Analgesic activity of Cissus quadrangularis linn with Zingiber officinale rosc in male wistar rats

Background: The global scenario, human beings are using various forms of treatment for relief of pain; among them, medicinal plant products have gained popularity because of its wide range of use and less side effects.Methods: Adult Albino rats of either sex were selected and divided into 5 groups. The Eddy’s hot plate was used and maintained temperature (55±0.5ºC), the animals were placed on the hot plate and the time taken for paw licking or jumping was recorded and considered as nociceptive response. The reaction time was observed on 0, 30, 60, and 90 minute.Results: The hot plate reaction time in sec was collected in the intervals of 0, 30, 60 and 90 minutes in all groups. Reaction times as follows: group III (Cissus quadrangularis Linn.) were 2.18±0.04, 3.13±0.05**, 5.83±0.05**, 5.39±0.04**;  Group IV (Zingiber officinale Rosc.) were 2.12±0.03, 4.13±0.04**, 7.43±0.07**, 7.16±0.06**; Group V Cissus quadrangularis Linn+ Zingiber officinale Rosc.) were 2.21±0.75, 4.67±0.98**, 8.15±0.89**, 9.02±0.75**; Group II (Dexamethasone) were 2.14±0.05, 5.53±0.05**, 8.14±0.06**, 10.08±0.10** respectively, Results are presented as mean±SEM, (n=6), *p<0.01, **p<0.05 dunnet test used as compared to control.Conclusions: Present study reveals that, the combination treatment of Zingiber officinale Rosc. + Cissus quadrangularis Linn. has been shown significant analgesic effect. High analgesic effect was observed with combination therapy; the effect was shown same as standard drug dexamethasone

The RCK2 domain of the human BKCa channel is a calcium sensor

Large conductance voltage and Ca2+-dependent K+ channels (BKCa) are activated by both membrane depolarization and intracellular Ca2+. Recent studies on bacterial channels have proposed that a Ca2+-induced conformational change within specialized regulators of K+ conductance (RCK) domains is responsible for channel gating. Each pore-forming α subunit of the homotetrameric BKCa channel is expected to contain two intracellular RCK domains. The first RCK domain in BKCa channels (RCK1) has been shown to contain residues critical for Ca2+ sensitivity, possibly participating in the formation of a Ca2+-binding site. The location and structure of the second RCK domain in the BKCa channel (RCK2) is still being examined, and the presence of a high-affinity Ca2+-binding site within this region is not yet established. Here, we present a structure-based alignment of the C terminus of BKCa and prokaryotic RCK domains that reveal the location of a second RCK domain in human BKCa channels (hSloRCK2). hSloRCK2 includes a high-affinity Ca2+-binding site (Ca bowl) and contains similar secondary structural elements as the bacterial RCK domains. Using CD spectroscopy, we provide evidence that hSloRCK2 undergoes a Ca2+-induced change in conformation, associated with an α-to-β structural transition. We also show that the Ca bowl is an essential element for the Ca2+-induced rearrangement of hSloRCK2. We speculate that the molecular rearrangements of RCK2 likely underlie the Ca2+-dependent gating mechanism of BKCa channels. A structural model of the heterodimeric complex of hSloRCK1 and hSloRCK2 domains is discussed

A Comparative Study of Three Different Chemical Vapor Deposition Techniques of Carbon Nanotube Growth on Diamond Films

This paper compares between the methods of growing carbon nanotubes (CNTs) on diamond substrates and evaluates the quality of the CNTs and the interfacial strength. One potential application for these materials is a heat sink/spreader for high-power electronic devices. The CNTs and diamond substrates have a significantly higher specific thermal conductivity than traditional heat sink/spreader materials making them good replacement candidates. Only limited research has been performed on these CNT/diamond structures and their suitability of different growth methods. This study investigates three potential chemical vapor deposition (CVD) techniques for growing CNTs on diamond: thermal CVD (T-CVD), microwave plasma-enhanced CVD (MPE-CVD), and floating catalyst thermal CVD (FCT-CVD). Scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (TEM) were used to analyze the morphology and topology of the CNTs. Raman spectroscopy was used to assess the quality of the CNTs by determining the ID/IG peak intensity ratios. Additionally, the CNT/diamond samples were sonicated for qualitative comparisons of the durability of the CNT forests. T-CVD provided the largest diameter tubes, with catalysts residing mainly at the CNT/diamond interface. The MPE-CVD process yielded non uniform defective CNTs, and FCT-CVD resulted in the smallest diameter CNTs with catalyst particles imbedded throughout the length of the nanotubes

