RNA from LPS-stirnulated macrophages induces the release of tumour necrosis factor-α and interleukin-1 by resident macrophages

The effect of exogenous RNA on many cellular functions has been studied in a variety of eukaryotic cells but there are few reports on macrophages. In the present study, it is demonstrated that cytoplasmatic RNA extracted from rat macrophages stimulated with Escherichia coli lipopolysaccharide (LPS), referred to as L-RNA, induced the release of TNF-α and IL-1 from monolayers of peritoneal resident macrophages. The activity of L-RNA was not altered by polymyxin B but was abolished by ribonuclease (RNase) pretreatment, indicating the absence of LPS contamination and that the integrity of the polynucleotide chain is essential for this activity. Both the poly A(−) and poly A(+) fractions obtained from L-RNA applied to oligo(dT)–cellulose chromatography induced TNF-α and IL-1 release. The L-RNA-induced cytokine release was inhibited by dexamethasone and seemed to be dependent on protein synthesis since this effect was abolished by cycloheximide or actinomycin-D. The LPS-stimulated macrophages, when pre-incubated with [5-3H]-uridine, secreted a trichloroacetic acid (TCA) precipitable material which was sensitive to RNase and KOH hydrolysis, suggesting that the material is RNA. This substance was also released from macrophage monolayers stimulated with IL-1β but not with TNF-α, IL-6 or IL-8. The substance secreted (3H-RNA) sediments in the 4–5S region of a 5–20% sucrose gradient. These results show that L-RNA induces cytokine secretion by macrophage monolayers and support the idea that, during inflammation, stimulated macrophages could release RNA which may further induce the release of cytokines by the resident cell population

Association of Anticholinergic Burden with Cognitive and Functional Status in a Cohort of Hospitalized Elderly: Comparison of the Anticholinergic Cognitive Burden Scale and Anticholinergic Risk Scale

Abstract Background Drugs with anticholinergic effects are associated with adverse events such as delirium and falls as well as cognitive decline and loss of independence. Objective The aim of the study was to evaluate the association between anticholinergic burden and both cognitive and functional status, according to the hypothesis that the cumulative anticholinergic burden, as measured by the Anticholinergic Cognitive Burden (ACB) Scale and Anticholinergic Risk Scale (ARS), increases the risk of cognitive decline and impairs activities of daily living. Methods This cross-sectional, prospective study (3-month telephone follow-up) was conducted in 66 Italian internal medicine and geriatric wards participating in the Registry of Polytherapies SIMI (Societa` Italiana di Medicina Interna) (REPOSI) study during 2010. The sample included 1,380 inpatients aged 65 years or older. Cognitive status was rated with the Short Blessed Test (SBT) and physical function with the Barthel Index. Each patient’s anticholinergic burden was evaluated using the ACB and ARS scores. Results The mean SBT score for patients treated with anticholinergic drugs was higher than that for patients receiving no anticholinergic medications as also indicated by the ACB scale, even after adjustment for age, sex, education, stroke and transient ischaemic attack [9.2 (95 % CI 8.6–9.9) vs. 8.5 (95 % CI 7.8–9.2); p = 0.05]. There was a dose–response relationship between total ACB score and cognitive impairment. Patients identified by the ARS had more severe cognitive and physical impairment than patients identified by the ACB scale, and the dose–response relationship between this score and ability to perform activities of daily living was clear. No correlation was found with length of hospital stay. Conclusions Drugs with anticholinergic properties identified by the ACB scale and ARS are associated with worse cognitive and functional performance in elderly patients. The ACB scale might permit a rapid identification of drugs potentially associated with cognitive impairment in a dose–response pattern, but the ARS is better at rating activities of daily living

Active surveillance in males with low- to intermediate-risk localized prostate cancer: A modern prospective cohort study

Purpose: To compare the clinical outcome of males with low-risk and favorable intermediate-risk prostate cancer managed within a standardized modern protocol of active surveillance. Materials and methods: This was a prospective cohort study with strict and expanded active surveillance criteria in males with prostate cancer. Baseline assessment included multiparametric magnetic resonance imaging (mpMRI), extended systematic biopsy, and software-based MR-targeted biopsy. Follow-up included biannual prostate-specific antigen (PSA) check, mpMRI, and control biopsy once a year for the first 2 years, and afterward mpMRI every 2 years with additional tests as clinically indicated. The primary outcome was the transition rate to active treatment. Results: A total of 51 patients were included: 17 (33%) and 34 (67%) followed protocols of strict (study arm 1) and expanded (study arm 2) active surveillance criteria, respectively. Median age and PSA were 65 years (IQR, 60-69 years) and 5.3 ng/mL (IQR, 4.5-7.7 ng/mL), respectively. At baseline, a median of 2 (IQR, 1-3) cores were positive out of 13 (IQR, 12-14) cores; 22 males (43%) had visible mpMRI lesions. Eight males (24%) in study arm 2 had Gleason score 3+4. After a median follow-up of 36 months (IQR, 24-48 mo), no patient in study arm 1 compared with 17 patients (33%) in arm 2 underwent active treatment (p<0.0005). Conclusions: Although expanding eligibility criteria leads to a greater transition rate to active treatment, active surveillance should be contemplated in well-selected males with favorable intermediate-risk prostate cancer as the curability window seems to be maintained

Active surveillance in males with low- to intermediate-risk localized prostate cancer: A modern prospective cohort study.

