of 33 patients infected with cutaneous leishmaniasis. The isolates were identified asLeishmania guyanensis,L. naiffi, andL. amazonensis. Most (64%) of the patients were male ranging in age from 18 to 58 years. Protein expression profiles of IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, and IL-17 cytokines were shown to vary significantly between infected and noninfected (control group) individuals and according to theLeishmaniaspecies. Infection caused byL. guyanensisaccounted for 73% of the cases and patients with this parasite also showed higher concentrations of IL-2, IFN-γ, IL-4, and IL-17 when compared to infection byL. amazonensis. Patients with infection caused byL. naiffishowed higher concentration of the cytokines analyzed when compared to uninfected patients; however, there was no statistically significant difference with the other species analyzed.

Primary mesenchymal tumors of the colon are extremely rare tumors among soft tissue sarcomas. These tumors are more aggressive and have poorer prognosis than adenocarcinoma of the colon. Here, we presented 3 cases of primary mesenchymal tumors of the colon. Their histopathological diagnoses are leiomyosarcoma, pleomorphic liposarcoma, and desmoplastic small round cell tumor, respectively. The rarity of primary mesenchymal tumors of the colon makes it difficult to approach the treatment and predict the prognosis of these rare tumors. © 2014 by The Turkish Society of Gastroenterology.

Several studies have demonstrated an association between polymorphisms in the insulin-like growth factor-1 (IGF-1) gene and IGF-1 serum levels. IGF-1 levels have been associated with cognitive functioning in older persons and growth hormone deficient patients. The present study investigates whether IGF-1 polymorphisms, IGF-1 levels, and cognition are interconnected in healthy adults. Data of 277 participants (mean age: 42.4 years) of the Amsterdam Growth and Health Longitudinal Study on IGF-1 promoter polymorphisms, IGF-1 serum level, spatial working memory (SWM), paired associate learning (PAL), and IQ tests were analyzed. (M)ANOVAs were applied to confirm the associations between IGF-1 polymorphisms and IGF-1 levels and between IGF-1 levels and cognition. Three groups were distinguished based on specific IGF-1 polymorphism alleles: a homozygote 192 bp/192 bp genotype, a heterozygote 192 bp/x genotype, and a noncarrier x/x genotype. Although different IGF-1 levels were found for the three genotypes, performance on all cognitive tasks and IQ measures was similar. Despite the associations between IGF-1 polymorphisms and IGF-1 levels, no association was found between cognition and IGF-1 levels. It seems that IGF-1 does not play a role in the cognitive performance of healthy middle-aged adults. Possible, IGF-1 fulfills a more developmental and protective role in cognition which becomes apparent during childhood, old-age, or disease. © 2014 Carmilla M. M. Licht et al.

Several studies have demonstrated an association between polymorphisms in the insulin-like growth factor-1 (IGF-1) gene and IGF-1 serum levels. IGF-1 levels have been associated with cognitive functioning in older persons and growth hormone deficient patients. The present study investigates whether IGF-1 polymorphisms, IGF-1 levels, and cognition are interconnected in healthy adults. Data of 277 participants (mean age: 42.4 years) of the Amsterdam Growth and Health Longitudinal Study on IGF-1 promoter polymorphisms, IGF-1 serum level, spatial working memory (SWM), paired associate learning (PAL), and IQ tests were analyzed. (M)ANOVAs were applied to confirm the associations between IGF-1 polymorphisms and IGF-1 levels and between IGF-1 levels and cognition. Three groups were distinguished based on specific IGF-1 polymorphism alleles: a homozygote 192 bp/192 bp genotype, a heterozygote 192 bp/x genotype, and a noncarrier x/x genotype. Although different IGF-1 levels were found for the three genotypes, performance on all cognitive tasks and IQ measures was similar. Despite the associations between IGF-1 polymorphisms and IGF-1 levels, no association was found between cognition and IGF-1 levels. It seems that IGF-1 does not play a role in the cognitive performance of healthy middle-aged adults. Possible, IGF-1 fulfills a more developmental and protective role in cognition which becomes apparent during childhood, old-age, or disease. © 2014 Carmilla M. M. Licht et al.

