Estimation of Dietary Sources and Flavonoid Intake in a Spanish Adult Population (EPIC-Spain)

Background

Epidemiologic studies have suggested associations between flavonoid intake and health benefits. Traditional Mediterranean diets consist of a high consumption of plant products rich in flavonoids.

Objective

This study estimates dietary flavonoid intake and main food sources in a Mediterranean population (Spanish adults).

Design

The study included 40,683 subjects aged 35 to 64 years from northern and southern regions of Spain who were included in the European Prospective Investigation into Cancer and Nutrition study Spanish cohort. Usual food intake was assessed by personal interviews using a computerized version of a validated diet history method. Expanded US Department of Agriculture databases for the flavonoid, isoflavone, and proanthocyanidin content were used.

Results

The median and mean of total flavonoids were 269.17 and 313.26 mg/day, respectively. The most abundant flavonoid subgroup was proanthocyanidins (60.1%), followed by flavanones (16.9%), flavan-3-ols (10.3%), flavonols (5.9%), anthocyanidins (5.8%), flavones (1.1%), and isoflavones (<0.01%). The main sources of total flavonoid intake were apples (23%), red wine (21%), unspecified fruit (12.8%), and oranges (9.3%).

Conclusions

These results should be very useful for evaluating the relationships between flavonoid intake and several diseases.     

Differential inflammatory status in rats susceptible or resistant to diet-induced obesity: effects of EPA ethyl ester treatment

Background  Obesity has been associated with a chronic low degree inflammatory response, characterized by an increase of inflammatory adipocytokines like tumoral necrosis factor-α (TNF-α), interleukin-6 (IL-6) as well as the synthesis of acute phase reactants such as haptoglobin. Aim of the study  To evaluate if impairments in the inflammatory response at the white adipose tissue (WAT) level could be involved in the mechanisms conferring susceptibility or resistance to high-fat diet-induced obesity (DIO). Methods  The expression levels of WAT genes and systemic markers related to inflammation were evaluated in two groups of rats fed with a high-fat diet during 15 days that showed either an early susceptibility (DIO) or resistance (DR) to develop obesity. We also tested the efficacy of the eicosapentaenoic (EPA) ω-3 fatty acid treatment (35 days) to potentially counteract the obesity-associated inflammatory features in DIO rats. Results  This trial showed that high-fat diet induces an increase on mRNA levels on TNF-α and haptoglobin in DIO animals (P < 0.05), while no significant changes were observed on DR rats. Furthermore, a significant increase in IL-6 mRNA (P < 0.05) was found in both DR and DIO rats. EPA-treatment caused a significant decrease in IL-6 mRNA (P < 0.05), without significant changes in haptoglobin mRNA levels in adipose tissue. An unexpected decrease was observed in haptoglobin serum levels (P < 0.05) in DIO rats, which was reverted to control values in EPA-treated animals. Conclusions  Our data suggest that obesity susceptibility or resistance may depend on the genetic make up related to inflammatory features, and support a role for ω-3 fatty acids in the prevention of obesity-associated inflammation in adipose tissue. In addition, our data do not support the hypothesis that serum haptoglobin is an acute phase protein expected to be positively related to increased adiposity in rats, at least in early and medium stages of DIO.     

Experience with miltefosine for persistent or relapsing visceral leishmaniasis in solid organ transplant recipients: A case series from Spain

The incidence of visceral leishmaniasis (VL) after solid organ transplantation (SOT) is increasing. The optimal therapy for post‐transplant VL remains unclear, as relapses after liposomal amphotericin B (L‐AmB) are common. Miltefosine has been shown to be effective for treating VL in immunocompetent patients, although data in the specific population of SOT recipients are lacking. In the setting of an outbreak of leishmaniasis occurring in Southwest Madrid, we reviewed our experience in 6 SOT recipients with persistent or relapsing VL who received a 28‐day course of miltefosine (2.5 mg/kg/day) as salvage therapy. All patients had been treated previously with L‐AmB as first‐line therapy. The incident episode of VL occurred at a median of 14 months after transplantation. Two patients experienced persistent infection and the remaining 4 had a relapse after a median interval of 168 days since the completion of the course of L‐AmB. All the patients had an apparent initial clinical improvement with miltefosine. However, VL relapsed in 3 of them (after a median interval of 46 days), which required retreatment with L‐AmB‐based regimens. Miltefosine therapy was followed by a prolonged secondary prophylaxis with L‐AmB in the only 2 cases with sustained clinical response and ongoing immunosuppression. No adverse effects associated with miltefosine were observed. Albeit limited, our experience suggests that miltefosine monotherapy likely has a limited utility to obtain a long‐lasting clinical response in complicated (persistent or relapsing) forms of post‐transplant VL, although its role in association with L‐AmB‐based secondary prophylaxis may merit further investigation.     

Does Schwann cell dedifferentiation originate dermal neurofibromas?

