Mario Jin

New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline

Background : In functional gastrointestinal (GI) disorders including functional dyspepsia (FD) and irritable bowel syndrome (IBS), there might be no small extent of contributions of psychosomatic factors. As a therapy for IBS patients, the effectiveness of antidepressants has been reported.

Induction of a 72-kDa heat-shock protein in cultured rat gastric mucosal cells and rat gastric mucosa by zinc L-carnosine.

An antiulcer drug, zinc l-carnosine (polaprezinc), provides gastric mucosal protection against various irritants. In this study, we evaluated the effects of zinc l-carnosine on expression of 72-kDa heat shock protein (HSP72, stress inducible HSP70), which is known as an endogenous cytoprotectant in a wide variety of cells, including rat gastric mucosa in vitro and in vivo. Expression of HSP72 after exposure to zinc l-carnosine, zinc sulfate, or l-carnosine (1–300 μM) in rat gastric mucosal cells (RGM1) and intragastric administration of zinc l-carnosine, zinc sulfate (30 or 100 mg/kg) and l-carnosine (76 mg/kg) was investigated by western blotting and densitometric analysis. Exposure to zinc l-carnosine and zinc sulfate increased the expression of HSP72 significantly in RGM1 cells. Intragastric administration of zinc l-carnosine and zinc sulfate showed significant increment in HSP72 in rat gastric mucosa also in vivo. The ability to induce HSP72 is significantly higher in zinc l-carnosine compared with zinc sulfate based on molecular concentration in vivo. However, l-carnosine did not increase the expression of HSP72 in vitro and in vivo. Zinc derivatives, especially zinc l-carnosine, could be a strong HSP72 (chaperon) inducer, which has been known to enhance mucosal protective ability.

Association of 72-kDa heat shock protein expression with adaptation to aspirin in rat gastric mucosa

It is well documented that gastric mucosa canincrease its resistance to mucosal damage caused byaspirin during repeated long-term administration ofaspirin. However, the underlying mechanism of thisadaptation is not well established. In the present study,we investigated the effect of long-term (chronic)administration of aspirin on expression of heat shockproteins (HSPs), which are known as endogenouscytoprotectants, in rat gastric mucosa. Rats were administeredaspirin (100 mg/kg) daily for up to 20 days. Aftervarious periods of aspirin administration, a high doseof aspirin (250 mg/kg) was administered, and the mucosal damage was assessed. Expression of heat shockproteins (HSPs) in gastric mucosa was evaluated byWestern blot. Intracellular localization of each HSP wasstudied immunohistochemically. ProstaglandinE2 (PGE2) and leukotriene B4(LTB4) levels were also investigated.Long-term aspirin administration resulted in developmentof resistance to aspirin-induced mucosal damage, and theincrease of HSP72 expression correlated with mucosal resistance to aspirin.No significant increase was observed in HSP60 and HSP90levels. Immunohistochemical study showed an increase ofHSP72 in the cytoplasm of mucosal surface cells. The PGE2 level was suppressed and nochange in the level of LTB4 was observed. Itis possible that HSP72 could play important roles ingastric mucosal adaptation when the PGE2level is suppressed by NSAIDs.

Differential Induction of HSP60 and HSP72 by Different Stress Situations in Rats (Correlation with Cerulein-Induced Pancreatitis)

We previously reported that water-immersionstress specifically induced the synthesis of a 60-kDaheat-shock protein (HSP60, chaperonin homolog) inpancreatic cells and preinduction of HSP60 completely prevented development of cerulein-inducedpancreatitis in the rat in an HSP60 quantitativelydependent manner. In order to study the cytoprotectivefunction of a 72-kDa heat-shock protein (HSP72,stress-inducible hsp70), the effect of specific preinduction ofHSP72 by hyperthermia on cerulein-induced pancreatitiswas investigated and compared with the effect ofpreinduction of HSP60 in this study. Expression of HSP60 and HSP72 in the pancreas wasinvestigated by immunoblot before and after waterimmersion or hyperthermia. Following pretreatment withwater-immersion stress or hyperthermia, the rats wereinjected with cerulein (40 μg/kg, intraperitoneally).The pancreas wet weight and serum amylase concentrationwere measured before and after cerulein injection.Hyperthermia (42.5°C, 20 min) specifically induced HSP72 in the pancreas. The synthesis of HSP60was specifically induced by water-immersion stress inthe pancreas. Cerulein-induced pancreatitis was clearlyprevented by specific preinduction of HSP60 by water-immersion stress. However, preinductionof HSP72 by hyperthermia had no preventive effect oncerulein-induced pancreatitis. Our findings suggest thatHSP60 and HSP72 have distinct functions in the pancreas, and their induction mechanisms arealso different in vivo. These results could be importantfor understanding the mechanism of “adaptivecytoprotection” in the pancreas mediated byheat-shock proteins.

Effect of preinduction of heat shock proteins on acetic acid-induced colitis in rats

In order to study the cytoprotective function ofheat shock proteins (HSPs) in vivo, the effect ofpreinduction of HSPs by hyperthermia on aceticacid-induced colitis was investigated. Expression of60-kDa, 72-kDa, and 90-kDa heat shock proteins (HSP60,HSP72, and HSP90, respectively) in rat colonic mucosawas investigated by Western blot analysis andimmunohistochemical study before and after hyperthermia. Following pretreatment with or withouthyperthermia, the rats received intrarectal infusion ofvarious doses of acetic acid. The colonic mucosal damagewas evaluated by macroscopic and microscopic assessments 24 hr after the intrarectal infusion of aceticacid. Expression of HSPs was significantly increased byhyperthermia in rat colonic mucosa. Immunohistochemicalstudy also showed the increments of HSPs in the colonic mucosal cells after hyperthermia.Acetic acid-induced colitis was dramatically preventedby pretreatment with hyperthermia when HSP72 and HSP90were preinduced. On the other hand, induction of HSP60 did not correlate with mucosalprotection. Our findings suggest that HSP72 and HSP90may have cytoprotective function against aceticacid-induced mucosal damage. These results may beimportant for understanding the mechanism of“adaptive cytoprotection” mediated byHSPs.

