Amines

Gabapentin, a γ-aminobutyric acid (GABA) analogue anticonvulsant, is also an effective analgesic agent in neuropathic and inflammatory, but not acute, pain systemically and intrathecally. Other clinical indications such as anxiety, bipolar disorder, and hot flashes have also been proposed. Since gabapentin was developed, several hypotheses had been proposed for its action mechanisms. They include selectively activating the heterodimeric GABA B receptors consisting of GABA B1a and GABA B2 subunits, selectively enhancing the NMDA current at GABAergic interneurons, or blocking AMPA-receptor-mediated transmission in the spinal cord, binding to the L-α-amino acid transporter, activating ATP-sensitive K + channels, activating hyperpolarization-activated cation channels, and modulating Ca 2+ current by selectively binding to the specific binding site of [ 3 H]gabapentin, the α 2 δ subunit of voltage-dependent Ca 2+ channels. Different mechanisms might be involved in different therapeutic actions of gabapentin. In this review, we summarized the recent progress in the findings proposed for the antinociceptive action mechanisms of gabapentin and suggest that the α 2 δ subunit of spinal N-type Ca 2+ channels is very likely the analgesic action target of gabapentin.

Intractable central post-stroke pain (CPSP) is one of the most common sequelae of stroke, but has been inadequately studied to date. In this study, we first determined the relationship between the lesion site and changes in mechanical or thermal pain sensitivity in a rat CPSP model with experimental thalamic hemorrhage produced by unilateral intra-thalamic collagenase IV (ITC) injection. Then, we evaluated the efficacy of gabapentin (GBP), an anticonvulsant that binds the voltage-gated Ca(2+) channel α2δ and a commonly used anti-neuropathic pain medication. Histological case-by-case analysis showed that only lesions confined to the medial lemniscus and the ventroposterior lateral/medial nuclei of the thalamus and/or the posterior thalamic nucleus resulted in bilateral mechanical pain hypersensitivity. All of the animals displaying CPSP also had impaired motor coordination, while control rats with intra-thalamic saline developed no central pain or motor deficits. GBP had a dose-relat...

It is critically important to accurately determine histidine since it is an indicator for many diseases when at an abnormal level. Here, an inexpensive and simple method using an amine-functionalized magnetic nanoparticle-based Ni 2+ −histidine affinity pair system was developed for highly sensitive and selective detection of histidine in human urine by photochemical vapor generation atomic spectrometry. Ni 2+ was first bound to the amine groups of the amine-functionalized magnetic nanoparticles and then liberated to solution via the highly specific interaction between the histidine and Ni 2+ in the presence of histidine. The liberated histidine−Ni 2+ complex was exposed to UV irradiation in the presence of formic acid to form gaseous nickel tetracarbonyl, which was separated from the sample matrix and determined by atomic absorption/fluorescence spectrometry. Compared to other methods, this approach promises high sensitivity, simplicity in design, and convenient operation. The need for organic solvents, enzymatic reactions, separation processes, chemical modification, expensive instrumentations, and sophisticated and complicated pretreatment is minimized with this strategy. A limit of detection of 1 nM was obtained and provided tens-to-hundreds of fold improvements over that achieved with conventional methods. The protocol was evaluated by analysis of several urine samples with good recoveries and showed great potential for practical application.

Numerous studies have suggested relationships between myeloperoxidase, inflammation, and atherosclerosis. MPO-derived reactive chlorinating species (RCS) attack membrane plasmalogens releasing ␣-chloro-fatty aldehydes (␣-Cl-FALDs) including 2-chlorohexadecanal (2-ClHDA). The molecular targets of ␣-Cl-FALDs are not known. The current study demonstrates 2-ClHDA adducts with ethanolamine glycerophospholipids and Fmoc-lysine. Utilizing electrospray ionization mass spectrometry, chlorinated adducts were observed that are apparent Schiff base adducts. Reduction of these Schiff base adducts with sodium cyanoborohydride resulted in a novel, stable adduct produced by the elimination of HCl. NMR further confirmed this structure. 2-ClHDA adducts with ethanolamine glycerophospholipids were also substrates for phospholipase D (PLD). The hydrolysis products were derivatized to pentafluorobenzoyl esters, and further structurally confirmed by GC-MS. Multiple molecular species of 2-ClHDA-N-modified ethanolamine glycerophospholipids were observed in endothelial cells treated with 2-ClHDA. These results show novel Schiff base adducts of ␣-Cl-FALDs with primary amines, which may represent an important fate of ␣-Cl-FALDs.

