Different effects of ghrelin, des-acyl ghrelin and obestatin on gastroduodenal motility in conscious rats

Three peptides, ghrelin, des-acyl ghrelin and obestatin are derived from a common prohormone, preproghrelin by posttranslational processing, originating from endocrine cells in the stomach. To examine the effects of these peptides, we applied the manometric measurement of gastrointestinal motility in freely moving conscious rat models. Ghrelin exerts stimulatory effects on the motility of antrum and duodenum in both fed and fasted state of animals. Des-acyl ghrelin exerts inhibitory effects on the motility of antrum, but not on the motility of duodenum in the fasted state of animals. Obestatin exerts inhibitory effects on the motility of antrum and duodenum in the fed state, but not in the fasted state of animals. NPY Y2 or Y4 receptors in the brain may mediate the action of ghrelin, CRF type 2 receptors in the brain mediate the action of des-acy ghrelin, whereas CRF type 1 and type 2 receptors in the brain mediate the action of obestatin. Vagal afferent pathways might be involved in the action of ghrelin, but not involved in the action of des-acyl ghrelin, whereas vagal afferent pathways might be partially involved in the action of obestatin.

Potential effects of mesenchymal stem cell derived extracellular vesicles and exosomal miRNAs in neurological disorders

Mesenchymal stem cells are multipotent cells that possess anti-inflammatory,antiapoptotic and immunomodulatory properties.The effects of existing drugs for neurodegenerative disorders such as Alzheimer’s disease are limited,thus mesenchymal stem cell therapy has been anticipated as a means of ameliorating neuronal dysfunction.Since mesenchymal stem cells are known to scarcely differentiate into neuronal cells in damaged brain after transplantation,paracrine factors secreted from mesenchymal stem cells have been suggested to exert therapeutic effects.Extracellular vesicles and exosomes are small vesicles released from mesenchymal stem cells that contain various molecules,including proteins,mRNAs and microRNAs.In recent years,administration of exosomes/extracellular vesicles in models of neurological disorders has been shown to improve neuronal dysfunctions,via exosomal transfer into damaged cells.In addition,various microRNAs derived from mesenchymal stem cells that regulate various genes and reduce neuropathological changes in various neurological disorders have been identified.This review summarizes the effects of exosomes/extracellular vesicles and exosomal microRNAs derived from mesenchymal stem cells on models of stroke,subarachnoid and intracerebral hemorrhage,traumatic brain injury,and cognitive impairments,including Alzheimer’s disease.

Anal cushion lifting method is a novel radical management strategy for hemorrhoids that does not involve excision or cause postoperative anal complications

AIM: To describe the anal cushion lifting(ACL) method with preliminary clinical results. METHODS: Between January to September 2007, 127 patients who received ACL method for hemorrhoid was investigated with informed consent. In this study, three surgeons who specialized in anorectal surgery performed the procedures. Patients with grade two or more severe hemorrhoids according to Goligher's classification were considered to be indicated for surgery. The patients were given the choice to undergo either the ACL method or theligation and excision method. ACL method is an original technique for managing hemorrhoids without excision. After dissecting the anal cushion from the internal sphincter muscle, the anal cushion was lifted to oral side and ligated at the proper position. Clinical characteristics and outcomes of patients were recorded including complications after surgery. RESULTS: A total of 127 patients were enrolled. Their median age was 42(19-84) years, and 74.8% were female. In addition, more than 99% of the patients had grade 3 or worse hemorrhoids. The median followup period was 26(0-88) mo, and the median operative time was 15(4-30) min. After surgery, analgesics were used for a median period of three days(0-21). Pain control was achieved using extra-oral analgesic drugs, although some patients required intravenous injections of analgesic drugs. The median duration of the patients' postoperative hospital stay was 7(2-13) d. A total of 10 complications(7.9%) occurred. Bleeding was observed in one patient and was successfully controlled with manual compression. Urinary retention occurred in 6 patients, but it disappeared spontaneously in all cases. Recurrent hemorrhoids developed in 3 patients after 36, 47, and 61 mo, respectively. No anal stenosis or persistent anal pain occurred. CONCLUSION: We consider that the ACL method might be better than all other current methods for managing hemorrhoids.