Electrical coupling of individual electrocatalytic oscillators.

The catalytic electro-oxidation of some small organic molecules is known to display kinetic instabilities, which reflect on potential and/or current oscillations. Under oscillatory conditions, those systems can be considered electrocatalytic oscillators and, therefore, can be described by their amplitude, frequency, and waveform. Just like mechanical oscillators, the electrocatalytic ones can be coupled and their dynamics can be changed by setting different coupling parameters. In the present work, we study the unidirectional coupling of electrocatalytic oscillators, namely, those comprehending the catalytic electro-oxidation of methanol and formic acid on polycrystalline platinum in acidic media under potentiostatic control. Herein, we explore two different scenarios (the coupling of compositionally identical and non-identical oscillators) and investigate the effects of the master's identity and of the coupling constant on the slave's dynamics. For the master (methanol)-slave (methanol) coupling, the oscillators exhibited phase lag synchronization and complete phase synchronization. On the other hand, for the master (formic acid)-slave (methanol) coupling, the oscillators exhibited complete phase synchronization with phase-locking with a 2:3 ratio, complete phase synchronization with phase-locking with a 1:2 ratio, phase lag synchronization, and complete phase synchronization. The obtained results suggest that both the master's identity and the coupling constant (sign and magnitude) are parameters that play an important role on the coupled systems, in such a way that even for completely different systems, synchronization could emerge by setting a suitable coupling constant. To the best of our knowledge, this is the first report concerning the electrical coupling of hidden N-shaped-negative differential resistance type systems.

Probing the surface fine structure through electrochemical oscillations.

In the course of (electro)catalytic reactions, reversible and irreversible changes, namely the formation of adsorbed poisons, catalyst degradation, surface roughening, etc., take place at distinct time-scales. Reading the transformations on the catalyst surface from the measurement of the reaction rates is greatly desirable but generally not feasible. Herein, we study the effect of random surface defects on Pt(100) electrodes toward the electro-oxidation of methanol in acidic media. The surface defects are gently generated in situ and their relative magnitudes are reproducibly controlled. The system was characterized under conventional conditions and investigated under an oscillatory regime. Oscillatory patterns were selected according to the presence of surface defects, and a continuous transition from large amplitude/low frequency oscillations (type L) on smooth surfaces to small amplitude/high frequency oscillations (type S) on disordered surfaces was observed. Importantly, self-organized potential oscillations were found to be much more sensitive to the surface structure than conventional electrochemical signatures or even other in situ characterization methods. As a consequence, we proved the possibility of following the surface fine structure in situ and in a non-invasive manner by monitoring the temporal evolution of oscillatory patterns. From a mechanistic point of view, we describe the role played by surface defects and of the adsorbed and partially oxidized, dissolved species on the oscillations of type S and L.

Safety of antitumour necrosis factor treatments in chronic rheumatic diseases: therapy discontinuations related to side effects.

