Compressive stress induces collective migration through cytoskeletal remodelling in nasal polyp epithelium.

BACKGROUND: Nasal polyps in the nasal cavity and mucous discharge inside the maxillary sinus exhibit compressive stress on the nasal mucosal epithelium. However, there have been only a few studies on how compressive stress impacts the human nasal mucosal epithelium. METHODOLOGY: We investigated the effect of compressive stress on collective migration, junctional proteins, transepithelial electri- cal resistance, epithelial permeability, and gene expression in well-differentiated normal human nasal epithelial (NHNE) cells and human nasal polyp epithelial (HNPE) cells. RESULTS: NHNE cells barely showed collective migration at compressive stress up to 150 mmH20. However, HNPE cells showed much greater degree of collective migration at a lower compressive stress of 100 mmH20. The cell migration of HNPE cells sub- jected to 100 mmH2O compression was significantly decreased at day 3 and was recovered to the status prior to the compressive stress by day 7, indicating that HNPE cells are relatively more sensitive to mechanical pressure than NHNE cells. Compressive stress also increased transepithelial electrical resistance and decreased epithelial permeability, indicating that the compressive stress disturbed the structural organization rather than physical interactions between cells. In addition, we found that compressive stress induced gene expressions relevant to airway inflammation and tissue remodelling in HNPE cells. CONCLUSION: Taken together, these findings demonstrate that compressive stress on nasal polyp epithelium is capable of inducing collective migration and induce increased expression of genes related to airway inflammation, innate immunity, and polyp remo- delling, even in the absence of inflammatory mediators.

A NWB-based dataset and processing pipeline of human single-neuron activity during a declarative memory task.

A challenge for data sharing in systems neuroscience is the multitude of different data formats used. Neurodata Without Borders: Neurophysiology 2.0 (NWB:N) has emerged as a standardized data format for the storage of cellular-level data together with meta-data, stimulus information, and behavior. A key next step to facilitate NWB:N adoption is to provide easy to use processing pipelines to import/export data from/to NWB:N. Here, we present a NWB-formatted dataset of 1863 single neurons recorded from the medial temporal lobes of 59 human subjects undergoing intracranial monitoring while they performed a recognition memory task. We provide code to analyze and export/import stimuli, behavior, and electrophysiological recordings to/from NWB in both MATLAB and Python. The data files are NWB:N compliant, which affords interoperability between programming languages and operating systems. This combined data and code release is a case study for how to utilize NWB:N for human single-neuron recordings and enables easy re-use of this hard-to-obtain data for both teaching and research on the mechanisms of human memory.

Successful intervention to mitigate an acetylcholinesterase inhibitor-induced rhinorrhea prescribing cascade: a case report.

WHAT IS KNOWN AND OBJECTIVE: A prescribing cascade if often treated by discontinuing both medications. We describe an intervention to mitigate a prescribing cascade while continuing a clinically necessary medication without negatively impacting the patient. CASE SUMMARY: A 77-year-old women experienced probable acetylcholinesterase inhibitor-induced rhinorrhea and subsequently self-medicated with diphenhydramine which lead to worsening cognitive function. We reduced the dose of the acetylcholinesterase inhibitor and discontinued the diphenhydramine. The symptoms of rhinorrhea were subsequently reduced without negatively impacting cognition. WHAT IS NEW AND CONCLUSION: This was the first published prescribing cascade intervention that did not require discontinuation of both medications, which may be emulated in future prescribing cascade cases.

Systems genetic and pharmacological analysis identifies candidate genes underlying mechanosensation in the von Frey test.

