La concentración plasmática de microARN-1-3p se asocia con fibrilación auricular subclínica en los pacientes con ictus criptogénico / Plasma levels of miRNA-1-3p are associated with subclinical atrial fibrillation in patients with cryptogenic stroke

Introducción y objetivos La identificación de biomarcadores de fibrilación auricular (FA) subclínica en los pacientes con ictus criptogénico (ICr) es de gran interés. Con dicho objetivo, se evaluó el perfil de microARN circulante de los pacientes con ICr y FA frente a aquellos en ritmo sinusal. Métodos Se incluyó a 64 pacientes con ICr consecutivos monitorizados mediante Holter subcutáneo. Se seleccionó a 18 pacientes (9 con FA y 9 en ritmo sinusal persistente) para determinación de 754 microARN mediante tecnología de alto rendimiento. Se incluyó a 9 pacientes adicionales con ictus y FA concomitante para guiar la selección de microARN. Los microARN de interés se replicaron en una cohorte independiente (n=46). La asociación de biomarcadores con FA a los 6 y 12 meses se analizó mediante regresión logística. Resultados Ocho microARN mostraron expresión diferencial entre los pacientes con y sin FA. El miR-1-3p, un regulador génico involucrado en la arritmogénesis cardiaca, fue el único que permaneció significativamente más elevado en pacientes con ICr y FA de la cohorte de repetición, y además mostró una discreta asociación con la carga arrítmica. Los valores de miR-1-3p por encima de la mediana y la fracción de eyección de la aurícula izquierda se asociaron de forma independiente con la presencia de FA a los 6 y 12 meses. Conclusiones En nuestra cohorte, los valores plasmáticos de miR-1-3p fueron más altos en los pacientes con ICr y FA en el seguimiento. Nuestros resultados indican que el miR-1-3p podría ser un nuevo biomarcador de FA oculta en los pacientes con ICr (AU)

Introduction and objectives Identifying biomarkers of subclinical atrial fibrillation (AF) is of most interest in patients with cryptogenic stroke (CrS). We sought to evaluate the circulating microRNA (miRNA) profile of patients with CrS and AF compared with those in persistent sinus rhythm. Methods Among 64 consecutive patients with CrS under continuous monitoring by a predischarge insertable monitor, 18 patients (9 with AF and 9 in persistent sinus rhythm) were selected for high-throughput determination of 754 miRNAs. Nine patients with concomitant stroke and AF were also screened to improve the yield of miRNA selection. Differentially expressed miRNAs were replicated in an independent cohort (n=46). Biological markers were stratified by the median and included in logistic regression analyses to evaluate their association with AF at 6 and 12 months. Results Eight miRNAs were differentially expressed between patients with and without AF. In the replication cohort, miR-1-3p, a gene regulator involved in cardiac arrhythmogenesis, was the only miRNA to remain significantly higher in patients with CrS and AF vs those in sinus rhythm and showed a modest association with AF burden. High (= above the median) miR-1-3p plasma values, together with a low left atrial ejection fraction, were independently associated with the presence of AF at 6 and 12 months. Conclusions In this cohort, plasma levels of miR-1-3p were elevated in CrS patients with subsequent AF. Our results preliminarily suggest that miR-1-3p could be a novel biomarker that, together with clinical parameters, could help identify patients with CrS and a high risk of occult AF (AU)

Developmental maturation of presynaptic ribbon numbers in chicken basilar-papilla hair cells and its perturbation by long-term overexpression of Wnt9a.

