Efficacy of nonviral gene transfer of human hepatocyte growth factor (HGF) against ischemic-reperfusion nerve injury in rats.

Ischemic neuropathy is common in subjects with critical limb ischemia, frequently causing chronic neuropathic pain. However, neuropathic pain caused by ischemia is hard to control despite the restoration of an adequate blood flow. Here, we used a rat model of ischemic-reperfusion nerve injury (IRI) to investigate possible effects of hepatocyte growth factor (HGF) against ischemic neuropathy. Hemagglutinating virus of Japan (HVJ) liposomes containing plasmids encoded with HGF was delivered into the peripheral nervous system by retrograde axonal transport following its repeated injections into the tibialis anterior muscle in the right hindlimb. First HGF gene transfer was done immediately after IRI, and repeated at 1, 2 and 3 weeks later. Rats with IRI exhibited pronounced mechanical allodynia and thermal hyperalgesia, decreased blood flow and skin temperature, and lowered thresholds of plantar stimuli in the hind paw. These were all significantly improved by HGF gene transfer, as also were sciatic nerve conduction velocity and muscle action potential amplitudes. Histologically, HGF gene transfer resulted in a significant increase of endoneurial microvessels in sciatic and tibial nerves and promoted nerve regeneration which were confirmed by morphometric analysis. Neovascularization was observed in the contralateral side of peripheral nerves as well. In addition, IRI elevated mRNA levels of P2X3 and P2Y1 receptors, and transient receptor potential vanilloid receptor subtype 1 (TRPV1) in sciatic nerves, dorsal root ganglia and spinal cord, and these elevated levels were inhibited by HGF gene transfer. In conclusion, HGF gene transfer is a potent candidate for treatment of acute ischemic neuropathy caused by reperfusion injury, because of robust angiogenesis and enhanced nerve regeneration.

Recovery of Shoulder Rotational Muscle Strength After Arthroscopic Bankart Repair.

BACKGROUND: Shoulder rotational muscles act as dynamic stabilizers of the glenohumeral joint, and the recovery of muscle strength plays an important role in stabilizing the joint during postoperative rehabilitation. However, temporal changes in muscle strength after arthroscopic Bankart repair have not been clarified. PURPOSE: To better understand the temporal recovery of shoulder rotational muscle strength after arthroscopic Bankart repair. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Isokinetic concentric shoulder rotational muscle strength was evaluated in 50 patients who were diagnosed with recurrent dislocations of the glenohumeral joint and treated with arthroscopic Bankart repair. RESULTS: The mean peak torque/weight and total work were reduced significantly at 1.5 months after surgery (P < .0001) and returned to preoperative levels by 6 months for external rotation and 4.5 months for internal rotation. The contralateral peak torque ratios reached preoperative levels by 6 months after surgery. The ipsilateral peak torque ratios were reduced between 1.5 and 3 months after surgery and returned to preoperative levels at 6 months for external rotation and 4.5 months for internal rotation. CONCLUSION: Isokinetic shoulder rotational muscle strength after arthroscopic Bankart repair recovered to preoperative levels by 6 months for external rotation and 4.5 months for internal rotation.

Therapeutic effect of exendin-4, a long-acting analogue of glucagon-like peptide-1 receptor agonist, on nerve regeneration after the crush nerve injury.

Glucagon-like peptide-1 (GLP-1) is glucose-dependent insulinotropic hormone secreted from enteroendocrine L cells. Its long-acting analogue, exendin-4, is equipotent to GLP-1 and is used to treat type 2 diabetes mellitus. In addition, exendin-4 has effects on the central and peripheral nervous system. In this study, we administered repeated intraperitoneal (i.p.) injections of exendin-4 to examine whether exendin-4 is able to facilitate the recovery after the crush nerve injury. Exendin-4 injection was started immediately after crush injury and was repeated every day for subsequent 14 days. Rats subjected to sciatic nerve crush exhibited marked functional loss, electrophysiological dysfunction, and atrophy of the tibialis anterior muscle (TA). All these changes, except for the atrophy of TA, were improved significantly by the administration of exendin-4. Functional, electrophysiological, and morphological parameters indicated significant enhancement of nerve regeneration 4 weeks after nerve crush. These results suggest that exendin-4 is feasible for clinical application to treat peripheral nerve injury.

Axonal-transport-mediated gene transduction in the interior of rat bone.

BACKGROUND: Gene transduction has been considered advantageous for the sustained delivery of proteins to specific target tissues. However, in the case of hard tissues, such as bone, local gene delivery remains problematic owing to anatomical accessibility limitations of the target sites. METHODOLOGY/PRINCIPAL FINDINGS: Here, we evaluated the feasibility of exogenous gene transduction in the interior of bone via axonal transport following intramuscular administration of a nonviral vector. A high expression level of the transduced gene was achieved in the tibia ipsilateral to the injected tibialis anterior muscle, as well as in the ipsilateral sciatic nerve and dorsal root ganglia. In sciatic transection rats, the gene expression level was significantly lowered in bone. CONCLUSIONS/SIGNIFICANCE: These results suggest that axonal transport is critical for gene transduction. Our study may provide a basis for developing therapeutic methods for efficient gene delivery into hard tissues.