WHAT IS KNOWN AND OBJECTIVE: The appearance of antitumor necrosis factor drugs (ATDs) has been a major advance in the management of these patients. However, due to the immunosuppressive effect of these therapies, side effects that require treatment discontinuations can appear. The purpose of this study was to evaluate the frequency of ATD discontinuation due to adverse drug effects (ADEs) and the influence of different factors such as diagnosis, ATD prescribed and concomitant disease-modifying antirheumatic drugs (DMARDs). METHODS: Observational study from a prospective cohort conducted in a tertiary hospital (1350 beds) in Spain. Data were obtained from the database of the Rheumatology Outpatient Unit of the hospital and patients' clinical files. Included patients had a diagnosis of RA or peripheral or axial SpA (ankylosing spondylitis, psoriatic SpA, non-radiographic SpA, SpA associated with inflammatory bowel disease or reactive arthritis) treated between November 2000 and March 2014 with infliximab (IFX), etanercept (ETN) or adalimumab (ADA). RESULTS AND DISCUSSION: Study cohort included 531 rheumatic patients (282 patients with RA, 53·1%, and 249 patients with SpA, 46·9%). ATDs were discontinued in 62 cases (11·7%) because of ADEs, mainly inmunogenicity and infections (mainly due to infusion reactions, 58·1%, and infections, 19·3%). ATD discontinuation was higher in the group of RA patients compared with SpA (44/282 (15·6%) in RA vs. 18/249 (7·23%) in SpA). The appearance of ADEs that led to drop out was more frequent in patients under IFX therapy (45 (18·6%) with IFX vs. 12 (7·59%) with ETN and 5 (3·81%) with ADA). We observed a significantly increased risk of ADEs when patients received IFX than when ETN or ADA were used (P < 0·001); 444 patients (83·6%) received DMARDs in combination with ATDs. The risk of ATD withdrawal was significantly higher in patients treated with leflunomide as compared to those who do not (OR = 1·984, P < 0·05). WHAT IS NEW AND CONCLUSION: Discontinuation of ATD due to ADEs is relatively frequent and it depends on the diagnosis and ATD administered. The risk of treatment discontinuation is higher in patients diagnosed with RA vs. SpA or treated with IFX (rather than with ETN or ADA). The addition of DMARDs to ATDs increased the frequency of treatment discontinuation, up to three concomitant medications. Leflunomide in combination with an ATD significantly increased the probability of treatment discontinuation due to adverse reactions.

Mechanism and model of the oscillatory electro-oxidation of methanol.

A mechanism for the kinetic instabilities observed in the galvanostatic electro-oxidation of methanol is suggested and a model developed. The model is investigated using stoichiometric network analysis as well as concepts from algebraic geometry (polynomial rings and ideal theory) revealing the occurrence of a Hopf and a saddle-node bifurcation. These analytical solutions are confirmed by numerical integration of the system of differential equations.

Verbascoside production in long-term Buddleja cordata Kunth cell suspension cultures.

Previously, our group reported the establishment of a white callus cell line of Buddleja cordata Kunth that is a high producer of the secondary metabolite, verbascoside (VB, also named acteoside), under suspension culture conditions. Here, we present experimental evidence of the sustained ability of that cellular line to grow and produce high amounts of VB for 5 years of continuous culture. Cellular line profiles were determined at the early (at the beginning) and late stages (at the end of 5 years of continuous subculturing) by analyzing relevant parameters of culture growth, i.e., specific growth rate [µ], doubling time [dt], and growth index [GI], as well as VB production. Late-stage cultures exhibited a 61% faster growth rate than early-stage subcultures, and 25 and 3% lower doubling time and growth index. The extents of growth phases were found to be different. Similar amounts of biomass were found (9.5 g and 9.4 g L-1). Verbascoside production increased parallel to cell growth; maximal yield level occurred in the mid-exponential phase and lasted until the end of the stationary phase (i.e., from the 15th to the 25th day and from the 9th to the 21st day for the early and late stages, correspondingly). The content of VB was higher in the late-stage culture (1.43 ± 0945 g L-1) than in the early-stage culture (1.21 ± 0.0286 g L-1). Productivity values point out the potential use of B. cordata cell line in the biotechnological production of VB and for research focused on the biochemistry of secondary metabolism.

Pattern formation in stiff oscillatory media with nonlocal coupling: a numerical study of the hydrogen oxidation reaction on Pt electrodes in the presence of poisons.

The impact of the strength of negative (desynchronizing) global coupling (NGC) on the spatiotemporal dynamics of an electrochemical relaxation oscillator is studied numerically with a prototypical model, the electro-oxidation of hydrogen in the presence of poisons. The results are compared with recent experiments. The NGC has a destabilizing effect on the homogeneous oscillations. Both, in theory and in experiments, the basic patterns found with increasing global coupling strength are modulated oscillations, target patterns (including an asymmetric variant), and modulated pulses, the average spatial inhomogeneity during an oscillation increasing with the intensity of the NGC. It is suggested that this scenario is typical for strong relaxation oscillations, and a comparison with an electrochemical oscillator exhibiting harmonic oscillations points to the fact that the critical coupling strength, upon which the complete synchronization is destroyed, is larger for relaxation oscillations than for harmonic oscillations. In addition, the numerical simulations predicted two- and three-phase cluster patterns at high coupling strength. Also in experiments cluster patterns were observed, however only in parameter regions of the local dynamics which were different from the one investigated in this study.

