Secretagogin expression in the mouse olfactory bulb under sensory impairments.

The interneurons of the olfactory bulb (OB) are characterized by the expression of different calcium-binding proteins, whose specific functions are not fully understood. This is the case of one of the most recently discovered, the secretagogin (SCGN), which is expressed in interneurons of the glomerular and the granule cell layers, but whose function in the olfactory pathway is still unknown. To address this question, we examined the distribution, generation and activity of SCGN-positive interneurons in the OB of two complementary models of olfactory impairments: Purkinje Cell Degeneration (PCD) and olfactory-deprived mice. Our results showed a significant increase in the density of SCGN-positive cells in the inframitral layers of olfactory-deprived mice as compared to control animals. Moreover, BrdU analyses revealed that these additional SCGN-positive cells are not newly formed. Finally, the neuronal activity, estimated by c-Fos expression, increased in preexisting SCGN-positive interneurons of both deprived and PCD mice -being higher in the later- in comparison with control animals. Altogether, our results suggest that the OB possesses different compensatory mechanisms depending on the type of alteration. Particularly, the SCGN expression is dependent of olfactory stimuli and its function may be related to a compensation against a reduction in sensory inputs.

Olfactory bulb plasticity ensures proper olfaction after severe impairment in postnatal neurogenesis.

The olfactory bulb (OB) neurons establish a complex network that ensures the correct processing of the olfactory inputs. Moreover, the OB presents a lifelong addition of new neurons into its existing circuitry. This neurogenesis is considered essential for the OB function. However, its functional impact on physiology and behavior is still unclear. Here, we investigate the mechanisms of OB plasticity that underlie bulbar physiology in relation to severe damage of neurogenesis. The neurogenesis of young mice was altered by ionizing radiation. Afterwards, both multi-channel olfactometry and electrophysiological studies were performed. Furthermore, neurogenesis and differentiation of the newly formed cells were assessed using bromodeoxyuridine labeling combined with a wide battery of neuronal markers. Our results demonstrate a reduction in both neurogenesis and volume of the OB in irradiated animals. The number of neuroblasts reaching the OB was reduced and their differentiation rate into interneurons selectively changed; some populations were noticeably affected whereas others remained preserved. Surprisingly, both olfactory detection and discrimination as well as electrophysiology presented almost no alterations in irradiated mice. Our findings suggest that after damaging postnatal neurogenesis, the neurochemical fate of some interneurons changes within a new biological scenario, while maintaining homeostasis and olfaction.

Transdentinal cell photobiomodulation using different wavelengths.

OBJECTIVE: The aim of this study was to investigate the effects of transdentinal irradiation with different light-emitting diode (LED) parameters on odontoblast-like cells (MDPC-23). METHODS AND MATERIALS: Human dentin discs (0.2 mm thick) were obtained, and cells were seeded on their pulp surfaces with complete culture medium (Dulbecco modified Eagle medium). Discs were irradiated from the occlusal surfaces with LED at different wavelengths (450, 630, and 840 nm) and energy densities (0, 4, and 25 J/cm(2)). Cell viability (methyltetrazolium assay), alkaline phosphatase activity (ALP), total protein synthesis (TP), and cell morphology (scanning electron microscopy) were evaluated. Gene expression of collagen type I (Col-I) was analyzed by quantitative polymerase chain reaction (PCR). Data were analyzed by the Mann-Whitney test with a 5% significance level. RESULTS: Higher cell viability (21.8%) occurred when the cells were irradiated with 630 nm LED at 25 J/cm(2). Concerning TP, no statistically significant difference was observed between irradiated and control groups. A significant increase in ALP activity was observed for all tested LED parameters, except for 450 nm at 4 J/cm(2). Quantitative PCR showed a higher expression of Col-I by the cells subjected to infrared LED irradiation at 4 J/cm(2). More attached cells were observed on dentin discs subjected to irradiation at 25 J/cm(2) than at 4 J/cm(2). CONCLUSION: The infrared LED irradiation at an energy density of 4 J/cm(2) and red LED at an energy density of 25 J/cm(2) were the most effective parameters for transdentinal photobiomodulation of cultured odontoblast-like cells.

