A near infra-red video system as a protective diagnostic for electron cyclotron resonance heating operation in the Wendelstein 7-X stellarator.

The Wendelstein 7-X stellarator is a large nuclear fusion device based at Max-Planck-Institut für Plasmaphysik in Greifswald in Germany. The main plasma heating system for steady state operation in W7-X is electron cyclotron resonance heating (ECRH). During operation, part of plama facing components will be directly heated by the non-absorbed power of 1 MW rf beams of ECRH. In order to avoid damages of such components made of graphite tiles during the first operational phase, a near infra-red video system has been developed as a protective diagnostic for safe and secure ECRH operation. Both the mechanical design housing the camera and the optical system are very flexible and respect the requirements of steady state operation. The full system including data acquisition and control system has been successfully tested in the vacuum vessel, including on-line visualization and data storage of the four cameras equipping the ECRH equatorial launchers of W7-X.

2D surface temperature measurement of plasma facing components with modulated active pyrometry.

In nuclear fusion devices, such as Tore Supra, the plasma facing components (PFC) are in carbon. Such components are exposed to very high heat flux and the surface temperature measurement is mandatory for the safety of the device and also for efficient plasma scenario development. Besides this measurement is essential to evaluate these heat fluxes for a better knowledge of the physics of plasma-wall interaction, it is also required to monitor the fatigue of PFCs. Infrared system (IR) is used to manage to measure surface temperature in real time. For carbon PFCs, the emissivity is high and known (ɛ ∼ 0.8), therefore the contribution of the reflected flux from environment and collected by the IR cameras can be neglected. However, the future tokamaks such as WEST and ITER will be equipped with PFCs in metal (W and Be/W, respectively) with low and variable emissivities (ɛ ∼ 0.1-0.4). Consequently, the reflected flux will contribute significantly in the collected flux by IR camera. The modulated active pyrometry, using a bicolor camera, proposed in this paper allows a 2D surface temperature measurement independently of the reflected fluxes and the emissivity. Experimental results with Tungsten sample are reported and compared with simultaneous measurement performed with classical pyrometry (monochromatic and bichromatic) with and without reflective flux demonstrating the efficiency of this method for surface temperature measurement independently of the reflected flux and the emissivity.

Denervación del sistema nervioso simpático renal: una nueva alternativa para tratar la hipertensión: reporte de un caso / Denervation of the renal sympathetic nervous system: a new alternative for treating hypertension: a case report

La presión arterial (PA) que persiste sobre140/90mmHg, aun cuando se utilicen tres o más fármacos antihipertensivos a dosis máximas toleradas, incluyendo un diurético, es definida como hipertensión arterial (HTA) resistente. La hiperactividad del sistema nervioso simpático renal influye críticamente en su fisiopatología. El año 2009 se publicó la denervación simpática o simpatectomía renal (DSR), técnica prometedora para tratar la hipertensión resistente, mediante radiofrecuencia. No existen reportes de su uso en Chile. El objetivo del caso es comunicar una nueva alternativa para tratarla HTA resistente, en términos del control de la PA. PRESENTACIÓNDEL CASO: Paciente varón, 64 años, con antecedentes de HTA resistente, infarto al miocardio y accidente vascular encefálico recuperado, fue evaluado para valorar posibilidad de realizar DSR, por persistencia de HTA a pesar de tratamiento con 4 fármacos hipotensores. Se citó en agosto del 2012 al Hospital Las Higueras, Talcahuano, constatándose asintomático,PA: 161/85mmHg, sin otras alteraciones al examen físico. Exámenes laboratorio normales. Se decidió intervenir un mes después, efectuándose el procedimiento sin complicaciones.PA: día post intervención 108/59mmHg; control a dos semanas148/87mmHg, sin usar hipotensores. DISCUSIÓN: La DSR puede reducir sustancialmente la PA (–27/–17mmHg al año). En Chile, existe una alta prevalencia de HTA y sólo un bajo porcentaje logra normalizar su PA mediante terapia no farmacológica y/o farmacológica. En este caso, se realizó seguimiento con control de PA a los tres, seis, nueve y doce meses, encontrándose valores significativamente menores. Actualmente mantiene su PA bajo control con 2 fármacos hipotensores...

