New bioanalytical platform based on the use of avidin for the successful exfoliation of multi-walled carbon nanotubes and the robust anchoring of biomolecules. Application for hydrogen peroxide biosensing.

We are reporting an innovative building-block for the development of biosensors based on the non-covalent functionalization of multi-walled carbon nanotubes (MWCNTs) with avidin (MWCNTs-avidin). In this work, at variance with previous reports, avidin has the double role of simultaneously being the exfoliating agent of MWCNTs and the platform for anchoring different biotinylated biomolecules. The optimum dispersion was obtained by sonicating for 5.0 min 0.50 mgmL-1 MWCNTs with 1.00 mgmL-1 avidin solution prepared in 50:50 v/v ethanol/water. As proof-of-concept, we immobilized biotinylated horseradish peroxidase (b-HRP) at glassy carbon electrodes (GCE) modified with MWCNTs-avidin to develop a hydrogen peroxide biosensor using hydroquinone as redox mediator. Surface plasmon resonance, electrochemical impedance spectroscopy, cyclic voltammetry and amperometry demonstrated that, even after the partial denaturation of avidin due to the drastic conditions used to functionalize the MWCNTs, it preserves the biorecognition properties and efficiently interacts with biotinylated horseradish peroxidase (b-HRP). The analytical characteristics of the resulting hydrogen peroxide biosensor are the following: linear range between 1.0 × 10-6 M and 1.4 × 10-5 M, sensitivity of (1.37 ±â€¯0.04) x 105 µAM-1, detection limit of 24 nM and reproducibility of 2.9%. The sensor was challenged with different samples, a mouthwash solution, human blood serum and milk, with very good performance.

Peptide-based biomaterials. Linking l-tyrosine and poly l-tyrosine to graphene oxide nanoribbons.

Peptide-based biomaterials are being studied actively in a variety of applications in materials science and biointerface engineering. Likewise, there has been ongoing exploration over the last few decades into the potential biological applications of carbon nanomaterials, motivated by their size, shape, structure and their unique physical and chemical properties. In recent years, the functionalization of carbon nanotubes and graphene has led to the preparation of bioactive carbon nanomaterials that are being used in biomedicine as structural elements and in gene therapy and biosensing. The present study proposes different strategies for the bonding of l-tyrosine and the homopolypeptide poly-l-tyrosine to graphene oxide nanoribbons (GONRs). The covalent attachment of l-tyrosine was undertaken by amidation of the α-amine group of tyrosine with the existing carboxylic groups in GONR and by means of esterification through phenol nucleophiles contained in their side chains. In both cases use was made of protective groups to address the functionalization with the desired reactive groups. The linking of GONRs to the PTyr was attempted according to two different strategies: either by ester bonding of commercial PTyr through its phenol side groups or by in situ ring-opening polymerization of an N-carboxyanhydride tyrosine derivative (NCA-Tyr) with Tyr-functionalized GONRs. These biofunctionalized nanomaterials were characterized by Raman and infrared spectroscopies, X-ray photoelectron spectroscopy, thermogravimetric analysis, transmission electron microscopy, fluorescence and electrochemical techniques. On the basis of their properties, prospects for the potential utilization of the prepared hybrid nanomaterials in different applications are also given.

Comparative study of the electrochemical behavior and analytical applications of (bio)sensing platforms based on the use of multi-walled carbon nanotubes dispersed in different polymers.

This review present a critical comparison of the electrochemical behavior and analytical performance of glassy carbon electrodes (GCE) modified with carbon nanotubes (CNTs) dispersed in different polymers: polyethylenimine (PEI), PEI functionalized with dopamine (PEI-Do), polyhistidine (Polyhis), polylysine (Polylys), glucose oxidase (GOx) and double stranded calf-thymus DNA (dsDNA). The comparison is focused on the analysis of the influence of the sonication time, solvent, polymer/CNT ratio, and nature of the polymer on the efficiency of the dispersions and on the electrochemical behavior of the resulting modified electrodes. The results allow to conclude that an adequate selection of the polymers makes possible not only an efficient dispersion of CNTs but also, and even more important, the building of successful analytical platforms for the detection of different bioanalytes like NADH, glucose, DNA and dopamine.

[Immunotherapy in high grade astrocytomas: principles and current state]. / Immunoterapia en astrocitomas de alto grado: principios y estado actual

It is generally accepted that tumour development promotes a systemic response leading to protect the host against cancer. However, tumours may as well elicit a partial immunodeficiency to avoid the development of a complete and active immune response. Since Bloom's first studies on immunotherapy to treat high grade gliomas in 1960, many attempts have been made from different medical specialties to use the immune system as a weapon against a great diversity of cancers. Main objective of this study is to outline the basic features of the immune response inside the Central Nervous System, the strategies employed by astrocytic tumours to evade body defences, and to provide an extended literature review on research on immunotherapy, especially concerning its patho-physiology and the clinical results achieved till date.

