Transnasal targeted delivery of therapeutics in central nervous system diseases: a narrative review.

Currently, neurointervention, surgery, medication, and central nervous system (CNS) stimulation are the main treatments used in CNS diseases. These approaches are used to overcome the blood brain barrier (BBB), but they have limitations that necessitate the development of targeted delivery methods. Thus, recent research has focused on spatiotemporally direct and indirect targeted delivery methods because they decrease the effect on nontarget cells, thus minimizing side effects and increasing the patient's quality of life. Methods that enable therapeutics to be directly passed through the BBB to facilitate delivery to target cells include the use of nanomedicine (nanoparticles and extracellular vesicles), and magnetic field-mediated delivery. Nanoparticles are divided into organic, inorganic types depending on their outer shell composition. Extracellular vesicles consist of apoptotic bodies, microvesicles, and exosomes. Magnetic field-mediated delivery methods include magnetic field-mediated passive/actively-assisted navigation, magnetotactic bacteria, magnetic resonance navigation, and magnetic nanobots-in developmental chronological order of when they were developed. Indirect methods increase the BBB permeability, allowing therapeutics to reach the CNS, and include chemical delivery and mechanical delivery (focused ultrasound and LASER therapy). Chemical methods (chemical permeation enhancers) include mannitol, a prevalent BBB permeabilizer, and other chemicals-bradykinin and 1-O-pentylglycerol-to resolve the limitations of mannitol. Focused ultrasound is in either high intensity or low intensity. LASER therapies includes three types: laser interstitial therapy, photodynamic therapy, and photobiomodulation therapy. The combination of direct and indirect methods is not as common as their individual use but represents an area for further research in the field. This review aims to analyze the advantages and disadvantages of these methods, describe the combined use of direct and indirect deliveries, and provide the future prospects of each targeted delivery method. We conclude that the most promising method is the nose-to-CNS delivery of hybrid nanomedicine, multiple combination of organic, inorganic nanoparticles and exosomes, via magnetic resonance navigation following preconditioning treatment with photobiomodulation therapy or focused ultrasound in low intensity as a strategy for differentiating this review from others on targeted CNS delivery; however, additional studies are needed to demonstrate the application of this approach in more complex in vivo pathways.

Angiogenesis in Free-Standing Two-Vasculature-Embedded Scaffold Extruded by Two-Core Laminar Flow Device.

Rapid construction of pre-vascular structure is highly desired for engineered thick tissue. However, angiogenesis in free-standing scaffold has been rarely reported because of limitation in growth factor (GF) supply into the scaffold. This study, for the 1st time, investigated angiogenic sprouting in free-standing two-vasculature-embedded scaffold with three different culture conditions and additional GFs. A two-core laminar flow device continuously extruded one vascular channel with human umbilical vein endothelial cells (HUVECs) and a 3 mg/ml type-1 collagen, one hollow channel, and a shell layer with 2% w/v gelatin-alginate (70:30) composite. Under the GF flowing condition, angiogenic sprouting from the HUVEC vessel had started since day 1 and gradually grew toward the hollow channel on day 10. Due to the medium flowing, the HUVECs showed elongated spindle-like morphology homogeneously. Their viability has been over 80% up to day 10. This approach could apply to vascular investigation, and drug discovery further, not only to the engineered thick tissue.

Deep learning-based quantitative estimation of lymphedema-induced fibrosis using three-dimensional computed tomography images.