A blood pressure (BP) that remains over140/90mmHg despite the use of three or more antihypertensive drugs at maximum tolerated doses, including a diuretic, is defined as resistant hypertension (HT). The hyperactivity of the sympathetic nervous system critically influences renal pathophysiology. In 2009, a publication showed that sympathetic renal denervation (SRD) or renal sympathectomy, was a promising radiofrequency technique for the treatment of resistant hypertension, with no reports in Chile. The aim of this case is to present a new alternative for the treatment of resistant hypertension, through the control of BP. CASE REPORT: A 64-yearoldmale, with a history of resistant hypertension, myocardial infarction and stroke without squeal, was evaluated at Las Higueras Hospital, Talcahuano, in august 2012, to assess the possibility of RSD, for the treatment of his resistant hypertension.The patient was asymptomatic with no findings in physical examination, but BP 161/58 mmHg. Laboratory results were normal. The procedure was performed, one month later, without complications. The day next to intervention BP 108/59 mmHg. Two weeks later control BP 148/87 mmHg without antihypertensive drugs. DISCUSSION: SDR can significantly reduce BP(-27/-17mmHg per year). In Chile, there is a high prevalence of hypertension and a low percentage of patients normalizes BPwith non-pharmacological and/or pharmacological treatment. The patient was controlled at three, six, nine and twelve month post SDR, with BP values significantly lower than pre-SDR. At present, patient BP is under management with two antihypertensive drugs...

A protection system for the JET ITER-like wall based on imaging diagnostics.

The new JET ITER-like wall (made of beryllium and tungsten) is more fragile than the former carbon fiber composite wall and requires active protection to prevent excessive heat loads on the plasma facing components (PFC). Analog CCD cameras operating in the near infrared wavelength are used to measure surface temperature of the PFCs. Region of interest (ROI) analysis is performed in real time and the maximum temperature measured in each ROI is sent to the vessel thermal map. The protection of the ITER-like wall system started in October 2011 and has already successfully led to a safe landing of the plasma when hot spots were observed on the Be main chamber PFCs. Divertor protection is more of a challenge due to dust deposits that often generate false hot spots. In this contribution we describe the camera, data capture and real time processing systems. We discuss the calibration strategy for the temperature measurements with cross validation with thermal IR cameras and bi-color pyrometers. Most importantly, we demonstrate that a protection system based on CCD cameras can work and show examples of hot spot detections that stop the plasma pulse. The limits of such a design and the associated constraints on the operations are also presented.

New field programmable gate array-based image-oriented acquisition and real-time processing applied to plasma facing component thermal monitoring.

During operation of present fusion devices, the plasma facing components (PFCs) are exposed to high heat fluxes. Understanding and preventing overheating of these components during long pulse discharges is a crucial safety issue for future devices like ITER. Infrared digital cameras interfaced with complex optical systems have become a routine diagnostic to measure surface temperatures in many magnetic fusion devices. Due to the complexity of the observed scenes and the large amount of data produced, the use of high computational performance hardware for real-time image processing is then mandatory to avoid PFC damages. At Tore Supra, we have recently made a major upgrade of our real-time infrared image acquisition and processing board by the use of a new field programmable gate array (FPGA) optimized for image processing. This paper describes the new possibilities offered by this board in terms of image calibration and image interpretation (abnormal thermal events detection) compared to the previous system.

Pacemaker endocarditis: approach for lead extraction in endocarditis with large vegetations.

We present the case of a patient with vegetations on a pacing lead from a pacemaker implanted 13 years previously. A new surgical technique for removal of infected leads was developed to avoid the increased risk of septic pulmonary embolism. The electrode with vegetations was removed without cardiopulmonary bypass using the direct surgical approach described.

Cell surface alteration in Epstein-Barr virus-transformed cells from patients with extreme insulin resistance.

An abnormality was detected in the morphology of the cell surface of Epstein-Barr virus-transformed lymphocytes of patients with genetic forms of insulin resistance. In cells from two patients with leprechaunism and two patients with type A extreme insulin resistance, scanning electron microscopy demonstrated a decrease in the percentage of the cell surface occupied by microvilli in cells from the patients with leprechaunism and type A insulin resistance compared with control cells. When cells from a healthy control subject and one of the patients with leprechaunism (Lep/Ark-1) were incubated with 125I-labeled insulin, there was a decrease in the percentage of 125I-insulin associated with microvilli on the cell surface. Thus, the decreased localization of insulin receptors with the microvillous region of the cell surface was in proportion to the decrease in microvilli.

Structural and functional analysis of the insulin receptor promoter.

