Celiac Disease Is a Risk Factor for Mature T and NK Cell Lymphoma: A Mendelian Randomization Study.

Celiac disease (CeD) is an immune-mediated disorder triggered by gluten ingestion that damages the small intestine. Although CeD has been associated with a higher risk for cancer, the role of CeD as a risk factor for specific malignancies, such as enteropathy-associated T-cell lymphoma (EATL), remains controversial. Using two-sample Mendelian randomization (2SMR) methods and the summarized results of large genome-wide association studies from public repositories, we addressed the causal relationship between CeD and eight different malignancies. Eleven non-HLA SNPs were selected as instrumental variables (IVs), and causality estimates were obtained using four 2SMR methods: random-effects inverse variance-weighted, weighted median estimation, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO). We identified a significant causal relationship between CeD and mature T/NK cell lymphomas. Under a multivariate Mendelian randomization model, we observed that the causal effect of CeD was not dependent on other known lymphoma risk factors. We found that the most instrumental IV was located in the TAGAP locus, suggesting that aberrant T cell activation might be relevant in the T/NK cell malignization process. Our findings provide new insights into the connection between immune imbalance and the development of severe comorbidities, such as EATL, in patients with CeD.

Vitamin D and Calcium as Key Potential Factors Related to Colorectal Cancer Prevention and Treatment: A Systematic Review.

Colorectal cancer (CRC) is currently considered one of the most common and lethal types of tumors. Nutrition is of notorious relevance, given its influence in CRC prevention and treatment. This systematic review aimed to revise and update the state of knowledge regarding the potential role of vitamin D and calcium as key factors involved in the prevention and treatment of CRC. A literature search was performed in PubMed and Web of Science. A total of eight studies were finally included in the present review. Vitamin D showed a protective role by promoting transcriptomic changes associated with antitumor effects. However, no significant effects of vitamin D were noted in the relapse-free survival of patients at 5 years. On the other hand, previous scientific evidence demonstrated that calcium regulates the expression of colonic proteins that decrease cell proliferation and increase cell differentiation. Nevertheless, an increased risk of associated serrated adenomas was found in response to calcium and calcium + vitamin D supplementation. Moreover, supplementation with both nutrients showed positive changes on relevant CRC biomarkers including TGFα, TGFß1, APC, ß-catenin and E-cadherin. In conclusion, vitamin D supplementation seems to have a protective effect in the prevention and treatment of CRC, while calcium intake showed contradictory effects as a prevention or treatment tool; therefore, further studies are necessary to well understand its relevance in patients with CRC.

Multidisciplinary Prehabilitation and Postoperative Rehabilitation for Avoiding Complications in Patients Undergoing Resection of Colon Cancer: Rationale, Design, and Methodology of the ONCOFIT Study.

ONCOFIT is a randomized clinical trial with a two-arm parallel design aimed at determining the influence of a multidisciplinary Prehabilitation and Postoperative Program (PPP) on post-surgery complications in patients undergoing resection of colon cancer. This intervention will include supervised physical exercise, dietary behavior change, and psychological support comparing its influence to the standard care. Primary and secondary endpoints will be assessed at baseline, at preoperative conditions, at the end of the PPP intervention (after 12 weeks) and 1-year post-surgery, and will include: post-surgery complications (primary endpoint); prolonged hospital length of stay; readmissions and emergency department call within 1-year after surgery; functional capacity; patient reported outcome measures targeted; anthropometry and body composition; clinical/tumor parameters; physical activity levels and sedentariness; dietary habits; other unhealthy habits; sleep quality; and fecal microbiota diversity and composition. Considering the feasibility of the present intervention in a real-life scenario, ONCOFIT will contribute to the standardization of a cost-effective strategy for preventing and improving health-related consequences in patients undergoing resection of colon cancer with an important clinical and economic impact, not only in the scientific community, but also in clinical practice.

Influence of Mediterranean Diet Adherence and Physical Activity on Bone Health in Celiac Children on a Gluten-Free Diet.

We aimed to assess the influence of the Mediterranean Diet adherence and physical activity (PA) on body composition, with a particular focus on bone health, in young patients with celiac disease (CD). The CD group (n = 59) included children with CD with a long (>18 months, n = 41) or recent (<18 months, n = 18) adherence to a gluten-free diet (GFD). The non-celiac group (n = 40) included non-celiac children. After adjusting for potential confounders, the CD group showed lower body weight (p = 0.034), lean mass (p = 0.003), bone mineral content (p = 0.006), and bone Z-score (p = 0.036) than non-celiac children, even when the model was further adjusted for adherence to a GFD for at least 18 months. Among CD children, spending greater time in vigorous physical activity was associated with higher lean mass (p = 0.020) and bone mineral density with evidence of statistical significance (p = 0.078) regardless of the time they followed a GFD. In addition, a greater Mediterranean Diet adherence was associated with a higher bone Z-score (p = 0.020). Moreover, lean mass was strongly associated with bone mineral density and independently explained 12% of its variability (p < 0.001). These findings suggest the importance of correctly monitoring lifestyle in children with CD regarding dietary habits and PA levels to improve lean mass and, consequently, bone quality in this population.

