Purging of acute myeloid leukemic cells by ether lipids and hyperthermia

Ether lipids (EL) and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemic cells. In this study, the combined effects of EL (ET-18-OCH3, ET-16-NHCOCH3, or BM 41.440) and hyperthermia on the growth of hematopoietic progenitors, myeloid leukemic cell lines, and leukemic cells obtained from patients with acute myeloid leukemia (AML) were examined to determine if this combination resulted in a greater selective killing of leukemic cells than that achieved by either EL or heat alone. When the cells were treated simultaneously with EL (50 micrograms/mL) and hyperthermia (42 degrees C) for one hour, the killing of leukemic cell line cells was enhanced considerably. Among the three EL, however, the combination of ET-18-OCH3 and heat seemed to be the most cytotoxic to leukemic cell line cells with no effect on the growth of hematopoietic progenitors. An increase in the duration of treatment with ET-18-OCH3 to four hours with heat added during the last hour resulted in a further reduction of leukemic cell line cells while sparing 50% of hematopoietic progenitors after cryopreservation. The combined treatment with ET-18-OCH3 and heat also inhibited the growth of leukemic progenitors obtained from AML patients by 97% to 100%. These data indicate that the combined treatment with EL and hyperthermia might offer an efficient means to eliminate myeloid leukemic cells in vitro.     

On the Ablation Behavior of Carbon Fiber-Reinforced Plastics during Laser Surface Treatment Using Pulsed Lasers

This contribution discusses the ablation phenomena observed during laser treatment of carbon fiber-reinforced plastics (CFRPs) with pulsed lasers observed employing laser sources with wavelengths of 355 nm, 1064 nm and 10.6 µm and pulse durations from picoseconds (11 ps) to microseconds (14 µs) are analyzed and discussed. In particular, the threshold fluence of the matrix material epoxy (EP) and the damage threshold of CFRP were calculated. Moreover, two general surface pretreatment strategies are investigated, including selective matrix removal and structure generation through indentation (ablation of both, matrix material and fibers) with a cross-like morphology. The surfaces obtained after the laser treatment are characterized by means of optical and scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy is employed for the analysis of composite and constituent materials epoxy and carbon fibers. As a result, different ablation mechanisms, including evaporation and delamination are observed, depending on the employed laser wavelength and pulse duration. For both 355 nm and 1064 nm wavelength, the laser radiation produces only partial ablation of the carbon fibers due to their higher absorption coefficient compared to the epoxy matrix. Although a selective matrix removal without residues is achieved using the pulsed CO₂ laser. Differently, both constituent materials are ablated with the nanosecond pulsed UV laser, producing indentations. The sum of the investigations has shown that existing theories of laser technology, such as the ablation threshold according to Liu et al., can be applied to composite materials only to a limited extent. Furthermore, it has been found that the pronounced heterogeneity of CFRP mostly leads to an inhomogeneous ablation result, both when creating grooves and during selective matrix removal, where the carbon fibers influence the ablation result by their thermal conductivity, depending on fiber direction. Finally, despite the material inhomogeneity, a scanning strategy has been developed to compensate the heterogeneous ablation results regarding structure depth, width and heat affected zone.     

The effects of membrane cholesterol and simvastatin on red blood cell deformability and ATP release

It is known that deformation of red blood cells (RBCs) is linked to ATP release from the cells. Further, membrane cholesterol has been shown to alter properties of the cell membrane such as fluidity and bending stiffness. Membrane cholesterol content is increased in some cardiovascular diseases, for example, in individuals with acute coronary syndromes and chronic stable angina, and therefore, because of the potential clinical relevance, we investigated the influence of altered RBC membrane cholesterol levels on ATP release. Because of the correlation between statins and reduced membrane cholesterol in vivo, we also investigated the effects of simvastatin on RBC deformation and ATP release. We found that reducing membrane cholesterol increases cell deformability and ATP release. We also found that simvastatin increases deformability by acting directly on the membrane in the absence of the liver, and that ATP release was increased for cells with enriched cholesterol after treatment with simvastatin.     

