Effect of antithyroid drugs on hydroxyl radical formation and alpha-1-proteinase inhibitor inactivation by neutrophils: therapeutic implications

The release of proteolytic enzymes and generation of strong oxidants such as the hydroxyl radical by activated neutrophils has been proposed to play an important role in mediating toxin-induced liver injury. The antithyroid drug propylthiouracil protects against liver injury induced by many hepatotoxic agents and markedly reduces mortality in patients with alcoholic liver disease. However, the mechanism(s) by which propylthiouracil protects against liver injury is not well understood. The present studies investigate the effect of antithyroid drugs on proteolytic enzyme activity and on hydroxyl radical generation from activated neutrophils. In the presence of hydrogen peroxide and chloride, neutrophil myeloperoxidase, an enzyme from the same gene superfamily as thyroid peroxidase, generates hypochlorous acid which inactivates alpha-1-proteinase inhibitor (A1PI) present in serum. This inactivation allows neutrophil-released proteolytic enzymes to attack cells. In the present study myeloperoxidase activity was inhibited fully at therapeutic concentrations by antithyroid drugs (propylthiouracil and methimazole). Antithyroid drugs fully prevented hypochlorous acid formation, and prevented neutrophil-mediated inactivation of A1PI, with concomitant blockage of proteolytic activity. Conversely, generation of both superoxide and hydroxyl radicals by activated neutrophils was unaffected by propylthiouracil. The production of these oxygen radicals was fully inhibited by the NADPH oxidase inhibitor diphenylene iodonium chloride, however. These studies indicate that antithyroid drugs are unlikely to prevent cell injury by inhibiting hydroxyl radical generation or by scavenging hydroxyl radicals, but are likely to exert their hepatoprotective anti-inflammatory action by inhibiting neutrophil myeloperoxidase, an enzyme akin to thyroid peroxidase.     

Aerobic bacterial spores as process indicators for protozoa cysts in water treatment plants.

The possibility of using aerobic spores as indicators (surrogates) of water treatment efficiency for the removal of Giardia cysts and Cryptosporidium oocysts was evaluated in a water treatment plant that supplies the Barcelona area of Spain. The water treatment consists of pre-chlorination, flocculation-sedimentation, double filtration (sand and granular activated carbon, GAC) with intermediate ozonation and post-chlorination. Aerobic spores significantly increased after GAC filtration, which indicated an active propagation of aerobic spore-formers. However, anaerobic (Clostridium) spores could be a good surrogate for Cryptosporidium oocysts, especially if their detection in samples at low concentrations was improved.     

The mouse Id2 and Id4 genes: structural organization and chromosomal localization

The development of an antigen presentation system based on the plum pox potyvirus (PPV) is here described. The amino-terminal part of PPV capsid protein was chosen as the site for expression of foreign antigenic peptides. Modifications in this site were engineered to avoid the capability of natural transmission by aphids of this PPV vector. As a first practical attempt, different forms of an antigenic peptide (single and tandem repetition) from the VP2 capsid protein of canine parvovirus (CPV) were expressed. Both chimeras are able to infect Nicotiana clevelandii plants with similar characteristics to wild-type virus and remain genetically stable after several plant passages. The antigenicity of purified chimeric virions was demonstrated, proving the suitability of this system for diagnostic purposes. Moreover, mice and rabbits immunized with chimeric virions developed CPV-specific antibodies, which showed neutralizing activity.     

Preventing discrimination against volunteers in prophylactic HIV vaccine trials: lessons from a phase II trial

OBJECTIVE: This was a randomized, double-blind, crossover study of 30 children with attention-deficit/hyperactivity disorder (ADHD) that evaluated the time course effects of four doses of Adderall (5, 10, 15, and 20 mg), an inactive control (placebo), and a positive control (clinical dose of methylphenidate). METHOD: For each treatment condition, a capsule was administered in the morning and assessments were performed in an analog classroom setting every 1.5 hours across the day. Subjective (teacher ratings of deportment and attention) and objective (scores on math tests) measures were obtained for each classroom session, and these measures were used to evaluate time-response and dose response effects of Adderall. RESULTS: For doses of Adderall greater than 5 mg, significant time course effects were observed. Rapid improvements on teacher ratings and math performance were observed by 1.5 hours after administration, and these effects dissipated by the end of the day. The specific pattern of time course effects depended on dose: the time of peak effects and the duration of action increased with dose of Adderall. CONCLUSIONS: This documentation of efficacy in a controlled study supports the addition of Adderall to the armamentarium of psychotropic medications for the treatment of ADHD. The differences in time-response patterns of Adderall and methylphenidate may help tailor treatment to meet specific clinical needs of different children with ADHD.     

Soldering mechanisms in materials and coatings for aluminum die casting

The stability against reaction with aluminum of materials and coatings commonly used in aluminum die casting was investigated. The materials considered here were H13 tool steel and Anviloy® 1150, whereas the coatings were TiN and CrN. Special model, freestanding, multilayered thin film structures were used in this study, in association with complementary differential scanning calorimetry and X-ray diffraction. The nature of the reactions (endo or exothermic) and their onset temperatures up to 1273 K were determined. Based on of these results, some activation energies for the different reactions taking place between aluminum and die material or between aluminum and coatings could be established. Different intermetallic compounds were formed in these reactions, which were identified by post mortem X-ray diffraction analysis. Anviloy® 1150 showed superior stability as compared to H13 tool steel, whereas CrN was more inert than TiN coatings. CrN exhibited the best performance among all materials and coatings considered here, although its practical application relies also on adhesion of the CrN coating to the die bulk material. The results are discussed on the lights of two recent models for soldering in aluminum die casting.     

Synthesis and characterization of polymers with pendent phosphonate groups

Soluble chloromethylated polystyrene and its copolymers with vinylidene chloride as well as poly(phenyl oxides) brominated in the side chains and in the ring were synthesized and characterized in detail by NMR. The halogenated polymers were phosphonylated with alkyl phosphites. Uncrosslinked polymers with pendent phosphonate groups were prepared in the presence of etheral solvents, which solvate the ionic intermediates of the Arbuzov reaction. These polyphosphonates are highly hygroscopic and are soluble in a variety of solvents. Their T_g's are in the range of 50–175°C. Their thermal behavior was analyzed on the basis of thermogravimetric measurements combined with mass-spectrometric analysis. Poly(styrene phosphonate) seems to be the most stable, and its thermal decomposition starts at ～330°C. The polymeric phosphonates are compatible with an unusually large number of polymeric systems and seem to form “true” polymeric alloys with acetylcellulose.     

Theodor Reik: On psychoanalysis and the unconscious compulsion to confess.

In 1924, Theodor Reik presented a series of lectures in Vienna, which resulted in the publication of the book, The Compulsion to Confess (1925/1959). It was Reik's claim that his conceptualization of the unconscious compulsion to confess was a "discovery" and suggested that it be incorporated in the theory and lexicon of classical psychoanalytic theory. It is from the socialization experiences of the child (the modification of instinctual impulses) that repression is experienced and thus the process of confession is an attempt to quell (unconsciously) feelings of guilt and need for self-punishment. The power of a hostile superego plays the pivotal role, according to Reik, in the development of the neurosis, and it is within the framework and dynamics of the Oedipal complex that unconscious confessions result. (PsycINFO Database Record (c) 2010 APA, all rights reserved)