In lymphedema, proinflammatory cytokine-mediated progressive cascades always occur, leading to macroscopic fibrosis. However, no methods are practically available for measuring lymphedema-induced fibrosis before its deterioration. Technically, CT can visualize fibrosis in superficial and deep locations. For standardized measurement, verification of deep learning (DL)-based recognition was performed. A cross-sectional, observational cohort trial was conducted. After narrowing window width of the absorptive values in CT images, SegNet-based semantic segmentation model of every pixel into 5 classes (air, skin, muscle/water, fat, and fibrosis) was trained (65%), validated (15%), and tested (20%). Then, 4 indices were formulated and compared with the standardized circumference difference ratio (SCDR) and bioelectrical impedance (BEI) results. In total, 2138 CT images of 27 chronic unilateral lymphedema patients were analyzed. Regarding fibrosis segmentation, the mean boundary F1 score and accuracy were 0.868 and 0.776, respectively. Among 19 subindices of the 4 indices, 73.7% were correlated with the BEI (partial correlation coefficient: 0.420-0.875), and 13.2% were correlated with the SCDR (0.406-0.460). The mean subindex of Index 2 [Formula: see text] presented the highest correlation. DL has potential applications in CT image-based lymphedema-induced fibrosis recognition. The subtraction-type formula might be the most promising estimation method.

Swallowing study using water-soluble contrast agents may increase aspiration sensitivity and antedate oral feeding without respiratory and drug complications: A STROBE-compliant prospective, observational, case-control trial.

Although the modified barium swallowing study (MBSS) is considered the gold standard for assessing aspiration risk, aspiration of lipid-soluble barium can cause chemical pneumonitis or impair radiologic interpretation of the lungs. Water-soluble contrast agents (WSCAs) may avoid these complications while maintaining sensitivity on aspiration. This prospective, observational, case-control cohort trial evaluated all patients >3 years old referred for swallowing study from September 2015 to November 2017. Repeat evaluations of individuals were excluded. High-risk patients were evaluated by WSCA (iohexol)-based swallowing study (WSS) and others by MBSS. The study included 829 evaluations of 762 patients. After excluding 74 evaluations, 365 WSSs and 390 MBSSs were performed. The most frequent underlying condition was brain lesion, followed by aspiration pneumonia. Aspiration occurred more frequently in WSS (147 patients: 40.3%) than in MBSS (36 patients: 9.2%) (P = .00). However, neither aspiration volume (6.72 cc [3.09-10.35] vs 5.53 cc [2.21-8.85]) nor radiographic alterations differed between the 2 groups (P > .05). Moreover, the swallowed (16.62 cc [8.45-24.79]) and aspirated amounts of iohexol were not correlated with radiologic changes or deterioration (P > .05). Switching to oral feeding following WSS was more frequent (164 patients: 44.9%), whereas aspiration pneumonia was not (P = .00). WSS did not prolong the interval to patient discharge (P = .06) or induce an allergic reaction or chemotoxicity over 1 week. The absence of aspiration-induced complications and adverse drug effects suggests that, compared with MBSS, WSS may increase aspiration sensitivity and early switching to oral feeding.

Targeted Delivery of Erythropoietin Hybridized with Magnetic Nanocarriers for the Treatment of Central Nervous System Injury: A Literature Review.

Although the incidence of central nervous system injuries has continued to rise, no promising treatments have been elucidated. Erythropoietin plays an important role in neuroprotection and neuroregeneration as well as in erythropoiesis. Moreover, the current worldwide use of erythropoietin in the treatment of hematologic diseases allows for its ready application in patients with central nervous system injuries. However, erythropoietin has a very short therapeutic time window (within 6-8 hours) after injury, and it has both hematopoietic and nonhematopoietic receptors, which exhibit heterogenic and phylogenetic differences. These differences lead to limited amounts of erythropoietin binding to in situ erythropoietin receptors. The lack of high-quality evidence for clinical use and the promising results of in vitro/in vivo models necessitate fast targeted delivery agents such as nanocarriers. Among current nanocarriers, noncovalent polymer-entrapping or polymer-adsorbing erythropoietin obtained by nanospray drying may be the most promising. With the incorporation of magnetic nanocarriers into an erythropoietin polymer, spatiotemporal external magnetic navigation is another area of great interest for targeted delivery within the therapeutic time window. Intravenous administration is the most readily used route. Manufactured erythropoietin nanocarriers should be clearly characterized using bioengineering analyses of the in vivo size distribution and the quality of entrapment or adsorption. Further preclinical trials are required to increase the therapeutic bioavailability (in vivo biological identity alteration, passage through the lung capillaries or the blood brain barrier, and timely degradation followed by removal of the nanocarriers from the body) and decrease the adverse effects (hematological complications, neurotoxicity, and cytotoxicity), especially of the nanocarrier.