LysCel is a cellulose-based material in which L-lysine molecules are grafted with their amino side chains to the cellulose hydroxyl groups. This modification increases considerably the mechanical strength and resistance of cellulosic structures toward water. It has been attributed to the formation of double salt bridges between lysine aminocarboxyl groups in the zwitterionic state. In order to characterize this unusual structure, we have performed high-resolution solid-state 15 N and 13 C CPMAS NMR experiments on LysCel samples labeled with 15 N in the R-position or ε-position. Furthermore, 13 C-15 N REDOR experiments were performed on LysCel where half of the aminocarboxyl groups were labeled in 1-position with 13 C and the other half in R-position with 15 N. The comparison with the 13 C and 15 N chemical shifts of L-leucine lyophilized at different pH shows that the aminocarboxyl groups of LysCel are indeed zwitterionic. The REDOR experiments indicate distances of about 3.5 Å between the carboxyl carbon and the nitrogen atoms of different aminocarboxyl groups, indicating that the latter are in close contact with each other. However, the data are not compatible with isolated aminocarboxyl dimers but indicate the assembly of zwitterionic aminocarboxyl dimers either in a flat ribbon or as tetramers, exhibiting similar intra-and interdimer 13 C · · · 15 N distances. This interaction of several aminocarboxyl groups is responsible for the zwitterionic state, in contrast to the gas phase, where amino acid dimers exhibiting two OHN hydrogen bonds are neutral.

A novel biocompatible chitosan passivated manganese doped zinc sulfide (Mn doped ZnS) nanophosphor has been synthesized through a simple aqueous precipitation reaction. Upon excitation with ultraviolet light, the quantum dots (QDs) emit an orange luminescence peaking at 590 nm, which is visible to the naked eye. These chitosan coated Mn doped ZnS QDs can have potential applications in bio-labeling, particularly in fluorescence-based imaging. One of the envisioned applications of these QDs is in improving the conventional, organic dye-reliant Fluorescence in situ Hybridization (FISH) technique, a widely used method for microbial detection. Here we demonstrate that the chitosan-capped Mn doped ZnS QDs are suitable for this purpose.

Aromatic amines represent one of the most important classes of industrial and environmental chemicals: many of them have been reported to be powerful carcinogens and mutagens, and/or hemotoxicants. Their toxicity has been studied also with quantitative structure-activity relationship (QSAR) methods: these studies are potentially suitable for investigating mechanisms of action and for estimating the toxicity of compounds lacking experimental determinations. In this paper, we first summarized the QSAR models for the rodent carcinogenicity of the aromatic amines. The gradation of potency of the carcinogenic amines depended firstly on their hydrophobicity, and secondly on electronic (reactivity, propensity to be metabolically transformed) and steric properties. On the contrary, the difference between carcinogenic and non-carcinogenic aromatic amines depended mainly on electronic and steric properties. These QSARs can be used directly for estimating the carcinogenicity of aromatic amines. A two-step prediction is possible: (1) estimation of yes/no activity; (2) if the answer from step 1 is yes, then prediction of the degree of potency. The QSARs for rodent carcinogenicity were put in a wider context by comparing them with those for: (a) Salmonella mutagenicity; (b) general toxicity; (c) enzymatic reactions; (d) physical-chemical reactions. This comparative QSAR exercise generated a coherent global picture of the action mechanisms of the aromatic amines. The QSARs for carcinogenicity were similar to those for Salmonella mutagenicity, thus pointing to a similar mechanism of action. On the contrary, the general toxicity QSARs (both in vitro and in vivo systems) were mostly based on hydrophobicity, pointing to an aspecific mechanism of action much simpler than that for carcinogenicity and mutagenicity. The oxidation of the amines (first step in the main metabolic pathway leading to carcinogenic and mutagenic species) had identical QSARs in both enzymatic and physical-chemical systems, thus providing evidence for the link between simple chemical reactions and those in biological systems. The results show that it is possible to generate mechanistically and statistically sound QSAR models for rodent carcinogenicity, and indirectly that the rodent bioassay is a reliable source of good quality data.