To compare the clinical outcome of males with low-risk and favorable intermediate-risk prostate cancer managed within a standardized modern protocol of active surveillance. This was a prospective cohort study with strict and expanded active surveillance criteria in males with prostate cancer. Baseline assessment included multiparametric magnetic resonance imaging (mpMRI), extended systematic biopsy, and software-based MR-targeted biopsy. Follow-up included biannual prostate-specific antigen (PSA) check, mpMRI, and control biopsy once a year for the first 2 years, and afterward mpMRI every 2 years with additional tests as clinically indicated. The primary outcome was the transition rate to active treatment. A total of 51 patients were included: 17 (33%) and 34 (67%) followed protocols of strict (study arm 1) and expanded (study arm 2) active surveillance criteria, respectively. Median age and PSA were 65 years (IQR, 60-69 years) and 5.3 ng/mL (IQR, 4.5-7.7 ng/mL), respectively. At baseline, a median of 2 (IQR, 1-3) cores were positive out of 13 (IQR, 12-14) cores; 22 males (43%) had visible mpMRI lesions. Eight males (24%) in study arm 2 had Gleason score 3+4. After a median follow-up of 36 months (IQR, 24-48 mo), no patient in study arm 1 compared with 17 patients (33%) in arm 2 underwent active treatment (p<0.0005). Although expanding eligibility criteria leads to a greater transition rate to active treatment, active surveillance should be contemplated in well-selected males with favorable intermediate-risk prostate cancer as the curability window seems to be maintained

Coagulant and antibacterial activities of the water-soluble seed lectin from Moringa oleifera

Aims: The aim of this work was to analyse the coagulant and antibacterial activities of lectin isolated from Moringa oleifera seeds that are used for water treatment. Methods and Results:  The water-soluble M. oleifera lectin (WSMoL) was separated from nonhemagglutinating components (NHC) by chitin chromatography. WSMoL fluorescence spectrum was not altered in the presence of ions that are often present in high concentrations in polluted waters. Seed extract, NHC and WSMoL showed coagulant activity on a turbid water model. Both NHC and WSMoL reduced the growth of Staphylococcus aureus, but only WSMoL caused a reduction in Escherichia coli. WSMoL was also more effective in reducing the growth of ambient lake water bacteria. Conclusions:  Data obtained from this study indicate that WSMoL is a potential natural biocoagulant for water, reducing turbidity, suspended solids and bacteria. Significance and Impact of the Study: Moringa oleifera seeds are a material effective in the treatment of water.The authors express their gratitude to the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) for research grants and fellowship (LCBBC, MLVO and PMGP), the Fundacao de Amparo a Ciencia e Tecnologia do Estado de Pernambuco (FACEPE) and the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) for financial support. Authors are grateful to Maria Barbosa Reis da Silva for the technical assistance and to David Pillard and Felix Nonnenmacher for English editing

Molecular fragmentation of wheat-germ agglutinin induced by food irradiation reduces its allergenicity in sensitised mice

WGA, an agglutinin from wheat germ which is largely responsible for many of wheat's allergies, was used as a model to investigate the action of ionising radiation on WGA's anti-nutritive effects in sensitised mice. Based on the molecular structure, the present study also examined the structural modification of WGA in relation to the range of dose. Structural integrity was monitored using HPLC, fluorescence spectrometry and circular dichroism. Results showed a loss of intrinsic activity and the formation of insoluble amorphous aggregates with a lack of native conformational structures after irradiation. Current findings suggest that the allergenic epitopes of WGA became less active and antigenic after high-dose radiation. the reduction of cytokines typical of allergic reactions, with decreased lymphocytic infiltrate, was observed in the gut of mice given irradiated versus native WGA. Food irradiation proved effective and safe in combating immunological and allergic effects of WGA. (C) 2011 Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Ministerio da Ciencia e Tecnologia (Brazilian)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao de Amparo a Ciencia e Tecnologia do Estado de Pernambuco (FACEPE)Univ Fed Pernambuco, Dept Bioquim, Recife, PE, BrazilUniv Fed Pernambuco, Dept Histol & Embriol, Recife, PE, BrazilUniv Fed Pernambuco, Dept Biofis & Radiobiol, Recife, PE, BrazilUniv Fed Pernambuco, Dept Antibiot, Recife, PE, BrazilUniv Estadual Oeste Parana, Ctr Engn & Ciencias Exatas, Toledo, BrazilUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, BrazilWeb of Scienc

Rivastigmine: an open-label, observational study of safety and effectiveness in treating patients with Alzheimer's disease for up to 5 years

BACKGROUND: Rivastigmine, a butyl- and acetylcholinesterase inhibitor, is approved for symptomatic treatment of Alzheimer's disease (AD). Data supporting the safety and efficacy of second-generation cholinesterase inhibitors, such as rivastigmine, are available for treatment up to 1 year, with limited data up to 2 1/2 years. The purpose of this report is to present safety and effectiveness data for rivastigmine therapy in patients with mild to moderately severe AD receiving treatment for up to 5 years. METHODS: An observational approach was used to study 37 patients with originally mild to moderate AD receiving rivastigmine as a therapy for AD in an open-label extension (ENA713, B352 Study Group, 1998). RESULTS: The initial trial demonstrated rivastigmine was well-tolerated and effective in terms of cognition, global functioning and activities of daily living. In this open label extension, high-dose rivastigmine therapy was safe and well tolerated over a 5-year period. Two thirds of the participants still enrolled at week 234 were in the original high-dose rivastigmine group during the double-blind phase, suggesting that early therapy may confer some benefit in delaying long-term progression of symptoms. CONCLUSIONS: Long-term cholinesterase inhibition therapy with rivastigmine was well tolerated, with no dropouts due to adverse effects past the initial titration period. Early initiation of treatment, with titration to high-dose therapy, may have an advantage in delaying progression of the illness