The avian basilar papilla is a valuable model system for exploring the developmental determination and differentiation of sensory hair cells and their innervation. In the mature basilar papilla, hair cells form a well-known continuum between two extreme types-tall and short hair cells-that differ strikingly in their innervation. Previous work identified Wnt9a as a crucial factor in this differentiation. Here, we quantified the number and volume of immunolabelled presynaptic ribbons in tall and short hair cells of chickens, from developmental stages shortly after ribbons first appear to the mature posthatching condition. Two longitudinal locations were sampled, responding to best frequencies of approximately 1 kHz and approximately 5.5 kHz when mature. We found significant reductions of ribbon number during normal development in the tall-hair-cell domains, but stable, low numbers in the short-hair-cell domains. Exposing developing hair cells to continuous, excessive Wnt9a levels (through virus-mediated overexpression) led to transiently abnormal high numbers of ribbons and a delayed reduction of ribbon numbers at all sampled locations. Thus, (normally) short-hair-cell domains also showed tall-hair-cell like behaviour, confirming previous findings (Munnamalai et al., 2017). However, at 3 weeks posthatching, ribbon numbers had decreased to the location-specific typical values of control hair cells at all sampled locations. Furthermore, as shown previously, mature hair cells at the basal, high-frequency location harboured larger ribbons than more apically located hair cells. This was true for both normal and Wnt9a-overexposed basilar papillae.

Benefits of EEG-Neurofeedback on the Modulation of Impulsivity in a Sample of Cocaine and Heroin Long-Term Abstinent Inmates: A Pilot Study.

The aim of this pilot study was to assess whether neurofeedback (NFB) can be useful in the treatment of impulsive behavior in long-term abstinent cocaine and heroin addicts. A single-blind sham-controlled NFB protocol was carried out to assess the effects of NFB on impulsivity in 20 (10 + 10) cocaine and heroin long-term abstinent addicts (Diagnostic and Statistical Manual of Mental Disorders [4th ed., text rev.; DSM-IV-TR]). Psychotic and neurologic diseases were excluded. Participants underwent 40 NFB sessions based on the very slow cortical potential range. Inhibitory deficits were specifically addressed through right and left prefrontal training. Clinical improvement was measured with Likert-type scales, the Hamilton Depression Rating Scale, and the State-Trait Anxiety Inventory, and impulsivity was assessed using the Barratt Impulsiveness Scale and the Continuous Performance Test. Although the results are preliminary due to the small sample size, the NFB-treated group showed a significant clinical improvement, including symptoms of anxiety and depression, with two differentiated time periods. No significant clinical improvement was found in the control group. A significant decrease in the post- versus pre-treatment measures of global impulsivity, nonplanning impulsivity, and error commission measures was found in the NFB-treated group; effect size (dKorr) in the pre-post control design was moderate. No significant change was found in the control group. Despite the limitations of this study, the results suggest that NFB is better than placebo in improving impulsivity and clinical symptoms of anxiety and depression in long-term abstinent cocaine- and heroin-dependent individuals.

Aerosol sources in subway environments.

Millions of people use rail subway public transport around the world, despite the relatively high particulate matter (PM) concentrations in these underground environments, requiring the identification and quantification of the aerosol source contributions to improve the air quality. An extensive aerosol monitoring campaign was carried out in eleven subway stations in the Barcelona metro system, belonging to seven subway lines. PM2.5 samples were collected during the metro operating hours and chemically analysed to determine major and trace elements, inorganic ions, and total carbon. The chemical compositions of subway components such as brake pads, rail tracks and pantographs were also determined. The mean PM2.5 concentrations varied widely among stations, ranging from 26 µg m-3 to 86 µg m-3. Subway PM2.5 was mainly constituted by Fe2O3 (30-66%), followed by carbonaceous matter (18-37%) for the old stations, while for new stations equipped with Platform Screen Doors (PSD) these percentages go down to 21-44% and 15-30%, respectively. Both the absolute concentrations and the relative abundance of key species differed for each subway station, although with common patterns within a given subway line. This is a result of the different emission chemical profiles in different subway lines (using diverse types of brakes and/or pantographs). The co-emission of different sources poses a problem for their separation by receptor models. Nevertheless, receptor modelling (Positive Matrix Factorization) was applied resulting in ten sources, five of them subway-specific: RailWheel, RailWheel+Brake, Brake_A, Brake_B, Pb. The sum of their contributions accounted for 43-91% of bulk PM2.5 for the old stations and 21-52% for the stations with PSD. The decrease of the activity during the weekends resulted in a decrease (up to 56%) in the subway-specific sources contribution to the -already lower- bulk PM2.5 concentrations compared to weekdays. The health-related elements are mainly apportioned (> 60%) by subway sources.

