NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases

Nerve growth factor (NGF) is known to intensify pain in various ways, so perturbing pertinent effects without negating its essential influences on neuronal functions could help the search for much-needed analgesics. Towards this goal, cultured neurons from neonatal rat trigeminal ganglia—a locus for craniofacial sensory nerves—were used to examine how NGF affects the Ca²⁺-dependent release of a pain mediator, calcitonin gene-related peptide (CGRP), that is triggered by activating a key signal transducer, transient receptor potential vanilloid 1 (TRPV1) with capsaicin (CAP). Measurements utilised neurons fed with or deprived of NGF for 2 days. Acute re-introduction of NGF induced Ca²⁺-dependent CGRP exocytosis that was inhibited by botulinum neurotoxin type A (BoNT/A) or a chimera of/E and/A (/EA), which truncated SNAP-25 (synaptosomal-associated protein with Mr = 25 k) at distinct sites. NGF additionally caused a Ca²⁺-independent enhancement of the neuropeptide release evoked by low concentrations (<100 nM) of CAP, but only marginally increased the peak response to ≥100 nM. Notably, BoNT/A inhibited CGRP exocytosis evoked by low but not high CAP concentrations, whereas/EA effectively reduced responses up to 1 µM CAP and inhibited to a greater extent its enhancement by NGF. In addition to establishing that sensitisation of sensory neurons to CAP by NGF is dependent on SNARE-mediated membrane fusion, insights were gleaned into the differential ability of two regions in the C-terminus of SNAP-25 (181–197 and 198–206) to support CAP-evoked Ca²⁺-dependent exocytosis at different intensities of stimulation.     

Interaction of Cucurbit[7]uril with Oxime K027, Atropine,and Paraoxon: Risky or Advantageous Delivery System?

Antidotes against organophosphates often possess physicochemical properties that mitigate their passage across the blood–brain barrier. Cucurbit[7]urils may be successfully used as a drug delivery system for bisquaternary oximes and improve central nervous system targeting. The main aim of these studies was to elucidate the relationship between cucurbit[7]uril, oxime K027, atropine, and paraoxon to define potential risks or advantages of this delivery system in a complex in vivo system. For this reason, in silico (molecular docking combined with umbrella sampling simulation) and in vivo (UHPLC—pharmacokinetics, toxicokinetics; acetylcholinesterase reactivation and functional observatory battery) methods were used. Based on our results, cucurbit[7]urils affect multiple factors in organophosphates poisoning and its therapy by (i) scavenging paraoxon and preventing free fraction of this toxin from entering the brain, (ii) enhancing the availability of atropine in the central nervous system and by (iii) increasing oxime passage into the brain. In conclusion, using cucurbit[7]urils with oximes might positively impact the overall treatment effectiveness and the benefits can outweigh the potential risks.     

THE INFLUENCE OF PRESSURE AND TEMPERATURE ON THE KINETICS OF VACUUM DRYING OF KETOPROFEN

ABSTRACT

This paper explores the influence of temperature and pressure on drying kinetics of 2-(3-benzoylphenil propionic acid) ketoprofen, in a vacuum dryer on laboratory scale, Experimentally determined relations between moisture content and drying rate vs time, were approximated with an exponential model. Model parameters were correlated with drying conditions (temperature, pressure) and defined by functions of their potentions.

From an energy balance of the process, a mathematical model for simulating dependence of sample temperature vs drying time, and moisture content of material, has been developed.

Simulation of the drying kinetics and sample temperature, by use of those functional dependencies shows good agreement with experimental results.     

Oxides of copper, ceria promoted copper, manganese and copper manganese on Al2O3 for the combustion of CO, ethyl acetate and ethanol

Combustion of CO, ethyl acetate and ethanol was studied over CuO_x/Al₂O₃, CuO_x–CeO₂/Al₂O₃, CuMn₂O₄/Al₂O₃ and Mn₂O₃/Al₂O₃ catalysts. It was found that modification of the alumina with ceria before subsequent copper oxide deposition increases the activity for combustion of CO substantially, but the effect of ceria was small on the combustion of ethyl acetate and ethanol. The activity increases with the CuO_x loading until crystalline CuO particles are formed, which contribute little to the total active surface. The CuO_x–CeO₂/Al₂O₃ catalyst is more active than the CuMn₂O₄/Al₂O₃ catalyst for the oxidation of CO but the CuMn₂O₄/Al₂O₃ catalyst is more active for the combustion of ethyl acetate and ethanol.

Thermal ageing and water vapour in the feed caused a modest decrease in activity and did not affect the CuO_x–CeO₂/Al₂O₃ and CuMn₂O₄/Al₂O₃ catalysts differently. In addition, no difference in intermediates formed over the two catalysts was observed.

Characterisation with XRD, FT-Raman and TPR indicates that the copper oxide is present as a copper aluminate surface phase on alumina at low loading. At high loading, bulk CuO crystallites are present as well. Modification of the alumina with ceria before the copper oxide deposition gives well dispersed copper oxide species and bulk CuO crystallites associated to the ceria, in addition to the two copper oxide species on the bare alumina. The distribution of copper species depends on the ceria and copper oxide loading. The alumina supported copper manganese oxide and manganese oxide catalysts consist mainly of crystalline CuMn₂O₄ and Mn₂O₃, respectively, on Al₂O₃.     

