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Datta Lt Col R. L.C.R.,Base Hospital Delhi Cantt ENT | Datta Lt Col K. L.C.K.,Physiology | Venkatesh Brig M.D. B.M.D.,MH Namkum
Medical Journal Armed Forces India | Year: 2010

Laryngopharyngeal Reflux (LPR) is a commonly occurring and recently described clinical entity due to the retrograde flow of gastric contents into the pharynx. It accounts for many symptoms of upper airway including hoarseness, chronic throat irritation and globus sensation. The sensitive laryngeal mucosa is prone to damage by the combination of acid and pepsin. The inflammatory changes that follow are presumed to cause the symptoms and predispose the individual to laryngeal disorders. Diagnosis can usually be made clinically based on symptoms and laryngeal signs but a 24 hour pH metry is essential to establish diagnosis. Treatment centres on lifestyle modifications, vocal hygiene measures and long term use of proton pump inhibitors. Recent research in this field may lead to a better understanding of the pathophysiology of the disease and change the way LPR is managed. Source

Large R.J.,Dundalk Institute of Technology | Hollywood M.A.,Dundalk Institute of Technology | Sergeant G.P.,Dundalk Institute of Technology | Thornbury K.D.,Dundalk Institute of Technology | And 3 more authors.
American Journal of Physiology - Cell Physiology | Year: 2010

Hyaluronan, a joint lubricant and regulator of synovial fluid content, is secreted by fibroblast-like synoviocytes lining the joint cavity, and secretion is greatly stimulated by Ca 2+-dependent protein kinase C. This study aimed to define synoviocyte membrane currents and channels that may influence synoviocyte Ca 2+ dynamics. Resting membrane potential ranged from -30 mV to -66 mV (mean -45 ± 8.60 mV, n = 40). Input resistance ranged from 0.54 GΩ to 2.6 GΩ (mean 1.28 ± 0.57 GΩ; v = 33). Cell capacitance averaged 97.97 ± 5.93 pF. Voltage clamp using C s+ pipette solution yielded a transient inward current that disappeared in Ca 2+-free solutions and was blocked by 1 μM nifedipine, indicating an L-type calcium current. The current was increased fourfold by the calcium channel activator FPL 64176 (300 nM). Using K + pipette solution, depolarizing steps positive to -40 mV evoked an outward current that showed kinetics and voltage dependence of activation and inactivation typical of the delayed rectifier potassium current. This was blocked by the nonspecific delayed rectifier blocker 4-aminopyridine. The synoviocytes expressed mRNA for four Kv1 subtypes (Kv1.1, Kv1.4, Kv1.5, and Kv1.6). Correolide (1 μM), margatoxin (100 nM), and α-dendrotoxin block these Kv1 subtypes, and all of these drugs significantly reduced synoviocyte outward current. The current was blocked most effectively by 50 nM κ-dendrotoxin, which is specific for channels containing a Kv1.1 subunit, indicating that Kv1.1 is critical, either as a homomultimeric channel or as a component of a heteromultimeric Kv1 channel. When 50 nM κ-dendrotoxin was added to current-clamped synoviocytes, the cells depolarized by >20 mV and this was accompanied by an increase in intracellular calcium concentration. Similarly, depolarization of the cells with high external potassium solution caused an increase in intracellular calcium, and this effect was greatly reduced by 1 μM nifedipine. In conclusion, fibroblast-like synoviocytes cultured from the inner synovium of the rabbit exhibit voltage-dependent inward and outward currents, including Ca 2+ currents. They thus express ion channels regulating membrane Ca 2+ permeability and electrochemical gradient. Since Ca 2+-dependent kinases are major regulators of synovial hyaluronan secretion, the synoviocyte ion channels are likely to be important in the regulation of hyaluronan secretion. Copyright © 2010 the American Physiological Society. Source

Mugler E.M.,Northwestern University | Goldrick M.,Northwestern University | Rosenow J.M.,Northwestern University | Tate M.C.,Northwestern University | Slutzky M.W.,Physiology
Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS | Year: 2015