Five-day rehabilitation of patients undergoing total knee arthroplasty using an end-effector gait robot as a neuromodulation blending tool for deafferentation, weight offloading and stereotyped movement: Interim analysis.

Deafferentation and weight offloading can increase brain and spinal motor neuron excitability, respectively. End-effector gait robots (EEGRs) can blend these effects with stereotyped movement-induced neuroplasticity. The authors aimed to evaluate the usefulness of EEGRs as a postoperative neuro-muscular rehabilitation tool. This prospective randomized controlled trial included patients who had undergone unilateral total knee arthroplasty (TKA). Patients were randomly allocated into two groups: one using a 200-step rehabilitation program in an EEGR or the other using a walker on a floor (WF) three times a day for five weekdays. The two groups were compared by electrophysiological and biomechanical methods. Since there were no more enrollments due to funding issues, interim analysis was performed. Twelve patients were assigned to the EEGR group and eight patients were assigned to the WF group. Although the muscle volume of the quadriceps and hamstring did not differ between the two groups, the normalized peak torque of the operated knee flexors (11.28 ± 16.04 Nm/kg) was improved in the EEGR group compared to that of the operated knee flexors in the WF group (4.25 ± 14.26 Nm/kg) (p = 0.04). The normalized compound motor action potentials of the vastus medialis (VM) and biceps femoris (BF) were improved in the EEGR group (p < 0.05). However, the normalized real-time peak amplitude and total, mean area under the curve of VM were decreased during rehabilitation in the EEGR group (p < 0.05). No significant differences were found between operated and non-operated knees in the EEGR group. Five-day EEGR-assisted rehabilitation induced strengthening in the knee flexors and the muscular reactivation of the BF and VM after TKA, while reducing the real-time use of the VM. This observation may suggest the feasibility of this technique: EEGR modulated the neuronal system of the patients rather than training their muscles. However, because the study was underpowered, all of the findings should be interpreted with the utmost caution.

Coaxial printing of double-layered and free-standing blood vessel analogues without ultraviolet illumination for high-volume vascularised tissue.

Human umbilical vein endothelial cells (HUVECs) and human aortic smooth muscle cells (HASMCs) were coaxially and continuously extruded without ultraviolet illumination using a microfluidic-based nozzle. Type I collagen (3 mg ml-1) containing HUVECs and a crosslinking reagent (100 mM CaCl2) were supplied as the core material. A mixture of 3 mg ml-1 of type I collagen (25%) and 1.8% weight volume-1 of sodium alginate (75%) was provided as the shell layer material surrounding the core material. The HUVECs were well proliferated at the core and reshaped into a monolayer formation along the axial direction of the scaffold. The HASMCs showed more than 90% cell viability in the shell layer. Fluorescent beads were passed through the inside channel of the scaffold with the HUVEC core and HASMC shell using an in-house connector. This double-layered scaffold showed higher angiogenesis in growth factor-free medium than the scaffold with only a HUVEC core. The HASMCs in the shell layer affected angiogenesis, extracellular matrix secretion, and outer diameter. The proposed technique could be applied to three-dimensional bioprinting for the production of high-volume vascularised tissue.

Magnetically guided targeted delivery of erythropoietin using magnetic nanoparticles: Proof of concept.

