Contribution of peripheral vanilloid receptor to the nociception induced by injection of spermine in mice

Polyamines (putrescine, spermidine and spermine) are important endogenous regulators of ion channels, such as vanilloid (TRPV1), glutamatergic (NMDA or AMPA/kainate) and acid-sensitive (ASIC) receptors. In the present study, we have investigated the possible nociceptive effect induced by polyamines and the mechanisms involved in this nociception in vivo. The subcutaneous (s.c.) injection of capsaicin (as positive control), spermine, spermidine or putrescine produced nociception with ED₅₀ of 0.16 (0.07-0.39) nmol/paw, 0.4 (0.2-0.7) μmol/paw, 0.3 (0.1-0.9) μmol/paw and 3.2 (0.9-11.5) μmol/paw, respectively. The antagonists of NMDA (MK801, 1 nmol/paw), AMPA/kainate (DNQX, 1 nmol/paw) or ASIC receptors (amiloride, 100 nmol/paw) failed to reduce the spermine-trigged nociception. However, the TRPV1 antagonists capsazepine or SB366791 (1 nmol/paw) reduced spermine-induced nociception, with inhibition of 81 ± 10 and 68 ± 9%, respectively. The previous desensitization with resiniferatoxin (RTX) largely reduced the spermine-induced nociception and TRPV1 expression in the sciatic nerve, with reductions of 82 ± 9% and 67 ± 11%, respectively. Furthermore, the combination of spermine (100 nmol/paw) and RTX (0.005 fmol/paw), in doses which alone were not capable of inducing nociception, produced nociceptive behaviors. Moreover, different concentrations of spermine (3-300 μM) enhanced the specific binding of [³H]-RTX to TRPV1 receptor. Altogether, polyamines produce spontaneous nociceptive effect through the stimulation of TRPV1, but not of ionotropic glutamate or ASIC receptors.     

Synthesis and antibacterial activity of silver nanoparticles against gram-positive and gram-negative bacteria

Synthesis of nanosized particles with antibacterial properties is of great interest in the development of new pharmaceutical products. Silver nanoparticles (Ag NPs) are known to have inhibitory and bactericidal effects. In this article we present the synthesis of Ag NPs prepared by chemical reduction from aqueous solutions of silver nitrate, containing a mixture of hydrazine hydrate and sodium citrate as reductants and sodium dodecyl sulfate as a stabilizer. The results of the characterization of the Ag NPs show agglomerates of grains with a narrow size distribution (from 40 to 60 nm), whereas the radii of the individual particles are between 10 and 20 nm. Finally, the antibacterial activity was measured by the Kirby-Bauer method. The results showed reasonable bactericidal activity against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The standard dilution micromethod, determining the minimum inhibitory concentration leading to inhibition of bacterial growth, is still under way. Preliminary results have been obtained. FROM THE CLINICAL EDITOR: In this paper the synthesis of Ag NPs via chemical reduction from aqueous solutions is discussed. Reasonable bactericidal activity against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus was demonstrated.     

<Emphasis Type="Italic">N</Emphasis>-Acetylcysteine prevents baker’s-yeast-induced inflammation and fever

Objetive and design  

To investigate whether N-acetylcysteine (NAC) alters baker’s-yeast-induced fever and inflammation.     

Carriage of antibiotic-resistant Escherichia coli among healthy children and home-raised chickens: a household study in a resource-limited setting

We have previously observed high rates of acquired antibiotic resistance in commensal Escherichia coli from healthy children living in urban areas of Bolivia and Peru, including resistance to tetracycline and quinolones, which are not routinely used in childhood. In this work we investigated acquired resistance in commensal E. coli from healthy children and home-raised chickens in 12 households from one of the previously surveyed urban area in Bolivia, to ascertain the possibility of human-animal exchange of resistant strains in similar settings. The resistance rates to ampicillin, tetracycline, chloramphenicol, streptomycin, and trimethoprim-sulphametoxazole were overall high (≥50%) and comparable between children and chickens, whereas those to quinolones were significantly higher in chickens (81% vs. 29% for nalidixic acid; 43% vs. 10% for ciprofloxacin). Molecular characterization of tetracycline- and quinolone-resistant isolates (n?=?66) from children and chickens of three selected households revealed a remarkable clonal diversity and, in some cases, the presence of the same resistant strains among children or among chickens living in the same household, but not between children and chickens. Several resistance plasmids were characterized, but inter-clonal plasmid dissemination was not detected. Overall, the results from the present study suggested that cross-transmission between children and home-raised chickens could not represent a major spreading mechanism for resistant E. coli in households of resource-limited settings with high human-animal promiscuity.     

