A Potential Role for Fructosamine-3-Kinase in Cataract Treatment

Cataracts are the major cause of blindness worldwide, largely resulting from aging and diabetes mellitus. Advanced glycation end products (AGEs) have been identified as major contributors in cataract formation because they alter lens protein structure and stability and induce covalent cross-linking, aggregation, and insolubilization of lens crystallins. We investigated the potential of the deglycating enzyme fructosamine-3-kinase (FN3K) in the disruption of AGEs in cataractous lenses. Macroscopic changes of equine lenses were evaluated after ex vivo intravitreal FN3K injection. The mechanical properties of an equine lens pair were evaluated after treatment with saline and FN3K. AGE-type autofluorescence (AF) was measured to assess the time-dependent effects of FN3K on glycolaldehyde-induced AGE-modified porcine lens fragments and to evaluate its actions on intact lenses after in vivo intravitreal FN3K injection of murine eyes. A potential immune response after injection was evaluated by analysis of IL-2, TNFα, and IFNγ using an ELISA kit. Dose- and time-dependent AF kinetics were analyzed on pooled human lens fragments. Furthermore, AF measurements and a time-lapse of macroscopic changes were performed on intact cataractous human eye lenses after incubation with an FN3K solution. At last, AF measurements were performed on cataractous human eyes after crossover topical treatment with either saline- or FN3K-containing drops. While the lenses of the equine FN3K-treated eyes appeared to be clear, the saline-treated lenses had a yellowish-brown color. Following FN3K treatment, color restoration could be observed within 30 min. The extension rate of the equine FN3K-treated lens was more than twice the extension rate of the saline-treated lens. FN3K treatment induced significant time-dependent decreases in AGE-related AF values in the AGE-modified porcine lens fragments. Furthermore, in vivo intravitreal FN3K injection of murine eyes significantly reduced AF values of the lenses. Treatment did not provoke a systemic immune response in mice. AF kinetics of FN3K-treated cataractous human lens suspensions revealed dose- and time-dependent decreases. Incubation of cataractous human eye lenses with FN3K resulted in a macroscopic lighter color of the cortex and a decrease in AF values. At last, crossover topical treatment of intact human eyes revealed a decrease in AF values during FN3K treatment, while showing no notable changes with saline. Our study suggests, for the first time, a potential additional role of FN3K as an alternative treatment for AGE-related cataracts.     

Optimised NSAIDs-loaded Biocompatible Nanoparticles

Nano-Micro Letters - In this formulation study, biocompatible non steroidal anti-inflammatory (NSAIDs)-loaded nanoparticles were designed as models to be further integrated in a prosthesis surface...     

Failure mechanisms and residual capacity of annealed glass/SGP laminated beams at room temperature

In construction industry, laminated glass is more and more used for transparent load-bearing building components. It is known that the residual load-carrying capacity after glass breakage of glass/PVB (polyvinyl butyral) laminates is relatively poor, mainly due to the limited stiffness and strength of PVB. For that reason, the failure behaviour of laminates composed with a stiffer and stronger interlayer material, called SentryGlas^® Plus (SGP), was investigated experimentally. Consequently, 1100 mm long test samples composed of two annealed float glass layers and one SGP interlayer were subjected to destructive in-plane four-points bending tests at room temperature. Subsequently, different stages were distinguished during the failure process, corresponding to a different number of broken glass layers. In spite of the relatively good interlayer material properties and in contradiction to what was expected, the observed post-failure safety was poor. However, the failure mechanisms observed were significantly different from those of glass/PVB beams: due to a lack of local delamination near the glass fracture zone, tear of the SGP interlayer occurred without preceding large visual interlayer elongations.     

Post-mortem evaluation following oncologic treatment of the functional and bacteriologic status of 25 permanent venous access devices

Permanent venous access devices allow long-term parenteral treatment under relatively safe and comfortable conditions. Nevertheless, this use is associated with some degree of (particularly infectious) morbidity. 25 permanent access devices were removed surgically in immediate autopsies and cultured. Some half were infected, with a clear prevalence (40%) for Staphylococcus coagulase negative. The results were related to clinical history and compared with the figures and conclusions of other studies. It is proposed that in certain situations cultures of native blood should be carried out more frequently through the permanent venous access, with a view to possible specific targeted antibiotic therapy associated with the heparinized lock.     

