4,714 research outputs found
Induction of apoptosis by photoexcited tetracyclic compounds derivitaves of benzo(b)thiopenes and pyridines
No full textThe antiproliferative activity, upon UVA irradiation, of two tetracyclic derivatives of benzo[b]thiophenes and pyridines, a benzo[b]thienopyridopyrimidone (1) and a thienocarboline (2), has been investigated in a panel of human tumor cell lines. The two compounds present a remarkable cytotoxicity after UVA irradiation (365 nm), reaching an IC50 of 0.1 microM in the leukaemia cell lines and 0.3-0.5 microM in the solid tumour cell lines. Their effect on the cell cycle was measured by flow cytometry in Jurkat cells. The compounds induce cell cycle perturbations and trigger a massive apoptosis as revealed by the externalisation of Annexin V-targeted residues at the outer plasmatic membrane. Furthermore the drugs induce, upon UVA irradiation significant variations of the mitochondrial potential (Deltapsi(mt)) measured by flow cytometry using the fluorochrome JC-1. In addition we characterized the mitochondrial production of reactive oxygen species (ROS) using the probe dihydroethidine (HE) and the oxidations of the mitochondrial phospholipid cardiolipin using the interacting probe nonyl acridine orange (NAO). Both compounds stimulate the production of ROS, and remarkably induce oxidation of cardiolipin. We have investigated the DNA-binding properties of these two compounds by means of UV-Vis spectroscopy and fluorescence. The two compounds exhibit a low affinity toward the macromolecule. The mode of binding was also investigated by means of flow linear dichroism (LD) which has revealed that the two compounds do not efficiently intercalate into DNA. Finally, the DNA-photocleavaging properties of the test compounds were studied on pBR322 plasmid DNA as a model. Only compound 1 is able to induce a significant production of single strand breaks only after digestion with the base excision repair enzyme Endo III. Altogether these data suggest that DNA is not a preferential target of these molecules and other subcellular structures may be responsible for their high phototoxic activity
Postmortem genetic testing for conventional autopsy-negative sudden unexplained death - An evaluation of different DNA extraction protocols and the feasibility of mutational analysis from archival paraffin-embedded heart tissue
No full textIF JCR 2007: 2.62
Self-compression of 4.9 µm pulses to sub-40 fs with 2 mJ energy in Zinc Sulfide
No full textNonlinear self-compression of few-cycle multi-mJ pulses at 4.9 µm in ZnS is presented. 80 fs input pulses are compressed to 37 fs with 2.1 mJ energy at a 1 kHz repetition rate. © 2024 The Author(s
Alzheimer's disease: pathophysiological implications of measurement of plasma cortisol, plasma dehydroepiandrosterone sulfate, and lymphocytic corticosteroid receptors
No full textAlzheimer's disease is often characterized by an increase in plasma cortisol without clinical evidence of hypercorticism. Twenty-three consecutive patients with Alzheimer's disease and 23 age- and sex-matched healthy controls were studied by measuring plasma cortisol and dehydroepiandrosterone sulfate (DHEAS) (by enzyme immunoassay), the number of type I and type II corticosteroid receptors in mononuclear leukocytes (by radioreceptorassay), and the lymphocyte subpopulations (by cytofluorimetry). Results are expressed in terms of median and range. In Alzheimer's disease, plasma cortisol was higher than in controls (median 0.74, range 0.47-1.21 vs 0.47, 0.36-0.77 mmol/L; p < 0.001). Plasma DHEAS, the DHEAS/cortisol ratio, and the number of type 11 corticosteroid receptors were significantly lower in AD than in controls (DHEAS: median 1.81, range 0.21-3.69 vs 3.51, 1.35-9.07 μmol/L; DHEAS/ cortisol: 2.04, range 0.3-5.8 vs 6.8, range 2.7-24 and type 11 receptors: 1219, 1000-2700 vs 1950, 10352750 receptors per cell; p < 0.001). No correlation was found between the hormonal parameters, age, and minimental test score. These data support the hypothesis of a dysregulation of the adrenal pituitary axis in Alzheimer's disease, which is probably the consequence of damage to target tissues by corticosteroid
Correction to: Chamoun et al., Bacterial pathogenesis and interleukin-17: interconnecting mechanisms of immune regulation, host genetics, and microbial virulence that influence severity of infection
No full textChamoun MN, Blumenthal A, Sullivan MJ, Schembri MA, Ulett GC. 2018. Bacterial pathogenesis and interleukin-17: interconnecting mechanisms of immune regulation, host genetics, and microbial virulence that influence severity of infection. Critical Reviews in Microbiology. https://doi.org/10.1080/1040841X.2018.1426556.
When the above article was first published online, the below three corrections were missed.
