Effect of low-level laser therapy (LLLT) on peripheral nerve regeneration using fibrin glue derived from snake venom

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Functional and morphometric differences between the early and delayed use of phototherapy in crushed median nerves of rats

This study evaluated the functional and quantitative differences between the early and delayed use of phototherapy in crushed median nerves. After a crush injury, low-level laser therapy (GaAs) was applied transcutaneously at the injury site, 3 min daily, with a frequency of five treatments per week for 2 weeks. In the early group, the first laser treatment started immediately after surgery, and in the delayed group, after 7 days. The grasping test was used for functional evaluation of the median nerve, before, 10, and 21 days after surgery, when the rats were killed. Three segments of the median nerve were analyzed histomorphometrically by light microscopy and computer analysis. The following features were observed: myelinated fiber and axon diameters, myelin sheath area, g-ratio, density and number of myelinated fibers, and area and number of capillaries. In the proximal segment (site of crush), the nerves of animals submitted to early and delayed treatment showed myelinated fiber diameter and myelin sheath area significantly larger compared to the untreated group. In the distal segment, the myelin sheath area was significantly smaller in the untreated animals compared to the delayed group. The untreated, early, and delayed groups presented a 50, 57, and 81% degree of functional recovery, respectively, at 21 days after injury, with a significant difference between the untreated and delayed groups. The results suggest that the nerves irradiated with low-power laser exhibit myelinated fibers of greater diameter and a better recovery of function.

Contribution of the retrotrapezoid nucleus/parafacial respiratory region to the expiratory-sympathetic coupling in response to peripheral chemoreflex in rats

Moraes DJ, Dias MB, Cavalcanti-Kwiatkoski R, Machado BH, Zoccal DB. Contribution of retrotrapezoid nucleus/parafacial respiratory region to the expiratory-sympathetic coupling in response to peripheral chemoreflex in rats. J Neurophysiol 108: 882-890, 2012. First published May 16, 2012; doi:10.1152/jn.00193.2012.-Central mechanisms of coupling between respiratory and sympathetic systems are essential for the entrainment between the enhanced respiratory drive and sympathoexcitation in response to hypoxia. However, the brainstem nuclei and neuronal network involved in these respiratory-sympathetic interactions remain unclear. Here, we evaluated whether the increase in expiratory activity and expiratory-modulated sympathoexcitation produced by the peripheral chemoreflex activation involves the retrotrapezoid nucleus/parafacial respiratory region (RTN/pFRG). Using decerebrated arterially perfused in situ rat preparations (60-80 g), we recorded the activities of thoracic sympathetic (tSN), phrenic (PN), and abdominal nerves (AbN) as well as the extracellular activity of RTN/pFRG expiratory neurons, and reflex responses to chemoreflex activation were evaluated before and after inactivation of the RTN/pFRG region with muscimol (1 mM). In the RTN/pFRG, we identified late-expiratory (late-E) neurons (n = 5) that were silent at resting but fired coincidently with the emergence of late-E bursts in AbN after peripheral chemoreceptor activation. Bilateral muscimol microinjections into the RTN/pFRG region (n = 6) significantly reduced basal PN frequency, mean AbN activity, and the amplitude of respiratory modulation of tSN (P < 0.05). With respect to peripheral chemoreflex responses, muscimol microinjections in the RTN/pFRG enhanced the PN inspiratory response, abolished the evoked late-E activity of AbN, but did not alter either the magnitude or pattern of the tSN reflex response. These findings indicate that the RTN/pFRG region is critically involved in the processing of the active expiratory response but not of the expiratory-modulated sympathetic response to peripheral chemoreflex activation of rat in situ preparations.

