Peptide concentration alters intermediate species in amyloid ß fibrillation kinetics.

The kinetic mechanism of amyloid aggregation remains to be fully understood. Investigations into the species present in the different kinetic phases can assist our comprehension of amyloid diseases and further our understanding of the mechanism behind amyloid ß (Aß) (1-40) peptide aggregation. Thioflavin T (ThT) fluorescence and transmission electron microscopy (TEM) have been used in combination to monitor Aß(1-40) aggregation in vitro at both normal and higher than standard concentrations. The observed fibrillation behaviour deviates, in several respects, from standard concepts of the nucleation-polymerisation models and shows such features as concentration-dependent non-linear effects in the assembly mechanism. Aß(1-40) fibrillation kinetics do not always follow conventional kinetic mechanisms and, specifically at high concentrations, intermediate structures become populated and secondary processes may further modify the fibrillation mechanism.

The goitrogenic efficiency of thioamides in a marine teleost, sea bream (Sparus auratus).

Studies on the role of thyroid hormones (THs) in teleost fish physiology have deployed the synthetic goitrogens, methimazol (MMI), propilthiouracil (PTU) and thiourea (TU) that are used to treat human hyperthyroidism. However, the action of the goitrogens, MMI, PTU and TU at different levels of the hypothalamic-pituitary-thyroid (HPT) axis in teleosts is largely unknown. The central importance of the hypothalamus and pituitary in a number of endocrine regulated systems and the cross-talk that occurs between different endocrine axes makes it pertinent to characterize the effects of MMI, PTU and TU, on several endpoints of the thyroid system. The marine teleost, sea bream (Sparus auratus) was exposed to MMI, PTU and TU (1mg/kg wet weight per day), via the diet for 21days. Radioimmunoassays (RIA) of plasma THs and ELISA of the TH carrier transthyretin (TTR) revealed that MMI was the only chemical that significantly reduced plasma TH levels (p<0.05), although both MMI and PTU significantly (p<0.05) reduced plasma levels of circulating TTR (p<0.05). Histological analysis of the thyroid tissue revealed modifications in thyrocyte activity that explain the reduced circulating levels of THs. MMI also significantly (p<0.05) up-regulated transcript abundance of liver deiodinase 1 and 2 while significantly (p<0.05) decreasing TRß expression in the pituitary, all hallmarks of HPT axis action of goitrogens in vertebrates. The results indicate that in the sea bream MMI is the most effective goitrogen followed by PTU and that TU (1mg/kg wet weight for 21days) failed to have a goitrogenic effect. The study highlights the non-uniform effect of goitrogens on the thyroid axis of sea bream and provides the basis for future studies of thyroid disrupting pollutants.

Dental hygiene work in a clinical trial.

UNLABELLED: Dental hygiene activities were developed as part of a randomized clinical trial designed to assess the safety of low-level mercury exposure from dental amalgam restorations. Along with dental-hygiene clinical work, a community programme was implemented after investigators noticed the poor oral hygiene habits of participants, and the need for urgent action to minimize oral health problems in the study population. OBJECTIVES: Clinical and community activity goal was to promote oral health and prevent new disease. Community activities involved participants and their fellow students and were aimed at providing education on oral health in a school environment. METHODS: Dental hygienists developed clinical work with prophylaxis, sealants application and topical fluoride and implemented the community programme with in-class sessions on oral health themes. Twice a month fluoride mouthrinses and bi-annual tooth brushing instructional activity took place. Participation at dental-hygiene activities, sealed teeth with no need of restoration and dental-plaque-index were measures used to evaluate success of the programme for the participants. RESULTS: Improvement in dental hygiene is shown by the decrease in dental plaque index scores (P < 0.0001); also sealants integrity is achieved in 86.3% of teeth. 888 (13.7%) teeth with sealants had to be restored or were lost. Children participated actively on dental hygiene activities. Teachers became aware of the problem and included oral-health in school curricula. CONCLUSION: Dental hygiene activities have shown to be helpful to promote dental hygiene, promote oral health and to provide school-age children with education on habits that will be important for their future good health.