The objective of this proof-of-concept study was to demonstrate the targeted delivery of erythropoietin (EPO) using magnetically guided magnetic nanoparticles (MNPs).MNPs consisting of a ferric-ferrous mixture (FeCl3·6H2O and FeCl2·4H2O) were prepared using a co-precipitation method. The drug delivery system (DDS) was manufactured via the spray-drying technique using a nanospray-dryer. The DDS comprised 7.5 mg sodium alginate, 150 mg MNPs, and 1000 IU EPO.Scanning electron microscopy revealed DDS particles no more than 500 nm in size. Tiny particles on the rough surfaces of the DDS particles were composed of MNPs and/or EPO, unlike the smooth surfaces of the only alginate particles. Transmission electron microscopy showed the tiny particles from 5 to 20 nm in diameter. Fourier-transform infrared spectroscopy revealed DDS peaks characteristic of MNPs as well as of alginate. Thermal gravimetric analysis presented that 50% of DDS weight was lost in a single step around 500°C. The mode size of the DDS particles was approximately 850 nm under in vivo conditions. Standard soft lithography was applied to DDS particles prepared with fluorescent beads using a microchannel fabricated to have one inlet and two outlets in a Y-shape. The fluorescent DDS particles reached only one outlet reservoir in the presence of a neodymium magnet. The neurotoxicity was evaluated by treating SH-SY5Y cells in 48-well plates (1 × 10 cells/well) with 2 µL of a solution containing sodium alginate (0.075 mg/mL), MNPs (1.5 mg/mL), or sodium alginate + MNPs. A cell viability assay kit was used to identify a 93% cell viability after MNP treatment and a 94% viability after sodium alginate + MNP treatment, compared with the control. As for the DDS particle neurotoxicity, a 95% cell viability was noticed after alginate-encapsulated MNPs treatment and a 93% cell viability after DDS treatment, compared with the control.The DDS-EPO construct developed here can be small under in vivo conditions enough to pass through the lung capillaries with showing the high coating efficiency. It can be guided using magnetic control without displaying significant neurotoxicity in the form of solution or particles.

Comparison of a novel algorithm quantitatively estimating epifascial fibrosis in three-dimensional computed tomography images to other clinical lymphedema grading methods.

No method has yet been approved for detecting lymphedema fibrosis before its progression. This study assessed the feasibility of computed tomography-based estimation of fibrosis. This observational, cross-sectional study included patients with lymphedema affecting one limb. Three types (maximum, mean, minimum) of computed tomography reticulation indexes were digitally calculated from trans-axial images using absorptive values, and the computed tomography reticulation indexes compared with clinical scales and measurements. Of 326 patients evaluated by at least one of lymphoscintigraphy, bio-electrical impedance, and computed tomography, 24 were evaluated by all three. The mean number of computed tomography scans in these patients was 109. Sixteen patients had breast cancer, seven had gynecologic cancers, and one had primary lymphedema. Mean computed tomography reticulation index (r = 0.52, p < 0.01) and maximal computed tomography reticulation index (r = 0.45, p < 0.05) were significantly associated with time from initial limb swelling to computed tomography. Mean computed tomography reticulation index (r = 0.86, p < 0.01), minimal computed tomography reticulation index (r = 0.79, p < 0.01), and maximal computed tomography reticulation index (r = 0.68, p < 0.01) were significantly associated with International Society of Lymphedema substage. Minimal computed tomography reticulation index correlated with 1-kHz-based bio-electrical impedance ratio (r = -0.46, p < 0.05) and with standardized proximal limb circumference difference ratio (r = 0.45, p < 0.05) of both limbs. Maximal computed tomography reticulation index had a sensitivity of 0.78, specificity of 0.60, and areas under the curve of 0.66 in detecting lymphoscintigraphic stage IV. The algorithm utilizing three-dimensional computed tomography images of epifascial fibrosis may be used as a marker for lymphedema duration, limb swelling, International Society of Lymphedema substage, and interstitial lymphatic fluids of lymphedema. The current approach shows promise in providing an additional method to assist in characterizing and monitoring lymphedema patients.

Immediate muscle strengthening by an end-effector type gait robot with reduced real-time use of leg muscles: A case series and review of literature.

