Effects of Rapid Weight Loss on Systemic and Adipose Tissue Inflammation and Metabolism in Obese Postmenopausal Women

PubMed Central

Iyengar, Neil M.; Walker, Jeanne M.; Milne, Ginger L.; Da Rosa, Joel Correa; Liang, Yupu; Giri, Dilip D.; Zhou, Xi Kathy; Pollak, Michael N.; Hudis, Clifford A.; Breslow, Jan L.; Holt, Peter R.; Dannenberg, Andrew J.

2017-01-01

Context: Obesity is associated with subclinical white adipose tissue inflammation, as defined by the presence of crown-like structures (CLSs) consisting of dead or dying adipocytes encircled by macrophages. In humans, bariatric surgery-induced weight loss leads to a decrease in CLSs, but the effects of rapid diet-induced weight loss on CLSs and metabolism are unclear. Objective: To determine the effects of rapid very-low-calorie diet-induced weight loss on CLS density, systemic biomarkers of inflammation, and metabolism in obese postmenopausal women. Design: Prospective cohort study. Setting: Rockefeller University Hospital, New York, NY. Participants: Ten obese, postmenopausal women with a mean age of 60.6 years (standard deviation, ±3.6 years). Main Outcome Measures: Effects on CLS density and gene expression in abdominal subcutaneous adipose tissue, cardiometabolic risk factors, white blood count, circulating metabolites, and oxidative stress (urinary isoprostane-M) were measured. Results: Obese subjects lost approximately 10% body weight over a mean of 46 days. CLS density increased in subcutaneous adipose tissue without an associated increase in proinflammatory gene expression. Weight loss was accompanied by decreased fasting blood levels of high-sensitivity C-reactive protein, glucose, lactate, and kynurenine, and increased circulating levels of free fatty acids, glycerol, β-hydroxybutyrate, and 25 hydroxyvitamin D. Levels of urinary isoprostane-M declined. Conclusion: Rapid weight loss stimulated lipolysis and an increase in CLS density in subcutaneous adipose tissue in association with changes in levels of circulating metabolites, and improved systemic biomarkers of inflammation and insulin resistance. The observed change in levels of metabolites (i.e., lactate, β-hydroxybutyrate, 25 hydroxyvitamin D) may contribute to the anti-inflammatory effect of rapid weight loss. PMID:29264516

Weight loss induced by bariatric surgery restores adipose tissue PNPLA3 expression.

PubMed

Wieser, Verena; Adolph, Timon E; Enrich, Barbara; Moser, Patrizia; Moschen, Alexander R; Tilg, Herbert

2017-02-01

Obesity and its related co-morbidities such as non-alcoholic fatty liver disease (NAFLD) are increasing dramatically worldwide. The genetic variation in Patatin-like phospholipase domain-containing protein 3 (PNPLA3), which is also called adiponutrin (ADPN), in residue 148 (I148M, rs738409) has been associated with NAFLD. However, the regulation and function of PNPLA3 in metabolic diseases remains unclear. Laparoscopic gastric banding (LAGB) of severely obese patients reduces body weight, liver and adipose tissue inflammation. In this study, we investigated whether weight loss induced by LAGB affected PNPLA3 expression in hepatic and adipose tissue. Liver and subcutaneous adipose tissue samples were collected from 28 severely obese patients before and 6 months after LAGB. PNPLA3 expression was assessed by quantitative real-time PCR. To understand whether inflammatory stimuli regulated PNPLA3 expression, we studied the effect of tumour necrosis factor alpha (TNFα) and lipopolysaccharide (LPS) on PNPLA3 expression in human adipocytes and hepatocytes. PNPLA3 was strongly expressed in the liver and clearly detectable in subcutaneous adipose tissue of obese patients. Weight loss induced by LAGB of severely obese patients led to significantly increased adipose, but not hepatic, tissue expression of PNPLA3. Subcutaneous PNPLA3 expression negatively correlated with body-mass-index, fasting glucose and fasting insulin. TNFα potently suppressed PNPLA3 expression in adipocytes but not hepatocytes. Weight loss induced by LAGB restored adipose tissue PNPLA3 expression which is suppressed by TNFα. Further studies will be required to determine the functional impact of PNPLA3 and its related genetic variation on adipose tissue inflammation and NAFLD. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of fluid absorption during holmium laser enucleation of prostate by breath ethanol technique.

PubMed

Shah, Hemendra N; Kausik, Vikram; Hegde, Sunil; Shah, Jignesh N; Bansal, Manish B

2006-02-01

In a prospective manner we studied various factors affecting fluid absorption during HoLEP. We also simultaneously evaluated changes in serum electrolytes and hemoglobin decrease during HoLEP. This prospective study comprised of 53 patients who underwent HoLEP at our institute. Irrigation fluid was normal saline tagged with ethanol (1% w/v). Intraoperatively a standard breath analyzer was used to monitor expired breath ethanol levels during the procedure at 10-minute intervals. Patients who absorbed irrigating fluid as indicated by positive intraoperative breath tests were considered absorbers. Serum electrolyte and hemoglobin estimations were done before and after surgery. Total irrigation time, amount of irrigation fluid used, weight of resected tissue and presence of capsular perforation were recorded. Statistical analysis was performed to observe the effects of various factors on the amount of intraoperative fluid absorption. Of 53 patients studied 14 (26.41%) demonstrated fluid absorption in the range of 213 to 930 ml (mean 459). Preoperative prostate weight, total irrigation time, amount of irrigation fluid used and resected tissue weight were all significantly greater in absorbers. Similarly, absorbers had a statistically significant decrease in hemoglobin level postoperatively. There was no statistically significant change in serum electrolytes between absorbers and nonabsorbers. Preoperative weight of prostate, total irrigation time, amount of irrigation fluid used and weight of resected tissue all directly influence the amount of fluid absorption during HoLEP. There is no significant change in serum electrolytes and no risk of the transurethral resection syndrome.

Dose equivalent near the bone-soft tissue interface from nuclear fragments produced by high-energy protons

NASA Technical Reports Server (NTRS)

Shavers, M. R.; Poston, J. W.; Cucinotta, F. A.; Wilson, J. W.

1996-01-01

During manned space missions, high-energy nucleons of cosmic and solar origin collide with atomic nuclei of the human body and produce a broad linear energy transfer spectrum of secondary particles, called target fragments. These nuclear fragments are often more biologically harmful than the direct ionization of the incident nucleon. That these secondary particles increase tissue absorbed dose in regions adjacent to the bone-soft tissue interface was demonstrated in a previous publication. To assess radiological risks to tissue near the bone-soft tissue interface, a computer transport model for nuclear fragments produced by high energy nucleons was used in this study to calculate integral linear energy transfer spectra and dose equivalents resulting from nuclear collisions of 1-GeV protons transversing bone and red bone marrow. In terms of dose equivalent averaged over trabecular bone marrow, target fragments emitted from interactions in both tissues are predicted to be at least as important as the direct ionization of the primary protons-twice as important, if recently recommended radiation weighting factors and "worst-case" geometry are used. The use of conventional dosimetry (absorbed dose weighted by aa linear energy transfer-dependent quality factor) as an appropriate framework for predicting risk from low fluences of high-linear energy transfer target fragments is discussed.

Epigenetics in adipose tissue, obesity, weight loss and diabetes

USDA-ARS?s Scientific Manuscript database

Given the role that the diet and other environmental factors play in the development of obesity and type 2 diabetes, the implication of different epigenetic processes is being investigated. Although it is well known that the environmental factors can cause cell type-dependent epigenetic changes, inc...

JTT-553, a novel Acyl CoA:diacylglycerol acyltransferase (DGAT) 1 inhibitor, improves glucose metabolism in diet-induced obesity and genetic T2DM mice.

PubMed

Tomimoto, Daisuke; Okuma, Chihiro; Ishii, Yukihito; Kobayashi, Akio; Ohta, Takeshi; Kakutani, Makoto; Imanaka, Tsuneo; Ogawa, Nobuya

2015-09-01

Type 2 diabetes mellitus (T2DM) arises primarily due to lifestyle factors and genetics. A number of lifestyle factors are known to be important in the development of T2DM, including obesity. JTT-553, a novel Acyl CoA:diacylglycerol acyltransferase 1 inhibitor, reduced body weight depending on dietary fat in diet-induced obesity (DIO) rats in our previous study. Here, the effect of JTT-553 on glucose metabolism was evaluated using body weight reduction in T2DM mice. JTT-553 was repeatedly administered to DIO and KK-A(y) mice. JTT-553 reduced body weight gain and fat weight in both mouse models. In DIO mice, JTT-553 decreased insulin, non-esterified fatty acid (NEFA), total cholesterol (TC), and liver triglyceride (TG) plasma concentrations in non-fasting conditions. JTT-553 also improved insulin-dependent glucose uptake in adipose tissues and glucose intolerance in DIO mice. In KK-A(y) mice, JTT-553 decreased glucose, NEFA, TC and liver TG plasma concentrations in non-fasting conditions. JTT-553 also decreased glucose, insulin, and TC plasma concentrations in fasting conditions. In addition, JTT-553 decreased TNF-α mRNA levels and increased GLUT4 mRNA levels in adipose tissues in KK-A(y) mice. These results suggest that JTT-553 improves insulin resistance in adipose tissues and systemic glucose metabolism through reductions in body weight. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

DNA methylation of the Klf14 gene region in whole blood cells provides prediction for the chronic inflammation in the adipose tissue.

PubMed

Iwaya, Chihiro; Kitajima, Hidetoshi; Yamamoto, Ken; Maeda, Yasutaka; Sonoda, Noriyuki; Shibata, Hiroki; Inoguchi, Toyoshi

2018-03-11

Krüppel-Like Factor 14 (KLF14) gene, which appears to be a master regulator of gene expression in the adipose tissue and have previously been associated with BMI and Type 2 diabetes (T2D) by large genome-wide association studies. In order to find predictive biomarkers for the development of T2D, it is necessary to take epigenomic changes affected by environmental factors into account. This study focuses on ageing and obesity, which are T2D risk factors, and examines epigenetic changes and inflammatory changes. We investigated DNA methylation changes in the Klf14 promoter region in different organs of mice for comparing aging and weight. We found that methylation levels of these sites were increased with aging and weight in the spleen, the adipose tissue, the kidney, the lung, the colon and the whole blood cells. In addition, in the spleen, the adipose tissue and the whole blood, these epigenetic changes were also significantly associated with inflammatory levels. Moreover, not only Klf14, but also expression levels of some downstream genes were decreased with methylation in the spleen, the adipose tissue and the whole blood cells. Taken together, our results suggest that methylation changes of Klf14 in those tissues may be associated with changes in gene expression and inflammation on the adipose tissue of obesity and T2D. In addition, the methylation changes in the whole blood cells may serve as a predictive epigenetic biomarker for the development of T2D. Copyright © 2018 Elsevier Inc. All rights reserved.

Chronic hyperprolactinemia evoked by disruption of lactotrope dopamine D2 receptors impacts on liver and adipocyte genes related to glucose and insulin balance.

PubMed

Luque, Guillermina María; Lopez-Vicchi, Felicitas; Ornstein, Ana María; Brie, Belén; De Winne, Catalina; Fiore, Esteban; Perez-Millan, Maria Inés; Mazzolini, Guillermo; Rubinstein, Marcelo; Becu-Villalobos, Damasia

2016-12-01

We studied the impact of high prolactin titers on liver and adipocyte gene expression related to glucose and insulin homeostasis in correlation with obesity onset. To that end we used mutant female mice that selectively lack dopamine type 2 receptors (D2Rs) from pituitary lactotropes (lacDrd2KO), which have chronic high prolactin levels associated with increased body weight, marked increments in fat depots, adipocyte size, and serum lipids, and a metabolic phenotype that intensifies with age. LacDrd2KO mice of two developmental ages, 5 and 10 mo, were used. In the first time point, obesity and increased body weight are marginal, although mice are hyperprolactinemic, whereas at 10 mo there is marked adiposity with a 136% increase in gonadal fat and a 36% increase in liver weight due to lipid accumulation. LacDrd2KO mice had glucose intolerance, hyperinsulinemia, and impaired insulin response to glucose already in the early stages of obesity, but changes in liver and adipose tissue transcription factors were time and tissue dependent. In chronic hyperprolactinemic mice liver Prlr were upregulated, there was liver steatosis, altered expression of the lipogenic transcription factor Chrebp, and blunted response of Srebp-1c to refeeding at 5 mo of age, whereas no effect was observed in the glycogenesis pathway. On the other hand, in adipose tissue a marked decrease in lipogenic transcription factor expression was observed when morbid obesity was already settled. These adaptive changes underscore the role of prolactin signaling in different tissues to promote energy storage. Copyright © 2016 the American Physiological Society.

Seed maturation associated transcriptional programs and regulatory networks underlying genotypic difference in seed dormancy and size/weight in wheat (Triticum aestivum L.).

PubMed

Yamasaki, Yuji; Gao, Feng; Jordan, Mark C; Ayele, Belay T

2017-09-16

Maturation forms one of the critical seed developmental phases and it is characterized mainly by programmed cell death, dormancy and desiccation, however, the transcriptional programs and regulatory networks underlying acquisition of dormancy and deposition of storage reserves during the maturation phase of seed development are poorly understood in wheat. The present study performed comparative spatiotemporal transcriptomic analysis of seed maturation in two wheat genotypes with contrasting seed weight/size and dormancy phenotype. The embryo and endosperm tissues of maturing seeds appeared to exhibit genotype-specific temporal shifts in gene expression profile that might contribute to the seed phenotypic variations. Functional annotations of gene clusters suggest that the two tissues exhibit distinct but genotypically overlapping molecular functions. Motif enrichment predicts genotypically distinct abscisic acid (ABA) and gibberellin (GA) regulated transcriptional networks contribute to the contrasting seed weight/size and dormancy phenotypes between the two genotypes. While other ABA responsive element (ABRE) motifs are enriched in both genotypes, the prevalence of G-box-like motif specifically in tissues of the dormant genotype suggests distinct ABA mediated transcriptional mechanisms control the establishment of dormancy during seed maturation. In agreement with this, the bZIP transcription factors that co-express with ABRE enriched embryonic genes differ with genotype. The enrichment of SITEIIATCYTC motif specifically in embryo clusters of maturing seeds irrespective of genotype predicts a tissue specific role for the respective TCP transcription factors with no or minimal contribution to the variations in seed dormancy. The results of this study advance our understanding of the seed maturation associated molecular mechanisms underlying variation in dormancy and weight/size in wheat seeds, which is a critical step towards the designing of molecular strategies for enhancing seed yield and quality.

Role of platelet activating factor in pathogenesis of acute pancreatitis in rats.

PubMed Central

Konturek, S J; Dembinski, A; Konturek, P J; Warzecha, Z; Jaworek, J; Gustaw, P; Tomaszewska, R; Stachura, J

1992-01-01

The importance of platelet activating factor in acute pancreatitis was examined by determining the tissue content of endogenous platelet activating factor and the protective effects of TCV-309, a highly selective platelet activating factor blocker, against caerulein induced pancreatitis in rats. Infusion of caerulein (10 micrograms/kg/h) for five hours resulted in about 70% increase in pancreatic weight, 22% rise in protein content, 50% reduction in tissue blood flow, nine fold increase in tissue level of platelet activating factor and 165% rise in plasma amylase as well as histological evidence of acute pancreatitis. Such infusion of caerulein in chronic pancreatic fistula rats caused a marked increase in protein output from basal secretion of 10 mg/30 minutes to 40 mg/30 minutes in the first hour of infusion followed by a decline in protein output to 15-20 mg/30 minutes in the following hours of the experiment. Exogenous platelet activating factor (50 micrograms/kg) injected ip produced similar alterations in weight, protein content, blood flow, and histology of the pancreas but the increment in serum amylase was significantly smaller and pancreatic secretion was reduced below the basal level. TCV-309 (50 micrograms/kg) given ip before caerulein or platelet activating factor administration significantly reduced the biochemical and morphological alterations caused by caerulein and abolished those induced by exogenous platelet activating factor. These results indicate that platelet activating factor plays an important role in the pathogenesis of acute pancreatitis probably by reducing the blood flow and increasing vascular permeability in the pancreas. PMID:1385272

Adipose tissue IL-8 is increased in normal weight women after menopause and reduced after gastric bypass surgery in obese women.

PubMed

Alvehus, Malin; Simonyte, Kotryna; Andersson, Therése; Söderström, Ingegerd; Burén, Jonas; Rask, Eva; Mattsson, Cecilia; Olsson, Tommy

2012-11-01

The menopausal transition is characterized by increased body fat accumulation, including redistribution from peripheral to central fat depots. This distribution is associated with an increased risk of type 2 diabetes and cardiovascular disease that are linked to low-grade inflammation. We determined whether postmenopausal women have higher levels of inflammatory markers, compared with premenopausal women. We also wanted to determine whether these markers are reduced by stable weight loss in obese women. Anthropometric data, blood samples and subcutaneous adipose tissue biopsies were collected from normal weight premenopausal and postmenopausal women and obese women before and 2 years after gastric bypass (GBP) surgery. Serum protein levels and adipose tissue gene expression of inflammatory markers were investigated. IL-8 expression in adipose tissue and circulating levels were higher in postmenopausal vs premenopausal women. IL-8 expression was associated with waist circumference, independent of menopausal status. IL-6 expression and serum levels of monocyte chemoattractant protein (MCP)-1 were higher in postmenopausal vs premenopausal women. Two years after GBP surgery, adipose expression of IL-8, tumour necrosis factor-α and MCP-1 decreased significantly. Serum insulin levels were associated with inflammation-related gene expression before GBP surgery, but these associations disappeared after surgery. Postmenopausal women have an increased inflammatory response in the subcutaneous fat and circulation. Inflammatory markers in adipose tissue decreased significantly after surgery-induced weight loss. This effect may be beneficial for metabolic control and reduced cardiovascular risk after weight loss. © 2011 Blackwell Publishing Ltd.

Selenium and mining in the Powder River Basin, Wyoming: Phase III - a preliminary survey of selenium concentrations in deer mice (Peromyscus maniculatus) livers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raisbeck, M.L.; Vance, G.F.; Steward, D.G.

1995-09-01

Samples of liver tissue from deer mice trapped on not-yet-mined areas and reclaimed areas at five surface coal mines in the Powder River Basin of northeastern Wyoming were analyzed for selenium. The overall mean concentration of selenium in wet weight liver tissue was 1.685 ppm. The mean value from not-yet-mined areas was 1.437 ppm; the mean value from reclaimed areas was 1.910 ppm (significant at p<0.1016). When one not-yet-mined outlier was removed, significance rose to p<0.0004. Mine-to-mine comparison of samples stratified by type (that is, by not-yet-mined or reclaimed), showed average tissue concentrations from the reclaimed area of Mine 1more » were also higher (p<0.0143) then not-yet-mined area samples at Mine 1. No statistically significant differences were found between mines for samples from not-yet-mined areas, and no statistically significant differences were found between Mines 2, 3, 4, and 5 for samples from reclaimed areas. Multiple analysis of variance using the factors: site (mine) and type (not-yet-mined or reclaimed) was not significantly significant (p<0.2115). Simple linear regression showed that selenium concentrations in dry tissue could easily be predicted from wet tissue selenium (r2=0.9775), demonstrating that percent water in the samples was relatively constant. Animal body weight in general was not a predictor for either wet or dry tissue selenium concentrations, but was related to body weight at the higher tissue concentrations of selenium encountered in samples from the reclaimed area at Mine 1. Mouse body weights at Mine 1 were higher on the reclaimed area than mouse body weights from the not-yet-mined area.« less

Effect of weight loss in obese dogs on indicators of renal function or disease.

PubMed

Tvarijonaviciute, A; Ceron, J J; Holden, S L; Biourge, V; Morris, P J; German, A J

2013-01-01

Obesity is a common medical disorder in dogs, and can predispose to a number of diseases. Human obesity is a risk factor for the development and progression of chronic kidney disease. To investigate the possible association of weight loss on plasma and renal biomarkers of kidney health. Thirty-seven obese dogs that lost weight were included in the study. Prospective observational study. Three novel biomarkers of renal functional impairment, disease, or both (homocysteine, cystatin C, and clusterin), in addition to traditional markers of chronic renal failure (serum urea and creatinine, urine specific gravity [USG], urine protein-creatinine ratio [UPCR], and urine albumin corrected by creatinine [UAC]) before and after weight loss in dogs with naturally occurring obesity were investigated. Urea (P = .043) and USG (P = .012) were both greater after weight loss than before loss, whilst UPCR, UAC, and creatinine were less after weight loss (P = .032, P = .006, and P = .026, respectively). Homocysteine (P < .001), cystatin C (P < .001) and clusterin (P < .001) all decreased upon weight loss. Multiple linear regression analysis revealed associations between percentage weight loss (greater weight loss, more lean tissue loss; r = -0.67, r(2) = 0.45, P < .001) and before-loss plasma clusterin concentration (greater clusterin, more lean tissue loss; r = 0.48, r(2) = 0.23, P = .003). These results suggest possible subclinical alterations in renal function in canine obesity, which improve with weight loss. Further work is required to determine the nature of these alterations and, most notably, the reason for the association between before loss plasma clusterin and subsequent lean tissue loss during weight management. Copyright © 2012 by the American College of Veterinary Internal Medicine.

System Model Network for Adipose Tissue Signatures Related to Weight Changes in Response to Calorie Restriction and Subsequent Weight Maintenance

PubMed Central

Montastier, Emilie; Villa-Vialaneix, Nathalie; Caspar-Bauguil, Sylvie; Hlavaty, Petr; Tvrzicka, Eva; Gonzalez, Ignacio; Saris, Wim H. M.; Langin, Dominique; Kunesova, Marie; Viguerie, Nathalie

2015-01-01

Nutrigenomics investigates relationships between nutrients and all genome-encoded molecular entities. This holistic approach requires systems biology to scrutinize the effects of diet on tissue biology. To decipher the adipose tissue (AT) response to diet induced weight changes we focused on key molecular (lipids and transcripts) AT species during a longitudinal dietary intervention. To obtain a systems model, a network approach was used to combine all sets of variables (bio-clinical, fatty acids and mRNA levels) and get an overview of their interactions. AT fatty acids and mRNA levels were quantified in 135 obese women at baseline, after an 8-week low calorie diet (LCD) and after 6 months of ad libitum weight maintenance diet (WMD). After LCD, individuals were stratified a posteriori according to weight change during WMD. A 3 steps approach was used to infer a global model involving the 3 sets of variables. It consisted in inferring intra-omic networks with sparse partial correlations and inter-omic networks with regularized canonical correlation analysis and finally combining the obtained omic-specific network in a single global model. The resulting networks were analyzed using node clustering, systematic important node extraction and cluster comparisons. Overall, AT showed both constant and phase-specific biological signatures in response to dietary intervention. AT from women regaining weight displayed growth factors, angiogenesis and proliferation signaling signatures, suggesting unfavorable tissue hyperplasia. By contrast, after LCD a strong positive relationship between AT myristoleic acid (a fatty acid with low AT level) content and de novo lipogenesis mRNAs was found. This relationship was also observed, after WMD, in the group of women that continued to lose weight. This original system biology approach provides novel insight in the AT response to weight control by highlighting the central role of myristoleic acid that may account for the beneficial effects of weight loss. PMID:25590576

Complement factor H is expressed in adipose tissue in association with insulin resistance.

PubMed

Moreno-Navarrete, José María; Martínez-Barricarte, Rubén; Catalán, Victoria; Sabater, Mònica; Gómez-Ambrosi, Javier; Ortega, Francisco José; Ricart, Wifredo; Blüher, Mathias; Frühbeck, Gema; Rodríguez de Cordoba, Santiago; Fernández-Real, José Manuel

2010-01-01

Activation of the alternative pathway of the complement system, in which factor H (fH; complement fH [CFH]) is a key regulatory component, has been suggested as a link between obesity and metabolic disorders. Our objective was to study the associations between circulating and adipose tissue gene expressions of CFH and complement factor B (fB; CFB) with obesity and insulin resistance. Circulating fH and fB were determined by enzyme-linked immunosorbent assay in 398 subjects. CFH and CFB gene expressions were evaluated in 76 adipose tissue samples, in isolated adipocytes, and in stromovascular cells (SVC) (n = 13). The effects of weight loss and rosiglitazone were investigated in independent cohorts. Both circulating fH and fB were associated positively with BMI, waist circumference, triglycerides, and inflammatory parameters and negatively with insulin sensitivity and HDL cholesterol. For the first time, CFH gene expression was detected in human adipose tissue (significantly increased in subcutaneous compared with omental fat). CFH gene expression in omental fat was significantly associated with insulin resistance. In contrast, CFB gene expression was significantly increased in omental fat but also in association with fasting glucose and triglycerides. The SVC fraction was responsible for these differences, although isolated adipocytes also expressed fB and fH at low levels. Both weight loss and rosiglitazone led to significantly decreased circulating fB and fH levels. Increased circulating fH and fB concentrations in subjects with altered glucose tolerance could reflect increased SVC-induced activation of the alternative pathway of complement in omental adipose tissue linked to insulin resistance and metabolic disturbances.

Hypolipidemic and anti-inflammatory effects of aorta and heart tissues of cattle and pigs in the atherosclerosis rat model.

PubMed

Chernukha, Irina M; Fedulova, Liliya V; Kotenkova, Elena A; Takeda, Shiro; Sakata, Ryoichi

2018-05-01

The aim of this study was to investigate the effects of aorta and heart tissues obtained from cattle and pigs on atherosclerosis disorders. Atherosclerosis model rats were provided with the respective diets consisting of aorta and heart tissues. Administration of each tissue suppressed body weight gain as compared to that of the control. In particular, the aorta tissues of pigs and cattle demonstrated significant suppressions in body weight gain in the model rats. The aorta tissues of pigs and cattle showed a significant increase and decrease in the serum high-density lipoproteins and atherogenic index, respectively, which was correlated with the increase in apolipoprotein A1. Hematological analysis revealed that aorta tissues of pigs and cattle clearly reduced the ratio of granulocytes/lymphocytes in the atherosclerosis rats. Serum vascular cellular adhesion molecule-1 levels in the atherosclerosis rats, which were administered these aorta tissues, were also significantly reduced. Additionally, there was an increase in von Willebrand factor in the rat serum. Based on the results obtained, the aorta tissues of pigs and cattle, in particular, demonstrated positive effects in the atherosclerosis rats due to the alteration of lipid metabolism and reduction in inflammation related to atherosclerosis. © 2018 Japanese Society of Animal Science.

Promoting Wound Healing Using Low Molecular Weight Fucoidan in a Full-Thickness Dermal Excision Rat Model

PubMed Central

Park, Jun-Hyeong; Choi, Seong-Hun; Park, Soo-Jin; Lee, Young Joon; Park, Jong Hyun; Song, Phil Hyun; Cho, Chang-Mo; Ku, Sae-Kwang; Song, Chang-Hyun

2017-01-01

Low molecular weight fucoidan (LMF) has been reported to possess anti-inflammatory and antioxidant activities. Thus, we examined the effects of LMF extracted from Undaria pinnatifida on dermal wounds. Five round dermal wounds were created on the dorsal back of rats, and they were then treated topically with distilled water (DW), Madecasol Care™ (MC) or LMF at 200, 100 and 50 mg/mL, twice a day for a week. There were dose-dependent increases in wound contraction in the groups receiving LMF but not in the MC group, compared with the DW. Histopathological examination revealed that LMF treatment accelerated wound healing, which was supported by increases in granular tissue formation on day four post-treatment but a decrease on day seven, accompanied by an evident reduction in inflammatory cells. In the LMF-treated wounds, collagen distribution and angiogenesis were increased in the granular tissue on days four and seven post-treatment. Immunoreactive cells for transforming growth factor-β1, vascular endothelial growth factor receptor-2 or matrix metalloproteinases 9 were also increased, probably due to tissue remodeling. Furthermore, LMF treatment reduced lipid peroxidation and increased antioxidant activities. These suggested that LMF promotes dermal wound healing via complex and coordinated antioxidant, anti-inflammatory and growth factor-dependent activities. PMID:28387729

Different effect of l-NAME treatment on susceptibility to decompression sickness in male and female rats.

PubMed

Mazur, Aleksandra; Buzzacott, Peter; Lambrechts, Kate; Wang, Qiong; Belhomme, Marc; Theron, Michael; Popov, Georgi; Distefano, Giovanni; Guerrero, Francois

2014-11-01

Vascular bubble formation results from supersaturation during inadequate decompression contributes to endothelial injuries, which form the basis for the development of decompression sickness (DCS). Risk factors for DCS include increased age, weight-fat mass, decreased maximal oxygen uptake, chronic diseases, dehydration, and nitric oxide (NO) bioavailability. Production of NO is often affected by diving and its expression-activity varies between the genders. Little is known about the influence of sex on the risk of DCS. To study this relationship we used an animal model of Nω-nitro-l-arginine methyl ester (l-NAME) to induce decreased NO production. Male and female rats with diverse ages and weights were divided into 2 groups: treated with l-NAME (in tap water; 0.05 mg·mL(-1) for 7 days) and a control group. To control the distribution of nitrogen among tissues, 2 different compression-decompression protocols were used. Results showed that l-NAME was significantly associated with increased DCS in female rats (p = 0.039) only. Weight was significant for both sexes (p = 0.01). The protocol with the highest estimated tissue pressures in the slower compartments was 2.6 times more likely to produce DCS than the protocol with the highest estimated tissue pressures in faster compartments. The outcome of this study had significantly different susceptibility to DCS after l-NAME treatment between the sexes, while l-NAME per se had no effect on the likelihood of DCS. The analysis also showed that for the appearance of DCS, the most significant factors were type of protocol and weight.

Dosimetry of {sup 210}Po in humans, caribou, and wolves in northern Canada

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas, P.A.

1994-06-01

Effective doses from {sup 210}Po intake with caribou meat were determined for human residents in Baker Lake and Snowdrift in the Northwest Territories of Canada and compared to doses calculated from reported {sup 210}Po tissue activities in Alaskan and British residents. Effective doses were calculated to separate body tissues, using ICRP 60 human weighting factors and the ICRP 30 metabolic model for {sup 210}Po. Baker Lake and Alaskan effective doses were similar at 0.4 mSv y{sup {minus}1} and slightly higher than Snowdrift doses (0.3 mSv y{sup {minus}1}). Alaskan tissue activities indicated higher effective doses to liver, bone surfaces and redmore » marrow and lower doses to spleen than the {sup 210}Po metabolic model (ICRP 1979a) predicts. Effective doses to Baker Lake and Snowdrift caribou and wolves, calculated from tissue activities, ranged from 7-20 mSv y{sup {minus}1} using human weighting factors for comparison to human doses only. Effective doses to northern Canadians and wildlife were, respectively, 7-11% and 1.8-5 times an estimated human background of 4 mSv y{sup {minus}} from all sources. 51 refs., 2 figs., 9 tabs.« less

Inverse association between brown adipose tissue activation and white adipose tissue accumulation in successfully treated pediatric malignancy1234

PubMed Central

Chalfant, James S; Smith, Michelle L; Hu, Houchun H; Dorey, Fred J; Goodarzian, Fariba; Fu, Cecilia H

2012-01-01

Background: Although the accumulation of white adipose tissue (WAT) is a risk factor for disease, brown adipose tissue (BAT) has been suggested to have a protective role against obesity. Objective: We studied whether changes in BAT were related to changes in the amounts of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in children treated for malignancy. Design: We examined the effect of BAT activity on weight, SAT, and VAT in 32 pediatric patients with cancer whose positron emission tomography–computed tomography (PET-CT) scans at diagnosis showed no BAT activity. Changes in weight, SAT, and VAT from diagnosis to remission for children with metabolically active BAT at disease-free follow-up (BAT+) were compared with those in children without visualized BAT when free of disease (BAT−). Results: Follow-up PET-CT studies (4.7 ± 2.4 mo later) after successful treatment of the cancer showed BAT+ in 19 patients but no active BAT (BAT−) in 13 patients. BAT+ patients, in comparison with BAT− patients, gained significantly less weight (3.3 ± 6.6% compared with 11.0 ± 11.6%; P = 0.02) and had significantly less SAT (18.2 ± 26.5% compared with 67.4 ± 71.7%; P = 0.01) and VAT (22.6 ± 33.5% compared with 131.6 ± 171.8%; P = 0.01) during treatment. Multiple regression analysis indicated that the inverse relations between BAT activation and measures of weight, SAT, and VAT persisted even after age, glucocorticoid treatment, and the season when the PET-CT scans were obtained were accounted for. Conclusion: The activation of BAT in pediatric patients undergoing treatment of malignancy is associated with significantly less adipose accumulation. This trial was registered at clinicaltrials.gov as NCT01517581. PMID:22456659

Antiobesity Effect of Exopolysaccharides Isolated from Kefir Grains.

PubMed

Lim, Juha; Kale, Madhuvanti; Kim, Dong-Hyeon; Kim, Hong-Seok; Chon, Jung-Whan; Seo, Kun-Ho; Lee, Hyeon Gyu; Yokoyama, Wallace; Kim, Hyunsook

2017-11-22

Physiological properties of water-soluble exopolysaccharides (EPS) and residues after EPS removal (Res) from the probiotic kefir were determined in high-fat (HF) diet-fed C57BL/6J mice. EPS solutions showed rheological properties and lower viscosity compared to those of β-glucan (BG). EPS significantly suppressed the adipogenesis of 3T3-L1 preadipocytes in a dose-dependent manner. Mice were fed HF diets containing 5% EPS, 5% BG, 8% Res, or 5% microcrystalline cellulose (control) for 4 weeks. Compared with the control, EPS supplementation significantly reduced HF diet-induced body weight gain, adipose tissue weight, and plasma very-low-density lipoprotein cholesterol concentration (P < 0.05). Res and BG significantly reduced body weight gain; however, reduction in adipose tissue weight was not statistically significant, suggesting that the antiobesity effect of EPS occurs due to viscosity and an additional factor. EPS supplementation significantly enhanced abundance of Akkermansia spp. in feces. These data indicate that EPS shows significant antiobesity effects possibly via intestinal microbiota alterations.

Differential Accumulation of Mercury and Selenium in Brown Trout Tissues of a High-Gradient Urbanized Stream in Colorado, USA.

PubMed

Herrmann, S J; Nimmo, D R; Carsella, J S; Herrmann-Hoesing, L M; Turner, J A; Gregorich, J M; Heuvel, B D Vanden; Nehring, R B; Foutz, H P

2016-02-01

Total mercury (THg) and selenium (Se) were analyzed by Inductively Coupled Plasma Mass Spectrometry in 11 internal and external tissues and stomach contents from 23 brown trout, Salmo trutta, of a 22.9-km reach of a high-gradient stream (upper Fountain Creek) in Colorado, USA, impacted by coal-fired power plants, shale deposits, and urbanization. Trout and water were sampled from four sites ranging from 2335 to 1818 m elevation. Lengths, weights, and ages of fish between pairs of the four sites were not significantly different. The dry weight (dw) to wet weight (ww) conversion factor for each tissue was calculated with egg-ovary highest at 0.379 and epaxial muscle fourth highest at 0.223. THg and Se in stomach contents indicated diet and not ambient water was the major source of Hg and Se bioaccumulated. Mean THg ww in kidney was 40.33 µg/kg, and epaxial muscle second highest at 36.76 µg/kg. None of the tissues exceeded the human critical threshold for Hg. However, all 23 trout had at least one tissue type that exceeded 0.02 mg/kg THg ww for birds, and four trout tissues exceeded 0.1 mg/kg THg ww for mammals, indicating that piscivorous mammals and birds should be monitored. Se concentrations in tissues varied depending on ww or dw listing. Mean Se dw in liver was higher than ovary at the uppermost site and the two lower sites. Liver tissue, in addition to egg-ovary, should be utilized as an indicator tissue for Se toxicity.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolfe, M.; Norman, D.

Birds and mammals exposed to waterborne mercury (Hg) and methylmercury (MeHg) were collected and/or sampled at Clear Lake, California, USA, to field test the predictive wildlife criteria model developed for the Great Lakes Water Quality Initiative (GLWQI). Tissue samples collected from sampled animals were analyzed for Hg and organochlorine residues, and for selected physiologic parameters known to be affected by Hg. All mammalian organ tissues analyzed contained less than 12 ppm total Hg, wet weight. All avian tissue samples analyzed contained less than 3 ppm total Hg, wet weight. No evidence of Hg-associated health effects was found. Tissue Hg residuesmore » were compared with water, sediment, and animal food samples to characterize bioaccumulation of mercury in the Clear Lake food web. Total Hg bioaccumulation factors for the Clear Lake site closest to the Hg source were: TL-2: 11,100; TL-3: 31,200; TL-4, 190,000. The results support the final wildlife criterion and suggest that the GLWQI model, with site-specific modifications, is predictive for other Hg-bearing aquatic systems.« less

Weight Management for Athletes and Active Individuals: A Brief Review.

PubMed

Manore, Melinda M

2015-11-01

Weight management for athletes and active individuals is unique because of their high daily energy expenditure; thus, the emphasis is usually placed on changing the diet side of the energy balance equation. When dieting for weight loss, active individuals also want to preserve lean tissue, which means that energy restriction cannot be too severe or lean tissue is lost. First, this brief review addresses the issues of weight management in athletes and active individuals and factors to consider when determining a weight-loss goal. Second, the concept of dynamic energy balance is reviewed, including two mathematical models developed to improve weight-loss predictions based on changes in diet and exercise. These models are now available on the Internet. Finally, dietary strategies for weight loss/maintenance that can be successfully used with active individuals are given. Emphasis is placed on teaching the benefits of consuming a low-ED diet (e.g., high-fiber, high-water, low-fat foods), which allows for the consumption of a greater volume of food to increase satiety while reducing energy intake. Health professionals and sport dietitians need to understand dynamic energy balance and be prepared with effective and evidence-based dietary approaches to help athletes and active individuals achieve their body-weight goals.

Polypropylene Surgical Mesh Coated with Extracellular Matrix Mitigates the Host Foreign Body Response

PubMed Central

Wolf, Matthew T.; Carruthers, Christopher A.; Dearth, Christopher L.; Crapo, Peter M.; Huber, Alexander; Burnsed, Olivia A.; Londono, Ricardo; Johnson, Scott A.; Daly, Kerry A.; Stahl, Elizabeth C.; Freund, John M.; Medberry, Christopher J.; Carey, Lisa E.; Nieponice, Alejandro; Amoroso, Nicholas J.; Badylak, Stephen F.

2013-01-01

Surgical mesh devices composed of synthetic materials are commonly used for ventral hernia repair. These materials provide robust mechanical strength and are quickly incorporated into host tissue; factors which contribute to reduced hernia recurrence rates. However, such mesh devices cause a foreign body response with the associated complications of fibrosis and patient discomfort. In contrast, surgical mesh devices composed of naturally occurring extracellular matrix (ECM) are associated with constructive tissue remodeling, but lack the mechanical strength of synthetic materials. A method for applying a porcine dermal ECM hydrogel coating to a polypropylene mesh is described herein with the associated effects upon the host tissue response and biaxial mechanical behavior. Uncoated and ECM coated heavy-weight BARD™ Mesh were compared to the light-weight ULTRAPRO™ and BARD™ Soft Mesh devices in a rat partial thickness abdominal defect overlay model. The ECM coated mesh attenuated the pro-inflammatory response compared to all other devices, with a reduced cell accumulation and fewer foreign body giant cells. The ECM coating degraded by 35 days, and was replaced with loose connective tissue compared to the dense collagenous tissue associated with the uncoated polypropylene mesh device. Biaxial mechanical characterization showed that all of the mesh devices were of similar isotropic stiffness. Upon explantation, the light-weight mesh devices were more compliant than the coated or uncoated heavy-weight devices. The present study shows that an ECM coating alters the default host response to a polypropylene mesh, but not the mechanical properties in an acute in vivo abdominal repair model. PMID:23873846

Negative regulatory role of PI3-kinase in TNF-induced tumor necrosis.

PubMed

Matschurat, Susanne; Blum, Sabine; Mitnacht-Kraus, Rita; Dijkman, Henry B P M; Kanal, Levent; De Waal, Robert M W; Clauss, Matthias

2003-10-20

Tissue factor is the prime initiator of blood coagulation. Expression of tissue factor in tumor endothelial cells leads to thrombus formation, occlusion of vessels and development of hemorrhagic infarctions in the tumor tissue, often followed by regression of the tumor. Tumor cells produce endogenous vascular endothelial growth factor (VEGF), which sensitizes endothelial cells for systemically administered tumor necrosis factor alpha (TNF alpha) and synergistically enhances the TNF-induced expression of tissue factor. We have analyzed the pathways involved in the induction of tissue factor in human umbilical cord vein endothelial cells (HUVECs) after combined stimulation with TNF and VEGF. By using specific low molecular weight inhibitors, we demonstrated that protein kinase C (PKC), p44/42 and p38 mitogen-activated protein (MAP) kinases, and stress-activated protein kinase (JNK) are essentially involved in the induction of tissue factor. In contrast, the application of wortmannin, an inhibitor of phosphatidylinositol 3 (PI3)-kinase, led to strongly enhanced expression of tissue factor in TNF- and VEGF-treated cells, implicating a negative regulatory role for PI3-kinase. In vivo, the application of wortmannin promoted the formation of TNF-induced hemorrhages and intratumoral necroses in murine meth A tumors. The co-injection of wortmannin lowered the effective dose of applied TNF. Therefore, it is conceivable that the treatment of TNF-sensitive tumors with a combination of TNF and wortmannin will ensure the selective damage of the tumor endothelium and minimize the risk of systemic toxicity of TNF. TNF-treatment in combination with specific inhibition of PI3-kinase is a novel concept in anti-cancer therapy. Copyright 2003 Wiley-Liss, Inc.

Low-maintenance energy requirements of obese dogs after weight loss.

PubMed

German, Alexander J; Holden, Shelley L; Mather, Nicola J; Morris, Penelope J; Biourge, Vincent

2011-10-01

Weight rebound after successful weight loss is a well-known phenomenon in humans and dogs, possibly due to the fact that energy restriction improves metabolic efficiency, reducing post-weight-loss maintenance energy requirements (MER). The aim of the present study was to estimate post-weight-loss MER in obese pet dogs that had successfully lost weight and did not subsequently rebound. A total of twenty-four obese dogs, successfully completing a weight management programme at the Royal Canin Weight Management Clinic, University of Liverpool (Wirral, UK), were included. In all dogs, a period of >14 d of stable weight ( < 1 % change) was identified post-weight loss, when food intake was constant and activity levels were stable (assessed via owners' diary records). Post-weight-loss MER was indirectly estimated by determining dietary energy consumption during this stable weight period. Multivariable linear regression was used to identify factors that were associated with post-weight-loss MER. The mean length of stable weight after weight loss was 54 (SD 34.1) d. During this time, MER was 285 (SD 54.8) kJ/kg(0.75) per d. The rate of prior weight loss and food intake during the weight-loss phase was positively associated with post-weight-loss MER, while the amount of lean tissue lost was negatively associated with post-weight-loss MER. MER are low after weight loss in obese pet dogs (typically only 10 % more than required during weight-loss MER), which has implications for what should constitute the optimal diet during this period. Preserving lean tissue during weight loss may maximise post-weight-loss MER and help prevent rebound.

Achieving Body Weight Adjustments for Feeding Status and Pregnant or Non-Pregnant Condition in Beef Cows

PubMed Central

Gionbelli, Mateus P.; Duarte, Marcio S.; Valadares Filho, Sebastião C.; Detmann, Edenio; Chizzotti, Mario L.; Rodrigues, Felipe C.; Zanetti, Diego; Gionbelli, Tathyane R. S.; Machado, Marcelo G.

2015-01-01

Background Beef cows herd accounts for 70% of the total energy used in the beef production system. However, there are still limited studies regarding improvement of production efficiency in this category, mainly in developing countries and in tropical areas. One of the limiting factors is the difficulty to obtain reliable estimates of weight variation in mature cows. This occurs due to the interaction of weight of maternal tissues with specific physiological stages such as pregnancy. Moreover, variation in gastrointestinal contents due to feeding status in ruminant animals is a major source of error in body weight measurements. Objectives Develop approaches to estimate the individual proportion of weight from maternal tissues and from gestation in pregnant cows, adjusting for feeding status and stage of gestation. Methods and Findings Dataset of 49 multiparous non-lactating Nellore cows (32 pregnant and 17 non-pregnant) were used. To establish the relationships between the body weight, depending on the feeding status of pregnant and non-pregnant cows as a function of days of pregnancy, a set of general equations was tested, based on theoretical suppositions. We proposed the concept of pregnant compound (PREG), which represents the weight that is genuinely related to pregnancy. The PREG includes the gravid uterus minus the non-pregnant uterus plus the accretion in udder related to pregnancy. There was no accretion in udder weight up to 238 days of pregnancy. By subtracting the PREG from live weight of a pregnant cow, we obtained estimates of the weight of only maternal tissues in pregnant cows. Non-linear functions were adjusted to estimate the relationship between fasted, non-fasted and empty body weight, for pregnant and non-pregnant cows. Conclusions Our results allow for estimating the actual live weight of pregnant cows and their body constituents, and subsequent comparison as a function of days of gestation and feeding status. PMID:25793770

Analysis of linear energy transfers and quality factors of charged particles produced by spontaneous fission neutrons from 252Cf and 244Pu in the human body.

PubMed

Endo, Akira; Sato, Tatsuhiko

2013-04-01

Absorbed doses, linear energy transfers (LETs) and quality factors of secondary charged particles in organs and tissues, generated via the interactions of the spontaneous fission neutrons from (252)Cf and (244)Pu within the human body, were studied using the Particle and Heavy Ion Transport Code System (PHITS) coupled with the ICRP Reference Phantom. Both the absorbed doses and the quality factors in target organs generally decrease with increasing distance from the source organ. The analysis of LET distributions of secondary charged particles led to the identification of the relationship between LET spectra and target-source organ locations. A comparison between human body-averaged mean quality factors and fluence-averaged radiation weighting factors showed that the current numerical conventions for the radiation weighting factors of neutrons, updated in ICRP103, and the quality factors for internal exposure are valid.

Complement Factor H Is Expressed in Adipose Tissue in Association With Insulin Resistance

PubMed Central

Moreno-Navarrete, José María; Martínez-Barricarte, Rubén; Catalán, Victoria; Sabater, Mònica; Gómez-Ambrosi, Javier; Ortega, Francisco José; Ricart, Wifredo; Blüher, Mathias; Frühbeck, Gema; Rodríguez de Cordoba, Santiago; Fernández-Real, José Manuel

2010-01-01

OBJECTIVE Activation of the alternative pathway of the complement system, in which factor H (fH; complement fH [CFH]) is a key regulatory component, has been suggested as a link between obesity and metabolic disorders. Our objective was to study the associations between circulating and adipose tissue gene expressions of CFH and complement factor B (fB; CFB) with obesity and insulin resistance. RESEARCH DESIGN AND METHODS Circulating fH and fB were determined by enzyme-linked immunosorbent assay in 398 subjects. CFH and CFB gene expressions were evaluated in 76 adipose tissue samples, in isolated adipocytes, and in stromovascular cells (SVC) (n = 13). The effects of weight loss and rosiglitazone were investigated in independent cohorts. RESULTS Both circulating fH and fB were associated positively with BMI, waist circumference, triglycerides, and inflammatory parameters and negatively with insulin sensitivity and HDL cholesterol. For the first time, CFH gene expression was detected in human adipose tissue (significantly increased in subcutaneous compared with omental fat). CFH gene expression in omental fat was significantly associated with insulin resistance. In contrast, CFB gene expression was significantly increased in omental fat but also in association with fasting glucose and triglycerides. The SVC fraction was responsible for these differences, although isolated adipocytes also expressed fB and fH at low levels. Both weight loss and rosiglitazone led to significantly decreased circulating fB and fH levels. CONCLUSIONS Increased circulating fH and fB concentrations in subjects with altered glucose tolerance could reflect increased SVC-induced activation of the alternative pathway of complement in omental adipose tissue linked to insulin resistance and metabolic disturbances. PMID:19833879

Altered Breast Development in Young Girls from an Agricultural Environment

PubMed Central

Guillette, Elizabeth A.; Conard, Craig; Lares, Fernando; Aguilar, Maria Guadalupe; McLachlan, John; Guillette, Louis J.

2006-01-01

In several human populations, the age at which female breast development begins is reported to have declined over the last five decades. Much debate has occurred over whether this reported decline has actually occurred and what factors contribute to it. However, geographical patterns reflecting earlier developmental onset in some human populations suggest environmental factors influence this phenomenon. These factors include interactions between genetic makeup, nutrition, and possible cumulative exposure to estrogens, both endogenous as well as environmental beginning during in utero development. We examined the onset of breast development in a group of peripubertal girls from the Yaqui Valley of Sonora, Mexico. We observed that girls from valley towns, areas using modern agricultural practices, exhibited larger breast fields than those of girls living in the foothills who exhibited similar stature [e.g., weight, height, body mass index (BMI)], and genetic background. Further, girls from valley towns displayed a poorly defined relationship between breast size and mammary gland development, whereas girls from the Yaqui foothills, where traditional ranching occurs, show a robust positive relationship between breast size and mammary size. The differences noted were obtained by a medically based exam involving morphometric analysis and palpation of tissues, in contrast to visual staging alone. In fact, use of the Tanner scale, involving visual staging of breast development for puberty, detected no differences between the study populations. Mammary tissue, determined by palpation, was absent in 18.5% of the girls living in agricultural areas, although palpable breast adipose tissue was present. No relationship was seen between mammary diameter and weight or BMI in either population. These data suggest that future in-depth studies examining mammary tissue growth and fat deposition in breast tissue are required if we are to understand environmental influences on these phenomena. PMID:16507474

Radiation Doses to Members of the U.S. Population from Ubiquitous Radionuclides in the Body: Part 3, Results, Variability, and Uncertainty

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watson, David J.; Strom, Daniel J.

This paper is part three of a three-part series investigating annual effective doses to residents of the United States from intakes of ubiquitous radionuclides, including radionuclides occurring naturally, radionuclides whose concentrations are technologically enhanced, and anthropogenic radionuclides. The radionuclides of interest are the 238U series (14 nuclides), the actinium series (headed by 235U; 11 nuclides), and the 232Th series (11 nuclides); primordial radionuclides 87Rb and 40K; cosmogenic and fallout radionuclides 14C and 3H; and purely anthropogenic radionuclides 137Cs-137mBa, 129I and 90Sr-90Y. This series of papers explicitly excludes intakes from inhaling 222Rn, 220Rn, and their short-lived decay products; it also excludesmore » intakes of radionuclides in occupational and medical settings. Part one reviewed, summarized, characterized, and grouped all published and some unpublished data for U.S. residents on ubiquitous radionuclide concentrations in tissues and organs. Part two described the methods used to organize the data collected in part one and segregate it into the ages and genders defined by the study, imputed missing values from the existing data, apportioned activity in bone, and imputed activity in hollow organ contents and the remainder of the body. This paper estimates equivalent doses to target tissues from source regions and maps target tissues to lists of tissues with International Commission on Radiation Protection (ICRP) tissue-weighting factors or to surrogate tissue regions when there is no direct match. Effective doses, using ICRP tissue-weighting factors recommended in 1977, 1990, and 2007, are then calculated, and an upper bound of variability of the effective dose is estimated by calculating the average coefficients of variation (CV), assuming all variance is due to variability. Most of the data were for adult males, whose average annual effective dose is estimated to be 337 μSv (CV = 0.65, geometric mean = 283 μSv, geometric standard deviation sG = 1.81) using 2007 ICRP tissue-weighting factors. This result is between the National Council on Radiation Protection & Measurements’ 1987 estimate of 390 μSv (using 1977 wTs) and its 2009 estimate of 285 μSv (using 2007 wTs) and is higher than the United Nations Scientific Committee on the Effects of Atomic Radiation’s 2000 estimate of 310 μSv (using 1990 wTs). The methods and software developed for this project are sufficiently detailed and sufficiently general to be usable with autopsy data from any or all countries.« less

Dual-energy contrast-enhanced digital mammography (DE-CEDM): optimization on digital subtraction with practical x-ray low/high-energy spectra

NASA Astrophysics Data System (ADS)

Chen, Biao; Jing, Zhenxue; Smith, Andrew P.; Parikh, Samir; Parisky, Yuri

2006-03-01

Dual-energy contrast enhanced digital mammography (DE-CEDM), which is based upon the digital subtraction of low/high-energy image pairs acquired before/after the administration of contrast agents, may provide physicians physiologic and morphologic information of breast lesions and help characterize their probability of malignancy. This paper proposes to use only one pair of post-contrast low / high-energy images to obtain digitally subtracted dual-energy contrast-enhanced images with an optimal weighting factor deduced from simulated characteristics of the imaging chain. Based upon our previous CEDM framework, quantitative characteristics of the materials and imaging components in the x-ray imaging chain, including x-ray tube (tungsten) spectrum, filters, breast tissues / lesions, contrast agents (non-ionized iodine solution), and selenium detector, were systemically modeled. Using the base-material (polyethylene-PMMA) decomposition method based on entrance low / high-energy x-ray spectra and breast thickness, the optimal weighting factor was calculated to cancel the contrast between fatty and glandular tissues while enhancing the contrast of iodized lesions. By contrast, previous work determined the optimal weighting factor through either a calibration step or through acquisition of a pre-contrast low/high-energy image pair. Computer simulations were conducted to determine weighting factors, lesions' contrast signal values, and dose levels as functions of x-ray techniques and breast thicknesses. Phantom and clinical feasibility studies were performed on a modified Selenia full field digital mammography system to verify the proposed method and computer-simulated results. The resultant conclusions from the computer simulations and phantom/clinical feasibility studies will be used in the upcoming clinical study.

Dietary overload lithium decreases the adipogenesis in abdominal adipose tissue of broiler chickens.

PubMed

Bai, Shiping; Pan, Shuqin; Zhang, Keying; Ding, Xuemei; Wang, Jianping; Zeng, Qiufeng; Xuan, Yue; Su, Zuowei

2017-01-01

To investigate the toxic effects of dietary overload lithium on the adipogenesis in adipose tissue of chicken and the role of hypothalamic neuropeptide Y (NPY) in this process, one-day-old male chicks were fed with the basal diet added with 0 (control) or 100mg lithium/kg diet from lithium chloride (overload lithium) for 35days. Abdominal adipose tissue and hypothalamus were collected at day 6, 14, and 35. As a percentage of body weight, abdominal fat decreased (p<0.001) at day 6, 14, and 35, and feed intake and body weight gain decreased during day 7-14, and day 15-35 in overload lithium treated broilers as compared to control. Adipocyte diameter and DNA content in abdominal adipose tissue were significantly lower in overload-lithium treatment than control at day 35, although no significant differences were observed at day 6 and 14. Dietary overload lithium decreased (p<0.01) transcriptional expression of preadipocyte proliferation makers ki-67 (KI67), microtubule-associated protein homolog (TPX2), and topoisomerase 2-alpha (TOP2A), and preadipocyte differentiation transcriptional factors peroxisome proliferator-activated receptor-γ (PPARγ), and CCAAT/enhancer binding protein (C/EBP) α mRNA abundance in abdominal adipose tissue. In hypothalamus, dietary overload lithium influenced (p<0.001) NPY, and NPY receptor (NPYR) 6 mRNA abundance at day 6 and 14, but not at day 35. In conclusion, dietary overload lithium decreased the adipogenesis in abdominal adipose tissue of chicken, which was accompanied by depressing transcriptional expression of adipogenesis-associated factors. Hypothalamic NPY had a potential role in the adipogenesis in abdominal adipose tissue of broilers with a short-term overload lithium treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

[Strategies for successful weight reduction - focus on energy balance].

PubMed

Weck, M; Bornstein, S R; Barthel, A; Blüher, M

2012-10-01

The prevalence of obesity and related health problems is increasing worldwide and also in Germany. It is well known that substantial and sustained weight loss is difficult to accomplish. Therefore, a variety of studies has been performed in order to specify causes for weight gain and create hypotheses for better treatment options. Key factors of this problem are an adaptation of energy metabolism, especially resting metabolic rate (RMR), non-exercise thermogenesis and diet induced thermogenesis. The extremely high failure rate (> 80%) to keep the reduced weight after successful weight loss is due to adaptation processes of the body to maintain body energy stores. This so called "adaptive thermogenesis" is defined as a smaller than predicted change of energy expenditure in response to changes in energy balance. Adaptive thermogenesis appears to be a major reason for weight regain. The foremost objective of weight-loss programs is the reduction in body fat. However, a concomitant decline in lean tissue can frequently be observed. Since lean body mass (LBM) represents a key determinant of RMR it follows that a decrease in lean tissue could counteract the progress of weight loss. Therefore, with respect to long-term effectiveness of weight reduction programs, the loss of fat mass while maintaining LBM and RMR seems desirable. In this paper we will discuss the mechanisms of adaptive thermogenesis and develop therapeutic strategies with respect to avoiding weight regain successful weight reduction. © Georg Thieme Verlag KG Stuttgart · New York.

Epigenetics in Adipose Tissue, Obesity, Weight Loss, and Diabetes12

PubMed Central

Martínez, J. Alfredo; Milagro, Fermín I.; Claycombe, Kate J.; Schalinske, Kevin L.

2014-01-01

Given the role that diet and other environmental factors play in the development of obesity and type 2 diabetes, the implication of different epigenetic processes is being investigated. Although it is well known that external factors can cause cell type-dependent epigenetic changes, including DNA methylation, histone tail modifications, and chromatin remodeling, the regulation of these processes, the magnitude of the changes and the cell types in which they occur, the individuals more predisposed, and the more crucial stages of life remain to be elucidated. There is evidence that obese and diabetic people have a pattern of epigenetic marks different from nonobese and nondiabetic individuals. The main long-term goals in this field are the identification and understanding of the role of epigenetic marks that could be used as early predictors of metabolic risk and the development of drugs or diet-related treatments able to delay these epigenetic changes and even reverse them. But weight gain and insulin resistance/diabetes are influenced not only by epigenetic factors; different epigenetic biomarkers have also been identified as early predictors of weight loss and the maintenance of body weight after weight loss. The characterization of all the factors that are able to modify the epigenetic signatures and the determination of their real importance are hindered by the following factors: the magnitude of change produced by dietary and environmental factors is small and cumulative; there are great differences among cell types; and there are many factors involved, including age, with multiple interactions between them. PMID:24425725

Epigenetics in adipose tissue, obesity, weight loss, and diabetes.

PubMed

Martínez, J Alfredo; Milagro, Fermín I; Claycombe, Kate J; Schalinske, Kevin L

2014-01-01

Given the role that diet and other environmental factors play in the development of obesity and type 2 diabetes, the implication of different epigenetic processes is being investigated. Although it is well known that external factors can cause cell type-dependent epigenetic changes, including DNA methylation, histone tail modifications, and chromatin remodeling, the regulation of these processes, the magnitude of the changes and the cell types in which they occur, the individuals more predisposed, and the more crucial stages of life remain to be elucidated. There is evidence that obese and diabetic people have a pattern of epigenetic marks different from nonobese and nondiabetic individuals. The main long-term goals in this field are the identification and understanding of the role of epigenetic marks that could be used as early predictors of metabolic risk and the development of drugs or diet-related treatments able to delay these epigenetic changes and even reverse them. But weight gain and insulin resistance/diabetes are influenced not only by epigenetic factors; different epigenetic biomarkers have also been identified as early predictors of weight loss and the maintenance of body weight after weight loss. The characterization of all the factors that are able to modify the epigenetic signatures and the determination of their real importance are hindered by the following factors: the magnitude of change produced by dietary and environmental factors is small and cumulative; there are great differences among cell types; and there are many factors involved, including age, with multiple interactions between them.

Erythropoietin Improves the Survival of Fat Tissue after Its Transplantation in Nude Mice

PubMed Central

Hamed, Saher; Egozi, Dana; Kruchevsky, Danny; Teot, Luc; Gilhar, Amos; Ullmann, Yehuda

2010-01-01

Background Autologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO) has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice. Methodology/Principal Findings Human fat tissue was injected subcutaneously into immunologically-compromised nude mice, and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of the 15-week study period, the extent of angiogenesis, apoptosis, and histology were assessed in the fat grafts. The results were compared to vascular endothelial growth factor (VEGF)-treated and phosphate-buffered saline (PBS)-treated fat grafts. The weight and volume of the EPO-treated grafts were higher than those of the PBS-treated grafts, whose weights and volumes were not different from those of the VEGF-treated grafts. EPO treatment also increased the expression of angiogenic factors and microvascular density, and reduced inflammation and apoptosis in a dose-dependent manner in the fat grafts. Conclusions/Significance Our data suggest that stimulation of angiogenesis by a cluster of angiogenic factors and decreased fat cell apoptosis account for potential mechanisms that underlie the improved long-term survival of fat transplants following EPO treatment. PMID:21085572

Erythropoietin improves the survival of fat tissue after its transplantation in nude mice.

PubMed

Hamed, Saher; Egozi, Dana; Kruchevsky, Danny; Teot, Luc; Gilhar, Amos; Ullmann, Yehuda

2010-11-15

Autologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO) has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice. Human fat tissue was injected subcutaneously into immunologically-compromised nude mice, and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of the 15-week study period, the extent of angiogenesis, apoptosis, and histology were assessed in the fat grafts. The results were compared to vascular endothelial growth factor (VEGF)-treated and phosphate-buffered saline (PBS)-treated fat grafts. The weight and volume of the EPO-treated grafts were higher than those of the PBS-treated grafts, whose weights and volumes were not different from those of the VEGF-treated grafts. EPO treatment also increased the expression of angiogenic factors and microvascular density, and reduced inflammation and apoptosis in a dose-dependent manner in the fat grafts. Our data suggest that stimulation of angiogenesis by a cluster of angiogenic factors and decreased fat cell apoptosis account for potential mechanisms that underlie the improved long-term survival of fat transplants following EPO treatment.

137Cs and 210Po in Pacific Walrus and Bearded Seal from St. Lawrence Island, Alaska

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamilton, T F; Seagars, D J; Jokela, T

2005-02-02

The activity concentration of Cesium-137 ({sup 137}Cs) and naturally-occurring Polonium-210 ({sup 210}Po) were measured in the muscle tissue, kidney and liver of Pacific walrus (Odobenus rosmarus divergens) and bearded seal (Erignathus barbatus) collected by native hunters from the Bering Sea. The mean {sup 137}Cs concentrations in muscle, liver and kidney of Pacific walrus were 0.07, 0.09 and 0.07 Bq kg{sup -1} (N= 5, wet weight), respectively, and 0.17, 0.10, and 0.17 Bq kg{sup -1} (N=2, wet weight), respectively, in bearded seal. In general, {sup 137}Cs tissue concentrations are significantly lower than those previously reported for mammals from other regions. Bymore » comparison, {sup 210}Po activity concentrations appear to be higher than those reported elsewhere but a larger variation. The mean {sup 210}Po concentration in the muscle tissue, liver and kidney of Pacific walrus (N=5, wet weight) were 28.7, 189, and 174 Bq kg{sup -1}, respectively. This compares with {sup 210}Po concentration values (N=2, wet weight) of 27, 207, and 68 Bq kg{sup -1} measured in the muscle tissue, liver and kidney, of bearded seal, respectively. Estimated bioaccumulation factors--as defined by the radionuclide concentration ratio between the target tissue to that in sea water--were two to three orders of magnitude higher for {sup 210}Po that those of {sup 137}Cs. We conclude from radiological dose estimates that ingestion of {sup 137}Cs in foods derived from walrus and seal will pose no threat to human health. This work has important implications for assessing health risks to Alaskan coastal communities concerned about the dumping of nuclear waste in the Russia Arctic.« less

Evaluation of radiation dose to anthropomorphic paediatric models from positron-emitting labelled tracers

NASA Astrophysics Data System (ADS)

Xie, Tianwu; Zaidi, Habib

2014-03-01

PET uses specific molecules labelled with positron-emitting radionuclides to provide valuable biochemical and physiological information. However, the administration of radiotracers to patients exposes them to low-dose ionizing radiation, which is a concern in the paediatric population since children are at a higher cancer risk from radiation exposure than adults. Therefore, radiation dosimety calculations for commonly used positron-emitting radiotracers in the paediatric population are highly desired. We evaluate the absorbed dose and effective dose for 19 positron-emitting labelled radiotracers in anthropomorphic paediatric models including the newborn, 1-, 5-, 10- and 15-year-old male and female. This is achieved using pre-calculated S-values of positron-emitting radionuclides of UF-NCI paediatric phantoms and published biokinetic data for various radiotracers. The influence of the type of anthropomorphic model, tissue weight factors and direct human- versus mouse-derived biokinetic data on the effective dose for paediatric phantoms was also evaluated. In the case of 18F-FDG, dosimetry calculations of reference paediatric patients from various dose regimens were also calculated. Among the considered radiotracers, 18F-FBPA and 15O-water resulted in the highest and lowest effective dose in the paediatric phantoms, respectively. The ICRP 103 updated tissue-weighting factors decrease the effective dose in most cases. Substantial differences of radiation dose were observed between direct human- versus mouse-derived biokinetic data. Moreover, the effect of using voxel- versus MIRD-type models on the calculation of the effective dose was also studied. The generated database of absorbed organ dose and effective dose for various positron-emitting labelled radiotracers using new generation computational models and the new ICRP tissue-weighting factors can be used for the assessment of radiation risks to paediatric patients in clinical practice. This work also contributes to a better understanding of the factors influencing patient-specific radiation dose calculation.

Localization of near-infrared contrast agents in tumors by intravital microscopy

NASA Astrophysics Data System (ADS)

Becker, Andreas; Schneider, Guenther; Riefke, Bjoern; Licha, Kai; Semmler, Wolfhard

1999-01-01

In this contribution we use intravital microscopy to study the dynamics of extravasation into normal and tumor tissue of several hydrophilic cyanine dyes used as near-infrared (NIR) contrast agents. The technique provides information about the angiographic properties of the dyes and about their interaction with tumor tissue under dynamic conditions in vivo. In our previous work we demonstrated that several NIR- absorbing fluorescent dyes enable in vivo fluorescence detection of tumors in mice and rats. However, the mechanism leading to dye accumulation and enhanced fluorescence in tumors is not fully understood. Increased extravasation of dyes into tumor tissue due to pathologically altered tumor vessels may be an important factor in this process. Indocyanine green (ICG) displayed predominantly intravascular distribution and rapid elimination resulting in enhanced fluorescence signal of vessels during the first 15 min after administration only. No elevated extravasation into tumor tissue was observed with ICG. A hydrophilic indotricarbocyanine derivative with a high molecular weight displayed prolonged intravascular distribution and increased fluorescence signal of the vasculature compared to surrounding tissue for up to five hours. Rapid extravasation and accumulation in tumor areas, yielding elevated contrast of tumors up to 15 min after administration, was observed with hydrophilic, low molecular weight indotricarbocyanine derivatives.

Correction of intermittent hypoxia reduces inflammation in obese subjects with obstructive sleep apnea

PubMed Central

Perrini, Sebastio; Quaranta, Vitaliano Nicola; Falcone, Vito Antonio; Kounaki, Stella; Ciavarella, Alessandro; Ficarella, Romina; Barbaro, Maria; Nigro, Pasquale; Carratù, Pierluigi; Natalicchio, Annalisa; Laviola, Luigi; Resta, Onofrio

2017-01-01

BACKGROUND. In obese subjects with obstructive sleep apnea (OSA), chronic intermittent hypoxia (CIH) may be linked to systemic and adipose tissue inflammation. METHODS. We obtained abdominal subcutaneous adipose tissue biopsies from OSA and non-OSA obese (BMI > 35) subjects at baseline and after 24 weeks (T1) of weight-loss intervention plus continuous positive airway pressure (c-PAP) or weight-loss intervention alone, respectively. OSA subjects were grouped according to good (therapeutic) or poor (subtherapeutic) adherence to c-PAP. RESULTS. At baseline, anthropometric and metabolic parameters, serum cytokines, and adipose tissue mRNA levels of obesity-associated chemokines and inflammatory markers were not different in OSA and non-OSA subjects. At T1, body weight was significantly reduced in all groups. Serum concentrations of IL-2, IL-4, IL-6, MCP-1, PDGFβ, and VEGFα were reduced by therapeutic c-PAP in OSA subjects and remained unaltered in non-OSA and subtherapeutic c-PAP groups. Similarly, adipose tissue mRNA levels of macrophage-specific (CD68, CD36) and ER stress (ATF4, CHOP, ERO-1) gene markers, as well as of IL-6, PDGFβ, and VEGFα, were decreased only in the therapeutic c-PAP group. CONCLUSION. CIH does not represent an additional factor increasing systemic and adipose tissue inflammation in morbid obesity. However, in subjects with OSA, an effective c-PAP therapy improves systemic and obesity-associated inflammatory markers. FUNDING. Ministero dell’Università e della Ricerca and Progetti di Rilevante Interesse Nazionale. PMID:28878129

Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity

PubMed Central

Verdeguer, Francisco; Soustek, Meghan S.; Hatting, Maximilian; Blättler, Sharon M.; McDonald, Devin; Barrow, Joeva J.

2015-01-01

Mitochondrial oxidative and thermogenic functions in brown and beige adipose tissues modulate rates of energy expenditure. It is unclear, however, how beige or white adipose tissue contributes to brown fat thermogenic function or compensates for partial deficiencies in this tissue and protects against obesity. Here, we show that the transcription factor Yin Yang 1 (YY1) in brown adipose tissue activates the canonical thermogenic and uncoupling gene expression program. In contrast, YY1 represses a series of secreted proteins, including fibroblast growth factor 21 (FGF21), bone morphogenetic protein 8b (BMP8b), growth differentiation factor 15 (GDF15), angiopoietin-like 6 (Angptl6), neuromedin B, and nesfatin, linked to energy expenditure. Despite substantial decreases in mitochondrial thermogenic proteins in brown fat, mice lacking YY1 in this tissue are strongly protected against diet-induced obesity and exhibit increased energy expenditure and oxygen consumption in beige and white fat depots. The increased expression of secreted proteins correlates with elevation of energy expenditure and promotion of beige and white fat activation. These results indicate that YY1 in brown adipose tissue controls antagonistic gene expression programs associated with energy balance and maintenance of body weight. PMID:26503783

Impact of perinatal exposure to high-fat diet and stress on responses to nutritional challenges, food-motivated behaviour and mesolimbic dopamine function.

PubMed

Romaní-Pérez, M; Lépinay, A L; Alonso, L; Rincel, M; Xia, L; Fanet, H; Caillé, S; Cador, M; Layé, S; Vancassel, S; Darnaudéry, M

2017-04-01

Energy-dense food exposure and stress during development have been suggested to contribute to obesity and metabolic disorders later in life. Although these factors are frequently associated, the effects of their combination have not yet been investigated. In this study, using an animal model, we examined the long-term impact of maternal high-fat diet (HFD) and early-life stress (ELS) on energy homoeostasis control and food motivation. Body weight growth under HFD, adipose tissue, body weight control in response to fasting and refeeding, food-motivated behaviour and mesolimbic dopamine function were examined in adult male offspring exposed to maternal HFD (during gestation and lactation) and/or ELS (maternal separation 3 h per day from postnatal day 2 to 14). Maternal HFD or ELS alone had no significant effect on offspring body weight; however, the combination of these factors exacerbated body weight gain when animals were exposed to HFD after weaning. There are no other significant combinatory effects of these perinatal events. In contrast, independently of the maternal diet, ELS disrupted body weight control during a fasting-refeeding procedure, increased adipose tissue mass and altered lipid metabolism. Finally, maternal HFD and ELS both resulted in exacerbated food-motivated behaviour and blunted dopamine release in the nucleus accumbens during palatable food consumption. We report a synergistic effect of perinatal HFD exposure and stress on the susceptibility to gain weight under HFD. However, ELS has a stronger impact than maternal HFD exposure on energy homoeostasis and food motivation in adult offspring. Altogether, our results suggest a programming effect of stress and nutrition supporting the hypothesis of the developmental origin of health and disease.

Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsu, Jer-Yuan; Crawley, Suzanne; Chen, Michael

Under homeostatic conditions, animals use well-defined hypothalamic neural circuits to help maintain stable body weight, by integrating metabolic and hormonal signals from the periphery to balance food consumption and energy expenditure1,2. In stressed or disease conditions, however, animals use alternative neuronal pathways to adapt to the metabolic challenges of altered energy demand3. Recent studies have identified brain areas outside the hypothalamus that are activated under these ‘non-homeostatic’ conditions4,5,6, but the molecular nature of the peripheral signals and brain-localized receptors that activate these circuits remains elusive. Here we identify glial cell-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) as a brainstem-restricted receptormore » for growth and differentiation factor 15 (GDF15). GDF15 regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses; we show that Gfral knockout mice are hyperphagic under stressed conditions and are resistant to chemotherapy-induced anorexia and body weight loss. GDF15 activates GFRAL-expressing neurons localized exclusively in the area postrema and nucleus tractus solitarius of the mouse brainstem. It then triggers the activation of neurons localized within the parabrachial nucleus and central amygdala, which constitute part of the ‘emergency circuit’ that shapes feeding responses to stressful conditions7. GDF15 levels increase in response to tissue stress and injury, and elevated levels are associated with body weight loss in numerous chronic human diseases8,9. By isolating GFRAL as the receptor for GDF15-induced anorexia and weight loss, we identify a mechanistic basis for the non-homeostatic regulation of neural circuitry by a peripheral signal associated with tissue damage and stress. These findings provide opportunities to develop therapeutic agents for the treatment of disorders with altered energy demand.« less

Determinants of Human Adipose Tissue Gene Expression: Impact of Diet, Sex, Metabolic Status, and Cis Genetic Regulation

PubMed Central

Viguerie, Nathalie; Montastier, Emilie; Maoret, Jean-José; Roussel, Balbine; Combes, Marion; Valle, Carine; Villa-Vialaneix, Nathalie; Iacovoni, Jason S.; Martinez, J. Alfredo; Holst, Claus; Astrup, Arne; Vidal, Hubert; Clément, Karine; Hager, Jorg; Saris, Wim H. M.; Langin, Dominique

2012-01-01

Weight control diets favorably affect parameters of the metabolic syndrome and delay the onset of diabetic complications. The adaptations occurring in adipose tissue (AT) are likely to have a profound impact on the whole body response as AT is a key target of dietary intervention. Identification of environmental and individual factors controlling AT adaptation is therefore essential. Here, expression of 271 transcripts, selected for regulation according to obesity and weight changes, was determined in 515 individuals before, after 8-week low-calorie diet-induced weight loss, and after 26-week ad libitum weight maintenance diets. For 175 genes, opposite regulation was observed during calorie restriction and weight maintenance phases, independently of variations in body weight. Metabolism and immunity genes showed inverse profiles. During the dietary intervention, network-based analyses revealed strong interconnection between expression of genes involved in de novo lipogenesis and components of the metabolic syndrome. Sex had a marked influence on AT expression of 88 transcripts, which persisted during the entire dietary intervention and after control for fat mass. In women, the influence of body mass index on expression of a subset of genes persisted during the dietary intervention. Twenty-two genes revealed a metabolic syndrome signature common to men and women. Genetic control of AT gene expression by cis signals was observed for 46 genes. Dietary intervention, sex, and cis genetic variants independently controlled AT gene expression. These analyses help understanding the relative importance of environmental and individual factors that control the expression of human AT genes and therefore may foster strategies aimed at improving AT function in metabolic diseases. PMID:23028366

Differentiating the Influences of Aging and Adiposity on Brain Weights, Levels of Serum and Brain Cytokines, Gastrointestinal Hormones, and Amyloid Precursor Protein.

PubMed

Banks, William A; Abrass, Christine K; Hansen, Kim M

2016-01-01

Aging and obesity exert important effects on disease. Differentiating these effects is difficult, however, because weight gain often accompanies aging. Here, we used a nested design of aged, calorically restricted, and refed rats to measure changes in brain and blood levels of cytokines and gastrointestinal hormones, brain amyloid precursor protein levels, and brain and body weights. By comparing groups and using path analysis, we found divergent influences of chronological aging versus body weight, our main findings being (i) changes in whole brain weight and serum macrophage colony-stimulating factor levels correlated better with body weight than with chronological aging, (ii) a decrease in brain cytokines and brain plasminogen activator inhibitor levels correlated better with chronological aging than with body weight, (iii) serum erythropoietin levels were influenced by both body weight and aging, (iv) serum plasminogen activator inhibitor, serum cytokines, and brain tumor necrosis factor were not influenced by aging or body weight, and (v) brain amyloid precursor protein more closely related to body weight and serum levels of gastrointestinal hormones than to brain weight, chronological aging, or cytokines. These findings show that although aging and body weight interact, their influences are distinct not only among various cytokines and hormones but also between the central nervous system and the peripheral tissue compartments. Published by Oxford University Press on behalf of the Gerontological Society of America 2014.

Apparent diffusion coefficient of the normal human brain for various experimental conditions

NASA Astrophysics Data System (ADS)

Moraru, Luminita; Dimitrievici, Lucian

2017-01-01

Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) is being increasingly used to assess both brain tissues and cerebrospinal fluid integrity. In this paper we study inter-site reproducibility of the apparent diffusion coefficient values for the main cerebral tissues such as gray matter, white matter and into cerebrospinal fluid and for three different stacks of slices that were spaced at L = 79.8, 84.9 and 90 mm. We assessed the impact of the attenuation factor and diffusion gradient on the results reproducibility.

Metabolically normal obese people are protected from adverse effects following weight gain

PubMed Central

Fabbrini, Elisa; Yoshino, Jun; Yoshino, Mihoko; Magkos, Faidon; Tiemann Luecking, Courtney; Samovski, Dmitri; Fraterrigo, Gemma; Okunade, Adewole L.; Patterson, Bruce W.; Klein, Samuel

2015-01-01

BACKGROUND. Obesity is associated with insulin resistance and increased intrahepatic triglyceride (IHTG) content, both of which are key risk factors for diabetes and cardiovascular disease. However, a subset of obese people does not develop these metabolic complications. Here, we tested the hypothesis that people defined by IHTG content and insulin sensitivity as “metabolically normal obese” (MNO), but not those defined as “metabolically abnormal obese” (MAO), are protected from the adverse metabolic effects of weight gain. METHODS. Body composition, multiorgan insulin sensitivity, VLDL apolipoprotein B100 (apoB100) kinetics, and global transcriptional profile in adipose tissue were evaluated before and after moderate (~6%) weight gain in MNO (n = 12) and MAO (n = 8) subjects with a mean BMI of 36 ± 4 kg/m2 who were matched for BMI and fat mass. RESULTS. Although the increase in body weight and fat mass was the same in both groups, hepatic, skeletal muscle, and adipose tissue insulin sensitivity deteriorated, and VLDL apoB100 concentrations and secretion rates increased in MAO, but not MNO, subjects. Moreover, biological pathways and genes associated with adipose tissue lipogenesis increased in MNO, but not MAO, subjects. CONCLUSIONS. These data demonstrate that MNO people are resistant, whereas MAO people are predisposed, to the adverse metabolic effects of moderate weight gain and that increased adipose tissue capacity for lipogenesis might help protect MNO people from weight gain–induced metabolic dysfunction. TRIAL REGISTRATION. ClinicalTrials.gov NCT01184170. FUNDING. This work was supported by NIH grants UL1 RR024992 (Clinical Translational Science Award), DK 56341 (Nutrition and Obesity Research Center), DK 37948 and DK 20579 (Diabetes Center Grant), and UL1 TR000450 (KL2 Award); a Central Society for Clinical and Translational Research Early Career Development Award; and by grants from the Longer Life Foundation and the Kilo Foundation. PMID:25555214

Reduction of Adipose Tissue Mass by the Angiogenesis Inhibitor ALS-L1023 from Melissa officinalis

PubMed Central

Park, Byung Young; Lee, Hyunghee; Woo, Sangee; Yoon, Miso; Kim, Jeongjun; Hong, Yeonhee; Lee, Hee Suk; Park, Eun Kyu; Hahm, Jong Cheon; Kim, Jin Woo; Shin, Soon Shik; Kim, Min-Young; Yoon, Michung

2015-01-01

It has been suggested that angiogenesis modulates adipogenesis and obesity. This study was undertaken to determine whether ALS-L1023 (ALS) prepared by a two-step organic solvent fractionation from Melissa leaves, which exhibits antiangiogenic activity, can regulate adipose tissue growth. The effects of ALS on angiogenesis and extracellular matrix remodeling were measured using in vitro assays. The effects of ALS on adipose tissue growth were investigated in high fat diet-induced obese mice. ALS inhibited VEGF- and bFGF-induced endothelial cell proliferation and suppressed matrix metalloproteinase (MMP) activity in vitro. Compared to obese control mice, administration of ALS to obese mice reduced body weight gain, adipose tissue mass and adipocyte size without affecting appetite. ALS treatment decreased blood vessel density and MMP activity in adipose tissues. ALS reduced the mRNA levels of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9), whereas ALS increased the mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) in adipose tissues. The protein levels of VEGF, MMP-2 and MMP-9 were also decreased by ALS in adipose tissue. Metabolic changes in plasma lipids, liver triglycerides, and hepatic expression of fatty acid oxidation genes occurred during ALS-induced weight loss. These results suggest that ALS, which has antiangiogenic and MMP inhibitory activities, reduces adipose tissue mass in nutritionally obese mice, demonstrating that adipose tissue growth can be regulated by angiogenesis inhibitors. PMID:26599360

Molecular forms of C-type natriuretic peptide in cerebrospinal fluid and plasma reflect differential processing in brain and pituitary tissues.

PubMed

Wilson, Michele O; Barrell, Graham K; Prickett, Timothy C R; Espiner, Eric A

2018-01-01

C-type natriuretic peptide (CNP) is a paracrine growth factor widely expressed within tissues of the central nervous system. Consistent with this is the high concentration of CNP in cerebrospinal fluid (CSF), exceeding levels in the systemic circulation. CNP abundance is high in hypothalamus and especially enriched in pituitary tissue where - in contrast to hypothalamus - processing to CNP-22 is minimal. Recently we have shown that dexamethasone acutely raises CNP peptides throughout the brain as well as in CSF and plasma. Postulating that molecular forms of CNP would differ in central tissues compared to forms in pituitary and plasma, we have characterized the molecular forms of CNP in tissues (hypothalamus, anterior and posterior pituitary gland) and associated fluids (CSF and plasma) using size-exclusion high performance liquid chromatography (SE-HPLC) and radioimmunoassay in control (saline-treated) and dexamethasone-treated adult sheep. Three immunoreactive-CNP components were identified which were consistent with proCNP (1-103), CNP-53 and CNP-22, but the presence and proportions of these different fragments differed among tissues. Peaks consistent with CNP-53 were the dominant form in all tissues and fluids. Peaks consistent with proCNP, conspicuous in hypothalamic extracts, were negligible in CSF whereas proportions of low molecular weight immunoreactivity (IR) consistent with CNP-22 were similar in hypothalamus, posterior pituitary gland and CSF. In contrast, in both plasma and the anterior pituitary gland, proportions of higher molecular weight IR, consistent with CNP-53 and proCNP, predominated, and low molecular weight IR consistent with CNP-22 was very low. After dexamethasone, proCNP like material - but not other forms - was increased in all samples except CSF, consistent with increased synthesis and secretion. In conclusion, immunoreactive forms of CNP in central tissues differ from those identified in anterior pituitary tissue and plasma - suggesting that the anterior pituitary gland may contribute to systemic levels of CNP in some physiological settings. Copyright © 2017 Elsevier Inc. All rights reserved.

A distinct adipose tissue gene expression response to caloric restriction predicts 6-mo weight maintenance in obese subjects.

PubMed

Mutch, David M; Pers, Tune H; Temanni, M Ramzi; Pelloux, Veronique; Marquez-Quiñones, Adriana; Holst, Claus; Martinez, J Alfredo; Babalis, Dimitris; van Baak, Marleen A; Handjieva-Darlenska, Teodora; Walker, Celia G; Astrup, Arne; Saris, Wim H M; Langin, Dominique; Viguerie, Nathalie; Zucker, Jean-Daniel; Clément, Karine

2011-12-01

Weight loss has been shown to reduce risk factors associated with cardiovascular disease and diabetes; however, successful maintenance of weight loss continues to pose a challenge. The present study was designed to assess whether changes in subcutaneous adipose tissue (scAT) gene expression during a low-calorie diet (LCD) could be used to differentiate and predict subjects who experience successful short-term weight maintenance from subjects who experience weight regain. Forty white women followed a dietary protocol consisting of an 8-wk LCD phase followed by a 6-mo weight-maintenance phase. Participants were classified as weight maintainers (WMs; 0-10% weight regain) and weight regainers (WRs; 50-100% weight regain) by considering changes in body weight during the 2 phases. Anthropometric measurements, bioclinical variables, and scAT gene expression were studied in all individuals before and after the LCD. Energy intake was estimated by using 3-d dietary records. No differences in body weight and fasting insulin were observed between WMs and WRs at baseline or after the LCD period. The LCD resulted in significant decreases in body weight and in several plasma variables in both groups. WMs experienced a significant reduction in insulin secretion in response to an oral-glucose-tolerance test after the LCD; in contrast, no changes in insulin secretion were observed in WRs after the LCD. An ANOVA of scAT gene expression showed that genes regulating fatty acid metabolism, citric acid cycle, oxidative phosphorylation, and apoptosis were regulated differently by the LCD in WM and WR subjects. This study suggests that LCD-induced changes in insulin secretion and scAT gene expression may have the potential to predict successful short-term weight maintenance. This trial was registered at clinicaltrials.gov as NCT00390637.

Computation and application of tissue-specific gene set weights.

PubMed

Frost, H Robert

2018-04-06

Gene set testing, or pathway analysis, has become a critical tool for the analysis of highdimensional genomic data. Although the function and activity of many genes and higher-level processes is tissue-specific, gene set testing is typically performed in a tissue agnostic fashion, which impacts statistical power and the interpretation and replication of results. To address this challenge, we have developed a bioinformatics approach to compute tissuespecific weights for individual gene sets using information on tissue-specific gene activity from the Human Protein Atlas (HPA). We used this approach to create a public repository of tissue-specific gene set weights for 37 different human tissue types from the HPA and all collections in the Molecular Signatures Database (MSigDB). To demonstrate the validity and utility of these weights, we explored three different applications: the functional characterization of human tissues, multi-tissue analysis for systemic diseases and tissue-specific gene set testing. All data used in the reported analyses is publicly available. An R implementation of the method and tissue-specific weights for MSigDB gene set collections can be downloaded at http://www.dartmouth.edu/∼hrfrost/TissueSpecificGeneSets. rob.frost@dartmouth.edu.

Predictors for cecal insertion time: the impact of abdominal visceral fat measured by computed tomography.

PubMed

Nagata, Naoyoshi; Sakamoto, Kayo; Arai, Tomohiro; Niikura, Ryota; Shimbo, Takuro; Shinozaki, Masafumi; Noda, Mitsuhiko; Uemura, Naomi

2014-10-01

Several factors affect the risk for longer cecal insertion time. The aim of this study was to identify the predictors of longer insertion time and to evaluate the effect of visceral fat measured by CT. This is a retrospective observational study. Outpatients for colorectal cancer screening who underwent colonoscopies and CT were enrolled. Computed tomography was performed in individuals who requested cancer screening and in those with GI bleeding. Information on obesity indices (BMI, visceral adipose tissue, and subcutaneous adipose tissue area), constipation score, history of abdominal surgery, poor preparation, fellow involvement, diverticulosis, patient discomfort, and the amount of sedation used was collected. The cecal insertion rate was 95.2% (899/944), and 899 patients were analyzed. Multiple regression analysis showed that female sex, lower BMI, lower visceral adipose tissue area, lower subcutaneous adipose tissue area, higher constipation score, history of surgery, poor bowel preparation, and fellow involvement were independently associated with longer insertion time. When obesity indices were considered simultaneously, smaller subcutaneous adipose tissue area (p = 0.038), but not lower BMI (p = 0.802) or smaller visceral adipose tissue area (p = 0.856), was associated with longer insertion time; the other aforementioned factors remained associated with longer insertion time. In the subanalysis of normal-weight patients (BMI <25 kg/m), a smaller subcutaneous adipose tissue area (p = 0.002), but not a lower BMI (p = 0.782), was independently associated with a longer insertion time. Longer insertion time had a positive correlation with a higher patient discomfort score (ρ = 0.51, p < 0.001) and a greater amount of midazolam use (ρ = 0.32, p < 0.001). This single-center retrospective study includes a potential selection bias. In addition to BMI and intra-abdominal fat, female sex, constipation, history of abdominal surgery, poor preparation, and fellow involvement were predictors of longer cecal insertion time. Among the obesity indices, high subcutaneous fat accumulation was the best predictive factor for easier passage of the colonoscope, even when body weight was normal.

3D Fast Spin Echo T2-weighted Contrast for Imaging the Female Cervix

NASA Astrophysics Data System (ADS)

Vargas Sanchez, Andrea Fernanda

Magnetic Resonance Imaging (MRI) with T2-weighted contrast is the preferred modality for treatment planning and monitoring of cervical cancer. Current clinical protocols image the volume of interest multiple times with two dimensional (2D) T2-weighted MRI techniques. It is of interest to replace these multiple 2D acquisitions with a single three dimensional (3D) MRI acquisition to save time. However, at present the image contrast of standard 3D MRI does not distinguish cervical healthy tissue from cancerous tissue. The purpose of this thesis is to better understand the underlying factors that govern the contrast of 3D MRI and exploit this understanding via sequence modifications to improve the contrast. Numerical simulations are developed to predict observed contrast alterations and to propose an improvement. Improvements of image contrast are shown in simulation and with healthy volunteers. Reported results are only preliminary but a promising start to establish definitively 3D MRI for cervical cancer applications.

IMPORTANCE OF THE DETERMINATION OF THE WEIGHT OF THE THYROID GLAND AND THE CLINICAL BIOLOGICAL FACTORS IN THE TREATMENT OF HYPERTHYRODISM WITH $sup 131$I

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clode, W.; Sobral, V.; Baptista, A.M.

1959-10-31

Clinical results are reviewed for a group of 117 patients treated for hyperthyroidism with iodine-131. The importance of clinical, biological, and physical factors on results is stressed. Various methods for determining thyroid mass are discussed. A visualization technique, called pneumothyroid, is described in which the thyroid volume is determined from a series of x rays and tomographs following the injection of air into the tissue surrounding the thyroid capsule. The apparatus used resembles that used in pneumothorax. This method was found superior to palpation for estimations of thyroid weight prior to calculation of iodine-131 dose. (C.H.)

Modifications of pancreatic diffusion MRI by tissue characteristics: what are we weighting for?

PubMed

Nissan, Noam

2017-08-01

Diffusion-weighted imaging holds the potential to improve the diagnosis and biological characterization of pancreatic disease, and in particular pancreatic cancer, which exhibits decreased values of the apparent diffusion coefficient (ADC). Yet, variable and overlapping ADC values have been reported for the healthy and the pathological pancreas, including for cancer and other benign conditions. This controversy reflects the complexity of probing the water-diffusion process in the pancreas, which is dependent upon multiple biological factors within this organ's unique physiological environment. In recent years, extensive studies have investigated the correlation between tissue properties including cellularity, vascularity, fibrosis, secretion and microstructure and pancreatic diffusivity. Understanding how the various physiological and pathological features and the underlying functional processes affect the diffusion measurement may serve to optimize the method for improved diagnostic gain. Therefore, the aim of the present review article is to elucidate the relationship between pancreatic tissue characteristics and diffusion MRI measurement. Copyright © 2017 John Wiley & Sons, Ltd.

Microporous silk fibroin scaffolds embedding PLGA microparticles for controlled growth factor delivery in tissue engineering.

PubMed

Wenk, Esther; Meinel, Anne J; Wildy, Sarah; Merkle, Hans P; Meinel, Lorenz

2009-05-01

The development of prototype scaffolds for either direct implantation or tissue engineering purposes and featuring spatiotemporal control of growth factor release is highly desirable. Silk fibroin (SF) scaffolds with interconnective pores, carrying embedded microparticles that were loaded with insulin-like growth factor I (IGF-I), were prepared by a porogen leaching protocol. Treatments with methanol or water vapor induced water insolubility of SF based on an increase in beta-sheet content as analyzed by FTIR. Pore interconnectivity was demonstrated by SEM. Porosities were in the range of 70-90%, depending on the treatment applied, and were better preserved when methanol or water vapor treatments were prior to porogen leaching. IGF-I was encapsulated into two different types of poly(lactide-co-glycolide) microparticles (PLGA MP) using uncapped PLGA (50:50) with molecular weights of either 14 or 35 kDa to control IGF-I release kinetics from the SF scaffold. Embedded PLGA MP were located in the walls or intersections of the SF scaffold. Embedment of the PLGA MP into the scaffolds led to more sustained release rates as compared to the free PLGA MP, whereas the hydrolytic degradation of the two PLGA MP types was not affected. The PLGA types used had distinct effects on IGF-I release kinetics. Particularly the supernatants of the lower molecular weight PLGA formulations turned out to release bioactive IGF-I. Our studies justify future investigations of the developed constructs for tissue engineering applications.

Impact of intra- and extra-osseous soft tissue composition on changes in bone mineral density with weight loss and regain.

PubMed

Bosy-Westphal, Anja; Later, Wiebke; Schautz, Britta; Lagerpusch, Merit; Goele, Kristin; Heller, Martin; Glüer, Claus-C; Müller, Manfred J

2011-07-01

Recent studies report a significant gain in bone mineral density (BMD) after diet-induced weight loss. This might be explained by a measurement artefact. We therefore investigated the impact of intra- and extra-osseous soft tissue composition on bone measurements by dual X-ray absorptiometry (DXA) in a longitudinal study of diet-induced weight loss and regain in 55 women and 17 men (19-46 years, BMI 28.2-46.8 kg/m(2)). Total and regional BMD were measured before and after 12.7 ± 2.2 week diet-induced weight loss and 6 months after significant weight regain (≥30%). Hydration of fat free mass (FFM) was assessed by a 3-compartment model. Skeletal muscle (SM) mass, extra-osseous adipose tissue, and bone marrow were measured by whole body magnetic resonance imaging (MRI). Mean weight loss was -9.2 ± 4.4 kg (P < 0.001) and was followed by weight regain in a subgroup of 24 subjects (+6.3 ± 2.9 kg; P < 0.001). With weight loss, bone marrow and extra-osseous adipose tissue decreased whereas BMD increased at the total body, lumbar spine, and the legs (women only) but decreased at the pelvis (men only, all P < 0.05). The decrease in BMD(pelvis) correlated with the loss in visceral adipose tissue (VAT) (P < 0.05). Increases in BMD(legs) were reversed after weight regain and inversely correlated with BMD(legs) decreases. No other associations between changes in BMD and intra- or extra-osseous soft tissue composition were found. In conclusion, changes in extra-osseous soft tissue composition had a minor contribution to changes in BMD with weight loss and decreases in bone marrow adipose tissue (BMAT) were not related to changes in BMD.