Signal Transduction Pathways in the Pentameric Ligand-Gated Ion Channels

The mechanisms of allosteric action within pentameric ligand-gated ion channels (pLGICs) remain to be determined. Using crystallography, site-directed mutagenesis, and two-electrode voltage clamp measurements, we identified two functionally relevant sites in the extracellular (EC) domain of the bacterial pLGIC from Gloeobacter violaceus (GLIC). One site is at the C-loop region, where the NQN mutation (D91N, E177Q, and D178N) eliminated inter-subunit salt bridges in the open-channel GLIC structure and thereby shifted the channel activation to a higher agonist concentration. The other site is below the C-loop, where binding of the anesthetic ketamine inhibited GLIC currents in a concentration dependent manner. To understand how a perturbation signal in the EC domain, either resulting from the NQN mutation or ketamine binding, is transduced to the channel gate, we have used the Perturbation-based Markovian Transmission (PMT) model to determine dynamic responses of the GLIC channel and signaling pathways upon initial perturbations in the EC domain of GLIC. Despite the existence of many possible routes for the initial perturbation signal to reach the channel gate, the PMT model in combination with Yen's algorithm revealed that perturbation signals with the highest probability flow travel either via the β1-β2 loop or through pre-TM1. The β1-β2 loop occurs in either intra- or inter-subunit pathways, while pre-TM1 occurs exclusively in inter-subunit pathways. Residues involved in both types of pathways are well supported by previous experimental data on nAChR. The direct coupling between pre-TM1 and TM2 of the adjacent subunit adds new insight into the allosteric signaling mechanism in pLGICs. © 2013 Mowrey et al

An experimental customer satisfaction index to evaluate the performance of city logistics services

© 2016 Vilnius Gediminas Technical University (VGTU) Press. Freight transport in urban areas entails benefits (i.e. free access to goods when needed), but also negative externalities (environmental, social and transportation impacts). In response to these problems, the concept of city logistics emerged, for the purpose of planning, organizing, coordinating and controlling physical and information flows in order to find a compromise between efficient freight distribution in urban areas and protection of the environment. A typical city logistics initiative is the Urban Freight Consolidation Centre (UFCC), the benefits of which are significant. Its financial issues though represent a huge problem for public administrations. However, a large customer network, comprising retailers participating in the initiative, could make the UFCC a self-financing scheme. The key to expanding the scheme is closely linked with marketing campaigns and customer care. Therefore, customer care analysis represents an important tool in developing UFCC schemes. In this paper, a new Customer Satisfaction Index (CSI) is proposed for evaluating UFCC service quality. The new index, named CSImod, is a modified version of the traditional CSI, but places greater emphasis on customer dissatisfaction, so as to analyse the most critical areas of the service with a view to improving them. The index has been tested using experimental data collected within the CIVITAS RENAISSANCE Project, in which the Bristol and Bath Freight Consolidation Centre (BBFCC) scheme was evaluated. The evaluation was done from a user perspective, i.e. the participating retailers. The CSImod places more importance on the most dissatisfied customers making it possible to understand why they are dissatisfied and with what. Thus, it is possible to intervene with the aim of improving those areas of the service that are perceived as the worst. In spite of the high level of satisfaction with the overall service provided by the BBFCC, thanks to the CSImod the analysis pointed out that some retailers are dissatisfied with the delivery time arrangements and also with deliveries that were getting wet, issues about which the BBFCC manager was totally unaware. The CSImod could be used by UFCC operators to extend the network of the retailers involved and could therefore provide an implicit solution for making the scheme self-financing

Retrospective Review of Positive Newborn Screening Results for Isovaleric Acidemia and Development of a Strategy to Improve the Efficacy of Newborn Screening in the UK