The olfactory system as a puzzle: playing with its pieces.

The mammalian olfactory bulb (OB) has all the features of a whole mammalian brain but in a more reduced space: neuronal lamination, sensory inputs, afferences, or efferences to other centers of the central nervous system, or a contribution of new neural elements. Therefore, it is widely considered as "a brain inside the brain." Although this rostral region has the same origin and general layering as the other cerebral cortices, some distinctive features make it very profitable in experimentation in neurobiology: the sensory inputs are driven directly on its surface, the main output can be accessed anatomically, and new elements appear in it throughout adult life. These three morphological characteristics have been manipulated to analyze further the response of the whole OB. The present review offers a general outlook into the consequences of such experimentation in the anatomy, connectivity and neurochemistry of the OB after (a) sensory deprivation, mainly by naris occlusion; (b) olfactory deinnervation by means of olfactory epithelium damage, olfactory nerve interruption, or even olfactory tract disruption; (c) the removal of the principal neurons of the OB; and (d) management of the arrival of newborn interneurons from the rostral migratory stream. These experiments were performed using surgical or chemical methods, but also by means of the analysis of genetic models, some of whose olfactory components are missing, colorless or mismatching within the wild-type scenario of odor processing.

Proposal for an electron antineutrino disappearance search using high-rate 8Li production and decay.

This paper introduces an experimental probe of the sterile neutrino with a novel, high-intensity source of electron antineutrinos from the production and subsequent decay of 8Li. When paired with an existing ∼1 kton scintillator-based detector, this = 6.4 MeV source opens a wide range of possible searches for beyond standard model physics via studies of the inverse beta decay interaction ν(e) + p → e+ + n. In particular, the experimental design described here has unprecedented sensitivity to ν(e) disappearance at Δm2 ∼ 1 eV2 and features the ability to distinguish between the existence of zero, one, and two sterile neutrinos.

Changes in the serotonergic system and in brain-derived neurotrophic factor distribution in the main olfactory bulb of pcd mice before and after mitral cell loss.

The serotonergic centrifugal system innervating the main olfactory bulb (MOB) plays a key role in the modulation of olfactory processing. We have previously demonstrated that this system suffers adaptive changes under conditions of a lack of olfactory input. The present work examines the response of this centrifugal system after mitral cell loss in the Purkinje cell degeneration (pcd) mutant mice. The distribution and density of serotonergic centrifugal axons were studied in the MOB of control and pcd mice, both before and after the loss of mitral cells, using serotonin (5-HT) and 5-HT transporter immunohistochemistry. Studies of the amount of 5-HT and its metabolite, 5-hydroxyindole acetic acid (5-HIAA), were performed by means of high-performance liquid chromatography (HPLC), and the relative amounts of brain-derived neurotrophin factor, BDNF, and its major receptor, tropomyosin-related kinase B (TrkB), were measured by Western blot. Our study revealed that the serotonergic system develops adaptive changes after, but not before, mitral cell loss. The lack of the main bulbar projection cells causes a decrease in the serotonergic input received by the MOB, whereas the number of serotonergic cells in the raphe nuclei remains constant. In addition, one of the molecules directly involved in serotonergic sprouting, the neurotrophin BDNF and its main receptor TrkB, underwent alterations in the MOBs of the pcd animals even before the loss of mitral cells. These data indicate that serotonergic function in the MOB is closely related to olfactory activity and that mitral cell loss induces serotonergic plastic responses.

Long-lasting changes in the anatomy of the olfactory bulb after ionizing irradiation and bone marrow transplantation.