Impact of oxygen availability on body weight management.

PubMed

Quintero, P; Milagro, F I; Campión, J; Martínez, J A

2010-05-01

Obesity is nowadays a major public health problem. The World Health Organization reported that globally 400 million adults are obese, and the situation seems to raise in the future. Furthermore, obesity is a major risk factor for a number of chronic diseases such as type 2 diabetes, cardiovascular diseases and the metabolic syndrome. Interestingly, several studies have reported that appetite suppression and body weight loss are frequently observed at high altitude. This observation has opened some possibilities for losing weight under hypoxia or living in altitude. Nevertheless, the triggering mechanisms for the decrease in energy intake in hypoxic conditions still remain unclear as well as the impact on body mass components. On the other hand, obese subjects often present a chronic inflammatory state on the adipose tissue that might have a strong relationship with onset and development of obesity-related diseases. Thus, it has been consistently reported that adipose tissue of obese subjects is poorly oxygenated and that this hypoxia state is a new potential risk factor for the chronic inflammation in obesity. In this sense, oxygen therapy is a common technique used in current medicine for the treatment of several diseases, while animal studies have demonstrated that treatment with hyperoxia produces some beneficial effects in different diseases related with lack of oxygen in several organs. In this article, we review the role of oxygen availability in body weight homeostasis and hypothesize the possible applicability of hypoxia and hyperoxia for the treatment of obesity and related disorders.

Protective Effects of 2-Dodecyl-6-Methoxycyclohexa-2,5 -Diene-1,4-Dione Isolated from Averrhoa Carambola L. (Oxalidaceae) Roots on High-Fat Diet-Induced Obesity and Insulin Resistance in Mice.

PubMed

Li, Juman; Wei, Xiaojie; Xie, Qiuqiao; Hoa Pham, Thi Thai; Wei, Jinbin; He, Ping; Jiao, Yang; Xu, Xiaohui; Giang Nguyen, Thi Huong; Wen, Qingwei; Huang, Renbin

2016-01-01

The roots of Averrhoa carambola L. (Oxalidaceae) have long been used as a traditional Chinese medicine for the treatment of diabetes and diabetes-related diseases. 2-dodecyl-6-methoxycycyclohexa-2,5-1,4-dione (DMDD) has been isolated from A. carambola L. roots, and this study was carried out to investigate the potential beneficial effects of DMDD on obesity and insulin resistance induced by a high-fat diet (HFD) in mice. C57BL/6J mice were fed a HFD for 16 weeks and orally administered DMDD (12.5, 25, or 50 mg/kg of body weight per day) and metformin (280 mg/kg of body weight per day) for the last 4 weeks. The body weights and adipose tissue weights as well as the serum levels of blood glucose, total cholesterol, triglycerides, free fatty acids, insulin, interleukin-6, and tumor necrosis factor-α were significantly decreased by DMDD, and the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor (Myd88) in the epididymal adipose tissue was downregulated by DMDD. In contrast, insulin sensitivity was enhanced. The results of the glucose tolerance tests, insulin tolerance tests, and insulin release tests indicated that there was a marked improvement in insulin secretion, and the areas under the curve corresponding to the three tests were also significantly decreased by DMDD. The activities of superoxide dismutase and glutathione peroxidase were simultaneously enhanced, whereas the content of malondialdehyde was decreased by DMDD in the liver homogenates of the C57BL/6J mice. In addition, hepatic steatosis and adipocyte hypertrophy, as assessed by H&E staining of liver and adipose tissues, were significantly improved by DMDD. These data suggest that MDD has potential benefits for the treatment of HFD-induced obesity and insulin resistance, and its effects may be associated with improvements in lipid metabolism and inhibition of the expression of TLR4 in adipose tissues. © 2016 The Author(s) Published by S. Karger AG, Basel.

A Weight-Loss Diet Including Coffee-Derived Mannooligosaccharides Enhances Adipose Tissue Loss in Overweight Men but Not Women

PubMed Central

St-Onge, Marie-Pierre; Salinardi, Taylor; Herron-Rubin, Kristin; Black, Richard M.

2013-01-01

Mannooligosaccharides (MOS), extracted from coffee, have been shown to promote a decrease in body fat when consumed as part of free-living, weight-maintaining diets. Our objective was to determine if MOS consumption (4 g/day), in conjunction with a weight-loss diet, would lead to greater reductions in adipose tissue compartments than placebo. We conducted a double-blind, placebo-controlled weight-loss study in which 60 overweight men and women consumed study beverages and received weekly group counseling for 12 weeks. Weight and blood pressure were measured weekly, and adipose tissue distribution was assessed at baseline and at end point using magnetic resonance imaging. A total of 54 subjects completed the study. Men consuming the MOS beverage had greater loss of body weight than men consuming the Placebo beverage (−6.0 ± 0.6% vs. −2.3 ± 0.5%, respectively, P < 0.05). Men consuming the MOS beverage also had reductions in total body volume (P < 0.0001), total (P < 0.0001), subcutaneous (P < 0.0001), and visceral (P < 0.05) adipose tissue that were greater than changes observed in those consuming the Placebo beverage. In women, changes in body weight and adipose tissue compartments were not different between groups. Adding coffee-derived MOS to a weight-loss diet enhanced both weight and adipose tissue losses in men, suggesting a potential functional use of MOS for weight management and improvement in adipose tissue distribution. More studies are needed to investigate the apparent gender difference in response to MOS consumption. PMID:21938072

Therapeutic modulation of growth factors and cytokines in regenerative medicine.

PubMed

Ioannidou, Effie

2006-01-01

Regeneration that takes place in the human body is limited throughout life. Therefore, when organs are irreparably damaged, they are usually replaced with an artificial device or donor organ. The term "regenerative medicine" covers the restoration or replacement of cells, tissues, and organs. Stem cells play a major role in regenerative medicine by providing the way to repopulate organs damaged by disease. Stem cells have the ability to self renew and to regenerate cells of diverse lineages within the tissue in which they reside. Stem cells could originate from embryos or adult tissues. Growth factors are proteins that may act locally or systemically to affect the growth of cells in several ways. Various cell activities, including division, are influenced by growth factors. Cytokines are a family of low-molecular-weight proteins that are produced by numerous cell types and are responsible for regulating the immune response, inflammation, tissue remodeling and cellular differentiation. Target cells of growth factors and cytokines are mesenchymal, epithelial and endothelial cells. These molecules frequently have overlapping activities and can act in an autocrine or paracrine fashion. A complex network of growth factors and cytokines guides cellular differentiation and regeneration in all organs and tissues. The aim of this paper is to review the role of growth factors and cytokines in different organs or systems and explore their therapeutic application in regenerative medicine. The role of stem cells combined with growth factors and cytokines in the regeneration of vascular and hematopoietic, neural, skeletal, pancreatic, periodontal, and mucosal tissue is reviewed. There is evidence that supports the use of growth factors and cytokines in the treatment of neurological diseases, diabetes, cardiovascular disease, periodontal disease, cancer and its complication, oral mucositis. After solving the ethical issues and establishing clear and reasonable regulations, regenerative medicine through stem cell application combined with specific growth factors and cytokines will have great potential in curing a variety of human diseases.

Clustering of haemostatic variables and the effect of high cashew and walnut diets on these variables in metabolic syndrome patients.

PubMed

Pieters, Marlien; Oosthuizen, Welma; Jerling, Johann C; Loots, Du Toit; Mukuddem-Petersen, Janine; Hanekom, Susanna M

2005-09-01

We investigated the effect of a high walnut and cashew diet on haemostatic variables in people with the metabolic syndrome. Factor analysis was used to determine how the haemostatic variables cluster with other components of the metabolic syndrome and multiple regression to determine possible predictors. This randomized, control, parallel, controlled-feeding trial included 68 subjects who complied with the Third National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol criteria. After a 3-week run-in following the control diet, subjects were divided into three groups receiving either walnuts or cashews (20 energy%) or a control diet for 8 weeks. The nut intervention had no significant effect on von Willebrand factor antigen, fibrinogen, factor VII coagulant activity, plasminogen activator inhibitor 1 activity, tissue plasminogen activator activity or thrombin activatable fibrinolysis inhibitor. Statistically, fibrinogen clustered with the body-mass-correlates and acute phase response factors, and factor VII coagulant activity clustered with high-density lipoprotein cholesterol (HDL-C). Tissue plasminogen activator activity, plasminogen activator inhibitor 1 activity and von Willebrand factor antigen clustered into a separate endothelial function factor. HDL-C and markers of obesity were the strongest predictors of the haemostatic variables. We conclude that high walnut and cashew diets did not influence haemostatic factors in this group of metabolic syndrome subjects. The HDL-C increase and weight loss may be the main focus of dietary intervention for the metabolic syndrome. Furthermore, diet composition may have only limited effects if weight loss is not achieved.

Enhanced Inflammation without Impairment of Insulin Signaling in the Visceral Adipose Tissue of 5α-Dihydrotestosterone-Induced Animal Model of Polycystic Ovary Syndrome.

PubMed

Milutinović, Danijela Vojnović; Nikolić, Marina; Veličković, Nataša; Djordjevic, Ana; Bursać, Biljana; Nestorov, Jelena; Teofilović, Ana; Antić, Ivana Božić; Macut, Jelica Bjekić; Zidane, Abdulbaset Shirif; Matić, Gordana; Macut, Djuro

2017-09-01

Polycystic ovary syndrome is a heterogeneous endocrine and metabolic disorder associated with abdominal obesity, dyslipidemia and insulin resistance. Since abdominal obesity is characterized by low-grade inflammation, the aim of the study was to investigate whether visceral adipose tissue inflammation linked to abdominal obesity and dyslipidemia could lead to impaired insulin sensitivity in the animal model of polycystic ovary syndrome.Female Wistar rats were treated with nonaromatizable 5α-dihydrotestosterone pellets in order to induce reproductive and metabolic characteristics of polycystic ovary syndrome. Glucose, triglycerides, non-esterified fatty acids and insulin were determined in blood plasma. Visceral adipose tissue inflammation was evaluated by the nuclear factor kappa B intracellular distribution, macrophage migration inhibitory factor protein level, as well as TNFα, IL6 and IL1β mRNA levels. Insulin sensitivity was assessed by intraperitoneal glucose tolerance test and homeostasis model assessment index, and through analysis of insulin signaling pathway in the visceral adipose tissue.Dihydrotestosterone treatment led to increased body weight, abdominal obesity and elevated triglycerides and non-esterified fatty acids, which were accompanied by the activation of nuclear factor kappa B and increase in macrophage migration inhibitory factor, IL6 and IL1β levels in the visceral adipose tissue. In parallel, insulin sensitivity was affected in 5α-dihydrotestosterone-treated animals only at the systemic and not at the level of visceral adipose tissue.The results showed that abdominal obesity and dyslipidemia in the animal model of polycystic ovary syndrome were accompanied with low-grade inflammation in the visceral adipose tissue. However, these metabolic disturbances did not result in decreased tissue insulin sensitivity. © Georg Thieme Verlag KG Stuttgart · New York.

10 CFR 835.203 - Combining internal and external equivalent doses.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Combining internal and external equivalent doses. 835.203 Section 835.203 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and... the radiation and tissue weighting factor values provided in § 835.2. [72 FR 31926, June 8, 2007] ...

10 CFR 835.203 - Combining internal and external equivalent doses.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Combining internal and external equivalent doses. 835.203 Section 835.203 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and... the radiation and tissue weighting factor values provided in § 835.2. [72 FR 31926, June 8, 2007] ...

10 CFR 835.203 - Combining internal and external equivalent doses.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Combining internal and external equivalent doses. 835.203 Section 835.203 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and... the radiation and tissue weighting factor values provided in § 835.2. [72 FR 31926, June 8, 2007] ...

10 CFR 835.203 - Combining internal and external equivalent doses.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Combining internal and external equivalent doses. 835.203 Section 835.203 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and... the radiation and tissue weighting factor values provided in § 835.2. [72 FR 31926, June 8, 2007] ...

An improved MCNP version of the NORMAN voxel phantom for dosimetry studies.

PubMed

Ferrari, P; Gualdrini, G

2005-09-21

In recent years voxel phantoms have been developed on the basis of tomographic data of real individuals allowing new sets of conversion coefficients to be calculated for effective dose. Progress in radiation studies brought ICRP to revise its recommendations and a new report, already circulated in draft form, is expected to change the actual effective dose evaluation method. In the present paper the voxel phantom NORMAN developed at HPA, formerly NRPB, was employed with MCNP Monte Carlo code. A modified version of the phantom, NORMAN-05, was developed to take into account the new set of tissues and weighting factors proposed in the cited ICRP draft. Air kerma to organ equivalent dose and effective dose conversion coefficients for antero-posterior and postero-anterior parallel photon beam irradiations, from 20 keV to 10 MeV, have been calculated and compared with data obtained in other laboratories using different numerical phantoms. Obtained results are in good agreement with published data with some differences for the effective dose calculated employing the proposed new tissue weighting factors set in comparison with previous evaluations based on the ICRP 60 report.

Overweight, Obesity and Weight Control

PubMed Central

Alexander, Marie M.; Stare, Fredrick J.

1967-01-01

Evidence is cited showing that overweight is a health hazard, but that this is primarily true only when the excess weight is due to an excess accumulation of adipose tissue. Diagnosis of frank obesity should be established by a careful interpretation of height-weight tables and of all other pertinent data. Although many factors play an etiologic role, obesity can occur only when caloric intake exceeds caloric output, and can be obviated only when this imbalance is reversed. Therefore prevention of weight gain, which should receive increasing attention, and also satisfactory weight loss, both require that caloric output be increased through added physical activity and that caloric intake be decreased through diminished consumption. Success depends on recognizing the fallacy of all misleading misinformation, and on establishing permanent habits of regular exercise and of moderation in eating and drinking. Suggestions are made that can be effective guidelines to a commonsense program of weight control. PMID:6045471

Weight Loss Decreases Inherent and Allergic Methacholine Hyperresponsiveness in Mouse Models of Diet-Induced Obese Asthma

PubMed Central

Ather, Jennifer L.; Chung, Michael; Hoyt, Laura R.; Randall, Matthew J.; Georgsdottir, Anna; Daphtary, Nirav A.; Aliyeva, Minara I.; Suratt, Benjamin T.; Bates, Jason H. T.; Irvin, Charles G.; Russell, Sheila R.; Forgione, Patrick M.; Dixon, Anne E.

2016-01-01

Obese asthma presents with inherent hyperresponsiveness to methacholine or augmented allergen-driven allergic asthma, with an even greater magnitude of methacholine hyperresponsiveness. These physiologic parameters and accompanying obese asthma symptoms can be reduced by successful weight loss, yet the underlying mechanisms remain incompletely understood. We implemented mouse models of diet-induced obesity, dietary and surgical weight loss, and environmental allergen exposure to examine the mechanisms and mediators of inherent and allergic obese asthma. We report that the methacholine hyperresponsiveness in these models of inherent obese asthma and obese allergic asthma manifests in distinct anatomical compartments but that both are amenable to interventions that induce substantial weight loss. The inherent obese asthma phenotype, with characteristic increases in distal airspace tissue resistance and tissue elastance, is associated with elevated proinflammatory cytokines that are reduced with dietary weight loss. Surprisingly, bariatric surgery–induced weight loss further elevates these cytokines while reducing methacholine responsiveness to levels similar to those in lean mice or in formerly obese mice rendered lean through dietary intervention. In contrast, the obese allergic asthma phenotype, with characteristic increases in central airway resistance, is not associated with increased adaptive immune responses, yet diet-induced weight loss reduces methacholine hyperresponsiveness without altering immunological variables. Diet-induced weight loss is effective in models of both inherent and allergic obese asthma, and our examination of the fecal microbiome revealed that the obesogenic Firmicutes/Bacteroidetes ratio was normalized after diet-induced weight loss. Our results suggest that structural, immunological, and microbiological factors contribute to the manifold presentations of obese asthma. PMID:27064658

Interleukin-15 Modulates Adipose Tissue by Altering Mitochondrial Mass and Activity

PubMed Central

Barra, Nicole G.; Palanivel, Rengasamy; Denou, Emmanuel; Chew, Marianne V.; Gillgrass, Amy; Walker, Tina D.; Kong, Josh; Richards, Carl D.; Jordana, Manel; Collins, Stephen M.; Trigatti, Bernardo L.; Holloway, Alison C.; Raha, Sandeep; Steinberg, Gregory R.; Ashkar, Ali A.

2014-01-01

Interleukin-15 (IL-15) is an immunomodulatory cytokine that affects body mass regulation independent of lymphocytes; however, the underlying mechanism(s) involved remains unknown. In an effort to investigate these mechanisms, we performed metabolic cage studies, assessed intestinal bacterial diversity and macronutrient absorption, and examined adipose mitochondrial activity in cultured adipocytes and in lean IL-15 transgenic (IL-15tg), overweight IL-15 deficient (IL-15−/−), and control C57Bl/6 (B6) mice. Here we show that differences in body weight are not the result of differential activity level, food intake, or respiratory exchange ratio. Although intestinal microbiota differences between obese and lean individuals are known to impact macronutrient absorption, differing gut bacteria profiles in these murine strains does not translate to differences in body weight in colonized germ free animals and macronutrient absorption. Due to its contribution to body weight variation, we examined mitochondrial factors and found that IL-15 treatment in cultured adipocytes resulted in increased mitochondrial membrane potential and decreased lipid deposition. Lastly, IL-15tg mice have significantly elevated mitochondrial activity and mass in adipose tissue compared to B6 and IL-15−/− mice. Altogether, these results suggest that IL-15 is involved in adipose tissue regulation and linked to altered mitochondrial function. PMID:25517731

The Visceral Adiposity Index: Relationship with cardiometabolic risk factors in obese and overweight postmenopausal women--a MONET group study.

PubMed

Elisha, Belinda; Messier, Virginie; Karelis, Antony; Coderre, Lise; Bernard, Sophie; Prud'homme, Denis; Rabasa-Lhoret, Rémi

2013-08-01

A recent study suggested visceral adipose index (VAI) as an indicator of adipose tissue distribution and function associated with cardiometabolic risk. We aim to examine the association between VAI and visceral adipose tissue (VAT), insulin sensitivity, and a large panel of associated cardiometabolic risk factors, and to determine if changes in VAI after weight loss intervention will reflect changes in VAT. We performed a secondary analysis using the data of 99 overweight and postmenopausal women that completed a 6-month weight loss program (Montreal Ottawa New Emerging Team Study). VAI was calculated according to the equation by Amato et al. (2010; Diabetes Care, 33(4):920-922). At baseline, VAI was associated with VAT (r = 0.284, p < 0.01) but not with subcutaneous adipose tissue (SAT) while body mass index (BMI) and waist circumference (WC) were significantly related to both. BMI and WC demonstrated significantly stronger predictive value of VAT accumulation (area under the curve = 0.84 and 0.86, respectively) than VAI (area under the curve = 0.61; p < 0.01). However, VAT, BMI, WC, and VAI were similarly related to fasting insulin and glucose disposal rates. After a 6-month weight loss program, VAI decreased significantly and similarly in both intervention groups (p < 0.01). In addition, the percentage of change in VAI showed the significantly weakest correlation (r = 0.25) with the percentage of change in VAT than BMI (r = 0.56; p < 0.01 for r comparisons) and was not a significant predictor of interindividual percentage of change in VAT while BMI accounted for 33.7%. VAI is a weak indicator of VAT function and did not predict changes in VAT after weight loss. Furthermore, this index was not superior to BMI or WC. However, VAI is a good indicator of metabolic syndrome.

Activity of blood coagulation and fibrinolysis during and after hydroxyethyl starch (HES) colloidal volume replacement.

PubMed

Omar, M N; Shouk, T A; Khaleq, M A

1999-06-01

To examine the effect of medium molecular weight hydroxyethyl starch on protein C levels and the changes in the activation state of blood platelets, coagulation and fibrinolyis during and after 5 day of its infusion. Fifty male patients (mean age: 47 years, range 45-50 years) who required prostatectomy for benign prostatic hyperplasia were divided into two equal groups. One group was given 15 mL/kg body weight (mean volume 1000 mL +/- 100 mL) of 6% hydroxyethyl starch (HES) 200/0.5, the other received an equal volume of 5% human albumin during the operation. Blood samples were collected immediately before infusion (baseline values) and at 20, 40, 60, 90, 240, and 480 min after the infusion started then daily for the next 5 days postoperatively. Hematocrit, factor VIII:C, thrombin-antithrombin III complex; the anticoagulant protein C levels; the fibrinolytic parameters tissue type plasminogen activator (t-PA), and the fibrinolytic product D-Dimer and the platelet aggregation activity were measured. The data obtained did not detect any significant differences between HES and human albumin in the plasma levels of thrombin-antithrombin III complex, protein C, tissue-type plasminogen activator and the fibrin split products D-Dimer. Factor VIII:C and platelet aggregation were significantly lower in the hydroxyethyl starch group in comparison with albumin. Baseline values were attained postoperatively for factor VIII:C and platelet aggregation by the first and fifth days, respectively. The lowering effect of medium molecular weight hydroxyethyl starch on factor VIII:C would not be attributed to increased proteolytic activity of protein C on this coagulation cofactor because there is a nonsignificant change in protein C levels.

Coprinus comatus Cap Inhibits Adipocyte Differentiation via Regulation of PPARγ and Akt Signaling Pathway

PubMed Central

Jang, Sun-Hee; Kang, Suk Nam; Jeon, Beong-Sam; Ko, Yeoung-Gyu; Kim, Hong-Duck; Won, Chung-Kil; Kim, Gon-Sup; Cho, Jae-Hyeon

2014-01-01

This study assessed the effects of Coprinus comatus cap (CCC) on adipogenesis in 3T3-L1 adipocytes and the effects of CCC on the development of diet-induced obesity in rats. Here, we showed that the CCC has an inhibitory effect on the adipocyte differentiation of 3T3-L1 cells, resulting in a significant decrease in lipid accumulation through the downregulation of several adipocyte specific-transcription factors, including CCAAT/enhancer binding protein β, C/EBPδ, and peroxisome proliferator-activated receptor gamma (PPARγ). Moreover, treatment with CCC during adipocyte differentiation induced a significant down-regulation of PPARγ and adipogenic target genes, including adipocyte protein 2, lipoprotein lipase, and adiponectin. Interestingly, the CCC treatment of the 3T3-L1 adipocytes suppressed the insulin-stimulated Akt and GSK3β phosphorylation, and these effects were stronger in the presence of an inhibitor of Akt phosphorylation, LY294002, suggesting that CCC inhibited adipocyte differentiation through the down-regulation of Akt signaling. In the animal study, CCC administration significantly reduced the body weight and adipose tissue weight of rats fed a high fat diet (HFD) and attenuated lipid accumulation in the adipose tissues of the HFD-induced obese rats. The size of the adipocyte in the epididymal fat of the CCC fed rats was significantly smaller than in the HFD rats. CCC treatment significantly reduced the total cholesterol and triglyceride levels in the serum of HFD rats. These results strongly indicated that the CCC-mediated decrease in body weight was due to a reduction in adipose tissue mass. The expression level of PPARγ and phospho-Akt was significantly lower in the CCC-treated HFD rats than that in the HFD obesity rats. These results suggested that CCC inhibited adipocyte differentiation by the down-regulation of major transcription factor involved in the adipogenesis pathway including PPARγ through the regulation of the Akt pathway in 3T3-L1 cells and HFD adipose tissue. PMID:25181477

Start of insulin therapy in patients with type 2 diabetes mellitus promotes the influx of macrophages into subcutaneous adipose tissue.

PubMed

Jansen, H J; Stienstra, R; van Diepen, J A; Hijmans, A; van der Laak, J A; Vervoort, G M M; Tack, C J

2013-12-01

Insulin therapy in patients with type 2 diabetes mellitus is accompanied by weight gain characterised by an increase in abdominal fat mass. The expansion of adipose tissue mass is generally paralleled by profound morphological and inflammatory changes. We hypothesised that the insulin-associated increase in fat mass would also result in changes in the morphology of human subcutaneous adipose tissue and in increased inflammation, especially when weight gain was excessive. We investigated the effects of weight gain on adipocyte size, macrophage influx, and mRNA expression and protein levels of key inflammatory markers within the adipose tissue in patients with type 2 diabetes mellitus before and 6 months after starting insulin therapy. As expected, insulin therapy significantly increased body weight. At the level of the subcutaneous adipose tissue, insulin treatment led to an influx of macrophages. When comparing patients gaining no or little weight with patients gaining >4% body weight after 6 months of insulin therapy, both subgroups displayed an increase in macrophage influx. However, individuals who had gained weight had higher protein levels of monocyte chemoattractant protein-1, TNF-α and IL-1β after 6 months of insulin therapy compared with those who had not gained weight. We conclude that insulin therapy in patients with type 2 diabetes mellitus improved glycaemic control but also induced body weight gain and an influx of macrophages into the subcutaneous adipose tissue. In patients characterised by a pronounced insulin-associated weight gain, the influx of macrophages into the adipose tissue was accompanied by a more pronounced inflammatory status. ClinicalTrials.gov: NCT00781495. The study was funded by European Foundation for the Study of Diabetes and the Dutch Diabetes Research Foundation.

Modified Treatment Algorithm for Pseudogynecomastia After Massive Weight Loss.

PubMed

Ziegler, Ulrich E; Lorenz, Udo; Daigeler, Adrien; Ziegler, Selina N; Zeplin, Philip H

2018-06-19

Pseudogynecomastia is the increased aggregation of fatty tissue in the area of the male breast with resultant female appearance. Two forms can appear: pseudogynecomastia after massive weight loss (pseudogynecomastia obese [PO]) and pseudogynecomastia, which is caused only by adipose tissue (pseudogynecomastia fat). For PO, only the Gusenoff classification with corresponding operative treatment options exists. However, this classification is limited by the fact that it underestimates the extensive variability of residual fat tissue and skin excess, both crucial factors for operative planning. For this reason, we propose a modification of the treatment algorithm for the Gusenoff classification based on our results to achieve more masculine results. A total of 43 male patients with PO were included in this retrospective study (grade 1a, n = 1; grade 1b, n = 1; grade 2, n = 17; grade 3, n = 24). Forty-two mastectomies with a free nipple-areola complex (NAC) transposition (grades 2 and 3) and 1 with a subcutaneous mastectomy (grade 1a) with periareolar lifting were performed. A retrospective chart review was performed to obtain data regarding age, body mass index, body mass index loss, weight loss, reason for weight loss, comorbidities, nicotine, and additional procedures, postoperative sensitive on the NAC transplants and complications. None of the free-nipple grafts were lost. Forty (95%) of 42 patients with mastectomy had a resensitivity on the NAC. For pseudogynecomastia, the treatment algorithm of the Gusenoff classification should be modified and adapted according to our recommendations to achieve more optimal masculine results.

Effects of perchlorate on growth of four wetland plants and its accumulation in plant tissues.

PubMed

He, Hongzhi; Gao, Haishuo; Chen, Guikui; Li, Huashou; Lin, Hai; Shu, Zhenzhen

2013-10-01

Perchlorate contamination in water is of concern because of uncertainties about toxicity and health effects, impact on ecosystems, and possible indirect exposure pathways to humans. Therefore, it is very important to investigate the ecotoxicology of perchlorate and to screen plant species for phytoremediation. Effects of perchlorate (20, 200, and 500 mg/L) on the growth of four wetland plants (Eichhornia crassipes, Acorus calamus L., Thalia dealbata, and Canna indica) as well as its accumulation in different plant tissues were investigated through water culture experiments. Twenty milligrams per liter of perchlorate had no significant effects on height, root length, aboveground part weight, root weight, and oxidizing power of roots of four plants, except A. calamus, and increasing concentrations of perchlorate showed that out of the four wetland plants, only A. calamus had a significant (p<0.05) dose-dependent decrease in these parameters. When treated with 500 mg/L perchlorate, these parameters and chlorophyll content in the leaf of plants showed significant decline contrasted to control groups, except the root length of E. crassipes and C. indica. The order of inhibition rates of perchlorate on root length, aboveground part weight and root weight, and oxidizing power of roots was: A. calamus > C. indica > T. dealbata > E. crassipes and on chlorophyll content in the leaf it was: A. calamus > T. dealbata > C. indica > E. crassipes. The higher the concentration of perchlorate used, the higher the amount of perchlorate accumulation in plants. Perchlorate accumulation in aboveground tissues was much higher than that in underground tissues and leaf was the main tissue for perchlorate accumulation. The order of perchlorate accumulation content and the bioconcentration factor in leaf of four plants was: E. crassipes > C. indica > T. dealbata > A. calamus. Therefore, E. crassipes might be an ideal plant with high tolerance ability and accumulation ability for constructing wetland to remediate high levels of perchlorate polluted water.

Reference-tissue correction of T2-weighted signal intensity for prostate cancer detection

NASA Astrophysics Data System (ADS)

Peng, Yahui; Jiang, Yulei; Oto, Aytekin

2014-03-01

The purpose of this study was to investigate whether correction with respect to reference tissue of T2-weighted MRimage signal intensity (SI) improves its effectiveness for classification of regions of interest (ROIs) as prostate cancer (PCa) or normal prostatic tissue. Two image datasets collected retrospectively were used in this study: 71 cases acquired with GE scanners (dataset A), and 59 cases acquired with Philips scanners (dataset B). Through a consensus histology- MR correlation review, 175 PCa and 108 normal-tissue ROIs were identified and drawn manually. Reference-tissue ROIs were selected in each case from the levator ani muscle, urinary bladder, and pubic bone. T2-weighted image SI was corrected as the ratio of the average T2-weighted image SI within an ROI to that of a reference-tissue ROI. Area under the receiver operating characteristic curve (AUC) was used to evaluate the effectiveness of T2-weighted image SIs for differentiation of PCa from normal-tissue ROIs. AUC (+/- standard error) for uncorrected T2-weighted image SIs was 0.78+/-0.04 (datasets A) and 0.65+/-0.05 (datasets B). AUC for corrected T2-weighted image SIs with respect to muscle, bladder, and bone reference was 0.77+/-0.04 (p=1.0), 0.77+/-0.04 (p=1.0), and 0.75+/-0.04 (p=0.8), respectively, for dataset A; and 0.81+/-0.04 (p=0.002), 0.78+/-0.04 (p<0.001), and 0.79+/-0.04 (p<0.001), respectively, for dataset B. Correction in reference to the levator ani muscle yielded the most consistent results between GE and Phillips images. Correction of T2-weighted image SI in reference to three types of extra-prostatic tissue can improve its effectiveness for differentiation of PCa from normal-tissue ROIs, and correction in reference to the levator ani muscle produces consistent T2-weighted image SIs between GE and Phillips MR images.

The effect of a short-term hypocaloric diet on liver gene expression and metabolic risk factors in obese women.

PubMed

Hietaniemi, M; Jokela, M; Rantala, M; Ukkola, O; Vuoristo, J T; Ilves, M; Rysä, J; Kesäniemi, Y

2009-03-01

Most gene expression studies examining the effect of obesity and weight loss have been performed using adipose tissue. However, the liver also plays a central role in maintaining energy balance. We wanted to study the effects of a hypocaloric diet on overall hepatic gene expression and metabolic risk factors. The study subjects were middle-aged, obese women. The diet intervention subjects (n=12) were on a hypocaloric, low-fat diet for 8 weeks with a daily energy intake of 5.0 MJ (1200 kcal), while the control subjects (n=19) maintained their weight. Liver biopsies were taken at the end of the diet period during a gallbladder operation. Hepatic gene expression was analyzed using microarrays by comparing the gene expression profiles from four subjects per group. A global decrease in gene expression was observed with 142 down-regulated genes and only one up-regulated gene in the diet intervention group. The diet resulted in a mean weight loss of 5% of body weight. Triglyceride and fasting insulin concentrations decreased significantly after the diet. The global decrease in hepatic gene expression was unexpected but the results are interesting, since they included several genes not previously linked to weight reduction. However, since the comparison was made only after the weight reduction, other factors in addition to weight loss may also have been involved in the differences in gene expression between the groups. The decrease in triglyceride and fasting plasma insulin concentrations is in accordance with results from previous weight-loss studies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cederkrantz, Elin; Andersson, Håkan; Bernhardt, Peter

Purpose: Ovarian cancer is often diagnosed at an advanced stage with dissemination in the peritoneal cavity. Most patients achieve clinical remission after surgery and chemotherapy, but approximately 70% eventually experience recurrence, usually in the peritoneal cavity. To prevent recurrence, intraperitoneal (i.p.) targeted α therapy has been proposed as an adjuvant treatment for minimal residual disease after successful primary treatment. In the present study, we calculated absorbed and relative biological effect (RBE)-weighted (equivalent) doses in relevant normal tissues and estimated the effective dose associated with i.p. administration of {sup 211}At-MX35 F(ab'){sub 2}. Methods and Materials: Patients in clinical remission after salvage chemotherapymore » for peritoneal recurrence of ovarian cancer underwent i.p. infusion of {sup 211}At-MX35 F(ab'){sub 2}. Potassium perchlorate was given to block unwanted accumulation of {sup 211}At in thyroid and other NIS-containing tissues. Mean absorbed doses to normal tissues were calculated from clinical data, including blood and i.p. fluid samples, urine, γ-camera images, and single-photon emission computed tomography/computed tomography images. Extrapolation of preclinical biodistribution data combined with clinical blood activity data allowed us to estimate absorbed doses in additional tissues. The equivalent dose was calculated using an RBE of 5 and the effective dose using the recommended weight factor of 20. All doses were normalized to the initial activity concentration of the infused therapy solution. Results: The urinary bladder, thyroid, and kidneys (1.9, 1.8, and 1.7 mGy per MBq/L) received the 3 highest estimated absorbed doses. When the tissue-weighting factors were applied, the largest contributors to the effective dose were the lungs, stomach, and urinary bladder. Using 100 MBq/L, organ equivalent doses were less than 10% of the estimated tolerance dose. Conclusion: Intraperitoneal {sup 211}At-MX35 F(ab'){sub 2} treatment is potentially a well-tolerated therapy for locally confined microscopic ovarian cancer. Absorbed doses to normal organs are low, but because the effective dose potentially corresponds to a risk of treatment-induced carcinogenesis, optimization may still be valuable.« less

Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin-deficient diabetes.

PubMed

Fu, Ling; John, Linu M; Adams, Sean H; Yu, Xing Xian; Tomlinson, Elizabeth; Renz, Mark; Williams, P Mickey; Soriano, Robert; Corpuz, Racquel; Moffat, Barbara; Vandlen, Richard; Simmons, Laura; Foster, Jessica; Stephan, Jean-Philippe; Tsai, Siao Ping; Stewart, Timothy A

2004-06-01

Hormonal control of metabolic rate can be important in regulating the imbalance between energy intake and expenditure that underlies the development of obesity. In mice fed a high-fat diet, human fibroblast growth factor 19 (FGF19) increased metabolic rate [1.53 +/- 0.06 liters O(2)/h.kg(0.75) (vehicle) vs. 1.93 +/- 0.05 liters O(2)/h.kg(0.75) (FGF19); P < 0.001] and decreased respiratory quotient [0.82 +/- 0.01 (vehicle) vs. 0.80 +/- 0.01 (FGF19); P < 0.05]. In contrast to the vehicle-treated mice that gained weight (0.14 +/- 0.05 g/mouse.d), FGF19-treated mice lost weight (-0.13 +/- 0.03 g/mouse.d; P < 0.001) without a significant change in food intake. Furthermore, in addition to a reduction in weight gain, treatment with FGF19 prevented or reversed the diabetes that develops in mice made obese by genetic ablation of brown adipose tissue or genetic absence of leptin. To explore the mechanisms underlying the FGF19-mediated increase in metabolic rate, we profiled the FGF19-induced gene expression changes in the liver and brown fat. In brown adipose tissue, chronic exposure to FGF19 led to a gene expression profile that is consistent with activation of this tissue. We also found that FGF19 acutely increased liver expression of the leptin receptor (1.8-fold; P < 0.05) and decreased the expression of acetyl coenzyme A carboxylase 2 (0.6-fold; P < 0.05). The gene expression changes were consistent with the experimentally determined increase in fat oxidation and decrease in liver triglycerides. Thus, FGF19 is able to increase metabolic rate concurrently with an increase in fatty acid oxidation.

Tuning mechanical performance of poly(ethylene glycol) and agarose interpenetrating network hydrogels for cartilage tissue engineering.

PubMed

Rennerfeldt, Deena A; Renth, Amanda N; Talata, Zsolt; Gehrke, Stevin H; Detamore, Michael S

2013-11-01

Hydrogels are attractive for tissue engineering applications due to their incredible versatility, but they can be limited in cartilage tissue engineering applications due to inadequate mechanical performance. In an effort to address this limitation, our team previously reported the drastic improvement in the mechanical performance of interpenetrating networks (IPNs) of poly(ethylene glycol) diacrylate (PEG-DA) and agarose relative to pure PEG-DA and agarose networks. The goal of the current study was specifically to determine the relative importance of PEG-DA concentration, agarose concentration, and PEG-DA molecular weight in controlling mechanical performance, swelling characteristics, and network parameters. IPNs consistently had compressive and shear moduli greater than the additive sum of either single network when compared to pure PEG-DA gels with a similar PEG-DA content. IPNs withstood a maximum stress of up to 4.0 MPa in unconfined compression, with increased PEG-DA molecular weight being the greatest contributing factor to improved failure properties. However, aside from failure properties, PEG-DA concentration was the most influential factor for the large majority of properties. Increasing the agarose and PEG-DA concentrations as well as the PEG-DA molecular weight of agarose/PEG-DA IPNs and pure PEG-DA gels improved moduli and maximum stresses by as much as an order of magnitude or greater compared to pure PEG-DA gels in our previous studies. Although the viability of encapsulated chondrocytes was not significantly affected by IPN formulation, glycosaminoglycan (GAG) content was significantly influenced, with a 12-fold increase over a three-week period in gels with a lower PEG-DA concentration. These results suggest that mechanical performance of IPNs may be tuned with partial but not complete independence from biological performance of encapsulated cells. © 2013 Elsevier Ltd. All rights reserved.

Chronic high-sucrose diet increases fibroblast growth factor 21 production and energy expenditure in mice.

PubMed

Maekawa, Ryuya; Seino, Yusuke; Ogata, Hidetada; Murase, Masatoshi; Iida, Atsushi; Hosokawa, Kaori; Joo, Erina; Harada, Norio; Tsunekawa, Shin; Hamada, Yoji; Oiso, Yutaka; Inagaki, Nobuya; Hayashi, Yoshitaka; Arima, Hiroshi

2017-11-01

Excess carbohydrate intake causes obesity in humans. On the other hand, acute administration of fructose, glucose or sucrose in experimental animals has been shown to increase the plasma concentration of anti-obesity hormones such as glucagon-like peptide 1 (GLP-1) and Fibroblast growth factor 21 (FGF21), which contribute to reducing body weight. However, the secretion and action of GLP-1 and FGF21 in mice chronically fed a high-sucrose diet has not been investigated. To address the role of anti-obesity hormones in response to increased sucrose intake, we analyzed mice fed a high-sucrose diet, a high-starch diet or a normal diet for 15 weeks. Mice fed a high-sucrose diet showed resistance to body weight gain, in comparison with mice fed a high-starch diet or control diet, due to increased energy expenditure. Plasma FGF21 levels were highest among the three groups in mice fed a high-sucrose diet, whereas no significant difference in GLP-1 levels was observed. Expression levels of uncoupling protein 1 (UCP-1), FGF receptor 1c (FGFR1c) and β-klotho (KLB) mRNA in brown adipose tissue were significantly increased in high sucrose-fed mice, suggesting increases in FGF21 sensitivity and energy expenditure. Expression of carbohydrate responsive element binding protein (ChREBP) mRNA in liver and brown adipose tissue was also increased in high sucrose-fed mice. These results indicate that FGF21 production in liver and brown adipose tissue is increased in high-sucrose diet and participates in resistance to weight gain. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Angiogenic Deficiency and Adipose Tissue Dysfunction Are Associated with Macrophage Malfunction in SIRT1−/− Mice

PubMed Central

Xu, Fen; Burk, David; Gao, Zhanguo; Yin, Jun; Zhang, Xia

2012-01-01

The histone deacetylase sirtuin 1 (SIRT1) inhibits adipocyte differentiation and suppresses inflammation by targeting the transcription factors peroxisome proliferator-activated receptor γ and nuclear factor κB. Although this suggests that adiposity and inflammation should be enhanced when SIRT1 activity is inactivated in the body, this hypothesis has not been tested in SIRT1 null (SIRT1−/−) mice. In this study, we addressed this issue by investigating the adipose tissue in SIRT1−/− mice. Compared with their wild-type littermates, SIRT1 null mice exhibited a significant reduction in body weight. In adipose tissue, the average size of adipocytes was smaller, the content of extracellular matrix was lower, adiponectin and leptin were expressed at 60% of normal level, and adipocyte differentiation was reduced. All of these changes were observed with a 50% reduction in capillary density that was determined using a three-dimensional imaging technique. Except for vascular endothelial growth factor, the expression of several angiogenic factors (Pdgf, Hgf, endothelin, apelin, and Tgf-β) was reduced by about 50%. Macrophage infiltration and inflammatory cytokine expression were 70% less in the adipose tissue of null mice and macrophage differentiation was significantly inhibited in SIRT1−/− mouse embryonic fibroblasts in vitro. In wild-type mice, macrophage deletion led to a reduction in vascular density. These data suggest that SIRT1 controls adipose tissue function through regulation of angiogenesis, whose deficiency is associated with macrophage malfunction in SIRT1−/− mice. The study supports the concept that inflammation regulates angiogenesis in the adipose tissue. PMID:22315447

Body fat distribution of overweight females with a history of weight cycling.

PubMed

Wallner, S J; Luschnigg, N; Schnedl, W J; Lahousen, T; Sudi, K; Crailsheim, K; Möller, R; Tafeit, E; Horejsi, R

2004-09-01

Weight cycling may cause a redistribution of body fat to the upper body fat compartments. We investigated the distribution of subcutaneous adipose tissue (SAT) in 30 overweight women with a history of weight-cycling and age-matched controls (167 normal weight and 97 overweight subjects). Measurements of SAT were performed using an optical device, the Lipometer. The SAT topography describes the thicknesses of SAT layers at 15 anatomically well-defined body sites from neck to calf. The overweight women with a history of weight cycling had significantly thicker SAT layers on the upper body compared to the overweight controls, but even thinner SAT layers on their legs than the normal weight women. An android fat pattern was attributed to overweight females and, even more pronounced, to the weight cyclers. The majority of normal weight women showed a gynoid fat pattern. Using stepwise discriminant analysis, 89.0% of all weight cyclers and overweight controls could be classified correctly into the two groups. These findings show the importance of normal weight maintenance as a health-promoting factor.

Adipokines in human breast milk.

PubMed

Kratzsch, Juergen; Bae, Yoon Ju; Kiess, Wieland

2018-01-01

The review describes the molecular characteristics of so far detected breast milk adipokines and ranks their breast milk level compared to the respective levels in maternal and infant blood. Moreover, analytical knowledge for measurements of breast milk adipokines will be delineated. Next, we summarized data about two main potential influencing factors on adipokine concentration in breast milk, maternal weight and pasteurization of milk. Finally, associations between adipokines in breast milk and weight gain in infants as well as the putative mechanisms for effects of breast milk adipokines on food intake and weight gain in later life will debated. Our findings suggest that a source of adipokines in human breast milk cannot be uniformly defined. In dependence on the ratio between serum and breast milk levels the major quantity of these proteins may be derived from peripheral tissues, from the breast tissue itself or from both. Thus, leptin and in part adiponectin levels in breast milk are dependent on a plenty of influencing factors with an important relevance of maternal anthropometric characteristics There is some evidence that leptin, adiponectin and ghrelin levels in breast milk may be associated with growth gain of infants and even with increased risk for being overweight during infancy or childhood. We hypothesize that a dysregulation in adipokine homeostasis in early life could promote obesity and metabolic disturbance in later life. Copyright © 2018 Elsevier Ltd. All rights reserved.

Therapeutic suppression of translation initiation factor eIF4E expression reduces tumor growth without toxicity

PubMed Central

Graff, Jeremy R.; Konicek, Bruce W.; Vincent, Thomas M.; Lynch, Rebecca L.; Monteith, David; Weir, Spring N.; Schwier, Phil; Capen, Andrew; Goode, Robin L.; Dowless, Michele S.; Chen, Yuefeng; Zhang, Hong; Sissons, Sean; Cox, Karen; McNulty, Ann M.; Parsons, Stephen H.; Wang, Tao; Sams, Lillian; Geeganage, Sandaruwan; Douglass, Larry E.; Neubauer, Blake Lee; Dean, Nicholas M.; Blanchard, Kerry; Shou, Jianyong; Stancato, Louis F.; Carter, Julia H.; Marcusson, Eric G.

2007-01-01

Expression of eukaryotic translation initiation factor 4E (eIF4E) is commonly elevated in human and experimental cancers, promoting angiogenesis and tumor growth. Elevated eIF4E levels selectively increase translation of growth factors important in malignancy (e.g., VEGF, cyclin D1) and is thereby an attractive anticancer therapeutic target. Yet to date, no eIF4E-specific therapy has been developed. Herein we report development of eIF4E-specific antisense oligonucleotides (ASOs) designed to have the necessary tissue stability and nuclease resistance required for systemic anticancer therapy. In mammalian cultured cells, these ASOs specifically targeted the eIF4E mRNA for destruction, repressing expression of eIF4E-regulated proteins (e.g., VEGF, cyclin D1, survivin, c-myc, Bcl-2), inducing apoptosis, and preventing endothelial cells from forming vessel-like structures. Most importantly, intravenous ASO administration selectively and significantly reduced eIF4E expression in human tumor xenografts, significantly suppressing tumor growth. Because these ASOs also target murine eIF4E, we assessed the impact of eIF4E reduction in normal tissues. Despite reducing eIF4E levels by 80% in mouse liver, eIF4E-specific ASO administration did not affect body weight, organ weight, or liver transaminase levels, thereby providing the first in vivo evidence that cancers may be more susceptible to eIF4E inhibition than normal tissues. These data have prompted eIF4E-specific ASO clinical trials for the treatment of human cancers. PMID:17786246

Weight Loss Composition is One-Fourth Fat-Free Mass: A Critical Review and Critique of This Widely Cited Rule

PubMed Central

Heymsfield, Steven B.; Cristina Gonzalez, M. C.; Shen, Wei; Redman, Leanne; Thomas, Diana

2014-01-01

Maximizing fat loss while preserving lean tissue mass and function is a central goal of modern obesity treatments. A widely cited rule guiding expected loss of lean tissue as fat-free mass (FFM) states that approximately one-fourth of weight loss will be FFM (i.e., ΔFFM/ΔWeight = ~0.25) with the remaining three-fourths fat mass. This review examines the dynamic relations between FFM, fat mass, and weight changes that follow induction of negative energy balance with hypocaloric dieting and/or exercise. Historical developments in the field are traced with the “Quarter FFM Rule” used as a framework to examine evolving concepts on obesity tissue, excess weight, and what is often cited as “Forbes’ Rule”. Temporal effects in the fractional contribution of FFM to changes in body weight are examined as are lean tissue moderating effects such as aging, inactivity, and exercise that frequently accompany structured low-calorie diet weight loss protocols. Losses of lean tissue with dieting typically tend to be small, raising questions about study design, power, and applied measurement method reliability. Our review elicits important questions related to the fractional loss of lean tissues with dieting and provides a foundation for future research on this topic. PMID:24447775

Body contouring surgery following bariatric surgery and dietetically induced massive weight reduction: a risk analysis.

PubMed

de Kerviler, S; Hüsler, R; Banic, A; Constantinescu, M A

2009-05-01

This study analyzed the impact of weight reduction method, preoperative, and intraoperative variables on the outcome of reconstructive body contouring surgery following massive weight reduction. All patients presenting with a maximal BMI >/=35 kg/m(2) before weight reduction who underwent body contouring surgery of the trunk following massive weight loss (excess body mass index loss (EBMIL) >/= 30%) between January 2002 and June 2007 were retrospectively analyzed. Incomplete records or follow-up led to exclusion. Statistical analysis focused on weight reduction method and pre-, intra-, and postoperative risk factors. The outcome was compared to current literature results. A total of 104 patients were included (87 female and 17 male; mean age 47.9 years). Massive weight reduction was achieved through bariatric surgery in 62 patients (59.6%) and dietetically in 42 patients (40.4%). Dietetically achieved excess body mass index loss (EBMIL) was 94.20% and in this cohort higher than surgically induced reduction EBMIL 80.80% (p < 0.01). Bariatric surgery did not present increased risks for complications for the secondary body contouring procedures. The observed complications (26.9%) were analyzed for risk factors. Total tissue resection weight was a significant risk factor (p < 0.05). Preoperative BMI had an impact on infections (p < 0.05). No impact on the postoperative outcome was detected in EBMIL, maximal BMI, smoking, hemoglobin, blood loss, body contouring technique or operation time. Corrective procedures were performed in 11 patients (10.6%). The results were compared to recent data. Bariatric surgery does not increase risks for complications in subsequent body contouring procedures when compared to massive dietetic weight reduction.

Acarbose versus trans-chalcone: comparing the effect of two glycosidase inhibitors on obese mice.

PubMed

Jalalvand, Fatemeh; Amoli, Mahsa M; Yaghmaei, Parichehreh; Kimiagar, Masoud; Ebrahim-Habibi, Azadeh

2015-06-01

Acarbose and trans-chalcone are glucosidase inhibitors whose beneficial effects have been demonstrated in diabetes. The present study aimed at investigating their potential effects in obesity. NMRI male mice (n = 48) were subjected to a high fat diet for four weeks, which induced an initial state of obesity. One control group was given normal rodent diet. Obese animals were then switched to normal rodent diet, and divided to four groups (n = 12 in each): untreated, sham (receiving grape seed oil), and experimental groups receiving acarbose and trans-chalcone (12 mg/kg) during eight weeks. Body weight, blood glucose and other biochemical parameters including triglycerides (TG), cholesterol, HDL, AST, and ALT were measured, as well as leptin, adiponectin, TNF-α, and total antioxidant capacity (TAC). Histological studies were performed on adipose cells and liver tissue samples. All factors were affected in a positive manner by acarbose, save for body weight, blood sugar and leptin levels, on which acarbose effects, although observable, were not statistically significant. Grape seed oil, used as a solvent for trans-chalcone was found to possess significant effect on TG and TAC, and had beneficial effects on other factors including liver enzymes and cholesterol. Trans-chalcone effects were significant on HDL, leptin and ALT. All compounds seemed to be able to affect fat deposition in liver tissue, and decrease the size of adipose tissue cells to some extent. In conclusion, the tested compounds were able to affect lipid accumulation in tissues and influence adipokines, which may result in an enhanced state with regard to inflammation and oxidative stress.

Whey protein and essential amino acids promote the reduction of adipose tissue and increased muscle protein synthesis during caloric restriction-induced weight loss in elderly, obese individuals.

PubMed

Coker, Robert H; Miller, Sharon; Schutzler, Scott; Deutz, Nicolaas; Wolfe, Robert R

2012-12-11

Excess adipose tissue and sarcopenia presents a multifaceted clinical challenge that promotes morbidity and mortality in the obese, elderly population. Unfortunately, the mortality risks of muscle loss may outweigh the potential benefits of weight loss in the elderly. We have previously demonstrated the effectiveness of whey protein and essential amino acids towards the preservation of lean tissue, even under the conditions of strict bedrest in the elderly. In the context of caloric restriction-based weight loss, we hypothesized that a similar formulation given as a meal replacement (EAAMR) would foster the retention of lean tissue through an increase in the skeletal muscle fractional synthesis rate (FSR). We also proposed that EAAMR would promote the preferential loss of adipose tissue through the increased energy cost of skeletal muscle FSR. We recruited and randomized 12 elderly individuals to an 8 week, caloric restriction diet utilizing equivalent caloric meal replacements (800 kcal/day): 1) EAAMR or a 2) competitive meal replacement (CMR) in conjunction with 400 kcal of solid food that totaled 1200 kcal/day designed to induce 7% weight loss. Combined with weekly measurements of total body weight and body composition, we also measured the acute change in the skeletal muscle FSR to EAAMR and CMR. By design, both groups lost ~7% of total body weight. While EAAMR did not promote a significant preservation of lean tissue, the reduction in adipose tissue was greater in EAAMR compared to CMR. Interestingly, these results corresponded to an increase in the acute skeletal muscle protein FSR. The provision of EAAMR during caloric restriction-induced weight loss promotes the preferential reduction of adipose tissue and the modest loss of lean tissue in the elderly population.

Understanding Thiel Embalming in Pig Kidneys to Develop a New Circulation Model

PubMed Central

Willaert, Wouter; De Vos, Marie; Van Hoof, Tom; Delrue, Louke; Pattyn, Piet; D’Herde, Katharina

2015-01-01

The quality of tissue preservation in Thiel embalmed bodies varies. Research on the administered embalming volume and its vascular distribution may elucidate one of the mechanisms of tissue preservation and allow for new applications of Thiel embalming. Vascular embalming with (group 1, n = 15) or without (group 2, n = 20) contrast agent was initiated in pig kidneys. The distribution of Thiel embalming solution in group 1 was visualized using computed tomography. The kidneys in both groups were then immersed in concentrated salt solutions to reduce their weight and volume. Afterwards, to mimic a lifelike circulation in the vessels, group 2 underwent pump-driven reperfusion for 120 minutes with either paraffinum perliquidum or diluted polyethylene glycol. The circulation was imaged with computed tomography. All of the kidneys were adequately preserved. The embalming solution spread diffusely in the kidney, but fluid accumulation was present. Subsequent immersion in concentrated salt solutions reduced weight (P < 0.01) and volume (P < 0.01). Reperfusion for 120 minutes was established in group 2. Paraffinum perliquidum filled both major vessels and renal tissue, whereas diluted polyethylene glycol spread widely in the kidney. There were no increases in weight (P = 0.26) and volume (P = 0.79); and pressure further decreased (P = 0.032) after more than 60 minutes of reperfusion with paraffinum perliquidum, whereas there were increases in weight (P = 0.005), volume (P = 0.032) and pressure (P < 0.0001) after reperfusion with diluted polyethylene glycol. Arterial embalming of kidneys results in successful preservation due to complete parenchymatous spreading. More research is needed to determine whether other factors affect embalming quality. Dehydration is an effective method to regain the organs’ initial status. Prolonged vascular reperfusion with paraffinum perliquidum can be established in this model without increases in weight, volume and pressure. PMID:25806527

Adaptation to Space: An Introduction

NASA Technical Reports Server (NTRS)

Hargens, Alan R.

1995-01-01

The cardiovascular and musculoskeletal systems are normally exposed to gradients of blood pressure and weight on Earth. These gradients increase blood pressure and tissue weight in dependent tissues of the body. Exposure to actual and simulated microgravity causes blood and tissue fluid to shift from the legs to the head. Studies of humans in space have documented facial edema, space motion sickness, decreased plasma volume, muscle atrophy, and loss of bone strength. Return of astronauts to Earth is accompanied by orthostatic intolerance, decreased neuromuscular coordination, and reduced exercise capacity. These factors decrease performance during descent from orbit and increase risk during emergency egress from the spacecraft. Models of simulated microgravity include 6 deg head-down tilt, immersion, and prolonged horizontal bedrest. Head-down tilt is the most accepted model and studies using this model of up to one year have been performed in Russia. Animal models which offer clear insights into the role of gravity on vertebrates include the developing giraffe and snakes from various habitats. Finally, possible countermeasures to speed readaptation of astronauts to gravity after prolonged space flight will be discussed.

Smooth Muscle-Mediated Connective Tissue Remodeling in Pulmonary Hypertension

NASA Astrophysics Data System (ADS)

Mecham, Robert P.; Whitehouse, Loren A.; Wrenn, David S.; Parks, William C.; Griffin, Gail L.; Senior, Robert M.; Crouch, Edmond C.; Stenmark, Kurt R.; Voelkel, Norbert F.

1987-07-01

Abnormal accumulation of connective tissue in blood vessels contributes to alterations in vascular physiology associated with disease states such as hypertension and atherosclerosis. Elastin synthesis was studied in blood vessels from newborn calves with severe pulmonary hypertension induced by alveolar hypoxia in order to investigate the cellular stimuli that elicit changes in pulmonary arterial connective tissue production. A two- to fourfold increase in elastin production was observed in pulmonary artery tissue and medial smooth muscle cells from hypertensive calves. This stimulation of elastin production was accompanied by a corresponding increase in elastin messenger RNA consistent with regulation at the transcriptional level. Conditioned serum harvested from cultures of pulmonary artery smooth muscle cells isolated from hypertensive animals contained one or more low molecular weight elastogenic factors that stimulated the production of elastin in both fibroblasts and smooth muscle cells and altered the chemotactic responsiveness of fibroblasts to elastin peptides. These results suggest that connective tissue changes in the pulmonary vasculature in response to pulmonary hypertension are orchestrated by the medial smooth muscle cell through the generation of specific differentiation factors that alter both the secretory phenotype and responsive properties of surrounding cells.

Amelioration of estrogen deficiency-induced obesity by collagen hydrolysate.

PubMed

Chiang, Tsay-I; Chang, I-Chang; Lee, Hsueh-Hui; Hsieh, Kuang Hui; Chiu, Yung-Wei; Lai, Te-Jen; Liu, Jer-Yuh; Hsu, Li-Sung; Kao, Shao-Hsuan

2016-01-01

Objectives: Menopausal transition with declining estrogen levels significantly affects the physiological properties of women and consequently contributes to a series of medical conditions, including obesity. Obesity is a crucial risk factor associated with cardiovascular diseases, diabetes mellitus, and breast cancer. Increasing dietary protein content improves satiety and energy expenditure. Thus, we hypothesize that supplementing with collagen, a common dietary protein, may alleviate menopause-induced obesity. Methods: We used ovariectomized (OVX) rats to mimic a menopausal human. The body weight of OVX rats significantly increased compared with that of sham-operated rats ( P <0.05), but uterus weight was decreased. Adipocyte size in perigonadal adipose tissue also increased ( P <0.05). Results: By contrast, OVX rats supplemented with aqueous collagen hydrolysate (2.5 mg/mL) exhibited significant attenuation in body weight gain and adipocyte enlargement ( P <0.05), but insignificant change in uterus weight. Further investigation indicated that collagen hydrolysate supplementation insignificantly affected the levels of dorsal fat, serum total cholesterol, and serum triacylglycerol. Levels of serum biochemical factors, calcium, phosphorus, and glucose were also insignificantly altered by collagen hydrolysate supplementation. Conclusion: Collagen hydrolysate supplementation reduced body weight gain and adipocyte enlargement in response to ovariectomy but slightly affected blood lipids, calcium, and glucose in both sham-operated and OVX rats. Collagen hydrolysate supplementation is beneficial in ameliorating estrogen deficiency-induced obesity and its associated risk factors.

Plasma zinc's alter ego is a low-molecular-weight humoral factor.

PubMed

Ou, Ou; Allen-Redpath, Keith; Urgast, Dagmar; Gordon, Margaret-Jane; Campbell, Gill; Feldmann, Jörg; Nixon, Graeme F; Mayer, Claus-Dieter; Kwun, In-Sook; Beattie, John H

2013-09-01

Mild dietary zinc deprivation in humans and rodents has little effect on blood plasma zinc levels, and yet cellular consequences of zinc depletion can be detected in vascular and other tissues. We proposed that a zinc-regulated humoral factor might mediate the effects of zinc deprivation. Using a novel approach, primary rat vascular smooth muscle cells (VSMCs) were treated with plasma from zinc-deficient (<1 mg Zn/kg) or zinc-adequate (35 mg Zn/kg, pair-fed) adult male rats, and zinc levels were manipulated to distinguish direct and indirect effects of plasma zinc. Gene expression changes were analyzed by microarray and qPCR, and incubation of VSMCs with blood plasma from zinc-deficient rats strongly changed the expression of >2500 genes, compared to incubation of cells with zinc-adequate rat plasma. We demonstrated that this effect was caused by a low-molecular-weight (∼2-kDa) zinc-regulated humoral factor but that changes in gene expression were mostly reversed by adding zinc back to zinc-deficient plasma. Strongly regulated genes were overrepresented in pathways associated with immune function and development. We conclude that zinc deficiency induces the production of a low-molecular-weight humoral factor whose influence on VSMC gene expression is blocked by plasma zinc. This factor is therefore under dual control by zinc.

Influence of Lipophilicity on Drug Partitioning into Sclera, Choroid-Retinal Pigment Epithelium, Retina, Trabecular Meshwork, and Optic Nerve

PubMed Central

Kadam, Rajendra S.

2010-01-01

In vitro bovine eye tissue/phosphate-buffered saline, pH 7.4, partition coefficients (Kt:b), in vitro binding to natural melanin, and in vivo delivery at 1 h after posterior subconjunctival injection in Brown Norway rats were determined for eight β-blockers. The Kt:b was in the order intact tissue, dry weight method ≥ intact tissue, wet weight method corrected for tissue water and drug in tissue water ≫ intact tissue, wet weight method > homogenized tissue. In intact tissue methods, Kt:b followed the order choroid-retinal pigment epithelium (RPE) > trabecular meshwork > retina > sclera ∼ optic nerve; propranolol > betaxolol > pindolol ∼ timolol ∼ metoprolol > sotalol ∼ atenolol ∼ nadolol. Intact tissue, wet weight log (Kt:b) correlated positively with log D for all tissues (R2 of 0.7–0.9). Log (melanin binding capacity) correlated positively with choroid-RPE log (Kt:b) (R2 of 0.5). With an increase in concentration, Kt:b decreased in trabecular meshwork for all β-blockers and for some lipophilic β-blockers in choroid-RPE and sclera. With an increase in drug lipophilicity, in vivo tissue distribution increased in choroid-RPE, iris-ciliary body, sclera, and cornea but exhibited a declining trend in retina, vitreous, and lens. In vitro bovine intact tissue, wet weight Kt:b correlated positively with rat in vivo tissue/vitreous humor distribution for sclera, choroid-RPE, and retina (R2 of 0.985–0.993). In vitro tissue partition coefficients might be useful in predicting in vivo drug distribution after trans-scleral delivery. Less lipophilic solutes exhibiting limited nonproductive binding in choroid-RPE might exhibit greater trans-scleral delivery to the retina and vitreous. PMID:19926800

Pathophysiology of obesity on knee joint homeostasis: contributions of the infrapatellar fat pad.

PubMed

Santangelo, Kelly S; Radakovich, Lauren B; Fouts, Josie; Foster, Michelle T

2016-05-01

Osteoarthritis (OA) is a debilitating condition characterized by inflammation, breakdown, and consequent loss of cartilage of the joints. Epidemiological studies indicate obesity is an important risk factor involved in OA initiation and progression. Traditional views propose OA to be a biomechanical consequence of excess weight on weight-bearing joints; however, emerging data demonstrates that systemic and local factors released from white adipose depots play a role. Hence, current views characterize OA as a condition exacerbated by a metabolic link related to adipose tissue, and not solely related to redistributed/altered weight load. Factors demonstrated to influence cartilage and bone homeostasis include adipocyte-derived hormones ("adipokines") and adipose depot released cytokines. Epidemiological studies demonstrate a positive relation between systemic circulating cytokines, leptin, and resistin with OA types, while the association with adiponectin is controversial. Local factors in joints have also been shown to play a role in OA. In particular, this includes the knee, a weight-bearing joint that encloses a relatively large adipose depot, the infrapatellar fat pad (IFP), which serves as a source of local inflammatory factors. This review summarizes the relation of obesity and OA as it specifically relates to the IFP and other integral supporting structures. Overall, studies support the concept that metabolic effects associated with systemic obesity also extend to the IFP, which promotes inflammation, pain, and cartilage destruction within the local knee joint environment, thus contributing to development and progression of OA.

Cytosolic Double-Stranded DNA as a Damage-Associated Molecular Pattern Induces the Inflammatory Response in Rat Pancreatic Stellate Cells: A Plausible Mechanism for Tissue Injury-Associated Pancreatitis

PubMed Central

Nakamura, Taichi; Ito, Tetsuhide; Igarashi, Hisato; Uchida, Masahiko; Hijioka, Masayuki; Oono, Takamasa; Fujimori, Nao; Niina, Yusuke; Suzuki, Koichi; Jensen, Robert T.; Takayanagi, Ryoichi

2012-01-01

Pancreatitis is an inflammatory disease of unknown causes. There are many triggers causing pancreatitis, such as alcohol, common bile duct stone, virus and congenital or acquired stenosis of main pancreatic duct, which often involve tissue injuries. Pancreatitis often occurs in sterile condition, where the dead/dying pancreatic parenchymal cells and the necrotic tissues derived from self-digested-pancreas were observed. However, the causal relationship between tissue injury and pancreatitis and how tissue injury could induce the inflammation of the pancreas were not elucidated fully until now. This study demonstrates that cytosolic double-stranded DNA increases the expression of several inflammatory genes (cytokines, chemokines, type I interferon, and major histocompatibility complex) in rat pancreatic stellate cells. Furthermore, these increase accompanied the multiple signal molecules genes, such as interferon regulatory factors, nuclear factor-kappa B, low-molecular-weight protein 2, and transporter associated with antigen processing 1. We suggest that this phenomenon is a plausible mechanism that might explain how cell damage of the pancreas or tissue injury triggers acute, chronic, and autoimmune pancreatitis; it is potentially relevant to host immune responses induced during alcohol consumption or other causes. PMID:22550608

Allele compensation in tip60+/- mice rescues white adipose tissue function in vivo.

PubMed

Gao, Yuan; Hamers, Nicole; Rakhshandehroo, Maryam; Berger, Ruud; Lough, John; Kalkhoven, Eric

2014-01-01

Adipose tissue is a key regulator of energy homestasis. The amount of adipose tissue is largely determined by adipocyte differentiation (adipogenesis), a process that is regulated by the concerted actions of multiple transcription factors and cofactors. Based on in vitro studies in murine 3T3-L1 preadipocytes and human primary preadipocytes, the transcriptional cofactor and acetyltransferase Tip60 was recently identified as an essential adipogenic factor. We therefore investigated the role of Tip60 on adipocyte differentiation and function, and possible consequences on energy homeostasis, in vivo. Because homozygous inactivation results in early embryonic lethality, Tip60+/- mice were used. Heterozygous inactivation of Tip60 had no effect on body weight, despite slightly higher food intake by Tip60+/- mice. No major effects of heterozygous inactivation of Tip60 were observed on adipose tissue and liver, and Tip60+/- displayed normal glucose tolerance, both on a low fat and a high fat diet. While Tip60 mRNA was reduced to 50% in adipose tissue, the protein levels were unaltered, suggesting compensation by the intact allele. These findings indicate that the in vivo role of Tip60 in adipocyte differentiation and function cannot be properly addressed in Tip60+/- mice, but requires the generation of adipose tissue-specific knock out animals or specific knock-in mice.

Regional Differences in Adipose Tissue Hormone/Cytokine Production Before and After Weight Loss in Abdominally Obese Women

PubMed Central

You, Tongjian; Wang, Xuewen; Murphy, Karin M.; Lyles, Mary F.; Demons, Jamehl L.; Yang, Rongze; Gong, Da-Wei; Nicklas, Barbara J.

2014-01-01

Objective To compare the regional differences in subcutaneous adipose tissue hormone/cytokine production in abdominally obese women during weight loss. Design and Methods Forty-two abdominally obese, older women underwent a 20-week weight loss intervention composed of hypocaloric diet with or without aerobic exercise (total energy expenditure: ~2800 kcal/week). Subcutaneous (gluteal and abdominal) adipose tissue biopsies were conducted before and after the intervention. Results Adipose tissue gene expression and release of leptin, adiponectin, and interleukin 6 (IL-6) were determined. The intervention resulted in significant weight loss (−10.1 ±0.7 kg, P<0.001). At baseline, gene expression of adiponectin were higher (P<0.01), and gene expression and release of IL-6 were lower (both P<0.05) in abdominal than in gluteal adipose tissue. After intervention, leptin gene expression and release were lower in both gluteal and abdominal adipose tissue compared to baseline (P<0.05 to P<0.01). Abdominal, but not gluteal, adipose tissue adiponectin gene expression and release increased after intervention (both P<0.05). Conclusion A 20-week weight loss program decreased leptin production in both gluteal and abdominal adipose tissue, but only increased adiponectin production from abdominal adipose tissue in obese women. This depot-specific effect may be of importance for the treatment of health complications associated with abdominal adiposity. PMID:24634403

Optimally designed collagen/polycaprolactone biocomposites supplemented with controlled release of HA/TCP/rhBMP-2 and HA/TCP/PRP for hard tissue regeneration.

PubMed

Kim, WonJin; Jang, Chul Ho; Kim, GeunHyung

2017-09-01

Collagen has been widely used as a very promising material to regenerate various tissues. It is a chief component of the extracellular matrix, and encourages various biological effects conducive to tissue regeneration. However, poor mechanical stability, low processability, and high level of water absorption can lead to impaired control of growth factor release and have impeded the use of collagen as a functional biomedical scaffold. Here, to overcome the shortcomings of collagen scaffolds, we have additively manufactured collagen/polycaprolactone (PCL) biocomposites supplemented with a bioceramic (hydroxyapatite (HA)/β-tricalcium-phosphate (TCP)) and two growth factors (recombinant human bone morphogenetic protein-2 [rhBMP-2] and platelet-rich plasma [PRP]). Various weight fractions of PCL in the collagen/PCL composites were manipulated to select optimal growth factor release and highly active cellular responses. After the optimal concentration of PCL in the collagen/PCL scaffold was determined, biocomposites supplemented with bioceramic/growth-factors were fabricated. Continuously released growth factors were assumed to increase the in vitro cellular activities of the osteoblast-like cells (MG63) cultured on the biocomposites. In vitro cellular responses, including osteogenic activities, were examined, and results showed that compared to the HA/TCP/rhBMP-2 supplemented scaffold the HA/TCP/PRP biocomposites provide significantly high cellular activities (cell proliferation: >1.3-fold) and mineralization (calcium deposition: >1.4-fold, osteocalcin: >2.6-fold) sufficient for regenerating bone tissue. Copyright © 2017. Published by Elsevier B.V.

Impact of polyunsaturated and saturated fat overfeeding on the DNA-methylation pattern in human adipose tissue: a randomized controlled trial.

PubMed

Perfilyev, Alexander; Dahlman, Ingrid; Gillberg, Linn; Rosqvist, Fredrik; Iggman, David; Volkov, Petr; Nilsson, Emma; Risérus, Ulf; Ling, Charlotte

2017-04-01

Background: Dietary fat composition can affect ectopic lipid accumulation and, thereby, insulin resistance. Diets that are high in saturated fatty acids (SFAs) or polyunsaturated fatty acids (PUFAs) have different metabolic responses. Objective: We investigated whether the epigenome of human adipose tissue is affected differently by dietary fat composition and general overfeeding in a randomized trial. Design: We studied the effects of 7 wk of excessive SFA ( n = 17) or PUFA ( n = 14) intake (+750 kcal/d) on the DNA methylation of ∼450,000 sites in human subcutaneous adipose tissue. Both diets resulted in similar body weight increases. We also combined the data from the 2 groups to examine the overall effect of overfeeding on the DNA methylation in adipose tissue. Results: The DNA methylation of 4875 Cytosine-phosphate-guanine (CpG) sites was affected differently between the 2 diets. Furthermore, both the SFA and PUFA diets increased the mean degree of DNA methylation in adipose tissue, particularly in promoter regions. However, although the mean methylation was changed in 1797 genes [e.g., alpha-ketoglutarate dependent dioxygenase ( FTO ), interleukin 6 ( IL6 ), insulin receptor ( INSR ), neuronal growth regulator 1 ( NEGR1 ), and proopiomelanocortin ( POMC )] by PUFAs, only 125 genes [e.g., adiponectin, C1Q and collagen domain containing ( ADIPOQ )] were changed by SFA overfeeding. In addition, the SFA diet significantly altered the expression of 28 transcripts [e.g., acyl-CoA oxidase 1 ( ACOX1 ) and FAT atypical cadherin 1 ( FAT1 )], whereas the PUFA diet did not significantly affect gene expression. When the data from the 2 diet groups were combined, the mean methylation of 1444 genes, including fatty acid binding protein 1 ( FABP1 ), fatty acid binding protein 2 ( FABP2 ), melanocortin 2 receptor ( MC2R ), MC3R , PPARG coactivator 1 α ( PPARGC1A ), and tumor necrosis factor ( TNF ), was changed in adipose tissue by overfeeding. Moreover, the baseline DNA methylation of 12 CpG sites that was annotated to 9 genes [e.g., mitogen-activated protein kinase 7 ( MAPK7 ), melanin concentrating hormone receptor 1 ( MCHR1 ), and splicing factor SWAP homolog ( SFRS8 )] was associated with the degree of weight increase in response to extra energy intake. Conclusions: SFA overfeeding and PUFA overfeeding induce distinct epigenetic changes in human adipose tissue. In addition, we present data that suggest that baseline DNA methylation can predict weight increase in response to overfeeding in humans. This trial was registered at clinicaltrials.gov as NCT01427140. © 2017 American Society for Nutrition.

Body composition in athletes: assessment and estimated fatness.

PubMed

Malina, Robert M

2007-01-01

The study of body composition attempts to partition and quantify body weight or mass into its basic components. Body weight is a gross measure of the mass of the body, which can be studied at several levels from basic chemical elements and specific tissues to the entire body. Body composition is a factor that can influence athletic performance and as such is of considerable interest to athletes and coaches. This article provides an overview of models and methods used for studying body composition, changes in body composition during adolescence and the transition into adulthood, and applications to adolescent and young adult athletes.

Oral and parenteral anticoagulants: new kids on the block.

PubMed

Aditya, S

2012-01-01

Well-documented drawbacks of traditional anticoagulants have lead to the quest for an ideal anticoagulant resulting in a surge of novel anticoagulant molecules. These newer agents directly target specific steps in coagulation cascade and include newer low molecular weight heparins (adomiparin), ultra low molecular weight heparins (semuloparin, RO-14), inhibitors of activated factor II (dabigatran, AZD0837), X (rivaroxaban, apixaban, edoxaban, betrixaban), IX (REG1,2), XI (antisense oligonucleotides, BMS 262084, clavatadine A), VII/tissue factor (tifacogin, PCI 274836, and BMS 593214), V (recomodulin, solulin), VIII (TB402), dual thrombin/factor X inhibitors (EP21709, tanogitran), and newer vitamin K antagonists (tecarfarin). Direct thrombin inhibitors and Factor X inhibitors are the most clinically advanced. This article discusses the recent advances in the development of novel targets of anticoagulants. Medline, EMBASE, cochrane database, medscape, SCOPUS, and clinicaltrials.gov were searched using terms "anticoagulants", "blood coagulation inhibitors", "anticoagulants and venous thromboembolism", "anticoagulants and atrial fibrillation", and "'antithrombins." Journal articles published from 2007 to 2012 discussing pharmacology and/or clinical trials were screened.

Irbesartan increased PPAR{gamma} activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Iwai, Masaru; Kanno, Harumi; Senba, Izumi

2011-03-04

Research highlights: {yields} Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. {yields} Irbesartan decreased white adipose tissue weight without affecting body weight. {yields} DNA-binding for PPAR{gamma} was increased in white adipose tissue in vivo by irbesartan. {yields} Irbesartan increased adipocyte number in white adipose tissue. {yields} Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPAR{gamma} agonistic action of an AT{sub 1} receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with amore » high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPAR{gamma} in white adipose tissue and the DNA-binding activity of PPAR{gamma} in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPAR{gamma} and improved adipose tissue dysfunction including insulin resistance.« less

Botulinum toxin A improves adipose tissue engraftment by promoting cell proliferation, adipogenesis and angiogenesis

PubMed Central

Tang, Qi; Chen, Chang; Wang, Xiaqi; Li, Wei; Zhang, Yan; Wang, Muyao; Jing, Wei; Wang, Hang; Guo, Weihua; Tian, Weidong

2017-01-01

Adipose tissue engraftment has become a well-established therapy in plastic and reconstructive surgery used to restore age-related or injury-related soft tissue loss. However, the unpredictable absorption rates limit its further application. Some clinicians have noted that more optimal aesthetic results are achieved when botulinum toxin A (BoNTA) is applied prior to adipose tissue grafting. In the present study, we transplanted allogeneic adipose tissue treated with or without BoNTA in SD rats in vivo. We subsequently evaluated the survival rate (weight, volume, apoptosis and cellular integrity) and revascularization of the adipose tissue. The results revealed that BoNTA improved the long-term weight and volume retention of the graft, and preserved cellular integrity. BoNTA significantly increased the expression levels of CD31 and vascular endothelial growth factor (VEGF), suggesting enhanced vasodilation and endothelial cell proliferation. In vitro, adipose-derived stem cells (ASCs) were isolated, identified and induced to proliferate and differentiate with or without BoNTA. Furthermore, to evaluate the proliferative, adipogenic and angiogenic ability of the ASCs, CCK-8 assay and Oil Red O staining were conducted. Gene and protein expression levels were analyzed by RT-qPCR and western blot analysis. The results revealed that 8×10−2 U/ml BoNTA as the optimal dose increased ASC proliferation and adipogenic differentiation capacity, as well as the expression level of the key cytokine of angiogenesis. On the whole, our findings indicate that BoNTA improves adipose tissue engraftment and promotes ASC regeneration, which could benefit future clinical applications. PMID:28731141

Significance of Epicardial and Intrathoracic Adipose Tissue Volume among Type 1 Diabetes Patients in the DCCT/EDIC: A Pilot Study

PubMed Central

Budoff, Matthew J.

2016-01-01

Introduction Type 1 diabetes (T1DM) patients are at increased risk of coronary artery disease (CAD). This pilot study sought to evaluate the relationship between epicardial adipose tissue (EAT) and intra-thoracic adipose tissue (IAT) volumes and cardio-metabolic risk factors in T1DM. Method EAT/IAT volumes in 100 patients, underwent non-contrast cardiac computed tomography in the Diabetes Control and Complications Trial /Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study were measured by a certified reader. Fat was defined as pixels’ density of -30 to -190 Hounsfield Unit. The associations were assessed using–Pearson partial correlation and linear regression models adjusted for gender and age with inverse probability sample weighting. Results The weighted mean age was 43 years (range 32–57) and 53% were male. Adjusted for gender, Pearson correlation analysis showed a significant correlation between age and EAT/IAT volumes (both p<0.001). After adjusting for gender and age, participants with greater BMI, higher waist to hip ratio (WTH), higher weighted HbA1c, elevated triglyceride level, and a history of albumin excretion rate of equal or greater than 300 mg/d (AER≥300) or end stage renal disease (ESRD) had significantly larger EAT/IAT volumes. Conclusion T1DM patients with greater BMI, WTH ratio, weighted HbA1c level, triglyceride level and AER≥300/ESRD had significantly larger EAT/IAT volumes. Larger sample size studies are recommended to evaluate independency. PMID:27459689

Protective effect of quercetin and/or l-arginine against nano-zinc oxide-induced cardiotoxicity in rats

NASA Astrophysics Data System (ADS)

Faddah, L. M.; Baky, Nayira A. Abdel; Mohamed, Azza M.; Al-Rasheed, Nouf M.; Al-Rasheed, Nawal M.

2013-04-01

The aim of this study was to investigate the protective role of quercetin and/or l-arginine against the cardiotoxic potency of zinc oxide nanoparticle (ZnO-NP)-induced cardiac infarction. ZnO-NPs (50 nm) were administered orally at either 600 mg or 1 g/kg body weight for 5 consecutive days. The results revealed that co-administration of quercetin and/or l-arginine (each 200 mg/kg body weight) daily for 3 weeks to rats intoxicated by either of the two doses markedly ameliorated increases in serum markers of cardiac infarction, including troponin T, creatine kinase-MB, and myoglobin, as well as increases in proinflammatory biomarkers, including tumor necrosis factor-α, interleukin-6, and C-reactive protein, compared with intoxicated, untreated rats. Each agent alone or in combination also successfully modulated the alterations in serum vascular endothelial growth factor, cardiac calcium concentration, and oxidative DNA damage as well as the increase in the apoptosis marker caspase 3 of cardiac tissue in response to ZnO-NP toxicity. In conclusion, early treatment with quercetin and l-arginine may protect cardiac tissue from infarction induced by the toxic effects of ZnO-NPs.

Sugar Potentiation of Fatty Acid and Triacylglycerol Accumulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhai, Zhiyang; Liu, Hui; Xu, Changcheng

Photosynthetically derived sugar provides carbon skeletons for lipid biosynthesis. We used mutants of Arabidopsis (Arabidopsis thaliana) and the expression of oleogenic factors to investigate relationships among sugar availability, lipid synthesis, and the accumulation of triacylglycerol (TAG) in leaf tissue. The adg1 mutation disables the small subunit of ADP-glucose pyrophosphorylase, the first step in starch synthesis, and the suc2 mutation disables a sucrose/proton symporter that facilitates sucrose loading from leaves into phloem. The adg1suc2 double mutant increases glucose plus sucrose content in leaves 80-fold relative to the wild type, total fatty acid (FA) content 1.8-fold to 8.3% dry weight, and TAGmore » more than 10-fold to 1.2% dry weight. The WRINKLED1 transcription factor also accumulates to higher levels in these leaves, and the rate of FA synthesis increases by 58%. Adding tt4, which disables chalcone synthase, had little effect, but adding the tgd1 mutation, which disables an importer of lipids into plastids to create adg1suc2tt4tgd1, increased total leaf FA to 13.5% dry weight and TAG to 3.8% dry weight, demonstrating a synergistic effect upon combining these mutations. Combining adg1suc2 with the sdp1 mutation, deficient in the predominant TAG lipase, had little effect on total FA content but increased the TAG accumulation by 66% to 2% dry weight. Expression of the WRINKLED1 transcription factor, along with DIACYLGLYCEROL ACYLTRANSFERASE1 and the OLEOSIN1 oil body-associated protein, in the adg1suc2 mutant doubled leaf FA content and increased TAG content to 2.3% dry weight, a level 4.6-fold higher than that resulting from expression of the same factors in the wild type.« less

Sugar Potentiation of Fatty Acid and Triacylglycerol Accumulation

DOE PAGES

Zhai, Zhiyang; Liu, Hui; Xu, Changcheng; ...

2017-10-01

Photosynthetically derived sugar provides carbon skeletons for lipid biosynthesis. We used mutants of Arabidopsis (Arabidopsis thaliana) and the expression of oleogenic factors to investigate relationships among sugar availability, lipid synthesis, and the accumulation of triacylglycerol (TAG) in leaf tissue. The adg1 mutation disables the small subunit of ADP-glucose pyrophosphorylase, the first step in starch synthesis, and the suc2 mutation disables a sucrose/proton symporter that facilitates sucrose loading from leaves into phloem. The adg1suc2 double mutant increases glucose plus sucrose content in leaves 80-fold relative to the wild type, total fatty acid (FA) content 1.8-fold to 8.3% dry weight, and TAGmore » more than 10-fold to 1.2% dry weight. The WRINKLED1 transcription factor also accumulates to higher levels in these leaves, and the rate of FA synthesis increases by 58%. Adding tt4, which disables chalcone synthase, had little effect, but adding the tgd1 mutation, which disables an importer of lipids into plastids to create adg1suc2tt4tgd1, increased total leaf FA to 13.5% dry weight and TAG to 3.8% dry weight, demonstrating a synergistic effect upon combining these mutations. Combining adg1suc2 with the sdp1 mutation, deficient in the predominant TAG lipase, had little effect on total FA content but increased the TAG accumulation by 66% to 2% dry weight. Expression of the WRINKLED1 transcription factor, along with DIACYLGLYCEROL ACYLTRANSFERASE1 and the OLEOSIN1 oil body-associated protein, in the adg1suc2 mutant doubled leaf FA content and increased TAG content to 2.3% dry weight, a level 4.6-fold higher than that resulting from expression of the same factors in the wild type.« less

Voluntary exercise improves murine dermal connective tissue status in high-fat diet-induced obesity.

PubMed

Lőrincz, Kende; Haluszka, Dóra; Kiss, Norbert; Gyöngyösi, Nóra; Bánvölgyi, András; Szipőcs, Róbert; Wikonkál, Norbert M

2017-04-01

Obesity is a risk factor for several cardiovascular and metabolic diseases. Its influence on the skin is less obvious, yet certain negative effects of adipose tissue inflammation on the dermis have been suggested. Excess weight is closely associated with sedentary behavior, so any increase in physical activity is considered beneficial against obesity. To investigate the effects of obesity and physical exercise on the skin, we established a mouse model in which mice were kept either on a high-fat diet or received standard chow. After the two groups achieved a significant weight difference, physical exercise was introduced to both. Animals were given the opportunity to perform voluntary exercise for 40 min daily in a hamster wheel for a period of 8 weeks. We evaluated the status of the dermis at the beginning and at the end of the exercise period by in vivo nonlinear microscopy. Obese mice kept on high-fat diet lost weight steadily after they started to exercise. In the high-fat diet group, we could detect significantly larger adipocytes and a thicker layer of subcutaneous tissue; both changes started to normalize after exercise. Nonlinear microscopy revealed an impaired collagen structure in obese mice that improved considerably after physical activity was introduced. With the ability to detect damage on collagen structure, we set out to address the question whether this process is reversible. With the use of a novel imaging method, we were able to show the reversibility of connective tissue deterioration as a benefit of physical exercise.

Biometric studies on the bivalves Astarte elliptica, A. borealis and A. montagui in Kiel Bay (Western Baltic Sea)

NASA Astrophysics Data System (ADS)

Schaefer, R.; Trutschler, K.; Rumohr, H.

1985-09-01

The three Astarte species were studied in June 1983 at two sites in Kiel Bay, “Süderfahrt” and “Schleimünde”, at 20 m depth. Shell length to live wet weight correlations are given for all three species; for A. elliptica also shell-free dry weight, shell dry weight, ash-free dry weight of the soft body and ash-free dry weight of the shell are recorded as functions of the shell length. In the logarithmic length/weight regression analysis the coefficients of slope for A. elliptica and A. borealis are 3. For A. montagui, that coefficient is significantly greater than 3. Weight conversion factors, calculated for A. elliptica, revealed a mean weight composition of 31.5 % water in the mantle cavity and tissue water, 64.5 % shell ash, 2.1 % organic content of shell, 1.7 % organic content of the soft body and 0.4 % ash of the soft body. An isometric growth of shell length and shell breadth is confirmed for A. borealis, while A. montagui exhibits positive allometric shell growth and changes its shape during life.

Diosmin Attenuates Methotrexate-Induced Hepatic, Renal, and Cardiac Injury: A Biochemical and Histopathological Study in Mice

PubMed Central

Khalifa, Hesham A.; Al-Quraishy, Saleh A.

2017-01-01

The current study was designed to investigate the beneficial role of diosmin, a biologically active flavonoid, against methotrexate- (MTX-) induced hepatic, renal, and cardiac injuries in mice. Male Swiss albino mice received a single intraperitoneal injection of MTX (at 20 mg/kg, body weight) either alone or in combination with oral diosmin (at 50 or 100 mg/kg body weight, for 10 days). Serum was used to evaluate tissue injury markers, while hepatic, renal, and cardiac tissue samples were obtained for determination of antioxidant activity as well as histopathological examination. Diosmin treatment ameliorated the MTX-induced elevation of serum alkaline phosphatase, aminotransferases, urea, creatinine, lactate dehydrogenase, and creatine kinases as well as plasma proinflammatory cytokines (interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha). Additionally, both diosmin doses significantly reduced tissue levels of malondialdehyde and nitric oxide and increased those of glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase, and catalase, compared to the MTX-intoxicated group. Histopathological examination showed that diosmin significantly minimized the MTX-induced histological alterations and nearly restored the normal architecture of hepatic, renal, and cardiac tissues. Based on these findings, diosmin may be a promising agent for protection against MTX-induced cytotoxicity in patients with cancer and autoimmune diseases. PMID:28819543

Radiation-Induced Esophagitis In Vivo and In Vitro Reveals That Epidermal Growth Factor Is a Potential Candidate for Therapeutic Intervention Strategy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Kyung Su; Jeon, Seong-Uk; Lee, Chan-Ju

Purpose: To establish and characterize radiation-induced esophagitis (RIE) in vivo and in vitro. Methods and Materials: Fractionated thoracic irradiation at 0, 8, 12, or 15 Gy was given daily for 5 days to Balb/c or C57Bl/6 mice. Changes in body weight gain and daily food intake were assessed. At the end of the study, we removed the esophagus and examined histology by hematoxylin and eosin staining, immune cell infiltration and apoptosis by fluorescence-activated cell sorting, and gene expression changes by quantitative real-time polymerase chain reaction. Het-1A human esophageal epithelial cells were irradiated at 6 Gy, treated with recombinant human growth factors, and examined for genemore » expression changes, apoptosis, proliferation, and signal transduction pathways. Results: We observed that irradiation at 12 Gy or 15 Gy per fraction produced significant reduction in body weight and decreased food intake in Balb/c mice but not as much in C57Bl/6 mice. Further analyses of Balb/c mice irradiated at 12 Gy/fraction revealed attenuated epithelium, inflamed mucosa, and increased numbers of infiltrating CD4+ helper T cells and apoptotic cells. Moreover, we found that expression of tissue inhibitor for metalloproteinase-1, plasminogen activator inhibitor-1, granulocyte macrophage-colony stimulating factor, vascular endothelial growth factor, and stromal-derived factor-1 were increased, whereas epidermal growth factor (EGF) was decreased. Irradiated Het-1A cells similarly showed a significant decrease in expression of EGF and connective tissue growth factor (CTGF). Treatment of EGF but not CTGF partially protected Het-1A cells from radiation-induced apoptosis and revealed phosphorylation of EGFR, AKT, and ERK signaling pathways. Conclusions: We established a mouse model of RIE in Balb/c mice with 12 Gy × 5 fractions, which showed reduced body weight gain, food intake, and histopathologic features similar to those of human esophagitis. Decreased EGF expression in the irradiated esophagus suggests that EGF may be a potential therapeutic intervention strategy to treat RIE.« less

Relationship between MRI-measured bone marrow adipose tissue and hip and spine bone mineral density in African-American and Caucasian participants: the CARDIA study.

PubMed

Shen, Wei; Scherzer, Rebecca; Gantz, Madeleine; Chen, Jun; Punyanitya, Mark; Lewis, Cora E; Grunfeld, Carl

2012-04-01

An increasing number of studies suggest that bone marrow adipose tissue (BMAT) might play a role in the pathogenesis of osteoporosis. Our previous study of Caucasian women demonstrated that there is an inverse relationship between BMAT and whole-body bone mineral density (BMD). It is unknown whether visceral adipose tissue (VAT), sc adipose tissue (SAT), and skeletal muscle had an effect on the relationship between BMAT and BMD. In the present study we investigated the relationship between pelvic, hip, and lumbar spine BMAT with hip and lumbar spine BMD in the population-based Coronary Artery Risk Development in Young Adults (CARDIA) sample with adjustment for whole-body magnetic resonance imaging (MRI)-measured VAT, SAT, and skeletal muscle. T1-weighted MRI was acquired for 210 healthy African-American and Caucasian men and women (age 38-52 yr). Hip and lumbar spine BMD were measured by dual-energy x-ray absorptiometry. Pelvic, hip, and lumbar spine BMAT had negative correlations with hip and lumbar spine BMD (r = -0.399 to -0.550, P < 0.001). The inverse associations between BMAT and BMD remained strong after adjusting for demographics, weight, skeletal muscle, SAT, VAT, total adipose tissue (TAT), menopausal status, lifestyle factors, and inflammatory markers (standardized regression coefficients = -0. 296 to -0.549, P < 0.001). Among body composition measures, skeletal muscle was the strongest correlate of BMD after adjusting for BMAT (standardized regression coefficients = 0.268-0.614, P < 0.05), with little additional contribution from weight, SAT, VAT, or total adipose tissue. In this middle-aged population, a negative relationship existed between MRI-measured BMAT and hip and lumbar spine BMD independent of demographics and body composition. These observations support the growing evidence linking BMAT with low bone density.

Relationship between MRI-Measured Bone Marrow Adipose Tissue and Hip and Spine Bone Mineral Density in African-American and Caucasian Participants: The CARDIA Study

PubMed Central

Scherzer, Rebecca; Gantz, Madeleine; Chen, Jun; Punyanitya, Mark; Lewis, Cora E.; Grunfeld, Carl

2012-01-01

Context: An increasing number of studies suggest that bone marrow adipose tissue (BMAT) might play a role in the pathogenesis of osteoporosis. Our previous study of Caucasian women demonstrated that there is an inverse relationship between BMAT and whole-body bone mineral density (BMD). It is unknown whether visceral adipose tissue (VAT), sc adipose tissue (SAT), and skeletal muscle had an effect on the relationship between BMAT and BMD. Objective: In the present study we investigated the relationship between pelvic, hip, and lumbar spine BMAT with hip and lumbar spine BMD in the population-based Coronary Artery Risk Development in Young Adults (CARDIA) sample with adjustment for whole-body magnetic resonance imaging (MRI)-measured VAT, SAT, and skeletal muscle. Design: T1-weighted MRI was acquired for 210 healthy African-American and Caucasian men and women (age 38–52 yr). Hip and lumbar spine BMD were measured by dual-energy x-ray absorptiometry. Results: Pelvic, hip, and lumbar spine BMAT had negative correlations with hip and lumbar spine BMD (r = −0.399 to −0.550, P < 0.001). The inverse associations between BMAT and BMD remained strong after adjusting for demographics, weight, skeletal muscle, SAT, VAT, total adipose tissue (TAT), menopausal status, lifestyle factors, and inflammatory markers (standardized regression coefficients = −0. 296 to −0.549, P < 0.001). Among body composition measures, skeletal muscle was the strongest correlate of BMD after adjusting for BMAT (standardized regression coefficients = 0.268–0.614, P < 0.05), with little additional contribution from weight, SAT, VAT, or total adipose tissue. Conclusion: In this middle-aged population, a negative relationship existed between MRI-measured BMAT and hip and lumbar spine BMD independent of demographics and body composition. These observations support the growing evidence linking BMAT with low bone density. PMID:22319043

Cell-Nonautonomous Mechanisms Underlying Cellular and Organismal Aging.

