Prostaglandin I suppresses the development of gut-brain axis disorder in irritable bowel syndrome in rats.

In this study, we attempted to clarify a role of prostaglandin (PG) I and its specific receptor, IP in the pathogenesis of irritable bowel syndrome (IBS) using a maternal separation (MS)-induced IBS model. Administration of beraprost (BPS), a specific IP agonist, improved visceral hypersensitivity and depressive state with decreased serum CRF level in the IBS rats. To clarify the mechanism of the effect of BPS, we performed serum metabolome analysis and 1-methylnicotinamide (1-MNA) was identified as a possible candidate for a clue metabolite of pathogenesis of IBS.

Epipericardial Fat Necrosis: A Retrospective Analysis in Japan.

Objective Epipericardial fat necrosis (EFN) has been considered to be a rare cause of acute chest pain, and especially important for emergency physicians. Chest computed tomography (CT) is often used for the diagnosis of EFN after excluding life-threatening states, such as acute coronary syndrome and pulmonary embolism. While the proportion of EFN patients who underwent chest CT in emergency departments is being clarified, little is still known about other departments in Japan.

Oxytocin acts centrally in the brain to improve leaky gut through the vagus nerve and a cannabinoid signaling in rats.

Brain oxytocin plays a role in gastrointestinal functions. Among them, oxytocin acts centrally to modulate gastrointestinal motility and visceral sensation. Intestinal barrier function, one of important gut functions, is also regulated by the central nervous system.

Centrally administered butyrate improves gut barrier function, visceral sensation and septic lethality in rats.

Short chain fatty acids readily crosses the gut-blood and blood-brain barrier and acts centrally to influence neuronal signaling. We hypothesized that butyrate, a short-chain fatty acid produced by bacterial fermentation, in the central nervous system may play a role in the regulation of intestinal functions. Colonic permeability and visceral sensation was evaluated in rats.

Activation of central adenosine A2B receptors mediate brain ghrelin-induced improvement of intestinal barrier function through the vagus nerve in rats.

Leaky gut that is a condition reflecting intestinal barrier dysfunction has been attracting attention for its relations with many diseases such as irritable bowel syndrome or Alzheimer dementia. We have recently demonstrated that ghrelin acts in the brain to improve leaky gut via the vagus nerve. In the present study, we tried to clarify the precise central mechanisms by which ghrelin improves intestinal barrier function through the vagus nerve.

Centrally administered orexin prevents lipopolysaccharide and colchicine induced lethality via the vagal cholinergic pathway in a sepsis model in rats.

Orexins are neuropeptides implicated in several physiological functions. Accumulating findings suggest a relationship between orexin and sepsis. A recent study demonstrated that orexin acts centrally to improve conditions in sepsis.

Ghrelin acts in the brain to block colonic hyperpermeability in response to lipopolysaccharide through the vagus nerve.

Brain ghrelin plays a role in gastrointestinal functions. Among them, ghrelin acts centrally to stimulate gastrointestinal motility and induce visceral antinociception. Intestinal barrier function, one of important gastrointestinal functions, is also controlled by the central nervous system.

Adenosine A receptor agonist induces visceral antinociception via 5-HT, 5-HT, dopamine D or cannabinoid CB receptors, and the opioid system in the central nervous system.

We have recently demonstrated that N(6)-cyclopentyladenosine (CPA), an adenosine A1 receptor agonist, acts centrally to induce a visceral antinociception. Since serotonin (5-HT), cannabinoid (CB), dopamine or opioid signaling in the central nervous system is involved in the regulation of visceral sensation, we made a hypothesis that the signaling may play a role in the CPA-induced visceral antinociception. Visceral sensation was evaluated by colonic distension-induced abdominal withdrawal reflex (AWR) in conscious rats.

5-HT receptors but not cannabinoid receptors in the central nervous system mediate levodopa-induced visceral antinociception in conscious rats.

We have recently demonstrated that levodopa acts centrally to induce antinociceptive action against colonic distension through dopamine D receptors in rats. Since serotonin (5-HT) and cannabinoid are involved in the regulation of visceral sensation, we hypothesized that they may contribute to levodopa-induced visceral antinociception. We evaluated visceral sensation by colonic distension-induced abdominal withdrawal reflex (AWR) in conscious rats.

Brain orexin improves intestinal barrier function via the vagal cholinergic pathway.

Orexins are neuropeptides that are implicated in a number of functions. With regard to the gastrointestinal functions, orexin acts centrally to regulate gastric secretion, gastrointestinal motility and visceral sensation. Little is however known about a role of central orexin in the control of intestinal barrier function.

Prostaglandin F2α Facilitates Platelet Activation by Acting on Prostaglandin E2 Receptor Subtype EP3 and Thromboxane A2 Receptor TP in Mice.

Platelets play an important role in both physiological hemostasis and pathological thrombosis. Thromboxane (TX) A and prostaglandin (PG) I are well known as a potent stimulator and an inhibitor of platelet function, respectively. Recently, PGE has also been reported to regulate platelet function via PGE receptor subtypes.

Central oxytocin signaling mediates the central orexin-induced visceral antinociception through the opioid system in conscious rats.

Central oxytocin is implicated in a wide variety of physiological functions. With regard to gastrointestinal functions, oxytocin acts centrally to regulate gastrointestinal motility. Visceral sensation is also known as one of key gastrointestinal functions which are controlled by the central nervous system (CNS).

Metformin inhibits visceral allodynia and increased gut permeability induced by stress in rats.

