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1.
Biochem Biophys Res Commun ; 663: 179-185, 2023 06 30.
Article in English | MEDLINE | ID: mdl-37121128

ABSTRACT

Docosahexaenoic acid (DHA), an omega-3 fatty acid, usually presents as a constituent of phospholipids in the cellular membrane. Lysophospholipid acyltransferase 3 (LPLAT3; AGPAT3) is the primary enzyme that incorporates DHA into phospholipids. LPLAT3-KO mice show male infertility and visual dysfunction accompanied by decreased phospholipids (PLs) containing DHA (PL-DHA) in the testis and retina, respectively. In this study, we evaluated the effect of diets consisting mainly of triacylglycerol-bound DHA (fish oil) and PL-bound DHA (salmon roe oil) on the amount of PL-DHA in a broad range of tissues and on reproductive functions. Both diets elevated phosphatidylcholines (PCs)-containing DHA in most tissues of wild type (WT) mice. Although LPLAT3-KO mice acquired a minimal amount of PC-DHA in the testes and sperm by eating either of the diets, reproductive function did not improve. The present study suggests that DHA-rich diets do not restore sufficient PL-DHA to improve male infertility in LPLAT3-KO mice. Alternatively, PL-DHA can be biosynthesized by LPLAT3 but not by external supplementation, which may be necessary for normal reproductive function.


Subject(s)
Fatty Acids, Omega-3 , Infertility, Male , Male , Mice , Animals , Humans , 1-Acylglycerophosphocholine O-Acyltransferase/genetics , Semen , Phospholipids , Diet , Docosahexaenoic Acids
2.
Mol Neurobiol ; 60(7): 3664-3677, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36918517

ABSTRACT

Dystrophin is the causative gene for Duchenne and Becker muscular dystrophy (DMD/BMD), and it produces full-length and short dystrophin, Dp427 and Dp71, respectively, in the brain. The existence of the different dystrophin molecular complexes has been known for a quarter century, so it is necessary to derive precise expression profiles of the molecular complexes in the brain to elucidate the mechanism of cognitive symptoms in DMD/BMD patients. In order to investigate the Dp71 expression profile in cerebellum, we employed Dp71-specific tag-insertion mice, which allowed for the specific detection of endogenous Dp71 in the immunohistochemical analysis and found its expressions in the glial cells, Bergmann glial (BG) cells, and astrocytes, whereas Dp427 was exclusively expressed in the inhibitory postsynapses within cerebellar Purkinje cells (PCs). Interestingly, we found different cell-type dependent dystrophin molecular complexes; i.e., glia-associated Dp71 was co-expressed with dystroglycan (DG) and dystrobrevinα, whereas synapse-associated Dp427 was co-expressed with DG and dystrobrevinß. Furthermore, we investigated the molecular relationship of Dp71 to the AQP4 water channel and the Kir4.1 potassium channel, and found biochemical associations of Dp71 with AQP4 and Kir4.1 in both the cerebellum and cerebrum. Immunohistochemical and cytochemical investigations revealed partial co-localizations of Dp71 with AQP4 and Kir4.1 in the glial cells, indicating Dp71 interactions with the channels in the BG cells and astrocytes. Taken together, different cell-types, glial cells and Purkinje neurons, in the cerebellum express different dystrophin molecular complexes, which may contribute to pathological and physiological processes through the regulation of the water/ion channel and inhibitory postsynapses.