Background and Aims: It is unclear whether changes in plasma levels of inflammatory markers could explain the link between ischemia and slow coronary flow (SCF). The aim of the study was to evaluate the plasma levels of high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and myeloperoxidase (MPO) during myocardial perfusion imaging (MPI) in SCF patients. Methods: The study population consisted of 53 SCF patients and 30 controls. Coronary flow rates were documented by TIMI frame count (TFC). Plasma levels of hsCRP, IL-6, MPO, and MPI were obtained in all participants. Results: hsCRP, IL-6 and MPO levels of SCF patients were higher than controls (hsCRP: 4.7 ± 2.5 vs. 1.7 ± 1.1 mg/L, p

Yazıcı, Alper (Balikesir Author), Context: Central serous chorioretinopathy (CSCR) is a poorly understood disease and the choroidal circulation abnormality induced by the plasminogen activator inhibitor type 1 (PAI-1) seems to be associated with the pathogenesis. There are many reports indicating that 4G/5G polymorphism of the PAI-1 gene is a risk factor for several diseases related to the elevated serum levels of PAI-1. Objective: To evaluate the 4G/5G polymorphism of the PAI-1 gene and its association with serum levels of PAI-1 in acute CSCR patients. Materials and methods: Sixty CSCR patients and 50 healthy control patients were included. The PAI-1 4G/5G was genotyped using the polymerase chain reaction-restriction technique. Serum PAI-1 level was measured using enzyme-linked immunosorbent assay. Demographic data consisting of age, sex, body mass index (BMI) as well as genotype disturbances and serum PAI-1 levels were compared between the groups. Statistical significance for differences in the serum PAI-1 levels of each group with different genotypes was also analyzed. Results: The CSCR group consisted of 40 male (66.7%) and 20 female (33.3%) patients with a mean age of 46.7 +/- 8.39 years. The control group consisted of 32 male (64%) and 18 female (36%) healthy subjects with a mean age of 45.8 +/- 8.39 years. There was no statistically significant difference between the groups in terms of age, sex and BMI. In the CSCR group the genotype frequencies were 4G/4G: 30% (n = 18), 4G/5G: 50% (n = 30), 5G/5G: 20% (n = 12) and in the control group genotype frequencies were 34% (n = 17), 42% (n = 21) and 24% (n = 12), respectively. There was no statistically significant difference in the distribution of genotypes among the groups (chi-squared, p = 0.70). The CSCR group had a significantly higher serum PAI-1 concentration than the control group (p = 0.001). In both groups the mean plasma PAI-1 concentration did not vary significantly among the different genotypes (p > 0.05). Discussion and conclusion: Although our results demonstrated that the patients with acute CSCR have higher serum PAI-1 concentrations than the controls, no significant difference was found in the genotype disturbances of the PAI-1 gene between the groups. The current study indicates that 4G/5G polymorphism in the promoter of the PAI-1 gene cannot be considered a risk factor for the elevated serum PAI-1 levels and consequent development of CSCR.

OBJECTIVE: Studies in animals have provided key evidence that antagonizing TNF-alpha is a viable therapeutic strategy for diffuse severe brain injury. This study is planned to prevent post-traumatic secondary tissue damages in rat diffuse severe brain injury model, which is induced by alone or combined administration of Etanercept and lithium chloride (LiCl). MATERIALS AND METHODS: Male SpragueDawley rats were used in the current study. Rats were divided into 5 groups. Trauma was not induced and treatment was not applied to rats of Sham group. For rats of Trauma+Saline group, saline 0.9% was administered via intraperitoneal (i.p.) route at dose of 1 mg/100 g body weight 1 hour after trauma. For rats of Trauma+Etanercept group, Etanercept was administered via i.p. route at dose of 5 mg/kg body weight 1 hour after trauma. For rats of Trauma+LiCl group, LiCl was administered via i.p. route at dose of 50 mg/kg body weight 1 hour after trauma. For rats of Etanercept+LiCl group, Etanercept and LiCl were administered via i.p. route at dose of 5 mg/kg body weight and 50 mg/kg body weight, respectively, 1 hour after trauma. Serum glial fibrillary acidic protein (GFAP) and Tau levels were analyzed with ELISA. For analyses H&E, TUNEL, GFAP and TNF-alpha staining methods were used. RESULTS: We demonstrate that Etanercept treatment reduced the TBI-induced brain tissues alteration, reduced the expression of TNF-alpha and improve edema and axonal swelling. We observed a significant decrease in TNF-alpha and GFAP positivity after LiCl was administered. CONCLUSIONS: The findings obtained in this study suggest that the combination therapy with Etanercept and LiCl decreased neuronal degeneration and alleviated secondary tissue damage in post-traumatic period.