Minimal local anesthetic volume for peripheral nerve block: a new ultrasound-guided, nerve dimension-based method

BACKGROUND AND OBJECTIVES: Nerve blocks using local anesthetics are widely used. High volumes are usually injected, which may predispose patients to associated adverse events. Introduction of ultrasound guidance facilitates the reduction of volume, but the minimal effective volume is unknown. In this study, we estimated the 50% effective dose (ED50) and 95% effective dose (ED95) volume of 1% mepivacaine relative to the cross-sectional area of the nerve for an adequate sensory block. METHODS: To reduce the number of healthy volunteers, we used a volume reduction protocol using the up-and-down procedure according to the Dixon average method. The ulnar nerve was scanned at the proximal forearm, and the cross-sectional area was measured by ultrasound. In the first volunteer, a volume of 0.4 mL/mm of nerve cross-sectional area was injected under ultrasound guidance in close proximity to and around the nerve using a multiple injection technique. The volume in the next volunteer was reduced by 0.04 mL/mm in case of complete blockade and augmented by the same amount in case of incomplete sensory blockade within 20 mins. After 3 up-and-down cycles, ED50 and ED95 were estimated. Volunteers and physicians performing the block were blinded to the volume used. RESULTS: A total 17 of volunteers were investigated. The ED50 volume was 0.08 mL/mm (SD, 0.01 mL/mm), and the ED95 volume was 0.11 mL/mm (SD, 0.03 mL/mm). The mean cross-sectional area of the nerves was 6.2 mm (1.0 mm). CONCLUSIONS: Based on the ultrasound measured cross-sectional area and using ultrasound guidance, a mean volume of 0.7 mL represents the ED95 dose of 1% mepivacaine to block the ulnar nerve at the proximal forearm.

Immunohistochemical evaluation of heat shock protein expression in normal canine nerve and peripheral nerve sheath tumours

Abnormal expression of heat shock proteins (HSPs) has been observed in many human neoplasms and such expression has prognostic, predictive and therapeutic implications. The aim of this study was to evaluate immunohistochemically the expression of HSP 27, HSP 32 and HSP 90 in normal canine peripheral nerves and in four benign and 15 malignant canine peripheral nerve sheath tumours (PNSTs). In normal nerve, all of the HSPs were detected in axons, epineurial fibroblasts and scattered Schwann cell bodies. Cytoplasmic expression of HSP 27 was more widespread and intense in benign PNSTs compared with malignant PNSTs (P <0.05). Widespread and intense nuclear expression of HSP 32 was also associated with benign tumours (P <0.01), while high HSP 90 immunoreactivity was detected in all tumours, suggesting that HSP 90 might represent a new therapeutic target.

Ultrasound-guided block of sciatic and femoral nerves: an anatomical study

The sheep is a popular animal model for human biomechanical research involving invasive surgery on the hind limb. These painful procedures can only be ethically justified with the application of adequate analgesia protocols. Regional anaesthesia as an adjunct to general anaesthesia may markedly improve well-being of these experimental animals during the postoperative period due to a higher analgesic efficacy when compared with systemic drugs, and may therefore reduce stress and consequently the severity of such studies. As a first step 14 sheep cadavers were used to establish a new technique for the peripheral blockade of the sciatic and the femoral nerves under sonographic guidance and to evaluate the success rate by determination of the colorization of both nerves after an injection of 0.5 mL of a 0.1% methylene blue solution. First, both nerves were visualized sonographically. Then, methylene blue solution was injected and subsequently the length of colorization was measured by gross anatomical dissection of the target nerves. Twenty-four sciatic nerves were identified sonographically in 12 out of 13 cadavers. In one animal, the nerve could not be ascertained unequivocally and, consequently, nerve colorization failed. Twenty femoral nerves were located by ultrasound in 10 out of 13 cadavers. In three cadavers, signs of autolysis impeded the scan. This study provides a detailed anatomical description of the localization of the sciatic and the femoral nerves and presents an effective and safe yet simple and rapid technique for performing peripheral nerve blocks with a high success rate.

Passive transfer of IgG anti-GM1 antibodies impairs peripheral nerve repair.

Anti-GM1 antibodies are present in some patients with autoimmune neurological disorders. These antibodies are most frequently associated with acute immune neuropathy called Guillain-Barré syndrome (GBS). Some clinical studies associate the presence of these antibodies with poor recovery in GBS. The patients with incomplete recovery have failure of nerve repair, particularly axon regeneration. Our previous work indicates that monoclonal antibodies can inhibit axon regeneration by engaging cell surface gangliosides (Lehmann et al., 2007). We asked whether passive transfer of human anti-GM1 antibodies from patients with GBS modulate axon regeneration in an animal model. Human anti-GM1 antibodies were compared with other GM1 ligands, cholera toxin B subunit and a monoclonal anti-GM1 antibody. Our results show that patient derived anti-GM1 antibodies and cholera toxin beta subunit impair axon regeneration/repair after PNS injury in mice. Comparative studies indicated that the antibody/ligand-mediated inhibition of axon regeneration is dependent on antibody/ligand characteristics such as affinity-avidity and fine specificity. These data indicate that circulating immune effectors such as human autoantibodies, which are exogenous to the nervous system, can modulate axon regeneration/nerve repair in autoimmune neurological disorders such as GBS.