The adult brain is considered to be a radioresistant organ since it is mainly composed of non-dividing cells. However, in adult animals there are a few neurogenic brain areas that are affected by ionizing radiation whose plasticity and capacity for recovery are still unclear. Here, mice were irradiated with a minimal lethal dose of radiation in order to determine its effects on the subventricular zone (SVZ), the rostral migratory stream (RMS), and the olfactory bulb (OB). These regions underwent a dramatic reduction in cell proliferation and ensuing morphological alterations, accompanied by a patent reactive gliosis. Bone marrow stem cell (BMSC) transplants were also performed after the radiation treatment to allow the mouse survival with a view to analyzing long-term effects. Normal proliferation rates were not recovered over time and although bone marrow-derived cells reached the brain, they were not incorporated into the SVZ-RMS-OB pathway in an attempt to rescue the damaged regions. Since neurogenesis produces new interneurones in the OB, thus feeding cell turnover, the volume and lamination of the OB were analyzed. The volume of the OB proved to be dramatically reduced at postnatal day 300 (P300), and this shrinkage affected the periependymal white matter, the granule cell layer, the external plexiform layer, and the glomerular layer. These results should be taken into account in cell therapies employing BMSC, since such cells reach the encephalon, although they cannot restore the damage produced in neurogenic areas. This study thus provides new insight into the long-term effects of ionizing radiation, widely employed in animal experimentation and even in clinical therapies for human beings.

[Basis for the clinical management of fire smoke poisoning "Docohumo Madrid 2010"]. / Bases del manejo clínico de la intoxicación por humo de incendios «Docohumo Madrid 2010¼

Poisoning by smoke is the main cause of morbidity and mortality in fires. Smoke is a mixture of carbonaceous particles suspended in hot air and toxic gases. Of these, carbon monoxide (CO) and primarily hydrocyanic acid (CNH), are those that provoke tissue anoxia. The clinical manifestations of smoke poisoning are variables. Some of the potential manifestations could be: eye irritation, sore throat, laryngeal stridor, dysphagia, carbonaceous sputum, cough, dyspnea, laryngospasm, bronchospasm, coronary syndrome, coma, hypoxemia, lactic acidosis, cyanosis and death. In the assessment of these patients the presence of soot in the nose, mouth or sputum suggests serious poisoning. Lactate levels higher than 10mmol/L indicates levels of cyanide major than 40micromole/L. The pulse co-oximetry has assumed an important step forward for the diagnosis, appraisal and monitoring of these patients. In the treatment it will be essential to assess the need of an early intubation. The administration of oxygen to the 100% will be essential. As an antidote to the cyanide, the first-choice is the hydroxocobalamin. Its administration has to be early. Its administration criteria are: patient who has inhaled smoke (remnants of soot in the mouth, pharynx or sputum) and has neurological disorder (confusion, coma, agitation, seizures) and also presents one of the following circumstances: bradypnea, respiratory arrest, cardiorespiratory arrest, shock, hypotension, lactate ≥8mmol/L or lactic acidosis. Logically, the rest of the management will be conventional depending on symptoms or complications.

Sexual dimorphic stages affect both proliferation and serotonergic innervation in the adult rostral migratory stream.

One of the sexual dimorphic differences in adult rodents is neural proliferation. Here we demonstrate that physiological hormone stages can modulate this proliferation in the adult forebrain. Female mice, both pregnant and synchronized in oestrus, exhibited higher proliferating cell percentages than males in both the rostral migratory stream (RMS) and the olfactory bulb (OB). Moreover, although the hormonal component also influenced the subventricular zone (SVZ), no differences in proliferation were observed in this region. In addition, both groups of females had higher numbers of serotonergic fibres in these regions. Serotonin may therefore be related to the mechanism of action by which hormones can affect cell proliferation of this brain region. We also evaluated cell death in the SVZ in males and females, finding that this was higher in the former. Taken together, our results support the idea that in female rodents more neuroblasts are able to reach the RMS and then proliferate, apoptosis being an additional mechanism affecting the low proliferation of cells in the RMS and OB in males. Thus, proliferation in the RMS is influenced by sexual dimorphism.

Distribution of neurocalcin-containing neurons reveals sexual dimorphism in the mouse olfactory bulb.

