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We characterized the adsorption and desorption of a-gel (a-form hydrated crystal) dispersions in aqueous media using a quartz crystal microbalance with dissipation monitoring (QCM-D) technique. The a-gel was formed from a mixture of N-[3-(dimethylamino)propyl]docosanamide (APA-22) L-lactic acid salt, 1-octadecanol (C18OH), and water. The solid substrate employed in this study as a model for hair was silica. The QCM-D measurements revealed that the a-gel dispersions yielded a rigid adsorption film on the negatively charged silica surface. The adsorption mass decreased with decreasing domain size (on the micrometer scale) of the a-gel dispersions. The adsorption film highly restricted the desorption of the a-gel from the silica surface even after rinsing with water. The adsorption film also exhibited excellent lubrication ability in aqueous media both before and after rinsing with water. We expect that the a-gel formed by APA-22 L-lactic acid is a potential ingredient for formulating an environment-friendly hair conditioner owing to its high adsorption, limited desorption, and excellent lubrication abilities on the solid surface. [ABSTRACT FROM AUTHOR]

This work covers the synthesis and characterisation of a new semicarbazone ligand derived from Mannich-base and its metal complexes. The title ligand (S,Z)-2-(1-(4-aminophenyl)-3-(4-(dimethylamino)phenyl)-3-((4- nitrophenyl)amino)propylidene)hydrazine-1-carboxamid was prepared from the reaction of the Mannich-base precursor (R)-1- (4-aminophenyl)-3-(4-(dimethylamino)phenyl)-3-((4-nitrophenyl)amino)propan-1-one with the semicarbazide in an ethanol medium. A series of metal complexes were prepared from the reaction of the ligand with the metal chloride of Co(II), Ni(II), Cu(II) and Cd(II) ion with a molar ratio of 2:1 (L:M) using EtOH as the reaction medium. The prepared compounds (precursor, ligand and complexes) were characterised using elemental analysis, melting point, metal content, magnetic susceptibility, conductance, FT-IR, UV-Vis and 1H and 13C-NMR. The characterisation data indicated the isolation of six and four coordinate monomeric complexes with the general formula; [M(L)2 (H2O)2 ]Cl2 (M= Co(II), Cu(II)), [Cd(L)2Cl2 ]2H2O and [Ni(L)2 ]Cl2 . The suggested geometry for the six-coordinate is a distorted octahedral arrangement. A square planar geometry about Ni atom was suggested for the Ni(II)-complex. The prepared compounds were tested against G-positive and G-negative bacterial strains and two fungi. The collected data indicated complexes became more effective, compared with the free ligand [ABSTRACT FROM AUTHOR]

A novel bimediator compound has been synthesized by covalently linking two redox mediators and used for fabrication of bimediator modified electrode to perform electrocatalytic oxidation and reduction of substrates. Ferrocene monocarboxylic acid and thionin have been linked via amide bond using ( N -3-Dimethylaminopropyl)- N ′-ethylcarbodiimide hydrochloride (EDC·HCl) and N -Hydroxy benzotriazole (HOBt) as cross-linking agents. The electrochemical characterization and surface characterization have confirmed the presence of both redox mediators in the bimediator compound on the modified electrode surface which has facilitated electron transfer between analyte and the electrode. The ferrocene has mediated electrocatalytic oxidation of dopamine at positive potentials while thionin has mediated electrocatalytic reduction of hydrogen peroxide at negative potentials. Effective utilization of this bimediator modified electrode has been examined under static and dynamic conditions by cyclic voltammetry and chronoamperometric techniques. Ferrocene has been found to oxidise dopamine at a potential of 0.35 V in the concentration range of 0.569 μM to 515 μM with a detection limit of 0.190 μM and sensitivity of 142 μA mM − 1 cm − 2 whereas thionin has been found to reduce hydrogen peroxide at a potential of − 0.3 V in the concentration range of 0.569 μM to 785 μM with a detection limit of 0.190 μM and sensitivity of 128 μA mM − 1 cm − 2 . This bimediator modified electrode has also been used for real sample analysis. [ABSTRACT FROM AUTHOR]

This work reports the reinforcing efficiency of carbon dots (CDs) in carboxylated acrylonitrile butadiene (XNBR) latex at very low concentration. Amine and carboxyl functionalized CDs have been synthesized from citric acid and glycine. The CDs are covalently conjugated to XNBR latex using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.HCl) and N-hydroxysuccinimide (NHS) as coupling agents. The covalent conjugation of CDs with XNBR latex has been confirmed by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS) and X-ray photoelectron spectroscopy (XPS). The optical properties of CDs and XNBR-CDs conjugate have been characterized by ultraviolet (UV) - visible, fluorescence spectroscopy, time-resolved fluorescence spectrophotometer and haze meter. The tensile stress-strain properties of XNBR latex dramatically increases by the addition of CDs to XNBR latex. The maximum tensile stress of 2 phr of CDs loaded XNBR latex is nearly 215% higher than the maximum tensile stress of neat XNBR latex. There is a concomitant decrease in the tan δ peak height and increase in the tan δ peak temperature of XNBR latex with the incorporation of CDs to XNBR latex. In addition, the storage modulus (G′) value of sample containing 2 phr of CDs is 161% higher than the storage modulus value (G′) of neat XNBR latex. The onset of degradation temperature (T i ) value of sample containing 4 phr of CDs is 40 °C higher than the T i value of neat XNBR latex. On the other hand, the maximum degradation temperature (T max ) of XNBR latex containing 1 phr of CDs is 11 °C higher than the T max value of neat XNBR latex. Morphology of pristine CDs and XNBR-CDs conjugate has been analyzed using transmission electron microscopy (TEM). To the best of our knowledge, this is the first report which analyzes the effect of CDs on the physico-mechanical properties of elastomer contrary to the other novel fillers of carbon family. [ABSTRACT FROM AUTHOR]

