Effectiveness of stellate ganglion block for the treatment of patulous eustachian tube: A case report.

A 56-year-old woman presented with a 2 months history of patulous eustachian tube. She had sudden weight loss after developing a cold, after which she had been experiencing disabling autophony and a sensation of blockage in the ear. She underwent stellate ganglion block in 8 months; her symptoms resolved subsequently.

Synthesis of new opioid derivatives with a propellane skeleton and their pharmacology. Part 2: Propellane derivatives with an amide side chain.

We designed and synthesized propellane derivatives with a 6- or 7-amide side chain on the basis of the active conformation of the κ selective agonist nalfurafine. The 6-amides showed high affinities for the κ receptor, and one of the 6ß-amides showed higher κ selectivity than nalfurafine. On the other hand, although the affinities of the 7-amides decreased compared to the 6-amides, some 7α-amides showed the highest selectivities for the κ receptor among the tested compounds. The affinities of 7ß-isomers were extremely low, which was postulated to result from the shielding effect of the 7ß-amide side chain against the lone electron pair on the 17-nitrogen. This is the first conformational information about the 7-amide side chain in propellane derivatives.

Synthesis of new opioid derivatives with a propellane skeleton and their pharmacologies: part 3, novel propellane derivatives with pentacyclic skeletons.

Previously reported propellane derivative KNT-42 preferred the κ receptor and functioned as a message part in the message-address concept, but its affinity for the κ receptor was not high. To improve affinity, we synthesized five pentacyclic propellane derivatives designed for the purpose of fixing the conformation of KNT-42. The etheno- and ethano-bridged derivatives SYK-347 and SYK-393 exhibited high affinity and selectivity for the κ receptor, whereas the other derivatives did not. These results would be due to the different ranges of movement of the basic nitrogens and less basicity of the nitrogens due to the electron withdrawing effect of the introduced hydroxy or keto group. SYK-347 and SYK-393 preferring the κ receptor were expected to be useful for designing selective ligands for opioid receptor types, especially the κ receptor.

Hormonal and Neurological Aspects of Dog Walking for Dog Owners and Pet Dogs.

The hormone oxytocin is involved in various aspects of the relationship between humans and animals. Dog walking is a common activity for dog owners and their dogs. The walk, of course, should be good for the health of the dog as well as its owner. In Experiment I, we assessed whether salivary oxytocin and cortisol in dog owners changed because of walking their dogs. Ten owners walked with their dogs and walked alone. Similar to other previous research, walking with a dog did not significantly change oxytocin and cortisol. Therefore, in Experiment II, we investigated the effect of dog walking on brain noradrenergic and GABAergic neural activity, as indicated by salivary MHPG and GABA, in 14 dog owners. Walking with a dog reduced salivary MHPG compared to walking alone, and MHPG was correlated negatively with GABA. Thus, dog walking activated GABAergic nerves in the brain and suppressed noradrenergic nerves, effectively relieving stress.

Delta-like 1 expression promotes goblet cell differentiation in Notch-inactivated human colonic epithelial cells.

Notch signaling has previously been implicated in the regulation of the cell fate of intestinal epithelial cells. However, the expression and function of Notch ligands in the human intestine remain largely unknown. In the present study, we showed that Notch ligands Delta-like 1 (Dll1) and Delta-like 4 (Dll4) are expressed in a goblet cell-specific manner in human colonic tissue. Additionally, we found that Dll1 and Dll4 expression was regulated in-parallel with Atoh1 and MUC2, which are both under the control of the Notch-Hes1 signaling pathway. Because knockdown of Dll1 expression completely abrogated the acquisition of the goblet cell phenotype in Notch-inactivated colonic epithelial cells, we postulate that Dll1 might function as a cis-acting regulatory element that induces undifferentiated cells to become goblet cells. Our results suggest a link between Dll1 expression and human goblet cell differentiation that might be mediated by a function that is distinct from its role as a Notch receptor ligand.

Musashi-1 suppresses expression of Paneth cell-specific genes in human intestinal epithelial cells.

