Malaria associated symptoms in pregnant women followed-up in Benin

<p>Abstract</p> <p>Background</p> <p>It is generally agreed that in high transmission areas, pregnant women have acquired a partial immunity to malaria and when infected they present few or no symptoms. However, longitudinal cohort studies investigating the clinical presentation of malaria infection in pregnant women in stable endemic areas are lacking, and the few studies exploring this issue are unconclusive.</p> <p>Methods</p> <p>A prospective cohort of women followed monthly during pregnancy was conducted in three rural dispensaries in Benin from August 2008 to September 2010. The presence of symptoms suggestive of malaria infection in 982 women during antenatal visits (ANV), unscheduled visits and delivery were analysed. A multivariate logistic regression was used to determine the association between symptoms and a positive thick blood smear (TBS).</p> <p>Results</p> <p>During routine ANVs, headache was the only symptom associated with a higher risk of positive TBS (aOR = 1.9; p < 0.001). On the occasion of unscheduled visits, fever (aOR = 5.2; p < 0.001), headache (aOR = 2.1; p = 0.004) and shivering (aOR = 3.1; p < 0.001) were significantly associated with a malaria infection and almost 90% of infected women presented at least one of these symptoms. Two thirds of symptomatic malaria infections during unscheduled visits occurred in late pregnancy and long after the last intermittent preventive treatment dose (IPTp).</p> <p>Conclusion</p> <p>The majority of pregnant women were symptomless during routine visits when infected with malaria in an endemic stable area. The only suggestive sign of malaria (fever) was associated with malaria only on the occasion of unscheduled visits. The prevention of malaria in pregnancy could be improved by reassessing the design of IPTp, i.e. by determining an optimal number of doses and time of administration of anti-malarial drugs.</p

Cardiac Alterations in Human African Trypanosomiasis (T.b. gambiense) with Respect to the Disease Stage and Antiparasitic Treatment

In Human African Trypanosomiasis (HAT), neurological symptoms dominate and cardiac involvement has been suggested. Because of increasing resistance to the available drugs for HAT, new compounds are desperately needed. Evaluation of cardiotoxicity is one parameter of drug safety, but without knowledge of the baseline heart involvement in HAT, cardiologic findings and drug-induced alterations will be difficult to interpret. The electrocardiogram (ECG) is a tool to evaluate cardiac involvement and the risk of arrythmias. We analysed the ECG of 465 HAT patients and compared them with the ECG of 61 healthy volunteers. In HAT patients the QTc interval was prolonged. This comprises a risk of fatal arrhythmias if new drugs with antiarrhythmic potential will be used. Further, repolarization changes and low voltage were more frequent than in healthy controls. This could be explained by an inflammation of the heart. Treatment of HAT was associated with appearance of repolarization changes but not with a QTc prolongation. These changes appear to be associated with the disease, but not with a specific drug. The main conclusion of this study is that heart involvement is frequent in HAT and mostly well tolerated. However, it can become relevant, if new compounds with antiarrhythmic potential will be used

Functional Amyloids Composed of Phenol Soluble Modulins Stabilize Staphylococcus aureus Biofilms

Staphylococcus aureus is an opportunistic pathogen that colonizes the skin and mucosal surfaces of mammals. Persistent staphylococcal infections often involve surface-associated communities called biofilms. Here we report the discovery of a novel extracellular fibril structure that promotes S. aureus biofilm integrity. Biochemical and genetic analysis has revealed that these fibers have amyloid-like properties and consist of small peptides called phenol soluble modulins (PSMs). Mutants unable to produce PSMs were susceptible to biofilm disassembly by matrix degrading enzymes and mechanical stress. Previous work has associated PSMs with biofilm disassembly, and we present data showing that soluble PSM peptides disperse biofilms while polymerized peptides do not. This work suggests the PSMs' aggregation into amyloid fibers modulates their biological activity and role in biofilms