Inmunoterapia en astrocitomas de alto grado: principios y estado actual / Immunotherapy in high grade astrocytomas: principles and current state

Desde hace tiempo se conoce que la presencia de un tumor origina en el organismo una reacción del sistema inmune enfocada a eliminar la amenaza que el desarrollo tumoral implica. Sin embargo, se van averiguando diferentes mecanismos por los cuales los tumores provocan un estado de inmunosupresión que dificulta el desarrollo de una reacción inmunitaria eficaz. La utilización del sistema inmune como arma frente a los astrocitomas de alto grado constituye una de las principales estrategias de investigación desde los primeros ensayos de Bloom en 1960, siendo hoy en día una práctica habitual en la terapia antineoplásica de múltiples disciplinas médicas. El objetivo de este estudio es describir las características de las reacciones inmunológicas del sistema nervioso central, los mecanismos utilizados por los tumores astrocitarios para despistar las defensas del organismo y las diferentes líneas de investigación llevadas a cabo hasta la fecha, mostrando sus bases fisiopatológicas y los resultados obtenidos, basándonos en una extensa revisión bibliográfica

It is generally accepted that tumour development promotes a systemic response leading to protect the host against cancer. However, tumours may as well elicit a partial immunodeficiency to avoid the development of a complete and active immune response. Since Bloom´s first studies on immunotherapy to treat high grade gliomas in 1960, many attempts have been made from different medical specialties to use the immune system as a weapon against a great diversity of cancers. Main objective of this study is to outline the basic features of the immune response inside the Central Nervous System, the strategies employed by astrocytic tumours to evade body defences, and to provide an extended literature review on research on immunotherapy, especially concerning its patho-physiology and the clinical results achieved till date

[Akinetic mutism related to hydrocephalus and cerebellar surgery treated with bromocriptine and ephedrine. A pathophysiological review]. / Mutismo acinético relacionado con hidrocefalia y cirugía cerebelosa tratado con bromocriptina y efedrina. Revisión fisiopatológica.

Akinetic mutism (AM) is a behavioral disorder characterized by impossibility to move or speak in awake patients. lt has been typically described as a transient disorder following posterior fossa tumour resection. Besides, AM may also appear after recurrent shunt failures in hydrocephalic patients, with no tendency towards improvement, either spontaneously or with shunt revisions. However successful treatment of this second type of AM has been achieved with bromocriptine. We present a patient who developed AM after a posterior fossa surgery complicated by ventriculitis and multiple hydrocephalic events. AM only improved with bromocriptine. We review AM pathophysiology. Although not well known, it appears to be quite different, depending on its cerebellar or hydrocephalic origin. Damage to dentate nucleus or its efferents (mainly of glutamate) should promote AM of cerebellar origin, while damage to paraventricular monoaminergic pathways could explain AM related to repeated shunt failures which has successful response to bromocriptine treatment. However, a more complete study of this disorder is required to ascertain its aetiology.

Mutismo acinético relacionado con hidrocefalia y cirugía cerebelosa tratado con bromocriptina y efedrina. Revisión fisiopatológica / Akinetic mutism related to hydrocephalus and cerebellar surgery treated with bromocriptine and ephedrine. A pathophysiological review

El mutismo acinético (MA) es un trastorno del comportamiento, caracterizado por la incapacidad para moverse o hablar en pacientes despiertos. Típicamente ha sido descrito como una complicación transitoria de la cirugía de tumores de fosa posterior. Sin embargo, el MA también puede aparecer tras múltiples fallos valvulares en pacientes hidrocefálicos. En estos casos, el MA no mejora espontáneamente, ni con revisiones valvulares, pero puede responder al tratamiento con bromocriptina. Presentamos una paciente con MA tras una cirugía de fosa posterior, complicada por una ventriculitis con dilataciones ventriculares repetidas, que sólo mejoró con bromocriptina. Revisamos la fisiopatología del MA. Aunque ésta no sea bien conocida, parece que la afectación del núcleo dentado y de sus eferencias (principalmente de glutamato) sería responsable del MA de origen cerebeloso, mientras que la afectación de las vías monoaminérgicas paraventriculares explicaría el MA relacionado con dilataciones ventriculares repetidas y que responde al tratamiento con bromocriptina. Aun así, se requiere un estudio más profundo de esta patología para aclarar su etiología

