Identifying psychosocial and familial correlates and the impact of the stressful life events in the onset of anorexia nervosa: Control-case study (ANOBAS): Psychosocial and familial correlates and stressful life events in AN.

Anorexia nervosa (AN) is a multifactorial illness. Although several studies have determined which factors could predispose AN, few studies have determined which factors could precipitate it. What is more, it has been suggested that having experienced stressful life events (SLE) could be related to the onset of AN. The aim of this study was to explore specific psychosocial and familial correlates and the impact of SLE in the onset of AN. Following a case-control design, 40 adolescents diagnosed with AN were matched to three control groups, 40 healthy adolescents, 40 adolescents with affective disorders, 40 adolescents with asthma and their families by sex, age and socioeconomic status. Diagnostic interviews K-DSADS and questionnaires were used. The results empathised that no specific predisposing correlates were found for AN. Similarly, the increase of the amount of SLE prior to the onset is an overall characteristic for psychiatric disorders, which in AN it is only specifically related to psychological correlates, but no to cortisol. In terms of specific SLE, those related to interpersonal problems were frequent at the onset of AN. The results highlight the consequences of SLEs in the emotional well-being of the AN adolescents, that could be specific for this psychopathology.

Dietary sources of sugars in adolescents' diet: the HELENA study.

OBJECTIVE: To report dietary sugars consumption and their different types and food sources, in European adolescents. METHODS: Food consumption data of selected groups were obtained from 1630 adolescents (45.6% males, 12.5-17.5 years) from the HELENA study using two nonconsecutive 24-h recalls. Energy intake, total sugars and free sugars were assessed using the HELENA-DIAT software. Multiple regression analyses were performed adjusting for relevant confounders. RESULTS: Total sugars intake (137.5 g/day) represented 23.6% and free sugars (110.1 g/day), 19% of energy intake. Girls had significantly lower intakes of energy, carbohydrates, total sugars and free sugars. 94% of adolescents had a consumption of free sugars above 10% of total energy intake. The main food contributor to free sugars was 'carbonated, soft and isotonic drinks,' followed by 'non-chocolate confectionary' and 'sugar, honey, jam and syrup.' Older boys and girls had significantly higher intakes of free sugars from 'cakes, pies and biscuits.' Free sugars intake was negatively associated with low socioeconomic status for 'non-chocolate confectionary' and 'sugar, honey and jam' groups; with low maternal educational level for carbonated and 'soft drinks,' 'sugar, honey and jam,' 'cakes and pies' and 'breakfast cereals' groups; and with high paternal educational level for 'carbonated and soft drinks' and 'chocolates' group. CONCLUSIONS: The majority (94%) of studied adolescents consumed free sugars above 10% of daily energy intake. Our data indicate a broad variety in foods providing free sugars. Continued efforts are required at different levels to reduce the intake of free sugars, especially in families with a low educational level.

Arteriovenous malformation of the iris. Two cases. / Malformación arteriovenosa iridiana. Dos casos.

CASE REPORT: A 50-year-old patient was seen during a regular follow up. The main complaint was decreased near-sight vision. Biomicroscopy showed a vascular malformation on the temporal sector of the iris in the left eye, diagnosed as an arteriovenous malformation. A second case of similar features is also presented. DISCUSSION: The vascular malformations of the iris may be asymptomatic and go unnoticed or cause recurrent spontaneous hyphemas. Treatment must be individualised and may range from observation to photocoagulation with laser, or even surgery.

The HLA-DQ2 genotype selects for early intestinal microbiota composition in infants at high risk of developing coeliac disease.