Chemosensory Cues to Conspecific Emotional Stress Activate Amygdala in Humans

Alarm substances are airborne chemical signals, released by an individual into the environment, which communicate emotional stress between conspecifics. Here we tested whether humans, like other mammals, are able to detect emotional stress in others by chemosensory cues. Sweat samples collected from individuals undergoing an acute emotional stressor, with exercise as a control, were pooled and presented to a separate group of participants (blind to condition) during four experiments. In an fMRI experiment and its replication, we showed that scanned participants showed amygdala activation in response to samples obtained from donors undergoing an emotional, but not physical, stressor. An odor-discrimination experiment suggested the effect was primarily due to emotional, and not odor, differences between the two stimuli. A fourth experiment investigated behavioral effects, demonstrating that stress samples sharpened emotion-perception of ambiguous facial stimuli. Together, our findings suggest human chemosensory signaling of emotional stress, with neurobiological and behavioral effects

Nitric oxide triggers a transient metabolic reprogramming in Arabidopsis

[EN] Nitric oxide (NO) regulates plant growth and development as well as responses to stress that enhanced its endogenous production. Arabidopsis plants exposed to a pulse of exogenous NO gas were used for untargeted global metabolomic analyses thus allowing the identification of metabolic processes affected by NO. At early time points after treatment, NO scavenged superoxide anion and induced the nitration and the S-nitrosylation of proteins. These events preceded an extensive though transient metabolic reprogramming at 6&#8201;h after NO treatment, which included enhanced levels of polyamines, lipid catabolism and accumulation of phospholipids, chlorophyll breakdown, protein and nucleic acid turnover and increased content of sugars. Accordingly, lipid-related structures such as root cell membranes and leaf cuticle altered their permeability upon NO treatment. Besides, NO-treated plants displayed degradation of starch granules, which is consistent with the increased sugar content observed in the metabolomic survey. The metabolic profile was restored to baseline levels at 24&#8201;h post-treatment, thus pointing up the plasticity of plant metabolism in response to nitroxidative stress conditions.This work was supported by grants BIO2011-27526 and BIO2014-56067-P from the Spanish Ministry of Economy and Competitiveness and FEDER funds. We thank support and comments from Danny Alexander (Metabolon Inc., USA) on metabolomic analyses.Leon Ramos, J.; Costa-Broseta, Á.; Castillo López Del Toro, MC. (2016). Nitric oxide triggers a transient metabolic reprogramming in Arabidopsis. Scientific Reports. 6:1-14. doi:10.1038/srep37945S1146Arc, E., Galland, M., Godin, B., Cueff, G. & Rajjou, L. Nitric oxide implication in the control of seed dormancy and germination. Front. Plant Sci. 4, 346 (2013).Beligni, M. V. & Lamattina, L. Nitric oxide stimulates seed germination and de-etiolation, and inhibits hypocotyl elongation, three light-inducible responses in plants. Planta 210, 215–221 (2000).Lozano-Juste, J. & León, J. Nitric oxide regulates DELLA content and PIF expression to promote photomorphogenesis in Arabidopsis. Plant Physiol. 156, 1410–1123 (2011).He, Y. et al. Nitric oxide represses the Arabidopsis floral transition. Science 305, 1968–1971 (2004).Tsai, Y. C., Delk, N. A., Chowdhury, N. I. & Braam, J. Arabidopsis potential calcium sensors regulate nitric oxide levels and the transition to flowering. Plant Signal. Behav. 2, 446–454 (2007).Manjunatha, G., Lokesh, V. & Neelwarne, B. Nitric oxide in fruit ripening: trends and opportunities. Biotechnol. Adv. 28, 489–499 (2010).Liu, F. & Guo, F. Q. Nitric oxide deficiency accelerates chlorophyll breakdown and stability loss of thylakoid membranes during dark-induced leaf senescence in Arabidopsis. PLoS One 8(2), e56345 (2013).Du, J. et al. Nitric oxide induces cotyledon senescence involving co-operation of the NES1/MAD1 and EIN2-associated ORE1 signalling pathways in Arabidopsis. J. Exp. Bot. 65, 4051–4063 (2014).Siddiqui, M. H., Al-Whaibi, M. H. & Basalah, M. O. Role of nitric oxide in tolerance of plants to abiotic stress. Protoplasma 248, 447–455 (2011).Arasimowicz-Jelonek, M. & Floryszak-Wieczorek, J. Nitric oxide: an effective weapon of the plant or the pathogen? Mol. Plant Pathol. 