Polimorfismos del gen Butirilcolinesterasa responsables de reacciones adversas en pacientes consumidores de “cocaína”

La butirilcolinesterasa humana (BChE; EC 3.1.1.8) es una enzima polimórfica sintetizada en el hígado y en el tejido adiposo, ampliamente distribuida en el organismo y encargada de hidrolizar algunos ésteres de colina como la procaína, ésteres alifáticos como el ácido acetilsalicílico, fármacos como la metilprednisolona, el mivacurium y la succinilcolina y drogas de uso y/o abuso como la heroína y la cocaína. Es codificada por el gen BCHE (OMIM 177400), habiéndose identificado más de 100 variantes, algunas no estudiadas plenamente, además de la forma más frecuente, llamada usual o silvestre. Diferentes polimorfismos del gen BCHE se han relacionado con la síntesis de enzimas con niveles variados de actividad catalítica. Las bases moleculares de algunas de esas variantes genéticas han sido reportadas, entre las que se encuentra las variantes Atípica (A), fluoruro-resistente del tipo 1 y 2 (F-1 y F-2), silente (S), Kalow (K), James (J) y Hammersmith (H). En este estudio, en un grupo de pacientes se aplicó el instrumento validado Lifetime Severity Index for Cocaine Use Disorder (LSI-C) para evaluar la gravedad del consumo de “cocaína” a lo largo de la vida. Además, se determinaron Polimorfismos de Nucleótido Simple (SNPs) en el gen BCHE conocidos como responsables de reacciones adversas en pacientes consumidores de “cocaína” mediante secuenciación del gen y se predijo el efecto delos SNPs sobre la función y la estructura de la proteína, mediante el uso de herramientas bio-informáticas. El instrumento LSI-C ofreció resultados en cuatro dimensiones: consumo a lo largo de la vida, consumo reciente, dependencia psicológica e intento de abandono del consumo. Los estudios de análisis molecular permitieron observar dos SNPs codificantes (cSNPs) no sinónimos en el 27.3% de la muestra, c.293A>G (p.Asp98Gly) y c.1699G>A (p.Ala567Thr), localizados en los exones 2 y 4, que corresponden, desde el punto de vista funcional, a la variante Atípica (A) [dbSNP: rs1799807] y a la variante Kalow (K) [dbSNP: rs1803274] de la enzima BChE, respectivamente. Los estudios de predicción In silico establecieron para el SNP p.Asp98Gly un carácter patogénico, mientras que para el SNP p.Ala567Thr, mostraron un comportamiento neutro. El análisis de los resultados permite proponer la existencia de una relación entre polimorfismos o variantes genéticas responsables de una baja actividad catalítica y/o baja concentración plasmática de la enzima BChE y algunas de las reacciones adversas ocurridas en pacientes consumidores de cocaína.

Regenerative capabilities of the rat seventh nerve using suture and collagen splint techniques: a comparative study

This paper discusses the effectiveness of repair procedures on the rat facial nerve using the current clinical surgical procedure of suturing nerve ends and a proposed technique utilizing splints made of collagen.

Investigation of the effect of macrophages and other leukocytes on hair cell regeneration in the avian inner ear

This paper investigates the relationship between hair cell proliferation and immunosuppression in chicks.

Density of myelinated nerve fibers in the chinchilla cochlea

This paper reviews a study to obtain baseline values for the density of myelinated nerve fibers of the chinchilla cochlea.

Behavior in pigeons during regeneration

This paper examines the recovery of the vestibular related head posture and balance ability in pigeons during regeneration of the vestibular system following ototoxic insult.

Cisplatin ototoxicity and hair cell regeneration in the zebrafish lateral line

Hair cell death and regeneration on the zebrafish posterior lateral line was investigated after cisplatin administration. Hair cell regeneration was first observed by 24 hours of recovery and was further analyzed after specific recovery intervals. Disruption of the notch signaling pathways by the y-secretase inhibitor DAPT resulted in an increase in hair cells at three days of recovery.