The insulin receptor plays a critical role in the maintenance of glucose homeostasis. Regulation of this key function must be under stringent controls. In order to study the regulation of insulin receptor gene expression, we have cloned, sequenced and characterized its promoter. The first exon of the insulin receptor gene is embedded in an unusual segment of DNA composed of Alu repeats. The promoter has the characteristics typical of a housekeeping gene. It is GC-rich and has multiple start sites of transcription. A 574 base pair fragment immediately upstream of the translation initiation site contains promoter activity when transfected into eukaryotic cell lines. Deletion analysis was performed to study promoter function. These studies showed that only 150 base pairs of promoter sequence were necessary for promoter function. This region contains three potential binding sites for the transcription factor, Sp1 and a TC box sequence. Furthermore, the fragment functions equally well in either orientation. We have defined an element in this region with enhancer function for both its homologous and a heterologous promoter. In addition, this region seems to contribute some degree of tissue specificity to insulin receptor gene expression.

Atypical antiinsulin receptor antibodies in a patient with type B insulin resistance and scleroderma.

We studied a 23-yr-old woman with scleroderma and type B insulin resistance. The association with autoimmune disease suggested that the insulin resistance resulted from autoantibodies to the insulin receptor. However, in preliminary studies, serum antireceptor antibodies were not detected in an assay that measures the ability of the antibodies to inhibit insulin binding to the insulin receptor. Antireceptor antibodies were subsequently detected by their ability to immunoprecipitate affinity-labeled receptors. After the patient had received immunosuppressive therapy with prednisone and cyclophosphamide for 3 months, her insulin resistance remitted, and she developed hypoglycemia. Simultaneously with the remission of insulin resistance, the titer of serum antireceptor antibody (measured by the immunoprecipitation assay) fell to less than 1% of the previous level. In a series of 21 patients, this is the first patient with antireceptor antibodies that bound to the insulin receptor without inhibiting insulin binding.

Defects in human insulin receptor gene expression.

The insulin receptor plays a central role in mediating the biological actions of insulin. We have used Epstein-Barr virus-transformed lymphocytes (EBV-lymphocytes) to investigate the receptor defects in patients with genetic forms of insulin resistance. Within the normal population, we found a close correlation between the number of insulin receptors on the surface of EBV-lymphocytes and the cellular content of insulin receptor mRNA. In addition, we have used the cloned human insulin receptor cDNA to investigate the nature of the mutations causing the reduction in the number of insulin receptors in EBV-lymphocytes from three insulin resistant patients. One patient with leprechaunism has a marked reduction in the level of receptor mRNA, which probably accounts for the extremely slow rate of receptor biosynthesis measured in this patient's cells. The remaining two patients with type A extreme insulin resistance are sisters, the products of a consanguineous marriage, who have normal levels of insulin receptor mRNA. We have previously shown that the insulin receptor precursor is synthesized at a normal rate in these patients' cells, thus suggesting a defect in the posttranslational processing of the receptor or in its translocation to the plasma membrane.

Insulin-receptor biosynthesis in cultured lymphocytes from an insulin-resistant patient (Rabson-Mendenhall syndrome). Evidence for defect before insertion of receptor into plasma membrane.

In some patients with genetic forms of extreme insulin resistance, there is a marked decrease in the number of insulin receptors on the cell surface. We studied an insulin-resistant patient (RM-1) with the Rabson-Mendenhall syndrome. As judged by insulin-binding studies, Epstein-Barr virus-transformed lymphocytes from patient RM-1 exhibit a 90% decrease in the number of insulin receptors. Similarly, with either lactoperoxidase-catalyzed radioiodination of cell surface receptors or biosynthetic labeling of receptors with [3H]glucosamine, we demonstrated an 80-90% decrease in the number of insulin receptors in cells from patient RM-1. Previous studies have shown that the marked decrease in insulin receptors of the Rabson-Mendenhall patient is not due to accelerated receptor degradation. Therefore, we investigated the possibility that a slow rate of receptor biosynthesis might account for the 90% reduction of insulin receptors in cells from this patient. Insulin-receptor biosynthesis proceeds through a glycoprotein precursor with an apparent Mr of 190,000. It undergoes endopeptidase cleavage and further posttranslational processing to yield the mature 135,000- and 95,000-Mr glycoprotein subunits. We studied the biosynthesis of the 190,000-Mr precursor and mature receptor subunits by a pulse-chase labeling technique with [2-3H]mannose. The time course of insulin-receptor biosynthesis appeared normal in cells from patient RM-1, despite a 10-fold reduction in the number of receptors on the cell surface. Parallel pulse-chase experiments with either [2-3H]mannose or [35S]methionine yielded the same results regardless of which label was employed. Thus, the receptor precursor in the Rabson-Mendenhall patient seems to be synthesized at a normal rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin receptor biosynthesis in cultured lymphocytes from insulin-resistant patients.