Formation and alteration of airborne particles in the subway environment.

Most particles in the rail subway environment are sub-micron sized ferruginous flakes and splinters generated mechanically by frictional wear of brake pads, wheels and rails. To better understand the mechanisms of formation and the alteration processes affecting inhalable particles in subways, PM samples (1-2.5 µm and 2.5-10 µm) were collected in the Barcelona Metro and then studied under a scanning electron microscope. Most particles in these samples are hematitic (up to 88%), with relatively minor amounts of mineral matter (up to 9%) and sulphates (up to 5%). Detailed microscopy (using back scattered and TEM-DRX imaging) reveals how many of the metallic particles comprise the metallic Fe nucleus surrounded by hematite (Fe2O3) and a coating of sulphate and chloride salts mixed with mineral matter (including Ca-carbonates, clay minerals and quartz). These observations record the emission of fine to ultrafine FePM by frictional wear at elevated temperatures that promote rapid partial (or complete) oxidation of the native metal. Water condensing on the PM surface during cooling leads to the adsorption of inorganic mineral particles that coat the iron oxide. The distinctively layered polymineralic structure that results from these processes is peculiar to particles generated in the subway environment and very different from PM typically inhaled outdoors.

Sunflower metallothionein family characterisation. Study of the Zn(II)- and Cd(II)-binding abilities of the HaMT1 and HaMT2 isoforms.

Plant metallothioneins (MTs) constitute a family of small Cys-rich proteins capable of coordinating metal ions, significantly differing from microbial and animal MTs. They are divided into four subfamilies depending on the Cys pattern in their sequence. In this work, the MT system of the sunflower plant (Helianthus annuus) has been defined, with ten genes coding for MTs (HaMT) belonging to the four plant MT subfamilies; three HaMT1, four HaMT2, one HaMT3 and two HaMT4 isoforms. The gene expression pattern and capacity to confer metal resistance to yeast cells have been analysed for at least one member of each subfamily. The divalent metal ion-binding abilities of HaMT1-2 and HaMT2-1 (the isoforms encoded by the most abundantly expressed HaMT1 and HaMT2 isogenes) have been characterised, as HaMT3 and HaMT4 were previously studied. Those isoforms constitute an optimum material to study the effect of Cys number variability on their coordination abilities, as they exhibit additional Cys residues regarding the canonical Cys pattern of each subfamily. Our results show that the variation in the number of Cys does not drastically modify their M(II)-binding abilities, but instead modulates the degree of heterogeneity of the corresponding recombinant syntheses. Significantly, the Zn(II)-HaMT1 complexes were highly susceptible to proteolytic cleavage. The recombinant Cd-MT preparations of both isoforms exhibit significant acid-labile sulphide content-Cd6S8 or Cd7S7 species. Overall results suggest that HaMT2-1 is probably associated with Cd(II) detoxification, in contrast to HaMT1-2, which may be more related to physiological functions, such as metal ion transport and delivery.

Attempted and completed suicide: not what we expected?

BACKGROUND: Suicide attempters and suicide completers are two overlapping but distinct suicide populations. This study aims to present a more accurate characterization by comparing populations of suicide attempters and completers from the same geographical area. METHODS: Samples and procedure: All cases of attempted suicide treated at the emergency room of the Corporacio Sanitària i Universitària Tauli Parc de Sabadell in 2008 (n=312) were compared with all completed suicides recorded in the same geographical area from 2008 to 2011 (n=86). Hospital and primary care records were reviewed for sociodemographic and clinical variables. STATISTICAL ANALYSIS: Chi-square, ANOVA, and Mann-Whitney U tests were used to identify characteristics related to suicide completion. RESULTS: Compared to suicide attempters, suicide completers were more likely to be male (73.3% vs. 37.8%; p<0.001), pensioners (73.7% vs. 23.4%; p<0.001), and people living alone (31.8% vs. 11.4%; p=0.006). Suicide completers more frequently presented somatic problems (71.7 vs. 15.7; p<0.001), Major Depressive Disorder (54.7% vs. 27.9%; p<0.001), and made use of more lethal methods (74.1 vs. 1.9; p<0.001). Suicide completers were more likely to have been followed by a primary care provider (50.0% vs. 16.0%; p<0.001). 92.3% of the suicides committed were completed during the first or second attempt. LIMITATIONS: Suicide completers were not evaluated using the psychological autopsy method. CONCLUSIONS: Despite presenting a profile of greater social and clinical severity, suicide completers are less likely to be followed by Mental Health Services than suicide attempters. Current prevention programs should be tailored to the specific profile of suicide completers.

