Comparison of the Effects of Botulinum Toxin Doses on Nerve Regeneration in Rats with Experimentally Induced Sciatic Nerve Injury.

This study was designed to compare the effects of various doses of botulinum neurotoxin A (BoNT/A) on nerve regeneration. Sixty-five six-week-old rats with sciatic nerve injury were randomly allocated to three experimental groups, a control group, and a sham group. The experimental groups received a single session of intraneural BoNT/A (3.5, 7.0, or 14 U/kg) injection immediately after nerve-crushing injury. The control group received normal intraneural saline injections after sciatic nerve injury. At three, six, and nine weeks after nerve damage, immunofluorescence staining, an ELISA, and toluidine blue staining was used to evaluate the regenerated nerves. Serial sciatic functional index analyses and electrophysiological tests were performed every week for nine weeks. A higher expression of GFAP, S100ß, GAP43, NF200, BDNF, and NGF was seen in the 3.5 U/kg and 7.0 U/kg BoNT/A groups. The average area and myelin thickness were significantly greater in the 3.5 U/kg and 7.0 U/kg BoNT/A groups. The sciatic functional index and compound muscle action potential amplitudes exhibited similar trends. These findings indicate that the 3.5 U/kg and 7.0 U/kg BoNT/A groups exhibited better nerve regeneration than the 14 U/kg BoNT/A and control group. As the 3.5 U/kg and the 7.0 U/kg BoNT/A groups exhibited no statistical difference, we recommend using 3.5 U/kg BoNT/A for its cost-effectiveness.

Improved anticancer efficacy of methyl pyropheophorbide-a-incorporated solid lipid nanoparticles in photodynamic therapy.

Photodynamic therapy (PDT) is a promising anticancer treatment because it is patient-friendly and non-invasive. Methyl pyropheophorbide-a (MPPa), one of the chlorin class photosensitizers, is a drug with poor aqueous solubility. The purpose of this study was to synthesize MPPa and develop MPPa-loaded solid lipid nanoparticles (SLNs) with improved solubility and PDT efficacy. The synthesized MPPa was confirmed 1H nuclear magnetic resonance (1H-NMR) spectroscopy and UV-Vis spectroscopy. MPPa was encapsulated in SLN via a hot homogenization with sonication. Particle characterization was performed using particle size and zeta potential measurements. The pharmacological effect of MPPa was evaluated using the 1,3-diphenylisobenzofuran (DPBF) assay and anti-cancer effect against HeLa and A549 cell lines. The particle size and zeta potential ranged from 231.37 to 424.07 nm and - 17.37 to - 24.20 mV, respectively. MPPa showed sustained release from MPPa-loaded SLNs. All formulations improved the photostability of MPPa. The DPBF assay showed that SLNs enhanced the 1O2 generation from MPPa. In the photocytotoxicity analysis, MPPa-loaded SLNs demonstrated cytotoxicity upon photoirradiation but not in the dark. The PDT efficacy of MPPa improved following its entrapment in SLNs. This observation suggests that MPPa-loaded SLNs are suitable for the enhanced permeability and retention effect. Together, these results demonstrate that the developed MPPa-loaded SLNs are promising candidates for cancer treatment using PDT.

Relation of exercise capacity to comprehensive physical functions in individuals with ischemic stroke.

BACKGROUND: Impaired motor control, balance, muscle strength, and respiratory function may affect the exercise capacity related to motor performance and activities in individuals with stroke. OBJECTIVE: To identify a physical parameter that the exercise capacity has the most significant relationship among physical parameters related to motor function, trunk control, balance, and motor performance and activities in individuals with ischemic stroke. METHODS: In total, 241 ischemic stroke patients were recruited in this retrospective study. The clinical measurements included the 6-minute walk test (6 MWT), Montreal cognitive assessment (MoCA), Fugl-Meyer assessment-lower extremity motor function (FMA-LE), trunk impairment scale (TIS), Berg balance scale (BBS), timed up and go test (TUG), 10-meter walk test (10 MWT), functional ambulation category (FAC), and functional independence measure (FIM). RESULTS: The 6 MWT was significantly correlated with the FMA-LE, BBS, TUG, 10 MWT, FAC, and FIM, indicating negative or positive moderate correlations. Additionally, the FMA-LE, TIS, BBS, TUG, 10 MWT, FAC, and FIM, excluding the 6 MWT, showed moderate to strong correlations with all of the other outcome measures, whereas the MoCA showed significant correlations only with the BBS and FIM. CONCLUSIONS: In this study, the exercise capacity has the most significant relationship with the TUG parameter in stroke patients. Additionally, we suggest that significant relationships between 6 MWT and other comprehensive physical functions measurements are closely related to walking ability in individuals with stroke.