The spectroscopic characteristics of the solid charge-transfer molecular complexes (CT) formed in the reaction of the electron donor 4-(aminomethyl) piperidine (4AMP) with the σ-acceptor iodine and the π-acceptors 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), 2,4,4,6-tetrabromo-2,5-cyclohexadienone (TBCHD) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) have been studied in chloroform at 25°C. These were investigated through electronic, infrared spectra and thermal analysis as well as elemental analysis. The results show that the formed solid CT-complexes have the formulas [(4AMP)I](+)I3(-), [(4AMP)(DDQ)2] and [(4AMP)(TBCHD)] while in the case of 4AMP-TCNQ reaction, a short-lived CT complex is formed followed by rapid N-substitution by TCNQ forming the final reaction product 7,7,8-tricyano-8-aminomethylpiperidinylquinodimethane [TCAMPQDM] in full agreement with the known reaction stoichiometries in solution as well as the elemental measurements and the thermal analysis confirmed the structure of the obtained compounds. The formation constant kCT, molar extinction coefficient εCT, free energy change ΔG(0) and CT energy ECT have been calculated for the CT-complexes [(4AMP)I](+)I3(-), [(4AMP)(DDQ)2] and [(4AMP)(TBCHD)].

Synthetic approaches to gabapentin bioconjugates that overcome the tendency of gabapentin to cyclize into its c-lactam are studied. Gabapentin was converted by N-acylation at its N-terminus into di-, tri-, and tetrapeptides (L-Ala-Gbp, L-Val-Gbp, L-Ala-L-Phe-Gbp, Gly-L-Ala-b-Ala-Gbp). Carboxyl-activated Boc-protected gabapentin was used to N-, O-, and S-acylate small peptides and hormones to give conjugates that could also provide prodrugs containing conformationally constrained gabapentin units. (A.R. Katritzky). NH O 1 2a O OH H 2 N Scheme 1. Intramolecular cyclization of gabapentin (Gbp) into 2-azaspiro[4,5]decan-3-one 2a.

Purpose: Evaluate the clinical comparability of new antiepileptic drugs (AEDs) in partial refractory epilepsy. Methods: Systematic review of randomized trials (RCTs) comparing a new AED (add-on treatment) with placebo or another AED. Primary outcomes: responder ( ‡50% seizure reduction) and withdrawal (tolerability) rates. Pooled estimates of odds ratios (ORs) and number needed treat/harm (NNT/NNH) taking into account baseline risk were derived by random-effects meta-analysis. Adjusted frequentist indirect comparisons between AEDs were estimated. Key Findings: Sixty-two placebo-controlled (12,902 patients) and eight head-to-head RCTs (1,370 patients) were included. Pooled ORs for responder and withdrawal rates (vs. placebo) were 3.00 [95% confidence interval (CI) 2.63-3.41] and 1.48 (1.30-1.68), respectively. Indirect comparisons of responder rate based on relative measurements of treatment effect (ORs) favored topiramate (1.52; 1.06-2.20) in comparison to all other AEDs, whereas gabapentin (0.67; 0.46-0.97) and lacosamide (0.66; 0.48-0.92) were less efficacious, without significant heterogeneity. When analyses were based on absolute estimates (NNTs), topiramate and levetiracetam were more efficacious, whereas gabapentin and tiagabine were less efficacious. Withdrawal rate was higher with oxcarbazepine (OR 1.60; 1.12-2.29) and topiramate (OR 1.68; 1.07-2.63), and lower with gabapentin (OR 0.65; 0.42-1.00) and levetiracetam (OR 0.62; 0.43-0.89). Significance: The differences found are of relatively small magnitude to allow a definitive conclusion about which new AED(s) has superior effectiveness. This uncertainty probably reflects the limitations of conclusions based on indirect evidence. The process of pharmacologic clinical decision making in partial refractory epilepsy probably depends more on other aspects, such as individual patient characteristics and pharmacoeconomics, than on available controlled randomized evidence.

