Elevated alanine aminotransferase independently predicts new onset of depression in employees undergoing health screening examinations.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of elevated alanine aminotransferase (ALT). NAFLD is associated with insulin resistance and hepatic inflammation. Similarly, patients with depression exhibit insulin resistance and increased inflammatory markers. However, no study has shown a clear association between elevated ALT and the development of depression. The aim of the study was to test whether elevated ALT, a surrogate marker for NAFLD, predicts the development of depression. METHOD: The present prospective cohort study investigated 12 180 employed adults referred for health examinations that included fasting blood tests and anthropometric measurements between 2003 and 2010. Exclusion criteria were: baseline minor/major depression, excessive alcohol consumption and other causes for ALT elevation. Depression was evaluated by the eight-item Patient Health Questionnaire (PHQ-8) score. RESULTS: The final cohort included 5984 subjects [69.4% men, aged 45.0 (s.d. = 10.24) years]. The incidence rate of minor and major depression was 3.8% and 1.4%, respectively. Elevated ALT was a significant independent predictor for the occurrence of minor [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.40-2.92] and major (OR 3.132, 95% CI 1.81-5.40) depression after adjusting for age, gender, body mass index, education level, serum levels of lipids, glucose, smoking and physical activity. Adding subjective health and affective state parameters (sleep disturbances, self-rated health, anxiety and burnout) as potential mediators only slightly ameliorated the association. Persistently elevated ALT was associated with the greatest risk for minor or major depression as compared with elevation only at baseline or follow-up (p for trend < 0.001). CONCLUSIONS: Elevated ALT was associated with developing depressive symptoms, thus suggesting that NAFLD may represent an independent modifiable risk factor for depression.

Ascertainment bias in dementias: a secondary to tertiary centre analysis in Central Italy and conceptual review.

BACKGROUND AND AIMS: Ascertainment bias (AB) indicates a bias of an evaluation centre in estimating the prevalence/incidence of a disease due to the specific expertise of the centre. The aim of our study was to evaluate classification of different types of dementia in new cases appearing in secondary and tertiary centres, in order to evidence possible occurrence of AB in the various (secondary to tertiary) dementia centres. METHODS: To assess the mechanism of AB, the rates of new cases of the different forms of dementia reported by different centres were compared. The centres involved in the study were 11 hospital-based centres including a tertiary centre, located in the University Department of Clinical Neurology. The tertiary centre is endowed with state-of-the-art diagnostic facilities and its scientific production is prominently focused on dementia with Lewy bodies (DLB) thus suggesting the possible occurrence of a bias. Four main categories of dementia were identified: Alzheimer's disease (AD), DLB, fronto-temporal dementia (FTD), vascular dementia (VaD), with other forms in a category apart. The classification rate of new cases of dementia in the tertiary centre was compared with rates reported by secondary centres and rates of recoding were calculated during a follow-up of 2 years. RESULTS: The study classified 2,042 newly diagnosed cases of dementia in a population of 1,370,000 inhabitants of which 315,000 were older than 65. AD was categorized in 48-52 % of cases, DLB in 25-28 %, FTD in 2-4 % and VaD in 17-28 %. During the 2-year follow-up the diagnosis was re-classified in 40 patients (3 %). The rate of recoding was 5 % in the tertiary centre, 2-8 % in referrals from secondary to tertiary centre, 2-10 % in recodings performed in secondary centres and addressed to tertiary centre. Recoding or percentages of new cases of AD or DLB were not different in the comparison between secondary or between secondary and tertiary centres. FTD and VaD were instead significantly recoded. CONCLUSION: The results of the study suggest that in a homogeneous area, AB is not interfering with diagnosis of AD or DLB.

MedJet--a new CO2-based disposable cleaning device allows safe and effective bowel cleansing during colonoscopy: a pilot study.