Subject(s)
Aquaporins , Potassium Channels, Inwardly Rectifying , Mice , Animals , Dystrophin/metabolism , Purkinje Cells/metabolism , Synapses/metabolism , Cerebellum/metabolism , Neuroglia/metabolism , Aquaporins/metabolism , Potassium Channels, Inwardly Rectifying/metabolism
3.
Medicina (Kaunas) ; 60(1)2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38276035

ABSTRACT

Postoperative loss of correction is a concern in cases of distal radius fracture with bone loss after surgery. The purpose of this study was to evaluate the usefulness of a ß-tricalcium phosphate (ß-TCP) with unidirectional pore structure (Affinos®: Kuraray Co., Ltd, Tokyo, Japan) with internal fixation in patients with bone defects during the correction of distal radius fractures. Thirty-nine patients (40 radii) treated between 2016 and August 2020 were included in the study. There were 8 males and 31 females; the mean age was 70.9 (32-88). The mean postoperative observation period was 14.6 (3.4-24) months. The bone defect that occurred in the surgery was filled with Affinos® and fixed with a locking plate. Radial inclination (RI), volar tilt (VT), and ulnar variance (UV) were evaluated after the operation and at the final observation. The start of absorption and the completion of replacement to the host bone of Affinos® were also evaluated. There were no complications associated with grafts of Affinos®. The mean time of translucent findings around artificial bone was 1.85 (0.5-6) months, and that of complete resorption was 10.6 (1.5-16.5) months after surgery. The mean RI was 21.82° after surgery and 21.16° at final observation. The mean VT was 8.54° after surgery and 8.50° at final observation. The mean UV was -0.3 mm after surgery and 0.5 mm at final observation. Affinos® was resorbed relatively early, and host bone formation was observed. Filling of unidirectional pore structure ß-TCP with internal fixation showed favorable outcomes in the surgery of distal radius fractures with bone defects.


Subject(s)
Calcium Phosphates , Radius Fractures , Wrist Fractures , Male , Female , Humans , Aged , Japan , Porosity , Radiography , Radius Fractures/surgery , Radius Fractures/diagnostic imaging , Range of Motion, Articular , Bone Plates , Fracture Fixation, Internal , Treatment Outcome
4.
Cell Mol Life Sci ; 79(2): 109, 2022 Jan 30.
Article in English | MEDLINE | ID: mdl-35098363

ABSTRACT

Duchenne muscular dystrophy (DMD), the most severe form of dystrophinopathies, is a fatal X-linked recessive neuromuscular disorder characterized by progressive muscle degeneration and various extents of intellectual disabilities. Physiological and pathological roles of the responsible gene, dystrophin, in the brain remain elusive due to the presence of multiple dystrophin products, mainly full-length dystrophin, Dp427, and the short product, Dp71. In this study, we generated a Dp71-specific hemagglutinin (HA) peptide tag-insertion mice to enable specific detection of intrinsic Dp71 expression by anti-HA-tag antibodies. Immunohistochemical detections in the transgenic mice demonstrated Dp71 expression not only at the blood-brain barrier, where astrocytic endfeet surround the microvessels, but also at the inhibitory postsynapse of hippocampal dentate granule neurons. Interestingly, hippocampal cornu ammonis (CA)1 pyramidal neurons were negative for Dp71, although Dp427 detected by anti-dystrophin antibody was clearly present at the inhibitory postsynapse, suggesting cell-type dependent dystrophin expressions. Precise examination using the primary hippocampal culture validated exclusive localization of Dp71 at the inhibitory postsynaptic compartment but not at the excitatory synapse in neurons. We further performed interactome analysis and found that Dp71 formed distinct molecular complexes, i.e. synapse-associated Dp71 interacted with dystroglycan (Dg) and dystrobrevinß (Dtnb), whereas glia-associated Dp71 did with Dg and dystrobrevinα (Dtna). Thus, our data indicate that Dp71 and its binding partners are relevant to the inhibitory postsynaptic function of hippocampal granule neurons and the novel Dp71-transgenic mouse provides a valuable tool to understand precise physiological expressions and functions of Dp71 and its interaction proteins in vivo and in vitro.