15, 406–416 (2014).Thomas, D. D. Breathing new life into nitric oxide signaling: A brief overview of the interplay between oxygen and nitric oxide. Redox Biol. 5, 225–33 (2015).Groβ, F., Durner, J. & Gaupels, F. Nitric oxide, antioxidants and prooxidants in plant defence responses. Front. Plant Sci. 4, 419 (2013).Astier, J. & Lindermayr, C. Nitric oxide-dependent posttranslational modification in plants: an update. Int. J. Mol. Sci. 13, 15193–15208 (2012).Hess, D. T. & Stamler, J. S. Regulation by S-nitrosylation of protein post-translational modification. J. Biol. Chem. 287, 4411–4418 (2012).Guerra, D. D. & Callis, J. Ubiquitin on the move: the ubiquitin modification system plays diverse roles in the regulation of endoplasmic reticulum- and plasma membrane-localized proteins. Plant Physiol. 160, 56–64 (2012).Skalska, K., Miller, J. S. & Ledakowicz, S. Trends in NO(x) abatement: a review. Sci. Total Environ. 408, 3976–3989 (2010).Pilegaard, K. Processes regulating nitric oxide emissions from soils. Phil. Transac. Royal Soc. London. Ser. B, Biol. Sci. 368, 20130126 (2013).Jaegle, L., Steinberger, L., Martin, R. V. & Chance, K. Global partitioning of NOx sources using satellite observations: Relative roles of fossil fuel combustion, biomass burning and soil emissions. Faraday Discus. 130, 407–423 (2005).Gupta, K. J., Fernie, A. R., Kaiser, W. M. & van Dongen, J. T. On the origins of nitric oxide. Trends Plant Sci. 16, 160–168 (2011).Mur, L. A. et al. Nitric oxide in plants: an assessment of the current state of knowledge. AoB Plants 5, pls052 (2013).Correa-Aragunde, N., Foresi, N. & Lamattina, L. Nitric oxide is a ubiquitous signal for maintaining redox balance in plant cells: regulation of ascorbate peroxidase as a case study. J. Exp. Bot. 66, 2913–2921 (2015).Noctor, G., Lelarge-Trouverie, C. & Mhamdi, A. The metabolomics of oxidative stress. Phytochemistry 112, 33–53 (2015).Allan, W. L., Simpson, J. P., Clark, S. M. & Shelp, B. J. Gamma-hydroxybutyrate accumulation in Arabidopsis and tobacco plants is a general response to abiotic stress: putative regulation by redox balance and glyoxylate reductase isoforms. J. Exp. Bot. 59, 2555–2564 (2008).Romero, L. C., Aroca, M. Á., Laureano-Marín, A. M., Moreno, I., García, I. & Gotor, C. Cysteine and cysteine-related signaling pathways in Arabidopsis thaliana. Mol. Plant 7, 264–276 (2014).Noctor, G. et al. Glutathione in plants: an integrated overview. Plant Cell Environ. 35, 454–484 (2012).Feussner, I. & Wasternack, C. The lipoxygenase pathway. Ann. Rev. Plant Biol. 53, 275–297 (2002).Green, M. A. & Fry, S. C. Vitamin C degradation in plant cells via enzymatic hydrolysis of 4-O-oxalyl-L-threonate. Nature 433, 83–87 (2005).Szarka, A., Tomasskovics, B. & Bánhegyi, G. The ascorbate-glutathione-α-tocopherol triad in abiotic stress response. Int. J. Mol. Sci. 13, 4458–4483 (2012).Hurlock, A. K., Roston, R. L., Wang, K. & Benning, C. Lipid trafficking in plant cells. Traffic 15, 915–932 (2014).Blokhina, O., Virolainen, E. & Fagerstedt, K. V. Antioxidants, oxidative damage and oxygen deprivation stress: a review. Ann. Bot. 91, 179–194 (2003).Yeats, T. H. & Rose, J. K. The formation and function of plant cuticles. Plant Physiol. 163, 5–20 (2013).Lozano-Juste, J. & León, J. Enhanced abscisic acid-mediated responses in nia1nia2noa1-2 triple mutant impaired in NIA/NR- and AtNOA1-dependent nitric oxide biosynthesis in Arabidopsis. Plant Physiol. 152, 891–903 (2010).Hörtensteiner, S. Update on the biochemistry of chlorophyll breakdown. Plant Mol Biol. 82, 505–17 (2013).Pruzinská, A. et al. Chlorophyll breakdown in senescent Arabidopsis leaves: characterization of chlorophyll catabolites and of chlorophyll catabolic enzymes involved in the degreening reaction. Plant Physiol. 