Background And Aim: Metformin has been shown to have anti-cytokine property. Lipopolysaccharide (LPS)-induced or repeated water avoidance stress (WAS)-induced visceral allodynia and increased gut permeability were pro-inflammatory cytokine-dependent responses, which were considered to be animal models of irritable bowel syndrome (IBS). We hypothesized that metformin improves symptoms in the patients with IBS by attenuating these visceral changes and tested the hypothesis in rats.

Role of the cannabinoid signaling in the brain orexin- and ghrelin-induced visceral antinociception in conscious rats.

We hypothesized that the cannabinoid (CB) system may mediate the brain orexin- or ghrelin-induced visceral antinociception. Intraperitoneal injection of either CB agonist, WIN 55212 or O-Arachidonoyl ethanolamine increased the threshold volume of colonic distension-induced abdominal withdrawal reflex in rats, suggesting CB could induce visceral antinociception. Pretreatment with either the CB or CB antagonist potently blocked the centrally injected orexin-A-induced antinociceptive action against colonic distension while CB but not CB antagonist blocked the brain ghrelin-induced visceral antinociception.

Ghrelin acts centrally to induce an antinociceptive action during colonic distension through the orexinergic, dopaminergic and opioid systems in conscious rats.

Increasing evidence implicates brain ghrelin in a wide variety of physiological functions. Among its gastrointestinal functions, ghrelin is known to act centrally to regulate gastrointestinal motility. Visceral sensation is one of the key gastrointestinal functions controlled by the central nervous system.

Prostaglandin I suppresses the development of diet-induced nonalcoholic steatohepatitis in mice.

Nonalcoholic steatohepatitis (NASH) is a hepatic manifestation of metabolic syndrome. Although the prostaglandin (PG)I receptor IP is expressed broadly in the liver, the role of PGI-IP signaling in the development of NASH remains to be determined. Here, we investigated the role of the PGI-IP system in the development of steatohepatitis using mice lacking the PGI receptor IP [IP-knockout (IP-KO) mice] and beraprost (BPS), a specific IP agonist.

Lovastatin inhibits visceral allodynia and increased colonic permeability induced by lipopolysaccharide or repeated water avoidance stress in rats.

Statins have been reported to block inflammatory somatic pain and have an anti-cytokine property. Lipopolysaccharide (LPS) or repeated water avoidance stress (WAS) induces visceral hypersensitivity and increases gut permeability in rats, which are mediated through proinflammatory cytokine-dependent pathways. Since visceral hypersensitivity with increased gut permeability plays a crucial role in the pathophysiology of irritable bowel syndrome (IBS), these above animal models are considered to simulate IBS.

Cigarette Smoke Extract Inhibits Platelet Aggregation by Suppressing Cyclooxygenase Activity.

The results of studies that were performed to determine whether cigarette smoking affects platelet function have been controversial, and the effects of nicotine- and tar-free cigarette smoke extract (CSE) on platelet function remain to be determined. The aim of this study was to determine the effect of CSE on platelet aggregation and to clarify the mechanism by which CSE affects platelet function. CSE inhibited murine platelet aggregation induced by 9,11-dideoxy-9α,11α-methanoepoxy-prosta-5Z,13E-dien-1-oic acid (U-46619), a thromboxane (TX) A receptor agonist, and that induced by collagen with respective IC values of 1.

Cold Exposure Related Fever with an Mediterranean Fever (MEFV) Gene Mutation.

Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease characterized by recurrent fever with serosal inflammation. We experienced a 53-year-old male who had been suffering from periodic attacks with slight fever and myalgia which were mainly triggered by cold exposure in winter. Although his clinical course did not satisfy the criteria for familial Mediterranean fever, heterozygous E148Q/M694I mutation in the Mediterranean fever (MEFV) gene was detected.

Glucagon-like peptide-1 analog, liraglutide, improves visceral sensation and gut permeability in rats.

Background And Aim: A glucagon-like peptide-1 analog, liraglutide, has been reported to block inflammatory somatic pain. We hypothesized that liraglutide attenuates lipopolysaccharide (LPS)-induced and repeated water avoidance stress (WAS)-induced visceral hypersensitivity and tested the hypothesis in rats.

Methods: The threshold of the visceromotor response induced by colonic balloon distention was measured to assess visceral sensation.

Adenosine A1 receptors mediate the intracisternal injection of orexin-induced antinociceptive action against colonic distension in conscious rats.

We have recently demonstrated that orexin acts centrally through the brain orexin 1 receptors to induce an antinociceptive action against colonic distension in conscious rats. Adenosine signaling is capable of inducing an antinociceptive action against somatic pain; however, the association between changes in the adenosinergic system and visceral pain perception has not been investigated. In the present study, we hypothesized that the adenosinergic system may be involved in visceral nociception, and thus, adenosine signaling may mediate orexin-induced visceral antinociception.

Levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain in conscious rats.

Levodopa possesses antinociceptive actions against several somatic pain conditions. However, we do not know at this moment whether levodopa is also effective to visceral pain. The present study was therefore performed to clarify whether levodopa is effective to visceral pain and its mechanisms.

Involvement of the dopaminergic system in the central orexin-induced antinociceptive action against colonic distension in conscious rats.

We have recently demonstrated that orexin acts centrally in the brain to induce antinociceptive action against colonic distension through orexin 1 receptors in conscious rats. Although the dopaminergic system can induce antinociceptive action for somatic pain, the association between changes in the dopaminergic system and visceral pain perception has not been investigated. In the present study, we hypothesized that the dopaminergic system may be involved in visceral nociception, and if so, the dopaminergic system may mediate the orexin-induced visceral antinociception.