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

Resilience, Cardiological Outcome, and Their Correlations With Anxious-Depressive Symptoms and Quality of Life in Patients With an Implantable Cardioverter Defibrillator

Background: Resilience is proven as a protective factor against the development of psychiatric disorders, and it has gained clinical relevance in the development and progression of cardiovascular pathology. The authors performed a longitudinal study on patients with implantable cardioverter defibrillator (ICD) with the primary aim to highlight the possible existence of a correlation between individual resilience capacity, depressive and anxiety symptoms, and quality of life in terms of outcomes. The secondary aim was to analyze the differences between patients with major cardiac events in the follow-up and patients without cardiac events with respect to the previous variables. Materials and Methods: A total of 80 patients enrolled in the Cardiology Unit were evaluated at T0 and during the follow-up through the following scales: the 14-item Resilience Scale (RS-14), the Hospital Anxiety and Depression Scale (HADS), and the World Health Organization Quality of Life-Brief Version (WHOQOL-Bref). Results: A significant linear correlation between resilience and all the areas of quality of life at T0, T1, and T2 emerged. A negative correlation between resilience and anxiety and depressive symptoms emerged, as well as between depression and anxiety and quality of life. Patients with cardiac events during the follow up have shown a worse quality of life and the onset of anxiety-depressive symptoms over time, without changes to the resilience scores. Patients without cardiac events showed an increasing trend in resilience scores. Discussion: Given the speed and simplicity of use of the RS-14 scale, it seems promising to further investigate the real clinical usefulness of this instrument in the cardiology field

Italian adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB 1.0): development and normative data

Background: Neuropsychological testing plays a cardinal role in the diagnosis and monitoring of Alzheimer’s disease. A major concern is represented by the heterogeneity of the neuropsychological batteries currently adopted in memory clinics and healthcare centers. The current study aimed to solve this issue. Methods: Following the initiative of the University of Washington’s National Alzheimer’s Coordinating Center (NACC), we presented the Italian adaptation of the Neuropsychological Test Battery of the Uniform Data Set (I-UDSNB). We collected data from 433 healthy Italian individuals and employed regression models to evaluate the impact of demographic variables on the performance, deriving the reference norms. Results: Higher education and lower age were associated with a better performance in the majority of tests, while sex affected only fluency tests and Digit Span Forward. Conclusions: The I-UDSNB offers a valuable and harmonized tool for neuropsychological testing in Italy, to be used in clinical and research settings

Structure and mechanism of human DNA polymerase η

The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites

Bioassay-Guided Evaluation of Antinociceptive Effect of N-Salicyloyltryptamine: A Behavioral and Electrophysiological Approach

We investigated the antinociceptive and nerve excitability effects of the N-salicyloyltryptamine (NST) NST-treated mice exhibited a significant decrease in the number of writhes when 100 and 200 mg/kg (i.p.) were administered (i.p.). This effect was not antagonized by naloxone (1.5 mg/kg, i.p.). NST inhibited the licking response of the injected paw when 100 and 200 mg/kg were administered (i.p.) to mice in the first and second phases of the formalin test. Because the antinociceptive effects could be associated with neuronal excitability inhibition, we performed the single sucrose gap technique and showed that NST (3.57 mM) significantly reduced (29.2%) amplitude of the compound action potential (CAP) suggesting a sodium channel effect induced by NST. Our results demonstrated an antinociceptive activity of the NST that could be, at least in part, associated to the reduction of the action potential amplitude. NST might represent an important tool for pain management

Comparison of health conditions treated with traditional and biomedical health care in a Quechua community in rural Bolivia

