Biodecolourisation of some industrial dyes by white-rot fungi

Eight white-rot fungal strains were screened for biodecolourisation of eight dyes commercially employed in various industries. Decolourisation of Poly R 478 was used as a standard to ascertain the dye-decolourisation potential of various fungi. All the fungi tested significantly decolourised Poly R 478 on solid agar medium. When tested in a nitrogen-limited broth medium, Dichomitus squalens, Irpex flavus, Phlebia spp. and Polyporus sanguineus were better industrial dye decolourisers than Phanerochaete chrysosporium.     

A randomised controlled trial of triple antiplatelet therapy (aspirin, clopidogrel and dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility

Background

Aspirin, dipyridamole and clopidogrel are effective in secondary vascular prevention. Combination therapy with three antiplatelet agents might maximise the benefit of antiplatelet treatment in the secondary prevention of ischaemic stroke.

Methodology/Principal Findings

A randomised, parallel group, observer-blinded phase II trial compared the combination of aspirin, clopidogrel and dipyridamole with aspirin alone. Adult patients with ischaemic stroke or transient ischaemic attack (TIA) within 5 years were included. The primary outcome was tolerability to treatment assessed as the number of patients completing randomised treatment. Recruitment was halted prematurely after publication of the ESPRIT trial (which confirmed that combined aspirin and dipyridamole is more effective than aspirin alone). 17 patients were enrolled: male 12 (71%), mean age 62 (SD 13) years, lacunar stroke syndrome 12 (71%), median stroke/TIA onset to randomisation 8 months. Treatment was discontinued in 4 of 9 (44%) patients receiving triple therapy vs. none of 8 taking aspirin (p = 0.08). One recurrent stroke occurred in a patient in the triple group who was noncompliant of all antiplatelet medications. The number of patients with adverse events and bleeding complications, and their severity, were significantly greater in the triple therapy group (p<0.01).

Conclusions/Significance

Long term triple antiplatelet therapy was asociated with a significant increase in adverse events and bleeding rates, and their severity, and a trend to increased discontinuations. However, the patients had a low risk of recurrence and future trials should focus on short term therapy in high risk patients characterised by a very recent event or failure of dual antiplatelet therapy.

Trial Registration

Controlled-Trials.com ISRCTN83673558     

Hematopoietic stem cell (CD34+) uptake of superparamagnetic iron oxide is enhanced by but not dependent on a transfection agent

Background aimsTracking the fate of cells after infusion would be a valuable asset for many stem cell therapies, but very few (cell) labels are approved for human therapeutic use. Superparamagnetic iron oxide particles (SPIO) can be internalized into stem cells in vitro to allow real-time tracking with gradient echo magnetic resonance imaging, but SPIO are approved for (diagnostic) imaging and not for (therapeutic) cell labeling in vivo. In this study, we investigated the possibility of labeling stem cells with an SPIO approved for patient use, albeit in a novel manner by enhancing uptake with the use of a transfection agent, also approved for patient use. Although there are many reports of hematopoietic stem cells being labeled with SPIO, there is some controversy regarding the efficiency of this and whether undifferentiated CD34+ progenitor (stem) cells are able to take up iron in the absence of a transfection agent to enhance the process.MethodsHuman CD34+ cells were treated in vitro as follows: incubation with (i) medium only (control), (ii) ferumoxide (Endorem) and (iii) ferumoxide (Endorem) plus exposure to a transfection agent (protamine sulfate). Cells were incubated for 2, 4 and 24 hours and assessed for viability, differentiation capacity and visualized in vitro with 3-T magnetic resonance imaging. The cells were also analyzed by means of flow cytometry and morphology examined by electron microscopy.ResultsCD34+ hematopoietic progenitor cells can internalize ferumoxide (Endorem) independently of a transfection agent. However, uptake of ferumoxide is enhanced after exposure to protamine sulfate. Iron labeling of CD34+ cells in this manner does not affect cell viability and does not appear to affect the potential of the cells to grow in culture. Iron-labeled CD34+ cells can be visualized in vitro on 3-T magnetic resonance image scanning.ConclusionsEndorem and protamine sulfate can be combined to promote iron oxide nanoparticle uptake by CD34+ cells, and this methodology can potentially be used to track the fate of cells in a clinical trial setting because both compounds are (separately) approved for clinical use.     

