5-Fluorouracil Treatment of CT26 Colon Cancer Is Compromised by Combined Therapy with IMMODIN

Due to the physiological complexity of the tumour, a single drug therapeutic strategy may not be sufficient for effective treatment. Emerging evidence suggests that combination strategies may be important to achieve more efficient tumour responses. Different immunomodulators are frequently tested to reverse the situation for the purpose of improving immune response and minimizing chemotherapy side effects. Immodin (IM) represents an attractive alternative to complement chemotherapy, which can be used to enhance the immune system after disturbances resulting from the side effects of chemotherapy. In the presented study, a model of CT26 tumor-bearing mice was used to investigate the effect of single IM or its combination with 5-fluorouracil (5-FU) on colon cancer cells. Our results highlight that the beneficial role of IM claimed in previous studies cannot be generalised to all chemotherapeutic drugs, as 5-FU toxicity was not increased. On the contrary, the chemotherapeutic anti-cancer efficacy of 5-FU was greatly compromised when combined with IM. Indeed, the combined treatment was significantly less effective regarding the tumour growth and animal survival, most probably due to the increased number of tumour-associated macrophages, and increased 5-FU cytotoxic effect related to kidneys and the liver.     

Determination of Intra- and Extracellular Metabolic Adaptations of 3D Cell Cultures upon Challenges in Real-Time by NMR

NMR flow devices provide longitudinal real-time quantitative metabolome characterisation of living cells. However, discrimination of intra- and extracellular contributions to the spectra represents a major challenge in metabolomic NMR studies. The present NMR study demonstrates the possibility to quantitatively measure both metabolic intracellular fingerprints and extracellular footprints on human control fibroblasts by using a commercially available flow tube system with a standard 5 mm NMR probe. We performed a comprehensive 3D cell culture system characterisation. Diffusion NMR was employed for intra- and extracellular metabolites separation. In addition, complementary extracellular footprints were determined. The implemented perfused NMR bioreactor system allowed the determination of 35 metabolites and intra- and extracellular separation of 19 metabolites based on diffusion rate differences. We show the reliability and sensitivity of NMR diffusion measurements to detect metabolite concentration changes in both intra- and extracellular compartments during perfusion with different selective culture media, and upon complex I inhibition with rotenone. We also demonstrate the sensitivity of extracellular footprints to determine metabolic variations at different flow rates. The current method is of potential use for the metabolomic characterisation of defect fibroblasts and for improving physiological comprehension.     

Light Triggers the Antiproliferative Activity of Naphthalimide-Conjugated (η6-arene)ruthenium(II) Complexes

We report the synthesis and characterization of three half-sandwich Ru(II) arene complexes [(η⁶-arene)Ru(N,N′)L][PF₆]₂ containing arene = p-cymene, N,N′ = bipyridine, and L = pyridine meta- with methylenenaphthalimide (C1), methylene(nitro)naphthalimide (C2), or methylene(piperidinyl)naphthalimide (C3). The naphthalimide acts as an antenna for photoactivation. After 3 h of irradiation with blue light, the monodentate pyridyl ligand had almost completely dissociated from complex C3, which contains an electron donor on the naphthalimide ring, whereas only 50% dissociation was observed for C1 and C2. This correlates with the lower wavelength and strong absorption of C3 in this region of the spectrum (λ_max = 418 nm) compared with C1 and C2 (λ_max = 324 and 323 nm, respectively). All the complexes were relatively non-toxic towards A549 human lung cancer cells in the dark, but only complex C3 exhibited good photocytoxicity towards these cancer cells upon irradiation with blue light (IC₅₀ = 10.55 ± 0.30 μM). Complex C3 has the potential for use in photoactivated chemotherapy (PACT).     

Shot-noise limited,supercontinuum-based optical coherence tomography

We present the first demonstration of shot-noise limited supercontinuum-based spectral domain optical coherence tomography (SD-OCT) with an axial resolution of ...     