Subject(s)
Dystroglycans/metabolism , Dystrophin-Associated Proteins/metabolism , Dystrophin/metabolism , Neuroglia/metabolism , Neuropeptides/metabolism , Synapses/metabolism , Animals , Blood-Brain Barrier/metabolism , Cells, Cultured , Dystroglycans/genetics , Dystrophin/genetics , Dystrophin-Associated Proteins/genetics , HEK293 Cells , Hippocampus/cytology , Hippocampus/metabolism , Humans , Mice, Transgenic , Microscopy, Confocal , Neurons/metabolism , Neuropeptides/genetics , Protein Binding
5.
Exp Anim ; 71(2): 214-223, 2022 May 20.
Article in English | MEDLINE | ID: mdl-34880157

ABSTRACT

Technique for Animal Knockout system by Electroporation (TAKE) is a simple and efficient method to generate genetically modified (GM) mice using the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) systems. To reinforce the versatility of electroporation used for gene editing in mice, the electric condition was optimized for vitrified-warmed mouse embryos, and applied to the fresh embryos from widely used inbred strains (C57BL/6NCr, BALB/cCrSlc, FVB/NJcl, and C3H/HeJJcl). The electric pulse settings (poring pulse: voltage, 150 V; pulse width, 1.0 ms; pulse interval, 50 ms; number of pulses, +4; transfer pulse: voltage, 20 V; pulse width, 50 ms; pulse interval, 50 ms; number of pulses, ±5) were optimal for vitrified-warmed mouse embryos, which could efficiently deliver the gRNA/Cas9 complex into the zygotes without zona pellucida thinning process and edit the target locus. These electric condition efficiently generated GM mice in widely used inbred mouse strains. In addition, electroporation using the electrode with a 5 mm gap could introduce more than 100 embryos within 5 min without specific pretreatment and sophisticated technical skills, such as microinjection, and exhibited a high developmental rate of embryos and genome-editing efficiency in the generated offspring, leading to the rapid and efficient generation of genome editing mice. The electric condition used in this study is highly versatile and can contribute to understanding human diseases and gene functions by generating GM mice more easily and efficiently.


Subject(s)
CRISPR-Cas Systems , Gene Editing , Animals , Gene Editing/methods , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Knockout
6.
PLoS One ; 14(10): e0224192, 2019.
Article in English | MEDLINE | ID: mdl-31626683

ABSTRACT

Whether or not depth perception influences brightness and/or lightness perception has been repeatedly discussed, and some studies have emphasized its importance. In addition, a small number of studies have empirically tested and shown the effect of depth inversion, such as seen in the Mach card illusion, on perceived lightness, and they interpreted such results in terms of lightness constancy. However, how perceived brightness changes contingent on depth inversion remains unexplained. Therefore, this study used the matching method to examine changes in brightness perception when depth inversion is observed. We created and used a three-dimensional (3D) concave object, composed of three sides made of card stock, which could be perceived as having two different shapes in 3D; it could be perceived as a horizontal concave object, corresponding to its actual physical structure, and as a convex standing object, similar in shape to a building. Participants observed this object as both a concave object and as a convex object, and judged the brightness of its surfaces during each observation. Our results show that the perception of the brightness of the object's surfaces clearly changed depending on the perception of depth. When the object was seen as convex, one part of the surface was perceived as darker than when the object was seen as concave, but the other part of the surface remained unchanged. Here we discuss the relationship between depth perception and brightness perception in terms of perceptual organization.


Subject(s)
Depth Perception , Form Perception , Visual Perception , Adult , Female , Humans , Male , Photic Stimulation , Young Adult
7.
J Ethnopharmacol ; 220: 1-8, 2018 Jun 28.
Article in English | MEDLINE | ID: mdl-29588201

