Ginger Essential Oil Ameliorates Cisplatin-Induced Nephrotoxicity in Mice

Purpose: To investigate the effect of ginger essential oil (GEO) in an experimental model of cisplatininduced nephrotoxicity.Methods: Male mice were divided into treatment six groups (n = 7), namely: Groups I (saline), II and III (cisplatin, 10 mg/kg, i.p.) euthanized in 3th and 6th days, respectively, and IV, V and IV (GEO, 100, 200 and 400 mg/kg/day, respectively, by gavage 3, 4, 5 and 6 days after cisplatin injection). Creatinine levels and protein/creatinine ratio were determined in plasma and urine, respectively. Bone morphogenic protein (BMP-7) and tumor necrosis factor (TNF-α) levels of kidney tissues were determined while mRNA expression levels were obtained using real-time polymerase chain reaction.Results: GEO treatment reduced significantly creatinine levels to 0.53 ± 0.02; 0.48 ± 0.008 and 0.46 ± 0.02 at 100, 200 and 400 mg/kg, respectively, compared with control (0.70 ± 0.01) [p<0.05] but increased protein : creatinine ratio to 0.21 ± 0.01, 0.22 ± 0.01, 0.24 ± 0.02 compared with control (0.06 ± 0.008) [p<0.05]. Pro-inflammatory TNF-α mRNA expression was decreased to 1.46 ± 0.21, 1.39 ± 0.19 and 1.36 ± 0.09, at GEO doses of 100, 200 and 400 mg/kg, respectively, while anti-fibrotic BMP-7 mRNA expression increased to 2.05 ± 0.26 and 2.44 ± 0.42 at doses of 200 and 400 mg/kg, respectively, compared with control (0.59 ± 0.39, p < 0.05).Conclusion: GEO treatment attenuates cisplatin-induced nephrotoxicity, in part, by modulating some inflammatory cytokines.Keywords: Zingiber officinale, Ginger, Roscoe, Essential oil, Nephrotoxicity, Cisplati

A novel determination of the local dark matter density

We present a novel study on the problem of constructing mass models for the Milky Way, concentrating on features regarding the dark matter halo component. We have considered a variegated sample of dynamical observables for the Galaxy, including several results which have appeared recently, and studied a 7- or 8-dimensional parameter space - defining the Galaxy model - by implementing a Bayesian approach to the parameter estimation based on a Markov Chain Monte Carlo method. The main result of this analysis is a novel determination of the local dark matter halo density which, assuming spherical symmetry and either an Einasto or an NFW density profile is found to be around 0.39 GeV cm$^{-3}$ with a 1-$\sigma$ error bar of about 7%; more precisely we find a $\rho_{DM}(R_0) = 0.385 \pm 0.027 \rm GeV cm^{-3}$ for the Einasto profile and $\rho_{DM}(R_0) = 0.389 \pm 0.025 \rm GeV cm^{-3}$ for the NFW. This is in contrast to the standard assumption that $\rho_{DM}(R_0)$ is about 0.3 GeV cm$^{-3}$ with an uncertainty of a factor of 2 to 3. A very precise determination of the local halo density is very important for interpreting direct dark matter detection experiments. Indeed the results we produced, together with the recent accurate determination of the local circular velocity, should be very useful to considerably narrow astrophysical uncertainties on direct dark matter detection.Comment: 31 pages,11 figures; minor changes in the text; two figures adde

Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: results of an international, cross-sectional study (COMORA)