Economic impact of severe asthma in Spain: multicentre observational longitudinal study

Objective: Estimate the economic impact of severe asthma from the Spanish social perspective through the estimation of the associated annual direct and indirect costs. Methods: Observational, longitudinal, retrospective study carried out in 20 Spanish secondary settings (Pulmonology and Allergy Services) among patients aged ≥18, diagnosed with severe asthma according to European Respiratory Society/American Thoracic Society consensus and who have not experienced an exacerbation in the previous 2 months. Asthma-related healthcare resource utilization as well as asthma-related days off work were collected over a retrospective 12-month period from medical records review (inclusion period: June to November 2016). Total costs were calculated by multiplying the natural resource units used within 1 year by the corresponding unit cost. Costs were expressed in Euros for 2018. Results: A total of 303 patients were included, mean age was 54 years old and 67% were women. There were 5.7 physician visits per patient (3.3 in secondary care). The most common pharmacologic treatment was fixed dose combination of inhaled corticosteroids/long-acting β2-adrenergic agonists (96.7%), followed by leukotriene receptor antagonists (57.1%). 134 patients (44.2%) had at least one severe asthma exacerbation (mean: 1.9 exacerbation/patient), of whom 22 patients required hospitalization, with a mean hospital stay of 10.9 days/patient. Mean sick leave due to severe asthma was 9.1 days per patient per year. Mean annual direct cost (confidence interval 95%) was €7472/patient (€6578–8612). The cost per exacerbation was €1410/patient. When indirect costs were added (€1082/patient [€564–1987]), the total annual mean cost rose to €8554/patient (€7411–10199). Conclusions: Taking the social perspective, the economic impact of severe asthma in Spain was estimated to be €8554/patient/year.     

The gut microbiota profile is associated with insulin action in humans

The role of the gut microbiota in the induction of metabolic diseases has now been increasingly recognized worldwide. Indeed, a specific gut microbiota has been shown to characterize lean versus obese phenotypes both in humans and mice. We have also recently demonstrated that a precise gut microbiota is associated with the host’s responsiveness to a high-fat diet. Therefore, we hypothesized that insulin resistance in humans could also be linked to a specific gut microbiota. To this aim, microbial DNA and RNA were extracted from the appendix contents of insulin-resistant versus insulin-sensitive obese subjects, matched for body mass index and age, and analyzed by DNA- and RNA-DGGE. Microbial DNA analysis showed that the patients fully segregated according to their degree of insulin action. Conversely, microbial RNA investigation showed that some degree of homology still existed between insulin-sensitive and insulin-resistant patients. Quantitative trait analysis, ordinary least squares regression, principal components regression, partial least squares, canonical correlation analysis, and canonical correspondence analysis also showed a net separation of the two phenotypes analyzed. We conclude that a specific gut microbial profile is associated with insulin action in humans.     

Single- and multiple-ascending-dose studies of the NS3 protease inhibitor asunaprevir in subjects with or without chronic hepatitis C

Hepatitis C virus (HCV) protease inhibitors combined with pegylated alfa interferon-ribavirin have demonstrated improved efficacy compared with pegylated alfa interferon-ribavirin alone for the treatment of chronic hepatitis C. Asunaprevir (BMS-650032), a novel HCV NS3 protease inhibitor in clinical development, was evaluated for safety, antiviral activity, and resistance in four double-blind, placebo-controlled, sequential-panel, single- and multiple-ascending-dose (SAD and MAD) studies in healthy subjects or subjects with chronic HCV genotype 1 infection. In SAD studies, subjects (healthy or with chronic HCV infection) were randomized to receive asunaprevir in dose groups of 10 to 1,200 mg or a placebo. In MAD studies, healthy subjects were randomized to receive asunaprevir in dose groups of 10 to 600 mg twice daily or a placebo for 14 days; subjects with HCV infection received asunaprevir in dose groups of 200 to 600 mg twice daily, or a placebo, for 3 days. Across all four studies, headache and diarrhea were the most frequent adverse events in asunaprevir recipients. Asunaprevir at doses of 200 to 600 mg resulted in rapid HCV RNA decreases from the baseline; maximal mean changes in HCV RNA over time were 2.7 and 3.5 log(10) IU/ml in the SAD and MAD studies, respectively. No enrichment of signature asunaprevir-resistant viral variants was detected. In conclusion, the novel NS3 protease inhibitor asunaprevir, when administered at single or multiple doses of 200 to 600 mg twice daily, is generally well tolerated, achieving rapid and substantial decreases in HCV RNA levels in subjects chronically infected with genotype 1 HCV.     

The potential antidepressant-like effect of imidazoline I2 ligand 2-BFI in mice

The compound 2-(2-benzofuranyl)-2-imidazoline (2-BFI) is a 2-imidazoline derivative that selectively inhibits the in vitro activity of monoamine oxidase-A and it is also an imidazoline I(2) agonist. However, the antidepressant potential of this compound and its mechanism of action have not been well defined. Therefore, in this study we investigated the antidepressant-like effect of 2-BFI in mice. 2-BFI (100 and 300μmol/kg, s.c.) significantly reduced the immobility time on the tail suspension test (TST) without changing locomotion in the open field test. The reduced the immobility time of 2-BFI (100μmol/kg, s.c.) was confirmed with the forced swimming test (FST). The antidepressant-like effect of 2-BFI (100μmol/kg, s.c.) in the TST was prevented by pretreatment with idazoxan (0.4μmol/kg, i.p., a I(2) site antagonist), methysergide (4μmol/kg, i.p., a non-selective serotonergic receptor antagonist) and haloperidol (0.1μmol/kg, i.p., a non-selective dopaminergic receptor antagonist). The anxiolytic effect of 2-BFI was also evaluated, using the elevated plus-maze test. 2-BFI (300μmol/kg, s.c.) was able to significantly increase the % of number of entries and the % of time spent in the open arms, indicating that it possesses an anxiolytic effect at high doses. In conclusion, these results suggest that the antidepressant-like effect of 2-BFI might involve serotonergic, dopaminergic and imidazoline systems, and then the imidazoline site could represent a new pharmacological target for the treatment of depression.