Small interfering RNA (siRNA)-based gene therapy represents a promising strategy for tumor treatment. Novel gene vectors that can achieve targeted delivery of siRNA to the tumor cells without causing any side effects are urgently needed. To this end, the large amino acid mimicking carbon dots with guanidinium functionalization (LAAM GUA-CDs) are designed and synthesized by choosing arginine and dopamine hydrochloride as precursors. LAAM GUA-CDs can load siRNA through the multiple hydrogen bonds between their guanidinium groups and phosphate groups in siRNA. Meanwhile, the amino acid groups at the edges of LAAM GUA-CDs endow them the capacity to target tumors. After loading siBcl-2 as a therapeutic agent, LAAM GUA-CDs/siBcl-2 has a high tumor inhibition rate of up to 68%, which is twice more than that of commercial Lipofectamine 2000. Furthermore, LAAM GUA-CDs do not cause side effect during antitumor treatment owing to their high tumor-targeting ability, thus providing a versatile strategy for tumor-targeted siRNA delivery and cancer therapy., (© 2023 Wiley-VCH GmbH.)

The disposition of toxicants is often affected by their binding to serum proteins, of which the most abundant in humans is serum albumin (HSA). There is increasing interest in the toxicities of environmentally persistent polychlorinated biphenyls (PCBs) with lower numbers of chlorine atoms (LC-PCBs) due to their presence in both indoor and outdoor air. PCB sulfates derived from metabolic hydroxylation and sulfation of LC-PCBs have been implicated in endocrine disruption due to high affinity-binding to the thyroxine-carrying protein, transthyretin. Interactions of these sulfated metabolites of LC-PCBs with HSA, however, have not been previously explored. We have now determined the relative HSA-binding affinities for a group of LC-PCBs and their hydroxylated and sulfated derivatives by selective displacement of the fluorescent probes 5-dimethylamino-1-naphthalenesulfonamide and dansyl-l-proline from the two major drug-binding sites on HSA (previously designated as Site I and Site II). Values for half-maximal displacement of the probes indicated that the relative binding affinities were generally PCB sulfate ≤ OH-PCB > PCB, although this affinity was site- and congener-selective. Moreover, specificity for Site II increased as the numbers of chlorine atoms increased. Thus, hydroxylation and sulfation of LC-PCBs result in selective interactions with HSA which may affect their overall retention and toxicity. [ABSTRACT FROM AUTHOR]

Long-acting opioid agonists methadone and l -α-acetylmethadol (LAAM) prevent withdrawal in opioid-dependent persons. Attempts to synthesize [ 11 C]-methadone for PET evaluation of brain disposition were unsuccessful. Owing, however, to structural and pharmacologic similarities, we aimed to develop [ 11 C] LAAM as a PET ligand to probe the brain exposure of long-lasting opioids in humans. This manuscript describes [ 11 C] LAAM synthesis and its biodistribution in mice. The radiochemical synthetic strategy afforded high radiochemical yield, purity and specific activity, thereby making the synthesis adaptable to automated modules. [ABSTRACT FROM AUTHOR]

The purpose of this study was to document the prevalence of Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) among urban and rural methadone maintenance treatment (MMT) patients and to examine differences in knowledge of HIV and HCV among this population. We compared 147 MMT patients attending urban versus rural clinics in Kunming, Yunnan, China, concerning their serostatus and knowledge of HIV and HCV. The rates of HIV and HCV seropositive status were higher among rural patients. Both urban and rural patients showed limited HIV and HCV knowledge. Recent opioid injection and geographic area were strong predictors of HIV and HCV serostatus. The lack of knowledge of HIV and HCV among both urban and rural MMT patients suggests the need to strengthen current HIV and HCV education programs in MMT clinics. In addition, prevention programs should take into consideration geographic characteristics of the target population. [ABSTRACT FROM AUTHOR]

Background/Aim: To inform understanding of the experience of long-term opiate maintenance and identify barriers to recovery. Methods: A qualitative systematic review. Results: 14 studies in 17 papers, mainly from the USA (65%), met inclusion criteria, involving 1,088 participants. Studies focused on methadone prescribing. Participants reported stability; however, many disliked methadone. Barriers to full recovery were primarily 'inward focused'. Conclusion: This is the first review of qualitative literature on long-term maintenance, finding that universal service improvements could be made to address reported barriers to recovery, including involving ex-users as positive role models, and increasing access to psychological support. Treatment policies combining harm minimisation and abstinence-orientated approaches may best support individualised recovery. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