PubMed

Medkour, Younes; Svistkova, Veronika; Titorenko, Vladimir I

2016-01-01

Cell-autonomous mechanisms underlying cellular and organismal aging in evolutionarily distant eukaryotes have been established; these mechanisms regulate longevity-defining processes within a single eukaryotic cell. Recent findings have provided valuable insight into cell-nonautonomous mechanisms modulating cellular and organismal aging in eukaryotes across phyla; these mechanisms involve a transmission of various longevity factors between different cells, tissues, and organisms. Herein, we review such cell-nonautonomous mechanisms of aging in eukaryotes. We discuss the following: (1) how low molecular weight transmissible longevity factors modulate aging and define longevity of cells in yeast populations cultured in liquid media or on solid surfaces, (2) how communications between proteostasis stress networks operating in neurons and nonneuronal somatic tissues define longevity of the nematode Caenorhabditis elegans by modulating the rates of aging in different tissues, and (3) how different bacterial species colonizing the gut lumen of C. elegans define nematode longevity by modulating the rate of organismal aging. Copyright © 2016. Published by Elsevier Inc.

From the Cover: Adipose tissue mass can be regulated through the vasculature

NASA Astrophysics Data System (ADS)

Rupnick, Maria A.; Panigrahy, Dipak; Zhang, Chen-Yu; Dallabrida, Susan M.; Lowell, Bradford B.; Langer, Robert; Judah Folkman, M.

2002-08-01

Tumor growth is angiogenesis dependent. We hypothesized that nonneoplastic tissue growth also depends on neovascularization. We chose adipose tissue as an experimental system because of its remodeling capacity. Mice from different obesity models received anti-angiogenic agents. Treatment resulted in dose-dependent, reversible weight reduction and adipose tissue loss. Marked vascular remodeling was evident in adipose tissue sections, which revealed decreased endothelial proliferation and increased apoptosis in treated mice compared with controls. Continuous treatment maintained mice near normal body weights for age without adverse effects. Metabolic adaptations in food intake, metabolic rate, and energy substrate utilization were associated with anti-angiogenic weight loss. We conclude that adipose tissue mass is sensitive to angiogenesis inhibitors and can be regulated by its vasculature.

Bioavailability and tissue distribution of Dechloranes in wild frogs (Rana limnocharis) from an e-waste recycling area in Southeast China.

PubMed

Li, Long; Wang, Wenyue; Lv, Quanxia; Ben, Yujie; Li, Xinghong

2014-03-01

Dechlorane Plus (DP), a flame retardant used as an alternative to decabromodiphenylether, has been frequently detected in organisms, indicating its bioaccumulation and biomagnification potential in aquatic and terrestrial species. However, little data is available on the bioaccumulation of DP in amphibians. Dechlorane Plus and its analogs (DPs) were detected in the liver, muscle and brain tissues of wild frogs (Rana limnocharis), which were collected from an e-waste recycling site, Southeast China. DP, Mirex, Dec 602 and a dechlorinated compound of DP (anti-Cl11-DP) varied in the range of 2.01-291, 0.650-179, 0.260-12.4, and not detected (nd)-8.67 ng/g lipid weight, respectively. No difference of tissue distribution was found for syn-DP, Mirex and Dec 602 between the liver and muscle tissue (liver/muscle concentration ratio close to 1, p > 0.05). However, higher retention was observed for anti-DP and anti-Cl11-DP in the frog muscle relative to the liver tissue (liver/muscle concentration ratio < 1, p < 0.05). Additionally, the blood-brain barrier was found to work efficiently to suppress these compounds entering brain tissues in this species (liver/brain concentration ratio > 1, p < 0.05), and the molecular weight was a key factor impacting the extent of the blood-brain barrier. Compared to levels in the muscle and brain tissue, a preferential enrichment of syn-DP was observed in the liver tissue, suggesting the occurrence of stereo-selective bioaccumulation in the wild frog. Copyright © 2014 The Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

The AAHKS Clinical Research Award: Intraosseous Regional Prophylaxis Provides Higher Tissue Concentrations in High BMI Patients in Total Knee Arthroplasty: A Randomized Trial.

PubMed

Chin, Seung Joon; Moore, Grant A; Zhang, Mei; Clarke, Henry D; Spangehl, Mark J; Young, Simon W

2018-07-01

Obesity is an established risk factor for periprosthetic joint infections after total knee arthroplasty (TKA). In obese patients, a larger dose of prophylactic vancomycin based on actual body weight is required to reach therapeutic concentrations. It is unclear how tissue concentrations are affected when intraosseous regional administration (IORA) is used in this population. This study compared tissue concentrations of low-dose vancomycin via IORA vs actual body weight-adjusted systemic intravenous (IV) dose in primary TKA. Twenty-two patients with a body mass index (BMI) >35 undergoing TKA were randomized into 2 groups. The IV group received 15 mg/kg (maximum of 2 g) of systemic IV vancomycin and the IORA group received 500 mg vancomycin into the tibia. Subcutaneous fat and bone samples were taken at regular intervals. Tissue antibiotic concentrations were measured using liquid chromatography coupled with tandem mass spectrometry. A blood sample was taken 1 to 2 hours after tourniquet deflation to measure systemic concentration. The mean BMI was 41.1 in the IORA group and 40.1 in the IV systemic group. The overall mean tissue concentration in subcutaneous fat was 39.3 μg/g in the IORA group and 4.4 μg/g in the IV systemic group (P < .01). Mean tissue concentrations in bones were 34.4 μg/g in the IORA group and 6.1 μg/g in the IV systemic group (P < .01). Low-dose IORA was effective in the high-BMI population group, providing tissue concentrations of vancomycin 5-9 times higher than systemic administration. IORA optimizes timing of vancomycin administration and provides high tissue antibiotic concentrations during TKA in this high-risk patient group. Copyright © 2018 Elsevier Inc. All rights reserved.

Diurnal Changes in Volume and Specific Tissue Weight of Crassulacean Acid Metabolism Plants 1

PubMed Central

Chen, Sheng-Shu; Black, Clanton C.

1983-01-01

The diurnal variations in volume and in specific weight were determined for green stems and leaves of Crassulacen acid metabolism (CAM) plants. Volume changes were measured by a water displacement method. Diurnal variations occurred in the volume of green CAM tissues. Their volume increased early in the light period reaching a maximum about mid-day, then the volume decreased to a minimum near midnight. The maximum volume increase each day was about 2.7% of the total volume. Control leaves of C3 and C4 plants exhibited reverse diurnal volume changes of 0.2 to 0.4%. The hypothesis is presented and supported that green CAM tissues should exhibit a diurnal increase in volume due to the increase of internal gas pressure from CO2 and O2 when their stomata are closed. Conversely, the volume should decrease when the gas pressure is decreased. The second hypothesis presented and supported was that the specific weight (milligrams of dry weight per square centimeter of green surface area) of green CAM tissues should increase at night due to the net fixation of CO2. Green CAM tissues increased their specific weight at night in contrast to control C3 and C4 leaves which decreased their specific weight at night. With Kalanchoë daigremontiana leaves, the calculated increase in specific leaf weight at night based on estimates of carbohydrate available for net CO2 fixation was near 6% and the measured increase in specific leaf weight was 6%. Diurnal measurements of CAM tissue water content were neither coincident nor reciprocal with their diurnal patterns of either volume or specific weight changes. PMID:16662833

Heavy metal concentrations in commercial deep-sea fish from the Rockall Trough

NASA Astrophysics Data System (ADS)

Mormede, S.; Davies, I. M.

2001-05-01

Samples of monkfish ( Lophius piscatorius), black scabbard ( Aphanopus carbo), blue ling ( Molva dypterygia), blue whiting ( Micromesistius poutassou) and hake ( Merluccius merluccius) were obtained from 400 to 1150 m depth on the continental slope of Rockall Trough west of Scotland. Muscle, liver, gill and gonad tissue were analysed for arsenic, cadmium, copper, lead, mercury and zinc by various atomic absorption techniques. Median concentrations of arsenic in the muscle tissue ranged from 1.25 to 8.63 mg/kg wet weight; in liver tissue from 3.04 to 5.72 mg/kg wet weight; cadmium in muscle tissue from <0.002 to 0.034 mg/kg wet weight, in liver tissue from 0.11 to 6.98 mg/kg wet weight; copper in the muscle from 0.12 to 0.29 mg/kg wet weight, in the liver from 3.47 to 11.87 mg/kg wet weight; lead levels in muscle from <0.002 to 0.009 mg/kg wet weight, respectively, and in liver tissue <0.05 mg/kg wet weight for all species. In general, the concentrations are similar to those previously published on deep-sea fish, and higher or similar to those published for shallow water counterparts. All metal levels in black scabbard livers are much higher than in the other fish, and between 2 and 30 times higher than the limits of the European Dietary Standards and Guidelines. Differences in accumulation patterns between species and elements, as well as between organs are described using univariate and multivariate statistics (scatterplots, discriminant analysis, triangular plots).

Effect of siRNA silencing of inducible co-stimulatory molecule on myocardial cell hypertrophy after cardiac infarction in rats.

PubMed

Wang, W M; Liu, Z; Chen, G

2016-05-20

As the most common cardiac disease, myocardial infarction is followed by hypertrophy of cardiac myocytes and reconstruction of ventricular structure. The up-regulation of a series of factors including metalloproteinases, inflammatory factors, and growth factors after primary infarction lead to the hypertrophy, apoptosis, necrosis, and fibroblast proliferation in cardiac muscle tissues. Recent studies have reported on the potency of small interfering RNA (siRNA) in treating cardiac diseases. We thus investigated the efficacy of inducible co-stimulatory molecule (ICOS)-specific siRNA silencing in myocardial hypertrophy in a cardiac infarction rat model. This cardiac infarction model was prepared by ligating the left anterior descending coronary artery. ICOS-siRNA treatment was administered in parallel with non-sense siRNA. After 18 days, the cross-sectional area of cardiac muscle tissues and the left ventricle weight index were measured, along with ICOS mRNA and protein expression levels, and pathological staining. Compared to those in the control groups, in myocardial infarcted rats, the application of ICOS-siRNA effectively decreased the left ventricle weight index, as well as the surface area of cardiac myocytes. Both mRNA and protein levels of ICOS were also significantly decreased. HE staining was consistent with these results. In conclusion, ICOS-targeted siRNA can effectively silence gene expression of ICOS, and provided satisfactory treatment efficacy for myocardial cell hypertrophy after infarction.

Physical training prevents body weight gain but does not modify adipose tissue gene expression

PubMed Central

Higa, T.S.; Bergamo, F.C.; Mazzucatto, F.; Fonseca-Alaniz, M.H.; Evangelista, F.S.

2012-01-01

The relationship of body weight (BW) with white adipose tissue (WAT) mass and WAT gene expression pattern was investigated in mice submitted to physical training (PT). Adult male C57BL/6 mice were submitted to two 1.5-h daily swimming sessions (T, N = 18), 5 days/week for 4 weeks or maintained sedentary (S, N = 15). Citrate synthase activity increased significantly in the T group (P < 0.05). S mice had a substantial weight gain compared to T mice (4.06 ± 0.43 vs 0.38 ± 0.28 g, P < 0.01). WAT mass, adipocyte size, and the weights of gastrocnemius and soleus muscles, lung, kidney, and adrenal gland were not different. Liver and heart were larger and the spleen was smaller in T compared to S mice (P < 0.05). Food intake was higher in T than S mice (4.7 ± 0.2 vs 4.0 ± 0.3 g/animal, P < 0.05) but oxygen consumption at rest did not differ between groups. T animals showed higher serum leptin concentration compared to S animals (6.37 ± 0.5 vs 3.11 ± 0.12 ng/mL). WAT gene expression pattern obtained by transcription factor adipocyte determination and differentiation-dependent factor 1, fatty acid synthase, malic enzyme, hormone-sensitive lipase, adipocyte lipid binding protein, leptin, and adiponectin did not differ significantly between groups. Collectively, our results showed that PT prevents BW gain and maintains WAT mass due to an increase in food intake and unchanged resting metabolic rate. These responses are closely related to unchanged WAT gene expression patterns. PMID:22666778

Reduction in obesity and coronary risk factors after high caloric exercise training in overweight coronary patients.

PubMed

Savage, Patrick D; Brochu, Martin; Poehlman, Eric T; Ades, Philip A

2003-08-01

The majority of patients with coronary heart disease (CHD) are overweight. However, little weight loss occurs with participation in a standard cardiac rehabilitation (CR) program. Fifteen overweight patients (average body mass index of 31.0 kg/m2) with CHD completed a 4-month exercise training program in a CR program. The exercise program consisted primarily of walking long duration (60-90 minutes per session) 5 to 7 days per week at a relatively low intensity of 50% to 60% of peak VO2. Measures of body composition by dual-energy x-ray absorptiometry, body fat distribution by computed tomography, plasma lipid-lipoprotein, glucose and insulin concentrations, and peak VO2 were obtained before and after the exercise intervention. Patients maintained an isocaloric diet throughout the study. Patients had reductions in total body weight (-4.6 kg), fat mass (-3.6 kg), percent body fat (-2.9%), and waist circumference (-5.6 cm) (all P <.001) while maintaining fat-free mass. Subcutaneous adipose tissue was reduced by 12% (P <.001) and visceral adipose tissue was lowered by 14% (P <.001). There were favorable changes in the lipid-metabolic profile with reductions in triglyceride levels (-23.7%), total cholesterol/HDL-C ratio (-14.3%), and fasting insulin levels (-22.3%) (all P <.05). Peak VO2 increased by 21.2% (P <.001). The present pilot study results suggest that a high caloric training exercise training program in the CR setting may be effective in promoting weight loss and improving coronary risk factors in overweight coronary patients. Although additional research with randomized control patients is needed, this alternative to traditional CR may be considered to maximize weight loss as part of a secondary prevention program.

Spatial heterogeneity of mercury bioaccumulation by walleye in Franklin D. Roosevelt Lake and the upper Columbia River, Washington

USGS Publications Warehouse

Munn, M.D.; Short, T.M.

1997-01-01

We examined mercury concentration in muscle of walleye Stizostedion vitreum from three reaches in Franklin D. Roosevelt Lake, a reservoir on the Columbia River, and from the upper Columbia River, an area contaminated by wastes from metal mining and associated processing activities. Our objectives were to describe the relation between size and age of walleyes and tissue concentrations of mercury and to compare mercury concentrations within a single reservoir system among spatially segregated cohorts. Overall, mercury concentrations in walleye muscle ranged from 0.11 to 0.44 mg/kg (wet weight) and were positively correlated with age, weight, and length of the fish. Mercury concentrations in walleyes varied spatially within the system; the highest concentrations were in fish from the lower and middle reaches of the reservoir. Condition factor of age-2+ fish was inversely related to tissue concentration of mercury and was lower in fish from the lower and middle reaches than in fish from the upper reach. Spatial patterns in condition factor and mercury in walleyes were unrelated to concentrations of total mercury in surficial bed sediments, which ranged from less than 0.05 to 2.8 mg/kg (dry weight). We suggest that the observed spatial differences in the concentrations of mercury in walleyes may be attributed to the fish preferring to spawn and forage in specific areas where the bioavailability of mercury varies due to local differences in the physical and chemical environment.

Improved angiogenesis and healing in crush syndrome by fibroblast growth factor-2-containing low-molecular-weight heparin (Fragmin)/protamine nanoparticles.

PubMed

Takikawa, Makoto; Nakamura, Shingo; Ishihara, Masayuki; Takabayashi, Yuki; Fujita, Masanori; Hattori, Hidemi; Kushibiki, Toshihiro; Ishihara, Miya

2015-06-15

We produced fibroblast growth factor (FGF)-2-containing low-molecular-weight heparin (Fragmin)/protamine nanoparticles (FGF-2 + F/P NPs). The purpose of this study was to evaluate the effectiveness of the local administration of FGF-2 + F/P NPs on repairing crush syndrome (CS)-injured lesions after compression release using a nonlethal and reproducible CS injury rat model. The hind limbs of the anesthetized rats were compressed for 6 h using 3.6 kg blocks, as previously described. The effects of administering FGF-2 + F/P NPs (group A), F/P NPs alone (group B), FGF-2 alone (group C), and saline (control; group D) were examined. Motor function, surface blood flow in the hind limbs, and the wet/dry weight ratio in the tibialis anterior muscle were examined for 1-28 d after the compression release. Histologic analyses were also performed. At the middle and late stages (3-28 d after the compression release), group A had higher scores in the motor function, improved blood flow, increased number of blood vessels, and faster recovered muscle tissue, compared with the other groups. There was no significant difference in enhanced edema in the tibialis anterior muscle among all groups. The local administration of FGF-2 + F/P NPs to a CS-injured lesion was effective in repairing damaged muscle tissue after compression release. Copyright © 2015 Elsevier Inc. All rights reserved.

Bioprinting Cellularized Constructs Using a Tissue-specific Hydrogel Bioink

PubMed Central

Skardal, Aleksander; Devarasetty, Mahesh; Kang, Hyun-Wook; Seol, Young-Joon; Forsythe, Steven D.; Bishop, Colin; Shupe, Thomas; Soker, Shay; Atala, Anthony

2016-01-01

Bioprinting has emerged as a versatile biofabrication approach for creating tissue engineered organ constructs. These constructs have potential use as organ replacements for implantation in patients, and also, when created on a smaller size scale as model "organoids" that can be used in in vitro systems for drug and toxicology screening. Despite development of a wide variety of bioprinting devices, application of bioprinting technology can be limited by the availability of materials that both expedite bioprinting procedures and support cell viability and function by providing tissue-specific cues. Here we describe a versatile hyaluronic acid (HA) and gelatin-based hydrogel system comprised of a multi-crosslinker, 2-stage crosslinking protocol, which can provide tissue specific biochemical signals and mimic the mechanical properties of in vivo tissues. Biochemical factors are provided by incorporating tissue-derived extracellular matrix materials, which include potent growth factors. Tissue mechanical properties are controlled combinations of PEG-based crosslinkers with varying molecular weights, geometries (linear or multi-arm), and functional groups to yield extrudable bioinks and final construct shear stiffness values over a wide range (100 Pa to 20 kPa). Using these parameters, hydrogel bioinks were used to bioprint primary liver spheroids in a liver-specific bioink to create in vitro liver constructs with high cell viability and measurable functional albumin and urea output. This methodology provides a general framework that can be adapted for future customization of hydrogels for biofabrication of a wide range of tissue construct types. PMID:27166839

Bioprinting Cellularized Constructs Using a Tissue-specific Hydrogel Bioink.

PubMed

Skardal, Aleksander; Devarasetty, Mahesh; Kang, Hyun-Wook; Seol, Young-Joon; Forsythe, Steven D; Bishop, Colin; Shupe, Thomas; Soker, Shay; Atala, Anthony

2016-04-21

Bioprinting has emerged as a versatile biofabrication approach for creating tissue engineered organ constructs. These constructs have potential use as organ replacements for implantation in patients, and also, when created on a smaller size scale as model "organoids" that can be used in in vitro systems for drug and toxicology screening. Despite development of a wide variety of bioprinting devices, application of bioprinting technology can be limited by the availability of materials that both expedite bioprinting procedures and support cell viability and function by providing tissue-specific cues. Here we describe a versatile hyaluronic acid (HA) and gelatin-based hydrogel system comprised of a multi-crosslinker, 2-stage crosslinking protocol, which can provide tissue specific biochemical signals and mimic the mechanical properties of in vivo tissues. Biochemical factors are provided by incorporating tissue-derived extracellular matrix materials, which include potent growth factors. Tissue mechanical properties are controlled combinations of PEG-based crosslinkers with varying molecular weights, geometries (linear or multi-arm), and functional groups to yield extrudable bioinks and final construct shear stiffness values over a wide range (100 Pa to 20 kPa). Using these parameters, hydrogel bioinks were used to bioprint primary liver spheroids in a liver-specific bioink to create in vitro liver constructs with high cell viability and measurable functional albumin and urea output. This methodology provides a general framework that can be adapted for future customization of hydrogels for biofabrication of a wide range of tissue construct types.

Ischemia postconditioning and mesenchymal stem cells engraftment synergistically attenuate ischemia reperfusion-induced lung injury in rats.

PubMed

Chen, Shuchen; Chen, Liangwan; Wu, Xiaonan; Lin, Jiangbo; Fang, Jun; Chen, Xiangqi; Wei, Shijin; Xu, Jianxin; Gao, Qin; Kang, Mingqiang

2012-11-01

It has been reported that ischemic postconditioning (IPO) or mesenchymal stem cell (MSC) engraftment could protect organs from ischemia/reperfusion (I/R) injury. We investigated the synergetic effects of combined treatment on lung injury induced by I/R. Adult Sprague-Dawley rats were randomly assigned to one of the following groups: sham-operated control, I/R, IPO, MSC engraftment, and IPO plus MSC engraftment. Lung injury was assessed by arterial blood gas analysis, the wet/dry lung weight ratio, superoxide dismutase level, malondialdehyde content, myeloperoxidase activity, and tissue histologic changes. Cytokine expression was detected using real-time polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay. Cell apoptosis was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end assay and annexin V staining. MSC engraftment or IPO alone markedly attenuated the lung wet/dry weight ratio, malondialdehyde and myeloperoxidase production, and lung pathologic injury and enhanced arterial partial oxygen pressure, superoxide dismutase content, inhibited pro-inflammatory cytokine levels, and decreased cell apoptosis in lung tissue, compared with the I/R group. In contrast, IPO pretreatment enhanced the protective effects of MSC on I/R-induced lung injury compared with treatment alone. Moreover, in the combined treatment group, the number of MSC engraftments in the lung tissue was increased, associated with enhanced survival of MSCs compared with MSC treatment alone. Additional investigation showed that IPO treatment increased expression of vascular endothelial growth factor and stromal cell-derived factor-1 in I/R lung tissue. IPO might contribute to the homing and survival of transplanted MSCs and enhance their therapeutic effects through improvement of the microenvironment of I/R injury. Copyright © 2012 Elsevier Inc. All rights reserved.

Organ and Effective Dose Coefficients for Cranial and Caudal Irradiation Geometries: Neutrons

NASA Astrophysics Data System (ADS)

Veinot, K. G.; Eckerman, K. F.; Hertel, N. E.; Hiller, M. M.

2017-09-01

With the introduction of new recommendations by ICRP Publication 103, the methodology for determining the protection quantity, effective dose, has been modified. The modifications include changes to the defined organs and tissues, the associated tissue weighting factors, radiation weighting factors, and the introduction of reference sex-specific computational phantoms (ICRP Publication 110). Computations of equivalent doses in organs and tissues are now performed in both the male and female phantoms and the sex-averaged values used to determine the effective dose. Dose coefficients based on the ICRP 103 recommendations were reported in ICRP Publication 116, the revision of ICRP Publication 74 and ICRU Publication 57. The coefficients were determined for the following irradiation geometries: anterior-posterior (AP), posterior-anterior (PA), right and left lateral (RLAT and LLAT), rotational (ROT), and isotropic (ISO). In this work, the methodology of ICRP Publication 116 was used to compute dose coefficients for neutron irradiation of the body with parallel beams directed upward from below the feet (caudal) and directed downward from above the head (cranial). These geometries may be encountered in the workplace from personnel standing on contaminated surfaces or volumes and from overhead sources. Calculations of organ and tissue absorbed doses for caudal and cranial exposures to neutrons ranging in energy from 10-9 MeV to 10 GeV have been performed using the MCNP6 radiation transport code and the adult reference voxel phantoms of ICRP Publication 110. At lower energies the effective dose per particle fluence for cranial and caudal exposures is less than AP orientations while above about 30 MeV the cranial and caudal values are greater.

Parecoxib reduced ventilation induced lung injury in acute respiratory distress syndrome.

PubMed

Meng, Fan-You; Gao, Wei; Ju, Ying-Nan

2017-03-29

Cyclooxygenase-2 (COX-2) contributes to ventilation induced lung injury (VILI) and acute respiratory distress syndrome (ARDS). The objective of present study was to observe the therapeutic effect of parecoxib on VILI in ARDS. In this parallel controlled study performed at Harbin Medical University, China between January 2016 and March 2016, 24 rats were randomly allocated into sham group (S), volume ventilation group/ARDS (VA), parecoxib/volume ventilation group/ARDS (PVA). Rats in the S group only received anesthesia; rats in the VA and PVA group received intravenous injection of endotoxin to induce ARDS, and then received ventilation. Rats in the VA and PVA groups were treated with intravenous injection of saline or parecoxib. The ratio of arterial oxygen pressure to fractional inspired oxygen (PaO 2 /FiO 2 ), the wet to dry weight ratio of lung tissue, inflammatory factors in serum and bronchoalveolar lavage fluid (BALF), and histopathologic analyses of lung tissue were examined. In addition, survival was calculated at 24 h after VILI. Compared to the VA group, in the PVA group, PaO 2 /FiO 2 was significantly increased; lung tissue wet to dry weight ratio; macrophage and neutrophil counts, total protein and neutrophil elastase levels in BALF; tumor necrosis factor-α, interleukin-1β, and prostaglandin E 2 levels in BALF and serum; and myeloperoxidase (MPO) activity, malondialdehyde levels, and Bax and COX-2 protein levels in lung tissue were significantly decreased, while Bcl-2 protein levels were significantly increased. Lung histopathogical changes and apoptosis were reduced by parecpxib in the PVA group. Survival was increased in the PVA group. Parecoxib improves gas exchange and epithelial permeability, decreases edema, reduces local and systemic inflammation, ameliorates lung injury and apoptosis, and increases survival in a rat model of VILI.

Oryzanol Modifies High Fat Diet-Induced Obesity, Liver Gene Expression Profile, and Inflammation Response in Mice.

PubMed

Wang, Long; Lin, Qinlu; Yang, Tao; Liang, Ying; Nie, Ying; Luo, Yi; Shen, Junjun; Fu, Xiangjin; Tang, Yiping; Luo, Feijun

2017-09-27

In Western countries and China, the dietary habit of high calories usually results in hyperlipidemia, which is closely associated with cardiovascular diseases. In the study, we investigated the antihyperlipidemic effect of oryzanol and its molecular mechanism in the high fat diet (HFD) mouse model. In total, 60 ICR mice were randomly divided into control group, HFD group, and HFD+Ory group. The mice from the HFD+Ory group were additionally fed with 100 mg/kg of oryzanol by intragastric administration. Our data indicated that oryzanol treatment for 10 weeks significantly reduced bodyweight, liver weight, and adipose tissues weight of the mice; lowered the contents of total cholesterol (TC), triglycerides (TG), and low density lipoprotein-cholesterol (LDL-C); and elevated high density lipoprotein-cholesterol (HDL-C) in the plasma of HFD mice. Compared with the HFD group, H&E staining showed that oryzanol treatment decreased the size of fat droplets of liver tissues and the size of adipocytes. Gene chip data found that oryzanol administration caused 32 genes to increase expressions while 60 genes had reduced expressions in the liver tissues of HFD mice. IPA software was used to analyze the protein interaction network and found that transcript factor NF-κB located in the central role of network, meaning NF-κB may have important function in the lipid-lowering effect of oryzanol. Western blotting and RT-qPCR confirmed that lipid metabolism-related gene expressions were obviously regulated by oryzanol administration. Oryzanol also inhibited expressions of inflammatory factor in the liver tissues of HDF mice. Taken together, our data indicate that oryzanol treatment can regulate lipid metabolism-related gene expressions and inhibit HDF-caused obesity in mice.

Green tea extract induces genes related to browning of white adipose tissue and limits weight-gain in high energy diet-fed rat.

PubMed

Chen, Li-Han; Chien, Yi-Wen; Liang, Chung-Tiang; Chan, Ching-Hung; Fan, Meng-Han; Huang, Hui-Yu

2017-01-01

Background: A wealth of research has reported on the anti-obesity effects of green tea extract (GTE). Although browning of white adipose tissue (WAT) has been reported to attenuate obesity, no study has disclosed the effects of GTE on browning in Sprague Dawley rats. Objectives: The aims of the study were to investigate the effects of GTE on anti-obesity and browning, and their underlying mechanisms. Methods: Four groups of rats (n=10/group) were used including a normal diet with vehicle treatment, and a high-energy diet (HED) with vehicle or GTE by oral gavage at 77.5 or 155 mg/kg/day for 8 weeks. Body weight, fat accumulation, and serum biochemical parameters were used to evaluate obesity. The gene expressions were analyzed using RT-qPCR and western blotting. Results: GTE modulated HED-induced body weight, fat accumulation, and serum levels of triacylglycerol, total cholesterol, low-density lipoprotein, free fatty acids, aspartate aminotransferase, and alanine aminotransferase. Moreover, GTE enhanced the serum high-density lipoprotein. Most importantly, the biomarkers of beige adipose tissue were up-regulated in WAT in GTE-given groups. GTE induced genes involved in different pathways of browning, and reduced transducin-like enhancer protein-3 in WAT. Conclusion: Our results suggest that GTE may improve obesity through inducing browning in HED-fed rats. Abbreviations : ALT: Alanine transaminase; AST: Aspartate transaminase; BAT: Brown adipose tissue; BMP-7: Bone morphogenetic protein-7; BW: Body weight; CIDEA: Cell death activator; CPT-1: Carnitine palmitoyltransferase-1; EFP: Epididymal fat pad; FFA: Free fatty acid; FGF-21: Fibroblast growth factor-21; GTE: Green tea extract; HDL: High-density lipoprotein; HED: high-energy diet; LDL: Low-density lipoprotein; MFP: Mesenteric fat pad; PGC-1α: Activates PPAR-γ coactivator-1; PPAR-γ: Peroxisome proliferator-activated receptor-γ; PRDM-16: PR domain containing 16; RFP: Renal fat pad; SD: Sprague Dawley; TC: Total cholesterol; TG: Triacylglycerol; TLE-3: Transducin-like enhancer protein-3: UCP-1: Uncoupling protein-1; WAT: White adipose tissue.

[Morphobiochemical adaptations to life on littoral in some sedentary gastropods].

PubMed

Aliakrinskaia, I O

2002-01-01

Adaptations to attachment, respiration, nutrition, and pollution of sedentary gastropods with cowl-shaped shell living in littoral conditions and prone to the influence of abiotic factors are analyzed. Weight properties of individual parts of the radular apparatus related to scrapping mode of nutrition are discussed. The content of hemoglobin in radular tissues of some representatives of Patellidae, Acmaeidae, and Siphonariidae families is comparatively evaluated.

The role of diet and exercise for the maintenance of fat-free mass and resting metabolic rate during weight loss.

PubMed

Stiegler, Petra; Cunliffe, Adam

2006-01-01

The incidence of obesity is increasing rapidly. Research efforts for effective treatment strategies still focus on diet and exercise programmes, the individual components of which have been investigated in intervention trials in order to determine the most effective recommendations for sustained changes in bodyweight. The foremost objective of a weight-loss trial has to be the reduction in body fat leading to a decrease in risk factors for metabolic syndrome. However, a concomitant decline in lean tissue can frequently be observed. Given that fat-free mass (FFM) represents a key determinant of the magnitude of resting metabolic rate (RMR), it follows that a decrease in lean tissue could hinder the progress of weight loss. Therefore, with respect to long-term effectiveness of weight-loss programmes, the loss of fat mass while maintaining FFM and RMR seems desirable. Diet intervention studies suggest spontaneous losses in bodyweight following low-fat diets, and current data on a reduction of the carbohydrate-to-protein ratio of the diet show promising outcomes. Exercise training is associated with an increase in energy expenditure, thus promoting changes in body composition and bodyweight while keeping dietary intake constant. The advantages of strength training may have greater implications than initially proposed with respect to decreasing percentage body fat and sustaining FFM. Research to date suggests that the addition of exercise programmes to dietary restriction can promote more favourable changes in body composition than diet or physical activity on its own. Moreover, recent research indicates that the macronutrient content of the energy-restricted diet may influence body compositional alterations following exercise regimens. Protein emerges as an important factor for the maintenance of or increase in FFM induced by exercise training. Changes in RMR can only partly be accounted for by alterations in respiring tissues, and other yet-undefined mechanisms have to be explored. These outcomes provide the scientific rationale to justify further randomised intervention trials on the synergies between diet and exercise approaches to yield favourable modifications in body composition.

Main characteristics of metabolically obese normal weight and metabolically healthy obese phenotypes.

PubMed

Teixeira, Tatiana F S; Alves, Raquel D M; Moreira, Ana Paula B; Peluzio, Maria do Carmo G

2015-03-01

In this review, the influence of fat depots on insulin resistance and the main characteristics of metabolically obese normal-weight and metabolically healthy obese phenotypes are discussed. Medline/PubMed and Science Direct were searched for articles related to the terms metabolically healthy obesity, metabolically obese normal weight, adipose tissue, and insulin resistance. Normal weight and obesity might be heterogeneous in regard to their effects. Fat distribution and lower insulin sensitivity are the main factors defining phenotypes within the same body mass index. Although these terms are interesting, controversies about them remain. Future studies exploring these phenotypes will help elucidate the roles of adiposity and/or insulin resistance in the development of metabolic alterations. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Correlation between CT numbers and tissue parameters needed for Monte Carlo simulations of clinical dose distributions

NASA Astrophysics Data System (ADS)

Schneider, Wilfried; Bortfeld, Thomas; Schlegel, Wolfgang

2000-02-01

We describe a new method to convert CT numbers into mass density and elemental weights of tissues required as input for dose calculations with Monte Carlo codes such as EGS4. As a first step, we calculate the CT numbers for 71 human tissues. To reduce the effort for the necessary fits of the CT numbers to mass density and elemental weights, we establish four sections on the CT number scale, each confined by selected tissues. Within each section, the mass density and elemental weights of the selected tissues are interpolated. For this purpose, functional relationships between the CT number and each of the tissue parameters, valid for media which are composed of only two components in varying proportions, are derived. Compared with conventional data fits, no loss of accuracy is accepted when using the interpolation functions. Assuming plausible values for the deviations of calculated and measured CT numbers, the mass density can be determined with an accuracy better than 0.04 g cm-3 . The weights of phosphorus and calcium can be determined with maximum uncertainties of 1 or 2.3 percentage points (pp) respectively. Similar values can be achieved for hydrogen (0.8 pp) and nitrogen (3 pp). For carbon and oxygen weights, errors up to 14 pp can occur. The influence of the elemental weights on the results of Monte Carlo dose calculations is investigated and discussed.

Full-driving soft robotic colonoscope in compliant colon tissue.

PubMed

Wang, Kundong; Ma, Jiayi; Wang, Feng; Wang, Zhiwu; Yan, Guozheng; Zhou, Yilu

2017-11-01

Robotic colonoscopy is an efficient examination method for finding malignant tumour in its early stage. This research developed a novel robotic endoscope with 13 mm diameter, 105 mm length and 22.3 g weight. A contact biomechanical model is proposed to increase the locomotion safety and efficiency in the soft tissue. The model shows that the friction difference between the robot and the tissue is a key factor to locomotion capability. A soft, full bellow with excellent compatibility was designed to package the robot body. The bellow increased the static friction and decreased the kinetic friction given the change in the contact state. The bellow is divided into three segments. Each segment is composed of a linear locomotor with micromotor, turbine-worm and wire wrapping-sliding mechanism. The robot is tested in in vivo pig colon, which revealed an excellent locomotion capability and safety in soft tissues.

Adiponectin, Resistin, and Visfatin in Childhood Obesity and Exercise.

PubMed

Jamurtas, Athanasios Z; Stavropoulos-Kalinoglou, Antonios; Koutsias, Stilianos; Koutedakis, Yiannis; Fatouros, Ioannis

2015-11-01

Childhood obesity is increasing alarmingly, and a strong association with chronic diseases has been established. Specific adipokines are released from the adipose tissue and relate with chronic diseases even in the pediatric population. Adiponectin levels are lower in obesity and increase with decreasing body weight. A few pediatric studies examining a possible relationship between resistin and obesity do not provide a clear picture. Most studies agree that visfatin levels appear elevated in childhood obesity. Exercise seems to increase adiponectin levels whereas resistin levels are reduced. The lack of data on the effects of acute and chronic exercise on visfatin levels precludes us from making safe conclusions as to what the effects of exercise (acute or chronic) would be on visfatin levels in children. Clearly, exercise has an impact on the adipose tissue and the release of adiponectin, resistin, and visfatin. However, other factors affect the secretion rate of these adipokines from the adipose tissue; these factors should also be taken into consideration when examining the effects of exercise on adipokines. Gender, age, body composition, physical activity levels, mode and intensity of exercise are some of the factors that should be looked into in future studies.

Diet-induced weight loss has chronic tissue-specific effects on glucocorticoid metabolism in overweight postmenopausal women.

PubMed

Stomby, A; Simonyte, K; Mellberg, C; Ryberg, M; Stimson, R H; Larsson, C; Lindahl, B; Andrew, R; Walker, B R; Olsson, T

2015-05-01

Tissue-specific glucocorticoid metabolism is altered in obesity, and may increase cardiovascular risk. This dysregulation is normalized by short-term calorie restriction and weight loss, an effect that varies with dietary macronutrient composition. However, tissue-specific glucocorticoid metabolism has not been studied during long-term (>6 months) dietary interventions. Therefore our aim was to test whether long-term dietary interventions, either a paleolithic-type diet (PD) or a diet according to Nordic nutrition recommendations (NNR) could normalize tissue-specific glucocorticoid metabolism in overweight and obese women. Forty-nine overweight/obese postmenopausal women were randomized to a paleolithic diet or a diet according to NNR for 24 months. At baseline, 6 and 24 months anthropometric measurements, insulin sensitivity, excretion of urinary glucocorticoid metabolites in 24-hour collections, conversion of orally administered cortisone to plasma cortisol and transcript levels of 11β hydroxysteroid dehydrogenase type 1 (11βHSD1) in subcutaneous adipose tissue were studied. Both diet groups achieved significant and sustained weight loss. Weight loss with the PD was greater than on NNR diet after 6 months (P<0.001) but similar at 24 months. Urinary measurement of 5α-reductase activity was increased after 24 months in both groups compared with baseline (P<0.001). Subcutaneous adipose tissue 11βHSD1 gene expression decreased at 6 and 24 months in both diet groups (P=0.036). Consistent with increased liver 11βHSD1, conversion of oral cortisone to cortisol increased at 6 months (P=0.023) but was unchanged compared with baseline by 24 months. Long-term weight loss in postmenopausal women has tissue-specific and time-dependent effects on glucocorticoid metabolism. This may alter local-tissue cortisol exposure contributing to improved metabolic function during weight loss.

Allele Compensation in Tip60+/− Mice Rescues White Adipose Tissue Function In Vivo

PubMed Central

Gao, Yuan; Hamers, Nicole; Rakhshandehroo, Maryam; Berger, Ruud; Lough, John; Kalkhoven, Eric

2014-01-01

Adipose tissue is a key regulator of energy homestasis. The amount of adipose tissue is largely determined by adipocyte differentiation (adipogenesis), a process that is regulated by the concerted actions of multiple transcription factors and cofactors. Based on in vitro studies in murine 3T3-L1 preadipocytes and human primary preadipocytes, the transcriptional cofactor and acetyltransferase Tip60 was recently identified as an essential adipogenic factor. We therefore investigated the role of Tip60 on adipocyte differentiation and function, and possible consequences on energy homeostasis, in vivo. Because homozygous inactivation results in early embryonic lethality, Tip60+/− mice were used. Heterozygous inactivation of Tip60 had no effect on body weight, despite slightly higher food intake by Tip60+/− mice. No major effects of heterozygous inactivation of Tip60 were observed on adipose tissue and liver, and Tip60+/− displayed normal glucose tolerance, both on a low fat and a high fat diet. While Tip60 mRNA was reduced to 50% in adipose tissue, the protein levels were unaltered, suggesting compensation by the intact allele. These findings indicate that the in vivo role of Tip60 in adipocyte differentiation and function cannot be properly addressed in Tip60+/− mice, but requires the generation of adipose tissue-specific knock out animals or specific knock-in mice. PMID:24870614

Fibroblast migration and proliferation during in vitro wound healing. A quantitative comparison between various growth factors and a low molecular weight blood dialysate used in the clinic to normalize impaired wound healing.

PubMed

Schreier, T; Degen, E; Baschong, W

1993-01-01

During the formation of granulation tissue in a dermal wound, platelets, monocytes and other cellular blood constituents release various peptide growth factors to stimulate fibroblasts to migrate into the wound site and proliferate, in order to reconstitute the various connective tissue components. The effect on fibroblast migration and proliferation of these growth factors, and of Solcoseryl (HD), a deproteinized fraction of calf blood used to normalize wound granulation and scar tissue formation, was quantified in vitro. The presence of basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta) and hemodialysate (HD) increased the number of cells in the denuded area, i.e., in the "wound space" of an artificially ruptured monolayer of LM-fibroblasts (mouse lung fibroblasts). When cell proliferation was blocked with Mitomycin C, in the first 24 h all factors, i.e., bFGF, PDGF, TGF-beta and HD, promoted cell migration, whereas after 48 h it became obvious that each factor stimulated both migration and proliferation, each in a characteristic way. The effects were significant and more distinct after 48 h, following the order: PDGF (46%) approximately bFGF (87%) > HD (45%) approximately TGF-beta (40%) > control (62%). The relative contributions of migration after inhibiting proliferation are given in brackets. The modulatory activity of HD was localized in its hydrophilic fraction. It was destroyed by acid hydrolysis. Furthermore, this activity could be blocked by protamine sulfate, an inhibitor blocking peptide growth factor receptor binding.

Sampling Strategies and Processing of Biobank Tissue Samples from Porcine Biomedical Models.

PubMed

Blutke, Andreas; Wanke, Rüdiger

2018-03-06

In translational medical research, porcine models have steadily become more popular. Considering the high value of individual animals, particularly of genetically modified pig models, and the often-limited number of available animals of these models, establishment of (biobank) collections of adequately processed tissue samples suited for a broad spectrum of subsequent analyses methods, including analyses not specified at the time point of sampling, represent meaningful approaches to take full advantage of the translational value of the model. With respect to the peculiarities of porcine anatomy, comprehensive guidelines have recently been established for standardized generation of representative, high-quality samples from different porcine organs and tissues. These guidelines are essential prerequisites for the reproducibility of results and their comparability between different studies and investigators. The recording of basic data, such as organ weights and volumes, the determination of the sampling locations and of the numbers of tissue samples to be generated, as well as their orientation, size, processing and trimming directions, are relevant factors determining the generalizability and usability of the specimen for molecular, qualitative, and quantitative morphological analyses. Here, an illustrative, practical, step-by-step demonstration of the most important techniques for generation of representative, multi-purpose biobank specimen from porcine tissues is presented. The methods described here include determination of organ/tissue volumes and densities, the application of a volume-weighted systematic random sampling procedure for parenchymal organs by point-counting, determination of the extent of tissue shrinkage related to histological embedding of samples, and generation of randomly oriented samples for quantitative stereological analyses, such as isotropic uniform random (IUR) sections generated by the "Orientator" and "Isector" methods, and vertical uniform random (VUR) sections.

Terahertz spectral unmixing based method for identifying gastric cancer

NASA Astrophysics Data System (ADS)

Cao, Yuqi; Huang, Pingjie; Li, Xian; Ge, Weiting; Hou, Dibo; Zhang, Guangxin

2018-02-01

At present, many researchers are exploring biological tissue inspection using terahertz time-domain spectroscopy (THz-TDS) techniques. In this study, based on a modified hard modeling factor analysis method, terahertz spectral unmixing was applied to investigate the relationships between the absorption spectra in THz-TDS and certain biomarkers of gastric cancer in order to systematically identify gastric cancer. A probability distribution and box plot were used to extract the distinctive peaks that indicate carcinogenesis, and the corresponding weight distributions were used to discriminate the tissue types. The results of this work indicate that terahertz techniques have the potential to detect different levels of cancer, including benign tumors and polyps.

Functional Body Composition and Related Aspects in Research on Obesity and Cachexia

PubMed Central

Müller, M.J.; Baracos, V.; Bosy-Westphal, A.; Dulloo, A.; Eckel, J.; Fearon, K.C.H.; Hall, K.D.; Pietrobelli, A.; Sørensen, T.I.A.; Speakman, J.; Trayhurn, P.; Visser, M.; Heymsfield, S.B.

2014-01-01

The 12th Stock Conference addressed body composition and related functions in two extreme situations, obesity and cancer cachexia. The concept of “functional body composition” integrates body components into regulatory systems relating the mass of organs and tissues to corresponding in vivo functions and metabolic processes. This concept adds to an understanding of organ/tissue mass and function in the context of metabolic adaptations to weight change and disease. During weight gain and loss there are associated changes in individual body components while the relationships between organ and tissue mass are fixed. Thus, an understanding of weight regulation involves an examination of organ-tissue regulation rather than of individual organ mass. The between organ/tissue mass relationships are associated with and explained by cross-talk between organs and tissues mediated by cytokines, hormones, and metabolites that are coupled with changes in body weight, composition, and function as observed in obesity and cancer cachexia. In addition to established roles in intermediary metabolism, cell function and inflammation, organ-tissue cross-talk mediators are determinants of body composition and its’ change with weight gain and loss. The 12th Stock Conference supported Michael Stocks’ concept of gaining new insights by integrating research ideas from obesity and cancer cachexia. The conference presentations provide an in-depth understanding of body composition and metabolism. PMID:24835453

Impact of high-fat diet and voluntary running on body weight and endothelial function in LDL receptor knockout mice.

PubMed

Langbein, Heike; Hofmann, Anja; Brunssen, Coy; Goettsch, Winfried; Morawietz, Henning

2015-05-01

Obesity and physical inactivity are important cardiovascular risk factors. Regular physical exercise has been shown to mediate beneficial effects in the prevention of cardiovascular diseases. However, the impact of physical exercise on endothelial function in proatherosclerotic low-density lipoprotein receptor deficient (LDLR(-/-)) mice has not been studied so far. Six-week-old male LDLR(-/-) mice were fed a standard diet or a high-fat diet (39 kcal% fat diet) for 20 weeks. The impact of high-fat diet and voluntary running on body weight and amount of white adipose tissue was monitored. Basal tone and endothelial function was investigated in aortic rings using a Mulvany myograph. LDLR(-/-) mice on high-fat diet had increased cumulative food energy intake, but also higher physical activity compared to mice on control diet. Body weight and amount of visceral and retroperitoneal white adipose tissue of LDLR(-/-) mice were significantly increased by high-fat diet and partially reduced by voluntary running. Endothelial function in aortae of LDLR(-/-) mice was impaired after 20 weeks on standard and high-fat diet and could not be improved by voluntary running. Basal tone showed a trend to be increased by high-fat diet. Voluntary running reduced body weight and amount of white adipose tissue in LDLR(-/-) mice. Endothelial dysfunction in LDLR(-/-) mice could not be improved by voluntary running. In a clinical context, physical exercise alone might not have an influence on functional parameters and LDL-C levels in patients with familial hypercholesterolemia. However, physical activity in these patients may be in general beneficial and should be performed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The Lymphatic Vasculature: Its Role in Adipose Metabolism and Obesity.

PubMed

Escobedo, Noelia; Oliver, Guillermo

2017-10-03

Obesity is a key risk factor for metabolic and cardiovascular diseases, and although we understand the mechanisms regulating weight and energy balance, the causes of some forms of obesity remain enigmatic. Despite the well-established connections between lymphatics and lipids, and the fact that intestinal lacteals play key roles in dietary fat absorption, the function of the lymphatic vasculature in adipose metabolism has only recently been recognized. It is well established that angiogenesis is tightly associated with the outgrowth of adipose tissue, as expanding adipose tissue requires increased nutrient supply from blood vessels. Results supporting a crosstalk between lymphatic vessels and adipose tissue, and linking lymphatic function with metabolic diseases, obesity, and adipose tissue, also started to accumulate in the last years. Here we review our current knowledge of the mechanisms by which defective lymphatics contribute to obesity and fat accumulation in mouse models, as well as our understanding of the lymphatic-adipose tissue relationship. Copyright © 2017 Elsevier Inc. All rights reserved.

Weight management for type 2 diabetes mellitus: global cardiovascular risk reduction.

PubMed

Lee, Michelle; Aronne, Louis J

2007-02-19

Most patients with type 2 diabetes mellitus are overweight or obese, and the relation between obesity, especially of the visceral compartment, and the risk for developing diabetes is well recognized. Excessive adipose tissue is associated with insulin resistance as well as the increased expression of proinflammatory cytokines and prothrombotic factors, all of which contribute to elevating the risk for coronary artery disease (CAD). In particular, abdominal obesity, or excess visceral adiposity, has been linked to a cluster of risk factors (high blood pressure, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, and impaired fasting glucose) that constitute the metabolic syndrome, the presence of which confers an increased risk for type 2 diabetes and cardiovascular disease. In fact, a large waist circumference, a surrogate measure of abdominal adiposity, is 1 of the main criteria for diagnosing the metabolic syndrome. Lifestyle modification is the first-line approach to the management of obesity and the metabolic syndrome. However, if patients are unable to achieve a weight loss of 5%-10% of initial body weight and improve cardiometabolic risk factors with lifestyle modification alone, physicians should consider using adjunctive long-term pharmacotherapy. A variety of approved and investigational pharmacologic agents, including sibutramine, orlistat, metformin, and rimonabant, have been shown to reduce weight and ameliorate metabolic syndrome components, thereby reducing cardiovascular risk. Such global risk reduction is crucial for patients with diabetes, in whom CAD is a major cause of mortality.

Factor for adipocyte differentiation 158 gene disruption prevents the body weight gain and insulin resistance induced by a high-fat diet.

PubMed

Hayashi, Takahiro; Nozaki, Yuriko; Nishizuka, Makoto; Ikawa, Masahito; Osada, Shigehiro; Imagawa, Masayoshi

2011-01-01

To clarify the molecular mechanism of adipocyte differentiation, we previously isolated a novel gene, factor for adipocyte differentiation (fad) 158, whose expression was induced during the earliest stages of adipogenesis, and its product was localized to the endoplasmic reticulum. We found that the knockdown of fad158 expression prevented the differentiation of 3T3-L1 cells into adipocytes. In addition, over-expression of fad158 promoted the differentiation of NIH-3T3 cells, which do not usually differentiate into adipocytes. Although these findings strongly suggest that fad158 has a crucial role in regulating adipocyte differentiation, the physiological role of the gene is still unclear. In this study, we generated mice in which fad158 expression was deleted. The fad158-deficient mice did not show remarkable changes in body weight or the weight of white adipose tissue on a chow diet, but had significantly lower body weights and fat mass than wild-type mice when fed a high-fat diet. Furthermore, although the disruption of fad158 did not influence insulin sensitivity on the chow diet, it improved insulin resistance induced by the high-fat diet. These results indicate that fad158 is a key factor in the development of obesity and insulin resistance caused by a high-fat diet.

Adaptive photoacoustic imaging using the Mallart-Fink focusing factor

NASA Astrophysics Data System (ADS)

Li, Meng-Lin

2008-02-01

Focusing errors caused by sound velocity heterogeneities widen the mainlobe and elevate the sidelobes, thus degrading both spatial and contrast resolutions in photoacoustic imaging. We propose an adaptive array-based photoacoustic imaging technique that uses the Mallart-Fink (MF) focusing factor weighting to reduce the effect of such focusing errors. The definition of the MF focusing factor indicates that the MF focusing factor at the main lobe of the point-spread function is high (close to 1, without speckle noise being present, which is the case in photoacoustic imaging), whereas it is low at the sidelobes. Based on this property, the elevated sidelobes caused by sound velocity heterogeneities in the tissue can be suppressed after being multiplied by the corresponding map of the MF focusing factor on each imaging point; thus the focusing quality can be improved. This technique makes no assumption of sources of focusing errors and directly suppresses the unwanted sidelobe contributions. Numerical experiments with near field phase screen and displaced phase screen models were performed here to verify the proposed adaptive weighting technique. The effect of the signal-to-noise ratio on the MF focusing factor is also discussed.

Microarray analysis of subcutaneous adipose tissue from mature cows with divergent body weight gain after feed restriction and realimentation

USDA-ARS?s Scientific Manuscript database

Body weight response to periods of feed restriction and realimentation is critical and relevant to the agricultural industry. The purpose of this study was to evaluate differentially expressed genes identified in subcutaneous adipose tissue collected from cows divergent in body weight (BW) gain afte...

Dicarbonyl stress in clinical obesity.

PubMed

Masania, Jinit; Malczewska-Malec, Malgorzata; Razny, Urszula; Goralska, Joanna; Zdzienicka, Anna; Kiec-Wilk, Beata; Gruca, Anna; Stancel-Mozwillo, Julita; Dembinska-Kiec, Aldona; Rabbani, Naila; Thornalley, Paul J

2016-08-01

The glyoxalase system in the cytoplasm of cells provides the primary defence against glycation by methylglyoxal catalysing its metabolism to D-lactate. Methylglyoxal is the precursor of the major quantitative advanced glycation endproducts in physiological systems - arginine-derived hydroimidazolones and deoxyguanosine-derived imidazopurinones. Glyoxalase 1 of the glyoxalase system was linked to anthropometric measurements of obesity in human subjects and to body weight in strains of mice. Recent conference reports described increased weight gain on high fat diet-fed mouse with lifelong deficiency of glyoxalase 1 deficiency, compared to wild-type controls, and decreased weight gain in glyoxalase 1-overexpressing transgenic mice, suggesting a functional role of glyoxalase 1 and dicarbonyl stress in obesity. Increased methylglyoxal, dicarbonyl stress, in white adipose tissue and liver may be a mediator of obesity and insulin resistance and thereby a risk factor for development of type 2 diabetes and non-alcoholic fatty liver disease. Increased methylglyoxal formation from glyceroneogenesis on adipose tissue and liver and decreased glyoxalase 1 activity in obesity likely drives dicarbonyl stress in white adipose tissue increasing the dicarbonyl proteome and related dysfunction. The clinical significance will likely emerge from on-going clinical evaluation of inducers of glyoxalase 1 expression in overweight and obese subjects. Increased transcapillary escape rate of albumin and increased total body interstitial fluid volume in obesity likely makes levels of glycation of plasma protein unreliable indicators of glycation status in obesity as there is a shift of albumin dwell time from plasma to interstitial fluid, which decreases overall glycation for a given glycemic exposure.

Metabolic factors, adipose tissue, and plasminogen activator inhibitor-1 levels in type 2 diabetes: findings from the look AHEAD study.

PubMed

Belalcazar, L Maria; Ballantyne, Christie M; Lang, Wei; Haffner, Steven M; Rushing, Julia; Schwenke, Dawn C; Pi-Sunyer, F Xavier; Tracy, Russell P

2011-07-01

Plasminogen activator inhibitor-1 (PAI-1) production by adipose tissue is increased in obesity, and its circulating levels are high in type 2 diabetes. PAI-1 increases cardiovascular risk by favoring clot stability, interfering with vascular remodeling, or both. We investigated in obese diabetic persons whether an intensive lifestyle intervention for weight loss (ILI) would decrease PAI-1 levels independently of weight loss and whether PAI-1 reduction would be associated with changes in fibrinogen, an acute phase reactant, or fibrin fragment D-dimer (D-dimer), a marker of ambient coagulation balance. We examined 1-year changes in PAI-1, D-dimer, and fibrinogen levels; adiposity; fitness; glucose; and lipid control with ILI in 1817 participants from Look AHEAD, a randomized trial investigating the effects of ILI, compared with usual care, on cardiovascular events in overweight or obese diabetic persons. Median PAI-1 levels decreased 29% with ILI and 2.5% with usual care (P < 0.0001). Improvements in fitness, glucose control, and high-density lipoprotein cholesterol were associated with decreased PAI-1, independently of weight loss (P = 0.03 for fitness, P < 0.0001 for others). Fibrinogen and D-dimer remained unchanged. Reductions in PAI-1 levels with ILI in obese diabetic individuals may reflect an improvement in adipose tissue health that could affect cardiovascular risk without changing fibrinogen or d-dimer levels. Clinical Trial Registration- URL: http://clinicaltrials.gov/ct2/show/NCT00017953. Unique identifier: NCT00017953.

Free amino acids exhibit anthozoan "host factor" activity: they induce the release of photosynthate from symbiotic dinoflagellates in vitro.

PubMed Central

Gates, R D; Hoegh-Guldberg, O; McFall-Ngai, M J; Bil, K Y; Muscatine, L

1995-01-01

Reef-building corals and other tropical anthozoans harbor endosymbiotic dinoflagellates. It is now recognized that the dinoflagellates are fundamental to the biology of their hosts, and their carbon and nitrogen metabolisms are linked in important ways. Unlike free living species, growth of symbiotic dinoflagellates is unbalanced and a substantial fraction of the carbon fixed daily by symbiont photosynthesis is released and used by the host for respiration and growth. Release of fixed carbon as low molecular weight compounds by freshly isolated symbiotic dinoflagellates is evoked by a factor (i.e., a chemical agent) present in a homogenate of host tissue. We have identified this "host factor" in the Hawaiian coral Pocillopora damicornis as a set of free amino acids. Synthetic amino acid mixtures, based on the measured free amino acid pools of P. damicornis tissues, not only elicit the selective release of 14C-labeled photosynthetic products from isolated symbiotic dinoflagellates but also enhance total 14CO2 fixation. Images Fig. 2 PMID:11607567

Free amino acids exhibit anthozoan "host factor" activity: they induce the release of photosynthate from symbiotic dinoflagellates in vitro.

PubMed

Gates, R D; Hoegh-Guldberg, O; McFall-Ngai, M J; Bil, K Y; Muscatine, L

1995-08-01

Reef-building corals and other tropical anthozoans harbor endosymbiotic dinoflagellates. It is now recognized that the dinoflagellates are fundamental to the biology of their hosts, and their carbon and nitrogen metabolisms are linked in important ways. Unlike free living species, growth of symbiotic dinoflagellates is unbalanced and a substantial fraction of the carbon fixed daily by symbiont photosynthesis is released and used by the host for respiration and growth. Release of fixed carbon as low molecular weight compounds by freshly isolated symbiotic dinoflagellates is evoked by a factor (i.e., a chemical agent) present in a homogenate of host tissue. We have identified this "host factor" in the Hawaiian coral Pocillopora damicornis as a set of free amino acids. Synthetic amino acid mixtures, based on the measured free amino acid pools of P. damicornis tissues, not only elicit the selective release of 14C-labeled photosynthetic products from isolated symbiotic dinoflagellates but also enhance total 14CO2 fixation.

Effects of High Intensity Interval Training on Pregnant Rats, and the Placenta, Heart and Liver of Their Fetuses.

PubMed

Songstad, Nils Thomas; Kaspersen, Knut-Helge Frostmo; Hafstad, Anne Dragøy; Basnet, Purusotam; Ytrehus, Kirsti; Acharya, Ganesh

2015-01-01

To investigate the effects of high intensity interval training (HIIT) on the maternal heart, fetuses and placentas of pregnant rats. Female Sprague-Dawley rats were randomly assigned to HIIT or sedentary control groups. The HIIT group was trained for 6 weeks with 10 bouts of high intensity uphill running on a treadmill for four minutes (at 85-90% of maximal oxygen consumption) for five days/week. After three weeks of HIIT, rats were mated. After six weeks (gestational day 20 in pregnant rats), echocardiography was performed to evaluate maternal cardiac function. Real-time PCR was performed for the quantification of gene expression, and oxidative stress and total antioxidant capacity was assessed in the tissue samples. Maternal heart weight and systolic function were not affected by HIIT or pregnancy. In the maternal heart, expression of 11 of 22 genes related to cardiac remodeling was influenced by pregnancy but none by HIIT. Litter size, fetal weight and placental weight were not affected by HIIT. Total antioxidant capacity, malondialdehyde content, peroxidase and superoxide dismutase activity measured in the placenta, fetal heart and liver were not influenced by HIIT. HIIT reduced the expression of eNOS (p = 0.03), hypoxia-inducible factor 1α (p = 0.04) and glutathione peroxidase 4.2 (p = 0.02) in the fetal liver and increased the expression of vascular endothelial growth factor-β (p = 0.014), superoxide dismutase 1 (p = 0.001) and tissue inhibitor of metallopeptidase 3 (p = 0.049) in the fetal heart. Maternal cardiac function and gene expression was not affected by HIIT. Although HIIT did not affect fetal growth, level of oxidative stress and total antioxidant capacity in the fetal tissues, some genes related to oxidative stress were altered in the fetal heart and liver indicating that protective mechanisms may be activated.

Effects of High Intensity Interval Training on Pregnant Rats, and the Placenta, Heart and Liver of Their Fetuses

PubMed Central

Hafstad, Anne Dragøy; Basnet, Purusotam; Ytrehus, Kirsti; Acharya, Ganesh

2015-01-01

Objective To investigate the effects of high intensity interval training (HIIT) on the maternal heart, fetuses and placentas of pregnant rats. Methods Female Sprague-Dawley rats were randomly assigned to HIIT or sedentary control groups. The HIIT group was trained for 6 weeks with 10 bouts of high intensity uphill running on a treadmill for four minutes (at 85–90% of maximal oxygen consumption) for five days/week. After three weeks of HIIT, rats were mated. After six weeks (gestational day 20 in pregnant rats), echocardiography was performed to evaluate maternal cardiac function. Real-time PCR was performed for the quantification of gene expression, and oxidative stress and total antioxidant capacity was assessed in the tissue samples. Results Maternal heart weight and systolic function were not affected by HIIT or pregnancy. In the maternal heart, expression of 11 of 22 genes related to cardiac remodeling was influenced by pregnancy but none by HIIT. Litter size, fetal weight and placental weight were not affected by HIIT. Total antioxidant capacity, malondialdehyde content, peroxidase and superoxide dismutase activity measured in the placenta, fetal heart and liver were not influenced by HIIT. HIIT reduced the expression of eNOS (p = 0.03), hypoxia-inducible factor 1α (p = 0.04) and glutathione peroxidase 4.2 (p = 0.02) in the fetal liver and increased the expression of vascular endothelial growth factor-β (p = 0.014), superoxide dismutase 1 (p = 0.001) and tissue inhibitor of metallopeptidase 3 (p = 0.049) in the fetal heart. Conclusions Maternal cardiac function and gene expression was not affected by HIIT. Although HIIT did not affect fetal growth, level of oxidative stress and total antioxidant capacity in the fetal tissues, some genes related to oxidative stress were altered in the fetal heart and liver indicating that protective mechanisms may be activated. PMID:26566220

The enhanced anti-tissue adhesive effect of injectable pluronic-HA hydrogel by poly(γ-glutamic acid).

PubMed

Kim, Manse; Hwang, Youngmin; Tae, Giyoong

2016-12-01

The stability of tissue barrier in physiological condition is a key factor to isolate the damaged site from adjacent tissue for anti-tissue adhesion. Although pluronic or pluronic-hyaluronic acid (HA) hydrogel as an injectable formulation can prevent tissue adhesion at the injection site, the anti-tissue adhesion effect is limited due to its poor stability. Herein, we prepared tissue barrier formulations composed of pluronic F127 (F127) and HA mixture (F127-HA) and the effect of the addition of poly(γ-glutamic acid) (PGA) was characterized. All of F127, HA, and F127-HA mixture showed the poor in vitro residence stability less than 3 days. However, by adding PGA into F127-HA mixture, their stability was significantly enhanced by the control of the molecular weight and concentration of PGA. Thus, F127-HA with 10wt% PGA (2000kDa) showed the long-term stability over 10 days. Similarly, the enhanced stability of F127-HA with PGA resulted in the enhanced and excellent in vivo anti-tissue adhesion effect, evidenced by histological analysis and grading of tissue adhesion. Therefore, F127-HA containing PGA could be applied as an efficient injectable tissue barrier for anti-tissue adhesion. Copyright © 2016 Elsevier B.V. All rights reserved.

Optimizing dual-energy x-ray parameters for the ExacTrac clinical stereoscopic imaging system to enhance soft-tissue imaging.

PubMed

Bowman, Wesley A; Robar, James L; Sattarivand, Mike

2017-03-01

Stereoscopic x-ray image guided radiotherapy for lung tumors is often hindered by bone overlap and limited soft-tissue contrast. This study aims to evaluate the feasibility of dual-energy imaging techniques and to optimize parameters of the ExacTrac stereoscopic imaging system to enhance soft-tissue imaging for application to lung stereotactic body radiation therapy. Simulated spectra and a physical lung phantom were used to optimize filter material, thickness, tube potentials, and weighting factors to obtain bone subtracted dual-energy images. Spektr simulations were used to identify material in the atomic number range (3-83) based on a metric defined to separate spectra of high and low-energies. Both energies used the same filter due to time constraints of imaging in the presence of respiratory motion. The lung phantom contained bone, soft tissue, and tumor mimicking materials, and it was imaged with a filter thickness in the range of (0-0.7) mm and a kVp range of (60-80) for low energy and (120,140) for high energy. Optimal dual-energy weighting factors were obtained when the bone to soft-tissue contrast-to-noise ratio (CNR) was minimized. Optimal filter thickness and tube potential were achieved by maximizing tumor-to-background CNR. Using the optimized parameters, dual-energy images of an anthropomorphic Rando phantom with a spherical tumor mimicking material inserted in his lung were acquired and evaluated for bone subtraction and tumor contrast. Imaging dose was measured using the dual-energy technique with and without beam filtration and matched to that of a clinical conventional single energy technique. Tin was the material of choice for beam filtering providing the best energy separation, non-toxicity, and non-reactiveness. The best soft-tissue-weighted image in the lung phantom was obtained using 0.2 mm tin and (140, 60) kVp pair. Dual-energy images of the Rando phantom with the tin filter had noticeable improvement in bone elimination, tumor contrast, and noise content when compared to dual-energy imaging with no filtration. The surface dose was 0.52 mGy per each stereoscopic view for both clinical single energy technique and the dual-energy technique in both cases of with and without the tin filter. Dual-energy soft-tissue imaging is feasible without additional imaging dose using the ExacTrac stereoscopic imaging system with optimized acquisition parameters and no beam filtration. Addition of a single tin filter for both the high and low energies has noticeable improvements on dual-energy imaging with optimized parameters. Clinical implementation of a dual-energy technique on ExacTrac stereoscopic imaging could improve lung tumor visibility. © 2017 American Association of Physicists in Medicine.

Enhancement of Lipid Metabolism and Hepatic Stability in Fat-Induced Obese Mice by Fermented Cucurbita moschata Extract

PubMed Central

Lee, Seung-Jin; Park, Na-Hye; Birhanu, Biruk Tesfaye; Mechesso, Abraham Fikru; Park, Ji-Yong; Park, Eun-Jin; Youn, Sun-Joo

2018-01-01

The aim of this study was to evaluate the potentials of fermented Cucurbita moschata extract (FCME) in the treatment of obesity and nonalcoholic fatty liver disease (NAFLD). Five-week-old male C57BL/6 mice were assigned to 6 groups and treated for 8 weeks by feeding the normal diet (ND) and high fat diet (HFD) with and without FCME. Changes in body weight gain and consumption of feed and water were recorded. Major organs, adipose tissues, and blood samples were collected after the experimental period. The serum lipid profile, histological features of liver and adipose tissues, and mRNA expression of different adipogenic/lipogenic genes from liver tissue were evaluated. The supplementation of FCME in HFD significantly prevented HFD-induced increment of bodyweight. The adipose tissue mass, liver enzymes, and plasma lipids were also reduced significantly (p < 0.05) by the consumption of FCME. The mRNA expressions of adipogenic/lipogenic genes (PPARγ, C/EBPα, C/EBPβ, C/EBPγ, and SREBP-1C) in FCME-treated obese mice were considerably (p < 0.05) suppressed. FCME showed its antiobesity potential by suppressing the body weight gain and by modulating the plasma lipids and liver enzymes through the regulation of adipogenic/lipogenic transcriptional factors. Fermented Cucurbita moschata could be an opportunistic agent in controlling obesity and fatty liver changes. PMID:29725353

Effects of Low-Molecular-Weight Fucoidan and High Stability Fucoxanthin on Glucose Homeostasis, Lipid Metabolism, and Liver Function in a Mouse Model of Type II Diabetes.

PubMed

Lin, Hong-Ting Victor; Tsou, Yu-Chi; Chen, Yu-Ting; Lu, Wen-Jung; Hwang, Pai-An

2017-04-07

The combined effects of low-molecular-weight fucoidan (LMF) and fucoxanthin (Fx) in terms of antihyperglycemic, antihyperlipidemic, and hepatoprotective activities were investigated in a mouse model of type II diabetes. The intake of LMF, Fx, and LMF + Fx lowered the blood sugar and fasting blood sugar levels, and increased serum adiponectin levels. The significant decrease in urinary sugar was only observed in LMF + Fx supplementation. LMF and Fx had ameliorating effects on the hepatic tissue of db/db mice by increasing hepatic glycogen and antioxidative enzymes, and LMF was more effective than Fx at improving hepatic glucose metabolism. As for glucose and lipid metabolism in the adipose tissue, the expression of insulin receptor substrate (IRS)-1, glucose transporter (GLUT), peroxisome proliferator-activated receptor gamma (PPARγ), and uncoupling protein (UCP)-1 mRNAs in the adipose tissue of diabetic mice was significantly upregulated by Fx and LMF + Fx, and levels of inflammatory adipocytokines, such as adiponectin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), were significantly modulated only by LMF + Fx supplementation. The efficacy of LMF + Fx supplementation on the decrease in urinary sugar and on glucose and lipid metabolism in the white adipose tissue of db/db mice was better than that of Fx or LMF alone, indicating the occurrence of a synergistic effect of LMF and Fx.

Understanding the Anatomic Basis for Obstructive Sleep Apnea Syndrome in Adolescents

PubMed Central

Kim, Christopher; Bagchi, Sheila; Keenan, Brendan T.; Comyn, François-Louis; Wang, Stephen; Tapia, Ignacio E.; Huang, Shirley; Traylor, Joel; Torigian, Drew A.; Bradford, Ruth M.; Marcus, Carole L.

2015-01-01

Rationale: Structural risk factors for obstructive sleep apnea syndrome (OSAS) in adolescents have not been well characterized. Because many adolescents with OSAS are obese, we hypothesized that the anatomic OSAS risk factors would be more similar to those in adults than those in children. Objectives: To investigate the anatomic risk factors in adolescents with OSAS compared with obese and lean control subjects using magnetic resonance imaging (MRI). Methods: Three groups of adolescents (age range: 12–16 yr) underwent MRI: obese individuals with OSAS (n = 49), obese control subjects (n = 38), and lean control subjects (n = 50). Measurements and Main Results: We studied 137 subjects and found that (1) obese adolescents with OSAS had increased adenotonsillar tissue compared with obese and lean control subjects; (2) obese OSAS adolescents had a smaller nasopharyngeal airway than control subjects; (3) the size of other upper airway soft tissue structures (volume of the tongue, parapharyngeal fat pads, lateral walls, and soft palate) was similar between subjects with OSAS and obese control subjects; (4) although there were no major craniofacial abnormalities in most of the adolescents with OSAS, the ratio of soft tissue to craniofacial space surrounding the airway was increased; and (5) there were sex differences in the pattern of lymphoid proliferation. Conclusions: Increased size of the pharyngeal lymphoid tissue, rather than enlargement of the upper airway soft tissue structures, is the primary anatomic risk factor for OSAS in obese adolescents. These results are important for clinical decision making and suggest that adenotonsillectomy should be considered as the initial treatment for OSAS in obese adolescents, a group that has poor continuous positive airway pressure adherence and difficulty in achieving weight loss. PMID:25835282

Immunohistochemical examination of effects of kefir, koumiss and commercial probiotic capsules on platelet derived growth factor-c and platelet derived growth factor receptor-alpha expression in mouse liver and kidney.

PubMed

Bakir, B; Sari, E K; Aydin, B D; Yildiz, S E

2015-04-01

We investigated using immunohistochemistry the effects of kefir, koumiss and commercial probiotic capsules on the expression of platelet derived growth factor-c (PDGF-C) and platelet derived growth factor receptor-alpha (PDGFR-α) in mouse liver and kidney. Mice were assigned to four groups: group 1 was given commercial probiotic capsules, group 2 was given kefir, group 3 was given koumiss and group 4 was untreated. After oral administration for 15 days, body weights were recorded and liver and kidney tissue samples were obtained. Hematoxylin and eosin staining was used to examine histology. PDGF-C and PDGFR-α in liver and kidney were localized using the streptavidin-biotin peroxidase complex method (ABC). We found that the weights of the mice in the kefir, koumiss and commercial probiotic capsules groups increased compared to the control group. No differences in liver and kidney histology were observed in any of the experimental groups. Kefir, koumiss and the commercial probiotic preparation increased PDGF-C and PDGFR-α expression.

Characterization of a heparin-binding growth factor from adenocarcinoma of the kidney.

PubMed

Mydlo, J H; Heston, W D; Fair, W R

1988-12-01

A polypeptide isolated from tissue extracts of renal adenocarcinoma was mitogenic for BALB/c 3T3 cells and human umbilical vein (HUV) cells in culture. It also demonstrated angiogenic ability using the chorioallantoic membrane bioassay. Using heparin-sepharose affinity chromatography the purified protein eluted with a NaCl concentration between 1.4 and 1.8 M and demonstrated a molecular weight of approximately 17,000 daltons based on SDS polyacrylamide gel electrophoresis. Half maximal stimulation of tritiated thymidine incorporation into BALB/c 3T3 cells was achieved by 1.6 ng./ml. of the heparin binding material. Western blot analysis using antibodies specific to basic fibroblast growth factor (bFGF) only or acidic FGF (aFGF) only demonstrated that the purified protein binds to the former and not the latter. The characteristics of this material, in effect the elution profile off heparin-Sepharose, the molecular weight, angiogenic activity and the results of western blot analysis, suggest that this growth factor is similar to the family of basic fibroblast growth factors.

Comparative analysis of dosimetry parameters for nuclear medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toohey, R.E.; Stabin, M.G.

For years many have employed the concept of ``total-body dose`` or ``whole-body dose,`` i.e., the total energy deposited in the body divided by the mass of the body, when evaluating the risks of different nuclear medicine procedures. The effective dose equivalent (H{sub E}), first described in ICRP Publication 26, has been accepted by some as a better quantity to use in evaluating the total risk of a procedure, but its use has been criticized by others primarily because the tissue weighting factors were intended for use in the radiation worker, rather than the nuclear medicine patient population. Nevertheless, in ICRPmore » Publication 52, the ICRP has suggested that the H{sub E} may be used in nuclear medicine. The ICRP also has published a compendium of dose estimates, including H{sub E} values, for various nuclear medicine procedures at various ages in ICRP Publication 53. The effective dose (E) of ICRP Publication 60 is perhaps more suitable for use in nuclear medicine, with tissue weighting factors based on the entire population. Other comparisons of H{sub E} and E have been published. The authors have used the program MIRDOSE 3.1 to compute total-body dose, H{sub E}, and E for 62 radiopharmaceutical procedures, based on the best current biokinetic data available.« less

INDIVIDUAL TISSUE TO TOTAL BODY-WEIGHT RELATIONSHIPS AND TOTAL, POLAR, AND NON-POLAR LIPIDS IN TISSUES OF HATCHERY LAKE TROUT

EPA Science Inventory

Tissue body weight relaltionships, total lipid, and major lipid subclasses were measured in 20 adult hatchery lake trout to obtain a more in-depth understanding of the major lipid compartments of the "lean" lake trout for use in modeling the disposition of xenobiotics. It is sug...

Canagliflozin, a sodium glucose cotransporter 2 inhibitor, attenuates obesity-induced inflammation in the nodose ganglion, hypothalamus, and skeletal muscle of mice.

PubMed

Naznin, Farhana; Sakoda, Hideyuki; Okada, Tadashi; Tsubouchi, Hironobu; Waise, T M Zaved; Arakawa, Kenji; Nakazato, Masamitsu

2017-01-05

Chronic inflammation in systemic organs, such as adipose tissue, nodose ganglion, hypothalamus, and skeletal muscles, is closely associated with obesity and diabetes mellitus. Because sodium glucose cotransporter 2 (SGLT2) inhibitors exert both anti-diabetic and anti-obesity effects by promoting urinary excretion of glucose and subsequent caloric loss, we investigated the effect of canagliflozin, an SGLT2 inhibitor, on obesity-induced inflammation in neural tissues and skeletal muscles of mice. High-fat diet (HFD)-fed male C57BL/6J mice were treated with canagliflozin for 8 weeks. Canagliflozin attenuated the HFD-mediated increases in body weight, liver weight, and visceral and subcutaneous fat weight. Additionally, canagliflozin decreased blood glucose as well as the fat, triglyceride, and glycogen contents of the liver. Along with these metabolic corrections, canagliflozin attenuated the increases in the mRNA levels of the proinflammatory biomarkers Iba1 and Il6 and the number of macrophages/microglia in the nodose ganglion and hypothalamus. In the skeletal muscle of HFD-fed obese mice, canagliflozin decreased inflammatory cytokine levels, macrophage accumulation, and the mRNA level of the specific atrophic factor atrogin-1. Canagliflozin also increased the mRNA level of insulin-like growth factor 1, protected against muscle mass loss, and restored the contractile force of muscle. These findings suggested that SGLT2 inhibition disrupts the vicious cycle of obesity and inflammation, not only by promoting caloric loss, but also by suppression of obesity-related inflammation in both the nervous system and skeletal muscle. Copyright © 2016 Elsevier B.V. All rights reserved.

Persistence and changes in bioavailability of dieldrin, DDE and heptachlor epoxide in earthworms over 45 years

USGS Publications Warehouse

Beyer, W. Nelson; Gale, Robert W.

2013-01-01

The finding of dieldrin (88 ng/g), DDE (52 ng/g), and heptachlor epoxide (19 ng/g) in earthworms from experimental plots after a single moderate application (9 kg/ha) 45 years earlier attests to the remarkable persistence of these compounds in soil and their continued uptake by soil organisms. Half-lives (with 95 % confidence intervals) in earthworms, estimated from exponential decay equations, were as follows: dieldrin 4.9 (4.3-5.7) years, DDE 5.3 (4.7-6.1) years, and heptachlor epoxide 4.3 (3.8-4.9) years. These half-lives were not significantly different from those estimated after 20 years. Concentration factors (dry weight earthworm tissue/dry weight soil) were initially high and decreased mainly during the first 11 years after application. By the end of the study, average concentration factors were 1.5 (dieldrin), 4.0 (DDE), and 1.8 (heptachlor epoxide), respectively.

Is the Susceptibility Vessel Sign on 3-Tesla Magnetic Resonance T2*-Weighted Imaging a Useful Tool to Predict Recanalization in Intravenous Tissue Plasminogen Activator?

PubMed

Yamamoto, N; Satomi, J; Harada, M; Izumi, Y; Nagahiro, S; Kaji, R

2016-09-01

The aim of this study was to investigate the independent factors associated with the absence of recanalization approximately 24 h after intravenous administration of tissue-type plasminogen activator (IV TPA). The previous studies have been conducted using 1.5-Tesla (T) magnetic resonance imaging (MRI). We studied whether the characteristics of 3-T MRI findings were useful to predict outcome and recanalization after IV tPA. Patients with internal carotid artery (ICA) or middle cerebral artery (MCA) (horizontal portion, M1; Sylvian portion, M2) occlusion and treated by IV tPA were enrolled. We studied whether the presence of susceptibility vessel sign (SVS) at M1 and low clot burden score on T2*-weighted imaging (T2*-CBS) on 3-T MRI were associated with the absence of recanalization. A total of 49 patients were enrolled (27 men; mean age, 73.9 years). MR angiography obtained approximately 24 h after IV tPA revealed recanalization in 21 (42.9 %) patients. Independent factors associated with the absence of recanalization included ICA or proximal M1 occlusion (odds ratio, 69.6; 95 % confidence interval, 5.05-958.8, p = 0.002). In this study, an independent factor associated with the absence of recanalization may be proximal occlusion of the cerebral arteries rather than SVS in the MCA or low T2*-CBS on 3-T MRI.

A low-protein diet induces body weight loss and browning of subcutaneous white adipose tissue through enhanced expression of hepatic fibroblast growth factor 21 (FGF21).

PubMed

Pérez-Martí, Albert; Garcia-Guasch, Maite; Tresserra-Rimbau, Anna; Carrilho-Do-Rosário, Alexandra; Estruch, Ramon; Salas-Salvadó, Jordi; Martínez-González, Miguel Ángel; Lamuela-Raventós, Rosa; Marrero, Pedro F; Haro, Diego; Relat, Joana

2017-08-01

Fibroblast growth factor 21 (FGF21) is considered a promising therapeutic candidate for the treatment of obesity. Since FGF21 production is regulated by various nutritional factors, we analyze the impact of low protein intake on circulating levels of this growth hormone in mice and in a sub cohort of the PREDIMED (Prevención con Dieta Mediterránea) trial. We also describe the role of hepatic FGF21 in metabolic adaptation to a low-protein diet (LPD). We fed control and liver-specific Fgf21 knockout (LFgf21KO) mice a LPD. This diet increased FGF21 production by inducing its overexpression in liver, and this correlated with a body weight decrease without changes in food intake. The LPD also caused FGF21-dependent browning in subcutaneous white adipose tissue (scWAT), as indicated by an increase in the expression of uncoupling protein 1 (UCP1). In a subgroup of 78 individuals from the PREDIMED trial, we observed an inverse correlation between protein intake and circulating FGF21 levels. Our results reinforce the involvement of FGF21 in coordinating energy homeostasis under a range of nutritional conditions. Moreover, here we describe an approach to increase the endogenous production of FGF21, which if demonstrated functional in humans, could generate a treatment for obesity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification of hepatic fibroblast growth factor 21 as a mediator in 17β-estradiol-induced white adipose tissue browning.

PubMed

Hua, Lun; Zhuo, Yong; Jiang, Dandan; Li, Jing; Huang, Xiaohua; Zhu, Yingguo; Li, Zhen; Yan, Lijun; Jin, Chao; Jiang, Xuemei; Che, Lianqiang; Fang, Zhengfeng; Lin, Yan; Xu, Shengyu; Li, Jian; Feng, Bin; Wu, De

2018-05-02

Both ovarian E2 and hepatic fibroblast growth factor 21 (FGF21) are critical for energy homeostasis and white adipose tissue browning. Estrogen receptor α (ERα) is abundantly expressed in liver. However, whether FGF21 has a role in E2-induced white adipose tissue browning remains uncertain. In this study, we showed that hepatic Fgf21 expression and secretion during estrus cycle changed with the tetradian oscillatory secretion of circulation E2 in adult, female mice, with their peak expressions and secretions at the proestrus. In addition, exogenous E2 robustly stimulated liver Fgf21 expression and elevated serum FGF21 concentrations, which induced browning gene expression and reduced the tissue weight in subcutaneous white adipose in mice with ovariectomies. The inhibitor of mammalian target of rapamycin (mTOR) and of ERα blocked the induction effect of E2 on the expression of Fgf21 in primary hepatocytes, which revealed that E2 might stimulate FGF21 expression via the ERα-mTOR pathway. Furthermore, FGF21 liver-specific deficiency abolished E2-induced white adipose browning in mice with ovariectomies. This study indicates that ovarian E2 increased liver FGF21 expression directly, which in turn, functioned as an endocrine signal to influence inguinal white adipose tissue browning.-Hua, L., Zhuo, Y., Jiang, D., Li, Jin., Huang, X., Zhu, Y., Li, Z., Yan, L., Jin, C., Jiang, X., Che, L., Fang, Z., Lin, Y., Xu, S. Li, Jia., Feng, B., Wu, D. Identification of hepatic fibroblast growth factor 21 as a mediator in 17β-estradiol-induced white adipose tissue browning.

[Gigantism with low serum level of growth hormone: a case report].

PubMed

Ran, X; Zhang, L; Xiong, P; Zhao, T; Tong, N; Li, X

2001-12-01

Gigantism with low or normal basal concentrations of growth hormone (GH) is a rare condition, possibly due to abnormal GH secretory patterns, enhanced tissue sensitivity to GH, or the existence of an unidentified growth promoting factor. Here we report an 11 year-old female case of gigantism with a normal pituitary gland. Her height was 181 cm, body weight 77 kg, and bone age 11.1 years. Her basal serum GH levels were lower than 1 ng/ml. The levels of T3, T4, FT3, FT4, TSH, E2, LH, FSH, PRL, PTC and ACTH were normal. Serum GH response to insulin-induced hypoglycemia or arginine stimulation tests was blunted. In this case, non-pulsatile GH secretion and enhanced tissue sensitivity to GH may induce hypersecretion of IGF-1 and the existence of an unidentified growth promoting factor or biologically active anti-GH receptor antibodies may cause clinical gigantism.

Contribution of trochanteric soft tissues to fall force estimates, the factor of risk, and prediction of hip fracture risk.

PubMed

Bouxsein, Mary L; Szulc, Pawel; Munoz, Fracoise; Thrall, Erica; Sornay-Rendu, Elizabeth; Delmas, Pierre D

2007-06-01

We compared trochanteric soft tissue thickness, femoral aBMD, and the ratio of fall force to femoral strength (i.e., factor of risk) in 21 postmenopausal women with incident hip fracture and 42 age-matched controls. Reduced trochanteric soft tissue thickness, low femoral aBMD, and increased ratio of fall force to femoral strength (i.e., factor of risk) were associated with increased risk of hip fracture. The contribution of trochanteric soft tissue thickness to hip fracture risk is incompletely understood. A biomechanical approach to assessing hip fracture risk that compares forces applied to the hip during a sideways fall to femoral strength may by improved by incorporating the force-attenuating effects of trochanteric soft tissues. We determined the relationship between femoral areal BMD (aBMD) and femoral failure load in 49 human cadaveric specimens, 53-99 yr of age. We compared femoral aBMD, trochanteric soft tissue thickness, and the ratio of fall forces to bone strength (i.e., the factor of risk for hip fracture, phi), before and after accounting for the force-attenuating properties of trochanteric soft tissue in 21 postmenopausal women with incident hip fracture and 42 age-matched controls. Femoral aBMD correlated strongly with femoral failure load (r2 = 0.73-0.83). Age, height, and weight did not differ; however, women with hip fracture had lower total femur aBMD (OR = 2.06; 95% CI, 1.19-3.56) and trochanteric soft tissue thickness (OR = 1.82; 95% CI, 1.01, 3.31). Incorporation of trochanteric soft tissue thickness measurements reduced the estimates of fall forces by approximately 50%. After accounting for force-attenuating properties of trochanteric soft tissue, the ratio of fall forces to femoral strength was 50% higher in cases than controls (0.92 +/- 0.44 versus 0.65 +/- 0.50, respectively; p = 0.04). It is possible to compute a biomechanically based estimate of hip fracture risk by combining estimates of femoral strength based on an empirical relationship between femoral aBMD and bone strength in cadaveric femora, along with estimates of loads applied to the hip during a sideways fall that account for thickness of trochanteric soft tissues. Our findings suggest that trochanteric soft tissue thickness may influence hip fracture risk by attenuating forces applied to the femur during a sideways fall and provide rationale for developing improved measurements of trochanteric soft tissue and for studying a larger cohort to determine whether trochanteric soft tissue thickness contributes to hip fracture risk independently of aBMD.

Influence of PAI-1 on adipose tissue growth and metabolic parameters in a murine model of diet-induced obesity.

PubMed

Morange, P E; Lijnen, H R; Alessi, M C; Kopp, F; Collen, D; Juhan-Vague, I

2000-04-01

An increased plasma plasminogen activator inhibitor-1 (PAI-1) level is a risk factor for myocardial infarction, particularly when associated with visceral obesity. Although the link between PAI-1 and obesity is well documented, little is known about the physiological relevance of PAI-1 production by adipose tissue. Therefore, we have compared adipose tissue development and insulin resistance plasma parameters in PAI-1-deficient mice (PAI-1(-/-)) and wild-type littermates (PAI-1(+/+)) in a model of nutritionally induced obesity. After 17 weeks of consuming a high-fat diet (HFD), PAI-1(+/+) mice showed marked obesity, with a 52% increase in body weight compared with mice that were kept on a standard fat diet (P<0.0001). This weight gain was accompanied by adipocyte hypertrophy and an increase in the number of stroma cells in the gonadal fat pad, expressed as stroma cells/adipocytes (0.67+/-0.05 versus 0.43+/-0. 02; P<0.001). In plasma, the HFD induced a marked increase in PAI-1 antigen (5.1+/-0.56 versus 2+/-0.22 ng/mL; P<0.001), fasting insulinemia (1.1+/-0.21 versus 0.21+/-0.04 ng/mL; P<0.001), and glycemia (7.4+/-0.5 versus 5+/-0.3 mmol/L; P<0.001), whereas plasma triglyceride levels were not affected. When we compared PAI-1(-/-) and PAI-1(+/+) mice on the HFD, PAI-1(-/-) mice gained weight faster than did PAI-1(+/+) mice, with a significant difference in body weight between 3 and 8 weeks of the diet (32+/-1.7 versus 26+/-1.6 g at 6 weeks; P<0.05). After 17 weeks of the HFD, its effect on weight gain and the number and size of adipocytes was similar in PAI-1(+/+) and PAI-1(-/-) mice. By contrast, the increase in the number of stroma cells presented by PAI-1(+/+) mice was not observed in PAI-1(-/-) mice. In obese PAI-1(-/-) mice, tissue-type PA activity and antigen levels in the gonadal fat pad were significantly higher than in obese PAI-1(+/+) mice (230+/-50 versus 47+/-20 arbitrary units/g, P<0.01; 40+/-13 versus 17+/-13 ng/g, P<0.05, respectively), whereas urokinase-type PA activity and antigen levels were similar in both groups. In plasma, nonobese PAI-1(-/-) mice displayed 62% higher insulin levels (P<0.05) than did PAI-1(+/+) mice. Obese PAI-1(-/-) mice displayed 68% higher triglyceride levels (P<0.01) and 21% lower glucose levels (P<0.05) than did PAI-1(+/+) mice. These data support an effect of PAI-1 on weight gain and adipose tissue cellularity in the induction of obesity in mice. Moreover, PAI-1 influences glucidolipidic metabolism. The elevated expression of PAI-1 observed in human obesity could be involved in mechanisms that control adipose tissue development.

The effect of peripheral chronic salsolinol administration on fat pad adipocytes morphological parameters.

PubMed

Aleksandrovych, Veronika; Kurnik, Magdalena; Białas, Magdalena; Bugajski, Andrzej; Thor, Piotr; Gil, Krzysztof

Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) is thought to regulate dopaminergic neurons and to act as a mediator in the neuroendocrine system. We have previously reported that exogenous salsolinol evokes enteric neuronal cell death, leading to the impairment of myenteric neurons density and abnormal intestinal transit in rats. We also observed significant reduction of body weight, related to the disrupted gastrointestinal homeostasis. e aim of current study was to evaluate the influence of prolonged salsolinol administration body weight, food intake, adipose tissue accumulation and fad pad adipocyte morphological parameters assessed by image analysis. Male Wistar rats were subjected to continuous intraperitoneal low dosing of salsolinol - 200 mg/kg in total with ALZET osmotic mini-pumps (Durtec, USA) for 2 or 4 weeks with either normal or high-fat diet. Appropriate groups served as the controls. Food intake, body weight were measured each morning. Both epididymal fat pads were dissected, weighted and processed for routine hematoxylin and eosin staining. e following parameters: cell area, perimeter, long and short axis, aspect ratio and circularity factor were assessed in stained specimens with the image analysis system (Multiscan, Poland). Salsolinol administration significantly reduced total body mass with no differences in total food intake between the groups. The epididymal fat pad weight over final body mass ratio was lower in salsolinol treated rats on high fat diet in comparison with the control groups. e area, perimeter, short and long axis of the fad pad adipocytes were significantly decreased in salsolinol treated animals in comparison with relevant controls. Salsolinol targets some regulatory mechanisms concerned with the basic rat metabolism. Prolonged peripheral salsolinol administration in rats significantly decreases the adipocyte size, and such effect is related to the weight loss and reduced adipose tissue accumulation.

The relationship of obesity to the metabolic syndrome.

PubMed

Lebovitz, Harold E

2003-03-01

Obese patients with the metabolic syndrome generally have a visceral (apple-shaped) fat distribution and are at an increased risk of macrovascular disease, while those with peripheral (pear-shaped) obesity tend not to have metabolic abnormalities and are at less risk. This difference appears to be related to the differing metabolic functions (and secretory products) of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), as well as the fact that VAT drains directly into the liver. Thus, it appears that increased VAT, but not SAT, is associated with both hepatic and peripheral biochemical abnormalities leading to insulin resistance and the associated metabolic syndrome. Insulin resistance is associated with VAT products, such as free fatty acids and their metabolites, as well as cytokines, such as tumour necrosis factor alpha (TNF-alpha). These factors may activate components of the inflammatory pathway such as nuclear factor kappa-B (NFkappaB), and inhibit insulin signalling. Insulin resistance is further associated with decreased levels of another tissue product, adiponectin. The incidence and prevalence of obesity is increasing at an unprecedented rate. The classic treatment of obesity is weight loss via lifestyle modification. However, prevention of obesity comorbidity can also be achieved by modifying the mechanisms by which obesity causes these comorbid conditions. For instance, it is now known that the peroxisome proliferator-activated receptor (PPAR) family of transcriptional regulators are crucial in regulating adipose tissue development and metabolism; this helps explain why compounds with PPARgamma agonist activity, e.g. thiazolidinediones, increase insulin action through their effects in regulating adipose tissue metabolism.

Ruscogenin inhibits lipopolysaccharide-induced acute lung injury in mice: involvement of tissue factor, inducible NO synthase and nuclear factor (NF)-κB.

PubMed

Sun, Qi; Chen, Ling; Gao, Mengyu; Jiang, Wenwen; Shao, Fangxian; Li, Jingjing; Wang, Jun; Kou, Junping; Yu, Boyang

2012-01-01

Acute lung injury is still a significant clinical problem with a high mortality rate and there are few effective therapies in clinic. Here, we studied the inhibitory effect of ruscogenin, an anti-inflammatory and anti-thrombotic natural product, on lipopolysaccharide (LPS)-induced acute lung injury in mice basing on our previous studies. The results showed that a single oral administration of ruscogenin significantly decreased lung wet to dry weight (W/D) ratio at doses of 0.3, 1.0 and 3.0 mg/kg 1 h prior to LPS challenge (30 mg/kg, intravenous injection). Histopathological changes such as pulmonary edema, coagulation and infiltration of inflammatory cells were also attenuated by ruscogenin. In addition, ruscogenin markedly decreased LPS-induced myeloperoxidase (MPO) activity and nitrate/nitrite content, and also downregulated expression of tissue factor (TF), inducible NO synthase (iNOS) and nuclear factor (NF)-κB p-p65 (Ser 536) in the lung tissue at three doses. Furthermore, ruscogenin reduced plasma TF procoagulant activity and nitrate/nitrite content in LPS-induced ALI mice. These findings confirmed that ruscogenin significantly attenuate LPS-induced acute lung injury via inhibiting expressions of TF and iNOS and NF-κB p65 activation, indicating it as a potential therapeutic agent for ALI or sepsis. Copyright © 2011 Elsevier B.V. All rights reserved.

