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Marten A Schults,
Peter W Nagle,
Sander S Rensen,
Roger W Godschalk,
Armelle Munnia,
Marco Peluso,
Sandra M Claessen, Jan W Greve,
Ann Driessen,
Froukje J Verdam,
Wim A Buurman,
Frederik J van Schooten,
Roland K Chiu
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ABSTRACT: Chronic inflammation is characterized by the influx of neutrophils and is associated with an increased production of reactive oxygen species that can damage DNA. Oxidative DNA damage is generally thought to be involved in the increased risk of cancer in inflamed tissues. We previously demonstrated that activated neutrophil mediated oxidative stress results in a reduction in nucleotide excision repair (NER) capacity, which could further enhance mutagenesis. Inflammation and oxidative stress are critical factors in the progression of nonalcoholic fatty liver disease that is linked with enhanced liver cancer risk. In this report, we therefore evaluated the role of neutrophils and the associated oxidative stress in damage recognition and DNA repair in steatotic livers of 35 severely obese subjects with either nonalcoholic steatohepatitis (NASH) (n=17) or steatosis alone (n=18). The neutrophilic influx in liver was assessed by myeloperoxidase (MPO) staining and the amount of oxidative DNA damage by measuring M(1)dG adducts. No differences in M(1)dG adduct levels were observed between patients with or without NASH and also not between individuals with high or low MPO immunoreactivity. However, we found that high expression of MPO in the liver, irrespective of disease status, reduced the damage recognition capacity as determined by staining for histone 2AX phosphorylation (γH2AX). This reduction in γH2AX formation in individuals with high MPO immunoreactivity was paralleled by a significant decrease in NER capacity as assessed by a functional repair assay, and was not related to cell proliferation. Thus, the observed reduction in NER capacity upon hepatic inflammation is associated with and may be a consequence of reduced damage recognition. These findings suggest a novel mechanism of liver cancer development in patients with nonalcoholic fatty liver disease.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 11/2011; 736(1-2):75-81. · 2.85 Impact Factor
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Valère J Goossens,
Steve A deJager,
Gert E Grauls,
Marij Gielen,
Robert F Vlietinck,
Catherine A Derom,
Ruth J F Loos,
Sander S Rensen,
Wim A Buurman, Jan W Greve,
Marleen A van Baak,
Petra F Wolffs,
Cathrien A Bruggeman,
Christian J P A Hoebe
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ABSTRACT: Adenovirus infection has been shown to increase adiposity in chickens, mice, and nonhuman primates. Adenovirus type 36 (Ad-36) DNA was detected in adipose tissues in these animal trials. In the United States, Ad-36 significantly correlates with obesity as illustrated by an Ad-36 seroprevalence of 30% in obese individuals and 11% in nonobese individuals. We investigated the possibility of a similar correlation of Ad-36 in Dutch and Belgian persons. In total, 509 serum samples were analyzed for Ad-36 antibodies using a serum neutralization assay. In addition, PCR was used to detect adenoviral DNA in visceral adipose tissue of 31 severely obese surgical patients. Our results indicated an overall Ad-36 seroprevalence of 5.5% increasing with age. BMI of Ad-36 seropositive humans was not significantly different from seronegative humans. No adenoviral DNA could be found using PCR on visceral adipose tissue. In conclusion, this first Ad-36 study in the Netherlands and in Belgium indicates that Ad-36 does not play a role as a direct cause of BMI increase and obesity in humans in Western Europe.
Obesity 12/2009; 19(1):220-1. · 4.28 Impact Factor
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ABSTRACT: This study compared the outcome of the Subjective Global Assessment (SGA) in preoperative surgical patients with objective measurements of muscle mass and strength and with biochemical data. A secondary aim was to test the influence of inflammatory activity on muscle strength.
Two hundred seventy-four consecutive patients who were admitted for elective major abdominal surgery were assessed using the SGA, anthropometry, muscle strength, and laboratory measurements (hemoglobin, protein, albumin, C-reactive protein, and lymphocytes). Normal values for midarm muscle circumference (MAMC) and handgrip strength were obtained in a healthy control group. For all other variables, normal values available for the Vietnamese population were used.
Of 274 patients (151 men, 123 women) assessed, 61 (22.3%) were classified as SGA class A (well nourished), 97 patients (35.4%) as class B (moderately malnourished), and 116 patients (42.3%) as class C (severely malnourished). There were significant differences in age, body weight, percentage of weight loss, triceps skinfold thickness, MAMC, and serum albumin across the three SGA classes. Almost all patients rated class A had normal MAMC and handgrip strength. However, a large proportion of patients rated as B or C also had normal MAMC and handgrip strength (38% of men, 50% of women). Handgrip strength per square meter correlated with serum albumin (r = 0.278, P < 0.001) and this correlation persisted when handgrip strength was controlled for MAMC (r = 0.296, P < 0.001 in men; r = 0.237, P < 0.01 in women).
The SGA correctly identifies patients with normal muscle mass and strength but a substantial number of patients rated SGA B or C have normal muscle mass and strength. Muscle strength is not only positively associated with muscle mass but also negatively with inflammatory activity.
Nutrition 04/2007; 23(4):283-91. · 3.03 Impact Factor
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ABSTRACT: This study was designed as an economic evaluation alongside a randomized clinical trial. The object of this study was to evaluate the 1-year cost-effectiveness of surgical treatment of morbid obesity comparing two operations.
100 patients were assigned randomly to vertical banded gastroplasty (VBG) or Lap-Band surgery. Both medical and non-medical costs were identified and measured. Costs data were combined with percentage Excess Weight Loss (%EWL) and with Quality Adjusted Life Years (QALYs) to obtain cost per %EWL and cost per QALY ratios.
At 1 year, the total costs were not significantly different between both groups (95% confidence interval E5,999-E1,765). Also, the QALY gain after surgery was not significantly different between the two groups. However, %EWL was significantly higher in the VBG group compared to the Lap-Band group, P-value .0001. The estimated incremental cost per %EWL was E105.83 (E1,885.91/-17.82). For the costs per QALY, the estimated ratio was dominant. The overall mortality in this study was 2%. 2 patients in the VBG group died within 30 days after surgery; 1 of these deaths was possibly related to the VBG procedure.
At 1 year after surgery, the costs and QoL of the two treatment modalities were found to be equal. Therefore, the selection of the procedure can be based on the clinical aspects, effectivity and safety at 1 year. In addition, the results of a long-term cost-effectiveness analysis (e.g. with a follow-up of 36 months) planned in the future can also be helpful in the selection of the preferred treatment.
Obesity Surgery 02/2006; 16(1):75-84. · 3.29 Impact Factor