BACKGROUND AND STUDY AIMS: Complete bowel cleansing is mandatory for effective colon cancer screening and surveillance. The aim of the current pilot study, which was conducted in humans, was to test the safety and efficiency of a newly developed disposable cleaning device, the MedJet, for intraprocedural bowel cleansing. PATIENTS AND METHODS: Patients with screening or surveillance colonoscopy after previous polypectomy were included. The colonoscope was first inserted to the cecum and the overall cleansing was assessed according to the Ottawa scale. The MedJet device was used if colon cleansing had been incomplete. The MedJet catheter was passed over the working channel of the colonoscope and the colon was cleaned during withdrawal. The MedJet device delivered controlled jets comprising compressed CO2 and minimal amounts of sterile water, which allowed disintegration and removal of residual stool. The efficiency of cleaning was assessed according to the Boston scale. RESULTS: A total of 32 patients (16 female; mean age 61 years) were treated with the device. No device-related adverse or serious adverse events were noted. MedJet application during withdrawal provided effective and significant improvement in bowel cleansing (P = 0.005). Furthermore, 18 adenomas and 1 colon cancer, which were hidden behind stool remnants, could be identified in 11 patients following use of the MedJet device. However, the withdrawal times were prolonged (11.4±6.0 minutes) due to the additional cleaning procedure. All patients tolerated the procedure well. CONCLUSIONS: The new MedJet device enabled highly effective and safe bowel cleansing during colonoscopy. The catheter-based system was easy to use and CO2 was applied for cleansing. The procedure was well tolerated by patients.

Activation of ethane C-H and C-C bonds by gas phase Th+ and U+: a theoretical study.

Two different approaches of density functional theory were used to analyze the C-H and C-C bond activation mechanisms during the reaction of bare Th(+) and U(+) ions with ethane. We report a complete exploration of the potential energy surfaces taking into consideration different spin states. According to B3LYP/SDD computations the double dehydrogenation of C(2)H(6) is thermodynamically favorable only in the case of Th(+). It is shown that the overall C-H and C-C bond activation processes are exothermic in the case of Th(+) and endothermic for U(+). In both cases, the C-C insertion transition state barrier exceeds the energy of the ground state reactants, preventing the observation of these species under thermal conditions.

Low-dose heparin for the prevention of post-ERCP pancreatitis: a randomized placebo-controlled trial.

BACKGROUND: As suggested by observational and animal studies, heparin has antiinflammatory effects that could prevent acute post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Low-molecular-weight heparin did not reduce the incidence of post-ERCP pancreatitis in a controlled study. The current study aimed to determine whether prophylactic administration of low-dose unfractionated heparin, which has potentially more antiinflammatory capability, can prevent acute post-ERCP pancreatitis. METHODS: Patients scheduled for ERCP in the authors' department were randomized to receive unfractionated heparin (5,000 IU) or placebo (saline solution 0.5 ml) administered subcutaneously 20 to 30 min before the ERCP. Patients who had undergone endoscopic sphincterotomy in the past were excluded from the study. Post-ERCP pancreatitis was defined according to criteria established by Cotton: abdominal pain combined with a threefold elevation of blood amylase 24 h after the ERCP. RESULTS: The study enrolled 106 patients. One patient was excluded from the analysis due to inaccessible papilla of Vater, leaving 51 patients in the heparin group and 54 in the placebo group, for a total of 105 patients (62 women and 43 men) with a mean age of 64.6 years. The rate of post-ERCP pancreatitis was not different between the groups (heparin, 4 patients, 7.8%; placebo, 4 patients, 7.4%). Two patients in each group experienced mild bleeding. CONCLUSIONS: The study did not demonstrate a significant effect of low-dose unfractionated heparin in the prevention of post-ERCP pancreatitis. A multicenter trial with a larger number of patients is needed to demonstrate a benefit from this drug.

Oxidative stress in Alzheimer patients in different stages of the disease.

Increasing evidence demonstrates that oxidative stress causes damage to cell function with aging and is involved in a number of age-related disorders including atherosclerosis, arthritis, and neurodegenerative disorders. Cellular changes show that oxidative stress is a condition that precedes the appearance of the hallmark pathologies of the disease, neurofibrillary tangles and senile plaques. The aim of this article is to analyze the different biomarkers of oxidative stress in Alzheimer patients, in different stages of the illness, and compare the results with a control group. A nutritional evaluation was carried out, including anthropometric and biological measures and a 3 day dietary record. The concentration of substances which react to thiobarbituric acid (TBARS) was measured as a marker of the degree of peroxidation using the HPLC method. The oxidation of proteins was analyzed by measuring the carbonyl groups in plasma. In addition, measurements were made of the total antioxidant activity in plasma and the activity of endogenous antioxidant enzymes such as gluthatione peroxidase, gluthatione reductase and superoxide dismutase. The total antioxidant plasmatic status of the patients with Alzheimer both in light-moderate phase and in advanced phase was lower than in the control. No significant differences were observed between the different stages of the disease in protein oxidation levels. Peroxidation was higher in patients in the advanced stage of the disease than in the control group. However, no significant differences were observed between the different stages of the disease. In this preliminary study, it was observed that Alzheimer patients in the light-moderate stage already present oxidative stress levels above those of the control group.