\ua9 2024 by the authors.Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015 and 2022 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.9 (2.0–9.6) and 4.0 (1.8–&gt;70) \ub5mol/L, respectively, and neither did Precision Newborn Screening via Collaborative Laboratory Integrated Reports (CLIR), which identified only 1/47 FP cases. However, among the TP cases, disease severity showed a correlation with initial C5C in ‘asymptomatic’ individuals (n = 17), demonstrating a median (range) C5C of 3.0 (1.8–7.1) whilst ‘clinically affected’ patients (n = 7), showed a median (range) C5C of 13.9 (7.7–70) \ub5mol/L. These findings allowed the introduction of dual cut-off values into the screening algorithm to reduce the incidence of FPs, with initial C5C results ≥ 5 \ub5mol/L triggering urgent referral, and those &gt;2.0 and &lt;5.0 \ub5mol/L prompting second-tier C5-isobar testing. This will avoid delayed referral in babies at particular risk whilst reducing the FP rate for the remainder

Gating at the Mouth of the Acetylcholine Receptor Channel: Energetic Consequences of Mutations in the αM2-Cap

Gating of nicotinic acetylcholine receptors from a C(losed) to an O(pen) conformation is the initial event in the postsynaptic signaling cascade at the vertebrate nerve-muscle junction. Studies of receptor structure and function show that many residues in this large, five-subunit membrane protein contribute to the energy difference between C and O. Of special interest are amino acids located at the two transmitter binding sites and in the narrow region of the channel, where C↔O gating motions generate a low↔high change in the affinity for agonists and in the ionic conductance, respectively. We have measured the energy changes and relative timing of gating movements for residues that lie between these two locations, in the C-terminus of the pore-lining M2 helix of the α subunit (‘αM2-cap’). This region contains a binding site for non-competitive inhibitors and a charged ring that influences the conductance of the open pore. αM2-cap mutations have large effects on gating but much smaller effects on agonist binding, channel conductance, channel block and desensitization. Three αM2-cap residues (αI260, αP265 and αS268) appear to move at the outset of channel-opening, about at the same time as those at the transmitter binding site. The results suggest that the αM2-cap changes its secondary structure to link gating motions in the extracellular domain with those in the channel that regulate ionic conductance

Water-Gated Charge Doping of Graphene Induced by Mica Substrates

We report on the existence of water-gated charge doping of graphene deposited on atomically flat mica substrates. Molecular films of water in units of ~0.4 nm-thick bilayers were found to be present in regions of the interface of graphene/mica hetero-stacks prepared by micromechanical exfoliation of kish graphite. The spectral variation of the G and 2D bands, as visualized by Raman mapping, shows that mica substrates induce strong p-type doping in graphene, with hole densities of $(9 \pm 2) \times 1012 cm${-2}$. The ultrathin water films, however, effectively block interfacial charge transfer, rendering graphene significantly less hole-doped. Scanning Kelvin probe microscopy independently confirmed a water-gated modulation of the Fermi level by 0.35 eV, in agreement with the optically determined hole density. The manipulation of the electronic properties of graphene demonstrated in this study should serve as a useful tool in realizing future graphene applications.Comment: 15 pages, 4 figures; Nano Letters, accepted (2012

Study of the properties of thermoset materials derived from epoxidized soybean oil and protein fillers