Akinetic mutism (AM) is a behavioral disorder characterized by impossibility to move or speak in awake patients. lt has been typically described as a transient disorder following posterior fossa tumour resection. Besides, AM may also appear after recurrent shunt failures in hydrocephalic patients, with no tendency towards improvement, either spontaneously or with shunt revisions. However successful treatment of this second type of AM has been achieved with bromocriptine. We present a patient who developed AM after a posterior fossa surgery complicated by ventriculitis and multiple hydrocephalic events. AM only improved with bromocriptine. We review AM pathophysiology. Although not well known, it appears to be quite different, depending on its cerebellar or hydrocephalic origin. Damage to dentate nucleus or its efferents (mainly of glutamate) should promote AM of cerebellar origin, while damage to paraventricular monoaminergic pathways could explain AM related to repeated shunt failures which has successful response to bromocriptine treatment. However, a more complete study of this disorder is required to ascertain its aetiology

[Management of recurrent trigeminal neuralgia after failed microvascular decompression]. / Manejo de la recidiva de la neuralgia del trigémino tras descompresión microvascular.

OBJECTIVE: To evaluate the surgical management of patients with trigeminal neuralgia after failed microvascular decompression. PATIENTS AND METHODS: Between 1993 and 2002, exploration of the posterior fossa was performed in 60 patients with trigeminal neuralgia. Records were analyzed retrospectively for those patients who needed another surgical procedure due to recurrence of pain, describing which procedure was performed, postoperative results and complications, and also the intraoperative findings when posterior fossa reexploration was realized. RESULTS: Eighteen patients had trigeminal neuralgia recurrence requiring a new surgical intervention, that consisted in a fossa posterior reexploration in nine patients and percutaneous radiofrequency termal rhizotomy in the other nine patients. Among the repeat operations, there was negative exploration in 7 patients (77%), and a partial sensory rhizotomy was performed. Most of thermocoagulations (5/9) were performed in old patients or patients with anestesic contraindication for the fossa posterior reexploration. CONCLUSION: Fossa posterior reexploration is an effective and safe surgical attitude in the treatment of recurrent trigeminal neuralgia after failed microvascular decompression. Partial sensory rhizotomy is recommended when the reexploration is negative.

Single forebrain ventricle without prosencephaly: agenesis of the corpus callosum with dehiscent fornices.

Coalescence of the cerebral ventricles with formation of a single forebrain ventricle is described in an unusual case of agenesis of the corpus callosum with dehiscent fornices and severe hydrocephalus. The cerebral hemispheres were fully cleaved. The detached fornices were widely separated from the thalami. The membrana tectoria was retroverted over the midbrain and cerebellum, where it joined the fornices and merged with a curved membranous ependymal dome which, at a great distance, circumvented the thalami as it extended toward the anterior commissure. Other anomalies included arhinencephaly, multiple subependymal heterotopias, and Dandy-Walker malformation. Similar malformations have been described as interhemispheric cysts, as (holo)prosencephaly, or as "midline telencephalic dysgenesis." The basic features of prosencephaly and agenesis of the corpus callosum are reviewed and compared to the present case.

Cocaine-induced intratumoral hemorrhage: case report and review of the literature.

A unique case is described of a 28-year-old man who had seizures and a hemorrhage within a previously unsuspected cerebellopontine angle schwannoma within minutes of nasally inhaling cocaine. A review of the literature on cocaine-induced seizures and cocaine-induced cerebral hemorrhage is also given.

Angiographically occult vascular malformations in childhood.

Five infants and children with angiographically occult vascular malformations of the brain detected by computed tomography (CT) are presented. Four malformations were located in the cerebral hemisphere, and one was in the brain stem. CT demonstrated high density lesions with little or no enhancement after infusion of the contrast material. The malformations were resected and histologically proven. All patients have done well. The pertinent literature is reviewed. These lesions are uncommon during infancy and childhood and mimic gliomas clinically and radiographically. The need for surgical extirpation of these lesions is stressed.

Coronary artery spasm in intact dogs induced by potassium and serotonin.

Although coronary artery spasm has been implicated as an important cause of myocardial ischemia in humans, an animal model of reversible segmental coronary constriction has not been described. To provoke coronary spasm in open-chest dogs, selected vasoconstricting agents adsorbed to viscous ion exchange gels were applied topically to the surface of epicardial coronary arteries. The procedure provided a sustained localized release of drug, and minimized effects on contiguous myocardium or on the systemic circulation. Segmental arterial constrictor responses were evaluated by sonomicrometry, arteriography, and electromagnetic flow measurements. Potassium evoked sustained constrictions or spasms, and concomitantly reduced flow by -42 +/- 4% (SE; n = 34). Serotonin likewise produced sustained decreases in flow of -22 +/- 6% (SE; n = 5). Other constrictors, including norepinephrine and angiotensin, failed to evoke sustained constrictions. Spasms nearly abolished reactive hyperemic responses elicited by temporary complete occlusion of the artery. Intravenous nitroglycerin and dihydropyridine calcium antagonists promptly relieved the spasms. Scanning electronmicroscopic examination of the intimal surface of arteries undergoing sustained spasm revealed no platelet thrombi. Thus, nonthrombotic, vasodilator-sensitive segmental coronary spasms were elicited by endogenous constrictors which may play a role in regulating flow to ischemic myocardium.