BACKGROUND: Musashi-1 (Msi-1) is a RNA-binding protein, known as a putative marker of intestinal stem cells (ISCs). However, little is known about the function of Msi-1 within human intestinal epithelial cells (IECs). Thus, the present study aimed to clarify the role of Msi-1 in differentiation and proliferation of IECs. METHODS: A human intestinal epithelial cell line stably expressing Msi-1 was established. Proliferation of the established cell lines was measured by bromodeoxyuridine incorporation, whereas differentiation were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of lineage-specific genes. Activities of the Notch and Wnt pathways were examined either by reporter assays or expression of downstream target genes. The distribution of Msi-1 and PLA2G2A expression in vivo was determined by immunohistochemistry. RESULTS: Constitutive expression of Msi-1 in IECs had no significant effect on cell proliferation, but suppressed expression of Paneth cell-specific genes, including PLA2G2A. Msi-1 appeared to suppress expression of the PLA2G2A gene at the mRNA level. Analysis of Notch and Wnt pathway activity, however, revealed no significant change upon Msi-1 expression. The expression of Msi-1 and PLA2G2A in vivo was restricted to IECs residing at the lowest part of the human intestinal crypt, but was clearly separated to within basal columnar cells or mature Paneth cells, respectively. CONCLUSIONS: Msi-1 suppresses expression of Paneth cell-specific genes in IECs, presumably through a pathway independent from Notch or Wnt. These findings suggest Msi-1 is a negative regulator of Paneth cell differentiation, an may contribute to maintain the undifferentiated phenotype of ISCs.

Flagellin stimulation suppresses IL-7 secretion of intestinal epithelial cells.

IL-7 is a cytokine, which regulates development, maintenance and proliferation of T lymphocytes within the human immune system. Production of IL-7 is observed in a sterile environment such as thymus or bone marrow. However, it is also known that intestinal epithelial cells (IECs) residing in close contact with numerous bacterial stimuli also produce IL-7. Here we show that secretion of IL-7 by IECs is significantly suppressed upon stimulation by various bacterial components, including flagellin. Analysis of the intracellular mechanism by which flagellin regulates IL-7 production revealed that flagellin down-regulates expression of the two major transcripts encoding IL-7. Surprisingly, such function of flagellin was independent from the known transcriptional regulation of the IL-7 gene, as no significant change was observed in the transcriptional activity regulated by the previously identified promoter region. As the stability of IL-7 mRNA also remained unchanged upon flagellin stimulation, results suggested the possible involvement of a yet unknown transcriptional regulation of the IL-7 gene. These results describe a novel regulation of IL-7 production by bacterial stimuli, presumably mediated via Toll-like receptors. The present system might contribute to regulate the local lymphocyte pool, in response to the gut luminal or sub-mucosal bacterial abundance.

Increased number of whistles of bottlenose dolphins, Tursiops truncatus, arising from interaction with people.

The acoustic mode is the most reasonable means for social animals such as dolphins to maintain contact in the underwater habitat, and has been developed since they moved to the sea. This study investigates variations in dolphin vocalizations under the following conditions in a captive environment: 1) before feeding (Pre-feeding), 2) during feeding (Feeding), 3) during free time without the presence of people (Free), 4) during interaction with people located upon a float (Float), 5) during interaction with people in the water (Water). During the experiments, a total of 2642 whistles were extracted from sonogram data using a spectrogram. About 44% of the total whistles were observed during Pre-feeding (1171/2642), and the number recorded during Free, when people were absent, was the smallest. The acoustic contours of dolphin whistles differed in different situations: convex, wave, and trill whistles were made repeatedly during Pre-feeding, thereby being more common at this time than at other times. The situation of Feeding saw an increased number of Upsweeps, which might be related to the use of echolocation. The lower frequencies were recorded during Pre-feeding, reflecting the emotion related to the dolphin's hunger. The results of this study indicate that dolphins increase their vocalization during interaction with people, suggesting that interactions with dolphins provide an effective treatment for human health problems, which is discussed with a reference article in this study. Vocal data obtained during contact with humans might serve as an important index for the dolphin-assisted therapy.

Horseback Riding Improves the Ability to Cause the Appropriate Action (Go Reaction) and the Appropriate Self-control (No-Go Reaction) in Children.

BACKGROUND: There are many obvious health benefits to riding, including developing a strong core and legs, but there are also many less obvious benefits, such as increased confidence and introspection. Few studies have addressed the effects of horseback riding on children and the mechanisms underlying how riding affects humans. We examined the effects of horseback riding on the ability to distinguish Go/No-go tasks and solve arithmetic problems in children. METHODS: The subjects were 34 boys and 72 girls, aged 10-12 years old, which were divided into three groups (horse riding, walking, and resting). They were healthy typical children, who performed the Go/No-go tasks and solved the arithmetic problems. The heart rate and heart rate variability of the children, and the three-dimensional acceleration of the children while walking horses, were examined. RESULTS: Riding on a half-breed horse or a pony improved the ability to perform Go/No-go tasks and solve arithmetic problems, possibly through sympathetic activity. Some horses, like the Kiso, might provide a healing effect to children through parasympathetic activity. Statistically significant differences in the three-dimensional acceleration and the autonomic activities were observed among the three horses. The acceleration in the Kiso horse group during walking in hand was significantly different from those involving the other two horses, indicating that the vibrations produced by these horses might modify the autonomic activities. CONCLUSION: The most important beneficial factor of horseback riding for children and for human health appears to be associated with the horse's vibrations, which may differ among horses. Riding some horses may improve the ability of children to respond with an appropriate action depending on the situation (Go reaction) or use self-control appropriately (No-go reaction), possibly through the activation of the sympathetic nervous system.

