Plant Polyphenols and Exendin-4 Prevent Hyperactivity and TNF-alpha Release in LPS-Treated In vitro Neuron/Astrocyte/Microglial Networks

Increasing evidence supports a decisive role for neuroinflammation in the neurodegenerative process of several central nervous system (CNS) disorders. Microglia are essential mediators of neuroinflammation and can regulate a broad spectrum of cellular responses by releasing reactive oxygen intermediates, nitric oxide, proteases, excitatory amino acids, and cytokines. We have recently shown that also in ex-vivo cortical networks of neurons, astrocytes and microglia, an increased level of tumor necrosis factor-alpha (TNF-α) was detected a few hours after exposure to the bacterial endotoxin lipopolysaccharide (LPS). Simultaneously, an atypical “seizure-like” neuronal network activity was recorded by multi-electrode array (MEA) electrophysiology. These effects were prevented by minocycline, an established anti-inflammatory antibiotic. We show here that the same inhibitory effect against LPS-induced neuroinflammation is exerted also by natural plant compounds, polyphenols, such as curcumin (CU, curcuma longa), crocin (CR, saffron), and resveratrol (RE, grape), as well as by the glucagon like peptide-1 receptor (GLP-1R) agonist exendin-4 (EX-4). The drugs tested also caused per-se early transient (variable) changes of network activity. Since it has been reported that LPS-induced neuroinflammation causes rearrangements of glutamate transporters in astrocytes and microglia, we suggest that neural activity could be putatively increased by an imbalance of glial glutamate transporter activity, leading to prolonged synaptic glutamatergic dysregulation

Mental disorders and work integration: a retrospective study in a northern italian town.

OBJECTIVES: THE PRESENT STUDY WAS CONDUCTED IN A VOCATIONAL INTEGRATION SERVICE OF A NORTHERN ITALIAN TOWN WITH TWO MAJOR AIMS: to assess vocational integration programs undertaken from 1(st) January 2004 to 1(st) January 2007; and to identify job tenure-associated predictors. METHODS: This is a retrospective study; we collected data such as gender, age, duration, type and outcome of the vocational integration program, and number of interventions performed by the vocational integration service. Self-report questionnaires were also used to assess the satisfaction of users, caregivers, practitioners, and of the company contacts involved in the study. RESULTS: The service has enrolled 84 users during the observation period. Out of these users, 64.3% of them still had their jobs after three years. Users, caregivers and company contacts expressed high levels of satisfaction for the support received by the vocational integration service. The company expressed less satisfaction for the collaboration received by the Departments of Mental Health (DMHs) that coached the users. The only variable associated to the outcome was the number of interventions that the users received before their placement on the job. CONCLUSIONS: Despite all the limits of this study, its results show that the chance of taking advantage of a supported job placement service has likely proven itself effective in helping people with mental disorders to obtain and maintain a competitive employment. Our results, however, also point to the necessity of implementing newer strategies meant to develop a greater integration among all services dealing with mentally ill people

Effects of nucleotides administration on growth performance and immune response of post-weaning piglets

The aim of this study was to assess the effect of nucleotides administration on growth perform- ance and immune response in post-weaning piglets. Twenty-eight male weaned piglets, homo- geneous for age and weight were randomly allocated to two experimental treatments. Treated group (T) was daily orally administered 0.8g/head of a mixture of nucleotides suspended in 2.1 mL water solution; while control group (C) received 2.1 mL saline solution. Body weight (BW) and average daily gain (ADG) were individually recorded weekly, while feed intake (FI), and gain:feed (G:F) were recorded and calculated on pen basis. Faecal score was evaluated every seven days. On day 0, 9, 18 and 27 blood samples were collected to determine IgA, IgG and haptoglobin concentration. At day 28 all piglets were sacrificed, and tissue samples of ileal Peyer\u2019s patches were collected for the evaluation of IL1a, IL1b, IL6, IL10, TNFa, TLR2, TLR4 and PPARc gene expression. Nucleotides supplementation significantly increased BW (17.37 vs. 19.00kg/pig; p 1\u20444 <.01), ADG (.351 vs. .400kg/d; p < .01), and FI (3.96 vs. 4.39kg/d; p < .01), but not G:F (.61 vs. .64; p 1\u20444 .29). Faecal consistency was not different between the experimental groups and no occurrence of diarrhoea was reported. IgA and IgG content in blood was not influenced by the treatment, as well as gene expression of inflammatory cytokines in Peyer\u2019s patches. The present trial shows that nucleotide administration is able to improve growth per- formance of post-weaning piglets, with no effects on inflammatory response and the expression of immune-related genes

Severe bleeding and absent ADP-induced platelet aggregation associated with inherited combined CalDAG-GEFI and P2Y12 deficiencies

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In vitro assessment of the effects of temperature on phagocytosis, reactive oxygen species production and apoptosis in bovine polymorphonuclear cells