[The psychobiology of learning and memory: fundamentals and recent advances]. / Psicobiología del aprendizaje y la memoria: fundamentos y avances recientes.

AIM: This review describes the concepts, temporal dynamics and main features of learning and memory systems from a comprehensive molecular, neuroanatomical, neurophysiological, cognitive and behavioural approach. DEVELOPMENT: Starting with molecular mechanisms of synaptic plasticity we describe the memory stages, implicit and explicit memory systems, working memory, remembering and forgetting. Each process is illustrated with examples of recent experimental and clinical research. CONCLUSIONS: Learning and memory are closely related brain processes which give rise to adaptive changes in behaviour. Implicit memory is a kind of unconscious and rigid memory for habits, which is based on brain regions processing perceptions and motor and emotional information, like the neocortex, the neostriatum, the cerebellum or the amygdala. Explicit or declarative memory is a conscious and flexible memory, hippocampus-dependent. Working memory is actually a system of executive cognition, based on interactions between the prefrontal cortex and other brain regions. The retrieval of complex memories consist of an active process of reconstruction of the past which incorporates new experiences of the subject who is remembering. The reactivation of memories can initiate genuine processes of reconsolidation and extinction. Forgetting could depend on alterations in the neural networks storing the information or, otherwise, on active processes which hinder consolidation or block the expression of the memories.

[The amigdaloid body: functional implications]. / La amígdala: implicaciones funcionales.

INTRODUCTION: The amygdaloid body is a structure localized to the temporal lobe in mammals, formed by different nuclei and traditionally associated with the emotion system of the brain. Some investigators have suggested an alternative function for the amygdaloid body, considering it to be part of the system modulating memory. Much of the experimental data supports both functions. DEVELOPMENT: The relation of the amygdaloid body with the emotions has been based on the study of the conditioning of fear, by which an emotionally neutral stimulus can cause emotional reactions due to its temporal association with an adverse stimulus. It has been shown that the amygdaloid body is necessary for learning and expressing this conditioning, and is therefore involved in emotional learning. With regard to the relation of the amygdaloid body with the modulation of memory, one should point out the results which show that it is not always necessary for learning and memory, but is necessary for showing the modulating effects of different substances on memory. The amygdaloid body modulates the storage of memory in other regions of the brain, such as the caudate nucleus and the hippocampus. CONCLUSIONS: Current data suggests that the whole amygdaloid complex is not involved in the two functions. However, the lateral and central nuclei participate in emotional learning whilst the basolateral nucleus is especially involved in modulation of the memory when emotional activation occurs.

[Sedation with remifentanil for tracheostomy in a pediatric patient]. / Sedación con remifentanilo para una traqueostomía en un paciente pediátrico.

Remifentanil is an ultra-short-acting opioid that is frequently used in adults for surgical anesthesia or conscious sedation, but its use in children is much less common. We report the case of a 7-year-old boy with lateral cervical tumors displacing all cervical and facial structures. An emergency tracheostomy was performed when he developed respiratory difficulty due to partial airway obstruction. Because of the size and location of the intraoral tumors and a history of bleeding, orotracheal intubation and other airway management techniques were ruled out. The tracheostomy was performed under local anesthesia and sedation with a perfusion of 0.05 x microgKg(-1) x min(-1) provided the necessary relaxation and immobility for surgery. Sedation under observation with monitoring is among the indications of remifentanil. Spontaneous breathing is maintained with infusions less than 0.05 to 0.1 microg x Kg(-1) x min(-1). In the case we report, the patient's risk of complete airway obstruction due to bleeding upon manipulation had to be assessed and compared with the respiratory depression that might possibly have been caused by remifentanil perfusion. We judged that the option of sedation would cause less morbidity and offered greater safety for the patient. The outcome of this case is consistent with reports that remifentanil is a good option for adequately sedating children who are breathing spontaneously.

[Psychobiology of consciousness: concepts, hypotheses and clinical and experimental observations]. / Psicobiología de la consciencia: conceptos, hipótesis y observaciones clínicas y experimentales.