The response of the different soybean metallothionein isoforms to cadmium intoxication.

Cadmium is a highly toxic heavy metal for both plants and animals. The presence of Cd in agricultural soils is of major concern regarding its entry into the food chain, since Cd compounds are readily taken up by plants, and accumulated in edible parts due to their high solubility. In this study, we first demonstrate the high capacity for Cd concentration of soybean grains. Consequently, we considered the study and characterization of the molecular determinants of Cd accumulation -such as metallothioneins (MT)- to be of major practical importance. We report here the first characterization of the soybean MT system, with the identification of nine genes (one of which is a truncated pseudogene), belonging to the four plant MT types. The most highly expressed of each type was chosen for further function analysis. All of them are expressed at high levels in soybean tissues: GmMT1, GmMT2 and GmMT3 in roots, shoots and seeds, and GmMT4 only in seeds. The corresponding recombinant soybean MTs, synthesized in Escherichia coli cells cultured in metal supplemented media, exhibit greater cadmium than zinc binding capacity. These results suggest a definite role of GmMTs in Cd(II) accumulation as one of the main responses of soybean to an overload of this metal.

[The laryngeal tube]. / El tubo laríngeo.

The laryngeal tube (VBM Medizintechnic GmbH, Sulz, Germany) is a supraglottic device designed for airway management in spontaneous or positive-pressure ventilation during anesthesia or in cardiopulmonary resuscitation. Currently, the tube is available in 4 versions: the standard laryngeal tube, the disposable tube (LT-D), the dual-lumen tube (with a tube for suction) (LTS II), and the disposable LTS (LTS-D). The design of the tube has been modified several times. It is easy to insert and the airway seal is more effective than that of the laryngeal mask. The incidence of complications is similar for both devices, though use of the laryngeal tube requires more adjustments. The standard tube is somewhat less effective than the ProSeal laryngeal mask, though the new LTS II has been improved considerably. The laryngeal tube is effective as an aid to management of the difficult airway. We reviewed the literature indexed on MEDLINE through December 2006 using the search terms laryngeal tube, anesthesia, equipment, and airway.

El tubo laríngeo / The laryngeal tube

El tubo laríngeo (TL) (VBM Medizintechnik GMBH,Sulz, Alemania) es un dispositivo supraglótico diseñadopara el manejo de la vía aérea en ventilación espontáneao controlada durante la anestesia o en resucitación cardiopulmonar.En la actualidad existen cuatro variantesdel TL: el TL estándar, el TL de un solo uso (TL-D), eltubo laríngeo succión II (TLS II) y el TLS desechable(TLS-D). El diseño del TL ha sido revisado en diferentesocasiones. Su inserción se realiza con facilidad. El selladode la vía aérea con el TL es más eficaz que con lamascarilla laríngea (ML). La incidencia de complicacioneses similar en los dos dispositivos, aunque el TLrequiere de más reajustes para su utilización. El TLestándar es algo menos efectivo que la ML Proseal, aunqueel nuevo TLS II ha sido mejorado significativamente.Es un dispositivo eficaz como ayuda en la resolucióndel manejo de la vía aérea difícil. Hemos revisado la literaturamédica existente hasta diciembre 2006 mediantebúsqueda en MEDLINE, utilizando los términos “laryngealtube”, “anaesthesia”, “equipment” and “airway” (AU)