OBJECTIVE: Intestinal dysbiosis has been associated with coeliac disease (CD), but whether the alterations are cause or consequence of the disease is unknown. This study investigated whether the human leukocyte antigen (HLA)-DQ2 genotype is an independent factor influencing the early gut microbiota composition of healthy infants at family risk of CD. DESIGN: As part of a larger prospective study, a subset (n=22) of exclusively breastfed and vaginally delivered infants with either high genetic risk (HLA-DQ2 carriers) or low genetic risk (non-HLA-DQ2/8 carriers) of developing CD were selected from a cohort of healthy infants with at least one first-degree relative with CD. Infant faecal microbiota was analysed by 16S rRNA gene pyrosequencing and real time quantitative PCR. RESULTS: Infants with a high genetic risk had significantly higher proportions of Firmicutes and Proteobacteria and lower proportions of Actinobacteria compared with low-risk infants. At genus level, high-risk infants had significantly less Bifidobacterium and unclassified Bifidobacteriaceae proportions and more Corynebacterium, Gemella, Clostridium sensu stricto, unclassified Clostridiaceae, unclassified Enterobacteriaceae and Raoultella proportions. Quantitative real time PCR also revealed lower numbers of Bifidobacterium species in infants with high genetic risk than in those with low genetic risk. In high-risk infants negative correlations were identified between Bifidobacterium species and several genera of Proteobacteria (Escherichia/Shigella) and Firmicutes (Clostridium). CONCLUSIONS: The genotype of infants at family risk of developing CD, carrying the HLA-DQ2 haplotypes, influences the early gut microbiota composition. This finding suggests that a specific disease-biased host genotype may also select for the first gut colonisers and could contribute to determining disease risk.

Differences in maternal behavior and development of their pups depend on the time of methamphetamine exposure during gestation period.

The present study examined the hypothesis that the extension of noxious effect of methamphetamine (MA) on maternal behavior and postnatal development on the pups may differ in dependence with time of application. Female rats were injected with MA (5 mg/kg) or saline during first (embryonic day (ED) 1-11) or second (ED 12-22) half of gestation. Our results demonstrated that MA exposure on ED 12-22 led to decreased birth weight and weight gained during lactation period relative to rats treated on ED 1-11. Both sexes treated prenatally with MA on ED 1-11 opened eyes earlier compared to animals treated on ED 12-22. As a matter of sensorimotor development application of MA on ED 1-11 impaired the righting reflex, while MA exposure on ED 12-22 impaired the performance of beam balance test in male rats. There were no differences in maternal behavior. Therefore, it seems that MA exposure in the first half of the gestation impaired the early sensorimotor development that is under control of the brain stem, while the MA exposure in the second half of gestation affected the beam balance performance that is dependent on the function of the cerebellum.

Massive lipid exudation and retinal detachment after combined brachytherapy and transpupillary thermotherapy in choroidal melanoma.

CASE REPORT: A 59 year-old male with choroidal melanoma in the left eye who underwent plaque brachytherapy (iodine 125). One week after surgery, massive exudation with retinal detachment and lipid exudation was observed. Evolution was assessed with funduscopy and ultrasound every month. Nine months after surgery transpupillary thermotherapy (TTT) was performed over the fluid-free irradiated residual tumour. Three months after this procedure, new retinal breaks appeared in the treated area with vitreous seeding that required enucleation. DISCUSSION: Combined treatment with plaque brachytherapy and TTT may associate severe complications that may require enucleation of the involved eye.

Do prenatally methamphetamine-exposed adult male rats display general predisposition to drug abuse in the conditioned place preference test?

Drug abuse of pregnant women is a growing problem. The effect of prenatal drug exposure may have devastating effect on development of the offsprings that may be long-term or even permanent. One of the most common drug abused by pregnant women is methamphetamine (MA), which is also the most frequently abused illicit drug in the Czech Republic. Our previous studies demonstrated that prenatal MA exposure alters behavior, cognition, pain and seizures in adult rats in sex-specific manner. Our most recent studies demonstrate that prenatal MA exposure makes adult rats more sensitive to acute injection of the same or related drugs than their controls. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the Conditioned place preference (CPP). Adult male rats were divided to: prenatally MA-exposed (5 mg/kg daily for the entire prenatal period), prenatally saline-exposed (1 ml/kg of physiological saline) and controls (without maternal injections). The following drugs were used in the CPP test in adulthood: MA (5 mg/kg), amphetamine (5 mg/kg), cocaine (5 and 10 mg/kg), morphine (5 mg/kg), MDMA (5 mg/kg) and THC (2 mg/kg). Our data demonstrated that prenatally MA-exposed rats displayed higher amphetamine-seeking behavior than both controls. MA as well as morphine induced drug-seeking behavior of adult male rats, however this effect did not differ based on the prenatal MA exposure. In contrast, prenatal MA exposure induced rather tolerance to cocaine than sensitization after the conditioning in the CPP. MDMA and THC did not induce significant effects. Even though the present data did not fully confirmed our hypotheses, future studies are planned to test the drug-seeking behavior also in self-administration test.