In some patients with genetic forms of extreme insulin resistance, the cause of insulin resistance is a marked (greater than or equal to 90%) reduction in the number of insulin receptors on the cell surface. In the present work, we describe studies of insulin receptor biosynthesis in Epstein-Barr virus (EBV)-transformed lymphocytes from three patients (A-1, A-5, and A-8) with type A extreme insulin resistance. Insulin receptors are composed of two major glycoprotein subunits (apparent molecular weight [Mr] of 135 and 95 kD), which are both derived from a common precursor molecule with Mr of 190 kD. In one patient (A-1), there was a marked reduction in the biosynthesis of both the 190-kD precursor and the mature receptor. Thus, in this patient, the defect appears to occur early in the biosynthetic pathway (i.e., before the synthesis of the 190-kD precursor). In contrast, in two sisters (A-5 and A-8) with type A extreme insulin resistance, biosynthesis of the 190-kD precursor proceeds at a normal rate. However, there appears to be a defect subsequent to the biosynthesis of the 190-kD precursor, but before the insertion of the mature receptor in the plasma membrane. Our observations suggest the existence of at least two distinct types of biosynthetic defects which may give rise to a marked reduction in the number of insulin receptors on the cell surface. In addition, for comparison, we have studied receptor biosynthesis in cultured EBV lymphocytes from a fourth patient (A-7) with type A extreme insulin resistance. Although the cells of patient A-7 have a normal number of insulin receptors, we have detected subtle abnormalities in the posttranslational processing of the insulin receptor precursor, which may be a biochemical marker for a postbinding defect that causes insulin resistance in this patient.

The insulin-stimulated receptor kinase is a tyrosine-specific casein kinase.

Insulin stimulates a kinase that phosphorylates tyrosines in the insulin receptor; this kinase is tightly associated with the insulin receptor itself. We now show that the insulin-stimulated casein kinase, present in solubilized, lectin-purified receptor preparations from rat liver, is indistinguishable from the insulin receptor kinase. As with phosphorylation of the insulin receptor, insulin selectively enhanced by 2-3-fold the phosphorylation of tyrosines in casein. The insulin-stimulated activities of both kinases were inactivated at 37 degrees C with the same t0.5 of 5 min and were identically affected by alkylating agents. Both receptor and casein kinase activities were specifically coprecipitated by anti-receptor antibodies or by insulin and anti-insulin antibodies. When the latter type of immune complexes were incubated with an excess of insulin, both kinase activities were quantitatively recovered. We therefore conclude that insulin-stimulated receptor and casein phosphorylations are probably catalyzed by a single enzyme which is tightly associated with the receptor itself. Now, by replacing casein for receptor as substrate, it is possible to measure the enzymatic activity of this receptor-related kinase itself, i.e. independent of the receptor as substrate. Detection of this activity is improved in the presence of certain alkylating agents. Use of artificial substrates (in combination with alkylating agents) is particularly important to dissect the functional components of the receptor complex, to study mechanisms of enzyme regulation and especially in situations where the available receptor for study is limited, e.g. fresh or cultured cells from patients.

Insulin stimulates phosphorylation of serine residues in soluble insulin receptors.

Using lectin affinity-purified receptor preparations from human hepatoma cells, insulin (10(-7)M) specifically stimulated phosphorylation of the 95,000 dalton (beta) subunit of its own receptor. Phospho-amino acid analysis of the receptor subunit revealed that insulin increased at least 2.5-fold the content of phosphoserine and of phosphotyrosine. In intact cells, the major effect of insulin is to increase the phosphoserine content of its receptor. These findings are the first demonstration of an insulin-stimulated serine kinase in a cell-free system.

An in vitro binding assay which differentiates benzodiazepine 'agonists' and 'antagonists'.