The laryngeal tube (VBM Medizintechnic GmbH, Sulz,Germany) is a supraglottic device designed for airwaymanagement in spontaneous or positive-pressureventilation during anesthesia or in cardiopulmonaryresuscitation. Currently, the tube is available in 4versions: the standard laryngeal tube, the disposable tube(LT-D), the dual-lumen tube (with a tube for suction)(LTS II), and the disposable LTS (LTS-D). The design ofthe tube has been modified several times. It is easy toinsert and the airway seal is more effective than that ofthe laryngeal mask. The incidence of complications issimilar for both devices, though use of the laryngeal tuberequires more adjustments. The standard tube issomewhat less effective than the ProSeal laryngeal mask,though the new LTS II has been improved considerably.The laryngeal tube is effective as an aid to management ofthe difficult airway. We reviewed the literature indexed onMEDLINE through December 2006 using the searchterms laryngeal tube, anesthesia, equipment, and airway (AU)

The efficiency of potassium removal during bicarbonate hemodialysis.

Patients on chronic hemodialysis often portray high serum [K+]. Although dietary excesses are evident in many cases, in others, the cause of hyperkalemia cannot be identified. In such cases, hyperkalemia could result from decreased potassium removal during dialysis. This situation could occur if alkalinization of body fluids during dialysis would drive potassium into the cell, thus decreasing the potassium gradient across the dialysis membrane. In 35 chronic hemodialysis patients, we compared two dialysis sessions performed 7 days apart. Bicarbonate or acetate as dialysate buffers were randomly assigned for the first dialysis. The buffer was switched for the second dialysis. Serum [K+], [HCO3-], and pH were measured in samples drawn before dialysis; 60, 120, 180, and 240 min into dialysis; and 60 and 90 min after dialysis. The potassium removed was measured in the dialysate. During the first 2 hr, serum [K+] decreased equally with both types of dialysates but declined more during the last 2 hr with bicarbonate dialysis. After dialysis, the serum [K+] rebounded higher with bicarbonate bringing the serum [K+] up to par with acetate. The lower serum [K+] through the second half of bicarbonate dialysis did not impair potassium removal (295.9 +/- 9.6 mmol with bicarbonate and 299.0 +/- 14.4 mmol with acetate). The measured serum K+ concentrations correlated with serum [HCO3-] and blood pH during bicarbonate dialysis but not during acetate dialysis. Alkalinization induced by bicarbonate administration may cause redistribution of K during bicarbonate dialysis but this does not impair its removal. The more marked lowering of potassium during bicarbonate dialysis occurs late in dialysis, when exchange is negligible because of a low gradient.

sis líquido" (GHB). Prevención. Tratamiento. El "éxtasis líquido" (GHB): ¿una droga de uso recreativo? Clínica biopsicosocial del consumidor y algunas propuestas terapéuticas / "Liquid ecstasy" (GHB): a recreational drug? Bio-psycho-social clinial profile of the consumer and some therapeutic proposals

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MTO: the second member of a Drosophila dual copper-thionein system.

Drosophila MTO metal binding features were analyzed for comparison with MTN, the paralogous Drosophila metallothionein, and to classify MTO as either zinc- or copper-thionein. This was achieved by a combination of in vivo, in vitro and in silico methodologies. All the results unambiguously classified MTO as a second Drosophila copper-thionein, putting Drosophila forward as the only metazoan in which any zinc-thionein has still to be reported. Interestingly, experimental data only showed minor differences in the coordinative behavior of both MTs, but provided a characteristic spectroscopic fingerprint, revealing the possible binding of chloride anions in certain metal-MTO aggregates.

[Association between ischemic heart disease and peptic ulcer. A case-control study]. / Asociación entre cardiopatía isquémica y ulcus péptico. Estudio de casos y controles.

