Abstract: This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt thereof, or an N-oxide thereof), which are positive allosteric modulators of one or more GABA-A receptors, e.g., which are peripherally restricted, positive allosteric modulators of one or more GABA-A receptors; e.g., which are positive allosteric modulators of one or more GABA-A receptors and which selectively target the peripheral nervous system and organs of the body, and which do not substantially pass through the blood-brain barrier. Said compounds are useful e.g., for the treatment of systemic diseases of the body, e.g., diseases in which modulation of one or more peripherally restricted GABA-A receptors is beneficial (e.g., diseases or disorders which are mediated by GABA-A neuronal activity. This disclosure also features pharmaceutical compositions containing the chemical entities described herein as well as methods of using same for the treatment of systemic diseases of the body.

Abstract: The present invention provides compounds and compositions which are positive allosteric modulators of GABA-A receptors that selectively target the peripheral nervous system and organs of the body, and which do not pass through the blood-brain barrier. The compounds and compositions of the present invention are useful for treatment of diseases or disorders which are mediated by GABA-A neuronal activity, such as, for example, visceral pain, gut motility, irritable bowel syndrome, functional abdominal pain, functional idiopathic diarrhea, inflammatory bowel diseases, drug induced pain, bile salt malabsorption, lactase or other carbohydrate intolerance.

Abstract: A method for treating conditions associated with impaired glucose control, involving inhibition of signalling by the greater splanchnic nerve leads to a significant improvement in oral glucose tolerance.

Abstract: Methods and devices for treating obesity. Pressure is applied to gastric walls in at least one segment of a stomach such that the pressure distends the gastric walls and induces satiety. A hollow capsule can be used to distend the gastric walls. Alternatively, a doughnut-shaped ring may be inflated to an amount sufficient to create intragastric tension and induce satiety. A c-ring including at least one balloon may be placed at a segment of the stomach, where the balloon inflates to a size that creates tension at the segment. A biocompatible material can be injected into the fundus and antrum of the stomach to stiffen the gastric wall to create a fullness feeling.

Abstract: Methods of treatment in subjects suffering from diabetes mellitus or obesity are provided. The methods comprise the step of administering an active agent directly to the small intestine in the subject. In particular, the active agent may be administered directly to the duodenum in the subject. The active agents useful in the treatments described herein include analgesic agents and, in particular, antinociceptive agents such as capsaicin, resiniferatoxin, and their analogs.

Abstract: A treatment device for endoscopic therapy of the present invention includes a suturing-ligating member having a distal end portion and a proximal end portion, that carries out at least one of suturing and ligation of biological tissue, a stopper provided to be movable forward or backward on an proximal end side of the suturing or ligating member, and stoppable by friction on the suturing-ligating member to maintain the biological tissue in a sutured or ligated state by the suturing-ligating member, and a suturing-ligation releasing member provided movable with relative to the suturing-ligating member to release the suturing-ligation state maintained by firctional stopping between the suturing-ligating member and the stopper by moving the releasing member to the proximal end portion side of the suturing-ligating member.

Abstract: The present invention is directed to a method of regulating gastrointestinal action in a subject using a stimulatory electrode and a sensor to provide retrograde feedback control of electrical stimulation to the GI tract.

Abstract: Methods of treatment in subjects suffering from diabetes mellitus or obesity are provided. The methods comprise the step of administering an active agent directly to the small intestine in the subject. In particular, the active agent may be administered directly to the duodenum in the subject. The active agents useful in the treatments described herein include analgesic agents and, in particular, antinociceptive agents such as capsaicin, resiniferatoxin, and their analogues.

Abstract: The present invention is directed to a method of regulating gastrointestinal action in a subject using a stimulatory electrode and a sensor to provide retrograde feedback control of electrical stimulation to the GI tract.

Abstract: Provided herein are methods for treating pain and for reducing the excitability of nociceptors, comprising administering a TGF-? antagonist. In some embodiments, a TGF-? antagonist is a monoclonal TGF-f3 neutralizing antibody or a fusion product comprising a monoclonal TGF-? neutralizing antibody, a soluble receptor, an antisense oligodeoxynucleotides (ODNs), a ribozymes, a small inhibitory RNA (siRNA), Smad 6, Smad7, or a small molecule that blocks TGF-? signaling.