Background The purpose of this study was to examine the effect of a 5-km run on blood leucocytes, acute-phase proteins and cytokines. In addition, cytokines were measured in the supernatants from whole-blood cell cultures incubated with lipolysaccharide (LPS).Methods Ten healthy, recreational trained, athletes (three women, seven men) volunteered for this investigation. Samples were drawn just before, immediately after and at 3 h, at 24h and at 48h after the race.Results Exercise induced a transient leucocytosis (P = 0.0002) and a mild acute-phase reaction with increase in plasma C-reactive protein (CRP) (P = 0.0115) but nor in serum amyloid A (SAA) concentrations. Although plasma interleukin 6 (IL-6) was undetectable and soluble interleukin-1 receptor type II (IL-1sRII) remained unchanged, interleukin-1 receptor antagonist (IL-1ra) concentrations were elevated directly after the race with a further increase at 3h (PConclusion These results suggest that a 5-km run elicits both the production of acute-phase mediators (leucocytosis and elevation of CRP) and anti-inflammatory counter-regulation as judged by the increase in circulating concentrations of IL-1ra, sTNFr p55, and sTNFrp75 and down-regulation of LPS-stimulated TNF-a! production.

Early diagnosis of hepatocellullar carcinoma (HCC) remains a challenge. The current practice of serum alpha-fetoprotein (AFP) measurement is inadequate. Here we utilized a proteomic approach to identify novel serum biomarkers for distinguishing HCC patients from non-cancer controls. We profiled the serum proteins in a group of 58 resectable HCC patients and 11 non-HCC chronic hepatitis B (HBV) carrier samples from the Singapore General Hospital (SGH) using the RayBio® L-Series 507 Antibody Array and found 113 serum markers that were significantly modulated between HCC and control groups. Selected potential biomarkers from this list were quantified using a multiplex sandwich enzyme-linked immunosorbent assay (ELISA) array in an expanded SGH cohort (126 resectable HCC patients and 115 non-HCC chronic HBV carriers (NC group)), confirming that serum prolactin and monocyte chemoattractant protein-1 (MCP-1) were significantly upregulated in HCC patients. This finding of serum MCP-1 elevation in HCC patients was validated in a separate cohort of serum samples from the Mochtar Riady Institute for Nanotechnology, Indonesia (98 resectable HCC, 101 chronic hepatitis B patients and 100 asymptomatic HBV/HCV carriers) by sandwich ELISA. MCP-1 and prolactin levels were found to correlate with AFP, while MCP-1 also correlated with disease stage. Subsequent receiver operating characteristic (ROC) analysis of AFP, prolactin and MCP-1 in the SGH cohort and comparing their area under the ROC curve (AUC) indicated that neither prolactin nor MCP-1 on their own performed better than AFP. However, the combination of AFP+MCP-1 (AUC, 0.974) had significantly superior discriminative ability than AFP alone (AUC, 0.942; p

BACKGROUND: Bronchopulmonary dysplasia (BPD) is an important cause of morbidity. The aim of this study was to evaluate the preventive effect of cytidine 5'-diphosphocholine (CDP-choline) treatment on hyperoxic lung injury in a neonatal rat model. METHODS: A total of 30 newborn pups were divided into control, hyperoxia, and hyperoxia + CDP-choline groups. After birth, pups in the control group were kept in room air and received saline injections, whereas those in hyperoxia and hyperoxia + CDP-choline groups were exposed to 95% O-2 and received daily injections of saline and CDP-choline throughout postnatal day 10, respectively. Histopathological scoring, radial alveolar count, lamellar body membrane protein expression, fibrosis, proinflammatory cytokine levels, lung tissue and bronchoalveolar lavage (BAL) fluid phospholipid content, and apoptosis were evaluated. RESULTS: Hyperoxia-induced severe lung damage was reduced significantly by CDP-choline treatment. Radial alveolar count and lamellar body membrane protein expression were significantly recovered, and the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive cells, active caspase-3 expression, and tissue proinflammatory cytokine levels were decreased by CDP-choline administration. Lung tissue and BAL phospholipid contents showed significant increases after COP-choline administration. CONCLUSION: These data show that COP-choline ameliorates hyperoxic lung injury in a neonatal rat model. It may therefore be suggested that CDP-choline may be a novel therapeutic option for the prevention of BPD.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:28:40Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:42:55Z : No. of bitstreams: 1 2-s2.0-84874805360.pdf: 1394575 bytes, checksum: 573bfb2af4add411de8aa3a8efac6c77 (MD5) Made available in DSpace on 2014-05-27T11:28:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-03-15 Background: Intestinal ischemia/reperfusion (IR) injury is a serious and triggering event in the development of remote organ dysfunction, from which the lung is the main target. This condition is characterized by intense neutrophil recruitment, increased microvascular permeability. Intestinal IR is also responsible for induction of adult respiratory distress syndrome, the most serious and life-threatening form of acute lung injury. The purpose of this study was to investigate the effect of annexin-A1 protein as an endogenous regulator of the organ remote injury induced by intestinal ischemia/reperfusion. Male C57bl/6 mice were subjected to intestinal ischemia, induced by 45 min occlusion of the superior mesenteric artery, followed by reperfusion. Results: The intestinal ischemia/reperfusion evoked a high intensity lung inflammation as indicated by the number of neutrophils as compared to control group. Treatment with annexin-A1 peptidomimetic Ac2-26, reduced the number of neutrophils in the lung tissue and increased its number in the blood vessels, which suggests a regulatory effect of the peptide Ac2-26 in the neutrophil migration. Moreover, the peptide Ac2-26 treatment was associated with higher levels of plasma IL-10. Conclusion: Our data suggest that the annexin-A1 peptidomimetic Ac2-26 treatment has a regulatory and protective effect in the intestinal ischemia/reperfusion by attenuation of the leukocyte migration to the lung and induction of the anti-inflammatory cytokine IL-10 release into the plasma. The anti-inflammatory action of annexin-A1 and its peptidomimetic described here may serve as a basis for future therapeutic approach in mitigating inflammatory processes due to intestinal ischemia/reperfusion. © 2013 Guido et al.; licensee BioMed Central Ltd. Department of Biology; Institute of Biosciences Letras e Ciências Exatas (IBILCE) São Paulo State University (UNESP), São José do Rio Preto, SP 15054-000 Department of Pharmacology Institute of Biomedical Sciences (ICB) University of São Paulo (USP), São Paulo, 05508-900 Department of Basic Science in Health Faculty of Medicine (FM) Federal University of Mato Grosso (UFMT), Mato Grosso, MT 78060-900 Department of Biology; Institute of Biosciences Letras e Ciências Exatas (IBILCE) São Paulo State University (UNESP), São José do Rio Preto, SP 15054-000