Does prenatal methamphetamine exposure induce cross-sensitization to cocaine and morphine in adult male rats?

The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to challenge dose of cocaine or morphine. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male offspring (prenatally MA- or saline-exposed) were divided to groups with challenge doses of saline (1 ml/kg), cocaine (5 mg/kg) or morphine (5 mg/kg). Behavior in unknown environment was examined in Laboras, nociception in Plantar test, and active drug-seeking behavior in conditioned place preference (CPP). Our data demonstrate that cocaine increased the exploratory activity in Laboras test in prenatally saline-exposed, but decreased it in prenatally MA-exposed rats. An analgesic effect of cocaine was demonstrated only by the tail withdrawal and it was independent of the prenatal drug exposure. CPP test showed that prenatal MA exposure induced rather tolerance than sensitization to cocaine. In contrast to cocaine effects, morphine decreased rearing activity in both, prenatally MA-exposed and saline-exposed rats, and locomotion only in prenatally MA-exposed rats in the Laboras. In the Plantar test, the results demonstrated that morphine had an analgesic effect in prenatally saline-exposed rats but this effect was suppressed in prenatally MA-exposed rats. In the CPP test morphine induced drug-seeking behavior, which however was not affected by prenatal drug exposure. Thus, our data demonstrate that there is a cross-effect between prenatal MA exposure and the challenge dose of other drug in adulthood, however drug-seeking behavior is not increased by prenatal MA exposure as we expected.

Potential health benefits of moderate alcohol consumption: current perspectives in research.

The benefits of moderate amounts of alcohol for a better health and longer life expectancy compared with abstinence have been suggested by the findings of numerous studies. However, controversies have emerged regarding the influence of confounding factors and the systematic errors that might have been inadvertently disregarded in the early studies. This review includes a description of the findings of those research studies published in the last 5 years on the effects of moderate alcohol consumption on all-cause mortality, CVD and inflammation, the immune system, insulin sensitivity, non-alcoholic fatty liver disease (NAFLD) and cancer. Promising evidences exist from both animal studies and human clinical trials regarding intermediate end-points of CHD and insulin sensitivity, such as HDL, adiponectin or fibrinogen. However, controversies and inconsistent findings exist regarding many of these diseases and related functions and biomarkers. Further research and human randomised-controlled trials with adequate standardisation of the study conditions are necessary in order to draw a comparison between studies, establish the causal effect of moderate alcohol intake on disease protection and reach consensus on the circumstances that allow the recommendation of moderate alcohol habitual intakes as a strategy for health maintenance.

Immunostimulatory effect of faecal Bifidobacterium species of breast-fed and formula-fed infants in a peripheral blood mononuclear cell/Caco-2 co-culture system.

Bifidobacterium spp. typical of the human intestinal microbiota are believed to influence the balance of immune responses in the intestinal mucosa. The aim of the present study was to investigate the effect of different bifidobacterial species and their mixtures in in vitro experiments with peripheral blood mononuclear cells (PBMC) and Caco-2 cells. Bifidobacterium adolescentis, B. angulatum, B. breve, B. catenulatum, B. infantis, B. longum and two combinations of these bifidobacteria simulating the species composition found in faecal samples from breast-fed (BF) and formula-fed (FF) infants were used. The levels of several cytokines were measured by direct stimulation of PBMC and by stimulation of a Caco-2/PBMC co-culture with bifidobacteria. B. catenulatum and B. breve were the strongest enhancers of interferon-γ (IFN-γ) production by direct stimulation of PBMC. B. longum was the highest inducer of IL-10 and the lowest TNF-α stimulus. In the Caco-2/PBMC system, B. breve was the highest inducer of IL-8 production by Caco-2 cells, significantly different from B. infantis, B. adolescentis and the FF mixture (P < 0·05). IFN-γ produced by PBMC stimulated with the BF mixture (containing 22 % B. breve, compared with 7 % in the FF mixture) was significantly higher compared with B. adolescentis, B. infantis and B. longum. B. adolescentis also inhibited IFN-γ production compared with the FF mixture and B. longum. The proportion of different Bifidobacterium strains seems to be an important determinant of the cytokine balance in the simulated intestinal environment studied. B. breve and the combination of the Bifidobacterium species typically found in the microbiota of BF infants have shown the most significant effects.