Mechanical sensitivity is commonly affected in chronic pain and other neurological disorders. To discover mechanisms of individual differences in punctate mechanosensation, we performed quantitative trait locus (QTL) mapping of the response to von Frey monofilament stimulation in BXD recombinant inbred (BXD) mice. Significant loci were detected on mouse chromosome (Chr) 5 and 15, indicating the location of underlying polymorphisms that cause heritable variation in von Frey response. Convergent evidence from public gene expression data implicates candidate genes within the loci: von Frey thresholds were strongly correlated with baseline expression of Cacna2d1, Ift27 and Csnk1e in multiple brain regions of BXD strains. Systemic gabapentin and PF-670462, which target the protein products of Cacna2d1 and Csnk1e, respectively, significantly increased von Frey thresholds in a genotype-dependent manner in progenitors and BXD strains. Real-time polymerase chain reaction confirmed differential expression of Cacna2d1 and Csnk1e in multiple brain regions in progenitors and showed differential expression of Cacna2d1 and Csnk1e in the dorsal root ganglia of the progenitors and BXD strains grouped by QTL genotype. Thus, linkage mapping, transcript covariance and pharmacological testing suggest that genetic variation affecting Cacna2d1 and Csnk1e may contribute to individual differences in von Frey filament response. This study implicates Cacna2d1 and Ift27 in basal mechanosensation in line with their previously suspected role in mechanical hypersensitivity. Csnk1e is implicated for von Frey response for the first time. Further investigation is warranted to identify the specific polymorphisms involved and assess the relevance of these findings to clinical conditions of disturbed mechanosensation.

Prostate cancer bone metastases acquire resistance to androgen deprivation via WNT5A-mediated BMP-6 induction.

BACKGROUND: Androgen ablation is the first-line therapy for patients with metastatic prostate cancer (CaP). However, castration resistance will eventually emerge. In the present study, we have investigated the role of bone morphogenetic protein-6 (BMP-6) in the development of castration-resistant prostate cancer (CRPC) in the context of bone metastases. METHODS: We initially investigated the clinical course of 158 men with advanced CaP who were treated with primary androgen deprivation therapy. To elucidate the underlying mechanism of CRPC in the context of bone metastases, we examined the impact of bone stromal cells on CaP in the absence of androgens using a co-culture model. RESULTS: In the 158 patients, we found that the median time to prostate-specific antigen progression was significantly shorter when bone metastases were present (14 months (95% CI, 10.2-17.8 months) vs 57 months (95% CI, 19.4-94.6 months)). These results suggest that bone-tumour interactions may accelerate castration resistance. Consistent with this hypothesis, in vitro co-cultures demonstrated that CaP cells proliferated under an androgen-depleted condition when incubated with bone stromal cells. Mechanistically, gene expression analysis using quantitative polymerase chain reaction arrays showed a dramatic induction of BMP-6 by CaP cell lines in the presence of bone stromal cells. Further studies revealed that WNT5A derived from bone stromal cells induced the expression of BMP-6 by CaP cells; BMP-6 in turn stimulated cellular proliferation of CaP cells in an androgen-deprived media via a physical interaction between Smad5 and ß-catenin. Intracellularly, WNT5A increased BMP-6 expression via protein kinase C/NF-κB pathway in CaP cell lines. CONCLUSIONS: These observations suggest that bone-CaP interaction leads to castration resistance via WNT5A/BMP-6 loop.

Intravenous Lacosamide in refractory nonconvulsive status epilepticus.

BACKGROUND: Many patients present with refractory Status epilepticus (SE) despite multiple anti-epileptic drugs (AEDs). Lacosamide (LCM) was recently approved as an adjunct AED for partial-onset seizures. It has unique mechanism of modulating voltage-gated sodium channels by enhancing their slow inactivation. LCM has demonstrated efficacy in animal models of pharmacoresistant seizures. To date, there are isolated anecdotal reports of LCM use in SE. OBJECTIVE: To report a single center experience with IV Lacosamide in patients with NCSE. METHODS: Pharmacy records were reviewed to identify patients with SE who received IV LCM in our institution. Data on demographics, response to therapy and adverse effects/outcomes were analyzed. All patients had continuous EEG monitoring. RESULTS: 10 patients (4 men, 6 women), age 16-90 years with refractory SE were given LCM. Eight patients were in focal non-convulsive SE (NCSE), 2 were in generalized non-convulsive SE. The etiologies included anoxic brain injury, idiopathic, encephalitis, tumor, posterior reversible encephalopathy syndrome (PRES), stroke, and AVM. IV LCM was added after traditional AEDs, including drug-induced coma in some, failed to control the SE. NCSE resolved in 7/10 patients whereas 1/10 patient showed partial response with cessation of NCSE but still frequent electrographic seizures and 2/10 patients were resistant to therapy. CONCLUSIONS: LCM is a useful adjunct in refractory NCSE. The IV formulation allows prompt administration in the intensive care unit setting. Response was seen especially in focal SE. Similar to other AEDs, response was poor in patients with postanoxic injury. Our data is limited by the small number of patients. Larger controlled studies are necessary to assess accurately the efficacy of IV LCM as an early treatment of SE.