BACKGROUND: De-afferentation or non-weight bearing induces rapid cortical and spinal α-motor neuron excitability. Author supposed that an end-effector type gait robot (EEGR) could provide patients with a training condition that was specific enough to activate rapid cortical/spinal neuroplasticity, leading to immediate muscle strengthening. The electromyographic and biomechanical comparisons were conducted. AIM: To compare the electromyographic activities of the thigh and shank muscles and isometric peak torque (PT) before and after walking training on a floor or in the end-effector gait robot. METHODS: Twelve outpatients without ambulatory dysfunction were recruited. Order of two interventions (5-min training on a floor at a comfortable pace or training in an EEGR with non-weight bearing on their feet and 100% guidance force at 2.1 km/h) were randomly chosen. Isometric PT, maximal ratio of torque development, amplitude of compound motor action potential (CMAP), and area under the curve (AUC) were evaluated before and 10 min after both interventions. RESULTS: The degree of PT improvement of the dominant knee flexors was larger in the EEGR than on the floor (9.6 ± 22.4 Nm/BW, P < 0.01). The EEGR-trained patients had greater PT improvement of the dominant knee extensors than those who trained on the floor (4.5 ± 28.1 Nm/BW, P < 0.01). However, all electromyographic activities of the thigh and shank muscles (peak CMAP, mean and peak AUC) were significantly lower for the use of the EEGR than walking on the floor. CONCLUSION: Immediate strengthening of the knee flexors and extensors was induced after the 5-min EEGR training, despite reduced muscular use.

Effects of robot-(Morning Walk®) assisted gait training for patients after stroke: a randomized controlled trial.

OBJECTIVE:: To investigate the effects of Morning Walk®-assisted gait training for patients with stroke. DESIGN:: Prospective randomized controlled trial. SETTING:: Three hospital rehabilitation departments (two tertiary and one secondary). PATIENTS:: We enrolled 58 patients with hemiparesis following a first-time stroke within the preceding year and with Functional Ambulation Category scores ⩾2. INTERVENTION:: The patients were randomly assigned to one of two treatment groups: 30 minutes of training with Morning Walk®, a lower limb rehabilitation robot, plus 1 hour of conventional physiotherapy (Morning Walk® group; n = 28); or 1.5 hour of conventional physiotherapy (control group; n = 30). All received treatment five times per week for three weeks. MAIN OUTCOME MEASUREMENTS:: The primary outcomes were walking ability, assessed using the Functional Ambulation Category scale, and lower limb function, assessed using the Motricity Index-Lower. Secondary outcomes included the 10 Meter Walk Test, Modified Barthel Index, Rivermead Mobility Index, and Berg Balance Scale scores. RESULTS:: A total of 10 patients were lost to follow-up, leaving a cohort of 48 for the final analyses. After training, all outcome measures significantly improved in both groups. In Motricity Index-Lower of the affected limb, the Morning Walk® group (∆mean ± SD; 19.68 ± 14.06) showed greater improvement ( p = .034) than the control group (∆mean ± SD; 11.70 ± 10.65). And Berg Balance Scale scores improved more ( p = .047) in the Morning Walk® group (∆mean ± SD; 14.36 ± 9.01) than the control group (∆mean ± SD; 9.65 ± 8.14). CONCLUSION:: Compared with conventional physiotherapy alone, our results suggest that voluntary strength and balance of stroke patients with hemiparesis might be improved with Morning Walk®-assisted gait training combined with conventional physiotherapy.

Therapeutic time window for the effects of erythropoietin on astrogliosis and neurite outgrowth in an in vitro model of spinal cord injury.

