Long-term effects of muscle-derived protein with molecular mass of 77 kDa (MDP77) on nerve regeneration

The long-term effects of the 77-kDa muscle-derived protein (MDP77) on motor and sensory nerve regeneration were examined in vivo. Fourteen-millimeter bridge grafts of the right sciatic nerve of SD rats were carried out with silicone tubes containing a solution of type I collagen together with 0, 5, 10, or 20 microg/ml recombinant human MDP77 (N = 10 in each group). Recovery of motor and sensory function was evaluated monthly by the maximal toe-spread index (TSI) and hot-plate test, respectively, for 6 months after the operation. Electrophysiology (nerve conduction velocity), histology (diameter and total number of the regenerated myelinated axons in the tube), and immunohistochemistry (total number of Schwann cells in the tube), as well as measurement of soleus muscle weight, were also performed at this time. Motor, but not sensory, function recovered rapidly in the MDP77-treated groups in a dose-dependent manner. Electrophysiological measurements and the ratio of soleus muscle weight corroborated the positive effects of MDP77 on motor nerve regeneration, but no facilitation of sensory nerve recovery was observed. Furthermore, histological and immunohistochemical evaluations suggested that MDP77 treatment accelerates Schwann cell migration, followed by enhanced maturation of regenerating axons, resulting in functional recovery of both the nerves and the atrophied, denervated muscle.     

Imaging of intraneural edema by using gadolinium-enhanced MR imaging: experimental compression injury

BACKGROUND AND PURPOSE: Compressive and entrapment neuropathies are diseases frequently observed on routine clinical examination. A definitive diagnosis based on clinical symptoms and neurologic findings alone is difficult in many cases, however, and electrophysiologic measurement is used as a supplementary diagnostic method. In this study, we examined to use protein tracers (Evans blue albumin or horseradish peroxidase) and gadolinium-enhanced MR imaging to determine the changes of blood-nerve barrier permeability in compressive neuropathies. METHODS: In dogs, the median nerve was compressed for 1 hour by using five kinds of clips with various strengths (7.5-90-g force). After clip removal, the combined tracers of Evans blue albumin and gadolinium or horseradish peroxidase was administered intravenously as a tracer. After the animals were euthenized, we compared gadolinium-enhanced MR images with Evans blue albumin distribution in the nerve under fluorescence microscopy. The horseradish peroxidase-injected specimens were observed by transmission electron microscopy. RESULTS: On enhanced MR imaging, intraneural enhancement was caused by 60- and 90-g-force compression after 1 hour. Marked extravasation of protein tracers in the nerve occurred where there was compression by 60- and 90-g-force compression, and capillaries in the nerve showed the opening of tight junction and an increase of vesicular transport under the electron microscopy. This situation indicated breakdown of the blood-nerve barrier, with consequent edema formation and was seen as enhancement on MR imaging. CONCLUSION: Gadolinium-enhanced MR imaging can detect morphologic and functional changes of blood-nerve barrier in the nerve induced by mechanical compression.     

Relation between vertical orientation and stability of acetabular component in the dysplastic hip simulated by nonlinear three-dimensional finite element method

In acetabular dysplasia, more vertical orientation of the acetabular component is often used to minimize the superolateral bone grafting. This study was designed to determine the effects of vertical orientation of the cup on the stability and polyethylene wear of the acetabular component in uncemented total hip arthroplasty (THA). Three-dimensional finite element models of the hemipelvis with dysplastic acetabulum were developed. Metal-backed hemispherical cups were placed in the true acetabulum with abduction angles of 35, 45, 55, and 65 degrees. It was found that more vertical orientation of the cup was associated with larger relative motion of the metal shell between the acetabulum and metal shell. Furthermore, tilting and torsional shear stresses in the model of the cup abduction angle of 65 degrees were found to be 1.7 times larger than that in the model with 35 degrees at the bone-metal shell interface. More vertically oriented cups caused larger contact stresses at the articulating surfaces of the polyethylene liners. The results suggest that the abduction angle of the acetabular component significantly influences cup loosening and polyethylene wear in THA.     