2-Methylbenzoic acid phenylhydrazide was polylithiated with excess lithium diisopropylamide, and the resulting polylithiated intermediate was condensed with methyl 4-dimethylaminobenzoate or methyl 4-methoxybenzoate to afford C-acylated intermediates that were immediately acid cyclized to afford 3-(4-(dimethylamino)-phenyl)-2-(phenylamino)isoquinolin-1(2 H)-one CHNO or 3-(4-methoxyphenyl)-2-(phenylamino)isoquinolin-1(2 H)-one CHNO. The polylithiated intermediate underwent N-acylation when it was condensed with methyl 4-methylbenzoate to give 2-methyl- N′-(4-methylbenzoyl)- N′-phenylbenzohydrazide CHNO. Crystals of CHNO 4a are triclinic, P $$ \overline{1} $$, a = 9.138(2) Å, b = 10.519(2) Å, c = 11.082(2) Å, α = 91.55(3)°, β = 108.92(3)°, γ = 111.16(3)°, Z = 2, V = 927.1(3) Å, R = 0.0711 and wR = 0.1828 for reflections with I > 2σ( I); crystals of CHNO 4b are monoclinic, P2/ c, a = 8.821(1) Å, b = 13.276(2) Å, c = 15.482(3) Å, β = 105.271(4)°, Z = 4, V = 1748.9(5) Å, R = 0.0416 and wR = 0.1030 for reflections with I > 2σ( I); crystals of CHNO 3 are orthorhombic, Pbca, a = 13.505(3) Å, b = 9.733(2) Å, c = 28.601(6) Å, Z = 8, V = 3759.4(13) Å, R = 0.1683 and wR = 0.3526 for reflections with I > 2σ( I). Index Abstract: X-ray crystal analysis was important for the confirmation of the structure of 3-(4-(dimethylamino)phenyl)-2-(phenylamino)isoquinolin-1(2 H)-one CHNO 4a, 3-(4-methoxyphenyl)-2-(phenylamino)isoquinolin-1(2 H)-one CHNO 4b, and 2-methyl- N′-(4-methylbenzoyl)- N′-phenylbenzohydrazide CHNO 3 prepared from polylithiated 2-methylbenzoicacid phenylhydrazide and methyl 4-dimethylaminobenzoate, methyl 4-methoxybenzoate, or methyl 4-methylbenzoate. Crystals of CHNO 4a are triclinic, P $$ \overline{1} $$, a = 9.138(2) Å, b = 10.519(2) Å, c = 11.082(2) Å, α = 91.55(3)°, β = 108.92(3)°, γ = 111.16(3)°, Z = 2, V = 927.1(3) Å, R = 0.0711 and wR = 0.1828 for reflections with I > 2σ( I); crystals of CHNO 4b are monoclinic, P2/ c, a = 8.821(1) Å, b = 13.276(2) Å, c = 15.482(3) Å, β = 105.271(4)°, Z = 4, V = 1748.9(5) Å, R = 0.0416 and wR = 0.1030 for reflections with I > 2σ( I); crystals of CHNO 3 are orthorhombic, Pbca, a = 13.505(3) Å, b = 9.733(2) Å, c = 28.601(6) Å, Z = 8, V = 3759.4(13) Å, R = 0.1683 and wR = 0.3526 for reflections with I > 2σ( I). [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Heroin dependence is a major health and social problem associated with increased morbidity and mortality that adversely affects social circumstances, productivity, and healthcare and law enforcement costs. In the UK and many other Western countries, both methadone and buprenorphine are recommended by the relevant agencies for detoxification from heroin and for opioid maintenance therapy. However, despite obvious benefi ts due to its unique pharmacotherapy (eg, greatly reduced risk of overdose), buprenorphine has largely failed to overtake methadone in managing opioid addiction. The experience from the developing world (based on data from India) is similar. In this article we compare the advantages and disadvantages of the use methadone and buprenorphine for the treatment of opioid addiction from both a developed and developing world perspective; and explore some of the reasons why buprenorphine has not fulfilled the expectations predicted by many in the addictions field. [ABSTRACT FROM AUTHOR]

The use of Pseudomonas stutzeri lipase (PSL) as a biocatalyst for aminolysis reactions with bulky substrates has been investigated. PSL compared favorably to Novozym® 435 (immobilized Candida antarctica lipase B, NOV435) in the aminolysis of various bulky methyl esters and amines. While NOV435 demonstrated a higher rate of aminolysis with methyl 2-phenylpropionic acid as the acyl donor, PSL outperformed NOV435 with secondary amines as the nucleophile. Methanol inhibition and a low affinity for bulky acyl donors were found to be the two main reasons for relatively low rates in the PSL-catalyzed aminolysis reactions. It was demonstrated that the use of molsieve 4A had a significant effect on the aminolysis rate and amide yield, since it enabled the effective removal of the inhibiting methanol from the reaction mixture. [ABSTRACT FROM AUTHOR]

Abstract: A donor acceptor substituted aromatic system 5-(4-dimethylamino-phenyl)-penta-2,4-dienoic acid (DMAPPDA) has been synthesized and its spectral properties have been explored on the basis of steady state absorption and fluorescence spectroscopy. Spectral features point largely towards a possible occurrence of photoinduced intramolecular charge transfer process from the donor NMe2 group to the acceptor acid group. Solvent dependency of the large Stokes’ shifted emission band and the calculated large excited state dipole moment support the polar character of the charge transfer excited state. Quantum yield calculations and effect of addition of acid and base on the steady state spectra were also performed to further scrutinize the excited state CT character. [ABSTRACT FROM AUTHOR]

A reliable and scalable route to racemic and highly enantiomerically enriched menthylamines exploits the technical product RAC-neomenthol as the starting material. The elaborated protocol is based on nucleophilic substitution of the hydroxy moiety by azide. Subsequent reduction and resolution with tartaric acid provides the desired optically enriched menthylamines. [ABSTRACT FROM AUTHOR]

Abstract: Gellan gum (GG) is an exopolysaccharide produced by Sphingomonas elodea. To develop a medical application for GG, in this study we prepared 26μm thick films of GG reacted with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) in 40% ethanol to obtain a cross-linked film (GG40) with 73% gel content and 52.4MPa tensile strength. In vitro biocompatibility tests, GG40 film exhibit nontoxic effects for L929 cells and inhibit absorption and activation of platelets. When implanted into rat subcutaneous tissue, the GG40 film caused minor inflammation in the early postoperative period. The results indicate that the effects of GG40 film on wound healing, wound size reduction (%) and collagen content are higher than those found in commercial products (Duoderm). Therefore, we conclude that the GG film developed in this study has potential for future use in surgical applications. [ABSTRACT FROM AUTHOR]

A highly efficient, green and simple solvent-free method for the synthesis of 1-amidoalkyl-2-naphthols via one-pot multi-components condensation of 2-naphthol, aromatic aldehydes and amides in the presence of catalytic amount of silica-supported molybdatophosphoric acid (H3PMo12O40.xH2O/SiO2,3.17 mol%) is described. The reactions proceed rapidly and the title compounds are produced in high to excellent yields. [ABSTRACT FROM AUTHOR]

