Reactions of CF3-enones with arenes under superelectrophilic activation: a pathway to trans-1,3-diaryl-1-CF3-indanes, new cannabinoid receptor ligands

4-Aryl-1,1,1-trifluorobut-3-en-2-ones ArCH[double bond, length as m-dash]CHCOCF3 (CF3-enones) react with arenes in excess of Brønsted superacids (TfOH, FSO3H) to give, stereoselectively, trans-1,3-diaryl-1-trifluoromethyl indanes in 35-85% yields. The reaction intermediates, the O-protonated ArCH[double bond, length as m-dash]CHC(OH(+))CF3 and the O,C-diprotonated ArHC(+)CH2C(OH(+))CF3 species, have been studied by means of (1)H, (13)C, (19)F NMR, and DFT calculations. Both types of the cations may participate in the reaction, depending on their electrophilicity and electron-donating properties of the arenes. The formation of CF3-indanes is a result of cascade reaction of protonated CF3-enones to form chemo-, regio- and stereoselectively three new C-C bonds. The obtained trans-1,3-diaryl-1-trifluoromethyl indanes were investigated as potential ligands for cannabinoid receptors CB1 and CB2 types. The most potent compound showed sub-micromolar affinity for both receptor subtypes with a 6-fold selectivity toward the CB2 receptor with no appreciable cytotoxicity toward SHSY5Y cells.

Der Redacteur der schwarzgelben Geißel: Die schwarzgelbe Fahne. Zusammenlauf: Entrüstung wegen dieses Reactions-Versuches: Der Redacteur der Geißel hat sich durch Verbreitung seiner schwarzgelben Tendenzen ...

Welsch (Projektbearbeiter): Meldung über das gewaltsame Eindringen in die Redaktion des Blattes 'Die Geißel' aus Anlaß der dortigen Hissung des Symbols der Reaktion, einer 'schwarzgelben' (eigentlich schwarz-goldenen) Fahne. Grundsätzlich positive Haltung zu den Geschehnissen

Flare-up reactions in severe drug hypersensitivity: infection or ongoing T-cell hyperresponsiveness

"Flare-up" reactions are late manifestations of severe T-cell-mediated drug hypersensitivity reactions. Management is anti-inflammatory treatment and avoiding unnecessary medicines. Symptoms like fever, lymph node swelling, and blood count abnormalities may lead to confusion with bacterial infections. For prompt recognition it is important to keep the differential diagnosis in mind.

The role of patch testing in the management of oral lichenoid reactions.

BACKGROUND AND OBJECTIVES The distinction of oral lichenoid reactions from oral lichen planus may be difficult in a clinical setting. Our aims were to ascertain the utility of patch testing to confirm the association of oral lichenoid reactions with dental restorations and to identify the benefits of replacement of restorations, primarily made of amalgam. METHODS Patients seen in an oral medicine unit over a 10-year period diagnosed with oral lichenoid reactions, with oral lichen planus resistant to treatment or with atypical lichenoid features were included in this study. All had been subjected to skin patch testing. Histopathology reports blinded to patch test results were scrutinized. Patch-test-positive subjects were advised to have their restorations replaced. All were followed up to determine disease resolution for at least 3 months thereafter. RESULTS Among 115 patients, 67.8% patients reacted positive to a dental material and nearly a quarter to mercury or amalgam. No correlation was found between pathology and skin patch testing results (P = 0.44). A total of 87 patients were followed up in clinic, and among 26 patch-test-positive patients who had their amalgam fillings replaced, moderate to complete resolution was noted in 81%. CONCLUSIONS Skin patch testing is a valuable tool to confirm clinically suspected oral lichenoid reactions. Pathology diagnoses of oral lichenoid reactions did not correlate with patch test results. Prospective studies are needed to ascertain that a clinically suspected oral lichenoid reaction with a positive patch test result may resolve after the replacement of amalgam fillings.