High-temperature tribological properties of CrAlN, CrAlSiN and AlCrSiN coatings

Cr-Al-Si-N coatings with high and low Cr/Al ratios (CrAlSiN and AlCrSiN, respectively) were deposited on WC substrates by cathodic arc and compared with a reference Cr-Al-N coating. The silicon content was close to 3 at.%. X-ray diffraction analysis showed that CrAlN and CrAlSiN coatings exhibited the cubic Cr(Al)N structure, whereas in AlCrSiN a mixture of cubic Cr(Al)N and wurtzite-type AlN was identified. All three coatings showed excellent thermal stability and oxidation resistance up to 800 °C. The tribological properties were evaluated by ball-on-disk tribometer in the temperature range 25-600 °C. Two materials were used as counterparts: alumina and 440C steel. Sliding against 440C steel balls led to the extensive wear of the balls and transfer of the ball material to the surface of the coatings. The coatings were not damaged. When sliding against alumina balls, the coating wear was low up to testing temperature 300 °C. At 400 °C, CrAlSiN coating was partially worn through. CrAlN and AlCrSiN coatings were almost immediately worn out at 600 °C. The analysis of the wear debris identified high-temperature adhesive failure of the coatings.     

Wear of Chromium Carbide-Copper Composites with Continuous Phases

A tribological study has been carried out on a new type of carbide-metal composite, in which the two phases form a continuous skeleton microstructure interwoven throughout the body. The composites' resistance to two-body abrasion is evaluated in a pin-on-drum set-up with diamond and SiC abrasive papers. Also sliding wear and friction tests with steel and alumina as counter materials were undertaken. The composites show promising tribological properties, comparable to those of established wear resistant materials. Scanning electron microscopy was used to study the worn surfaces. The implications of the skeleton microstructure on the abrasive wear resistance are discussed on the basis of a wear model for multiphase materials.     

The experience of homeless women: An exploration of housing histories and the meaning of home

The exploratory study with homeless women presented in this paper aims to highlight two shortcomings in the current literature on homelessness, which accompany the predominant conceptualisation of ‘home’ as a place of safety and security, and homelessness as a primarily structural issue characterised by ‘residential instability’. The first is the paucity of research on homeless women in their own right and the second the lack of studies which examine underlying reasons for residential instability from homeless women's own perspectives. An intensive, small sample interview study was carried out with 12 regular women users of a day centre for homeless people (Brighton, south of England). They were asked about their patterns of residence, reasons for moving, definitions of ‘house’, ‘home’, and ‘ideal home’, and they gave their housing histories in some detail. In a quantitative analysis, their patterns of moving and definitions of ‘home’ were compared to those of a group of securely housed women. Number of moves was comparable in both groups, but for the homeless women the majority of moves had been made to avoid abuse and social services relocations. Whilst all of the securely housed women could confidently define a difference in meaning between a ‘house’ and a ‘home’, only 3 of the 12 homeless women did. They equated ‘home’ with safety and security, the same terms used in the literature to define what housing means, and the two most salient features largely absent in homeless women's experience of housing. The meaning of home is further explored in a qualitative analysis, where the themes of safety and security—or rather their absence in abusive relationships—are traced through the homeless women's childhood, adolescence and adulthood. These exploratory findings question an easy equation between ‘residential instability’ and homelessness, and highlight the need to investigate further the reasons why women leave housing, and the relationship this has to an understanding of what ‘home’ means. Whilst current formulations suggest that the homelessness of women is a problem, and housing the solution, this study suggests that housing is the problem—homelessness may well be a solution.     

Single fundamental-mode output power exceeding 6 mW from VCSELs with a shallow surface relief

A single fundamental-mode output power of 6.5 mW was achieved from an 850-nm vertical-cavity surface-emitting laser (VCSEL) with a shallow surface relief, the highest single-mode power ever reported using this technique. The VCSELs were fabricated from epitaxial material grown to yield an antiphase reflection from the topmost layer. A circular surface relief, acting as a mode discriminator, was etched in the center to reduce the mirror loss for the fundamental mode. This "inverted" surface-relief technique offers relaxed etch depth control and, therefore, improves reproducibility and yield.     

Darstellung,Konfigurationen und NMR-Daten der Säuren CH3(SR)  CHCOOH (R  C6H5, CH2C6H5, CH2COOH)

Preparation, Configurations and N.M.R. Dates of the Acids CH₃(SR)CHCOOH (R  C₆H₅, CH₂C₆H₅, CH₂COOH) The cis and trans isomers of the acids CH₃(SR)CHCOOH (R  C₆H₅, CH₂C₆H₅, CH₂COOH) were prepared by addition of HSR to CH₃CCCOOH in alkaline water solution and by alkaline hydrolysis of CH₃C(SR)₂CH₂COOC₂H₅ (R  C₆H₅, CH₂C₆H₅, CH₂COOC₂H₅). The oxidation products CH₃C(SO₂R)  CHCOOH (R  C₆H₅, CH₂COOH) were also prepared. The n.m.r. dates of the acids were obtained and some relations between them were discussed.     

High-power operation of highly reliable narrow stripe pseudomorphicsingle quantum well lasers emitting at 980 nm

Ridge waveguide pseudomorphic InGaAs/GaAs/AlGaAs single-quantum-well lasers exhibiting record high quantum efficiencies and high output power densities (105 mW per facet from a 6 μm wide stripe) at a lasing wavelength of 980 nm are discussed that were fabricated from a graded index separate confinement heterostructure grown by molecular beam epitaxy. Life testing at an output power of 30 mW per uncoated facet reveals a slow gradual degradation during the initial 500 h of operation after which the operating characteristics of the lasers become stable. The emission wavelength, the high output power, and the fundamental lateral mode operation render these lasers suitable for pumping Er³⁺-doped fiber amplifiers