Oral supplementation with omega-3 fatty acids and inflammation markers in patients with chronic kidney disease in hemodialysis.

Chronic kidney disease (CKD) is an increasingly common public health problem that increases the risk of death because of cardiovascular complications by 2-3 times compared with the general population. This research concerns a prospective, randomized, double-blind study in patients with CKD undergoing hemodialysis. The participants were assigned to 1 of 2 groups: the study group (group A; 46 patients) received 4 capsules (2.4 g) of omega-3 fatty acids daily during the 12-week intervention, while patients in the control group (group B; 47 patients) received 4 capsules of paraffin oil. The patients' general characteristics, nutritional indicators, renal disease markers and inflammatory markers (C-reactive protein, interleukin (IL)-6, IL-10, and tumour necrosis factor alpha (TNF-α)) were evaluated. No differences were found between the general characteristics of the patients (P < 0.05), and no differences were shown in the nutritional indicators and markers of kidney disease (P < 0.05). Patients in group A showed significant decreases in levels of C-reactive protein, IL-6, TNF-α, and the IL-10/IL-6 ratio after 12 weeks of supplementation (P < 0.05). Patients in group B did not show any significant changes in concentrations of inflammatory markers during the intervention (P < 0.05). In conclusion, oral supplementation with omega-3 fatty acids produces a significant decrease in the concentrations of inflammation markers in patients with chronic kidney disease on hemodialysis. Novelty Oral supplementation with omega-3 fatty acids produced significant decreases in the concentrations of inflammation markers. This supplementation could be given to patients with uremic syndrome and coronary heart disease to reduce cardiovascular risk.

Association of Body Mass Index and Serum Markers of Tissue Damage with Postoperative Pain. The Role of Lactate Dehydrogenase for Postoperative Pain Prediction.

OBJECTIVES: i) To analyze the association of body mass index (BMI) and some serum tissue damage markers with postoperative pain. ii) To establish a biochemical marker cutoff point able to predict moderate to severe postoperative pain. DESIGN: Cross-sectional study. SUBJECTS: Ninety-six adult male patients from Southern Spain (55 ± 13 years old) who underwent an inguinal hernioplasty. METHODS: Postoperative pain (eight hours after surgery) was assessed through a visual analog scale (VAS). Moderate to severe pain was defined as a VAS > 50 mm. BMI was calculated and medication, alcohol consumption, and smoking habit registered. Eight hours after surgery, some serum markers such as fibrinogen, lactate dehydrogenase (LDH), C-reactive protein, cortisol, creatine kinase, glutamic-pyruvic, glutamic oxaloacetic, and gamma-glutamyltransferase transaminases were determined by standard procedures. RESULTS: After adjusting for potential confounders, BMI was not associated with postoperative pain (P > 0.05). Serum fibrinogen was associated with greater postoperative pain (ß = 0.333, P < 0.05). Serum LDH concentration was strongly associated with greater postoperative pain (ß = 0.606, P < 0.001). Alcohol consumption was associated with higher postoperative pain (ß = 0.212, P < 0.05). No associations were observed regarding age, tobacco consumption, and the rest of serum markers studied. Serum LDH concentration was able to discriminate between presence/absence of moderate to severe postoperative pain (receiver operating characteristic area under the curve = 0.655, P ≤ 0.01). An LDH concentration >204 IU/L was associated with a three-times increased odds ratio of moderate to severe postoperative pain. CONCLUSIONS: Contrary to expectations, greater BMI was not associated with higher postoperative pain. Notwithstanding, the assessment of serum LDH might provide useful information to predict moderate to severe postoperative pain.

Fermented goat milk improves antioxidant status and protects from oxidative damage to biomolecules during anemia recovery.