Carcinoma-specific Ulex europaeus agglutinin-I binding glycoproteins of human colorectal carcinoma and its relation to carcinoembryonic antigen.

PubMed

Matsushita, Y; Yonezawa, S; Nakamura, T; Shimizu, S; Ozawa, M; Muramatsu, T; Sato, E

1985-08-01

Glycoproteins binding to Ulex europaeus agglutinin-I (UEA-I) lectin, which recognizes the terminal alpha-L-fucose residue, were analyzed in 18 cases of human colorectal carcinoma by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by the Western blotting method. In the distal large bowel (descending and sigmoid colon and rectum), high-molecular-weight glycoproteins binding to UEA-I existed in carcinoma tissue but not in normal mucosa. In the proximal large bowel (ascending and transverse colon), high-molecular-weight glycoproteins binding to UEA-I were found both in normal mucosa and in carcinoma tissue, whereas those from the carcinoma tissue had an apparently lower molecular weight as compared to the weight of those from the normal mucosa. Thus there is a biochemical difference in UEA-I binding glycoproteins between the normal mucosa and the carcinoma tissue, although in our previous histochemical study no difference was observed in UEA-I binding glycoproteins of the proximal large bowel between the carcinoma tissue and the normal mucosa. Furthermore, carcinoembryonic antigen from the carcinoma tissue was found to have the same electrophoretical mobility as the UEA-I binding glycoproteins.

Changes in arm tissue composition with slowly progressive weight-lifting among women with breast cancer-related lymphedema.

PubMed

Zhang, Xiaochen; Brown, Justin C; Paskett, Electra D; Zemel, Babette S; Cheville, Andrea L; Schmitz, Kathryn H

2017-07-01

Studies in breast cancer-related lymphedema (BRCL) have exclusively examined total arm volume, but not the specific tissue composition that contributes to total volume. We evaluated baseline differences in arm tissue composition [fat mass, lean mass, bone mineral content (BMC), and bone mineral density (BMD)] between the affected and unaffected arms in women with BRCL. We compared changes in arm tissue composition and self-reported lymphedema symptoms after 1 year of weight-lifting versus control. We utilized data from physical activity and lymphedema trial that included 141 women with BRCL. Arm tissue composition was quantified using dual-energy X-ray absorptiometry. The severity of lymphedema was quantified using self-report survey. Weight-lifting was performed at community fitness facilities. At baseline, the affected arm had more fat (∆ = 89.7 g; P < 0.001) and lean mass (∆ = 149.1 g; P < 0.001), but less BMC (∆ = -3.2 g; P < 0.001) and less BMD (∆ = -5.5 mg/cm 2 ; P = 0.04) than the unaffected arm. After 12 months of weight-lifting, composition of the affected arm was improved: lean mass (71.2 g; P = 0.01) and BMD (14.0 mg/cm 2 ; P = 0.02) increased, arm fat percentage decreased (-1.5%; P = 0.003). Composition of the unaffected arm was only improved in lean mass (65.2 g; P = 0·04). Increases in lean mass were associated with less severe BCRL symptoms. Among women with BRCL, slowly progressive weight-lifting could improve arm tissue composition. Changes in arm tissue composition predict changes in symptom burden. Investigating the combined effects of exercise and weight loss on arm tissue composition and BCRL symptoms may provide additional insight into the benefits of lifestyle modification on lymphedema biology.

Mercury concentrations in gonad, liver, and muscle of white sturgeon Acipenser transmontanus in the lower Columbia River.

PubMed

Webb, M A H; Feist, G W; Fitzpatrick, M S; Foster, E P; Schreck, C B; Plumlee, M; Wong, C; Gundersen, D T

2006-04-01

This study determined the partitioning of total mercury in liver, gonad, and cheek muscle of white sturgeon (Acipenser transmonatus) in the lower Columbia River. The relationship between tissue mercury concentrations and various physiologic parameters was assessed. White sturgeon were captured in commercial fisheries in the estuary and Bonneville, The Dalles, and John Day Reservoirs. Condition factor (CF), relative weight (Wr), and gonadosomatic index (GSI) were determined for each fish (n = 57). Gonadal tissue was examined histologically to determine sex and stage of maturity. Liver (n = 49), gonad (n = 49), and cheek muscle (n = 57) were analyzed for total mercury using cold-vapor atomic fluorescence spectrophotometry. Tissue protein concentrations were measured by ultraviolet-visible spectroscopy. Plasma was analyzed for testosterone (T), 11-ketotestosterone (KT), and 17ss-estradiol (E2) using radioimmunoassay. Mean tissue mercury concentrations were higher in muscle compared with liver and gonad at all sampling locations, except Bonneville Reservoir where mean liver mercury content was the highest tissue concentration observed in the study. Significant negative correlations between plasma androgens (T and KT) and muscle mercury content and plasma E2 and liver mercury content were found. A significant positive linear relationship between white sturgeon age and liver mercury concentrations was evident. Significant negative correlations between CF and relative weight and gonad and liver mercury content were found. In addition, immature male sturgeon with increased gonad mercury content had decreased GSIs. These results suggest that mercury, in the form of methylmercury, may have an effect on the reproductive potential of white sturgeon.

Growth of Murine Splenic Tissue Is Suppressed by Lymphotoxin β-Receptor Signaling (LTβR) Originating from Splenic and Non-Splenic Tissues.

PubMed

Milićević, Novica M; Nohroudi, Klaus; Schmidt, Friederike; Schmidt, Hendrik; Ringer, Cornelia; Sorensen, Grith Lykke; Milićević, Živana; Westermann, Jürgen

2016-01-01

Development and maintenance of secondary lymphoid organs such as lymph nodes and spleen essentially depend on lymphotoxin β-receptor (LTβR) signaling. It is unclear, however, by which molecular mechanism their size is limited. Here, we investigate whether the LTβR pathway is also growth suppressing. By using splenic tissue transplantation it is possible to analyze a potential contribution of LTβR signaling inside and outside of the implanted tissue. We show that LTβR signaling within the endogenous spleen and within non-splenic tissues both significantly suppressed the regeneration of implanted splenic tissue. The suppressive activity positively correlated with the total number of LTβR expressing cells in the animal (regenerate weights of 115 ± 8 mg in LTβR deficient recipients and of 12 ± 9 mg in wild-type recipients), affected also developed splenic tissue, and was induced but not executed via LTβR signaling. Two-dimensional differential gel electrophoresis and subsequent mass spectrometry of stromal splenic tissue was applied to screen for potential factors mediating the LTβR dependent suppressive activity. Thus, LTβR dependent growth suppression is involved in regulating the size of secondary lymphoid organs, and might be therapeutically used to eradicate tertiary lymphoid tissues during autoimmune diseases.

Growth of Murine Splenic Tissue Is Suppressed by Lymphotoxin β-Receptor Signaling (LTβR) Originating from Splenic and Non-Splenic Tissues

PubMed Central

Schmidt, Friederike; Schmidt, Hendrik; Ringer, Cornelia; Sorensen, Grith Lykke; Milićević, Živana; Westermann, Jürgen

2016-01-01

Development and maintenance of secondary lymphoid organs such as lymph nodes and spleen essentially depend on lymphotoxin β-receptor (LTβR) signaling. It is unclear, however, by which molecular mechanism their size is limited. Here, we investigate whether the LTβR pathway is also growth suppressing. By using splenic tissue transplantation it is possible to analyze a potential contribution of LTβR signaling inside and outside of the implanted tissue. We show that LTβR signaling within the endogenous spleen and within non-splenic tissues both significantly suppressed the regeneration of implanted splenic tissue. The suppressive activity positively correlated with the total number of LTβR expressing cells in the animal (regenerate weights of 115 ± 8 mg in LTβR deficient recipients and of 12 ± 9 mg in wild-type recipients), affected also developed splenic tissue, and was induced but not executed via LTβR signaling. Two-dimensional differential gel electrophoresis and subsequent mass spectrometry of stromal splenic tissue was applied to screen for potential factors mediating the LTβR dependent suppressive activity. Thus, LTβR dependent growth suppression is involved in regulating the size of secondary lymphoid organs, and might be therapeutically used to eradicate tertiary lymphoid tissues during autoimmune diseases. PMID:27936003

Delay in weight bearing in surgically treated tibial shaft fractures is associated with impaired healing: a cohort analysis of 166 tibial fractures.

PubMed

Houben, I B; Raaben, M; Van Basten Batenburg, M; Blokhuis, T J

2018-04-09

The relation between timing of weight bearing after a fracture and the healing outcome is yet to be established, thereby limiting the implementation of a possibly beneficial effect for our patients. The current study was undertaken to determine the effect of timing of weight bearing after a surgically treated tibial shaft fracture. Surgically treated diaphyseal tibial fractures were retrospectively studied between 2007 and 2015. The timing of initial weight bearing (IWB) was analysed as a predictor for impaired healing in a multivariate regression. Totally, 166 diaphyseal tibial fractures were included, 86 cases with impaired healing and 80 with normal healing. The mean age was 38.7 years (range 16-89). The mean time until IWB was significantly shorter in the normal fracture healing group (2.6 vs 7.4 weeks, p < 0.001). Correlation analysis yielded four possible confounders: infection requiring surgical intervention, fracture type, fasciotomy and open fractures. Logistic regression identified IWB as an independent predictor for impaired healing with an odds ratio of 1.13 per week delay (95% CI 1.03-1.25). Delay in initial weight bearing is independently associated with impaired fracture healing in surgically treated tibial shaft fractures. Unlike other factors such as fracture type or soft tissue condition, early resumption of weight bearing can be influenced by the treating physician and this factor therefore has a direct clinical relevance. This study indicates that early resumption of weight bearing should be the treatment goal in fracture fixation. 3b.

Regulation of the Fibrosis and Angiogenesis Promoter SPARC/Osteonectin in Human Adipose Tissue by Weight Change, Leptin, Insulin, and Glucose

PubMed Central

Kos, Katrina; Wong, Steve; Tan, Bee; Gummesson, Anders; Jernas, Margareta; Franck, Niclas; Kerrigan, David; Nystrom, Fredrik H.; Carlsson, Lena M.S.; Randeva, Harpal S.; Pinkney, Jonathan H.; Wilding, John P.H.

2009-01-01

OBJECTIVE Matricellular Secreted Protein, Acidic and Rich in Cysteine (SPARC), originally discovered in bone as osteonectin, is a mediator of collagen deposition and promotes fibrosis. Adipose tissue collagen has recently been found to be linked with metabolic dysregulation. Therefore, we tested the hypothesis that SPARC in human adipose tissue is influenced by glucose metabolism and adipokines. RESEARCH DESIGN AND METHODS Serum and adipose tissue biopsies were obtained from morbidly obese nondiabetic subjects undergoing bariatric surgery and lean control subjects for analysis of metabolic markers, SPARC, and various cytokines (RT-PCR). Additionally, 24 obese subjects underwent a very-low-calorie diet of 1,883 kJ (450 kcal)/day for 16 weeks and serial subcutaneous-abdominal-adipose tissue (SCAT) biopsies (weight loss: 28 ± 3.7 kg). Another six lean subjects underwent fast-food–based hyperalimentation for 4 weeks (weight gain: 7.2 ± 1.6 kg). Finally, visceral adipose tissue explants were cultured with recombinant leptin, insulin, and glucose, and SPARC mRNA and protein expression determined by Western blot analyses. RESULTS SPARC expression in human adipose tissue correlated with fat mass and was higher in SCAT. Weight loss induced by very-low-calorie diet lowered SPARC expression by 33% and increased by 30% in adipose tissue of subjects gaining weight after a fast-food diet. SPARC expression was correlated with leptin independent of fat mass and correlated with homeostasis model assessment–insulin resistance. In vitro experiments showed that leptin and insulin potently increased SPARC production dose dependently in visceral adipose tissue explants, while glucose decreased SPARC protein. CONCLUSIONS Our data suggest that SPARC expression is predominant in subcutaneous fat and its expression and secretion in adipose tissue are influenced by fat mass, leptin, insulin, and glucose. The profibrotic effects of SPARC may contribute to metabolic dysregulation in obesity. PMID:19509023

The Influence of Smoking on Disability Following Hospitalization for Musculoskeletal Disorders

DTIC Science & Technology

1998-01-01

Physical Medicine and Rehabilitation . 1998 ;79:366-374. Winslow E, Bohannon N, Brunton SA, Mayhew HE. Lifestyle modification: weight control, exercise ...penetrates only its peripheral 10-25%. Thus, smoking’s effect of reducing blood flow may further limit the supply of nutrients to the damaged tissue. This...eliminated during cardiac, stroke, and other types of rehabilitation , it is not yet considered as a risk factor for unsuccessful rehabilitation

Zanthoxylum piperitum DC ethanol extract suppresses fat accumulation in adipocytes and high fat diet-induced obese mice by regulating adipogenesis.

PubMed

Gwon, So Young; Ahn, Ji Yun; Kim, Tae Wan; Ha, Tae Youl

2012-01-01

This study was conducted to determine the anti-obesity effects of Zanthoxylum piperitum DC fruit ethanol extract (ZPE) in 3T3-L1 adipocytes and obese mice fed a high-fat diet. We evaluated the influence of the addition of ZPE to a high-fat diet on body weight, adipose tissue weight, serum and hepatic lipids in C57BL/6 mice. In addition, adipogenic gene expression was determined by Western blot and real-time reverse transcription-PCR analysis. We assessed the effect of ZPE on 3T3-L1 preadipocyte differentiation. ZPE reduced weight gain, white adipose tissue mass, and serum triglyceride and cholesterol levels (p<0.05) in high-fat diet-fed C57BL/6 mice. ZPE decreased lipid accumulation and PPARγ, C/EBPα, SREBP-1, and FAS protein and mRNA levels in the liver. ZPE inhibited in vitro adipocyte differentiation in a dose-dependent manner and significantly attenuated adipogenic transcription factors, such as PPARγ, C/EBPα, and SREBP-1 in 3T3L1 cells. These findings suggest that Z. piperitum DC exerts an anti-obesity effect by inhibiting adipogenesis through the downregulation of genes involved in the adipogenesis pathway.

The influence of bioglass nanoparticles on the biodegradation and biocompatibility of poly (3-hydroxybutyrate) scaffolds.

PubMed

Hajiali, Hadi; Hosseinalipour, Mohammad; Karbasi, Saeed; Shokrgozar, Mohammad Ali

2012-11-01

Nanocomposite scaffolds have been developed in order to achieve better mechanical and physiological properties in bone tissue engineering applications. In this study, reinforced poly (3-hydroxybutyrate) (PHB) composite scaffolds made with different weight ratios of nanobioglass (0, 2.5, 5, 7.5, and 10 wt%) and various porosities (70, 80 and 90 wt% of NaCl) were prepared by the salt leaching process. The scaffolds were placed in a PBS solution and their weight loss was measured. The biocompatibility of samples was examined in vitro using the MG63 cell line by indirect test, cell proliferation, and alkaline phosphatase (ALP) assays. Cell attachment on the surface of the scaffolds was observed by scanning electron microscopy (SEM). The biodegradation results showed that increasing the volume fraction of porosity and concentration of bioglass nanoparticles enhanced the weight loss of the scaffolds. The cell study demonstrated that a certain concentration of nanobioglass (7.5 wt%) in the scaffolds can significantly improve cell proliferation, inducing better osteoconductivity, compared to that of the pure PHB scaffolds and controls. In addition, the SEM results showed high cell attachment on these samples. All these factors indicate that samples with 7.5 wt% nanobioglass are a promising scaffold for bone tissue engineering.

Estimation of ellagic acid and/or repaglinide effects on insulin signaling, oxidative stress, and inflammatory mediators of liver, pancreas, adipose tissue, and brain in insulin resistant/type 2 diabetic rats.

PubMed

Amin, Mohamed M; Arbid, Mahmoud S

2017-02-01

Even though ellagic acid has previously been valued in many models of cancer, so far its full mechanistic effect as a natural antiapoptotic agent in the prevention of type 2 diabetes complications has not been completely elucidated, which was the goal of this study. We fed albino rats a high-fat fructose diet (HFFD) for 2 months to induce insulin resistance/type 2 diabetes and then treated the rats with ellagic acid (10 mg/kg body weight, orally) and/or repaglinide (0.5 mg/kg body weight, orally) for 2 weeks. At the serum level, ellagic acid challenged the consequences of HFFD, significantly improving the glucose/insulin balance, liver enzymes, lipid profile, inflammatory cytokines, redox level, adipokines, ammonia, and manganese. At the tissue level (liver, pancreas, adipose tissue, and brain), ellagic acid significantly enhanced insulin signaling, autophosphorylation, adiponectin receptors, glucose transporters, inflammatory mediators, and apoptotic markers. Remarkably, combined treatment with both ellagic acid and repaglinide had a more pronounced effect than treatment with either alone. These outcomes give new insight into the promising molecular mechanisms by which ellagic acid modulates numerous factors induced in the progression of diabetes.

Maternal obesity and overnutrition alter fetal growth rate and cotyledonary vascularity and angiogenic factor expression in the ewe.

PubMed

Ma, Yan; Zhu, Mei J; Zhang, Liren; Hein, Sarah M; Nathanielsz, Peter W; Ford, Stephen P

2010-07-01

In pregnant sheep, maternal:fetal exchange occurs across placentomes composed of placental cotyledonary and uterine caruncular tissues. Recently, we reported that fetal weights of obese (OB) ewes [fed a diet of 150% of National Research Council (NRC) recommendations] were approximately 30% greater than those of control (C) ewes (fed a diet 100% of NRC recommendations) at midgestation (MG), but fetal weights were similar in late gestation (LG). Transplacental nutrient exchange is dependent on placental blood flow, which itself is dependent on placental vascularity. The current study investigated whether the observed initial faster and subsequent slower fetal growth rate of OB compared with C was associated with changes in cotyledonary vascularity and expression of angiogenic factors (vascular endothelial growth factor, fibroblast growth factor-2, placental growth factor, angiopoietin-1 and -2). Cotyledonary arteriole diameters were markedly greater (P < 0.05) in OB than C ewes at MG, but while arteriole diameter of C ewes increased (P < 0.05) from MG to LG, they remained unchanged in OB ewes. Cotyledonary arterial angiogenic factors mRNA and protein expression were lower (P < 0.05) in OB than C ewes at MG and remained low from MG to LG. In contrast, mRNA levels of angiogenic factors in C ewes declined from high levels at MG to reach those of OB ewes by LG. The increase in cotyledonary arteriole diameter in early to MG may function to accelerate fetal growth rate in OB ewes, while the decreased cotyledonary arterial angiogenic factors from MG-LG may function to protect the fetus from excessive placental vascular development, increased maternal nutrient delivery, and excessive weight gain.

Maternal obesity and overnutrition alter fetal growth rate and cotyledonary vascularity and angiogenic factor expression in the ewe

PubMed Central

Ma, Yan; Zhu, Mei J.; Zhang, Liren; Hein, Sarah M.; Nathanielsz, Peter W.

2010-01-01

In pregnant sheep, maternal:fetal exchange occurs across placentomes composed of placental cotyledonary and uterine caruncular tissues. Recently, we reported that fetal weights of obese (OB) ewes [fed a diet of 150% of National Research Council (NRC) recommendations] were ∼30% greater than those of control (C) ewes (fed a diet 100% of NRC recommendations) at midgestation (MG), but fetal weights were similar in late gestation (LG). Transplacental nutrient exchange is dependent on placental blood flow, which itself is dependent on placental vascularity. The current study investigated whether the observed initial faster and subsequent slower fetal growth rate of OB compared with C was associated with changes in cotyledonary vascularity and expression of angiogenic factors (vascular endothelial growth factor, fibroblast growth factor-2, placental growth factor, angiopoietin-1 and -2). Cotyledonary arteriole diameters were markedly greater (P < 0.05) in OB than C ewes at MG, but while arteriole diameter of C ewes increased (P < 0.05) from MG to LG, they remained unchanged in OB ewes. Cotyledonary arterial angiogenic factors mRNA and protein expression were lower (P < 0.05) in OB than C ewes at MG and remained low from MG to LG. In contrast, mRNA levels of angiogenic factors in C ewes declined from high levels at MG to reach those of OB ewes by LG. The increase in cotyledonary arteriole diameter in early to MG may function to accelerate fetal growth rate in OB ewes, while the decreased cotyledonary arterial angiogenic factors from MG-LG may function to protect the fetus from excessive placental vascular development, increased maternal nutrient delivery, and excessive weight gain. PMID:20427725

The effects on weight loss and gene expression in adipose and hepatic tissues of very-low carbohydrate and low-fat isoenergetic diets in diet-induced obese mice.

PubMed

Yamazaki, Tomomi; Okawa, Sumire; Takahashi, Mayumi

2016-01-01

Obesity is caused by excessive fat or carbohydrate intake. The improvement of obesity is an important issue, especially in Western societies. Both low-carbohydrate diet (LCD) and low-fat diet (LFD) are used to achieve weight loss in humans. To clarify the mechanisms underlying LCD-induced weight loss, especially in early stage, we compared the gene expression in liver, white adipose tissue (WAT) and brown adipose tissue (BAT) of a very-low carbohydrate diet (VLCD)- and LFD-fed diet-induced obese (DIO) mice. DIO male ddY mice were divided into high-fat diet (HFD), and isoenergetic VLCD and LFD groups. Pair-feeding was performed in the VLCD and LFD groups. Three weeks later, the body, liver, WAT and BAT were weighed and the serum and hepatic lipids, the mRNA expression levels in each tissue, and energy metabolism were analyzed. The caloric intake of the VLCD-fed mice was initially reduced but was subsequently restored. The total energy intake was similar in the VLCD- and LFD-fed mice. There was a similar decrease in the BW of the VLCD- and LFD-fed mice. The VLCD-fed mice had elevated levels of serum fibroblast growth factor 21 (FGF21) and ketone bodies, which are known to increase energy expenditure. The browning of WAT was observed to a greater extent in the VLCD-fed mice. Moreover, in the VLCD-fed mice, BAT activation was observed, the weight of the BAT was decreased, and the expression of G-protein-coupled receptor 120, type 2 iodothyronine deiodinase, and FGF21 in BAT was extremely increased. Although the energy expenditure of the VLCD- and LFD-fed mice did not differ, that of the VLCD-fed mice was sometimes higher during the dark cycle. Hepatic TG accumulation was reduced in LFD-fed mice due to their decreased fatty acid uptake but not in the VLCD-fed mice. The pro-inflammatory macrophage ratio was increased in the WAT of VLCD-fed mice. After 3 weeks, the isoenergetic VLCD- and LFD-fed DIO mice showed similar weight loss. The VLCD-fed mice increased serum concentration of FGF21 and ketone bodies, and marker mRNA levels of browning in WAT, activation in BAT and hepatic lipogenesis.

Does atrial natriuretic factor protect against right ventricular overload II. Tissue binding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ou, L.C.; Yen, S.; Sardella, G.L.

1989-10-01

Previous studies have led us to hypothesize that the physiological significance of the diuretic and pulmonary vaso-relaxant effects of atrial natriuretic factor (ANF) is to protect the right heart. This study was designed to evaluate the relative importance of various peripheral tissues as sites of ANF action by tracing the temporal pattern of distribution of {sup 125}I-ANF and quantitating the specific binding sites. An in vivo approach, utilizing trace amount of {sup 125}I-ANF was adopted to simulate physiological conditions. {sup 125}I-ANF injected either intravenously or intra-arterially was quickly bound to peripheral tissues with less than 5% remaining in the circulationmore » after 1 min. The relative binding capacity was greatest in the lung, followed by the kidney, right ventricle, adrenal gland, and left ventricle. The magnitude of specific ANF binding sites per gram of tissue weight followed a similar order. The data demonstrate that ANF released under all circumstances is quickly bound to the target organs, particularly the lung and the kidney, and suggest that these two organs could be the most important target organs of ANF. This evidence provides further support for the proposed hypothesis that a major evolutionary role of ANF is the protection of the right ventricle from mechanical loads.« less

[Systemic and local mechanisms leading to cachexia in cancer].

PubMed

Grabiec, Kamil; Burchert, Marta; Milewska, Marta; Błaszczyk, Maciej; Grzelkowska-Kowalczyk, Katarzyna

2013-12-31

Cachexia is a multifactorial syndrome of atrophy of skeletal muscle and adipose tissue, resulting in progressive loss of body weight associated with low quality of life and poor prognosis in cancer. Studies on experimental animal models and observations on patients have shown that the soluble factors secreted by tumor cells and tissues of the patient can participate in regulation of the wasting process. Cachexia is often accompanied by anorexia, which is caused by predominance of signals inhibiting appetite in the hypothalamus, such as release of proopiomelanocortin and anorexigenic action of proinflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α). Cachexia is also accompanied by extensive metabolic changes consisting of increase of resting energy expenditure and disturbance of carbohydrate, protein and lipid metabolism. Increased expression of protein uncoupling phosphorylation leads to increased thermogenesis in skeletal muscle. Tumor tissue hypoxia caused by its growth beyond blood vessels activates the transcription factor HIF-1, which results in increase in glycolysis, and leads to lactic acid accumulation and activation of the energy inefficient Cori cycle. Loss of fat tissue is caused by increase of lipolysis induced by lipid-mobilizing factor (LMF) and proinflammatory cytokines. Skeletal muscle wasting in cachexia is caused by a reduction of protein synthesis at the stage of initiation and elongation of translation and the simultaneous increase of protein degradation via ubiquitin-dependent and lysosomal pathways. The main mediators of skeletal muscle wasting in cancer are proteolysis-inducing factor (PIF), proinflammatory cytokines, and angiotensin II acting through increased levels of reactive oxygen species (ROS) and nuclear factor NF-κB activation, as well as glucocorticoid activated FOXO transcription factors and myostatin. Understanding of the complexity of the interaction of factors produced by the tumor and the patient's body may form the basis for the development of effective treatments for cachexia in cancer and other pathological conditions.

[Effects of excess folic acid on growth and metabolism of water-soluble vitamins in weaning rats].

PubMed

Fukuwatari, Tsutomu; Shibata, Katsumi

2008-02-01

In order to determine the tolerable upper intake level of folic acid in humans, we investigated the effects of excessive folic acid administration on the body weight gain, food intake, tissue weight, and metabolism of B-group vitamins in weaning rats. The rats were freely fed ordinary diet containing 0.0002% folic acid (control diet) or the same diet with 0.01%, 0.1%, or 1.0% folic acid for 29 days. The body weight gains and food intakes did not differ among the four groups. Diarrhea was not seen even in the 1.0% group. Excess folic acid did not affect the tissue weights of the brain, heart, liver, kidney, spleen, lung, or testis, or urinary excretion of other B-group vitamins. These results clearly showed that feeding a diet containing up to 1.0% folic acid did not affect the food intake, body weight gain, tissue weight, or urinary excretion of B-group vitamins in weaning rats.

Dechlorane Plus flame retardant in terrestrial raptors from northern China.

PubMed

Chen, Da; Wang, Yan; Yu, Lehuan; Luo, Xiaojun; Mai, Bixian; Li, Shaoshan

2013-05-01

While a number of studies have addressed the environmental presence and behavior of the Dechlorane Plus (DP) flame retardant, there is still a dearth of information in terrestrial ecosystems. The present study revealed that median ∑DP (including anti- and syn-DP isomers) concentrations ranged from 10 to 810 ng/g lipid weight in muscle and liver tissues of six terrestrial raptor species collected in 2004-2006 from Beijing, China. Some concentrations rival the greatest DP burdens ever reported in global wildlife. Significant, positive correlations were observed between fanti (concentration ratio of anti-isomer to ∑DP) and ∑DP concentrations in the Eurasian sparrowhawk (Accipiter nisus) tissues. These results suggested that the DP burdens could be substantially driven by the accumulation of the anti-isomer in terrestrial birds. The tissue-specific accumulation of DP further suggested that factors (e.g., hepatic binding enzymes) other than lipid solubility could be important in determining tissue deposition of DP. Copyright © 2013 Elsevier Ltd. All rights reserved.

Multispectral image enhancement for H&E stained pathological tissue specimens

NASA Astrophysics Data System (ADS)

Bautista, Pinky A.; Abe, Tokiya; Yamaguchi, Masahiro; Ohyama, Nagaaki; Yagi, Yukako

2008-03-01

The presence of a liver disease such as cirrhosis can be determined by examining the proliferation of collagen fiber from a tissue slide stained with special stain such as the Masson's trichrome(MT) stain. Collagen fiber and smooth muscle, which are both stained the same in an H&E stained slide, are stained blue and pink respectively in an MT-stained slide. In this paper we show that with multispectral imaging the difference between collagen fiber and smooth muscle can be visualized even from an H&E stained image. In the method M KL bases are derived using the spectral data of those H&E stained tissue components which can be easily differentiated from each other, i.e. nucleus, cytoplasm, red blood cells, etc. and based on the spectral residual error of fiber weighting factors are determined to enhance spectral features at certain wavelengths. Results of our experiment demonstrate the capability of multispectral imaging and its advantage compared to the conventional RGB imaging systems to delineate tissue structures with subtle colorimetric difference.

Amelioration of estrogen-deficiency-induced obesity by Ocimum gratissimum

PubMed Central

Chao, Pei-Yu; Chiang, Tsay-I; Chang, I-Chang; Tsai, Fang-Ling; Lee, Hsueh-Hui; Hsieh, Kuanghui; Chiu, Yung-Wei; Lai, Te-Jen; Liu, Jer-Yuh; Hsu, Li-Sung; Shih, Yang-Chia

2017-01-01

Objectives: Menopausal transition in women initiates with declining estrogen levels and is followed by significant changes in their physiological characteristics. These changes often lead to medical conditions, such as obesity, which is correlated with chronic low-grade/subclinical inflammation. Ocimum gratissimum L. is a food spice or traditional herb in many countries; the plant is rich in antioxidants, which possess anti-inflammation activities and multitude of other therapeutic functions. Methods: In this study, we evaluated effects of O. gratissimum extract (OGE) in preventing obesity by using ovariectomized (OVX) animal models to mimic menopausal women. Methods: OVX rats showed increase in body weight and in adipocyte size in perigonadal adipose tissue (p <0.05) and decrease in uterus weight. By contrast, OGE (0.2 mg/ml) significantly reduced body weight gain and adipocyte in OVX rats and showed insignificant changes in uterus weight. Further investigation indicated that OGE exerted no influence on levels of dorsal fat, serum total cholesterol, and serum triacylglycerol and on serum biochemical factors, calcium, phosphorus, and glucose. Conclusion: These findings suggested that OGE dietary supplements may be useful in controlling body weight of menopausal women. PMID:28824328

Amelioration of estrogen-deficiency-induced obesity by Ocimum gratissimum.

PubMed

Chao, Pei-Yu; Chiang, Tsay-I; Chang, I-Chang; Tsai, Fang-Ling; Lee, Hsueh-Hui; Hsieh, Kuanghui; Chiu, Yung-Wei; Lai, Te-Jen; Liu, Jer-Yuh; Hsu, Li-Sung; Shih, Yang-Chia

2017-01-01

Objectives: Menopausal transition in women initiates with declining estrogen levels and is followed by significant changes in their physiological characteristics. These changes often lead to medical conditions, such as obesity, which is correlated with chronic low-grade/subclinical inflammation. Ocimum gratissimum L. is a food spice or traditional herb in many countries; the plant is rich in antioxidants, which possess anti-inflammation activities and multitude of other therapeutic functions. Methods: In this study, we evaluated effects of O . gratissimum extract (OGE) in preventing obesity by using ovariectomized (OVX) animal models to mimic menopausal women. Methods: OVX rats showed increase in body weight and in adipocyte size in perigonadal adipose tissue ( p <0.05) and decrease in uterus weight. By contrast, OGE (0.2 mg/ml) significantly reduced body weight gain and adipocyte in OVX rats and showed insignificant changes in uterus weight. Further investigation indicated that OGE exerted no influence on levels of dorsal fat, serum total cholesterol, and serum triacylglycerol and on serum biochemical factors, calcium, phosphorus, and glucose. Conclusion: These findings suggested that OGE dietary supplements may be useful in controlling body weight of menopausal women.

Postmenopausal weight status, body composition and body fat distribution in relation to parameters of menstrual and reproductive history.

PubMed

Kirchengast, S; Gruber, D; Sator, M; Huber, J

1999-10-24

In the present study the association between menstrual and reproductive history patterns and weight status, fat distribution and body composition during postmenopause was tested. In 106 healthy postmenopausal women ranging in age from 48 to 58 years (x = 53.7 year) the weight status was classified according to the recommendations of the WHO. Additionally body composition was estimated by dual energy X-ray absorptiometry and fat distribution was calculated using the fat distribution index. Weight status, body composition and fat distribution were correlated with self-reported parameters of menstrual and reproductive history (age at menarche, average cycle length, number of births, age at first and last birth, average pregnancy weight gain, age at menopause). It was shown that number of births, age at first birth and pregnancy weight gain were related significantly to the postmenopausal weight status, body composition and fat distribution. An early first birth a low number of births and a high weight gain during pregnancies can be assumed as risk factors for overweight, a higher amount of adipose tissue, android fat patterning and therefore for the development of the metabolic syndrome during postmenopause. In contrast no adverse effect of menstrual and reproductive parameters on postmenopausal bone mass was found.

Effects of Platelet-Rich Plasma (PRP) on a Model of Renal Ischemia-Reperfusion in Rats.

PubMed

Martín-Solé, Oriol; Rodó, Joan; García-Aparicio, Lluís; Blanch, Josep; Cusí, Victoria; Albert, Asteria

2016-01-01

Renal ischemia-reperfusion injury is a major cause of acute renal failure, causing renal cell death, a permanent decrease of renal blood flow, organ dysfunction and chronic kidney disease. Platelet-rich plasma (PRP) is an autologous product rich in growth factors, and therefore able to promote tissue regeneration and angiogenesis. This product has proven its efficacy in multiple studies, but has not yet been tested on kidney tissue. The aim of this work is to evaluate whether the application of PRP to rat kidneys undergoing ischemia-reperfusion reduces mid-term kidney damage. A total of 30 monorrenal Sprague-Dawley male rats underwent renal ischemia-reperfusion for 45 minutes. During ischemia, PRP (PRP Group, n = 15) or saline solution (SALINE Group, n = 15) was administered by subcapsular renal injection. Control kidneys were the contralateral organs removed immediately before the start of ischemia in the remaining kidneys. Survival, body weight, renal blood flow on Doppler ultrasound, kidney weight, kidney volume, blood biochemistry and histopathology were determined for all subjects and kidneys, as applicable. Correlations between these variables were searched for. The PRP Group showed significantly worse kidney blood flow (p = 0.045) and more histopathological damage (p<0.0001). Correlations were found between body weight, kidney volume, kidney weight, renal blood flow, histology, and serum levels of creatinine and urea. Our study provides the first evidence that treatment with PRP results in the deterioration of the kidney's response to ischemia-reperfusion injury.

Effects of Platelet-Rich Plasma (PRP) on a Model of Renal Ischemia-Reperfusion in Rats

PubMed Central

Martín-Solé, Oriol; Rodó, Joan; García-Aparicio, Lluís; Blanch, Josep; Cusí, Victoria; Albert, Asteria

2016-01-01

Renal ischemia-reperfusion injury is a major cause of acute renal failure, causing renal cell death, a permanent decrease of renal blood flow, organ dysfunction and chronic kidney disease. Platelet-rich plasma (PRP) is an autologous product rich in growth factors, and therefore able to promote tissue regeneration and angiogenesis. This product has proven its efficacy in multiple studies, but has not yet been tested on kidney tissue. The aim of this work is to evaluate whether the application of PRP to rat kidneys undergoing ischemia-reperfusion reduces mid-term kidney damage. A total of 30 monorrenal Sprague-Dawley male rats underwent renal ischemia-reperfusion for 45 minutes. During ischemia, PRP (PRP Group, n = 15) or saline solution (SALINE Group, n = 15) was administered by subcapsular renal injection. Control kidneys were the contralateral organs removed immediately before the start of ischemia in the remaining kidneys. Survival, body weight, renal blood flow on Doppler ultrasound, kidney weight, kidney volume, blood biochemistry and histopathology were determined for all subjects and kidneys, as applicable. Correlations between these variables were searched for. The PRP Group showed significantly worse kidney blood flow (p = 0.045) and more histopathological damage (p<0.0001). Correlations were found between body weight, kidney volume, kidney weight, renal blood flow, histology, and serum levels of creatinine and urea. Our study provides the first evidence that treatment with PRP results in the deterioration of the kidney’s response to ischemia-reperfusion injury. PMID:27551718

Nicotine improves obesity and hepatic steatosis and ER stress in diet-induced obese male rats.

PubMed

Seoane-Collazo, Patricia; Martínez de Morentin, Pablo B; Fernø, Johan; Diéguez, Carlos; Nogueiras, Rubén; López, Miguel

2014-05-01

Nicotine, the main addictive component of tobacco, promotes body weight reduction in humans and rodents. Recent evidence has suggested that nicotine acts in the central nervous system to modulate energy balance. Specifically, nicotine modulates hypothalamic AMP-activated protein kinase to decrease feeding and to increase brown adipose tissue thermogenesis through the sympathetic nervous system, leading to weight loss. Of note, most of this evidence has been obtained in animal models fed with normal diet or low-fat diet (LFD). However, its effectiveness in obese models remains elusive. Because obesity causes resistance towards many factors involved in energy homeostasis, the aim of this study has been to compare the effect of nicotine in a diet-induced obese (DIO) model, namely rats fed a high-fat diet, with rats fed a LFD. Our data show that chronic peripheral nicotine treatment reduced body weight by decreasing food intake and increasing brown adipose tissue thermogenesis in both LFD and DIO rats. This overall negative energy balance was associated to decreased activation of hypothalamic AMP-activated protein kinase in both models. Furthermore, nicotine improved serum lipid profile, decreased insulin serum levels, as well as reduced steatosis, inflammation, and endoplasmic reticulum stress in the liver of DIO rats but not in LFD rats. Overall, this evidence suggests that nicotine diminishes body weight and improves metabolic disorders linked to DIO and might offer a clear-cut strategy to develop new therapeutic approaches against obesity and its metabolic complications.

Anomalously Fast Diffusion of Targeted Carbon Nanotubes in Cellular Spheroids.

PubMed

Wang, Yichun; Bahng, Joong Hwan; Che, Quantong; Han, Jishu; Kotov, Nicholas A

2015-08-25

Understanding transport of carbon nanotubes (CNTs) and other nanocarriers within tissues is essential for biomedical imaging and drug delivery using these carriers. Compared to traditional cell cultures in animal studies, three-dimensional tissue replicas approach the complexity of the actual organs and enable high temporal and spatial resolution of the carrier permeation. We investigated diffusional transport of CNTs in highly uniform spheroids of hepatocellular carcinoma and found that apparent diffusion coefficients of CNTs in these tissue replicas are anomalously high and comparable to diffusion rates of similarly charged molecules with molecular weights 10000× lower. Moreover, diffusivity of CNTs in tissues is enhanced after functionalization with transforming growth factor β1. This unexpected trend contradicts predictions of the Stokes-Einstein equation and previously obtained empirical dependences of diffusivity on molecular mass for permeants in gas, liquid, solid or gel. It is attributed to the planar diffusion (gliding) of CNTs along cellular membranes reducing effective dimensionality of diffusional space. These findings indicate that nanotubes and potentially similar nanostructures are capable of fast and deep permeation into the tissue, which is often difficult to realize with anticancer agents.

'Multi-associations': predisposed to misinterpretation of peripheral tissue oxygenation and circulation in neonates.

PubMed

Pichler, Gerhard; Pocivalnik, Mirjam; Riedl, Regina; Pichler-Stachl, Elisabeth; Morris, Nicholas; Zotter, Heinz; Müller, Wilhelm; Urlesberger, Berndt

2011-08-01

Interpretation of peripheral circulation in ill neonates is crucial but difficult. The aim was to analyse parameters potentially influencing peripheral oxygenation and circulation. In a prospective observational cohort study in 116 cardio-circulatory stable neonates, peripheral muscle near-infrared spectroscopy (NIRS) with venous occlusion was performed. Tissue oxygenation index (TOI), mixed venous oxygenation (SvO(2)), fractional oxygen extraction (FOE), fractional tissue oxygen extraction (FTOE), haemoglobin flow (Hbflow), oxygen delivery (DO(2)), oxygen consumption (VO(2)), and vascular resistance (VR) were assessed. Correlation coefficients between NIRS parameters and demographic parameters (gestational age, birth weight, age, actual weight, diameter of calf, subcutaneous adipose tissue), monitoring parameters (heart rate, arterial oxygen saturation (SaO(2)), mean blood pressure (MAP), core/peripheral temperature, central/peripheral capillary refill time) and laboratory parameters (haemoglobin concentration (Hb-blood), pCO(2)) were calculated. All demographic parameters except for Hbflow and DO(2) correlated with NIRS parameters. Heart rate correlated with TOI, SvO(2), VO(2) and VR. SaO(2) correlated with FOE/FTOE. MAP correlated with Hbflow, DO(2), VO(2) and VR. Core temperature correlated with FTOE. Peripheral temperature correlated with all NIRS parameters except VO(2). Hb-blood correlated with FOE and VR. pCO(2) levels correlated with TOI and SvO(2). The presence of multiple interdependent factors associated with peripheral oxygenation and circulation highlights the difficulty in interpreting NIRS data. Nevertheless, these findings have to be taken into account when analysing peripheral oxygenation and circulation data.

Effects of biological and technical factors on brain and muscle cholinesterases in Nile tilapia, Oreochromis niloticus: implications for biomonitoring neurotoxic contaminations.

PubMed

Pathiratne, A; Chandrasekera, L W H U; De Seram, P K C

2008-02-01

Influence of body length, body weight, gender, sexual maturity, and tissue storage on brain and muscle cholinesterases (ChE) in Nile tilapia was evaluated considering its potential use in biomonitoring neurotoxic contaminations in tropical environments. Results show that ChE activities in both tissues decreased significantly with increased total length (4-24.5 cm) or body weight (1-186 g) of the fish and the relationships were curvilinear. Comparisons of the slopes and elevations of the regression lines of the logarithmic ChE and body size relationships of males with those of females indicated that gender had no significant effect on the body size-specific ChE activities. Response of the ChE of sexually mature males to chlorpyrifos exposure was similar to that of females. Gonadal maturity stage of this fish does not seem to influence ChE activities. Storage of tissues at -80 degrees C for 28 days had no significant effect on ChE activities in the control fish and the fish exposed to carbofuran. However, a partial reactivation of brain ChE activities was observed in the fish exposed to carbosulfan after 28 days of storage. The results emphasize the importance of consideration of body size of the fish and storage time of the tissues in order to formulate accurate conclusions about the neurotoxic chemical exposure when ChE of the fish is used in biomonitoring programs.

A rapid total reflection X-ray fluorescence protocol for micro analyses of ion profiles in Arabidopsis thaliana

NASA Astrophysics Data System (ADS)

Höhner, Ricarda; Tabatabaei, Samaneh; Kunz, Hans-Henning; Fittschen, Ursula

2016-11-01

The ion homeostasis of macro and micronutrients in plant cells and tissues is a fundamental requirement for vital biochemical pathways including photosynthesis. In nature, ion homeostasis is affected mainly by three processes: 1. Environmental stress factors, 2. Developmental effects, and 3. Loss or gain-of-function mutations in the plant genome. Here we present a rapid total reflection X-ray fluorescence (TXRF) protocol that allows for simultaneous quantification of several elements such as potassium (K), calcium (Ca), sulfur (S), manganese (Mn) and strontium (Sr) in Arabidopsis thaliana leaf specimens. Our procedure is cost-efficient and enables precise, robust and highly reproducible measurements on tissue samples as small as 0.3 mg dry weight. As shown here, we apply the TXRF procedure to detect accurately the early replacement of K by Na ions in leaves of plants exposed to soil salinity, a globally increasing abiotic stress factor. Furthermore, we were able to prove the existence of a leaf development-dependent ion gradient for K, Ca, and other divalent ions in A. thaliana; i.e. old leaves contain significantly lower K but higher Ca than young leaves. Lastly, we show that our procedure can be readily applied to reveal subtle differences in tissue-specific ion contents of plant mutants. We employed independent A. thaliana kea1kea2 loss-of-function mutants that lack KEA1 and KEA2, two highly active chloroplast K exchange proteins. We found significantly increased K levels specifically in kea1kea2 mutants, i.e. 55 mg ∗ g- 1 dry weight, compared to 40 mg ∗ g- 1 dry weight in wild type plants. The TXRF procedure can be supplemented with Flame atomic absorption (FAAS) and emission spectrometry (FAES) to expand the detection range to sodium (Na) and magnesium (Mg). Because of the small sample amounts required, this method is especially suited to probe individual leaves in single plants or even specific leaf areas. Therefore, TXRF represents a powerful method to gain detailed quantitative insights into I) the effect of environmental stress on plant ion homeostasis, II) ion gradients between plant tissues, and III) ion levels in plant mutants with compromised growth or heterogeneous phenotypes.

Diet-Induced Obesity Affects Muscle Regeneration After Murine Blunt Muscle Trauma-A Broad Spectrum Analysis.

PubMed

Xu, Pengfei; Werner, Jens-Uwe; Milerski, Sebastian; Hamp, Carmen M; Kuzenko, Tatjana; Jähnert, Markus; Gottmann, Pascal; de Roy, Luisa; Warnecke, Daniela; Abaei, Alireza; Palmer, Annette; Huber-Lang, Markus; Dürselen, Lutz; Rasche, Volker; Schürmann, Annette; Wabitsch, Martin; Knippschild, Uwe

2018-01-01

Injury to skeletal muscle affects millions of people worldwide. The underlying regenerative process however, is a very complex mechanism, time-wise highly coordinated, and subdivided in an initial inflammatory, a regenerative and a remodeling phase. Muscle regeneration can be impaired by several factors, among them diet-induced obesity (DIO). In order to evaluate if obesity negatively affects healing processes after trauma, we utilized a blunt injury approach to damage the extensor iliotibialis anticus muscle on the left hind limb of obese and normal weight C57BL/6J without showing any significant differences in force input between normal weight and obese mice. Magnetic resonance imaging (MRI) of the injury and regeneration process revealed edema formation and hemorrhage exudate in muscle tissue of normal weight and obese mice. In addition, morphological analysis of physiological changes revealed tissue necrosis, immune cell infiltration, extracellular matrix (ECM) remodeling, and fibrosis formation in the damaged muscle tissue. Regeneration was delayed in muscles of obese mice, with a higher incidence of fibrosis formation due to hampered expression levels of genes involved in ECM organization. Furthermore, a detailed molecular fingerprint in different stages of muscle regeneration underlined a delay or even lack of a regenerative response to injury in obese mice. A time-lapse heatmap determined 81 differentially expressed genes (DEG) with at least three hits in our model at all-time points, suggesting key candidates with a high impact on muscle regeneration. Pathway analysis of the DEG revealed five pathways with a high confidence level: myeloid leukocyte migration, regulation of tumor necrosis factor production, CD4-positive, alpha-beta T cell differentiation, ECM organization, and toll-like receptor (TLR) signaling. Moreover, changes in complement-, Wnt-, and satellite cell-related genes were found to be impaired in obese animals after trauma. Furthermore, histological satellite cell evaluation showed lower satellite cell numbers in the obese model upon injury. Ankrd1, C3ar1, Ccl8, Mpeg1 , and Myog expression levels were also verified by qPCR. In summary, increased fibrosis formation, the reduction of Pax7 + satellite cells as well as specific changes in gene expression and signaling pathways could explain the delay of tissue regeneration in obese mice post trauma.

Mechanism of body weight reducing effect of oral boric Acid intake.

PubMed

Aysan, Erhan; Sahin, Fikrettin; Telci, Dilek; Erdem, Merve; Muslumanoglu, Mahmut; Yardımcı, Erkan; Bektasoglu, Huseyin

2013-01-01

Objective. The effect of oral boric acid intake on reducing body weight has been previously demonstrated although the mechanism has been unclear. This research study reveals the mechanism. Subjects. Twelve mice were used, in groups of six each in the control and study groups. For five days, control group mice drank standard tap water while during the same time period the study group mice drank tap water which contains 0.28 mg/250 mL boric acid. After a 5-day period, gene expression levels for uncoupling proteins (UCPs) in the white adipose tissue (WAT), brown adipose tissue (BAT), and skeletal muscle tissue (SMT) and total body weight changes were analyzed. Results. Real time PCR analysis revealed no significant change in UCP3 expressions, but UCP2 in WAT (P: 0.0317), BAT (P: 0.014), and SMT (P: 0.0159) and UCP1 in BAT (P: 0.026) were overexpressed in the boric acid group. In addition, mice in the boric acid group lost body weight (mean 28.1%) while mice in the control group experienced no weight loss but a slight weight gain (mean 0.09%, P < 0.001). Conclusion. Oral boric acid intake causes overexpression of thermogenic proteins in the adipose and skeletal muscle tissues. Increasing thermogenesis through UCP protein pathway results in the accelerated lipolysis and body weight loss.

An approach to assessing stochastic radiogenic risk in medical imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolbarst, Anthony B.; Hendee, William R.; Department of Radiology, Mayo Clinic, Rochester, Minnesota 55901

2011-12-15

Purpose: This letter suggests a formalism, the medical effective dose (MED), that is suitable for assessing stochastic radiogenic risks in diagnostic medical procedures. Methods: The MED is derived from radiobiological and probabilistic first principals, including: (1) The independence of radiation-induced biological effects in neighboring voxels at low doses; (2) the linear no-threshold assumption for stochastic radiation injury (although other dose-response relationships could be incorporated, instead); (3) the best human radiation dose-response data currently available; and (4) the built-in possibility that the carcinogenic risk to an irradiated organ may depend on its volume. The MED involves a dose-risk summation over irradiatedmore » voxels at high spatial resolution; it reduces to the traditional effective dose when every organ is irradiated uniformly and when the dependence of risk on organ volumes is ignored. Standard relative-risk tissue weighting factors can be used with the MED approach until more refined data become available. Results: The MED is intended for clinical and phantom dosimetry, and it provides an estimate of overall relative radiogenic stochastic risk for any given dose distribution. A result of the MED derivation is that the stochastic risk may increase with the volume of tissue (i.e., the number of cells) irradiated, a feature that can be activated when forthcoming radiobiological research warrants it. In this regard, the MED resembles neither the standard effective dose (E) nor the CT dose index (CTDI), but it is somewhat like the CT dose-length product (DLP). Conclusions: The MED is a novel, probabilistically and biologically based means of estimating stochastic-risk-weighted doses associated with medical imaging. Built in, ab initio, is the ability to link radiogenic risk to organ volume and other clinical factors. It is straightforward to implement when medical dose distributions are available, provided that one is content, for the time being, to accept the relative tissue weighting factors published by the International Commission of Radiological Protection (ICRP). It requires no new radiobiological data and avoids major problems encountered by the E, CTDI, and CT-E formalisms. It makes possible relative inter-patient dosimetry, and also realistic intercomparisons of stochastic risks from different protocols that yield images of comparable quality.« less

Appropriate Use of Effective Dose in Radiation Protection and Risk Assessment.

PubMed

Fisher, Darrell R; Fahey, Frederic H

2017-08-01

Effective dose was introduced by the ICRP for the single, over-arching purpose of setting limits for radiation protection. Effective dose is a derived quantity or mathematical construct and not a physical, measurable quantity. The formula for calculating effective dose to a reference model incorporates terms to account for all radiation types, organ and tissue radiosensitivities, population groups, and multiple biological endpoints. The properties and appropriate applications of effective dose are not well understood by many within and outside the health physics profession; no other quantity in radiation protection has been more confusing or misunderstood. According to ICRP Publication 103, effective dose is to be used for "prospective dose assessment for planning and optimization in radiological protection, and retrospective demonstration of compliance for regulatory purposes." In practice, effective dose has been applied incorrectly to predict cancer risk among exposed persons. The concept of effective dose applies generally to reference models only and not to individual subjects. While conceived to represent a measure of cancer risk or heritable detrimental effects, effective dose is not predictive of future cancer risk. The formula for calculating effective dose incorporates committee-selected weighting factors for radiation quality and organ sensitivity; however, the organ weighting factors are averaged across all ages and both genders and thus do not apply to any specific individual or radiosensitive subpopulations such as children and young women. Further, it is not appropriate to apply effective dose to individual medical patients because patient-specific parameters may vary substantially from the assumptions used in generalized models. Also, effective dose is not applicable to therapeutic uses of radiation, as its mathematical underpinnings pertain only to observed late (stochastic) effects of radiation exposure and do not account for short-term adverse tissue reactions. The weighting factors incorporate substantial uncertainties, and linearity of the dose-response function at low dose is uncertain and highly disputed. Since effective dose is not predictive of future cancer incidence, it follows that effective dose should never be used to estimate future cancer risk from specific sources of radiation exposure. Instead, individual assessments of potential detriment should only be based on organ or tissue radiation absorbed dose, together with best scientific understanding of the corresponding dose-response relationships.

Organ and effective dose coefficients for cranial and caudal irradiation geometries: photons

DOE PAGES

Veinot, K. G.; Eckerman, K. F.; Hertel, N. E.

2015-05-02

With the introduction of new recommendations of the International Commission on Radiological Protection (ICRP) in Publication 103, the methodology for determining the protection quantity, effective dose, has been modified. The modifications include changes to the defined organs and tissues, the associated tissue weighting factors, radiation weighting factors and the introduction of reference sex-specific computational phantoms. Computations of equivalent doses in organs and tissues are now performed in both the male and female phantoms and the sex-averaged values used to determine the effective dose. Dose coefficients based on the ICRP 103 recommendations were reported in ICRP Publication 116, the revision ofmore » ICRP Publication 74 and ICRU Publication 57. The coefficients were determined for the following irradiation geometries: anterior-posterior (AP), posterior-anterior (PA), right and left lateral (RLAT and LLAT), rotational (ROT) and isotropic (ISO). In this work, the methodology of ICRP Publication 116 was used to compute dose coefficients for photon irradiation of the body with parallel beams directed upward from below the feet (caudal) and directed downward from above the head (cranial). These geometries may be encountered in the workplace from personnel standing on contaminated surfaces or volumes and from overhead sources. Calculations of organ and tissue kerma and absorbed doses for caudal and cranial exposures to photons ranging in energy from 10 keV to 10 GeV have been performed using the MCNP6.1 radiation transport code and the adult reference phantoms of ICRP Publication 110. As with calculations reported in ICRP 116, the effects of charged-particle transport are evident when compared with values obtained by using the kerma approximation. At lower energies the effective dose per particle fluence for cranial and caudal exposures is less than AP orientations while above similar to 30 MeV the cranial and caudal values are greater.« less

Organ and effective dose coefficients for cranial and caudal irradiation geometries: photons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Veinot, K. G.; Eckerman, K. F.; Hertel, N. E.

With the introduction of new recommendations of the International Commission on Radiological Protection (ICRP) in Publication 103, the methodology for determining the protection quantity, effective dose, has been modified. The modifications include changes to the defined organs and tissues, the associated tissue weighting factors, radiation weighting factors and the introduction of reference sex-specific computational phantoms. Computations of equivalent doses in organs and tissues are now performed in both the male and female phantoms and the sex-averaged values used to determine the effective dose. Dose coefficients based on the ICRP 103 recommendations were reported in ICRP Publication 116, the revision ofmore » ICRP Publication 74 and ICRU Publication 57. The coefficients were determined for the following irradiation geometries: anterior-posterior (AP), posterior-anterior (PA), right and left lateral (RLAT and LLAT), rotational (ROT) and isotropic (ISO). In this work, the methodology of ICRP Publication 116 was used to compute dose coefficients for photon irradiation of the body with parallel beams directed upward from below the feet (caudal) and directed downward from above the head (cranial). These geometries may be encountered in the workplace from personnel standing on contaminated surfaces or volumes and from overhead sources. Calculations of organ and tissue kerma and absorbed doses for caudal and cranial exposures to photons ranging in energy from 10 keV to 10 GeV have been performed using the MCNP6.1 radiation transport code and the adult reference phantoms of ICRP Publication 110. As with calculations reported in ICRP 116, the effects of charged-particle transport are evident when compared with values obtained by using the kerma approximation. At lower energies the effective dose per particle fluence for cranial and caudal exposures is less than AP orientations while above similar to 30 MeV the cranial and caudal values are greater.« less

Compounds of psoriasis with obesity and overweight.

PubMed

Owczarczyk-Saczonek, Agnieszka; Placek, Waldemar

2017-08-24

Many epidemiological studies have confirmed the relationship of obesity and psoriasis, and it is believed that obesity is an independent risk factor for its development and is associated with a worse prognosis. Furthermore, the reduction of body weight, using low-calorie diet combined with exercise, reduces the severity of psoriasis.Visceral adipose tissue is the largest endocrine organ, producing proinflammatory cytokines (TNF-α, IL-6, IL-17) and adipokines (adiponectin, omentin, chemerin). They participate in the development of dyslipidemia, insulin resistance, diabetes, and consequently of the cardiovascular diseases. Macrophages of visceral adipose tissue have a special role and they increase significantly in obesity. They are responsible for the development of inflammation in adipose tissue and produce inflammatory cytokines (TNF alpha, IL-6, Il-8, Il-17, Il-18, MCP-1) and other adipokines: resistin, visfatin, retinol-binding protein 4. This explains the concept of «psoriatic march «and observations of the frequent coexistence of psoriasis with obesity. Inflammation associated with systemic disease, fanned by pro-inflammatory cytokines and adipokines produced by the visceral adipose tissue lead to the development of insulin resistance, endothelial cell damage. Endothelial dysfunction predisposes to the formation of atherosclerotic plaques and faster development of cardiovascular events. Complication of obesity is the development of non-alcoholic fatty liver disease (NAFLD), which states twice as likely in patients with plaque psoriasis and is associated with the severity of the disease. Another consequence is the development of depression. Probably the proinflammatory cytokines can interact with metabolism of neurotransmitters. Obesity also has a significant impact on the treatment of psoriasis, increasing the risk of adverse effects of systemic drugs, reducing the efficacy of biological agents which dose should be adjusted to the weight of the patient. It is a factor responsible for the increased volume of distribution and it causes low titter of drug concentration.

Degradation behavior of, and tissue response to photo-crosslinked poly(trimethylene carbonate) networks.

PubMed

Rongen, Jan J; van Bochove, Bas; Hannink, Gerjon; Grijpma, Dirk W; Buma, Pieter

2016-11-01

Photo-crosslinked networks prepared from three-armed methacrylate functionalized PTMC oligomers (PTMC-tMA macromers) are attractive materials for developing an anatomically correct meniscus scaffold. In this study, we evaluated cell specific biocompatibility, in vitro and in vivo degradation behavior of, and tissue response to, such PTMC networks. By evaluating PTMC networks prepared from PTMC-tMA macromers of different molecular weights, we were able to assess the effect of macromer molecular weight on the degradation rate of the PTMC network obtained after photo-crosslinking. Three photo-crosslinked networks with different crosslinking densities were prepared using PTMC-tMA macromers with molecular weights 13.3, 17.8, and 26.7 kg/mol. Good cell biocompatibility was demonstrated in a proliferation assay with synovium derived cells. PTMC networks degraded slowly, but statistically significant, both in vitro as well as subcutaneously in rats. Networks prepared from macromers with higher molecular weights demonstrated increased degradation rates compared to networks prepared from initial macromers of lowest molecular weight. The degradation process took place via surface erosion. The PTMC networks showed good tissue tolerance during subcutaneous implantation, to which the tissue response was characterized by the presence of fibrous tissue and encapsulation of the implants. Concluding, we developed cell and tissue biocompatible, photo-crosslinked PTMC networks using PTMC-tMA macromers with relatively high molecular weights. These photo-crosslinked PTMC networks slowly degrade by a surface erosion process. Increasing the crosslinking density of these networks decreases the rate of surface degradation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2823-2832, 2016. © 2016 Wiley Periodicals, Inc.

STUDIES ON THE INTERMEDIARY CARBOHYDRATE METABOLISM OF AQUATIC ANIMALS

PubMed Central

DuBois, Kenneth P.; Geiling, E. M. K.; McBride, Arthur F.; Thomson, John F.

1948-01-01

1. Liver, kidney, brain, skeletal muscle, and cardiac muscle from one newborn and three adult long-snouted dolphins (Stenella plagiodon) were obtained for enzyme studies. 2. All of the dolphin tissues exhibited cytochrome oxidase, succinic dehydrogenase, and malic dehydrogenase activity. Considerable differences in the enzyme activities of the various tissues were noted, with cardiac muscle exhibiting the highest respiratory enzyme activity. The enzyme activities of dolphin tissues were lower than those of the corresponding rat tissues. 3. All of the dolphin tissues exhibited adenosine triphosphatase activity which was accelerated by magnesium and manganese but, in contrast to rat tissues, was only slightly activated by calcium. 4. Measurements of the distribution of acid-soluble phosphorus in dolphin tissues indicated that glycolysis in all of the tissues examined proceeded through the Emden-Meyerhof phosphorylation scheme. 5. The average glycogen content of dolphin skeletal muscle was 0.98 per cent as compared with 0.16 to 0.20 per cent for rat skeletal muscle. The high glycogen content of dolphin skeletal muscle indicates a ready source of substrate for glycolysis even during submergence when the blood supply may be differentially shunted to other organs. 6. Measurements of the organ weights of dolphins showed that the lungs occupy over three times and the liver one-half as much of the total body weight as do these organs in the rat. The heart and the thyroid gland of the dolphin are also larger in proportion to the total body weight than in the rat while the relative weights of the other tissues in the two species are about the same. PMID:18904758

The mammalian iris-ciliary complex affects organization and synthesis of cytoskeletal proteins of organ and tissue cultured lens epithelial cells.

PubMed

Banerjee, A; Emanuel, K; Parafina, J; Bagchi, M

1992-10-01

A water soluble growth inhibitor was isolated from the mammalian ocular iris-ciliary complex. The molecular weight of this protein is 10 kD or lower as determined by ultrafiltration fractionation. The iris-ciliary (IC) complex water soluble protein(s) significantly inhibits synthesis of lower molecular weight proteins of the epithelial cells of the organ cultured mammalian ocular lens. It was also found that this inhibitory effect of IC is mediated via the structural organization of the lens. Monolayer cultures of the lens epithelial cells exposed to IC did not manifest any inhibition of their protein synthesis. Moreover, these tissue cultured lens epithelial (TCLE) cells showed a significant increase in their protein synthetic activities in response to the presence of IC factors in the culture medium. It is postulated that the IC activity is modulated via either the lens capsule, an extracellular matrix, or due to the specific organization of the intact lens. The specific effects of IC on the cytoskeletal organization and synthesis in the organ cultured lens epithelial (OCLE) and TCLE cells were also examined. Both groups, treated with IC factors, manifested significant alterations in their protein synthetic activities and cytoskeletal architecture. The 3H-leucine incorporation experiments showed that alpha-actin and alpha-tubulin synthesis is partially inhibited by IC factors in OCLE cells but vimentin synthesis is not, whereas in TCLE cells all of them showed increased synthesis in response to IC factors. Turnover rates of these proteins in both OCLE and TCLE cells were also computed. The immunofluorescence and microscopic evaluation of OCLE and TCLE cells exposed to IC factors illustrated significant alteration in the cytoarchitecture of the filaments. We demonstrate that an inhibitor(s) molecule of 10 kD or lower size isolated from IC inhibited protein synthesis of OCLE cells and stimulated protein synthesis in TCLE cells. The IC factor also affects the synthesis and organization of cytoskeletal filaments of both the OCLE and TCLE cells.

Metals in tissues of migrant semipalmated sandpipers (Calidris pusilla) from Delaware Bay, New Jersey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burger, Joanna, E-mail: burger@biology.rutgers.edu; Environmental and Occupational Health Sciences Institute; Gochfeld, Michael

2014-08-15

There is an abundance of field data on levels of metals for feathers in a variety of birds, but relatively few data for tissues, especially for migrant species from one location. In this paper we examine the levels of arsenic, cadmium, chromium, lead, manganese, mercury and selenium in muscle, liver, brain, fat and breast feathers from migrant semipalmated sandpipers (Calidris pusilla) collected from Delaware Bay, New Jersey. Our primary objectives were to (1) examine variation as a function of tissue, (2) determine the relationship of metal levels among tissues, and (3) determine the selenium:mercury molar ratio in different tissues sincemore » selenium is thought to protect against mercury toxicity. We were also interested in whether the large physiological changes that occur while shorebirds are on Delaware Bay (e.g. large weight gains in 2–3 weeks) affected metal levels, especially in the brain. There were significant differences among tissues for all metals. The brain had the lowest levels of arsenic and cadmium, and was tied for the lowest levels of all other metals except lead and selenium. Correlations among metals in tissues were varied, with mercury levels being positively correlated for muscle and brain, and for liver and breast feathers. Weights vary among individuals at the Delaware Bay stopover, as they arrive light, and gain weight prior to migration north. Bird weight and levels of arsenic, cadmium, and selenium in the brain were negatively correlated, while they were positively correlated for lead. There was no positive correlation for mercury in the brain as a function of body weight. The selenium:mercury molar ratio varied significantly among tissues, with brain (ratio of 141) and fat having the highest ratios, and liver and breast feathers having the lowest. In all cases, the ratio was above 21, suggesting the potential for amelioration of mercury toxicity. - Highlights: • Metal levels were examined for migrant semipalmated sandpipers. • There were differences in metal levels among internal tissues. • Brain had the lowest levels of arsenic and cadmium. • Bird weight and arsenic, cadmium, and selenium levels in brain were negatively correlated. • Selenium:mercury molar ratio varied among tissues (21–141, suggesting protection)« less

Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1.

PubMed

Johnen, Heiko; Lin, Shu; Kuffner, Tamara; Brown, David A; Tsai, Vicky Wang-Wei; Bauskin, Asne R; Wu, Liyun; Pankhurst, Greg; Jiang, Lele; Junankar, Simon; Hunter, Mark; Fairlie, W Douglas; Lee, Nicola J; Enriquez, Ronaldo F; Baldock, Paul A; Corey, Eva; Apple, Fred S; Murakami, Maryann M; Lin, En-Ju; Wang, Chuansong; During, Matthew J; Sainsbury, Amanda; Herzog, Herbert; Breit, Samuel N

2007-11-01

Anorexia and weight loss are part of the wasting syndrome of late-stage cancer, are a major cause of morbidity and mortality in cancer, and are thought to be cytokine mediated. Macrophage inhibitory cytokine-1 (MIC-1) is produced by many cancers. Examination of sera from individuals with advanced prostate cancer showed a direct relationship between MIC-1 abundance and cancer-associated weight loss. In mice with xenografted prostate tumors, elevated MIC-1 levels were also associated with marked weight, fat and lean tissue loss that was mediated by decreased food intake and was reversed by administration of antibody to MIC-1. Additionally, normal mice given systemic MIC-1 and transgenic mice overexpressing MIC-1 showed hypophagia and reduced body weight. MIC-1 mediates its effects by central mechanisms that implicate the hypothalamic transforming growth factor-beta receptor II, extracellular signal-regulated kinases 1 and 2, signal transducer and activator of transcription-3, neuropeptide Y and pro-opiomelanocortin. Thus, MIC-1 is a newly defined central regulator of appetite and a potential target for the treatment of both cancer anorexia and weight loss, as well as of obesity.

Nonmuscle Tissues Contribution to Cancer Cachexia

PubMed Central

Stemmler, Britta

2015-01-01

Cachexia is a syndrome associated with cancer, characterized by body weight loss, muscle and adipose tissue wasting, and inflammation, being often associated with anorexia. In spite of the fact that muscle tissue represents more than 40% of body weight and seems to be the main tissue involved in the wasting that occurs during cachexia, recent developments suggest that tissues/organs such as adipose (both brown and white), brain, liver, gut, and heart are directly involved in the cachectic process and may be responsible for muscle wasting. This suggests that cachexia is indeed a multiorgan syndrome. Bearing all this in mind, the aim of the present review is to examine the impact of nonmuscle tissues in cancer cachexia. PMID:26523094

Foetal and lactational exposure to alcohol increases oxidative capacity of brown adipose tissue in the rat. A possible relationship to cot death.

PubMed Central

Huttunen, P.; Kortelainen, M. L.; Hirvonen, J.

1989-01-01

The effect was studied of chronic alcohol intake in the rat during pregnancy and lactation on the brown adipose tissue (BAT) in pups. The idea was to find a possible relationship to cot death since in some cot death victims increased amounts of BAT have been observed. Exposure to ethanol increased the relative weight of the brown adipose tissue in pups and enhanced both its total protein content and the activities of the oxidative enzymes, succinate dehydrogenase and cytochrome oxidase. In the BAT of pups sympathetic activity, as demonstrated by noradrenaline, was also increased by long-term exposure to alcohol. In theory, an increased thermogenic capacity of the BAT in the newborn together with other factors such as emotional stress and infections could lead to death from hyperthermia, in which case only non-specific morphological signs would be found in the cadaver. PMID:2605116

Pregnancy Complicated by Obesity Induces Global Transcript Expression Alterations in Visceral and Subcutaneous Fat

PubMed Central

Bashiri, Asher; Heo, Hye J.; Ben-Avraham, Danny; Mazor, Moshe; Budagov, Temuri; Einstein, Francine H.; Atzmon, Gil

2014-01-01

Maternal obesity is a significant risk factor for development of both maternal and fetal metabolic complications. Increase in visceral fat and insulin resistance is a metabolic hallmark of pregnancy, yet little is known how obesity alters adipose cellular function and how this may contribute to pregnancy morbidities. We sought to identify alterations in genome-wide transcription expression in both visceral (omental) and abdominal subcutaneous fat deposits in pregnancy complicated by obesity. Visceral and abdominal subcutaneous fat deposits were collected from normal weight and obese pregnant women (n=4/group) at time of scheduled uncomplicated cesarean section. A genome-wide expression array (Affymetrix Human Exon 1.0 st platform), validated by quantitative real-time PCR, was utilized to establish the gene transcript expression profile in both visceral and abdominal subcutaneous fat in normal weight and obese pregnant women. Global alteration in gene expression was identified in pregnancy complicated by obesity. These regions of variations lead to identification of indolethylamine N-methyltransferase (INMT), tissue factor pathway inhibitor-2 (TFPI-2), and ephrin type-B receptor 6 (EPHB6), not previously associated with fat metabolism during pregnancy. In addition, subcutaneous fat of obese pregnant women demonstrated increased coding protein transcripts associated with apoptosis compared to lean counterparts. Global alteration of gene expression in adipose tissue may contribute to adverse pregnancy outcomes associated with obesity. PMID:24696292

Critical roles of mucin-1 in sensitivity of lung cancer cells to tumor necrosis factor-alpha and dexamethasone.

PubMed

Xu, Menglin; Wang, Xiangdong

2017-08-01

Lung cancer is the leading cause of death from cancer. Mucins are glycoproteins with high molecular weight, responsible for cell growth, differentiation, and signaling, and were proposed to be correlated with gene heterogeneity of lung cancer. Here, we report aberrant expression of mucin genes and tumor necrosis factor receptors in lung adenocarcinoma tissues compared with normal tissues in GEO datasets. Mucin-1 (MUC1) gene was selected and considered as the target gene; furthermore, the expression pattern of adenocarcinomic cells (A549, H1650, or H1299 cells) was validated under the stimulation with tumor necrosis factor-alpha (TNFα) or dexamethasone (DEX), separately. MUC1 gene interference was done to A549 cells to show its role in sensitivity of lung cancer cells to TNFα and DEX. Results of our experiments indicate that MUC1 may regulate the influence of inflammatory mediators in effects of glucocorticoids (GCs), as a regulatory target to improve therapeutics. It shows the potential effect of MUC1 and GCs in lung adenocarcinoma (LADC), which may help in LADC treatment in the future.

Polyphenolic extract from Hibiscus sabdariffa reduces body fat by inhibiting hepatic lipogenesis and preadipocyte adipogenesis.

PubMed

Kao, Erl-Shyh; Yang, Mon-Yuan; Hung, Chia-Hung; Huang, Chien-Ning; Wang, Chau-Jong

2016-01-01

Diets high in fat lead to excess lipid accumulation in adipose tissue, which is a crucial factor in the development of obesity, hepatitis, and hyperlipidemia. In this study, we investigated the anti-obesity effect of Hibiscus sabdariffa extract (HSE) in vivo. Hamsters fed a high-fat diet (HFD) develop symptoms of obesity, which were determined based on body weight changes and changes in plasma and serum triglycerides, free fatty acid concentrations, total cholesterol levels, LDL-C levels, HDL-C levels, and adipocyte tissue weight. HFD-fed hamsters were used to investigate the effects of HSE on symptoms of obesity such as adipogenesis and fatty liver, loss of blood glucose regulation, and serum ion imbalance. Interestingly, HSE treatment effectively reduced the effects of the HFD in hamsters in a dose-dependent manner. Further, after inducing maturation of preadipocytes, Hibiscus sabdariffa polyphenolic extract (HPE) was shown to suppress the adipogenesis of adipocytes. However, HPE does not affect the viability of preadipocytes. Therefore, both HSE and HPE are effective and viable treatment strategies for preventing the development and treating the symptoms of obesity.

Combined Monte Carlo and path-integral method for simulated library of time-resolved reflectance curves from layered tissue models

NASA Astrophysics Data System (ADS)

Wilson, Robert H.; Vishwanath, Karthik; Mycek, Mary-Ann

2009-02-01

Monte Carlo (MC) simulations are considered the "gold standard" for mathematical description of photon transport in tissue, but they can require large computation times. Therefore, it is important to develop simple and efficient methods for accelerating MC simulations, especially when a large "library" of related simulations is needed. A semi-analytical method involving MC simulations and a path-integral (PI) based scaling technique generated time-resolved reflectance curves from layered tissue models. First, a zero-absorption MC simulation was run for a tissue model with fixed scattering properties in each layer. Then, a closed-form expression for the average classical path of a photon in tissue was used to determine the percentage of time that the photon spent in each layer, to create a weighted Beer-Lambert factor to scale the time-resolved reflectance of the simulated zero-absorption tissue model. This method is a unique alternative to other scaling techniques in that it does not require the path length or number of collisions of each photon to be stored during the initial simulation. Effects of various layer thicknesses and absorption and scattering coefficients on the accuracy of the method will be discussed.

(n-3) Fatty Acids Alleviate Adipose Tissue Inflammation and Insulin Resistance: Mechanistic Insights12

PubMed Central

Kalupahana, Nishan S.; Claycombe, Kate J.; Moustaid-Moussa, Naima

2011-01-01

Obesity is associated with the metabolic syndrome, a significant risk factor for developing type 2 diabetes and cardiovascular diseases. Chronic low-grade inflammation occurring in the adipose tissue of obese individuals is causally linked to the pathogenesis of insulin resistance and the metabolic syndrome. Although the exact trigger of this inflammatory process is unknown, adipose tissue hypoxia, endoplasmic reticular stress, and saturated fatty acid–mediated activation of innate immune processes have been identified as important processes in these disorders. Furthermore, macrophages and T lymphocytes have important roles in orchestrating this immune process. Although energy restriction leading to weight loss is the primary dietary intervention to reverse these obesity-associated metabolic disorders, other interventions targeted at alleviating adipose tissue inflammation have not been explored in detail. In this regard, (n-3) PUFA of marine origin both prevent and reverse high-fat-diet–induced adipose tissue inflammation and insulin resistance in rodents. We provide an update on the pathogenesis of adipose tissue inflammation and insulin resistance in obesity and discuss potential mechanisms by which (n-3) PUFA prevent and reverse these changes and the implications in human health. PMID:22332072

Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications.

PubMed

Vernochet, Cecile; Damilano, Federico; Mourier, Arnaud; Bezy, Olivier; Mori, Marcelo A; Smyth, Graham; Rosenzweig, Anthony; Larsson, Nils-Göran; Kahn, C Ronald

2014-10-01

Mitochondrial dysfunction in adipose tissue occurs in obesity, type 2 diabetes, and some forms of lipodystrophy, but whether this dysfunction contributes to or is the result of these disorders is unknown. To investigate the physiological consequences of severe mitochondrial impairment in adipose tissue, we generated mice deficient in mitochondrial transcription factor A (TFAM) in adipocytes by using mice carrying adiponectin-Cre and TFAM floxed alleles. These adiponectin TFAM-knockout (adipo-TFAM-KO) mice had a 75-81% reduction in TFAM in the subcutaneous and intra-abdominal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT), causing decreased expression and enzymatic activity of proteins in complexes I, III, and IV of the electron transport chain (ETC). This mitochondrial dysfunction led to adipocyte death and inflammation in WAT and a whitening of BAT. As a result, adipo-TFAM-KO mice were resistant to weight gain, but exhibited insulin resistance on both normal chow and high-fat diets. These lipodystrophic mice also developed hypertension, cardiac hypertrophy, and cardiac dysfunction. Thus, isolated mitochondrial dysfunction in adipose tissue can lead a syndrome of lipodystrophy with metabolic syndrome and cardiovascular complications. © FASEB.

Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies.

PubMed

Manna, Prasenjit; Jain, Sushil K

2015-12-01

Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue in development of these risk factors, and potential strategies to regulate body weight loss/gain for better health benefits.

Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies

PubMed Central

Manna, Prasenjit

2015-01-01

Abstract Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue in development of these risk factors, and potential strategies to regulate body weight loss/gain for better health benefits. PMID:26569333

Gravity of Living Systems: May the Force Be With You

NASA Technical Reports Server (NTRS)

Hargens, Alan R.; Holton, Emily M. (Technical Monitor)

1998-01-01

Gravity, the force which shapes the architecture of organisms from single cells to dinosaurs, has been the most constant environmental factor during the evolution of species on Earth. With long-duration space flight, an understanding of how gravity affects living systems gains greater urgency in order to maintain the health and performance of crews who will explore the solar system. For example, the cardiovascular and musculoskeletal systems are normally exposed to gravitational gradients of blood pressure and weight on Earth. Such gradients increase blood pressure and tissue weight in dependent tissues of the body. Thus, from a physiologic standpoint, these systems are greatly affected by altered gravity. Exposure to actual and simulated microgravity causes blood and tissue fluid to shift from the legs to the head. Studies of humans in space have documented facial edema, space adaptation syndrome, decreased plasma volume, muscle atrophy, and loss of bone strength. Return of astronauts to Earth is accompanied by orthostatic intolerance, decreased neuromuscular coordination, and reduced exercise capacity. These factors decrease performance during descent from orbit and increase risk during emergency egress from the space craft. Models of simulated microgravity include 60 head-down tilt, immersion, and prolonged horizontal bedrest. Head-down tilt and dry immersion are the most accepted models and studies using these models of up to one year have been performed in Russia. Sensitive animal models which offer clear insights into the role of gravity on structure and function include the developing giraffe and snakes from various habitats. Finally, possible countermeasures to speed readaptation of astronauts to gravity after prolonged space flight include exercise, lower body negative pressure, and centrifugation.

Serum osteopontin concentration is decreased by exercise-induced fat loss but is not correlated with body fat percentage in obese humans.

PubMed

You, Jeong Soon; Ji, Hye-In; Chang, Kyung Ja; Yoo, Myung Chul; Yang, Hyung-In; Jeong, In-Kyung; Kim, Kyoung Soo

2013-08-01

To evaluate the extent to which fat mass contributes to serum osteopontin (OPN) concentration, we investigated whether serum OPN levels are decreased by exercise-induced fat mass loss and whether they are associated with body fat percentage in obese humans. Twenty‑three female college students were recruited to participate in an 8‑week body weight control program. Body composition [body weight, soft lean mass, body fat mass, body fat percentage, waist-hip ratio and body mass index (BMI)] were assessed prior to and following the program. Serum lipid profiles and serum adiponectin, leptin and osteopontin levels were measured from serum collected prior to and following the program. To understand the effect of fat mass loss on the serum levels of adipokine, which is mainly produced in adipose tissue, the leptin and adiponectin levels were also measured prior to and following the program. Serum leptin levels (mean ± standard error of the mean) decreased significantly following the program (from 9.82±0.98 to 7.23±0.67 ng/ml) and were closely correlated with body fat percentage. In addition, serum adiponectin levels were negatively correlated with body fat percentage, while serum adiponectin levels were not significantly altered. By contrast, serum OPN levels decreased significantly following the program (from 16.03±2.34 to 10.65±1.22 ng/ml). However, serum OPN levels were not correlated with body fat percentage, suggesting that serum OPN levels are controlled by several other factors in humans. In conclusion, a high expression of OPN in adipose tissues may not be correlated with serum OPN levels in obese humans. Thus, tissues or physiological factors other than fat mass may have a greater contribution to the serum OPN levels.

The promising effect of linagliptin and/or indole-3-carbinol on experimentally-induced polycystic ovarian syndrome.

PubMed

Kabel, Ahmed M; Al-Shehri, Aisha H; Al-Talhi, Rehab A; Abd Elmaaboud, Maaly A

2017-08-01

Polycystic ovarian syndrome (PCOS) is one of the most common medical conditions that lead to female infertility worldwide. The aim of this study was to assess the effect of linagliptin and/or indole-3-carbinol (I3C) on PCOS in female rats. Fifty female Wistar rats were randomly allocated into five equal groups: Control group; Letrozole-induced PCOS group; Letrozole + Linagliptin group; Letrozole + I3C group and Letrozole + Linagliptin + I3C group. Body weight, body mass index, Lee index and ovarian indices were determined. Plasma levels of luteinizing hormone (LH), free testosterone, estradiol, progesterone, prolactin, fasting blood glucose (FBG) and fasting plasma insulin were measured. Quantitative Insulin Sensitivity Check Index (QUICKI) was calculated. Tissue antioxidant status, transforming growth factor beta 1 (TGF-β1), tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10) and Nrf2/HO-1 content were assessed. Histopathological and immunohistochemical examination of the ovaries were done. Linagliptin and/or I3C induced significant decrease in tissue TGF-β1, TNF-α, IL-10, plasma free testosterone, luteinizing hormone, progesterone, estradiol, FBG and insulin levels associated with significant improvement of insulin resistance whereas tissue Nrf2/HO-1 content and antioxidant enzymes were significantly increased compared to PCOS group. In addition, final body weight, final body mass and Lee indices were significantly decreased compared to PCOS group. Also, there was significant improvement of the ovarian morphology compared to PCOS group. This improvement was significant with linagliptin/I3C combination compared to the use of each of these drugs alone. In conclusion, linagliptin/I3C combination might represent a beneficial therapeutic modality for amelioration of PCOS. Copyright © 2017 Elsevier B.V. All rights reserved.

Brown adipose tissue in young adults who were born preterm or small for gestational age.

PubMed

Kistner, Anna; Rydén, Henric; Anderstam, Björn; Hellström, Ann; Skorpil, Mikael

2018-06-27

Brown adipose tissue (BAT) is present and functions to dissipate energy as heat in young adults and can be assessed using magnetic resonance imaging (MRI) to estimate the voxel fat fraction, i.e. proton density fat fraction (PDFF). It is hypothesized that subjects born preterm or small for gestational age (SGA) may exhibit disrupted BAT formation coupled to metabolic factors. Our purpose was to assess the presence of BAT in young adults born extremely preterm or SGA in comparison with controls. We studied 30 healthy subjects (median age, 21 years): 10 born extremely preterm, 10 full term but SGA and 10 full term with a normal birth weight (controls). We utilized an MRI technique combining multiple scans to enable smaller echo spacing and an advanced fat-water separation method applying graph cuts to estimate B0 inhomogeneity. We measured supraclavicular/cervical PDFF, R2*, fat volume, insulin-like growth factor 1, glucagon, thyroid stimulating hormone and the BAT-associated hormones fibroblast growth factor 21 and irisin. The groups did not significantly differ in supraclavicular/cervical PDFF, R2*, fat volume or hormone levels. The mean supraclavicular/cervical PDFF was equivalent between the groups (range 75-77%). Young adults born extremely preterm or SGA show BAT development similar to those born full term at a normal birth weight. Thus, the increased risk of cardiovascular and metabolic disorders in these groups is not due to the absence of BAT, although our results do not exclude possible BAT involvement in this scenario. Larger studies are needed to understand these relationships.

Anthropometric, metabolic, psychosocial and dietary factors associated with dropout in overweight and obese postmenopausal women engaged in a 6-month weight loss programme: a MONET study.

PubMed

Messier, Virginie; Hayek, Jessy; Karelis, Antony D; Messier, Lyne; Doucet, Eric; Prud'homme, Denis; Rabasa-Lhoret, Rémi; Strychar, Irene

2010-04-01

The objective of the present study was to examine anthropometric, metabolic, psychosocial and dietary factors associated with dropout in a 6-month weight loss intervention aimed at reducing body weight by 10 %. The study sample included 137 sedentary, overweight and obese postmenopausal women, participating in a weight loss intervention that consisted of either energy restriction (ER) or ER with resistance training (ER+RT). Anthropometric (BMI, percent lean body mass, percent fat mass, visceral adipose tissue and waist circumference), metabolic (total energy expenditure, RMR, insulin sensitivity and fasting plasma levels of leptin and ghrelin), psychosocial (body esteem, self-esteem, stress, dietary restraint, disinhibition, hunger, quality of life, self-efficacy, perceived benefits for controlling weight and perceived risk) and dietary (3-d food record) variables were measured. Thirty subjects out of 137 dropped out of the weight loss programme (22 %), with no significant differences in dropout rates between those in the ER and the ER+RT groups. Overall, amount of weight loss was significantly lower in dropouts than in completers ( - 1.7 (sd 3.5) v. - 5.6 (sd 4.3) kg, P < 0.05); weekly weight loss during the first 4 weeks was also significantly lower. Dropouts consumed fewer fruit servings than completers (1.7 (sd 1.1) v. 2.7 (sd 1.53), P < 0.05) and had higher insulin sensitivity levels (12.6 (sd 3.8) v. 11.1 (sd 2.8) mg glucose/min per kg fat-free mass, P < 0.05). The present results suggest that the rate of weight loss during the first weeks of an intervention plays an important role in the completion of the programme. Thus, participants with low rates of initial weight loss should be monitored intensely to undertake corrective measures to increase the likelihood of completion.

Differential effect of weight loss with low-fat diet or high-fat diet restriction on inflammation in the liver and adipose tissue of mice with diet-induced obesity

USDA-ARS?s Scientific Manuscript database

We studied the effects of weight loss induced by either a low-fat normal diet or restriction of high-fat diet on hepatic steatosis, inflammation in the liver and adipose tissue, and blood monocytes of obese mice. In mice with high-fat diet-induced obesity, weight loss was achieved by switching from ...

Lycium chinense Improves Post-Menopausal Obesity via Regulation of PPAR-γ and Estrogen Receptor-α/β Expressions.

PubMed

Kim, Mi Hye; Kim, Eun-Jung; Choi, You Yeon; Hong, Jongki; Yang, Woong Mo

2017-01-01

The fruit of Lycium chinense Miller (Solanaceae) is used as a functional food and a medicinal herb for treating many specific health concerns. Weight gain induced by estrogen deficiency is a problem for post-menopausal women around the globe. The present study investigates the effects of aqueous extract of L. chinense (LC) on post-menopausal obesity. Female C57BL/6 mice were ovariectomized and fed on high-fat diet (HFD) for 12 weeks to induce post-menopausal obesity. LC extract (1[Formula: see text]mg/kg and 10[Formula: see text]mg/kg) was orally administrated for 6 weeks with continuous HFD feeding. Ovarian adipose tissues and uterus were weighed. Serum triglyceride, cholesterol, LDL-cholesterol and fasting glucose levels were analyzed. The expressions of adipocyte-specific factors and estrogen receptors (ERs) were investigated. Additionally, lipid accumulation was confirmed in differentiated 3T3-L1 adipocytes. Increased body weight due to post-menopausal obesity was ameliorated about 14.7% and 17.76% by treatment of 1[Formula: see text]mg/kg and 10[Formula: see text]mg/kg LC, respectively. LC treatment reduced both of serum lipid and fasting blood glucose levels. Adipocyte hypertrophy and fatty liver were ameliorated in LC-treated groups. In LC-treated adipocyte cells, lipid accumulation was significantly inhibited. The expression of perilipin in adipose tissues was decreased by LC. In addition, expression of PPAR-[Formula: see text] protein was down-regulated in adipose tissues and differentiated adipocytes, while GLUT4 expression was increased in adipose tissues by LC treatment. Moreover, LC treatment up-regulated the expressions of ER-[Formula: see text]/[Formula: see text] accompanied with increased uterine weight. These results showed the ameliorative effects of LC on overweight after menopause. Post-menopausal obesity may be improved by LC treatment.

Specific Macronutrients Exert Unique Influences on the Adipose-Liver Axis to Promote Hepatic Steatosis in Mice.

PubMed

Duwaerts, Caroline C; Amin, Amin M; Siao, Kevin; Her, Chris; Fitch, Mark; Beysen, Carine; Turner, Scott M; Goodsell, Amanda; Baron, Jody L; Grenert, James P; Cho, Soo-Jin; Maher, Jacquelyn J

2017-09-01

The factors that distinguish metabolically healthy obesity from metabolically unhealthy obesity are not well understood. Diet has been implicated as a determinant of the unhealthy obesity phenotype, but which aspects of the diet induce dysmetabolism are unknown. The goal of this study was to investigate whether specific macronutrients or macronutrient combinations provoke dysmetabolism in the context of isocaloric, high-energy diets. Mice were fed 4 high-energy diets identical in calorie and nutrient content but different in nutrient composition for 3 weeks to 6 months. The test diets contained 42% carbohydrate (sucrose or starch) and 42% fat (oleate or palmitate). Weight and glucose tolerance were monitored; blood and tissues were collected for histology, gene expression, and immunophenotyping. Mice gained weight on all 4 test diets but differed significantly in other metabolic outcomes. Animals fed the starch-oleate diet developed more severe hepatic steatosis than those on other formulas. Stable isotope incorporation showed that the excess hepatic steatosis in starch-oleate-fed mice derived from exaggerated adipose tissue lipolysis. In these mice, adipose tissue lipolysis coincided with adipocyte necrosis and inflammation. Notably, the liver and adipose tissue abnormalities provoked by starch-oleate feeding were reproduced when mice were fed a mixed-nutrient Western diet with 42% carbohydrate and 42% fat. The macronutrient composition of the diet exerts a significant influence on metabolic outcome, independent of calories and nutrient proportions. Starch-oleate appears to cause hepatic steatosis by inducing progressive adipose tissue injury. Starch-oleate phenocopies the effect of a Western diet; consequently, it may provide clues to the mechanism whereby specific nutrients cause metabolically unhealthy obesity.

A study of T2-weighted MR image texture features and diffusion-weighted MR image features for computer-aided diagnosis of prostate cancer

NASA Astrophysics Data System (ADS)

Peng, Yahui; Jiang, Yulei; Antic, Tatjana; Giger, Maryellen L.; Eggener, Scott; Oto, Aytekin

2013-02-01

The purpose of this study was to study T2-weighted magnetic resonance (MR) image texture features and diffusionweighted (DW) MR image features in distinguishing prostate cancer (PCa) from normal tissue. We collected two image datasets: 23 PCa patients (25 PCa and 23 normal tissue regions of interest [ROIs]) imaged with Philips MR scanners, and 30 PCa patients (41 PCa and 26 normal tissue ROIs) imaged with GE MR scanners. A radiologist drew ROIs manually via consensus histology-MR correlation conference with a pathologist. A number of T2-weighted texture features and apparent diffusion coefficient (ADC) features were investigated, and linear discriminant analysis (LDA) was used to combine select strong image features. Area under the receiver operating characteristic (ROC) curve (AUC) was used to characterize feature effectiveness in distinguishing PCa from normal tissue ROIs. Of the features studied, ADC 10th percentile, ADC average, and T2-weighted sum average yielded AUC values (+/-standard error) of 0.95+/-0.03, 0.94+/-0.03, and 0.85+/-0.05 on the Phillips images, and 0.91+/-0.04, 0.89+/-0.04, and 0.70+/-0.06 on the GE images, respectively. The three-feature combination yielded AUC values of 0.94+/-0.03 and 0.89+/-0.04 on the Phillips and GE images, respectively. ADC 10th percentile, ADC average, and T2-weighted sum average, are effective in distinguishing PCa from normal tissue, and appear robust in images acquired from Phillips and GE MR scanners.

Hypoglycemia in a dog with a leiomyoma of the gastric wall producing an insulin-like growth factor II-like peptide.

PubMed

Boari, A; Barreca, A; Bestetti, G E; Minuto, F; Venturoli, M

1995-06-01

A 12-year-old mixed-breed male dog was referred to the Clinica Medica Veterinaria of Bologna University for recurrent episodes of seizures due to hypoglycemia with abnormally low plasma insulin levels (18 pmol/l). Resection of a large leiomyoma (780 g) of the gastric wall resulted in a permanent resolution of the hypoglycemic episodes. Insulin-like growth factors I and II (IGF-I and -II) were measured by RIA in serum before and after surgery and in tumor tissue. Results were compared to the serum concentration of 54 normal and to the tissue concentration observed in eight non-hypoglycemic dog gastric wall extracts. Before surgery, circulating immunoreactive IGF-I was 0.92 nmol/l, which is significantly lower than the control values (16.92 +/- 8.44 nmol/l, range 3.53-35.03), while IGF-II was 152 nmol/l, which is significantly higher than the control values (42.21 +/- 3.75, range 31.99-50.74). After surgery, IGF-I increased to 6.80 nmol/l while IGF-II decreased to 45.52 nmol/l. Tumor tissue IGF-II concentration was higher than normal (5.66 nmol/kg tissue as compared to a range in normal gastric wall tissue of 1.14-3.72 nmol/kg), while IGF-I was 0.08 nmol/kg tissue, which is close to the lowest normal value (range in controls, 0.08-1.18 nmol/kg). Partial characterization of IGF-II immunoreactivity extracted from tissue evidenced a molecular weight similar to that of mature IGF-II, thus excluding that peptide released by the tumor is a precursor molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

Rescue of the colony-stimulating factor 1 (CSF-1)-nullizygous mouse (Csf1(op)/Csf1(op)) phenotype with a CSF-1 transgene and identification of sites of local CSF-1 synthesis.