The author ‘Antje Blumenthal’ was wrongly affiliated to the affiliation “cSchool of Chemistry and Molecular Biosciences, and Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Australia”. Now this affiliation has been removed for this author.
The affiliation ‘bTranslational Research Institute, The University of Queensland Diamantina Institute, Woolloongabba, Australia’ of the author ‘Antje Blumenthal’ should read ‘bThe University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia’.
In Table 3, the sentence ‘Benefit of manipulating IL-17 levels to improve immunization strategies M. tuberculosis’ should read “Benefit of manipulating IL-17 levels to improve immunization strategies against M. tuberculosis”.No Full Tex
Generation of 22-mJ, 2.0-ps Pulses from a 1-kHz Ho:YLF Regenerative Chirped Pulse Amplifier
No full textWe report a CW-pumped Ho:YLF regenerative amplifier (RA) delivering pulses with 22.5-mJ energy and 2.0-ps duration at 1 kHz. The RA emitting at 2051 nm is broadband-seeded and implemented in a chirped pulse amplification system. © 2024 The Author(s
Arrhythmogenic cardiomyopathy: electrical instability and intercalated disc abnormalities in transgenic mice
No full textAims: Mutations in genes encoding desmosomal proteins have been implicated in the pathogenesis of arrhythmogenic right ventricular cardiomyopathy (ARVC). However, the consequences of these mutations in early disease stages are unknown. We investigated
whether mutation-induced intercalated disc remodeling impacts on electrophysiological properties before the onset of cell death and replacement fibrosis.
Methods and Results: Transgenic mice with cardiac overexpression of mutant Desmoglein2 (Dsg2) Dsg2-N271S (Tg-NS/L) were studied before and after the onset of cell death and replacement fibrosis. Mice with cardiac overexpression of wild-type Dsg2 and wild-type
mice served as controls. Assessment by electron microscopy established that intercellular space widening at the desmosomes/adherens junctions occurred in Tg-NS/L mice before the onset of necrosis and fibrosis. At this stage, epicardial mapping in Langendorff-perfused
hearts demonstrated prolonged ventricular activation time, reduced longitudinal and transversal conduction velocities, and increased arrhythmia inducibility. A reduced action
potential upstroke velocity due to a lower Na+ current density was also observed at this stage
of the disease. Furthermore, co-immunoprecipitation demonstrated an in vivo interaction
between Dsg2 and the Na+ channel protein NaV1.5.
Conclusion: Intercellular space widening at the level of the intercalated disc (desmosomes/fascia adherens junctions) and a concomitant reduction in action potential upstroke velocity, as a consequence of lower Na+ current density, leads to slowed conduction and increased arrhythmia susceptibility at disease stages preceding the onset of necrosis and replacement
fibrosis. The demonstration of an in vivo interaction between Dsg2 and NaV1.5 provides a
molecular pathway for the observed electrical disturbances during the early ARVC stages
Shear Bond Strength of Orthodontic Brackets Luted with RMGIC After Er:YAG Laser Etching with Two Pulse Modes Using a Digitally Controlled "X-Runner" Handpiece
No full textObjective: To compare the shear bond strength (SBS) values of orthodontic brackets luted using a resin-modified glass ionomer cement (RMGIC) on enamel surfaces etched using either an Er:YAG laser in two different working modes, or a conventional etching protocol, including phosphoric acid.
Materials and methods: Sixty healthy human premolars were randomly allocated to three experimental groups (n = 20) and etched with: Group 1: Er:YAG laser in super-short pulse (SSP) mode (100 mJ, 20 Hz, 2 W); Group 2: Er:YAG laser in quantum square pulse mode (120 mJ, 10 Hz, 1.2 W) using a digitally controlled handpiece (“X-Runner”); Group 3 (control): 5.25% sodium hypochlorite pretreatment, then 37% phosphoric acid for 15 sec. Stainless steel brackets were bonded using light-curing RMGIC for orthodontic bonding. After term cycling (1800 cycles), SBS testing was performed using a universal testing machine. After debonding, both enamel and bracket surfaces were examined to determine the amount of RMGIC still present on the surfaces.
Results: Group 3 surfaces gave the lowest mean SBS (10.6104 ± 2.66196 MPa), whereas Group 1 provided the highest 1 (13.1795 ± 3.37904 MPa), which was significantly different from the control (Group 3, p = 0.0226). Group 2 provided intermediate values (11.8486 ± 0.59832 MPa) nonsignificantly different from the control or from SSP (p = 0.4215 and p = 0.3082, respectively).
Conclusions: Er:YAG laser treatment in SSP mode of enamel surfaces for orthodontic bonding provided higher SBS and a shear behavior of the luting material similar to the conventional acid-etching procedures, making it a viable alternative to acid etching
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