AIM: To determine whether patients with ischemic heart disease (IHD) are at higher risk for peptic ulcer (PU). MATERIAL AND METHODS: We performed a case-control study. The patients were selected by simple random sampling of clinical histories. CASES: 310 patients with IHD (angina pectoris, myocardial infarct or both). CONTROLS: 310 patients without IHD, paired by age, sex and tobacco consumption. Data were obtained by review of the patients' clinical histories. Response variable: diagnosis of peptic ulcer by endoscopy, esophagogastroduodenal transit or surgery. The odds ratio (OR) was determined by logistic regression, adjusting for the effect of confounding variables and risk for PU. RESULTS: The mean age of the patients was 72.7 years (SD 8.6) and 70% were men. PU was found in 18.7% of the patients and in 12.3% of the controls with an adjusted OR of 1.77 (95% CI: 1.12-2.77; p = 0.01). This effect was produced at the expense of duodenal ulcer with an adjusted OR of 2.22 (95% CI: 1.29-3.74; p = 0.003). The adjusted OR of gastric ulcer was 1.13 (95% CI: 0.45-2.82; p = 0.8). CONCLUSIONS: After adjusting for the effect of confounding variables and risk factors for the development of PU, this disease was more frequent in the group of patients with IHD.

A new insight into metallothionein (MT) classification and evolution. The in vivo and in vitro metal binding features of Homarus americanus recombinant MT.

We report the synthesis and characterization of a Homarus americanus MT-cDNA (MTH) through retrotranscription of MTH-mRNA from metal-injected lobsters. Heterologous Escherichia coli expression in zinc- and copper-supplemented medium was achieved for MTH, the two domains betabetaMTH and betaalphaMTH and three site-directed mutants, betabetaC9H, betaalphaC37H, and betaalphaE31C/T34C. The in vivo conformed metal complexes and the in vitro substituted cadmium aggregates were characterized. Major stoichiometries of M(II)6-MTH for the entire MTH and M(II)3-betabetaMTH and M(II)3-betaalphaMTH for the independent domains fully validated our expression system. A low affinity binding site for a seventh Zn(II) in the in vivo synthesized MTH was located in the betaalpha domain. Additionally, minor M(II)4 species were found for each domain. Both single Cys to His mutations exhibited a similar reduction of their in vivo zinc binding ability but differed in their cadmium binding behavior when compared with the wild-type forms. Conversely, the double mutant showed an enhanced zinc and cadmium binding capacity. In vivo synthesis of MTH and of its independent domains in the presence of copper only afforded heterometallic copper-zinc species. These findings allow consideration of MTH as a zinc thionein and question the view of all crustacea MT structures as copper thioneins. Furthermore, a new approach for the evolutionary and functional classification of MT is proposed, based on the stoichiometry of metal-MT species and molecular phylogenetic analysis.

Zinc(II) is required for the in vivo and in vitro folding of mouse copper metallothionein in two domains.

We postulate that zinc(II) is a keystone in the structure of physiological mouse copper metallothionein 1 (Cu-MT 1). Only when Zn(II) is coordinated does the structure of the in vivo- and in vitro-conformed Cu-MT species consist of two additive domains. Therefore, the functionally active forms of the mammalian Cu-MT may rely upon a two-domain structure. The in vitro behaviour of the whole protein is deduced from the Cu titration of the apo and Zn-containing forms and compared with that of the independent fragments using CD, UV-vis, ESI-MS and ICP-AES. We propose the formation of the following Cu, Zn-MT species during Zn/Cu replacement in Zn7-MT: (Zn4)alpha(Cu4Zn1)beta-MT, (Cu3Zn2)alpha(Cu4Zn1)beta-MT and (Cu4Zn1)alpha(Cu6)beta-MT. The cooperative formation of (Cu3Zn2)alpha(Cu4Zn1)beta-MT from (Zn4)alpha(Cu4Zn1)beta-MT indicates that the preference of Cu(I) for binding to the beta domain is only partial and not absolute, as otherwise accepted. Homometallic Cu-MT species have been obtained either from the apoform of MT or from Zn7-MT after total replacement of zinc. In these species, copper distribution cannot be inferred from the sum of the independent alpha and beta fragments. The in vivo synthesis of the entire MT in Cu-supplemented media has afforded Cu7Zn3-MT [(Cu3Zn2)alpha(Cu4Zn1)beta-MT], while that of alpha MT has rendered a mixture of Cu4Zn1-alpha MT (40%), Cu5Zn1-alpha MT (20%) and Cu7-alpha MT (40%). In the case of beta MT, a mixture of Cu6-beta MT (25%) and Cu7-beta MT (75%) was recovered [1]. These species correspond to some of those conformed in vitro and confirm that Zn(II) is essential for the in vivo folding of Cu-MT in a Cu-rich environment. A final significant issue is that common procedures used to obtain mammalian Cu6-beta MT from native sources may not be adequate.

