Association of Coagulation Activation with Clinical Complications in Sickle Cell Disease

Background: The contribution of hypercoagulability to the pathophysiology of sickle cell disease (SCD) remains poorly defined. We sought to evaluate the association of markers of coagulation and platelet activation with specific clinical complications and laboratory variables in patients with SCD. Design and Methods: Plasma markers of coagulation activation (D-dimer and TAT), platelet activation (soluble CD40 ligand), microparticle-associated tissue factor (MPTF) procoagulant activity and other laboratory variables were obtained in a cohort of patients with SCD. Tricuspid regurgitant jet velocity was determined by Doppler echocardiography and the presence/history of clinical complications was ascertained at the time of evaluation, combined with a detailed review of the medical records. Results: No significant differences in the levels of D-dimer, TAT, soluble CD40 ligand, and MPTF procoagulant activity were observed between patients in the SS/SD/Sb 0 thalassemia and SC/Sb + thalassemia groups. Both TAT and D-dimer were significantly correlated with measures of hemolysis (lactate dehydrogenase, indirect bilirubin and hemoglobin) and soluble vascular cell adhesion molecule-1. In patients in the SS/SD/Sb 0 thalassemia group, D-dimer was associated with a history of stroke (p = 0.049), TAT was associated with a history of retinopathy (p = 0.0176), and CD40 ligand was associated with the frequency of pain episodes (p = 0.039). In multivariate analyses, D-dimer was associated with reticulocyte count, lactat

Regulation of Inflammatory Gene Expression in PBMCs by Immunostimulatory Botanicals

Many hundreds of botanicals are used in complementary and alternative medicine for therapeutic use as antimicrobials and immune stimulators. While there exists many centuries of anecdotal evidence and few clinical studies on the activity and efficacy of these botanicals, limited scientific evidence exists on the ability of these botanicals to modulate the immune and inflammatory responses. Using botanogenomics (or herbogenomics), this study provides novel insight into inflammatory genes which are induced in peripheral blood mononuclear cells following treatment with immunomodulatory botanical extracts. These results may suggest putative genes involved in the physiological responses thought to occur following administration of these botanical extracts. Using extracts from immunostimulatory herbs (Astragalus membranaceus, Sambucus cerulea, Andrographis paniculata) and an immunosuppressive herb (Urtica dioica), the data presented supports previous cytokine studies on these herbs as well as identifying additional genes which may be involved in immune cell activation and migration and various inflammatory responses, including wound healing, angiogenesis, and blood pressure modulation. Additionally, we report the presence of lipopolysaccharide in medicinally prepared extracts of these herbs which is theorized to be a natural and active component of the immunostimulatory herbal extracts. The data presented provides a more extensive picture on how these herbs may be mediating their biological effects on the immune and inflammatory responses

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

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Not AvailableThere is a shred of evidence to suggest that Emblica officinalis Gaertn, the botanical name for amla seeds, has greater medicinal potential than amla fruit. We conducted this work to assess the anti-inflammatory, antibacterial, and antioxidant capacities of E. officinalis seed extracts. The bioactive components from the seeds were fractionated using chloroform, hexane, methanol, and diethyl ether, according to the polarity of the solvents. The total amount of phenolic and flavonoid was estimated. Both the reducing power and antioxidant capacities of the extracts were evaluated using the DPPH (1,1-diphenyl-2-picryl-hydrazyl) technique. 15-lipoxygenase (LOX) was inhibited by seed extracts at doses ranging from 5 to 25 micrograms. In silico docking was employed to assess the results. Some human pathogenic microorganisms were tested for their antibacterial activity using the agar disc diffusion method. Escherichia coli, Proteus vulgaris, and Klebsiella pneumonia were inhibited by a methanolic extract with an IC50 value of 58g, making it the most common organic solvent extract. Methanolic extracts also showed good antioxidant and antibacterial activity. Our investigation led us to discover that amla seeds have anti-inflammatory, antioxidant, and antibacterial effectsNot Availabl

Molecular- and organelle-based predictive paradigm underlying recovery by left ventricular assist device support

Je suis convaincu que d’une certaine manière tout texte est autobiographique…Jacques Derrida Qu’est-ce qu’une biographie pour un philosophe ? Heidegger a dit d’Aristote : « il naquit, il travailla, il mourut ». Il souligne ainsi que les faits biographiques n’ont pas beaucoup d’importance pour la pensée. Il en est de même dans la littérature. Depuis Proust, une étude biographique à la manière de Lanson est considérée comme plus nuisible qu’utile pour la compréhension d’une œuvre littéraire. Or..