Olfactory sexual dimorphism has mainly been described in the vomeronasal system, in relation to reproductive behavior, while evidence of sexual dimorphism in the main olfactory bulb (OB) remains scarce. There are no data indicating sex-related differences in the neurochemistry of intrinsic olfactory elements. Neurocalcin (NC) is a calcium-binding protein that is expressed in specific neuronal populations of the central nervous system. Here we analyzed by immunohistochemistry the NC-containing neurons in the mouse main OB, comparing both their quantities and their locations between male and female animals. NC cell density was higher in males than in females in specific locations of the glomerular layer, the external plexiform layer, the mitral cell layer, and the internal plexiform layer. This divergence in the numbers of NC cells was especially patent in central rostrocaudal levels. The NC-containing neurons exhibiting sexual divergence were identified as both juxtaglomerular and short-axon cells. This is the first description of sexual dimorphism regarding neurons belonging to the mouse main OB. According to their distribution in the OB, neurocalcin-immunoreactive interneurons could reflect a sexually dimorphic regulation of specific odorants.

Changes in cell migration and survival in the olfactory bulb of the pcd/pcd mouse.

Postnatally, the Purkinje cell degeneration mutant mice lose the main projecting neurons of the main olfactory bulb (OB): mitral cells (MC). In adult animals, progenitor cells from the rostral migratory stream (RMS) differentiate into bulbar interneurons that modulate MC activity. In the present work, we studied changes in proliferation, tangential migration, radial migration patterns, and the survival of these newly generated neurons in this neurodegeneration animal model. The animals were injected with bromodeoxyuridine 2 weeks or 2 months before killing in order to label neuroblast incorporation into the OB and to analyze the survival of these cells after differentiation, respectively. Both the organization and cellular composition of the RMS and the differentiation of the newly generated neurons in the OB were studied using specific markers of glial cells, neuroblasts, and mature neurons. No changes were observed in the cell proliferation rate nor in their tangential migration through the RMS, indicating that migrating neuroblasts are only weakly responsive to the alteration in their target region, the OB. However, the absence of MC does elicit differences in the final destination of the newly generated interneurons. Moreover, the loss of MC also produces changes in the survival of the newly generated interneurons, in accordance with the dramatic decrease in the number of synaptic targets available.

Sex differences in catechol contents in the olfactory bulb of control and unilaterally deprived rats.

The dopaminergic system plays important roles in the modulation of olfactory transmission. The present study examines the distribution of dopaminergic cells and the content of dopamine (DA) and its metabolites in control and deprived olfactory bulbs (OB), focusing on the differences between sexes. The content of DA and of its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were measured by HPLC. The morphology and distribution of dopaminergic neurons were studied using tyrosine hydroxylase (TH) immunohistochemistry. Cells were typified with TH-parvalbumin, TH-cholecystokinin or TH-neurocalcin double-immunofluorescence assays. Biochemical analyses revealed sex differences in the content of DA and of its metabolites. In normal conditions, the OBs of male rats had higher concentrations of DA, DOPAC and HVA than the OBs of females. The immunohistochemical data pointed to sex differences in the number of TH-immunopositive cells (higher in male than in female rats). Colocalization analyses revealed that dopaminergic cells constitute a different cell subpopulation from those labelled after parvalbumin, cholecystokinin or neurocalcin immunostaining. Unilateral olfactory deprivation caused dramatic alterations in the dopaminergic system. The DA content and the density of dopaminergic cells decreased, the contents of DA and DOPAC as well as TH immunoreactivity were similar in deprived males and females and, finally, the metabolite/neurotransmitter ratio increased. Our results show that the dopaminergic modulation of olfactory transmission seems to differ between males and females and that it is regulated by peripheral olfactory activity. A possible role of the dopaminergic system in the sexually different olfactory sensitivity, discrimination and memory is discussed.

Changes in the serotonergic system in the main olfactory bulb of rats unilaterally deprived from birth to adulthood.