The Combitube in elective surgery: a report of 200 cases.

BACKGROUND: The Combitube has proved to be a valuable device for securing the airway in cases of difficult intubation. This study investigated the effectiveness of the Combitube in elective surgery during both mechanical and spontaneous ventilation. METHODS: Two hundred patients classified as American Society of Anesthesiologists physical status I and II, with normal airways, scheduled for elective surgery were randomly allocated into two groups: nonparalyzed, spontaneously breathing (n = 100); or paralyzed, mechanically ventilated (n = 100). After induction of general anesthesia and insertion of the Combitube, oxygen saturation, end-tidal carbon dioxide and isoflurane concentration, systolic and diastolic blood pressure and heart rate, as well as breath-by-breath spirometry data were obtained every 5 min. RESULTS: In 97% of patients, it was possible to maintain oxygenation, ventilation, and respiratory mechanics, as well as hemodynamic stability during either mechanical or spontaneous ventilation for the entire duration of surgery. The duration of surgery was between 15 and 155 min. CONCLUSIONS: The results of this study suggest that the Combitube is an effective and safe airway device for continued management of the airway in 97% of elective surgery cases.

Metallothionein-III prevents glutamate and nitric oxide neurotoxicity in primary cultures of cerebellar neurons.

Metallothionein (MT)-III, a member of the MT family of metal-binding proteins, is mainly expressed in the CNS and is abundant in glutamatergic neurons. Results in genetically altered mice indicate that MT-III may play neuroprotective roles in the brain, but the mechanisms through which this protein functions have not been elucidated. The aim of this work was to assess whether MT-III is able to prevent glutamate neurotoxicity and to identify the step of the neurotoxic process interfered with by MT-III. Glutamate neurotoxicity in cerebellar neurons in culture is mediated by excessive activation of glutamate receptors, increased intracellular calcium, and increased nitric oxide. It is shown that MT-III prevented glutamate- and nitric oxide-induced neurotoxicity in a dose-dependent manner, with nearly complete protection at 0.3-1 microgram/ml. MT-III did not prevent the glutamate-induced rise of intracellular calcium level but reduced significantly the nitric oxide-induced formation of cyclic GMP. Circular dichroism analysis revealed that nitric oxide triggers the release of the metals coordinated to the cysteine residues of MT-III, indicative of the S(Cys)-nitrosylation of the protein. Therefore, the present results indicate that MT-III can quench pathological levels of nitric oxide, thus preventing glutamate and nitric oxide neurotoxicity.

Drosophila MTN: a metazoan copper-thionein related to fungal forms.

Two Drosophila metallothioneins (MT) have been reported: MTN, a 40 residue peptide including 10 Cys, and MTO, a 43 residue peptide including 12 Cys. However, neither functional nor evolutionary analyses for either of the Drosophila MT are available. Here, heterologous expression of Mtn in Escherichia coli is reported. The metal binding abilities of the Cu- and Zn-MTN complexes conformed in vivo, as well as the features of the Cd- and Cu-aggregates produced by metal replacement in vitro, have been determined by atomic emission spectrometry, circular dichroism and electrospray ionization mass spectrometry. Primary structure relationships with other MT have been examined. The results indicate a close resemblance of MTN to fungal copper-thioneins.