BACKGROUND: Iron deficiency anemia (IDA) is one of the most common nutritional problems in the world, and it is accepted that reactive oxygen species (ROS) production is altered during IDA. The aim of this study was to assess the influence of fermented goat and cow milks on enzymatic antioxidant activities and gene expression, and their role in protecting from oxidative damage during anemia recovery. RESULTS: After feeding the fermented milks-based diets (cow or goat), a significant elevation of some antioxidant endogenous enzymes was found, together with an increase in total antioxidant status (TAS), and a decrease in 8-hydroxy-2'-deoxyguanosine (8-OHdG) was recorded in animals consuming fermented goat milk-based diet. In contrast, DNA strand breaks, hydroperoxides, 15-F2t-isoprostanes and protein carbonyl groups were lower in some tissues in animals fed fermented goat milk-based diet, revealing an improvement in both systemic and cellular antioxidant activity of plasma and tissues due to fermented goat milk consumption. CONCLUSION: Fermented goat milk consumption induces a protective increase in TAS together with lower oxidative damage biomarkers, revealing that the milk protects main cell bioconstituents (lipids, protein, DNA, prostaglandins) from evoked oxidative damage during anemia recovery. © 2016 Society of Chemical Industry.

Fermented goat milk consumption improves melatonin levels and influences positively the antioxidant status during nutritional ferropenic anemia recovery.

The aim of the current study was to assess the influence of fermented goat or cow milk on melatonin levels and antioxidant status and during anemia recovery. Eighty male Wistar rats were placed on a pre-experimental period of 40 days and randomly divided into two groups, a control group receiving normal-Fe diet (45 mg kg(-1)) and the Fe-deficient group receiving low-Fe diet (5 mg kg(-1)). Then, the rats were fed with fermented goat or cow milk-based diets with a normal-Fe content or Fe-overload (450 mg kg(-1)) for 30 days. After 30 days of feeding the fermented milks, the total antioxidant status (TAS) was higher in both groups of animals fed fermented goat milk with the normal-Fe content. Plasma and urine 8-OHdG were lower in control and anemic rats fed fermented goat milk. Melatonin and corticosterone increased in the anemic groups during Fe replenishment with both fermented milks. Urine isoprostanes were lower in both groups fed fermented goat milk. Lipid and protein oxidative damage were higher in all tissues with fermented cow milk. During anemia instauration, an increase in melatonin was observed, a fact that would improve the energy metabolism and impaired inflammatory signaling, however, during anemia recovery, fermented goat milk had positive effects on melatonin and TAS, even in the case of Fe-overload, limiting the evoked oxidative damage.

Folic acid supplemented goat milk has beneficial effects on hepatic physiology, haematological status and antioxidant defence during chronic Fe repletion.

The aim of the current study was to asses the effect of goat or cow milk-based diets, either normal or Fe-overloaded and folic acid supplement on some aspects of hepatic physiology, enzymatic antioxidant defence and lipid peroxidation in liver, brain and erythrocyte of control and anaemic rats after chronic Fe repletion. 160 male Wistar rats were placed on 40 d in two groups, a control group receiving normal-Fe diet and the Fe-deficient group receiving low Fe diet. Lately, the rats were fed with goat and cow milk-based diets during 30 d, with normal-Fe content or Fe-overload and either with normal folic or folic acid supplemented. Fe-overload increased plasma alanine transaminase and aspartate transaminase levels when cow milk was supplied. Dietary folate supplementation reduced plasma transaminases levels in animals fed goat milk with chronic Fe overload. A remarkable increase in the superoxide dismutase activity was observed in the animals fed cow milk. Dietary folate supplement lead to a decrease on the activity of this enzyme in all the tissues studied with both milk-based diets. A concomitant increment in catalase was also observed. The increase in lipid peroxidation products levels in rats fed cow milk with Fe-overload, suggest an imbalance in the functioning of the enzymatic antioxidant defence. In conclusion, dietary folate-supplemented goat milk reduces both plasma transaminases levels, suggesting a hepatoprotective effect and has beneficial effects in situation of Fe-overload, improving the antioxidant enzymes activities and reducing lipid peroxidation.

Influence of cow or goat milk consumption on antioxidant defence and lipid peroxidation during chronic iron repletion.