BACKGROUND: The objective of this study was to investigate the underlying molecular mechanisms and the therapeutic time window for preventing astrogliosis with erythropoietin (EPO) treatment after in vitro modeled spinal cord injury (SCI). METHODS: Cultured rat spinal cord astrocytes were treated with kainate and scratching to generate an in vitro model of SCI. EPO (100U/mL or 300U/mL) was added immediately or 2, 4, or 8 hours after injury. Some cultures were also treated with AG490, an inhibitor of the EPO-EPO receptor (EpoR) pathway mediator Janus kinase 2 (JAK2). To evaluate neurite extension, rat embryonic spinal cord neurons were seeded onto astrocyte cultures and treated with EPO immediately after injury in the presence or absence of anti-EpoR antibody. RESULTS: EPO treatment at up to 8 hours after injury reduced the expression of axonal growth inhibiting molecules (glial fibrillary acidic protein, vimentin, and chondroitin sulfate proteoglycan), cytoskeletal regulatory proteins (Rho-associated protein kinase and ephephrin A4), and proinflammatory cytokines (tumor necrosis factor-alpha, transforming growth factor-beta, and phosphorylated-Smad3) in a dosedependent manner (P < .001). Most effects peaked with EPO treatment 2-4hours after injury. Additionally, EPO treatment up to 4 hours after injury promoted expression of the EpoR (>2-fold) and JAK2 (>3-fold) in a dose-dependent manner (P < .001), whereas co-treatment with AG490 precluded these effects (P < .001). EPO treatment up to 4hours after injury also enhanced axonal b-III tubulin-immunoreactivity (>12-fold), and this effect was precluded by co-treatment with an anti-EpoR antibody (P < .001). CONCLUSIONS: EPO treatment within 8 hours after injury reduced astrogliosis, and EPO treatment within 4 hours promoted neurite outgrowth. EPO therapy immediately after spinal cord injury may regulate glia to generate an environment permissive of axonal regeneration.

Enhanced Reality Showing Long-Lasting Analgesia after Total Knee Arthroplasty: Prospective, Randomized Clinical Trial.

To overcome the limitation of short-term efficacy of virtual reality (VR), an enhanced reality (ER) analgesia, (combination of the VR, real-time motion capture, mirror therapy [MT]) involving a high degree of patients' presence or embodiment was explored. Patients, who underwent unilateral total knee arthroplasty (TKA), received ER analgesia. The duration was 5 times a week, for 2 weeks for one group and 5 times a week, for 1 week in the other. Visual Analogue Scale (VAS) at rest and during movement, active knee range of motion (ROM) for flexion and extension were measured repeatedly. After screening 157 patients, 60 were included. Pre-interventional evaluation was performed at 6.7 days and ER was initiated at 12.4 days after surgery. Evaluation was performed at 5, 12, 33 days after the initiation of ER. Analgesia in the 2 week therapy group was effective until the third evaluation (p = 0.000), whereas in the other group, it was effective only until the second evaluation (p = 0.010). Improvement in ROM in the 2 week group was also maintained until the third evaluation (p = 0.037, p = 0.009). It could lay the foundations for the development of safe and long-lasting analgesic tools.

Feasibility and Neurobehavioral Changes of 10-Day Simulated Microgravity in Acute Ischemic Stroke Patients.

OBJECTIVE: The aim of the study was to investigate feasibility and functional changes of simulated microgravity with 6-degree head-down-tilt (HDT) bed rest in acute ischemic stroke. DESIGN: Patients without lesions in the cingulate cortex and/or cerebellum were enrolled. They underwent HDT for 30 minutes twice per day for 10 weekdays. Systolic blood pressure, diastolic blood pressure, and heart rate were measured before the HDT, immediately after, and also 30 minutes after the stop. Mini-Mental State Examination, Geriatric Depression Scale, Neurobehavioral Tests (i.e., span test, finger-tapping test, continuous performance test, and trail-making test) were conducted before and after the 10-day HDT. RESULTS: One male and four female patients (median age = 64.6 yrs [SD = 10.5 yrs]) were recruited. Changes in the finger-tapping test (57.80 [SD = 40.96 ] vs. 85.80 [SD = 0.46], P = 0.08) and in the digit span backward test (3.60 [SD = 1.14] vs. 1.42 [SD = 1.75], P = 0.07) were noticed. Few changes were found in other scales. No significant changes in systolic blood pressure, diastolic blood pressure, or heart rate were observed, and no adverse effects occurred. CONCLUSIONS: The 6-degree HDT revealed no adverse effects on the cardiovascular system, showing nonsignificant increment in the finger-tapping test (representative of motor speed and performance) and nonsignificant reduction in the digit backward span test (representative of spatial memory).

Velopharyngeal Incoordination Caused by Phenytoin-Induced Toxicity.