The synthesis of asymmetrically bridged calix[4]arene and tetrathiacalix[4]arene amido crown derivatives has been achieved by the aminolysis of distal diester derivatives of calix[4]arene and tetrathiacalix[4]arene with 1,2-diaminopropane or 1,2-diaminocyclohexane (stereoisomeric mixture, mainly trans). The title compounds have been characterised by detailed analysis of their NMR spectra. The assignment of NMR signals and stereo differentiation in the amido crown ring formation has been studied using a chiral shift reagent. [ABSTRACT FROM AUTHOR]

A series of X,Y-substituted benzhydryl acetates (1-3) were subjected to solvolysis in various binary methanol/water and ethanol/water mixtures at 25 °C. The LFER equation log k = sf(Ef + Nf) was used to derive the nucleofuge-specific parameters (Nf and sf) for an SN1 type reaction in 60 % and 80 % aqueous methanol. It has been established that X,Y-substituted benzhydryl acetates produce almost parallel correlation lines, so the average sf = 0.9 has been taken for calculation of the nucleofugality parameters from a single rate constant in some solvent mixtures. In comparison with other leaving groups for which the nucleofugality has already been determined, acetates are the poorest nucleofuges. [ABSTRACT FROM AUTHOR]

A new, simple, inexpensive, and sensitive method for the simultaneous spectrophotometric determination of Cu(II) and Pd(II) by H-point standard addition method and derivative spectrophotometry is described. 4- Phenylpiperazinecarbodithioate (PPDTC) in an anionic micellar solution of SLS was used as a reagent at pH 4. The experimental parameters, such as pH, type of surfactant, concentration of reagent, and surfactant used, were optimized to minimize the errors. The linear ranges of the method were 0.1-10 and 0.1-11 μg mL-1 for Cu(II) and Pd(II), respectively. The results of applying H-point standard addition and fourth derivative spectrophotometry showed that Cu(II) and Pd(II) can be determined simultaneously with detection limits of 0.12 and 0.11 μg mL-1 respectively. Therefore, the method of H-point standard addition and fourth derivative spectrophotometry was used for resolving overlapped spectra for the determination of Cu(II) and Pd(II). This method was successfully applied to the determination of these metals in synthetic and real samples. [ABSTRACT FROM AUTHOR]

A series of amino acid ester derivatives containing 5-fluorouracil were synthesized using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) and N-hydroxybenzotriazole (HOBt) as a coupling agent. The structures of the products were assigned by NMR, MS, IR etc. The in vitro antitumor activity tests against leukaemia HL-60 and liver cancer BEL-7402 indicated that (R)-ethyl 2-(2-(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)-3-(4-hydroxyphenyl) propanoate showed more inhibitory effect against BEL-7402 than 5-FU. [ABSTRACT FROM AUTHOR]

Abstract: Grapes are rich in bioactive phenolics. However, most of them remain in the by-product after juice processing, and only a minor part pass to the juice. Our aim was to obtain a resveratrol-enriched white grape juice based on UVC-treated berries in combination with different conditions during juice production. Postharvest UVC treatment of berries enabled the further selective stilbenes enrichment of the juice, especially resveratrol. Macerating enzymes did not modify the phenolic profile but increased juice yield up to 30%, keeping its phenolic concentration, and thus reducing the phenolics remaining in the by-product. Maceration with Na2S2O5 was critical to increase the phenolic content in the juice whereas β-cyclodextrin only tended to increase the stilbenes content. Optimum conditions for juice production (maceration for 2 h at 45 °C with 0.2% Na2S2O5) using UVC-treated grape berries significantly increased stilbenes concentration (up to 35-fold over the control), without affecting the sensory properties of the juice. The phenolic (resveratrol)-enriched grape juice obtained here could be an ideal alternative to wine in the search of grape-derived health benefits. Industrial relevance: The aim of this study is to obtain a resveratrol-enriched grape juice by combining postharvest UV-C treatment of grape berries with several technological approaches in the juice processing. Results obtained indicate that maceration for 2 h at 45 °C with 0.2% Na2S2O5 using UVC-treated grape berries significantly increased phenolic concentration, especially stilbenes (up to 35-fold over the control), without affecting the sensory properties of the juice. The resveratrol-enriched juice has an added-value compared to the conventional ones and could exert more health benefits due to its improved phenolic profile. [Copyright &y& Elsevier]

Abstract: Dietary intake of whole-grain foods is associated with a decreased risk of chronic diseases such as diabetes, obesity and heart disease. In addition to dietary fibre, various phytochemicals have been suggested to contribute to the health effects of whole grain products. This review focuses on phenolic compounds in rye (Secale cereale L.), which is one of the major bread grains in Europe. Data on phenolic concentrations in rye grain and foods, their bioavailability to tissues and effects in vivo, and their potential contributions to health are presented. Phenolic compounds in rye, such as phenolic acids, alkylresorcinols and lignans, are concentrated in the outer layers of the grain. Phenolic acids are the major phenolic compounds in whole grain rye (103–300mg/100g grain), ferulic acid being the most abundant. Rye lignans are present at concentrations of 2mg/100g grain and had been shown to be converted by the intestinal microflora to the mammalian lignans enterodiol and enterolactone in human intervention studies. Alkylresorcinols (36–320mg/100g grain), which have been found to be incorporated into human erythrocyte membranes, are of particular interest due to their potential use as biomarkers of the intake of rye and wheat. [Copyright &y& Elsevier]

Levo-alpha-acetylmethadol maintenance (LAAM) was compared to methadone maintenance (MM) on the behavioral performance of 315 heroin addicts before, during, and after 12 months of fully subsidized treatment. Assessments of drug use, criminal behavior, HIV risk behaviors, and employment and residential status were obtained at treatment intake and at 6, 12, and 18 months after admission. Treatment retention and in-treatment suppression of heroin use were significantly better for the LAAM group than for the MM group. Improvements were also noted during treatment in criminal behavior, criminal justice involvement, and employment status, and there were reductions in injection HIV risk and number of sexual partners. Most significant effects were primarily related to active participation in maintenance treatment. Under subsidized treatment, retention rates were two to four times that of similar clients in local community programs during the same period. LAAM was a useful and a potentially important addition to treatment options for opiate addiction, conferring greater retention and opiate suppression benefits. Its removal from application provides a historical lesson concerning the introduction of new medications into addiction health services. [ABSTRACT FROM AUTHOR]