Graphene Oxide Nanoparticles Having Long Wavelength Absorbing Chlorins for Highly-Enhanced Photodynamic Therapy with Reduced Dark Toxicity.

The long wavelength absorbing photosensitizer (PS) is important in allowing deeper penetration of near-infrared light into tumor tissue for photodynamic therapy (PDT). A suitable drug delivery vehicle is important to attain a sufficient concentration of PS at the tumor site. Presently, we developed graphene oxide (GO) nanoparticles containing long wavelength absorbing PS in the form of the chlorin derivative purpurin-18-N-ethylamine (maximum absorption wavelength [λmax] 707 nm). The GO-PS complexes comprised a delivery system in which PS was loaded by covalent and noncovalent bonding on the GO nanosheet. The two GO-PS complexes were fully characterized and compared concerning their synthesis, stability, cell viability, and dark toxicity. The GO-PS complexes produced significantly-enhanced PDT activity based on excellent drug delivery effect of GO compared with PS alone. In addition, the noncovalent GO-PS complex displayed higher photoactivity, corresponding with the pH-induced release of noncovalently-bound PS from the GO complex in the acidic environment of the cells. Furthermore, the noncovalently bound GO‒PS complex had no dark toxicity, as their highly organized structure prevented GO toxicity. We describe an excellent GO complex-based delivery system with significantly enhanced PDT with long wavelength absorbing PS, as well as reduced dark toxicity as a promising cancer treatment.

Tumor Size-Dependent Anticancer Efficacy of Chlorin Derivatives for Photodynamic Therapy.

Photodynamic therapy (PDT) with a suitable photosensitizer molecule is a promising anticancer treatment. We evaluated two chlorin molecules as potential photosensitizers, methyl pyropheophorbide a (MPPa) and N-methoxyl purpurinimide (NMPi), against A549 human lung adenocarcinoma cells in vitro as well as in A549 tumor-bearing mice in vivo. Cell viability, microscopy, and fluorescence-activated cell sorting (FACS) analyses were performed for the in vitro studies. MPPa and NMPi showed high phototoxicity in vitro, which was dependent on the concentration of the photosensitizers as well as the light irradiation time. In the animal study, tumor volume change, tumor surface alterations, and hematoxylin & eosin (H&E) and terminal deoxyribonucleotidyl transferse-mediated dUTP nick-end labelling (TUNEL) staining analyses were performed and compared between small (tumor volume of 50 mm³) size of initial tumors. MPPa and NMPi showed high anticancer efficacy against small-size tumors, indicating that early treatment with PDT is effective. Especially, repeated two times PDT with NMPi allowed almost complete eradication against small-size tumors. However, MPPa and NMPi were not effective against large-size tumors. In conclusion, the two chlorin derivatives, MPPa and NMPi, show good anticancer efficacy as promising photosensitizers for PDT in vitro and in vivo. Moreover, their activity in vivo was significantly dependent on the initial tumor size in mice, which confirms the importance of early cancer treatment.

Continuous Preparation of Hollow Polymeric Nanocapsules Using Self-Assembly and a Photo-Crosslinking Process of an Amphiphilic Block Copolymer.

This paper presents a fabrication method of hollow polymeric nanocapsules (HPNCs). The HPNCs were examined to reduce light trapping in an organic light emitting diodes (OLED) device by increasing the refractive index contrast. They were continuously fabricated by the sequential process of self-assembly and photo-crosslinking of an amphiphilic block copolymer of SBR-b-PEGMA, poly(styrene-r-butadiene)-b-poly(poly(ethylene glycol) methyl ether methacrylate) in a flow-focusing microfluidic device. After the photo-crosslinking process, the produced HPNCs have a higher resistance to water and organic solvents, which is applicable to the fabrication process of optical devices. The morphology and hollow structure of the produced nanocapsules were determined by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). Also, their size control was examined by varying the ratio of inlet flow rates and the morphological difference was studied by changing the polymer concentration. The size was measured by dynamic light scattering (DLS). The refractive index of the layer with and without the HPNCs was measured, and a lower refractive index was obtained in the HPNCs-dispersed layer. In future work, the light extraction efficiency of the HPNCs-dispersed OLED will be examined.

Diagnostic Value of Ganglion Cell-Inner Plexiform Layer Thickness in Glaucoma With Superior or Inferior Visual Hemifield Defects.