Thyroid blockade during a radiation emergency in iodine-rich areas: effect of a stable-iodine dosage

We examined the effect of stable iodine on thyroid gland blockade in patients with hyperthyroidism in order to make a preliminary evaluation of the appropriate dose of iodine prophylaxis in the event of a radiation emergency in Japan in which radioiodine is released to the environment. Eight patients were orally given single doses of 50 mg or 100 mg of potassium iodide, which contained 38 mg and 76 mg of iodide, respectively. Both doses significantly suppressed a thyroid uptake of (123)I for 24 h (p = 0.03). The protective effects at 24 h were 73.3% and 79.5%, respectively. No side effects were observed during the trial. The present study demonstrates that a single oral administration of 38 mg of iodide produces a thyroid-blocking effect equivalent to that of 76 mg of iodide, suggesting that a reevaluation of the stable iodine dosage during radiation emergencies in iodine-rich areas such as Japan is warranted.     

Developmental toxicity of estrogenic chemicals on rodents and other species

ABSTRACT  Antenatal sex-hormone exposure induces lesions in mouse reproductive organs, which are similar to those in humans exposed in utero to a synthetic estrogen, diethylstilbestrol. The developing organisms including rodents, fish and amphibians are particularly sensitive to exposure to estrogenic chemicals during a critical window. Exposure to estrogens during the critical period induces long-term changes in reproductive as well as non-reproductive organs, including persistent molecular alterations. The antenatal mouse model can be utilized as an indicator of possible long-term consequences of exposure to exogenous estrogenic compounds including possible environmental endocrine disrupters. Many chemicals released into the environment potentially disrupt the endocrine system in wildlife and humans, some of which exhibit estrogenic activity by binding to the estrogen receptors. Estrogen responsive genes, therefore, need to be identified to understand the molecular basis of estrogenic actions. In order to understand molecular mechanisms of estrogenic chemicals on developing organisms, we are identifying estrogen responsive genes using cDNA microarray, quantitative RT-PCR, and differential display methods, and genes related to the estrogen-independent vaginal changes in mice induced by estrogens during the critical window. In this review, discussion of our own findings related to endocrine distuptor issue will be provided.     

Potentiation of proopiomelanocortin gene expression in cultured pituitary cells by benzodiazepines

BACKGROUND: Benzodiazepines are frequently used not only as a part of general anesthesia but also for the purpose of sedation during regional anesthesia. Effects of these drugs on the hypothalamic-pituitary-adrenal axis activity have been studied, but are still controversial. It is not known whether benzodiazepines affect expression of proopiomelanocortin, precursor protein of adrenocorticotropic hormone and related peptides. METHODS: AtT20PL cell line, a clone of AtT20/D16v mouse corticotroph tumor cells stably transfected with approximately 0.7 kilobases (kb) of the rat proopiomelanocortin 5' promoter-luciferase fusion gene, was used. In the presence or absence of diazepam or midazolam, cells were stimulated by corticotropin-releasing hormone (CRH) or forskolin. Proopiomelanocortin gene expression was estimated by measurement of luciferase activity. Furthermore, to study the mechanism of benzodiazepine effects, cyclic adenosine 3',5'-monophosphate (cyclic AMP) efflux was measured by enzyme immunoassay. RESULTS: Diazepam and midazolam dose-dependently increased the proopiomelanocortin gene expression induced by CRH or forskolin. The potentiating effect was not affected by benzodiazepine receptor antagonists flumazenil and PK11195, but was abolished by a cyclic AMP-dependent protein kinase inhibitor H89. Cyclic AMP efflux induced by CRH or forskolin was also enhanced by diazepam and midazolam. In the presence of isobutylmethylxanthine, a nonspecific phosphodiesterase inhibitor, potentiation of proopiomelanocortin gene expression and enhancement of cyclic AMP efflux by benzodiazepines were not observed. CONCLUSIONS: Benzodiazepines potentiate the effect of CRH or forskolin on proopiomelanocortin gene expression. The potentiating effect is not mediated by the benzodiazepine receptors, but its mechanism probably involves inhibition of phosphodiesterase.     

A case of thoracic disc herniation with sudden onset paraplegia on toilet straining: case report

Thoracic disc herniation is less common rather than cervical or lumbar herniation. Cases of sudden onset without trauma are especially rare. Generally, the neurological onset of disc herniation is caused by mechanical cord compression due to a protruded disc, and its onset is usually gradual. Ischemia is also considered as a factor of neurological onset. We report a case of a 78-year-old male with sudden paraplegia while straining at the toilet. T2 weighted MR image on admission showed mild disc protrusion at the level of Th8-9 and intramedullary high signal intensity below the Th8-9 level. We speculate that Valsalva-like maneuver had led to the congestion of vertebral venous plexus or compression of the anterior spinal artery, and spinal ischemia occurred.     