PubMed

Ryan, G R; Dai, X M; Dominguez, M G; Tong, W; Chuan, F; Chisholm, O; Russell, R G; Pollard, J W; Stanley, E R

2001-07-01

Colony-stimulating factor 1 (CSF-1) regulates the survival, proliferation, and differentiation of mononuclear phagocytes. It is expressed as a secreted glycoprotein or proteoglycan found in the circulation or as a biologically active cell-surface glycoprotein. To investigate tissue CSF-1 regulation, CSF-1-null Csf1(op)/Csf1(op) mice expressing transgenes encoding the full-length membrane-spanning CSF-1 precursor driven by 3.13 kilobases of the mouse CSF-1 promoter and first intron were characterized. Transgene expression corrected the gross osteopetrotic, neurologic, weight, tooth, and reproductive defects of Csf1(op)/Csf1(op) mice. Detailed analysis of one transgenic line revealed that circulating CSF-1, tissue macrophage numbers, hematopoietic tissue cellularity, and hematopoietic parameters were normalized. Tissue CSF-1 levels were normal except for elevations in 4 secretory tissues. Skin fibroblasts from the transgenic mice secreted normal amounts of CSF-1 but also expressed some cell-surface CSF-1. Also, lacZ driven by the same promoter/first intron revealed beta-galactosidase expression in hematopoietic, reproductive, and other tissue locations proximal to CSF-1 cellular targets, consistent with local regulation by CSF-1 at these sites. These studies indicate that the 3.13-kilobase promoter/first intron confers essentially normal CSF-1 expression. They also pinpoint new cellular sites of CSF-1 expression, including ovarian granulosa cells, mammary ductal epithelium, testicular Leydig cells, serous acinar cells of salivary gland, Paneth cells of the small intestine, as well as local sites in several other tissues.

Regulation of the clock gene expression in human adipose tissue by weight loss.

PubMed

Pivovarova, O; Gögebakan, Ö; Sucher, S; Groth, J; Murahovschi, V; Kessler, K; Osterhoff, M; Rudovich, N; Kramer, A; Pfeiffer, A F H

2016-06-01

The circadian clock coordinates numerous metabolic processes to adapt physiological responses to light-dark and feeding regimens and is itself regulated by metabolic cues. The implication of the circadian clock in the regulation of energy balance and body weight is widely studied in rodents but not in humans. Here we investigated (1) whether the expression of clock genes in human adipose tissue is changed by weight loss and (2) whether these alterations are associated with metabolic parameters. Subcutaneous adipose tissue (SAT) samples were collected before and after 8 weeks of weight loss on an 800 kcal per day hypocaloric diet (plus 200 g per day vegetables) at the same time of the day. Fifty overweight subjects who lost at least 8% weight after 8 weeks were selected for the study. The expression of 10 clock genes and key metabolic and inflammatory genes in adipose tissue was determined by quantitative real-time PCR. The expression of core clock genes PER2 and NR1D1 was increased after the weight loss. Correlations of PERIOD expression with body mass index (BMI) and serum total, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol levels and of NR1D1 expression with total and LDL cholesterol were found that became non-significant after correction for multiple testing. Clock gene expression levels and their weight loss-induced changes tightly correlated with each other and with genes involved in fat metabolism (FASN, CPT1A, LPL, PPARG, PGC1A, ADIPOQ), energy metabolism (SIRT1), autophagy (LC3A, LC3B) and inflammatory response (NFKB1, NFKBIA, NLRP3, EMR1). Clock gene expression in human SAT is regulated by body weight changes and associated with BMI, serum cholesterol levels and the expression of metabolic and inflammatory genes. Our data confirm the tight crosstalk between molecular clock and metabolic and inflammatory pathways involved in adapting adipose tissue metabolism to changes of the energy intake in humans.

Vascular endothelial growth factor receptor 1 (VEGFR1) tyrosine kinase signaling facilitates granulation tissue formation with recruitment of VEGFR1+ cells from bone marrow.

PubMed

Park, Keiichi; Amano, Hideki; Ito, Yoshiya; Mastui, Yoshio; Kamata, Mariko; Yamazaki, Yasuharu; Takeda, Akira; Shibuya, Masabumi; Majima, Masataka

2018-06-01

Vascular endothelial growth factor (VEGF)-A facilitates wound healing. VEGF-A binds to VEGF receptor 1 (VEGFR1) and VEGFR2 and induces wound healing through the receptor's tyrosine kinase (TK) domain. During blood flow recovery and lung regeneration, expression of VEGFR1 is elevated. However, the precise mechanism of wound healing, especially granulation formation on VEGFR1, is not well understood. We hypothesized that VEGFR1-TK signaling induces wound healing by promoting granulation tissue formation. A surgical sponge implantation model was made by implanting a sponge disk into dorsal subcutaneous tissue of mice. Granulation formation was estimated from the weight of the sponge and the granulation area from the immunohistochemical analysis of collagen I. The expression of fibroblast markers was estimated from the expression of transforming growth factor-beta (TGF-β) and cellular fibroblast growth factor-2 (FGF-2) using real-time PCR (polymerase chain reaction) and from the immunohistochemical analysis of S100A4. VEGFR1 TK knockout (TK -/- ) mice exhibited suppressed granulation tissue formation compared to that in wild-type (WT) mice. Expression of FGF-2, TGF-β, and VEGF-A was significantly suppressed in VEGFR1 TK -/- mice, and the accumulation of VEGFR1 + cells in granulation tissue was reduced in VEGFR1 TK -/- mice compared to that in WT mice. The numbers of VEGFR1 + cells and S100A4 + cells derived from bone marrow (BM) were higher in WT mice transplanted with green fluorescent protein (GFP) transgenic WT BM than in VEGFR1 TK -/- mice transplanted with GFP transgenic VEGFR1 TK -/- BM. These results indicated that VEGFR1-TK signaling induced the accumulation of BM-derived VEGFR1 + cells expressing F4/80 and S100A4 and contributed to granulation formation around the surgically implanted sponge area in a mouse model.

Short-term oleoyl-estrone treatment affects capacity to manage lipids in rat adipose tissue

PubMed Central

Salas, Anna; Noé, Véronique; Ciudad, Carlos J; Romero, M Mar; Remesar, Xavier; Esteve, Montserrat

2007-01-01

Background Short-term OE (oleoyl-estrone) treatment causes significant decreases in rat weight mainly due to adipose tissue loss. The aim of this work was to determine if OE treatment affects the expression of genes that regulate lipid metabolism in white adipose tissue. Results Gene expression in adipose tissue from female treated rats (48 hours) was analysed by hybridization to cDNA arrays and levels of specific mRNAs were determined by real-time PCR. Treatment with OE decreased the expression of 232 genes and up-regulated 75 other genes in mesenteric white adipose tissue. The use of real-time PCR validate that, in mesenteric white adipose tissue, mRNA levels for Lipoprotein Lipase (LPL) were decreased by 52%, those of Fatty Acid Synthase (FAS) by 95%, those of Hormone Sensible Lipase (HSL) by 32%, those of Acetyl CoA Carboxylase (ACC) by 92%, those of Carnitine Palmitoyltransferase 1b (CPT1b) by 45%, and those of Fatty Acid Transport Protein 1 (FATP1) and Adipocyte Fatty Acid Binding Protein (FABP4) by 52% and 49%, respectively. Conversely, Tumour Necrosis Factor (TNFα) values showed overexpression (198%). Conclusion Short-term treatment with OE affects adipose tissue capacity to extract fatty acids from lipoproteins and to deal with fatty acid transport and metabolism. PMID:17725831

Short-term oleoyl-estrone treatment affects capacity to manage lipids in rat adipose tissue.

PubMed

Salas, Anna; Noé, Véronique; Ciudad, Carlos J; Romero, M Mar; Remesar, Xavier; Esteve, Montserrat

2007-08-28

Short-term OE (oleoyl-estrone) treatment causes significant decreases in rat weight mainly due to adipose tissue loss. The aim of this work was to determine if OE treatment affects the expression of genes that regulate lipid metabolism in white adipose tissue. Gene expression in adipose tissue from female treated rats (48 hours) was analysed by hybridization to cDNA arrays and levels of specific mRNAs were determined by real-time PCR. Treatment with OE decreased the expression of 232 genes and up-regulated 75 other genes in mesenteric white adipose tissue. The use of real-time PCR validate that, in mesenteric white adipose tissue, mRNA levels for Lipoprotein Lipase (LPL) were decreased by 52%, those of Fatty Acid Synthase (FAS) by 95%, those of Hormone Sensible Lipase (HSL) by 32%, those of Acetyl CoA Carboxylase (ACC) by 92%, those of Carnitine Palmitoyltransferase 1b (CPT1b) by 45%, and those of Fatty Acid Transport Protein 1 (FATP1) and Adipocyte Fatty Acid Binding Protein (FABP4) by 52% and 49%, respectively. Conversely, Tumour Necrosis Factor (TNFalpha) values showed overexpression (198%). Short-term treatment with OE affects adipose tissue capacity to extract fatty acids from lipoproteins and to deal with fatty acid transport and metabolism.

[The use of the T2-weighted turbo-spin-echo sequence in studying the neurocranium. A comparison with the conventional T2-weighted spin-echo sequence].

PubMed

Siewert, C; Hosten, N; Felix, R

1994-07-01

T2-weighted spin-echo imaging is the standard screening procedure in MR imaging of the neurocranium. We evaluated fast spin-echo T2-weighted imaging (TT2) of the neurocranium in comparison to conventional spin-echo T2-weighted imaging (T2). Signal-to-noise and contrast-to-noise ratio of normal brain tissues (basal ganglia, grey and white matter, CSF fluid) and different pathologies were calculated. Signal-to-noise ratio and contrast-to-noise ratio were significantly higher in TT2 than in T2 (with the exception of gray-to-white matter contrast). Tissues with increased content of water protons (mobile protons) showed the highest contrast to surrounding tissues. The increased signal intensity of fat must be given due attention in fatty lesions. Because the contrast-to-noise ratio between white matter and basal ganglia is less in TT2, Parkinson patients have to be examined by conventional T2. If these limitations are taken into account, fast spin-echo T2-weighted imaging is well appropriate for MR imaging of the neurocranium, resulting in heavy T2-weighting achieved in a short acquisition time.

Effective and organ doses from common CT examinations in one general hospital in Tehran, Iran

NASA Astrophysics Data System (ADS)

Khoramian, Daryoush; Hashemi, Bijan

2017-09-01

Purpose: It is well known that the main portion of artificial sources of ionizing radiation to human results from X-ray imaging techniques. However, reports carried out in various countries have indicated that most of their cumulative doses from artificial sources are due to CT examinations. Hence assessing doses resulted from CT examinations is highly recommended by national and international radiation protection agencies. The aim of this research has been to estimate the effective and organ doses in an average human according to 103 and 60 ICRP tissue weighting factor for six common protocols of Multi-Detector CT (MDCT) machine in a comprehensive training general hospital in Tehran/Iran. Methods: To calculate the patients' effective dose, the CT-Expo2.2 software was used. Organs/tissues and effective doses were determined for about 20 patients (totally 122 patients) for every one of six typical CT protocols of the head, neck, chest, abdomen-pelvis, pelvis and spine exams. In addition, the CT dosimetry index (CTDI) was measured in the standard 16 and 32 cm phantoms by using a calibrated pencil ionization chamber for the six protocols and by taking the average value of CT scan parameters used in the hospital compared with the CTDI values displayed on the console device of the machine. Results: The values of the effective dose based on the ICRP 103 tissue weighting factor were: 0.6, 2.0, 3.2, 4.2, 2.8, and 3.9 mSv and based on the ICRP 60 tissue weighting factor were: 0.9, 1.4, 3, 7.9, 4.8 and 5.1 mSv for the head, neck, chest, abdomen-pelvis, pelvis, spine CT exams respectively. Relative differences between those values were -22, 21, 23, -6, -31 and 16 percent for the head, neck, chest, abdomen-pelvis, pelvis, spine CT exams, respectively. The average value of CTDIv calculated for each protocol was: 27.32 ± 0.9, 18.08 ± 2.0, 7.36 ± 2.6, 8.84 ± 1.7, 9.13 ± 1.5, 10.42 ± 0.8 mGy for the head, neck, chest, abdomen-pelvis and spine CT exams, respectively. Conclusions: The highest organ doses delivered by various CT exams were received by brain (15.5 mSv), thyroid (19.00 mSv), lungs (9.3 mSv) and bladder (9.9 mSv), bladder (10.4 mSv), stomach (10.9 mSv) in the head, neck, chest, and the abdomen-pelvis, pelvis, and spine respectively. Except the neck and spine CT exams showing a higher effective dose compared to that reported in Netherlands, other exams indicated lower values compared to those reported by any other country.

Design, fabrication and characterization of oxidized alginate-gelatin hydrogels for muscle tissue engineering applications.

PubMed

Baniasadi, Hossein; Mashayekhan, Shohreh; Fadaoddini, Samira; Haghirsharifzamini, Yasamin

2016-07-01

In this study, we reported the preparation of self cross-linked oxidized alginate-gelatin hydrogels for muscle tissue engineering. The effect of oxidation degree (OD) and oxidized alginate/gelatin (OA/GEL) weight ratio were examined and the results showed that in the constant OA/GEL weight ratio, both cross-linking density and Young's modulus enhanced by increasing OD due to increment of aldehyde groups. Furthermore, the degradation rate was increased with increasing OD probably due to decrement in alginate molecular weight during oxidation reaction facilitated degradation of alginate chains. MTT cytotoxicity assays performed on Wharton's Jelly-derived umbilical cord mesenchymal stem cells cultured on hydrogels with OD of 30% showed that the highest rate of cell proliferation belong to hydrogel with OA/GEL weight ratio of 30/70. Overall, it can be concluded from all obtained results that the prepared hydrogel with OA/GEL weight ratio and OD of 30/70 and 30%, respectively, could be proper candidate for use in muscle tissue engineering. © The Author(s) 2016.

Effects of exercise training on chronic inflammation in obesity : current evidence and potential mechanisms.

PubMed

You, Tongjian; Arsenis, Nicole C; Disanzo, Beth L; Lamonte, Michael J

2013-04-01

Chronic, systemic inflammation is an independent risk factor for several major clinical diseases. In obesity, circulating levels of inflammatory markers are elevated, possibly due to increased production of pro-inflammatory cytokines from several tissues/cells, including macrophages within adipose tissue, vascular endothelial cells and peripheral blood mononuclear cells. Recent evidence supports that adipose tissue hypoxia may be an important mechanism through which enlarged adipose tissue elicits local tissue inflammation and further contributes to systemic inflammation. Current evidence supports that exercise training, such as aerobic and resistance exercise, reduces chronic inflammation, especially in obese individuals with high levels of inflammatory biomarkers undergoing a longer-term intervention. Several studies have reported that this effect is independent of the exercise-induced weight loss. There are several mechanisms through which exercise training reduces chronic inflammation, including its effect on muscle tissue to generate muscle-derived, anti-inflammatory 'myokine', its effect on adipose tissue to improve hypoxia and reduce local adipose tissue inflammation, its effect on endothelial cells to reduce leukocyte adhesion and cytokine production systemically, and its effect on the immune system to lower the number of pro-inflammatory cells and reduce pro-inflammatory cytokine production per cell. Of these potential mechanisms, the effect of exercise training on adipose tissue oxygenation is worth further investigation, as it is very likely that exercise training stimulates adipose tissue angiogenesis and increases blood flow, thereby reducing hypoxia and the associated chronic inflammation in adipose tissue of obese individuals.

Loss of body weight and fat and improved lipid profiles in obese rats fed apple pomace or apple juice concentrate.

PubMed

Cho, Kyung-Dong; Han, Chan-Kyu; Lee, Bog-Hieu

2013-09-01

The purpose of this study was to investigate the influence of apple pomace (AP) and apple juice concentrate (AC) supplementation on body weight and fat loss as well as lipid metabolism in obese rats fed a high-fat diet. Diet-induced obese rats were assigned to three groups (n=8 for each group): high fat diet (HFD) control, HFD containing 10% (w/w) AP, and HFD containing 10% (w/w) AC. There was also a normal diet group (n=8). After 5 weeks, body weight gain, adipose tissue weight, serum and hepatic lipid profiles, liver morphology, and adipocyte size were measured. Body weight gain, white adipose tissue (WAT) weight, serum total cholesterol, low-density lipoprotein cholesterol and triglyceride concentrations, epididymal adipocyte size, and lesion scores were significantly lower and serum high-density lipoprotein cholesterol concentration and brown adipose tissue weights were significantly higher in the AP and AC groups compared with the HFD group. In addition, atherogenic indices in the AP and AC groups were significantly lower than in the HFD group. These results indicate that supplementing apple products such as AP and AC may help suppress body weight and WAT gain, as well as improve lipid profiles in diet-induced obese rats.

Loss of Body Weight and Fat and Improved Lipid Profiles in Obese Rats Fed Apple Pomace or Apple Juice Concentrate

PubMed Central

Cho, Kyung-Dong; Han, Chan-Kyu

2013-01-01

Abstract The purpose of this study was to investigate the influence of apple pomace (AP) and apple juice concentrate (AC) supplementation on body weight and fat loss as well as lipid metabolism in obese rats fed a high-fat diet. Diet-induced obese rats were assigned to three groups (n=8 for each group): high fat diet (HFD) control, HFD containing 10% (w/w) AP, and HFD containing 10% (w/w) AC. There was also a normal diet group (n=8). After 5 weeks, body weight gain, adipose tissue weight, serum and hepatic lipid profiles, liver morphology, and adipocyte size were measured. Body weight gain, white adipose tissue (WAT) weight, serum total cholesterol, low-density lipoprotein cholesterol and triglyceride concentrations, epididymal adipocyte size, and lesion scores were significantly lower and serum high-density lipoprotein cholesterol concentration and brown adipose tissue weights were significantly higher in the AP and AC groups compared with the HFD group. In addition, atherogenic indices in the AP and AC groups were significantly lower than in the HFD group. These results indicate that supplementing apple products such as AP and AC may help suppress body weight and WAT gain, as well as improve lipid profiles in diet-induced obese rats. PMID:23909905

Examination of rare earth element concentration patterns in freshwater fish tissues.

PubMed

Mayfield, David B; Fairbrother, Anne

2015-02-01

Rare earth elements (REEs or lanthanides) were measured in ten freshwater fish species from a reservoir in Washington State (United States). The REE distribution patterns were examined within fillet and whole body tissues for three size classes. Total concentrations (ΣREE) ranged from 0.014 to 3.0 mg kg(-1) (dry weight) and averaged 0.243 mg kg(-1) (dry weight). Tissue concentration patterns indicated that REEs accumulated to a greater extent in organs, viscera, and bone compared to muscle (fillet) tissues. Benthic feeding species (exposed to sediments) exhibited greater concentrations of REEs than pelagic omnivorous or piscivorous fish species. Decreasing REE concentrations were found with increasing age, total length or weight for largescale and longnose suckers, smallmouth bass, and walleye. Concentration patterns in this system were consistent with natural conditions without anthropogenic sources of REEs. These data provide additional reference information with regard to the fate and transport of REEs in freshwater fish tissues in a large aquatic system. Copyright © 2014 Elsevier Ltd. All rights reserved.

Galloylglucoses of low molecular weight as mordant in electron microscopy. I. Procedure, and evidence for mordanting effect

PubMed Central

1976-01-01

Gallotannin, consisting mainly of low molecular weight esters such as penta- and hexagalloylglucoses (commercially available as tannic acid produced from Turkish nutgall), can be used for increasing and diversifying tissue contrast in electron microscopy. When applied on tissue specimens previously fixed by conventional methods (aldehydes and OsO4), the low molecular weight galloylglucoses (LMGG) penetrate satisfactorily the cells and induce general high contrast with fine delineation of extra- and intracellular structures, especially membranes. In some features, additional details of their intimate configuration are revealed. Various experimental conditions tested indicate that the LMGG display a complex effect on fixed tissues: they act primarily as a mordant between osmium-treated structures and lead, and concomitantly stabilize some tissue components against extraction incurred during dehydration and subsequent processing. Experiments with aldehyde blocking reagents (sodium borohydride and glycine) suggested that the LMGG mordanting effect is not dependent on residual aldehydes groups in tissues. PMID:783172

Can we produce heparin/heparan sulfate biomimetics using "mother-nature" as the gold standard?

PubMed

Farrugia, Brooke L; Lord, Megan S; Melrose, James; Whitelock, John M

2015-03-05

Heparan sulfate (HS) and heparin are glycosaminoglycans (GAGs) that are heterogeneous in nature, not only due to differing disaccharide combinations, but also their sulfate modifications. HS is well known for its interactions with various growth factors and cytokines; and heparin for its clinical use as an anticoagulant. Due to their potential use in tissue regeneration; and the recent adverse events due to contamination of heparin; there is an increased surge to produce these GAGs on a commercial scale. The production of HS from natural sources is limited so strategies are being explored to be biomimetically produced via chemical; chemoenzymatic synthesis methods and through the recombinant expression of proteoglycans. This review details the most recent advances in the field of HS/heparin synthesis for the production of low molecular weight heparin (LMWH) and as a tool further our understanding of the interactions that occur between GAGs and growth factors and cytokines involved in tissue development and repair.

Are liver and renal lesions in East Greenland polar bears (Ursus maritimus) associated with high mercury levels?

PubMed

Sonne, Christian; Dietz, Rune; Leifsson, Pall S; Asmund, Gert; Born, Erik W; Kirkegaard, Maja

2007-04-17

In the Arctic, polar bears (Ursus maritimus) bio-accumulate mercury as they prey on polluted ringed seals (Phoca hispida) and bearded seals (Erignathus barbatus). Studies have shown that polar bears from East Greenland are among the most mercury polluted species in the Arctic. It is unknown whether these levels are toxic to liver and kidney tissue. We investigated the histopathological impact from anthropogenic long-range transported mercury on East Greenland polar bear liver (n = 59) and kidney (n = 57) tissues. Liver mercury levels ranged from 1.1-35.6 microg/g wet weight and renal levels ranged from 1-50 microg/g wet weight, of which 2 liver values and 9 kidney values were above known toxic threshold level of 30 microg/g wet weight in terrestrial mammals. Evaluated from age-correcting ANCOVA analyses, liver mercury levels were significantly higher in individuals with visible Ito cells (p < 0.02) and a similar trend was found for lipid granulomas (p = 0.07). Liver mercury levels were significantly lower in individuals with portal bile duct proliferation/fibrosis (p = 0.007) and a similar trend was found for proximal convoluted tubular hyalinisation in renal tissue (p = 0.07). Based on these relationships and the nature of the chronic inflammation we conclude that the lesions were likely a result of recurrent infections and ageing but that long-term exposure to mercury could not be excluded as a co-factor. The information is important as it is likely that tropospheric mercury depletion events will continue to increase the concentrations of this toxic heavy metal in the Sub Arctic and Arctic marine food webs.

A beta cell ATGL-lipolysis/adipose tissue axis controls energy homeostasis and body weight via insulin secretion in mice.

PubMed

Attané, Camille; Peyot, Marie-Line; Lussier, Roxane; Poursharifi, Pegah; Zhao, Shangang; Zhang, Dongwei; Morin, Johane; Pineda, Marco; Wang, Shupei; Dumortier, Olivier; Ruderman, Neil B; Mitchell, Grant A; Simons, Brigitte; Madiraju, S R Murthy; Joly, Erik; Prentki, Marc

2016-12-01

To directly assess the role of beta cell lipolysis in insulin secretion and whole-body energy homeostasis, inducible beta cell-specific adipose triglyceride lipase (ATGL)-deficient (B-Atgl-KO) mice were studied under normal diet (ND) and high-fat diet (HFD) conditions. Atgl flox/flox mice were cross-bred with Mip-Cre-ERT mice to generate Mip-Cre-ERT /+ ;Atgl flox/flox mice. At 8 weeks of age, these mice were injected with tamoxifen to induce deletion of beta cell-specific Atgl (also known as Pnpla2), and the mice were fed an ND or HFD. ND-fed male B-Atgl-KO mice showed decreased insulinaemia and glucose-induced insulin secretion (GSIS) in vivo. Changes in GSIS correlated with the islet content of long-chain saturated monoacylglycerol (MAG) species that have been proposed to be metabolic coupling factors for insulin secretion. Exogenous MAGs restored GSIS in B-Atgl-KO islets. B-Atgl-KO male mice fed an HFD showed reduced insulinaemia, glycaemia in the fasted and fed states and after glucose challenge, as well as enhanced insulin sensitivity. Moreover, decreased insulinaemia in B-Atgl-KO mice was associated with increased energy expenditure, and lipid metabolism in brown (BAT) and white (WAT) adipose tissues, leading to reduced fat mass and body weight. ATGL in beta cells regulates insulin secretion via the production of signalling MAGs. Decreased insulinaemia due to lowered GSIS protects B-Atgl-KO mice from diet-induced obesity, improves insulin sensitivity, increases lipid mobilisation from WAT and causes BAT activation. The results support the concept that fuel excess can drive obesity and diabetes via hyperinsulinaemia, and that an islet beta cell ATGL-lipolysis/adipose tissue axis controls energy homeostasis and body weight via insulin secretion.

Epicardial fat gene expression after aerobic exercise training in pigs with coronary atherosclerosis: relationship to visceral and subcutaneous fat.

PubMed

Company, Joseph M; Booth, Frank W; Laughlin, M Harold; Arce-Esquivel, Arturo A; Sacks, Harold S; Bahouth, Suleiman W; Fain, John N

2010-12-01

Epicardial adipose tissue (EAT) is contiguous with coronary arteries and myocardium and potentially may play a role in coronary atherosclerosis (CAD). Exercise is known to improve cardiovascular disease risk factors. The purpose of this study was to investigate the effect of aerobic exercise training on the expression of 18 genes, measured by RT-PCR and selected for their role in chronic inflammation, oxidative stress, and adipocyte metabolism, in peri-coronary epicardial (cEAT), peri-myocardial epicardial (mEAT), visceral abdominal (VAT), and subcutaneous (SAT) adipose tissues from a castrate male pig model of familial hypercholesterolemia with CAD. We tested the hypothesis that aerobic exercise training for 16 wk would reduce the inflammatory profile of mRNAs in both components of EAT and VAT but would have little effect on SAT. Exercise increased mEAT and total heart weights. EAT and heart weights were directly correlated. Compared with sedentary pigs matched for body weight to exercised animals, aerobic exercise training reduced the inflammatory response in mEAT but not cEAT, had no effect on inflammatory genes but preferentially decreased expression of adiponectin and other adipocyte-specific genes in VAT, and had no effect in SAT except that IL-6 mRNA went down and VEGFa mRNA went up. We conclude that 1) EAT is not homogeneous in its inflammatory response to aerobic exercise training, 2) cEAT around CAD remains proinflammatory after chronic exercise, 3) cEAT and VAT share similar inflammatory expression profiles but different metabolic mRNA responses to exercise, and 4) gene expression in SAT cannot be extrapolated to VAT and heart adipose tissues in exercise intervention studies.

Cafeteria diet overfeeding in young male rats impairs the adaptive response to fed/fasted conditions and increases adiposity independent of body weight.

PubMed

Castro, H; Pomar, C A; Picó, C; Sánchez, J; Palou, A

2015-03-01

We analyzed the effects of a short exposure to a cafeteria diet during early infancy in rats on their metabolic response to fed/fasting conditions in key tissues involved in energy homeostasis. Ten-day-old male pups were fed a control or a cafeteria diet for 12 days and then killed under ad libitum feeding conditions or 12 h fasting. The expression of key genes related to energy metabolism in liver, retroperitoneal white adipose tissue (WAT) and hypothalamus were analyzed. Despite no differences in body weight, cafeteria-fed animals had almost double the fat mass of control rats. They also showed higher food intake, higher leptinemia and altered hypothalamic expression of Neuropetide Y, suggesting a dysfunction in the control of food intake. Unlike controls, cafeteria-fed animals did not decrease WAT expression of Pparg, sterol regulatory element binding transcription factor 1 or Cidea under fasting conditions, and displayed lower Pnpla2 expression than controls. In liver, compared with controls, cafeteria animals presented: (i) lower expression of genes related with fatty acid uptake and lipogenesis under ad libitum-fed conditions; (ii) higher expression of fatty acid oxidation-related genes and glucokinase under fasting conditions; (iii) greater expression of leptin and insulin receptors; and higher protein levels of insulin receptor and the pAMPK/AMPK ratio. A short period of exposure to a cafeteria diet in early infancy in rat pups is enough to disturb the metabolic response to fed/fasting conditions in key tissues involved in energy homeostasis, particularly in WAT, and hence induces an exacerbated body fat accumulation and increased metabolic risk, with no apparent effects on body weight.

Epicardial fat gene expression after aerobic exercise training in pigs with coronary atherosclerosis: relationship to visceral and subcutaneous fat

PubMed Central

Booth, Frank W.; Laughlin, M. Harold; Arce-Esquivel, Arturo A.; Sacks, Harold S.; Bahouth, Suleiman W.; Fain, John N.

2010-01-01

Epicardial adipose tissue (EAT) is contiguous with coronary arteries and myocardium and potentially may play a role in coronary atherosclerosis (CAD). Exercise is known to improve cardiovascular disease risk factors. The purpose of this study was to investigate the effect of aerobic exercise training on the expression of 18 genes, measured by RT-PCR and selected for their role in chronic inflammation, oxidative stress, and adipocyte metabolism, in peri-coronary epicardial (cEAT), peri-myocardial epicardial (mEAT), visceral abdominal (VAT), and subcutaneous (SAT) adipose tissues from a castrate male pig model of familial hypercholesterolemia with CAD. We tested the hypothesis that aerobic exercise training for 16 wk would reduce the inflammatory profile of mRNAs in both components of EAT and VAT but would have little effect on SAT. Exercise increased mEAT and total heart weights. EAT and heart weights were directly correlated. Compared with sedentary pigs matched for body weight to exercised animals, aerobic exercise training reduced the inflammatory response in mEAT but not cEAT, had no effect on inflammatory genes but preferentially decreased expression of adiponectin and other adipocyte-specific genes in VAT, and had no effect in SAT except that IL-6 mRNA went down and VEGFa mRNA went up. We conclude that 1) EAT is not homogeneous in its inflammatory response to aerobic exercise training, 2) cEAT around CAD remains proinflammatory after chronic exercise, 3) cEAT and VAT share similar inflammatory expression profiles but different metabolic mRNA responses to exercise, and 4) gene expression in SAT cannot be extrapolated to VAT and heart adipose tissues in exercise intervention studies. PMID:20947714

Role of the parameters involved in the plan optimization based on the generalized equivalent uniform dose and radiobiological implications

NASA Astrophysics Data System (ADS)

Widesott, L.; Strigari, L.; Pressello, M. C.; Benassi, M.; Landoni, V.

2008-03-01

We investigated the role and the weight of the parameters involved in the intensity modulated radiation therapy (IMRT) optimization based on the generalized equivalent uniform dose (gEUD) method, for prostate and head-and-neck plans. We systematically varied the parameters (gEUDmax and weight) involved in the gEUD-based optimization of rectal wall and parotid glands. We found that the proper value of weight factor, still guaranteeing planning treatment volumes coverage, produced similar organs at risks dose-volume (DV) histograms for different gEUDmax with fixed a = 1. Most of all, we formulated a simple relation that links the reference gEUDmax and the associated weight factor. As secondary objective, we evaluated plans obtained with the gEUD-based optimization and ones based on DV criteria, using the normal tissue complication probability (NTCP) models. gEUD criteria seemed to improve sparing of rectum and parotid glands with respect to DV-based optimization: the mean dose, the V40 and V50 values to the rectal wall were decreased of about 10%, the mean dose to parotids decreased of about 20-30%. But more than the OARs sparing, we underlined the halving of the OARs optimization time with the implementation of the gEUD-based cost function. Using NTCP models we enhanced differences between the two optimization criteria for parotid glands, but no for rectum wall.

The parallel-antiparallel signal difference in double-wave-vector diffusion-weighted MR at short mixing times: A phase evolution perspective

NASA Astrophysics Data System (ADS)

Finsterbusch, Jürgen

2011-01-01

Experiments with two diffusion weightings applied in direct succession in a single acquisition, so-called double- or two-wave-vector diffusion-weighting (DWV) experiments at short mixing times, have been shown to be a promising tool to estimate cell or compartment sizes, e.g. in living tissue. The basic theory for such experiments predicts that the signal decays for parallel and antiparallel wave vector orientations differ by a factor of three for small wave vectors. This seems to be surprising because in standard, single-wave-vector experiments the polarity of the diffusion weighting has no influence on the signal attenuation. Thus, the question how this difference can be understood more pictorially is often raised. In this rather educational manuscript, the phase evolution during a DWV experiment for simple geometries, e.g. diffusion between parallel, impermeable planes oriented perpendicular to the wave vectors, is considered step-by-step and demonstrates how the signal difference develops. Considering the populations of the phase distributions obtained, the factor of three between the signal decays which is predicted by the theory can be reproduced. Furthermore, the intermediate signal decay for orthogonal wave vector orientations can be derived when investigating diffusion in a box. Thus, the presented “phase gymnastics” approach may help to understand the signal modulation observed in DWV experiments at short mixing times.

Arctigenin Inhibits Adipogenesis by Inducing AMPK Activation and Reduces Weight Gain in High-Fat Diet-Induced Obese Mice.

PubMed

Han, Yo-Han; Kee, Ji-Ye; Park, Jinbong; Kim, Hye-Lin; Jeong, Mi-Young; Kim, Dae-Seung; Jeon, Yong-Deok; Jung, Yunu; Youn, Dong-Hyun; Kang, JongWook; So, Hong-Seob; Park, Raekil; Lee, Jong-Hyun; Shin, Soyoung; Kim, Su-Jin; Um, Jae-Young; Hong, Seung-Heon

2016-09-01

Although arctigenin (ARC) has been reported to have some pharmacological effects such as anti-inflammation, anti-cancer, and antioxidant, there have been no reports on the anti-obesity effect of ARC. The aim of this study is to investigate whether ARC has an anti-obesity effect and mediates the AMP-activated protein kinase (AMPK) pathway. We investigated the anti-adipogenic effect of ARC using 3T3-L1 pre-adipocytes and human adipose tissue-derived mesenchymal stem cells (hAMSCs). In high-fat diet (HFD)-induced obese mice, whether ARC can inhibit weight gain was investigated. We found that ARC reduced weight gain, fat pad weight, and triglycerides in HFD-induced obese mice. ARC also inhibited the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα) in in vitro and in vivo. Furthermore, ARC induced the AMPK activation resulting in down-modulation of adipogenesis-related factors including PPARγ, C/EBPα, fatty acid synthase, adipocyte fatty acid-binding protein, and lipoprotein lipase. This study demonstrates that ARC can reduce key adipogenic factors by activating the AMPK in vitro and in vivo and suggests a therapeutic implication of ARC for obesity treatment. J. Cell. Biochem. 117: 2067-2077, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Traumatic Hemothorax Blood Contains Elevated Levels of Microparticles that are Prothrombotic but Inhibit Platelet Aggregation.

PubMed

Mitchell, Thomas A; Herzig, Maryanne C; Fedyk, Chriselda G; Salhanick, Marc A; Henderson, Aaron T; Parida, Bijaya K; Prat, Nicolas J; Dent, Daniel L; Schwacha, Martin G; Cap, Andrew P

2017-06-01

Autotransfusion of shed blood from traumatic hemothorax is an attractive option for resuscitation of trauma patients in austere environments. However, previous analyses revealed that shed hemothorax (HX) blood is defibrinated, thrombocytopenic, and contains elevated levels of D-dimer. Mixing studies with normal pooled plasma demonstrated hypercoagulability, evoking concern for potentiation of acute traumatic coagulopathy. We hypothesized that induction of coagulopathic changes by shed HX blood may be due to increases in cellular microparticles (MP) and that these may also affect recipient platelet function. Shed HX blood was obtained from 17 adult trauma patients under an Institutional Review Board approved prospective observational protocol. Blood samples were collected every hour up to 4 h after thoracostomy tube placement. The corresponding plasma was isolated and frozen for analysis. The effects of shed HX frozen plasma (HFP) and isolated HX microparticles (HMP) on coagulation and platelet function were assessed through mixing studies with platelet-rich plasma at various dilutions followed by analysis with thromboelastometry (ROTEM), platelet aggregometry (Multiplate), enzyme-linked immunosorbent assays, and flow cytometry. Furthermore, HFP was assessed for von Willebrand factor antigen levels and multimer content, and plasma-free hemoglobin. ROTEM analysis demonstrated that diluted HFP and isolated HMP samples decreased clotting time, clotting formation time, and increased α angle, irrespective of sample concentrations, when compared with diluted control plasma. Isolated HMP inhibited platelet aggregation in response to adenosine diphosphate, arachidonic acid, and collagen. HFP contained elevated levels of fibrin-degradation products and tissue factor compared with control fresh frozen plasma samples. MP concentrations in HFP were significantly increased and enriched in events positive for phosphatidylserine, tissue factor, CD235, CD45, CD41a, and CD14. von Willebrand factor (vWF) multimer analysis revealed significant loss of high molecular weight multimers in HFP samples. Plasma-free hemoglobin levels were 8-fold higher in HFP compared with fresh frozen plasma. HFP induces plasma hypercoagulability that is likely related to increased tissue factor and phosphatidylserine expression originating from cell-derived MP. In contrast, platelet dysfunction is induced by HMP, potentially aggravated by depletion of high molecular weight multimers of vWF. Thus, autologous transfusion of shed traumatic hemothorax blood may induce a range of undesirable effects in patients with acute traumatic coagulopathy.

Potential beneficial effect of some adipokines positively correlated with the adipose tissue content on the cardiovascular system.

PubMed

Sawicka, Magdalena; Janowska, Joanna; Chudek, Jerzy

2016-11-01

Obesity is a risk factor of cardiovascular diseases. However, in the case of heart failure, obese and overweight patients have a more favourable prognosis compared to patients who have a normal body weight. This phenomenon is referred to as the "obesity paradox," and it is explained by, among others, a positive effect of adipokines produced by adipose tissue, particularly by the tissue located in the direct vicinity of the heart and blood vessels. The favourable effect on the cardiovascular system is mostly associated with adiponectin and omentin, but the levels of these substances are reduced in obese patients. Among the adipokines which levels are positively correlated with the adipose tissue content, favourable activity is demonstrated by apelin, progranulin, chemerin, TNF-α (tumour necrosis factor-)α, CTRP-3 (C1q/tumour necrosis factor (TNF) related protein), leptin, visfatin and vaspin. This activity is associated with the promotion of regeneration processes in the damaged myocardium, formation of new blood vessels, reduction of the afterload, improvement of metabolic processes in cardiomyocytes and myocardial contractile function, inhibition of apoptosis and fibrosis of the myocardium, as well as anti-inflammatory and anti-atheromatous effects. The potential use of these properties in the treatment of heart failure and ischaemic heart disease, as well as in pulmonary hypertension, arterial hypertension and the limitation of the loss of cardiomyocytes during cardioplegia-requiring cardiosurgical procedures, is studied. The most advanced studies focus on analogues of apelin and progranulin. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Weight Measurement and Volumetric Displacement of Breast Implants and Tissue Expanders: Why Port and Shell Volumes Matter in Breast Reconstruction, Augmentation, and Revision.

PubMed

Wenzel, Chad G; Wacholtz, William F; Janssen, David A; Bengtson, Bradley P

2015-10-01

There are significant differences in weight and volumetric characteristics between silicone and saline breast implants of which most plastic surgeons are unaware. Phase I of this study was a weight measurement focused on recording differences in the weight of saline volumes instilled versus recorded weights of saline implants and expanders. Phase II compared displaced volume differences of tissue expanders with instilled volumes. As a result of this study, surgeons should now be able to precisely calculate the volume created for breast pocket development, allowing for accurate matching of expander and final breast implant. Copyright © 2015 Elsevier Inc. All rights reserved.

Gel filtration applied to the study of lipases and other esterases

PubMed Central

Downey, W. K.; Andrews, P.

1965-01-01

1. Sephadex G-100 and G-200 gel-filtration columns were calibrated for molecular-weight estimation with proteins of known molecular weights, and used to study the composition of several lipase or esterase preparations. 2. Enzymes from cow's milk, rat adipose tissue and pig pancreas were detected in the column effluents by their ability to liberate free acid from emulsified tributyrin at pH 8·5. 3. Four tributyrinases were detected in preparations from individual cow's milks. Molecular weights 62000, 75000 and 112000 were estimated for three of them, but although the fourth may be of unusually low molecular weight an estimate was not possible. 4. Extracts of rat adipose tissue apparently contained six tributyrinases (molecular weights 39000, 47000, 55000, 68000, 75000 and 200000) but the relative amounts of these enzymes varied widely from rat to rat. 5. Tributyrinase activity in juice expressed from pig pancreatic tissue was due mainly to one enzyme (molecular weight 42000). On the other hand, activity in extracts of acetone-dried pancreas was confined to material of molecular weight > 106, which may be an aggregated form of the lower-molecular-weight enzyme. 6. Activity in fractionated wheat-germ extracts was assayed with emulsified triacetin substrate, and was evidently due to one enzyme (molecular weight 51000). 7. Some problems arising in the application of gel filtration to the study of lipase–esterase systems were indicated. PMID:14340054

The effect of total knee arthroplasty on body weight.

PubMed

Lee, Gwo-Chin; Cushner, Fred D; Cannella, Laura Y; Scott, W Norman

2005-03-01

This prospective study quantified the weight change in 20 consecutive patients undergoing total knee arthroplasty. Resected bone, soft tissues, and bone reamings were collected during surgery and weighed using a digital scale at the end of the procedure. Results were compared to the cumulative weights of the prosthesis, bone cement, patellar component, and polyethylene liner. Average weight of the resected bone and soft tissues was 167.71 g for men and 130.13 g for women. Mean weight of the implanted prosthesis and cement used was 509.92 g for men and 422.56 g for women. Men tended to receive a larger-sized prosthesis than women. Overall, the average weight gain as a result of knee arthroplasty was 345.54 g for men and 292.44 g for women. This translates to an insignificant increase in body weight.

Phospholipases D1 and D2 Suppress Appetite and Protect against Overweight.

PubMed

Trujillo Viera, Jonathan; El-Merahbi, Rabih; Nieswandt, Bernhard; Stegner, David; Sumara, Grzegorz

2016-01-01

Obesity is a major risk factor predisposing to the development of peripheral insulin resistance and type 2 diabetes (T2D). Elevated food intake and/or decreased energy expenditure promotes body weight gain and acquisition of adipose tissue. Number of studies implicated phospholipase D (PLD) enzymes and their product, phosphatidic acid (PA), in regulation of signaling cascades controlling energy intake, energy dissipation and metabolic homeostasis. However, the impact of PLD enzymes on regulation of metabolism has not been directly determined so far. In this study we utilized mice deficient for two major PLD isoforms, PLD1 and PLD2, to assess the impact of these enzymes on regulation of metabolic homeostasis. We showed that mice lacking PLD1 or PLD2 consume more food than corresponding control animals. Moreover, mice deficient for PLD2, but not PLD1, present reduced energy expenditure. In addition, deletion of either of the PLD enzymes resulted in development of elevated body weight and increased adipose tissue content in aged animals. Consistent with the fact that elevated content of adipose tissue predisposes to the development of hyperlipidemia and insulin resistance, characteristic for the pre-diabetic state, we observed that Pld1-/- and Pld2-/- mice present elevated free fatty acids (FFA) levels and are insulin as well as glucose intolerant. In conclusion, our data suggest that deficiency of PLD1 or PLD2 activity promotes development of overweight and diabetes.

ALLOMETRIC LENGTH-WEIGHT RELATIONSHIPS FOR BENTHIC PREY OF AQUATIC WILDLIFE IN COASTAL MARINE HABITATS

EPA Science Inventory

We developed models to estimate the soft tissue content of benthic marine invertebrates that are prey for aquatic wildlife. Allometric regression models of tissue wet weight with shell length for 10 species of benthic invertebrates had r2 values ranging from 0.29 for hermit crabs...

Tissue proteomics of the low-molecular weight proteome using an integrated cLC-ESI-QTOFMS approach.

PubMed

Alvarez, MeiHwa Tanielle Bench; Shah, Dipti Jigar; Thulin, Craig D; Graves, Steven W

2013-05-01

Analysis of the protein/peptide composition of tissue has provided meaningful insights into tissue biology and even disease mechanisms. However, little has been published regarding top down methods to investigate lower molecular weight (MW) (500-5000 Da) species in tissue. Here, we evaluate a tissue proteomics approach involving tissue homogenization followed by depletion of large proteins and then cLC-MS (where c stands for capillary) analysis to interrogate the low MW/low abundance tissue proteome. In the development of this method, sheep heart, lung, liver, kidney, and spleen were surveyed to test our ability to observe tissue differences. After categorical tissue differences were demonstrated, a detailed study of this method's reproducibility was undertaken to determine whether or not it is suitable for analyzing more subtle differences in the abundance of small proteins and peptides. Our results suggest that this method should be useful in exploring the low MW proteome of tissues. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Improved systemic metabolism and adipocyte biology in miR-150 knockout mice.

PubMed

Kang, Minsung; Liu, Xiaobing; Fu, Yuchang; Timothy Garvey, W

2018-06-01

Short non-coding micro-RNAs (miRNAs) are post-transcriptional factors that directly regulate protein expression by degrading or inhibiting target mRNAs; however, the role of miRNAs in obesity and cardiometabolic disease remains unclarified. Based on our earlier study demonstrating that miR-150 influences lipid metabolism, we have studied effects of miR-150 on systemic metabolism and adipocyte biology. Metabolic phenotypes including body weight, food intake, body composition, glucose tolerance and insulin sensitivity were assessed in WT and global miR-150 KO male mice fed a high-fat diet. Molecular changes in epididymal adipose tissue were evaluated through qRT-PCR and Western blotting. miR-150 KO mice displayed lower body weight characterized by a reduction in % fat mass while % lean mass was increased. Lower body weight was associated with reduced food consumption and an increase in circulating leptin concentrations, as well as enhanced insulin sensitivity and glucose tolerance compared with WT mice. Absence of miR-150 resulted in increased mTOR expression known to participate in increased leptin production leading to reduction of food intake. Expression of PGC-1α, another target gene of miR-150, was also increased together with upregulation of PPARα and glycerol kinase in adipose tissue as well as other genes participating in triglyceride degradation and lipid oxidation. miR-150 KO mice showed metabolic benefits accompanied by reduced body weight, decreased energy intake, and enhanced lipid metabolism. miR-150 may represent both a biomarker and novel therapeutic target regarding obesity and insulin resistance. Copyright © 2018. Published by Elsevier Inc.

Vacuum-assisted breast biopsy with 7-gauge, 8-gauge, 9-gauge, 10-gauge, and 11-gauge needles: how many specimens are necessary?

PubMed

Preibsch, Heike; Baur, Astrid; Wietek, Beate M; Krämer, Bernhard; Staebler, Annette; Claussen, Claus D; Siegmann-Luz, Katja C

2015-09-01

Published national and international guidelines and consensus meetings on the use of vacuum-assisted biopsy (VAB) give different recommendations regarding the required numbers of tissue specimens depending on needle size and imaging method. To evaluate the weights of specimens obtained with different VAB needles to facilitate the translation of the required number of specimens between different breast biopsy systems and needle sizes, respectively. Five different VAB systems and seven different needle sizes were used: Mammotome® (11-gauge (G), 8-G), Vacora® (10-G), ATEC Sapphire™ (9-G), 8-G Mammotome® Revolve™, and EnCor Enspire® (10-G, 7-G). We took 24 (11-G) or 20 (7-10-G) tissue cores from a turkey breast phantom. The mean weight of a single tissue core was calculated for each needle size. A matrix, which allows the translation of the required number of tissue cores for different needle sizes, was generated. Results were compared to the true cumulative tissue weights of consecutively harvested tissue cores. The mean tissue weights obtained with the 11-G / 10-G Vacora® / 10-G Enspire® / 9-G / 8-G Original / 8-G Revolve™ / 7-G needles were 0.084 g / 0.142 g / 0.221 g / 0.121 g / 0.192 g / 0.334 g / 0.363 g, respectively. The calculated required numbers of VAB tissue cores for each needle size build the matrix. For example, the minimum calculated number of required cores according to the current German S3 guideline is 20 / 12 / 8 / 14 / 9 / 5 / 5 for needles of 11-G / 10-G Vacora® / 10-G Enspire® / 9-G / 8-G Original / 8-G Revolve™ / 7-G size. These numbers agree with the true cumulative tissue weights. The presented matrix facilitates the translation of the required number of VAB specimens between different needle sizes and thereby eases the implementation of current guidelines and consensus recommendations into clinical practice. © The Foundation Acta Radiologica 2014.

Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres

NASA Astrophysics Data System (ADS)

Skala, Melissa C.; Crow, Matthew J.; Wax, Adam; Izatt, Joseph A.

2009-02-01

Molecular imaging is a powerful tool for investigating disease processes and potential therapies in both in vivo and in vitro systems. However, high resolution molecular imaging has been limited to relatively shallow penetration depths that can be accessed with microscopy. Optical coherence tomography (OCT) is an optical analogue to ultrasound with relatively good penetration depth (1-2 mm) and resolution (~1-10 μm). We have developed and characterized photothermal OCT as a molecular contrast mechanism that allows for high resolution molecular imaging at deeper penetration depths than microscopy. Our photothermal system consists of an amplitude-modulated heating beam that spatially overlaps with the focused spot of the sample arm of a spectral-domain OCT microscope. Validation experiments in tissue-like phantoms containing gold nanospheres that absorb at 532 nm revealed a sensitivity of 14 parts per million nanospheres (weight/weight) in a tissue-like environment. The nanospheres were then conjugated to anti-EGFR, and molecular targeting was confirmed in cells that over-express EGFR (MDA-MB-468) and cells that express low levels of EGFR (MDA-MB-435). Molecular imaging in three-dimensional tissue constructs was confirmed with a significantly lower photothermal signal (p<0.0001) from the constructs composed of cells that express low levels of EGFR compared to the over-expressing cell constructs (300% signal increase). This technique could potentially augment confocal and multiphoton microscopy as a method for deep-tissue, depth-resolved molecular imaging with relatively high resolution and target sensitivity, without photobleaching or cytotoxicity.

Evaluating nephrotoxicity of high-molecular-weight organic compounds in drinking water from lignite aquifers

USGS Publications Warehouse

Bunnell, J.E.; Tatu, C.A.; Lerch, H.E.; Orem, W.H.; Pavlovic, N.

2007-01-01

High-molecular-weight organic compounds such as humic acids and/or fulvic acids that are naturally mobilized from lignite beds into untreated drinking-water supplies were suggested as one possible cause of Balkan endemic nephropathy (BEN) and cancer of the renal pelvis. A lab investigation was undertaken in order to assess the nephrotoxic potential of such organic compounds using an in vitro tissue culture model. Because of the infeasibility of exposing kidney tissue to low concentrations of organics for years in the lab, tangential flow ultrafiltration was employed to hyperconcentrate samples suitable for discerning effects in the short time frames necessitated by tissue culture systems. Effects on HK-2 kidney cells were measured using two different cell proliferation assays (MTT and alamarBlue). Results demonstrated that exposure of kidney tissue to high-molecular-weight organics produced excess cell death or proliferation depending on concentration and duration of exposure. Copyright ?? Taylor & Francis Group, LLC.

Stevioside ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by downregulating the NF-{kappa}B pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Zhiquan; Xue, Liqiong; Guo, Cuicui

Highlights: Black-Right-Pointing-Pointer Stevioside ameliorates high-fat diet-induced insulin resistance. Black-Right-Pointing-Pointer Stevioside alleviates the adipose tissue inflammation. Black-Right-Pointing-Pointer Stevioside reduces macrophages infiltration into the adipose tissue. Black-Right-Pointing-Pointer Stevioside suppresses the activation of NF-{kappa}B in the adipose tissue. -- Abstract: Accumulating evidence suggests that adipose tissue is the main source of pro-inflammatory molecules that predispose individuals to insulin resistance. Stevioside (SVS) is a widely used sweetener with multiple beneficial effects for diabetic patients. In this study, we investigated the effect of SVS on insulin resistance and the pro-inflammatory state of adipose tissue in mice fed with a high-fat diet (HFD). Oral administration ofmore » SVS for 1 month had no effect on body weight, but it significantly improved fasting glucose, basal insulin levels, glucose tolerance and whole body insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of several inflammatory cytokines in adipose tissue, including TNF-{alpha}, IL6, IL10, IL1{beta}, KC, MIP-1{alpha}, CD11b and CD14. Moreover, macrophage infiltration in adipose tissue was remarkably reduced by SVS. Finally, SVS significantly suppressed the nuclear factor-kappa b (NF-{kappa}B) signaling pathway in adipose tissue. Collectively, these results suggested that SVS may ameliorate insulin resistance in HFD-fed mice by attenuating adipose tissue inflammation and inhibiting the NF-{kappa}B pathway.« less

Weight-dependent changes of immune system in adipose tissue: Importance of leptin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caspar-Bauguil, S.; Groupe de Recherche et d'Etude en Nutrition; Cousin, B.

2006-07-15

Ancestral lymphoid cells reside in adipose tissues, and their numbers are highly altered in obesity. Leptin, production of which is correlated to fat mass, is strongly involved in the relationships between adipose tissues and immune system. We investigated in epididymal (EPI) and inguinal (ING) fat pads to determine whether 1) lymphocyte phenotypes were correlated to the tissue weight and 2) leptin was involved in such relationships. Immunohistological analyses revealed a tight relationship between the T and NK lymphocytes of the stromal vascular fraction and adipocytes. We identified a significant negative and positive correlation between EPI weight and the percentage ofmore » NK and total T cells respectively by cytofluorometric analyses. The NK and ancestral {gamma}{delta} T cell contents were directly dependent of leptin since they increased significantly in high-fat (HF) diet mice but not in leptin-deficient (ob/ob) mice as compared to control. By contrast, the {alpha}{beta} T cell content seemed independent of leptin because their percentages increased significantly with the EPI weight whatever the type of mice (control, HF, ob/ob). The present study suggests that adipose tissues present, according to their localization, different immunological mechanisms that might be involved in the regulation of adipose cells functions and proliferations.« less

Parameters and computer software for the evaluation of mass attenuation and mass energy-absorption coefficients for body tissues and substitutes.

PubMed

Okunade, Akintunde A

2007-07-01

The mass attenuation and energy-absorption coefficients (radiation interaction data), which are widely used in the shielding and dosimetry of X-rays used for medical diagnostic and orthovoltage therapeutic procedures, are strongly dependent on the energy of photons, elements and percentage by weight of elements in body tissues and substitutes. Significant disparities exist in the values of percentage by weight of elements reported in literature for body tissues and substitutes for individuals of different ages, genders and states of health. Often, interested parties are in need of these radiation interaction data for body tissues or substitutes with percentage by weight of elements and intermediate energies that are not tabulated in literature. To provide for the use of more precise values of these radiation interaction data, parameters and computer programs, MUA_T and MUEN_T are presented for the computation of mass attenuation and energy-absorption coefficients for body tissues and substitutes of arbitrary percentage-by-weight elemental composition and photon energy ranging between 1 keV (or k-edge) and 400 keV. Results are presented, which show that the values of mass attenuation and energy-absorption coefficients obtained from computer programs are in good agreement with those reported in literature.

Diffusion-weighted magnetic resonance imaging of uterine cervical cancer.

PubMed

Liu, Ying; Bai, Renju; Sun, Haoran; Liu, Haidong; Wang, Dehua

2009-01-01

To determine the feasibility of diffusion-weighted magnetic resonance (MR) imaging (DWI) of uterine cervical cancer and to investigate whether the apparent diffusion coefficient (ADC) values of cervical cancer differ from those of normal cervix and whether they could indicate the histologic type and the pathologic grade of tumor. Forty-two female patients with histopathologically proven uterine cervical cancer and 15 female patients with uterine leiomyomas underwent preoperative MR examinations using a 1.5-T clinical scanner (GE 1.5T Twin-Speed Infinity with Excite II scanner; GE Healthcare, Waukesha, Wis). Scanning sequences included T2-weighted fast spin-echo imaging, T2-weighted fast spin-echo with fat suppression imaging, T1-weighted spin-echo imaging, and DWI with diffusion factors of 0 and 1000 s/mm2. Parameters evaluated consisted of ADC values of uterine cervical cancer and normal cervix. Histologic specimens were stained with hematoxylin and eosin. The cellular densities of 32 uterine cervical cancers were calculated, which were regarded as the ratio of the total area of tumor cell nuclei divided by the area of sample image. Apparent diffusion coefficient value was statistically different (P = 0.000) between normal and cancerous tissue in the uterine cervix; the former one was (mean [SD], 1.50 [0.16]) x 10(-3) mm2/s, and the latter one was (0.88 [0.15]) x 10(-3) mm2/s. Apparent diffusion coefficient value of squamous carcinoma was statistically lower than that of adenocarcinoma (P = 0.040). The ADC value of uterine cervical cancer correlated negatively with cellular density (r = -0.711, P = 0.000) and the grading of tumor (r = -0.778, P = 0.000). Diffusion-weighted MR imaging has a potential ability to differentiate between normal and cancerous tissue in the uterine cervix, and it can indicate the histologic type of uterine cervical cancer as well. The ADC value of uterine cervical cancer represents tumor cellular density, thus providing a new method for evaluating the pathologic grading of tumor.

The association between measurement sites of visceral adipose tissue and cardiovascular risk factors after caloric restriction in obese Korean women.

PubMed

Lee, Hye-Ok; Yim, Jung-Eun; Lee, Jeong-Sook; Kim, Young-Seol; Choue, Ryowon

2013-02-01

Quantities as well as distributions of adipose tissue (AT) are significantly related to cardiovascular disease (CVD) risk factors and can be altered with caloric restriction. This study investigated which cross-sectional slice location of AT is most strongly correlated with changes in CVD risk factors after caloric restriction in obese Korean women. Thirty-three obese pre-menopausal Korean women (32.4 ± 8.5 yrs, BMI 27.1 ± 2.3 kg/m(2)) participated in a 12 weeks caloric restriction program. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured using computed tomography (CT) scans at the sites of L2-L3, L3-L4, and L4-L5. Fasting serum levels of glucose, insulin, triglyceride, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), leptin and homeostasis model assessment-insulin resistance (HOMA-IR) were observed. Pearson's partial correlation coefficients were used to assess the relationship between AT measurement sites and changes in CVD risk factors after calorie restriction. When calories were reduced by 350 kcal/day for 12 weeks, body weight (-2.7%), body fat mass (-8.2%), and waist circumference (-5.8%) all decreased (P < 0.05). In addition, following caloric restriction, serum levels of glucose (-4.6%), TC (-6.2%), LDL-C (-5.3%), leptin (-17.6%) and HOMA-IR (-18.2%) decreased significantly (P < 0.05) as well. Changes in VAT at the level of L3-L4 were significantly greater than those at other abdominal sites, and these changes were correlated with changes in TC (P < 0.05), LDL-C (P < 0.001), SBP (P < 0.001) and HOMA-IR (P < 0.01). These results show that VAT at L3-L4 had a stronger correlation with CVD risk factors than with other AT measurement sites after caloric restriction.

Reversal of mineral ion homeostasis and soft-tissue calcification of klotho knockout mice by deletion of vitamin D 1α-hydroxylase

PubMed Central

Ohnishi, Mutsuko; Nakatani, Teruyo; Lanske, Beate; Razzaque, M. Shawkat

2011-01-01

Changes in the expression of klotho, a β-glucuronidase, contribute to the development of features that resemble those of premature aging, as well as chronic renal failure. Klotho knockout mice have increased expression of the sodium/phosphate cotransporter (NaPi2a) and 1α-hydroxylase in their kidneys, along with increased serum levels of phosphate and 1,25-dihydroxyvitamin D. These changes are associated with widespread soft-tissue calcifications, generalized tissue atrophy, and a shorter lifespan in the knockout mice. To determine the role of the increased vitamin D activities in klotho knockout animals, we generated klotho and 1α-hydroxylase double-knockout mice. These double mutants regained body weight and developed hypophosphatemia with a complete elimination of the soft-tissue and vascular calcifications that were routinely found in klotho knockout mice. The markedly increased serum fibroblast growth factor 23 and the abnormally low serum parathyroid hormone levels, typical of klotho knockout mice, were significantly reversed in the double-knockout animals. These in vivo studies suggest that vitamin D has a pathologic role in regulating abnormal mineral ion metabolism and soft-tissue anomalies of klotho-deficient mice. PMID:19225558

Effects of chlorpyrifos on in vitro sex steroid production and thyroid follicular development in adult and larval Lake Sturgeon, Acipenser fulvescens.

PubMed

Brandt, Catherine; Burnett, Duncan C; Arcinas, Liane; Palace, Vince; Gary Anderson, W

2015-08-01

Chlorpyrifos is a widely used organophosphate pesticide that has previously been shown to enter waterways in biologically relevant concentrations and has the potential to disrupt both thyroid hormone and sex steroid biosynthesis in vertebrates. Because gonadal maturation and larval development in Lake Sturgeon, Acipenser fulvescens, potentially coincide with the application of chlorpyrifos we examined the effects of chlorpyrifos on both thyroid follicular development in larval Lake Sturgeon, and sex hormone synthesis in adult Lake Sturgeon. For the first time, the present study reports steroidogenesis from testicular and ovarian tissue in Lake Sturgeon using an established in vitro bioassay. Furthermore, incubating gonad tissue with 5, 500 or 2000ngmL(-1) chlorpyrifos revealed an inhibitory effect on testosterone synthesis in both testicular (control, 40.29pgmg(-1) tissue wet weight(-1)h(-1) compared to experimental, 21.84pgmg(-1) tissue wet weight(-1)h(-1)) and ovarian (control, 33.83pgmg(-1) tissue wet weight(-1)h(-1) compared to experimental, 15.19pgmg(-1) tissue wet weight(-1)h(-1)) tissue. In a second series of experiments, larval Lake Sturgeon were exposed to equivalent concentrations of chlorpyrifos as above for 10days (d) between hatch and the onset of exogenous feeding. Larvae from each treatment group were raised until 67days post hatch (dph) and growth rates were compared alongside key indicators of thyroid follicle growth. Chlorpyrifos treatment had no effect on the measured indicators of thyroid follicular development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Supplementation of chitosan alleviates high-fat diet-enhanced lipogenesis in rats via adenosine monophosphate (AMP)-activated protein kinase activation and inhibition of lipogenesis-associated genes.

PubMed

Chiu, Chen-Yuan; Chan, Im-Lam; Yang, Tsung-Han; Liu, Shing-Hwa; Chiang, Meng-Tsan

2015-03-25

This study investigated the role of chitosan in lipogenesis in high-fat diet-induced obese rats. The lipogenesis-associated genes and their upstream regulatory proteins were explored. Diet supplementation of chitosan efficiently decreased the increased weights in body, livers, and adipose tissues in high-fat diet-fed rats. Chitosan supplementation significantly raised the lipolysis rate; attenuated the adipocyte hypertrophy, triglyceride accumulation, and lipoprotein lipase activity in epididymal adipose tissues; and decreased hepatic enzyme activities of lipid biosynthesis. Chitosan supplementation significantly activated adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and attenuated high-fat diet-induced protein expressions of lipogenic transcription factors (PPAR-γ and SREBP1c) in livers and adipose tissues. Moreover, chitosan supplementation significantly inhibited the expressions of downstream lipogenic genes (FAS, HMGCR, FATP1, and FABP4) in livers and adipose tissues of high-fat diet-fed rats. These results demonstrate for the first time that chitosan supplementation alleviates high-fat diet-enhanced lipogenesis in rats via AMPK activation and lipogenesis-associated gene inhibition.

[Construction of injectable tissue engineered adipose tissue with fibrin glue scaffold and human adipose-derived stem cells transfected by lentivirus vector expressing hepatocyte growth factor].

PubMed

Zhu, Yuanzheng; Yi, Yangyan; Yang, Shuifa; Zhang, Jing; Wu, Shu; Wang, Zhaohui

2017-09-01

To discuss the possibility of constructing injectable tissue engineered adipose tissue, and to provide a new approach for repairing soft tissue defects. Human adipose-derived stem cells (hADSCs) were extracted from the lipid part of human liposuction aspirate by enzymatic digestion and identified by morphological observation, flow cytometry, and adipogenic induction. The hADSCs underwent transfection by lentivirus vector expressing hepatocyte growth factor and green fluorescent protein (HGF-GFP-LVs) of different multiplicity of infection (MOI, 10, 30, 50, and 100), the transfection efficiency was calculated to determine the optimum MOI. The hADSCs transfected by HGF-GFP-LVs of optimal MOI and being adipogenic inducted were combined with injectable fibrin glue scaffold, and were injected subcutaneously into the right side of the low back of 10 T-cell deficiency BALB/c female nude mice (transfected group); non-HGF-GFP-LVs transfected hADSCs (being adipogenic inducted) combined with injectable fibrin glue scaffold were injected subcutaneously into the left side of the low back (untransfected group); and injectable fibrin glue scaffold were injected subcutaneously into the middle part of the neck (blank control group); 0.4 mL at each point. Twelve weeks later the mice were killed and the implants were taken out. Gross observation, wet weight measurement, HE staining, GFP fluorescence labeling, and immunofluorescence staining were performed to assess the in vivo adipogenic ability of the seed cells and the neovascularization of the grafts. The cultured cells were identified as hADSCs. Poor transfection efficiency was observed in MOI of 10 and 30, the transfection efficiency of MOI of 50 and 100 was more than 80%, so the optimum MOI was 50. Adipose tissue-like new-born tissues were found in the injection sites of the transfected and untransfected groups after 12 weeks of injection, and no new-born tissues was found in the blank control group. The wet-weight of new-born tissue in the transfected group [(32.30±4.06) mg] was significantly heavier than that of the untransfected group [(25.27±3.94) mg] ( t =3.929, P =0.001). The mature adipose cells in the transfected group [(126.93±5.36) cells/field] were significantly more than that in the untransfected group [(71.36±4.52) cells/field] ( t =30.700, P =0.000). Under fluorescence microscopy, some of the single cell adipocytes showed a network of green fluorescence, indicating the presence of GFP labeled exogenous hADSCs in the tissue. The vascular density of new-born tissue of the transfected group [(16.37±2.76)/field] was significantly higher than that of the untransfected group [(9.13±1.68)/field] ( t =8.678, P =0.000). The hADSCs extracted from the lipid part after liposuction can be used as seed cells. After HGF-GFP-LVs transfection and adipose induction, the hADSCs combined with injectable fibrin glue scaffold can construct mature adipose tissue in vivo , which may stimulate angiogenesis, and improve retention rate of new-born tissue.

The effects of chronic testosterone administration on body weight, food intake, and fat weight were age-dependent.

PubMed

Iwasa, Takeshi; Matsuzaki, Toshiya; Yiliyasi, Mayila; Yano, Kiyohito; Irahara, Minoru

2017-11-01

Previously, we showed that chronic testosterone administration increased body weight (BW) and food intake (FI), but did not alter fat weight, in young female rats. To examine our hypothesis that the effects of androgens on BW, FI and body composition might be age-dependent, the effects of chronic testosterone administration were evaluated in rats of different ages; i.e., young and middle-aged rats. Although chronic testosterone administration increased BW gain, FI, and feed efficiency in both young and middle-aged rats, it increased visceral fat weight in middle-aged rats, but not in young rats. Therefore, it is possible that testosterone promotes the conversion of energy to adipose tissue and exacerbates fat accumulation in older individuals. In addition, although the administration of testosterone increased the serum leptin level, it did not alter hypothalamic neuropeptide Y mRNA expression in middle-aged rats. On the contrary, the administration of testosterone did not affect the serum leptin levels of young rats. Thus, testosterone might induce hypothalamic leptin resistance, which could lead to fat accumulation in older individuals. Testosterone might disrupt the mechanisms that protect against adiposity and hyperphagia and represent a risk factor for excessive body weight and obesity, especially in older females. Copyright © 2017 Elsevier Inc. All rights reserved.

The effect of weight change on changes in breast density measures over menopause in a breast cancer screening cohort.

PubMed

Wanders, Johanna Olga Pauline; Bakker, Marije Fokje; Veldhuis, Wouter Bernard; Peeters, Petra Huberdina Maria; van Gils, Carla Henrica

2015-05-30

High weight and high percentage mammographic breast density are both breast cancer risk factors but are negatively correlated. Therefore, we wanted to obtain more insight into this apparent paradox. We investigated in a longitudinal study how weight change over menopause is related to changes in mammographic breast features. Five hundred ninety-one participants of the EPIC-NL cohort were divided into three groups according to their prospectively measured weight change over menopause: (1) weight loss (more than -3.0 %), (2) stable weight (between -3.0 % and +3.0 %), and (3) weight gain (more than 3.0 %). SPSS GLM univariate analysis was used to determine both the mean breast measure changes in, and the trend over, the weight change groups. Over a median period of 5 years, the mean changes in percent density in these groups were -5.0 % (95 % confidence interval (CI) -8.0; -2.1), -6.8 % (95 % CI -9.0; -4.5), and -10.2 % (95 % CI -12.5; -7.9), respectively (P-trend = 0.001). The mean changes in dense area were -16.7 cm(2) (95 % CI -20.1; -13.4), -16.4 cm(2) (95 % CI -18.9; -13.9), and -18.1 cm(2) (95 % CI -20.6; -15.5), respectively (P-trend = 0.437). Finally, the mean changes in nondense area were -6.1 cm(2) (95 % CI -11.9; -0.4), -0.6 cm(2) (95 % CI -4.9; 3.8), and 5.3 cm(2) (95 % CI 0.9; 9.8), respectively (P-trend < 0.001). Going through menopause is associated with a decrease in both percent density and dense area. Owing to an increase in the nondense tissue, the decrease in percent density is largest in women who gain weight. The decrease in dense area is not related to weight change. So the fact that both high percent density and high weight or weight gain are associated with high postmenopausal breast cancer risk can probably not be explained by an increase (or slower decrease) of dense area in women gaining weight compared with women losing weight or maintaining a stable weight. These results suggest that weight and dense area are presumably two independent postmenopausal breast cancer risk factors.

A clinical perspective of obesity, metabolic syndrome and cardiovascular disease.

PubMed

Han, Thang S; Lean, Mike Ej

2016-01-01

The metabolic syndrome is a condition characterized by a special constellation of reversible major risk factors for cardiovascular disease and type 2 diabetes. The main, diagnostic, components are reduced HDL-cholesterol, raised triglycerides, blood pressure and fasting plasma glucose, all of which are related to weight gain, specifically intra-abdominal/ectopic fat accumulation and a large waist circumference. Using internationally adopted arbitrary cut-off values for waist circumference, having metabolic syndrome doubles the risk of cardiovascular disease, but offers an effective treatment approach through weight management. Metabolic syndrome now affects 30-40% of people by age 65, driven mainly by adult weight gain, and by a genetic or epigenetic predisposition to intra-abdominal/ectopic fat accumulation related to poor intra-uterine growth. Metabolic syndrome is also promoted by a lack of subcutaneous adipose tissue, low skeletal muscle mass and anti-retroviral drugs. Reducing weight by 5-10%, by diet and exercise, with or without, anti-obesity drugs, substantially lowers all metabolic syndrome components, and risk of type 2 diabetes and cardiovascular disease. Other cardiovascular disease risk factors such as smoking should be corrected as a priority. Anti-diabetic agents which improve insulin resistance and reduce blood pressure, lipids and weight should be preferred for diabetic patients with metabolic syndrome. Bariatric surgery offers an alternative treatment for those with BMI ≥ 40 or 35-40 kg/m(2) with other significant co-morbidity. The prevalence of the metabolic syndrome and cardiovascular disease is expected to rise along with the global obesity epidemic: greater emphasis should be given to effective early weight-management to reduce risk in pre-symptomatic individuals with large waists.

A clinical perspective of obesity, metabolic syndrome and cardiovascular disease

PubMed Central

Lean, Mike EJ

2016-01-01

The metabolic syndrome is a condition characterized by a special constellation of reversible major risk factors for cardiovascular disease and type 2 diabetes. The main, diagnostic, components are reduced HDL-cholesterol, raised triglycerides, blood pressure and fasting plasma glucose, all of which are related to weight gain, specifically intra-abdominal/ectopic fat accumulation and a large waist circumference. Using internationally adopted arbitrary cut-off values for waist circumference, having metabolic syndrome doubles the risk of cardiovascular disease, but offers an effective treatment approach through weight management. Metabolic syndrome now affects 30–40% of people by age 65, driven mainly by adult weight gain, and by a genetic or epigenetic predisposition to intra-abdominal/ectopic fat accumulation related to poor intra-uterine growth. Metabolic syndrome is also promoted by a lack of subcutaneous adipose tissue, low skeletal muscle mass and anti-retroviral drugs. Reducing weight by 5–10%, by diet and exercise, with or without, anti-obesity drugs, substantially lowers all metabolic syndrome components, and risk of type 2 diabetes and cardiovascular disease. Other cardiovascular disease risk factors such as smoking should be corrected as a priority. Anti-diabetic agents which improve insulin resistance and reduce blood pressure, lipids and weight should be preferred for diabetic patients with metabolic syndrome. Bariatric surgery offers an alternative treatment for those with BMI ≥ 40 or 35–40 kg/m2 with other significant co-morbidity. The prevalence of the metabolic syndrome and cardiovascular disease is expected to rise along with the global obesity epidemic: greater emphasis should be given to effective early weight-management to reduce risk in pre-symptomatic individuals with large waists. PMID:26998259

Paternally Expressed, Imprinted Insulin-Like Growth Factor-2 in Chorionic Villi Correlates Significantly with Birth Weight

PubMed Central

Demetriou, Charalambos; Abu-Amero, Sayeda; Thomas, Anna C.; Ishida, Miho; Aggarwal, Reena; Al-Olabi, Lara; Leon, Lydia J.; Stafford, Jaime L.; Syngelaki, Argyro; Peebles, Donald; Nicolaides, Kypros H.; Regan, Lesley; Stanier, Philip; Moore, Gudrun E.

2014-01-01

Context Fetal growth involves highly complex molecular pathways. IGF2 is a key paternally expressed growth hormone that is critical for in utero growth in mice. Its role in human fetal growth has remained ambiguous, as it has only been studied in term tissues. Conversely the maternally expressed growth suppressor, PHLDA2, has a significant negative correlation between its term placental expression and birth weight. Objective The aim of this study is to address the role in early gestation of expression of IGF1, IGF2, their receptors IGF1R and IGF2R, and PHLDA2 on term birth weight. Design Real-time quantitative PCR was used to investigate mRNA expression of IGF1, IGF2, IGF1R, IGF2R and PHLDA2 in chorionic villus samples (CVS) (n = 260) collected at 11–13 weeks' gestation. Expression was correlated with term birth weight using statistical package R including correction for several confounding factors. Results Transcript levels of IGF2 and IGF2R revealed a significant positive correlation with birth weight (0.009 and 0.04, respectively). No effect was observed for IGF1, IGF1R or PHLDA2 and birth weight. Critically, small for gestational age (SGA) neonates had significantly lower IGF2 levels than appropriate for gestational age neonates (p = 3·6×10−7). Interpretation Our findings show that IGF2 mRNA levels at 12 weeks gestation could provide a useful predictor of future fetal growth to term, potentially predicting SGA babies. SGA babies are known to be at a higher risk for type 2 diabetes. This research reveals an imprinted, parentally driven rheostat for in utero growth. PMID:24454871

Protective effects of the herbal medicine goshajinkigan in a rat model of non-alcoholic fatty liver disease.

PubMed

Hirotani, Yoshihiko; Doi, Ayae; Takahashi, Tomoki; Umezawa, Hanako; Urashima, Yoko; Myotoku, Mitiaki

2012-12-01

This study was designed to investigate the effect of an herbal medicine-goshajinkigan (GJ)-on the regulation of total body weight, as well as liver and adipose tissue weights in rats fed a highfat diet (HFD) and drinking of 30% sucrose (HFDS) (HFD; the rats received 19.6% energy from carbohydrates, 18.2% from proteins, and 62.2% from lipids; total energy, 506 kcal/100 g). Control rats were fed a standard diet (the rats received 60.5% energy from carbohydrates, 26.2% from proteins, and 13.3% from lipids; total energy, 360 kcal/100 g). Over a period of 12 weeks, rats were allowed free access to either the standard diet or HFDS containing 0, 1, or 3% GJ. In comparison with the control group, the HFDS rats showed a significant decrease in overall body weight and adipose tissue weight, and an increase in liver weight at 12 weeks. GJ treatment significantly reversed the HFDS-induced decrease in body and adipose tissue weight and reduced the elevated liver weight dose-dependently. Similarly, GJ reduced the elevated serum aspartate aminotransferase levels observed in HFDS rats. These results suggest that GJ may have the potential to alleviate damage to the liver in subjects with long-term consumption of HFDS.

Mechanisms for the anti-obesity actions of bofutsushosan in high-fat diet-fed obese mice.

PubMed

Kobayashi, Shinjiro; Kawasaki, Yuki; Takahashi, Tatsuo; Maeno, Hironori; Nomura, Masaaki

2017-01-01

The Kampo medicine bofutsushosan (BTS; Pulvis ledebouriellae compositae ; Fang Feng Tong Sheng San ) has been used as an anti-obesity treatment in overweight patients. In this study, we assessed the underlying physiological changes induced by BTS in obese mice maintained on a high-fat diet. Male ICR mice were fed a 60% kcal fat diet for 5 weeks starting at 4 weeks of age and then fed the same diet with administration of water (control) or aqueous BTS extract (1.0-2.0 g/kg) for 25 days. Body weight, wet weight of isolated white adipose tissue, and obesity-related serum parameters (glucose, lipids, leptin, adiponectin) were measured after treatment. The mRNA expression levels of leptin, adiponectin, and UCP1 in the adipose tissues were determined by quantitative real-time polymerase chain reaction after the first 5 days of treatment. Bofutsushosan (1.5-2.0 g/kg) significantly decreased total body weight and total wet weight of white adipose tissue isolated from subcutaneous (retroperitoneal) and visceral regions (epididymal, mesenteric, and perirenal). At 2.0 g/kg, BTS also decreased total fat mass, visceral fat mass, and ratio of fat mass to body weight as measured by computed tomography, and significantly decreased epididymal adipocyte size after 14 and 25 days' treatment. Twenty-five days' treatment lowered serum glucose, insulin, leptin, and triglycerides, and reduced homeostasis model assessment-insulin resistance. Alternatively, 2.0 g/kg BTS significantly increased mRNA levels of adiponectin, leptin, and UCP1 in interscapular brown adipose tissue but not epididymal white adipose tissue after 5 days' administration. In the early administration period, BTS increased mRNA expression levels of leptin, adiponectin, and UCP1 in brown adipose tissues. With longer administration, BTS improved insulin resistance, and subsequently reduced serum levels of leptin and triglyceride in parallel with decreased visceral white adipose tissue volume and adipocyte size.

Biodistribution mechanisms of therapeutic monoclonal antibodies in health and disease.

PubMed

Tabrizi, Mohammad; Bornstein, Gadi Gazit; Suria, Hamza

2010-03-01

The monoclonal antibody market continues to witness an impressive rate of growth and has become the leading source of expansion in the biologic segment within the pharmaceutical industry. Currently marketed monoclonal antibodies target a diverse array of antigens. These antigens are distributed in a variety of tissues such as tumors, lungs, synovial fluid, psoriatic plaques, and lymph nodes. As the concentration of drug at the proximity of the biological receptor determines the magnitude of the observed pharmacological responses, a significant consideration in effective therapeutic application of monoclonal antibodies is a thorough understanding of the processes that regulate antibody biodistribution. Monoclonal antibody distribution is affected by factors such as molecular weight, blood flow, tissue and tumor heterogeneity, structure and porosity, target antigen density, turnover rate, and the target antigen expression profile.

Factors that Affect the Content of Cadmium, Nickel, Copper and Zinc in Tissues of the Knee Joint.

PubMed

Roczniak, Wojciech; Brodziak-Dopierała, Barbara; Cipora, Elżbieta; Jakóbik-Kolon, Agata; Kluczka, Joanna; Babuśka-Roczniak, Magdalena

2017-08-01

Osteoarthritis causes the degradation of the articular cartilage and periarticular bones. Trace elements influence the growth, development and condition of the bone tissue. Changes to the mineral composition of the bone tissue can cause degenerative changes and fractures. The aim of the research was to determine the content of cadmium (Cd), nickel (Ni), copper (Cu) and zinc (Zn) in the tibia, the femur and the meniscus in men and women who underwent a knee replacement surgery. Samples were collected from 50 patients, including 36 women and 14 men. The determination of trace elements content were performed by ICP-AES method, using Varian 710-ES. Average concentration in the tissues of the knee joint teeth amounted for cadmium 0.015, nickel 0.60, copper 0.89 and zinc 80.81 mg/kg wet weight. There were statistically significant differences in the content of cadmium, copper and zinc in different parts of the knee joint. There were no statistically significant differences in the content of cadmium, nickel, copper and zinc in women and men in the examined parts of the knee joint. Among the elements tested, copper and nickel showed a high content in the connective tissue (the meniscus) compared to the bone tissue (the tibia and the femur).

Factors secreted from dental pulp stem cells show multifaceted benefits for treating acute lung injury in mice.

PubMed

Wakayama, Hirotaka; Hashimoto, Naozumi; Matsushita, Yoshihiro; Matsubara, Kohki; Yamamoto, Noriyuki; Hasegawa, Yoshinori; Ueda, Minoru; Yamamoto, Akihito

2015-08-01

Acute respiratory distress syndrome (ARDS) is a severe inflammatory disorder characterized by acute respiratory failure, resulting from severe, destructive lung inflammation and irreversible lung fibrosis. We evaluated the use of stem cells derived from human exfoliated deciduous teeth (SHEDs) or SHED-derived serum-free conditioned medium (SHED-CM) as treatments for bleomycin (BLM)-induced mice acute lung injury (ALI), exhibiting several pathogenic features associated with the human disease ARDS. Mice with BLM-induced ALI with or without SHED or SHED-CM treatment were examined for weight loss and survival. The lung tissue was characterized by histological and real-time quantitative polymerase chain reaction analysis. The effects of SHED-CM on macrophage differentiation in vitro were also assessed. A single intravenous administration of either SHEDs or SHED-CM attenuated the lung injury and weight loss in BLM-treated mice and improved their survival rate. Similar recovery levels were seen in the SHEDs and SHED-CM treatment groups, suggesting that SHED improves ALI by paracrine mechanisms. SHED-CM contained multiple therapeutic factors involved in lung-regenerative mechanisms. Importantly, SHED-CM attenuated the BLM-induced pro-inflammatory response and generated an anti-inflammatory/tissue-regenerating environment, accompanied by the induction of anti-inflammatory M2-like lung macrophages. Furthermore, SHED-CM promoted the in vitro differentiation of bone marrow-derived macrophages into M2-like cells, which expressed high levels of Arginase1, CD206 and Ym-1. Our results suggest that SHED-secreted factors provide multifaceted therapeutic effects, including a strong M2-inducing activity, for treating BLM-induced ALI. This work may open new avenues for research on stem cell-based ARDS therapies. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Neuroprotective Potential of Mesenchymal Stem Cell-Based Therapy in Acute Stages of TNBS-Induced Colitis in Guinea-Pigs

PubMed Central

Robinson, Ainsley M.; Miller, Sarah; Payne, Natalie; Boyd, Richard; Sakkal, Samy; Nurgali, Kulmira

2015-01-01

Background & Aims The therapeutic benefits of mesenchymal stem cells (MSCs), such as homing ability, multipotent differentiation capacity and secretion of soluble bioactive factors which exert neuroprotective, anti-inflammatory and immunomodulatory properties, have been attributed to attenuation of autoimmune, inflammatory and neurodegenerative disorders. In this study, we aimed to determine the earliest time point at which locally administered MSC-based therapies avert enteric neuronal loss and damage associated with intestinal inflammation in the guinea-pig model of colitis. Methods At 3 hours after induction of colitis by 2,4,6-trinitrobenzene-sulfonate (TNBS), guinea-pigs received either human bone marrow-derived MSCs, conditioned medium (CM), or unconditioned medium by enema into the colon. Colon tissues were collected 6, 24 and 72 hours after administration of TNBS. Effects on body weight, gross morphological damage, immune cell infiltration and myenteric neurons were evaluated. RT-PCR, flow cytometry and antibody array kit were used to identify neurotrophic and neuroprotective factors released by MSCs. Results MSC and CM treatments prevented body weight loss, reduced infiltration of leukocytes into the colon wall and the myenteric plexus, facilitated repair of damaged tissue and nerve fibers, averted myenteric neuronal loss, as well as changes in neuronal subpopulations. The neuroprotective effects of MSC and CM treatments were observed as early as 24 hours after induction of inflammation even though the inflammatory reaction at the level of the myenteric ganglia had not completely subsided. Substantial number of neurotrophic and neuroprotective factors released by MSCs was identified in their secretome. Conclusion MSC-based therapies applied at the acute stages of TNBS-induced colitis start exerting their neuroprotective effects towards enteric neurons by 24 hours post treatment. The neuroprotective efficacy of MSC-based therapies can be exerted independently to their anti-inflammatory effects. PMID:26397368

Dosimetry of 3 CBCT devices for oral and maxillofacial radiology: CB Mercuray, NewTom 3G and i-CAT.

PubMed

Ludlow, J B; Davies-Ludlow, L E; Brooks, S L; Howerton, W B

2006-07-01

Cone beam computed tomography (CBCT), which provides a lower dose, lower cost alternative to conventional CT, is being used with increasing frequency in the practice of oral and maxillofacial radiology. This study provides comparative measurements of effective dose for three commercially available, large (12'') field-of-view (FOV), CBCT units: CB Mercuray, NewTom 3G and i-CAT. Thermoluminescent dosemeters (TLDs) were placed at 24 sites throughout the layers of the head and neck of a tissue-equivalent human skull RANDO phantom. Depending on availability, the 12'' FOV and smaller FOV scanning modes were used with similar phantom positioning geometry for each CBCT unit. Radiation weighted doses to individual organs were summed using 1990 (E(1990)) and proposed 2005 (E(2005 draft)) ICRP tissue weighting factors to calculate two measures of whole-body effective dose. Dose as a multiple of a representative panoramic radiography dose was also calculated. For repeated runs dosimetry was generally reproducible within 2.5%. Calculated doses in microSv [corrected] (E(1990), E(2005 draft)) were NewTom3G (45, 59), i-CAT (135, 193) and CB Mercuray (477, 558). These are 4 to 42 times greater than comparable panoramic examination doses (6.3 microSv [corrected] 13.3 mSv). Reductions in dose were seen with reduction in field size and mA and kV technique factors. CBCT dose varies substantially depending on the device, FOV and selected technique factors. Effective dose detriment is several to many times higher than conventional panoramic imaging and an order of magnitude or more less than reported doses for conventional CT.

Regulating exposure of the lens of the eye to ionising radiations.

PubMed

Thorne, M C

2012-06-01

The International Commission on Radiological Protection (ICRP) has reviewed recent epidemiological evidence suggesting that, for the lens of the eye, the threshold in absorbed dose for the induction of deleterious health effects is about 0.5 Gy. On this basis, the Commission recommends that for occupational exposure in planned exposure situations, the equivalent dose limit for the lens of the eye should be 20 mSv in a year, averaged over defined periods of 5 yr, with exposure not exceeding 50 mSv in any single year. This paper summarises the data that have been taken into account by the ICRP and critically examines whether the proposed downward revision of the dose limit is justified. Overall, it is concluded that the accumulating radiobiological and epidemiological evidence makes it more appropriate to treat cataract induction as a stochastic rather than a deterministic effect. Within this framework, it is illogical to have the same dose limit for the lens of the eye as for the whole body irradiated uniformly. This could be addressed either by removing the special dose limit for the lens of the eye, assigning it an appropriate tissue weighting factor and including it in the computation of the effective dose, or through a composite approach involving the use of a tissue weighting factor for effective dose computations together with a special limit on the equivalent dose to the lens of the eye to ensure that no individual was subject to an unacceptably high risk of induction of clinically significant cataracts.

Amelioration of fatty liver index in patients with type 2 diabetes on ipragliflozin: an association with glucose-lowering effects.

PubMed

Takase, Takahiro; Nakamura, Akinobu; Miyoshi, Hideaki; Yamamoto, Chiho; Atsumi, Tatsuya

2017-03-31

In this study, we investigated the ameliorating effects of ipragliflozin on fatty liver in patients with type 2 diabetes. The factors that influenced the amelioration of fatty liver were also examined. Analysis included data of 21 Japanese patients with type 2 diabetes obtained from our prospective observational study. After obtaining patients' informed consent, once-daily ipragliflozin (50 mg/day) was given for 16 weeks. In addition to several clinical parameters, body composition was also compared before and after 16 weeks of treatment. The extent of fatty liver was estimated using a fatty liver index (FLI). After 16 weeks, FLI significantly decreased, from 70.1 ± 19.4 to 60.3 ± 25.5 (p = 0.0009) as well as levels of fasting plasma glucose (FPG), HbA1c, body weight, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and fat mass. To reveal the factors influencing the FLI changes observed on ipragliflozin treatment, correlations between changes in FLI and several other measured parameters were examined. Changes in FPG (correlation coefficient = 0.4683, p = 0.0323) and HbA1c (correlation coefficient = 0.4383, p = 0.0469) showed significant positive correlations with changes in FLI. On the other hand, no correlations of changes in FLI were observed with body weight, VAT, SAT nor fat mass. In conclusion, ipragliflozin ameliorated FLI in Japanese patients with type 2 diabetes. Improvement in FLI was associated with that of glucose intolerance.

Diagnostic performance of conventional MRI parameters and apparent diffusion coefficient values in differentiating between benign and malignant soft-tissue tumours.

PubMed

Song, Y; Yoon, Y C; Chong, Y; Seo, S W; Choi, Y-L; Sohn, I; Kim, M-J

2017-08-01

To compare the abilities of conventional magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) in differentiating between benign and malignant soft-tissue tumours (STT). A total of 123 patients with STT who underwent 3 T MRI, including diffusion-weighted imaging (DWI), were retrospectively analysed using variate conventional MRI parameters, ADC mean and ADC min . For the all-STT group, the correlation between the malignant STT conventional MRI parameters, except deep compartment involvement, compared to those of benign STT were statistically significant with univariate analysis. Maximum diameter of the tumour (p=0.001; odds ratio [OR], 8.97) and ADC mean (p=0.020; OR, 4.30) were independent factors with multivariate analysis. For the non-myxoid non-haemosiderin STT group, signal heterogeneity on axial T1-weighted imaging (T1WI; p=0.017), ADC mean , and ADC min (p=0.001, p=0.001), showed significant differences with univariate analysis between malignancy and benignity. Signal heterogeneity in axial T1WI (p=0.025; OR, 12.64) and ADC mean (p=0.004; OR, 33.15) were independent factors with multivariate analysis. ADC values as well as conventional MRI parameters were useful in differentiating between benign and malignant STT. The ADC mean was the most powerful diagnostic parameter in non-myxoid non-haemosiderin STT. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

The effects of dietary lead on growth, bioaccumulation and antioxidant capacity in sea cucumber, Apostichopus japonicus.

PubMed

Wang, Jing; Ren, Tongjun; Han, Yuzhe; Zhao, Yang; Liao, Mingling; Wang, Fuqiang; Jiang, Zhiqiang

2015-09-01

Three different diets amended with lead nitrate [Pb(NO3)2] (100, 500 and 1000mg Pb/kg dry weight) and a Pb-free control diet (1.03mg Pb/kg dry weight) were fed to sea cucumber (Apostichopus japonicus) for 30 days. The patterns of Pb accumulation over time were determined in various tissues (body wall, intestine and respiratory tree), as well as growth performance and antioxidant enzymes activities. Pb accumulation in body wall and intestine increased with time in all dietary Pb treatments. When fed the highest Pb diet, the body wall exhibited the greatest Pb burden (16.37mg Pb/kg tissue wet weight), while Pb content in the intestine (2.68mg Pb/kg tissue wet weight) and the respiratory tree (1.78mg Pb/kg tissue wet weight) were lower than Pb content in the body wall by day 30. The body weight gain (BWG), specific growth rate (SGR) and survival rate (SR) had not been affected by 30 days oral administration of Pb supplemented diet. However, the antioxidant enzymes activities [superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)] of test groups were lower than control group in body wall and malondialdehyde (MDA) concentration in the body wall was opposite after 30 days in sea cucumbers. In summary, this work reports toxic effects in sea cucumber, A. japonicus, after dietary exposure to Pb. Copyright © 2015 Elsevier B.V. All rights reserved.

Energy metabolism, fuel selection and body weight regulation

PubMed Central

Galgani, J; Ravussin, E

2010-01-01

Energy homeostasis is critical for the survival of species. Therefore, multiple and complex mechanisms have evolved to regulate energy intake and expenditure to maintain body weight. For weight maintenance, not only does energy intake have to match energy expenditure, but also macronutrient intake must balance macronutrient oxidation. However, this equilibrium seems to be particularly difficult to achieve in individuals with low fat oxidation, low energy expenditure, low sympathetic activity or low levels of spontaneous physical activity, as in addition to excess energy intake, all of these factors explain the tendency of some people to gain weight. Additionally, large variability in weight change is observed when energy surplus is imposed experimentally or spontaneously. Clearly, the data suggest a strong genetic influence on body weight regulation implying a normal physiology in an ‘obesogenic’ environment. In this study, we also review evidence that carbohydrate balance may represent the potential signal that regulates energy homeostasis by impacting energy intake and body weight. Because of the small storage capacity for carbohydrate and its importance for metabolism in many tissues and organs, carbohydrate balance must be maintained at a given level. This drive for balance may in turn cause increased energy intake when consuming a diet high in fat and low in carbohydrate. If sustained over time, such an increase in energy intake cannot be detected by available methods, but may cause meaningful increases in body weight. The concept of metabolic flexibility and its impact on body weight regulation is also presented. PMID:19136979

Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance

PubMed Central

Svensson, H; Wetterling, L; Bosaeus, M; Odén, B; Odén, A; Jennische, E; Edén, S; Holmäng, A; Lönn, M

2016-01-01

Background/Objectives: Pregnancy is accompanied by fat gain and insulin resistance. Changes in adipose tissue morphology and function during pregnancy and factors contributing to gestational insulin resistance are incompletely known. We sought to characterize adipose tissue in trimesters 1 and 3 (T1/T3) in normal weight (NW) and obese pregnant women, and identify adipose tissue-related factors associated with gestational insulin resistance. Subjects/Methods: Twenty-two NW and 11 obese women were recruited early in pregnancy for the Pregnancy Obesity Nutrition and Child Health study. Examinations and sampling of blood and abdominal adipose tissue were performed longitudinally in T1/T3 to determine fat mass (air-displacement plethysmography); insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR); size, number and lipolytic activity of adipocytes; and adipokine release and density of immune cells and blood vessels in adipose tissue. Results: Fat mass and HOMA-IR increased similarly between T1 and T3 in the groups; all remained normoglycemic. Adipocyte size increased in NW women. Adipocyte number was not influenced, but proportions of small and large adipocytes changed oppositely in the groups. Lipolytic activity and circulating adipocyte fatty acid-binding protein increased in both groups. Adiponectin release was reduced in NW women. Fat mass and the proportion of very large adipocytes were most strongly associated with T3 HOMA-IR by multivariable linear regression (R2=0.751, P<0.001). Conclusions: During pregnancy, adipose tissue morphology and function change comprehensively. NW women accumulated fat in existing adipocytes, accompanied by reduced adiponectin release. In comparison with the NW group, obese women had signs of adipocyte recruitment and maintained adiponectin levels. Body fat and large adipocytes may contribute significantly to gestational insulin resistance. PMID:26563815

Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance.