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Bofutsushosan (fangfengtongshengsan in Chinese, BTS) is a formula in traditional Japanese Kampo medicine and Chinese medicine comprising 18 crude drugs that is used for treating obesity and metabolic syndrome. AIM OF THE STUDY: We evaluated the promotive effects of BTS on lipid and cholesterol elimination in mice. MATERIALS AND METHODS: Mice were reared with a high-fat diet containing boiled water extract of BTS for 30 days, and their biochemical parameters as well as the weight and lipid content of feces were measured. We also measured cholesterol uptake into Caco-2 cells cultured with or without BTS extract. RESULTS: The body weight and amounts of visceral fat and subcutaneous fat on day 28; the weights of epididymal, perirenal, and mesenteric fat; and the serum concentrations of triglyceride, glucose, and hemoglobin A1c on day 30 were significantly lower in the BTS extract-treated groups than in the control in a dose-dependent manner. The amounts of lipid and cholesterol in the feces collected from day 6-23 were significantly greater than in the control. When Caco-2 cells were incubated with BTS extract, the uptake of cholesterol into cells was significantly reduced in a concentration-dependent manner. Among the components of BTS, the methanol extracts of Platycodi Radix and Zingiberis Rhizoma contribute but the extracts of Ephedrae Herba and Rhei Rhizoma counteract the suppressive effect of BTS on cholesterol uptake into Caco-2 cells. CONCLUSIONS: BTS has beneficial effects on obesity and metabolic syndrome, and its mechanisms of action include the promotion of lipid elimination and the inhibition of cholesterol absorption in the intestine.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Lipid Metabolism/drug effects , Metabolic Syndrome/drug therapy , Obesity/drug therapy , Animals , Body Weight/drug effects , Caco-2 Cells , Cholesterol/metabolism , Diet, High-Fat/adverse effects , Feces , Humans , Intra-Abdominal Fat/metabolism , Male , Mice , Mice, Inbred C57BL
8.
Front Pharmacol ; 8: 805, 2017.
Article in English | MEDLINE | ID: mdl-29184495

ABSTRACT

Memory impairments in Alzheimer's disease (AD) occur due to degenerated axons and disrupted neural networks. Since only limited recovery is possible after the destruction of neural networks, preventing axonal degeneration during the early stages of disease progression is necessary to prevent AD. Polygalae Radix (roots of Polygala tenuifolia; PR) is a traditional herbal medicine used for sedation and amnesia. In this study, we aimed to clarify and analyze the preventive effects of PR against memory deficits in a transgenic AD mouse model, 5XFAD. 5XFAD mice demonstrated memory deficits at the age of 5 months. Thus, the water extract of Polygalae Radix (PR extract) was orally administered to 4-month-old 5XFAD mice that did not show signs of memory impairment. After consecutive administrations for 56 days, the PR extract prevented cognitive deficit and axon degeneration associated with the accumulation of amyloid ß (Aß) plaques in the perirhinal cortex of the 5XFAD mice. PR extract did not influence the formation of Aß plaques in the brain of the 5XFAD mice. In cultured neurons, the PR extract prevented axonal growth cone collapse and axonal atrophy induced by Aß. Additionally, it prevented Aß-induced endocytosis at the growth cone of cultured neurons. Our previous study reported that endocytosis inhibition was enough to prevent Aß-induced growth cone collapse, axonal degeneration, and memory impairments. Therefore, the PR extract possibly prevented axonal degeneration and memory impairment by inhibiting endocytosis. PR is the first preventive drug candidate for AD that inhibits endocytosis in neurons.

9.
Article in English | MEDLINE | ID: mdl-28808474

ABSTRACT

Streptococcus pneumoniae (S. pneumoniae) causes sinusitis. The general treatment of S. pneumonia sinusitis is by using antibiotics; however, one of their serious problems is the attenuation of their effect. Shin'iseihaito (Xinyiqingfeitang), a formula of Japanese traditional Kampo medicine, has been used for the treatment of sinusitis in Japan. In this study, we investigated the efficacy of Shin'iseihaito against S. pneumoniae-caused sinusitis in mice. Oral administration of Shin'iseihaito extract (SSHT) decreased the nasal colonization of S. pneumoniae in both prophylactic and therapeutic treatments, respectively, and the former was more effective than the latter. Histopathological analysis revealed that the epithelial tissue from S. pneumoniae-infected nose under SSHT treatment recovered the tissue destruction in comparison to infected nose. We also confirmed this result by scanning electron microscopic analysis. Murine peritoneal macrophages from SSHT-treated mice had significant phagocytic activity in comparison to those from untreated group. We also found that tumor necrosis factor-α, interleukin-1ß, interleukin-6, and monocyte chemotactic protein-1 levels and the migration of macrophages from S. pneumoniae-infected mice with the treatment with SSHT were increased compared to those from untreated group. Our data suggest that Shin'iseihaito may be useful for the treatment of S. pneumoniae-induced sinusitis.