[Goya, his deafness and his time]. / Goya, su sordera y su tiempo.

We have made a bibliographyc review of the most important otology books from the end of the XVIII to the begining of the XIX century. We propose several hipothesis of the diagnoses and treatment of Goya's deafness in relation to the contemporary otological advances.

[Cochlear implants using the Ultracision harmonic scalpel]. / Implantación coclear con bisturí armónico Ultracision.

We have evaluated the utility, indications and disadvantages of the Ultracision harmonic scalpel, in the cochlear implants, and his advantages compare to other electrocoagulation's systems. These aspects were evaluated in 50 cases of cochlear implants, made along the last years. We concluded that the Ultracision harmonic scalpel is indicated, mainly, in the otology field, in these situations in wich the cochlear implant is in the cochlea, and is mandatory the use of an electrocoagulation system. In this situation, the Ultracision harmonic scalpel was quick, safe and sure, and with many advantages, over the traditional scalpel and the bipolar diathermy.

Angiogenesis: an update.

Angiogenesis is the neovascularization or formation of new blood vessels from the established microcirculation. It is particularly important and indispensable in a large number of normal and pathological processes during pre- and post-natal life, including neoplasia, inflammation, wound repair and collaterization in response to ischemic stimuli. The current interest in the role of neovascularization in the transition from hyperplasia to neoplasia, as well as in the tumour growth and metastasis, has brought about a large number of studies on angiogenesis. The complex processes of neovascularization, quiescent in the adult organism, may occur rapidly in several circumstances, with the implication of the following events: a) endothelial cell (EC) and pericyte activation; b) basal lamina degradation; c) migration and proliferation of EC and pericytes; d) formation of a new capillary vessel lumen; e) appearance of pericytes around the new capillaries; f) development of a new basal lamina; g) capillary loop formation; h) persistence or involution, and differentiation of the new vessels; and i) capillary network formation and, eventually, organization into larger microvessels. The use of numerous "in vivo" and "in vitro" systems has facilitated the assessment of angiogenesis control, in which angiogenic (fibroblast growth factors, vascular endothelial growth factor, platelet endothelial growth factor, E series prostaglandin, angiogenin, monobutyrin) and antiangiogenic (cartilage-derived angiogenic inhibitor, thrombospondin, protamine, platelet factor 4, interferon, angiostatic antibiotics, steroids) substances intervene. Heparin and heparin sulphate also play a key role in these mechanisms. A greater knowledge of angiogenesis control may lead to the development of a potential therapy in angiogenesis-related processes.

Microvascular pericytes: a review of their morphological and functional characteristics.

A hundred years after the first description, many aspects of pericytes remain to be examined. Mesenchymal in origin, pericytes form an incomplete envelopment around the endothelial cells and within the microvascular basement membrane of capillaries and postcapillary venules. Morphologically, they appear as long, slender, polymorphic cells, showing an elongated cell body, from which arise longitudinal and circumferential branches. Cell bodies and cytoplasmic processes of pericytes, as well as the endothelial cells, are enveloped by the same basal lamina, except for where they make direct contacts with each other. The pericyte/endothelial cell contacts are peg and socket, adhesion plaques and gap junctions, making up structural mechanisms for force transmission and a possible receptor system for cells, in which the pericyte and endothelial cells respond to secondary signals generated in the other cells. Electron microscopic studies have revealed an elaborate network of cytoplasmic filaments. Pericyte intermediate filament proteins show species and tissue differences, expressing vimentin or vimentin and desmin. The pericytes also express protein typical of contractile cells, i.e. smooth muscle-specific isoforms of actin and myosin, cyclic GMP-protein kinase and tropomyosin. A gradual transition is observed between pericytes and smooth muscle cells in both terminal arterioles and venules. Several general functions for the pericytes have been postulated: contractability; permeability regulator; integrity maintainer; endothelial cell growth modulator; and cell progenitor with considerable mesenchymal potential.