Analysis of 2D periodic nanostructures with an oxide overlayer via spectroscopic ellipsometry.

The accurate nondestructive determination of the shapes or critical dimensions of periodic nanostructures is essential to the current integrated-circuits technology. Optical critical dimension (OCD) metrology is fast, nondestructive, and can be used in air, allows higher sampling rates compared to the non-optical methods such as scanning electron microscopy (SEM) or atomic-force microscopy (AFM), and does not damage the sample. The data are typically analyzed via rigorous coupled-wave analysis (RCWA), where the sample is modeled as a series of layers whose dimensional parameters are determined by a least-squares fit. The layers are typically approximated as a combination of core material and ambient. Oxide overlayers and surface roughness are common, however, and call into question two-phase approximation. In this study, a structure that is periodic in two dimensions and that is coated with a thin (3 nm) oxide was studied, and an extension of the RCWA method that allows structural information to be extracted from optical data even in the presence of oxide overlayers or surface roughness was developed.

Dual function of Zn2+ on the intrinsic excitability of dopaminergic neurons in rat substantia nigra.

Despite the presence of Zn(2+) in high levels in Parkinson brain, it is not yet clearly answered whether and how Zn(2+) alters the electrical activity of neurons in substantia nigra (SN). Here we show that Zn(2+) alters the intrinsic activity of nigral dopamine neurons in dual ways, that is, excitation or inhibition, by modulating the gating properties of a transient A-type K(+) (K(A)) channel. Depending on the holding potential, Zn(2+) could reduce or enhance a transient outward K(+) current (I(A)) in nigral dopamine neurons. Zn(2+) slowed the kinetics of both I(A) activation and inactivation with the rate of activation much more reduced than that of inactivation. Zn(2+) also increased the rate of release from I(A) inactivation. Both activation and inactivation I(A) curves were shifted by Zn(2+) towards positive potentials, but the positive shift of the inactivation curve was much greater than that of the activation curve. We propose that all these effects of Zn(2+) on K(A) channel gating properties underlie the dual mode of Zn(2+) action on I(A), that is, attenuation or potentiation depending on membrane potential. As a result, Zn(2+) increased a bursting activity of a nigral dopamine neuron elicited by anodal break excitation presumably through I(A) reduction at a hyperpolarizing state, whereas Zn(2+) decreased its tonic activity at either resting or depolarizing states where I(A) was increased. This was further supported by the observations that 4-aminopyridine (4-AP), a well-known K(A) channel blocker, strengthened or counteracted the effect of Zn(2+) on the intrinsic excitability of nigral dopamine neurons.

Nondestructive analysis of coated periodic nanostructures from optical data.

Optical data are essential for the accurate nondestructive determination of profiles of periodic structures in integrated-circuit technology. In rigorous coupled-wave analysis, the sample is generally modeled as layers consisting of a single material and the ambient. We extend present capabilities to the analysis of structures with overlayers and demonstrate our approach by determining quantitatively the thicknesses of top, sidewall, and bottom oxides of deliberately and naturally oxidized structures.

Hyperglycaemia, hypercholesterolaemia and the risk for developing gastric dysplasia.