Inducible expression of the long pentraxin PTX3 in the central nervous system.

PTX3 is a prototypic long pentraxin consisting of a C terminal 203-amino acid pentraxin-like domain coupled with an N-terminal 178-amino acid unrelated portion. PTX3 is induced by primary proinflammatory signals in various cell types, most prominently macrophages and endothelial cells. Other long pentraxins, such as murine or rat neuronal pentraxin 1 (NP1) and human neuronal pentraxin 2 (NPTX2), are expressed in the central nervous system (CNS). The present study was designed to investigate whether PTX3 is expressed in the brain and to define the structures and cells involved. Intracerebroventricular (i.c.v.), but not i.v., injection of LPS induced high levels of PTX3 mRNA in the mouse brain. In contrast NP1 is constitutively expressed in the murine CNS and is not modulated by LPS administration. I.c.v. IL-1beta was also a potent inducer of PTX3 expression in the CNS, whereas TNFalpha was substantially less effective and IL-6 induced a barely detectable signal. Central administration of LPS and IL-1 induced PTX3 also in the periphery (heart), whereas the reverse did not occur. Expression of PTX3 was also observed in the brain of mice infected with Candida albicans (C. albicans) or Cryptococcus neoformans. (C. neoformans). The kinetics of PTX3 gene induction were consistently different between C. albicans- and C. neoformans-infected mice, according to the diverse outcome of the CNS immune reaction. In situ hybridization revealed that i.c.v. injection of LPS induced a strong PTX3 expression in presumptive glial cells, in the white matter (corpus callosum, fimbria) and meningeal pia mater as well as in dentate gyrus hilus and granule cells. No constitutive expression of PTX3 was detected. Central expression of PTX3 may amplify mechanisms of innate resistance and damage in the CNS. The possibility of a direct interaction of PTX3 with neuronal cells, as suggested for NPTX2, remains to be explored.

Tumor necrosis factor is a brain damaging cytokine in cerebral ischemia.

Two contrasting roles, one beneficial and the injurious, have been proposed for tumor necrosis factor (TNF) in the pathogenesis of cerebral ischemia. Reported here are results obtained in a standard model of permanent focal cortical ischemia in rats, in which the volume of cerebral infarction is measured after permanent occlusion of the middle cerebral artery. Administration of neutralizing anti-rat TNF antibodies (P114) into the brain cortex significantly reduced ischemic brain damage (85% reduced infarct volume as compared with preimmune-treated controls). Similar results were achieved by systemic administration of CNI-1493, a recently described tetravalent guanylhydrazone compound, which effectively inhibited endogenous brain TNF synthesis and conferred significant protection against the development of cerebral infarction (80% reduced infarct volume as compared with vehicle controls treated 1 h postischemia with 10 mg/kg). P114 anti-TNF and CNI-1493 were each cerebroprotective when given within a clinically relevant time window for up to 2 h after the onset of ischemia. These findings establish an important, pathophysiological role of TNF in mediating the progression of ischemic brain damage, and suggest that inhibiting TNF with CNI-1493 may be beneficial in the future treatment of stroke.

Overexpression of interleukin-6 in the central nervous system of transgenic mice increases central but not systemic proinflammatory cytokine production.