Expression of corticotropin-releasing factor in inflamed tissue is required for intrinsic peripheral opioid analgesia.

Immune cell-derived opioid peptides can activate opioid receptors on peripheral sensory nerves to inhibit inflammatory pain. The intrinsic mechanisms triggering this neuroimmune interaction are unknown. This study investigates the involvement of endogenous corticotropin-releasing factor (CRF) and interleukin-1beta (IL-1). A specific stress paradigm, cold water swim (CWS), produces potent opioid receptor-specific antinociception in inflamed paws of rats. This effect is dose-dependently attenuated by intraplantar but not by intravenous alpha-helical CRF. IL-1 receptor antagonist is ineffective. Similarly, local injection of antiserum against CRF, but not to IL-1, dose-dependently reverses this effect. Intravenous anti-CRF is only inhibitory at 10(4)-fold higher concentrations and intravenous CRF does not produce analgesia. Pretreatment of inflamed paws with an 18-mer 3'-3'-end inverted CRF-antisense oligodeoxynucleotide abolishes CWS-induced antinociception. The same treatment significantly reduces the amount of CRF extracted from inflamed paws and the number of CRF-immunostained cells without affecting gross inflammatory signs. A mismatch oligodeoxynucleotide alters neither the CWS effect nor CRF immunoreactivity. These findings identify locally expressed CRF as the predominant agent to trigger opioid release within inflamed tissue. Endogenous IL-1, circulating CRF or antiinflammatory effects, are not involved. Thus, an intact immune system plays an essential role in pain control, which is important for the understanding of pain in immunosuppressed patients with cancer or AIDS.

Strain and excursion of the sciatic, tibial, and plantar nerves during a modified straight leg raising test

A modified straight leg raising (SLR) in which ankle dorsiflexion is performed before hip flexion has been suggested to diagnose distal neuropathies such as tarsal tunnel syndrome. This study evaluates the clinical hypothesis that strain in the nerves around the ankle and foot caused by ankle dorsiflexion can be further increased with hip flexion. Linear displacement transducers were inserted into the sciatic, tibial, and plantar nerves and plantar fascia of eight embalmed cadavers to measure strain during the modified SLR. Nerve excursion was measured with a digital calliper. Ankle dorsiflexion resulted in a significant strain and distal. excursion of the tibial nerve. With the ankle in dorsiflexion, the proximal excursion and tension increase in the sciatic nerve associated with hip flexion were transmitted distally along the nerve from the hip to beyond the ankle. As hip flexion had an impact on the nerves around the ankle and foot but not on the plantar fascia, the modified SLR may be a useful test to differentially diagnose plantar heel pain. Although the modified SLR caused the greatest increase in nerve strain nearest the moving joint, mechanical forces acting on peripheral nerves are transmitted well beyond the moving joint. (c) 2006 Orthopaedic Research Society.

Pupillary shapes in response to electrical stimulation of the sclera of peripheral cornea in cats and porcines

