No abstract available.
Fistula* ; Perilymph*

The aim of this study was to determine the effects of transplanted neural differentiated human mesenchymal stem cells (hMSCs) in a guinea pig model of auditory neuropathy. In this study, hMSCs were pretreated with a neural-induction protocol and transplanted into the scala tympani of the guinea pig cochlea 7 days after ouabain injury. A control model was made by injection of Hanks balanced salt solution alone into the scala tympani of the guinea pig cochlea 7 days after ouabain injury. We established the auditory neuropathy guinea pig model using 1 mM ouabain application to the round window niche. After application of ouabain to the round window niche, degeneration of most spiral ganglion neurons (SGNs) without the loss of hair cells within the organ of Corti and increasing the auditory brain responses (ABR) threshold were found. After transplantation of neural differentiated hMSCs, the number of SGNs was increased, and some of the SGNs expressed immunoreactivity with human nuclear antibody under confocal laser scanning microscopy. ABR results showed mild hearing recovery after transplantation. Based on an auditory neuropathy animal model, these findings suggest that it may be possible to replace degenerated SGNs by grafting stem cells into the scala tympani.
Animals ; Cardiotonic Agents/toxicity ; Cochlea/drug effects/pathology ; Disease Models, Animal ; Female ; Guinea Pigs ; Hearing Loss, Central/chemically induced/pathology/*therapy ; Humans ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/*cytology ; Neurogenesis ; Ouabain/toxicity ; Spiral Ganglion/pathology ; Transplantation, Heterologous

PURPOSE: Although the pudendal nerve terminal motor latency (PNTML) is normally used, there is no definite test that accurately reflects the function of the pudendal nerve. This study was undertaken to determine the relative accuracy of the various methods in measuring the function of the pudendal nerve. METHODS: Thirty one female patients (age 51.3+/-15.7) with a defecation disorder (constipation 20, fecal incontinence 11) were evaluated prospectively using a neurophysiologic test and balloon reflex manometry. Five parameters such as the right and left PNTML, anal mucosal electrosensitivity, latency and the amplitude of the rectoanal contractile reflex (RACR) were analyzed statistically for their correlation. RESULTS: There was no significant inter-test correlation among the parameters. However, the intra-test correlations between the parameters such as the right and left PNTML (r=0.9629, P<0.001)/latency and the RACR amplitude (r= -0.3770, P=0.0366) were found to be significant. CONCLUSION: The accuracy of these tests in evaluating the pudendal neuropathy could not be determined. However, because it can be assumed that a measurement of the RACR in addition to RNTML is technically accurate, it there will need to be more study for it to be used as an alternative to a PNTML measurement.
Defecation ; Fecal Incontinence ; Female ; Humans ; Manometry ; Prospective Studies ; Pudendal Nerve* ; Pudendal Neuralgia ; Reflex

Solitary rectal ulcer syndrome (SRUS) is a rare disorder characterized by rectal ulceration associated with typical histological features and disturbed defecatory behaviour from the passage of blood and mucus. While the cause of SRUS is yet unknown, the rectal prolapse and the paradoxical contraction of pelvic floor muscles have been considered the most important factors. The diagnosis is made usually on the basis of clinical symptoms, endoscopic appearance, and histology. Despite the terminology of SRUS, patients often show multiple lesions instead of just a single lesion or polypoid lesions instead of ulcerative lesions. Polypoid lesions, especially when combined with histologic findings of colitis cystica profunda, may sometimes be mis-interpreted as cancer. We report the case of one female patient with SRUS with out-growing polypoid lesion, which was misdiagnosed as invasive cancer on endoscopic biopsy.
Biopsy ; Colitis ; Diagnosis ; Female ; Humans ; Mucus ; Muscles ; Pelvic Floor ; Rectal Prolapse ; Ulcer*

BACKGROUND AND OBJECTIVES: This study was aimed to explore the effects of the 5-hydroxytryptamine (5-HT) on potassium currents in rat vestibular nuclear neurons. MATERIALS AND METHOD: Sprague-Dawley rats aged 14 to 16 days were anesthetized with ether and decapitated. After enzymatic digestion, the portion of medial vestibular nucleus neuron was removed by micropunching and gently agitated. The dissociated neurons were transferred into a recording chamber mounted on an inverted microscope and whole-cell membrane currents were recorded at room temperature by using standard patch-clamp techniques. RESULTS: When cells were held at -70 mV and depolarized from -60 mV to +40 mV in 10 mV increments, sustained outward potassium currents were evoked. The response of medial vestibular nuclear neurons to 5-HT was not uniform. The outward potassium currents were increased in 17 of 40 cells and decreased in 23 of 40 cells. 5-carboxamidotryptamine, 5-HT1 agonist increased the outward potassium currents of the medial vestibular nuclear cell. alpha-methyl-5-hydroxytryptamine, 5-HT2 agonist decreased the outward potassium currents of the medial vestibular nuclear cell. CONCLUSION: These results suggest that 5-HT affects the potassium currents of the cell with different effects according to the receptor subtype on which it acts.
Animals ; Digestion ; Dihydroergotamine ; Ether ; Membranes ; Neurons* ; Patch-Clamp Techniques ; Potassium Channels ; Potassium* ; Rats* ; Rats, Sprague-Dawley ; Serotonin 5-HT1 Receptor Agonists ; Serotonin 5-HT2 Receptor Agonists ; Serotonin* ; Vestibular Nuclei