Abstract: The present invention is directed to a method of regulating gastrointestinal action in a subject using a stimulatory electrode and a sensor to provide retrograde feedback control of electrical stimulation to the GI tract. The invention is further directed to a method for reducing weight in a subject, again using a stimulatory electrode and a sensor to provide retrograde feedback control of electrical stimulation to the stomach. The invention is further directed to a method of providing electrical field stimulation to a gastrointestinal organ, as well as a method of providing an electrical potential gradient in a gastrointestinal organ. Further provided is a method of stimulating the vagus nerve of a subject. Additionally provided is a method of placing a device in the gastrointestinal tract or wall of a subject from the exterior of the subject, using a needle to insert the device.

Abstract: A method is disclosed for distending a body lumen in the performance of endoscopic retrograde cholangiopancreatography (ERCP). The method comprises insufflating the body lumen with contrast agent to distend the body lumen. The contrast agent includes gas.

Abstract: The present invention is directed to a method of stimulating the vagus nerve of a subject.

Abstract: A medical apparatus including: a projecting member; an introducing sheath; an extrusion member inside the introducing sheath, at a proximal side of the projecting member and movable in an axial direction with respect to the introducing sheath; a cover sheath outside the introducing sheath, the introducing sheath being movable between a first and second position with respect to the cover sheath; an introducing sheath manipulating section at a proximal side of the introducing sheath; an extrusion member manipulating section at a proximal side of the extrusion member; a cover sheath manipulating section at a proximal side of the cover sheath; and a release member on the cover sheath manipulating section and/or the introducing sheath manipulating section to release a fixation between the extrusion member manipulating section and the introducing sheath manipulating section when the introducing sheath is disposed on the first or second position.

Abstract: The disclosure provides a method of treatment for obesity, in an individual in need thereof, by administering electrical stimulation at dual sites in the gastrointestinal tract. The electrical stimulations are administered by positioning bipolar stimulatory electrodes in contact with the gastric and dudenol cavities, along afferent vagal neural pathways, in the gastrointestinal tract. The electrical stimulations thus administered, activate the vagal afferents associated with the gastric and dudenol sites in the gastrointestinal tract. The activation of vagal afferents modulates the gastrointestinal peptide satiety hormones. Further, the disclosure provides a method of treatment for eating disorders, in an individual in need thereof, by administering electrical stimulation at dual sites, along afferent vagal neural pathways, in the gastrointestinal tract.

Abstract: There is provided an endoscopic system. The system comprises a flexible endoscope insertable into a first tubular organ from a natural opening of a human body. The system further comprises an opening member which forms on a wall part of the first tubular organ an opening used to insert the endoscope into an abdominal cavity from the first tubular organ in the body, an anastomosing member which is able to anastomoses the first tubular organ with a second tubular organ in the abdominal cavity, and a cutting member with which the second tubular organ is able to be cut.

Abstract: The present invention relates to a method of providing electrical stimulation to a liver of a subject which includes providing one or more stimulatory electrodes to the liver of the subject and providing electrical stimulation to the liver of the subject. The invention further relates to methods of reducing risk factors of metabolic syndrome, treating diabetes, treating a subject having eating disorders and reducing glucose levels of a subject using methods of the present invention.

Abstract: There is provided an endoscopic system. The system comprises a flexible endoscope insertable into a first tubular organ from a natural opening of a human body. The system further comprises an opening member which forms on a wall part of the first tubular organ an opening used to insert the endoscope into an abdominal cavity from the first tubular organ in the body, an anastomosing member which is able to anastomoses the first tubular organ with a second tubular organ in the abdominal cavity, and a cutting member with which the second tubular organ is able to be cut.

Abstract: Provided herein are methods of treating gastrointestinal motility disorders by targeting the dopamine 3 receptor (D3R). A D3R agonist is administered to a subject to decrease gastrointestinal motility to treat the disorder. A D3R antagonist is administered to a subject to decrease gastrointestinal motility to treat the disorder.

Abstract: A tissue puncturing system used to suture tissues in a body cavity including: an endoscope; a flexible sheath having a distal portion provided with at least a side opening and a lumen, through which an endoscope may pass; at least one mechanism for puncturing tissue disposed in the flexible sheath, and having a pointed end, which is movable from a first position to a second position; and an operation mechanism for moving the mechanism for puncturing between the first and second positions.