Spontaneous failure of a passable laminated glass floor element

It is well-known that thermally toughened safety glass is subjected to a certain risk of spontaneous failure due to nickel sulphide particles included in the material. However, the present contribution focuses on a very uncommon case in which two out of three glass layers of a thermally toughened laminated slab of a passable floor element failed spontaneously.After initial on-site observations, witness interviews and reconstruction of the exact circumstances of the failure, no direct external cause such as hard or soft body impact, and local heating could be found. Consequently, the laminated glass slab was further investigated in the laboratory. During the laboratory analysis, several techniques have been used, such as crack pattern analysis, optical microscopy, and FEG scanning electron microscopy.As a result of the failure analysis, a nickel sulphide particle could be clearly detected. Based on striking similarities, a.o. in the crack pattern, breakage of the underlying glass layer of the laminate could be attributed to nickel sulphide as well.A method to assess the probability of failure of a double NiS failure is proposed. In spite of the design philosophy followed by the designer, in which the probability of this failure mode was not considered to be significant, this failure and risk analysis demonstrated clearly its importance for building practice.     

Spontaneous cytotoxicity of cultured human cell lines mediated by normal peripheral blood lymphocytes. III. Kinetic parameters

The mechanism of spontaneous cell-mediated cytotoxicity (SCMC) of cultured cell lines has been investigated and compared with antibody-dependent cell-mediated cytotoxicity (ADCMC) by detailed kinetic analysis. The mechanism of SCMC resembles that of an enzyme, as does ADCMC where effector cells are analogous to an enzyme and the 51Cr-labeled target cells are analogous to the substrate. Temporal kinetic studies revealed an induction period of about 1 hr before significant 51Cr release for SCMC, but not for ADCMC. This induction period is not due to differences in effector-target affinity between SCMC and ADCMC. On the basis of kinetic analysis it was shown that SCMC approaches simple Michaelis-Menten enzyme kinetics, allowing determination of a Michaelis constant, Km, and maximal velocity, Vmax, for the interaction between a given effector and target cell. The Km values thus determined were found to be identical for the lysis of several target cell lines of varying SCMC susceptibility to effector cells from a given donor, whereas Vmax values for lysis of different target cells varied considerably. However, effector cells isolated from the peripheral blood of different donors exhibited different Km values for the target cells tested. Moreover, the Km value obtained for ADCMC effected by a given donor's lymphocytes was found equal to the Km value obtained for SCMC by that donor.     

The lactobin A and amylovorin L471 encoding genes are identical, and their distribution seems to be restricted to the species Lactobacillus amylovorus that is of interest for cereal fermentations

Lactobin A and amylovorin L471 are two bacteriocins produced by the phenotypically different strains Lactobacillus amylovorus LMG P-13139 and L. amylovorus DCE 471, respectively. A 110-bp PCR fragment of the structural gene of lactobin A was obtained from total genomic DNA of L. amylovorus LMG P-13139, which was used as a probe to isolate a 3.6-kb HindIII chromosomal fragment for sequencing. PCR amplification revealed that both the structural genes of both the bacteriocins lactobin A and amylovorin L471 were identical. These bacteriocins will be further referred to as amylovorin L. Amylovorin L can be defined as a small, strongly hydrophobic, antibacterial peptide consisting of 50 amino acids. It is synthesized as a precursor peptide of 65 amino acids processed at a characteristic double-glycine proteolytic cleavage site. Amylovorin L hence belongs to the class II bacteriocins. It has a narrow inhibitory spectrum, being most active towards Lactobacillus delbrueckii subsp. bulgaricus LMG 6901(T). Among 38 strains of the Lactobacillus acidophilus DNA homology group, another 6 L. amylovorus strains were also inhibitory towards the L. delbrueckii subsp. bulgaricus LMG 6901(T) strain. The lactobin A or amylovorin L471 structural genes could be detected in the genomes of three of these L. amylovorus strains, but only after extensive PCR amplification, indicating that the inhibitory substances were slightly different. The bacteriocins were characterized as small (approximately 4800 Da), heat-stable peptides that were active in a wide pH range (2.2-8.0). Finally, preliminary experiments indicated that the production of amylovorin L by L. amylovorus DCE 471 took place during a natural rye fermentation, indicating its potential importance in the development of a functional (probiotic) starter culture for cereal fermentations.     