: Pregabalin (PGB) is an L-type, voltage-dependent, calcium-channel blocker, useful for the treatment of neuropathy pain and some forms of seizures. We report the case of a 64-year-old woman who developed full-blown parkinsonism after PGB administration. : A female patient who developed diabetic sensory-motor polyneuropathy began treatment with gabapentin 300 mg plus amitriptyline 25 mg at the age of 56 years, with good tolerance. Eight years later, PGB 150 mg was added, after 3 months she developed a parkinsonian-like syndrome with axial symptoms, bilateral symmetric postural tremor, bradykinesia, and rigidity in both upper and lower limbs. Unified Parkinson's Disease Rating Scale motor score was 27/108 points at this time. Clear link to PGB introduction as well as symmetric limb involvement and symptom intensity made us suspect drug-induced parkinsonism. Pregabalin was withdrawn. Six months later, the patient had almost completely recovered; her Unified Parkinson's Disease Rating Scale motor score dropped to 4/108; and 3 months after that, it was 0. : Although some cases of tremor were reported in clinical trials on PGB, to our knowledge, this is the first report of full-blown parkinsonism associated with PGB use. Vigilance of PGB-treated patients is recommended.

The joint toxicity of nonylamine and decylamine and of atrazine and decylamine was evaluated in assays with the green alga Selenastrum capricornutum based on an isobologram method. In this method, curves of constant response, isoboles, are plotted versus concentrations of two toxicants. The response parameter was growth rate based on biomass, and several response levels were used. Dose-response curves were developed for dilution series using fixed ratios between concentrations in toxic units of the compounds. Probit and Weibull dose-response curves were then determined by nonlinear regression. A model for isoboles for partially similar action was used when applicable. The no-effect concentration (NEC or EC0) was estimated based on a newly proposed model containing median effective concentration (EC50) and EC0 as explicit variables. Results show that nonylamine and decylamine are nearly concentration additive at EC50 and EC10 (similarity parameter ϭ 0.70-0.76) and to a lesser extent at EC0. By contrast, the mixtures of atrazine and decylamine show antagonism in that atrazine acts as an antidote to decylamine. The shapes of these isoboles are independent of response level. The EC50 values (mg/L) for chemicals acting singly were 0.090 (nonylamine), 0.039 to 0.044 (decylamine), and 0.225 (atrazine). In order to determine NEC effectively, the level of inhibition must be fairly low, with observed growth rates between 0.6 and 1.0 times the average growth rate of the controls.

A rapid, sensitive and accurate high-performance liquid chromatographic method with UV detection was developed and validated for the quantification of gabapentin in human plasma. Gabapentin was quantified using pre-column derivatization with 1-fluoro-2,4-dinitrobenzene following protein precipitation of plasma with acetonitrile. Amlodipine was used as internal standard. The chromatographic separation was carried out on a Nova-Pak C 18 column using a mixture of 50 mM NaH 2 PO 4 (pH = 2.5)-acetonitrile (30:70, v/v) as mobile phase with UV detection at 360 nm. The flow rate was set at 1.5 ml/min. The method was linear over the range of 0.05-5 g/ml of gabapentin in plasma (r 2 > 0.999). The within-day and between-day precision values were in the range of 2-5%. The limit of quantification of the method was 0.05 g/ml. The method was successfully used to study the pharmacokinetics of gabapentin in healthy volunteers.