The paper analyses methadone treatment in Copenhagen - as it is described by methadone users and staff at different outpatient centres. The starting point is a theoretical model distinguishing between two different approaches to methadone treatment: 'palliative' and 'curative'. Included in the model are three dimensions (1) treatment goals at the methadone centres (abstinence vs. stabilisation) (2) treatment focus (focus on addiction vs. focus on the consequences of addiction) and (3) conceptualisation of methadone (methadone as similar to or different from heroin). The paper shows that there is a discrepancy between the attitudes of the staff and those of the users. While the staff favour an almost clear-cut palliative approach to methadone treatment, defining curative goals as both unrealistic and as belonging to the past, the users prefer an approach that does not exclude the goal of abstinence and does not focus on the consequences of drug use alone but also on their problematic relationship to drugs (legal as well as illegal). Furthermore, the users' attitudes towards methadone are far more ambivalent than the staff's. For the users, methadone is not just medicine; it is also a dependence-producing and 'dangerous' drug. [ABSTRACT FROM AUTHOR]

Abstract: Carbolithiation of a range of substituted stilbenes and styrenes with dithianyllithiums is described, leading to the rapid, efficient and stereocontrolled assembly of highly functionalized dithiane intermediates for acyl-equivalents synthesis. [Copyright &y& Elsevier]

Abstract: α-Hydroxyketones are oxidatively cyclized with o-phenylenediamines in toluene at 120°C under an atmosphere of air in the presence of a catalytic amount of a copper catalyst along with powdered 4A molecular sieves to afford the corresponding quinoxalines in high yields. The reaction is applicable to a wide range of α-hydroxyketones which have various aryl and alkyl groups attached to carbonyl carbon. [Copyright &y& Elsevier]

Abstract: Described herein is the first total synthesis and structural confirmation of cepharadione A, a naturally occurring DNA damaging agent. Also reported is the synthesis of cepharadione B, a closely related natural product, as well as the biological evaluation of both natural products. Finally, the preparation and biological evaluation of novel dioxoaporphine analogues is described. [Copyright &y& Elsevier]

Abstract: Resveratrol ((E)-3,4′,5-trihydroxy-stilbene), a phytoalexin found in various plants, shows non-selective cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) inhibition. In order to find more selective COX inhibitors a series of bridged stilbene derivatives was synthesized and evaluated for their ability to inhibit both COX-1 and COX-2 in vitro. The compounds showed a high rate of COX-1 inhibition with the most potent compounds exhibiting submicromolar IC50 values and high selectivity indices. A prediction model for COX-inhibiting activity was also developed using the classical LIE approach resulting in consistent docking data for our molecule sample. Phenyl substituted 1,2-dihydronaphthalene derivatives and 1H-indene derivatives therefore represent a novel class of highly selective COX-1 inhibitors and land promising candidates for in vivo studies. [Copyright &y& Elsevier]

Elastic collagen gel ( e-gel) was prepared from salmon atelocollagen fibrillar gel reinforced by 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) mediated cross-linking ( f-gel). The preparation consisted of a simple heat treatment of the f-gel at 80 °C, in which the f-gel drastically shrank and the collagen fibril structure was deformed. The e-gel obtained showed rubber-like elasticity; its stress–strain behavior little changed through repeated stretching. The elongation at the breaking point was approximately 230%. Furthermore, normal human osteoblasts showed good attachment and proliferation on the e-gel. These results suggest its potential to be utilized for the development of tissue engineering. [ABSTRACT FROM AUTHOR]

Abstract: The Rh(I)-catalyzed PKR of 1-phenylsulfonyl-1,2-octadien-7-ynes and their aza derivatives exclusively produced the corresponding 9-phenylsulfonylbicyclo[4.3.0]nona-1,6-dien-8-ones and no 4-(phenylsulfonylmethylidene)bicyclo[3.3.0]oct-1-en-3-ones could be detected. Thus, the ring-closing pattern was found to be the same as those of the previously reported 3-phenylsulfonyl-1,2-octadien-7-yne derivatives. However, the formation of 4-(phenylsulfonylmethylidene)-7-oxabicyclo[3.3.0]oct-1-en-3-ones was observed as a minor product when the 5-oxa congeners were used. In addition, a larger ring-sized product, 10-phenylsulfonyl-5-azabicyclo[5.3.0]deca-1,7-dien-9-one derivative, was obtained from the 6-aza derivative of 1-phenylsulfonyl-1,2-nonadien-8-yne. [Copyright &y& Elsevier]

The study contributes to the characterization of an original reactive pressure swing distillation system. The methyl acetate (MeAc) transesterification with ethanol (EtOH) to produce methanol (MeOH) and ethyl acetate (EtAc) is shown as illustrative example. The streams outside the units are evaluated by the ∞/∞ analysis to provide insights on the process behavior. Two simpler systems with recycling stream are also presented. The ∞/∞ analysis allows checking the interrelation of the system streams without any column design consideration. Unfeasible regions, low limit values, multiplicity regions, discontinuities, control difficulties, recommendable operation conditions and column profile combinations are predicted and discussed. All these information are useful to establish an early and suitable system design strategy. [Copyright &y& Elsevier]

The concept of opioid equianalgesia, limitations in current dose conversion systems, equianalgesic dose tables, and computer assisted dose conversions are discussed. Conversions for methadone, fentanyl and hydromorphone are described. [ABSTRACT FROM AUTHOR]