PubMed

Svensson, H; Wetterling, L; Bosaeus, M; Odén, B; Odén, A; Jennische, E; Edén, S; Holmäng, A; Lönn, M

2016-04-01

Pregnancy is accompanied by fat gain and insulin resistance. Changes in adipose tissue morphology and function during pregnancy and factors contributing to gestational insulin resistance are incompletely known. We sought to characterize adipose tissue in trimesters 1 and 3 (T1/T3) in normal weight (NW) and obese pregnant women, and identify adipose tissue-related factors associated with gestational insulin resistance. Twenty-two NW and 11 obese women were recruited early in pregnancy for the Pregnancy Obesity Nutrition and Child Health study. Examinations and sampling of blood and abdominal adipose tissue were performed longitudinally in T1/T3 to determine fat mass (air-displacement plethysmography); insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR); size, number and lipolytic activity of adipocytes; and adipokine release and density of immune cells and blood vessels in adipose tissue. Fat mass and HOMA-IR increased similarly between T1 and T3 in the groups; all remained normoglycemic. Adipocyte size increased in NW women. Adipocyte number was not influenced, but proportions of small and large adipocytes changed oppositely in the groups. Lipolytic activity and circulating adipocyte fatty acid-binding protein increased in both groups. Adiponectin release was reduced in NW women. Fat mass and the proportion of very large adipocytes were most strongly associated with T3 HOMA-IR by multivariable linear regression (R(2)=0.751, P<0.001). During pregnancy, adipose tissue morphology and function change comprehensively. NW women accumulated fat in existing adipocytes, accompanied by reduced adiponectin release. In comparison with the NW group, obese women had signs of adipocyte recruitment and maintained adiponectin levels. Body fat and large adipocytes may contribute significantly to gestational insulin resistance.

Sequential weighted Wiener estimation for extraction of key tissue parameters in color imaging: a phantom study

NASA Astrophysics Data System (ADS)

Chen, Shuo; Lin, Xiaoqian; Zhu, Caigang; Liu, Quan

2014-12-01

Key tissue parameters, e.g., total hemoglobin concentration and tissue oxygenation, are important biomarkers in clinical diagnosis for various diseases. Although point measurement techniques based on diffuse reflectance spectroscopy can accurately recover these tissue parameters, they are not suitable for the examination of a large tissue region due to slow data acquisition. The previous imaging studies have shown that hemoglobin concentration and oxygenation can be estimated from color measurements with the assumption of known scattering properties, which is impractical in clinical applications. To overcome this limitation and speed-up image processing, we propose a method of sequential weighted Wiener estimation (WE) to quickly extract key tissue parameters, including total hemoglobin concentration (CtHb), hemoglobin oxygenation (StO2), scatterer density (α), and scattering power (β), from wide-band color measurements. This method takes advantage of the fact that each parameter is sensitive to the color measurements in a different way and attempts to maximize the contribution of those color measurements likely to generate correct results in WE. The method was evaluated on skin phantoms with varying CtHb, StO2, and scattering properties. The results demonstrate excellent agreement between the estimated tissue parameters and the corresponding reference values. Compared with traditional WE, the sequential weighted WE shows significant improvement in the estimation accuracy. This method could be used to monitor tissue parameters in an imaging setup in real time.

Distinct effects of calorie restriction on adipose tissue cytokine and angiogenesis profiles in obese and lean mice

PubMed Central

2012-01-01

Background Obesity associates with low-grade inflammation and adipose tissue remodeling. Using sensitive high-throughput protein arrays we here investigated adipose tissue cytokine and angiogenesis-related protein profiles from obese and lean mice, and in particular, the influence of calorie restriction (CR). Methods Tissue samples from visceral fat were harvested from obese mice fed with a high-fat diet (60% of energy), lean controls receiving low-fat control diet as well as from obese and lean mice kept under CR (energy intake 70% of ad libitum intake) for 50 days. Protein profiles were analyzed using mouse cytokine and angiogenesis protein array kits. Results In obese and lean mice, CR was associated with 11.3% and 15.6% reductions in body weight, as well as with 4.0% and 4.6% reductions in body fat percentage, respectively. Obesity induced adipose tissue cytokine expressions, the most highly upregulated cytokines being IL-1ra, IL-2, IL-16, MCP-1, MIG, RANTES, C5a, sICAM-1 and TIMP-1. CR increased sICAM-1 and TIMP-1 expression both in obese and lean mice. Overall, CR showed distinct effects on cytokine expressions; in obese mice CR largely decreased but in lean mice increased adipose tissue cytokine expressions. Obesity was also associated with increased expressions of angiogenesis-related proteins, in particular, angiogenin, endoglin, endostatin, endothelin-1, IGFBP-3, leptin, MMP-3, PAI-1, TIMP-4, CXCL16, platelet factor 4, DPPIV and coagulation factor III. CR increased endoglin, endostatin and platelet factor 4 expressions, and decreased IGFBP-3, NOV, MMP-9, CXCL16 and osteopontin expressions both in obese and lean mice. Interestingly, in obese mice, CR decreased leptin and TIMP-4 expressions, whereas in lean mice their expressions were increased. CR decreased MMP-3 and PAI-1 only in obese mice, whereas CR decreased FGF acidic, FGF basic and coagulation factor III, and increased angiogenin and DPPIV expression only in lean mice. Conclusions CR exerts distinct effects on adipocyte cytokine and angiogenesis profiles in obese and lean mice. Our study also underscores the importance of angiogenesis-related proteins and cytokines in adipose tissue remodeling and development of obesity. PMID:22748184

THE ABSCOPAL EFFECT OF X IRRADIATION ON BONE GROWTH IN RATS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pappas, A.M.; Cohen, J.

1963-06-01

The abscopal effect of irradiation (that which is evident at a distance from the irradiated volume but within the same organism) was investigated in rats. It was possible to demonstrate the effects on growth locally and abscopally when x-ray doses of 400 and 800 r were delivered to the lower extremity and when 800 r was delivered to the knee alone. A distinction between abscopal effects after local irradiation and systemic effects after whole-body irradiation is discussed. The weights of control and irradiated animals were similar for the first 21 days, during which period they did not exhibit any untowardmore » effects of irradiation. However, after 21 days there was a decrease in weight gain, which persisted until the 72nd day. Group A (controls) was the heaviest group, with a mean weight of 412 g. Group B (800 r to the left hind extremity) had a mean weight of 378. Group C (400 r to the left hind extremity) and Group D (800 r to the left knee) exhibited mean weights of 391 and 394 g, respectively. Roentgenographic measurements revealed that all animals receiving irradiation had retardation in the growth of the irradiated tibiae, which were shorter than both the control and the contralateral (unirradiated) tibiae. Only the animals that had received 800 r to their leff hind extremity showed significant differences in the lengths of their unirradiated bones compared with the bones of the control animals of Group A, that is, a significant abscopal growth retardation. Although the abscopal effect appeared to be associated with the volume of tissue irradiated, the way this effect is mediated is not known. The weight gains of the animals demonstrated a strong association between decrease in weight gain, the volume of tissue irradiated, and the dose administered. The impaired weight gsin roughly paralleled the abscopal retardation of bone growth. The animals which received the highest dose of irradiation, 800 r, to the largest volume of tissue, 10% of the body volume, revealed the greatest deviation from the control group. It is concluded that irradiation effects in animals are composites of the responses of the whole organism to the injury, of the responses of local tissues, and vessels at their level of tissue organization, and of the responses of individual cells. All of these responses may be interdependent. The evidence indicates that a systemic inhibition of all bone growth and weight gain occurs when a sufficient volume of tissue is irradiated at a sufficiently high dosage. (BBB)« less

Dairy Foods in a Moderate Energy Restricted Diet Do Not Enhance Central Fat, Weight, and Intra-Abdominal Adipose Tissue Losses nor Reduce Adipocyte Size or Inflammatory Markers in Overweight and Obese Adults: A Controlled Feeding Study

PubMed Central

Van Loan, Marta D.; Keim, Nancy L.; Adams, Sean H.; Souza, Elaine; Woodhouse, Leslie R.; Thomas, Anthony; Witbracht, Megan; Gertz, Erik R.; Piccolo, Brian; Bremer, Andrew A.; Spurlock, Michael

2011-01-01

Background. Research on dairy foods to enhance weight and fat loss when incorporated into a modest weight loss diet has had mixed results. Objective. A 15-week controlled feeding study to determine if dairy foods enhance central fat and weight loss when incorporated in a modest energy restricted diet of overweight and obese adults. Design. A 3-week run-in to establish energy needs; a 12-week 500 kcal/d energy reduction with 71 low-dairy-consuming overweight and obese adults randomly assigned to diets: ≤1 serving dairy/d (low dairy, LD) or ≤4 servings dairy/d (adequate dairy, AD). All foods were weighed and provided by the metabolic kitchen. Weight, fat, intra-abdominal adipose tissue (IAAT), subcutaneous adipose tissue (SAT) macrophage number, SAT inflammatory gene expression, and circulating cytokines were measured. Results. No diet differences were observed in weight, fat, or IAAT loss; nor SAT mRNA expression of inflammation, circulating cytokines, fasting lipids, glucose, or insulin. There was a significant increase (P = 0.02) in serum 25-hydroxyvitamin D in the AD group. Conclusion. Whether increased dairy intake during weight loss results in greater weight and fat loss for individuals with metabolic syndrome deserves investigation. Assessment of appetite, hunger, and satiety with followup on weight regain should be considered. PMID:21941636

Increased expression of high mobility group box protein 1 and vascular endothelial growth factor in placenta previa.

PubMed

Xie, Han; Qiao, Ping; Lu, Yi; Li, Ying; Tang, Yuping; Huang, Yiying; Bao, Yirong; Ying, Hao

2017-12-01

Placenta previa is often associated with preterm delivery, reduced birth weight, a higher frequency of placental accreta and postpartum haemorrhage, and increased likelihood of blood transfusion. The present study aimed to examine the expression of high mobility group box protein 1 (HMGB1) in the placenta of women with or without placenta previa. The study group consisted of placental tissues obtained from women with or without placenta previa. The expression levels of HMGB1 and vascular endothelial growth factor (VEGF) were evaluated in the placental tissues using reverse transcription‑quantitative polymerase chain reaction, western blotting and immunohistochemistry. The mRNA expression levels of HMGB1 and VEGF were significantly increased in the placenta previa group compared with in the normal group. In addition, the placenta previa group exhibited increased HMGB1 and VEGF staining in vascular endothelial cells and trophoblasts. There were no significant differences in the expression of HMGB1 or VEGF between groups with or without placenta accreta or postpartum haemorrhage. The present study hypothesised that the increased expression of HMGB1 in the placenta may be associated with the pathogenesis of placenta previa by regulating the expression of the proangiogenic factor VEGF.

Cytokines in single layer amnion allografts compared to multilayer amnion/chorion allografts for wound healing.

PubMed

Koob, Thomas J; Lim, Jeremy J; Zabek, Nicole; Massee, Michelle

2015-07-01

Human amniotic membrane allografts have proven effective at improving healing of cutaneous wounds. The mechanism of action for these therapeutic effects is poorly understood but is thought to involve the resident growth factors present in near term amniotic tissue. To determine the relative cytokine contribution of the amnion and chorion in amniotic allografts, the content of 18 cytokines involved in wound healing were measured in samples of PURION® Processed dehydrated amnion, chorion, and amnion/chorion membrane (dHACM) grafts by multiplex enzyme-linked immunosorbent assay array. Both amnion and chorion contained similar amounts of each factor when normalized per dry weight; however, when calculated per surface area of tissue applied to a wound, amnion contained on average only 25% as much of each factor as the chorion. Therefore, an allograft containing both amnion and chorion would contain four to five times more cytokine than a single layer amnion allograft alone. Both single layer amnion and multilayer allografts containing amnion and chorion are currently marketed for wound repair. To examine the role of tissue processing technique in cytokine retention, cytokine contents in representative dehydrated single layer wound care products were measured. The results demonstrated that cytokine content varied significantly among the allografts tested, and that PURION® Processed single layer amnion grafts contained more cytokines than other single layer products. These results suggest that PURION® Processed dHACM contains substantially more cytokines than single layer amnion products, and therefore dHACM may be more effective at delivering growth factors to a healing wound than amnion alone. © 2014 Wiley Periodicals, Inc.

Comparison of unsupervised classification methods for brain tumor segmentation using multi-parametric MRI.

PubMed

Sauwen, N; Acou, M; Van Cauter, S; Sima, D M; Veraart, J; Maes, F; Himmelreich, U; Achten, E; Van Huffel, S

2016-01-01

Tumor segmentation is a particularly challenging task in high-grade gliomas (HGGs), as they are among the most heterogeneous tumors in oncology. An accurate delineation of the lesion and its main subcomponents contributes to optimal treatment planning, prognosis and follow-up. Conventional MRI (cMRI) is the imaging modality of choice for manual segmentation, and is also considered in the vast majority of automated segmentation studies. Advanced MRI modalities such as perfusion-weighted imaging (PWI), diffusion-weighted imaging (DWI) and magnetic resonance spectroscopic imaging (MRSI) have already shown their added value in tumor tissue characterization, hence there have been recent suggestions of combining different MRI modalities into a multi-parametric MRI (MP-MRI) approach for brain tumor segmentation. In this paper, we compare the performance of several unsupervised classification methods for HGG segmentation based on MP-MRI data including cMRI, DWI, MRSI and PWI. Two independent MP-MRI datasets with a different acquisition protocol were available from different hospitals. We demonstrate that a hierarchical non-negative matrix factorization variant which was previously introduced for MP-MRI tumor segmentation gives the best performance in terms of mean Dice-scores for the pathologic tissue classes on both datasets.

Omega-3 fatty acids prevent early-life antibiotic exposure-induced gut microbiota dysbiosis and later-life obesity.

PubMed

Kaliannan, K; Wang, B; Li, X-Y; Bhan, A K; Kang, J X

2016-06-01

Early-life antibiotic exposure can disrupt the founding intestinal microbial community and lead to obesity later in life. Recent studies show that omega-3 fatty acids can reduce body weight gain and chronic inflammation through modulation of the gut microbiota. We hypothesize that increased tissue levels of omega-3 fatty acids may prevent antibiotic-induced alteration of gut microbiota and obesity later in life. Here, we utilize the fat-1 transgenic mouse model, which can endogenously produce omega-3 fatty acids and thereby eliminates confounding factors of diet, to show that elevated tissue levels of omega-3 fatty acids significantly reduce body weight gain and the severity of insulin resistance, fatty liver and dyslipidemia resulting from early-life exposure to azithromycin. These effects were associated with a reversal of antibiotic-induced dysbiosis of gut microbiota in fat-1 mice. These results demonstrate the beneficial effects of omega-3 fatty acids on antibiotic-induced gut dysbiosis and obesity, and suggest the potential utility of omega-3 supplementation as a safe and effective means for the prevention of obesity in children who are exposed to antibiotics.

Anti-Inflammatory Effects of Ethanol Extract of Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes), in Mice with Ulcerative Colitis.

PubMed

Qin, Mingming; Geng, Yan; Lu, Zhenming; Xu, Hongyu; Shi, Jin-Song; Xu, Xin; Xu, Zheng-Hong

2016-01-01

This study investigated the anti-inflammatory activity of ethanol extracts of Hericium erinaceus in the inflammatory bowel disease (IBD) model. Twenty C57BL/6 mice were exposed to 2% (w/v) dextran sulfate sodium (DSS) in their drinking water for 7 d to induce acute intestinal inflammation. Orally administrated ethanol extract of H. erinaceus (HEEE) (250 mg/kg/d and 500 mg/kg/d body weight) could significantly (P < 0.05) improve body weight and colon length and decreased the intestinal bleeding of DSS-treated mice compared with DSS-treated mice not given HEEE. HEEE markedly reduced DSS-induced myeloperoxidase accumulation in colon tissues, attenuated histological change in the neutrophils and lymphocyte infiltration, and protected the mucosal epithelium. Mechanistically, HEEE ameliorated colitis not only by suppressing the production of inflammatory mediators including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in colon tissues but also by adjusting the production of nitric oxide, malondialdehyde, and superoxide dismutase in serum to suppress the oxidative stress. These results suggest that HEEE can be applied as a protective agent in the treatment of IBDs.

Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications

PubMed Central

Vernochet, Cecile; Damilano, Federico; Mourier, Arnaud; Bezy, Olivier; Mori, Marcelo A.; Smyth, Graham; Rosenzweig, Anthony; Larsson, Nils-Göran; Kahn, C. Ronald

2014-01-01

Mitochondrial dysfunction in adipose tissue occurs in obesity, type 2 diabetes, and some forms of lipodystrophy, but whether this dysfunction contributes to or is the result of these disorders is unknown. To investigate the physiological consequences of severe mitochondrial impairment in adipose tissue, we generated mice deficient in mitochondrial transcription factor A (TFAM) in adipocytes by using mice carrying adiponectin-Cre and TFAM floxed alleles. These adiponectin TFAM-knockout (adipo-TFAM-KO) mice had a 75–81% reduction in TFAM in the subcutaneous and intra-abdominal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT), causing decreased expression and enzymatic activity of proteins in complexes I, III, and IV of the electron transport chain (ETC). This mitochondrial dysfunction led to adipocyte death and inflammation in WAT and a whitening of BAT. As a result, adipo-TFAM-KO mice were resistant to weight gain, but exhibited insulin resistance on both normal chow and high-fat diets. These lipodystrophic mice also developed hypertension, cardiac hypertrophy, and cardiac dysfunction. Thus, isolated mitochondrial dysfunction in adipose tissue can lead a syndrome of lipodystrophy with metabolic syndrome and cardiovascular complications.—Vernochet, C., Damilano, F., Mourier, A., Bezy, O., Mori, M. A., Smyth, G., Rosenzweig, A., Larsson, N.-G., Kahn, C. R. Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications. PMID:25005176

The Metabolic Phenotype in Obesity: Fat Mass, Body Fat Distribution, and Adipose Tissue Function.

PubMed

Goossens, Gijs H

2017-01-01

The current obesity epidemic poses a major public health issue since obesity predisposes towards several chronic diseases. BMI and total adiposity are positively correlated with cardiometabolic disease risk at the population level. However, body fat distribution and an impaired adipose tissue function, rather than total fat mass, better predict insulin resistance and related complications at the individual level. Adipose tissue dysfunction is determined by an impaired adipose tissue expandability, adipocyte hypertrophy, altered lipid metabolism, and local inflammation. Recent human studies suggest that adipose tissue oxygenation may be a key factor herein. A subgroup of obese individuals - the 'metabolically healthy obese' (MHO) - have a better adipose tissue function, less ectopic fat storage, and are more insulin sensitive than obese metabolically unhealthy persons, emphasizing the central role of adipose tissue function in metabolic health. However, controversy has surrounded the idea that metabolically healthy obesity may be considered really healthy since MHO individuals are at increased (cardio)metabolic disease risk and may have a lower quality of life than normal weight subjects due to other comorbidities. Detailed metabolic phenotyping of obese persons will be invaluable in understanding the pathophysiology of metabolic disturbances, and is needed to identify high-risk individuals or subgroups, thereby paving the way for optimization of prevention and treatment strategies to combat cardiometabolic diseases. © 2017 The Author(s) Published by S. Karger GmbH, Freiburg.

Implementation of a non-lethal biopsy punch monitoring program for mercury in smallmouth bass, Micropterus dolomieu Lacepède, from the Eleven Point River, Missouri

USGS Publications Warehouse

Ackerson, J.R.; Schmitt, C.J.; McKee, M.J.; Brumbaugh, W.G.

2013-01-01

A non-lethal biopsy method for monitoring mercury (Hg) concentrations in smallmouth bass (Micropterus dolomieu; smallmouth) from the Eleven Point River in southern Missouri USA was evaluated. A biopsy punch was used to remove a muscle tissue plug from the area immediately below the anterior dorsal fin of 31 smallmouth. An additional 35 smallmouth (controls) were held identically except that no tissue plug was removed. After sampling, all fish were held in a concrete hatchery raceway for 6 weeks. Mean survival at the end of the holding period was 97 % for both groups. Smallmouth length, weight and Fulton’s condition factor at the end of the holding period were also similar between plugged and non-plugged controls, indicating that the biopsy procedure had minimal impact on growth under these conditions. Tissue plug Hg concentrations were similar to smallmouth Hg data obtained in previous years by removing the entire fillet for analysis.

Implementation of a non-lethal biopsy punch monitoring program for mercury in smallmouth bass, Micropterus dolomieu Lacepede, from the Eleven Point River, Missouri

USGS Publications Warehouse

Ackerson, R.J.; McKee, J.M.; Schmitt, C.J.; Brumbaugh, William G.

2014-01-01

A non-lethal biopsy method for monitoring mercury (Hg) concentrations in smallmouth bass (Micropterus dolomieu; smallmouth) from the Eleven Point River in southern Missouri USA was evaluated. A biopsy punch was used to remove a muscle tissue plug from the area immediately below the anterior dorsal fin of 31 smallmouth. An additional 35 smallmouth (controls) were held identically except that no tissue plug was removed. After sampling, all fish were held in a concrete hatchery raceway for 6 weeks. Mean survival at the end of the holding period was 97 % for both groups. Smallmouth length, weight and Fulton’s condition factor at the end of the holding period were also similar between plugged and non-plugged controls, indicating that the biopsy procedure had minimal impact on growth under these conditions. Tissue plug Hg concentrations were similar to smallmouth Hg data obtained in previous years by removing the entire fillet for analysis.

Optical biopsy using fluorescence spectroscopy for prostate cancer diagnosis

NASA Astrophysics Data System (ADS)

Wu, Binlin; Gao, Xin; Smith, Jason; Bailin, Jacob

2017-02-01

Native fluorescence spectra are acquired from fresh normal and cancerous human prostate tissues. The fluorescence data are analyzed using a multivariate analysis algorithm such as non-negative matrix factorization. The nonnegative spectral components are retrieved and attributed to the native fluorophores such as collagen, reduced nicotinamide adenine dinucleotide (NADH), and flavin adenine dinucleotide (FAD) in tissue. The retrieved weights of the components, e.g. NADH and FAD are used to estimate the relative concentrations of the native fluorophores and the redox ratio. A machine learning algorithm such as support vector machine (SVM) is used for classification to distinguish normal and cancerous tissue samples based on either the relative concentrations of NADH and FAD or the redox ratio alone. The classification performance is shown based on statistical measures such as sensitivity, specificity, and accuracy, along with the area under receiver operating characteristic (ROC) curve. A cross validation method such as leave-one-out is used to evaluate the predictive performance of the SVM classifier to avoid bias due to overfitting.

MR-guided conformal heating of canine prostate using interstitial applicators

NASA Astrophysics Data System (ADS)

Nau, William H.; Diederich, Chris J.; Ross, Anthony; Butts, R. K.; Rieke, Viola; Bouley, Donna; Gill, Harchi; Daniel, Bruce; Sommer, Graham

2003-06-01

MRI compatible, multi-element ultrasound applicators were fabricated using cylindrical piezoceramic transducers sectored to 180 degrees to provide angular directional heating. The applicators were designed to be inserted into standard 13 or 14 gage brachytherapy catheters integrated with water-cooling. Two applicators were inserted transperinealy into the posterior region of a canine prostate. Power output ranged from 5-15 W per element during the 15 minute heating period. Phase-sensitive gradient-recalled MR imaging was used to monitor the treatment in real-time on a 0.5 Tesla MRT system. Gadolinium-enhanced T1 weighted images and diffusion-weighted images were obtained to view the regions which had been ablated during the heating procedure. Upon euthanasia, the prostate was removed, axially sectioned, and stained with TTC to reveal any regions of remaining viable tissue. Results from this study indicated a large volume of ablated tissue within the prostate which was highly correlated to the regions in the T1-weighted and diffusion-weighted images which had decreased intensity, and to the 52C contour displayed in the images obtained during the treatment. This study demonstrates the ability to control thermal coagulation within a targeted tissue volume while protecting surrounding tissue from thermal damage.

EPA-enriched phospholipids ameliorate cancer-associated cachexia mainly via inhibiting lipolysis.

PubMed

Du, Lei; Yang, Yu-Hong; Wang, Yu-Ming; Xue, Chang-Hu; Kurihara, Hideyuki; Takahashi, Koretaro

2015-12-01

Excessive loss of fat mass is considered as a key feature of body weight loss in cancer-associated cachexia (CAC). It affects the efficacy and tolerability of cancer therapy and reduces the quality and length of cancer patients' lives. The aim of the present study was to evaluate the effects of EPA-enriched phospholipids (EPA-PL) derived from starfish Asterias amurensis on cachectic weight loss in mice bearing S180 ascitic tumor, and TNF-α-stimulated lipolysis in 3T3-L1 adipocytes and to elucidate the possible mechanisms involved. Our findings revealed that oral administration of EPA-PL at 100 mg per kg body weight (BW) per day for 14 days prevented body weight loss in CAC mice by preserving the white adipose tissue (WAT) mass. We found that serum levels of nonesterified fatty acid (NEFA) and pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α) and interleukin (IL)-6 increased in CAC mice but decreased significantly after oral treatment of EPA-PL. In addition, EPA-PL treatment also suppressed the overexpression of several key lipolytic factors and raised the mRNA levels of some adipogenic factors in the WAT of CAC mice. Moreover, treatment of EPA-PL (200 and 400 μM) markedly inhibited TNF-α-stimulated lipolysis in adipocytes. Furthermore, the antilipolytic effects of EPA-PL were stimulated by the extracellular signal-regulated kinase 1/2 (ERK 1/2) inhibitor PD 98059 and blocked via the AMP-activated protein kinase (AMPK) inhibitor compound C and the phosphoinositide-3-kinase (PI3K) inhibitor LY 294002. Taken together, these data suggest that the dietary EPA-PL ameliorates CAC mainly via inhibiting lipolysis and at least in part for recovering the function of adipogenesis.

Factors which modulate the rates of skeletal muscle mass loss in non-small cell lung cancer patients: a pilot study.

PubMed

Atlan, Philippe; Bayar, Mohamed Amine; Lanoy, Emilie; Besse, Benjamin; Planchard, David; Ramon, Jordy; Raynard, Bruno; Antoun, Sami

2017-11-01

Advanced non-small cell lung cancer (NSCLC) is associated with weight loss which may reflect skeletal muscle mass (SMM) and/or total adipose tissue (TAT) depletion. This study aimed to describe changes in body composition (BC) parameters and to identify the factors unrelated to the tumor which modulate them. SMM, TAT, and the proportion of SMM to SMM + TAT were assessed with computed tomography. Estimates of each BC parameter at follow-up initiation and across time were derived from a mixed linear model of repeated measurements with a random intercept and a random slope. The same models were used to assess the independent effect of gender, age, body mass index (BMI), and initial values on changes in each BC parameter. Sixty-four patients with stage III or IV NSCLC were reviewed. The mean ± SD decreases in body weight and SMM were respectively 59 ± 3 g/week (P < 0.03) and 7 mm 2 /m 2 /week (P = 0.0003). During follow-up, no changes were identified in TAT nor in muscle density or in the proportion of SMM to SMM + TAT, estimated at 37 ± 2% at baseline. SMM loss was influenced by initial BMI (P < 0.0001) and SMM values (P = 0.0002): the higher the initial BMI or SMM values, the greater the loss observed. Weight loss was greater when the initial weight was heavier (P < 0.0001). Our results demonstrate that SMM wasting in NSCLC is lower when initial SMM and BMI values are low. These exploratory findings after our attempt to better understand the intrinsic factors associated with muscle mass depletion need to be confirmed in larger studies.

Kinematic and dynamic gait compensations in a rat model of lumbar radiculopathy and the effects of tumor necrosis factor-alpha antagonism

PubMed Central

2011-01-01

Introduction Tumor necrosis factor-α (TNFα) has received significant attention as a mediator of lumbar radiculopathy, with interest in TNF antagonism to treat radiculopathy. Prior studies have demonstrated that TNF antagonists can attenuate heightened nociception resulting from lumbar radiculopathy in the preclinical model. Less is known about the potential impact of TNF antagonism on gait compensations, despite being of clinical relevance. In this study, we expand on previous descriptions of gait compensations resulting from lumbar radiculopathy in the rat and describe the ability of local TNF antagonism to prevent the development of gait compensations, altered weight bearing, and heightened nociception. Methods Eighteen male Sprague-Dawley rats were investigated for mechanical sensitivity, weight-bearing, and gait pre- and post-operatively. For surgery, tail nucleus pulposus (NP) tissue was collected and the right L5 dorsal root ganglion (DRG) was exposed (Day 0). In sham animals, NP tissue was discarded (n = 6); for experimental animals, autologous NP was placed on the DRG with or without 20 μg of soluble TNF receptor type II (sTNFRII, n = 6 per group). Spatiotemporal gait characteristics (open arena) and mechanical sensitivity (von Frey filaments) were assessed on post-operative Day 5; gait dynamics (force plate arena) and weight-bearing (incapacitance meter) were assessed on post-operative Day 6. Results High-speed gait characterization revealed animals with NP alone had a 5% decrease in stance time on their affected limbs on Day 5 (P ≤0.032). Ground reaction force analysis on Day 6 aligned with temporal changes observed on Day 5, with vertical impulse reduced in the affected limb of animals with NP alone (area under the vertical force-time curve, P <0.02). Concordant with gait, animals with NP alone also had some evidence of affected limb mechanical allodynia on Day 5 (P = 0.08) and reduced weight-bearing on the affected limb on Day 6 (P <0.05). Delivery of sTNFRII at the time of NP placement ameliorated signs of mechanical hypersensitivity, imbalanced weight distribution, and gait compensations (P <0.1). Conclusions Our data indicate gait characterization has value for describing early limb dysfunctions in pre-clinical models of lumbar radiculopathy. Furthermore, TNF antagonism prevented the development of gait compensations subsequent to lumbar radiculopathy in our model. PMID:21871102

The role of lean body mass and physical activity in bone health in children.

PubMed

Baptista, Fátima; Barrigas, Carlos; Vieira, Filomena; Santa-Clara, Helena; Homens, Pedro Mil; Fragoso, Isabel; Teixeira, Pedro J; Sardinha, Luís B

2012-01-01

In the context of physical education curricula, markers of physical fitness (e.g., aerobic capacity, muscular strength, flexibility, and body mass index or body fat) are usually evaluated in reference to health standards. Despite their possible mediating role in the relationship between weight-bearing or muscle forces and features of bone tissue, these attributes of fitness may not be the most relevant to predict skeletal health. It is therefore important to analyze the relative contribution of these factors to the variability in bone tissue of different parts of the skeleton, and to analyze it by gender, as sensitivity to mechanical loading can diverge for boys and girls. We compared the effects of habitual physical activity (PA) and lean mass, as surrogates of weight-bearing and muscle forces, and of physical fitness (aerobic and muscle capacity of lower and upper limbs) on bone mineral content (BMC) and size of total body, lumbar spine, femoral neck, and 1/3 radius in 53 girls and 64 boys from 7.9 to 9.7 years of age. After controlling for bone age, body mass, body height, and calcium intake, lean mass was the most important predictor of bone size and/or mineral in both genders (p < 0.05), while habitual weight-bearing PA positively influenced BMC in boys (p < 0.05). The effect of muscle in bone was not determined by PA and fitness score did not explain bone variability. Femoral neck was the bone site more closely associated with mechanical loading factors; boys with a PA > 608 counts/min/day (~105 min/day of moderate and vigorous intensity) showed 13-20% more BMC than those with less physical activity, and girls with a lean mass >19 kg showed 12-19% more BMC than those with less lean mass. These findings suggest that lean mass was the most important predictor of bone size and/or mineralization in both genders, while habitual weight-bearing PA appears to positively impact on bone mineral in prepubertal boys and that both lean mass and PA need to be considered in physical education curricula and other health-enhancing programs.

Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol.

PubMed

Martinez, Jessica A; Chalasani, Pavani; Thomson, Cynthia A; Roe, Denise; Altbach, Maria; Galons, Jean-Philippe; Stopeck, Alison; Thompson, Patricia A; Villa-Guillen, Diana Evelyn; Chow, H-H Sherry

2016-07-19

Two-thirds of U.S. adult women are overweight or obese. High body mass index (BMI) and adult weight gain are risk factors for a number of chronic diseases, including postmenopausal breast cancer. The higher postmenopausal breast cancer risk in women with elevated BMI is likely to be attributable to related metabolic disturbances including altered circulating sex steroid hormones and adipokines, elevated pro-inflammatory cytokines, and insulin resistance. Metformin is a widely used antidiabetic drug that has demonstrated favorable effects on metabolic disturbances and as such may lead to lower breast cancer risk in obese women. Further, the anti-proliferative effects of metformin suggest it may decrease breast density, an accepted biomarker of breast cancer risk. This is a Phase II randomized, double-blind, placebo-controlled trial of metformin in overweight/obese premenopausal women who have elements of metabolic syndrome. Eligible participants will be randomized to receive metformin 850 mg BID (n = 75) or placebo (n = 75) for 12 months. The primary endpoint is change in breast density, based on magnetic resonance imaging (MRI) acquired fat-water features. Secondary outcomes include changes in serum insulin levels, serum insulin-like growth factor (IGF)-1 to insulin-like growth factor binding protein (IGFBP)-3 ratio, serum IGF-2 levels, serum testosterone levels, serum leptin to adiponectin ratio, body weight, and waist circumference. Exploratory outcomes include changes in metabolomic profiles in plasma and nipple aspirate fluid. Changes in tissue architecture as well as cellular and molecular targets in breast tissue collected in a subgroup of participants will also be explored. The study will evaluate whether metformin can result in favorable changes in breast density, select proteins and hormones, products of body metabolism, and body weight and composition. The study should help determine the potential breast cancer preventive activity of metformin in a growing population at risk for multiple diseases. ClinicalTrials.gov Identifier: NCT02028221 . Registered on January 2, 2014. Grant #: 1R01CA172444-01A1 awarded on Sept 11, 2013.

High Molecular Weight Fibroblast Growth Factor-2 in the Human Heart Is a Potential Target for Prevention of Cardiac Remodeling

PubMed Central

Santiago, Jon-Jon; McNaughton, Leslie J.; Koleini, Navid; Ma, Xin; Bestvater, Brian; Nickel, Barbara E.; Fandrich, Robert R.; Wigle, Jeffrey T.; Freed, Darren H.; Arora, Rakesh C.; Kardami, Elissavet

2014-01-01

Fibroblast growth factor 2 (FGF-2) is a multifunctional protein synthesized as high (Hi-) and low (Lo-) molecular weight isoforms. Studies using rodent models showed that Hi- and Lo-FGF-2 exert distinct biological activities: after myocardial infarction, rat Lo-FGF-2, but not Hi-FGF-2, promoted sustained cardioprotection and angiogenesis, while Hi-FGF-2, but not Lo-FGF-2, promoted myocardial hypertrophy and reduced contractile function. Because there is no information regarding Hi-FGF-2 in human myocardium, we undertook to investigate expression, regulation, secretion and potential tissue remodeling-associated activities of human cardiac (atrial) Hi-FGF-2. Human patient-derived atrial tissue extracts, as well as pericardial fluid, contained Hi-FGF-2 isoforms, comprising, respectively, 53%(±20 SD) and 68% (±25 SD) of total FGF-2, assessed by western blotting. Human atrial tissue-derived primary myofibroblasts (hMFs) expressed and secreted predominantly Hi-FGF-2, at about 80% of total. Angiotensin II (Ang II) up-regulated Hi-FGF-2 in hMFs, via activation of both type 1 and type 2 Ang II receptors; the ERK pathway; and matrix metalloprotease-2. Treatment of hMFs with neutralizing antibodies selective for human Hi-FGF-2 (neu-AbHi-FGF-2) reduced accumulation of proteins associated with fibroblast-to-myofibroblast conversion and fibrosis, including α-smooth muscle actin, extra-domain A fibronectin, and procollagen. Stimulation of hMFs with recombinant human Hi-FGF-2 was significantly more potent than Lo-FGF-2 in upregulating inflammation-associated proteins such as pro-interleukin-1β and plasminogen-activator-inhibitor-1. Culture media conditioned by hMFs promoted cardiomyocyte hypertrophy, an effect that was prevented by neu-AbHi-FGF-2 in vitro. In conclusion, we have documented that Hi-FGF-2 represents a substantial fraction of FGF-2 in human cardiac (atrial) tissue and in pericardial fluid, and have shown that human Hi-FGF-2, unlike Lo-FGF-2, promotes deleterious (pro-fibrotic, pro-inflammatory, and pro-hypertrophic) responses in vitro. Selective targeting of Hi-FGF-2 production may, therefore, reduce pathological remodelling in the human heart. PMID:24827991

High molecular weight fibroblast growth factor-2 in the human heart is a potential target for prevention of cardiac remodeling.

PubMed

Santiago, Jon-Jon; McNaughton, Leslie J; Koleini, Navid; Ma, Xin; Bestvater, Brian; Nickel, Barbara E; Fandrich, Robert R; Wigle, Jeffrey T; Freed, Darren H; Arora, Rakesh C; Kardami, Elissavet

2014-01-01

Fibroblast growth factor 2 (FGF-2) is a multifunctional protein synthesized as high (Hi-) and low (Lo-) molecular weight isoforms. Studies using rodent models showed that Hi- and Lo-FGF-2 exert distinct biological activities: after myocardial infarction, rat Lo-FGF-2, but not Hi-FGF-2, promoted sustained cardioprotection and angiogenesis, while Hi-FGF-2, but not Lo-FGF-2, promoted myocardial hypertrophy and reduced contractile function. Because there is no information regarding Hi-FGF-2 in human myocardium, we undertook to investigate expression, regulation, secretion and potential tissue remodeling-associated activities of human cardiac (atrial) Hi-FGF-2. Human patient-derived atrial tissue extracts, as well as pericardial fluid, contained Hi-FGF-2 isoforms, comprising, respectively, 53%(±20 SD) and 68% (±25 SD) of total FGF-2, assessed by western blotting. Human atrial tissue-derived primary myofibroblasts (hMFs) expressed and secreted predominantly Hi-FGF-2, at about 80% of total. Angiotensin II (Ang II) up-regulated Hi-FGF-2 in hMFs, via activation of both type 1 and type 2 Ang II receptors; the ERK pathway; and matrix metalloprotease-2. Treatment of hMFs with neutralizing antibodies selective for human Hi-FGF-2 (neu-AbHi-FGF-2) reduced accumulation of proteins associated with fibroblast-to-myofibroblast conversion and fibrosis, including α-smooth muscle actin, extra-domain A fibronectin, and procollagen. Stimulation of hMFs with recombinant human Hi-FGF-2 was significantly more potent than Lo-FGF-2 in upregulating inflammation-associated proteins such as pro-interleukin-1β and plasminogen-activator-inhibitor-1. Culture media conditioned by hMFs promoted cardiomyocyte hypertrophy, an effect that was prevented by neu-AbHi-FGF-2 in vitro. In conclusion, we have documented that Hi-FGF-2 represents a substantial fraction of FGF-2 in human cardiac (atrial) tissue and in pericardial fluid, and have shown that human Hi-FGF-2, unlike Lo-FGF-2, promotes deleterious (pro-fibrotic, pro-inflammatory, and pro-hypertrophic) responses in vitro. Selective targeting of Hi-FGF-2 production may, therefore, reduce pathological remodelling in the human heart.

Biexponential characterization of prostate tissue water diffusion decay curves over an extended b-factor range.

PubMed

Mulkern, Robert V; Barnes, Agnieszka Szot; Haker, Steven J; Hung, Yin P; Rybicki, Frank J; Maier, Stephan E; Tempany, Clare M C

2006-06-01

Detailed measurements of water diffusion within the prostate over an extended b-factor range were performed to assess whether the standard assumption of monoexponential signal decay is appropriate in this organ. From nine men undergoing prostate MR staging examinations at 1.5 T, a single 10-mm-thick axial slice was scanned with a line scan diffusion imaging sequence in which 14 equally spaced b factors from 5 to 3,500 s/mm(2) were sampled along three orthogonal diffusion sensitization directions in 6 min. Due to the combination of long scan time and limited volume coverage associated with the multi-b-factor, multidirectional sampling, the slice was chosen online from the available T2-weighted axial images with the specific goal of enabling the sampling of presumed noncancerous regions of interest (ROIs) within the central gland (CG) and peripheral zone (PZ). Histology from prescan biopsy (n=9) and postsurgical resection (n=4) was subsequently employed to help confirm that the ROIs sampled were noncancerous. The CG ROIs were characterized from the T2-weighted images as primarily mixtures of glandular and stromal benign prostatic hyperplasia, which is prevalent in this population. The water signal decays with b factor from all ROIs were clearly non-monoexponential and better served with bi- vs. monoexponential fits, as tested using chi(2)-based F test analyses. Fits to biexponential decay functions yielded intersubject fast diffusion component fractions in the order of 0.73+/-0.08 for both CG and PZ ROIs, fast diffusion coefficients of 2.68+/-0.39 and 2.52+/-0.38 microm(2)/ms and slow diffusion coefficients of 0.44+/-0.16 and 0.23+/-0.16 um(2)/ms for CG and PZ ROIs, respectively. The difference between the slow diffusion coefficients within CG and PZ was statistically significant as assessed with a Mann-Whitney nonparametric test (P<.05). We conclude that a monoexponential model for water diffusion decay in prostate tissue is inadequate when a large range of b factors is sampled and that biexponential analyses are better suited for characterizing prostate diffusion decay curves.

Bioaccumulation of metals in the soft tissue of Patella aspera: Application of metal/shell weight indices

NASA Astrophysics Data System (ADS)

Cravo, A.; Bebianno, M. J.

2005-11-01

Patella aspera limpets were taken from a marine clean site (MCS) and an estuarine contaminated site (ECS). The concentrations of Fe, Mn, Zn, Cu, Cd, Ni and Co were determined individually over the available size range. Since there were significant differences in the soft tissue weight between populations, but shell characteristics were similar (length and weight), metal/shell weight indices (MSI) were calculated in order to compare populations. For both populations iron, zinc and manganese/shell weight indices were consistently higher, in the order Fe ≫ Zn ≫ Mn than those of Cu, Ni, Co and Cd. The results exhibited a marked intra- and inter-population variability. The highest intra-variability was observed at ECS, particularly where a strong effect of shell weight upon the metal accumulation in the soft tissue was evident. Due to this effect, the comparison of populations was carried out between three selected shell weight ranges representative of light shells (0.45-1.95 g), intermediate shells (2.95-4.45 g) and heavy shells (5.45-7.33 g). The results indicate that, in general, MSI at ECS (a sewage contaminated site), except for Cd, was higher than at MCS possibly reflecting a higher environmental bioavailability of these metals. The resolution between populations was higher when the smallest range of limpets was considered and it decreased with the increase of shell weight. The highest discrimination amongst populations was found for zinc/shell weight index that showed much higher values than those of Mn, Cu, Cd, Ni and Co/shell weight indices, and spatial differentiation between populations persisted amongst the selected shell weight ranges.

Inflammatory Pathways Regulated by Tumor Necrosis Receptor-Associated Factor 1 Protect From Metabolic Consequences in Diet-Induced Obesity.

PubMed

Anto Michel, Nathaly; Colberg, Christian; Buscher, Konrad; Sommer, Björn; Pramod, Akula Bala; Ehinger, Erik; Dufner, Bianca; Hoppe, Natalie; Pfeiffer, Katharina; Marchini, Timoteo; Willecke, Florian; Stachon, Peter; Hilgendorf, Ingo; Heidt, Timo; von Zur Muhlen, Constantin; von Elverfeldt, Dominik; Pfeifer, Dietmar; Schüle, Roland; Kintscher, Ulrich; Brachs, Sebastian; Ley, Klaus; Bode, Christoph; Zirlik, Andreas; Wolf, Dennis

2018-03-02

The coincidence of inflammation and metabolic derangements in obese adipose tissue has sparked the concept of met-inflammation. Previous observations, however, suggest that inflammatory pathways may not ultimately cause dysmetabolism. We have revisited the relationship between inflammation and metabolism by testing the role of TRAF (tumor necrosis receptor-associated factor)-1, an inhibitory adapter of inflammatory signaling of TNF (tumor necrosis factor)-α, IL (interleukin)-1β, and TLRs (toll-like receptors). Mice deficient for TRAF-1, which is expressed in obese adipocytes and adipose tissue lymphocytes, caused an expected hyperinflammatory phenotype in adipose tissue with enhanced adipokine and chemokine expression, increased leukocyte accumulation, and potentiated proinflammatory signaling in macrophages and adipocytes in a mouse model of diet-induced obesity. Unexpectedly, TRAF-1 -/- mice were protected from metabolic derangements and adipocyte growth, failed to gain weight, and showed improved insulin resistance-an effect caused by increased lipid breakdown in adipocytes and UCP (uncoupling protein)-1-enabled thermogenesis. TRAF-1-dependent catabolic and proinflammatory cues were synergistically driven by β3-adrenergic and inflammatory signaling and required the presence of both TRAF-1-deficient adipocytes and macrophages. In human obesity, TRAF-1-dependent genes were upregulated. Enhancing TRAF-1-dependent inflammatory pathways in a gain-of-function approach protected from metabolic derangements in diet-induced obesity. These findings identify TRAF-1 as a regulator of dysmetabolism in mice and humans and question the pathogenic role of chronic inflammation in metabolism. © 2018 American Heart Association, Inc.

Ginsenoside Rb1 Treatment Attenuates Pulmonary Inflammatory Cytokine Release and Tissue Injury following Intestinal Ischemia Reperfusion Injury in Mice

PubMed Central

Zhou, Zhen; Meng, Qing-tao; Sun, Qian; Su, Wating; Xia, Zhengyuan; Xia, Zhong-yuan

2015-01-01

Objective. Intestinal ischemia reperfusion (II/R) injury plays a critical role in remote organ dysfunction, such as lung injury, which is associated with nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. In the present study, we tested whether ginsenoside Rb1 attenuated II/R induced lung injury by Nrf2/HO-1 pathway. Methods. II/R injury was induced in male C57BL/6J mice by 45 min of superior mesenteric artery (SMA) occlusion followed by 2 hours of reperfusion. Ginsenoside Rb1 was administrated prior to reperfusion with or without ATRA (all-transretinoic acid, the inhibitor of Nrf2/ARE signaling pathway) administration before II/R. Results. II/R induced lung histological injury, which is accompanied with increased levels of malondialdehyde (MDA), interleukin- (IL-) 6, and tumor necrosis factor- (TNF-) α but decreased levels of superoxide dismutase (SOD) and IL-10 in the lung tissues. Ginsenoside Rb1 reduced lung histological injury and the levels of TNF-α and MDA, as well as wet/dry weight ratio. Interestingly, the increased Nrf2 and HO-1 expression induced by II/R in the lung tissues was promoted by ginsenoside Rb1 treatment. All these changes could be inhibited or prevented by ATRA. Conclusion. Ginsenoside Rb1 is capable of ameliorating II/R induced lung injuries by activating Nrf2/HO-1 pathway. PMID:26161243

Effects of post-fracture non-weight-bearing immobilization on muscle atrophy, intramuscular and intermuscular adipose tissues in the thigh and calf.

PubMed

Yoshiko, Akito; Yamauchi, Koun; Kato, Takayuki; Ishida, Koji; Koike, Teruhiko; Oshida, Yoshiharu; Akima, Hiroshi

2018-06-09

Disuse and/or a non-weight-bearing condition changes muscle composition, with decreased skeletal muscle tissue and increased fat within (intramuscular adipose tissue, IntraMAT) and between (intermuscular adipose tissue, InterMAT) given muscles. Excessive adipose tissue contributes to dysfunctional and metabolically impaired muscle. How these adipose tissues change during orthopedic treatment (e.g., cast immobilization, daily use of crutches) is not well documented. This study aimed to quantify changes in IntraMAT, InterMAT, and thigh and calf muscle tissue during orthopedic treatment. We studied 8 patients with fifth metatarsal bone or fibular fractures. The ankle joint involved underwent plaster casting for approximately 4 weeks, with crutches used during that time. Axial T1-weighted MRI at the mid-thigh and a 30% proximal site at the calf were obtained to measure IntraMAT and InterMAT cross-sectional areas (CSAs) and skeletal muscle tissue CSA before treatment and 4 weeks afterward. Thigh and calf muscle tissue CSAs were significantly decreased from before to after treatment: thigh, 85.8 ± 7.6 to 77.1 ± 7.3 cm 2 ; calf, 53.3 ± 5.5 to 48.9 ± 5.0 cm 2 (p < 0.05). None of the IntraMAT or InterMAT changes was statistically significant. There was a relation between the percentage change of thigh IntraMAT CSA and muscle tissue CSA (r s  = -0.86, p < 0.01). The 4 weeks of treatment primarily induced skeletal muscle atrophy with less of an effect on IntraMAT or InterMAT. There is a risk of increasing IntraMAT relatively by decreasing skeletal muscle tissue size during orthopedic treatment.

Hyaluronan influence on the onset of chondrogenic differentiation of mesenchymal stem cells.

PubMed

Dvorakova, Jana; Velebny, Vladimir; Kubala, Lukas

2008-10-01

Hyaluronan (HA) is an abundant component of chondrogenic tissue hence it is often used as a fundamental constituent in cartilage tissue substitutes. However, effects of different molecular weight HA on chondrogenic differentiation are not clear. The aim was to evaluate modulation of mesenchymal stem cell (MSC) early chondrogenesis by HA of molecular weights 100, 600 and 1 500 kDa. HA was applied on MSCs cultured in a pellet system for one, two and three weeks. Chondrogenesis was evaluated by determinations of gene expression of transcription factor Sox-9 and extracellular matrix proteins collagen type II and XI, aggrecan, and COMP by Real-Time PCR and completed with histological analysis. Upon chondrogenic induction, the respective pellets revealed active transcription of the chondrogenic genes together with proceeding accumulation of glycosaminoglycan (GAG) rich extracellular matrix. Sox-9 was also expressed in non-chondrogenic MSC controls. HA treated pellets were not significantly influenced on day 7 of culture. However, on day 14, lowered expression in some of the extracellular matrix proteins appeared together with a moderately smaller amount of GAG content in pellet sections. Nevertheless, the analysis on day 21 has demonstrated that HA did not affect the outcome of the differentiation by the end of the culture. Any difference regarding the molecular weight of the HA was not found. It could be speculated that HA induced a time shift in the phase of the dominant matrix protein onset which was in full compensated by the end of the evaluated time period. Thus, data suggest that HA of any tested molecular weight does not significantly modulate chondrogenesis of MSCs in pellet system.

Effect of hypocaloric diet-induced weight loss in obese women on plasma apelin and adipose tissue expression of apelin and APJ.

PubMed

Castan-Laurell, Isabelle; Vítkova, Michaela; Daviaud, Danièle; Dray, Cédric; Kováciková, Michaela; Kovacova, Zuzana; Hejnova, Jindriska; Stich, Vladimir; Valet, Philippe

2008-06-01

Apelin is a novel adipokine acting on APJ receptor, regulated by insulin and tumor necrosis factor-alpha (TNF-alpha) in adipose tissue (AT). Plasma apelin levels are increased in obese hyperinsulinemic subjects. The aim was to investigate whether the hypocaloric diet associated with weight loss modifies the elevated plasma apelin levels and the expression of apelin and APJ receptor in AT in obese women. Fasting plasma levels of apelin and TNF-alpha as well as mRNA levels of apelin and APJ in AT were measured before and after a 12-week hypocaloric weight-reducing diet in 20 obese women (body mass index (BMI) before diet 32.2+/-6.4 kg/m(2)). Twelve healthy women with a BMI of 20.7+/-0.6 kg/m(2) served as reference. Plasma levels of apelin and TNF-alpha were higher in obese compared with lean controls. The hypocaloric diet resulted in a significant decrease of BMI to 29.8+/-6.3 kg/m(2), plasma insulin (8.16+/-0.73 to 6.58+/-0.66 mU/l), apelin (369+/-25 pg/ml to 257+/-12 pg/ml), TNF-alpha levels (0.66+/-0.04 pg/ml to 0.56+/-0.04 pg/ml), and AT mRNAs of apelin and APJ. In addition, changes in AT mRNA apelin were related to changes in AT mRNA APJ levels. The hypocaloric diet associated with weight loss reduces the increased plasma and AT expression of apelin in obese women. This reduced apelin expression in AT could contribute to decreased circulating apelin levels.

IL-34 is associated with obesity, chronic inflammation, and insulin resistance.

PubMed

Chang, Eun-Ju; Lee, Seul Ki; Song, Young Sook; Jang, Yeon Jin; Park, Hye Soon; Hong, Joon Pio; Ko, A Ra; Kim, Dae Yeon; Kim, Jong-Hyeok; Lee, Yeon Ji; Heo, Yoon-Suk

2014-07-01

IL-34 is a recently identified alternative ligand for colony-stimulating factor-1 (CSF-1) receptor. IL-34 and CSF-1 are regulators of differentiation, proliferation, and survival in mononuclear phagocytes. Here, we investigated the IL-34 serum concentration and expression in human adipose tissues and any associations with insulin resistance. We recruited 19 nondiabetic obese women, 9 type 2 diabetic women, and 27 normal-weight women. Metabolic parameters, abdominal fat distribution, serum IL-34 concentration, and IL-34 mRNA expression were measured in abdominal sc adipose tissue (SAT) and visceral adipose tissue (VAT). In addition, the expression/secretion and putative effects of IL-34 were assessed in human differentiated adipocytes. Serum IL-34 concentration was measured before and 5 to 9 months after laparoscopic Roux-en-Y gastric bypass surgery was performed on the 20 obese patients. Regardless of diabetes status, obese patients demonstrated significantly higher serum IL-34 concentrations than controls. Serum IL-34 was significantly and positively correlated with insulin resistance-related metabolic parameters. IL-34 mRNA was significantly higher in VAT than SAT. IL-34 was expressed in adipocytes as well as nonadipocytes, and expression was significantly higher during adipogenesis. In differentiated adipocytes, the expression/secretion of IL-34 was enhanced by TNFα and IL-1β. In addition, IL-34 augmented fat accumulation and inhibited the stimulatory effects of insulin on glucose transport. Moreover, serum IL-34 was significantly decreased after Roux-en-Y gastric bypass-induced weight loss. The present study demonstrates, for the first time, that IL-34 is expressed in human adipose tissues and the circulating concentration is significantly elevated in obese patients. This suggests that IL-34 is associated with insulin resistance.

β3-Adrenergic receptors, adipokines and neuroendocrine activation during stress induced by repeated immune challenge in male and female rats.

PubMed

Csanova, Agnesa; Hlavacova, Natasa; Hasiec, Malgorzata; Pokusa, Michal; Prokopova, Barbora; Jezova, Daniela

2017-05-01

The main hypothesis of the study is that stress associated with repeated immune challenge has an impact on β 3 -adrenergic receptor gene expression in the brain. Sprague-Dawley rats were intraperitoneally injected with increasing doses of lipopolysaccharide (LPS) for five consecutive days. LPS treatment was associated with body weight loss and increased anxiety-like behavior. In LPS-treated animals of both sexes, β 3 -receptor gene expression was increased in the prefrontal cortex but not the hippocampus. LPS treatment decreased β 3 -receptor gene expression in white adipose tissue with higher values in males compared to females. In the adipose tissue, LPS reduced peroxisome proliferator-activated receptor-gamma, leptin and adiponectin gene expression, but increased interleukin-6 expression, irrespective of sex. Repeated immune challenge resulted in increased concentrations of plasma aldosterone and corticosterone with higher values of corticosterone in females compared to males. Concentrations of dehydroepiandrosterone (DHEA) in plasma were unaffected by LPS, while DHEA levels in the frontal cortex were lower in the LPS-treated animals compared to the controls. Thus, changes of DHEA levels in the brain take place irrespective of the changes of this neurosteroid in plasma. We have provided the first evidence on stress-induced increase in β 3 -adrenergic receptor gene expression in the brain. Greater reduction of β 3 -adrenergic receptor expression in the adipose tissue and of the body weight gain by repeated immune challenge in male than in female rats suggests sex differences in the role of β 3 -adrenergic receptors in the metabolic functions. LPS-induced changes in adipose tissue regulatory factors and hormone concentrations might be important for coping with chronic infections.

A history of obesity leaves an inflammatory fingerprint in liver and adipose tissue

PubMed Central

Fischer, I P; Irmler, M; Meyer, C W; Sachs, S J; Neff, F; Hrabě de Angelis, M; Beckers, J; Tschöp, M H; Hofmann, S M; Ussar, S

2018-01-01

Background/Objectives: Dieting is a popular yet often ineffective way to lower body weight, as the majority of people regain most of their pre-dieting weights in a relatively short time. The underlying molecular mechanisms driving weight regain and the increased risk for metabolic disease are still incompletely understood. Here we investigate the molecular alterations inherited from a history of obesity. Methods: In our model, male high-fat diet (HFD)-fed obese C57BL/6J mice were switched to a low caloric chow diet, resulting in a decline of body weight to that of lean mice. We measured body composition, as well as metrics of glucose, insulin and lipid homeostasis. This was accompanied by histological and gene expression analysis of adipose tissue and liver to assess adipose tissue inflammation and hepatosteatosis. Moreover, acute hypothalamic response to (re-) exposure to HFD was assessed by qPCR. Results & Conclusions: Within 7 weeks after diet switch, most obesity-associated phenotypes, such as body mass, glucose intolerance and blood metabolite levels were reversed. However, hepatic inflammation, hepatic steatosis as well as hypertrophy and inflammation of perigonadal, but not subcutaneous, adipocytes persisted in formerly obese mice. Transcriptional profiling of liver and perigonadal fat revealed an upregulation of pathways associated with immune function and cellularity. Thus, we show that weight reduction leaves signs of inflammation in liver and perigonadal fat, indicating that persisting proinflammatory signals in liver and adipose tissue could contribute to an increased risk of formerly obese subjects to develop the metabolic syndrome upon recurring weight gain. PMID:28901330

Central pedicled breast reduction technique in male patients after massive weight loss.

PubMed

Stoff, Alexander; Velasco-Laguardia, Fernando J; Richter, Dirk F

2012-03-01

Male patients after massive weight loss often suffer from redundant skin and soft tissue in the anterior and lateral chest region, causing various deformities of pseudogynecomastia. Techniques with free or pedicled nipple-areola complex (NAC) transposition are widely accepted. The authors present their approach to male breast reduction with preservation of the NAC on a central dermoglandular pedicle and a wide elliptical tissue excision of breast and lateral thorax tissue in combination with liposuction. Male breast reduction was performed on patients after moderate to massive weight loss due to diet or bariatric procedures. Former procedures included free nipple-areola grafts or inferior pedicled techniques for NAC preservation. As a modification, we performed a central pedicled breast reduction on nine male patients with excessive liposuction of the pedicle and a horizontal elliptical skin removal, allowing for sufficient tissue removal at the lateral thorax. From October 2010 until June 2011, nine male patients had central pedicled breast reconstructions after massive weight loss. Mean age was 29.1 years, mean preoperative body mass index was 29.2, and mean preoperative weight loss was 63.9 kg. The chest wall improvement was rated "very good" by eight patients. No major complications occurred in all nine patients. Male chest deformities after massive weight loss can be dealt by several approaches. The optimal scar positioning and the preservation of NAC may be the most challenging aspects of these procedures. Therefore, the preservation of the NAC on a central dermoglandular pedicle with a horizontal submammary scar course may optimize the esthetic outcome.

Zinc-α2-glycoprotein expression in adipose tissue of obese postmenopausal women before and after weight loss and exercise + weight loss.

PubMed

Ge, Shealinna; Ryan, Alice S

2014-08-01

Zinc-Alpha 2-Glycoprotein (ZAG) has recently been implicated in the regulation of adipose tissue metabolism due to its negative association with obesity and insulin resistance. The purpose of this study is to investigate the relationships between adipose tissue ZAG expression and central obesity, and the effects of six-months of weight loss (WL) or aerobic exercise + weight loss (AEX + WL) on ZAG expression. A six-month, longitudinal study of 33 healthy, overweight or obese postmenopausal women (BMI: 25-46 kg/m(2)) was conducted. Abdominal and gluteal adipose tissue samples were obtained before and after AEX + WL (n = 17) and WL (n = 16). ZAG expression was determined by RT-PCR. Prior to interventions, abdominal ZAG expression was negatively correlated with visceral fat (r = -0.50, P < 0.005), sagittal diameter (r = -0.42, P < 0.05), and positively related to VO(2)max (r = 0.37, P < 0.05). Gluteal ZAG expression was negatively correlated with weight, fat-free mass, visceral fat, resting metabolic rate, and fasting insulin (r = -0.39 to -0.50, all P < 0.05). Abdominal ZAG mRNA levels increased, though not significantly, 5% after AEX + WL and 11% after WL. Gluteal ZAG mRNA levels also did not change significantly with AEX + WL and WL. Abdominal ZAG expression may be important in central fat accumulation and fitness but only modestly increase (nonsignificantly) with weight reduction alone or with aerobic training in obese postmenopausal women. Published by Elsevier Inc.

High and Low Molecular Weight Hyaluronic Acid Differentially Regulate Human Fibrocyte Differentiation

PubMed Central

Maharjan, Anu S.; Pilling, Darrell; Gomer, Richard H.

2011-01-01

Background Following tissue injury, monocytes can enter the tissue and differentiate into fibroblast-like cells called fibrocytes, but little is known about what regulates this differentiation. Extracellular matrix contains high molecular weight hyaluronic acid (HMWHA; ∼2×106 Da). During injury, HMWHA breaks down to low molecular weight hyaluronic acid (LMWHA; ∼0.8–8×105 Da). Methods and Findings In this report, we show that HMWHA potentiates the differentiation of human monocytes into fibrocytes, while LMWHA inhibits fibrocyte differentiation. Digestion of HMWHA with hyaluronidase produces small hyaluronic acid fragments, and these fragments inhibit fibrocyte differentiation. Monocytes internalize HMWHA and LMWHA equally well, suggesting that the opposing effects on fibrocyte differentiation are not due to differential internalization of HMWHA or LMWHA. Adding HMWHA to PBMC does not appear to affect the levels of the hyaluronic acid receptor CD44, whereas adding LMWHA decreases CD44 levels. The addition of anti-CD44 antibodies potentiates fibrocyte differentiation, suggesting that CD44 mediates at least some of the effect of hyaluronic acid on fibrocyte differentiation. The fibrocyte differentiation-inhibiting factor serum amyloid P (SAP) inhibits HMWHA-induced fibrocyte differentiation and potentiates LMWHA-induced inhibition. Conversely, LMWHA inhibits the ability of HMWHA, interleukin-4 (IL-4), or interleukin-13 (IL-13) to promote fibrocyte differentiation. Conclusions We hypothesize that hyaluronic acid signals at least in part through CD44 to regulate fibrocyte differentiation, with a dominance hierarchy of SAP>LMWHA≥HMWHA>IL-4 or IL-13. PMID:22022512

Stromal regulation of vessel stability by MMP14 and TGFβ

PubMed Central

Sounni, Nor E.; Dehne, Kerstin; van Kempen, Leon; Egeblad, Mikala; Affara, Nesrine I.; Cuevas, Ileana; Wiesen, Jane; Junankar, Simon; Korets, Lidiya; Lee, Jake; Shen, Jennifer; Morrison, Charlotte J.; Overall, Christopher M.; Krane, Stephen M.; Werb, Zena; Boudreau, Nancy; Coussens, Lisa M.

2010-01-01

Innate regulatory networks within organs maintain tissue homeostasis and facilitate rapid responses to damage. We identified a novel pathway regulating vessel stability in tissues that involves matrix metalloproteinase 14 (MMP14) and transforming growth factor beta 1 (TGFβ1). Whereas plasma proteins rapidly extravasate out of vasculature in wild-type mice following acute damage, short-term treatment of mice in vivo with a broad-spectrum metalloproteinase inhibitor, neutralizing antibodies to TGFβ1, or an activin-like kinase 5 (ALK5) inhibitor significantly enhanced vessel leakage. By contrast, in a mouse model of age-related dermal fibrosis, where MMP14 activity and TGFβ bioavailability are chronically elevated, or in mice that ectopically express TGFβ in the epidermis, cutaneous vessels are resistant to acute leakage. Characteristic responses to tissue damage are reinstated if the fibrotic mice are pretreated with metalloproteinase inhibitors or TGFβ signaling antagonists. Neoplastic tissues, however, are in a constant state of tissue damage and exhibit altered hemodynamics owing to hyperleaky angiogenic vasculature. In two distinct transgenic mouse tumor models, inhibition of ALK5 further enhanced vascular leakage into the interstitium and facilitated increased delivery of high molecular weight compounds into premalignant tissue and tumors. Taken together, these data define a central pathway involving MMP14 and TGFβ that mediates vessel stability and vascular response to tissue injury. Antagonists of this pathway could be therapeutically exploited to improve the delivery of therapeutics or molecular contrast agents into tissues where chronic damage or neoplastic disease limits their efficient delivery. PMID:20223936

Bioaccumulation and tissue distribution of antibiotics in wild marine fish from Laizhou Bay, North China.

PubMed

Liu, Sisi; Bekele, Tadiyose-Girma; Zhao, Hongxia; Cai, Xiyun; Chen, Jingwen

2018-08-01

Information about bioaccumulation and tissue distribution of antibiotics in wild marine fish is still limited. In the present study, tissue levels, bioaccumulation and distribution patterns of 9 sulfonamide (SA), trimethoprim (TMP), 5 fluoroquinolone (FQ), and 4 macrolide (ML) antibiotics were investigated in gill, muscle, kidney, and liver tissues of seven wild fish species collected from Laizhou Bay, North China in 2016. All the 19 antibiotics were detected in these fish tissues with the total concentrations ranging from 22ng/g dry weight (dw) to 500ng/g dw. The mean values of logarithm bioaccumulation factors (BAFs) in the gills, muscles, kidneys, and livers ranged from 2.2 to 4.8, 1.9 to 4.0, 2.5 to 4.9, and 2.5 to 5.4, respectively. Log BAFs of antibiotics in these tissues significantly increased (r=0.61-0.77, p<0.001) with their logarithm values of liposome-water distribution coefficient (D lipw ) except in the muscles, suggesting that D lipw can well assess the bioaccumulation potentials of antibiotics in phospholipid-rich tissues. In general, the SAs, TMP, and FQs were primarily accumulated in the muscles and the MLs were primarily in the livers, which may be related to their toxicokinetic processes of these marine fish. The present study for the first time reported the tissue distribution patterns of antibiotics in wild marine fish. Copyright © 2018 Elsevier B.V. All rights reserved.

Comparison of the effects of letrozole and cabergoline on vascular permeability, ovarian diameter, ovarian tissue VEGF levels, and blood PEDF levels, in a rat model of ovarian hyperstimulation syndrome.

PubMed

Şahin, Nur; Apaydın, Nesin; Töz, Emrah; Sivrikoz, Oya Nermin; Genç, Mine; Turan, Gülüzar Arzu; Cengiz, Hakan; Eskicioğlu, Fatma

2016-05-01

To evaluate the effects of letrozole and cabergoline in a rat model of ovarian hyperstimulation syndrome (OHSS). In this prospective, controlled experimental study, the 28 female Wistar rats were divided into four subgroups (one non-stimulated control and three OHSS-positive groups: placebo, letrozole, and cabergoline). To induce OHSS, rats were injected with 10 IU of pregnant mare serum gonadotropin from day 29 to day 32 of life, followed by subcutaneous injection of 30 IU hCG on day 33. Letrozole rats received with a single dose of 0.1 mg/kg letrozole via oral gavage, on the hCG day. Cabergoline rats received with a single dose of 100 µg/kg cabergoline via oral gavage, on the hCG day. All animals were compared in terms of body weight, vascular permeability (VP), ovarian diameter, ovarian tissue VEGF expression (assessed via immunohistochemical staining), and blood pigment epithelium-derived growth factor (PEDF) levels. The OHSS-positive placebo group (group 2) exhibited the highest VP, ovarian diameter, extent of VEGF staining, and lowest PEDF level, as expected. No significant difference was evident between the letrozole and cabergoline groups in terms of any of body weight; VP; PEDF level; ovarian diameter; or the staining intensity of, or percentage staining for, VEGF in ovarian tissues. Letrozole and cabergoline were equally effective to prevent OHSS, reducing the ovarian diameter, VP, and PEDF and VEGF levels to similar extents.

Ferulic acid in the treatment of post-diabetes testicular damage: relevance to the down regulation of apoptosis correlates with antioxidant status via modulation of TGF-β1, IL-1β and Akt signalling.

PubMed

Roy, Souvik; Metya, Satyajit Kumar; Rahaman, Noorjaman; Sannigrahi, Santanu; Ahmed, Faiqa

2014-01-01

The aim of this study was to investigate the protective effect of ferulic acid at different doses (50 mg kg(-1) alternative day and 50 mg kg(-1) daily) on the streptozotocin (STZ)-induced post-diabetes rat testicular damage. Diabetes was induced by a single intraperitoneal injection of STZ (50 mg/kg). Rats treated with ferulic acid were given once a day orally for 10 weeks, starting 3 days after STZ injection. Testis tissue and blood samples were collected for investigating biochemical analysis, antioxidant status, sperm parameters, and histopathological, immunohistochemical and apoptotic studies. Treatment with ferulic acid to diabetic rats significantly improved the body weight, testis weight, serum insulin level, serum testosterone level and sperm parameters (viability, motility and count). Histopathological study also revealed that ferulic acid-treated diabetic rats showed an improved histological appearance. Our data indicated that significant reduction in the activity of apoptosis by using terminal deoxyuridine triphosphate nick end-labelling and reduced expression of transforming growth factor-β1 and interleukin-1β in the testis tissue of ferulic acid-treated diabetic rats. Conversely, it was also revealed that ferulic acid-treated diabetic rats markedly enhanced the serine/threonine protein kinase protein expression in the testis tissue. Our result suggests that ferulic acid inhibits testicular damage in diabetic rats by declining oxidative stress. Copyright © 2013 John Wiley & Sons, Ltd.

The effect of dentin on the pulp tissue dissolution capacity of sodium hypochlorite and calcium hydroxide.

PubMed

Slutzky-Goldberg, Iris; Hanut, Aiham; Matalon, Shlomo; Baev, Valery; Slutzky, Hagay

2013-08-01

Sodium hypochlorite (NaOCl) and calcium hydroxide (Ca[OH]2) have tissue dissolution capacity. The aim of this study was to evaluate the potential effect of dentin on their tissue dissolution capacity in a novel dentin model. Dentin models were prepared from 25 freshly extracted human molar teeth; the crowns were separated from the roots, and a rectangular inner shape was prepared. Pulp tissue samples adjusted to similar weights of 6.5 ± 0.2 mg were randomly divided into 6 groups: NaOCl groups in test tubes or dentin models for 1 hour, Ca(OH)2 groups in test tubes or dentin models for 1 week, and control groups saline in test tubes or dentin models for 1 week. The final weights after the experimental period were checked and compared with the initial weights. The differences were statistically analyzed. The tissue dissolution capacity of Ca(OH)2 was affected by the presence of dentin. Similarly, NaOCl lost its effect on the pulp tissue after incubation in dentin. Comparison between all test groups showed highly significant differences (P < .001). Dentin has a detrimental effect on the ability of NaOCl and Ca(OH)2 to dissolve pulp tissue. The dentin model appears to be an efficient tool for the study of interactions between local endodontic medicaments, dentin, and pulp tissue. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Dietary intake and adipose tissue content of long-chain n-3 PUFAs and subsequent 5-y change in body weight and waist circumference.

PubMed

Jakobsen, Marianne U; Madsen, Lise; Skjøth, Flemming; Berentzen, Tina L; Halkjær, Jytte; Tjønneland, Anne; Schmidt, Erik B; Sørensen, Thorkild Ia; Kristiansen, Karsten; Overvad, Kim

2017-05-01

Background: Adding long-chain n-3 (ω-3) polyunsaturated fatty acids (PUFAs) to a rodent diet reduces fat mass and prevents the development of obesity, but evidence of a similar effect in humans is rather limited. Objectives: We investigated the associations between dietary intake and adipose tissue content of long-chain n-3 PUFAs and subsequent 5-y change in body weight and waist circumference in humans. Effect modification by the carbohydrate:protein ratio and glycemic index was also investigated. Design: A total of 29,152 participants included in the Diet, Cancer, and Health cohort were followed. Dietary intake was assessed with the use of a validated 192-item semiquantitative food-frequency questionnaire. Adipose tissue content of fatty acids was determined by gas chromatography in a random sample of the cohort ( n = 1660). Anthropometric measurements were taken at baseline and 5 y later. Associations were investigated with the use of a linear regression model. Results: For high (1.22 g/d) compared with low (0.28 g/d) total n-3 PUFA intake, the difference in 5-y weight change was 147.6 g (95% CI: -42.3, 337.5 g); P -trend = 0.088. No associations between the individual n-3 PUFAs eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid were observed. Intake of n-3 PUFAs was not associated with a 5-y change in waist circumference. For high (0.16%) compared with low (0.06%) adipose tissue content of EPA, the difference in 5-y weight change was -649.6 g (95% CI: -1254.2, -44.9 g); P -trend = 0.027. No associations between total n-3 PUFA, docosapentaenoic acid, and docosahexaenoic acid and 5-y weight change were observed. Adipose tissue content of n-3 PUFAs was not associated with 5-y change in waist circumference. No effect modification by carbohydrate:protein ratio or glycemic index was found. Conclusion: Dietary intake and adipose tissue content of long-chain n-3 PUFAs were neither consistently nor appreciably associated with change in body weight or waist circumference. © 2017 American Society for Nutrition.

New Internet search volume-based weighting method for integrating various environmental impacts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ji, Changyoon, E-mail: changyoon@yonsei.ac.kr; Hong, Taehoon, E-mail: hong7@yonsei.ac.kr

Weighting is one of the steps in life cycle impact assessment that integrates various characterized environmental impacts as a single index. Weighting factors should be based on the society's preferences. However, most previous studies consider only the opinion of some people. Thus, this research proposes a new weighting method that determines the weighting factors of environmental impact categories by considering public opinion on environmental impacts using the Internet search volumes for relevant terms. To validate the new weighting method, the weighting factors for six environmental impacts calculated by the new weighting method were compared with the existing weighting factors. Themore » resulting Pearson's correlation coefficient between the new and existing weighting factors was from 0.8743 to 0.9889. It turned out that the new weighting method presents reasonable weighting factors. It also requires less time and lower cost compared to existing methods and likewise meets the main requirements of weighting methods such as simplicity, transparency, and reproducibility. The new weighting method is expected to be a good alternative for determining the weighting factor. - Highlight: • A new weighting method using Internet search volume is proposed in this research. • The new weighting method reflects the public opinion using Internet search volume. • The correlation coefficient between new and existing weighting factors is over 0.87. • The new weighting method can present the reasonable weighting factors. • The proposed method can be a good alternative for determining the weighting factors.« less

Adiponectin, C-reactive protein, fibrinogen and tissue plasminogen activator antigen levels among glucose-intolerant women with and without histories of gestational diabetes.

PubMed

Kim, C; Christophi, C A; Goldberg, R B; Perreault, L; Dabelea, D; Marcovina, S M; Pi-Sunyer, X; Barrett-Connor, E

2016-01-01

To examine concentrations of biomarkers (adiponectin, C-reactive protein, fibrinogen and tissue plasminogen-activator antigen) associated with glucose homeostasis and diabetes risk by history of gestational diabetes (GDM). We conducted a secondary analysis of the Diabetes Prevention Program, a randomized trial of lifestyle intervention or metformin for diabetes prevention. At baseline, participants were overweight and had impaired glucose tolerance. Biomarkers at baseline and 1 year after enrolment were compared between parous women with (n = 350) and without histories of GDM (n = 1466). Cox proportional hazard models evaluated whether history of GDM was associated with diabetes risk, after adjustment for baseline biomarker levels as well as for change in biomarker levels, demographic factors and anthropometrics. At baseline, women with histories of GDM had lower adiponectin (7.5 μg/ml vs. 8.7 μg/ml; p < 0.0001) and greater log C-reactive protein (-0.90 mg/l vs. -0.78 mg/l, p = 0.04) levels than women without histories of GDM, but these associations did not persist after adjustment for demographic factors. Fibrinogen and tissue plasminogen-activator antigen were similar between women with and without histories of GDM. Women with and without histories of GDM had a similar pattern of changes in biomarkers within randomization arm. Adjustment for age, race/ethnicity, baseline weight, change in weight, baseline biomarker level and change in biomarker level did not significantly alter the association between history of GDM, and diabetes risk. Among women with impaired glucose tolerance, biomarkers in women with and without histories of GDM are similar and respond similarly to lifestyle changes and metformin. Adjustment for biomarker levels did not explain the higher risk of diabetes observed in women with histories of GDM. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

Rebamipide attenuates 5-Fluorouracil-induced small intestinal mucositis in a mouse model.

PubMed

Kim, Hyun Jin; Kim, Jin Hyun; Moon, Won; Park, Jongha; Park, Seun Ja; Song, Geun Am; Han, Seung Hee; Lee, Jong Hun

2015-01-01

5-Fluorouracil (5-FU)-induced intestinal mucositis is one of the most common morbidities in chemotherapy and involves the reactive oxygen species (ROS) system, apoptosis, and inflammatory cytokines. Rebamipide exerts a mucosal-protective effect, mediated through several mechanisms. The aim of this study was to evaluate the effects of rebamipide in 5-FU-induced mouse small-intestinal mucositis. BALB/c mice were assigned randomly to four groups; (1) control group (n=10; receiving saline orally for 6 d), (2) rebamipide group (n=10; 150 mg/kg rebamipide for 6 d orally), (3) 5-FU group (n=10; 30 mg/kg 5-FU for 5 d, intraperitoneally (i.p.)), and (4) rebamipide +5-FU group (n=10; 150 mg/kg rebamipide for 6 d orally and 30 mg/kg 5-FU for 5 d, i.p.). Body weights and diarrhea scales were assessed. At day 5, the mice were sacrificed. Small intestinal tissue was used for: (1) hematoxylin and eosin (HE) staining for determination of small intestinal villi height, (2) terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay, (3) immunohistochemistry for inducible nitric oxide synthase (iNOS), F4/80, and transforming growth factor (TGF)-β1, (4) measurement of serum and tissue GSH levels, and (5) measurement of serum tumor necrosis factor (TNF)-α levels. Rebamipide attenuated the severity of mucosal injury reflected by body weight changes, degrees of diarrhea, and heights of villi. Rebamipide reduced the expression of iNOS and TGF-β1, apoptosis, macrophage accumulation, serum TNF-α levels, and prevented reductions in serum and tissue glutathione (GSH) levels by 5-FU administration. These results suggest that rebamipide promotes several mechanisms of mucosal protection and attenuated the 5-FU-induced mucosal injury. In conclusion, administration of rebamipide may have significant protective effects against 5-FU-induced intestinal mucositis.

A feasibility study of perennial/annual plant species to restore soils contaminated with heavy metals

NASA Astrophysics Data System (ADS)

Zacarías, Montserrat; Beltrán, Margarita; Gilberto Torres, Luis; González, Abelardo

A feasibility study was carried out to evaluate the application of perennial/annual plant species in a phytoextraction process of a previously washed industrial urban soil contaminated by nickel, arsenic and cupper. The plant species selected for this study were Ipomea (Ipomea variada); grass (Poa pratensis); grass mixture (Festuca rubra, Cynodon dactylon, Lolium multiforum, Pennisetum sp.); Monks Cress (Tropaeolum majus); ficus (Ficus benajamina) and fern (Pteris cretica). Soil was characterized and it presented the following heavy metals concentrations (dry weight): 80 mg of Ni/kg, 456-656 mg of As/kg and 1684-3166 mg of Cu/kg. Germination and survival in contaminated soil tests were conducted, from these, P. pratensis was discarded and the rest of plant species tested were used for the phytoextraction selection test. After 4 months of growth, biomass production was determined, and content of Ni, As and Cu was analyzed in plant’s tissue. Metal biological absorption coefficient (BAC), bio-concentration factor (BCF) and translocation factor (TF), were calculated. Regarding to biomass generation it was observed, in every case, an inhibition of the plant growth compared with blanks sown in a non contaminated soil; inhibition ranged from 22.5% for the Monk cress to 98% for Ipomea. Even though the later presented high BAC, BCF and TF, its growth was severely inhibited, and therefore, due its low biomass generation, it is not recommended for phytoextraction under conditions for this study. Heavy metals concentrations in plant’s tissue (dry weight) were as high as 866 mg Cu/kg and 602 mg As/kg for grass mixture; and 825 mg As/kg was observed for Monks cress. Grass mixture and monks cress had high BAC, BCF and TF, also they had high metal concentrations in its plants tissues and the lowest growth inhibition rates; hence the application in phytoextraction processes of these plants is advisable.

Optimization of nanoparticles for cardiovascular tissue engineering.

PubMed

Izadifar, Mohammad; Kelly, Michael E; Haddadi, Azita; Chen, Xiongbiao

2015-06-12

Nano-particulate delivery systems have increasingly been playing important roles in cardiovascular tissue engineering. Properties of nanoparticles (e.g. size, polydispersity, loading capacity, zeta potential, morphology) are essential to system functions. Notably, these characteristics are regulated by fabrication variables, but in a complicated manner. This raises a great need to optimize fabrication process variables to ensure the desired nanoparticle characteristics. This paper presents a comprehensive experimental study on this matter, along with a novel method, the so-called Geno-Neural approach, to analyze, predict and optimize fabrication variables for desired nanoparticle characteristics. Specifically, ovalbumin was used as a protein model of growth factors used in cardiovascular tissue regeneration, and six fabrication variables were examined with regard to their influence on the characteristics of nanoparticles made from high molecular weight poly(lactide-co-glycolide). The six-factor five-level central composite rotatable design was applied to the conduction of experiments, and based on the experimental results, a geno-neural model was developed to determine the optimum fabrication conditions. For desired particle sizes of 150, 200, 250 and 300 nm, respectively, the optimum conditions to achieve the low polydispersity index, higher negative zeta potential and higher loading capacity were identified based on the developed geno-neural model and then evaluated experimentally. The experimental results revealed that the polymer and the external aqueous phase concentrations and their interactions with other fabrication variables were the most significant variables to affect the size, polydispersity index, zeta potential, loading capacity and initial burst release of the nanoparticles, while the electron microscopy images of the nanoparticles showed their spherical geometries with no sign of large pores or cracks on their surfaces. The release study revealed that the onset of the third phase of release can be affected by the polymer concentration. Circular dichroism spectroscopy indicated that ovalbumin structural integrity is preserved during the encapsulation process. Findings from this study would greatly contribute to the design of high molecular weight poly(lactide-co-glycolide) nanoparticles for prolonged release patterns in cardiovascular engineering.

Quantitative phosphoproteomics using acetone-based peptide labeling: Method evaluation and application to a cardiac ischemia/reperfusion model

PubMed Central

Wijeratne, Aruna B.; Manning, Janet R.; Schultz, Jo El J.; Greis, Kenneth D.

2013-01-01

Mass spectrometry (MS) techniques to globally profile protein phosphorylation in cellular systems that are relevant to physiological or pathological changes have been of significant interest in biological research. In this report, an MS-based strategy utilizing an inexpensive acetone-based peptide labeling technique known as reductive alkylation by acetone (RABA) for quantitative phosphoproteomics was explored to evaluate its capacity. Since the chemistry for RABA-labeling for phosphorylation profiling had not been previously reported, it was first validated using a standard phosphoprotein and identical phosphoproteomes from cardiac tissue extracts. A workflow was then utilized to compare cardiac tissue phosphoproteomes from mouse hearts not expressing FGF2 vs. hearts expressing low molecular weight fibroblast growth factor-2 (LMW FGF2) to relate low molecular weight fibroblast growth factor-2 (LMW FGF2) mediated cardioprotective phenomena induced by ischemia/reperfusion (I/R) injury of hearts, with downstream phosphorylation changes in LMW FGF2 signaling cascades. Statistically significant phosphorylation changes were identified at 14 different sites on 10 distinct proteins including some with mechanisms already established for LMW FGF2-mediated cardioprotective signaling (e.g. connexin-43), some with new details linking LMW FGF2 to the cardioprotective mechanisms (e.g. cardiac myosin binding protein C or cMyBPC), and also several new downstream effectors not previously recognized for cardio-protective signaling by LMW FGF2. Additionally, one of the phosphopeptides, cMyBPC/pSer-282, identified was further verified with site-specific quantification using an SRM (selected reaction monitoring)-based approach that also relies on isotope labeling of a synthetic phosphopeptide with deuterated acetone as an internal standard. Overall, this study confirms that the inexpensive acetone-based peptide labeling can be used in both exploratory and targeted quantification phosphoproteomic studies to identify and verify biologically-relevant phosphorylation changes in whole tissues. PMID:24016359

Belowground plant development measured with magnetic resonance imaging (MRI): exploiting the potential for non-invasive trait quantification using sugar beet as a proxy

PubMed Central

Metzner, Ralf; van Dusschoten, Dagmar; Bühler, Jonas; Schurr, Ulrich; Jahnke, Siegfried

2014-01-01

Both structural and functional properties of belowground plant organs are critical for the development and yield of plants but, compared to the shoot, much more difficult to observe due to soil opacity. Many processes concerning the belowground plant performance are not fully understood, in particular spatial and temporal dynamics and their interrelation with environmental factors. We used Magnetic Resonance Imaging (MRI) as a noninvasive method to evaluate which traits can be measured when a complex plant organ is monitored in-vivo while growing in the soil. We chose sugar beet (Beta vulgaris ssp. vulgaris) as a model system. The beet consists mainly of root tissues, is rather complex regarding tissue structure and responses to environmental factors, and thereby a good object to test the applicability of MRI for 3D phenotyping approaches. Over a time period of up to 3 months, traits such as beet morphology or anatomy were followed in the soil and the effect of differently sized pots on beet fresh weight calculated from MRI data was studied. There was a clear positive correlation between the pot size and the increase in fresh weight of a sugar beet over time. Since knowledge of the development of internal beet structures with several concentric cambia, vascular and parenchyma rings is still limited, we consecutively acquired 3D volumetric images on individual plants using the MRI contrast parameter T2 to map the development of rings at the tissue level. This demonstrates that MRI provides versatile protocols to non-invasively measure plant traits in the soil. It opens new avenues to investigate belowground plant performance under adverse environmental conditions such as drought, nutrient shortage, or soil compaction to seek for traits of belowground organs making plants more resilient to stress. PMID:25278947

Technical Note: Relation between dual-energy subtraction of CT images for electron density calibration and virtual monochromatic imaging.

PubMed

Saito, Masatoshi

2015-07-01

For accurate tissue inhomogeneity correction in radiotherapy treatment planning, the author previously proposed a simple conversion of the energy-subtracted computed tomography (CT) number to an electron density (ΔHU-ρe conversion), which provides a single linear relationship between ΔHU and ρe over a wide ρe range. The purpose of the present study was to reveal the relation between the ΔHU image for ρe calibration and a virtually monochromatic CT image by performing numerical analyses based on the basis material decomposition in dual-energy CT. The author determined the weighting factor, α0, of the ΔHU-ρe conversion through numerical analyses of the International Commission on Radiation Units and Measurements Report-46 human body tissues using their attenuation coefficients and given ρe values. Another weighting factor, α(E), for synthesizing a virtual monochromatic CT image from high- and low-kV CT images, was also calculated in the energy range of 0.03 < E < 5 MeV, assuming that cortical bone and water were the basis materials. The mass attenuation coefficients for these materials were obtained using the xcom photon cross sections database. The effective x-ray energies used to calculate the attenuation were chosen to imitate a dual-source CT scanner operated at 80-140 and 100-140 kV/Sn. The determined α0 values were 0.455 for 80-140 kV/Sn and 0.743 for 100-140 kV/Sn. These values coincided almost perfectly with the respective maximal points of the calculated α(E) curves located at approximately 1 MeV, in which the photon-matter interaction in human body tissues is exclusively the incoherent (Compton) scattering. The ΔHU image could be regarded substantially as a CT image acquired with monoenergetic 1-MeV photons, which provides a linear relationship between CT numbers and electron densities.

[THE FACTORS OF THE PROGRESSION OF METABOLIC DISORDERS IN THE PANCREAS IN PATIENTS WITH ASSOCIATED CLINICAL VARIANTS OF THE CHRONIC PANCREATITIS AND TYPE 2 DIABETES MELLITUS].

PubMed

Zhuravlyova, L V; Shekhovtsova, Y O

2015-01-01

The purpose of the present study was to determine the causal factors of the progression of metabolic disorders in pancreatic tissue and their relationships in patients with assotiated clinical variants of chronic pancreatitis (CP) and type 2 diabetes mellitus (T2DM). The study involved of 76 patients with CP and T2DM. The causes of progression of metabolic disorders in the pancreas in patients with associated clinical variants of CP and T2DM has been analyzed. The most significant of them were insulin resistance and abdominal obesity, which promotes early formation of the metabolic syndrome and the activation of fibrogenesis and steatosis in the pancreas and is caused by dyslipidemia, impaired glucose metabolism and the development of systemic inflammation and imbalance of adipocytokines. The relationships between adipocytokines, body weight and individual components of the metabolic syndrome in patients with CP and T2DM suggests the involvement of these hormones of adipose tissue in the formation of the metabolic syndrome and its components.

[Issues of osteoporosis in present-day medicine].

PubMed

Benevolenskaia, L I

2003-01-01

Osteoporosis (OP) is a systemic metabolic lesion of the skeleton involving a reduced osseous tissue weight and an impaired microarchitectonics, which worsens the bone strength and contributes to a higher risk of bone fractures. An essential spread of OP and of osteoporotic fractures among populations in various countries, including Russia, a high-severity outcome, and big economic expenses related with treatment and rehabilitation are indicative of a high social OP significance. OP is a multi-factor pathology provoked by impaired processes in osseous remodeling with a higher resorption of osseous tissue and a reduced osteogenesis. A study of molecular mechanisms of intercellular interaction in OP resulted in discovering new elements in the family of tumor necrosis factor (TNF) and their ligands and receptors (RANKL-RANK-OPG), which are of primary importance in osteoclastogenesis and which are molecular mediators in many regulatory effects. The key drugs applicable to prevention and treatment of OP are also described in the article. The current methods of OP prevention and treatment improve the bone quality and reduce the incidence rate of fracture in an essential share of patients.

The influence of gravity and wind on land plant evolution.

PubMed

Niklas, K J

1998-07-01

Aspects of the engineering theory treating the elastic stability of vertical stems and cantilevered leaves supporting their own weight and additional wind-induced forces (drag) are reviewed in light of biomechanical studies of living and fossil terrestrial plant species. The maximum height to which arborescent species can grow before their stems elastically buckle under their own weight is estimated by means of the Euler-Greenhill formula which states that the critical buckling height scales as the 1/3 power of plant tissue-stiffness normalized with respect to tissue bulk density and as the 2/3 power of stem diameter. Data drawn from living plants indicate that progressively taller plant species employ stiffer and lighter-weight plant tissues as the principal stiffening agent in their vertical stems. The elastic stability of plants subjected to high lateral wind-loadings is governed by the drag torque (the product of the drag force and the height above ground at which this force is applied), which cannot exceed the gravitational bending moment (the product of the weight of aerial organs and the lever arm measured at the base of the plant). Data from living plants indicate that the largest arborescent plant species rely on massive trunks and broad, horizontally expansive root crowns to resist drag torques. The drag on the canopies of these plants is also reduced by highly flexible stems and leaves composed of tissues that twist and bend more easily than tissues used to stiffen older, more proximal stems. A brief review of the fossil record suggests that modifications in stem, leaf, and root morphology and anatomy capable of simultaneously coping with self-weight and wind-induced drag forces evolved by Devonian times, suggesting that natural selection acting on the elastic stability of sporophytes occurred early in the history of terrestrial plants.

Growth and regeneration in cultivated fragments of the boreal deep water sponge Geodia barretti Bowerbank, 1858 (Geodiidae, Tetractinellida, Demospongiae).

PubMed

Hoffmann, Friederike; Rapp, Hans Tore; Zöller, Tobias; Reitner, Joachim

2003-01-23

A cultivation method has been developed for the boreal deep-water sponge Geodia barretti (Demospongiae, Geodiidae), a species which is common in the deep Norwegian fjords. The species is known to contain secondary metabolites which are biologically active. Choanosomal fragments of 2-4 cm(3) (approximately 3-7 g) were kept in half-open systems. Cicatrisation and regeneration processes were surveyed by histological examination during 8 months of cultivation. During the first weeks, the weight of the fragments decreased. However, after about 6 weeks the weight equalled the original weight, and after 1 year the weight had increased by about 40% compared to the original weight. The initial decrease was due to complex healing processes and the regeneration of the cortex, a sterrastral layer typical for the family of the Geodiidae. We document, for the first time, the complete cortex reconstruction in an adult G. barretti, as well as the development of egg cells during cultivation. Our study represents the first attempt at biotechnological production of boreal sponge tissue. For successful farming of G. barretti and other boreal and arctic sponges, however, further investigation is needed on factors stimulating growth and secondary metabolite production in the target species.

Lipid mobilising factors specifically associated with cancer cachexia.