This work describes the controlled immobilization of a recognized allergen, beta-lactoglobulin, onto gold transducers with the aim of optimizing the elaboration of a biosensor directed against allergen-produced antibodies. This protein was immobilized on both amine-and acid-terminated thiol self-assembled monolayers, and the influence on its affinity to a specific IgG was investigated. For amine-terminated layers, the -lactoglobulin was immobilized via its surface acid functions implying an activation step with 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride/ester of N-hydroxysuccinimide (EDC-NHS). Conversely, the grafting on acid-terminated layer takes advantage of the accessible amine groups that react with the activated acidalkylthiols. The resulting layers of -lactoglobulin were then submitted to various concentrations of rabbit serum containing -lactoglobulin specific rabbit immunoglobulin (rIgG), and the antigen/antibody affinity was evaluated using modulated polarization-infrared absorption spectroscopy (PM-IRRAS) and Fourier transform surface plasmon resonance (FT-SPR). Even though for similar concentration, the amount of adsorbed -lactoglobulin was identical on both surfaces, atomic force microscopy (AFM) images showed a better dispersion for amine-terminated layers. Moreover, the affinity to specific IgG, estimated under static conditions by PM-IRRAS and under dynamic conditions by SPR, was different. Grafting -lactoglobulin via its acid groups gave an affinity constant 3 times higher than its immobilization via its amine groups despite the fact that the amount of accessible recognition sites appeared to be similar for both systems. This work underlines the importance of the involved chemical groups upon protein immobilization on their biological activity and will be essential for the construction of nondirect biosensors for detecting specific immunoglobulin E (IgE) of allergens.

A systematic survey was made of some 25 amines, including several newly synthesized ones, to assess their inhibitory effect in the enzymatic crosslinking of fibrin. Compounds were selected from the point of view of different basicities and side-chain substitutions.

Mutagenic heterocyclic amines (HAs) are formed at low levels during cooking of meat and fish, and some of them are considered to be possible human carcinogens. The formation of HAs may be affected by the presence of synthetic or naturally occurring antioxidants. In the present study the effect of virgin olive oil (VOO) phenolic compounds, identified and quantified by LC-MS, on the formation of HAs in a model system was evaluated. An aqueous solution of creatinine, glucose, and glycine was heated in the presence of two samples of VOO differing only in the composition of phenolic compounds. The addition of VOO to the model system inhibited the formation of 2-amino-3methylimidazo[4,5-f]quinoxaline (IQx), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) by between 30 and 50% compared with the control. Fresh-made olive oil, which contained a high amount of dihydroxyphenylethanol derivatives, inhibited HA formation more than a 1-year-old oil did. The inhibition of HA formation was also verified using phenolic compounds extracted from VOO.

Medical error is now clearly established as one of the most significant problems facing the American health care system. Anecdotal evidence, studies of human cognition, and analysis of high-reliability organizations all predict that despite excellent training, human error is unavoidable. When an error occurs and is recognized, providers have a duty to disclose the error. Yet disclosure of error to patients, families, and hospital colleagues is a difficult and/or threatening process for most physicians. A more thorough understanding of the ethical and social contract between physicians and their patients as well as the professional milieu surrounding an error may improve the likelihood of its disclosure. Key among these is the identification of institutional factors that support disclosure and recognize error as an unavoidable part of the practice of medicine. Using a case-based format, this article focuses on the communication of error with patients, families, and colleagues and grounds error disclosure in the cultural milieu of medial ethics.

Despite indications that GA (glutaraldehyde)-crosslinked tissues remain prone to long-term degradation and calcification, it is still the reagent of choice in the fixation of bioprosthetic heart valves. We have shown previously that increased GA concentrations and diamine extension of cross-links with lysine incorporation lead to mitigated in vivo calcification, mainly of porcine aortic-wall tissue. The present study was performed to assess the correlation between the cross-link density of all three commonly used tissue types [PW (porcine aortic wall), PL (porcine aortic leaflet) and BP (bovine pericardium)] and tissue calcification in the subcutaneous rat model after GA treatment with or without lysine. The effect of lysine enhancement, and increased GA concentration in the presence of lysine, resulted in significant increases in tissue cross-linking in all three tissue types. Although increased GA concentration on its own resulted in decreased calcification without an increase in cross-link density, overall positive correlations were found between denaturation temperature and RPD (resistance towards protease degradation) [correlation coefficient (ρ) values: ρ PW = 0.922, ρ PL = 0.783 and ρ BP = 0.955], whereas negative correlations existed between RPD and calcification (ρ PW = −0.836, ρ PL = −0.929 and ρ BP = −0.579). The combination of lysine enhancement and an increase in GA concentration from 0.2 to 3 % resulted in 79, 44 and 56 % decreases in calcification in PW, PL and BP. In the case of BP, a decrease in calcification of 81 % could be achieved merely by adding lysine extension to low-concentration (0.2 %) GA cross-linking. Thus it is concluded that the increase in cross-link density achieved by lysine incorporation, and by increased GA concentration in the presence of lysine, results in significant and marked decreases in calcification of all three types of tissues commonly used in bioprosthetic heart valves.