Importance of Ca(2+) modifications for osseointegration of smooth and moderately rough anodized titanium implants - a removal torque and histological evaluation in rabbit

Background: Incorporation of Ca²⁺ into the titania of anodized titanium surfaces has been found to enhance osseointegration. It provides a stable surface when the ions are incorporated into the oxide layer during the anodizing process. The Ca²⁺ may suggestively be prominent sites for mineral induction, attract proteins, and catalyze intracellular cascades. Purpose: The aim of the present study was to evaluate the osseointegration of smooth (S_a < 0.5 µm) and moderately rough (S_a 1.0–2.0 µm) commercially pure titanium implants, with and without Ca²⁺, in order to reflect on the importance of surface chemistry in relation to topography. Materials and Methods: Anodized implants with (OxCa) or without Ca²⁺ (Ox), blasted implants (Bl), and blasted anodized implants, with (BlOxCa) or without Ca²⁺ (BlOx), were inserted in rabbit femur and tibia. The implant surfaces were characterized using interferometry, scanning electron microscopy, and X‐ray photoelectron spectroscopy prior to implant installation. Removal torque (RTQ) measurements were executed on all implants after a healing period of 12 weeks. The implants were, thereafter, removed en bloc with surrounding tissues and prepared for histological evaluations. Results: RTQ measurements of tibial implants revealed significantly higher values for BlOxCa implants (90.7 ± 23.3 Ncm) compared to OxCa (64.6 ± 18.2 Ncm) and BlOx implants (69.7 ± 17.5 Ncm) (p = 0.029). Ca²⁺ modification of smooth implants placed in the femur did not reveal any differences. Conclusion: Ca²⁺ modification of smooth implants resulted in similar interfacial shear strength as moderately rough implants and Ca²⁺ modification of moderately rough implants demonstrated the significantly strongest interfacial shear strength when placed in rabbit tibia. This possibly demonstrated surface chemistry compensating for lesser roughness.     

Prediagnostic circulating carotenoid levels and the risk of non-Hodgkin lymphoma: the Multiethnic Cohort

This analysis examined the association of non-Hodgkin lymphoma (NHL) with prediagnostic carotenoid levels, a marker for a diet rich in fruits and vegetables. We conducted a nested case-control study within the Multiethnic Cohort with 271 NHL cases and 538 controls matched on sex, ethnicity, location (Hawaii or Los Angeles), birth year, date and time of blood draw, and hours fasting before blood draw. Serum carotenoid levels were obtained by high-pressure liquid chromatography with photodiode array detection. Conditional logistic regression was used to calculate odds ratios (ORs) according to tertiles of serum carotenoids and trend tests using continuous variables. Higher total serum carotenoids (OR(T3 vs T1) = 0.66 [0.46-0.96]; P(trend) = .02), lycopene (OR = 0.54 [0.38-0.78]; P(trend) = .003), and α-cryptoxanthin (OR = 0.53 [0.36-0.78]; P(trend) = .003) were associated with a lower risk of NHL. For retinol (OR = 0.90 [0.61-1.33]; P(trend) = .04), a statistically significant inverse linear trend was detected. Risk estimates remained unchanged with adjustment for NHL risk factors and were similar in analyses stratified by sex and ethnicity; heterogeneity with NHL subtype was detected only for β-carotene. Other carotenoids, including α-carotene, β-carotene, lutein, β-cryptoxanthin, and zeaxanthin, showed no association with risk. These data provide support for a protective role of carotenoid-rich fruits and vegetables in the etiology of NHL.     

On the symmetry of siblings: automated single-cell tracking to quantify the behavior of hematopoietic stem cells in a biomimetic setup

The interplay between hematopoietic stem and progenitor cells (HSPC) and their local microenvironment is a key mechanism for the organization of hematopoiesis. To quantitatively study this process, a time-resolved analysis of cellular dynamics at the single-cell level is an essential prerequisite. One way to generate sufficient amounts of appropriate data is automatic single-cell tracking using time-lapse video microscopy. We describe and apply newly developed computational algorithms that allow for an automated generation of high-content data of single-cell characteristics at high temporal and spatial resolution, together with the reconstruction and statistical evaluation of complete genealogical histories. This methodology has been applied to the particular example of purified primary human HSPCs in bioengineered culture conditions. The combination of genealogical information and dynamic profiles of cellular properties identified a marked symmetry between sibling HSPCs regarding cell cycle time, but also migration speed and growth kinetics. Furthermore, we demonstrate that this symmetry of HSPC siblings can be altered by exogenous cues of the local biomimetic microenvironment. Using the example of HSPC growth in biomimetic culture systems, we show that our approach provides a valuable tool for the quantitative analysis of dynamic single-cell features under defined in?vitro conditions, allowing for integration of functional and genealogical data. The efficiency and accuracy of our approach pave the way for new and intriguing insights into the organizational principles of developmental patterns and the respective influence of exogenous cues not limited to the study of primary HSPCs.