10.
Exp Brain Res ; 235(10): 3013-3022, 2017 10.
Article in English | MEDLINE | ID: mdl-28721518

ABSTRACT

To perceive the external world stably, humans must integrate and manage continuous streams of information from various sensory modalities, in addition to drawing on past experiences and knowledge. In this study, we introduce a novel visuo-tactile illusion elicited by a visual-depth-reversal stimulus. The stimulus (a model of a building) was constructed so as to produce the same retinal image as an opaque cuboid, although it actually consisted of only three PVC boards forming a three-dimensional corner with the hollow inside facing the observer. Participants holding the model in their palm, therefore, observed, with both eyes or one eye, a building model that could be interpreted as either a concave or a convex cuboid. That is, tactile information from the contact surface contradicted the visual interpretation of a convex cuboid. Questionnaire and experimental results, however, showed that the building model was stably viewed as a standing cuboid, particularly under monocular observation. Participants also reported feeling a stable touch of the shrinking base of the apparently standing building model, thus ignoring the veridical contact surface. Given that the visual-tactile information was unchanged with or without the illusion and that the experimental task was tactile estimation, it is remarkable that participants failed to perceive actual touch based on the object's appearance. Results indicate the complexity and flexibility of visual-tactile integration processes. We also discuss the possibility that object knowledge influences visual-tactile integration.


Subject(s)
Illusions/physiology , Size Perception/physiology , Touch Perception/physiology , Visual Perception/physiology , Adult , Female , Humans , Male , Vision, Binocular/physiology , Vision, Monocular/physiology , Young Adult
11.
J Biomed Opt ; 21(8): 86009, 2016 08 01.
Article in English | MEDLINE | ID: mdl-27548771

ABSTRACT

We investigated the optical properties of a near-infrared (NIR) fluorochrome, di-ß-cyclodextrin-binding indocyanine derivative (TK-1), and its pharmacokinetic differences with indocyanine green (ICG). TK-1 was designed to have hydrophilic cyclodextrin molecules and, thus, for higher water solubility and smaller particle sizes than the plasma protein-bound ICG. We compared optical properties such as the absorption and fluorescence spectra, quantum yield, and photostability between both dyes in vitro. In addition, we subcutaneously injected a 1 mM solution of TK-1 or ICG into the hind footpad of rats and observed real-time NIR fluorescence intensities in their femoral veins and accompanying lymphatics at the exposed groin site to analyze the dye pharmacokinetics. These optical experiments demonstrated that TK-1 has high water solubility, a low self-aggregation tendency, and high optical and chemical stabilities. Our in vivo imaging showed that TK-1 was transported via peripheral venous flow and lymphatic flow, whereas ICG was drained only through lymphatics. The results of this study showed that lymphatic and venous transport can be differentially regulated and is most likely influenced primarily by particle size, and that TK-1 can enable real-time NIR fluorescence imaging of whole fluids and solute movement via both microvessels and lymphatics, which conventional ICG cannot achieve.