Differential expression of functional nucleoside transporters in non-differentiated and differentiated human endothelial progenitor cells.

Extracellular adenosine removal is via human equilibrative nucleoside transporters 1 (hENT1) and 2 (hENT2) in the endothelium, thus regulating adenosine-induced revascularization and angiogenesis. Since human endothelial progenitor cells (hEPCs) promote revascularization, we hypothesize differential expression of nucleoside transporters in hEPCs. hEPCs were cultured 3 (hEPC-3d) or 14 (hEPC-14d) days. RT-PCR for prominin 1, CD34, octamer-4, kinase insert domain receptor, oxidized low-density lipoprotein (lectin-like) receptor 1 and tyrosine endothelial kinase was used to evaluate phenotypic differentiation. Flow cytometry was used to estimate CD34(+)/KDR(-) (non-differentiated), CD34(-)/KDR(+) (differentiated) or CD34(+)/KDR(+) (mixed) cell populations. Adenosine transport was measured in absence or presence of sodium, S-(4-nitrobenzyl)-6-thio-inosine (NBTI, 1-10 µM), inosine, hypoxanthine or guanine (0.1-5 mM), hENTs protein abundance by western blot, and hENTs, hCNT1, hCNT2 and hCNT3 mRNA expression by real time RT-PCR. hEPC-3d cells were CD34(+)/KDR(-) compared with hEPC-14d cells that were CD34(-)/KDR(+). hEPC-3d cells exhibit hENT1-like adenosine transport (NBTI-sensitive, Na(+)-independent), which is absent in hEPC-14d cells. hEPC-14d cells exhibit two transport components: component 1 (NBTI insensitive, Na(+)-independent) and component 2 (NBTI insensitive, Na(+)-dependent, Hill coefficient ∼1.8), the latter resembling CNT3-like transport. hEPC-3d cells express hENT1 protein and mRNA, which is reduced (∼90%) in hEPC-14d cells, but instead only hCNT3 mRNA is expressed in this cell type. hENT2, hCNT1 and hCNT2 were undetectable in hEPCs. Thus, hEPCs exhibit a differential expression of hENT1 and hCNT3 functional nucleoside transporters, which could be related with its differentiation stage.

Immunomodulatory effect of fibres, probiotics and synbiotics in different life-stages.

Chronic diseases associated to modern lifestyle habits are usually related to immune system malfunction. In this context, since diet is very well-known to modulate host resistance to infectious and inflammatory processes, the consumption of fibre and probiotics seems to be a promising nutritional tool for immune system modulation in different populations. Health effects of dietary fibres and probiotics have been extensively documented in numerous epidemiological and intervention studies, especially their beneficial effect on intestinal microbiota with important clinical implications in the prevention and/or treatment of infectious and inflammatory diseases. Mechanisms may include modulation of the functional properties of the microbiota, epithelial cells, dendritic cells and immune cell types. Prebiotics have been extensively reported to affect the composition of the gut microbiota, stimulating directly or indirectly putative beneficial gut commensals other than lactic acid bacteria, opening promising areas of research for the discovery of new probiotic strains and synbiotic combinations. Age-related changes in gut physiology, microbiota and mucosal immune response are well established. Moreover, exposure to different challenges during life such as early encounter of environmental insults in the newborn, infant formula feeding, antibiotic treatment, gastrointestinal diseases and stress, also interferes with the normal development and balance of the healthy gut microbiota. Therefore, the current short review gives an overview of today's main aspects of the effect of fibres, probiotics and synbiotics on the immune system in different life-stages.

