Preclinical evaluation of a novel water-soluble chlorin E6 derivative (BLC 1010) as photosensitizer for the closure of the neovessels

In the present study, photodynamic activity of a novel photosensitizer (PS), Chlorin e(6)-2.5 N-methyl-d-glucamine (BLC 1010), was evaluated using the chorioallantoic membrane (CAM) as an in vivo model. After intravenous (i.v.) injection of BLC 1010 into the CAM vasculature, the applicability of this drug for photodynamic therapy (PDT) was assessed in terms of fluorescence pharmacokinetics, i.e. leakage from the CAM vessels, and photothrombic activity. The influence of different PDT parameters including drug and light doses on the photodynamic activity of BLC 1010 has been investigated. It was found that, irrespective of drug dose, an identical continuous decrease in fluorescence contrast between the drug inside and outside the blood vessels was observed. The optimal treatment conditions leading to desired vascular damage were obtained by varying drug and light doses. Indeed, observable damage was achieved when irradiation was performed at light doses up to 5 J/cm(2) 1 min after i.v. injection of drug doses up to 0.5 mg/kg body weight(b.w.). However, when irradiation with light doses of more than 10 J/cm(2) was performed 1 min after injection of drug doses up to 2 mg/kg body weight, this led to occlusion of large blood vessels. It has been demonstrated that it is possible to obtain the desired vascular occlusion and stasis with BLC 1010 for different combinations of drug and/or light doses.     

Unraveling virus identity by detection of depleted probes with capillary electrophoresis

With the emergence of new viral infections and pandemics, there is a need to develop faster methods to unravel the virus identities in a large number of clinical samples. This report describes a virus identification method featuring high throughput, high resolution, and high sensitivity detection of viruses. Identification of virus is based on liquid hybridization of different lengths of virus-specific probes to their corresponding viruses. The probes bound to target sequences are removed by a biotin–streptavidin pull-down mechanism and the supernatant is analyzed by capillary electrophoresis. The probes depleted from the sample appear as diminished peaks in the electropherograms and the remaining probes serve as calibrators to align peaks in different capillaries. The virus identities are unraveled by a signal processing and peak detection algorithm developed in-house. Nine viruses were used in the study to demonstrate how the system works to unravel the virus identity in single and double virus infections. With properly designed probes, the system is able to distinguish closely related viruses. The system takes advantage of the high resolution feature of capillary electrophoresis to resolve probes that differ by length. The method may facilitate virus identity screen from more candidate viruses with an automated 4-color DNA sequencer.     

Surface modifications of illite in concentrated lime solutions investigated by pyridine adsorption

The surface properties and functionality of an illite-containing clay mineral in alkaline solutions containing increasing quantities of calcium hydroxide were investigated using FTIR monitored pyridine adsorption at various temperatures. Results showed that the binding behavior of electron donor pyridine molecules to illite platelets is mostly governed by electron acceptor sites located at the edges of the clay particles. The binding of bulky hydrated calcium ions at the surface of the illite platelets decreases the surface area of illite. Moderate thermal treatments up to 450 °C do not affect the structure of the clay mineral but strongly decrease the number of Lewis and Brönsted sites available at the edges of the clay platelets.     

Onset of itinerant ferromagnetism associated with semiconductor-metal transition in Ti<Subscript><Emphasis Type="Italic">x</Emphasis></Subscript>Nb<Subscript>1 − <Emphasis Type="Italic">x</Emphasis></Subscript>CoSn half Heusler solid solution compounds

In this paper, the magnetic and transport properties of the Ti _x Nb_{1 − x} CoSn solid solution compounds with half Heusler cubic MgAgAs-type structure have been studied. This work shows the onset of ferromagnetism associated with a semiconductor to metal transition. The transition occurs directly from ferromagnetic metal to semiconducting state as it is the case in the TiCo _x Ni_{1 − x} Sn series studied previously. A weak quantity of Ti in NbCoSn is suffcient to allow the appearance of ferromagnetic order and metallic state. The variations of the Curie temperature as a function of saturation and effective paramagnetic moments are related to the itinerant ferromagnetism model. A comparison is made with the TiCoSn _x Sb_{1 − x} series (also studied previously), where the transition from TiCoSn ferromagnetic metal to non-magnetic semiconductor TiCoSb occurs through an intermediate metallic Pauli-like state.      