Subject(s)
Indocyanine Green/metabolism , Lymphatic Vessels/diagnostic imaging , Veins/diagnostic imaging , Animals , Fluorescence , Infrared Rays , Rats
12.
J Tradit Complement Med ; 6(3): 252-6, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27419089

ABSTRACT

Shin'iseihaito (Magnolia Flower Lung-Clearing Decoction; xin yí qing fèi tang), a formula of traditional Japanese kampo medicine ( rì ben hàn yi) and traditional Chinese medicine (TCM; zhong yi), has been used for the treatment of chronic sinusitis. The objective of this study was to evaluate the anti-allergic effect of shin'iseihaito on murine allergic reaction induced by nasal sensitization using ovalbumin (OVA) as an antigen. Extract of shin'iseihaito (SSHT) could reduce the eosinophil, serum IgE and interleukin (IL)-4 levels, while increased the interferon (IFN)-γ levels in allergic mouse. Furthermore, allergic-murine serum treated with SSHT could not activate passive cutaneous anaphylaxis (PCA) reaction in murine model. Thus, our study showed that SSHT may possess anti-allergic activity. We suggested that SSHT may contribute to inhibit the exacerbation of allergic reaction induced by nasal sensitization.

13.
Plast Reconstr Surg Glob Open ; 2(8): e196, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25426379

ABSTRACT

BACKGROUND: Secondary lymphedema is a common complication of cancer therapy, but options for treating lymphedema are essentially ineffective and limited. On the contrary, lymphangiogenic growth factors accelerate lymphangiogenesis and improve lymphedema. METHODS: Rat tail models of lymphedema were assigned to groups that received either daily topical basic fibroblast growth factor (bFGF) or saline (control) groups. Tail volume was measured, and the function of the lymphatic system was evaluated as the fluorescence intensity of indocyanine green every 3 days. The mRNA levels of vascular endothelial growth factor (VEGF)-C and VEGF-D and the protein levels of VEGF-C were evaluated at postoperative days (PODs) 7, 14, and 28. The subcutaneous and deep areas and lymphatic vessel density were histologically determined at PODs 7, 14, and 28. RESULTS: Tail volume was significantly larger in the control than in the bFGF group (P < 0.05). The intensity of indocyanine green fluorescence significantly decreased earlier in the bFGF group (P < 0.05). The mRNA and protein levels of VEGF-C were upregulated in the bFGF group at POD 14 (P < 0.01). Both subcutaneous and deep tissues gradually withered in both groups but more rapidly in the bFGF, than in the control group, reaching statistically significant differences in the subcutaneous and deeper areas at POD 14 (P < 0.05). Lymphatic vessel density was significantly higher in the bFGF than in the control group at POD 14 (P < 0.05). CONCLUSIONS: Topical bFGF induces lymphangiogenesis and improves lymphedema in the rat tail model.

14.
Pain ; 155(10): 1976-85, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25016218

ABSTRACT

Patients with complex regional pain syndrome (CRPS) often complain of abnormal sensations beyond the affected body part, but causes of this spread of musculoskeletal manifestations into contiguous areas remain unclear. In addition, immobilization can predispose to the development of CRPS. We examined functional, biochemical, and histological alterations in affected parts, including contiguous zones, using an animal model. Ten-week-old male Wistar rats were assigned to 5 groups: a normal group receiving no treatment, a sham operation group with surgical exploration, an immobilization group with surgical exploration plus internal knee joint immobilization, a surgical neuropathy group prepared by spinal nerve ligation (SNL) of the left L5 nerve root, and a surgical neuropathy+immobilization group with simultaneous SNL and knee joint immobilization. Mechanical allodynia and knee contracture were compared between groups, and tissues were harvested for histological assessments and gene and protein expression analyses. Neither surgical procedures nor immobilization induced detectable mechanical sensitivity. However, the addition of nerve injury resulted in detectable mechanical allodynia, and immobilization not only accelerated hyperalgesia, but also resulted in muscle fibrosis. Nerve growth factor (NGF) and other mediators of neurogenic inflammation were highly expressed not only in denervated muscles, but also in innervated muscles in contiguous areas, suggesting the spread of NGF production beyond the myotome of the injured nerve. Transforming growth factor ß was involved in the development of contracture in CRPS. These findings imply that neuroinflammatory components play major roles in the progression and dispersion of both sensory pathologies and pathologies that are exacerbated by immobilization.