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:28:33Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:32:18Z : No. of bitstreams: 1 2-s2.0-84874511518.pdf: 447094 bytes, checksum: b79744f190efab28202a9a9e0a1d266c (MD5) Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:28:33Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:32:18Z : No. of bitstreams: 1 2-s2.0-84874511518.pdf: 447094 bytes, checksum: b79744f190efab28202a9a9e0a1d266c (MD5) Made available in DSpace on 2014-05-27T11:28:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-28 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:28:33Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:32:18Z : No. of bitstreams: 1 2-s2.0-84874511518.pdf: 447094 bytes, checksum: b79744f190efab28202a9a9e0a1d266c (MD5) Made available in DSpace on 2014-05-27T11:28:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-28 Made available in DSpace on 2014-05-27T11:28:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-28 Made available in DSpace on 2014-05-27T11:28:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-28 This study was designed to determine the genotoxicity of a supraphysiological dose of triiodothyronine (T3) in both obese and calorie-restricted obese animals. Fifty male Wistar rats were randomly assigned to one of the two following groups: control (C; n = 10) and obese (OB; n = 40). The C group received standard food, whereas the OB group was fed a hypercaloric diet for 20 weeks. After this period, half of the OB animals (n = 20) were subjected to a 25%-calorie restriction of standard diet for 8 weeks forming thus a new group (OR), whereas the remaining OB animals were kept on the initial hypercaloric diet. During the following two weeks, 10 OR animals continued on the calorie restriction diet, whereas the remaining 10 rats of this group formed a new group (ORS) given a supraphysiological dose of T3 (25 μg/100 g body weight) along with the calorie restriction diet. Similarly, the remaining OB animals were divided into two groups, one that continued on the hypercaloric diet (OB, n = 10), and one that received the supraphysiological dose of T3 (25 μg/100 g body weight) along with the hypercaloric diet (OS, n = 10) for two weeks. The OB group showed weight gain, increased adiposity, insulin resistance, increased leptin levels and genotoxicity; T3 administration in OS animals led to an increase in genotoxicity and oxidative stress when compared with the OB group. The OR group showed weight loss and normalized levels of adiposity, insulin resistance, serum leptin and genotoxicity, thus having features similar to those of the C group. On the other hand, the ORS group, compared to OR animals, showed higher genotoxicity. Our results indicate that regardless of diet, a supraphysiological dose of T3 causes genotoxicity and potentiates oxidative stress. © 2013 de Sibio et al. Department of Internal Medicine Botucatu Medical School - University of Sao Paulo State (UNESP), Botucatu, SP Department of Pathology Botucatu Medical School - University of Sao Paulo State (UNESP), Botucatu, SP Department of Biostatistics Biosciences Institute - University of Sao Paulo State (UNESP), Botucatu, SP Department of Internal Medicine Botucatu Medical School - University of Sao Paulo State (UNESP), Botucatu, SP Department of Pathology Botucatu Medical School - University of Sao Paulo State (UNESP), Botucatu, SP Department of Biostatistics Biosciences Institute - University of Sao Paulo State (UNESP), Botucatu, SP