The role of the pericytes of the adventitial microcirculation in the arterial intimal thickening.

Segments of rat femoral arteries, with one collateral each, occluded between ligatures and dissected from surrounding tissue, developed intimal thickening, with or without ligation of their collaterals. Numerous newly-formed capillaries from the surrounding arterial microcirculation growing into the adventitia, tunica media and intimal thickening were demonstrated by means of serial longitudinal sections, predominantly in the ostium of the collateral. When the ligatures were applied without damaging the microcirculation surrounding the artery and the normal continuity of the adventitial vessels was unchanged, earlier presence of intimal thickening was observed. When the fibrous layers of the adventitia were removed at the moment of the arterial ligation, the continuity between newly-formed vessels of the neoadventitia and those growing into the media and neointima was much more evident. It was then noted that the pericytes constituted a major component of the intimal thickening. The introduction of contrast material in microcirculation confirmed the connections between newly-formed adventitial and intimal vessels. At the beginning of the experiment, autoradiographic studies showed an increased DNA synthesis in the cells of preformed postcapillary venules and capillaries of surrounding arterial microcirculation and later in those of the newly-formed vessels growing into the arterial wall. These results indicate that newly-formed capillaries derived from surrounding arterial microcirculation penetrate the wall of the occluded arterial segments and contribute to the intimal thickening formation. It is likely that the pericytes and endothelial cells (EC) of these ingrowing vessels are sources of myointimal cells at the intimal thickening and of endothelium at the luminal surface, respectively.

Participation of angiogenesis from rat femoral veins in the neovascularization of adjacent occluded arteries.

The neovascularization of the arterial wall in human and experimental pathology has been demonstrated. The occlusion of the of the rat femoral artery is a suitable model for the study of these angiogenesis processes. Newly formed capillaries growing into the arterial wall have been described in this model. The origin of these ingrowing capillaries has been attribute to the preformed surrounding venules and capillaries. The contribution of the adjacent femoral vein with a supplementary population of vascular sprouts could also be possible. To test this hypothesis in half of the occluded arteries, the adventitia was removed from the side facing the femoral vein. Between 1 and 3 days after surgery several alterations were found both in the endothelial cells and the smooth muscle cells of the tunica media. Between 3 and 6 days, solid or canalized endothelial sprouts were observed arising from the femoral vein. By days 4 and 6, newly formed capillaries grew into the adventitia and tunica media of the femoral artery. Some of them, penetrated the internal elastic lamina. This microvascular penetration from the femoral vein was more prominent in the area of the ostium of the collateral and when the adventitia was removed. Some ingrowing capillaries were in continuity with the endothelial cells of the arterial neointima. At days 7 and 8, regressing capillaries were observed in the neomicrovasculature network between artery and vein, with a selective loss of the smaller vessels. From day 9 onwards, fewer and larger vascular channels were present between the femoral vein and the femoral artery. An arterial neolumen contained what appeared to be circulating "fresh" blood. Quantitatively, the venous neocapillary density increased from days 4 to 6 and then declined significantly by day 8. The arterial neocapillary density increased form days 4 to 8 and declined significantly by day 12. Moreover, both densities were significantly greater when the arterial adventitia was removed. The perfusion with barium solution showed the presence of the contrast material in the newly formed vessels, the lumen of the femoral vein, and the neolumen of the occluded arterial segment. The present findings indicate that putative angiogenic molecules released form the occluded arterial segment may reach the adjacent wall of the vein inducing neovascularization from it. The vein vascular sprouts are connected to the ingrowing capillaries in the occluded arterial wall and to the neocapillaries form the preexisting pericytic microvasculature. When the arterial adventitia were removed up to 2 times greater vein neocapillary's density was observed suggesting an easily access of the putative angiogenic factors to the vein.