BACKGROUND AND OBJECTIVES: Reports of neural differentiation of mesenchymal stem cells suggest the possibility that these cells may serve as a source for stem cell-based regenerative medicine to treat neurological disorders. The purpose of this study was to generate neural cells by differentiation of bone marrow-derived mesenchymal stem cells that isolated from human mastoid process. MATERIALS AND METHOD: Human mesenchymal stem cells (hMSCs) isolated from human mastoid process bone marrow during mastoidectomy for chronic otitis media surgery were characterized using fluorescence-activated cell sorter. Induction of neural differentiation from hMSCs was performed using mitogenic factors (basic fibroblast growth factor, epidermal growth factor, forskolin, isobutylmethylxanthine), and the characterization of differentiated hMSCs was performed using immunohistochemistry, RT-PCR and whole cell patch clamp technique. RESULTS: hMSCs from bone marrow of mastoid process were isolated and cultured. Differentiated cells from hMSCs expressed mRNA transcripts for neuron specific markers, TUJ1 and neurofilament proteins (NF-L, NF-M) as determined by RT-PCR, and neuron specific markers, suhc as NeuN, TUJ1, microtubule-associated protein-2 (MAP2) and glial fibrillary acidic protein by immunohistochemistry. These cells showed voltagedependent sodium currents that was blocked by tetrodotoxin. CONCLUSION: hMSCs, which were isolated from human mastoid process bone marrow, were one of the good sources for stem cell-based regenerative medicine to treat neurological disorders.
Bone Marrow ; Cell Differentiation ; Epidermal Growth Factor ; Fibroblast Growth Factors ; Forskolin ; Glial Fibrillary Acidic Protein ; Humans ; Immunohistochemistry ; Mastoid ; Mesenchymal Stromal Cells ; Nervous System Diseases ; Neurofilament Proteins ; Neurons ; Otitis Media ; Regenerative Medicine ; RNA, Messenger ; Sodium ; Temporal Bone

BACKGROUND AND OBJECTIVES: Inner hair cells (IHCs) of the organ of Corti change the external sound stimulus into the electrical signal and transmit this signal to the auditory cortex through afferent nerve fibers. Outer hair cells (OHCs) control the sound transmission function of IHC. OHCs respond with a somatic shape change to alterations in their membrane potential and this electromotile response is believed to provide mechanical feedback to the basilar membrane. Efferent nerve fibers which arise from the superior olivary nucleus in the midbrain and transmit to OHCs through medial olivocochlear bundle use acetylcholine (ACh) as a neurotransmitter. The cholinergic response of OHCs' alpha-9 nicotinic ACh receptor increase the Ca2+ influx, which control OHCs' electromotility by changing a membrane potential. In this research, the effect of ACh on the K+ current in OHC of guinea pig was studied, and the change of OHC length by ACh was studied. MATERIALS AND METHODS: Using the extracted OHC from a guinea pig potassium currents induced by ACh were recorded using the whole-cell patch clamp technique. The change of OHC length when ACh was applied was observed. RESULTS: 1) ACh increases voltage-dependent K+ current in OHC. 2) In the condition, which Ca2+-dependent K+ current is blocked by removing Ca2+ from intra-cellular fluid, ACh has no effect on K+ current in OHC. 3) ACh increases OHC length. CONCLUSION: These experimental results show that ACh from the medial olivocochlear efferent system regulates mobility of OHC, increases the Ca2+-dependent K+ currents in OHC.
Acetylcholine* ; Animals ; Auditory Cortex ; Basilar Membrane ; Calcium ; Guinea Pigs ; Hair* ; Membrane Potentials ; Mesencephalon ; Nerve Fibers ; Neurotransmitter Agents ; Olivary Nucleus ; Organ of Corti ; Potassium Channels ; Potassium*