Subject(s)
Causalgia/physiopathology , Hyperalgesia/physiopathology , Knee Joint/physiopathology , Animals , Causalgia/metabolism , Causalgia/pathology , Cytokines/metabolism , Disease Models, Animal , Hyperalgesia/metabolism , Hyperalgesia/pathology , Immobilization , Inflammation Mediators/metabolism , Knee Joint/metabolism , Knee Joint/pathology , Male , Nerve Growth Factor/metabolism , Pain Measurement , Pain Threshold/physiology , Physical Stimulation , Rats , Rats, Wistar
15.
Microsurgery ; 34(7): 568-75, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24889188

ABSTRACT

In this report, we present the results of investigation of the effects of prostaglandin E1 (PGE1) on entrapment neuropathy using a diabetic rat. A total of 60 male Sprague-Dawley rats were used in the study. The model of tibial nerve entrapment neuropathy associated with diabetes mellitus was created by streptozotocin-induced diabetic rats reared in cages with wire grid flooring. Rats were assigned to four groups: nondiabetic (n = 15), untreated diabetic (n = 15), diabetic treated with 30 µg/kg PGE1 (n = 15), and diabetic treated with 100 µg/kg PGE1 (n = 15). Pain tests and electrophysiological tests were performed at 0, 2, and 4 weeks, and assessments of gait, histology, and mRNA expression levels were performed at 4 weeks after initiating the PGE1 administration. In the 30 and 100 µg groups, the mechanical withdrawal thresholds measured by pain tests at 4 weeks (36.2 ± 16.4 g and 31.7 ± 15.3 g, respectively) and the motor conduction velocity (24.0 ± 0.2 m/s and 24.4 ± 0.3 m/s, respectively) were significantly higher than the untreated diabetic group (all P < 0.05) and lower than the nondiabetic group (all P < 0.001). In the gait analysis, the mean intensities in the 30 and 100 µg group (128.0 ± 20.1 a.u. and 109.0 ± 27.8 a.u., respectively) were significantly higher than the untreated diabetic (P < 0.01) and were not significantly different from the nondiabetic group (P = 0.81). Fiber density (P = 0.46) and fiber diameter (P = 0.15) did not show any significant differences. PGE1 significantly decreased nerve growth factor (NGF) mRNA and increased vascular endothelial growth factor (VEGF) mRNA in the tibial nerve (both P < 0.01). In conclusion, neurological deteriorations of diabetic rats were alleviated with PGE1, which is associated with inhibition of NGF and enhancement of VEGF at the entrapment site.


Subject(s)
Diabetic Neuropathies/physiopathology , Alprostadil , Animals , Diabetic Neuropathies/drug therapy , Gait , Hyperalgesia , Male , Nerve Compression Syndromes/drug therapy , Nerve Compression Syndromes/physiopathology , Rats, Sprague-Dawley
16.
PLoS One ; 8(2): e57721, 2013.
Article in English | MEDLINE | ID: mdl-23469058

