Ilias P. Doulamis

The effect of biological age on the metabolic responsiveness of mice fed a high-fat diet

Mice are widely used in studies investigating the effect of diet on metabolic risk factors, such as lipid profiles and plasma glucose levels. An important factor that is usually not taken into account is the biological age of the experimental models. The up-to-date identified experimental confounders do not cover all the parameters that may affect the results of animal studies. The aim of this study was to investigate the effects of a high-fat diet on the metabolic profile, hepatic and renal function in mice of differing ages. For this purpose two groups of male C57BL/6J mice were used, consisting of 10-week-old mice and 54-week-old mice in each group. Both groups followed identical high-fat diets for 12 weeks. The younger mice showed smaller increases in body weight, serum total cholesterol, glucose and urea levels while they had higher increases in high-density lipoprotein cholesterol levels than the older mice. Our results indicate the necessity to consider an experimental animal’s age as a confounding factor when researching or interpreting metabolic studies. Age adjustment is warranted in all animal research while a uniform approach regarding the age of the animal models should be applied in experimental studies.

Water Soluble Vitamin E Administration in Wistar Rats with Non-alcoholic Fatty Liver Disease

Objective: A diet rich in fat is associated with hepatic fat deposition [steatosis; non-alcoholic fatty liver disease (NAFLD)]. The exact cause of NAFLD however, is still unknown. The aim of this study was to assess the effect of a water-soluble formulation of vitamin E on a dietary-induced-NAFLD animal model. Methods: Adult male Wistar rats (n=20) were allocated to 2 groups: Controls (Group A, n=6), which received a standard chow diet for 24 weeks and a High Cholesterol group (HC: n=14), which received a standard chow diet enriched with cholesterol for the first 14 weeks of the experiment (t1). At t1, the HC group was divided into: Group HC(B), which received a high-saturated-fat/high-cholesterol (HSF/HCH) diet and Group HC(C), which followed the same HSF/HCH diet but was also administered water soluble vitamin E (10 IU/kg body weight/day), for 10 more weeks. Results: At the end of the study, group HC(C) exhibited significantly lower mean total cholesterol (T-CHOL) than group HC(B) (p<0.001). No significant differences were observed between HC(C) and Control groups in blood glucose and serum lipid concentrations. Liver Function Tests did not vary between all groups at the end of the study. Animals in group HC(B) exhibited higher SGOT at the end of the study compared with the beginning of the study (p<0.05). Group HC(B) exhibited the highest scores in steatosis, and grading (according to the NAFLD scoring system) in the histopathological analysis (p≤0.001 in all cases). Conclusions: Vitamin E seems to exert a hypolipidemic and hepatoprotective role in the presence of a HSF/HCH atherogenic diet in a rat model.

Correlation between mesenteric fat thickness and serum apolipoproteins in patients with peripheral arterial occlusive disease

BackgroundVisceral fat possesses the most detrimental potential for cardiovascular morbidity through the release of adipokines, as well as metabolic and proinflammatory mediators, which adversely affect metabolic and vascular homeostasis. Among the different types of visceral adipose tissue, mesenteric fat is considered particularly detrimental, due to its close proximity to the portal circulation, affecting directly the liver, which is the main regulator of body metabolic homeostasis. Mesenteric fat can be reliably estimated using abdominal ultrasonography, the only available imaging method able to depict individual mesenteric leaves. Aim of the present study was to investigate the correlation of mesenteric fat thickness (MFT) with serum apolipoprotein levels in patients undergoing digital subtraction angiography in a single center.Methods35 male patients with peripheral arterial disease were examined. After careful examination of the periumbilical area, the mesenteric leaves were identified. The maximal distance between each pair of sequential leaves was measured, and the mean value of the three thickest leaves was determined as the mesenteric fat thickness. Six apolipoprotein fasting serum concentrations were measured using a Luminex proteomics platform (xMAP Multiplex immunoassay): apolipoprotein A-I (apoAI), apolipoprotein A-II (apoAII), apolipoprotein B (apoB), apolipoprotein C-II (apoCII), apolipoprotein C-III (apoCIII) and apolipoprotein E (apoE).ResultsMFT correlated with apoAII and apoB serum concentrations. The correlations with apoAII and apoB remained significant following correction for BMI. No correlations were noted between MFT and serum apoAI, apoCII, apoCIII or apoE levels before or after adjustment for BMI.ConclusionsOur study indicates that MFT is significantly correlated with the concentration of atherogenic low density lipoproteins particles, as well as with apoAII, a determinant of free fatty acids levels. No correlation was observed between mesenteric fat thickness and very low density lipoprotein or chylomicron particles concentration.