Production of inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6), in the brain is increased in various diseases. To investigate the relationships between the effect of overproduction of IL-6 in the brain on central and peripheral production of TNF, IL-1 beta and IL-6 itself, we used transgenic mice (NSE-hIL-6) where neuronal human IL-6 expression under the control of the neuronal specific enolase promoter results in astrocytosis and gliosis. These mice had higher cerebral endogenous IL-6 (12-fold), IL-1 beta (12-fold) and TNF (4-fold) production measured in brain homogenates after intracerebroventricular (i.c.v.) injection of 2.5 micrograms LPS, lipopolysaccharide (LPS) than wild-type mice (no TNF or IL-1 were detectable in saline-injected NSE or control mice). Cerebral cytokines production was also increased in NSE-hIL-6 mice treated i.p. with LPS doses that do not normally induce cytokines in the brain. The induction of peripheral (serum or spleen) TNF, IL-1 beta or IL-6 was the same in all these experiments in NSE-hIL-6 and wild-type mice. Furthermore, using microglial cell clone pretreated in vitro with IL-6, we noted an increase in LPS-induced TNF and IL-6 production and proliferation of pretreated cells than control. This study indicates that overproduction of IL-6 in the central nervous system (CNS) may ultimately result in increased central production of inflammatory cytokines, probably due to increased proliferation and activation of the cells which produce cytokine in the CNS.

Systemic interleukin 10 administration inhibits brain tumor necrosis factor production in mice.

Interleukin 10 is an antiinflammatory cytokine and inhibits the production of tumor necrosis factor. We have previously found that intracerebroventricular (i.c.v.) administration of recombinant human interleukin 10 inhibits brain tumor necrosis factor production induced by an i.c.v. injection of lipopolysaccharide in mice. In view of its possible pharmacological use, we have now studied whether interleukin 10 administered peripherally could inhibit brain tumor necrosis factor production. Mice were injected with recombinant human interleukin 10 (20 microg/mouse, i.v.) 10 min-24 h before lipopolysaccharide (2.5 microg, i.c.v.). Tumor necrosis factor was measured, using a bioassay, in brain homogenates 90 min after lipopolysaccharide. Recombinant human interleukin 10 administered i.v. between 10 min and 6 h before lipopolysaccharide markedly inhibited brain tumor necrosis factor production. We also measured the production of tumor necrosis factor by whole blood of these mice, and it was also markedly inhibited by recombinant human interleukin 10 treatment. In conclusion, systemic recombinant human interleukin 10 administration inhibits brain tumor necrosis factor production. suggesting its usefulness in tumor necrosis factor-mediated pathologies of the central nervous system.

A glucocorticoid receptor-independent mechanism for neurosteroid inhibition of tumor necrosis factor production.

We investigated the effect of two neurosteroids, pregnenolone and dehydroepiandrosterone sulfate on lipopolysaccharide-induced tumor necrosis factor (TNF) production in vivo and in vitro. Dehydroepiandrosterone sulfate (0.3-30 mg/kg, i.p.) inhibited serum TNF induced by lipopolysaccharide (2.5 micrograms/mouse, i.p.), without affecting the induction of serum corticosterone. Intracerebroventricular (i.c.v.) administration of dehydroepiandrosterone sulfate (0.2-5 micrograms/mouse) also inhibited brain TNF induced by i.c.v. lipopolysaccharide (2.5 micrograms/mouse). Dehydroepiandrosterone sulfate and pregnenolone (10(-6)-10(-4) M) inhibited TNF production in vitro by lipopolysaccharide-stimulated human peripheral blood mononuclear cells or by the human THP-1 cell line, suggesting that this action might also be relevant in humans. We obtained two lines of evidence that neurosteroids do not inhibit TNF via the glucocorticoid receptor. (1) Dehydroepiandrosterone sulfate and pregnenolone did not activate the alpha 1-acid glycoprotein promoter, a typical effect of glucocorticoids mediated by the glucocorticoid receptor, while strong activation of this promoter was observed with dexamethasone. (2) The inhibitory effect of dehydroepiandrosterone sulfate and pregnenolone on TNF production was not reversed by the glucocorticoid receptor antagonist, mifepristone (RU38486). On the contrary the inhibitory effect of dexamethasone, a classical glucocorticoid and inhibitor of TNF synthesis, was completely reversed by RU38486.

MK 801 and dexamethasone reduce both tumor necrosis factor levels and infarct volume after focal cerebral ischemia in the rat brain.

