Niki Malliaraki

Decreased Total and Corrected Antioxidant Capacity in Patients with Inflammatory Bowel Disease

Oxidative stress and depletion of antioxidants may play a key role in the pathogenesis of inflammatory bowel disease (IBD)-related intestinal damage. A new automated assay for the determination of blood total antioxidant capacity (TAC), based on the crocin bleaching method, has been used for the measurement of TAC and corrected TAC (cTAC) in patients with ulcerative colitis (UC) and Crohns disease (CD) in comparison to healthy controls (HC). Ninety-four patients with UC, 97 patients with CD, and 72 HC were included in this study. Serum TAC was measured in all patients and controls on an Olympus AU-600 chemistry analyzer using a TAC kit. cTAC was calculated from TAC after subtraction of the interactions due to endogenous uric acid, bilirubin and albumin. Mean serum TAC as well as cTAC levels were significantly lower in both UC and CD patients compared with HC (P<0.0001). Patients with active UC had no different TAC and cTAC compared to those with inactive disease. Patients with active CD had significantly lower mean TAC compared to those with inactive disease but cTAC was not different between the two phases of disease activity. Patients with proctitis had significantly higher TAC and cTAC compared to patients with left-sided colitis and total colitis. In CD patients no association between disease localization and these markers was found. TAC and cTAC are significantly reduced in IBD patients compared with controls irrespective of disease activity. The decreased antioxidant defenses may be a primary phenomenon severely compromising the mucosa and therefore increase susceptibility to oxidative tissue damage.

Serum hepcidin and prohepcidin concentrations in inflammatory bowel disease.

Background Anemia is an important complication of inflammatory bowel disease (IBD). Recent data suggest that hepcidin is a major mediator of anemia with a central role in iron homeostasis and metabolism. The aim of this study was to evaluate the serum levels of hepcidin and its prohormone, prohepcidin, in patients with IBD in comparison with healthy controls. Methods One hundred patients with IBD [49 ulcerative colitis (UC), 51 Crohns disease (CD)] and 102 healthy controls were enrolled. Serum hepcidin and prohepcidin levels were measured by commercially available enzyme-linked immunosorbent assays kits. Their relationship with clinical and laboratory parameters of UC and CD was assessed. Results Median hepcidin levels were significantly higher in both patients with UC and patients with CD compared with healthy controls (P<0.0001). Median prohepcidin levels were significantly lower in patients with IBD compared with healthy controls (P=0.03). In the univariate analysis, serum hepcidin was significantly negatively correlated (r=−0.36, P=0.0003), whereas serum prohepcidin was positively correlated (r=0.65, P<0.0001) with the hemoglobin levels. Significant correlations of both hepcidin (r=0.34, P=0.0007) and prohepcidin (r=−0.21, P=0.04) with ferritin levels were found in patients with IBD. Serum hepcidin was also correlated with disease activity (for UC, r=0.36, P=0.009) and C-reactive protein (r=0.29, P=0.004). After multivariate analysis serum hepcidin levels remained significantly correlated with ferritin (P=0.0008) and disease activity (for UC, P=0.004). Conclusion Serum hepcidin and prohepcidin levels are significantly altered in patients with IBD compared with healthy controls. This finding suggests a substantial role of these two hormones in the development of anemia in IBD.

Plasma antioxidant capacity in morbidly obese patients before and after weight loss.

Background: Oxidative stress may play a critical role in the pathogenesis and development of obesity-associated co-morbidities. Reactive oxygen and nitrogen species are produced as a consequence of normal aerobic metabolism and removed and/or inactivated in vivo by both endogenous (uric acid, bilirubin, thiols) and diet-derived (exogenous) antioxidants. The purpose of this study is to measure the total plasma antioxidant capacity (TAC), as well as the corrected TAC (cTAC, an index of exogenous provided antioxidants) in morbidly obese patients before and after surgical weight reduction. Methods: 16 morbidly obese (5 male and 11 female) candidates for surgical intervention, median age 34 (range 22-56) years, median weight 128 (range 96-186) kg, median excess weight 62 (range 28-115) kg and median BMI 44.4 (range 33.7-60.1) kg/m2 were evaluated before and 6 months after implantation of an intragastric balloon. 15 healthy blood donors (4 male and 11 female) on a normal diet, median age 35 (range 21-52) years, median weight 64.3 (range 46-78) kg and median BMI 24.2 (range 23.7-25.2) kg/m2 were also evaluated. Blood samples for routine clinical chemistry, TAC and cTAC determination were drawn, and weight and BMI calculation were performed once in the control group, and in the morbidly obese patients (MO) before and 6 months after the balloon implantation. Results: 6 months after balloon placement, weight and BMI of the MO patients were statistically significantly reduced from the preoperative values (P<0.001). Plasma TAC and cTAC values in the MO group were significantly lower preoperatively, compared to the control group (P<0.05 and P<0.001 respectively). cTAC values in the MO patients increased significantly following weight loss (P<0.001) and were restored to normal. However, the postoperative TAC values in the MO group did not change significantly and remained lower than in the normal controls. A significant decrease (P<0.001) in uric acid values was also noticed in the MO group after weight loss. Conclusion: Plasma TAC and cTAC values are impaired in morbidly obese patients. Weight loss from an intragastric balloon is associated with significant increase in plasma cTAC values. Plasma TAC values, after the weight loss remain unchanged, possibly due to a decrease in uric acid, an important endogenous antioxidant.