139, 52–63 (2005).Hirashima, M., Tanaka, R. & Tanaka, A. Light-independent cell death induced by accumulation of pheophorbide a in Arabidopsis thaliana. Plant Cell Physiol. 50, 719–29 (2009).Zottini, M., Costa, A., De Michele, R., Ruzzene, M., Carimi, F. & Lo Schiavo, F. Salicylic acid activates nitric oxide synthesis in Arabidopsis. J Exp Bot. 58, 1397–1405 (2007).Mainz, E. R. et al. Monitoring intracellular nitric oxide production using microchip electrophoresis and laser-induced fluorescence detection. Analytical Methods 4, 414–420 (2012).Vandelle, E. & Delledonne, M. Peroxynitrite formation and function in plants. Plant Sci. 181, 534–539 (2011).Minocha, R., Majumdar, R. & Minocha, S. C. Polyamines and abiotic stress in plants: a complex relationship. Front. Plant Sci. 5, 175 (2014).Parsons H. T., Yasmin, T. & Fry, S. C. Alternative pathways of dehydroascorbic acid degradation in vitro and in plant cell cultures: novel insights into vitamin C catabolism. Biochem. J. 440, 375–383 (2011).Hou, Q., Ufer, G. & Bartels, D. Lipid signalling in plant responses to abiotic stress. Plant Cell Environ. 39, 1029–4108 (2016).Zhou, X. R., Callahan, D. L., Shrestha, P., Liu, Q., Petrie, J. R. & Singh, S. P. Lipidomic analysis of Arabidopsis seed genetically engineered to contain DHA. Front. Plant Sci. 5, 41 (2014).Pohl, C. H. & Kock, J. L. Oxidized fatty acids as inter-kingdom signaling molecules. Molecules 19, 1273–1285 (2014).Araújo, W. L., Tohge, T., Ishizaki, K., Leaver, C. J. & Fernie, A. R. Protein degradation-an alternative respiratory substrate for stressed plants. Trends Plant Sci. 16, 489–498 (2011).Sakamoto, W. & Takami, T. Nucleases in higher plants and their possible involvement in DNA degradation during leaf senescence. J. Exp. Bot. 65, 3835–3843 (2014).Del Duca, S., Serafini-Fracassini, D. & Cai, G. Senescence and programmed cell death in plants: polyamine action mediated by transglutaminase. Front. Plant Sci. 5, 120 (2014).Franco, M. C. & Estévez, A. G. Tyrosine nitration as mediator of cell death. Cell. Mol. Life Sci. 71, 3939–3950 (2014).Palumbo, A., Fiore, G., Di Cristo, C., Di Cosmo, A. & d’Ischia, M. NMDA receptor stimulation induces temporary alpha-tubulin degradation signalled by nitric oxide-mediated tyrosine nitration in the nervous system of Sepia officinalis. Biochem. Biophys. Res. Commun. 293, 1536–1543 (2002).Wang, Y. Y., Lin, S. Y., Chuang, Y. H., Mao, C. H., Tung, K. C. & Sheu, W. H. Protein nitration is associated with increased proteolysis in skeletal muscle of bile duct ligation-induced cirrhotic rats. Metabolism 59, 468–472 (2010).Castillo, M. C., Lozano-Juste, J., González-Guzmán, M., Rodriguez, L., Rodriguez, P. L. & León, J. Inactivation of PYR/PYL/RCAR ABA receptors by tyrosine nitration may enable rapid inhibition of ABA signaling by nitric oxide in plants. Sci. Signal. 8(392), ra89 (2015).Blaise, G. A., Gauvin, D., Gangal, M. & Authier, S. Nitric oxide, cell signaling and cell death. Toxicology 208, 177–192 (2005).Brüne, B. Nitric oxide: NO apoptosis or turning it ON? Cell Death Differ. 10, 864–869 (2003).Wang, Y., Chen, C., Loake, G. J. & Chu, C. Nitric oxide: promoter or suppressor of programmed cell death? Prot. Cell 1, 133–142 (2010).Serrano, I., Romero-Puertas, M. C., Sandalio, L. M. & Olmedilla, A. The role of reactive oxygen species and nitric oxide in programmed cell death associated with self-incompatibility. J. Exp. Bot. 66, 2869–2876 (2015).Huang, S., Hill, R. D. & Stasolla, C. Plant hemoglobin participation in cell fate determination. Plant Signal. Behavior 9, e29485 (2014).Maes, M. B., Scharpé, S. & De Meester, I. Dipeptidyl peptidase II (DPPII), a review. Clin. Chim. Acta 380, 31–49 (2007).Gibbs, D. J. et al. Nitric oxide sensing in plants is mediated by proteolytic control of group VII ERF transcription factors. Mol. Cell 53, 369–379 (2014).Kitamura, K. Inhibition of the Arg/N-end rule pathway-mediated proteolysis by dipeptide-mimetic molecules. Amino Acids 48, 235–243 (2016).Duek, P. D., Elmer, M. V., van Oosten, V. R. & Fankhauser C. The degradation of HFR1, a putative bHLH class transcription factor involved in light signaling, is regulated by phosphorylation and requires COP1. Curr Biol. 14, 2296–2301 (2004)