Short Leukocyte Telomere Length Precedes Clinical Expression of AtherosclerosisNovelty and Significance: The Blood-and-Muscle Model

Rationale: Short telomere length (TL) in leukocytes is associated with atherosclerotic cardiovascular disease (ASCVD). It is unknown whether this relationship stems from having inherently short leukocyte TL (LTL) at birth or a faster LTL attrition thereafter. LTL represents TL in the highly proliferative hematopoietic system, whereas TL in skeletal muscle represents a minimally replicative tissue. Objective: We measured LTL and muscle TL (MTL) in the same individuals with a view to obtain comparative metrics for lifelong LTL attrition and learn about the temporal association of LTL with ASCVD. Methods and Results: Our Discovery Cohort comprised 259 individuals aged 63±14 years (mean±SD), undergoing surgery with (n=131) or without (n=128) clinical manifestation of ASCVD. In all subjects, MTL adjusted for muscle biopsy site (MTLA) was longer than LTL and the LTL-MTLA gap similarly widened with age in ASCVD patients and controls. Age- and sex-adjusted LTL (P=0.005), but not MTLA (P=0.90), was shorter in patients with ASCVD than controls. The TL gap between leukocytes and muscle (LTL-MTLA) was wider (P=0.0003), and the TL ratio between leukocytes and muscle (LTL/MTLA) was smaller (P=0.0001) in ASCVD than in controls. Findings were replicated in a cohort comprising 143 individuals. Conclusions: This first study to apply the blood-and-muscle TL model shows more pronounced LTL attrition in ASCVD patients than controls. The difference in LTL attrition was not associated with age during adulthood suggesting that increased attrition in early life is more likely to be a major explanation of the shorter LTL in ASCVD patients. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02176941.

A population-based analysis of a rare oncologic entity: Malignant pancreatic tumors in children

PURPOSE To examine the clinicopathological characteristics and prognosis of pediatric patients with malignant pancreatic tumors in a population-based cohort. METHODS The Surveillance, Epidemiology, and End Results (SEER) database was utilized to identify all pediatric patients with malignant pancreatic tumors, diagnosed between 1973 and 2013. Kaplan-Meier analysis was performed to determine median and five-year overall survival (OS) rates. Univariate survival analysis was executed using the log-rank test. Cox proportional hazards model was used to identify variables independently associated with mortality. RESULTS A total of 114 patients with pancreatic malignancies were identified. Median patient age was 16years and the majority of patients were white (64%) females (61.4%). The most prevalent histologic subtype was neuroendocrine tumors (35.1%), whereas pancreatoblastoma was more common during the first decade of life (P<0.001). Distant metastases were noted in 41.7% of the patients, while 33.3% and 25% had localized and regional disease respectively. Five-year OS rates were 77%, 66.4% and 64.8% for patients with pancreatoblastoma, neuroendocrine and epithelial tumors respectively. No death was observed in the solid pseudopapillary tumor group. Only history of having cancer-directed surgery (CDS) was significantly associated with lower overall mortality (HR: 5.1, 95% CI: 2.1, 12.4). CONCLUSION Pancreatic malignancies are rare in children. Their prognosis is variable and only CDS was independently associated with superior survival. EVIDENCE RATING/CLASSIFICATION Prognosis study, Level II.

A sirtuin 1/MMP2 prognostic index for myocardial infarction in patients with advanced coronary artery disease

BACKGROUND Sirtuin 1 (SIRT1) appears to play a protective role against endothelial dysfunction and oxidative stress. Instead, matrix metalloproteinase 2 (MMP2) is involved in acute coronary events, by promoting tissue remodeling. This study sought to determine the clinical value of a prognostic index arising from the combination of these two biomarkers for myocardial infarction (MI) in patients with advanced coronary artery disease. METHODS Eighty-one patients with advanced coronary artery disease planned for open heart surgery were prospectively enrolled. Serum levels of SIRT1 and MMP2 were measured by ELISA. To look at the relation of these mediators with clinical characteristics, pre-operative data and patients demographics were collected. RESULTS SIRT1 levels correlated marginally with a history of hypertension (ρ=0.2, p=0.084) and inversely with baseline urea (ρ=0.25, p=0.056). When performing additional adjustment, low SIRT1 levels were independently associated with diabetes mellitus 2(DM2) and subjects with SIRT1 <2.95ng/mL were more prone to present DM2 (82% sensitivity and 62% specificity). The index of low SIRT1 and high MMP2 respectively correlated with patients history of MI (ρ=0.3, p=0.01) and marginally with presence or history of atrial fibrillation (AF) (ρ=0.213, p=0.076). When adjusting for anthropometric and comorbidities, the combined index tended to have an association with impaired ejection fraction (EF)<55% (p=0.059). CONCLUSIONS The combined index of low SIRT1 and high MMP2 exhibited a significant correlation with history of MI and EF, promoting a potential prognostic tool for MI incidence in patients regardless their coronary artery disease status.