Nutritional Calcium Supply Dependent Calcium Balance,Bone Calcification and Calcium Isotope Ratios in Rats

Serum calcium isotopes (δ^44/42Ca) have been suggested as a non-invasive and sensitive Ca balance marker. Quantitative δ^44/42Ca changes associated with Ca flux across body compartment barriers relative to the dietary Ca and the correlation of δ^44/42Ca_Serum with bone histology are unknown. We analyzed Ca and δ^44/42Ca by mass-spectrometry in rats after two weeks of standard-Ca-diet (0.5%) and after four subsequent weeks of standard- and of low-Ca-diet (0.25%). In animals on a low-Ca-diet net Ca gain was 61 ± 3% and femur Ca content 68 ± 41% of standard-Ca-diet, bone mineralized area per section area was 68 ± 15% compared to standard-Ca-diet. δ^44/42Ca was similar in the diets, and decreased in feces and urine and increased in serum in animals on low-Ca-diet. δ^44/42Ca_Bone was higher in animals on low-Ca-diet, lower in the diaphysis than the metaphysis and epiphysis, and unaffected by gender. Independent of diet, δ^44/42Ca_Bone was similar in the femora and ribs. At the time of sacrifice, δ^44/42Ca_Serum inversely correlated with intestinal Ca uptake and histological bone mineralization markers, but not with Ca content and bone mineral density by µCT. In conclusion, δ^44/42Ca_Bone was bone site specific, but mechanical stress and gender independent. Low-Ca-diet induced marked changes in feces, serum and urine δ^44/42Ca in growing rats. δ^44/42Ca_Serum inversely correlated with markers of bone mineralization.     

Zur Rolle von EDA-Komplexen bei kationischen Polymerisationen. VI[1]. Wechselwirkung von Halogenidionen mit organischen aπ-Elektronenacceptoren

The Role of Donor-Acceptor Complexes in Cationic Polymerisations. The Interaction of Halide Ions with Organic aπ-Acceptors The anions of salts of the type Kat⁺X⁻ (Kat⁺  Li⁺, Na⁺, Et₄N⁺; X⁻  Cl⁻, Br⁻, I⁻) form donor-acceptor complexes with organic a π-acceptors. The long-wave charge-transfer absorption show a bathochrome shift with higher periodic numbers of X⁻ and increasing electron affinity of the acceptors Acc. Strong acceptors form radical ions very rapidly with X  I and slowly with X  Br. Cl. The interactions in the system Kat⁺X⁻ → Acc are influenced by solvents in a very complex way. As acceptors they interact preferably with the halide ion X⁻ and, hence, reduce its donicity for the competing acceptor Acc. As donors they change the dissociation of the ion pair Kat⁺X⁻ by solvation of the cation Kat⁺ and influence in that indirect way also the donicity of X⁻ for the acceptor Acc.     

Immunsuppressiva-Antigen-Konjugate. VIII. Darstellung von 6-Mercaptopurin-Protein-Konjugaten nach dem Azid-Verfahren

Immunosuppressant-Antigen Conjugates. VIII. Preparation of 6-Thiopurine-Protein Conjugates by the Azide Method 6-Carboxymethyl-thiopurine was coupled with human serum albumin (HSA) and bovine serum globuline in the presence of a water soluble carbodiimide. Under these conditions, reaction of HSA with the carbodiimide led to electrophoretically detectable changes. Therefore, further conjugates were prepared by the azide method. The used azides, N-(6-benzylthiopurin- and 6-methylthiopurin-9-yl)-acetyl azide, were obtained from the hydrazides. The prepared conjugates contained upto 4.2% thiopurine, determined by spectrophotometry. It was not possible to obtain an azide from purinyl-(6)-thioacethydrazide.     

Absolute characterization of high numerical aperture microscope objectives utilizing a dipole scatterer

Measuring the aberrations of optical systems is an essential step in the fabrication of high precision optical components. Such a characterization is usually ba...