Autologous mesenchymal stem cell treatment increased T regulatory cells with no effect on disease activity in two systemic lupus erythematosus patients.

Mesenchymal stem cells (MSCs) exert suppressive effects in several disease models including lupus prone mice. However, autologous MSC therapy has not been tested in human systemic lupus erythematosus (SLE). We evaluate the safety and efficacy of bone marrow (BM)-derived MSCs in two SLE patients; the suppressor effect of these cells in-vitro and the change in CD4+CD25+FoxP3+ T regulatory (Treg) cells in response to treatment. Two females (JQ and SA) of 19 and 25 years of age, fulfilling the 1997 American College of Rheumatology (ACR) criteria for SLE were infused with autologous BM-derived MSCs. Disease activity indexes and immunological parameters were assessed at baseline, 1, 2, 7 and 14 weeks. Peripheral blood lymphocyte (PBL) subsets and Treg cells were quantitated by flow cytometry, and MSCs tested for in-vitro suppression of activation and proliferation of normal PBLs. No adverse effects or change in disease activity indexes were noted during 14 weeks of follow-up, although circulating Treg cells increased markedly. Patient MSCs effectively suppressed in-vitro PBL function. However, JQ developed overt renal disease 4 months after infusion. MSC infusion was without adverse effects, but did not modify initial disease activity in spite of increasing CD4+CD25+FoxP3+ cell counts. One patient subsequently had a renal flare. We speculate that the suppressive effects of MSC-induced Treg cells might be dependent on a more inflammatory milieu, becoming clinically evident in patients with higher degrees of disease activity.

Interplay between human leukocyte antigen genes and the microbial colonization process of the newborn intestine.

Coeliac disease (CD) development involves genetic (HLA-DQ2/DQ8) and environmental factors. Herein, the influence of the HLA-DQ genotype on the gut colonization process of breast-fed children was determined. A cohort of 20 newborns, with at least one first-degree relative with CD, were classified according to their HLA-DQ genotype into high, intermediate and low genetic risk groups, showing 24-28%, 7-8% and less than 1% probability to develop CD, respectively. Faecal microbiota was analysed at 7 days, 1 and 4 months of children's age by fluorescence in situ hybridization. When considering all data, Gram-negative bacteria and Bacteroides-Prevotella group proportions were higher (P<0.05) in the high than in the intermediate and low genetic risk groups. E. coli, Streptococcus-Lactococcus, E. rectale-C. coccoides, sulphate-reducing bacteria, C. lituseburense and C. histolyticum group proportions were also significantly higher (P<0.05) in the high than in the low genetic risk group. Correlations between these bacterial groups and the genetic risk were also detected (P<0.05). In addition, the number and type of CD relative seemed to influence (P<0.050) these bacterial proportions in children at CD risk. At 4 months of age, similar relationships were established between the high genetic risk to develop CD and the proportions of Streptococcus-Lactococcus (P<0.05), E. rectale-C. coccoides (P<0.05), C. lituseburense (P<0.05), C. histolyticum (P<0.05), Bacteroides-Prevotella (P<0.10) groups and total Gram-negative bacteria (P<0.05). The results suggest a relationship between HLA-DQ genes and the gut microbial colonization process that could lead to a change in the way this disorder is investigated.

Evolution of serum biochemical indicators in anorexia nervosa patients: a 1-year follow-up study.