Both cluster of differentiation (CD)4+ and CD8+ T lymphocytes play key roles in immunity to Brucella, in part because they secrete interferon (IFN)- and activate bactericidal functions in macrophages. Therefore, use of markers of macrophage activation may have diagnostic and prognostic significance. High-mobility group-box 1 protein (HMGB1), a late-onset pro-inflammatory cytokine, is secreted by activated macrophages. Soluble hemoglobin scavenger receptor (sCD163) is a specific marker of anti-inflammatory macrophages. The aim of this study was to investigate the diagnostic value of HMGB1 and sCD163 concentrations in brucellosis and its various clinical forms. Serum HMGB1 and sCD163 concentrations in 49 brucellosis patients were compared with those in 52 healthy control subjects. Both serum HMGB1 and sCD163 concentrations were significantly higher in brucellosis patients than in healthy controls (P

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:28:10Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:48:06Z : No. of bitstreams: 1 2-s2.0-84872204045.pdf: 559294 bytes, checksum: c00bda75a01a0ae1686efb971eaf1f48 (MD5) Made available in DSpace on 2014-05-27T11:28:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-01-16 Background: Hepatic encephalopathy (HE) is a severe complication in patients with hepatic cirrhosis, which causes numerous hospital admissions and deaths. Antibiotics are the best options in HE treatment, but head-to-head comparisons between these drugs are scarce. Erythromycin combines the antimicrobial effect and prokinetic properties in the same drug, but it has never been used in HE treatment. Our aim was to evaluate the efficacy of erythromycin as an HE treatment.Methods: We achieved a randomized controlled trial of adult patients with HE and hepatic cirrhosis admitted in our hospital. After randomization, the subjects received either erythromycin 250 mg or neomycin 1 g orally QID until hospital discharge or prescription of another antibiotic. All subjects were blindly evaluated every day towards quantifying clinical, neuropsychometric, hepatic and renal exams. Statistical analysis was employed to compare the groups and correlate the variables with hospitalization duration.Results: 30 patients were evaluated (15 treated with each drug). At hospital admission, the groups were homogeneous, but the erythromycin group subjects achieved a shorter hospitalization stay (p = 0.032) and a more expressive reduction in alanine aminotranspherase levels (p = 0.026). Hospitalization duration was positively correlated with C reactive protein levels measured previous to (p = 0.015) and after treatment (p = 0.01).Conclusions: In the sample evaluated erythromycin was associated with significant reductions in hospital stay and in alanine aminotranspherase values. Hospitalization time was positive correlated with C reactive protein levels measured before and after the treatments. © 2013 Romeiro et al.; licensee BioMed Central Ltd. Department of Internal Medicine Faculdade de Medicina de Botucatu UNESP - Universidade Estadual Paulista, Botucatu Biological and Health Sciences Institute Campus Médio Araguaia UFMT -Universidade Federal do Mato Grosso, Barra do Garças Health Sciences Center UNCISAL - Universidade Estadual de Ciências da Saúde de Alagoas, Maceió Department of Physics and Biophysics Instituto de Biociências de Botucatu UNESP - Universidade Estadual Paulista, Botucatu Department of Internal Medicine - Botucatu Medical School UNESP- Universidade Estadual Paulista, Distrito de Rubião Jr. s/n zip code 18 608 917, Botucatu, São Paulo Department of Internal Medicine Faculdade de Medicina de Botucatu UNESP - Universidade Estadual Paulista, Botucatu Department of Physics and Biophysics Instituto de Biociências de Botucatu UNESP - Universidade Estadual Paulista, Botucatu Department of Internal Medicine - Botucatu Medical School UNESP- Universidade Estadual Paulista, Distrito de Rubião Jr. s/n zip code 18 608 917, Botucatu, São Paulo

Glucose-stimulated insulin secretion (GSIS) is essential to the control of metabolic fuel homeostasis. The impairment of GSIS is a key element of β-cell failure and one of causes of type 2 diabetes mellitus (T2DM). Although the KATP channel-dependent mechanism of GSIS has been broadly accepted for several decades, it does not fully describe the effects of glucose on insulin secretion. Emerging evidence has suggested that other mechanisms are involved. The present study demonstrated that geniposide enhanced GSIS in response to the stimulation of low or moderately high concentrations of glucose, and promoted glucose uptake and intracellular ATP levels in INS-1 cells. However, in the presence of a high concentration of glucose, geniposide exerted a contrary role on both GSIS and glucose uptake and metabolism. Furthermore, geniposide improved the impairment of GSIS in INS-1 cells challenged with a high concentration of glucose. Further experiments showed that geniposide modulated pyruvate carboxylase expression and the production of intermediates of glucose metabolism. The data collectively suggest that geniposide has potential to prevent or improve the impairment of insulin secretion in β-cells challenged with high concentrations of glucose, likely through pyruvate carboxylase mediated glucose metabolism in β-cells. © 2013 Liu et al.