Chronic inflammatory demyelinating polyradiculoneuropathy in a patient with Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract that is frequently accompanied by systemic complications. Neuropathologies have not been well investigated as extraintestinal manifestations of CD. We herein report the case of a 36-year-old man with CD who presented with progressive weakness and numbness. A neurological examination and the results of a nerve conduction study and a sural nerve biopsy led to a diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Plasma exchanges were initially effective; however, the effects gradually declined starting 10 days after the plasma exchange (PE). These results suggest that humoral factors may play an important role in CIDP associated with CD.

Endoscopic ultrasound with double-balloon endoscopy for the diagnosis of inverted Meckel's diverticulum: a case report.

INTRODUCTION: Inverted Meckel's diverticulum has usually been misdiagnosed in the cases based on computed tomography images presented in the literature. The final diagnosis was made intra-operatively or by pathology reports after surgery. Despite this, preoperative diagnosis could be made successfully by using endoscopic ultrasound with double-balloon endoscopy prior to surgery. CASE PRESENTATION: A 60-year-old Japanese woman with severe anemia complained of several episodes of black stool over the preceding 2 years. Abdominal computed tomography showed a 3.0-cm low-density tumor in the ileum, suggesting a diagnosis of intestinal lipoma. Examination of the tumor by endoscopic ultrasound with double-balloon endoscopy revealed a hypo-echoic layer corresponding to the muscularis propria, and a hyper-echoic layer corresponding to the fat tissue. These findings, which suggested that the tumor included areas outside the intestinal serosa, are not typical for a lipoma, despite the existence of a hyper-echoic layer corresponding to fatty tissue. We then considered a diagnosis of inverted Meckel's diverticulum. CONCLUSION: Lipoma and inverted Meckel's diverticulum are difficult to differentially diagnose by computed tomography. Polypectomy is the preferred therapeutic approach when a lipoma is present; however, polypectomy in a patient with Meckel's diverticulum requires full-thickness resection. Situations where polypectomy is performed without preparing for full-thickness resection can be avoided by first making a precise diagnosis using double-balloon endoscopy and endoscopic ultrasound.

Requirement of Notch activation during regeneration of the intestinal epithelia.

Notch signaling regulates cell differentiation and proliferation, contributing to the maintenance of diverse tissues including the intestinal epithelia. However, its role in tissue regeneration is less understood. Here, we show that Notch signaling is activated in a greater number of intestinal epithelial cells in the inflamed mucosa of colitis. Inhibition of Notch activation in vivo using a gamma-secretase inhibitor resulted in a severe exacerbation of the colitis attributable to the loss of the regenerative response within the epithelial layer. Activation of Notch supported epithelial regeneration by suppressing goblet cell differentiation, but it also promoted cell proliferation, as shown in in vivo and in vitro studies. By utilizing tetracycline-dependent gene expression and microarray analysis, we identified a novel group of genes that are regulated downstream of Notch1 within intestinal epithelial cells, including PLA2G2A, an antimicrobial peptide secreted by Paneth cells. Finally, we show that these functions of activated Notch1 are present in the mucosa of ulcerative colitis, mediating cell proliferation, goblet cell depletion, and ectopic expression of PLA2G2A, thereby contributing to the regeneration of the damaged epithelia. This study showed the critical involvement of Notch signaling during intestinal tissue regeneration, regulating differentiation, proliferation, and antimicrobial response of the epithelial cells. Thus Notch signaling is a key intracellular molecular pathway for the proper reconstruction of the intestinal epithelia.

Increased production of antioxidative sesaminol glucosides from sesame oil cake through fermentation by Bacillus circulans strain YUS-2.

Bacillus circulans strain YUS-2 was isolated as the strongest antioxidant-producer in fermentation of sesame oil cake (SOC, defatted residue yielded from sesame seed oil production). Two major strong antioxidants from fermented SOC were purified and identified as known sesaminol triglucoside and sesaminol diglucoside, however, our results demonstrated that the fermentation process with B. circulans YUS-2 was highly effective to gain the extraction efficiency of the sesaminol glucosides.