BACKGROUND AND OBJECTIVES: Aminoglycoside antibiotics are widely used for the treatment of infection caused by Gram-negative bacilli, but prolonged exposure to it can cause permanent hearing loss since are reported to interrupt the function of medial olivocochlear bundle. This study was designed to explore the effects of several aminoglycoside antibiotics on acetylcholine, the neurotransmitter of medial olivocochlear bundle, and how it affects potassium currents of the guinea pig outer hair cells. MATERIALS AND METHOD: Using extracted outer hair cells from Guinea pigs, potassium currents induced by acetylcholine were recorded using the whole-cell patch clamp technique. The effects of different aminoglycoside antibiotics on the potassium current were also studied. RESULTS: Acetylcholine increased the potassium currents of outer hair cells. All of aminoglycoside antibiotics tested such as neomycin, streptomycin, gentamicin, and amikacin decreased the acetylcholine-induced potassium current. CONCLUSION: These experimental results suggest that aminoglycoside antibiotics have effects on the membrane potential of outer hair cells regulated by acetylcholine, which is thought to be one of the mechanisms of aminoglycoside ototoxicity.
Acetylcholine ; Amikacin ; Aminoglycosides ; Animals ; Anti-Bacterial Agents* ; Gentamicins ; Guinea Pigs ; Hair* ; Hearing Loss ; Membrane Potentials ; Neomycin ; Neurotransmitter Agents ; Potassium* ; Streptomycin

PURPOSE: Neoplastic development is a multistep process that involves the accumulation of genetic alterations in proto- oncogenes, DNA repair genes, and tumor suppressor genes. Molecular studies in carcinoma have shown the high frequency of loss of heterozygosity (LOH) in some specific chromosome regions, but LOH on the HCC chromosome has not been thoroughly investigated in Korea. LOH is considered to be phenotypes of genomic instability. We investigated the genetic instability and microsatellite alterations of chromosome 5, 8, 13 and 17 in hepatocellular carcinoma (HCC). METHODS: Microsatellite alteration analysis was performed using polymerase chain reaction with 12 polymorphic microsatellite markers (BAT26, D5S123, D5S346, D8S254, D8S261, D8S262, D13S153, D13S159, D13S171, D17S250, D17S796, TP53) in 37 surgically resected HCCs and their respective non-tumorous counterparts. Pairs of tumorous part and normal tissue in the same patient were compared and then the size of microsatellite markers was measured. RESULTS: MSI was detected in 3 samples and LOH was detected in 51 samples of 37 cases. Fractional allelic loss (FAL) was above 0.2 in 10 cases and was correlate with high grade of HCC. we could detect only 1 case of LOH in D8S254 marker, which was advanced cancer. Markers D5S123 and D5S346 showed 2 and 3 cases of LOH, respectively. Markers D8S262, D17S250 and D17S796 had LOH and were significantly correlated with tumor grade. CONCLUSION: According to the results, our data revealed that specific LOH, rather than MSI, may be involved in hepatocarcinogenesis. LOH may be a useful tool for following HCC patients because the high frequency of LOH correlates with poor prognosis of HCC.
Carcinoma, Hepatocellular* ; Chromosomes, Human, Pair 5* ; DNA Repair ; Genes, Tumor Suppressor ; Genomic Instability ; Humans ; Korea ; Loss of Heterozygosity ; Microsatellite Instability ; Microsatellite Repeats* ; Oncogenes ; Phenotype ; Polymerase Chain Reaction ; Prognosis

PURPOSE: Many reports have shown that the efficacy of intravesical therapy for bladder cancer is, in part, limited by the poor penetration of drugs into the urothelium. The present study evaluated the effect of glyceryl monooleate (GMO) on the delivery and penetration of paclitaxel into the bladder of rabbits, when given as an intravesical dose. MATERIALS AND METHODS: The urine, plasma, and tissue pharmacokinetics were determined in rabbits treated for 120min with paclitaxel (500g/20ml) by an intravesical instillation. Two formulation of GMO/paclitaxel were evaluated, according to the proportion of water, 15% and 30%, with Taxol was used as a control. The animals were observed for clinical signs of toxicity, and necropsy performed. RESULTS: At 120min post-instillation, the bladders were emptied and excised. The urine paclitaxel concentrations were decreased by 39.6 and 41.2% in the two experimental groups, and by 25.2% in the control group. The paclitaxel concentrations in the urothelium were 53 and 56% of the urine concentration in the two experimental groups, respectively, but by only 11% in the control group. The concentration then declined exponentially in the underlying capillary perfused tissues, reaching equilibrium at a depth of 1,400-1,700um. The plasma concentrations were extremely low compared with those in the urine and bladder tissues, and were not associated with clinical toxicity. CONCLUSIONS: These results indicate that GMO improves the delivery of paclitaxel and increases the concentration in the bladder tissue. These results suggest that the intravesical delivery of GMO/paclitaxel/water provide a significant bladder tissue targeting advantage, and that paclitaxel represents a viable candidate drug for intravesical bladder cancer therapy.
Administration, Intravesical* ; Animals ; Capillaries ; Drug Delivery Systems* ; Paclitaxel* ; Pharmacokinetics ; Plasma ; Rabbits* ; Urinary Bladder ; Urinary Bladder Neoplasms ; Urothelium ; Water