Total and corrected antioxidant capacity in hemodialyzed patients

BackgroundOxidative stress may play a critical role in the vascular disease of end stage renal failure and hemodialysis patients. Studies, analyzing either discrete analytes and antioxidant substances, or the integrated total antioxidant activity of human plasma during hemodialysis, give contradictory results.MethodsRecently, we have introduced a new automated method for the determination of Total Antioxidant Capacity (TAC) of human plasma. We have serially measured TAC and corrected TAC (cTAC: after subtraction of the interactions due to endogenous uric acid, bilirubin and albumin) in 10 patients before the onset of the dialysis session, 10 min, 30 min, 1 h, 2 h and 3 h into the procedure and after completion of the session.ResultsOur results indicate that TAC decreases, reaching minimum levels at 2 h. However, corrected TAC increases with t1/2 of about 30 min. We then repeated the measurements in 65 patients undergoing dialysis with different filters (36 patients with ethylene vinyl alcohol copolymer resin filter -Eval-, 23 patients with two polysulfone filters -10 with F6 and 13 with PSN140-, and 6 patients with hemophan filters). Three specimens were collected (0, 30, 240 min). The results of this second group confirm our initial results, while no significant difference was observed using either filter.ConclusionsOur results are discussed under the point of view of possible mechanisms of modification of endogenous antioxidants, and the interaction of lipid- and water-soluble antioxidants.

Evaluation of bone disease in multiple myeloma: a correlation between biochemical markers of bone metabolism and other clinical parameters in untreated multiple myeloma patients.

INTRODUCTION Multiple myeloma (MM) is characterised by an uncoupled bone formation/resorption process resulting in osteolysis. Osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) are markers of osteoblastic activity, whereas pyridinoline products and the cross-linked aminoterminal of type I collagen (NTx) reflect bone destruction. In this study, these markers were studied in relation to bone disease severity and other clinical parameters of MM activity. METHODS Serum calcium, creatinine, CRP, beta 2 microglobulin (b(2)M), M-component, OC, BAP and free urine pyridoline (Pyd) and deoxypyridinoline (Dpd), free urine Dpd and NTx were determined in 38 newly diagnosed MM patients. X-ray examination defined the degree of bone involvement. Patients were classified according to the Durie-Salmon staging system. RESULTS NTx, free urine Pyd + Dpd, and free urine Dpd increased with increasing degree of bone involvement. NTx was significantly higher in stages II and III compared to stage I (mean values: 100.7, 163.5 and 208.3 nmol BCE/mM creat, respectively, p < 0.002). Free urine Pyd + Dpd correlated positively with b(2)M and CRP. OC was increased in stages I and II compared to III (p < 0.005) and was inversely correlated with NTx, free urine Pyd + Dpd, and free urine Dpd alone. CONCLUSIONS The measurement of bone turnover markers in MM provides significant information regarding disease progression and should be included in the evaluation of MM patients.

Effects of tumor necrosis factor alpha inhibition with infliximab on lipid levels and insulin resistance in patients with inflammatory bowel disease.