An in vitro test which discriminates benzodiazepine "agonists' and 'antagonists' has been developed by exploiting the apparent differences in modulation of the benzodiazepine receptor by these classes of compounds. In the presence of 10 microM GABA, the potency of benzodiazepine 'agonists' (i.e., compounds which bind to the benzodiazepine receptor with a relatively high affinity and share pharmacologic properties with benzodiazepines) to displace [3H]3-carboethoxy-beta-carboline is significantly increased. In contrast, the potency of benzodiazepine 'antagonists' (compounds which have been demonstrated to antagonize some of the pharmacologic actions of benzodiazepines) is not altered by GABA. Several chemically diverse classes of compound have been examined in this test, and within the limited number of compounds examined, this test accurately predicts 'agonist' and 'antagonist' actions in vivo.

Pentobarbital: dual actions to increase brain benzodiazepine receptor affinity.

The binding of [3H]diazepam to benzodiazepine receptors was studied in extensively washed membranes of rat cerebral cortex in the presence of the depressant barbiturate, pentobarbital. Pentobarbital, like the endogenous neurotransmitter gamma-aminobutyric acid (GABA), increased the basal binding and also potentiated the GABA-enhanced binding of [3H]diazepam to benzodiazepine receptors by increasing the apparent affinity of [3H]diazepam for the benzodiazepine receptor. The concentrations of pentobarbital necessary to elicit these effects in vitro are the same as those observed after treatment with pharmacologically relevant doses, suggesting that a common neurochemical association may exist between these types of compounds.

Characterization of benzodiazepine receptors in primary cultures of fetal mouse brain and spinal cord neurons.

Primary cultures of fetal mouse brain and spinal cord were examined for the presence of binding sites for [3H]diazepam. Both brain and spinal cord cultures contain high affinity binding sites which resemble benzodiazepine receptors found in mammalian CNS with respect to both pharmacologic profile and response to exogenously applied GABA. These observations, coupled with the electrophysiologic properties of these cells suggest that primary cultures of fetal mouse brain and spinal cord may be valid models for studying the role and regulation of the benzodiazepine receptor.

Correlation between benzodiazepine receptor occupation and anticonvulsant effects of diazepam.

The benzodiazepines are potent anticonvulsants for a wide variety of experimental and clinical seizure disorders. The demonstration of saturable, high-affinity and stereospecific binding sites for the benzodiazepines in the mammalian central nervous system suggests the presence of pharmacological receptors mediating the anticonvulsant properties of these compounds. The good correlation between the anticonvulsant potencies of a series of benzodiazepines and their ability to inhibit 3H-diazepam binding in vitro further supports this hypothesis, but evidence for a direct interaction between benzodiazepines and their receptors, and a subsequent inhibition of seizure activity (or elevation of seizure threshold) is lacking. Recent reports from our laboratory and others have demonstrated the feasibility of labelling benzodiazepine receptors in vivo following parental administration of tritiated benzodiazepine. This technique permits one to study the relationship between the anticonvulsant activity of the benzodiazepines in vivo and the number of 'drug-occupied' receptors in vitro. We now report that there is an excellent correlation between benzodiazepine receptor occupancy by diazepam and protection against pentylenetetrazol-induced seizures. Furthermore, these results demonstrate that only a small fraction of benzodiazepine receptors need be occupied to produce a complete anticonvulsant effect.

Inosine, an endogenous ligand of the brain benzodiazepine receptor, antagonizes pentylenetetrazole-evoked seizures.

Partially purified extracts of bovine brain were previously found to inhibit competitively the binding of [3H]-diazepam to rat brain synaptosomal membranes. The purines inosine and hypoxanthine were subsequently identified as the compounds responsible for this inhibitory activity. Intracerebroventricular administration of inosine to mice of the C3H/HEN and NIH general purpose strains caused a dose- and time-dependent increase in the latency to clonicotonic seizures produced by intraperitoneal administration of the convulsant pentylenetetrazole. Intracerebroventricular administration of equimolar doses of 2'-deoxyinosine, which is more potent than inosine in inhibiting the binding of [3H]diazepam in vitro, significantly increased pentylenetetrazole-evoked seizure latency. In contrast, both 7-methylinosine and thymidine were ineffective in inhibiting the in vitro binding of [3H]diazepam and increasing the latency to pentylenetetrazole-induced seizures in vivo. These results suggest that endogenously occurring purines such as inosine exhibit diazepam like effects when administered intracerebroventricularly, and these effects may be related to the interaction of inosine and related compounds with benzodiazepine receptors in the central nervous system.