20 research outputs found

    Regulation of inflammatory responses to Bordetella pertussis by N(G)-monomethyl-L-arginine in mice intranasally infected.

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    To investigate effect of MMLA, an inhibitor of nitric oxide (NO) production, on regulation of inflammatory responses to Bordetella pertussis infection, mice were infected intranasally, and treated with various concentrations of MMLA. Ten days after infection, mice treated with MMLA at dosage of 100 mg/kg, given intraperitoneally in a single dose or for 5 consecutive days, showed at histopathologic examination, a significant decrease of intensity of inflammation (scores, 0.6 +/- 0.2 and 0.9 +/- 0.5 respectively). A decrease of cellular accumulation of neutrophils and lymphocytes in the bronchoalveolar lavage (BAL) fluid was observed in infected mice treated with MMLA, especially at dosage of 10 mg/kg, given in a single dose intraperitoneally. In addition, BP-infected mice treated with MMLA (100 mg/kg, intraperitoneally) for 5 consecutive days showed higher mortality rate than untreated mice infected with B. pertussis, and the number of B. pertussis in lungs of mice treated with MMLA was significantly increased. However, MMLA treatment of infected mice had some effect on levels of IFN-gamma and nitrite/nitrate (end-stable products of NO) in the BAL fluid. This study indicates that NO may play a role either as microbiocidal agent or as a modulator of immune regulation, inasmuch as it may upregulate tissue inflammatory response to B. pertussis

    The broad-spectrum activity of perampanel: state of the art and future perspective of AMPA antagonism beyond epilepsy

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    Glutamate is the brain’s main excitatory neurotransmitter. Glutamatergic neurons primarily compose basic neuronal networks, especially in the cortex. An imbalance of excitatory and inhibitory activities may result in epilepsy or other neurological and psychiatric conditions. Among glutamate receptors, AMPA receptors are the predominant mediator of glutamate-induced excitatory neurotransmission and dictate synaptic efficiency and plasticity by their numbers and/or properties. Therefore, they appear to be a major drug target for modulating several brain functions. Perampanel (PER) is a highly selective, noncompetitive AMPA antagonist approved in several countries worldwide for treating different types of seizures in various epileptic conditions. However, recent data show that PER can potentially address many other conditions within epilepsy and beyond. From this perspective, this review aims to examine the new preclinical and clinical studies—especially those produced from 2017 onwards—on AMPA antagonism and PER in conditions such as mesial temporal lobe epilepsy, idiopathic and genetic generalized epilepsy, brain tumor-related epilepsy, status epilepticus, rare epileptic syndromes, stroke, sleep, epilepsy-related migraine, cognitive impairment, autism, dementia, and other neurodegenerative diseases, as well as provide suggestions on future research agenda aimed at probing the possibility of treating these conditions with PER and/or other AMPA receptor antagonists

    Kinetic models for optimal control of wealth inequalities

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    We introduce and discuss optimal control strategies for kinetic models for wealth distribution in a simple market economy, acting to minimize the variance of the wealth density among the population. Our analysis is based on a finite time horizon approximation, or model predictive control, of the corresponding control problem for the microscopic agents' dynamic and results in an alternative theoretical approach to the taxation and redistribution policy at a global level. It is shown that in general the control is able to modify the Pareto index of the stationary solution of the corresponding Boltzmann kinetic equation, and that this modification can be exactly quantified. Connections between previous Fokker-Planck based models and taxation-redistribution policies and the present approach are also discussed

    Lactitol and neomycin: monotherapy or combined therapy in the prevention and treatment of hepatic encephalopathy?

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    The beneficial effect of disaccharides, lactulose and lactitol, in prevention adn treatment of hepatic encephalopathy is well established but their use in combination with neomycin is still controversial. We studied in vitro the fecal bacterial growth, acid and gas formation in presence of lactitol (beta-galactoside-sorbitol) and neomycin alone or in combination. The results indicate that neomycin only inhibits the growth of susceptible bacteria (E. coli, Staph. aureus) which, conversely, are poor lactitol fermenters. The resistant organisms (Lactobacillus acidophilus, Clostridium perfringens) that are efficient disacchride fermenters continue to metabolize lactitol still when antibiotic is added. Addition of lactitol 10% increaded the inhbitory effect of neomycin on bacterial growth by 25-50% within 60-70 min. These preliminary data suggest that lactitol and neomycin may have additional or symergistic effects in vivo when used together in presence of favourable intestinal microbial environment

    Acid tolerance and fecal recovery following oral administration of Saccharomyces cerevisiae.

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    Probiotic micoorganisms to be used os biotherapeutic agents have to resist the rigors of theupper human gastrointestinal tract. In this study we evaluated the acid tolerance in vitro and the fecal recovery in vivo after oral administration of a Saccharomyces cerevisiae strain to healthy volunteers. At the lowest pH value (pH 7.0 the release of S. cerevisiae in buffer solutions increased. The selected yeast strain showed good tolerance to low pH wihich mimic the gastric envitornment the feces of 6 (37.5%) of the 16 healthy, treated volunteers. Based on the results of the present experiments the yeast studied can be considered a strain that tolerates adverse conditions comparable to those of the human gastrointestinal tract, and when administered orally may colonize the bowel of healthy volunteers adn even replace resident Candida species
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