PubMed Central

Beck, S. A.; Tisdale, M. J.

1991-01-01

Both urine and plasma from mice and humans with cancer cachexia have been shown to contain higher levels of lipid mobilising activity than normal controls, even after acute starvation. There was no significant increase in the urinary lipid mobilising activity of either mice or humans after acute starvation, suggesting that the material in the cachectic situation was probably not due to an elevation of hormones normally associated with the catabolic state in starvation. Further characterisation of the lipid mobilising activity in the urine of cachectic mice using Sephadex G50 exclusion chromatography showed four distinct peaks of activity of apparent molecular weights of greater than 20, 3, 1.5 and less than 0.7 kDa. No comparable peaks of activity were found in the urine of a non tumour-bearing mouse. The high molecular weight activity was probably formed by aggregation of low molecular weight material, since treatment with 0.5 M NaCl caused dissociation to material with a broad spectrum of molecular weights between 3 and 0.7 kDa. Lipolytic species of similar molecular weights were also found in the urine of cachectic cancer patients, but not in normal urine even after 24 h starvation. The lipid mobilising species may be responsible for catabolism of host adipose tissue in the cachectic state. PMID:2069843

Characteristics of lambs fed concentrates or grazed on ryegrass to traditional or heavy slaughter weights. II. Wholesale cuts and tissue accretion.

PubMed

Borton, R J; Loerch, S C; McClure, K E; Wulf, D M

2005-06-01

Targhee x Hampshire lambs (average BW 24 +/- 1 kg) were used to determine the effect of finishing on concentrate or by grazing ryegrass forage on slaughter weights of 52 kg (N) or 77 kg (H) on tissue accretion and lamb wholesale cutout. When fed to similar slaughter weights, the wholesale cuts of concentrate-fed lambs were heavier (P < 0.05) than the same cuts from forage-fed lambs; however, when expressed as a percentage of side weight, carcasses of forage-fed lambs had a higher (P < 0.001) percentage of leg than concentrate-fed lambs. Increasing slaughter weight from 52 to 77 kg resulted in a 1-kg increase in loin weight for lambs finished on concentrate and a 0.60-kg increase for lambs finished on forage (diet x slaughter weight, P < 0.03); however, the increased loin weight for lambs finished on concentrate was due largely to increased fat deposition. For lambs slaughtered at 77 kg, those finished on forage had more lean mass in the leg, loin, rack, and shoulder than those finished on concentrate, but lean mass in these cuts did not differ between diets for lambs slaughtered at 52 kg (diet x slaughter weight, P < 0.01). At the normal slaughter weight (52 kg), concentrate-fed lambs had 50% more dissectible fat than forage-fed lambs, whereas at the heavy slaughter weight, a 79% greater amount of dissectible fat was observed for concentrate- vs. forage-fed lambs (diet x slaughter weight, P < 0.001). Lean and fat accretion rates were higher (P < 0.001) for concentrate-fed lambs than for forage-fed lambs. The lean-to-fat ratio of forage-fed lambs was higher (P < 0.001) than that of concentrate-fed lambs; however, forage finishing decreased accretion rates of all tissues compared with concentrate feeding, and these differences between forage and concentrate feeding were magnified at heavier slaughter weights.

The effects of chronic testosterone administration on body weight, food intake, and adipose tissue are changed by estrogen treatment in female rats.

PubMed

Iwasa, Takeshi; Matsuzaki, Toshiya; Yano, Kiyohito; Yanagihara, Rie; Tungalagsuvd, Altankhuu; Munkhzaya, Munkhsaikhan; Mayila, Yiliyasi; Kuwahara, Akira; Irahara, Minoru

2017-07-01

In females, estrogens play pivotal roles in preventing excess body weight (BW) gain. On the other hand, the roles of androgens in female BW, appetite, and energy metabolism have not been fully examined. We hypothesized that androgens' effects on food intake (FI) and BW regulation change according to the estrogens' levels. To evaluate this hypothesis, the effects of chronic testosterone administration in ovariectomized (OVX) female rats with or without estradiol supplementation were examined in this study. Chronic testosterone administration decreased BW, FI, white adipose tissue (WAT) weight, and adipocyte size in OVX rats, whereas it increased BW, WAT weight, and adipocyte size in OVX with estradiol-administered rats. In addition, chronic testosterone administration increased hypothalamic CYP19a1 mRNA levels in OVX rats, whereas it did not alter CYP19a1 mRNA levels in OVX with estradiol-administered rats, indicating that conversion of testosterone to estrogens in the hypothalamus may be activated in testosterone-administered OVX rats. Furthermore, chronic testosterone administration decreased hypothalamic TNF-α mRNA levels in OVX rats, whereas it increased hypothalamic IL-1β mRNA levels in OVX with estradiol-administered rats. On the other hand, IL-1β and TNF-α mRNA levels in visceral and subcutaneous WAT and liver were not changed by chronic testosterone administration in both groups. These data indicate that the effects of chronic testosterone administration on BW, FI, WAT weight, and adipocyte size were changed by estradiol treatment in female rats. Testosterone has facilitative effects on BW gain, FI, and adiposity under the estradiol-supplemented condition, whereas it has inhibitory effects in the non-supplemented condition. Differences in the responses of hypothalamic factors, such as aromatase and inflammatory cytokines, to testosterone might underlie these opposite effects. Copyright © 2017 Elsevier Inc. All rights reserved.

[Study on effect of cordyceps sinensis on early-stage silicotic pulmonary fibrosis in rabbits].

PubMed

Liu, Qianzhong; Zhang, Wei; Cui, Hongfu; Ying, Yanhong

2014-07-01

To establish a rabbit model of silicotic pulmonary fibrosis and to investigate the effect of cordyceps sinensis in this model. Thirty healthy male white rabbits were randomly divided into control group, silicosis model group, and intervention group. The rabbits in silicosis model group and intervention group received endotracheal perfusion of silicon dioxide suspension (120 mg/kg), and the control group was treated with the same volume of saline. All the rabbits were sacrificed 30 days later. The lung coefficient was calculated by comparing the lung weight and body weight; the right lung tissue was stained with hematoxylin-eosin (HE). The content of hydroxyproline in lung tissue was measured by alkaline hydrolysis. The mRNA levels of transforming growth factor beta 1 (TGF-β₁) and mothers against decapentaplegic homolog 7 (Smad7) in rabbit lung sections were determined by real-time PCR. No abnormalities were observed by HE staining in the lung tissues of control group, while fibrosis and silicotic nodules were discovered in the silicosis model group and intervention group. The lung coefficient and the content of hydroxyproline in lung tissue were significantly higher in the silicosis model group than in the control group and intervention group (P < 0.05 or P < 0.01). Compared with the control group, the silicosis model group and intervention group had significantly increased TGF-β₁ mRNA levels but significantly reduced Smad7 mRNA levels (P < 0.02). Compared with the silicosis model group, the intervention group had a significantly reduced TGF-β₁ mRNA level but a significantly increased Smad7 mRNA level (P < 0.05). Cordyceps sinensis is able to reduce the expression of TGF-β₁ mRNA and increase the expression of Smad7 mRNA in lung tissues of rabbits with silicotic pulmonary fibrosis, and thus postpone the progression of fibrosis.

Adipocytokines, neuropeptide Y and insulin resistance in overweight women with gynoid and android type of adipose tissue distribution.

PubMed

Orbetzova, Maria M; Koleva, Daniela I; Mitkov, Mitko D; Atanassova, Iliana B; Nikolova, Julia G; Atanassova, Pepa K; Genchev, Gencho D

2012-01-01

The AIM of the study was to compare the levels of certain adipose tissue hormones in women with the two main morphological types of obesity - android and gynoid obesity. The study included 2 groups of age- and weight-matched women with android (n = 32) and gynoid (n = 27) type of obesity, and a group of age-matched healthy women (n = 24) with normal weight and body constitution. Leptin, resistin, tumour necrosis factor alpha (TNFalpha), neuropeptide Y (NPY), glucose and insulin were measured. HOMA index was calculated. Leptin levels in the women with gynoid obesity did not differ significantly from those in the controls and the women with android obesity. The controls had significantly lower leptin levels compared with the android obesity women. NPY was significantly higher in the control women compared to the women with android obesity and did not differ significantly between the two groups of obese women. TNFalpha levels in all groups were very similar. Resistin did not show significant differences between all groups but tended to have the lowest levels in the controls. In the women with android obesity, insulin was significantly higher than that in the women with gynoid obesity and the controls. Insulin resistance was found in the women with android obesity only. Basal insulin and HOMA index in the women with gynoid obesity did not differ significantly from the values in the control group. The results from this study contribute to understanding the association of adipose tissue hormones and insulin resistance in obesity. When adipose tissue is predominantly distributed in the abdominal area at similar amount and percentage of body fats, leptin production is higher and insulin resistance develops. In the gynoid type of adipose tissue predisposition, overt insulin resistance is not found, leptin levels does not differ significantly from those in the control group.

Effects of boron on structure and antioxidative activities of spleen in rats.

PubMed

Hu, Qianqian; Li, Shenghe; Qiao, Enmei; Tang, Zhongtao; Jin, Erhui; Jin, Guangming; Gu, Youfang

2014-04-01

In order to determine the relationship between boron and development of the spleen, especially in the promoting biological effects, we examined the effects of different levels of boron on weight, organ index, microstructure, and antioxidative activities of the spleen in rats. Sprague-Dawley (SD) rats were selected and treated with different concentrations of boron, and then, the organs were resected and weighed. One half of the tissue was fixed and embedded in paraffin to observe tissue structure changes. The other half of the tissue was homogenated for determining the antioxidant activities. The results showed that 40 mg/L of boron could increase weight, organ indexes, and antioxidant capacity of spleens and improve the spleen tissue structure, while the boron concentration above 80 mg/L could decrease weight, organ indexes, and antioxidant capacity of spleens and damage the spleen tissue structure. The higher the concentration, the more serious the damage was. Especially at the concentration of 640 mg/L, it could significantly inhibit the development of the spleen and even exhibit toxic effect. Hence, low boron concentration played a protective role in the development of the spleen, while high boron concentration could damage the organs and even produce toxic effect.

Vibration Training Triggers Brown Adipocyte Relative Protein Expression in Rat White Adipose Tissue

PubMed Central

Sun, Chao; Zeng, Ruixia; Cao, Ge; Song, Zhibang; Zhang, Yibo; Liu, Chang

2015-01-01

Recently, vibration training is considered as a novel strategy of weight loss; however, its mechanisms are still unclear. In this study, normal or high-fat diet-induced rats were trained by whole body vibration for 8 weeks. We observed that the body weight and fat metabolism index, blood glucose, triglyceride, cholesterol, and free fatty acid in obesity rats decreased significantly compared with nonvibration group (n = 6). Although intrascapular BAT weight did not change significantly, vibration enhanced ATP reduction and increased protein level of the key molecule of brown adipose tissue (BAT), PGC-1α, and UCP1 in BAT. Interestingly, the adipocytes in retroperitoneal white adipose tissue (WAT) became smaller due to vibration exercise and had higher protein level of the key molecule of brown adipose tissue (BAT), PGC-1α, and UCP1 and inflammatory relative proteins, IL-6 and TNFα. Simultaneously, ATP content and PPARγ protein level in WAT became less in rats compared with nonvibration group. The results indicated that vibration training changed lipid metabolism in rats and promoted brown fat-like change in white adipose tissues through triggering BAT associated gene expression, inflammatory reflect, and reducing energy reserve. PMID:26125027

Liquid chromatography tandem mass spectrometry method using solid-phase extraction and bead-beating-assisted matrix solid-phase dispersion to quantify the fungicide tebuconazole in controlled frog exposure study: analysis of water and animal tissue.

PubMed

Hansen, Martin; Poulsen, Rikke; Luong, Xuan; Sedlak, David L; Hayes, Tyrone

2014-11-01

This paper presents the development, optimization, and validation of a LC-MS/MS methodology to determine the concentration of the antifungal drug and fungicide tebuconazole in a controlled exposure study of African clawed frogs (Xenopus laevis). The method is validated on animal tank water and on tissue from exposed and non-exposed adult X. laevis. Using solid-phase extraction (SPE), the analytical method allows for quantification of tebuconazole at concentrations as low as 3.89 pg mL(-1) in 10 mL water samples. Using bead-beating-assisted matrix solid-phase dispersion (MSPD), it was possible to quantify tebuconazole down to 0.63 pg mg(-1) wet weight liver using 150 mg tissue. The deuterated analogue of tebuconazole was used as internal standard, and ensured method accuracy in the range 80.6-99.7% for water and 68.1-109% for tissue samples. The developed method was successfully applied in a 4-week X. laevis repeated-exposure study, revealing high levels of tebuconazole residues in adipose and liver tissue, and with experimental bioconcentration factors up to 18,244 L kg(-1).

Chitosan-plasmid nanoparticle formulations for IM and SC delivery of recombinant FGF-2 and PDGF-BB or generation of antibodies.

PubMed

Jean, M; Smaoui, F; Lavertu, M; Méthot, S; Bouhdoud, L; Buschmann, M D; Merzouki, A

2009-09-01

Growth factor therapy is an emerging treatment modality that enhances tissue vascularization, promotes healing and regeneration and can treat a variety of inflammatory diseases. Both recombinant human growth factor proteins and their gene therapy are in human clinical trials to heal chronic wounds. As platelet-derived growth factor-bb (PDGF-BB) and fibroblast growth factor-2 (FGF-2) are known to induce chemotaxis, proliferation, differentiation, and matrix synthesis, we investigated a non-viral means for gene delivery of these factors using the cationic polysaccharide chitosan. Chitosan is a polymer of glucosamine and N-acetyl-glucosamine, in which the percentage of the residues that are glucosamine is called the degree of deacetylation (DDA). The purpose of this study was to express PDGF-BB and FGF-2 genes in mice using chitosan-plasmid DNA nanoparticles for the controlled delivery of genetic material in a specific, efficient, and safe manner. PDGF-BB and FGF-2 genes were amplified from human tissues by RT-PCR. To increase the secretion of FGF-2, a recombinant 4sFGF-2 was constructed bearing eight amino-acid residues of the signal peptide of FGF-4. PCR products were inserted into the expression vector pVax1 to produce recombinant plasmids pVax1-4sFGF2 and pVax1-PDGF-BB, which were then injected into BALB/C mice in the format of polyelectrolyte nanocomplexes with specific chitosans of controlled DDA and molecular weight, including 92-10, 80-10, and 80-80 (DDA-number average molecular weight or M(n) in kDa). ELISA assays on mice sera showed that recombinant FGF-2 and PDGF-BB proteins were efficiently expressed and specific antibodies to these proteins could be identified in sera of injected mice, but with levels that were clearly dependent on the specific chitosan used. We found high DDA low molecular weight chitosans to be efficient protein expressors with minimal or no generation of neutralizing antibodies, while lowering DDA resulted in greater antibody levels and correspondingly lower levels of detected recombinant protein. Histological analyses corroborated these results by revealing greater inflammatory infiltrates in lower DDA chitosans, which produced higher antibody titers. We found, in general, a more efficient delivery of the plasmids by subcutaneous than by intramuscular injection. Specific chitosan carriers were identified to be either efficient non-toxic therapeutic protein delivery systems or vectors for DNA vaccines.

Ileal transposition surgery produces ileal length-dependent changes in food intake, body weight, gut hormones and glucose metabolism in rats.

PubMed

Ramzy, A R; Nausheen, S; Chelikani, P K

2014-03-01

Enhanced stimulation of the lower gut is hypothesized to play a key role in the weight loss and resolution of diabetes following bariatric surgeries. Ileal transposition (IT) permits study of the effects of direct lower gut stimulation on body weight, glucose homeostasis and other metabolic adaptations without the confounds of gastric restriction or foregut exclusion. However, the underlying mechanisms and the length of the ileum sufficient to produce metabolic benefits following IT surgery remain largely unknown. To determine the effects of transposing varying lengths of the ileum to upper jejunum on food intake, body weight, glucose tolerance and lower gut hormones, and the expression of key markers of glucose and lipid metabolism in skeletal muscle and adipose tissue in rats. Adult male Sprague-Dawley rats (n=9/group) were subjected to IT surgery with translocation of 5, 10 or 20 cm of the ileal segment to proximal jejunum or sham manipulations. Daily food intake and body weight were recorded, and an intraperitoneal glucose tolerance test was performed. Blood samples were assayed for hormones and tissue samples for mRNA (RT-qPCR) and/or protein abundance (immunoblotting) of regulatory metabolic markers. We demonstrate that IT surgery exerts ileal length-dependent effects on multiple parameters including: (1) decreased food intake and weight gain, (2) improved glucose tolerance, (3) increased tissue expression and plasma concentrations of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), and decreased leptin concentrations and (4) upregulation of key markers of glucose metabolism (glucose transporter-4 (GLUT-4), insulin receptor substrate 1 (IRS-1), adenosine monophosphate-activated protein kinase (AMPK), hexokinase (HK) and phosphofructokinase (PFK)) together with a downregulation of lipogenic markers (fatty acid synthase (FAS)) in muscle and adipose tissue. Together, our data demonstrate that the reduction in food intake and weight gain, increase in lower gut hormones, glycemic improvements and associated changes in tissue metabolic markers following IT surgery are dependent on the length of the transposed ileum.

Effect of antemortem and postmortem factors on ( sup 3 H)MK-801 binding in the human brain: Transient elevation during early childhood

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kornhuber, J.; Mack-Burkhardt, F.; Konradi, C.

1989-01-01

The effect of a number of antemortem and postmortem factors on ({sup 3}H)MK-801 binding was investigated under equilibrium conditions in the frontal cortex of human brains of 38 controls. Binding values transiently increased during the early postnatal period reaching a maximum at the age of about 2 years. After age 10 years ({sup 3}H)MK-801 binding sites disappeared at 5.7% per decade. The storage time of brain tissue had a reducing effect on these binding sites. There was no effect of gender, brain weight or postmortem time interval and the binding sites were bilaterally symmetrically distributed in the frontal cortex.

The concentration and distribution of 2,3,7,8-dibenzo-p-dioxins/-furans in chickens

NASA Technical Reports Server (NTRS)

Ferrario, J.; Byrne, C.

2000-01-01

The concentrations of the 2,3,7,8-Cl substituted dibenzo-p-dioxins/-furans (PCDDs/PCDFs) were determined in the edible tissues of whole chicken fryers and compared with the values found in their abdominal fat. The values are presented both on a whole weight basis and on a lipid adjusted basis for each tissue. While there is a marked difference in the concentration of the 2,3,7,8-dibenzo-p-dioxins in the edible tissues expressed on a whole weight basis, the lipid-adjusted concentrations of the individual dioxins were not statistically different in the various tissues. This validates the use of lipid adjusted concentrations of 2,3,7,8-PCDDs/PCDFs in abdominal fat for the determination of the presence of these compounds in different tissues.

Programming of metabolic effects in C57BL/6JxFVB mice by exposure to bisphenol A during gestation and lactation.

PubMed

van Esterik, J C J; Dollé, M E T; Lamoree, M H; van Leeuwen, S P J; Hamers, T; Legler, J; van der Ven, L T M

2014-07-03

The global rise in prevalence of obesity is not fully explained by genetics or life style factors. The developmental origins of health and disease paradigm suggests that environmental factors during early life could play a role. In this perspective, perinatal exposure to bisphenol A (BPA) has been indicated as a programming factor for obesity and related metabolic disorders later in life. Here we study early life programming by BPA using an experimental design that is relevant for human exposure. C57BL/6JxFVB hybrid mice were exposed during gestation and lactation via maternal feed to 8 non-toxic doses (0-3000 μg/kg body weight/day (μg/kg bw/d)) of BPA. After weaning, offspring were followed for 20 weeks without further exposure. Adult male offspring showed dose-dependent increases of body and liver weights, no effects on fat pad weights and a dose-dependent decrease in circulating glucagon. Female offspring showed a dose-dependent decrease in body weight, liver, muscle and fat pad weights, adipocyte size, serum lipids, serum leptin and adiponectin. Physical activity was decreased in exposed males and suggested to be increased in exposed females. Brown adipose tissue showed slightly increased lipid accumulation in males and lipid depletion in females, and ucp1 expression was dose-dependently increased in females. The effects in females were more reliable and robust than in males due to wide confidence intervals and potential confounding by litter size for male data. The lowest derived BMDL (lower bound of the (two-sided) 90%-confidence interval for the benchmark dose) of 233 μg/kg bw/d (for interscapular weight in females) was below the proposed BMDL of 3633 μg/kg bw/d as a basis for tolerable daily intake. Although these results suggest that BPA can program for an altered metabolic phenotype, the sexual dimorphism of effects and diversity of outcomes among studies similar in design as the present study do not mark BPA as a specific obesogen. The consistency within the complex of observed metabolic effects suggests that upstream key element(s) in energy homeostasis are modified. Sex-dependent factors contribute to the final phenotypic outcome. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Early potential effects of resveratrol supplementation on skeletal muscle adaptation involved in exercise-induced weight loss in obese mice.

PubMed

Sun, Jingyu; Zhang, Chen; Kim, MinJeong; Su, Yajuan; Qin, Lili; Dong, Jingmei; Zhou, Yunhe; Ding, Shuzhe

2018-04-01

Exercise and resveratrol supplementation exhibit anti-obesity functions in the long term but have not been fully investigated yet in terms of their early potential effectiveness. Mice fed with high-fat diet were categorized into control (Cont), exercise (Ex), resveratrol supplementation (Res), and exercise combined with resveratrol supplementation (Ex ＋ Res) groups. In the four-week period of weight loss, exercise combined with resveratrol supplementation exerted no additional effects on body weight loss but significantly improved whole-body glucose and lipid homeostasis. The combined treatment significantly decreased intrahepatic lipid content but did not affect intramyocellular lipid content. Moreover, the treatment significantly increased the contents of mtDNA and cytochrome c, the expression levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha and its downstream transcription factors, and the activities of ATPase and citrate synthase. However, exercise, resveratrol, and their combination did not promote myofiber specification toward slow-twitch type. The effects of exercise combined with resveratrol supplementation on weight loss could be partly due to enhanced mitochondrial biogenesis and not to fiber-type shift in skeletal muscle tissues. [BMB Reports 2018; 51(4): 200-205].

Catalpol ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by suppressing the JNK and NF-κB pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Jun, E-mail: hustzhj@hust.edu.cn; Xu, Gang; Ma, Shuai

Catalpol, a bioactive component from the root of Rehmannia glutinosa, has been shown to possess hypoglycemic effects in type 2 diabetic animal models, however, the underlying mechanisms remain poorly understood. Here we investigated the effect of catalpol on high-fat diet (HFD)-induced insulin resistance and adipose tissue inflammation in mice. Oral administration of catalpol at 100 mg/kg for 4 weeks had no effect on body weight of HFD-induced obese mice, but it significantly improved fasting glucose and insulin levels, glucose tolerance and insulin tolerance. Moreover, macrophage infiltration into adipose tissue was markedly reduced by catalpol. Intriguingly, catalpol also significantly reduced mRNA expressionsmore » of M1 pro-inflammatory cytokines, but increased M2 anti-inflammatory gene expressions in adipose tissue. Concurrently, catalpol significantly suppressed the c-Jun NH2-terminal kinase (JNK) and nuclear factor-kappa B (NF-κB) signaling pathways in adipose tissue. Collectively, these results suggest that catalpol may ameliorate HFD-induced insulin resistance in mice by attenuating adipose tissue inflammation and suppressing the JNK and NF-κB pathways, and thus provide important new insights into the underlying mechanisms of the antidiabetic effect of catalpol. - Highlights: • Catalpol ameliorates high-fat diet (HFD)-induced insulin resistance in mice. • Catalpol reduces adipose tissue macrophage infiltration in HFD-fed mice. • Catalpol regulates M1 and M2 inflammatory gene expression in obese adipose tissue. • Catalpol suppresses the JNK and NF-κB signaling pathways in obese adipose tissue.« less

Gene Variants of TCF7L2 Influence Weight Loss and Body Composition During Lifestyle Intervention in a Population at Risk for Type 2 Diabetes

PubMed Central

Haupt, Axel; Thamer, Claus; Heni, Martin; Ketterer, Caroline; Machann, Jürgen; Schick, Fritz; Machicao, Fausto; Stefan, Norbert; Claussen, Claus D.; Häring, Hans-Ulrich; Fritsche, Andreas; Staiger, Harald

2010-01-01

OBJECTIVE The impact of the diabetes risk gene transcription factor 7-like 2 (TCF7L2) on body weight is unclear. As TCF7L2 is expressed in adipose tissue and involved in Wnt-dependent regulation of adipogenesis, we studied the impact of TCF7L2 variants on body composition and weight loss during lifestyle intervention. RESEARCH DESIGN AND METHODS We genotyped 309 German subjects at increased risk for type 2 diabetes for single nucleotide polymorphisms (SNPs) rs7903146, rs12255372, rs11196205, and rs7895340 in TCF7L2 and performed oral glucose tolerance tests before and after a 9-month lifestyle intervention. Fat distribution was quantified using whole-body magnetic resonance imaging/spectroscopy in a subgroup of 210 subjects. RESULTS After adjustment for confounding variables, we observed a negative impact of the type 2 diabetes allele of SNP rs7903146 on change in BMI (P = 0.0034) and on changes in nonvisceral (P = 0.0032) and visceral fat (P = 0.0165) during lifestyle intervention. An association of rs7903146 with lifestyle intervention-induced changes in insulin secretion, glucose concentrations, liver fat, or insulin sensitivity were not detected (all P > 0.2). Essentially the same results were obtained with SNP rs1255372. In contrast, we found no effects of SNPs rs11196205 and rs7895340 on change in BMI (all P ≥ 0.5). CONCLUSIONS Our data reveal that diabetes-associated alleles of TCF7L2 are associated with less weight loss in response to lifestyle intervention. Thus, diabetes-associated TCF7L2 gene variation predicts the success of lifestyle intervention in terms of weight loss and determines individual susceptibility toward environmental factors. PMID:20028944

Physiologically Based Pharmacokinetic Model for Terbinafine in Rats and Humans

PubMed Central

Hosseini-Yeganeh, Mahboubeh; McLachlan, Andrew J.

2002-01-01

The aim of this study was to develop a physiologically based pharmacokinetic (PB-PK) model capable of describing and predicting terbinafine concentrations in plasma and tissues in rats and humans. A PB-PK model consisting of 12 tissue and 2 blood compartments was developed using concentration-time data for tissues from rats (n = 33) after intravenous bolus administration of terbinafine (6 mg/kg of body weight). It was assumed that all tissues except skin and testis tissues were well-stirred compartments with perfusion rate limitations. The uptake of terbinafine into skin and testis tissues was described by a PB-PK model which incorporates a membrane permeability rate limitation. The concentration-time data for terbinafine in human plasma and tissues were predicted by use of a scaled-up PB-PK model, which took oral absorption into consideration. The predictions obtained from the global PB-PK model for the concentration-time profile of terbinafine in human plasma and tissues were in close agreement with the observed concentration data for rats. The scaled-up PB-PK model provided an excellent prediction of published terbinafine concentration-time data obtained after the administration of single and multiple oral doses in humans. The estimated volume of distribution at steady state (Vss) obtained from the PB-PK model agreed with the reported value of 11 liters/kg. The apparent volume of distribution of terbinafine in skin and adipose tissues accounted for 41 and 52%, respectively, of the Vss for humans, indicating that uptake into and redistribution from these tissues dominate the pharmacokinetic profile of terbinafine. The PB-PK model developed in this study was capable of accurately predicting the plasma and tissue terbinafine concentrations in both rats and humans and provides insight into the physiological factors that determine terbinafine disposition. PMID:12069977

Childhood factors associated with mammographic density in adult women.

PubMed

Lope, Virginia; Pérez-Gómez, Beatriz; Moreno, María Pilar; Vidal, Carmen; Salas-Trejo, Dolores; Ascunce, Nieves; Román, Isabel González; Sánchez-Contador, Carmen; Santamariña, María Carmen; Carrete, Jose Antonio Vázquez; Collado-García, Francisca; Pedraz-Pingarrón, Carmen; Ederra, María; Ruiz-Perales, Francisco; Peris, Mercé; Abad, Soledad; Cabanes, Anna; Pollán, Marina

2011-12-01

Growth and development factors could contribute to the development of breast cancer associated with an increase in mammographic density. This study examines the influence of certain childhood-related, socio-demographic and anthropometric variables on mammographic density in adult woman. The study covered 3574 women aged 45-68 years, participating in breast cancer-screening programmes in seven Spanish cities. Based on a craniocaudal mammogram, blind, anonymous measurement of mammographic density was made by a single radiologist, using Boyd's semiquantitative scale. Data associated with the early stages of life were obtained from a direct survey. Ordinal logistic regression and generalised linear models were employed to estimate the association between mammographic density and the variables covered by the questionnaire. Screening programme was introduced as a random effects term. Age, number of children, body mass index (BMI) and other childhood-related variables were used as adjustment variables, and stratified by menopausal status. A total of 811 women (23%) presented mammographic density of over 50%, and 5% of densities exceeded 75%. Our results show a greater prevalence of high mammographic density in women with low prepubertal weight (OR: 1.18; 95% CI: 1.02-1.36); marked prepubertal height (OR: 1.25; 95% CI: 0.97-1.60) and advanced age of their mothers at their birth (>39 years: OR: 1.28; 95% CI: 1.03-1.60); and a lower prevalence of high mammographic density in women with higher prepubertal weight, low birth weight and earlier menarche. The influence of these early-life factors may be explained by greater exposure to hormones and growth factors during the development of the breast gland, when breast tissue would be particularly susceptible to proliferative and carcinogenic stimulus.

Molecular mechanisms of the antiglycative and cardioprotective activities of Psidium guajava leaves in the rat diabetic myocardium.

PubMed

Soman, Sowmya; Rajamanickam, Chellam; Rauf, Arun A; Madambath, Indira

2016-12-01

Antiglycative potential of Psidium guajava L. (Myrtaceae) leaves has been established. However, the molecular basis of its antiglycative potential remains unknown. The ethyl acetate fraction of P. guajava leaves (PGEt) was evaluated to determine the cardioprotective effect and its mechanism of action compared to quercetin. After the induction of diabetes by streptozotocin (55 mg/kg body weight), PGEt and quercetin (50 mg/kg body weight) was administered for 60 days. Rats were grouped as follows: Group C: Control, Group D: Diabetic, Group D + E: Diabetic rats treated with PGEt, Group D + Q: Diabetic rats treated with quercetin. The antiglycative potential was evaluated by assaying glycosylated haemoglobin, serum fructosamine and advanced glycation end product levels. The differential receptor for advanced glycation end products and nuclear factor kappa B (NFκB) protein levels was determined by western blot and the transcript level changes of connective tissue growth factor (CTGF), brain natriuretic peptide (BNP) and TGF-β1 in heart tissue were assessed by RT-PCR analysis. Glycated haemoglobin and serum fructosamine levels were found to be enhanced in diabetic rats when compared with control. Administration of PGEt significantly reduced the glycated haemoglobin and fructosamine levels to a larger extent than quercetin treated diabetic rats. PGEt reduced the translocation of NFκB from cytosol to nucleus when compared with diabetic rats. Expression of TGF-β1, CTGF and BNP was downregulated in PGEt treated groups compared with diabetic controls. Administration of PGEt ameliorated diabetes associated changes in the myocardium to a greater extent than quercetin.

Pharmacological interference with tissue hypercatabolism in tumour-bearing rats.

PubMed Central

Tessitore, L; Costelli, P; Baccino, F M

1994-01-01

Marked loss of body weight and profound waste of both skeletal muscle and white adipose tissue occur in rats into which the ascites hepatoma Yoshida AH-130 has been transplanted, associated with marked perturbations in the hormonal homoeostasis and the presence of circulating tumour necrosis factor and high plasma levels of prostaglandin E2 [Tessitore, Costelli and Baccino (1993) Br. J. Cancer 67, 15-23]. On the basis of previous findings, the present study examined whether the development of cachexia in this model system could be significantly affected by adrenalectomy or by pharmacological treatments that may interfere with proximal or distal mediators of tissue hypercatabolism. In no instance was tumour growth modified. Medroxyprogesterone acetate, an anabolic-hormone-like drug, was completely ineffective. In adrenalectomized animals, although changes such as the elevation of plasma triacylglycerols and corticosterone were corrected, the general course of cachexia was not modified. A partial prevention of muscle waste was observed with acetylsalicylic acid, a non-steroidal anti-inflammatory drug, or with leupeptin, a proteinase inhibitor. Insulin afforded the most significant preservation of muscle protein and adipose-tissue mass, which were maintained close to control values even 10 days after transplantation. The effects of insulin on gastrocnemius muscle and liver protein content were exerted by slowing down protein turnover, mainly enhancing synthesis. Consistently, the total free amino acid concentration in the gastrocnemius of insulin-treated rats 10 days after tumour transplantation was close to that of controls. Although treatment with insulin decreased plasma corticosterone to normal values, it did not modify the circulating level of tumour necrosis factor. On the whole these data show that it seems possible to prevent, at least in part, the tissue waste that characterizes cancer cachexia by purely pharmacological means. PMID:8166661

Dietary Leucine - An Environmental Modifier of Insulin Resistance Acting on Multiple Levels of Metabolism

PubMed Central

Macotela, Yazmin; Emanuelli, Brice; Bång, Anneli M.; Espinoza, Daniel O.; Boucher, Jeremie; Beebe, Kirk; Gall, Walter; Kahn, C. Ronald

2011-01-01

Environmental factors, such as the macronutrient composition of the diet, can have a profound impact on risk of diabetes and metabolic syndrome. In the present study we demonstrate how a single, simple dietary factor—leucine—can modify insulin resistance by acting on multiple tissues and at multiple levels of metabolism. Mice were placed on a normal or high fat diet (HFD). Dietary leucine was doubled by addition to the drinking water. mRNA, protein and complete metabolomic profiles were assessed in the major insulin sensitive tissues and serum, and correlated with changes in glucose homeostasis and insulin signaling. After 8 weeks on HFD, mice developed obesity, fatty liver, inflammatory changes in adipose tissue and insulin resistance at the level of IRS-1 phosphorylation, as well as alterations in metabolomic profile of amino acid metabolites, TCA cycle intermediates, glucose and cholesterol metabolites, and fatty acids in liver, muscle, fat and serum. Doubling dietary leucine reversed many of the metabolite abnormalities and caused a marked improvement in glucose tolerance and insulin signaling without altering food intake or weight gain. Increased dietary leucine was also associated with a decrease in hepatic steatosis and a decrease in inflammation in adipose tissue. These changes occurred despite an increase in insulin-stimulated phosphorylation of p70S6 kinase indicating enhanced activation of mTOR, a phenomenon normally associated with insulin resistance. These data indicate that modest changes in a single environmental/nutrient factor can modify multiple metabolic and signaling pathways and modify HFD induced metabolic syndrome by acting at a systemic level on multiple tissues. These data also suggest that increasing dietary leucine may provide an adjunct in the management of obesity-related insulin resistance. PMID:21731668

Inflammation, Oxidative Stress, and Obesity

PubMed Central

Fernández-Sánchez, Alba; Madrigal-Santillán, Eduardo; Bautista, Mirandeli; Esquivel-Soto, Jaime; Morales-González, Ángel; Esquivel-Chirino, Cesar; Durante-Montiel, Irene; Sánchez-Rivera, Graciela; Valadez-Vega, Carmen; Morales-González, José A.

2011-01-01

Obesity is a chronic disease of multifactorial origin and can be defined as an increase in the accumulation of body fat. Adipose tissue is not only a triglyceride storage organ, but studies have shown the role of white adipose tissue as a producer of certain bioactive substances called adipokines. Among adipokines, we find some inflammatory functions, such as Interleukin-6 (IL-6); other adipokines entail the functions of regulating food intake, therefore exerting a direct effect on weight control. This is the case of leptin, which acts on the limbic system by stimulating dopamine uptake, creating a feeling of fullness. However, these adipokines induce the production of reactive oxygen species (ROS), generating a process known as oxidative stress (OS). Because adipose tissue is the organ that secretes adipokines and these in turn generate ROS, adipose tissue is considered an independent factor for the generation of systemic OS. There are several mechanisms by which obesity produces OS. The first of these is the mitochondrial and peroxisomal oxidation of fatty acids, which can produce ROS in oxidation reactions, while another mechanism is over-consumption of oxygen, which generates free radicals in the mitochondrial respiratory chain that is found coupled with oxidative phosphorylation in mitochondria. Lipid-rich diets are also capable of generating ROS because they can alter oxygen metabolism. Upon the increase of adipose tissue, the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), was found to be significantly diminished. Finally, high ROS production and the decrease in antioxidant capacity leads to various abnormalities, among which we find endothelial dysfunction, which is characterized by a reduction in the bioavailability of vasodilators, particularly nitric oxide (NO), and an increase in endothelium-derived contractile factors, favoring atherosclerotic disease. PMID:21686173

Zinc-α2-glycoprotein, a lipid mobilizing factor, is expressed in adipocytes and is up-regulated in mice with cancer cachexia

PubMed Central

Bing, Chen; Bao, Yi; Jenkins, John; Sanders, Paul; Manieri, Monia; Cinti, Saverio; Tisdale, Michael J.; Trayhurn, Paul

2004-01-01

Zinc-α2-glycoprotein (ZAG), a 43-kDa protein, is overexpressed in certain human malignant tumors and acts as a lipid-mobilizing factor to stimulate lipolysis in adipocytes leading to cachexia in mice implanted with ZAG-producing tumors. Because white adipose tissue (WAT) is an endocrine organ secreting a wide range of protein factors, including those involved in lipid metabolism, we have investigated whether ZAG is produced locally by adipocytes. ZAG mRNA was detected by RT-PCR in the mouse WAT depots examined (epididymal, perirenal, s.c., and mammary gland) and in interscapular brown fat. In WAT, ZAG gene expression was evident in mature adipocytes and in stromal-vascular cells. Using a ZAG Ab, ZAG protein was located in WAT by Western blotting and immunohistochemistry. Mice bearing the MAC16-tumor displayed substantial losses of body weight and fat mass, which was accompanied by major increases in ZAG mRNA and protein levels in WAT and brown fat. ZAG mRNA was detected in 3T3-L1 cells, before and after the induction of differentiation, with the level increasing progressively after differentiation with a peak at days 8–10. Both dexamethasone and a β3 agonist, BRL 37344, increased ZAG mRNA levels in 3T3-L1 adipocytes. ZAG gene expression and protein were also detected in human adipose tissue (visceral and s.c.). It is suggested that ZAG is a new adipose tissue protein factor, which may be involved in the modulation of lipolysis in adipocytes. Overexpression in WAT of tumor-bearing mice suggests a local role for adipocyte-derived ZAG in the substantial reduction of adiposity of cancer cachexia. PMID:14983038

Conjugated linoleic acid reduces body weight gain in ovariectomized female C57BL/6J mice.

PubMed

Kanaya, Noriko; Chen, Shiuan

2010-10-01

Estrogen is an important protective factor against obesity in females. Therefore, postmenopausal women have a higher rate of obesity than premenopausal women, which is associated with age-related loss of ovary function. It has been reported that a diet containing conjugated linoleic acid (CLA) reduced body weight and body fat mass in the animal model as well as in human trials. We hypothesized that ingestion of CLA would reduce body weight gain in ovariectomized (OVX) female C57BL/6J mice that is a model for postmenopausal women. We further hypothesized that body weight reduction may improve obesity-related complication. To test this hypothesis, the OVX mice were fed with a high-fat diet containing CLA for 3 months. Mice had significantly reduced body weight gain compared with OVX mice fed with a high-fat diet without CLA. Although CLA was effective in slowing down body weight gain of both sham and OVX mice, analysis of adipocyte size and number suggested different mechanisms for loss of fat tissue in these 2 groups of mice. Treatment with CLA did not increase liver weight and accumulation of fat in the livers of OVX mice. Furthermore, CLA intake did not change insulin resistance. Our results indicate that CLA is functional as an antiobesity supplement in the mouse model for postmenopausal women and that the antiobesity effect of CLA is not estrogen related. Copyright © 2010 Elsevier Inc. All rights reserved.

Diet Change After Sleeve Gastrectomy Is More Effective for Weight Loss Than Surgery Only.

PubMed

Rossell, Joana; González, Marta; Mestres, Núria; Pardina, Eva; Ricart-Jané, David; Peinado-Onsurbe, Julia; Baena-Fustegueras, Juan Antonio

2017-10-01

Bariatric surgery with or without diet change has become one of the most effective treatments for obesity. The objective of this study was to observe the effects of vertical sleeve gastrectomy (VSG) and diet change in Sprague-Dawley rats on both body and tissue weights. Eighteen rats were fed with a standard chow diet (SCD) (C group), and 36 rats were fed with a high-fat diet (HFD) (diet-induced obesity (DIO) group). After 8 weeks, the animals underwent VSG, sham surgery or no surgery (NS). After surgery, a third of the rats fed with the HFD changed to the SCD (DIO + C group). Body weight, food and energy intake were recorded daily during the experiment (12 weeks). Food efficiency (%) (FE) was determined from weekly weight gain and weekly kilocalorie consumed measurements. The DIO group had higher and significant weight gain than the C group at the time of surgery (p < 0.001). The major weight loss (WL) was observed in the DIO + C-VSG group, during the 4 weeks after surgery. Adipose tissues in the DIO + C-VSG group were drastically reduced and had a weight similar to those in the C-VSG group. VSG and the diet change combination led to a greater WL, which was maintained during the 4 weeks post-surgery, leading to a normalization of body weight. VSG and diet change also affected most of the tissues, not only adipose, showing a global change in whole body composition.

Dietary mannitol increased the absorption of calcium and magnesium in rats.

PubMed

Xiao, J; Sakaguchi, E; Min, X; Kawasaki, K

2016-08-01

The effect of mannitol on bone-related mineral absorption and retention and the mechanism was investigated in this study. Fourteen 8-week-old male Wistar rats in experiment 1 and same number and age cecectomized Wistar male rats in experiment 2 were divided into two subgroups of seven animals, respectively, fed diets containing 0 or 4% mannitol for 28 days. Mineral balance tests were determined twice during days 8-12 and days 22-26, and the rats were slaughtered on day 28 both in experiment 1 and experiment 2. The whole caecum and colon were collected with the content to analyse tissue weight, content weight, content's pH and moisture, organic acids' concentration and mineral levels. In experiment 1, Ca absorption and retention and Mg absorption were significantly increased by mannitol feeding during days 8-12. Caecal total weight, tissue weight and content weight were increased, the pH of caecum and colon was reduced, and the concentrations of caecal short-chain fatty acids (SCFAs) were modified by mannitol feeding. In experiment 2, during days 8-12 and days 22-26, Ca absorption and retention were significantly lowered by mannitol feeding in cecectomized rats; however, mannitol feeding decreased Mg absorption during days 8-12, but did not impact Mg retention. Colonic total weight, tissue weight and content weight were significantly increased, and colonic pH was reduced by mannitol feeding. In conclusion, dietary mannitol increased the absorption of Ca and Mg and the caecum markedly contributed to this promoting effect of mannitol. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Novel "omics" approach for study of low-abundance, low-molecular-weight components of a complex biological tissue: regional differences between chorionic and basal plates of the human placenta.

PubMed

Kedia, Komal; Nichols, Caitlin A; Thulin, Craig D; Graves, Steven W

2015-11-01

Tissue proteomics has relied heavily on two-dimensional gel electrophoresis, for protein separation and quantification, then single protein isolation, trypsin digestion, and mass spectrometric protein identification. Such methods are predominantly used for study of high-abundance, full-length proteins. Tissue peptidomics has recently been developed but is still used to study the most highly abundant species, often resulting in observation and identification of dozens of peptides only. Tissue lipidomics is likewise new, and reported studies are limited. We have developed an "omics" approach that enables over 7,000 low-molecular-weight, low-abundance species to be surveyed and have applied this to human placental tissue. Because the placenta is believed to be involved in complications of pregnancy, its proteomic evaluation is of substantial interest. In previous research on the placental proteome, abundant, high-molecular-weight proteins have been studied. Application of large-scale, global proteomics or peptidomics to the placenta have been limited, and would be challenging owing to the anatomic complexity and broad concentration range of proteins in this tissue. In our approach, involving protein depletion, capillary liquid chromatography, and tandem mass spectrometry, we attempted to identify molecular differences between two regions of the same placenta with only slightly different cellular composition. Our analysis revealed 16 species with statistically significant differences between the two regions. Tandem mass spectrometry enabled successful sequencing, or otherwise enabled chemical characterization, of twelve of these. The successful discovery and identification of regional differences between the expression of low-abundance, low-molecular weight biomolecules reveals the potential of our approach.

The parasitic castration and gigantism of Lymnaea truncatula infected with the larval stages of Fasciola hepatica.

PubMed

Wilson, R A; Denison, J

1980-01-01

The shells of Lymnaea truncatula infected with the larval stages of Fasciola hepatica were significantly longer than those of comparable uninfected controls. The dry mass (tissue, shell + parasite) of the same infected snails, 56 days after infection, was approximately twice that of the controls (tissue + shell). The increased mass of infected snails was not due to a disproportionate increase in shell weight relative to tissues. Infected snails maintained at 20 degrees C had virtually ceased egg production by 21 days post-infection whereas control snails continued to lay eggs steadily for the duration of the experiment. The dry mass of snail tissue plus the cumulative dry weight of eggs produced was taken as an indication of the ability of control snails to generate biomass. Similarly the tissue mass plus cumulative egg weight and parasite weight was taken as an indication of the ability of the infected snails to generate biomass. The control and infected snails were not significantly different in this respect indicating that the gigantism of infected snails could be the result of a switch in nutrient supply from reproduction to somatic tissue growth and parasite growth. Castration was brought about 17-21 days after infection as a result of the direct consumption of the ovotestis by a proportion of the redial population. In a separate experiment it was demonstrated that a population of infected snails maintained at 20 degrees C survived as long as a similar group of control snails. The findings with this host-parasite system are discussed in relation to possible mechanisms causing castration and gigantism in other digene-snail interactions, and in relation to parasitic castration in other groups. It is concluded that the observed gigantism of infected snails is more likely to have a nutritional rather than endocrine origin.

Rapid tissue dissolution efficiency of electrically-activated sodium hypochlorite on bovine muscle.

PubMed

Ertugrul, Ihsan Furkan; Maden, Murat; Orhan, Ekim Onur; Ozkorucuklu, Sabriye Percin; Aglarca, Ali Vasfi

2014-10-01

Sodium hypochlorite (NaOCl) is a common antimicrobial and tissue-dissolving irrigant. The aim of this in vitro study is to evaluate and compare dissolution capacities of sodium hypochlorite solutions after electrically activation (E-NaOCl) on bovine muscle specimens at various time periods and concentrations. Three sodium hypochlorite solutions of 1.25%, 2.5%, and 5% were tested at 3-min. and 5-min. with and without activation by electrically. Distilled water and NaOCl solutions without electrically activation were used as controls. Pieces of bovine muscle tissue (34 ± 2 mg) were placed in 10 mL of each solution at room temperature. In the group of E-NaOCl, electrically activation was performed through the potentiostat. The tissue specimens were weighed before and after treatment, and the percentage of weight loss was calculated. Weight loss of the tissue increased with the concentration of E-NaOCl and NaOCl. Higher concentration and electrically activation considerably enhanced the efficacy of sodium hypochlorite. The effect of electrically activation on tissue dissolution was much greater than that of same concentrations in the groups of NaOCl (P < 0.001). Tissue weight loss was significantly higher in 2.5% and 5% E-NaOCl at 3 min. than in 2.5% and 5% NaOCl at 5 min. (P < 0.05). There were not any significant differences between the 2.5% E-NaOCl and 5% NaOCl at 5 min. (P > 0.05). Electrically activation can improve the tissue-dissolving effectiveness of sodium hypochlorite.

Body size and composition in different somatotypes of Japanese college-aged women.

PubMed

Komiya, S; Masuda, T; Ube, M; Mitsuzono, R

1996-01-01

The purpose of this study was to determine differences in body size, composition and structure between three somatotypes of Japanese college-aged women. The study sample consisted of 30 sedentary female college students between 18 and 20 years of age. Ten subjects had an endomorphic ectomorph somatotype (mean weight 41.95 kg), 10 had an endomorph-ectomorph somatotype (mean weight 47.12 kg) and the remaining subjects had a mesomorphic endomorph somatotype (mean weight 55.37 kg). The mean heights for these groups did not differ significantly. The mesomorphic endomorph group had a higher gross weight and a higher percentage of all adipose variables than the other two groups, though these measurements were not significantly different between the endomorph-ectomorph and the endomorphic ectomorph groups. The mean lean body weight (LBW) for the mesomorphic endomorph group was significantly larger than that of the other two groups. The endomorph-ectomorph group had the next largest LBW, and the mean for the endomorphic ectomorph group was significantly smaller than that of the other two groups. Inversely, mean values of LBW/weight(WT), LBW/total adipose tissue weight (TATW) ratio and total body water/WT were significantly lower for the mesomorphic endomorph group than for the other two groups. Furthermore, the ratios of internal adipose tissue to weight (IATW)/WT and subcutaneous adipose tissue to IATW (SATW)/IATW did not differ significantly between groups. In conclusion, college-aged women of different somatotypes within the same age and height range varied in body composition. Consequently, the notion of a small frame is incorrect. An accurate assessment of the human body's composition may provide a valuable insight into the ideal weight for optimal physiologic function.

Differential induction of peroxisomal beta-oxidation enzymes by clofibric acid and aspirin in piglet tissues.

PubMed

Yu, X X; Odle, J; Drackley, J K

2001-11-01

Peroxisomal beta-oxidation (POX) of fatty acids is important in lipid catabolism and thermogenesis. To investigate the effects of peroxisome proliferators on peroxisomal and mitochondrial beta-oxidation in piglet tissues, newborn pigs (1-2 days old) were allowed ad libitum access to milk replacer supplemented with 0.5% clofibric acid (CA) or 1% aspirin for 14 days. CA increased ratios of liver weight to body weight (P < 0.07), kidney weight to body weight (P < 0.05), and heart weight to body weight (P < 0.001). Aspirin decreased daily food intake and final body weight but increased the ratio of heart weight to body weight (P < 0.01). In liver, activities of POX, fatty acyl-CoA oxidase (FAO), total carnitine palmitoyltransferase (CPT), and catalase were 2.7-, 2.2-, 1.5-fold, and 33% greater, respectively, for pigs given CA than for control pigs. In heart, these variables were 2.2-, 4.1-, 1.9-, and 1.8-fold greater, respectively, for pigs given CA than for control pigs. CA did not change these variables in either kidney or muscle, except that CPT activity was increased approximately 110% (P < 0.01) in kidney. Aspirin increased only hepatic FAO and CPT activities. Northern blot analysis revealed that CA increased the abundance of catalase mRNA in heart by approximately 2.2-fold. We conclude that 1) POX and CPT in newborn pigs can be induced by peroxisomal proliferators with tissue specificity and 2) the relatively smaller induction of POX in piglets (compared with that in young or adult rodents) may be related to either age or species differences.

Dietary Caprylic Acid (C8:0) Does Not Increase Plasma Acylated Ghrelin but Decreases Plasma Unacylated Ghrelin in the Rat

PubMed Central

Lemarié, Fanny; Beauchamp, Erwan; Dayot, Stéphanie; Duby, Cécile; Legrand, Philippe; Rioux, Vincent

2015-01-01

Focusing on the caprylic acid (C8:0), this study aimed at investigating the discrepancy between the formerly described beneficial effects of dietary medium chain fatty acids on body weight loss and the C8:0 newly reported effect on food intake via ghrelin octanoylation. During 6 weeks, Sprague-Dawley male rats were fed with three dietary C8:0 levels (0, 8 and 21% of fatty acids) in three experimental conditions (moderate fat, caloric restriction and high fat). A specific dose-response enrichment of the stomach tissue C8:0 was observed as a function of dietary C8:0, supporting the hypothesis of an early preduodenal hydrolysis of medium chain triglycerides and a direct absorption at the gastric level. However, the octanoylated ghrelin concentration in the plasma was unchanged in spite of the increased C8:0 availability. A reproducible decrease in the plasma concentration of unacylated ghrelin was observed, which was consistent with a decrease in the stomach preproghrelin mRNA and stomach ghrelin expression. The concomitant decrease of the plasma unacylated ghrelin and the stability of its acylated form resulted in a significant increase in the acylated/total ghrelin ratio which had no effect on body weight gain or total dietary consumption. This enhanced ratio measured in rats consuming C8:0 was however suspected to increase (i) growth hormone (GH) secretion as an increase in the GH-dependent mRNA expression of the insulin like growth Factor 1 (IGF-1) was measured (ii) adipocyte diameters in subcutaneous adipose tissue without an increase in the fat pad mass. Altogether, these results show that daily feeding with diets containing C8:0 increased the C8:0 level in the stomach more than all the other tissues, affecting the acylated/total ghrelin plasma ratio by decreasing the concentration of circulating unacylated ghrelin. However, these modifications were not associated with increased body weight or food consumption. PMID:26196391

Omentectomy added to Roux-en-Y gastric bypass surgery: a randomized, controlled trial.

PubMed

Dillard, Troy H; Purnell, Jonathan Q; Smith, Mark D; Raum, William; Hong, Dennis; Laut, Jamie; Patterson, Emma J

2013-01-01

Excess visceral adipose tissue predicts for incipient diabetes mellitus and cardiovascular disease. Human data are mixed regarding the benefits of selective visceral adipose tissue reduction. We investigated the effects of omentectomy added to laparoscopic Roux-en-Y gastric bypass on glucose homeostasis and lipids, inflammatory markers, and adipokines 90 days postoperatively in nondiabetic patients at the Legacy Good Samaritan Hospital and Oregon Health and Science University (Portland, OR). A single-blind, randomized study of laparoscopic Roux-en-Y gastric bypass plus omentectomy versus laparoscopic Roux-en-Y gastric bypass alone in 28 subjects (7 men and 21 women). The groups were matched at baseline for gender, age, and body mass index (BMI). The eligibility criteria included age ≥18 years, BMI ≥40 and <50 kg/m(2) without co-morbid conditions or BMI ≥35 and <50 kg/m(2) with co-morbid conditions. The primary outcome measures were changes in the fasting plasma glucose, insulin, and homostatic model assessment of insulin resistance. The secondary measures were BMI and the high-sensitivity C-reactive protein, tumor necrosis factor-α, interleukin, total and high-molecular-weight adiponectin, fibrinogen, and plasminogen activator inhibitor-1 levels. After surgery, the BMI decreased significantly in both groups and was not different at the follow-up point. Although many outcome parameters improved with weight loss in both groups postoperatively, only the omentectomy group experienced statistically significant decreases in fasting glucose (P < .05), total (P = .004) and very-low-density lipoprotein (P = .001) cholesterol, and an increase in the high-molecular-weight/total adiponectin ratio (P = .013). Omentectomy added to laparoscopic Roux-en-Y gastric bypass results in favorable changes in glucose homeostasis, lipid levels, and adipokine profile at 90 days postoperatively. These data support the hypothesis that selective ablation of visceral adipose tissue conveys metabolic benefits in nondiabetic humans. Copyright © 2013 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Assessing the multiscale architecture of muscular tissue with Q-space magnetic resonance imaging: Review.

PubMed

Hoffman, Matthew P; Taylor, Erik N; Aninwene, George E; Sadayappan, Sakthivel; Gilbert, Richard J

2018-02-01

Contraction of muscular tissue requires the synchronized shortening of myofibers arrayed in complex geometrical patterns. Imaging such myofiber patterns with diffusion-weighted MRI reveals architectural ensembles that underlie force generation at the organ scale. Restricted proton diffusion is a stochastic process resulting from random translational motion that may be used to probe the directionality of myofibers in whole tissue. During diffusion-weighted MRI, magnetic field gradients are applied to determine the directional dependence of proton diffusion through the analysis of a diffusional probability distribution function (PDF). The directions of principal (maximal) diffusion within the PDF are associated with similarly aligned diffusion maxima in adjacent voxels to derive multivoxel tracts. Diffusion-weighted MRI with tractography thus constitutes a multiscale method for depicting patterns of cellular organization within biological tissues. We provide in this review, details of the method by which generalized Q-space imaging is used to interrogate multidimensional diffusion space, and thereby to infer the organization of muscular tissue. Q-space imaging derives the lowest possible angular separation of diffusion maxima by optimizing the conditions by which magnetic field gradients are applied to a given tissue. To illustrate, we present the methods and applications associated with Q-space imaging of the multiscale myoarchitecture associated with the human and rodent tongues. These representations emphasize the intricate and continuous nature of muscle fiber organization and suggest a method to depict structural "blueprints" for skeletal and cardiac muscle tissue. © 2016 Wiley Periodicals, Inc.

Weight trajectory over 20 years and likelihood of mild cognitive impairment or dementia among older women

PubMed Central

LeBlanc, Erin S.; Rizzo, Joanne H.; Pedula, Kathryn L.; Yaffe, Kristine; Ensrud, Kristine E.; Cauley, Jane; Cawthon, Peggy M.; Cummings, Steven; Hillier, Teresa A.

2017-01-01

Background/Objectives The association between weight change and cognition is controversial. We examined the association between 20-year weight change and cognitive function in late life. Design Cohort study. Setting Study of Osteoporotic Fractures (SOF). Participants 1,289 older, community-dwelling women (mean baseline age 68 [65–81] and 88 [82–102] at cognitive testing). Measurements SOF participants had body weight measured repeatedly over 20 years (mean 8 weights). Adjudicated cognitive status was classified as normal (n=775) or mild cognitive impairment (MCI)/dementia (n=514) at Year 20. Logistic models were used to evaluate whether absolute weight change, rate of weight loss per year, presence of abrupt, unrecovered weight loss, and weight variability were associated with MCI or dementia. Results Women with greater rate of weight loss over 20 years had increased chance of developing MCI or dementia. In age/education/clinic-adjusted “base” models, each 0.5 kg/year decrease resulted in 30% increased odds of MCI/dementia (OR=1.30 [95% CI: 1.14, 1.49]). After adjustment for age, education, clinic, depression, and walking speed, there was 17% (OR=1.17 [95% CI: 1.02, 1.35]) increased odds of MCI/dementia for each 0.5 kg/year decrease in weight. In base models, variability in weight was significant. Each 1% average deviation from each woman’s predicted weight curve was associated with 11% increased odds of MCI/dementia (OR=1.11 [95% CI: 1.04, 1.18]). The estimate was attenuated after full adjustment (OR=1.06 [95% CI: 0.99, 1.14]). The presence of an abrupt weight decline was not associated with MCI/dementia. Conclusions Rate of weight loss over 20 years was associated with development of MCI or dementia in women surviving past 80 years, suggesting that nutritional status, social-environmental factors, and/or adipose tissue function and structure may affect cognitive function with aging. PMID:27991654

Intrapartum sacral stress fracture due to pregnancy-related osteoporosis: a case report.

PubMed

Oztürk, Gülcan; Külcü, Duygu Geler; Aydoğ, Ece

2013-01-01

Low back pain (LBP) and hip pain frequently occur during pregnancy and postpartum period. Although pelvic and mechanic lesions of the soft tissues are most responsible for the etiology, sacral fracture is also one of the rare causes. A 32-year-old primigravid patient presented with LBP and right hip pain which started 3 days after vaginal delivery. Although direct radiographic examination was normal, magnetic resonance imaging of the sacrum revealed sacral stress fracture. Lumbar spine and femoral bone mineral density showed osteoporosis as a risk factor. There were no other risk factors such as trauma, excessive weight gain, and strenuous physical activity. It is considered that the patient had sacral fatigue and insufficiency fracture in intrapartum period. The patient's symptoms subsided in 3 months after physical therapy and rest. In conclusion, sacral fractures during pregnancy and postpartum period, especially resulting from childbirth, are very rare. To date, there are two cases in the literature. In cases who even do not have risk factors related to vaginal delivery such as high birth weight infant and the use of forceps, exc., sacral fracture should be considered in the differential diagnosis of LBP and hip pain started soon after child birth. Pregnancy-related osteoporosis may lead to fracture during vaginal delivery.

Anti-obesity effects of Rapha diet® preparation in mice fed a high-fat diet

PubMed Central

Kim, Jihyun; Kyung, Jangbeen; Kim, Dajeong; Choi, Ehn-Kyoung; Bang, Paul

2012-01-01

The anti-obesity activities of Rapha diet® preparation containing silkworm pupa peptide, Garcinia cambogia, white bean extract, mango extract, raspberry extract, cocoa extract, and green tea extract were investigated in mice with dietary obesity. Male C57BL/6 mice were fed a high-fat diet (HFD) containing 3% Rapha diet® preparation for 8 weeks, and blood and tissue parameters of obesity were analyzed. The HFD markedly enhanced body weight gain by increasing the weights of epididymal, perirenal, and mesenteric adipose tissues. The increased body weight gain induced by HFD was significantly reduced by feeding Rapha diet® preparation, in which decreases in the weight of abdominal adipose tissue and the size of abdominal adipocytes were confirmed by microscopic examination. Long-term feeding of HFD increased blood triglycerides and cholesterol levels, leading to hepatic lipid accumulation. However, Rapha diet® preparation not only reversed the blood lipid levels, but also attenuated hepatic steatosis. The results indicate that Rapha diet® preparation could improve HFD-induced obesity by reducing both lipid accumulation and the size of adipocytes. PMID:23326287

Strychnine inhibits inflammatory angiogenesis in mice via down regulation of VEGF, TNF-α and TGF-β.

PubMed

Saraswati, Sarita; Agarwal, S S

2013-05-01

Strychnine is known to possess anti-inflammatory and antitumour activity, but its roles in tumour angiogenesis, the key step involved in tumour growth and metastasis, and the involved molecular mechanism are still unknown. We aimed to investigate the effects of strychnine on key components of inflammatory angiogenesis in the murine cannulated sponge implant angiogenesis model. Polyester-polyurethane sponges, used as a framework for fibrovascular tissue growth, were implanted in Swiss albino mice and strychnine (0.25, and 0.5 mg/kg/day) was given through installed cannulas for 9 days. The implants collected at day 9 postimplantation were processed for the assessment of haemoglobin (Hb), myeloperoxidase (MPO), N-acetylglucosaminidase (NAG) and collagen used as indexes for angiogenesis, neutrophil and macrophage accumulation and extracellular matrix deposition, respectively. Relevant inflammatory, angiogenic and fibrogenic cytokines were also determined. Strychnine treatment attenuated the main components of the fibrovascular tissue, wet weight, vascularization (Hb content), macrophage recruitment (NAG activity), collagen deposition and the levels of vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF)-α and transforming growth factor (TGF-β). A regulatory function of strychnine on multiple parameters of main components of inflammatory angiogenesis has been revealed giving insight into the potential therapeutic underlying the actions of strychnine. Copyright © 2013 Elsevier Inc. All rights reserved.

Magnetization transfer studies of the fast and slow tissue water diffusion components in the human brain.

PubMed

Mulkern, Robert V; Vajapeyam, Sridhar; Haker, Steven J; Maier, Stephan E

2005-05-01

Magnetization transfer (MT) properties of the fast and slow diffusion components recently observed in the human brain were assessed experimentally. One set of experiments, performed at 1.5 T in healthy volunteers, was designed to determine whether the amplitudes of fast and slow diffusion components, differentiated on the basis of biexponential fits to signal decays over a wide range of b-factors, demonstrated a different or similar magnetization transfer ratio (MTR). Another set of experiments, performed at 3 T in healthy volunteers, was designed to determine whether MTRs differed when measured from high signal-to-noise images acquired with b-factor weightings of 350 vs 3500 s/mm2. The 3 T studies included measurements of MTR as a function of off-resonance frequency for the MT pulse at both low and high b-factors. The primary conclusion drawn from all the studies is that there appears to be no significant difference between the magnetization transfer properties of the fast and slow tissue water diffusion components. The conclusions do not lend support to a direct interpretation of the 'components' of the biexponential diffusion decay in terms of the 'compartments' associated with intra- and extracellular water. Copyright 2004 John Wiley & Sons, Ltd.

High intensity interval training improves liver and adipose tissue insulin sensitivity.

PubMed

Marcinko, Katarina; Sikkema, Sarah R; Samaan, M Constantine; Kemp, Bruce E; Fullerton, Morgan D; Steinberg, Gregory R

2015-12-01

Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine-alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC.

COMPARISON OF THE EFFECTS OF TWO AR ANTAGONISTS ON ANDROGEN DEPENDENT TISSUES WEIGHTS AND HORMONE LEVELS IN MALE RATS AND ON EXPRESSION OF THREE ANDROGEN DEPENDENT GENES IN THE VENTRAL PROSTATE

EPA Science Inventory

Comparison of the effects of two AR antagonists on tissue weights and hormone levels in male rats and on expression of three androgen dependent genes in the ventral prostate
VS Wilson, CR Wood, GA Held, CS Lambright, JS Ostby, JR Furr, LE Gray Jr. US EPA, ORD, NHEERL, RTD, ...

A correlation between the weight of visceral adipose tissue and selected anthropometric indices: an autopsy study.

PubMed

Edston, E

2013-06-01

Several anthropometric indices are used as an estimation of the true amount of body fat, e.g. the body mass index (BMI). These indices correlate well with each other and with non-invasive measurements of total body fat and visceral adipose tissue. The indices generally show a strong correlation with cardiovascular disease and diabetes mellitus. Direct measurement of visceral adipose tissue by weight (VAW) from autopsy cases positively correlates with the anthropometric indices. VAW also positively correlates with fatty tissue thickness at separate locations, i.e. renal capsular and epicardial fatty tissue. VAW is positively correlated with the severity of cardiosclerosis and diabetes mellitus, but there is no significant difference in VAW between deaths from cardiovascular complications and other natural deaths. Different anthropometric indices and non-invasive methods have been used to estimate the total burden of body fat. Increased visceral adipose tissue is believed to involve elevated risk for cardiovascular disease, type 2 diabetes, chronic kidney disease and hypertension. At present, the optimal method to estimate the visceral and total amount of fat remains undecided. In the present study of 201 autopsy cases, direct measurement of visceral adipose tissue by weight (VAW) has been compared to common anthropometric indices, namely body mass index (BMI), waist-to-hip ratio (W/Hip ratio), waist-to-height ratio (W/Height ratio), body adiposity index (BAI), waist circumference and abdominal wall thickness. The prevalence and severity of cardiovascular disease, diabetes mellitus and cause of death were also correlated with the anthropometric data. The outcome was that all anthropometric measurements showed a significant positive correlation with the weight of visceral adipose tissue, and the r-value of the comparison to waist circumference was the highest (r = 0.82). Thickness of fatty tissue enveloping the kidneys and heart, as well as heart weight, was also strongly correlated with VAW. VAW was significantly higher in men compared with women, and in diabetes mellitus compared with non-diabetic patients. VAW was also positively correlated with the severity of coronary artery sclerosis. On the contrary, there was no significant difference between high and low VAW comparing between deaths from cardiovascular complications and natural deaths from other causes. The conclusion is that the anthropometric measurements give a good approximation of the real amount of visceral fat, and that waist circumference and W/Height ratio show the best correlations. © 2013 The Author. Clinical Obesity © 2013 International Association for the Study of Obesity.

HA metabolism in skin homeostasis and inflammatory disease.

PubMed

Kavasi, Rafaela-Maria; Berdiaki, Aikaterini; Spyridaki, Ioanna; Corsini, Emanuela; Tsatsakis, Aristidis; Tzanakakis, George; Nikitovic, Dragana

2017-03-01

Hyaluronan (HA), an unsulfated glycosaminoglycan, is an important component of the complex extracellular matrix network which surrounds and supports cells in tissues. HA is detected in all vertebrate tissues, but the bulk of HA is produced and deposited in the skin. In this review we focus on the role of HA in skin-associated inflammatory disease and wound healing. Properties of HA are directly dependent on its molecular weight. Thus, high molecular weight HA (HMWHA) is deposited in normal tissues during homeostasis and promotes their stability whereas low molecular weight HA fragments (LMWHA), on the other hand, may arise from enzymatic or chemical activities. The degradation of HMWHA to LMWHA fragments, often leads to the generation of biologically active oligosaccharides with different properties and postulated functions in wound scar formation and inflammation. More detailed studies of HA involvement in skin-associated inflammatory disease may result in novel treatment modalities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Determination of arsenic species in edible periwinkles (Littorina littorea) by HPLC-ICPMS and XAS along a contamination gradient

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whaley-Martin, K. J.; Koch, I.; Reimer, K. J.

Arsenic is naturally found in the tissues of marine animals, usually as the non-toxic arsenical arsenobetaine, but exposure to elevated arsenic concentrations in the environment may alter the arsenic species distribution within tissues of the organism. This study examined the arsenic species in the tissues of the marine periwinkle (Littorina littorea) along an arsenic concentration gradient in the sediment. The arsenicals in L. littorea were examined using the complementary analytical methods high performance liquid chromatography coupled with inductively coupled plasma mass spectrometry (HPLC–ICPMS) and X-ray absorption spectroscopy (XAS). Total arsenic concentrations in the periwinkle tissues ranged from 56 to 840more » mg · kg -1 dry weight (equivalent to 13 to 190 mg · kg -1 wet weight). Inorganic arsenicals were found to be positively correlated with total arsenic concentrations (R 2 = 0.993) and reached 600 mg · kg -1 dry weight, the highest reported to date in marine organisms. These high inorganic arsenic concentrations within this low trophic organism pose a potential toxicological risk to higher trophic consumers.« less

Caloric restriction induces energy-sparing alterations in skeletal muscle contraction, fiber composition and local thyroid hormone metabolism that persist during catch-up fat upon refeeding

PubMed Central

De Andrade, Paula B. M.; Neff, Laurence A.; Strosova, Miriam K.; Arsenijevic, Denis; Patthey-Vuadens, Ophélie; Scapozza, Leonardo; Montani, Jean-Pierre; Ruegg, Urs T.; Dulloo, Abdul G.; Dorchies, Olivier M.

2015-01-01

Weight regain after caloric restriction results in accelerated fat storage in adipose tissue. This catch-up fat phenomenon is postulated to result partly from suppressed skeletal muscle thermogenesis, but the underlying mechanisms are elusive. We investigated whether the reduced rate of skeletal muscle contraction-relaxation cycle that occurs after caloric restriction persists during weight recovery and could contribute to catch-up fat. Using a rat model of semistarvation-refeeding, in which fat recovery is driven by suppressed thermogenesis, we show that contraction and relaxation of leg muscles are slower after both semistarvation and refeeding. These effects are associated with (i) higher expression of muscle deiodinase type 3 (DIO3), which inactivates tri-iodothyronine (T3), and lower expression of T3-activating enzyme, deiodinase type 2 (DIO2), (ii) slower net formation of T3 from its T4 precursor in muscles, and (iii) accumulation of slow fibers at the expense of fast fibers. These semistarvation-induced changes persisted during recovery and correlated with impaired expression of transcription factors involved in slow-twitch muscle development. We conclude that diminished muscle thermogenesis following caloric restriction results from reduced muscle T3 levels, alteration in muscle-specific transcription factors, and fast-to-slow fiber shift causing slower contractility. These energy-sparing effects persist during weight recovery and contribute to catch-up fat. PMID:26441673

Molecular insights into the role of white adipose tissue in metabolically unhealthy normal weight and metabolically healthy obese individuals.

PubMed

Badoud, Flavia; Perreault, Maude; Zulyniak, Michael A; Mutch, David M

2015-03-01

Obesity is a risk factor for the development of type 2 diabetes and cardiovascular disease. However, it is now recognized that a subset of individuals have reduced cardiometabolic risk despite being obese. Paradoxically, a subset of lean individuals is reported to have high risk for cardiometabolic complications. These distinct subgroups of individuals are referred to as metabolically unhealthy normal weight (MUNW) and metabolically healthy obese (MHO). Although the clinical relevance of these subgroups remains debated, evidence shows a critical role for white adipose tissue (WAT) function in the development of these phenotypes. The goal of this review is to provide an overview of our current state of knowledge regarding the molecular and metabolic characteristics of WAT associated with MUNW and MHO. In particular, we discuss the link between different WAT depots, immune cell infiltration, and adipokine production with MUNW and MHO. Furthermore, we also highlight recent molecular insights made with genomic technologies showing that processes such as oxidative phosphorylation, branched-chain amino acid catabolism, and fatty acid β-oxidation differ between these phenotypes. This review provides evidence that WAT function is closely linked with cardiometabolic risk independent of obesity and thus contributes to the development of MUNW and MHO. © FASEB.

Anti-obesity and pro-diabetic effects of hemochromatosis.

PubMed

Abbas, Mousa Al; Abraham, Deveraprabu; Kushner, James P; McClain, Donald A

2014-10-01

Levels of tissue iron contribute to determining diabetes risk, but little is known about the effects of higher iron levels on weight, and on the interaction of weight and iron overload on diabetes risk. Therefore, the effect of iron on body mass index and diabetes in individuals with iron overload from hereditary hemochromatosis (HH), compared to non-HH siblings and historical controls was examined. Chart reviews were performed on a cohort of adults (age ≥40, N = 101) with the common C282Y/C282Y HFE genotype, compared to wild type siblings (N = 32) and comparable NHANES cohorts, with respect to body mass index and diabetes status. Males with HH have lower body mass index (BMI) than control siblings. Females had a trend toward decreased BMI that was not significant, possibly related to decreased degrees of iron overload. In both males and females, increased rates of diabetes were seen, especially in the overweight or obese. High tissue iron levels may be both pro- and anti-diabetic. The prevalence of obesity and diabetes in HH is likely dependent upon the degree of iron overload, caloric intake, and other genetic and environmental factors, contributing to the observed heterogeneity in the frequency of disease-related morbidities in HH. Copyright © 2014 The Obesity Society.

Anti-Obesity and Pro-Diabetic Effects of Hemochromatosis

PubMed Central

Abbas, Mousa Al; Abraham, Deveraprabu; Kushner, James P.; McClain, Donald A.

2014-01-01

Objective Levels of tissue iron contribute to determining diabetes risk, but little is known about the effects of higher iron levels on weight, nor on the interaction of weight and iron overload on diabetes risk. We therefore examined the effect of iron on body mass index and diabetes in individuals with iron overload from hereditary hemochromatosis (HH), compared to non-HH siblings and historical controls. Methods Chart reviews were performed on a cohort of adults (age ≥40, N=101) with the common C282Y/C282Y HFE genotype, compared to wild type siblings (N=32) and comparable NHANES cohorts, with respect to body mass index and diabetes status. Results Males with HH have lower body mass index (BMI) than control siblings. Females had a trend toward decreased BMI that was not significant, possibly related to decreased degrees of iron overload. In both males and females, increased rates of diabetes were seen, especially in the overweight or obese. Conclusions High tissue iron levels may be both pro- and anti-diabetic. The prevalence of obesity and diabetes in HH is likely dependent upon the degree of iron overload, caloric intake, and other genetic and environmental factors, contributing to the observed heterogeneity in the frequency of disease-related morbidities in HH. PMID:25044717

The use and interpretation of anthropometric measures in cancer epidemiology: A perspective from the world cancer research fund international continuous update project.

PubMed

Bandera, Elisa V; Fay, Stephanie H; Giovannucci, Edward; Leitzmann, Michael F; Marklew, Rachel; McTiernan, Anne; Mullee, Amy; Romieu, Isabelle; Thune, Inger; Uauy, Ricardo; Wiseman, Martin J

2016-12-01

Anthropometric measures relating to body size, weight and composition are increasingly being associated with cancer risk and progression. Whilst practical in epidemiologic research, where population-level associations with disease are revealed, it is important to be aware that such measures are imperfect markers of the internal physiological processes that are the actual correlates of cancer development. Body mass index (BMI), the most commonly used marker for adiposity, may mask differences between lean and adipose tissue, or fat distribution, which varies across individuals, ethnicities, and stage in the lifespan. Other measures, such as weight gain in adulthood, waist circumference and waist-to-hip ratio, contribute information on adipose tissue distribution and insulin sensitivity. Single anthropometric measures do not capture maturational events, including the presence of critical windows of susceptibility (i.e., age of menarche and menopause), which presents a challenge in epidemiologic work. Integration of experimental research on underlying dynamic genetic, hormonal, and other non-nutritional mechanisms is necessary for a confident conclusion of the overall evidence in cancer development and progression. This article discusses the challenges confronted in evaluating and interpreting the current evidence linking anthropometric factors and cancer risk as a basis for issuing recommendations for cancer prevention. © 2016 UICC.

AAPM/RSNA physics tutorials for residents: MR imaging: brief overview and emerging applications.

PubMed

Jacobs, Michael A; Ibrahim, Tamer S; Ouwerkerk, Ronald

2007-01-01

Magnetic resonance (MR) imaging has become established as a diagnostic and research tool in many areas of medicine because of its ability to provide excellent soft-tissue delineation in different areas of interest. In addition to T1- and T2-weighted imaging, many specialized MR techniques have been designed to extract metabolic or biophysical information. Diffusion-weighted imaging gives insight into the movement of water molecules in tissue, and diffusion-tensor imaging can reveal fiber orientation in the white matter tracts. Metabolic information about the object of interest can be obtained with spectroscopy of protons, in addition to imaging of other nuclei, such as sodium. Dynamic contrast material-enhanced imaging and recently proton spectroscopy play an important role in oncologic imaging. When these techniques are combined, they can assist the physician in making a diagnosis or monitoring a treatment regimen. One of the major advantages of the different types of MR imaging is the ability of the operator to manipulate image contrast with a variety of selectable parameters that affect the kind and quality of the information provided. The elements used to obtain MR images and the factors that affect formation of an MR image include MR instrumentation, localization of the MR signal, gradients, k-space, and pulse sequences. RSNA, 2007

Diagnostic criteria for selenium toxicosis in aquatic birds: dietary exposure, tissue concentrations, and macroscopic effects

USGS Publications Warehouse

Albers, P.H.; Green, D.E.; Sanderson, C.J.

1996-01-01

A feeding study with mallard ducks (Anas platyrhynchos) was conducted during March-July, 1988 in Laurel, Maryland, to identify diagnostic criteria for selenium toxicosis in birds. One-year-old male mallards in groups of 21 were fed diets containing 0, 10, 20, 40, or 80 parts per million (ppm) selenium, as seleno-DL-methionine, for 16 weeks. All ducks receiving 80 ppm died. Ducks receiving 40 or 80 ppm selenium consumed less feed than ducks in the other treatment groups. Body weights of ducks receiving 40 or 80 ppm selenium declined during the study. The post-breeding molt was delayed in ducks receiving 40 ppm; most ducks receiving 80 ppm selenium died prior to the onset of molt. At necropsy, numerous abnormalities were observed in ducks that died but only a small number of abnormalities were observed in ducks surviving to the end of the study in the 40 ppm group. Weights of the heart, spleen, and pancreas were mostly lower and weights of the kidney were higher for ducks dying during the study than for euthanized ducks. Liver weights were unaffected. Selenium accumulated in soft tissues approximately in proportion to dietary concentrations. Selenium concentrations in tissues of all ducks that died were different from those of surviving ducks in the 0, 10, and 20 ppm groups, but were not different from those of surviving ducks in the 40 ppm group. Proposed diagnostic criteria for fatal chronic selenosis were derived from body weight, macroscopic abnormalities, organ weights, and concentrations of selenium in the liver. Proposed diagnostic criteria for non-fatal chronic selenosis were derived from body weight, plumage condition, macroscopic abnormalities, concentrations of selenium in the liver, reproductive failure, and alterations of blood and tissue chemistries. Lead or dioxin poisoning have diagnostic criteria most similar to selenium toxicosis.

Protection by dimethyl fumarate against diabetic cardiomyopathy in type 1 diabetic mice likely via activation of nuclear factor erythroid-2 related factor 2.

PubMed

Hu, Xinyue; Rajesh, Mohanraj; Zhang, Jian; Zhou, Shanshan; Wang, Shudong; Sun, Jian; Tan, Yi; Zheng, Yang; Cai, Lu

2018-05-01

Oxidative stress and inflammation play key roles in the development of diabetic cardiomyopathy (DCM). Dimethyl fumarate (DMF), an FDA approved medicine for relapsing multiple sclerosis, has manifested its antioxidant and anti-inflammatory function mostly in the central nervous system. In this study, we investigated whether DMF could attenuate the development of DCM. Type 1 diabetes mouse model was established using multiple low-dose streptozotocin, and the diabetic mice were treated with DMF (10 mg/kg body weight) for 3 months. Cardiac functions were determined using echocardiography. Oxidative stress, pro-inflammatory cytokines and pro-fibrotic markers were determined with commercially available kits, real-time quantitative PCR or western blot techniques. DCM was characterized by diminished cardiac function, accompanied by oxidative stress and enhanced expression of pro-inflammatory cytokines. Diabetic cardiac tissue exhibited marked fibrosis, revealed by extracellular matrix deposition as determined by Sirius red staining of the myocardial tissues. Furthermore, Nrf2 and its downstream effectors were repressed in diabetic myocardium. On the contrary, diabetic animals treated with DMF exhibited blunted oxidative stress, inflammation, fibrosis and this correlated with Nrf2 activation. Our findings suggest that DMF could potentially thwart diabetes-induced myocardial tissue injury, likely via activation of Nrf2 function, providing firm impetus for future repurposing of DMF in the management of DCM. Copyright © 2018 Elsevier B.V. All rights reserved.

Genipin ameliorates diet-induced obesity via promoting lipid mobilization and browning of white adipose tissue in rats.

PubMed

Guan, Lili; Gong, Dezheng; Yang, Sirao; Shen, Nana; Zhang, Sai; Li, Yuchen; Wu, Qiong; Yuan, Bo; Sun, Yiping; Dai, Ning; Zhu, Liang; Zou, Yuan

2018-04-01

Genipin is the major active component of Gardeniae fructus and has been shown to ameliorate diabetes and insulin resistance in rat models. In this study, we first investigated the effect of genipin on obesity and the related lipid metabolism mechanisms in diet-induced obese rats. Our results showed that genipin reduced body weight, food intake, and visceral fat mass; ameliorated dyslipidemia, glucose intolerance, insulin intolerance, adipocyte hypertrophy, and hepatic steatosis; and reduced serum tumor necrosis factor-α level in diet-induced obese rats. Quantitative real-time reverse-transcription polymerase chain reaction results further illustrated that genipin promoted lipolysis and β-oxidation of fatty acid by upregulating gene expressions of hormone-sensitive lipase and adipose triglyceride lipase in white adipose tissue (WAT) and peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase 1α in hepatic tissue. Moreover, genipin promoted browning of WAT by upregulating the mRNA and protein levels of uncoupling protein 1 and PRD1-BF1-RIZ1 homologous domain containing 16 in WAT. Additionally, genipin inhibited gene expressions of activin receptor-like kinase 7, tumor necrosis factor-α, and interlukin-6 in WAT. These results indicated that genipin had a potential therapeutic role in obesity, in which regulation of lipid mobilization and browning of WAT were involved. Copyright © 2018 John Wiley & Sons, Ltd.

Influence of insulin-like growth factor-I (IGF-I) on nerve autografts and tissue-engineered nerve grafts.

PubMed

Fansa, Hisham; Schneider, Wolfgang; Wolf, Gerald; Keilhoff, Gerburg

2002-07-01

To overcome the problems of limited donor nerves for nerve reconstruction, we established nerve grafts made from cultured Schwann cells and basal lamina from acellular muscle and used them to bridge a 2-cm defect of the rat sciatic nerve. Due to their basal lamina and to viable Schwann cells, these grafts allow regeneration that is comparable to autologous nerve grafts. In order to enhance regeneration, insulin-like growth factor (IGF-I) was locally applied via osmotic pumps. Autologous nerve grafts with and without IGF-I served as controls. Muscle weight ratio was significantly increased in the autograft group treated with IGF-I compared to the group with no treatment; no effect was evident in the tissue-engineered grafts. Autografts with IGF-I application revealed a significantly increased axon count and an improved g-ratio as indicator for "maturity" of axons compared to autografts without IGF-I. IGF-I application to the engineered grafts resulted in a decreased axon count compared to grafts without IGF-I. The g-ratio, however, revealed no significant difference between the groups. Local administration of IGF-I improves axonal regeneration in regular nerve grafts, but not in tissue-engineered grafts. Seemingly, in these grafts the interactive feedback mechanisms of neuron, glial cell, and extracellular matrix are not established, and IGF-I cannot exert its action as a pleiotrophic signal. Copyright 2002 Wiley Periodicals, Inc.

Analysis of iron, zinc, selenium and cadmium in paraffin-embedded prostate tissue specimens using inductively coupled plasma mass-spectrometry

USGS Publications Warehouse

Sarafanov, A.G.; Todorov, T.I.; Kajdacsy-Balla, A.; Gray, Michael A.; MacIas, V.; Centeno, J.A.

2008-01-01

Formalin-fixed paraffin-embedded (FFPE) tissue specimens represent a valuable and abundant resource of pathologic material for various biomedical studies. In the present study, we report the application of high-resolution inductively coupled mass-spectrometry (ICP-MS) for quantification of Fe, Zn, Se and Cd in FFPE prostate tissue. These elements have a possible role in the development of prostate diseases: while Zn and Se are needed for a healthy prostate, Cd shows multiple toxic and carcinogenic effects. Excessive accumulation of Fe induces the production of highly reactive hydroxyl radical species, which may play a role in cancer etiopathogenesis. To assess whether the levels of these metals in the FFPE prostate tissue represent their original content, we compared their levels with those in the fresh tissue (on dry weight basis) in samples obtained from 15 patients. We found that in FFPE tissue, the recoveries of Se, Fe, Cd and Zn were progressively decreased, 97??11% (r=0.88), 82??22% (r=0.86), 59??23% (r=0.69) and 24??11% (r=0.38), respectively. Thus, the use of correction factors, determined as k=0.16 for Se, k=0.20 for Fe, k=0.27 for Cd and k=0.67 for Zn, is required to estimate the retrospective levels of these elements in the parental non-processed fresh (wet) prostate tissue. The technique used in this study enables the analysis of archival FFPE prostate tissue for the concentrations of Fe, Zn, Se and Cd to study association between the levels of these metals and prostate disease. ?? 2008.

Kinetic model of cadmium accumulation and elimination and metallothionein response in Ruditapes decussatus.

PubMed

Serafim, Angela; Bebianno, Maria João

2007-05-01

The aim of the present study was to determine the response of metallothionein (MT) during Cd accumulation and elimination in different tissues of the estuarine bivalve Ruditapes decussatus exposed to two nominal Cd concentrations (4 and 40 microg/L) for 40 d, followed by a depuration period of 50 d. Cadmium was accumulated in all tissues of R. decussatus at both exposure concentrations, and the accumulation was tissue dependent. Use of the kinetic model showed that in the gills and remaining tissues, Cd was assimilated faster at the beginning of the exposure and decreased with time, possibly limited by the diffusion rate of this metal within the cell. In the digestive gland, however, the Cd was continuously accumulated. This could reflect that the Cd uptake rate is considerably higher than the loss rate and, therefore, that this tissue has a higher capacity to accumulate Cd compared to the other two tissues. Moreover, the application of this kinetic model in the different subcellular fractions showed that the bioconcentration factor was significantly higher in the low-molecular-weight fraction (where MT is found), suggesting that this fraction binds Cd faster, with a high uptake rate (K(u) = 32/d), and eliminates this metal more slowly (K(1) = 0.005/d). During the depuration phase, MT decreased simultaneously with Cd elimination in all tissues, although with a shorter half-life. In conclusion, the MT response prevented Cd in the tissues of R. decussatus from interfering in the normal clam metabolism; therefore, MT acts as a detoxification mechanism of Cd.

Contact Nd:YAG tonsillectomy: effects on weight loss and recovery.

PubMed

Maloney, R W

1991-01-01

Contact Nd:YAG tonsillectomy using synthetic sapphire blades appears to meet or exceed standards established by spot monopolar cautery. Subjects' percentage of weight loss and return to work/social activities was measured and the laser group displayed less percentage of weight loss, faster return to pre-operative weight, and less recovery time than the comparative cautery group. Because of the unique nature of Nd:YAG laser light combined with sapphire blades, special consideration should be given to these accessories by physicians before attempting tissue cutting and vessel coagulation. The author believes that the extent of physician training and proficiency may be key to the success of soft tissue head and neck applications, such as tonsillectomy, which will have an effect on the outcome of clinical data.

[Recent development in research and management of cancer anorexia-cachexia syndrome].

PubMed

Inui, Akio

2005-06-01

Cachexia is among the most debilitating and life-threatening aspects of cancer, and is more common in children and elderly patients. Associated with anorexia, fat and muscle tissue wasting, psychological distress, and a lower quality of life, cachexia arises from a complex interaction between the cancer and the host. This process results from a failure of the adaptive feeding response seen in simple starvation and includes cytokine production, release of lipid-mobilizing and proteolysis-inducing factors, and alterations in intermediary metabolism. Cytokines play a pivotal role in long-term inhibition of feeding by mimicking the hypothalamic effect of excessive negative feedback signaling from leptin, a hormone secreted by adipose tissue, which is an integral component of the homeostatic loop of body weight regulation. This could be done by persistent inhibition of feeding-stimulatory circuitry including neuropeptide Y. Cachexia should be suspected in patients with cancer if an involuntary weight loss of greater than five percent of premorbid weight occurs within a 3-6-month period. The two major options for pharmacological therapy have been either progestational agents or corticosteroids. However, knowledge of the mechanisms of cancer anorexia-cachexia syndrome has led to, and continues to lead to, effective therapeutic interventions for several aspects of the syndrome. These include antiserotonergic drugs, gastroprokinetic agents, branched-chain amino acids, eicosapentanoic acid, cannabinoids, melatonin, and thalidomide-all of which act on the feeding-regulatory circuitry to increase appetite and inhibit tumor-derived catabolic factors to antagonize tissue wasting and/or host cytokine release. The outcomes of drug studies in cancer cachexia should focus on the symptomatic and quality-of-life advantages rather than simply on nutritional end points, since the survival of cachexia cancer patients may be limited to weeks or months due to the incurable nature of the underlying malignancy. Communication among physicians and other health care professionals provides the patient with a multidisciplinary approach to care. The patient record will be an excellent resource to document a plan of care and patient responses to treatment. Psychological distress and psychiatric disorders are common among cancer patients. These problems are also as common among the family members of people with cancer. The use of psychological and behavioral interventions in cancer is increasing, and recent studies have suggested that some of these techniques may affect quality of life and, perhaps, survival rates. Evaluations of relaxation, hypnosis, and short-term group psychotherapy have suggested some benefit with regard to anorexia and fatigue, although the population most likely to benefit from these interventions has not yet been determined. Because weight loss shortens the survival time of cancer patients and decreases performance status, effective therapy would extend patient survival and improve quality of life.

Differential effects of cobalt and mercury on lipid metabolism in the white adipose tissue of high-fat diet-induced obesity mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawakami, Takashige, E-mail: tkawakami@ph.bunri-u-ac.jp; Hanao, Norihide; Nishiyama, Kaori

Metals and metalloid species are involved in homeostasis in energy systems such as glucose metabolism. Enlarged adipocytes are one of the most important causes of obesity-associated diseases. In this study, we studied the possibility that various metals, namely, CoCl{sub 2}, HgCl{sub 2}, NaAsO{sub 2} and MnCl{sub 2} pose risk to or have beneficial effects on white adipose tissue (WAT). Exposure to the four metals resulted in decreases in WAT weight and the size of enlarged adipocytes in mice fed a high-fat diet (HFD) without changes in liver weight, suggesting that the size and function of adipocytes are sensitive to metals.more » Repeated administration of CoCl{sub 2} significantly increased serum leptin, adiponectin and high-density lipoprotein (HDL) cholesterol levels and normalized glucose level and adipose cell size in mice fed HFD. In contrast, HgCl{sub 2} treatment significantly decreased serum leptin level with the down-regulation of leptin mRNA expression in WAT and a reduction in adipocyte size. Next, we tried to investigate possible factors that affect adipocyte size. Repeated exposure to HgCl{sub 2} significantly decreased the expression levels of factors upon the regulation of energy such as the PPARα and PPARγ mRNA expression levels in adipocytes, whereas CoCl{sub 2} had little effect on those genes expressions compared with that in the case of the mice fed HFD with a vehicle. In addition, repeated administration of CoCl{sub 2} enhanced AMPK activation in a dose-dependent manner in the liver, skeletal muscle and WAT; HgCl{sub 2} treatment also enhanced AMPK activation in the liver. Thus, both Co and Hg reduced WAT weight and the size of enlarged adipocytes, possibly mediated by AMKP activation in the mice fed HFD. However, inorganic cobalt may have a preventive role in obesity-related diseases through increased leptin, adiponectin and HDL-cholesterol levels, whereas inorganic mercury may accelerate the development of such diseases. These results may lead to the development of new approaches to establishing the role of metals in adipose tissue of obesity-related diseases. -- Highlights: ► The effects of metals on enlarged white adipose tissue (WAT) were studied. ► As, Hg, Mn and Co ions reduced the size of enlarged adipocytes. ► Co{sup 2+} increased serum leptin and adiponectin levels with AMPK activation in WAT. ► Hg{sup 2+} decreased serum leptin level and leptin mRNA expression in WAT. ► Metal exposure affects the adipocyte size and the function of WAT.« less

Antidiabetic effect of Scoparia dulcis: effect on lipid peroxidation in streptozotocin diabetes.

PubMed

Pari, L; Latha, M

2005-03-01

Oxidative damage has been suggested to be a contributory factor in the development and complications of diabetes. The antioxidant effect of an aqueous extract of Scoparia dulcis, an indigenous plant used in Ayurvedic medicine in India was studied in rats with streptozotocin-induced diabetes. Oral administration of Scoparia dulcis plant extract (SPEt) (200 mg/kg body weight) for 3 weeks resulted in a significant reduction in blood glucose and an increase in plasma insulin. The aqueous extract also resulted in decreased free radical formation in tissues (liver and kidney) studied. The decrease in thiobarbituric acid reactive substances (TBARS) and hydroperoxides (HPX) and increase in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH) and glutathione-S-transferase (GST) clearly show the antioxidant properties of SPEt in addition to its antidiabetic effect. The effect of SPEt at 200 mg/kg body weight was better than glibenclamide, a reference drug.

Hypothalamic Leptin and Ghrelin Signaling as Targets for Improvement in Metabolic Control.