PURPOSE: To determine the diagnostic value of the ganglion cell-inner plexiform layer (GCIPL) thickness in glaucomatous eyes with superior or inferior visual hemifield defects. PATIENTS AND METHODS: Eighty-five patients with glaucoma (42 isolated superior hemifield defects and 43 isolated inferior hemifield defects) and 46 normal subjects were enrolled. All patients underwent Cirrus high-definition optical coherence tomography and standard automated perimetry. The area under the receiver operating characteristic curve (AUC) was calculated to determine the diagnostic ability of the GCIPL and peripapillary retinal nerve fiber layer (pRNFL). RESULTS: In the superior hemifield defect glaucoma group, the best parameters for discriminating normal eyes from glaucomatous eyes were the inferotemporal GCIPL thickness (0.942), inferior quadrant RNFL thickness (0.974), and 7 o'clock sector RNFL thickness (0.999). For diagnosing inferior hemifield defect glaucoma, the AUCs of all GCIPL parameters (0.331 to 0.702) were significantly lower than that of the superior quadrant RNFL thickness (0.866, P<0.05). CONCLUSIONS: The diagnostic ability of GCIPL parameters was similar to that of the pRNFL parameters in superior hemifield defect glaucoma. However, the diagnostic performance of the GCIPL parameters was significantly inferior to those of the pRNFL parameters in eyes with inferior hemifield defect glaucoma.

Activation timing patterns of the abdominal and leg muscles during the sit-to-stand movement in individuals with chronic hemiparetic stroke.

[Purpose] The purpose of this study was to determine the activation timing patterns of abdominal and leg muscles during the sit-to-stand movement in individuals with chronic hemiparetic stroke. [Subjects] Twenty adults with chronic hemiparetic stroke participated in this study. [Methods] Subjects performed five sit-to-stand movements at a self-selected velocity without using their hands. Surface electromyography was used to measure the reaction time of the bilateral transverse abdominis/internal oblique, rectus femoris, and tibialis anterior muscles during the sit-to-stand movement. [Results] There were significant differences in the reaction time between the affected and unaffected sides of the abdominal and leg muscles. Muscles on the unaffected side had faster reaction time than those on the affected side. Activation of the transverse abdominis/internal oblique muscles was delayed relative to activation of the tibialis anterior muscle during the sit-to-stand movement. [Conclusion] Our findings provide information that may aid clinicians in the examination and management of paretic muscles for transfers in individuals with chronic hemiparetic stroke.

Gold nanorod-photosensitizer complex obtained by layer-by-layer method for photodynamic/photothermal therapy in vitro.

Gold nanorod (GNR)-photosensitizer (PS) complex was prepared using anionic PS (sodium salt of purpurin-18) and cationic poly(allylamine hydrochloride) by layer-by-layer method, and was characterized by transmission electron microscopy, UV-vis spectroscopy, and zeta potential. The GNR-PS complex is a promising agent for synergistic (photothermal and photodynamic) therapy (PTT/PDT), in which PTT generates heat as well as operates the PS release which maximize the following PDT activity. The combined dual therapy, PTT followed by PDT, exhibits a significantly higher photocytotoxicity result based on synergistic effect of hyperthermia from PTT as well as singlet oxygen photogeneration from PDT.

Trunk muscles strength as a risk factor for nonspecific low back pain: a pilot study.

OBJECTIVE: To investigate the effects of asymptomatic back muscle weakness and spinal deformity on low back pain (LBP). METHODS: Sixty healthy subjects without LBP participated in this study. Radiography and an isokinetic/isometric dynamometer were used to respectively measure spinal scoliosis/lordosis and the strength of the trunk flexors/extensors. After 2 years, 48 subjects visited the hospital again and LBP episodes, its severity and the Korean version of the Oswestry Disability Index were assessed. Differences between the group with LBP and the group without LBP were evaluated and the association with LBP incidence and severity was determined. RESULTS: Sex, age, and trunk strength were significantly different in both group. Sex and age were significantly positive associated with LBP incidence. The isometric trunk flexor and extensor strength, maximum isokinetic trunk flexor and extensor strength were significantly and negatively associated with the LBP severity. The maximum isokinetic trunk extensor and maximum isometric trunk extensor strength was significantly negative associated with the LBP incidence. CONCLUSION: LBP incidence is associated with isometric and isokinetic trunk extensor weakness, whereas LBP severity is associated with age, sex, isokinetic trunk extensor and flexor weakness, isometric trunk extensor and flexor weakness.