Brain-machine interfaces that directly translate attempted speech from the speech motor areas could change the lives of people with complete paralysis. However, it remains uncertain exactly how speech production is encoded in cortex. Improving this understanding could greatly improve brain-machine interface design. Specifically, it is not clear to what extent the different levels of speech production (phonemes, or speech sounds, and articulatory gestures, which describe the movements of the articulator muscles) are represented in the motor cortex. Using electrocorticographic (ECoG) electrodes on the cortical surface, we recorded neural activity from speech motor and premotor areas during speech production. We decoded both gestures and phonemes using the neural signals. Overall classification accuracy was higher for gestures than phonemes. In particular, gestures were better represented in the primary sensorimotor cortices, while phonemes were better represented in more anterior areas. © 2015 IEEE. Source

Levick J.R.,Physiology | Michel C.C.,Imperial College London
Cardiovascular Research | Year: 2010

Microvascular fluid exchange (flow Jv) underlies plasma/interstitial fluid (ISF) balance and oedematous swelling. The traditional form of Starling's principle has to be modified in light of insights into the role of ISF pressures and the recognition of the glycocalyx as the semipermeable layer of endothelium. Sum-of-forces evidence and direct observations show that microvascular absorption is transient in most tissues; slight filtration prevails in the steady state, even in venules. This is due in part to the inverse relation between filtration rate and ISF plasma protein concentration; ISF colloid osmotic pressure (COP) rises as Jv falls. In some specialized regions (e.g. kidney, intestinal mucosa), fluid absorption is sustained by local epithelial secretions, which flush interstitial plasma proteins into the lymphatic system. The low rate of filtration and lymph formation in most tissues can be explained by standing plasma protein gradients within the intercellular cleft of continuous capillaries (glycocalyx model) and around fenestrations. Narrow breaks in the junctional strands of the cleft create high local outward fluid velocities, which cause a disequilibrium between the subglycocalyx space COP and ISF COP. Recent experiments confirm that the effect of ISF COP on Jv is much less than predicted by the conventional Starling principle, in agreement with modern models. Using a two-pore system model, we also explore how relatively small increases in large pore numbers dramatically increase Jv during acute inflammation. © 2010 The Author. Source

Cai Y.,Uppsala University | Edin F.,Uppsala University | Jin Z.,Physiology | Alexsson A.,Uppsala University | And 6 more authors.
Acta Biomaterialia | Year: 2016

Cochlear implants (CI) have been used for several decades to treat patients with profound hearing loss. Nevertheless, results vary between individuals, and fine hearing is generally poor due to the lack of discrete neural stimulation from the individual receptor hair cells. A major problem is the deliverance of independent stimulation signals to individual auditory neurons. Fine hearing requires significantly more stimulation contacts with intimate neuron/electrode interphases from ordered axonal re-growth, something current CI technology cannot provide. Here, we demonstrate the potential application of micro-textured nanocrystalline diamond (NCD) surfaces on CI electrode arrays. Such textured NCD surfaces consist of micrometer-sized nail-head-shaped pillars (size 5 × 5 μm2) made with sequences of micro/nano-fabrication processes, including sputtering, photolithography and plasma etching. The results show that human and murine inner-ear ganglion neurites and, potentially, neural progenitor cells can attach to patterned NCD surfaces without an extracellular matrix coating. Microscopic methods revealed adhesion and neural growth, specifically along the nail-head-shaped NCD pillars in an ordered manner, rather than in non-textured areas. This pattern was established when the inter-NCD pillar distance varied between 4 and 9 μm. The findings demonstrate that regenerating auditory neurons show a strong affinity to the NCD pillars, and the technique could be used for neural guidance and the creation of new neural networks. Together with the NCD's unique anti-bacterial and electrical properties, patterned NCD surfaces could provide designed neural/electrode interfaces to create independent electrical stimulation signals in CI electrode arrays for the neural population. Statement of Significance Cochlear implant is currently a successful way to treat sensorineural hearing loss and deafness especially in children. Although clinically successful, patients' fine hearing cannot be completely restored. One problem is the amount of the electrodes; 12-20 electrodes are used to replace the function of 3400 inner hair cells. Intense research is ongoing aiming to increase the number of electrodes. This study demonstrates the use of nanocrystalline diamond as a potential nerve-electrode interface. Micrometer-sized nanocrystalline diamond pillars showed high affinity to regenerated human neurons, which grew into a pre-defined network based on the pillar design. Our findings are of particular interest since they can be applied on any silicon-based implant to increase electrode count and to achieve individual neuron stimulation patterns. © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. Source

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