Aim: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder which is reported as the hepatic manifestation of metabolic syndrome with an increased risk of cardiovascular events. Patients with NAFLD are also at risk of future cardiac events independently of metabolic syndrome. The aim of this study was to examine serum concentrations of heart type fatty acid binding protein (H-FABP) in NAFLD and to investigate its correlations with metabolic parameters and subclinical atherosclerosis. Patients and methods: A total of 34 patients with NAFLD and 35 healthy subjects were enrolled in the study. NAFLD patients had elevated liver enzymes and steatosis graded on ultrasonography. Healthy subjects had normal liver enzymes and no steatosis on ultrasonography. H-FABP levels were measured using an enzyme linked immunosorbent assay (ELISA) method and correlations with metabolic parameters and subclinical atherosclerosis were examined. Subclinical atherosclerosis was determined with carotid artery intima-media thickness (CIMT) which was measured by high resolution B mode ultrasonography. Results: H-FABP levels were elevated in patients with NAFLD (16.3 ± 4.0 ng/ml) when compared with healthy controls (13.8 ± 2.1 ng/ml; p < 0.001). NAFLD patients had significantly higher CIMT than the controls had (0.64 ± 0.17 mm vs. 0.43 ± 0.14 mm, p = 0.009). The H-FABP concentrations were significantly positively correlated with body mass index (r = 0.255, p = 0.042), fasting blood glucose level (r = 0.300, p = 0.013), CIMT (r = 0.335, p = 0.043), and homeostasis model assessment-estimated insulin resistance (HOMA-IR; r = 0.156, p = 0.306). In multiple linear regression analysis, H-FABP levels were only independently associated with CIMT (p = 0.04) Conclusion: Serum H-FABP concentrations increase in patients with NAFLD. Our results may not only suggest that H-FABP is a marker of subclinical myocardial damage in patients with NAFLD but also of subclinical atherosclerosis, independent of metabolic syndrome and cardiac risk factors. © 2013 Urban & Vogel.

Our aim was to investigate effects of chronic hypoxia on endocrine function in pediatric patients with cyanotic congenital heart disease (CHD). Thirty patients with cyanotic CHD (16 boys, 14 girls), and 35 control subjects (22 boys, 13 girls) were enrolled. Age means of patients and controls were 4.37+/-4.51 and 4.28+/-4.96 years, respectively. Standard deviation scores (SDS) of height and weight were significantly lower among patients compared to controls. Mean fasting glucose levels were 75+/-15 mg/dL and 83+/-12 mg/dL among patients and controls, respectively (p=0.033). Insulin-like growth factor (IGF) 1 and its SDS were significantly lower among patients (p=0.010). There was no significant difference in ACTH and cortisol levels between groups. ACTH levels were very low in six patients. Oxygen saturation level was positively correlated with ACTH (p=0.041, r=0.439) and negatively correlated with HOMA-IR (p=0.046, r=-0.420) and insulin (p=0.017, r=-0.494). There was no difference in insulin resistance between groups. Chronic hypoxia has negative impact on growth by reducing IGF-1 along with the nutritional deficiency in children with cyanotic CHD. ACTH-adrenal axis is also affected. While cyanotic CHD has decreased serum glucose level, it had no effect on insulin level and insulin resistance. Negative correlations between oxygen saturation, and HOMA-IR, fasting insulin levels, have suggested that these patients should be monitorized for insulin resistance.

This study was designed to determine serum Fetuin-A levels and establish whether serum Fetuin-A level is related with insulin resistance, oxidative stress, ovarian hyperandrogenism and dyslipidemia in women with polycystic ovary syndrome (PCOS). Twenty-two patients with PCOS and twenty-one healthy control women were evaluated in this controlled clinical study. Serum Fetuin-A, lipid fractions, glucose, insulin, malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), superoxide dismutase (SOD) and other hormone (gonadotropins, androgens) levels were measured. The estimate of insulin resistance was calculated by homeostasis model assessment (HOMA-R). The women with PCOS had significantly higher serum fasting glucose, insulin, luteinizing hormone (LH), MDA, Fetuin-A levels, and LH/follicle-stimulating hormone (FSH) ratio, free androgen index (FAI), HOMA-IR than healthy women. However, sex hormone-binding globulin (SHBG) and GSH levels were significantly lower in patients with PCOS compared with controls. Fetuin-A was positively correlated with insulin, HOMA-IR and FAI. Multiple regression analysis revealed that FAI was strong predictor of serum Fetuin-A level. Serum Fetuin-A level was related with insulin resistance and ovarian hyperandrogenism in women with PCOS. These results suggest that Fetuin-A may have a role in triggering the processes leading to insulin resistance and androgen excess in PCOS. © 2013 Informa UK Ltd.