Despite Fe deficiency and overload having been widely studied, no studies are available about the influence of milk consumption on antioxidant defence and lipid peroxidation during the course of these highly prevalent cases. The objective of the present study was to assess the influence of cow or goat milk-based diets, either with normal or Fe-overload, on antioxidant defence and lipid peroxidation in the liver, brain and erythrocytes of control and anaemic rats after chronic Fe repletion. Weanling male rats were randomly divided into two groups: a control group receiving a normal-Fe diet (45 mg/kg) and an anaemic group receiving a low-Fe diet (5 mg/kg) for 40 d. Control and anaemic rats were fed goat or cow milk-based diets, either with normal Fe or Fe-overload (450 mg/kg), for 30 or 50 d. Fe-deficiency anaemia did not have any effect on antioxidant enzymes or lipid peroxidation in the organs studied. During chronic Fe repletion, superoxide dismutase (SOD) activity was higher in the group of animals fed the cow milk diet compared with the group consuming goat milk. The slight modification of catalase and glutathione peroxidise activities in animals fed the cow milk-based diet reveals that these enzymes are unable to neutralise and scavenge the high generation of free radicals produced. The animals fed the cow milk diet showed higher rates of lipid peroxidation compared with those receiving the goat milk diet, which directly correlated with the increase in SOD activity. It was concluded that goat milk has positive effects on antioxidant defence, even in a situation of Fe overload, limiting lipid peroxidation.

Severe nutritional iron-deficiency anaemia has a negative effect on some bone turnover biomarkers in rats.

BACKGROUND: The role of iron (Fe) in bone formation and disease have not received much attention, a fact that is interesting given the known biochemical role that this mineral has upon collagen maturation together with the high prevalence of Fe-deficiency anaemia worldwide. AIM: To investigate the changes in bone formation, resorption and mineral content in developing rats with induced nutritional Fe-deficiency anaemia. METHODS: Thirty male Wistar rats were divided into two groups, a control group receiving AIN-93G diet with normal-Fe content and an anaemic group receiving AIN-93G diet with low-Fe content for 40 days. Both diets were prepared with an adequate calcium (Ca) and phosphorus (P) content. The most representative serum bone turnover biomarkers and femur and sternum calcium and phosphorus content, together with sternum Fe content were determined in both experimental groups. RESULTS: In anaemic rats, bone matrix formation diminished as revealed by the lower amount of procollagen type I N-terminal propeptide. Bone resorption process increased in Fe deficiency as shown by the increase of serum parathyroid hormone, tartrate-resistant acid phosphatase and levels of degradation products from C-terminal telopeptides of type I collagen released to the serum. In addition, mineralization process was affected by Fe deficiency, because Ca and P content in femur decreased markedly. CONCLUSIONS: Fe-deficiency anaemia had a significant impact upon bone, affecting bone mineralization, decreasing the matrix formation and increasing bone resorption, therefore it is of great interest to assess bone status in situation of Fe-deficiency anaemia.

Se bioavailability and glutathione peroxidase activity in iron deficient rats.

Little information is available on the relationship of Se deposit in target organs and GPx activity in iron deficiency anemia. As red blood cells (RBCs) play a crucial role on Se metabolism and during Fe deficiency anemia a lower count of RBCs is featured, we aimed to investigate the influence of this pathology on Se bioavailability and the relationship with antioxidant status. 20 male Wistar rats were randomly divided into two groups, a control group receiving AIN-93G diet with normal Fe content (45mg/kg diet) and the Fe-deficient group receiving AIN-93G diet with low Fe content (5mg/kg diet) for 40 days. Both diets were prepared with an adequate Se content (0.180mg/kg diet). The digestive and metabolic utilization of Se, the distribution in target organ, the GPx activity and TBARS production were measured after receiving the diets. Se retention increased (P<0.001) in the anemic group, fact that contributes to keep the enzymatic antioxidant activity of GPx in normal levels and the tendency observed is that stored Se increased in the organs, especially in kidney (P<0.01), however, a lower Se deposit was found in sternum of anemic rats (P<0.001). The lower count of RBCs featured in this pathology (P<0.001) causes a decrease of Se concentration in sternum meanwhile the increase in kidney deposit is a consequence of the lower urinary losses (P<0.001).

Effect of synergic dietary calcium enrichment and induced ferropenic anemia on antioxidant enzymes activity in rats.

OBJECTIVE: The aim of this study was to examine the synergism of dietary calcium enrichment (added to goat's or cow's milk) and induced nutritional ferropenic anemia on oxidative status. METHODS: Control rats and rats with induced nutritional ferropenic anemia were fed for 14 d with diets containing normal (5000 mg/kg) or double (10 000 mg/kg) the recommended calcium content. Thiobarbituric acid-reactive substances in plasma were measured, as were the activities of the antioxidant enzyme catalase, copper/zinc superoxide dismutase, and glutathione peroxidase in erythrocyte cytosol. RESULTS: Dietary calcium enrichment did not affect oxidative stress as assessed by thiobarbituric acid-reactive substances; however, it significantly upregulated the activities of some antioxidant enzymes examined in the erythrocyte cytosol. In particular, adding calcium to standard or milk-based diets significantly increased glutathione peroxidase activity in control and anemic rats and copper/zinc superoxide dismutase activity in control rats. CONCLUSION: The increased activities of glutathione peroxidase and copper/zinc superoxide dismutase induced by dietary calcium enrichment suggest that calcium supplementation may protect against oxidative stress even in nutritionally induced ferropenic anemia.

