Auditory gating in the ventral striatum and auditory cortex : the role of stimulus-locking and the influence of discrimination learning

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2014

Improved cardiac gating and patient monitoring in high field magnetic resonance imaging by means of electrocardiogram signal processing

Magdeburg, Univ., Fak. für Elektrotechnik und Informationstechnik, Diss., 2015

Effect of rufinamide on gating properties of voltage-gated sodium channel Na(v)1.7

Background: Voltage-gated sodium channels (Nav1.x) are important players in chronic pain. A particular interest has grown in Nav1.7, expressed in nociceptors, since mutations in its gene are associated to two inherited pain syndromes or insensitivity to pain. Rufinamide, a drug used to treat refractory epilepsy such as the Lennox-Gastaut syndrome, has been shown to reduce the number of action potentials in cortical neurons without completely blocking Na channels. Aim: The goal of this study was to investigate the effect of rufinamide on Nav1.7 current. Methods and results: Whole-cell patch clamp experiments were performed using HEK293 cells stably expressing Nav1.7. Rufinamide significantly decreased peak sodium current by 28.3, 21.2 and 12.5% at concentrations of 500, 100 and 50μM respectively (precise EC50 could not be calculated since higher rufinamide concentrations could not be achieved in physiological buffer solution). No significant difference on the V1/2 of voltage-dependence of activation was seen; however a shift in the steady-state inactivation curve was observed (-82.6 mV to -88.8 mV and -81.8 to -87.6 mV for 50 and 100 μM rufinamide respectively, p <0.005). Frequency-dependent inhibition of Nav1.7 was also influenced by the drug. One hundred μM rufinamide reduced the peak sodium current (in % of the peak current taken at the first sweep of a train of 50) from 90.8 to 80.8% (5Hz), 88.7 to 71.8% (10 Hz), 69.1 to 49.2% (25 Hz) and 22.3 to 9.8% (50 Hz) (all p <0.05). Onset of fast inactivation was not influenced by the drug since no difference in the time constant of current decay was observed. Conclusion: In the concentration range of plasma level in human treated for epilepsy, 15 μM, rufinamide only minimally blocks Nav1.7. However, it stabilizes the inactivated state and exerts frequencydependent inhibition of Nav1.7. These pharmacological properties may be of use in reducing ectopic discharges as a causal and symptom related contributor of neuropathic pain syndrome.

Endogenous opioid peptides in parasympathetic, sympathetic and sensory nerves in the guinea-pig heart.

Research has suggested that exogenous opioid substances can have direct effects on cardiac muscle or influence neurotransmitter release via presynaptic modulation of neuronal inputs to the heart. In the present study, multiple-labelling immunohistochemistry was employed to determine the distribution of endogenous opioid peptides within the guinea-pig heart. Approximately 40% of cardiac ganglion cells contained immunoreactivity for dynorphin A (1-8), dynorphin A (1-17) and dynorphin B whilst 20% displayed leu-enkephalin immunoreactivity. Different populations of opioid-containing ganglion cells were identified according to the co-existence of opioid immunoreactivity with immunoreactivity for somatostatin and neuropeptide Y. Immunoreactivity for prodynorphin-derived peptides was observed in many sympathetic axons in the heart and was also observed, though to a lesser extent, in sensory axons. Leu-enkephalin immunoreactivity was observed in occasional sympathetic and sensory axons. No immunoreactivity was observed for met-enkephalin-arg-gly-leu or for beta-endorphin. These results demonstrate that prodynorphin-derived peptides are present in parasympathetic, sympathetic and sensory nerves within the heart, but suggest that only the prodynorphin gene is expressed in guinea-pig cardiac nerves. This study has shown that endogenous opioid peptides are well placed to regulate cardiac function via both autonomic and sensory pathways.

Consumers’ sensory acceptability of pork from immunocastrated male pigs

Boar taint is the off-odour or off flavour of cooked pork. Currently, the most common method of controlling boar taint is surgical castration. However, immunocastration has been used in some parts of the world as an alternative to surgical castration. The aim of this study was to evaluate the sensory acceptability of meat from immunocastrated pigs (IM) compared with meat from females (FE), surgically castrated (CM) and entire males (EM). Twenty animals of each type were evaluated by 201 consumers in 20 sessions. Longissimus thoracis muscle of the different animals was cooked in an oven at 180 °C for 10 min. Consumers scored the odour and the flavour of the meat in a 9-point category scale without an intermediate level. There were no significant differences in consumer’s evaluation of meat from IM, CM, and FE. In contrast, EM meat presented a higher percentage of dissatisfied scores and was significantly (P & 0.05) less accepted than meat from CM, IM and FE. Consumers’ acceptability of EM meat was always lower, independently of its androstenone levels. However meat with low levels of androstenone was more accepted that meat with medium or high levels of this substance. It can be concluded that immunocastration produced pork that was accepted by the consumers, and was indistinguishable from pork from CM or FE.