BACKGROUND/GOALS: Gastric dysplasia is believed to be the penultimate stage of gastric carcinogenesis. Few studies have evaluated whether there is a relationship between such risk factors and gastric dysplasia. This case-control study was conducted to investigate the associations between obesity, serum glucose, lipids and gastric dysplasia. STUDY: Endoscopic findings and pathology specimens were reviewed from 1 July 1997 to 31 December 2006 in the Health Promotion Center. One hundred thirty patients have the dysplasia in the stomach during screening endoscopy. The same number of controls was evaluated and matched to the gastric dysplasia group for age and gender. RESULT: The univariate analysis showed that the dysplasia risk was slightly increased among persons with a higher low-density lipoprotein, lower high-density lipoprotein, impaired fasting glucose and higher total cholesterol. However, a higher body mass index and higher triglyceride level were not associated with the diagnosis of gastric dysplasia. In the multivariate-adjusted model, a higher low-density lipoprotein cholesterol and glucose were strongly associated with an increased risk of dysplasia compared to the controls. However, the body mass index, triglyceride and total cholesterol were not associated with the risk for dysplasia. CONCLUSION: Hyperglycaemia and low-density lipoprotein cholesterol appear to be associated with the risk for gastric dysplasia. Further epidemiologic studies including a large cohort of patients with gastric dysplasia and adenocarcinoma are needed to clarify the association of low-density lipoprotein cholesterol, serum glucose and gastric carcinogenesis.

Mechanical and heat sensitization of cutaneous nociceptors in rats with experimental peripheral neuropathy.

This study examined whether or not the properties of cutaneous nociceptive fibers are altered in the neuropathic state by comparing lumbars 5 and 6 spinal nerve ligation (SNL) rats with sham-operated controls. The rats with the unilateral SNL developed mechanical allodynia in the ipsilateral hind limb, whereas the sham group did not. Two to 5 weeks after the neuropathic or sham surgery, rats were subjected to single fiber-recording experiments to examine the properties of afferent fibers in the sural and plantar nerves. A total of 224 afferents in the C- and Adelta-ranges were characterized in the neuropathic and sham groups. Spontaneous activity was observed in 16 of 155 fibers in the neuropathic group and one of 69 fibers in the sham group. The response threshold of both the C- and Adelta-fibers to mechanical stimuli was lower in the neuropathic group than the sham group. The afferent fibers responsive to heat stimuli were all C-fibers, and none were Adelta-fibers. The response threshold of the C-fibers to the heat stimuli was lower in the neuropathic group than the sham group. The magnitude of the responses of both C- and Adelta-fibers to the suprathreshold intensity of the mechanical stimulus was greater in the neuropathic group than the sham group. However, the magnitude of the responses of C-fibers to the suprathreshold intensity of the heat stimulus in the neuropathic group was not different from that in the sham group. These results suggest that after a partial peripheral nerve injury, the nociceptors on the skin supplied by an uninjured nerve become sensitized to both mechanical and heat stimuli. This nociceptor sensitization can contribute to neuropathic pain.

Electro-acupuncture relieves chronic visceral hyperalgesia in rats.

Acupuncture treatment is one of the most desirable choices for the management of pain including chronic visceral pain, but its scientific evidence and laws of action are not very clear at this point. In this study, we examined the immediate and cumulative effects of electro-acupuncture (EA) on chronic visceral pain induced by colorectal distention (CRD) stimuli in rats using an irritable bowel syndrome (IBS) model (a chronic visceral hypersensitivity model). The results demonstrated that EA could significantly depress both abnormally increased abdominal withdrawal reflex (AWR) scores and the magnitude of electromyograms (EMGs) recorded from the rectus abdominis in response to CRD stimulation at strengths of 20, 40, 60, and 80 mmHg. Repeated EA treatment for 14 days showed that the effects of EA on both abnormal AWRs and EMGs appeared 2-4 days after the start of the EA application session, gradually enhanced to its maximum within 8-12 days, and lasted 5 days after EA treatment stopped. These data provide evidence that visceral pain associated with the rat IBS model can be effectively treated by EA and opens up the possibility of clinical treatment of chronic visceral pain with acupuncture.