Background: Patients with rheumatoid arthritis (RA) are at increased risk of developing comorbid conditions.<p></p> Objectives: To evaluate the prevalence of comorbidities and compare their management in RA patients from different countries worldwide.<p></p> Methods Study design: international, cross-sectional. Patients: consecutive RA patients. Data collected: demographics, disease characteristics (activity, severity, treatment), comorbidities (cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and psychiatric disorders).<p></p> Results: Of 4586 patients recruited in 17 participating countries, 3920 were analysed (age, 56±13 years; disease duration, 10±9 years (mean±SD); female gender, 82%; DAS28 (Disease Activity Score using 28 joints)–erythrocyte sedimentation rate, 3.7±1.6 (mean±SD); Health Assessment Questionnaire, 1.0±0.7 (mean±SD); past or current methotrexate use, 89%; past or current use of biological agents, 39%. The most frequently associated diseases (past or current) were: depression, 15%; asthma, 6.6%; cardiovascular events (myocardial infarction, stroke), 6%; solid malignancies (excluding basal cell carcinoma), 4.5%; chronic obstructive pulmonary disease, 3.5%. High intercountry variability was observed for both the prevalence of comorbidities and the proportion of subjects complying with recommendations for preventing and managing comorbidities. The systematic evaluation of comorbidities in this study detected abnormalities in vital signs, such as elevated blood pressure in 11.2%, and identified conditions that manifest as laboratory test abnormalities, such as hyperglycaemia in 3.3% and hyperlipidaemia in 8.3%.<p></p> Conclusions: Among RA patients, there is a high prevalence of comorbidities and their risk factors. In this multinational sample, variability among countries was wide, not only in prevalence but also in compliance with recommendations for preventing and managing these comorbidities. Systematic measurement of vital signs and laboratory testing detects otherwise unrecognised comorbid conditions.<p></p&gt

B Physics at the Tevatron: Run II and Beyond

This report provides a comprehensive overview of the prospects for B physics at the Tevatron. The work was carried out during a series of workshops starting in September 1999. There were four working groups: 1) CP Violation, 2) Rare and Semileptonic Decays, 3) Mixing and Lifetimes, 4) Production, Fragmentation and Spectroscopy. The report also includes introductory chapters on theoretical and experimental tools emphasizing aspects of B physics specific to hadron colliders, as well as overviews of the CDF, D0, and BTeV detectors, and a Summary.Comment: 583 pages. Further information on the workshops, including transparencies, can be found at the workshop's homepage: http://www-theory.lbl.gov/Brun2/. The report is also available in 2-up http://www-theory.lbl.gov/Brun2/report/report2.ps.gz or chapter-by-chapter http://www-theory.lbl.gov/Brun2/report

Serotonergic signalling suppresses ataxin 3 aggregation and neurotoxicity in animal models of Machado-Joseph disease

Polyglutamine diseases are a class of dominantly inherited neurodegenerative disorders for which there is no effective treatment. Here we provide evidence that activation of serotonergic signalling is beneficial in animal models of Machado-Joseph disease. We identified citalopram, a selective serotonin reuptake inhibitor, in a small molecule screen of FDA-approved drugs that rescued neuronal dysfunction and reduced aggregation using a Caenorhabditis elegans model of mutant ataxin 3-induced neurotoxicity. MOD-5, the C. elegans orthologue of the serotonin transporter and cellular target of citalopram, and the serotonin receptors SER-1 and SER-4 were strong genetic modifiers of ataxin 3 neurotoxicity and necessary for therapeutic efficacy. Moreover, chronic treatment of CMVMJD135 mice with citalopram significantly reduced ataxin 3 neuronal inclusions and astrogliosis, rescued diminished body weight and strikingly ameliorated motor symptoms. These results suggest that small molecule modulation of serotonergic signalling represents a promising therapeutic target for Machado-Joseph disease.This work was supported by Fundação para a Ciência e Tecnologia (FCT) and COMPETE through the projects ‘[PTDC/SAU-GMG/112617/2009] (to P.M.) and [EXPL/ BIM-MEC/0239/2012] (to A.T.C.)’, by National Ataxia foundation (to P.M.), by Ataxia UK (to P.M.), by National Institutes of Health (NIH) ‘[GM038109, GM081192, AG026647, and NS047331] (to R.I.M.)’, by The Chicago Biomedical Consortium (to R.I.M.) and by the Ellison Medical Foundation (to R.I.M.). A.T.C., A.J., S.E., L.S.S., C.B., S.D.S., A.S.F. and A.N.C. were supported by the FCT individual fellowships SFRH/BPD/79469/2011, SFRH/BD/76613/2011, SFRH/BD/78554/2011, SFRH/BD/ 84650/2012, SFRH/BPD/74452/2010, SFRH/BD/78388/ 2011, SFRH/BPD/91562/2012 and SFRH/BD/51059/2010, respectively. FCT fellowships are co-financed by POPH, QREN, Governo da República Portuguesa and EU/FSE.info:eu-repo/semantics/publishedVersio