Induction of a 72-kDa Heat Shock Protein and Cytoprotection Against Thioacetamide-Induced Liver Injury in Rats

Heat shock proteins are ubiquitous intracellularproteins induced by various physiological stress-relatedevents. A 72-kDa heat shock protein (HSP72) has beenreported to be an endogenous cytoprotectant in variety of cells in vitro . In order tostudy the cytoprotective function of HSP72 in the liver,the effect of preinduction of HSP72 in rat liver bysystemic hyperthermia on thioacetamide-induced hepatic injury was investigated in this study.Expression of HSP72 in the liver was investigated byimmunoblot and densitometric analysis. Rats wereinjected with thioacetamide (100 mg/kg, subcutaneously)with or without preinduction of HSP72 byhyperthermia. Serum AST and ALT concentrations weremeasured before and after thioacetamide injection inboth group. Histologic alteration of the liver wasevaluated also. Systemic hyperthermia (42.5°C, 20min) significantly induced HSP72 in the liver.Thioacetamide-induced hepatic injury was clearlyprevented by preinduction of HSP72 by hyperthermia.Prevention of hepatocyte damage was more clear in the areaaround central veins where HSP72 induction was apparent.Our findings might suggest that HSP72 has an importantfunction in the liver with respect to cytoprotection. These results might be important forunderstanding the mechanism of “adaptivecytoprotection” in the liver mediated by thefunction of heat shock proteins as “molecularchaperons” as reported in vitro.

Disseminated intra-abdominal cystic lymphangiomatosis with severe intestinal bleeding. A case report.

We describe cystic lymphangiomatosis with intestinal bleeding developing multiple lymphangiomas in the small intestine, mesentery, mesocolon, omentum, retroperitoneum, and spleen. Small intestinal fluorography showed multiple polypoid lesions, mainly in the jejunum. Ultrasonography, computed tomography, and magnetic resonance imaging showed diffuse cystic tumors in the mesentery and spleen. Cystic lymphangiomatosis was proved by histologic findings of the biopsied specimen at laparotomy.

Large Brunner’s Gland Hyperplasia Treated with Modified Endoscopic Submucosal Dissection

Brunner’s glands are mucosal and submucosal alkalinesecreting glands that are most commonly located in the duodenum, especially in the first part of the duodenum, although they are rarely found in the pylorus and jejunum. Hyperplasia of these glands is normally seen in 2% of upper gastrointestinal (GI) endoscopies [1]. Five percent to 10% of benign duodenal tumors are caused by lesions of Brunner’s gland [2]. They are usually asymptomatic and lesions are discovered incidentally but they can occasionally cause symptoms such as GI hemorrhage and obstruction when they reach sizes >2 cm [3, 4]. In this paper, we report a case of large hyperplasia of Brunner’s gland successfully treated by modified endoscopic submucosal dissection (ESD) technique.

Selective adenosine A2A receptor agonist, ATL‐146e, attenuates stress‐induced gastric lesions in rats

Background:  Activation of adenosine A2A receptors reduces the production of various pro‐inflammatory cytokines and suppresses neutrophil activation. Water‐immersion restraint is well known to cause gastric mucosal lesions due to stress. The pathogenesis of stress‐induced gastric mucosal lesions is characterized by activation of inflammatory cells and production of inflammatory cytokines. Agonists of adenosine A2A receptors are known to be anti‐inflammatory, but the effects of these compounds on the development of gastric mucosal lesions has not been reported. In the present study, the effect of a potent and selective adenosine A2A receptor agonist, ATL‐146e, on water‐immersion stress‐induced gastric mucosal lesions was studied.

Selective A2A adenosine agonist ATL-146e attenuates acute lethal liver injury in mice

Backgroundd-Galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury is an experimental model of fulminant hepatic failure in which tumor necrosis factor-α (TNF-α) plays a pivotal role. We examined the effects of a highly selective adenosine A2A receptor agonist (ATL-146e) on GalN/LPS-induced fulminant hepatic failure.MethodsMice were given an intraperitoneal dose of GalN (800 mg/g body weight)/LPS (100 ng/g body weight) with and without ATL-146e (0.01 µg/kg) treatment. Liver injury was assessed biochemically and histologically. Also, TNF-α levels in the serum were determined.ResultsThe serum liver enzyme (ALT) level in vehicle-treated mice was 20 960 ± 2800 IU/ml and was reduced by 63% to 7800 ± 1670 IU/ml by treatment with 0.01 µg/kg per minute ATL146e, P < 0.05. Treatment with ATL-146e significantly reduced serum TNF-α and greatly reduced inflammation assessed by histopathologic examination compared with control mice treated with GalN/LPS. ATL-146e also reduced lethality at 12 h from 65% to 13%.ConclusionThe present findings suggest that the highly selective adenosine A2A receptor agonist (ATL-146e) prevents endotoxin-induced lethal liver injury by suppression of TNF-α secretion.