ABSTRACT

Tumor necrosis factor-α plays important roles in immune system development, immune response regulation, and T-cell-mediated tissue injury. The present study assessed the net value of anti-tumor necrosis factor-α treatment in terms of functional recovery and inhibition of hypersensitivity after peripheral nerve crush injury. We created a right sciatic nerve crush injury model using a Sugita aneurysm clip. Animals were separated into 3 groups: the first group received only a skin incision; the second group received nerve crush injury and intraperitoneal vehicle injection; and the third group received nerve crush injury and intraperitoneal etanercept (6 mg/kg). Etanercept treatment improved recovery of motor nerve conduction velocity, muscle weight loss, and sciatic functional index. Plantar thermal and von Frey mechanical withdrawal thresholds recovered faster in the etanercept group than in the control group. On day 7 after crush injury, the numbers of ED-1-positive cells in crushed nerves of the control and etanercept groups were increased compared to that in the sham-treated group. After 21 days, ED-1-positive cells had nearly disappeared from the etanercept group. Etanercept reduced expression of interleukin-6 and monocyte chemotactic and activating factor-1 at the crushed sciatic nerve. These findings demonstrate the utility of etanercept, in terms of both enhancing functional recovery and suppressing hypersensitivity after nerve crush. Etanercept does not impede the onset or progression of Wallerian degeneration, but optimizes the involvement of macrophages and the secretion of inflammatory mediators.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Neuralgia/complications , Neuralgia/drug therapy , Peripheral Nerve Injuries/complications , Animals , Anti-Inflammatory Agents/therapeutic use , Axons/drug effects , Axons/physiology , Behavior, Animal/drug effects , Electrophysiological Phenomena/drug effects , Etanercept , Hyperalgesia/complications , Hyperalgesia/drug therapy , Immunoglobulin G/pharmacology , Immunoglobulin G/therapeutic use , Interleukin-6/biosynthesis , Interleukin-6/genetics , Macrophages/drug effects , Macrophages/metabolism , Muscle, Skeletal/drug effects , Muscle, Skeletal/pathology , Neuralgia/metabolism , Neuralgia/physiopathology , Organ Size/drug effects , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Receptors, Tumor Necrosis Factor/therapeutic use , Regeneration/drug effects , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/genetics , Wallerian Degeneration/complications
17.
Nagoya J Med Sci ; 75(3-4): 181-92, 2013 Aug.
Article in English | MEDLINE | ID: mdl-24640174

ABSTRACT

A small, light, ball-joint device called PinFix, which can instantly convert a simple percutaneous cross pin fracture fixation system into a rigid external fracture fixation system based on truss structure, was developed. The purpose of this study was to compare the mechanical load and breaking strength of this truss-structure-based fixation system to that of the conventionally used external cantilever structure-based fixation system. Three types of mechanical loading tests, axial, bending, and torsion, were performed on an artificial fractured bone treated with either three-dimensional PinFix fixation, two-dimensional PinFix fixation, or conventional external fixation. The three- and two-dimensional PinFix fixations showed significantly more stiffness than conventional fixation on all three loading tests. Finite element analysis was next performed to calculate the stress distribution of the parts in PinFix and in the conventional fixator. The applied stress to the rod and connectors of PinFix was much less than that of the conventional external fixator. These results reflected the physical characteristic of truss structure in which applied load is converted to pure tension or compression forces along the members of the PinFix. In conclusion, PinFix is a simple fracture fixation system that has a truss-structure with a high rigidity.


Subject(s)
External Fixators , Fracture Fixation/instrumentation , Fractures, Bone/surgery , Biomechanical Phenomena , Compressive Strength , Equipment Design , Finite Element Analysis , Fracture Fixation/methods , Humans , Materials Testing , Stress, Mechanical
18.
Acta Orthop Belg ; 78(5): 603-10, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23162956

ABSTRACT

A prospective multicenter clinical study evaluated, using the Hand20 and hand diagram, the disability, incidence, location, and predictive factors of residual wrist pain 18 months after volar locking plate fixation of distal radius fracture in 122 patients. The average Hand20 score and numeric rating scores for pain were 13.1 +/- 18.2 and 2.1 +/- 23, respectively. Fifty-seven patients indicated that they had pain. Among those patients, 25 had ulnar pain and 45 had radial pain. The incidence of radial-sided wrist pain was higher than ulnar-sided wrist pain. Logistic regression analysis showed that female sex and intra-articular fracture significantly correlated with radial-sided wrist pain. Volar locking plate fixation maintained anatomical reduction; however, a significant number of patients complained of residual wrist pain.


Subject(s)
Bone Plates , Intra-Articular Fractures/surgery , Radius Fractures/surgery , Adult , Aged , Aged, 80 and over , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Pain Measurement , Risk Factors
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