Protective effects of N-acetylcystein and atorvastatin against renal and hepatic injury in a rat model of intestinal ischemia-reperfusion

AIM OF THE STUDY We sought to examine whether the separate and combined effect of N-acetylcystein (NAC) and atorvastatin prevented hepatic and renal tissue injury induced by intestinal ischemia-reperfusion (I/R). MATERIAL AND METHODS 40 male Wistar rats were allocated into 5 experimental groups; Control (n=8): sham, I/R (n=8): rats underwent occlusion of superior mesenteric artery for 45min, Atorvastatin (n=8): rats received 10mg/kg atorvastatin, NAC (n=8): rats received 160mg/kg NAC, NAC&Atorvastatin (n=8): rats received both aforementioned agents. Administration of the agents was facilitated by oral gavage 24h before I/R. Serum levels of urea, creatinine, transaminases, IL-1β, IL-6, TNF-α, ICAM-1, as well as liver and kidney histopathological examination were evaluated. RESULTS Pretreatment with either NAC or Atorvastatin or their combination led to lower levels of transaminases and ICAM-1 (2.75±0.46, 2.88±0.84 and 1.5±0.76 respectively for NAC, Atorvastatin and I/R groups), while only their combination led to lower ratios of IL-1, IL-6 and TNF-α than I/R group (1.3±0.12 vs 1.94±0.54, 1.21±0.11 vs 2.12±0.96 and 1.33±0.11 vs 2.14±0.77, respectively). NAC was associated with enhanced renal tissue histology, while atorvastatin was found superior in protecting hepatic tissue degenaration. CONCLUSIONS Both agents, seperately and combined, seem to exhibited tissue-specific protective activity against intestinal I/R induced injury.

Transumbilical Roux-en-Y gastric bypass in morbidly obese patients: A systematic review.

BACKGROUND Transumbilical single-incision Roux-en-Y gastric bypass constitutes a delicate technique of the conventional laparoscopic approach, which is the gold standard for the treatment of obesity. METHODS In order to investigate its efficacy and feasibility, PubMed was searched up to April 25th, 2015. Ten studies reporting on 247 patients with a mean age of 37.3 years were eligible. RESULTS Mean preoperative Body Mass Index was 42.4 kg/m(2). Most common comorbidities were diabetes and dyslipidemia. Mean operative time was 128.5 min and mean length of hospital stay was 3.3 days. No conversions to open surgery were reported. CONCLUSION Clinical outcomes of the transumbilical Roux-en-Y gastric bypass appear to be comparable with those of the conventional laparoscopic one. However, more trials are necessary to elucidate all of its aspects.

Comparison of the short-term oxidative stress response in National League basketball and soccer adolescent athletes.

Physical exercise is considered protective against oxidative stress-related disorders. However, there is increasing evidence that strenuous activity may induce increased oxidative stress response. This study investigated the impact of vigorous physical activity on serum oxidative stress markers in 36 soccer and 12 basketball National League adolescent athletes 40 minutes before and 15 minutes after a National League game. Serum total peroxide, fibrinogen, polymorphonuclear (PMN) elastase, and myeloperoxidase levels were determined. No significant differences in any of the measured parameters were observed before the match. Soccer players exhibited significantly lower total peroxide (P < .05) and higher PMN elastase concentrations (P < .05) than that of the basketball athletes after the game. A number of important differences between these 2 sports, such as duration or total aerobic and anaerobic demands, may affect oxidative status. These parameters need to be further examined in order to elucidate the different effects of these 2 sports on postexercise oxidative status.

Solid pseudopapillary and malignant pancreatic tumors in childhood: A systematic review and evidence quality assessment

A systematic review of 32 studies reporting on 489 children with pancreatic tumors was performed. The most prevalent histologic subtype was solid pseudopapillary tumor (SPT) (61.3%). Pancreaticoduodenectomy was the most commonly performed operation (48%). Neoadjuvant chemo/radiotherapy was utilized in 3.9, 36.2, 25, and 27.8% of patients with SPTs, pancreatoblastomas (PBLs), neuroendocrine tumors, and exocrine carcinomas, respectively. Adjuvant chemotherapy (75.6%) and radiation (34%) were most commonly utilized in PBLs. All‐cause mortality was highest in exocrine carcinomas (50%). Overall, 98.8% of patients with SPTs survived. PBL exhibited the highest recurrence rate (14.7%) within a mean of 23.5 months.