The serotonergic system plays a key role in the modulation of olfactory processing. The present study examined the plastic response of this centrifugal system after unilateral naris occlusion, analysing both serotonergic afferents and receptors in the main olfactory bulb. After 60 days of sensory deprivation, the serotonergic system exhibited adaptive changes. Olfactory deprivation caused a general increase in the number of fibres immunopositive for serotonin but not of those immunopositive for the serotonin transporter. HPLC data revealed an increase in serotonin levels but not in those of its major metabolite, 5-hydroxyindole acetic acid, resulting in a decrease in the 5-hydroxyindole acetic acid/serotonin ratio. These changes were observed not only in the deprived but also in the contralateral olfactory bulb. Double serotonin-tyrosine hydroxylase immunolabelling revealed that the glomerular regions of the deprived olfactory bulb with a high serotonergic fibre density showed a strong reduction in tyrosine hydroxylase. Finally, the serotonin(2A) receptor distribution density and the number of juxtaglomerular cells immunopositive for serotonin(2A) receptor remained unaltered after olfactory deprivation. Environmental stimulation modulated the serotonergic afferents to the olfactory bulb. Our results indicate the presence of a bilateral accumulation of serotonin in the serotonergic axon network, with no changes in serotonin(2A) receptor density after unilateral olfactory deprivation.

Differential effects of unilateral olfactory deprivation on noradrenergic and cholinergic systems in the main olfactory bulb of the rat.

The lack of environmental olfactory stimulation produced by sensory deprivation causes significant changes in the deprived olfactory bulb. Olfactory transmission in the main olfactory bulb (MOB) is strongly modulated by centrifugal systems. The present report examines the effects of unilateral deprivation on the noradrenergic and cholinergic centrifugal systems innervating the MOB. The morphology, distribution, and density of positive axons were studied in the MOBs of control and deprived rats, using dopamine-beta-hydroxylase (DBH)-immunohistochemistry and acetylcholinesterase (AChE) histochemistry in serial sections. Catecholamine content was compared among the different groups of MOBs (control, contralateral, and ipsilateral to the deprivation) using high-performance liquid chromatography analysis. Sensory deprivation revealed that the noradrenergic system developed adaptive plastic changes after olfactory deprivation, including important modifications in its fiber density and distribution, while no differences in cholinergic innervation were observed under the same conditions. The noradrenergic system underwent an important alteration in the glomerular layer, in which some glomeruli showed a dense noradrenergic innervation that was not detected in control animals. The DBH-positive glomeruli with the highest noradrenergic fiber density were compared with AChE-stained sections and it was observed that the strongly noradrenergic-innervated glomeruli were always atypical glomeruli (characterized by their strong degree of cholinergic innervation). In addition to the morphological findings, our biochemical data revealed that olfactory deprivation caused a decrease in the content of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid in the ipsilateral MOB in comparison to the contralateral and control MOBs, together with an increase in noradrenaline levels in both the ipsilateral and contralateral MOBs. Our results show that regulation of the noradrenergic centrifugal system in the MOB depends on environmental olfactory stimulation and that it is highly reactive to sensory deprivation. By contrast, the cholinergic system is fairly stable and does not exhibit clear changes after the loss of sensory inputs.

Desarrollo y manejo de indicadores para mejorar la gestión de la asistencia. Una herramienta que puede ser útil a pesar de sus limitaciones / Development and use of indicators to improve assistant management in a hospital. A useful tool in spite of its limitations

La política del Hospital Puerta de Hierro de fomentar el uso de indicadores para la gestión ha sido desarrollada en diferentes ámbitos a partir de una estrategia común que adopta formas diferentes según el lugar de implantación. La aplicación hospitalaria general se centró en el estudio, selección, recopilación y difusión de información; la información más importante en la aplicación a los cuidados enfermeros fue la de activar y automatizar fuentes de información específicas; en un servicio clínico con su propio sistema de información, toma la forma de un proceso informático de cálculo; y en el caso de consultas externas su función fue la de priorizar indicadores incluidos en el Sistema de Información

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Estrategias terapéuticas inmunológicas contra el tabaco: una revisión / Immunological therapeutic strategies against tobacco: a review

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Heterogeneous targeting of centrifugal inputs to the glomerular layer of the main olfactory bulb.