Influence of nutritional iron deficiency anemia on DNA stability and lipid peroxidation in rats.

OBJECTIVE: Oxidative stress results from an imbalance between the formation and neutralization of pro-oxidants. Disturbance of the pro-oxidant/antioxidant balance is also considered to be a causative factor underlying oxidative damage to cellular molecules, such as DNA, causing strand breaks. There is considerable controversy about the antioxidant status in iron-deficiency anemia (IDA), but scant information is available regarding DNA integrity. In the present study, we investigated the relation between DNA stability and hepatic antioxidant capacity in rats with induced IDA. METHODS: Peripheral DNA damage was assessed using an alkaline comet assay. Further, the hepatic antioxidant enzyme glutathione peroxidase and the production of thiobarbituric acid-reactive substances were measured in control rats and in those with induced IDA. RESULTS: Comparison of the control and anemic rats showed no differences in thiobarbituric acid-reactive substances production in the cytosolic fraction of hepatic cells. Nor were there any differences in liver glutathione peroxidase enzyme activity or DNA stability, as demonstrated by the percentage of DNA in the head (90.77 in control rats versus 88.23 in anemic rats), tail (9.23 in control rats versus 11.76 in anemic rats), and olive tail moment (0.155 in control rats versus 0.141 in anemic rats). CONCLUSION: IDA does not affect DNA stability or lipid peroxidation in rats, suggesting that there is enough compensatory capacity to keep antioxidant defenses high.

Calcium-enriched goats' milk aids recovery of iron status better than calcium-enriched cows' milk, in rats with nutritional ferropenic anaemia.

Ca-Fe interactions are known, but no studies are available about the effects of Ca-enriched goat or cow milk on Fe status in nutritional ferropenic anaemia (NFA). To examine this matter, control and Fe-deficient rats were fed for 14 d with goat or cow milk diets containing either normal or high Ca content (5000 or 10,000 mg/kg diet), and different indices and parameters related to iron status were measured. The apparent digestibility coefficient (ADC) and the Fe retention/intake (R/I) ratio were higher in control and anaemic rats fed goat milk diet (G diet), despite high-Ca content. Ca enrichment decreased Fe stores in liver and sternum in anaemic rats fed cow milk diet (C diet), however G diet did not modify Fe content in the organs studied in control and anaemic rats. In anaemic rats, Ca-supplementation decreased haematocrit, but platelets and serum Fe were not affected, however, in control rats platelets increased except for Ca-enriched G diet, this fact reveals that Ca-Fe interaction is minimized with G diet. Serum ferritin was always higher in rats fed G vs. C diet, both in control and anaemic rats fed either normal or Ca-enriched diets. Ca-supplementation decreased ferritin levels in control and anaemic rats fed C diet and also, though to a lesser extent, in those given the G diet. This indicates that with this G diet there is a better recovery of body Fe stores in anaemic rats, despite Ca-supplementation. In this study it is noteworthy that despite high Ca content, a goat milk diet resulted in minimal Ca-Fe interactions and did not adversely affect Fe status in rats with NFA.

Effects of lifestyle modification and lipid intake variations on patients with peripheral vascular disease.

The aim of the present study was to evaluate the effects of diets enriched in monounsaturated fatty acids (MUFA) (olive oil) or MUFA plus n-3 polyunsaturated fatty acids (PUFA) (olive oil plus fish oil), associated with an intervention program that focused on lifestyle habits, physical performance, plasma lipids, and lipoprotein composition in patients with peripheral vascular disease (PVD). A 15-month longitudinal nutritional and lifestyle intervention study was carried out with 24 free-living male patients aged 58.0 +/- 2.2 years diagnosed with PVD (Fontaine grade II). The patients were clinically evaluated and counseled to change their dietary and lifestyle habits for six months, after this period they consumed an olive oil-based diet for three months: after a three-month wash-out period, their diet was supplemented with a combination of fish oil and olive oil for the final three months. Lifestyle interventions resulted in a significant decrease in cigarette smoking and an increase in physical activity. Claudicometry was lower at the end of the study than at the beginning. Intake of the fish oil supplement led to significant changes in lipid lipoprotein composition, decreasing low-density lipoprotein (LDL) cholesterol. The lifestyle intervention program, together with a high intake of olive plus fish oil, seems to produce important beneficial effects in nutritional management, physical performance, and clinical parameters of PVD patients.