The value of 'positive' clinical signs for weakness, sensory and gait disorders in conversion disorder: a systematic and narrative review.

Experts in the field of conversion disorder have suggested for the upcoming DSM-V edition to put less weight on the associated psychological factors and to emphasise the role of clinical findings. Indeed, a critical step in reaching a diagnosis of conversion disorder is careful bedside neurological examination, aimed at excluding organic signs and identifying 'positive' signs suggestive of a functional disorder. These positive signs are well known to all trained neurologists but their validity is still not established. The aim of this study is to provide current evidence regarding their sensitivity and specificity. We conducted a systematic search on motor, sensory and gait functional signs in Embase, Medline, PsycINfo from 1965 to June 2012. Studies in English, German or French reporting objective data on more than 10 participants in a controlled design were included in a systematic review. Other relevant signs are discussed in a narrative review. Eleven controlled studies (out of 147 eligible articles) describing 14 signs (7 motor, 5 sensory, 2 gait) reported low sensitivity of 8-100% but high specificity of 92-100%. Studies were evidence class III, only two had a blinded design and none reported on inter-rater reliability of the signs. Clinical signs for functional neurological symptoms are numerous but only 14 have been validated; overall they have low sensitivity but high specificity and their use should thus be recommended, especially with the introduction of the new DSM-V criteria.

Expression of substance P and preprotachykinin mRNA by primary sensory neurons in culture: regulation by factors present in peripheral and central target tissues.

Primary sensory neurons display various neuronal phenotypes which may be influenced by factors present in central or peripheral targets. In the case of DRG cells expressing substance P (SP), the influence of peripheral or central targets was tested on the neuronal expression of this neuropeptide. DRG cells were cultured from chick embryo at E6 or E10 (before or after establishment of functional connections with targets). Preprotachykinin mRNA was visualized in DRG cell cultures by either Northern blot or in situ hybridization using an antisense labeled riboprobe, while the neuropeptide SP was detected by immunostaining with a monoclonal antibody. In DRG cell cultures from E10, only 60% of neurons expressed SP. In contrast, DRG cell cultures performed at E6 showed a significant hybridization signal and SP-like immunoreactivity in virtually all the neurons (98%). The addition of extracts from muscle, skin, brain or spinal cord to DRG cells cultured at E6 reduced by 20% the percentage of neurons which express preprotachykinin mRNA and SP-like immunoreactivity. Our results indicate that factors issued from targets inhibit SP-expression by a subset of primary sensory neurons and act on the transcriptional control of preprotachykinin gene.

Physical and Sensory Disability Strategy and Action Plan 2012-2015 (PDF 1.180KB)

A strategy to improve outcomes, services and support for people in Northern Ireland who have a physical, communication or sensory disability.

Physical and Sensory Disability Strategy and Action Plan 2011-2015 - Summary of the feedback and findings from the public consultation (PDF 248KB)

On 27 January 2011 the Department of Health, Social Services and Public Safety (DHSSPS) launched a three month public consultation for a new draft Physical and Sensory Disability Strategy and Action Plan (2011-2015). åÊ The aim of the consultation was to provide the opportunity for a range of different stakeholders (public authorities and organisations, individuals including persons with disabilities and community and voluntary organisations) from across Northern Ireland to give feedback on the suggested priorities and challenges detailed in the document. The Department recognised the need for a new Disability Strategy and Action Plan not least to address new and developing challenges and opportunities. These include: åÊ • Obligations taken by the UK and NI in signing and ratifying the UN Convention on the Rights of Persons with Disabilities; åÊ • New innovations and models of care, support and treatment available within health and social care; åÊ • The current demographic trends and financial constraints being faced by everyone. åÊ åÊ åÊ

Ultrastructure and chaetotaxy of sensory eeceptors in the cercaria of a species of Allopodocotyle Pritchard, 1966 (Digenea: Opecoelidae)