BACKGROUND: Long-term studies on the evolution of serum biochemical indicators in anorexia nervosa (AN) patients during treatment are lacking in the literature. Thus, a 1-year follow-up of serum biochemical parameters in a homogeneous group of AN patients was performed. METHODS: Fourteen restricting-type AN patients were studied on admission to hospital, after 1 month of inpatient treatment and after 6 and 12 months after admission. RESULTS: Red blood cell count (RBC) and haemoglobin, serum glucose, total protein and the enzyme activities aspartate aminotransferase (AST), alkaline phosphatase (AlP), lactate dehydrogenase (LDH) and creatine kinase (CK) were significantly lower in patients on admission than in the control group. Total protein, high-density lipoprotein cholesterol (HDL-c), AST, AlP and CK showed significant changes among time points (anova, P < 0.05). Significant correlations were found between the change in RBC, haemoglobin, haematocrit, and the change in weight and body mass index (r = 0.74-0.86; P < 0.01). High cholesterol and amylase activity were found at all time points. While AST, LDH and CK reached control values within 6 months of treatment, AlP was always lower. CONCLUSION: Serum AlP, hypercholesterolaemia and RBC seem to need longer periods of treatment with further weight gain to fully normalize. Therefore, these parameters should be monitored in AN patients long-term follow-up.

[Corneal manifestations in systemic diseases]. / Manifestaciones corneales en las enfermedades sistémicas.

Systemic diseases affecting the cornea have a wide range of manifestations. The detailed study of all pathologies that cause corneal alteration is unapproachable, so we have centered our interest in the most prevalent or characteristic of them. In this paper we have divided these pathologies in sections to facilitate their study. Pulmonar and conective tissue (like colagen, rheumatologic and idiopathic inflamatory diseases), dermatologic, cardiovascular, hematologic, digestive and hepatopancreatic diseases with corneal alteration are described. Endocrine and metabolic diseases, malnutrition and carential states are also studied, as well as some otorhinolaryngologic and genetic diseases that affect the cornea. Finally, a brief report of ocular toxicity induced by drugs is referred.

Changes in the immune system are conditioned by nutrition.

Undernutrition due to insufficient intake of energy and macronutrients and/or due to deficiencies in specific micronutrients impairs the immune system, suppressing immune functions that are fundamental to host protection. The most consistent abnormalities are seen in cell-mediated immunity, complement system, phagocyte function, cytokine production, mucosal secretory antibody response, and antibody affinity. There is a number of physiological situations such as ageing and performance of intense physical exercise associated with an impairment of some immune parameters' response. Nutrition can influence the extent of immune alteration in both of them. There are also numerous pathological situations in which nutrition plays a role as a primary or secondary determinant of some underlying immunological impairments. This includes obesity, eating disorders (anorexia nervosa and bulimia nervosa), food hypersensitivity and gastrointestinal disorders as some examples. The implications of nutrition on immune function in these disorders are briefly reviewed.

[Feeding and assessment of nutritional status of spanish adolescents (AVENA study). Evaluation of risks and interventional proposal. I.Methodology]. / Alimentación y valoración del estado nutricional de los adolescentes españoles (estudio AVENA). Evaluación de riesgos y propuesta de intervención. I. descripción metodológica del proyecto.

BACKGROUND: Adolescence is a decisive period in human life due to the multiple physiological and psychological changes that take place. These changes will condition both nutritional requirements and eating/physical activity behavior. It has been demonstrated that these "adolescence" factors are of significant influence in health status during adult life. Due to its importance and adequate development the project has been granted by the Fondo de Investigación Sanitaria of the Institute of Health Carlos III. OBJECTIVE: To develop a methodology to evaluate the health and nutritional status of a representative population of Spanish adolescents. Specific attention is paid to three specific health problems: obesity, anorexia nervosa/bulimia, dislipidemia. METHODOLOGY: The following magnitudes will be studied: 1) dietary intake, food habits and nutrition knowledge; 2) daily physical activity and personal approach; 3) physical condition; 4) anthropometry and body composition; 5) hematobiochemical study: plasma lipid phenotypic and metabolic profile, blood cell counts; 6) genotipic profile of cardiovascular risk lipid factors; 7) immune function profile related to nutritional status; 8) psychological profile. CONCLUSION: This project includes the co-ordinate activity of five Spanish centers of five different cities (Granada, Madrid, Murcia, Santander, Zaragoza). Each center is specialized in a specific area and will be responsible for the corresponding part of the study. From the data obtained, we will elaborate a specific intervention program in order to improve nutrition and neutralize the risk for nutritional related problems in adolescence. By this, we will contribute to improve the health status of the Spanish population in the new millennium.