Antiviral effect of sulfated sialyl lipid against a clinical strain of adenovirus

PURPOSE: Currently, there is no antiviral drug for adenovirus(AdV). We have reported that sulfated sialyl lipid(NMSO) 3, a NMSO, has an antiviral effect against AdV prototype strains. We evaluated the antiviral inhibitory effect and the mechanism of NMSO 3 against AdV strains from patients with conjunctivitis in vitro. METHODS: Viruses used for the experiment were clinically isolated AdV type 3(AdV 3), AdV type 4(AdV 4), type 8(ADV 8), AdV type 19(AdV 19), and type 37(AdV 37). We examined three antiviral agents, i.e., NMSO 3, cidofovir(HPMPC), and zalcitabine(ddC). 50% effective concentration(EC50), 50% cytotoxic concentration(CC50), and selectivity index(SI) of compounds were determined for AdV infection in HEp-2 cells using 3-(4,5-dimetyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) methods. We also evaluated the anti-AdV activity of NMSO 3 when it was added during the stage of virus adsorption. RESULTS: NMSO 3, HPMPC, and ddC showed an inhibitory effect against all five AdV clinical strains. The EC50 values of NMSO3 were lower than those of HPMPC and ddC. NMSO 3 exhibited minimal cytotoxicity. NMSO 3 inhibited AdV infection only when it was added during the stage of virus adsorption. CONCLUSIONS: NMSO 3 inhibited the replication of all clinical AdV serotypes tested. NMSO 3 was the most potent and selective anti-AdV compound. The mechanism of anti-AdV activity by NMSO 3 was inhibition of viral adsorption to cells.     

(+)-Nantenine isolated from Nandina domestica Thunb. inhibits adrenergic pressor responses in pithed rats

The effects of (+)-nantenine on various pressor responses, recently reported exerting competitive antagonistic activity at the alpha1-adrenoceptor/5-hydroxytryptamine (5-HT)2A receptor, were examined in vivo. (+)-Nantenine (0.03-3 mg/kg) caused a dose-dependent inhibition of the pressor response to phenylephrine (alpha1-adrenoceptor agonist) or 5-HT (5-HT receptor agonist) in both anesthetized and pithed rats. The pressor response to UK 14304 (5-Bromo-N-[2-imidazolin-2-yl]-6-quinoxalinamine) (an alpha2-adrenoceptor agonist) was inhibited by (+)-nantenine (0.003-3 mg/kg) in pithed rats in a dose-dependent manner without affecting the angiotensin II-induced pressor response in anesthetized rats. The pressor response to sympathetic nerve stimulation was also inhibited by (+)-nantenine (0.3-3 mg/kg) in a dose-dependent manner. (+)-Nantenine (3 mg/kg) facilitated the norepinephrine release induced by sympathetic nerve stimulation in pithed rats. In the guinea pig vas deferens, the initial component of contractions induced by electrical field stimulation was enhanced by (+)-nantenine (1-30 microM) in a concentration-dependent manner, while the later component was inhibited by it. These data suggest that (+)-nantenine has antagonistic activities on alpha1-adrenoceptors, alpha2-adrenoceptors and 5-HT2A receptors in pithed rats.     

Modified Gluteus Maximus V-Y Advancement Flap for Reconstruction of Perineal Defects After Resection of Intrapelvic Recurrent Rectal Cancer: Report of a Case

Technical advances in myocutaneous flap preparation have resulted in primary reconstruction now being generally indicated for malignant tumors extensively infiltrating the pelvic cavity and perineum. Pelvic tumor resection can dramatically improve the health-related quality of life (QOL) of patients with locally recurrent rectal cancer complicated by infection and pain. However, the removal of a wide area of perineum by these two procedures often leaves a large dead space. A gluteal thigh muscle, rectus abdominis muscle, or pedicle myocutaneous flap is usually made to reconstruct such extensive perineal defects. The subject of this case report was a 76-year-old woman with recurrent rectal cancer in the pelvis after abdominoperineal resection. The large pelvic tumor, which was causing severe pain, was resected and the extensive perineal defects were reconstructed using a modified maximus V-Y advancement flap. The operating time was approximately 30min, and the pain after surgery was much less severe. Moreover, she could walk the day after surgery and returned to normal daily life without requiring prolonged bed rest. No infection developed in the intrapelvic dead space postoperatively. This technique proved very useful for improving the patient's QOL.