Therapists under influence – Patient strategies and therapist reactions

Therapists having a positive influence on patients is a common view of psychotherapy. There is, however, an influence of patients on therapists too, which has received less attention. The more restricted and rigid patients are, the more limited the interpersonal behavior of others with which the get along well. In line with social psychological, interpersonal and clinical models they try to bring the therapist into an interpersonal position which suits them well. With 60 patients, common strategies have been rated: Good mood, Positive feedback, Negative feedback, Agenda setting, Provoking a response from the therapist, Negative reports about third persons, Fait accompli, Supplication, Self-promotion, Avoidance of contents, und Emotional avoidance. The rating procedure, frequencies, and therapist reactions upon these patient strategies will be reported

DNA-DAMAGING REACTIONS OF NEOCARZINOSTATIN (ANTIBIOTICS, DNA REPAIR, CYTOTOXICITY)

Sensitive assays utilizing a cell-free and an intracellular system were employed to study the molecular bases of the DNA-damaging reactions of neocarzinostatin (NCS). In the cell-free DNA system, super-helical form I DNA from the bacteriophage PM2 was used as the substrate. The three forms of DNA present after treatment with NCS were separated by agarose gel electrophoresis. When NCS-damaged DNA was assayed under neutral conditions, there was a progressive decrease in the amount of surviving form I DNA and a corresponding increase in form II (nicked, relaxed circular) DNA, but very little increase in form III (linear duplex) DNA. This indicates that NCS introduces primarily single-strand breaks. However later studies showed that there were some site-specific double-strand breaks mediated by NCS on PM2 DNA. Seven such specific sites were mapped on the PM2 genome. When the damage was assayed under nondenaturing alkaline conditions or with the apurinic/apyrimidinic endonuclease IV, there was a slightly greater decrease in the amount of surviving form I DNA compared with neutral conditions indicating the presence of some alkali-labile sites.^ NCS-mediated DNA damage and repair were examined with cultured Chinese hamster ovary (CHO) cells using either alkaline elution for analysis of single-strand breaks or neutral elution for analysis of double-strand breaks. Most of the strand breaks introduced by NCS were capable of being rejoined. However, there was a small amount of residual DNA damage remaining unrejoined at 24-hr after removal of the drug. The amount of residual DNA damage was higher in a CHO mutant cell line (EM9) having a higher sensitivity to killing by NCS than its parental strain (AA8). Other lesions, DNA-protein complexes and alkali-labile sites, were detected after NCS treatment but they constituted only a small fraction of the DNA damage.^ Based on the above information, it can be postulated that NCS introduces some very lethal DNA damage. It is likely that the lethal lesions are a subset of the total DNA lesions representing the residual DNA damage. This DNA damage may be composed of site-specific, unrejoinable double-strand breaks and are thus the primary lesion leading to NCS-mediated lethality.^

Reactions of African immigrants living in Houston, Texas, to the American media and legislation regarding female circumcision

Female circumcision was almost unheard of in the United States a few years ago. The recent influx of African immigrants has increased media attention to the subject, leading to laws criminalizing female circumcision. This study examines the reactions of African immigrants living in Houston, Texas, to media portrayal and legislation regarding female circumcision in an attempt to understand the effectiveness of U.S. laws, and media messages in deterring the practice. ^ Through literature reviews the study looks at how female circumcision is portrayed in the Houston Chronicle, and gives detailed discussion of laws regarding it. Attitudes, beliefs, experiences and reactions of African immigrants towards the practice and American's perceptions of female circumcision is examined via a series of case studies. ^ Data show that media and laws portray female circumcision negatively and make little attempt to understand the cultural practice, generating outrage among Africans who would like to see changes in the practice. ^

Der Ruf : Aus: Actions and reactions

Wolfgang Weisl

MONITORING ENZYME REACTIONS BY FAST ATOM BOMBARDMENT MASS SPECTROMETRY

The potential for the direct analysis of enzyme reactions by fast atom bombardment (FAB) mass spectrometry has been investigated. Conditions are presented for the maintenance of enzymatic activity under FAB conditions along with FAB mass spectrometric data showing that these conditions can be applied to solutions of enzyme and substrate to follow enzymatic reactions inside the mass spectrometer in real-time. In addition, enzyme kinetic behavior under FAB mass spectrometric conditions is characterized using trypsin and its assay substrate, TAME, as an enzyme-substrate reaction model. These results show that two monitoring methods can be utilized to follow reactions by FAB mass spectrometry. The advantages of each method are discussed and illustrated by obtaining kinetic parameters from the direct analysis of enzyme reactions with assay or peptide substrates. ^