Dermal neurofibromas are characteristic of neurofibromatosis type one (NF1), and their developmental origin still unsolved. Although NF1 loss is required for neurofibroma initiation, some features of these benign tumors resemble a skin injury state and cutaneous trauma or other insults might support tumor development. Since adult terminal Schwann cells ensheathing nerve endings are able to dedifferentiate into a progenitor‐like state in response to nerve crushing, we hypothesized that dedifferentiation of NF1^?/? Schwann cells could be at the origin of human dermal neurofibromas. In support of this, here we show that CDH19 (a marker specific of Schwann cell precursors) and Schwann cell dedifferentiation marker SOX2 are significantly upregulated in NF1 tumors. We posit that onset of nerve regeneration might have a role in dermal neurofibroma initiation via dedifferentiation of NF1^?/? Schwann cells.     

Distribution of neuropeptide FF-like immunoreactivity in the brain of Dermophis mexicanus (Amphibia; Gymnophiona): comparison with FMRFamide immunoreactivity

Neuropeptide FF (NPFF) is an FMRFamide-related peptide widely distributed in the mammalian brain. NPFF immunohistochemistry labeled cell bodies in a few locations and dense fiber networks throughout the brain. Recently, the distribution of NPFF immunoreactive (NPFF-ir) cells and fibers in the brain of anuran and urodele amphibians was studied and, as in mammals, significant species differences were noted. To further assess general and derived features of the NPFF-containing neuron system in amphibians, we have investigated the distribution of NPFF-ir cell bodies and fibers in the brain of the gymnophionan Dermophis mexicanus by means of an antiserum against bovine NPFF. This distribution was compared to that of FMRFamide immunoreactivity. Major traits shared with anurans and urodeles were the abundant fiber labeling in the ventral telencephalon, hypothalamus, isthmus, ventrolateral medulla and dorsal spinal cord. In addition, in the three amphibian orders the majority of the NPFF-ir cells were located in the preoptic-hypothalamic region. However, distinct particular features were present in the gymnophionan such as the lack of NPFF-ir cells in the telencephalon, brainstem and spinal cord and the absence of NPFF-ir fibers in the hypophysis and the olfactory bulbs. This pattern was distinct from that observed for FMRFamide distribution. Striking differences were noted in the pallium, caudal hypothalamus and midbrain tegmentum where FMRFamide-containing cells were localized. The present results in Dermophis support the idea that data from gymnophionans must be included when stating the amphibian condition of a given system because important variations are obvious when gymnophionans are compared with anurans and urodeles.     

Efectividad de un programa de estiramientos sobre los niveles de ansiedad de los trabajadores de una plataforma logística: un estudio controlado aleatorizado

ObjectiveTo study the influence of a short programme of stretching exercises on anxiety levels of workers in a Spanish logistic company.MethodA controlled clinical trial was carried out by means of an inter-subject design of random homogeneous blocks. Participants were assigned to the experimental group (n = 67), treated with a programme of stretching exercises of 10-minute duration after working hours for a period of 3 months, or to the untreated control group (n = 67). The primary result variable was anxiety, and the secondary variables were burnout syndrome, quality of life and flexibility. An analysis of covariance (ANCOVA) by intention to treat was performed on each of the result variables by controlling the baseline scores, the age and the practice of introjective activities outside the program, with the size effect calculated by means of the partial eta-squared value (η²).ResultsThe results of the ANCOVA showed a moderate effect of the stretching exercise programme on the levels of anxiety (η² = 0,06; P = .004). Other effects found were substantial for flexibility (η² = 0,13; P < .001); moderately high for bodily pain (η² = 0,08; P = .001), and moderate for vitality (η² = 0,05; P = .016); mental health (η² = 0,05; P = .017); general health (η² = 0,04; P = .028) and exhaustion (η² = 0,04; P = .025).ConclusionsThe implementation of a short programme of stretching exercises in the work place was effective for reducing levels of anxiety, bodily pain and exhaustion, and for raising levels of vitality, mental health, general health and flexibility. This type of intervention could be seen as a low-cost strategy for improving the well-being of workers.     

Inhibition of GTP cyclohydrolase attenuates tumor growth by reducing angiogenesis and M2‐like polarization of tumor associated macrophages

GTP cyclohydrolase (GCH1) is the key‐enzyme to produce the essential enzyme cofactor, tetrahydrobiopterin. The byproduct, neopterin is increased in advanced human cancer and used as cancer‐biomarker, suggesting that pathologically increased GCH1 activity may promote tumor growth. We found that inhibition or silencing of GCH1 reduced tumor cell proliferation and survival and the tube formation of human umbilical vein endothelial cells, which upon hypoxia increased GCH1 and endothelial NOS expression, the latter prevented by inhibition of GCH1. In nude mice xenografted with HT29‐Luc colon cancer cells GCH1 inhibition reduced tumor growth and angiogenesis, determined by in vivo luciferase and near‐infrared imaging of newly formed blood vessels. The treatment with the GCH1 inhibitor shifted the phenotype of tumor associated macrophages from the proangiogenic M2 towards M1, accompanied with a shift of plasma chemokine profiles towards tumor‐attacking chemokines including CXCL10 and RANTES. GCH1 expression was increased in mouse AOM/DSS‐induced colon tumors and in high grade human colon and skin cancer and oppositely, the growth of GCH1‐deficient HT29‐Luc tumor cells in mice was strongly reduced. The data suggest that GCH1 inhibition reduces tumor growth by (i) direct killing of tumor cells, (ii) by inhibiting angiogenesis, and (iii) by enhancing the antitumoral immune response.