Oral testosterone undecanoate (Andriol) supplement therapy improves the quality of life for men with testosterone deficiency.

In a single-blind, placebo-controlled study, the effects of a 3-month oral administration of 160 mg/day testosterone undecanoate (Andriol) on the quality of life of men with testosterone deficiency were evaluated. The subjects included ten men with primary hypogonadism and 29 with andropause with sexual dysfunction as the most common problem. The changes in subjective symptoms were evaluated by the PNUH QoL scoring system and the St. Louis University Questionnaire for androgen deficiency in aging males (ADAM). Digital rectal examination (DRE) was performed and serum testosterone, prostate-specific antigen (PSA) and liver profile were monitored. Testosterone undecanoate treatment (n = 33) significantly improved sexual dysfunction and symptom scores of metabolic, cardiopulmonary, musculoskeletal and gastrointestinal functions compared to baseline and to placebo (n = 6). ADAM score also significantly improved after 3 months of treatment. Serum testosterone was significantly increased compared to pretreatment levels only in the testosterone undecanoate group. In the placebo group, no significant changes compared to baseline were found for testosterone levels and QoL questionnaires. No abnormal findings were detected on DRE or laboratory findings in either group. Adverse events, such as gastrointestinal problems and fatigue, were mild and self-limiting. It is concluded that androgen supplement therapy with oral testosterone undecanoate (Andriol) restores the quality of life through improvement of general body functions in men with testosterone deficiency.

Efficacy of low-dose clarithromycin triple therapy and tinidazole-containing triple therapy for Helicobacter pylori eradication.

BACKGROUND: Proton pump inhibitor-based triple therapies are recommended as the first-line treatment for Helicobacter pylori eradication. AIM: To evaluate the efficacies of low-dose clarithromycin triple therapy and tinidazole-containing triple therapy in a metronidazole resistance prevalent area and to compare the efficacies with standard triple therapy. METHODS: In a randomized, multicentre, prospective study, a total of 352 patients with duodenal ulcer or non-ulcer dyspepsia were randomly divided into three groups according to the administered regimen: OAC250 group (omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 250 mg), OAC500 group (omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg) and OTC group (omeprazole, 20 mg, tinidazole, 500 mg, and clarithromycin, 500 mg). The three groups received each regimen twice daily for 7 days. Upper gastrointestinal endoscopy was performed before and 4 weeks after treatment. H. pylori status was determined by rapid urease test and 13C urea breath test. RESULTS: The eradication rates in the OAC250, OAC500 and OTC groups were 76.2%, 65.7% and 64.8% (95% confidence interval: 67.9-84.4%, 56.7-74.8% and 55.7-73.9%), respectively, by intention-to-treat analysis (P=0.149) and 92.8%, 87.2% and 84.1% (95% confidence interval: 84.4-97.3%, 77.9-93.8% and 73.9-91.2%), respectively, by per protocol analysis (P=0.088). All regimens were well tolerated and compliance was excellent. CONCLUSIONS: Both low-dose clarithromycin triple therapy and tinidazole-containing triple therapy are effective and safe regimens for H. pylori eradication.

The changes in expression of three subtypes of TTX sensitive sodium channels in sensory neurons after spinal nerve ligation.