AIM: An updated revision of the main concepts, hypothesis and clinical and experimental data about the psychobiology of consciousness. DEVELOPMENT: It describes the nature, characteristics and neural correlated of consciousness and discuss about the capacity of the human brain to understand the conscious mind. CONCLUSIONS: Consciousness is a subjective, qualitative and unified mental state which originates behavioural flexibility. Qualia are the sensory qualities of the conscious experience. They are an executive summary of a great amount of information. Consciousness seems be mainly based on cortical mechanisms, although the thalamus and the arousal subcortical systems could have an enabling role in giving rise to it. The brain could generate consciousness by mechanisms of resonance, synchronization and/ or integration of the activity of different cortical and subcortical regions. Human brain could not have evolved enough as for understanding how objective matter becomes subjective imagination.

Analysis of the transthyretin-like (TTL) gene family in Ostertagia ostertagi--comparison with other strongylid nematodes and Caenorhabditis elegans.

The transthyretin-like (ttl) gene family is one of the largest conserved nematode-specific gene families, coding for a group of proteins with significant sequence similarity to transthyretins (TTR) and transthyretin-related proteins (TRP). In the present study, we investigated the ttl family in Ostertagia ostertagi (a nematode of the abomasum of cattle). Mining of expressed sequence tag (EST) databases revealed the presence of at least 18 ttl genes in O. ostertagi (Oo-ttl), most of which are constitutively transcribed from the free-living, third larval stage onwards. The full-length cDNA of one of these genes (Oo-ttl-1) was amplified and cloned for recombinant expression. Western blot analysis using a specific antiserum showed that the native protein Oo-TTL-1 was highly present in the excretory-secretory (ES) products of adults of O. ostertagi. The protein was immunolocalized to the pseudocoelomic fluid of adult worms. A phylogenetic-bioinformatic analysis of all amino acid sequence data for TTL proteins from a range of strongylid nematodes showed that they could be divided into at least five different classes. This classification was based on conserved amino acids in the first TTL signature domain and the number and location of cysteine residues. The biological role(s) of the TTLs in nematode biology is still unclear. A theoretical three-dimensional model of Oo-TTL-1 indicated that it had a similar structure to TTRs (i.e., containing ß-sheets, arranged in a ß-sandwich). In contrast to TTRs, competitive binding studies using recombinant Oo-TTL-1 indicated that the protein was devoid of any hydrophobic ligand- or thyroid hormone-binding properties. Finally, combinatorial analysis by double-stranded RNA interference of five ttl genes in the free-living nematode Caenorhabditis elegans did not reveal any visible phenotypes. More information on the transcription profile and tissue distribution of TTLs in nematodes is needed to provide new insights into the biological role of this gene family.

Regulation of transthyretin by thyroid hormones in fish.

Transthyretin (TTR) is a thyroid hormone-binding protein (THBP) which in its tetrameric form transports thyroid hormones (THs), thyroxine (T(4)) and triiodothyronine (T(3)) in the blood of vertebrates. The principal site of production of TTR is the liver but in the sea bream TTR mRNA is also present in the heart, intestine and brain. The regulation of TTR is unstudied in fish and the normal circulating level of this THBP is unknown. The aim of the present study was to establish factors which regulate TTR production in fish. As a first step a number of tools were generated; sea bream recombinant TTR (sbrTTR) and specific sbrTTR antisera which were used to establish an ELISA (enzyme-linked immunosorbent assay) for measuring TTR plasma levels. Subsequently, an experiment was conducted to determine the influence of THs on TTR production. Circulating physiological levels of TTR in sea bream determined by ELISA are approximately 3.8microgml(-1). Administration of T(3) and T(4) to sea bream significantly increased (p<0.001 and p<0.005, respectively) the concentration of circulating TTR ( approximately or = 11.5microgml(-1)) in relation to control fish, but did not change gene transcription in the liver. Methimazol (MMI) an antithyroid agent, failed to significantly reduce circulating THs below control levels but significantly increased (p<0.005) plasma TTR levels (approximately or = 10.8microgml(-1)) and decreased (p<0.05) transcription in the liver. Future studies will aim to elucidate in more detail these regulatory pathways.