The centrifugal systems innervating the olfactory bulb are important elements in the functional regulation of the olfactory pathway. In this study, the selective innervation of specific glomeruli by serotonergic, noradrenergic and cholinergic centrifugal axons was analyzed. Thus, the morphology, distribution and density of positive axons were studied in the glomerular layer of the main olfactory bulb of the rat, using serotonin-, serotonin transporter- and dopamine-beta-hydroxylase-immunohistochemistry and acetylcholinesterase histochemistry in serial sections. Serotonin-, serotonin transporter-immunostaining and acetylcholinesterase-staining revealed a higher heterogeneity in the glomerular layer of the main olfactory bulb than previously reported. In this sense, four types of glomeruli could be identified according to their serotonergic innervation. The main distinctive feature of these four types of glomeruli was their serotonergic fibre density, although they also differed in their size, morphology and relative position throughout the rostro-caudal main olfactory bulb. In this sense, some specific regions of the glomerular layer were occupied by glomeruli with a particular morphology and a characteristic serotonergic innervation pattern that was consistent from animal to animal. Regarding the cholinergic system, we offer a new subclassification of glomeruli based on the distribution of cholinergic fibres in the glomerular structure. Finally, the serotonergic and cholinergic innervation patterns were compared in the glomerular layer. Sexual differences concerning the density of serotonergic fibres were observed in the atypical glomeruli (characterized by their strong cholinergic innervation). The present report provides new data on the heterogeneity of the centrifugal innervation of the glomerular layer that constitutes the morphological substrate supporting the existence of differential modulatory levels among the entire glomerular population.

Asma por sensibilización a cucaracha (Blatella germanica): a propósito de dos casos en marineros / Cockroach (Blatella germanica) sensibilization asthma: two cases report in the navy

La Blatella germanica es una especie de cucaracha que, con frecuencia, infesta los buques de guerra y que puede ser perjudicial para la salud humana, produciendo, entre otras enfermedades, episodios de asma bronquial de etiologia alérgica. Describimos dos casos de asma bronquial en marineros profesionales en los que se demostró una sensibilización a Blatella germanica. Ambos pacientes referían antecedentes, previos a su ingreso en la Armada, que podrían explicar la sensibilización a cucaracha que presentaban; aunque es posible que la exposición de forma crónica, en los barcos, a alergenos de cucaracha pudiese ser el desencadenante de los episodios de asma por los que consultaron. Los dos pacientes además de estar sensibilizados a Blatella germanica tenían otras sensibilizaciones, diferentes en cada caso, que podrían estar relacionadas con la alergia a cucarachas. Uno de ellos, in vitro, también estaba sensibilizado a Ascaris y Anisakis y el otro tenia pruebas cutáneas positivas con Periplaneta americana, otra especie de cucaracha. Hallazgos que, en los dos casos, estarían justificados por una similar alergenicidad entre las proteínas de todas estas especies. La alergia a cucaracha es una patología que, pensamos; debería descartarse en todo el personal embarcado que padece asma bronquial (AU)

Reversible inhibition of mitochondrial complex IV activity in PBMC following acute smoking.

Smoking causes a decrease of mitochondrial complex IV activity in chronic smokers. However, it is not known if this toxic effect is due to the acute effect of cigarette smoke itself or is a secondary phenomenon related to other smoking factors. The study assessed mitochondrial respiratory chain function in peripheral blood mononuclear cells of 15 healthy nonsmoker individuals before smoking (t0), immediately after smoking five cigarettes in 45 min (t1) and 24 h later (t2). Blood carboxyhaemoglobin (COHb) and carbon monoxide concentrations in exhaled air (COEA) were determined to ascertain smoke inhalation status. After acute smoking, COHb increased from 0.5 +/- 0.3% to 3.3 +/- 1.5%, and COEA from 2.9 +/- 2.5 to 26.1 +/- 9.9 ppm. Complex II and III enzyme activities did not change along the study. Complex IV activity showed a 23% inhibition at t1 but returned to initial (to) levels at t2. A decay in oxygen consumption was observed after the correction for mitochondrial content. Lipid peroxidation of cell membranes remained unchanged. Short-time smoking causes an acute and reversible mitochondrial complex IV inhibition in human mononuclear cells. These results suggest that smoke itself is one of the causes for the decrease of complex IV activity observed in chronic smokers.