[EN] Novel bio-based thermoset formulations were prepared by using epoxidized soybean oil (ESBO), nadic methyl anhydride as a hardener and with different types of proteins as fillers. In the first part of the study, the effect of the protein-type (wheat gluten, soy protein, casein and ovalbumin) on cured ESBO materials was investigated. Thermal and mechanical properties were characterized by flexural tests, Shore D hardness, Charpy impact tests, Vicat softening temperature and heat deflection temperature. In addition, a study of the morphology of fractured surfaces by scanning electron microscopy was carried out. In general, the addition of protein-based fillers improved the mechanical and thermal properties. It was found that the highest increase of thermal and mechanical properties was achieved by ovalbumin. In the second part of the work, the effect of the total amount of ovalbumin filler was studied. Bio-based thermoset materials from ESBO and 15 wt % ovalbumin improved flexural modulus more than 150 % when compared to the unfilled material. Similar evolution was observed for other mechanical properties. Moreover, the brittleness of this composition was the minimum from the studied systems. A direct relationship between energy absorption capacity and morphologies of the failure surface was evidenced by SEM.This work is a part of the project IPT-310000-2010-037,"ECOTEXCOMP: Research and development of textile structures useful as reinforcement of composite materials with marked ecological character" funded by the "Ministerio de Ciencia e Innovacion", with an aid of 189540.20 euros, within the "Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica 2008-2011" and funded by the European Union through FEDER funds, Technology Fund 2007-2013, "Operational Programme on R+D+I for and on behalf of the companies". Also, Generalitat Valenciana ACOMP/2012/087 is acknowledged for financial support.Fombuena Borrás, V.; Sánchez Nacher, L.; Samper Madrigal, MD.; Juárez Varón, D.; Balart Gimeno, RA. (2013). Study of the properties of thermoset materials derived from epoxidized soybean oil and protein fillers. Journal of the American Oil Chemists' Society. 90(3):449-457. https://doi.org/10.1007/s11746-012-2171-2S449457903Alonso MV, Oliet M, Garcia J, Rodriguez F, Echeverria J (2006) Gelation and isoconversional kinetic analysis of lignin-phenol-formaldehyde resol resins cure. Chem Eng J 122:159–166Altuna FI, Esposito LH, Ruseckaite RA, Stefani PM (2011) Thermal and mechanical properties of anhydride-cured epoxy resins with different contents of bio-based epoxidized soybean oil. J Appl Polym Sci 120:789–798Boquillon N, Fringant C (2000) Polymer networks derived from curing of epoxidised linseed oil: influence of different catalysts and anhydride hardeners. Polymer 41:8603–8613Boquillon N, Elbez G, Schonfeld U (2004) Properties of wheat straw particleboards bonded with different types of resin. J Wood Sci 50:230–235Chakrapani S, Crivello JV (1998) Synthesis and photoinitiated cationic polymerization of epoxidized castor oil and its derivatives. J Macromol Sci-Pure Appl Chem A35:1–20Chen F, Zhang JW (2009) A new approach for morphology control of poly(butylene adipate-co-terephthalate) and soy protein blends. Polymer 50:3770–3777Cuq B, Contard N, Guilbert S (1998) Proteins as agricultural polymers for packaging production. Am Assoc Cereal Chem 75:1–9Czub P (2006) Application of modified natural oils as reactive diluents for epoxy resins. Macromol Symp 242:60–64DdS Martini, Braga BA, Samios D (2009) On the curing of linseed oil epoxidized methyl esters with different cyclic dicarboxylic anhydrides. Polymer 50:2919–2925Dogan E, Kuesefoglu S (2008) Synthesis and in situ foaming of biodegradable malonic acid ESO polymers. J Appl Polym Sci 110:1129–1135Espinosa-Perez J, Wiesenborn DP, Tostenson K, Ulven CA, Tatlari M (2007) Preparation and partial characterization of canola-based epoxy resins for bio-based plastic composites. ASABE Annual International Meeting, 076079, Minneapolis, MNJin H, Zhang L, Chen F (2003) Effects of lignin as a filler on properties of soy protein plastics. I Lignosulfonate. J Appl Polym Sci 88:3284–3290Liu ZS, Erhan SZ, Calvert PD (2007) Solid freeform fabrication of epoxidized soybean oil/epoxy composite with bis or polyalkyleneamine curing agents. Compos Part A Appl Sci Manuf 38:87–93Matejka L, Lovy J, Pokorny S, Bouchal K, Dusek K (1983) Curing epoxy-resins with anhydrides—model reactions and reaction-mechanism. J Polym Sci Part A Polym Chem 21:2873–2885Miyagawa H, Mohanty AK, Drzal LT, Misra M (2005) Nanocomposites from bio-based epoxy and single-wall carbon nanotubes: synthesis, and mechanical and thermo-physical properties evaluation. Nanotechnology 16:118–124Mohamed A, Finkenstadt VL, Gordon SH, Palmquist DE (2010) Thermal and mechanical properties of compression-molded pMDI-reinforced PCL/gluten composites. J Appl Polym Sci 118:2778–2790Montero de Espinosa L, Ronda JC, Galià M, Cádiz V (2008) A new enone-containing triglyceride derivative as precursor of thermosets from renewable resources. J Polym Sci Part A Polym Chem 46:6843–6850Park SJ, Jin FL, Lee JR (2004) Synthesis and thermal properties of epoxidized vegetable oil. Macromol Rapid Commun 25:724–727Pfister DP, Baker RJ, Henna HP, Lu Y, Larock CR (2008) Preparation and properties of tung oil-based composites using spent germ as a natural filler. J Appl Polym Sci 108:3618–3625Reiznautt QB, Garcia ITS, Samios D (2009) Oligoesters and polyesters produced by the curing of sunflower oil epoxidized biodiesel with cis-cyclohexane dicarboxylic anhydride: synthesis and characterization. Mater Sci Eng C Mater Biol Appl 29:2302–2311Rüsch Gen Klaas M, Warwel S (1999) Complete and partial epoxidation of plant oils by lipase-catalyzed perhydrolysis. Ind Crops Prod 9:125–132Sailaja RRN, Girija BG, Madras G, Balasubramanian N (2008) Effect of compatibilization on mechanical and thermal properties of polypropylene—soy flour composites. J Mater Sci 43:64–67Samper MD, Fombuena V, Boronat T, García-Sanoguera D, Balart R (2012) Thermal and mechanical characterization of epoxy resins (ELO and ESO) cured with anhydrides. J Am Oil Chem Soc 89(8):1521–1528Sharma S (2008) Fabrication and characterization of polymer blends and composites derived from biopolymers. Philosophy Materials Science and Engineering. Graduate School of Clemson University, ClemsonSharma BK, Liu Z, Adhvaryu A, Erhan SZ (2008) One-pot synthesis of chemically modified vegetable oils. J Agric Food Chem 56:3049–3056Sue HJ, Wang S, Jane J (1997) Morphology and mechanical behaviour of engineering soy plastics. J Polym 38:5035Wang S, Sue HJ, Jane J (1996) Effects of polyhydric alcohols on the mechanical properties of soy protein plastics. J Macromol Sci Pure Appl Chem A33:557–569Wazzan AA, Al-Turaif HA, Abdelkader AF (2006) Influence of submicron TiO2 particles on the mechanical properties and fracture characteristics of cured epoxy resin. Polym Plastics Technol Eng 45:1155–116