Arterial wall neovascularization induced by glycerol.

An intense and significant neovascularization, with numerous capillaries growing into the media layer of the rat femoral artery, was demonstrated when glycerol was administered into the interstitium between the femoral vein and the femoral artery. The maximum microvascularization was observed at days 7 and 9 after glycerol administration. Afterwards, involution of the majority of the newly-formed microvessels in the arterial wall occurred. Other substances containing glycerol in their molecules, such as triacetyl-glycerol and tributyril-glycerol, failed to produce significant neovascularization in the media layer of the femoral artery. Neovascularization of the arterial wall was preceded by a considerable decrease in the number of the smooth muscle cells, which experienced apoptosis and necrobiosis, disappearing in extense areas of the arterial segment affected by glycerol. Coinciding with neovascularization and microvascular involution, repopulation of the media layer by smooth muscle cells was observed.

Contribution of the proximal and distal nerve stumps to peripheral nerve regeneration in silicone chambers.

The specific contribution of the proximal and distal nerve stumps across an 8 mm gap within silicone chamber regeneration models was studied. For this, proximal and distal (Group A), distal and distal (Group B) and proximal and proximal (Group C) nerve stumps were placed in opposite ends of silicone chambers. In all the groups, a tissue cable forms between the nerve stumps, demonstrating that, without distinction, proximal or distal stumps can stimulate the growth of other proximal or distal stumps. Furthermore, in Group B, the newly formed pseudo-nerve, in the absence of regenerating axons, contains a number of Schwann cells significantly similar to Group A, which confirms that proliferation and migration of Schwann cells do not require axonal presence or contact. Likewise, the findings demonstrate that, with the exception of the axons, the distal stump contributes to the peripheral nerve regeneration in the same way as the proximal stump. Finally, when proximal stumps are placed in both the opposite ends of the silicone chamber, Schwann cells and regenerating axons grow into the chamber gap from both inserts, and myelination also proceeds from both ends to the centre of the chambers.

Behavior of postcapillary venule pericytes during postnatal angiogenesis.

Autogeneic bone marrow was implanted into an artificially created cavity in a segment of rat sciatic nerve, after removal of nerve fascicles, without damaging the epineurium or surrounding microcirculation. Under these conditions, the bone marrow induces capillary growth and forms granulation tissue from surrounding tissues, the behavior of pericytes being studied in the preformed (preexisting) postcapillary venules of the latter. Beginning 20 h after bone marrow implantation, the pericytes of the preexisting postcapillary venules hypertrophy, with shortening of their processes, prominent nucleoli, dispersal of ribosomes into their free form, fragmentation of basal lamina, and increased DNA synthesis. The number of contact surfaces between pericytes and endothelium is noticeably lower than in controls. Many pericytes are in mitosis. Cells with a shape transitional between pericytes and interstitial fibroblast-like cells appear. In some cases, Monastral Blue (MB) was used as a marker of the cells in preexisting venule walls of the graft bed. In the earlier stages of the experiment, the MB labelling is restricted to the cytoplasm of pericytes and endothelial cells of postcapillary venules, and to the macrophages that occur in the space between pericytes and endothelium. Furthermore, the marker continues to be observed, at a later stage, in some of the following cells: pericytes and endothelial cells of the newly formed vessels, macrophages migrating into the interstitium, transitional cells between pericytes and fibroblasts, and typical fibroblasts of the granulation tissue. The present study provides greater evidence that preformed microvasculature pericytes are substantially activated during postnatal angiogenesis and granulation tissue formation, suggesting that they may contribute to the origin of new pericytes and fibroblasts.

Astrocyte responses in human optic nerve head with primary open-angle glaucoma.