A rat model of Urtica ferox neuropathy.

A species of stinging nettle, Urtica ferox, is indigenous to New Zealand and has caused deaths in animals and humans. We previously reported a human case of acute polyneuropathy due to U. ferox stings. We developed an experimental animal model of U. ferox toxin neuropathy to determine its neurophysiological and pathological characteristics. Male Wistar rats received either normal saline or fluid from U. ferox trichomes by injection into the epineurium of the left sciatic nerve. Neurophysiological and histological studies were carried out 5, 14 and 28 days after administration. Toxin-injected rats developed paresis of the left leg by 14 days with recovery by 28 days. Compound muscle action potentials amplitudes on the left side of toxin-administered rats at day 14 were significantly reduced compared to the right uninjected side. Toxin-injected nerves at days 5 and 14 showed a reduction in the number of myelinated fibres compared to the saline-injected nerves and frequency distributions of myelinated fibres showed a shift to smaller fibres. U. ferox neurotoxin thus produced a transient neuropathy in rat peripheral nerves with neurophysiological and pathological features suggestive of axonopathy. The identity and mechanism of action of the toxin responsible for neuropathy are uncertain.

Bone mass assessment in naval crew members by quantitative ultrasound technique.

OBJECTIVE: Of necessity, naval crews live in confined spaces when on board warships, which may lead to decreased bone mass and to subsequent bone fractures. Therefore, we investigated the bone mass of crew members and the relationship between bone mass and lifestyle factors. METHODS: We selected 1510 crew members of the Japan Maritime Self-Defense Force. All were men between 18 and 58 years of age. We measured their bone mass by applying quantitative ultrasound (QUS) to the calcaneus. In addition, we reviewed daily milk consumption, levels of physical exercise, type of on-board job, fracture history, nutritional supplementation habits, and body mass index (BMI). RESULTS: Bone mass values were lower than the published mean values for Japanese men across the twenties to forties age groups. CONCLUSIONS: The factors found to be related to bone mass in this study were age, type of on-board job, exercise level, and milk consumption. Lifestyle factors are usually within our control. Our data suggest that moderate levels of regular exercise and milk consumption may maintain bone mass.

Nonviral retrograde gene transfer of human hepatocyte growth factor improves neuropathic pain-related phenomena in rats.

Peripheral nerve injury occasionally causes chronic neuropathic pain with hyperalgesia and allodynia. However, its treatment is difficult. Here, we used a chronic constriction injury (CCI) model in rats to investigate the effects on experimental neuropathic pain of the human hepatocyte growth factor (HGF) gene delivered into the nervous system by retrograde axonal transport following its repeated intramuscular transfer, using liposomes containing the hemagglutinating virus of Japan (HVJ). CCI (control) rats exhibited marked mechanical allodynia and thermal hyperalgesia, and decreased blood flow in sciatic nerve and hind paw. All these changes were significantly reversed by HGF gene transfer. In the sciatic nerve in HGF-treated rats, the size-frequency distributions for myelinated and unmyelinated axons each showed a rightward shift, the number of myelinated axons >5 microm in diameter was significantly increased, and the mean diameter of unmyelinated axons was significantly increased (versus CCI rats). Levels of P2X3, P2X4, and P2Y1 receptor mRNAs, and of interleukin-6 (IL-6) and activating transcription factor 3 (ATF3) mRNAs, were elevated in the ipsilateral dorsal root ganglia and/or sciatic nerve by CCI, and these levels were decreased by HGF gene transfer. These results may point toward a potential new treatment strategy for chronic neuropathic pain in this model.

The growth rate of the humerus: long-term follow-up of treatment of solitary bone cyst of the proximal humerus using cannulated screws: a case report.

Although the growth of the proximal epiphysis of the humerus is thought to contribute 80% of the total increase in humeral length, few articles have provided evidence for this. A 9-year-old boy with a pathological fracture at the humeral neck, owing to a solitary bone cyst, was treated by the decompression method using cannulated screws for 7.5 years. During this period, we measured the longitudinal humeral bone growth. The value obtained for the longitudinal growth contribution of the proximal humerus was 88% in this particular case.

Diagnostic efficacy of thin slice CT in osteoid osteoma of the thoracic spine: report of two cases.

We present a 24-year-old man and a 31-year-old woman who complained of persistent back pain with osteoid osteoma of the thoracic spine. Computed tomography (CT) revealed a round sclerotic lesion in the posterior element of the thoracic spine, although their plain radiographs showed no abnormalities except a slight scoliosis. The patients underwent total excision of the tumor via a posterior approach. They are currently asymptomatic with no recurrence of the lesion and have returned to full activity. The thin slice CT is one of the most important diagnostic tools for osteoid osteoma of the spine.