Introduction TNF-&agr; is a critical mediator of inflammation with an important role in metabolic profile and insulin resistance. The regulation of these parameters by TNF-&agr; in inflammatory bowel disease (IBD) is, however, poorly understood. The aim of this study was to assess the in-vivo TNF-&agr;-mediated regulation of insulin resistance and of lipid levels in patients with IBD. Methods Twenty-two patients with IBD (eight females; 19 Crohns disease) received infliximab according to treating physicians assessment at weeks 0, 2 and 6 from baseline and subsequently every 8 weeks and were prospectively followed for 14 weeks. Fasting insulin, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein A1 (apo-A1), apolipoprotein B100 and lipoprotein a were measured in serum at baseline and at week 14. Insulin resistance was calculated with the use of the Homeostasis Model Assessment index. Results Infliximab therapy induced clinical response or remission in 19 of the 22 patients. C-reactive protein levels were significantly decreased by week 14. Body mass index was increased in all patients. No difference was observed in insulin levels, Homeostasis Model Assessment index, triglycerides, LDL cholesterol, apolipoprotein B100 and lipoprotein a. In contrast, total cholesterol, HDL cholesterol and apo-A1 levels were significantly increased from baseline. Conclusion TNF-&agr; inhibition does not alter insulin resistance in IBD patients. In contrast, total cholesterol, HDL cholesterol and apo-A1 levels are significantly increased after infliximab treatment compared with baseline. The importance of these alterations needs to be clarified in future studies.

Alendronate reduces serum TNFα and IL-1β, increases neutrophil counts, and improves bone mineral density and bone metabolism indices in patients with chronic idiopathic neutropenia (CIN)-associated osteopenia/osteoporosis

The current study was undertaken to investigate the effect of alendronate on bone mineral density (BMD), bone metabolism markers, and serum bone-resorbing cytokines in patients with chronic idiopathic neutropenia (CIN)-associated osteopenia/osteoporosis. Sixteen randomly selected women, 7 with CIN-associated osteoporosis and 9 with CIN-associated osteopenia, and 14 age- and menopausal status-matched healthy volunteers, were enrolled in the study. Patients received 10 mg alendronate daily per os for 360 sdays and studies were done before treatment (day 0) and at varying time points during the study. We found that patients’ BMD measurements increased by 5.32% after treatment, and that the elevated serum osteocalcin (OC), a bone formation marker, decreased by day 30, normalized by day 90, and increased again by day 270 of treatment. Elevated values of patients’ urine deoxypyridinoline (Dpd) and N-telopeptide of type I of collagen (NTx), two bone resorption markers, returned to the control range by day 30 and decreased thereafter. Increased levels of patients’ serum tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β), two bone resorbing cytokines, returned to the control range by day 30 and decreased thereafter. Peripheral blood neutrophil counts increased by day 30 and continued to rise thereafter, reaching a mean value higher than 2650 neutrophils per µl of blood on day 360. Interestingly, alendronate-induced changes in the levels of both cytokines correlated inversely with the respective changes in neutrophil counts and BMD measurements, and positively with the changes in the respective means of urine NTx and Dpd values. All these findings indicate that alendronate is effective in treating CIN-associated osteopenia/osteoporosis, and that the beneficial effect of the compound may lie, at least in part, in its property to inhibit the production of TNFα and IL-1β by cells of the monocyte/macrophage system, in which osteoclasts are included.

Subclinical Hypothyroidism and Lipid Abnormalities in Older Women Attending a Vascular Disease Prevention Clinic: Effect of Thyroid Replacement Therapy

The authors evaluated the frequency and type of lipid disorders associated with subclinical hypothyroidism (SH) in older women referred to their university vascular disease prevention clinic. They also assessed the results of thyroid replacement therapy. Fasting serum lipid profiles and thyroid function tests were measured in 333 apparently healthy women (mean age: 71.8 ±7 years). These women were divided into 3 groups: group I: 60-69 years old (n =132); group II: 70-79 years old (n =153); group III: 80-89 years old (n = 48). SH was defined as a serum thyrotropin concentration higher than 3.20 mIU/mL with a normal free thyroxine concentration. The prevalence of SH was 7.5%. Thyrotropin was higher than 3.20 mU/mL in 25 women; 7 (5.3%), 14 (9.2%), and 4 (8.3%) in groups I, II, and III, respectively. Low-density lipoprotein cholesterol (LDL-C) concentrations were higher in the women with SH (p = 0.037). The mean values of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC/HDL- C ratio, lipoprotein (a) (Lp[a]), apolipoprotein A-I (apo AI) apolipoprotein B100 (apo B) and apo B/apo A ratio were higher and triglycerides (TG) were lower, compared with those with normal levels of thyrotropin. However, none of these differences reached significance. Restoration of euthyroid status (thyroxine: 50-100 μg/day) in 17 SH women significantly improved TC (p=0.017), LDL-C (p=0.014), TC/HDL-C (p=0.05), LDL-C/HDL-C (p=0.03), apo B (p=0.013), and Lp(a) (p= 0.0005) values. SH is relatively common in older women attending a vascular disease prevention clinic. Thyroid hormone replacement therapy significantly improved serum lipids. In particular, the reduction in LDL-C and Lp(a) concentrations may be of clinical benefit.