Methyl and ethyl 2-(2-oxo-2,3-dihydro-3 H-indol-3-ylidene)acetates react with aromatic amines to give products of regioselective addition at the α-position of the activated exocyclic C=C bond, methyl and ethyl 2-arylamino-2-(2-oxo-2,3-dihydro-1 H-indol-3-yl)acetates. [ABSTRACT FROM AUTHOR]

The kinetics for the reaction of C6H5with propene has been measured by cavity ring-down spectrometry (CRDS) at temperatures 296−496 K under an Ar pressure of 40 Torr. The total rate constant can be given by the following Arrhenius expression (in units of cm3mol-1s-1):  k(C6H5 C3H6) 1011.93±0.06exp−(1512 ± 51)/T. Density functional and higher level of theory calculations (up to the G2M level) have been carried out to provide additional insights about the mechanism of this reaction, and we also performed transition state theory (TST) calculation for the rate constant prediction. Our theoretical kinetic calculations predict that the C6H5addition to the terminal CH2site in propene is dominant at the temperature range of our CRDS measurements. However, the H-abstraction channel forming benzene and the allyl radical becomes increasingly important at higher temperatures. The total high-pressure limiting rate constant calculated on the basis of the G2M reaction barriers is in reasonable agreement with the experimental values. [ABSTRACT FROM AUTHOR]

Previous studies have shown that the carboxyl groups in hyaluronic acid (HA) could be activated by 1-ethy 1-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC)/ N-hydroxysuccinimide (NHS) to form intermediate O-acylisoureas, which can chemically bind to exposed amino groups on the tendon surface, leading to improved gliding ability. However, the optimal ratio and concentrations of the components in this chemical mixture were not investigated. The purpose of this study was to optimize the constituents of this tissue engineering approach to tendon surface modification, to reduce friction and improve durability. Peroneus longus (PL) tendons ( n = 40) were harvested from adult mongrel dogs along with the A2 pulley obtained from the ipsilateral hind paw. After the gliding resistance of the normal PL tendon was measured, the tendons were treated under varying concentrations of HA (0.5, 1, and 2%) and EDC/NHS (0.05, 0.25, and 1%) mixed with a 10% gelatin. Tendon friction was measured for 1000 cycles of simulated flexion/extension motion. Following testing, the residual HA on the tendon surface was evaluated by immunohistochemisty. The gliding resistance of the untreated PL tendons had a mean value of 0.087 ± 0.021 N. After surface treatment, there was no significant difference in friction due to HA concentration alone, but the concentration of EDC/NHS and the interaction between HA concentration and EDC/NHS concentration had a significant effect on friction. Regardless of HA concentration, the friction after 1000 cycles was significantly decreased in preparations which included a 1% concentration of EDC/NHS. The tendons with lower gliding resistance presented a smoother surface on light microscopy and maintained more residual HA on the tendon surface. By varying the relative concentrations of HA, EDC, and NHS it is possible to optimize the effect of surface treatment on friction and durability in a canine extrasynovial tendon in vitro. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1555-1561, 2006 [ABSTRACT FROM AUTHOR]

Knowledge of how methadone disposition may fluctuate during the course of maintenance treatment is presently limited. This study investigated long-term fluctuations in methadone pharmacokinetics in five methadone maintenance patients who participated in two 24-hour testing sessions separated by at least one year. Results indicated substantial fluctuations between sessions in dose-corrected average steady-state plasma (R)-methadone concentrations (Cav), ranging from a 51% decrease to a 466% increase. These fluctuations were not consistently associated with changes in methadone dose or self-reported withdrawal status. The plasma (S)-:(R)-methadone Cav ratio increased significantly (12%, P = 0.04) between the sessions, suggesting a different pattern of long-term change in the pharmacokinetics of each enantiomer over time. The pronounced and variable fluctuations in methadone disposition evident in these patients highlight the need for an individualized approach to patient dosing and monitoring. [ABSTRACT FROM AUTHOR]

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To compare the effects of levo-alpha-acetylmethadol (LAAM) and methadone maintenance (MM) on treatment retention and abstinence from opiate use. A two-group experimental design with patients randomly assigned (2 : 1 LAAM : MM) to receive LAAM (three doses per week) or methadone (daily dosing). A community clinic in Los Angeles, California. A total of 315 patients seeking LAAM or methadone maintenance. LAAM or methadone maintenance, plus ancillary services available to all patients. LAAM and methadone dose levels varied according to clinical judgement. Electrocardiograms were administered to LAAM patients monthly. Treatment status at 26-week follow-up and number of days retained in treatment, weekly clinical urine tests and 26-week research urine test. LAAM and methadone patients did not differ on treatment retention. LAAM patients were less likely to test positive for opiate use during treatment (40% versus 60%) and at 26-week follow up (39.8% versus 60.2%). Benefits of LAAM were confined to patients ( n = 204) still in treatment at 26 weeks (33% positive in patients receiving LAAM and 61% in patients receiving methadone). No adverse events, cardiological or otherwise, were observed with LAAM administration. LAAM is an effective medication for the treatment of opiate dependence with clinical advantages due not only to the reduction of opiate use but also to the alternate-day dosing schedule. LAAM may be more effective than methadone in promoting abstinence from opiate use among patients for whom LAAM is an acceptable alternative to methadone. [ABSTRACT FROM AUTHOR]

Abstract: Molecules of electronically excited 2-[4-(dimethylamino)phenyl]-3-hydroxy-4H-chromene-4-one (a fluorescent probe) co-exist in the normal (N *) and tautomeric (T *) forms and emit radiation in different spectral regions. The positions (expressed in wave numbers, ν) and intensities (I) of the emission bands are strongly affected by the ability of the medium''s molecules to participate in hydrogen bonding with the probe. In such cases, I N*, I N*/I T*, ν N*, ν N* + ν T* or ν N* − ν T*, depend on the concentration (over a certain range) or its base-10 logarithm (log) of the component interacting with the probe. These relationships form the basis for a quantitative assay of such compounds in binary mixtures. On the other hand, the log(I N*/I T*) versus ν N* + ν T* or ν N* − ν T* relationships demonstrate unique features that can be used to distinguish components (alcohols) interacting with the probe and to quantify their contents. The prospects for the analytical application of these findings are outlined briefly. [Copyright &y& Elsevier]