<p>Abstract</p> <p>Background</p> <p>The objective of the present study was to reveal patterns in the treatment of health conditions in a Quechua-speaking community in the Bolivian Andes based on plant use data from traditional healers and patient data from a primary health care (PHC) service, and to demonstrate similarities and differences between the type of illnesses treated with traditional and biomedical health care, respectively.</p> <p>Methods</p> <p>A secondary analysis of plant use data from semi-structured interviews with eight healers was conducted and diagnostic data was collected from 324 patients in the community PHC service. Health conditions were ranked according to: (A) the percentage of patients in the PHC service diagnosed with these conditions; and (B) the citation frequency of plant use reports to treat these conditions by healers. Healers were also queried about the payment modalities they offer to their patients.</p> <p>Results</p> <p>Plant use reports from healers yielded 1166 responses about 181 medicinal plant species, which are used to treat 67 different health conditions, ranging from general symptoms (e.g. fever and body pain), to more specific ailments, such as arthritis, biliary colic and pneumonia. The results show that treatment offered by traditional medicine overlaps with biomedical health care in the case of respiratory infections, wounds and bruises, fever and biliary colic/cholecystitis. Furthermore, traditional health care appears to be complementary to biomedical health care for chronic illnesses, especially arthritis, and for folk illnesses that are particularly relevant within the local cultural context. Payment from patients to healers included flexible, outcome contingent and non-monetary options.</p> <p>Conclusion</p> <p>Traditional medicine in the study area is adaptive because it corresponds well with local patterns of morbidity, health care needs in relation to chronic illnesses, cultural perceptions of health conditions and socio-economic aspects of health care. The quantitative analysis of plant use reports and patient data represents a novel approach to compare the contribution of traditional and biomedical health care to treatment of particular health conditions.</p

Fungal diversity associated to the olive moth, prays oleae Bernard : a survey for potential entomopathogenic fungi

Olive production is one of the main agricultural activities in Portugal. In the region of Trás-os-Montes this crop has been considerably affected by Prays oleae. In order to evaluate the diversity of fungi on P. oleae population of Trás-os-Montes olive orchards, larvae and pupae of the three annual generations (phyllophagous, antophagous and carpophagous) were collected and evaluated for fungal growth on their surface. From the 3828 larvae and pupae, a high percentage of individuals exhibited growth of a fungal agent (40.6%), particularly those from the phyllophagous generation. From all the moth generations, a total of 43 species from 24 genera were identified, but the diversity and abundance of fungal species differed between the three generations. Higher diversity was found in the carpophagous generation, followed by the antophagous and phyllophagous generations. The presence of fungi displaying entomopathogenic features was highest in the phyllophagous larvae and pupae, being B. bassiana the most abundant taxa. The first report of B. bassiana presence on P. oleae could open new strategies for the biocontrol of this major pest in olive groves, since the use of an already adapted species increases the guarantee of success of a biocontrol approach. The identification of antagonistic fungi able to control agents that cause major olive diseases, such as Verticillium dahliae, will benefit future biological control approaches for limiting this increasingly spreading pathogen.This work was supported by Science and Technology Foundation (Fundação para a Ciência e Tecnologia – FCT) project PTDC/AGR-AAM/102600/2008 “Entomopathogenic fungi associated to olive pests: isolation, characterization and selection for biological control”. The first author is grateful to the Science and Technology Foundation for the PhD grant SFRH/BD/44265/2008

Blood Pressure Lowering With Nilvadipine in Patients With Mild-to-Moderate Alzheimer Disease Does Not Increase the Prevalence of Orthostatic Hypotension

BACKGROUND: Hypertension is common among patients with Alzheimer disease. Because this group has been excluded from hypertension trials, evidence regarding safety of treatment is lacking. This secondary analysis of a randomized controlled trial assessed whether antihypertensive treatment increases the prevalence of orthostatic hypotension (OH) in patients with Alzheimer disease. METHODS AND RESULTS: Four hundred seventy‐seven patients with mild‐to‐moderate Alzheimer disease were randomized to the calcium‐channel blocker nilvadipine 8 mg/day or placebo for 78 weeks. Presence of OH (blood pressure drop ≥20/≥10 mm Hg after 1 minute of standing) and OH‐related adverse events (dizziness, syncope, falls, and fractures) was determined at 7 follow‐up visits. Mean age of the study population was 72.2±8.2 years and mean Mini‐Mental State Examination score was 20.4±3.8. Baseline blood pressure was 137.8±14.0/77.0±8.6 mm Hg. Grade I hypertension was present in 53.4% (n=255). After 13 weeks, blood pressure had fallen by −7.8/−3.9 mm Hg for nilvadipine and by −0.4/−0.8 mm Hg for placebo (P<0.001). Across the 78‐week intervention period, there was no difference between groups in the proportion of patients with OH at a study visit (odds ratio [95% CI]=1.1 [0.8–1.5], P=0.62), nor in the proportion of visits where a patient met criteria for OH, corrected for number of visits (7.7±13.8% versus 7.3±11.6%). OH‐related adverse events were not more often reported in the intervention group compared with placebo. Results were similar for those with baseline hypertension. CONCLUSIONS: This study suggests that initiation of a low dose of antihypertensive treatment does not significantly increase the risk of OH in patients with mild‐to‐moderate Alzheimer disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02017340