Ascertainment, meta-analysis and reporting of adverse reactions in clinical trials of antibiotics

The ascertainment and analysis of adverse reactions to investigational agents presents a significant challenge because of the infrequency of these events, their subjective nature and the low priority of safety evaluations in many clinical trials. A one year review of antibiotic trials published in medical journals demonstrates the lack of standards in identifying and reporting these potentially fatal conditions. This review also illustrates the low probability of observing and detecting rare events in typical clinical trials which include fewer than 300 subjects. Uniform standards for ascertainment and reporting are suggested which include operational definitions of study subjects. Meta-analysis of selected antibiotic trials using multivariate regression analysis indicates that meaningful conclusions may be drawn from data from multiple studies which are pooled in a scientifically rigorous manner. ^

NEMOHIFI: An Affective HiFi Agent

This demo concerns a recently developed prototype of an emotionally-sensitive autonomous HiFi Spoken Conversa- tional Agent, called NEMOHIFI. The baseline agent was developed by the Speech Technology Group (GTH) and has recently been integrated with an emotional engine called NEMO (Need-inspired Emotional Model) to enable it to adapt to users emotion and respond to the users using ap- propriate expressive speech. NEMOHIFI controls and man- ages the HiFi audio system, and for end users, its functions equate a remote control, except that instead of clicking, the user interacts with the agent using voice. A pairwise com- parison between the baseline (non-adaptive) and NEMO- HIFI is also presented.

CONSCIÊNCIA E EMOÇÃO: O EFEITO DO PRIMING AFETIVO SUBLIMINAR EM TAREFAS DE ATENÇÃO

Esta tese revisou duas linhas de pesquisa, desenvolvidas nas últimas décadas: o estudo de efeitos de estimulação subliminar priming , e de desencadeamento de reações emocionais por estímulos controlados. Este estudo tem o objetivo de combinar tais linhas para o estudo da consciência com pré-preparo afetivo: efeito de estímulos de conteúdo aversivo, subliminares e supraliminares, sobre a cognição, pela análise do desempenho em tarefa de atenção. Três tarefas experimentais foram realizadas por 35 indivíduos em laboratório de neuropsicologia: a tarefa base onde testamos à detecção de alvo visual simples, e a mesma tarefa de base, porém com estímulos distratores aversivos intercalados, de forma supraliminar ou subliminar (500 ms ou 50 ms de duração), em blocos aleatorizados entre os indivíduos. Calcularam-se índices de detectabilidade e critério de resposta, que serviram para a comparação estatística entre condições (medidas repetidas). Os resultados mostram uma mudança significativa do índice critério , indicando mudança de estratégia na presença de distratores subliminares aversivos. Concluiu-se que a tarefa subliminar fez um efeito destruidor ou devastador na tarefa supraliminar, cometendo menos falso-alarmes protegendo a tarefa supraliminar, tendo um efeito protetor . Os resultados são discutidos no contexto da relevância de influências emocionais sobre o comportamento para a Psicologia da Saúde.