Abstract: The most commonly used anti-adhesion device for separation and isolation of wounded tissues after surgery is the polymeric film. In this study, a new anti-adhesion membrane based on polygalacturonic acid (PGA) has been synthesized, and its biocompatibility and anti-adhesion capabilities evaluated. The PGA film was reacted with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) to obtain a cross-linked PGA film with an 86% gel content and a 47% water content when immersed in aqueous solution. This PGA–EDC film did not show any evidence of cytotoxic effects since it did not induce any significant increase in cytoplasmic LDH release from the L929 cells in contact with it. When implanted into rats, the PGA–EDC film exhibited a most promising anti-adhesion potential with only 1 out of 21 rats operated not forming any tissue adhesion. This anti-adhesion potency is significantly higher than that found for Seprafilm™ and untreated rats where 11 out of 21 and 18 out of 21 operated rats, respectively, formed tissue adhesions. The implanted PGA–EDC film did not elicit any acute inflammatory reaction based on the results of histological examination and peritoneal fluid leukocytes analysis. The newly developed PGA–EDC film thus has a great potential for future use in clinical applications. [Copyright &y& Elsevier]

Catalytic properties of monoamino oxidase (MAO) in a homogeneous reaction of oxidation and a heterogeneous reaction of bioelectrocatalytic oxidation of benzylamine by derivatives of phenothiazine and phenoxazine (artificial electron acceptors) is studied. The efficiency of electroenzymic catalysis involving Methylene Blue and MAO immobilized on the electrode is comparable to that of homogeneous enzymic catalysis. When immobilized in a film of polymer electrolyte Eastman AQ-29, Methylene Blue and Toluidine Blue efficiently carry electrons from the reduced redox center of immobilized MAO onto a glassy-carbon electrode. Dependence of the oxidation current of these compounds on the concentration of the benzylamine substrate is studied and it is shown that the enzymic reaction is the limiting stage in a bioelectrocatalytic process. This conclusion gives grounds for using the dependence of the anodic current on the monoamine concentration as a calibration plot when assaying biogenic amines. [ABSTRACT FROM AUTHOR]

Two studies were conducted to investigate the effectiveness of contingency management techniques in promoting punctual counseling attendance among methadone maintenance patients. In Study 1, 50 participants were recruited from an inner-city methadone maintenance program. Study 1 used an A-B-A design with baseline, intervention, and return-to-baseline phases. On-time attendance was reinforced during the intervention phase with a voucher that was redeemable for a draw out of a box containing 100 tokens with values varying from 0.00 dollars to 100.00 dollars. Methadone maintenance patients who exhibited poor attendance during baseline showed a significant positive response during the contingency management intervention phase. Study 2 used the same design as Study 1 except that the 52 participants were randomized into reinforcement groups that received either the variable rate of reinforcement as in Study 1 or a fixed value reinforcer of 3.25 dollars. As in Study 1, Poor Attenders significantly improved counseling attendance during the intervention. There were no differences between the variable and fixed reinforcement groups. Overall, results suggest that targeting Poor Attenders with contingency management techniques may be a cost-effective method of improving counseling attendance. Targeting Poor Attenders early in treatment may be especially important for improving treatment outcomes. [ABSTRACT FROM AUTHOR]

(R)- and (S)-Methadones and levo-α-acetylmethadol (LAAM) have been synthesised starting from lipase-catalysed acylation of dimethylaminopropan-2-ol. An approach to the synthesis of (R)-bufuralol is also presented. [Copyright &y& Elsevier]

l-α-acetylmethadol is a long-acting narcotic analgesic that is used in the treatment of opiate addiction. However, the drug has been associated with cases of QT interval prolongation and ventricular arrhythmia. To understand the mechanism underlying these clinical findings, we examined the effects of l-α-acetylmethadol on the cloned human cardiac K+ channels HERG (human ether-a-go-go-related gene), KvLQT1/minK and Kv4.3. Using patch clamp electrophysiology, we found that l-α-acetylmethadol inhibited HERG channel currents in a voltage-dependent manner displaying an IC50 value of 3 μM. The major active metabolite of l-α-acetylmethadol, noracetylmethadol, inhibited HERG with an estimated IC50 values of 12 μM. l-α-acetylmethadol had little or no effect on Kv4.3 or KvLQT1/minK K+ channel currents at concentration up to 10 μM. We conclude that the proarrhythmic effects of l-α-acetylmethadol are due to specific blockade of the HERG cardiac K+ channel and that its active metabolite noracetylmethadol may provide a safer alternative in the treatment of opiate addiction. [Copyright &y& Elsevier]