Carglumic acid enhances rapid ammonia detoxification in classical organic acidurias with a favourable risk-benefit profile: A retrospective observational study

BACKGROUND: Isovaleric aciduria (IVA), propionic aciduria (PA) and methylmalonic aciduria (MMA) are inherited organic acidurias (OAs) in which impaired organic acid metabolism induces hyperammonaemia arising partly from secondary deficiency of N-acetylglutamate (NAG) synthase. Rapid reduction in plasma ammonia is required to prevent neurological complications. This retrospective, multicentre, open-label, uncontrolled, phase IIIb study evaluated the efficacy and safety of carglumic acid, a synthetic structural analogue of NAG, for treating hyperammonaemia during OA decompensation. METHODS: Eligible patients had confirmed OA and hyperammonaemia (plasma NH3 > 60 μmol/L) in ≥1 decompensation episode treated with carglumic acid (dose discretionary, mean (SD) first dose 96.3 (73.8) mg/kg). The primary outcome was change in plasma ammonia from baseline to endpoint (last available ammonia measurement at ≤18 hours after the last carglumic acid administration, or on Day 15) for each episode. Secondary outcomes included clinical response and safety. RESULTS: The efficacy population (received ≥1 dose of study drug and had post-baseline measurements) comprised 41 patients (MMA: 21, PA: 16, IVA: 4) with 48 decompensation episodes (MMA: 25, PA: 19, IVA: 4). Mean baseline plasma ammonia concentration was 468.3 (±365.3) μmol/L in neonates (29 episodes) and 171.3 (±75.7) μmol/L in non-neonates (19 episodes). At endpoint the mean plasma NH3 concentration was 60.7 (±36.5) μmol/L in neonates and 55.2 (±21.8) μmol/L in non-neonates. Median time to normalise ammonaemia was 38.4 hours in neonates vs 28.3 hours in non-neonates and was similar between OA subgroups (MMA: 37.5 hours, PA: 36.0 hours, IVA: 40.5 hours). Median time to ammonia normalisation was 1.5 and 1.6 days in patients receiving and not receiving concomitant scavenger therapy, respectively. Although patients receiving carglumic acid with scavengers had a greater reduction in plasma ammonia, the endpoint ammonia levels were similar with or without scavenger therapy. Clinical symptoms improved with therapy. Twenty-five of 57 patients in the safety population (67 episodes) experienced AEs, most of which were not drug-related. Overall, carglumic acid seems to have a good safety profile for treating hyperammonaemia during OA decompensation. CONCLUSION: Carglumic acid when used with or without ammonia scavengers, is an effective treatment for restoration of normal plasma ammonia concentrations in hyperammonaemic episodes in OA patients