A series of 3-aminoquinazolinediones was synthesized and evaluated for its antibacterial and DNA gyrase activity. The SAR around the quinazolinedione core was explored and the optimal substitutions were combined to give two compounds, 2r and 2s, with exceptional enzyme potency (IC 50 = 0.2 lM) and activity against Gram-positive organisms (MIC's = 0.015-0.06 l g/mL).

A gas chromatography-mass spectrometry (GC-MS) method has been proposed for the simultaneous determination of aliphatic and aromatic amines in indoor and outdoor air samples. The method includes pre-concentration of the compounds by percolating the air samples through the acidic solution, ion-pair extraction with bis-2-ethylhexylphosphate (BEHPA), derivatisation of compounds with isobutyl chloroformate (IBCF) and their GC-MS analysis. Aliphatic and aromatic amines were isolated from aqueous samples using BEHPA as ion-pair reagent and derivatised with IBCF for their chromatographic analysis. Aliphatic and aromatic amines were then analysed with GC-MS in both electron impact (EI) and positive and negative ion chemical ionisation (PNICI) mode as their isobutyloxycarbonyl (isoBOC) derivatives. The obtained recoveries ranged from 75.6 to 96.8% and the precision of this method, as indicated by the relative standard deviations (R.S.D.) was within the range of 1.0-4.4%. The detection limits obtained from calculations by using GC-MS results based on S/N: 3 were within the range of 0.08-0.01 ng/m 3 .

Arylamines and aminopyridines form a class of potentially genotoxic impurities (PGIs) that can be present at trace levels in active pharmaceutical ingredients (APIs). A generic method was developed that allows the analysis of a selected set of these solutes at sub-ppm level relative to the drug substance. A highly concentrated solution of the pharmaceutical compound is analyzed by LC-MS using a single quadrupole mass spectrometer in the selected ion monitoring (SIM) mode. Since a number of target compounds show little or no retention in the reversed-phase LC setup, a fast and simple derivatization procedure using hexylchloroformate was applied. The amide derivatives of the PGI result in a higher molecular weight (more specific ion for SIM) and better chromatographic behavior. The methodology, consisting of a dual run on respectively a non-derivatized and a derivatized sample, was validated and applied to a selection of pharmaceutical substances. The method was found to be sufficiently sensitive and robust and is applicable in a QA/QC environment.

Quantitative analysis of target compounds with liquid chromatography atmospheric pressure ionization mass spectrometry is sometimes hampered by adduct formation. In these situations, cationization with alkali metal ions instead of proton addition is often observed in the positive mode. This work studies the process of adduct formation and investigates potential strategies to control this phenomenon. Paclitaxel, a pharmaceutical chemotherapeutic agent, was used as a model compound. Electrospray (ESI), atmospheric pressure chemical ionization (APCI) and sonic spray ionization (SSI) are evaluated and compared. The work was performed on two different instruments, allowing to evaluate different ionization behavior for different source design for electrospray, if any. Different mobile phase additives were compared, including acetic acid, formic acid, ammonium formate and a range of primary amines. Continuous infusion was used for a fast screening, to detect optimal conditions. These were then further investigated in detail by LC-MS. The results indicate that electrospray is the more sensitive interface for this compound on the investigated apparatus. Unacceptable quantitative data were acquired without additives in the mobile phase. Generally, additives increased the reproducibility significantly. A response of mainly one ion was achieved with dodecylamine/acetic acid and acetic acid/sodium acetate. The data also point out the importance of evaluating adduct formation for compounds prone to this phenomenon during method development, especially in view of accurate quantitation.