Discrepancy between exercise performance, body composition, and sex steroid response after a six-week detraining period in professional soccer players.

Purpose The aim of this study was to examine the effects of a six-week off-season detraining period on exercise performance, body composition, and on circulating sex steroid levels in soccer players. Methods Fifty-five professional male soccer players, members of two Greek Superleague Teams (Team A, n = 23; Team B, n = 22), participated in the study. The first two weeks of the detraining period the players abstained from any physical activity. The following four weeks, players performed low-intensity (50%–60% of VO2max) aerobic running of 20 to 30 minutes duration three times per week. Exercise performance testing, anthropometry, and blood sampling were performed before and after the six-week experimental period. Results Our data showed that in both teams A and B the six-week detraining period resulted in significant reductions in maximal oxygen consumption (60,31±2,52 vs 57,67±2,54; p<0.001, and 60,47±4,13 vs 58,30±3,88; p<0.001 respectively), squat-jump (39,70±3,32 vs 37,30±3,08; p<0.001, and 41,05±3,34 vs 38,18±3,03; p<0.001 respectively), and countermovement-jump (41,04±3,99 vs 39,13±3,26; p<0.001 and 42,82±3,60 vs 40,09±2,79; p<0.001 respectively), and significant increases in 10-meters sprint (1,74±0,063 vs 1,79±0,064; p<0.001, and 1,73±0,065 vs 1,78±0,072; p<0.001 respectively), 20-meters sprint (3,02±0,05 vs 3,06±0,06; p<0.001, and 3,01±0,066 vs 3,06±0,063; p<0.001 respectively), body fat percentage (Team A; p<0.001, Team B; p<0.001), and body weight (Team A; p<0.001, Team B; p<0.001). Neither team displayed any significant changes in the resting concentrations of total-testosterone, free-testosterone, dehydroepiandrosterone-sulfate, Δ4-androstenedione, estradiol, luteinizing hormone, follicle-stimulating hormone, and prolactin. Furthermore, sex steroids levels did not correlate with exercise performance parameters. Conclusion Our results suggest that the six-week detraining period resulted in a rapid loss of exercise performance adaptations and optimal body composition status, but did not affect sex steroid resting levels. The insignificant changes in sex steroid concentration indicate that these hormones were a non-contributing parameter for the observed negative effects of detraining on exercise performance and body composition.

Vitamin D and exercise performance in professional soccer players.

Aim The current study had two aims. The primary purpose was to examine the association between serum vitamin D levels and the ergometric evaluation of muscle strength, aerobic capacity, and speed in professional soccer players. The secondary aim was to evaluate the effects of the soccer off-season period on serum vitamin D levels. Methods Sixty-seven Caucasian male soccer players (age 25.6±6.2 and height 1.81±0.08 m), members of two Greek Superleague Soccer teams and one Football-league championship team participated in this study. Exercise performance testing for the determination of squat jump (SJ), countermovement jump (CMJ), 10 (10 m) and 20 meters (20 m) sprint performance, maximal oxygen consumption (VO2max), anthropometry, and blood sampling were performed before (pre) and after (post) the six-week off-season period. Results Analysis of our results showed the following: (a) a significant correlations between serum vitamin D levels and performance parameters in both pre (SJ; P<0.001, CMJ; P<0.001, VO2max; P<0.001, 10 m; P<0.001, and 20 m; P<0.001) and post (SJ; P<0.001, CMJ; P<0.001, VO2max; P = 0.006, 10 m; P<0.001, and 20 m; P<0.001) experimental sessions. (b) Vitamin D concentration increased significantly (P<0.001) following the six-week off-season period compared to baseline, while at the same time all measured performance parameters decreased (SJ; P<0.001, CMJ; P<0.001, 10 m; P<0.001, 20 m; P<0.001, VO2max; P<0.001). Discussion Our findings suggest that vitamin D levels are associated with the ergometric evaluation of muscle strength, as expressed by SJ and CMJ, sprinting capacity, and VO2max in professional soccer players, irrespective the levels of performance. Furthermore, our data reaffirm the importance of UVB on serum vitamin D levels. Moreover, reductions in exercise training stress may also have beneficial effects on vitamin D levels, suggesting a possible association of its levels and the training-induced stress. Our results indicate a possibly bidirectional interaction between soccer performance indices and vitamin D levels.