Heat stress exerts a direct negative effect on farm animal health, triggering physiological responses. Environmental high temperature induces immunosuppression in dairy cows, increasing the risk of mastitis and milk somatic cell counts. The influence of heat stress on leukocytes activities has not been fully elucidated. The present in vitro study was aimed at assessing whether the exposure to temperature simulating conditions of severe whole body hyperthermia affects defensive functions of bovine blood polymorphonuclear cells. Blood was collected from seven clinically healthy, multiparous, late lactating Holstein cows. After isolation, PMN were incubated at either 39 or 41\ua0\ub0C. Phagocytosis, respiratory burst and apoptosis were then investigated. The selected temperatures of 39\ua0\ub0C or 41\ua0\ub0C mimicked conditions of normothermia or severe heat stress, respectively. Phagocytosis assay was carried out by measuring the fluorescence of phagocyted fluorescein-labelled E. coli bioparticles. The modulation of oxidative burst activity was studied by the cytochrome C reduction method. Apoptosis was determined by measuring the activities of two enzymes that play an effector role in the process, namely Caspase-3 and Caspase-7. Statistical analyses were performed using SPSS 22.0. A Student t-test for paired samples and a Generalised Estimating Equation were used based on data distribution. The phagocytosis rate was reduced ( 1237%, P\ua0<\ua00.01) when PMN were incubated for 2\ua0h at 41\ua0\ub0C, when compared to phagocytosis rate measured at 39\ua0\ub0C. The oxidative burst, as determined by extracellular production of reactive oxygen species (ROS), was also reduced by the exposure of cells to 41\ua0\ub0C compared to 39\ua0\ub0C. Such reduction ranged between 122 and 1221% (P\ua0<\ua00.05). Apoptosis rate was not affected by different temperatures. The results reported in this study suggest that phagocytosis and ROS production in PMN exposed to severe high temperature are impaired, partially explaining the higher occurrence of infections during periods of hot weather

Prevalence of disease and relationships between laboratory phenotype and bleeding severity in platelet primary secretion defects

BACKGROUND: The prevalence of platelet primary secretion defects (PSD) among patients with bleeding diathesis is unknown. Moreover, there is paucity of data on the determinants of bleeding severity in PSD patients. OBJECTIVE: To determine the prevalence of PSD in patients with clinical bleeding and to study the relationships between the type of platelet defect and bleeding severity. METHODS: Data on patients referred for bleeding to the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan (Italy) in the years between 2008 and 2012 were retrieved to study the prevalence of PSD. Demographic, clinical and laboratory information on 32 patients with a diagnosis of PSD was used to compare patients with or without associated medical conditions and to investigate whether or not the type and extension of platelet defects were associated with the bleeding severity score (crude and age-normalized) or with the age at first bleeding requiring medical attention. RESULTS: The estimated prevalence of PSD among 207 patients with bleeding diathesis and bleeding severity score above 4 was 18.8% (95% confidence interval [CI]: 14.1-24.7%). Patients without associated medical conditions had earlier age of first bleeding (18 vs 45 years; difference: -27 years; 95% CI: -46 to -9 years) and different platelet functional defect patterns (Fisher's exact test of the distribution of patterns, P\u200a=\u200a0.007) than patients with accompanying medical conditions. The type and extension of platelet defect was not associated with the severity of bleeding. CONCLUSIONS: PSD is found in approximately one fifth of patients with clinical bleeding. In patients with PSD, the type and extension of laboratory defect was not associated with bleeding severit

The effects of superoxide dismutase-rich melon pulp concentrate on inflammation, antioxidant status and growth performance of challenged post-weaning piglets

Piglets can often suffer impaired antioxidant status and poor immune response during post-weaning, especially when chronic inflammation takes place, leading to lower growth rates than expected. Oral administration of dietary antioxidant compounds during this period could be a feasible way to balance oxidation processes and increase health and growth performance. The aim of the trial was to study the effects of an antioxidant feed supplement (melon pulp concentrate) that contains high concentration of the antioxidant superoxide dismutase (SOD) on inflammation, antioxidant status and growth performance of lipopolysaccharide (LPS) challenged weaned piglets. In total, 48 weaned piglets were individually allocated to four experimental groups in a 2 72 factorial design for 29 days. Two different dietary treatments were adopted: (a) control (CTR), fed a basal diet, (b) treatment (MPC), fed the basal diet plus 30 g/ton of melon pulp concentrate. On days 19, 21, 23 and 25 half of the animals within CTR and MPC groups were subjected to a challenge with intramuscular injections of an increasing dosage of LPS from Escherichia coli (serotype 0.55:B5) (+) or were injected with an equal amount of PBS solution ( 12). Blood samples were collected at the beginning of the trial and under the challenge period for interleukin 1\u3b2, interleukin 6, tumour necrosis factor \u3b1, haptoglobin, plasma SOD activity, total antioxidant capacity, reactive oxygen species, red blood cells and plasma resistance to haemolysis, and 8-oxo-7, 8-dihydro-2\u2019-deoxyguanosine. Growth performance was evaluated weekly. A positive effect of melon pulp concentrate was evidenced on total antioxidant capacity, half-haemolysis time of red blood cells, average daily gain (ADG) and feed intake, while LPS challenge increased pro-inflammatory cytokines and haptoglobin serum concentrations, with a reduced feed intake and gain : feed (G : F). The obtained results show that oral SOD supplementation with melon pulp concentrate ameliorates the total antioxidant capacity and the half-haemolysis time in red blood cell of post-weaning piglets, with positive results on growing performance

A Review on the Role of EPA and DHA Through Goat Nutrition to Human Health : Could they be Effective both to Animals and Humans?

Goat\u2019s milk is high digestible and useful for a number of human health problems, but this product could be further increased in its beneficial effects on immune response both at animal and human level through the use of dietary n-3 polyunsaturated fatty acids (PUFAs) sources in goat diet. In the last decade, the interest on n-3 PUFAs, in particular eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6), has increased due to their proved positive effects on human health. These two PUFAs must be provided with the diet both in human and animals. Anyway EPA and DHA can be successfully transferred into milk and thus can be available to human consumption with positive related effects on immune response. But what is the best dietary source of EPA and DHA in goat diet? The most promising and investigated raw material seems to be fish oil, but the interest in alternative n-3 PUFAs-rich sources, such as algae, is increasing. The EPA and DHA mechanisms of action, affecting metabolic and pathological pathways, must be still elucidated in goats, especially for what concern the use of dietary algae. The inclusion of fish oil and algae in the diet of dairy goat can increase the healthy properties of milk with consequential health benefit in human