Focal cerebral ischemia in rats produces elevated levels of tumor necrosis factor (TNF)alpha in the ischemic brain region. To better understand the modulation of TNF during brain ischemia processes we carried out studies in a model of permanent middle cerebral artery occlusion (MCAo) in the rat. In non-treated ischemic animals, the maximum expression of TNF was observed at 12 h (246.1+/-33 U/g) in the ischemic cortex and declined reaching near zero levels 24 h after MCAo. Given 10 min after MCAo, MK 801 (3 mg/kg, i.p.), a non-competitive NMDA receptor antagonist, exerted significant neuroprotection as measured by 47% reduction of total volume of infarction (P < 0.01 vs. ischemic-control). At the high dose of 3 mg/kg i.p., dexamethasone (DEX), which is known to reduce brain edema, decreased infarct size by 50% (P < 0.01 vs. ischemic-control). Both MK 801 and DEX reduced TNF production in the ipsilateral cortex of ischemic animals by 61 and 73%, respectively (P < 0.01 vs. ischemic-control). The data indicate that TNF levels increase after brain infarction, whereas they are reduced by neuroprotective agents, such as MK 801 and DEX, which act on different cellular levels.

Neurosteroid levels are increased in vivo after LPS treatment and negatively regulate LPS-induced TNF production.

Neuroactive steroids such as dehydroepiandrosterone sulfate and pregnenolone inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) production. Corticosteroids not only inhibit TNF production but their levels are increased in vivo after endotoxin injection, thus representing a feedback system that limits TNF production. We wondered whether the same could be true for neuroactive steroids. Thus, the possibility that neuroactive steroids might be increased concomitantly to TNF induction in vivo in mice treated with LPS was investigated. Increased plasma and hippocampal levels of allopregnanolone (but not of dehydroepiandrosterone or pregnenolone) were found 90 min after LPS injection. Allopregnanolone and progesterone (IC50 10- 7 and 10- 9 M, respectively) also inhibited TNF production by mouse peritoneal macrophages in vitro at concentrations in the range of those detected in vivo. These findings suggest that neuroactive steroids may act as endogenous inhibitors of cerebral and systemic TNF production.

Endogenous nitric oxide production by human monocytic cells regulates LPS-induced TNF production.

The ability to produce nitric oxide (NO) of human monocytes macrophages is object of debate. While studying the regulation of tumor necrosis factor (TNF) synthesis induced by endotoxin (LPS) in a human cell line of monocyte origin (THP-1) and in human peripheral blood mononuclear cells (PBMC) we found an indirect evidence of such production. We showed that L-N-monomethyl-arginine (L-NMMA), an inhibitor of NO synthase, and hemoglobin, a chelator of NO, are able to significantly reduce TNF synthesis, indicating that NO production is induced by LPS and contributes to the induction of TNF. Since NO is a known cytostatic agent, we also studied the cytostatic effect of LPS, and demonstrated that it is reverted by L-NMMA. Although we were unable to show any nitrites/nitrates accumulation in the culture media, taken together our data give an indirect evidence of a physiologically relevant LPS-induced NO production in human monocytes-macrophages.

Tumor necrosis factor is increased in the spinal cord of an animal model of motor neuron degeneration.

Autoimmunity and oxidative/excitotoxic damage are considered as possible pathogenetic mechanisms in amyotrophic lateral sclerosis (ALS). As tumor necrosis factor (TNF) is implicated in autoimmune diseases, including experimental autoimmune encephalomyelitis, and can be neurotoxic, we studied TNF production in a proposed animal model of ALS, the mnd mouse. These mice develop symptoms (progressive weakness of the limbs) as late as at 7 months of age. We measured TNF in serum, brain and spinal cord of mnd mice at 3 and 7 months of age. TNF was detectable in the brain and spinal cord (but not in the serum) at 7 months, while no TNF was detected in mnd mice at 3 months (asymptomatic) or in control mice of the same genetic background and the same age. Immunohistochemistry confirmed localization of TNF-alpha in motor neurons situated in the ventral horn of the spinal cord of 7-month old mnd mice. These results suggest the possibility of testing inhibitors of TNF production in this disease.

Dental enamel defects and screening for coeliac disease.