PURPOSE: To identify and characterize astrocyte responses and reactivation in human optic nerve heads from patients with primary open-angle glaucoma. METHODS: Fifteen optic nerve heads with primary open-angle glaucoma and 13 normal controls were fixed in 4% paraformaldehyde, paraffin embedded, and stained for immunofluorescence and immunoperoxidase. The antibodies used were against glial fibrillary acidic protein (GFAP) and against neural cell adhesion molecule (N-CAM). RESULTS: Two subpopulations of type 1 astrocytes exist in the normal optic nerve. Type 1A astrocytes express only glial fibrillary acidic protein and type 1B express both glial fibrillary acidic protein and neural cell adhesion molecule. These are the major cell subpopulations in the lamina cribrosa and prelaminar regions. In primary open angle glaucoma, type 1B astrocytes in the prelaminar region showed increased immunoreactivity for glial fibrillary acidic protein and neural cell adhesion molecule, and cytoplasmic enlargement with thicker and longer cytoplasmic processes. At the level of the lamina cribrosa, type 1B astrocytes appeared round and the cell bodies were no longer in the cribriform plates but located in the nerve bundles. Type 1A astrocytes were not observed in the glaucomatous optic nerve head. CONCLUSIONS: Astrocyte responses in primary open angle glaucoma may underlie cellular changes that lead to axonal damage and optic nerve head remodeling. These responses may have pathogenic significance for glaucomatous optic neuropathy.

Study of Bacillus sp. culture conditions to promote production of unhairing proteases.

The substitution of chemical depilatory agents in the leather industry by proteolytic enzymes produced by Bacillus species has an important economical and environmental impact. In previous assays, a Bacillus sp. showing a promising depilatory activity was isolated. In this paper, a culture medium that stimulated the synthesis and segregation of depilatory proteases, was selected. The influence of pH, oxygen supply rate (KLaC*), and inoculum age was evaluated on cell growth and protease production. Assays were carried out in lab bioreactors (1.2-1.4 l) at 37 degrees C. Five different media that differed in carbon and nitrogen sources were tested. pH ranged from 4.0 to 8.5. KLaC* varied between 40 and 470 mmol/lh. The best medium culture for protease production contained: nutrient broth (Britania) 8 g/l, yeast extract (Britania) 3 g/l, and mineral salts. Protease production was more effective at pH of 6.7, KLaC* of 360 mmol/lh, and inoculum age of 12 hours. These experimental conditions led to the following results: maximum proteolytic activity 2700 U/ml, overall volumetric protease productivity 300 u/ml-h, average specific growth rate 0.62 h-1, and average specific protease production rate 2.50 x 10(5) U/gh.

[Fiber endoscopy of the nasopharynx: its indications]. / La fibroendoscopia del cavum: sus indicaciones.

The AA have planned a series of indications regarding the endoscopy of the nasoopharynx. Among 631 explorations done in a three-year term, normal findings were seen in 260 subjects. In the other cases several aspects of the inflammatory or neoplastic pathology could be verified. One individual showed an esthesioneuroblastoma in an early evolutive stage.

[The influence of hypercholesterolemia and noise on human auditory function]. / Influencia de la hipercolesterolemia y el ruido en la audición humana.

A cross-sectional study on occupational noise exposure and hypercholesterolemia was conducted in a group of 1.209 workers exposed to industrial noise. Clinical examinations and audiograms were compared in exposed and not exposed subjects to noise. There was a strong relationship between severe noise induced hearing loss and hypercholesterolemia in all de workers. But the relationship was not convincing when the workers were considered stratified in groups of age, because the number of hard of hearing labourers with high levels of cholesterol, increases as they get older. The AA, support the point of view that the age is an important confounding factor, and in their study there is no relation between noise induced hearing loss and hypercholesterolemia.

[Diagnostic role of the biopsy in angiofibroma of the cavum]. / Papel diagnóstico de la biopsia en el angiofibroma de cavum.

The AA. inform about the case of a child, 13, with an antro-choanal Polyp of angiofibromatous structure, diagnosed as Angiofibroma. Though in the greater number of instances the arteriography is enough to support the suspicion, the confirmation through histopathology is compulsory.