Ovenbird (Seiurus aurocapilla) Territory Placement Near Seismic Lines is Influenced by Forest Regeneration and Conspecific Density

The boreal forest of western Canada is being dissected by seismic lines used for oil and gas exploration. The vast amount of edge being created is leading to concerns that core habitat will be reduced for forest interior species for extended periods of time. The Ovenbird (Seiurus aurocapilla) is a boreal songbird known to be sensitive to newly created seismic lines because it does not include newly cut lines within its territory. We examined multiple hypotheses to explain potential mechanisms causing this behavior by mapping Ovenbird territories near lines with varying states of vegetation regeneration. The best model to explain line exclusion behavior included the number of neighboring conspecifics, the amount of bare ground, leaf-litter depth, and canopy closure. Ovenbirds exclude recently cut seismic lines from their territories because of lack of protective cover (lower tree and shrub cover) and because of reduced food resources due to large areas of bare ground. Food reduction and perceived predation risk effects seem to be mitigated once leaf litter (depth and extent of cover) and woody vegetation cover are restored to forest interior levels. However, as conspecific density increases, lines are more likely to be used as landmarks to demarcate territorial boundaries, even when woody vegetation cover and leaf litter are restored. This behavior can reduce territory density near seismic lines by changing the spatial distribution of territories. Landmark effects are longer lasting than the effects from reduced food or perceived predation risk because canopy height and tree density take >40 years to recover to forest interior levels. Mitigation of seismic line impacts on Ovenbirds should focus on restoring forest cover as quickly as possible after line cutting.

The variation in transparency of amniotic membrane used in ocular surface regeneration

Background/aims: Scant consideration has been given to the variation in structure of the human amniotic membrane (AM) at source or to the significance such differences might have on its clinical transparency. Therefore, we applied our experience of quantifying corneal transparency to AM. Methods: Following elective caesarean, AM from areas of the fetal sac distal and proximal (ie, adjacent) to the placenta was compared with freeze-dried AM. The transmission of light through the AM samples was quantified spectrophotometrically; also, tissue thickness was measured by light microscopy and refractive index by refractometry. Results: Freeze-dried and freeze-thawed AM samples distal and proximal to the placenta differed significantly in thickness, percentage transmission of visible light and refractive index. The thinnest tissue (freeze-dried AM) had the highest transmission spectra. The thickest tissue (freeze-thawed AM proximal to the placenta) had the highest refractive index. Using the direct summation of fields method to predict transparency from an equivalent thickness of corneal tissue, AM was found to be up to 85% as transparent as human cornea. Conclusion: When preparing AM for ocular surface reconstruction within the visual field, consideration should be given to its original location from within the fetal sac and its method of preservation, as either can influence corneal transparency.

Nerve terminal GABAA receptors activate Ca2+/calmodulin-dependent signaling to inhibit voltage-gated Ca2+ influx and glutamate release

-Aminobutyric acid type A (GABAA) receptors, a family of Cl-permeable ion channels, mediate fast synaptic inhibition as postsynaptically enriched receptors for -aminobutyric acid at GABAergic synapses. Here we describe an alternative type of inhibition mediated byGABAA receptors present on neocortical glutamatergic nerve terminals and examine the underlying signaling mechanism(s). By monitoring the activity of the presynaptic CaM kinase II/synapsin I signaling pathway in isolated nerve terminals, we demonstrate that GABAA receptor activation correlated with an increase in basal intraterminal [Ca2]i. Interestingly, this activation of GABAA receptors resulted in a reduction of subsequent depolarization-evoked Ca2 influx, which thereby led to an inhibition of glutamate release. To investigate how the observed GABAA receptor-mediated modulation operates, we determined the sensitivity of this process to the Na-K-2Cl cotransporter 1 antagonist bumetanide, as well as substitution of Ca2 with Ba2, or Ca2/calmodulin inhibition by W7. All of these treatments abolished the modulation by GABAA receptors. Application of selective antagonists of voltage-gated Ca2 channels (VGCCs) revealed that the GABAA receptor-mediated modulation of glutamate release required the specific activity of L- and R-type VGCCs. Crucially, the inhibition of release by these receptors was abolished in terminals isolated from R-type VGCC knock-out mice. Together, our results indicate that a functional coupling between nerve terminal GABAA receptors and L- or R-type VGCCs is mediated by Ca2/calmodulin-dependent signaling. This mechanism provides a GABA-mediated control of glutamatergic synaptic activity by a direct inhibition of glutamate release.

Refashioning local government and inner-city regeneration: The Salford experience

This paper explores the role of local government in urban regeneration in England. The first part describes local-central government relations during recent decades. It concludes that 'actually occurring' regeneration fuses top-down and bottom-up priorities and preferences, as well as path dependencies created by past decisions and local relations. The second part illustrates this contention by examining the regeneration of inner-city Salford over a 25-year period. It describes Salford City Council's approach in achieving the redevelopment of the former Salford Docks and how this created the confidence for the council to embark on further regeneration projects. Yet the top-down decision-making model has failed to satisfy local expectations, creating apathy which threatens the Labour government's desire for active citizens in regeneration projects.