CONSCIÊNCIA E EMOÇÃO: O EFEITO DO PRIMING AFETIVO SUBLIMINAR EM TAREFAS DE ATENÇÃO

Esta tese revisou duas linhas de pesquisa, desenvolvidas nas últimas décadas: o estudo de efeitos de estimulação subliminar priming , e de desencadeamento de reações emocionais por estímulos controlados. Este estudo tem o objetivo de combinar tais linhas para o estudo da consciência com pré-preparo afetivo: efeito de estímulos de conteúdo aversivo, subliminares e supraliminares, sobre a cognição, pela análise do desempenho em tarefa de atenção. Três tarefas experimentais foram realizadas por 35 indivíduos em laboratório de neuropsicologia: a tarefa base onde testamos à detecção de alvo visual simples, e a mesma tarefa de base, porém com estímulos distratores aversivos intercalados, de forma supraliminar ou subliminar (500 ms ou 50 ms de duração), em blocos aleatorizados entre os indivíduos. Calcularam-se índices de detectabilidade e critério de resposta, que serviram para a comparação estatística entre condições (medidas repetidas). Os resultados mostram uma mudança significativa do índice critério , indicando mudança de estratégia na presença de distratores subliminares aversivos. Concluiu-se que a tarefa subliminar fez um efeito destruidor ou devastador na tarefa supraliminar, cometendo menos falso-alarmes protegendo a tarefa supraliminar, tendo um efeito protetor . Os resultados são discutidos no contexto da relevância de influências emocionais sobre o comportamento para a Psicologia da Saúde.

On the electronic nature of low-barrier hydrogen bonds in enzymatic reactions

The electronic nature of low-barrier hydrogen bonds (LBHBs) in enzymatic reactions is discussed based on combined low temperature neutron and x-ray diffraction experiments and on high level ab initio calculations by using the model substrate benzoylacetone. This molecule has a LBHB, as the intramolecular hydrogen bond is described by a double-well potential with a small barrier for hydrogen transfer. From an “atoms in molecules” analysis of the electron density, it is found that the hydrogen atom is stabilized by covalent bonds to both oxygens. Large atomic partial charges on the hydrogen-bonded atoms are found experimentally and theoretically. Therefore, the hydrogen bond gains stabilization from both covalency and from the normal electrostatic interactions found for long, weak hydrogen bonds. Based on comparisons with other systems having short-strong hydrogen bonds or LBHBs, it is proposed that all short-strong and LBHB systems possess similar electronic features of the hydrogen-bonded region, namely polar covalent bonds between the hydrogen atom and both heteroatoms in question.

Farnesol is utilized for isoprenoid biosynthesis in plant cells via farnesyl pyrophosphate formed by successive monophosphorylation reactions

The ability of Nicotiana tabacum cell cultures to utilize farnesol (F-OH) for sterol and sesquiterpene biosynthesis was investigated. [3H]F-OH was readily incorporated into sterols by rapidly growing cell cultures. However, the incorporation rate into sterols was reduced by greater than 70% in elicitor-treated cell cultures whereas a substantial proportion of the radioactivity was redirected into capsidiol, an extracellular sesquiterpene phytoalexin. The incorporation of [3H]F-OH into sterols was inhibited by squalestatin 1, suggesting that [3H]F-OH was incorporated via farnesyl pyrophosphate (F-P-P). Consistent with this possibility, N. tabacum proteins were metabolically labeled with [3H]F-OH or [3H]geranylgeraniol ([3H]GG-OH). Kinase activities converting F-OH to farnesyl monophosphate (F-P) and, subsequently, F-P-P were demonstrated directly by in vitro enzymatic studies. [3H]F-P and [3H]F-P-P were synthesized when exogenous [3H]F-OH was incubated with microsomal fractions and CTP. The kinetics of formation suggested a precursor–product relationship between [3H]F-P and [3H]F-P-P. In agreement with this kinetic pattern of labeling, [32P]F-P and [32P]F-P-P were synthesized when microsomal fractions were incubated with F-OH and F-P, respectively, with [γ-32P]CTP serving as the phosphoryl donor. Under similar conditions, the microsomal fractions catalyzed the enzymatic conversion of [3H]GG-OH to [3H]geranylgeranyl monophosphate and [3H]geranylgeranyl pyrophosphate ([3H]GG-P-P) in CTP-dependent reactions. A novel biosynthetic mechanism involving two successive monophosphorylation reactions was supported by the observation that [3H]CTP was formed when microsomes were incubated with [3H]CDP and either F-P-P or GG-P-P, but not F-P. These results document the presence of at least two CTP-mediated kinases that provide a mechanism for the utilization of F-OH and GG-OH for the biosynthesis of isoprenoid lipids and protein isoprenylation.