Specific dental enamel defects (DEDs) in permanent teeth are frequently observed in coeliac patients. We examined the permanent teeth in 6949 secondary school children living in Trieste (78% of 8724 children born between 1978 and 1982). Children with DEDs were tested for serum antigliadin antibodies (AGAs) and antiendomysium antibodies (AEAs), and those positive for serum AGAs and/or AEAs underwent intestinal biopsy. Specific DEDs were observed in 52 children (0.59% of the total population examined). Serum AGAs and/or AEAs were positive in 10 cases. Nine patients underwent intestinal biopsy (one refused) and in four cases a flat mucosa was documented (one with short stature, three completely asymptomatic). The known incidence of CD in the study area was 1:1000 before the study programme and 1:670 (an increase of 44%) after it. Dental enamel inspection may be utilized for detecting undiagnosed coeliac disease in symptom-free schoolchildren. This clinical test is probably less sensitive than serum AGA screening test, but deserves some consideration because it is cheap, easy to perform and well accepted by the population.

Oncogenic activation of FOXR1 by 11q23 intrachromosomal deletion-fusions in neuroblastoma.

Neuroblastoma tumors frequently show loss of heterozygosity of chromosome 11q with a shortest region of overlap in the 11q23 region. These deletions are thought to cause inactivation of tumor suppressor genes leading to haploinsufficiency. Alternatively, micro-deletions could lead to gene fusion products that are tumor driving. To identify such events we analyzed a series of neuroblastomas by comparative genomic hybridization and single-nucleotide polymorphism arrays and integrated these data with Affymetrix mRNA profiling data with the bioinformatic tool R2 (http://r2.amc.nl). We identified three neuroblastoma samples with small interstitial deletions at 11q23, upstream of the forkhead-box R1 transcription factor (FOXR1). Genes at the proximal side of the deletion were fused to FOXR1, resulting in fusion transcripts of MLL-FOXR1 and PAFAH1B2-FOXR1. FOXR1 expression has only been detected in early embryogenesis. Affymetrix microarray analysis showed high FOXR1 mRNA expression exclusively in the neuroblastomas with micro-deletions and rare cases of other tumor types, including osteosarcoma cell line HOS. RNAi silencing of FOXR1 strongly inhibited proliferation of HOS cells and triggered apoptosis. Expression profiling of these cells and reporter assays suggested that FOXR1 is a negative regulator of fork-head box factor-mediated transcription. The neural crest stem cell line JoMa1 proliferates in culture conditional to activity of a MYC-ER transgene. Over-expression of the wild-type FOXR1 could functionally replace MYC and drive proliferation of JoMa1. We conclude that FOXR1 is recurrently activated in neuroblastoma by intrachromosomal deletion/fusion events, resulting in overexpression of fusion transcripts. Forkhead-box transcription factors have not been previously implicated in neuroblastoma pathogenesis. Furthermore, this is the first identification of intrachromosomal fusion genes in neuroblastoma.

[Prevalence of malnutrition and influence of oral nutritional supplementation on nutritional status in institutionalized elderly]. / Prevalencia de desnutrición e influencia de la suplementación nutricional oral sobre el estado nutricional en ancianos institucionalizados.

BACKGROUND: Nutritional supplementation might be an effective strategy for improving the nutritional status and the quality of life of institutionalized fragile elderly. OBJECTIVES: The prevalence of malnutrition and its relation with disease, and the influence of dietary supplementation by means of oral formulas on the nutritional status of elderly nursing home residents were assessed. METHODS: Two studies were carried out, one a cross-sectional survey in 31 subjects and the other a longitudinal-sectional survey in 19 subjects, both groups living in a public nursing home in the city of Murcia (SE Spain). Body mass index (BMI), serum albumin concentration (ALB) and geriatric nutritional risk index (GNRI) were assessed as markers of potential malnutrition. Illnesses were ascertained from medical records. RESULTS AND DISCUSSION: The prevalence of malnutrition of the total collective was high (39%), and especially in the fragile subjects (50%). The administration of oral nutritional supplements in the usual diet for 12 months significantly increased ALB and GNRI, and had no effect on body weigh and BMI. Jointly, these effects decreased the in the number of subjects at high nutritional risk and increased the number of subjects with a low or zero risk of malnutrition. CONCLUSION: The administration of oral nutritional supplements in the usual diet of this elderly collective is an effective clinical strategy in nutritional therapy.