The effects of changes of ankle strength and range of motion according to aging on balance.

OBJECTIVE: To investigate the changes of ankle strength and range of motion with aging and which of the ankle strength and range of motion are contributed to balance. METHODS: Sixty healthy people (24 men and 36 women) have undergone tests for ankle strength and range of motion, using Biodex System 4 Pro; a one-leg balance, including postural sway and stability index using a Balance System; in which data were collected in a self-reported Desmond fall risk questionnaire. RESULTS: Participants are classified into 3 groups by age (group 1, 20-40 years; group 2, 40-65 years; group 3, over 65 years). Stability index and postural sway is significantly increased with aging. Ankle plantarflexor strength and ankle eversion range of motion is significantly decreased with aging. Pearson's correlation revealed that ankle plantarflexor strength is significantly correlated with anterior/posterior sway, and ankle eversion range of motion is significantly correlated with medial/lateral sway in the aged group (over 65 years). CONCLUSION: Stability, ankle plantarflexor strength, and eversion range of motion is declined with aging. In addition, strength of ankle plantarflexor and eversion range of motion is significantly correlated with balance stability. Further studies are needed for programs to improve the strength of plantarflexor, and range of motion of eversion of the ankle are beneficial in improving balance, stability, and prevention of falling in the elderly.

Effects of the progressive walking-to-running technique on gait kinematics, ultrasound imaging, and motor function in spastic diplegic cerebral palsy - an experimenter-blind case study.

PURPOSE: The purpose of this study was to investigate the effects of the progressive walking-to-running technique (PWRT) in a child with spastic diplegic cerebral palsy (CP). DESIGN: A single case study with pre-/post-test. SUBJECT: An 11-year-old male, diagnosed with spastic diplegic CP. METHODS: The PWRT was provided for 60 minutes a day, 2 times a week for 12 weeks. Gross motor function tests, ultrasound imaging, hand-held dynamometer, and the Vicon motion capture system were used to determine motor function, muscle size and strength, and gait kinematics. RESULTS: Gross motor function was improved after the intervention. The size of right and left rectus femoris and tibialis anterior muscles in their contracted states were enhanced by 1.36, 5.09, 83.74, and 54.37%, respectively. Associated muscle strength was also increased by 58.8, 30.8, 28.0, and 118.2% in both rectus femoris and tibialis anterior muscles. Left stride length, walking speed, maximal flexion-extension angular excursion of the hip joint were enhanced by 95.7, 87.8, and 100.4% after PWRT, respectively. CONCLUSIONS: Our novel walking-running training paradigm was effective for restoring gait and running ability in a child with spastic diplegic CP.

Pure red cell aplasia caused by acute hepatitis a.

Pure red cell aplasia is characterized as a normocytic anemia associated with reticulocytopenia and the absence of erythroblasts in the bone marrow. Pure red cell aplasia can be induced by various causes such as thymoma, connective tissue disease, viral infection, lymphoma, and adverse drug reactions. There have been only a few reports of pure red cell aplasia associated with acute viral hepatitis A. In Korea, no case of pure red cell aplasia caused by acute hepatitis A has yet been reported. We recently experienced a case of acute viral hepatitis A complicated by pure red cell aplasia. The patient was successfully treated with corticosteroids. Here we report this case and review the literature.

The effects of etomidate on the contraction of pregnant rat uterine smooth muscle.

BACKGROUND: It has been reported that etomidate has the relaxant effects on vascular, tracheal, and non-pregnant uterine smooth muscle in vitro. The purpose of this study was to investigate the relaxant effects of etomidate on the contraction of the pregnant rat uterine smooth muscle. METHODS: Uterine muscle tissues were obtained from pregnant rats (n = 15). The uterine segments were mounted in organ baths filled with Krebs solution. After oxytocin-induced contractile activity had been established, etomidate in incremental concentrations (10(-7) to 10(-3) M) was added cumulatively to the bath, each administered 20 min apart, and resultant changes in contractile activity were continuously recorded. EC5 (effective concentration of 5% reduction), EC25, EC50, EC75, and EC95 on active tension were calculated using a probit model. RESULTS: Etomidate (10(-7) to 10(-3) M) induced dose-dependent decreases in amplitude and frequency of uterine contraction. The EC50 of etomidate on active tension were 5.91 x 10(-5) M. CONCLUSIONS: These results demonstrate that etomidate had inhibitory effects on pregnant rat uterine muscle at supraclinical concentration (5.91 x 10(-5) M).