Human ageing is accompanied with deterioration in endocrine functions the most notable and well characterized of which being the decrease in the production of sex hormones. Current research literature suggests that low sex hormone concentration may be among the key mechanism for sarcopenia and muscle weakness. Within the European large scale MYOAGE project, the role of sex hormones, estrogens and testosterone, in causing the aging-related loss of muscle mass and function was further investigated. Hormone replacement therapy (HRT) in women is shown to diminish age-associated muscle loss, loss in fast muscle function (power), and accumulation of fat in skeletal muscle. Further HRT raises the protein synthesis rate in skeletal muscle after resistance training, and has an anabolic effect upon connective tissue in both skeletal muscle and tendon, which influences matrix structure and mechanical properties. HRT influences gene expression in e.g. cytoskeletal and cell-matrix proteins, has a stimulating effect upon IGF-I, and a role in IL-6 and adipokine regulation. Despite low circulating steroid-hormone level, postmenopausal women have a high local concentration of steroidogenic enzymes in skeletal muscle.

Metabolomics is increasingly being applied towards the identification of biomarkers for disease diagnosis, prognosis and risk prediction. Unfortunately among the many published metabolomic studies focusing on biomarker discovery, there is very little consistency and relatively little rigor in how researchers select, assess or report their candidate biomarkers. In particular, few studies report any measure of sensitivity, specificity, or provide receiver operator characteristic (ROC) curves with associated confidence intervals. Even fewer studies explicitly describe or release the biomarker model used to generate their ROC curves. This is surprising given that for biomarker studies in most other biomedical fields, ROC curve analysis is generally considered the standard method for performance assessment. Because the ultimate goal of biomarker discovery is the translation of those biomarkers to clinical practice, it is clear that the metabolomics community needs to start “speaking the same language” in terms of biomarker analysis and reporting-especially if it wants to see metabolite markers being routinely used in the clinic. In this tutorial, we will first introduce the concept of ROC curves and describe their use in single biomarker analysis for clinical chemistry. This includes the construction of ROC curves, understanding the meaning of area under ROC curves (AUC) and partial AUC, as well as the calculation of confidence intervals. The second part of the tutorial focuses on biomarker analyses within the context of metabolomics. This section describes different statistical and machine learning strategies that can be used to create multi-metabolite biomarker models and explains how these models can be assessed using ROC curves. In the third part of the tutorial we discuss common issues and potential pitfalls associated with different analysis methods and provide readers with a list of nine recommendations for biomarker analysis and reporting. To help readers test, visualize and explore the concepts presented in this tutorial, we also introduce a web-based tool called ROCCET (ROC Curve Explorer & Tester, http://www.roccet.ca). ROCCET was originally developed as a teaching aid but it can also serve as a training and testing resource to assist metabolomics researchers build biomarker models and conduct a range of common ROC curve analyses for biomarker studies. Electronic supplementary material The online version of this article (doi:10.1007/s11306-012-0482-9) contains supplementary material, which is available to authorized users.

Apelin, a novel multifunctional peptide implicated in the regulation of the cardiovascular system, including blood pressure and cardiac function control, has been postulated to be involved in the pathophysiology of hypertension and hypertensive heart disease. The aim of this study was to investigate, for the first time, whether the effects of apelin's chronic application might be involved in deoxycorticosterone acetate-salt-induced hypertensive rats (DOCA-salt rats). In this study, 8-10-week-old male Wistar rats were divided into four groups: control, control + apelin, DOCA-salt rats, DOCA-salt rats + apelin. Deoxycorticosterone Acetate (25 mg/kg of body weight) was injected subcutaneously, twice a week for 4 weeks. These rats received NaCl 1% instead of tap water for drinking during the experimental period. Later, rats were randomly treated with pyroglutamylated apelin-13 (200 µg. kg-1. day-1 intraperitonealy) for 17 days. The concentrations of apelin, endothelin-1, angiotensin-converting enzyme, angiotensinogen, and angiotensin II were analyzed in the plasma. The mRNA level of apelin and apelin receptor were determined in the heart and aorta tissue by real-time polymerase chain reaction, respectively. It was found that apelin reduces blood pressure in DOCA-salt rats. Apelin can be used as a therapeutic agent in the treatment of hypertension in the future. © 2013 Informa Healthcare USA, Inc., 2011 SBE001, This study was supported by Pamukkale University Research Fund (Project no: 2011 SBE001).

