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21.
Introduction
Cerebral malaria (CM) is a potentially fatal cerebrovascular disease of complex pathogenesis caused by Plasmodium falciparum. Hydrogen sulfide (HS) is a physiological gas, similar to nitric oxide and carbon monoxide, involved in cellular metabolism, vascular tension, inflammation, and cell death. HS treatment has shown promising results as a therapy for cardio- and neuro- pathology. This study investigates the effects of fast (NaHS) and slow (GYY4137) HS-releasing drugs on the growth and metabolism of P. falciparum and the development of P. berghei ANKA CM. Moreover, we investigate the role of free plasma thiols and cell surface thiols in the pathogenesis of CM.Methods
P. falciparum was cultured in vitro with varying doses of HS releasing drugs compared with artesunate. Growth and metabolism were quantified. C57Bl/6 mice were infected with P. berghei ANKA and were treated with varying doses and regimes of HS-releasing drugs. Free plasma thiols and cell surface thiols were quantified in CM mice and age-matched healthy controls.Results
HS-releasing drugs significantly and dose-dependently inhibited P. falciparum growth and metabolism. Treatment of CM did not affect P. berghei growth, or development of CM. Interestingly, CM was associated with lower free plasma thiols, reduced leukocyte+erythrocyte cell surface thiols (infection day 3), and markedly (5-fold) increased platelet cell surface thiols (infection day 7).Conclusions
HS inhibits P. falciparum growth and metabolism in vitro. Reduction in free plasma thiols, cell surface thiols and a marked increase in platelet cell surface thiols are associated with development of CM. HS drugs were not effective in vivo against murine CM. 相似文献22.
23.
Early Weight Loss with Liraglutide 3.0 mg Predicts 1‐Year Weight Loss and is Associated with Improvements in Clinical Markers
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24.
Jared M. Baeten Renee Heffron Lara Kidoguchi Nelly R. Mugo Elly Katabira Elizabeth A. Bukusi Stephen Asiimwe Jessica E. Haberer Jennifer Morton Kenneth Ngure Nulu Bulya Josephine Odoyo Edna Tindimwebwa Craig Hendrix Mark A. Marzinke Norma C. Ware Monique A. Wyatt Susan Morrison Harald Haugen Andrew Mujugira Deborah Donnell Connie Celum Partners Demonstration Project Team 《PLoS medicine》2016,13(8)
BackgroundAntiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings.ConclusionsIntegrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year. 相似文献
25.
Anne-Marie Lundsgaard Jacob B. Holm Kim A. Sjøberg Kirstine N. Bojsen-Møller Lene S. Myrmel Even Fjære Benjamin A.H. Jensen Trine S. Nicolaisen Janne R. Hingst Sine L. Hansen Sophia Doll Philip E. Geyer Atul S. Deshmukh Jens J. Holst Lise Madsen Karsten Kristiansen Jørgen F.P. Wojtaszewski Erik A. Richter Bente Kiens 《Cell metabolism》2019,29(1):50-63.e4
26.
Laura Kofoed Kjær Vanja Cejvanovic Trine Henriksen Torben Hansen Oluf Pedersen Cramer Kjeldahl Christensen 《Free radical research》2019,53(6):694-703
The relationship between RNA and DNA oxidation and pharmacological treatment has not been systematically investigated in patients with type 2 diabetes (T2D). We aimed to investigate the association between pharmacological treatments and levels of urinary markers of nucleic acid oxidation in T2D patients. Vejle Diabetes Biobank cohort data was nested into nationwide registry data. Multiple logistic regression was used to associate drug usage with risk of high (above median) RNA and DNA oxidation. Data from 2664 T2D patients (64% male, age range: 25–75) were included. Questionnaire-validated lipid lowering drug use was associated with low RNA oxidation (Odds ratio, OR 0.71, 95% CI: [0.59–0.87]). Insulin and non-specific antidiabetic drugs were associated with low DNA oxidation (insulin: OR 0.60, 95% CI [0.49–0.73]). Oral antidiabetics were associated with high DNA oxidation and RNA oxidation (OR 1.30, 95% CI [1.10–1.53] and OR 1.26, 95% CI [1.07–1.29]). Our findings indicate that diabetes-related drugs are associated with RNA and DNA oxidation and further studies are required to determine causality in T2D patients. 相似文献
27.
Jason Olsen Gunbharpur Singh Gill Riston Haugen Steven L. Matzner Jake Alsdurf David H. Siemens 《Ecology and evolution》2019,9(20):11532-11544
Most transplant experiments across species geographic range boundaries indicate that adaptation to stressful environments outside the range is often constrained. However, the mechanisms of these constraints remain poorly understood. We used extended generation crosses from diverged high and low elevation populations. In experiments across low elevation range boundaries, there was selection on the parental lines for abiotic stress‐tolerance and resistance to herbivores. However, in support of a defense‐tolerance trade‐off, extended generation crosses showed nonindependent segregation of these traits in the laboratory across a drought‐stress gradient and in the field across the low elevation range boundary. Genotypic variation in a marker from a region of the genome containing a candidate gene (MYC2) was associated with change in the genetic trade‐off. Thus, using crosses and forward genetics, we found experimental genetic and molecular evidence for a pleiotropic trade‐off that could constrain the evolution of range expansion. 相似文献
28.
A minimum of 20 porbeagles Lamna nasus were observed circling the Alba oil platform (UK North Sea) over several days in July 2014. Although schools of fish often aggregate around oil platforms, less is known about their ability to aggregate pelagic sharks and L. nasus are rarely seen at the surface. This unusual observation provides new insights into L. nasus behaviour and habitat use and the potential role of offshore artificial structures on pelagic predators. 相似文献
29.
Trine Johansen Cathrine Rein Carlson Anne-Brit Kolstø 《FEMS microbiology letters》1996,136(3):325-328
Abstract Ribosornal RNA operon organisation was analysed in two Bacillus cereus strains of different chromosome size, ATCC 10987 (5.4 Mb) and F0837/76 (2.4 Mb). We estimated that there were twelve and nine copies of the rRNA operons in these two strains, respectively. In B. cereus ATCC 10987 six rRNA operons were less than 10 kb apart, while in B. cereus F0837/76 four rRNA operons were similarly clustered. The origin of replication was located in the vicinity of a rRNA operon in both strains. 相似文献
30.