Phenytoin induces lymphoid proliferation, resulting in complications that can range from tissue hyperplasia to lymphoma. Some of the complications resolve spontaneously after drug discontinuation. This report describes for the first time a case of dysphagia with lack of velopharyngeal coordination and nasopharyngeal reflux combined with massive palatine tonsillar hypertrophy. The condition did not develop before phenytoin administration, was induced by phenytoin, and spontaneously resolved upon drug discontinuation. The patient was referred for a video-fluoroscopic swallowing study owing to a recurring nasal reflux of foods that had developed since phenytoin administration. The video-fluoroscopic swallowing study revealed incidentally that the large bilateral elongated masses extended downward into the larynx and disturbed velar elevation. This finding was confirmed by computed tomography of the neck, which showed that palatine tonsillar hypertrophy disturbed the laryngopharynx on both sides. The symptoms (sleep apnea and nasal reflux) and the abnormal imaging findings disappeared without surgery approximately 1 month after drug discontinuation. This case suggests that dysphagia related to phenytoin-induced lymphoid hypertrophy may be treated by phenytoin discontinuation followed by a sufficient amount of time to allow symptom resolution rather than by prompt surgery.

A Model of Glial Scarring Analogous to the Environment of a Traumatically Injured Spinal Cord Using Kainate.

OBJECTIVE: To develop an in vitro model analogous to the environment of traumatic spinal cord injury (SCI), the authors evaluated change of astrogliosis following treatments with kainate and/or scratch, and degree of neurite outgrowth after treatment with a kainate inhibitor. METHODS: Astrocytes were obtained from the rat spinal cord. Then, 99% of the cells were confirmed to be GFAP-positive astrocytes. For chemical injury, the cells were treated with kainate at different concentrations (10, 50 or 100 µM). For mechanical injury, two kinds of uniform scratches were made using a plastic pipette tip by removing strips of cells. For combined injury (S/K), scratch and kainate were provided. Cord neurons from rat embryos were plated onto culture plates immediately after the three kinds of injuries and some cultures were treated with a kainate inhibitor. RESULTS: Astro-gliosis (glial fibrillary acidic protein [GFAP], vimentin, chondroitin sulfate proteoglycan [CSPG], rho-associated protein kinase [ROCK], and ephrin type-A receptor 4 [EphA4]) was most prominent after treatment with 50 µM kainate and extensive scratch injury in terms of single arm (p<0.001) and in the S/K-induced injury model in view of single or combination (p<0.001). Neurite outgrowth in the seeded spinal cord (ß-III tubulin) was the least in the S/K-induced injury model (p<0.001) and this inhibition was reversed by the kainate inhibitor (p<0.001). CONCLUSION: The current in vitro model combining scratch and kainate induced glial scarring and inhibitory molecules and restricted neurite outgrowth very strongly than either the mechanically or chemically-induced injury model; hence, it may be a useful tool for research on SCI.

Intermittent Oroesophageal Tube Feeding via the Airway in Patients With Dysphagia.

OBJECTIVE: To investigate the feasibility of the use of the oropharyngeal airway (OPA) during intermittent oroesophageal tube (IOET) feeding. METHODS: Ten patients, who were evaluated using the videofluoroscopic swallowing study (VFSS), were enrolled. One patient withdrew from the study during the study period. Tube insertion time with and without OPA use was recorded in the same patients in a random order during the VFSS. Patients who could safely undergo IOET feeding were then randomly allocated to 2 groups (OPA and non-OPA). Satisfaction Questionnaire with Gastrostomy Feeding (SAGA-8) scores and pneumonia incidence were assessed on the 3rd and 10th day after the VFSS. Non-parametric analysis was used for statistical analyses. RESULTS: The IOET insertion time was significantly shorter in the OPA group than in the non-OPA group (17.72±5.79 vs. 25.41±10.41 seconds; p=0.017). Complications were not significantly different between the 2 groups (p=0.054). Furthermore, although there were no significant differences in the SAGA-8 scores (25.50±2.38 vs. 21.40±3.13; p=0.066), which reflect the patient/caregiver satisfaction and the ease of tube insertion, patients in the OPA group tended to be more satisfied with the feeding procedure. CONCLUSION: Although the small size of the study cohort is a limitation of our study, the use of the OPA appears to be beneficial during IOET feeding in patients with dysphagia.