Identification of Codon 146 KRAS Variants in Isolated Epidermal Nevus and Multiple Lesions in Oculoectodermal Syndrome: Confirmation of the Phenotypic Continuum of Mosaic RASopathies

Mosaic RASopathies are a molecularly heterogeneous group of (neuro)cutaneous syndromes with high phenotypical variability. Postzygotic variants in KRAS have been described in oculoectodermal syndrome (OES), encephalocraniocutaneous lipomatosis (ECCL) and epidermal nevus syndrome (ENS). This study confirms the continuum of mosaic neurocutaneous RASopathies showing codon 146 KRAS variants in an individual with OES and, for the first time, in an individual with (isolated) epidermal nevus. The presence of a nevus psiloliparus in individuals with OES indicates that this finding is not specific for ECCL and highlights the phenotypical overlap between ECCL and OES. The presence of the somatic KRAS variant in the nevus psiloliparus resolves the underlying molecular etiology of this fatty-tissue nevus. In addition, this finding refutes the theory of non-allelic twin-spotting as an underlying hypothesis to explain the concurrent presence of two different mosaicisms in one individual. The identification of codon 146 KRAS variants in isolated epidermal nevus introduces a new hot spot for this condition, which is useful for increasing molecular genetic testing using targeted gene sequencing panels.     

Glucocorticoid regulation of natural cytotoxicity: effects of cortisol on the phenotype and function of a cloned human natural killer cell line

PURPOSE: to demonstrate and document TIPSS-induced changes of the perfusion pattern of the liver with special reference to several rheologic, morphologic, functional and biochemical parameters. Our analysis was based on a study in 100 consecutive cases. PATIENTS AND METHODS: Evaluation and assessment of the following parameters before and within a 30-day post TIPSS period: portosystemic gradient; morphologic delineation of the portal circulation; invasive scintigraphic determination of the portal perfusion fraction (PPF) and the total liver perfusion (GLP); transcatheter intraarterial flow change measurement; serum levels of albumin and bilirubin; assessment of hepatic encephalopathy by appropriate testing; assessment of recurrent variceal bleeding RESULTS: by TIPSS variceal filling was widely reduced; as assessed morphologically and rheologically portal liver perfusion was significantly reduced. However, there was immediate onset of compensated liver perfusion by increased arterial inflow. Total liver perfusion was not significantly altered. In TIPSS portal decompression was readily achieved with reduction of the portosystemic gradient from an average of 24 mmHg to 10.5 mmHg. In our series we could not demonstrate an increased incidence of hepatic encephalopathy during the 30-day post TIPSS period. Bilirubin levels were significantly increased after TIPSS from 2.45 to 2.61 mg/dl (p = 0.0067), while albumin levels were not altered. Early mortality was 4% and early re-bleeding rate 3%, respectively. CONCLUSION: the concept of TIPSS represents an individually calibrated H-shunt. The significant reduction of post TIPSS portal perfusion appears to be compensated by increased arterial inflow. This is reflected by invasive flow measurement results and by the clinical results. Letality of TIPSS is low.     

Class AB CMOS amplifiers with high efficiency

A new class AB CMOS operational-amplifier principle is presented. A transconductance amplifier based on this principle exhibits small-signal characteristics comparable to those of a conventional OTA. It has, however, a superior current efficiency and its settling time is not slew-rate limited. The new class AB principle can also be used in an output stage with a well-defined quiescent current, a rail-to-rail output swing, and a good driving capability. A two-stage amplifier with both the input and output stages based on the new principle has been realized. It features a rail-to-rail input and output common-mode range, a gain-bandwidth of 370-kHz, a settling time of less than 5 μs independent of the applied step, and a power consumption of 247 μW. It drives a resistive load of 3 kΩ in parallel with a capacitive load of 400 pF when operated on a 2.5-V/-2.5-V power supply