State of the art in the delivery of photosensitizers for photodynamic therapy

In photodynamic therapy, one of the problems limiting the use of many photosensitizers (PS) is the difficulty in preparing pharmaceutical formulations that enable their parenteral administration. Due to their low water solubility, the hydrophobic PS cannot be simply injected intravenously. Different strategies, including polymer-PS conjugation or encapsulation of the drug in colloidal carriers such as oil-dispersions, liposomes and polymeric particles, have been investigated. Although these colloidal carriers tend to accumulate selectively in tumour tissues, they are rapidly taken up by the mononuclear phagocytic system. In order to reduce this undesirable uptake by phagocytic cells, long-circulating carriers that consist of surface modified carriers have been developed. Moreover, considerable effort has been directed towards using other types of carriers to improve tumour targeting and to minimize the side effects. One of the approaches is to entrap PS into the lipophilic core of low-density lipoproteins (LDL) without altering their biological properties. The LDL receptor pathway is an important factor in the selective accumulation of PS in tumour tissue owing to the increased number of LDL receptors on the proliferating cell surface. Specific targeting can also be achieved by binding of monoclonal antibodies or specific tumour-seeking molecules to PS or by the coating of PS loaded carriers.     

Photoluminescent nematic liquid crystalline elastomer actuators

Nematic liquid crystalline elastomer (LCE) actuators possessing both photoluminescent (PL) and stimuli-responsive functions were fabricated and studied. PL-dyes (1-pyrenemethyl acrylate and 4-bromo-2,6-bis-(1?-methyl-benzimidazolyl) pyridine loaded with Eu(III) ion) were synthesised and characterised, and then the dyes were mixed with an acrylate side-on liquid crystalline monomer, a cross-linker and a photo-initiator. Through magnetic field alignment, well-defined LCE micropillar PL actuators were fabricated from the mixed samples by a method combining soft lithography and photo-polymerisation/photo-cross-linking. Microscopic observations indicated that the LCE micropillars showed reversible thermomechanical deformation at the nematic-to-isotropic transition temperature. During the reversible contraction and extension process, the LCE actuator containing 1-pyrenemethyl moieties showed stable photoluminescence, while for the LCE actuator doped with 4-bromo-2,6-bis-(1-methyl-benzimidazolyl)pyridine/Eu(III) complex, the PL emission was quenched at about 100°C, which was before the pillars contraction occurring at a higher temperature. When cooled down to room temperature, the contracted LCE micropillars recovered their original shape and the initial PL emission state. The micron-sized LCE actuators can be used for thermomechanical devices and machines with different PL functions at the same time.     

Comparison of interactions between beta-hairpin decapeptides and SDS/DPC micelles from experimental and simulation data

Background  

We applied a combined experimental and computational approach to ascertain how peptides interact with host and microbial membrane surrogates, in order to validate simulation methodology we hope will enable the development of insights applicable to the design of novel antimicrobial peptides. We studied the interactions of two truncated versions of the potent, but cytotoxic, antimicrobial octadecapeptide protegrin-1, PC-72 [LCYCRRRFCVC] and PC-73 [CYCRRRFCVC].     

RNA synthetic activity of glutamate dehydrogenase

The activity of glutamate dehydrogenase (GDH), an important enzyme in carbon and nitrogen metabolism, is routinely assayed by photometry. The RNA synthetic activity of the enzyme provides new technologies for assaying its activity. The enzyme was made to synthesize RNAs in the absence of DNA and total RNA but with different mixes of the four nucleoside triphosphates (NTPs) in order to investigate the RNA characteristics. RNase VI (hydrolyzes base-paired residues) digested the poly (U,A) RNA completely because the U and A residues were evenly distributed to produce many base-paired regions. Therefore, the synthesis of RNA by GDH was by random addition of NTPs. The RNA synthetic activity of the enzyme was at least 50-fold more active in the deamination than in the amination direction, thus providing a robust technology for assay of the enzyme's activity. cDNAs prepared from the RNAs were subjected to restriction fragment differential display polymerase chain reaction analyses. Sequencing of the cDNA fragments showed that some of the RNA synthesized by GDH shared sequence homology with total RNA. Database searches showed that the RNA fragments shared sequence homologies with the G proteins, adenosine triphosphatase, calmodulin, phosphoenol pyruvate (PEP) carboxylase, and PEP carboxykinase, thus explaining the molecular mode of their functions in signal transduction.