Our previous studies showed that the ectopic discharges in injured sensory neurons and mechanical allodynia that developed after spinal nerve ligation were significantly reduced by application of a low concentration of tetrodotoxin (TTX) to the corresponding dorsal root ganglion (DRG) of the ligated spinal nerve. Based on these data, we hypothesized that expression of TTX-sensitive sodium channels is up-regulated in the injured sensory neurons and that such up-regulation plays an important role in the generation of ectopic discharges and thus pain behaviors in spinal nerve ligated neuropathic rats. To test this hypothesis, the present study examined the changes in three subtypes of TTX-sensitive sodium channels in the DRG after spinal nerve ligation. The changes in the total amount of mRNA for alpha-subunits of sodium channel brain type I (type I), brain type II (type II) and brain type III (type III) were determined by RNase protection assays (RPA). The population of DRG neurons expressing type III sodium channel protein was examined by an immunohistochemical method with antibodies to type III sodium channels. In the normal DRG, the level of mRNA for the type I sodium channel is high while that for type II and type III is very low. After spinal nerve ligation, the expression of type III mRNA was significantly increased at 16-h postoperatively (PO), doubled by 3 days PO and then was maintained at this high level until the end of the experiment (7 days PO). By contrast, the amount of mRNA for type I and type II sodium channels started to decrease at 1 day PO and were reduced to 25-50% of the normal control levels by 7 days after nerve ligation. Neurons showing positive immunostaining for type III sodium channels were rare ( approximately 3.2% of total population) in the normal DRG but increased after nerve ligation to 21% and 15% of the total neuronal population by 1 day and 7 days PO, respectively. Type III immunoreactivity was found preferentially in medium to large sized neurons. Thus the majority of neurons with cell bodies having diameters > or =40 microm became type III-positive after nerve ligation. The data indicate that the increased expression of type III sodium channels in axotomized sensory neurons may be the critical factor for the TTX sensitivity of ectopic discharges in injured sensory neurons and thus the generation of ectopic discharges and neuropathic pain behaviors in spinal nerve ligated rats.

Attenuation of Zn2+ neurotoxicity by aspirin: role of N-type Ca2+ channel and the carboxyl acid group.

Synaptically released Zn2+ ions enter into neurons primarily through voltage-gated Ca2+ channels (VGCC) or N-methyl-d-aspartate (NMDA) receptors, which can mediate pathological neuronal death. We studied the possibility (and underlying mechanisms) that aspirin, known to prevent NMDA neurotoxicity, would also attenuate Zn2+ neurotoxicity. Administration of 3 to 10 mM aspirin, in cortical cell cultures, attenuated the evolution of neuronal death following exposure to 300 microM Zn2+ for 30 min. This neuroprotective effect of aspirin was attributable to the prevention of Zn2+ ion entry. Aspirin interfered with inward currents and an increase in [Ca2+]i through VGCC and selective binding of omega-conotoxin, sensitive to N-type Ca2+ channel. The omega-conotoxins GVIA or MVIIC, the selective inhibitors of N-type Ca2+ channels, attenuated Zn2+ neurotoxicity. Aspirin derivatives lacking the carboxyl acid group did not reduce Zn2+ neurotoxicity. The present findings suggest that aspirin prevents Zn2+-mediated neuronal death by interfering with VGCC, and its action specifically requires the carboxyl acid group.

Development of purinergic sensitivity in sensory neurons after peripheral nerve injury in the rat.

Purinoceptors are present in the cell bodies as well as in both peripheral and central terminals of many sensory neurons, where they may play a role in sensory transmission, including pain. After peripheral nerve injury at the spinal nerve level, some axotomized afferent neurons develop ongoing discharges (ectopic discharges) that originate in the dorsal root ganglion (DRG). In the present study, we attempted to determine whether or not purinergic sensitivity develops in injured sensory neurons which display ectopic discharges, as well as in silent units. The L(4) and L(5) spinal nerves were ligated in Sprague-Dawley rats. Four to 21 days after the surgery, the DRGs with attached dorsal roots and spinal nerves were removed and ectopic discharges were recorded from teased dorsal root fascicles using an in vitro recording set-up. The results showed that 75.6 and 65.1% of the chronically axotomized DRG neurons displaying ectopic discharges enhanced their activity after application of adenosine 5'-triphosphate (ATP, 1 mM) or alpha,beta-methylene ATP (mATP, 100 microM), respectively. In addition, application of these purinoceptor agonists evoked activity in 7 of 28 axotomized DRG neurons, which did not show ongoing discharges. In contrast, only 1 of 34 DRG neurons acutely isolated from normal rats (no previous spinal nerve ligation) responded to either mATP or ATP. In most of the tested units, mATP-induced enhancement of ectopic discharges was blocked by non-specific P2X receptor antagonists, PPADS or suramin. The data from the present study suggest that purinergic sensitivity develops in DRG neurons after chronic axotomy and that this purinergic sensitivity is likely to be mediated by P2X purinoceptors. This acquired purinergic sensitivity may play an important functional role in the enhancement of ectopic discharges and exacerbation of pain upon sympathetic activation in the neuropathic pain state.