Suprasellar cysts: surgical treatment and results.

The purpose of this paper is to present the clinical picture, diagnostic studies, and treatment of 5 cases of suprasellar cyst. The clinical symptoms and signs result from increased intracranial pressure without lateralizing signs (midline syndrome) and direct compression of the adjacent structures (hypothalmopituitary syndrome). The findings of computerized transmission tomography (CTT) and cerebral angiography in patients with suprasellar cyst are very similar to those of severe hydrocephalus. Cerebral angiography, however, reveals in inordinate mass effect in the parasellar area. Even though the location of the parasellar cyst is well demonstrated on postventriculoperitoneal shunt CTT scans, pneumonencephalography is necessary to confirm the diagnosis. We treated our patients with uni- or bilateral ventriculoperitoneal shunts, followed by craniotomy and cystosubarachnoid marsupialization. Cystoperitoneal shunting was performed after craniotomy in some instances, in place of it in others.

Percutaneous epidural neurostimulation in modulation of paraplegic spasticity. Six case reports.

Six cases of paraplegic, post-traumatic spasticity, alleviated by percutaneous epidural neurostimulation with temporary or permanent implanted neuroelectrodes from the L1 to L4 intervertebral levels are presented. Modulation of this spasticity and secondary beneficial physiological effects were achieved, including regulation of bowel regimens, production of sweating and piloerection below the level of the lesion, and morning erections. The main advantages of percutaneous epidural neurostimulation in modulating spasticity are the avoidance of destructive neurosurgical procedures, the regulation of secondary physiological and autonomic responses, the avoidance of antispasticity medications, and the reversibility of the neurostimulation procedure.

Physiopathology and a new treatment of chronic subdural hematoma in children.

Chronic collections of fluid in the subdural spaces may result from trauma or may complicate meningitis. The etiological factor, or factors, which contribute to chronicity of subdural fluid in children remains obscure. We postulate that one possible mechanism is the progressive stretching and narrowing of the cortical veins, bridging the subarachnoid and subdural spaces to enter the superior sagittal sinus. This process ultimately leads to thrombosis of these 'hanging veins'. Narrowing and angulation of these veins could result in elevated back pressure favoring the formation of a transudate. 16 children who had progressive and persistent collections of xanthochromic fluid in the subdural spaces secondary to trauma or infection who were treated previously either with subdural tap, burr holes, subdural peritoneal shunt, craniotomy, stripping of membranes and/or a combination of these, were treated by lowering and advancing the superior sagittal sinus with its overlying sagittal suture and performing a duraplasty. This new surgical technique is directed to improve venous drainage from the superior anastomotic vein into the superior sagittal sinus. Angiographic follow-up showed that only 2 patients still have evidence of fluid collection: the rest of the patients showed normal arterial phases, the medullary system was minimally filled and all of these showed remarkable improvement of the venous drainage throughout the superficial cortical veins with no evidence of hanging veins. Intellectual development of these children following lowering of the superior sagittal sinus showed that 8 patients (50%) were normal or above normal; 5 patients (31.2%) were retarded and 3 patients (18.7%) were borderline.

Radiation myelopathy in children.

Three children, 1 with medulloblastoma, 1 with anaplastic cerebellar tumor, and 1 with acute lymphocytic leukemia, received craniospinal irradiation with an estimated cord dose between 1,100 and 1,200 rets. All 3 patients after a latent period of seven to eight months developed subacute transverse myelopathy. The myelopathy was cervical in 2 patients and thoracic in 1. Spinal fluid examination showed high protein levels in 2 patients. Myelography demonstrated a swollen cord in 2 patients and normal appearance in 1. Autopsy in 1 patient disclosed a necrotizing myelopathy. The findings suggest that children tolerate less well than adults what previously have been considered safe doses of radiation to the spinal cord.

A new surgical approach to the treatment of coronal synostosis.

The authors described a surgical technique for the treatment of unilateral coronal synstosis, which they have carried out successfully in 16 children. Frontal craniotomy, removal of the lesser wing of the sphenoid, orbital unroofing, and removal of the entire orbital rim are recommended as essential elements of carnio-orbital reconstruction in the treatment of plagiocephaly.