Targeting the cell cycle in breast cancer: towards the next phase

Deregulation of the cell cycle is a hallmark of cancer that enables limitless cell division. To support this malignant phenotype, cells acquire molecular alterations that abrogate or bypass control mechanisms in signaling pathways and cellular checkpoints that normally function to prevent genomic instability and uncontrolled cell proliferation. Consequently, therapeutic targeting of the cell cycle has long been viewed as a promising anti-cancer strategy. Until recently, attempts to target the cell cycle for cancer therapy using selective inhibitors have proven unsuccessful due to intolerable toxicities and a lack of target specificity. However, improvements in our understanding of malignant cell-specific vulnerabilities has revealed a therapeutic window for preferential targeting of the cell cycle in cancer cells, and has led to the development of agents now in the clinic. In this review, we discuss the latest generation of cell cycle targeting anti-cancer agents for breast cancer, including approved CDK4/6 inhibitors, and investigational TTK and PLK4 inhibitors that are currently in clinical trials. In recognition of the emerging population of ER+ breast cancers with acquired resistance to CDK4/6 inhibitors we suggest new therapeutic avenues to treat these patients. We also offer our perspective on the direction of future research to address the problem of drug resistance, and discuss the mechanistic insights required for the successful implementation of these strategies.     

Some features ofNitella chloroplasts as revealed by the electron microscope

Summary Nitella chloroplasts when extruded from the large internodal cells and examined with the electron microscope often show daughter plastids in various stages of division as well as occasional external plastid protuberances. In the individual plastids the main mass of the chloroplast material appears to be concentrated in the outer portion of the plastid leaving a somewhat spongy interior. The extruded contents of ruptured plastids often contain particles of around 500 Å in diameter.Deceased, March 14, 1953     

CD11/CD18 cell surface adhesion glycoproteins: Discordance of monocyte function and expression in response to stimulation

The adherence of blood leukocytes to vascular endothelium precedes their diapedesis into the extravascular space. These processes require the expression of adherence glycoproteins on the cell surface of the leukocyte. The relative importance of these adherence molecules is so far poorly understood. However, there is evidence to suggest that a disparity exists between the surface receptor expression of these glycoproteins and leukocyte adherence to vascular endothelial cells in culture. We have investigated the importance of each of the adhesion glycoproteins CD11a, CD11b, and CD11c in mediating the adherence of human monocytes to endothelial cells in culture. We have also investigated the chronological relationship between changes in monocyte adherence to endothelial cells and the surface expression of CD11a, CD11b, and CD11c following stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP). The increase in adherence occurred within 1 minute, but declined if monocytes were preincubated with fMLP for up to 30 minutes. The surface expression of adherence molecules demonstrated a significant increase in CD11a and CD11b in the presence of fMLP after 10 min and was maintained while monocyte adherence to endothelium declined. These changes in surface receptor expression were quantitated using an immunolabeling technique. It is suggested that fMLP stimulation of monocyte adherence is unlikely to be solely dependent on increased surface receptor expression of adhesion molecules.     

Ionic and respiratory regulation in rainbow trout during rapid transfer to seawater

Summary Ionic and respiratory parameters of large rainbow trout were measured during freshwater to seawater transfer. Branchial Cl^– efflux increased immediately on transfer and urine excretion of Cl^– increased after 14 h. Branchial Na⁺ efflux however did not start to build up until 4–5 h after transfer and there was no increase in urinary Na⁺ excretion. These differences are discussed.The acid/base balance showed no major changes but arterial fell greatly on transfer but by 5 h had returned to 82% of the normal level. After 24 h arterial had decreased markedly again and this continued to the end of the experiment. On seawater transfer oxygen consumption fell gradually for 5 h and then rapidly increased back to the freshwater value. Possible explanations of these observations are discussed in relation to gill morphology and function during the transfer period.