PubMed

Frago, Laura M; Chowen, Julie A

2015-01-01

Metabolic homeostasis requires a tight balance between energy intake and energy expenditure; hence, the physiological circuits implicated in the regulation of energy metabolism must be able to quickly adjust to changes in either side of the equation. Circulating orexigenic and anorexigenic factors, including ghrelin and leptin, are produced in the gastrointestinal tract and adipose tissue, respectively, in relation to an individual's nutritional status. These signals interact with central metabolic circuits to regulate the production and secretion of neuropeptides implicated in the control of appetite and energy expenditure. However, this physiological equilibrium can be perturbed by diverse processes, with weight gain occurring due to a positive energy balance and weight loss taking place if there is a negative energy balance. If a situation of positive energy balance continues for an extended period of time, excess weight is accumulated and this can eventually result in obesity. Obesity has become one of the most important health problems facing the industrialized world, indicating that metabolic equilibrium is frequently disrupted. Understanding how and why this occurs will allow new therapeutical targets to be identified.

Dietary sodium, adiposity, and inflammation in healthy adolescents.

PubMed

Zhu, Haidong; Pollock, Norman K; Kotak, Ishita; Gutin, Bernard; Wang, Xiaoling; Bhagatwala, Jigar; Parikh, Samip; Harshfield, Gregory A; Dong, Yanbin

2014-03-01

To determine the relationships of sodium intake with adiposity and inflammation in healthy adolescents. A cross-sectional study involved 766 healthy white and African American adolescents aged 14 to 18 years. Dietary sodium intake was estimated by 7-day 24-hour dietary recall. Percent body fat was measured by dual-energy x-ray absorptiometry. Subcutaneous abdominal adipose tissue and visceral adipose tissue were assessed using magnetic resonance imaging. Fasting blood samples were measured for leptin, adiponectin, C-reactive protein, tumor necrosis factor-α, and intercellular adhesion molecule-1. The average sodium intake was 3280 mg/day. Ninety-seven percent of our adolescents exceeded the American Heart Association recommendation for sodium intake. Multiple linear regressions revealed that dietary sodium intake was independently associated with body weight (β = 0.23), BMI (β = 0.23), waist circumference (β = 0.23), percent body fat (β = 0.17), fat mass (β = 0.23), subcutaneous abdominal adipose tissue (β = 0.25), leptin (β = 0.20), and tumor necrosis factor-α (β = 0.61; all Ps < .05). No relation was found between dietary sodium intake and visceral adipose tissue, skinfold thickness, adiponectin, C-reactive protein, or intercellular adhesion molecule-1. All the significant associations persisted after correction for multiple testing (all false discovery rates < 0.05). The mean sodium consumption of our adolescents is as high as that of adults and more than twice the daily intake recommended by the American Heart Association. High sodium intake is positively associated with adiposity and inflammation independent of total energy intake and sugar-sweetened soft drink consumption.

Dietary Sodium, Adiposity, and Inflammation in Healthy Adolescents

PubMed Central

Pollock, Norman K.; Kotak, Ishita; Gutin, Bernard; Wang, Xiaoling; Bhagatwala, Jigar; Parikh, Samip; Harshfield, Gregory A.; Dong, Yanbin

2014-01-01

OBJECTIVES: To determine the relationships of sodium intake with adiposity and inflammation in healthy adolescents. METHODS: A cross-sectional study involved 766 healthy white and African American adolescents aged 14 to 18 years. Dietary sodium intake was estimated by 7-day 24-hour dietary recall. Percent body fat was measured by dual-energy x-ray absorptiometry. Subcutaneous abdominal adipose tissue and visceral adipose tissue were assessed using magnetic resonance imaging. Fasting blood samples were measured for leptin, adiponectin, C-reactive protein, tumor necrosis factor-α, and intercellular adhesion molecule-1. RESULTS: The average sodium intake was 3280 mg/day. Ninety-seven percent of our adolescents exceeded the American Heart Association recommendation for sodium intake. Multiple linear regressions revealed that dietary sodium intake was independently associated with body weight (β = 0.23), BMI (β = 0.23), waist circumference (β = 0.23), percent body fat (β = 0.17), fat mass (β = 0.23), subcutaneous abdominal adipose tissue (β = 0.25), leptin (β = 0.20), and tumor necrosis factor-α (β = 0.61; all Ps < .05). No relation was found between dietary sodium intake and visceral adipose tissue, skinfold thickness, adiponectin, C-reactive protein, or intercellular adhesion molecule-1. All the significant associations persisted after correction for multiple testing (all false discovery rates < 0.05). CONCLUSIONS: The mean sodium consumption of our adolescents is as high as that of adults and more than twice the daily intake recommended by the American Heart Association. High sodium intake is positively associated with adiposity and inflammation independent of total energy intake and sugar-sweetened soft drink consumption. PMID:24488738

Selecting the correct weighting factors for linear and quadratic calibration curves with least-squares regression algorithm in bioanalytical LC-MS/MS assays and impacts of using incorrect weighting factors on curve stability, data quality, and assay performance.

PubMed

Gu, Huidong; Liu, Guowen; Wang, Jian; Aubry, Anne-Françoise; Arnold, Mark E

2014-09-16

A simple procedure for selecting the correct weighting factors for linear and quadratic calibration curves with least-squares regression algorithm in bioanalytical LC-MS/MS assays is reported. The correct weighting factor is determined by the relationship between the standard deviation of instrument responses (σ) and the concentrations (x). The weighting factor of 1, 1/x, or 1/x(2) should be selected if, over the entire concentration range, σ is a constant, σ(2) is proportional to x, or σ is proportional to x, respectively. For the first time, we demonstrated with detailed scientific reasoning, solid historical data, and convincing justification that 1/x(2) should always be used as the weighting factor for all bioanalytical LC-MS/MS assays. The impacts of using incorrect weighting factors on curve stability, data quality, and assay performance were thoroughly investigated. It was found that the most stable curve could be obtained when the correct weighting factor was used, whereas other curves using incorrect weighting factors were unstable. It was also found that there was a very insignificant impact on the concentrations reported with calibration curves using incorrect weighting factors as the concentrations were always reported with the passing curves which actually overlapped with or were very close to the curves using the correct weighting factor. However, the use of incorrect weighting factors did impact the assay performance significantly. Finally, the difference between the weighting factors of 1/x(2) and 1/y(2) was discussed. All of the findings can be generalized and applied into other quantitative analysis techniques using calibration curves with weighted least-squares regression algorithm.

Removal of inhibitor(s) of the polymerase chain reaction from formalin fixed, paraffin wax embedded tissues.

PubMed

An, S F; Fleming, K A

1991-11-01

A problem associated with use of the polymerase chain reaction to amplify specific DNA fragments from formalin fixed, paraffin wax embedded tissues is the not infrequent failure of amplification. One possible reason for this could be the presence of inhibitor(s), which interfere with the activity of the reaction. It has been shown that such inhibitor(s) exist when amplifying the human beta globin gene (which exists in human genomic DNA as a single copy gene) from routine clinical samples. A variety of methods to remove such inhibitor(s) were investigated. The results indicate that inhibitor(s) are removed by proteinase K digestion, followed by purification with phenol/chloroform, and centrifugation through a Centricon-30 membrane (30,000 molecular weight cut off). Other factors, including the length and concentration of the DNA sequence to be amplified, can also affect amplification.

[Sarcopenia: toward its clinical utilisation].

PubMed

Bijlsma, Astrid Y; Meskers, Carel G M; Westendorp, Rudi G J; Maier, Andrea B

2013-01-01

Sarcopenia is a term that was introduced to describe 'low muscle mass'. There is no consensus definition for sarcopenia; a variety of criteria are being used to establish the diagnosis of 'sarcopenia'. Depending on the criteria used, the prevalence of sarcopenia in elderly varies from 7% to over 50%. The presence of sarcopenia often remains unrecognized when the loss of muscle mass is replaced by fat and connective tissue; body weight thus remains stable or even increases. Sarcopenia can be detected by measuring muscle mass with dual-energy X-ray absorptiometry (DEXA) or bioimpedance analysis (BIA). Besides the generation of strength, muscle tissue is an important internal organ involved in protein storage, glucose regulation, hormonal homeostasis and cellular communication. Systemic, cellular, neuromechanical factors and lifestyle are linked to the pathophysiology of sarcopenia. Sarcopenia is associated with higher mortality, dependency in activities of daily living, toxicity of chemotherapy, and disturbed glucose regulation.

Overview of Brain Microdialysis

PubMed Central

Chefer, Vladimir I.; Thompson, Alexis C.; Zapata, Agustin; Shippenberg, Toni S.

2010-01-01

The technique of microdialysis enables sampling and collecting of small-molecular-weight substances from the interstitial space. It is a widely used method in neuroscience and is one of the few techniques available that permits quantification of neurotransmitters, peptides, and hormones in the behaving animal. More recently, it has been used in tissue preparations for quantification of neurotransmitter release. This unit provides a brief review of the history of microdialysis and its general application in the neurosciences. The authors review the theoretical principles underlying the microdialysis process, methods available for estimating extracellular concentration from dialysis samples (i.e., relative recovery), the various factors that affect the estimate of in vivo relative recovery, and the importance of determining in vivo relative recovery to data interpretation. Several areas of special note, including impact of tissue trauma on the interpretation of microdialysis results, are discussed. Step-by-step instructions for the planning and execution of conventional and quantitative microdialysis experiments are provided. PMID:19340812

Hg concentrations and related risk assessment in coral reef crustaceans, molluscs and fish from New Caledonia.

PubMed

Chouvelon, Tiphaine; Warnau, Michel; Churlaud, Carine; Bustamante, Paco

2009-01-01

There is a dramatic lack of data on Hg levels in marine organisms from tropical areas, and in particular from New Caledonia. For the first time, this study reports the total Hg concentrations in the tissues of several marine taxa from the New Caledonian lagoon. Seafood from both wild and farmed populations was considered. Hg concentrations varied over three orders of magnitudes according to factors including species, age (size/weight), trophic level, lifestyle and geographical origin. Taking into account the edible tissues, estimations of the amount of flesh that should be consumed by a 60-kg person to reach the Hg Provisional Tolerable Weekly Intake (PTWI) reveal acceptable risk for Human health in general. However, a risk was clearly identified in one site of the lagoon (i.e. Grande Rade) where high Hg concentrations were measured. These concentrations were higher than values reported in the current literature.

Hypothalamic KLF4 mediates leptin's effects on food intake via AgRP

PubMed Central

Imbernon, Monica; Sanchez-Rebordelo, Estrella; Gallego, Rosalia; Gandara, Marina; Lear, Pamela; Lopez, Miguel; Dieguez, Carlos; Nogueiras, Ruben

2014-01-01

Krüppel-like factor 4 (KLF4) is a zinc-finger-type transcription factor expressed in a range of tissues that plays multiple functions. We report that hypothalamic KLF4 represents a new transcription factor specifically modulating agouti-related protein (AgRP) expression in vivo. Hypothalamic KLF4 colocalizes with AgRP neurons and is modulated by nutritional status and leptin. Over-expression of KLF4 in the hypothalamic arcuate nucleus (ARC) induces food intake and increases body weight through the specific stimulation of AgRP, as well as blunting leptin sensitivity in lean rats independent of forkhead box protein 01 (FoxO1). Down-regulation of KLF4 in the ARC inhibits fasting-induced food intake in both lean and diet-induced obese (DIO) rats. Silencing KLF4, however, does not, on its own, enhance peripheral leptin sensitivity in DIO rats. PMID:24944903

Hypothalamic KLF4 mediates leptin's effects on food intake via AgRP.

PubMed

Imbernon, Monica; Sanchez-Rebordelo, Estrella; Gallego, Rosalia; Gandara, Marina; Lear, Pamela; Lopez, Miguel; Dieguez, Carlos; Nogueiras, Ruben

2014-07-01

Krüppel-like factor 4 (KLF4) is a zinc-finger-type transcription factor expressed in a range of tissues that plays multiple functions. We report that hypothalamic KLF4 represents a new transcription factor specifically modulating agouti-related protein (AgRP) expression in vivo. Hypothalamic KLF4 colocalizes with AgRP neurons and is modulated by nutritional status and leptin. Over-expression of KLF4 in the hypothalamic arcuate nucleus (ARC) induces food intake and increases body weight through the specific stimulation of AgRP, as well as blunting leptin sensitivity in lean rats independent of forkhead box protein 01 (FoxO1). Down-regulation of KLF4 in the ARC inhibits fasting-induced food intake in both lean and diet-induced obese (DIO) rats. Silencing KLF4, however, does not, on its own, enhance peripheral leptin sensitivity in DIO rats.

Chronic sublethal effects of San Francisco Bay sediments on nereis (neanthes) arenaceodentata; bioaccumulation from bedded sediments. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, D.; Dillon, T.M.

1993-09-01

In previous studies with San Francisco Bay sediments, minimal chronic sublethal effects were detected (Miscellaneous Paper D-93-1 and another Miscellaneous Paper in preparation by Moore and Dillon). To ensure that the lack of effects was not due to a lack of contaminant uptake, a bioaccumulation experiment was conducted. Bioaccumulation from bedded sediments was evaluated following a 9-week exposure with the marine polychaete worm Nereis (Neanthes) arenaceodentata. Two sediments were evaluated, a contaminated San Francisco Bay test sediment and a clean control sediment from Sequim, WA. Animals were exposed as early juveniles through adulthood. Tissues were analyzed for metals, polyaromatic hydrocarbonsmore » (PAHs), polychlorinated biphenyls (PCBs), and pesticides. Worms exposed to the contaminated San Francisco Bay sediment had significantly higher tissue residues of silver (0.30 mg/kg dry weight) and tributyltin (0.298 mg/kg dry weight). Conversely, tissue residues of control animals were significantly higher in cadmium (0.67 mg/kg dry weight) and lead (1.89 mg/kg dry weight). Small Amounts (0.02 mg/kg dry weight) of aldrin and dieldrin were measured in worms exposed to the contaminated sediment, while dieldrin and 8-BHC were found in Bioaccumulation, Neanthes, Chronic sublethal, San Francisco Bay, Dredged, Material, Sediment.« less

Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verreth, Wim; Verhamme, Peter; Pelat, Michael

2003-09-01

Weight-loss in obese insulin-resistant, but not in insulin-sensitive, persons reduces CHD risk. It is not known to what extent changes in the adipose gene expression profile are important for reducing CHD risk. We studied the effect of diet restriction-induced weight-loss on gene expression in adipose tissue, atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia and insulin-resistance are associated with hypertension, impaired left ventricle function and accelerated atherosclerosis in those mice. Diet restriction during 12 weeks caused a 45% weight-loss and changes in the gene expression in adipose tissue of PPARa and PPAR? and ofmore » key genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. These changes were associated with increased insulin-sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. Thus, induction of PPARa and PPAR? in adipose tissue is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight-loss. Our observations point to the critical role of PPARs in the pathogenesis of cardiovascular features of the metabolic syndrome.« less

Transgenic rescue of adipocyte glucose-dependent insulinotropic polypeptide receptor expression restores high fat diet-induced body weight gain.

PubMed

Ugleholdt, Randi; Pedersen, Jens; Bassi, Maria Rosaria; Füchtbauer, Ernst-Martin; Jørgensen, Signe Marie; Kissow, Hanne-Louise; Nytofte, Nikolaj; Poulsen, Steen Seier; Rosenkilde, Mette Marie; Seino, Yutaka; Thams, Peter; Holst, Peter Johannes; Holst, Jens Juul

2011-12-30

The glucose-dependent insulinotropic polypeptide receptor (GIPr) has been implicated in high fat diet-induced obesity and is proposed as an anti-obesity target despite an uncertainty regarding the mechanism of action. To independently investigate the contribution of the insulinotropic effects and the direct effects on adipose tissue, we generated transgenic mice with targeted expression of the human GIPr to white adipose tissue or beta-cells, respectively. These mice were then cross-bred with the GIPr knock-out strain. The central findings of the study are that mice with GIPr expression targeted to adipose tissue have a similar high fat diet -induced body weight gain as control mice, significantly greater than the weight gain in mice with a general ablation of the receptor. Surprisingly, this difference was due to an increase in total lean body mass rather than a gain in total fat mass that was similar between the groups. In contrast, glucose-dependent insulinotropic polypeptide-mediated insulin secretion does not seem to be important for regulation of body weight after high fat feeding. The study supports a role of the adipocyte GIPr in nutrient-dependent regulation of body weight and lean mass, but it does not support a direct and independent role for the adipocyte or beta-cell GIPr in promoting adipogenesis.

Step changes in leaf oil accumulation via iterative metabolic engineering.

PubMed

Vanhercke, Thomas; Divi, Uday K; El Tahchy, Anna; Liu, Qing; Mitchell, Madeline; Taylor, Matthew C; Eastmond, Peter J; Bryant, Fiona; Mechanicos, Anna; Blundell, Cheryl; Zhi, Yao; Belide, Srinivas; Shrestha, Pushkar; Zhou, Xue-Rong; Ral, Jean-Philippe; White, Rosemary G; Green, Allan; Singh, Surinder P; Petrie, James R

2017-01-01

Synthesis and accumulation of plant oils in the entire vegetative biomass offers the potential to deliver yields surpassing those of oilseed crops. However, current levels still fall well short of those typically found in oilseeds. Here we show how transcriptome and biochemical analyses pointed to a futile cycle in a previously established Nicotiana tabacum line, accumulating up to 15% (dry weight) of the storage lipid triacylglycerol in leaf tissue. To overcome this metabolic bottleneck, we either silenced the SDP1 lipase or overexpressed the Arabidopsis thaliana LEC2 transcription factor in this transgenic background. Both strategies independently resulted in the accumulation of 30-33% triacylglycerol in leaf tissues. Our results demonstrate that the combined optimization of de novo fatty acid biosynthesis, storage lipid assembly and lipid turnover in leaf tissue results in a major overhaul of the plant central carbon allocation and lipid metabolism. The resulting further step changes in oil accumulation in the entire plant biomass offers the possibility of delivering yields that outperform current oilseed crops. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The Whitening of Brown Fat and Its Implications for Weight Management in Obesity.

PubMed

Shimizu, Ippei; Walsh, Kenneth

2015-06-01

Systemic inflammation resulting from dysfunction of white adipose tissue (WAT) accelerates the pathologies of diabetes and cardiovascular diseases. In contrast to WAT, brown adipose tissue (BAT) is abundant in mitochondria that produce heat by uncoupling respiratory chain process of ATP synthesis. Besides BAT's role in thermogenesis, accumulating evidence has shown that it is involved in regulating systemic metabolism. Studies have analyzed the "browning" processes of WAT as a means to combat obesity, whereas few studies have focused on the impact and molecular mechanisms that contribute to obesity-linked BAT dysfunction--a process that is associated with the "whitening" of this tissue. Compared to WAT, a dense vascular network is required to support the high energy consumption of BAT. Recently, vascular rarefaction was shown to be a significant causal factor in the whitening of BAT in mouse models. Vascular insufficiency leads to mitochondrial dysfunction and loss in BAT and contributes to systemic insulin resistance. These data suggest that BAT "whitening," resulting from vascular dysfunction, can impact obesity and obesity-linked diseases. Conversely, agents that promote BAT function could have utility in the treatment of these conditions.

Ganoderma Lucidum Protects Rat Brain Tissue Against Trauma-Induced Oxidative Stress.

PubMed

Özevren, Hüseyin; İrtegün, Sevgi; Deveci, Engin; Aşır, Fırat; Pektanç, Gülsüm; Deveci, Şenay

2017-10-01

Traumatic brain injury causes tissue damage, breakdown of cerebral blood flow and metabolic regulation. This study aims to investigate the protective influence of antioxidant Ganoderma lucidum ( G. lucidum ) polysaccharides (GLPs) on brain injury in brain-traumatized rats. Sprague-Dawley conducted a head-traumatized method on rats by dropping off 300 g weight from 1 m height. Groups were categorized as control, G. lucidum , trauma, trauma+ G. lucidum (20 mL/kg per day via gastric gavage). Brain tissues were dissected from anesthetized rats 7 days after injury. For biochemical analysis, malondialdehyde, glutathione and myeloperoxidase values were measured. In histopathological examination, neuronal damage in brain cortex and changes in blood brain barrier were observed. In the analysis of immunohistochemical and western blot, p38 mitogen-activated protein kinase, vascular endothelial growth factor and cluster of differentiation 68 expression levels were shown. These analyzes demonstrated the beneficial effects of GLPs on brain injury. We propose that GLPs treatment after brain injury could be an alternative treatment to decraseing inflammation and edema, preventing neuronal and glial cells degeneration if given in appropriate dosage and in particular time intervals.

Tissue-Specific Analysis of Secondary Metabolites Creates a Reliable Morphological Criterion for Quality Grading of Polygoni Multiflori Radix.

PubMed

Liang, Li; Xu, Jun; Liang, Zhi-Tao; Dong, Xiao-Ping; Chen, Hu-Biao; Zhao, Zhong-Zhen

2018-05-08

In commercial herbal markets, Polygoni Multiflori Radix (PMR, the tuberous roots of Polygonum multiflorum Thunb.), a commonly-used Chinese medicinal material, is divided into different grades based on morphological features of size and weight. While more weight and larger size command a higher price, there is no scientific data confirming that the more expensive roots are in fact of better quality. To assess the inherent quality of various grades and of various tissues in PMR and to find reliable morphological indicators of quality, a method combining laser microdissection (LMD) and ultra-performance liquid chromatography triple-quadrupole mass spectrometry (UPLC-QqQ-MS/MS) was applied. Twelve major chemical components were quantitatively determined in both whole material and different tissues of PMR. Determination of the whole material revealed that traditional commercial grades based on size and weight of PRM did not correspond to any significant differences in chemical content. Instead, tissue-specific analysis indicated that the morphological features could be linked with quality in a new way. That is, PMR with broader cork and phloem, as seen in a transverse section, were typically of better quality as these parts are where the bioactive components accumulate. The tissue-specific analysis of secondary metabolites creates a reliable morphological criterion for quality grading of PMR.

Comparison of microdialysis sampling perfusion fluid components on the foreign body reaction in rat subcutaneous tissue.

PubMed

Keeler, Geoffrey D; Durdik, Jeannine M; Stenken, Julie A

2014-06-16

Microdialysis sampling is a commonly used technique for collecting solutes from the extracellular space of tissues in laboratory animals and humans. Large molecular weight solutes can be collected using high molecular weight cutoff (MWCO) membranes (100kDa or greater). High MWCO membranes require addition of high molecular weight dextrans or albumin to the perfusion fluid to prevent fluid loss via ultrafiltration. While these perfusion fluid additives are commonly used during microdialysis sampling, the tissue response to the loss of these compounds across the membrane is poorly understood. Tissue reactions to implanted microdialysis sampling probes containing different microdialysis perfusion fluids were compared over a 7-day time period in rats. The base perfusion fluid was Ringer's solution supplemented with either bovine serum albumin (BSA), rat serum albumin (RSA), Dextran-70, or Dextran-500. A significant inflammatory response to Dextran-70 was observed. No differences in the tissue response between BSA and RSA were observed. Among these agents, the BSA, RSA, and Dextran-500 produced a significantly reduced inflammatory response compared to the Dextran-70. This work demonstrates that use of Dextran-70 in microdialysis sampling perfusion fluids should be eliminated and replaced with Dextran-500 or other alternatives. Copyright © 2013 Elsevier B.V. All rights reserved.

Zinc-α2-Glycoprotein Expression in Adipose Tissue of Obese Postmenopausal Women before and after Weight Loss with and without Exercise

PubMed Central

Ge, Shealinna; Ryan, Alice S.

2014-01-01

Objective Zinc-Alpha 2-Glycoprotein (ZAG) has recently been implicated in the regulation of adipose tissue metabolism due to its negative association with obesity and insulin resistance. The purpose of this study is to investigate the relationships between adipose tissue ZAG expression and central obesity, and the effects of six-months of weight loss (WL) or aerobic exercise + weight loss (AEX+WL) on ZAG expression. Design and Methods A six-month, longitudinal study of 33 healthy, overweight or obese postmenopausal women (BMI: 25–46 kg/m2) was conducted. Abdominal and gluteal adipose tissue samples were obtained before and after AEX+WL (n=17) and WL (n=16). ZAG expression was determined by RT-PCR. Results Prior to interventions, abdominal ZAG expression was negatively correlated with visceral fat (r=−0.50, P<0.005), sagittal diameter (r=−0.42, P<0.05), and positively related to VO2max (r=0.37, P<0.05). Gluteal ZAG expression was negatively correlated with weight, fat-free mass, visceral fat, resting metabolic rate, and fasting insulin (r=−0.39 to −0.50, all P<0.05). Abdominal ZAG mRNA levels increased, though not significantly, 5% after AEX+WL and 11% after WL. Gluteal ZAG mRNA levels also did not change significantly with AEX+WL and WL. Conclusions Abdominal ZAG expression may be important in central fat accumulation and fitness that modestly but not significantly increases with weight reduction alone or with aerobic training in obese postmenopausal women. PMID:24929893

Inflammation in Polycystic Ovary Syndrome: Underpinning of insulin resistance and ovarian dysfunction

PubMed Central

González, Frank

2012-01-01

Chronic low-grade inflammation has emerged as a key contributor to the pathogenesis of Polycystic Ovary Syndrome (PCOS). A dietary trigger such as glucose is capable of inciting oxidative stress and an inflammatory response from mononuclear cells (MNC) of women with PCOS, and this phenomenon is independent of obesity. This is important because MNC-derived macrophages are the primary source of cytokine production in excess adipose tissue, and also promote adipocyte cytokine production in a paracrine fashion. The proinflammatory cytokine tumor necrosis factor-α (TNFα) is a known mediator of insulin resistance. Glucose-stimulated TNFα release from MNC along with molecular markers of inflammation are associated with insulin resistance in PCOS. Hyperandrogenism is capable of activating MNC in the fasting state, thereby increasing MNC sensitivity to glucose; and this may be a potential mechanism for promoting diet-induced inflammation in PCOS. Increased abdominal adiposity is prevalent across all weight classes in PCOS, and this inflamed adipose tissue contributes to the inflammatory load in the disorder. Nevertheless, glucose ingestion incites oxidative stress in normal weight women with PCOS even in the absence of increased abdominal adiposity. In PCOS, markers of oxidative stress and inflammation are highly correlated with circulating androgens. Chronic suppression of ovarian androgen production does not ameliorate inflammation in normal weight women with the disorder. Furthermore, in vitro studies have demonstrated the ability of pro-inflammatory stimuli to upregulate the ovarian theca cell steroidogenic enzyme responsible for androgen production. These findings support the contention that inflammation directly stimulates the polycystic ovary to produce androgens. PMID:22178787

IGFBP4 Is Required for Adipogenesis and Influences the Distribution of Adipose Depots.

PubMed

Maridas, David E; DeMambro, Victoria E; Le, Phuong T; Mohan, Subburaman; Rosen, Clifford J

2017-10-01

Insulinlike growth factor (IGF) I induces adipogenesis in vitro. IGF-binding protein 4 (IGFBP4) is highly expressed in adipocytes and osteoblasts and is inhibitory of IGFs in vitro. We previously reported that Igfbp4 null mice (Igfbp4-/-) had decreased fat proportions at 8 and 16 weeks of age. However, the mechanism leading to the reduced adiposity remains unknown. The purpose of this study was to elucidate how IGFBP4 mediates adipose tissue development in vivo. Our results showed that inguinal and gonadal white adipose tissue (gWAT) from Igfbp4-/- mice had decreased weights and Pparγ expression. Cultures of primary bone marrow stromal cells (BMSCs) and ear mesenchymal stem cells (eMSCs) from mutant mice showed reduced adipogenesis. Both BMSCs and eMSC had a strong induction of Igfbp4 expression during adipogenesis. Furthermore, the increase in phosphorylated Akt (p-Akt), a downstream target of IGF-I signaling, in wild-type cells, was blunted in mutant eMSCs. On a high-fat diet (HFD) there were sexual differences in adipocyte expansion of Igfbp4-/- mice. Mutant males gained weight by expanding their white fat depots. However, Igfbp4-/- female mice were protected against diet-induced obesity. Ovariectomized Igfbp4-/- female mice gained weight in a manner similar to that seen in ovariectomized controls. Thus, Igfbp4 is required for inguinal fat expansion in female mice but not in male mice. However, gWAT expansion, which is prevented by estrogen during HFD, does not require Igfbp4. Copyright © 2017 Endocrine Society.

Leptin and its role in lipid metabolism.

PubMed

Hynes, G R; Jones, P J

2001-06-01

Since the discovery of leptin in 1994, a considerable amount of research has focused on leptin as a central regulator of body weight. In the animal model, research has demonstrated leptin action through hypothalamic centres altering both satiety and energy expenditure. In contrast to animal studies, it is unlikely that leptin functioning in the human system exerts such a profound role in body weight regulation. Human studies suggest that leptin levels are strongly correlated with both percentage fat mass and body mass index, in accordance with the proposed 'lipostatic theory'. Current research suggests the existence of a unique inter-relationship between dietary fat, leptin expression and leptin action within the peripheral system. More specifically, it has been demonstrated that polyunsaturated fatty acid (PUFA) intake influences adipose tissue expression of leptin, and of several lipogenic enzymes and transcription factors. In addition, leptin stimulates triglyceride depletion in white adipose tissue without increasing free fatty acid release, thus favouring fatty acids versus glucose as a fuel source. Recent studies suggest that the reduction in adipose hypertrophy observed with n-3 PUFA-containing fish oil feeding might involve a leptin-specific process. A large amount of evidence supports direct functioning of leptin in peripheral lipid metabolism in vivo and in vitro. It is possible that PUFAs will maintain an efficient level of circulating leptin, thus preventing leptin insensitivity and weight gain. There has been much recent progress in clinical leptin research, from energy expenditure to leptin analogue efficacy; the purpose of the present review is to summarize our current understanding of leptin functioning.

Colonic Absorption of Low-Molecular-Weight Metabolites Influenced by the Intestinal Microbiome: A Pilot Study.

PubMed

Matsumoto, Mitsuharu; Ooga, Takushi; Kibe, Ryoko; Aiba, Yuji; Koga, Yasuhiro; Benno, Yoshimi

2017-01-01

Low-molecular-weight metabolites produced by the intestinal microbiome play a direct role in health and disease. However, little is known about the ability of the colon to absorb these metabolites. It is also unclear whether these metabolites are bioavailable. Here, metabolomics techniques (capillary electrophoresis with time-of-flight mass spectrometry, CE-TOFMS), germ-free (GF) mice, and colonized (Ex-GF) mice were used to identify the colonic luminal metabolites transported to colonic tissue and/or blood. We focused on the differences in each metabolite between GF and Ex-GF mice to determine the identities of metabolites that are transported to the colon and/or blood. CE-TOFMS identified 170, 246, 166, and 193 metabolites in the colonic feces, colonic tissue, portal plasma, and cardiac plasma, respectively. We classified the metabolites according to the following influencing factors: (i) the membrane transport system of the colonocytes, (ii) metabolism during transcellular transport, and (iii) hepatic metabolism based on the similarity in the ratio of each metabolite between GF and Ex-GF mice and found 62 and 22 metabolites that appeared to be absorbed from the colonic lumen to colonocytes and blood, respectively. For example, 11 basic amino acids were transported to the systemic circulation from the colonic lumen. Furthermore, many low-molecular-weight metabolites influenced by the intestinal microbiome are bioavailable. The present study is the first to report the transportation of metabolites from the colonic lumen to colonocytes and somatic blood in vivo, and the present findings are critical for clarifying host-intestinal bacterial interactions.

Early postnatal feed restriction reduces liver connective tissue levels and affects H3K9 acetylation state of regulated genes associated with protein metabolism in low birth weight pigs.

PubMed

Nebendahl, Constance; Görs, Solvig; Albrecht, Elke; Krüger, Ricarda; Martens, Karen; Giller, Katrin; Hammon, Harald M; Rimbach, Gerald; Metges, Cornelia C

2016-03-01

Intrauterine growth retardation is associated with metabolic consequences in adulthood. Since our previous data indicate birth weight-dependent effects of feed restriction (R) on protein degradation processes in the liver, it should be investigated whether effects on connective tissue turnover are obvious and could be explained by global changes of histone H3K9me3 and H3K9ac states in regulated genes. For this purpose, female littermate pigs with low (U) or normal (N) birth weight were subjected to 3-week R (60% of ad libitum fed controls) with subsequent refeeding (REF) for further 5 weeks. The 3-week R-period induced a significant reduction of connective tissue area by 43% in the liver of U animals at 98 d of age, which was not found in age-matched N animals. Of note, after REF at 131 d of age, in previously feed-restricted U animals (UR), the percentage of mean connective tissue was only 53% of ad libitum fed controls (UK), indicating a persistent effect. In U animals, R induced H3K9 acetylation of regulated genes (e.g. XBP1, ERLEC1, GALNT2, PTRH2), which were inter alia associated with protein metabolism. In contrast, REF was mostly accompanied by deacetylation in U and N animals. Thus, our epigenetic data may give a first explanation for the observed birth weight-dependent differences in this connective tissue phenotype. Copyright © 2015 Elsevier Inc. All rights reserved.

75 FR 42067 - Certain Tissue Paper Products From the People's Republic of China: Notice of Continuation of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-20

... tissue paper products covered by the order are cut-to-length sheets of tissue paper having a basis weight..., and/or die cut. The tissue paper subject to the order is in the form of cut-to-length sheets of tissue... folded, and may be packaged by banding or wrapping with paper or film, by placing in plastic or film bags...

Light controls phospholipase A2α and β gene expression in Citrus sinensis

PubMed Central

Liao, Hui-Ling; Burns, Jacqueline K.

2010-01-01

The low-molecular weight secretory phospholipase A2α (CssPLA2α) and β (CsPLA2β) cloned in this study exhibited diurnal rhythmicity in leaf tissue of Citrus sinensis. Only CssPLA2α displayed distinct diurnal patterns in fruit tissues. CssPLA2α and CsPLA2β diurnal expression exhibited periods of approximately 24 h; CssPLA2α amplitude averaged 990-fold in the leaf blades from field-grown trees, whereas CsPLA2β amplitude averaged 6.4-fold. Diurnal oscillation of CssPLA2α and CsPLA2β gene expression in the growth chamber experiments was markedly dampened 24 h after transfer to continuous light or dark conditions. CssPLA2α and CsPLA2β expressions were redundantly mediated by blue, green, red and red/far-red light, but blue light was a major factor affecting CssPLA2α and CsPLA2β expression. Total and low molecular weight CsPLA2 enzyme activity closely followed diurnal changes in CssPLA2α transcript expression in leaf blades of seedlings treated with low intensity blue light (24 μmol m−2 s−1). Compared with CssPLA2α basal expression, CsPLA2β expression was at least 10-fold higher. Diurnal fluctuation and light regulation of PLA2 gene expression and enzyme activity in citrus leaf and fruit tissues suggests that accompanying diurnal changes in lipophilic second messengers participate in the regulation of physiological processes associated with phospholipase A2 action. PMID:20388744

Abdominoplasty and seroma: a prospective randomised study comparing scalpel and handheld electrocautery dissection.

PubMed

Marsh, Dan J; Fox, Andreas; Grobbelaar, Adriaan O; Chana, Jagdeep S

2015-02-01

Seroma formation remains a significant problem in abdominoplasty procedures--the cause of which remains to be elucidated. It has been suggested that one of the causative factors for seroma formation is the use of handheld electrocautery as opposed to scalpel for abdominal flap dissection. Prospective trial in 102 consecutive abdominoplasty patients randomised to have abdominal flap dissection with either handheld electrocautery device on 'coagulation setting' or sharp dissection with scalpel and monopolar electrocautery forceps for haemostasis. In all other aspects the surgical technique was identical between the two groups. All drains were removed at 48 h, irrespective of drain volume. Primary outcome measure is postoperative seroma formation on clinical examination, secondary outcome measures are drain volume, weight of tissue removed, effect of liposuction and patient BMI. Both study groups were similar in demographics with no significant difference in weight of tissue excised, BMI, drain output or post operative complictions. There was no significant difference in seroma formation rates between the handheld electrocautery group (17.2%) and the sharp dissection group (20.1%). Overall, the seroma rate was 18.6%. Liposuction to the flanks at the time of abdominoplasty was found to significantly increase the incidence of seroma, compared to patients having abdominoplasty alone. Use of handheld electrocautery rather than scalpel for tissue dissection does not lead to increased seroma formation in abdominoplasty patients. Concomitant liposuction at the time of abdominoplasty increases the risk of seroma formation compared to patients having abdominoplasty alone. Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Meng; Cao, Xia; Jia, Qingli

Triacylglycerol (TAG) is the main storage lipid in plant seeds and the major form of plant oil used for food and, increasingly, for industrial and biofuel applications. Several transcription factors, including FUSCA3 (At3 g26790, FUS3), are associated with embryo maturation and oil biosynthesis in seeds. However, the ability of FUS3 to increase TAG biosynthesis in other tissues has not been quantitatively examined. Here, we evaluated the ability of FUS3 to activate TAG accumulation in non-seed tissues. Overexpression of FUS3 driven by an estradiol-inducible promoter increased oil contents in Arabidopsis seedlings up to 6% of dry weight; more than 50-fold overmore » controls. Eicosenoic acid, a characteristic fatty acid of Arabidopsis seed oil, accumulated to over 20% of fatty acids in cotyledons and leaves. These large increases depended on added sucrose, although without sucrose TAG increased three- to four-fold. Inducing the expression of FUS3 in tobacco BY2 cells also increased TAG accumulation, and co-expression of FUS3 and diacylglycerol acyltransferase 1 (DGAT1) further increased TAG levels to 4% of dry weight. BY2 cell growth was not altered by FUS3 expression, although Arabidopsis seedling development was impaired, consistent with the ability of FUS3 to induce embryo characteristics in non-seed tissues. Microarrays of Arabidopsis seedlings revealed that FUS3 overexpression increased the expression of a higher proportion of genes involved in TAG biosynthesis than genes involved in fatty acid biosynthesis or other lipid pathways. Together these results provide additional insights into FUS3 functions in TAG metabolism and suggest complementary strategies for engineering vegetative oil accumulation.« less

Ashitaba (Angelica Keiskei) Exudate Prevents Increases in Plasminogen Activator Inhibitor-1 Induced by Obesity in Tsumura Suzuki Obese Diabetic Mice.

PubMed

Ohta, Mitsuhiro; Fujinami, Aya; Oishi, Katsutaka; Kobayashi, Norihiro; Ohnishi, Katsunori; Ohkura, Naoki

2018-04-30

Angelica keiskei koidzumi (ashitaba) is consumed as a traditional folk medicine and health food in Japan. Ashitaba extract contains abundant flavonoids containing chalcones. Plasminogen activator inhibitor-1 (PAI-1) is the primary physiological inhibitor of tissue plasminogen activator. Excessive amounts of PAI-1 in plasma disrupt the fibrinolytic balance and promote a prothrombotic state with which thrombosis and cardiovascular diseases are associated. In the present study, we investigated the effects of ashitaba yellow exudate (AE) on enhanced PAI-1 levels in Tsumura Suzuki obese diabetic (TSOD) mice. AE significantly decreased food efficiency and plasma PAI-1 in TSOD mice but did not affect lean control Tsumura Suzuki nonobese (TSNO) mice. AE also decreased some parameters in the plasma, such as glucose, insulin, tumor necrosis factor alpha (TNF-α) and gains in body weight, subcutaneous, mesenteric fat weight in TSOD mice but had little effect on these parameters in TSNO mice. Levels of adipose PAI-1 were significantly higher in TSOD than in TSNO mice. Major sources of plasma PAI-1 are thought to be adipose tissue and liver. AE significantly suppressed PAI-1 protein levels in the livers of both TSOD and TSNO mice. These results suggest that AE decreased plasma PAI-1 levels by suppressing both the adipose tissue retention of PAI-1 protein and liver PAI-1 production in TSOD mice. Supplementing the diet with AE might help to prevent thrombotic diseases or alleviate the risk of thrombotic diseases as well as to suppress metabolic state in obese individuals.

Carbamylated erythropoietin ameliorates the metabolic stress induced in vivo by severe chronic hypoxia

PubMed Central

Fantacci, Monica; Bianciardi, Paola; Caretti, Anna; Coleman, Thomas R.; Cerami, Anthony; Brines, Michael; Samaja, Michele

2006-01-01

Ischemia and chronic hypoxia (CH) trigger a variety of adverse effects arising from metabolic stress that injures cells. In response to reduced O2, hypoxia-inducible factor 1α (HIF-1α) activates erythropoietin (Epo) as well as many other target genes that counteract the effects of O2 deficiency. Epo produced by the kidney stimulates erythrocyte production, leading to decreased HIF-1α production by improved tissue O2 delivery. However, Epo is produced by many other tissues, and it is currently unclear to what extent, if any, locally produced Epo modulates HIF-1α expression. Derivatives of Epo that possess tissue-protective activities but do not stimulate erythropoiesis [e.g., carbamylated Epo (CEpo)] are useful tools with which to determine whether exogenous Epo modulates HIF-1α in the absence of changes in hemoglobin concentration. We compared the effects of CH (6.5% O2 for 10 days) with or without CEpo administered by daily s.c. injection (10 μg/kg of body weight). CEpo administration did not alter the survival rate, weight loss, or increased hemoglobin concentration associated with CH. Therefore, CEpo does not directly suppress HIF-mediated erythropoiesis. CEpo does, however, prevent CH-induced neuronal increases of HIF-1α and Epo receptor-associated immunoreactivity (a measure of stress) while reducing the apoptotic index. In contrast, the myocardium did not exhibit increased HIF-1α expression during CH, although CEpo did reduce the apoptotic index. These observations therefore demonstrate that CEpo administration reduces the metabolic stress caused by severe CH, resulting in improved cellular survival independent of erythrocyte production. PMID:17090665

How Does Physical Activity Help Build Healthy Bones?

MedlinePlus

... Share Facebook Twitter Pinterest Email Print How does physical activity help build healthy bones? Bones are living tissue. Weight-bearing physical activity causes new bone tissue to form, and this ...

Activation of natriuretic peptides and the sympathetic nervous system following Roux-en-Y gastric bypass is associated with gonadal adipose tissues browning

PubMed Central

Neinast, Michael D.; Frank, Aaron P.; Zechner, Juliet F.; Li, Quanlin; Vishvanath, Lavanya; Palmer, Biff F.; Aguirre, Vincent; Gupta, Rana K.; Clegg, Deborah J.

2015-01-01

Objective Roux-en-Y gastric bypass (RYGB) is an effective method of weight loss and remediation of type-2 diabetes; however, the mechanisms leading to these improvements are unclear. Additionally, adipocytes within white adipose tissue (WAT) depots can manifest characteristics of brown adipocytes. These ‘BRITE/beige’ adipocytes express uncoupling protein 1 (UCP1) and are associated with improvements in glucose homeostasis and protection from obesity. Interestingly, atrial and B-type natriuretic peptides (NPs) promote BRITE/beige adipocyte enrichment of WAT depots, an effect known as “browning.” Here, we investigate the effect of RYGB surgery on NP, NP receptors, and browning in the gonadal adipose tissues of female mice. We propose that such changes may lead to improvements in metabolic homeostasis commonly observed following RYGB. Methods Wild type, female, C57/Bl6 mice were fed a 60% fat diet ad libitum for six months. Mice were divided into three groups: Sham operated (SO), Roux-en-Y gastric bypass (RYGB), and Weight matched, sham operated (WM-SO). Mice were sacrificed six weeks following surgery and evaluated for differences in body weight, glucose homeostasis, adipocyte morphology, and adipose tissue gene expression. Results RYGB and calorie restriction induced similar weight loss and improved glucose metabolism without decreasing food intake. β3-adrenergic receptor expression increased in gonadal adipose tissue, in addition to Nppb (BNP), and NP receptors, Npr1, and Npr2. The ratio of Npr1:Npr3 and Npr2:Npr3 increased in RYGB, but not WM-SO groups. Ucp1 protein and mRNA, as well as additional markers of BRITE/beige adipose tissue and lipolytic genes increased in RYGB mice to a greater extent than calorie-restricted mice. Conclusions Upregulation of Nppb, Npr1, Npr2, and β3-adrenergic receptors in gonadal adipose tissue following RYGB was associated with increased markers of browning. This browning of gonadal adipose tissue may underpin the positive effect of RYGB on metabolic parameters and may in part be mediated through upregulation of natriuretic peptides. PMID:25973390

Feeding feedlot steers fish oil alters the fatty acid composition of adipose and muscle tissue.

PubMed

Wistuba, T J; Kegley, E B; Apple, J K; Rule, D C

2007-10-01

Sixteen steers (441±31.7kg initial body weight) consumed two high concentrate diets with either 0 or 3% fish oil to determine the impact of fish oil, an omega-3 fatty acid source, on the fatty acid composition of beef carcasses. Collected tissue samples included the Longissimus thoracis from the 6th to 7th rib section, ground 10th to 12th rib, liver, subcutaneous adipose tissue adjacent to the 12th rib, intramuscular adipose tissue in the 6th to 7th rib sections, perirenal adipose tissue, and brisket adipose tissue. Including fish oil in the diet increased most of the saturated fatty acids (P<0.01) and proportions of polyunsaturated fatty acids (P<0.06), and decreased (P<0.01) proportions of monounsaturated fatty acids. Dietary fish oil increased (P<0.01) levels of omega-3 fatty acids in sampled tissues, resulting in lower (P<0.01) omega-6:omega-3 ratios. The weight percentages of C20:5 and C22:6 in tissue may provide the recommended daily allowance for humans. Fish oil may have a role in beef niche marketing if there are no deleterious effects on consumer satisfaction.

Assessment of Impact of Weight Loss on Left and Right Ventricular Functions and Value of Tissue Doppler Echocardiography in Obese Patients.

PubMed

Yuksel, Isa Oner; Akar Bayram, Nihal; Koklu, Erkan; Ureyen, Cagin Mustafa; Kucukseymen, Selcuk; Arslan, Sakir; Bozkurt, Engin

2016-06-01

In our study, we aimed to evaluate the effect of weight loss on left and right ventricular functions in obese patients. Thirty patients with a BMI greater than 30 kg/m(2) and without any exclusion criteria were included in the study. Left ventricular systolic and diastolic functions were assessed with conventional and tissue Doppler echocardiography (TDE). At the end of 3 months, echocardiographic examination was repeated in patients with weight loss for cardiac function evaluation and it was compared to the baseline echocardiographic parameters. At the end of 3 months of weight loss period, conventional Doppler echocardiography revealed an improvement in diastolic functions with an increase in mitral E-wave, a decrease in mitral A-wave and an increase in E/A ratio. Deceleration time and isovolumetric relaxation time were ascertained shortened and Tei index decreased. TDE showed an increase in left ventricular lateral wall systolic wave (Sm) and E-wave velocity (Em). Mitral septal annular isovolumetric acceleration time (IVA), Sm and Em, were found to be increased, whereas Tei index was ascertained reduced. Right ventricular tissue Doppler examination following weight loss revealed an increase in RV- IVA, RV-Sm, and RV-Em, and a decrease in Tei index. We disclosed that left ventricular structural changes and diastolic dysfunction occur in obese patients, and by weight loss, these abnormalities may be reversible which we demonstrated both by conventional and TDE. In addition, obesity might impair RV function as well, and we observed an enhancement in right ventricular functions by weight loss. © 2016, Wiley Periodicals, Inc.

Association between subcutaneous white adipose tissue and serum 25-hydroxyvitamin D in overweight and obese adults.

PubMed

Piccolo, Brian D; Dolnikowski, Gregory; Seyoum, Elias; Thomas, Anthony P; Gertz, Erik R; Souza, Elaine C; Woodhouse, Leslie R; Newman, John W; Keim, Nancy L; Adams, Sean H; Van Loan, Marta D

2013-08-26

Cholecalciferol is known to be deposited in human adipose tissue, but it is not known whether 25-hydroxyvitamin D (25(OH)D) is found in detectable concentrations. Therefore, our objective was to determine whether 25(OH)D is detectable in subcutaneous white adipose tissue (SWAT) in overweight and obese persons enrolled in a twelve week energy restricted diet. Baseline and post-intervention gluteal SWAT biopsies were collected from 20 subjects participating in a larger clinical weight loss intervention. LC-MS/MS was utilized to determine SWAT 25(OH)D concentrations. Serum 25(OH)D and 1,25(OH)2D were measured by RIA. Body composition was assessed by dual energy x-ray absorptiometry. SWAT 25(OH)D concentrations were 5.8 ± 2.6 nmol/kg tissue and 6.2 ± 2.7 nmol/kg tissue pre- and post-intervention SWAT, respectively. There was a significant positive association between SWAT 25(OH)D concentration and serum 25(OH)D concentration (r = 0.52, P < 0.01). Both SWAT and serum 25(OH)D concentrations did not significantly change after a twelve-week period of energy restriction with approximately 5 kg of fat loss. In conclusion, we have demonstrated our LC-MS/MS method can detect 25(OH)D3 in human subcutaneous fat tissue from overweight and obese individuals and is consistent with previously reported concentrations in swine. Additionally, our findings of no significant changes in SWAT 25(OH)D3 or serum 25(OH)D after a 6% loss of total body weight and 13% reduction in total fat provides the first human evidence that adipose 25(OH)D does not likely contribute to serum 25(OH)D with moderate weight loss; whether this is also the case with larger amounts of weight loss is unknown. Weight loss alone is not sufficient to increase serum 25(OH)D and increases in dietary or dermal biosynthesis of vitamin D appear to be the most critical contributors to in vitamin D status.

Cascaded systems analysis of noise and detectability in dual-energy cone-beam CT

PubMed Central

Gang, Grace J.; Zbijewski, Wojciech; Webster Stayman, J.; Siewerdsen, Jeffrey H.

2012-01-01

Purpose: Dual-energy computed tomography and dual-energy cone-beam computed tomography (DE-CBCT) are promising modalities for applications ranging from vascular to breast, renal, hepatic, and musculoskeletal imaging. Accordingly, the optimization of imaging techniques for such applications would benefit significantly from a general theoretical description of image quality that properly incorporates factors of acquisition, reconstruction, and tissue decomposition in DE tomography. This work reports a cascaded systems analysis model that includes the Poisson statistics of x rays (quantum noise), detector model (flat-panel detectors), anatomical background, image reconstruction (filtered backprojection), DE decomposition (weighted subtraction), and simple observer models to yield a task-based framework for DE technique optimization. Methods: The theoretical framework extends previous modeling of DE projection radiography and CBCT. Signal and noise transfer characteristics are propagated through physical and mathematical stages of image formation and reconstruction. Dual-energy decomposition was modeled according to weighted subtraction of low- and high-energy images to yield the 3D DE noise-power spectrum (NPS) and noise-equivalent quanta (NEQ), which, in combination with observer models and the imaging task, yields the dual-energy detectability index (d′). Model calculations were validated with NPS and NEQ measurements from an experimental imaging bench simulating the geometry of a dedicated musculoskeletal extremities scanner. Imaging techniques, including kVp pair and dose allocation, were optimized using d′ as an objective function for three example imaging tasks: (1) kidney stone discrimination; (2) iodine vs bone in a uniform, soft-tissue background; and (3) soft tissue tumor detection on power-law anatomical background. Results: Theoretical calculations of DE NPS and NEQ demonstrated good agreement with experimental measurements over a broad range of imaging conditions. Optimization results suggest a lower fraction of total dose imparted by the low-energy acquisition, a finding consistent with previous literature. The selection of optimal kVp pair reveals the combined effect of both quantum noise and contrast in the kidney stone discrimination and soft-tissue tumor detection tasks, whereas the K-edge effect of iodine was the dominant factor in determining kVp pairs in the iodine vs bone task. The soft-tissue tumor task illustrated the benefit of dual-energy imaging in eliminating anatomical background noise and improving detectability beyond that achievable by single-energy scans. Conclusions: This work established a task-based theoretical framework that is predictive of DE image quality. The model can be utilized in optimizing a broad range of parameters in image acquisition, reconstruction, and decomposition, providing a useful tool for maximizing DE-CBCT image quality and reducing dose. PMID:22894440

Body composition and cross-sectional areas of limb lean tissues in Olympic weight lifters.

PubMed

Kanehisa, H; Ikegawa, S; Fukunaga, T

1998-10-01

The cross-sectional area (CSAs) of bone and muscle tissues in the forearm, upper arm, lower leg, and thigh and body composition were determined by B-mode ultrasound and underwater weighing methods, respectively for 56 college Olympic weight lifters and 28 age-matched non-athletes to investigate the magnitude of musculoskeletal development in the strength-trained athletes belonging to the weight-classified sports event. The average value of fat-free mass (FFM) for the weight lifters ranked 12.6 kg above the regression line of FFM on stature for untrained subjects. In the weight lifters, however, the percentage of fat mass to body mass was also highly correlated to body mass index. Bone and muscle CSAs in every site were significantly larger in the weight lifter than in the untrained subjects with relative differences of 22 to 58% and 17 to 56%, respectively. Moreover, as a result of regression analysis for the mixed data from weight lifters and untrained subjects, significant correlation was found between bone and muscle CSAs in every site (r = 0.620 to 0.791, P < 0.05). The differences in lean (bone + muscle) CSA were still significant in all sites except for the lower leg even when the difference in body size was statistically controlled. The comparisons between the weight lifters and untrained subjects on the lean CSA ratios of site to site and muscle CSA ratios of flexors to extensors indicated that the weight lifters had achieved a high relative distribution of lean tissues in the arms and a dominant development in elbow and knee extensors. Thus, the present results suggested that participation in weight lifting exercises for a long period could increase bone CSA as well as muscle CSA, and induce in the participants a noticeable enlargement in given sites and muscle groups responsible for performing the Olympic lifts.

Weight gain - unintentional

MedlinePlus

... Cushing syndrome Underactive thyroid, or low thyroid (hypothyroidism) Polycystic ovary syndrome Menopause Pregnancy Bloating, or swelling due to a buildup of fluid in the tissues can cause weight gain. This may be due to menstruation, heart ...

Use of sedimentary metals to predict metal concentrations in black mussel (Mytilus galloprovincialis) tissue and risk to human health (Sydney estuary, Australia).

PubMed

Birch, G F; Apostolatos, C

2013-08-01

Filter-feeding bivalves have been used extensively as an indicator of ecosystem condition and in management of estuarine environments. The current study aimed to determine whether sedimentary metals could predict metal concentrations in tissue of filter-feeding mussels (Mytilus galloprovincialis) and to identify areas of the estuary where mussel consumption posed a human health risk. Mussel tissue Cu and Zn concentrations (wet weight) were below guideline values for human consumption in all parts of the waterway, whereas Pb tissue concentrations exceed these guidelines (2.0 μg g(-1) wet weight) in the upper reaches of some embayments of the estuary. Concentrations of Cu and Pb in the fine fraction (<62.5 μm) of bottom sediment reasonably predicted concentrations (dry weight) of these metals in mussel tissue (r (2) =0.460 and p=0.001 and r (2) =0.669 and p<0.0001, respectively) as these materials are resuspendable and available to filter-feeding estuarine animals, whereas total sediment and mussel tissue were poorly related. Lead concentrations (>350 μg g(-1)) in fine sediments indicated areas of this estuary where human health was at risk due to high tissue concentrations of this metal. These results give encouragement for the use of the metal concentration in fine sediments as an indicator of estuarine condition and risk to human health in this waterway. Mussels were distributed in all parts of the estuary, even in areas where metal concentrations exceeded sediment quality guidelines.

Preparation of a nano emodin transfersome and study on its anti-obesity mechanism in adipose tissue of diet-induced obese rats

PubMed Central

2014-01-01

Objective To describe the preparation of nano emodin transfersome (NET) and investigate its effect on mRNA expression of adipose triglyceride lipase (ATGL) and G0/G1 switch gene 2 (G0S2) in adipose tissue of diet-induced obese rats. Methods NET was prepared by film-ultrasonic dispersion method. The effects of emodin components at different ratios on encapsulation efficiency were investigated.The NET envelopment rate was determined by ultraviolet spectrophotometry. The particle size and Zeta potential of NET were evaluated by Zetasizer analyzer. Sixty male SD rats were assigned to groups randomly. After 8-week treatment, body weight, wet weight of visceral fat and the percentage of body fat (PBF) were measured. Fasting blood glucose and serum lipid levels were determined. The adipose tissue section was HE stained, and the cellular diameter and quantity of adipocytes were evaluated by light microscopy. The mRNA expression of ATGL and G0S2 from the peri-renal fat tissue was assayed by RT-PCR. Results The appropriate formulation was deoxycholic acid sodium salt vs. phospholipids 1:8, cholesterol vs. phospholipids 1:3, vitamin Evs. phospholipids 1:20, and emodin vs. phospholipid 1:6. Zeta potential was −15.11 mV, and the particle size was 292.2 nm. The mean encapsulation efficiency was (69.35 ± 0.25)%. Compared with the obese model group, body weight, wet weight of visceral fat, PBF and mRNA expression of G0S2 from peri-renal fat tissue were decreased significantly after NET treatment (all P < 0.05), while high-density lipoprotein cholesterol (HDL-C), the diameter of adipocytes and mRNA expression of ATGL from peri-renal fat tissue were increased significantly (all P < 0.05). Conclusion The preparation method is simple and reasonable. NET with negative electricity was small and uniform in particle size, with high encapsulation efficiency and stability. NET could reduce body weight and adipocyte size, and this effect was associated with the up-regulation of ATGL, down-regulation of G0S2 expression in the adipose tissue, and improved insulin sensitivity. PMID:24641917

[Smoking and changes in body weight: can physiopathology and genetics explain this association?].

PubMed

Chatkin, Raquel; Chatkin, José Miguel

2007-01-01

Tobacco use is the leading preventable cause of death in most countries, including Brazil. Smoking cessation is an important strategy for reducing the morbidity and mortality associated with tobacco-related diseases. An inverse relationship between nicotine use and body weight has been reported, in which body weight tends to be lower among smokers than among nonsmokers. Smoking abstinence results in an increase in body weight for both males and females. On average, sustained quitters gain from 5 to 6 kg, although approximately 10% gain more than 10 kg. Pharmacological treatment for smoking cessation attenuates weight gain. The importance of smoking cessation as a contributing cause of the current obesity epidemic has been little studied. In the USA, the rate of obesity attributable to smoking cessation has been estimated at approximately 6.0 and 3.2% for males and females, respectively. Although the mechanisms are unclear, there is evidence that dopamine and serotonin are appetite suppressants. The administration of nicotine, regardless of the delivery system, acutely raises the levels of these neurotransmitters in the brain, reducing the need for energy intake and consequently suppressing appetite. In addition, nicotine has a direct effect on adipose tissue metabolism, influencing the rate of weight gain following smoking cessation. Leptin, ghrelin and neuropeptide Y are substances that might constitute factors involved in the inverse relationship between nicotine and body mass index, although their roles as determinants or consequences of this relationship have yet to be determined.

Comparison of hip geometry, strength, and estimated fracture risk in women with anorexia nervosa and overweight/obese women.

PubMed

Bachmann, Katherine Neubecker; Fazeli, Pouneh K; Lawson, Elizabeth A; Russell, Brian M; Riccio, Ariana D; Meenaghan, Erinne; Gerweck, Anu V; Eddy, Kamryn; Holmes, Tara; Goldstein, Mark; Weigel, Thomas; Ebrahimi, Seda; Mickley, Diane; Gleysteen, Suzanne; Bredella, Miriam A; Klibanski, Anne; Miller, Karen K

2014-12-01

Data suggest that anorexia nervosa (AN) and obesity are complicated by elevated fracture risk, but skeletal site-specific data are lacking. Traditional bone mineral density (BMD) measurements are unsatisfactory at both weight extremes. Hip structural analysis (HSA) uses dual-energy X-ray absorptiometry data to estimate hip geometry and femoral strength. Factor of risk (φ) is the ratio of force applied to the hip from a fall with respect to femoral strength; higher values indicate higher hip fracture risk. The objective of the study was to investigate hip fracture risk in AN and overweight/obese women. This was a cross-sectional study. The study was conducted at a Clinical Research Center. PATIENTS included 368 women (aged 19-45 y): 246 AN, 53 overweight/obese, and 69 lean controls. HSA-derived femoral geometry, peak factor of risk for hip fracture, and factor of risk for hip fracture attenuated by trochanteric soft tissue (φ(attenuated)) were measured. Most HSA-derived parameters were impaired in AN and superior in obese/overweight women vs controls at the narrow neck, intertrochanteric, and femoral shaft (P ≤ .03). The φ(attenuated) was highest in AN and lowest in overweight/obese women (P < .0001). Lean mass was associated with superior, and duration of amenorrhea with inferior, HSA-derived parameters and φ(attenuated) (P < .05). Mean φ(attenuated) (P = .036), but not femoral neck BMD or HSA-estimated geometry, was impaired in women who had experienced fragility fractures. Femoral geometry by HSA, hip BMD, and factor of risk for hip fracture attenuated by soft tissue are impaired in AN and superior in obesity, suggesting higher and lower hip fracture risk, respectively. Only attenuated factor of risk was associated with fragility fracture prevalence, suggesting that variability in soft tissue padding may help explain site-specific fracture risk not captured by BMD.

Serrapeptase and nattokinase intervention for relieving Alzheimer's disease pathophysiology in rat model.

PubMed

Fadl, N N; Ahmed, H H; Booles, H F; Sayed, A H

2013-07-01

Serrapeptase (SP) and nattokinase (NK) are proteolytic enzymes belonging to serine proteases. In this study, we hypothesized that SP and NK could modulate certain factors that are associated with Alzheimer's disease (AD) pathophysiology in the experimental model. Oral administration of aluminium chloride (AlCl3) in a dose of 17 mg/kg body weight (bw) daily for 45 days induced AD-like pathology in male rats with a significant increase in brain acetylcholinesterase (AchE) activity, transforming growth factor β (TGF-β), Fas and interleukin-6 (IL-6) levels. Meanwhile, AlCl3 supplementation produced significant decrease in brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) when compared with control values. Also, AlCl3 administration caused significant decline in the expression levels of disintegrin and metalloproteinase domain 9 (ADAM9) and a disintegrin and metalloproteinase domain 10 (ADAM10) genes in the brain. Histological investigation of brain tissue of rat model of AD showed neuronal degeneration in the hippocampus and focal hyalinosis with cellular as well as a cellular amyloid plaques formation. Oral administration of SP or NK in a rat model of AD daily for 45 days resulted in a significant decrease in brain AchE activity, TGF-β, Fas and IL-6 levels. Also, the treatment with these enzymes produced significant increase in BDNF and IGF-1 levels when compared with the untreated AD-induced rats. Moreover, both SP and NK could markedly increase the expression levels of ADAM9 and ADAM10 genes in the brain tissue of the treated rats. These findings were well confirmed by the histological examination of the brain tissue of the treated rats. The present results support our hypothesis that the oral administration of proteolytitc enzymes, SP and/or NK, would have an effective role in modulating certain factors characterizing AD. Thus, these enzymes may have a therapeutic application in the treatment of AD.

Comparison of Hip Geometry, Strength, and Estimated Fracture Risk in Women With Anorexia Nervosa and Overweight/Obese Women

PubMed Central

Bachmann, Katherine Neubecker; Fazeli, Pouneh K.; Lawson, Elizabeth A.; Russell, Brian M.; Riccio, Ariana D.; Meenaghan, Erinne; Gerweck, Anu V.; Eddy, Kamryn; Holmes, Tara; Goldstein, Mark; Weigel, Thomas; Ebrahimi, Seda; Mickley, Diane; Gleysteen, Suzanne; Bredella, Miriam A.; Klibanski, Anne

2014-01-01

Context: Data suggest that anorexia nervosa (AN) and obesity are complicated by elevated fracture risk, but skeletal site-specific data are lacking. Traditional bone mineral density (BMD) measurements are unsatisfactory at both weight extremes. Hip structural analysis (HSA) uses dual-energy X-ray absorptiometry data to estimate hip geometry and femoral strength. Factor of risk (φ) is the ratio of force applied to the hip from a fall with respect to femoral strength; higher values indicate higher hip fracture risk. Objective: The objective of the study was to investigate hip fracture risk in AN and overweight/obese women. Design: This was a cross-sectional study. Setting: The study was conducted at a Clinical Research Center. Patients: Patients included 368 women (aged 19–45 y): 246 AN, 53 overweight/obese, and 69 lean controls. Main Outcome Measures: HSA-derived femoral geometry, peak factor of risk for hip fracture, and factor of risk for hip fracture attenuated by trochanteric soft tissue (φattenuated) were measured. Results: Most HSA-derived parameters were impaired in AN and superior in obese/overweight women vs controls at the narrow neck, intertrochanteric, and femoral shaft (P ≤ .03). The φattenuated was highest in AN and lowest in overweight/obese women (P < .0001). Lean mass was associated with superior, and duration of amenorrhea with inferior, HSA-derived parameters and φattenuated (P < .05). Mean φattenuated (P = .036), but not femoral neck BMD or HSA-estimated geometry, was impaired in women who had experienced fragility fractures. Conclusions: Femoral geometry by HSA, hip BMD, and factor of risk for hip fracture attenuated by soft tissue are impaired in AN and superior in obesity, suggesting higher and lower hip fracture risk, respectively. Only attenuated factor of risk was associated with fragility fracture prevalence, suggesting that variability in soft tissue padding may help explain site-specific fracture risk not captured by BMD. PMID:25062461

The use of low molecular weight heparin-pluronic nanogels to impede liver fibrosis by inhibition the TGF-β/Smad signaling pathway.

PubMed

Lee, Ju-Hee; Lee, Hyunseung; Joung, Yoon Ki; Jung, Kyung Hee; Choi, Jong-Hoon; Lee, Don-Haeng; Park, Ki Dong; Hong, Soon-Sun

2011-02-01

Low molecular weight heparin (LH) has been reported to have anti-fibrotic and anti-cancer effects. To enhance the efficacy and minimize adverse effects of LH, a low molecular weight heparin-pluronic nanogel (LHP) was synthesized by conjugating carboxylated pluronic F127 to LH. The LHP reduced anti-coagulant activity by about 33% of the innate activity. Liver fibrosis was induced by the injection of 1% dimethylnitrosamine (DMN) in rats, and LH or LHP (1000 IU/kg body weight) was treated once daily for 4 weeks. LHP administration prevented DMN-mediated liver weight loss and decreased the values of aspartate transaminase, alanine transaminase, total bilirubin, and direct bilirubin. LHP markedly reduced the fibrotic area compared to LH. Also, LHP potently inhibited mRNA or protein expression of alpha-smooth muscle actin, collagen type I, matrix metalloproteinase-2, and tissue inhibitor of metalloproteinase-1 compared to LH, in DMN-induced liver fibrosis. In addition, LHP decreased the expression of transforming growth factor-β(1) (TGF-β(1)), p-Smad 2, and p-Smad 3, which are all important molecules of the TGF-β/Smad signaling pathway. The results support an LHP shows anti-fibrotic effect in the liver via inhibition of the TGF-β/Smad pathway as well as by the elimination of the extracellular matrix. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Effect of selenium and omega-3 fatty acids on selected risk factors for heart disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mathews, A.H.; Hancock, R.C.; Christensen, M.J.

1986-03-01

Male weanling Sprague-Dawley rats were fed for 6 months a Torula yeast basal diet supplemented with one of three levels of Selenium (Se) (0, 0.1, or 1.0 ppm as Na/sub 2/-SeO/sub 3/), with or without a marine oil supplement (MaxEPA, Seven Seas, Hull, Eng.) added at 5% in a 3 x 2 factorial design. Dependent variables measured included: liver and platelet Se-glutathione peroxidase, (Se-GSH-Px); weight gain; relative weights (percent of body weight) of heart and a standardized section of aorta; and ADP-induced platelet aggregation. Dietary Se supplementation increased weight gain, liver and platelet Se-GSH-Px, and decreased relative heart and aortamore » weight (p < .001). MaxEPA significantly decreased platelet Se-GSH-Px (p < .05). Histological examination showed focal disruption of elastic fibers in aortic segments from rats fed the following diets: 0 Se without MaxEPA, 0 Se with MaxEPA, and 0.1 Se with MaxEPA. There were no significant differences in platelet aggregation among dietary groups. These findings suggest the following: (1) Se may be required for maintenance of normal integrity of the elastic tissue of the aortic wall; (2) high levels of polyunsaturates in the diet may compromise the protective effect of Se on elastic fibers in the aortic wall.« less

Healthy Nordic diet downregulates the expression of genes involved in inflammation in subcutaneous adipose tissue in individuals with features of the metabolic syndrome.

PubMed

Kolehmainen, Marjukka; Ulven, Stine M; Paananen, Jussi; de Mello, Vanessa; Schwab, Ursula; Carlberg, Carsten; Myhrstad, Mari; Pihlajamäki, Jussi; Dungner, Elisabeth; Sjölin, Eva; Gunnarsdottir, Ingibjörg; Cloetens, Lieselotte; Landin-Olsson, Mona; Akesson, Björn; Rosqvist, Fredrik; Hukkanen, Janne; Herzig, Karl-Heinz; Dragsted, Lars O; Savolainen, Markku J; Brader, Lea; Hermansen, Kjeld; Risérus, Ulf; Thorsdottir, Inga; Poutanen, Kaisa S; Uusitupa, Matti; Arner, Peter; Dahlman, Ingrid

2015-01-01

Previously, a healthy Nordic diet (ND) has been shown to have beneficial health effects close to those of Mediterranean diets. The objective was to explore whether the ND has an impact on gene expression in abdominal subcutaneous adipose tissue (SAT) and whether changes in gene expression are associated with clinical and biochemical effects. Obese adults with features of the metabolic syndrome underwent an 18- to 24-wk randomized intervention study comparing the ND with the control diet (CD) (the SYSDIET study, carried out within Nordic Centre of Excellence of the Systems Biology in Controlled Dietary Interventions and Cohort Studies). The present study included participants from 3 Nordic SYSDIET centers [Kuopio (n = 20), Lund (n = 18), and Oulu (n = 18)] with a maximum weight change of ±4 kg, highly sensitive C-reactive protein concentration <10 mg/L at the beginning and the end of the intervention, and baseline body mass index (in kg/m²) <38. SAT biopsy specimens were obtained before and after the intervention and subjected to global transcriptome analysis with Gene 1.1 ST Arrays (Affymetrix). Altogether, 128 genes were differentially expressed in SAT between the ND and CD (nominal P < 0.01; false discovery rate, 25%). These genes were overrepresented in pathways related to immune response (adjusted P = 0.0076), resulting mainly from slightly decreased expression in the ND and increased expression in the CD. Immune-related pathways included leukocyte trafficking and macrophage recruitment (e.g., interferon regulatory factor 1, CD97), adaptive immune response (interleukin32, interleukin 6 receptor), and reactive oxygen species (neutrophil cytosolic factor 1). Interestingly, the regulatory region of the 128 genes was overrepresented for binding sites for the nuclear transcription factor κB. A healthy Nordic diet reduces inflammatory gene expression in SAT compared with a control diet independently of body weight change in individuals with features of the metabolic syndrome. © 2015 American Society for Nutrition.

SU-F-I-40: Impact of Scan Length On Patient Dose in Abdomen/pelvis CT Diagnosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, I; Song, J; Kim, K

Purpose: To analysis the impact of scan length on patient doses in abdomen/pelvis CT diagnosis of each hospital. Methods: Scan length of 7 hospitals from abdomen/pelvis CT diagnosis was surveyed in Korea. Surveyed scan lengths were additional distance above diaphragm and distance below pubic symphysis except for standard scan range between diaphragm and pubic symphysis. Patient dose was estimated for adult male and female according to scan length of each hospital. CT-Expo was used to estimate the patient dose under identical equipment settings (120 kVp, 100 mAs, 10 mm collimation width, etc.) except scan length. Effective dose was calculated bymore » using tissue weighting factor of ICRP 103 recommendation. Increase rate of effective dose was calculated comparing with effective dose of standard scan range Results: Scan lengths of abdomen/pelvis CT diagnosis of each hospital were different. Also effective dose was increased with increasing the scan length. Generally increasing the distance above diaphragm caused increase of effective dose of male and female, but increasing the distance below pubic symphysis caused increase of effective dose of male. Conclusion: We estimated the patient dose according to scan length of each hospital in abdomen/pelvis CT diagnosis. Effective dose was increased by increasing the scan length because dose of organs with high tissue weighting factor such as lung, breast, testis were increased. Scan length is important factor on patient dose in CT diagnosis. If radiologic technologist interested in patient dose, decreasing the unnecessary scan length will decrease the risk of patients from radiation. This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI13C0004).« less

Adiponectin/resistin interplay in serum and in adipose tissue of obese and normal-weight individuals.

PubMed

Jonas, Marta Izabela; Kurylowicz, Alina; Bartoszewicz, Zbigniew; Lisik, Wojciech; Jonas, Maurycy; Domienik-Karlowicz, Justyna; Puzianowska-Kuznicka, Monika

2017-01-01

The interplay between adiponectin and resistin, the two adipokines of opposite effects, may determine the metabolic profile of obese individuals and development of obesity-related complications. The current study was conducted to assess how adiponectin/resistin interplay in sera and adipose tissues may influence the metabolic profile of obese and normal-weight subjects. Concentrations of adiponectin and resistin were measured on protein level by immunoassay in visceral and subcutaneous adipose tissues from 50 obese (body mass index > 40 kg/m 2 ) and 28 normal-weight (body mass index 20-24.9 kg/m 2 ) individuals. Simultaneously expression of ADIPOQ and RETN (encoding adiponectin and resistin, respectively) was assessed on mRNA level by real-time PCR. ADIPOQ mRNA (P = 0.0001) and adiponectin protein (P = 0.0013) levels were lower, while RETN mRNA (P = 0.0338) and resistin (P < 0.0001)-higher in subcutaneous adipose tissues of obese subjects. ADIPOQ and RETN mRNA levels did not correlate with protein concentrations in the investigated adipose tissues. In obesity adiponectin serum concentrations correlated positively with ADIPOQ mRNA in subcutaneous adipose tissue (P = 0.005) and negatively with protein levels in visceral adipose tissue (P = 0.001). Obesity was associated with higher adiponectin-resistin index value in sera (P < 0.0001) and decreased in subcutaneous adipose tissue (P < 0.001), but only adiponectin-resistin index measured in sera was significantly higher in obese with the metabolic syndrome (P = 0.04). Obesity affects synthesis of adiponectin and resistin mainly in subcutaneous adipose tissue. The adiponectin-resistin index assessed in the adipose tissues has a different prognostic value compared to the adiponectin-resistin index in serum and does not reflect a metabolic risk in obese individuals.

Obesity, regional body fat distribution, and the metabolic syndrome in older men and women.

PubMed

Goodpaster, Bret H; Krishnaswami, Shanthi; Harris, Tamara B; Katsiaras, Andreas; Kritchevsky, Steven B; Simonsick, Eleanor M; Nevitt, Michael; Holvoet, Paul; Newman, Anne B

2005-04-11

The metabolic syndrome is a disorder that includes dyslipidemia, insulin resistance, and hypertension and is associated with an increased risk of diabetes and cardiovascular disease. We determined whether patterns of regional fat deposition are associated with metabolic syndrome in older adults. A cross-sectional study was performed that included a random, population-based, volunteer sample of Medicare-eligible adults within the general communities of Pittsburgh, Pa, and Memphis, Tenn. The subjects consisted of 3035 men and women aged 70 to 79 years, of whom 41.7% were black. Metabolic syndrome was defined by Adult Treatment Panel III criteria, including serum triglyceride level, high-density lipoprotein cholesterol level, glucose level, blood pressure, and waist circumference. Visceral, subcutaneous abdominal, intermuscular, and subcutaneous thigh adipose tissue was measured by computed tomography. Visceral adipose tissue was associated with the metabolic syndrome in men who were of normal weight (odds ratio, 95% confidence interval: 2.1, 1.6-2.9), overweight (1.8, 1.5-2.1), and obese (1.2, 1.0-1.5), and in women who were of normal weight (3.3, 2.4-4.6), overweight (2.4, 2.0-3.0), and obese (1.7, 1.4-2.1), adjusting for race. Subcutaneous abdominal adipose tissue was associated with the metabolic syndrome only in normal-weight men (1.3, 1.1-1.7). Intermuscular adipose tissue was associated with the metabolic syndrome in normal-weight (2.3, 1.6-3.5) and overweight (1.2, 1.1-1.4) men. In contrast, subcutaneous thigh adipose tissue was inversely associated with the metabolic syndrome in obese men (0.9, 0.8-1.0) and women (0.9, 0.9-1.0). In addition to general obesity, the distribution of body fat is independently associated with the metabolic syndrome in older men and women, particularly among those of normal body weight.

Bullet Retarding Forces in Ballistic Gelatin by Analysis of High Speed Video

DTIC Science & Technology

2012-12-28

through tissue. The permanent cavity may be enlarged if the tissue is stretched beyond the elastic limit by the temporary cavity. The temporary...cavity arises because the retarding force accelerates tissue which then stretches until the combination of inertia, weight, and elasticity causes it to...spring back into place. Inelastic tissues such as liver, spleen, and brain stretch much less than elastic tissues such as 1 Distribution A

[Inhibition of osthole for resorption of rats femur tissue in vitro].

PubMed

Zhou, Jian; Ren, Xue-mei; Ma, Xiao-ni; Gao, Yu-hai; Yan, Li-juan; Shi, Wen-gui; Chen, Ke-ming

2015-09-01

To investigate osthole effect on femoral tissue resorption activity of rat in vitro. Six SD rats weighted (80 ± 5) g were used to isolate and culture femoral tissue (diaphyses and metaphysis) in vitro. The cultured tissue were devided into control group, estradiol group and osthole group. The femoral tissue was treated with final concentration of 1 x 10(-5) mol/L osthole and 1 x 10(-8) mol/L estradiol culture in vitro at 48 hours after cultured. Tartrate-resistant acid phosphatase (StrACP) activity, glucose and Lactic acid content, StrACP, MCSF (Macrophage colony stimulating factor) and CTSK (Cathepsin K) mRNA was detected by Real-Time RT-PCR were detected. Concetration of Alkaline phosphatase activity were 2226 and 2498 in 1 x 10(-5) mol/L osthole and 1 x 10(-8) mol/L estradiol respectively. As compared with control group, the activity of StrACP of 1 x 10(-5) mol/L osthole and 1 x 10(-8) mol/L estradiol were inhibited at 6, 9, 12 days (P < 0.05); under treatment of in l x 10(-5) mol/L osthole, the content of Lactic acid were increased and the content of glucose were decreased at 3, 6, 9 days (P < 0.05); StrACP, MCSF and CTSK mRNA expression level were inhibited at 6, 9 days (P < 0.05). Osthole can inhibit bone resorption and raise the level of nutrition metabolism of femurs tissue.

Isolation and expression analysis of FTZ-F1 encoding gene of black rock fish ( Sebastes schlegelii)

NASA Astrophysics Data System (ADS)

Shafi, Muhammad; Wang, Yanan; Zhou, Xiaosu; Ma, Liman; Muhammad, Faiz; Qi, Jie; Zhang, Quanqi

2013-03-01

Sex related FTZ-F1 is a transcriptional factor regulating the expression of fushi tarazu (a member of the orphan nuclear receptors) gene. In this study, FTZ-F1 gene ( FTZ-F1) was isolated from the testis of black rockfish ( Sebastes schlegeli) by homology cloning. The full-length cDNA of S. schlegeli FTZ-F1 ( ssFTZ-F1) contained a 232bp 5' UTR, a 1449bp ORF encoding FTZ-F1 (482 amino acid residules in length) with an estimated molecular weight of 5.4kD and a 105bp 3' UTR. Sequence, tissue distribution and phylogenic analysis showed that ssFTZ-F1 belonged to FTZ group, holding highly conserved regions including I, II and III FTZ-F1 boxes and an AF-2 hexamer. Relatively high expression was observed at different larva stages. In juveniles (105 days old), the transcript of ssFTZ-F1 can be detected in all tissues and the abuncance of the gene transcript in testis, ovary, spleen and brain was higher than that in other tissues. In mature fish, the abundance of gene transcript was higher in testis, ovary, spleen and brain than that in liver (trace amount), and the gene was not transcribed in other tissues. The highest abundance of gene transcript was always observed in gonads of both juvenile and mature fish. In addition, the abundance of gene transcript in male tissues were higher than that in female tissue counterparts ( P<0.05).

Effects of kefir on ischemia-reperfusion injury.

PubMed

Yener, A U; Sehitoglu, M H; Ozkan, M T A; Bekler, A; Ekin, A; Cokkalender, O; Deniz, M; Sacar, M; Karaca, T; Ozcan, S; Kurt, T

2015-01-01

We aimed to investigate the effect of kefir on Ischemia-Reperfusion (I/R) injury on rats. 24 male Sprague-Dawley rats between 250-350 g were selected. Rats were divided into three groups, and there were eight rats in each group. Rats were fed for 60 days. All of the rats were fed with the same diet for the first 30 days. In the second thirty days, kefir [10 cc/kg/day body weight (2 x 109 cfu/kg/day)] was added to the diet of the study group by gavage method. In all groups, lung and kidney tissues were removed after the procedure and rats were sacrificed. The biochemical and histopathological changes were observed in the lung and kidney within the samples. Serum urea, creatinine and tumor necrosis factor (TNF-α) were determined. Kefir + I/R groups was compared with I/R groups, a significant decrease (p < 0.05) was seen in Lipid peroxidation (MDA) levels of lung and renal tissues. Superoxide dismutase (SOD), Catalase (CAT) and Glutathione peroxidase (GSH-Px) activities of lung and kidney tissues decreased in I/R groups (p < 0.05). The enzyme activities in Kefir + I/R groups of renal tissues were significantly (p < 0.05) higher than I/R, not significantly different in lung tissues (p < 0.05). Kefir reduced the levels of serum urea, creatinine and TNF-α significantly.   This would be useful in this model against ischemia/reperfusion, and shows the protective effect of kefir in tissue and serum functions.

Biexponential Characterization of Prostate Tissue Water Diffusion Decay Curves Over an Extended b-factor Range

PubMed Central

Mulkern, Robert V.; Barnes, Agnieszka Szot; Haker, Steven J.; Hung, Yin P.; Rybicki, Frank J.; Maier, Stephan E.; Tempany, Clare M.C.

2006-01-01

Detailed measurements of water diffusion within the prostate over an extended b-factor range were performed to assess whether the standard assumption of monoexponential signal decay is appropriate in this organ. From nine men undergoing prostate MR staging exams at 1.5 T, a single 10 mm thick axial slice was scanned with a line scan diffusion imaging (LSDI) sequence in which 14 equally spaced b- factors from 5 to 3500 s/mm2 were sampled along three orthogonal diffusion sensitization directions in 6 minutes. Due to the combination of long scan time and limited volume coverage associated with the multi-b- factor, multi-directional sampling, the slice was chosen online from the available T2-weighted axial images with the specific goal of enabling the sampling of presumed non-cancerous regions of interest (ROI’s) within the central gland (CG) and peripheral zone (PZ). Histology from pre-scan biopsy (N = 9) and post-surgical resection (N = 4) was subsequently employed to help confirm that the ROIs sampled were non-cancerous. The CG ROIs were characterized from the T2-weighted images as primarily mixtures of glandular and stromal benign prostatic hyperplasia (BPH) which is prevalent in this population. The water signal decays with b- factor from all ROI’s were clearly non-monoexponential and better served with bi- vs monoexponential fits, as tested using λ2 based F-test analyses. Fits to biexponential decay functions yielded inter-subject fast diffusion component fractions on the order of 0.73 ± 0.08 for both CG and PZ ROIs, fast diffusion coefficients of 2.68 ± 0.39 and 2.52 ± 0.38 μm2/ms and slow diffusion coefficients of 0.44 ± 0.16 and 0.23 ± 0.16 um2/ms for CG and PZ ROI’s, respectively. The difference between the slow diffusion coefficients within CG and PZ was statistically significant as assessed with a Mann-Whitney non-parametric test (P < 0.05). We conclude that a monoexponential model for water diffusion decay in prostate tissue is inadequate when a large range of b- factors is sampled and that biexponential analyses are better suited for characterizing prostate diffusion decay curves. PMID:16735177

Viscoelastic properties of bovine orbital connective tissue and fat: constitutive models

PubMed Central

Yoo, Lawrence; Gupta, Vijay; Lee, Choongyeop; Kavehpore, Pirouz

2012-01-01

Reported mechanical properties of orbital connective tissue and fat have been too sparse to model strain–stress relationships underlying biomechanical interactions in strabismus. We performed rheological tests to develop a multi-mode upper convected Maxwell (UCM) model of these tissues under shear loading. From 20 fresh bovine orbits, 30 samples of connective tissue were taken from rectus pulley regions and 30 samples of fatty tissues from the posterior orbit. Additional samples were defatted to determine connective tissue weight proportion, which was verified histologically. Mechanical testing in shear employed a triborheometer to perform: strain sweeps at 0.5–2.0 Hz; shear stress relaxation with 1% strain; viscometry at 0.01–0.5 s−1 strain rate; and shear oscillation at 1% strain. Average connective tissue weight proportion was 98% for predominantly connective tissue and 76% for fatty tissue. Connective tissue specimens reached a long-term relaxation modulus of 668 Pa after 1,500 s, while corresponding values for fatty tissue specimens were 290 Pa and 1,100 s. Shear stress magnitude for connective tissue exceeded that of fatty tissue by five-fold. Based on these data, we developed a multimode UCM model with variable viscosities and time constants, and a damped hyperelastic response that accurately described measured properties of both connective and fatty tissues. Model parameters differed significantly between the two tissues. Viscoelastic properties of predominantly connective orbital tissues under shear loading differ markedly from properties of orbital fat, but both are accurately reflected using UCM models. These viscoelastic models will facilitate realistic global modeling of EOM behavior in binocular alignment and strabismus. PMID:21207094

Mechanism of QHF-cisplatin against hepatocellular carcinoma in a mouse model.

PubMed

Chen, Tao; Yuan, Shen-Jun; Wang, Jing; Hu, Wei

2015-09-21

To study the effects of QHF-cisplatin on H22 hepatocellular carcinoma (HCC) and their mechanisms of action. Sixty BALB/c mice were randomly divided into a model group (n = 48) and a normal control group (n = 12). An HCC xenograft tumor was created by injecting H22 cells directly into the liver parenchyma of the mice. The 48 BALB/c mice in the model group were randomly divided into four groups: QHF, DDP (cisplatin), QHF plus DDP, and model control. The inhibitory effects of these drugs on tumor growth were evaluated by calculating the rate of tumor growth inhibition. The mice were examined by observing their general condition, body weight and survival time. Changes in tumor tissue were observed under an optical microscope. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and α-fetoprotein (AFP) levels in serum were measured. Hepatocyte growth factor (HGF), c-mesenchymal-epithelial transition (c-Met) factor, phosphorylated (p)-c-Met, p38, p-p38, extracellular signal-regulated kinase (ERK), p-ERK and vascular endothelial growth factor (VEGF) levels were evaluated in tumor and liver tissues using western blotting. Compared with the DDP group, a lower incidence of toxic reactions and a higher survival time were observed in the QHF plus DDP group. Tumor weight was significantly lower in the QHF, DDP and QHF plus DDP groups than in the model control group (0.24 ± 0.07, 0.18 ± 0.03 and 0.14 ± 0.01 g vs 0.38 ± 0.05 g, respectively), and the differences were statistically significant (P < 0.01). The rate of tumor growth inhibition in the QHF, DDP and QHF plus DDP groups was 38.7%, 52.6% and 63.5%, respectively. AST, ALT and AFP levels in serum were significantly lower in the QHF, DDP and QHF plus DDP groups compared to the model control group (P < 0.05). Similarly, HGF, p-c-Met, p-p38, p-ERK and VEGF levels in tumor tissue were significantly lower in the QHF, DDP and QHF plus DDP groups (P < 0.05). QHF and DDP have an antiangiogenic effect on H22 HCC in mice. QHF inhibits tumor growth via blocking the HGF/c-Met signaling pathway, inhibiting p38, ERK and VEGF signaling.

Lightweight Breast Implants: A Novel Solution for Breast Augmentation and Reconstruction Mammaplasty

PubMed Central

Govrin-Yehudain, Jacky; Dvir, Haim; Preise, Dina; Govrin-Yehudain, Orel; Govreen-Segal, Dael

2015-01-01

Breast augmentation and reconstruction mammaplasty have been in practice for decades and are highly prevalent surgeries performed worldwide. While overall patient satisfaction is high, common long-term effects include breast tissue atrophy, accelerated ptosis and inframammary fold breakdown. Increasing evidence attributes these events to the durative loading and compressive forces introduced by the breast implants. Mechanical challenges exceeding the elastic capacity of the breast tissue components, eventually lead to irreversible tissue stretching, directly proportional to the introduced mass. Thus, it is suggested that, contrary to long-standing dogmas, implant weight, rather than its volume, stands at the basis of future tissue compromise and deformation. A novel lightweight implant has been developed to address the drawbacks of traditional breast implants, which demonstrate equivalence between their size and weight. The B-Lite® breast implant (G&G Biotechnology Ltd., Haifa, Israel) design allows for a reduction in implant weight of up to 30%, while maintaining the size, form, and function of traditional breast implants. The CE-marked device can be effectively implanted using standard of care procedures and has been established safe for human use. Implantation of the B-Lite® breast implant is projected to significantly reduce the inherent strains imposed by standard implants, thereby conserving tissue stability and integrity over time. In summary, this novel, lightweight breast implant promises to reduce breast tissue compromise and deformation and subsequent reoperation, further improving patient safety and satisfaction. PMID:26333989

High intensity interval training improves liver and adipose tissue insulin sensitivity

PubMed Central

Marcinko, Katarina; Sikkema, Sarah R.; Samaan, M. Constantine; Kemp, Bruce E.; Fullerton, Morgan D.; Steinberg, Gregory R.

2015-01-01

Objective Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine–alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. Conclusions These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC. PMID:26909307

A Standardized Rat Model of Volumetric Muscle Loss Injury for the Development of Tissue Engineering Therapies

DTIC Science & Technology

2012-12-01

isometric tetanic force (Po) of 28.4% and 32.5% at 2 and 4 months. Importantly, Po corrected for differences in body weight and muscle wet weights were...development, we removed progres- sively larger amounts of muscle tissue followed by a mea- surement of maximal isometric force (Po). The final model, and...indicated by increased collagen deposition (Fig. 2). The scarred area and the area immediately adjacent to it contained disorganized muscle fibers

Viscosupplementation for treatment of osteoarthritis: from initial discovery to current status and results.

PubMed

Balazs, Endre A

2004-01-01

Viscosupplementation is a therapeutic modality based on the replacement of synovial fluid or exudates with an elastoviscous hyaluronan solution. The first clinical trials were carried out on race horses with painful osteoarthritis of traumatic origin. In the early 1970s, the clinical trials were extended to painful osteoarthritis in humans. Analgesic effects lasting longer than the residence time of the injected hyaluronan in joints were reported both in horses and humans. The hyaluronan used was a noninflammatory fraction of the molecule with an average molecular weight of 2-3 million at a 1% concentration. The analgesic effect of this elastoviscous hyaluronan solution was demonstrated in behavioral animal pain models. Later it was shown that the elastoviscous properties of hyaluronan solutions are the determining factors in reducing pain-elicited nerve activity in both normal and inflamed cat and rat joints. It also was demonstrated in animal arthritis models that elastoviscous hyaluronan solutions promote the healing of traumatic intra-articular wounds. From the mid-1980s, several hyaluronan preparations of greatly varying average molecular weight but with the same concentration were introduced as viscosupplementation-based therapeutic agents. The elastoviscous properties of these solutions varied also, because of the greatly varying average molecular weights (0.5-6.0 million), imitating the rheological properties of either healthy or pathological synovial fluid. Currently, viscosupplementation products available worldwide vary greatly in their elastoviscous properties, and their dosage is not standardized in terms of frequency of injections required or in regard to the removal of exudates before injection. The question of which patient at what stage of the disease responds best with long-lasting pain relief to the many therapeutic products marketed with greatly varying elastoviscous properties has not yet been answered. At the same time, viscosupplementation was introduced, the same highly elastoviscous hyaluronan solutions also were applied in ophthalmic surgery as viscosurgical tools to protect sensitive tissues in the eye during surgery and to be used as soft instruments for tissue manipulation. Modified hyaluronan products (gels) also were introduced for augmentation of the intercellular matrix in tissues (viscoaugmentation) and for separating tissues to prevent adhesions and excessive scar formation (viscoseparation). Hyaluronan and its derivatives (gels) also have been used for drug delivery. The therapeutic use of highly elastoviscous solutions and gels of hyaluronan and its derivatives to build intercellular matrices for supplementation, regeneration, and developing new tissues introduced the concept of matrix engineering into medical practice.

Influence of Maternal Undernutrition and Overfeeding on Cardiac Ciliary Neurotrophic Factor Receptor and Ventricular Size in Fetal Sheep

PubMed Central

Dong, Feng; Ford, Stephen P.; Nijland, Mark J.; Nathanielsz, Peter W.; Ren, Jun

2008-01-01

Intrauterine nutrition status is reported to correlate with risk of cardiovascular diseases in adulthood. Either under- or over-nutrition during early to mid gestation contributes to altered fetal growth and ventricular geometry. This study was designed to examine myocardial expression of ciliary neurotrophic factor receptor α (CTNFRα) and its down-stream mediator signal transducer and activator of transcription 3 (STAT3) on maternal under- or over-nutrition-induced changes in fetal heart weight. Multiparous ewes were fed with 50% (nutrient-restricted, NR), 100% (control) or 150% (overfed, OF) of NRC requirements from 28 to 78 days of gestation (dG; Term 148 dG). Ewes were euthanized on day 78, and the gravid uteri and fetuses recovered. Ventricular protein expression of CTNFRα, STAT3, phosphorylated STAT3, insulin-like growth factor I receptor (IGF-1R) and IGF binding protein 3 (IGFBP3) were quantitated using western blot. Plasma cortisol levels were higher in both NR and OF fetuses whereas plasma IGF-1 levels were lower and higher, in NR and OF fetuses. Fetal weights were reduced by 29.9% in NR ewes and were increased by 22.2% in fetuses from OF ewes compared to control group. Nutrient restriction did not affect fetal heart or ventricular weights whereas overfeeding increased heart and ventricular weights. Protein expression of CTNFRα in fetal ventricular tissue was reduced in OF group whereas STAT3 and pSTAT3 levels were reduced in both NR and OF groups. Expression of IGF-1R and IGFBP3 was unaffected in either NR or OF group. These data suggested that compared with maternal undernutrition, intrauterine overfeeding during early to mid gestation is associated with increases fetal blood concentrations of cortisol and IGF-1 in association with ventricular hypertrophy where reduced expression of CNTFRα and STAT3 may play a role. PMID:17869083