Complestatin is a noncompetitive peptide antagonist of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors: secure blockade of ischemic neuronal death.

Complestatin, a peptide derived from Streptomyces, was found to protect cultured cortical neurons from excitotoxicity induced by N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), or kainate. This neuroprotective behavior of complestatin was attributed to a blockade of Ca2+ ion entry and accumulation, after the activation of NMDA and AMPA/kainate receptors. Complestatin reversibly interfered with NMDA- and AMPA-mediated excitatory synaptic transmission. Complestatin also protected cortical neurons from prolonged deprivation of oxygen and glucose, more effectively than combined antagonists of NMDA and AMPA/kainate receptors. Neurotoxicity, evolving within 1 to 2 days after continuous exposure to combined NMDA and AMPA/kainate antagonists, was not observed in cortical cell cultures that were exposed to complestatin. Finally, complestatin dose dependently prevented neuronal death evolving within the inner nuclear and ganglion cell layers, after transient retinal ischemia. We conclude that complestatin possesses novel pharmacological properties that effectively prevent excitotoxicity under certain pathological conditions.

Gastric lymphangioma.

Gastric lymphangioma is a rare benign gastric tumor composed of unilocular or multilocular lymphatic spaces. On gastrofiberscopy a submucosal tumor covered with smooth transparent normal mucosa is revealed in the stomach with or without a stalk. Endoscopic ultrasonography has become an indispensable tool for differentiating these gastric tumors. Treatment of lymphangioma depends on its size, location, and presence of complications. Endoscopic resection is safe and easy and plays an important role in confirming the diagnosis and treatment of the tumors especially of small-sized ones. We report a case of gastric lymphangioma in a 68-yr-old woman who presented with nausea and vague epigastric discomfort for two months. She was diagnosed by gastrofiberscopy with endoscopic ultrasonography and treated successfully with endoscopic resection by strip biopsy method.

Ion channels associated with the ectopic discharges generated after segmental spinal nerve injury in the rat.

In an attempt to identify important ion channels contributing to the generation of ectopic discharges, the present study examined the effects of ion channel blockers on ectopic discharges of injured sensory neurons after spinal nerve ligation. The main focus of the study was to examine the effect of the sodium channel blocker, tetrodotoxin (TTX), in order to identify important subtype(s) (i.e. TTX-sensitive and TTX-resistant) of sodium channels that are involved in ectopic discharge generation. In addition, the effects of potassium and calcium channel blockers were also tested for comparison with the results of previous studies. The dorsal root ganglion (DRG) of the injured segment was removed along with the dorsal root (DR) and the spinal nerve 7-14 days after spinal nerve ligation in the rat. The tissue was placed in an in-vitro recording chamber consisting of multiple compartments that were independently perfused with 35 degrees C artificial cerebrospinal fluid (ACSF). Single unit recordings were made from teased DR fibers. Once a spontaneously active unit was found and characterized, ACSF containing a channel blocker was perfused to the DRG, the site where almost all ectopic discharges originate after spinal nerve ligation. All the recorded spontaneously active units were found to be Abeta and Adelta fibers (no C fibers were detected). Perfusion of the DRG with a sodium channel blocker (lidocaine) at a dose much less than that required to block conduction of action potentials, significantly inhibited ectopic discharges in all recorded fibers. In addition, ectopic discharges were inhibited by TTX perfused to the DRG at a dose much lower (average of 22.1 nM) than that required to block TTX-resistant subtypes of sodium channels. The data suggest that TTX-sensitive sodium channels are likely to be involved in the generation of ectopic discharges. The present study also confirmed the results of previous studies on the additional potential roles of potassium and calcium channels, thus suggesting that multiple ion channels are likely to be involved in the generation of ectopic discharges.