Previous investigations of sensory systems in opecoelid cercariae have focused on chaetotaxy and ultrastructure of sensory receptors. They revealed chaetotaxic patterns within family, genus, and species as well as different receptors. Chaetotaxic and ultrastructural observations have rarely been combined. We investigated the ultrastructure of cercarial sensory receptors in conjunction with chaetotaxy and neuromorphology in a species of Allopodocotyle. Cercariae were treated with acetylthiocholine iodide and silver nitrate, and some were processed for light, scanning (SEM), and transmission (TEM) electron microscopy. Five nerve regions were distinguished. Chaetotaxy was consistent with that of other opecoelids. Five types of receptors were distinguished with SEM. Types differed in number of cilium-like structures (one or more), length of cilium-like structure (short, moderately long, or long), presence or absence of a tegumentary collar, and length of tegumentary collar (low, moderately low, or very high). Internal ultrastructure of some types revealed unsheathed cilium-like structures, basal body, and thickened nerve collars. Possible subtegumentary and sheathed receptors are introduced. Some receptor types were site-specific. For example, receptors with multiple cilium-like structures were concentrated on cephalic region whereas receptors with short cilium-like structure were widespread throughout most regions. Ultrastructure and site-specificity observations suggest that most receptors are mechanoreceptors.

External morphology of sensory structures of fourth instar larvae of neotropical species of phlebotomine sand flies (Diptera: Psychodidae) under scanning electron microscopy

In the present study, some morphological structures of antennae, maxillary palps and caudal setae of fourth instar larvae of laboratory-reared phlebotomine sand flies (Lutzomyia longipalpis, L. migonei, L. evandroi, L. lenti, L. sericea, L. whitmani and L. intermedia) of the State of Ceará, Brazil, were examined under scanning electron microscopy. The antennal structures exhibited considerable variation in the morphology and position. A prominent digitiform distal segment has been observed only on the antenna of species of the subgenus Nyssomyia. The taxonomic relevance of this and other antennal structure is discussed. The papiliform structures found in the maxillae and the porous structures of the caudal setae of all species examined may have chemosensory function. Further studies with transmission electron microscopy are needed to better understand the physiological function of these external structures.

Angiotensinergic innervation of the kidney: Localization and relationship with catecholaminergic postganglionic and sensory nerve fibers.

We describe an angiotensin (Ang) II-containing innervation of the kidney. Cryosections of rat, pig and human kidneys were investigated for the presence of Ang II-containing nerve fibers using a mouse monoclonal antibody against Ang II (4B3). Co-staining was performed with antibodies against synaptophysin, tyrosine 3-hydroxylase, and dopamine beta-hydroxylase to detect catecholaminergic efferent fibers and against calcitonin gene-related peptide to detect sensory fibers. Tagged secondary antibodies and confocal light or laser scanning microscopy were used for immunofluorescence detection. Ang II-containing nerve fibers were densely present in the renal pelvis, the subepithelial layer of the urothelium, the arterial nervous plexus, and the peritubular interstitium of the cortex and outer medulla. They were infrequent in central veins and the renal capsule and absent within glomeruli and the renal papilla. Ang II-positive fibers represented phenotypic subgroups of catecholaminergic postganglionic or sensory fibers with different morphology and intrarenal distribution compared to their Ang II-negative counterparts. The Ang II-positive postganglionic fibers were thicker, produced typically fusiform varicosities and preferentially innervated the outer medulla and periglomerular arterioles. Ang II-negative sensory fibers were highly varicose, prevailing in the pelvis and scarce in the renal periphery compared to the rarely varicose Ang II-positive fibers. Neurons within renal microganglia displayed angiotensinergic, cate-cholaminergic, or combined phenotypes. Our results suggest that autonomic fibers may be an independent source of intrarenal Ang II acting as a neuropeptide co-transmitter or neuromodulator. The angiotensinergic renal innervation may play a distinct role in the neuronal control of renal sodium reabsorption, vasomotion and renin secretion.

Report of the National Physical and Sensory Disability Database Development Committee

The need for information on the health service needs of people with physical and/or sensory disabilities was first highlighted in Shaping a Healthier Future, a document which outlined the national strategy for effective healthcare in the 1990s. This strategy document identified the establishment of a national database as the means of gathering such information Download the Report here