Fentanyl is devoid of major effects on coronary vasoreactivity and myocardial metabolism in experimental animals

Experiments were designed to determine the effects of fentanyl on coronary vascular tone and energetic state of the heart. Both arterial and arteriolar responses were assessed; particular attention was directed to epicardial vessels. Four experimental methods and three animal species were used. Isolated canine coronary artery rings with and without endothelium were suspended in organ chambers, and changes in their tension were measured. Fentanyl (100 ng/ml) had no effect on resting tension of unstimulated rings on a contraction evoked by serotonin 10-8 to 10-4 M. In rings with endothelium, the opioid had a minimal depressant effect on the contractile response to phenylephrine. Tension of vessels precontracted with serotonin (3 x 10-7 M), or phenylephrine (10-5 M) was unchanged following fentanyl at 10, 30, 70, or 150 ng/ml. Computerized quantitative angiography was used in intact pigs anesthetized with ketamine to determine the effects of fentanyl on coronary artery diameters of vessels with or without endothelium. Intravenous fentanyl 50 and 250 μg/kg had no effect on vessel diameters. Isolated perfused rat hearts were used to assess fentanyl effects upon coronary flow and arteriolar tone and upon myocardial energy state. Coronary blood flow was not altered by fentanyl (100 ng/ml) and was unchanged following washout of the drug. The heart maintained a normal energy status prior to and following fentanyl treatment. These data demonstrate that, under the conditions tested, fentanyl is devoid of major effects on the coronary circulation and upon myocardial metabolism.link_to_subscribed_fulltex