Bacterial peritonitis is a severe complication in patients with cirrhosis and ascites and despite antibiotic treatment, the inflammatory response to infection may induce renal dysfunction leading to death. This investigation evaluated the effect of TNF-a blockade on the inflammatory response and mortality in cirrhotic rats with induced bacterial peritonitis treated or not with antibiotics. Sprague-Dawley rats with carbon-tetrachloride-induced cirrhosis were treated with an intraperitoneal injection of 109 CFU of Escherichia coli diluted in 20 mL of sterile water to induce bacterial peritonitis and randomized to receive subcutaneously-administered placebo, ceftriaxone, anti-TNF-a mAb and ceftriaxone, or anti-TNF-a mAb alone. No differences were observed between groups at baseline in respect to renal function, liver hepatic tests, serum levels of nitrite/nitrate and TNF-a. Treatment with ceftriaxone reduced mortality (73.3%) but differences did not reach statistical significance as compared to placebo. Mortality in rats treated with ceftriaxone and anti-TNF-a mAb was significantly lower than in animals receiving placebo (53% vs. 100%, p

Background: In a planned International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) worldwide study on reference intervals (RIs), a common panel of serum samples is to be measured by laboratories from different countries, and test results are to be compared through conversion using linear regression analysis. This report presents a validation study that was conducted in collaboration with four laboratories. Methods: A panel composed of 80 sera was prepared from healthy individuals, and 45 commonly tested analytes (general chemistry, tumor markers, and hormones) were measured on two occasions 1 week apart in each laboratory. Reduced major-axis linear regression was used to convert reference limits (LL and UL). Precision was expressed as a ratio of the standard error of converted LL or UL to the standard deviation (SD) comprising RI (approx. 1/4 of the RI width corresponding to between-individual SD). The allowable and optimal levels of error for the SD ratio (SDR) were set as

Aims and background The optimal treatment of cancer cachexia remains unknown. In this study, we compared the efficacy of three different treatment modalities in the management of cancer cachexia. Methods Sixty-two assessable cachectic cancer patients were randomized to one of the following three arms: 1) megesterol acetate (MA) plus meloxicam (n = 23); 2) MA plus meloxicam plus oral eicosapentaenoic acid (EPA)-enriched nutritional supplement (n = 21); or 3) meloxicam plus oral EPA-enriched nutritional supplement (n = 18). Treatment duration was 3 months. Results The treatment arms were well balanced at baseline. The primary efficacy (body weight and lean body mass) and secondary efficacy (body mass index, quality of life, and serum levels of IL-6 and TNF-α) parameters improved after treatment in all three arms. There were no statistically significant differences between treatment groups in the mean percentage changes in all efficacy parameters from baseline to end of study. Conclusions MA plus meloxicam or EPA supplement plus meloxicam may be effective treatment options in the management of cancer cachexia. The combined use of these agents does not provide further advantages.

All tissues can be damaged by ionizing radiation. Early biomarkers of radiation injury are critical for triage, treatment and follow-up of large numbers of people exposed to ionizing radiation after terrorist attacks or radiological accident, and for prediction of normal tissue toxicity before, during and after a treatment by radiotherapy. The comparative proteomic approach is a promising and powerful tool for the discovery of new radiation biomarkers. In association with multivariate statistics, proteomics enables measurement of the level of hundreds or thousands of proteins at the same time and identifies set of proteins that can discriminate between different groups of individuals. Human serum and plasma are the preferred samples for the study of normal and disease-associated proteins. Extreme complexity, extensive dynamic range, genetic and physiological variations, protein modifications and incompleteness of sampling by two-dimensional electrophoresis and mass spectrometry represent key challenges to reproducible, high-resolution, and high-throughput analyses of serum and plasma proteomes. The future of radiation research will possibly lie in molecular networks that link genome, transcriptome, proteome and metabolome variations to radiation pathophysiology and serve as sensors of radiation disease. This chapter reviews recent advances in proteome analysis of serum and plasma as well as its applications to radiation biology and radiation biomarker discovery for both radiation exposure and radiation tissue toxicity. © Springer Science+Business Media Dordrecht 2013.

A 76-year-old woman underwent surgery for pelvic mass, during which a 13 x 8-cm right ovarian tumor was discovered. On histopathological examination, she was diagnosed with an endodermal sinus tumor with right tubal metastasis. The patient was treated with four cycles of Bleomycin, Etoposide and Cisplatin. She died of disseminated disease four years later.