Ataxic gait following total gastrectomy for gastric cancer.

A 58-year-old woman, who had undergone total gastrectomy for early gastric cancer 9 years previously, visited the outpatient clinic complaining of progressive difficulty in walking for 15 d. Laboratory examinations showed macrocytic anemia and a decreased serum vitamin B12 concentration and increased serum concentrations of folate, vitamin E and copper. Magnetic resonance imaging showed multifocal high signal intensities along the posterior column of the cervical and thoracic spinal cord. Treatment consisted of intramuscular injections of vitamin B12 for 7 d, which increased her serum level of vitamin B12 to normal. This was followed by weekly intramuscular injections of vitamin B12 for another 2 wk and oral administration of vitamin B12 three times per day. After comprehensive rehabilitation for 4 wk, she showed sufficient improvements in strength and ataxic gait, enabling her to return to her normal daily activities.

Preemptive Femoral Nerve Block Could Reduce the Rebound Pain After Periarticular Injection in Total Knee Arthroplasty.

BACKGROUND: We evaluated the effectiveness of postoperative pain management using intraoperative periarticular injection (PAI) and/or electromyography-guided preoperative femoral nerve block (FNB) in knees undergoing total knee arthroplasty (TKA). METHODS: This study included 90 patients (90 knees) who underwent primary TKA. Thirty patients received a single injection of electromyography-guided FNB, 30 received intraoperative PAI, and 30 received both. Pain at rest and while moving was evaluated by a visual analog scale (VAS) at 0, 4, 8, 24, and 48 hours. Postoperative range of motion, time to walking, amount of opioid consumption, and complications were analyzed. RESULTS: VAS immediately after surgery was significantly higher in the FNB group than in the PAI and combined groups, but did not differ significantly in the latter 2 groups. VAS after 4 and 8 hours showed similar results. VAS after 24 hours was significantly higher in the PAI than in the FNB and combined groups. After 48 hours, there were no differences among the 3 groups. Total opioid consumption was lower in the combined than in the FNB and PAI groups. Postoperative range of motion and time to walking were similar in the 3 groups. CONCLUSION: PAI was more effective than FNB during the early (0-8 hours) postoperative period after TKA. Patients treated with PAI, however, experienced rebound pain at 24 hours. The combination of PAI and FNB may provide greater postoperative pain management than either alone for the first 24 hours after TKA.

The effects of removable denture on swallowing.

OBJECTIVE: To investigate the relationship between removable dentures and swallowing and describe risks. METHODS: Twenty-four patients with removable dentures who were referred for videofluoroscopic swallowing study (VFSS) were enrolled. We evaluated the change of swallowing function using VFSS before and after the removal of the removable denture. The masticatory performance by Kazunori's method, sensation of oral cavity by Christian's method, underlying disease, and National Institutes of Health Stroke Scale for level of consciousness were collected. Functional dysphagia scales, including the oral transit time (OTT), pharyngeal transit time (PTT), percentage of oral residue, percentage of pharyngeal residue, oropharyngeal swallow efficiency (OPSE), and presence of aspiration were measured. RESULTS: Four patients dropped out and 20 patients were analyzed (stroke, 13 patients; pneumonia, 3 patients; and others, 4 patients). The mean age was 73.3±11.4 years. There were significant differences before and after the removal of the denture for the OTT. OTT was significantly less after the removal of the denture (8.87 vs. 4.38 seconds, p=0.01). OPSE increased remarkably after the removal of the denture, but without significance (18.24%/sec vs. 25.26%/sec, p=0.05). The OTT and OPSE, while donning a removable denture, were correlated with the masticatory performance (OTT, p=0.04; OPSE, p=0.003) and sensation of oral cavity (OTT, p=0.006; OPSE, p=0.007). CONCLUSION: A removable denture may have negative effects on swallowing, especially OTT and OPSE. These affects may be caused by impaired sensation of the oral cavity or masticatory performance induced by the removable denture.