Desempenho, sanidade animal e qualidade de filés de tilápias alimentadas com ração suplementada com biomassa bacteriana / Performance, animal health and fillets quality of tilapia fed diets supplemented with bacterial biomass

A aquicultura moderna é um dos setores de produção de alimentos que mais cresce no mundo. A tilápia, além de possuir grandes vantagens produtivas, origina produtos com grande aceitação pelo mercado. Em sua nutrição, podem ser utilizados aditivos com finalidades zootécnicas, pigmentantes ou antioxidantes. Este estudo objetivou avaliar o efeito da suplementação da dieta de tilápias com biomassa de Rubrivivax gelatinosus sobre o desempenho zootécnico e a saúde dos animais (histologia e hematologia) e sobre as características de qualidade dos filés (pH, composição químico-bromatológica, cor e rancidez). O experimento contou com seis tratamentos, compostos de um grupo controle, sem aditivos, um grupo contendo pigmentante comercial e quatro grupos com a biomassa nas concentrações de 175, 350, 700 e 1400mg/kg. Peixes pesando 21,42±5,65g foram criados por 74 dias em sistema com recirculação de água e, posteriormente, foram abatidos para a realização das análises. Não foram encontradas diferenças para os resultados das análises de desempenho, histológicas e hematológicas. Os filés dos grupos alimentados com os aditivos apresentaram menor umidade que o grupo controle, e os filés dos grupos alimentados com biomassa apresentaram as maiores teores proteicos. Não houve diferenças entre os tratamentos para os valores de pH, lipídeos e cinzas. Quanto à cor dos filés, todos os tratamentos com aditivos aumentaram a intensidade de vermelho. Em todos os tratamentos, a rancidez dos filés foi crescente durante o armazenamento, embora em menores valores nos filés dos grupos tratados com as maiores concentrações de biomassa. A biomassa de R. gelatinosus não promoveu alterações no desempenho nem na saúde animal e mostrou-se capaz de melhorar os aspectos de qualidade e conservação dos filés.

Modern aquaculture is one of the fastest growing food sectors in the world. Beyond having productivity advantages, tilapia fish yields products with great market acceptance. For its nutrition, additives aiming at increasing zootechnical, pigmenting or antioxidant features may be used. This study aimed to evaluate the effect of the supplementation of tilapia diets with Rubrivivax gelatinosus biomass on the performance and the health of animals (histology and hematology), and on the quality of fillets (pH, proximate composition, color and rancidity). The experiment comprised six treatments, made of a control group with no additives, a group containing commercial pigments and four groups with biomass at 175, 350, 700 and 1400 mg/kg. Fish weighing 21.42±5.65g were reared for 74 days in a system with water recirculation and slaughtered for analyzes. No differences were detected for performance, histological and hematological analyzes. Fillets of the groups fed additives had lower moisture content than the control group while the fillets of the groups fed the biomass had the highest protein percentages. No differences were detected among treatments for pH​, lipids and ash values. Regarding to the color of the fillets, all treatments with additives increased redness. For all treatments, rancidity in the fillets increased during storage, although the groups treated with the highest biomass concentrations had the lowest values. R. gelatinosus biomass did not change performance and animal health, and proved to be capable of improving fillets quality features and conservation.

The pro-longevity gene FoxO3 is a direct target of the p53 tumor suppressor.

FoxO transcription factors have a conserved role in longevity, and act as tissue-specific tumor suppressors in mammals. Several nodes of interaction have been identified between FoxO transcription factors and p53, a major tumor suppressor in humans and mice. However, the extent and importance of the functional interaction between FoxO and p53 have not been fully explored. Here, we show that p53 regulates the expression of FoxO3, one of the four mammalian FoxO genes, in response to DNA damaging agents in both mouse embryonic fibroblasts and thymocytes. We find that p53 transactivates FoxO3 in cells by binding to a site in the second intron of the FoxO3 gene, a genomic region recently found to be associated with extreme longevity in humans. While FoxO3 is not necessary for p53-dependent cell cycle arrest, FoxO3 appears to modulate p53-dependent apoptosis. We also find that FoxO3 loss does not interact with p53 loss for tumor development in vivo, although the tumor spectrum of p53-deficient mice appears to be affected by FoxO3 loss. Our findings indicate that FoxO3 is a p53 target gene, and suggest that FoxO3 and p53 are part of a regulatory transcriptional network that may have an important role during aging and cancer.