FeCl 2 catalyzes the oxidative C-C cross-coupling of tertiary amines with terminal alkynes into propargylamines using (t-BuO) 2 as oxidant. The reaction can be applied to aromatic and aliphatic amines and alkynes without solvent. High chemoselectivity for aminomethyl groups is due to a steric factor.

Biochemically modified proteins have attracted significant attention due to their widespread applications as biomaterials. For instance, chemically modified gelatin derivatives have been widely explored to develop hydrogels for tissue engineering and regenerative medicine applications. Among the reported methods, modification of gelatin with methacrylic anhydride (MA) stands out as a convenient and efficient strategy to introduce functional groups and form hydrogels via photopolymerization. Combining light-activation of modified gelatin with soft lithography has enabled the materialization of microfabricated hydrogels. So far, this gelatin derivative has been referred to in the literature as gelatin methacrylate, gelatin methacrylamide, or gelatin methacryloyl, with the same abbreviation of GelMA. Considering the complex composition of gelatin and the presence of different functional groups on the amino acid residues, both hydroxyl groups and amine groups can possibly react with met...

A new bacterial test system for detection of genotoxic compounds was developed, based on two new Salmonella typhimurium tester strains, TGO1 and TGO2. Both strains contain a gene fusion between a strong SOS-promotor, P cda , and the gfp gene, which allows detection of genotoxic compounds that induce the SOS response. SOS induction was detected by means of flow cytometry. TGO1 showed an increased sensitivity to N-methyl-N -nitro-N-nitrosoguanidine compared with a previously developed strain, which had an Escherichia coli strain as host instead of S. typhimurium.

Neural networks were trained using whole ion mobility spectra from a standardized database of 3137 spectra for 204 chemicals at various concentrations. Performance of the network was measured by the success of classification into ten chemical classes. Eleven stages for evaluation of spectra and of spectral pre-processing were employed and minimums established for response thresholds and spectral purity. After optimization of the database, network, and pre-processing routines, the fraction of successful classifications by functional group was 0.91 throughout a range of concentrations. Network classification relied on a combination of features, including drift times, number of peaks, relative intensities, and other factors apparently including peak shape. The network was opportunistic, exploiting different features within different chemical classes. Application of neural networks in a two-tier design where chemicals were first identified by class and then individually eliminated all but one false positive out of 161 test spectra. These findings establish that ion mobility spectra, even with low resolution instrumentation, contain sufficient detail to permit the development of automated identification systems.

3 , all of which contain the linear or nearly linear two-coordinate [Ag(NH 3 ) 2 ] + ion. The 109 Ag CP/MAS NMR spectra show centrebands and associated spinning sideband manifolds typical for systems with moderately large shielding anisotropy, and splittings due to indirect 1 J( 109 Ag, 14 N) spin-spin coupling. Spinning sideband analysis was used to determine the 109 Ag shielding anisotropy and asymmetry parameters 1s and h from these spectra, yielding anisotropies in the range 1500-1600 ppm and asymmetry parameters in the range 0-0.3. Spectra were also recorded for 15 N and (for the selenate) 77 Se. In all cases the number of resonances observed is as expected for the crystallographic asymmetric units. The crystal structure of the selenate is reported for the first time. One-bond ( 107,109 Ag, 15 N) coupling constants are found to have magnitudes in the range 60-65 Hz. Density functional calculations of the Ag shielding tensor for model systems yield results that are in good agreement with the experimentally determined shielding parameters, and suggest that in the solid compounds 1s and h are reduced and increased, respectively, from the values calculated for the free [Ag(NH 3 ) 2 ] + ion (1920 ppm and 0, respectively), primarily as a result of cation-cation interactions, for which there is evidence from the presence of metal-over-metal stacks of [Ag(NH 3 ) 2 ] + ions in the solid-state structures of these compounds.