Rationale: LAAM (α-l-acetylmethadol) is a derivative of the synthetic mu-opiate agonist methadone and is one of the four isomers of acetylmethadol. Methadone and LAAM have similar pharmacological properties and both are approved medications for the treatment of heroin dependency disorders. Few studies have reported on the pharmacology of acetylmethadol's other isomers and most of these have focused on their potential analgesic activity. Objectives: The purpose of the present investigation was to examine the discriminative stimulus effects of LAAM, the other isomers of acetylmethadol, and methadone in rats trained to discriminate heroin from water, and to compare the duration of the discriminative stimulus effects of heroin, methadone, and LAAM. Methods: Long-Evans rats were trained to discriminate 0.3 mg/kg heroin from water under a fixed ratio 10 (FR10) schedule of food reinforcement. Doseresponse functions for heroin, methadone, LAAM, three other isomers of acetylmethadol: α-d-acetylmethadol, βd-acetylmethadol, β-l-acetylmethadol, and its precursor, β-l-methadol were examined. Additionally, the time course effects for heroin, methadone, and LAAM were examined. Results: LAAM and methadone dose-dependently occasioned heroin-like discriminative stimulus effects. Two of acetylmethadol's isomers, α-d-acetylmethadol and β-d-acetylmethadol, were more potent than LAAM in producing heroin-like effects. The β-l-methadol precursor and β-l-acetylmethadol did not fully substitute for heroin's discriminative stimulus. LAAM elicited heroin-like discriminative stimulus effects for at least 6 h and generated partial generalization up to 36 h following administration. Conclusions: Methadone, LAAM, β-d-acetylmethadol and α-d-acetylmethadol, but not β-l-acetylmethadol and β-l-methadol evoke heroinlike discriminative stimulus effects. [ABSTRACT FROM AUTHOR]

Levo-alpha-acetylmethadol (LAAM) pharmacotherapy was offered to twelve patients who continued illicit opioid abuse after $ eleven months in methadone maintenance treatment. After 6-8 weeks on LAAM, plasma concentrations of the norLAAM metabolite varied significantly by LAAM dosing day, plasma adrenocorticotropin (ACTH) concentrations were significantly increased compared to methadone, and two of the seven subjects remaining inLAAMtreatment were free of illicit opioids and nonprescribed methadone. After one year, one of five remaining subjects was using illicit opioids, and three were using nonprescribed methadone. While subject acceptance of LAAM was high, subjects were not in a “steady-state,” with evidence of ongoing illicit opioid abuse. [ABSTRACT FROM PUBLISHER]

Mated Crl:CD VAF/Plus female rats, in a range-finding study (n = 5-6 per dose) and a subsequent definitive study (n = 30 per dose) were used to determine the developmental toxicity, including the teratogenic potential of levo-alpha-acetylmethadol (LAAM) hydrochloride, in tolerant rats. Tolerance was induced by initially administering the drug by gavage (10 ml/kg) at 2 mg/kg/day and increasing the dose every 2 weeks for 12 weeks until the doses of 2, 6, 9, 12, and 15, or 2, 6, and 12 mg/kg/day were achieved in the range-finding or definitive study, respectively. Females were then mated to stock males and treated throughout mating and gestation. Controls received distilled water on a similar regimen. The range-finding experiment was used for initial clinical evaluations and to determine tissue concentrations of LAAM and metabolites. In plasma, liver, and brain collected from dams and fetuses pooled by litter on gestation day 20, LAAM and its two N-demethylated metabolites, norLAAM and dinorLAAM, showed dose-dependent increases in concentration and in tissue to plasma ratios. Tissue to dam plasma ratios were highest in dam liver (17-60), intermediate in fetal liver (3-16), and fetal brain (3-14), and lowest in dam brain (0.8-5.6) and fetal plasma (0.3-2.1). In the definitive study, caesarean section examinations were performed following euthanization on gestation day 20 on all surviving females followed by teratologic examination of the fetuses. Drug-related outcomes, including increased activity, secondary hair loss, scabbing, focal swelling, and material around the nose, were exhibited by all groups receiving LAAM. Maternal toxicity was evident as decreased body weights, with maximum reduction at the 6-mg/kg/day dose, and reduction in feed consumption. There was also evidence of developmental toxicity in the form of postimplantation losses at all doses of LAAM. There were no deaths attributable to LAAM. No grossly observable visceral or skeletal anomalies related to LAAM were observed in the fetuses. In conclusion, the no-observable-effect level when administered to tolerant rats was less than 2 mg/kg/day with regard to clinical signs, body weight, body weight gain, and feed consumption, and with regard to developmental toxicity as reflected by postimplantation losses. Despite maternal and developmental toxicity, there was no evidence of selective fetal toxicity or teratogenic activity attributable to LAAM. [ABSTRACT FROM AUTHOR]

This study examines prevalence rates for DSM-III-R anxiety and affective disorders in three follow-up samples of opioid addicts who were treated with methadone maintenance. At least one anxiety disorder was diagnosed in 55% of the total sample. Affective disorders were found in 58%. At least one anxiety disorder coexisted with at least one affective disorder in 36% of the sample. The research demonstrates that opiate addiction in this sample is most often associated with other comorbid psychopathology. It suggests a need for thorough assessment for general psychopathology in opioid addicts entering addiction treatment, especially assessment for anxiety and affective, disorders. It also suggests the need for treatment that focuses on diagnosed mental disorders in addition to drug counseling for the substance abuse disorder. [ABSTRACT FROM AUTHOR]

Aims. LAAM, a long-acting opioid agonist, was approved by the US Food and Drug Administration in 1993 for use in licensed narcotic treatment programs. These programs have the exclusive authority in the United States to dispense methadone and LAAM for the treatment of opiate dependence. The purpose of this report is to describe the course of LAAM's implementation and to document some of the factors that have influenced the time course and extent of this process . Design. Narcotic treatment programs approved for LAAM use were contacted by telephone at three timepoints following the FDA approval of LAAM in 1993 . Findings. Regulatory hurdles have been the most significant factor in slowing the use of LAAM. Some clinics have enthusiastically moved LAAM into mainstream use with great success. At other clinics LAAM implementation has been impeded by staff resistance and management reluctance. Some specific clinical practices, such as provision of adequate dose levels and flexible dosing practices, appear to be associated with superior clinical response, but issues of staff and organizational attitude toward the new medication are probably the most important impediments to a more positive response . Conclusions. The tasks involved with introducing a new opiate agonist treatment into mainstream use in the United States are numerous and complex. Clinical policies, fiscal issues and regulatory factors must all be addressed. The introduction of LAAM into the treatment system provides some useful lessons as other new addiction pharmacotherapies are moved into mainstream use. [ABSTRACT FROM AUTHOR]