Purpose: We have reported that the changes in the pupillary shape in response to electrical stimulation of the branches of the ciliary nerves in cats. (Miyagawa et al. PLoS One, 2014). This study investigates the changes in the pupillary shapes in response to electrical stimulations of the sclera of peripheral cornea in cats and porcines. Methods: Two enucleated eyes of two cats and three enucleated porcine eyes were studied. Trains of biphasic pulses (current, 3 mA; duration, 2 ms/phase; frequency, 40 Hz) were applied using a tungsten electrode (0.3mm diameter). The stimulation was performed at every 45 degree over the entire circular region on the sclera near the cornea. The pupillary images were recorded before and 4 s (cat) and 10 s (pig) after the stimulation and the change in the pupil diameter (Δr) was quantified. The pupillary images were obtained with a custom-built compact wavefront aberrometer (Uday et al. J Cataract Refract Surg, 2013). Results: In a cat eye, the pupil was dilated by the electrical stimulation at six out of eight orientations (before stimulation pupil diameter r=10.10±0.49 mm, Δr=0.33±0.12 mm). The pupil dilated only toward the electrode (relative eccentricity of the pupil center to the pupil diameter change amount rdec=1.15±0.28). In the porcine eyes, the pupils were constricted by the electrical stimulations at the temporal and nasal orientations (r=10.04±0.57 mm, Δr=1.52±0.70 mm). The pupils contracted symmetrically (rdec=0.30±0.12). Conclusions: With electrical stimulation in the sclera of the peripheral cornea, asymmetric mydriasis in cat eyes and symmetrical miosis in porcine eyes were observed. Under the assumption that the electrical stimulation stimulated both muscles that contribute to the pupil control, our hypothesis proposed here is that the pupil dilator is stronger than the pupil sphincter in cat, and pupil sphincter is stronger than pupil dilator in porcine.

Accommodative response to electrical stimulation of the sclera of peripheral cornea in cats and porcines

Purpose: We have reported that the changes in the accommodative response to electrical stimulation of the branches of the ciliary nerves in cats. (Miyagawa et al, PLoS One, 2014). We have also reported that no robust accommodative responses to the electrical stimulations of the sclera of peripheral cornea (SSPC) were observed in enucleated porcine eyes (Mihashi et al, VPOptics, 2014). In this study, accommodative responses to SSPC stimulation in cats and porcines were investigated. Methods: Two eyes of two cats under anesthesia and after they were sacrificed were studied. Three enucleated porcine eyes obtained from a local slaughterhouse were also studied. Trains of biphasic pulses (current, 3 mA; duration, 2 ms/phase; frequency, 40 Hz) were applied using a tungsten electrode (0.3mm diameter) from several orientations. Wavefront sensing with a compact wavefront aberrometer (Uday et al J Cataract Refract Surg, 2013) were performed before and 4 s (cat) and 10 s (pig) after the stimulations and wavefront aberrations including spherical errors were analyzed over a 4-mm pupil area. Results: In the first cat under anesthesia, at three out of seven stimulus positions, 0.2 D hyperopic accommodative responses were observed and in two orientations, myopic responses were observed. For the other cat, weak accommodative responses including astigmatic changes were observed. In the sacrificed condition of the second cat, 0.1 D myopic response was observed for one stimulus orientation and the smaller responses were observed at six out of eight stimulus positions. No accommodative responses were elicited for the enucleated porcine eyes. Conclusions: In the anesthetized cats, electrical stimulation of the SSPC induced accommodative responses; the responses were unstable and weaker than the responses by the ciliary nerve stimulations we observed in our previous study. Small accommodative responses were observed after one of two cats had been sacrificed, but no accommodative responses were detected in the enucleated porcine eyes. Further studies are needed to confirm difference in the accommodation functions in the two species.

Clinically indicated replacement versus routine replacement of peripheral venous catheters (Review)

Background Centers for Disease Control Guidelines recommend replacement of peripheral intravenous (IV) catheters every 72 to 96 hours. Routine replacement is thought to reduce the risk of phlebitis and bacteraemia. Catheter insertion is an unpleasant experience for patients and replacement may be unnecessary if the catheter remains functional and there are no signs of inflammation. Costs associated with routine replacement may be considerable. Objectives To assess the effects of removing peripheral IV catheters when clinically indicated compared with removing and re-siting the catheter routinely.

New Patterns in Global Television : Peripheral Vision

Over recent decades, the flow of television programmes and services between nations has prompted concerns about `Cultural Imperialism', the idea that the powerful metropolitan nations at the centre of the world system are breaking down the integrity and autonomy of the peripheral countries. New Patterns in Global Television challenges that notion by showing that some of the countries outside the traditionally dominant centres have now developed strong television industries of their own, and have been expanding into regional markets, especially - but not exclusively - where linguistic and cultural similarities exist. This book brings together contributions from specialist researchers on the most dynamic of these regions: Latin America, India, the Middle East, Greater China and, in the English-speaking world, Canada and Australia. It provides the first comprehensive overview of the new patterns of flow in international television programme exchange and service provision in the satellite era, patterns unrecognised by the perspective of the prevailing theoretical orthodoxies in international communication research and policy.